WO2020211787A1

WO2020211787A1 - Pharmaceutical preparation, system comprising same, preparation method therefor and application thereof

Info

Publication number: WO2020211787A1
Application number: PCT/CN2020/084970
Authority: WO
Inventors: 张洁; 唐培克
Original assignee: 湖州依诺唯新药物制剂有限公司
Priority date: 2019-04-15
Filing date: 2020-04-15
Publication date: 2020-10-22
Also published as: CN111821257A; CN113573697A

Abstract

A pharmaceutical preparation, a system comprising same, a preparation method therefor and an application thereof. The pharmaceutical preparation comprises water and a local anesthetic; the local anesthetic in the pharmaceutical preparation comprises a dissolved and an undissolved local anesthetic; the mass percentage of the local anesthetic in the pharmaceutical preparation is more than 2%, and the mass percentage of the dissolved local anesthetic in the pharmaceutical preparation is less than 1%; the local anesthetic can be lidocaine, tetracaine, bupivacaine, articaine, cinchocaine, dibucaine, etidocaine, levobupivacaine, methacaine, prilocaine, ropivacaine, trimacaine, benzocaine, or procaine; and the sum of the mass percentages of the components in the pharmaceutical preparation is 100%. The system comprises a cover film containing a mesh adhesive layer, a barrier film and an adhesion layer. In many analgesic applications, the described system can achieve 6, 12, 18, 24, 36, or even 48 hours or longer of continuous analgesia.

Description

Pharmaceutical preparation, system containing the same, preparation method and application thereof

This application claims the priority of the Chinese patent application CN201910299964.3 whose filing date is April 15, 2019. This application quotes the full text of the aforementioned Chinese patent application.

Technical field

The invention relates to a pharmaceutical preparation, a system containing the same, and a preparation method and application thereof.

Background technique

Local anesthetic preparations are used to prevent or treat skin or mucous membrane pain, for example: 2% lidocaine hydrochloride gel is used to relieve pain related to sunburn; Enna (English name EMLA) is a kind of lidocaine An emulsion of low-point eutectic oil drops with prilocaine, which is used for anesthesia of intact skin before surgery with pain; Lidoderm is a solidified gel patch containing 5% lidocaine, which is used to relieve banding Postherpetic neuralgia (the skin itself is intact); Pliaglis is an emulsion containing 7% lidocaine and 7% tetracaine low-point eutectic oil drop-shaped emulsion, which is used for painful intact skin before surgery Anesthesia. However, each of the above-mentioned local anesthetic preparations has serious limitations. For example: Lidocaine hydrochloride gel cannot anesthetize intact skin; prilocaine in EMLA can cause methemoglobinemia; tetracaine in Pliaglis can cause allergic reactions related to ester local anesthetics, and tetracaine can It is hydrolyzed, so Pliaglis must be stored in refrigeration to reduce the rate of hydrolysis; Lidoderm cannot anesthetize complete skin within 120 minutes or even 4 hours, and Lidoderm cannot be used for more than 12 hours each time. However, the common limitation of the above-mentioned local anesthetic preparations is that they cannot achieve long-term continuous and safe analgesic effects.

In the treatment of many diseases, the ideal product is capable of 6, 12, 18, 24, 36, or even 48 hours or longer continuous analgesia. Therefore, seeking a safe, long-term and continuous safe analgesic effect is a problem that needs to be solved urgently.

In addition, in order to achieve the long-term analgesic effect of water-containing pharmaceutical preparations on the affected area, it is important to keep the drug layer applied to the affected area in place and retain the volatile components (water) in it, because after losing enough volatile components , The ability of pharmaceutical preparations to deliver effective ingredients into the skin may be greatly reduced. Therefore, seeking a drug formulation that is resistant to flow and a system that can ensure that the water of the drug formulation does not evaporate is also a problem that needs to be solved urgently.

Human body surfaces that are not covered by skin or mucous membranes, such as surgical incisions, burns and scald surfaces, wound surfaces, etc. These open human body surfaces often require analgesia. The characteristic of open human body surfaces is the absorption of foreign substances, such as local anesthetics. Absorption, there is no barrier like skin. Therefore, if a local anesthetic preparation without sustained-release function is placed on an open human surface, for example, if 2% lidocaine hydrochloride commonly used in hospitals is applied to the surface of burns and scalds, the local anesthetic contained in the preparation will be very It is quickly absorbed into the systemic blood circulation, resulting in high blood drug concentration that may cause serious side effects and a short duration of analgesic effect. For this reason, seeking a pharmaceutical preparation that can achieve sustained-release effects is also an urgent problem to be solved. .

Incisional analgesia after surgery is a common requirement. Nowadays, the commonly used method is to use analgesic pumps to transfer drugs that act on the central nervous system, such as fentanyl and dolanidine, into the patient's body. These drugs enter the brain tissue after passing through the blood-brain barrier and bind to related pain receptors to achieve the purpose of analgesia. But all these central nervous system analgesics may cause serious side effects, such as respiratory depression and addiction. Therefore, the use of local anesthetics without central nervous function to control postoperative incision pain would be a significant improvement. However, as mentioned above, the local anesthetic preparation for surgical incision pain relief must release the local anesthetic contained in it in a slow-release manner. According to this idea, the product Exparel recently launched by Pacira Company uses a specially formulated local anesthetic bupivacaine to replace or reduce the amount of central nervous analgesics, which has been welcomed by doctors and patients. However, Exparel has many weaknesses: (1) The liposomes encapsulating bupivacaine in the preparation are unstable, so Exparel must be stored and transported under refrigeration; (2) Exparel must be injected with up to 20 needles along the surgical incision. It is very inconvenient and time-consuming to use; (3) The need for analgesia after surgery is generally at least 2-3 days, but the effective analgesic effect of Exparel is only 24 hours. Therefore, it is also an urgent problem to find a pharmaceutical preparation that can achieve analgesia of incisions after long-term surgery, can be conveniently used, and can be transported and stored at room temperature.

Summary of the invention

The technical problem to be solved by the present invention is to overcome the defect that the local anesthetic preparations in the prior art cannot achieve long-term continuous and safe analgesic effects, and to provide a novel pharmaceutical preparation, a system containing the same, and a preparation method and application thereof .

The pharmaceutical preparation of the present invention and the system containing it are mainly applied to the human body surface (intact skin or open human body surface) that needs analgesia, and can obtain 6, 12, 18, 24, 36, 48 hours or even longer Continuous and safe analgesic effect.

The pharmaceutical preparation of the present invention also has the advantages of room temperature storage and convenient use. In analgesic applications, the pharmaceutical preparation of the present invention can replace traditional central nervous anesthetics, thereby avoiding the serious side effects of central nervous anesthetics.

The present invention solves the above technical problems through the following technical solutions:

The present invention provides a pharmaceutical preparation comprising water and a local anesthetic; the local anesthetic in the pharmaceutical preparation includes a dissolved local anesthetic and an undissolved local anesthetic; the local anesthetic in the pharmaceutical preparation The mass percentage of the drug in the pharmaceutical preparation is more than 2% and not 100%; the mass percentage of the dissolved local anesthetic in the pharmaceutical preparation is less than 1% and is not 0; the drug The local anesthetics in the preparation are lidocaine, tetracaine, bupivacaine, articaine, cinchocaine, dibucaine, eticaine, levobupivacaine, mepivacaine, and propylamine Caine, ropivacaine, trimecaine, benzocaine or procaine; the total mass percentage of each component in the pharmaceutical preparation is 100%.

In the above-mentioned pharmaceutical preparations, the pharmaceutical preparations may preferably further contain a pH buffering pair, the pH buffering pair is dissolved in the water in the pharmaceutical preparation to form a pH buffering solution; the pH buffering solution makes the dissolved part The mass percentage of the anesthetic in the pharmaceutical preparation is less than 1% and not zero.

In the above-mentioned pharmaceutical preparations, the pH buffer pair refers to the so-called "pH buffer pair" in the field of biochemistry, that is, the two substances constituting the conjugate acid-base pair of the pH buffer solution.

In the above-mentioned pharmaceutical preparation, the pH buffer pair may be, for example, a pH buffer pair commonly used in the field of biochemistry, and the pH value of the pH buffer solution formed by it can reduce the concentration of the dissolved local anesthetic in the pharmaceutical preparation. The mass percentage should be controlled below 1% and not 0. The pH buffer pair can be, for example, a pH buffer pair that can effectively resist changes in the pH value of the pharmaceutical preparation in the range of pH 7-13, preferably a pH buffer composed of disodium hydrogen phosphate and sodium dihydrogen phosphate Yes, a pH buffer pair composed of dipotassium hydrogen phosphate and potassium dihydrogen phosphate, a pH buffer pair composed of sodium tetraborate and sodium hydroxide or a pH buffer pair composed of tris and HCl, more preferably hydrogen phosphate A pH buffer pair composed of disodium and sodium dihydrogen phosphate or a pH buffer pair composed of sodium tetraborate and sodium hydroxide, and more preferably a pH buffer pair composed of disodium hydrogen phosphate and sodium dihydrogen phosphate. The pH buffering solution formed by the pH buffering pair can resist the change of the pH value of the pharmaceutical preparation caused by the entry of external substances. The infiltration of these external substances includes the infiltration of body fluids or sweat, contact with air, and the infiltration of other substances after contact with other drugs used at the same time.

When the pH buffer pair is a pH buffer pair composed of disodium hydrogen phosphate and sodium dihydrogen phosphate, the molar concentration of the pH buffer pair in the pharmaceutical preparation is preferably 0.02-0.4 mol/L, more preferably The ground is 0.05-0.3 mol/L or 0.1-0.3 mol/L, and more preferably 0.08-0.22 mol/L.

Wherein, the aforementioned molar concentration unit mol/L refers to the molar amount of the pH buffer pair per liter of the pharmaceutical preparation.

Wherein, preferably, the ratio of the molar concentration of sodium dihydrogen phosphate to the molar concentration of disodium hydrogen phosphate in the pharmaceutical preparation is 14:1-19:1. For example, a pH buffer pair consisting of 0.19 mol/L disodium hydrogen phosphate and 0.01 mol/L sodium dihydrogen phosphate can be used; wherein, 0.19 mol/L disodium hydrogen phosphate means that the pharmaceutical preparation contains 0.19 moles per liter. Disodium hydrogen phosphate, 0.01 mol/L sodium dihydrogen phosphate refers to 0.01 mole of sodium dihydrogen phosphate per liter of the pharmaceutical preparation.

In the above-mentioned pharmaceutical preparations, the pH of the pharmaceutical preparations can be, for example, 7-13, preferably 7-11 or 7.5-9.5.

Among them, preferably, during the preparation of the pharmaceutical preparation, the pH buffer pair is selected to control the pH value of the pharmaceutical preparation within the aforementioned range; more preferably, during the preparation of the pharmaceutical preparation, the Before the pH buffer pair, an alkaline substance is used to adjust the pH value of the system to the aforementioned range, and then the pH buffer pair that can form a pH buffer solution corresponding to the pH value is added; the alkaline substance is preferably One or more of sodium tripolyphosphate, sodium bicarbonate, sodium hydroxide, and potassium hydroxide, more preferably sodium hydroxide and/or potassium hydroxide, and still more preferably sodium hydroxide.

In the above-mentioned pharmaceutical preparations, the mass percentage of the local anesthetics in the pharmaceutical preparations in the pharmaceutical preparations can also be 3% or more, 4% or more, 5% or more, 8% or more, or 10% or more, for example, 3%. %-15%, 4%-10% or 5%-8%.

In the above pharmaceutical preparation, the dissolved local anesthetic refers to a local anesthetic dissolved in water in the pharmaceutical preparation.

In the above-mentioned pharmaceutical preparation, the mass percentage of the dissolved local anesthetic in the pharmaceutical preparation may also be less than 0.7%, 0.5%-0.7% or less than 0.5%.

In the above pharmaceutical preparations, the undissolved local anesthetic refers to a local anesthetic that is not dissolved in water in the pharmaceutical preparation.

In the above-mentioned pharmaceutical preparations, the local anesthetic in the pharmaceutical preparations is preferably lidocaine, tetracaine or bupivacaine, more preferably lidocaine or tetracaine, further more preferably lidocaine because.

Among the above-mentioned pharmaceutical preparations, the pharmaceutical preparation preferably includes a suspending agent, which may be a suspending agent conventionally used in the field, the suspending agent is preferably carbomer, and the type of the suspending agent is preferably The location is Pemulen TR-2 or Carbopol 971, and the manufacturer is Lubrizol, USA. The mass percentage of the suspension in the pharmaceutical preparation is preferably 0.10%-0.50%.

In the above-mentioned pharmaceutical preparations, the pharmaceutical preparations preferably include a thickening agent. The addition of a thickening agent can increase the viscosity of the pharmaceutical preparation and reduce the flow of the pharmaceutical preparation applied to the skin from the target area of the skin or other tissues. open. The thickening agent is preferably one or more of xanthan gum, starch, carbomer and cellulose, more preferably xanthan gum, starch, hydroxyethyl cellulose and hydroxypropyl cellulose One or more of. The mass percentage of the thickener in the pharmaceutical preparation is preferably 0.2%-8%, more preferably 1%-6%, and still more preferably 2%-5%.

In the above-mentioned pharmaceutical preparations, the pharmaceutical preparations preferably include glycerol and/or propylene glycol; the mass percentage of the glycerol and/or propylene glycol in the pharmaceutical preparations is preferably 2%-25%.

In the above-mentioned pharmaceutical preparations, the pharmaceutical preparations preferably include a gel forming agent. The mass percentage of the gel forming agent in the pharmaceutical preparation is preferably 0.2%-10%, preferably 0.2%-5%, more preferably 0.5%-4%, and still more preferably 1.0 %-3.0%.

Among them, the gel forming agent is preferably one or more of xanthan gum, uronic acid and uronic acid salt, more preferably xanthan gum, uronic acid or uronic acid salt, and further more preferably xanthan A mixture of native gum and acid or a mixture of xanthan gum and sodium sulfate.

Among them, there are two types of the said acid, one is cross-linked acid and the other is non-cross-linked acid. The acid may be a cross-linked acid, a non-cross-linked acid, or a mixture of a cross-linked acid and a non-cross-linked acid.

Among them, the salt of salt is preferably sodium salt of salt. There are two types of the sodium carboxylate, one is cross-linked sodium acrylate and the other is non-cross-linked sodium acrylate. The said sodium phosphate may be cross-linked sodium phosphate, non-cross-linked sodium phosphate, or a mixture of cross-linked sodium phosphate and non-cross-linked sodium sulfate.

Wherein, more than 95% by weight of the qualitative acid in the qualitative acid is preferably non-crosslinked plasmonic acid, and more preferably 98% to 100% by weight of the qualitative acid is non-crosslinked plasmonic acid.

Among them, preferably more than 95% by weight of the sodium arginate is non-cross-linked sodium acrylate, and more preferably 98% by weight to 100% by weight is non-cross-linked sodium acrylate.

Among the above-mentioned pharmaceutical preparations, the pharmaceutical preparations preferably include a gel. The mass percentage of the glue in the pharmaceutical preparation is preferably 0.1-30%, more preferably 0.5-15%, or 1%-5%. The glue may be any substance that makes the pharmaceutical preparation sticky, such as xanthan gum, polyvinyl alcohol or polyvinylpyrrolidone. Thus, the glue can make the pharmaceutical preparation sticky, so when the pharmaceutical preparation is applied to the skin or wound to form a thin layer of the pharmaceutical preparation, and then further covered with a covering film, the covering film can It is stuck on a thin layer of pharmaceutical preparations.

In the above-mentioned pharmaceutical preparations, the pharmaceutical preparations preferably include a substance that can be crosslinked. The mass percentage of the crosslinkable substance in the pharmaceutical preparation is preferably 0.1-30%, more preferably 0.5-15%, or 1%-5%. The cross-linkable substance may be any substance that is not antagonistic to other components of the pharmaceutical preparation (that is, does not affect the efficacy) but can be cross-linked by the corresponding cross-linking agent. If the cross-linkable substance in the pharmaceutical preparation is a glue, it can be called a cross-linkable glue. The crosslinkable substance may be a crosslinkable glue or a crosslinkable substance without glue function. The crosslinkable substance may be a substance that undergoes a crosslinking reaction with a corresponding crosslinking agent in the cover film, for example, polyvinyl alcohol or polyvinylpyrrolidone.

For example, the material that can be crosslinked is polyvinyl alcohol; and in the cover film, the crosslinking agent corresponding to polyvinyl alcohol can be sodium borate, glutaraldehyde, glyoxal, maleic acid, citric acid, Trisodium trimetaphosphate, sodium hexametaphosphate, dianhydride, succinic acid or sulfosuccinic acid. When the sodium borate (or other cross-linking agent) in the cover film enters the pharmaceutical preparation containing polyvinyl alcohol, the sodium borate will undergo a cross-linking reaction with the polyvinyl alcohol, thereby making the pharmaceutical preparation from a semi-solid (such as a cream Non-solid properties) solidify into a solid state. Preferably, the mass percentage of the polyvinyl alcohol in the pharmaceutical preparation is preferably 0.1-30%, more preferably 0.5-15%, or 1%-5%.

When the pharmaceutical preparation contains a substance that can be crosslinked, and the covering film contains a corresponding crosslinking agent, the purpose is to achieve better use effects in the following use scenarios: covering film covering/wrapping coating Covering the drug preparation layer, when the crosslinking agent diffuses from the cover film into the drug preparation layer, the crosslinking agent can undergo a crosslinking reaction with the corresponding "crosslinkable substance" in the drug preparation layer to solidify the preparation layer .

When the cover film covers the drug preparation layer, the following process occurs: the crosslinking agent (such as a substance containing boron) in the cover film diffuses into the preparation, causing the cross-linkable substance in the drug preparation ( Such as polyvinyl alcohol), so that the drug formulation solidifies and adheres to the cover film. In this way, when the planned administration time is over, the covering film can be removed at the same time to remove the solidified and attached preparations. In this way, there is no residual preparation on the skin, and the patient does not need to wash the skin.

For another example, the material that can be cross-linked is polyvinylpyrrolidone; and the corresponding cross-linking agent in the cover film can be N,N'-methylenebisacrylamide (N,N'-methylenebisacrylamide).

Among the above-mentioned pharmaceutical preparations, the pharmaceutical preparation is semi-solid and preferably has immobility; or the pharmaceutical preparation has immobility; the immobility means that the pharmaceutical preparation in a container is During 12 hours of standing after stirring, the surface does not flow to a horizontal surface. The medicinal preparation having the above-mentioned semi-solid or immobility can prevent or reduce the loss of the medicinal preparation applied to the skin or surgical incision from the application site.

In the present invention, "semi-solid" refers to a form between liquid and solid. For example, face cream and peanut butter are "semi-solid" at room temperature.

In the above-mentioned pharmaceutical preparation, when the local anesthetic is tetracaine, preferably, the mass percentage of tetracaine in the pharmaceutical preparation in the pharmaceutical preparation is more than 0.5%, and the pharmaceutical preparation dissolves The mass percentage of tetracaine in the pharmaceutical preparation is less than 0.1%.

In the above-mentioned pharmaceutical preparations, the local anesthetic is preferably lidocaine. Preferably, the mass percentage of lidocaine in the pharmaceutical preparation in the pharmaceutical preparation is more than 2% or 3%, and the mass percentage of lidocaine dissolved in the pharmaceutical preparation in the pharmaceutical preparation It is 1% or less.

Compared with the compound pharmaceutical preparations in the present invention and on the market (products containing two or more local anesthetic ingredients, such as Enna), the pharmaceutical preparations using lidocaine as a single local anesthetic have better advantages:( 1) It is safer, easier to approve, and can be used for a long time (this is because lidocaine is the most commonly used local anesthetic, and its safety is generally known, and it can be used continuously for more than three months); (2) Anesthetize the whole skin within 120 minutes, even within 90 minutes (the ability to anesthetize the complete skin within 90 minutes or 120 minutes is also very important, because the patient’s pain is relieved in time, especially after herpes zoster neuralgia. Pain is very important to the patient).

In the above-mentioned pharmaceutical preparations, the pharmaceutical preparations may not contain lipid substances, and the pharmaceutical preparations at this time may be referred to as non-lipid pharmaceutical preparations. Wherein, the lipid substance refers to the conventional lipid substance in the art, usually refers to one or more of animal fat, vegetable fat and other fatty substance, and the other fatty substance refers to medicine. Fatty substances other than animal fat and vegetable fat approved by the Supervision Bureau.

The pharmaceutical preparation of the present invention can also be a hydrogel pharmaceutical preparation, which is especially suitable for a pharmaceutical preparation placed into the incision tissue before the surgical incision is sutured. The hydrogel pharmaceutical preparation is based on the aforementioned pharmaceutical preparations and further contains gel-forming preparations. And the mass percentage of the gel forming agent in the hydrogel pharmaceutical preparation is 0.2%-5%. The hydrogel pharmaceutical preparation containing the gel forming agent in the above mass percentage is in the form of a hydrogel, and the incision tissue can be inserted before the surgical incision is sutured, and then the surgical incision can be sutured, which can well control the incision pain after the operation.

In the above-mentioned hydrogel pharmaceutical preparation, the mass percentage of the gel forming agent in the hydrogel pharmaceutical preparation is preferably 0.5%-4%, more preferably 1.0%-3.0%.

In the above hydrogel pharmaceutical preparations, the gel forming agent may be a gel forming agent that can be safely absorbed by body tissues in the prior art. The preferred and more preferred solutions of the gel forming agent are as described above.

In the aforementioned hydrogel pharmaceutical preparation, the concentration of the dissolved local anesthetic in the hydrogel pharmaceutical preparation is preferably 10 mg/ml or less, more preferably 5 mg/ml or less.

In the above hydrogel pharmaceutical preparations, the concentration of the local anesthetic in the hydrogel pharmaceutical preparations in the hydrogel pharmaceutical preparations is preferably 20 mg/ml or more, more preferably 40 mg/ml or more , And more preferably 60 mg/ml or more.

In the above-mentioned hydrogel pharmaceutical preparation, the mass percentage of the undissolved local anesthetic in the hydrogel pharmaceutical preparation accounts for more than 80% of the local anesthetic in the hydrogel pharmaceutical preparation.

In the above-mentioned hydrogel pharmaceutical preparation, the pH value of the hydrogel pharmaceutical preparation is preferably 7.4-9.2, more preferably 7.4-9.0, still more preferably 7.8-8.8, and still more preferably 7.9 -8.4.

In a preferred embodiment of a hydrogel pharmaceutical preparation, the gel-forming agent is sodium sulfate, and the mass percentage of the gel-forming agent in the hydrogel pharmaceutical preparation is 0.2%-4%. The pH buffer pair is a pH buffer pair composed of disodium hydrogen phosphate and sodium dihydrogen phosphate, the local anesthetic is lidocaine or bupivacaine, and the pH value of the hydrogel pharmaceutical preparation is 7.8-8.8; The concentration of the local anesthetic in the hydrogel pharmaceutical preparation in the hydrogel pharmaceutical preparation is 20 mg/ml or more or 40 mg/ml or more; the dissolved local anesthetic is in the hydrogel drug The concentration in the preparation is less than 5 mg/ml.

In a preferred embodiment of a hydrogel pharmaceutical preparation, the gel forming agent is a hydrogel or an acid salt, and the mass percentage of the gel forming agent in the hydrogel pharmaceutical preparation is 0.2%-10% , Preferably 0.2-5%, the pH buffer solution formed by the pH buffer pair makes the pH of the hydrogel pharmaceutical preparation 7.8-8.8, and the dissolved local anesthetic is coagulated in the water The concentration in the gel pharmaceutical preparation is 5 mg/ml or less, and the concentration of the local anesthetic in the hydrogel pharmaceutical preparation in the hydrogel pharmaceutical preparation is more than 20 mg/ml. The mass percentage of the gel forming agent in the hydrogel pharmaceutical preparation is preferably 0.3%-3%. The pH buffer pair is preferably a pH buffer pair composed of disodium hydrogen phosphate and sodium dihydrogen phosphate. The local anesthetic is preferably lidocaine or bupivacaine. The salt of salt is preferably sodium qualitate, and more than 95% by weight of the sodium qualitate is non-crosslinked sodium qualitate, and more preferably 98% by weight to 100% by weight of sodium qualitate is Non-crosslinked sodium phosphate. The pH value of the hydrogel pharmaceutical preparation is preferably 7.8-8.5. The concentration of the local anesthetic in the hydrogel pharmaceutical preparation in the hydrogel pharmaceutical preparation is preferably more than 40 mg/ml.

In the above hydrogel pharmaceutical preparations, the hydrogel pharmaceutical preparations may not contain lipid substances, and the hydrogel pharmaceutical preparations at this time may be referred to as non-fat pharmaceutical preparations. Wherein, the lipid substance refers to the conventional lipid substance in the art, usually refers to one or more of animal fat, vegetable fat and other fatty substance, and the other fatty substance refers to medicine. Fatty substances other than animal fat and vegetable fat approved by the Supervision Bureau.

Regarding the following lidocaine-containing preparations, the inventors wish to explain that when preparing the xanthan gum-free preparations of the present invention and containing dissolved and undissolved lidocaine, the preparations are heated to Lidocaine’s melting point temperature (approximately 68 degrees Celsius) is above, and then quickly stirred to melt the undissolved lidocaine particles into a liquid state and be broken into small “oil droplets” suspended in the formulation, and cool to After room temperature, suspended small "oil droplets" become small suspended crystal particles. Although the formulation contains suspending agents such as Pemulen TR-2, hydroxyethyl cellulose, hydroxypropyl cellulose or starch, all of which can function to suspend small undissolved lidocaine particles, the inventor found The small lidocaine particles in these suspensions will crystallize into larger crystals (more than 1 mm in length) as the storage time increases. The presence of lidocaine in the form of large crystals will make the distribution of lidocaine in the preparation uneven, which may affect the anesthetic effect. The inventor unexpectedly found that if xanthan gum is added to the formulation, the lidocaine in it will not crystallize into visible-scale crystals.

Therefore, the present invention also provides a pharmaceutical preparation, the pharmaceutical preparation is a preparation containing lidocaine, the preparation containing lidocaine contains lidocaine, xanthan gum and water, and the preparation containing lidocaine The lidocaine in the preparation includes dissolved lidocaine and undissolved lidocaine; the sum of the mass percentages of the components in the lidocaine-containing preparation is 100%.

Among the above-mentioned lidocaine-containing preparations, preferably, the pharmaceutical preparation is a lidocaine-containing preparation, and the lidocaine-containing preparation contains lidocaine, xanthan gum, polyvinyl alcohol, and water, and The lidocaine in the lidocaine-containing preparation includes dissolved lidocaine and undissolved lidocaine; the sum of the mass percentages of the components in the lidocaine-containing preparation is 100%.

In the above-mentioned lidocaine-containing preparation, preferably, the mass percentage of the sum of dissolved lidocaine and undissolved lidocaine in the lidocaine-containing preparation in the lidocaine-containing preparation It is 2% or more and not 100%; the mass percentage of the dissolved lidocaine in the lidocaine-containing preparation is 1% or less, and not 0. More preferably, the mass percentage of the dissolved lidocaine in the lidocaine-containing preparation is 0.1%-1%.

In the above-mentioned lidocaine-containing preparation, the lidocaine-containing preparation may further contain a pH buffer pair composed of disodium hydrogen phosphate and sodium dihydrogen phosphate. Wherein, the mass percentage of the disodium hydrogen phosphate in the lidocaine-containing formulation may be, for example, 0.1%, and the mass percentage of the sodium dihydrogen phosphate in the lidocaine-containing formulation may be, for example, 4. %.

In the above-mentioned lidocaine-containing preparation, the mass percentage of lidocaine in the lidocaine-containing preparation is preferably greater than 1.5%, and not 100%, more preferably 2%-8%, for example, 5%.

In the above-mentioned lidocaine-containing preparation, the mass percentage of the dissolved lidocaine in the lidocaine-containing preparation is preferably less than 1% or less than 0.5%, and is not zero.

In the above-mentioned lidocaine-containing preparation, the mass percentage of xanthan gum in the lidocaine-containing preparation is preferably greater than 0.1%, and not 100%; more preferably 0.2%-10%; furthermore preferably The ground is 0.5%-6% or 1-6%, for example, it can be 1% or 3%.

The above-mentioned lidocaine-containing preparation may also contain hydroxypropyl cellulose, and the mass percentage of the hydroxypropyl cellulose in the lidocaine-containing preparation is preferably more than 1% and not 100%. %; more preferably 1%-5%, for example, 3%.

In the above-mentioned lidocaine-containing preparation, the lidocaine-containing preparation further contains polyvinyl alcohol; the mass percentage of the polyvinyl alcohol in the lidocaine-containing preparation is preferably 0.1-30%, It is more preferably 0.5-15%, and still more preferably 1%-5%.

In the above-mentioned lidocaine-containing preparation, preferably, the lidocaine-containing preparation comprises the following components (or consists of the following components) lidocaine, xanthan gum and water; the lidocaine-containing preparation The mass percentage of lidocaine in the preparation is 2%-8%; the mass percentage of the dissolved lidocaine in the lidocaine-containing preparation is less than 1%, and is not 0, preferably 0.6% or less or 0.5% or less, and not 0, such as 0.1%-1%; the mass percentage of the xanthan gum in the lidocaine-containing preparation is greater than 0.1%, preferably 0.2% -10%, more preferably 1%-6%; water is the balance.

In the above-mentioned lidocaine-containing preparation, preferably, the lidocaine-containing preparation includes the following components (or consists of the following components) lidocaine, polyvinyl alcohol and water; the lidocaine-containing preparation The mass percentage of lidocaine in the compound is 2%-8%; the mass percentage of the dissolved lidocaine in the lidocaine-containing preparation is 1% or less, and is not 0, preferably 0.6 % Or less or 0.5% or less, and is not 0, such as 0.1%-1%; the mass percentage of the polyvinyl alcohol in the lidocaine-containing preparation is greater than 0.1%, preferably 0.2%- 10%, more preferably 1%-6%; water is the balance.

In the above-mentioned lidocaine-containing preparation, preferably, the lidocaine-containing preparation includes the following components (or consists of the following components) lidocaine, xanthan gum, polyvinyl alcohol and water; the lidocaine-containing preparation The mass percentage of lidocaine in the preparation of caine is 2%-8%; the mass percentage of the dissolved lidocaine in the preparation containing lidocaine is less than 1%, and is not 0, which is more Preferably it is 0.6% or less or 0.5% or less, and is not 0, more preferably 0.1%-1%; the mass percentage of the xanthan gum in the lidocaine-containing preparation is greater than 0.1%, preferably The content is 0.2%-10%, more preferably 1%-6%; the mass percentage of the polyvinyl alcohol in the lidocaine-containing preparation is greater than 0.1%, preferably 0.2%-10%, More preferably, it is 1%-6%; water is the balance.

The above-mentioned pharmaceutical preparations of the present invention (refer to the aforementioned various pharmaceutical preparations, such as hydrogel pharmaceutical preparations, non-lipid pharmaceutical preparations or preparations containing lidocaine), can be used for the analgesia of open body surface pain It is also suitable for the analgesia of intact skin (such as the skin of neuralgia after herpes zoster) and close to intact skin.

The present invention provides a cover film, which includes a barrier film layer and an adsorption layer.

Wherein, the covering film is preferably a medical covering film. "Cover film" includes "medical cover film". When the cover film is used for medical purposes, those skilled in the art know that a medical cover film is used.

Wherein, the barrier film layer is a barrier film conventionally used in the medical field, and the barrier film may be a material impermeable to water vapor or a material with limited water vapor permeability, such as polyethylene film, ethylene-vinyl acetate copolymer film (abbreviated as , EVA film) or polyurethane film.

Wherein, the adsorption layer can be a material that can adsorb or retain water-containing pharmaceutical preparations in the prior art, for example, can be a non-woven fabric with strong absorption. One side of the adsorption layer can be glued to the barrier film layer, and one side of the adsorption layer can also be composited on the barrier film layer by hot pressing.

Preferably, the covering film (for example, a medical covering film) contains a crosslinking agent. The crosslinking agent is preferably dispersed in the material of the adsorption layer. The cross-linking agent can undergo a cross-linking reaction with the cross-linkable substance in the pharmaceutical preparation, preferably a boron-containing substance, such as sodium borate, or N,N'-methylene bisamide N,N'-methylenebisacrylamide, or glutaraldehyde, glyoxal, maleic acid, citric acid, trisodium trimetaphosphate, sodium hexametaphosphate, dianhydride, succinic acid or sulfosuccinic acid. Wherein, the covering film (such as a medical covering film) contains a crosslinking agent higher than 0.01 mg/per square centimeter, preferably higher than 0.1 mg/per square centimeter, or 0.01 mg-100 mg/per square centimeter, more preferably It is 0.02-0.2mg/per square centimeter.

Wherein, preferably, the cover film (for example, a medical cover film) further includes a net-like glue layer, one side of the adsorption layer is compounded on the barrier film layer, and the net-like glue layer is compounded on the adsorption layer (As shown in Figure 1) the area of the non-adhesive area of the reticulated adhesive layer accounts for more than 10% of the total area of the reticulated adhesive layer, and is not 100%. The net-like glue layer is used to fix the pharmaceutical preparation on the surface of the human body tissue, and more preferably completely seal the cover formed by the cover film (such as a medical cover film) and the surface of the human body tissue In the space. When the cover film is used, the side of the net-like glue layer of the cover film is in contact with the drug preparation layer and the skin.

The network adhesive layer only needs to have areas without adhesive and areas with adhesive. Generally speaking, the areas without adhesive and areas with adhesive are evenly distributed. For example, the net-like glue layer is a glue net composed of curves and/or straight lines. Preferably, the mesh glue layer is a glue net composed of a set of parallel warp threads and a set of parallel weft threads. More preferably, the warp threads and the weft threads are arranged vertically. More preferably, the distance between two adjacent warp threads is equal to the distance between two adjacent weft threads. Here, it should be noted that the warp threads and the weft threads on the net-like glue layer constitute areas with glue, and the other areas on the net-like glue layer except the warp threads and the weft threads constitute no glue. area.

Wherein, the thickness of the reticulated adhesive layer is preferably 0.01 mm-0.75 mm, more preferably 0.05 mm-0.75 mm, and still more preferably 0.25 mm-0.75 mm.

Among them, preferably, the glue of the network glue layer can be a medical pressure-sensitive glue that is insoluble in water, preferably organic silica gel and/or acrylic glue.

Wherein, the network adhesive layer can be adhered to the other side of the adsorption layer by spraying in the prior art.

Wherein, preferably, the area of the glue-free area of the network adhesive layer accounts for more than 30% of the total area of the network adhesive layer. More preferably, the area of the glue-free area of the network adhesive layer accounts for more than 50% of the total area of the network adhesive layer. More preferably, the area of the glue-free area of the network adhesive layer accounts for more than 70% of the total area of the network adhesive layer, for example, it may be 70%-90%.

Wherein, preferably, the length stretch rate of the covering film (such as a medical covering film) in all directions is more than 10%, for example, it can be 10%-30%. Covering films (such as medical cover films) having the above-mentioned stretch rate are more comfortable when used in joints and muscles.

The present invention also provides a system for fixing the aforementioned pharmaceutical preparations on the skin. The system includes the aforementioned pharmaceutical preparations (refers to the aforementioned various pharmaceutical preparations, such as hydrogel pharmaceutical preparations, non-fat pharmaceutical preparations or Lidocaine-containing preparations) and covering films (referring to the aforementioned covering films), the covering films (such as medical covering films) are used to cover the pharmaceutical preparations applied on the surface of human body tissues to reduce or prevent Evaporation of water and protect the preparation from being wiped off by clothes, or cross-link the cross-linkable substance in the covered pharmaceutical preparation by the cross-linking agent contained in the cover film (such as medical cover film) and solidify the drug preparation , Or the pharmaceutical preparation is completely enclosed in a closed space formed by the covering film (such as a medical covering film) and the surface of human body tissue.

The surface of the human body tissue is the surface of intact skin or the surface of open human tissue or the surface of incomplete skin, the surface of the incomplete skin is preferably the surface of a burn or a surgical incision, and the surface of the open human tissue is Burns and scalds, surgical incisions, or damaged skin caused by disease or trauma.

In the above system, as mentioned above, when the pharmaceutical preparation contains a glue, because the pharmaceutical preparation is sticky, when the pharmaceutical preparation is applied to the surface of human body tissues, a covering film (such as a medical covering The film) sticks to the drug preparation layer.

In the above system, as mentioned above, when the pharmaceutical preparation contains a substance that can be crosslinked, and the covering film (such as a medical covering film) contains a corresponding crosslinking agent, the crosslinking agent may A cross-linking reaction occurs with the cross-linkable substance in the pharmaceutical preparation to achieve a better use effect as described above.

More preferably, when the pharmaceutical preparation contains polyvinyl alcohol, the covering film (for example, a medical covering film) contains a substance containing boron elements, such as sodium borate, or glutaraldehyde, glyoxal, maleic acid, and lemon. Acid, trisodium trimetaphosphate, sodium hexametaphosphate, dianhydride, succinic acid or sulfosuccinic acid.

More preferably, when the pharmaceutical preparation contains polyvinylpyrrolidone, the covering film (for example, a medical covering film) contains N,N'-methylenebisamide amide.

In the above system, preferably, the outer edge of the covering film (for example, the medical covering film) is separated from the outer edge of the preparation layer formed by the pharmaceutical preparation with a length of more than 5 mm, for example, 2-4 cm.

The present invention also provides a system for fixing a pharmaceutical preparation on the skin, the pharmaceutical preparation is the aforementioned pharmaceutical preparation, the pharmaceutical preparation is a pharmaceutical preparation containing a substance that can be cross-linked; the cover film It is the cover film as described above, and the cover film is a cover film containing a crosslinking agent (for example, a medical cover film).

Among them, preferably, the pharmaceutical preparation is the aforementioned pharmaceutical preparation (such as a preparation containing lidocaine).

The present invention also provides a system for fixing a pharmaceutical preparation on the skin, the pharmaceutical preparation is the aforementioned pharmaceutical preparation, the pharmaceutical preparation is a pharmaceutical preparation containing a substance that can be crosslinked; the covering film is As for the aforementioned cover film, the cover film is a cover film containing a crosslinking agent (for example, a medical cover film), but does not contain a network glue layer.

The present invention also provides a method for using the system for fixing a pharmaceutical preparation on the skin as described above, which comprises the following steps: smearing and covering the surface of the human tissue to be treated with the pharmaceutical preparation to form a pharmaceutical preparation layer, Then, the covering film is applied to cover the drug preparation layer; alternatively, the drug preparation is applied to the adsorption layer or the net-like glue layer of the cover film to form a drug preparation layer, and then the drug preparation layer is covered on the surface in need of treatment. Surface of human tissue.

Regarding the use method, because the pharmaceutical preparation contains a glue (preferably a cross-linkable substance), the covering film will be fixed on the pharmaceutical preparation layer, and no additional fixing method is required.

When the pharmaceutical preparation contains a substance that can be crosslinked and the cover film contains a corresponding crosslinking agent, after the cover film contacts the drug preparation layer, the crosslinking agent in the cover film diffuses into the drug preparation In the layer, a cross-linking reaction occurs with the cross-linkable substance therein, so that the drug preparation layer is cured and the cured drug preparation layer is adhered to the cover film. Therefore, when using this system, wait for enough time for the curing process to complete. Preferably, this curing process is completed within the planned medication time. When using a system without a reticulated glue layer, the drug preparation is not completely enclosed in a closed space because the edge of the drug preparation layer is not sealed with the skin by the reticulated glue layer in the aforementioned system. Theoretically, the edge portion of the drug preparation layer will lose part of the water contained in it due to evaporation, which may affect the absorption of the drug. However, for a relatively large area of the drug preparation layer, the decrease in drug absorption in a small part of the edge area will not affect its overall efficacy. The cover film without the network adhesive layer is easier to manufacture and lower cost.

The present invention also provides a preparation method of the aforementioned pharmaceutical preparations (referring to the aforementioned various pharmaceutical preparations, such as hydrogel pharmaceutical preparations, non-fat pharmaceutical preparations or preparations containing lidocaine), the preparation method comprising The following steps are as follows: the components in the pharmaceutical preparation are mixed uniformly.

In the above preparation method, the preparation method preferably includes the following steps: (1) mixing the remaining components of the pharmaceutical preparation except the local anesthetic to obtain a mixed solution; (2) The mixed solution is heated after mixing with the local anesthetic, and then cooled to room temperature.

Wherein, in step (2), the heating temperature is preferably 75-85°C, for example, it may be 80°C.

Wherein, in step (2), the heating is preferably performed under stirring.

The present invention also provides one of the aforementioned pharmaceutical preparations (refers to the aforementioned various pharmaceutical preparations, such as hydrogel pharmaceutical preparations, non-fat pharmaceutical preparations or preparations containing lidocaine) or the fixation of the pharmaceutical preparations on the skin Application of the above system in the preparation of a medicine for the treatment of pain; the pain is herpes zoster pain, post-herpetic nerve damage pain, neuroma pain, phantom limb pain, diabetic peripheral neuralgia, joint pain, bone Arthritis pain, back pain, pain caused by gout, pain caused by soft tissue injury, pain caused by incision after surgery, pain caused by skin breakage caused by disease or trauma, pain caused by burns, or pain during burn removal.

The present invention also provides an application of the aforementioned system (comprising the pharmaceutical preparation and the system for fixing the pharmaceutical preparation on the skin) in the preparation of a medical device or a medical device/drug combination product for treating pain; the pain As mentioned earlier.

The present invention also provides a treatment method that uses the aforementioned pharmaceutical preparation or the system for fixing the pharmaceutical preparation on the skin to treat pain; the pain is as described above; the treatment method includes the following steps: The formed preparation layer is completely enclosed in a closed space formed by a covering film (such as a medical covering film) and the surface of human body tissue.

In the above-mentioned treatment method, the treatment method may also include the following steps: smearing the pharmaceutical preparation on the covering film (for example, a medical covering film), and then fixing the preparation layer formed by the pharmaceutical preparation on the covering film. In a closed space formed by a membrane (such as a medical covering film) and the surface of the human body tissue.

In the above treatment method, the treatment method may include the following steps: applying the pharmaceutical preparation on the surface of the human body tissue to form a preparation layer, and then covering the preparation layer with the covering film (for example, a medical covering film), The preparation layer is fixed in a closed space formed by the covering film (such as a medical covering film) and the surface of the human body tissue.

In the above treatment method, the cover film (for example, a medical cover film) may be a cover film (for example, a medical cover film) conventionally used in the art, preferably a cover film as described above (for example, a medical cover film).

In the above-mentioned treatment method, when the pharmaceutical preparation is applied to intact skin or close to intact skin (such as the skin of postherpetic neuralgia or the skin of joint pain), it is preferable to keep the pharmaceutical preparation in the human The body tissue surface time is 6 hours or more, 8 hours or more, 12 hours or more, 18 hours or more, 24 hours or more, or 30 hours or more. When the pharmaceutical preparation is applied to burn pain or burn pain during scab removal, the time to keep the pharmaceutical preparation on the surface of the human body tissue can be relatively short, preferably 5min-50min, but it can also be based on Pain needs to last longer, such as more than 3 hours, more than 6 hours, more than 8 hours, more than 12 hours, more than 18 hours, more than 24 hours, or more than 30 hours. When the pharmaceutical preparation is applied to the incision after surgery, preferably, the time for keeping the pharmaceutical preparation on the surface of the human body tissue is more than 2 hours, more preferably 2 hours to 48 hours, and still more preferably 6 hours-24 hours.

In the above-mentioned treatment method, preferably, the thickness of the pharmaceutical preparation on the surface of the human body tissue is maintained at 0.1 mm or more, 0.2 mm or more, 0.5 mm or more, 1 mm or more, or 2 mm or more.

In the above treatment method, when the pain to be treated is herpes zoster pain, postherpetic neuralgia or diabetic peripheral neuralgia, one of the treatment methods preferably includes the following steps: When applied to the central area of the covering film (such as medical covering film) defined in the aforementioned system (when there is a network adhesive layer, it is the central area of the network adhesive layer) so that the mesh adhesive layer is The edge area is not coated by the pharmaceutical preparation, and a covering film with a preparation layer (such as a medical covering film) is obtained; then the covering film with a preparation layer (such as a medical covering film) is covered on the painful On the surface of the human body tissue of the part, and the preparation layer is brought into contact with the surface of the human body tissue of the painful part, or the preparation layer is brought into contact with and covers the surface of the human body tissue of the painful part, the edge The area is bonded to the skin outside the human body tissue surface at the painful part to fix the preparation layer on the skin outside the human body tissue surface at the painful part and complete the preparation layer Enclosed in a closed space composed of the covering film (for example, medical covering film) and the human body tissue surface of the painful part; wherein, the outer edge of the covering film (for example, medical covering film) is away from the preparation layer The length or distance of the outer edge is more than 5 mm; the thickness of the preparation layer is more than 0.1 mm, preferably more than 0.5 mm; the preparation layer and the covering film (such as medical covering film) are kept in the human The time on the surface of the body tissue is more than 6 hours.

In the above treatment methods and similar treatment methods, the "central area" refers to the area on the cover film that is in contact with the drug formulation, and the "edge area" refers to the area on the cover film that is not in contact with the drug agent.

Preferably, the area and shape of the covering film with a preparation layer (for example, a medical covering film) can cover most or all of the human body tissue surface of the painful part.

Preferably, the edge area adheres to the skin of the painless skin area around the surface of the painful human body tissue.

In the above treatment method, the preparation layer is completely enclosed in the enclosed space. When the barrier film used in the barrier film layer is a material impermeable to water vapor, the moisture in the formulation layer will not evaporate, so that the moisture in the formulation layer can be well maintained. When the barrier film used in the barrier film layer has a certain water vapor permeability, the moisture in the formulation layer will evaporate. At this time, it can be based on the moisture content in the formulation layer and the required use time. The water vapor permeability of the barrier film is reasonably selected, and the barrier film selected according to the above principles will ensure that the transdermal absorption rate of the active ingredients in the formulation layer is not affected within the required use time.

Preferably, the pharmaceutical preparation contains a substance that can be crosslinked, and the covering film (such as a medical covering film) contains a crosslinking agent corresponding to the substance that can be crosslinked (such as a pharmaceutical preparation containing a substance that can be crosslinked). The cross-linked material is polyvinyl alcohol, and the cover film (for example, a medical cover film) contains the cross-linking agent sodium boride corresponding to the polyvinyl alcohol). In this way, after the cross-linking agent in the cover film (such as the medical cover film) contacts the drug preparation layer, the cross-linking agent will diffuse into the drug preparation layer and undergo a cross-linking reaction with the cross-linkable substance, thereby causing all The semi-solid drug preparation layer is cured and adhered to the cover film (for example, a medical cover film). After the planned medication time is over, the covering film (for example, medical covering film) can be removed at the same time to remove the cured drug preparation layer adhered to the covering film (for example, medical covering film).

Or, when the pain to be treated is herpes zoster pain, postherpetic neuralgia or diabetic peripheral neuralgia, the second treatment method preferably includes the following steps: coating the pharmaceutical preparation on A preparation layer is formed on the surface of the human body tissue at the painful part; and then a covering film (such as a medical covering film) as described above that is larger than the preparation layer is covered with the preparation layer, and the center of the covering film The area (when there is a net-like glue layer, the central area of the net-like glue layer) covers the preparation layer and the edge area does not touch the preparation layer. The edge area is between the surface of the human body tissue at the painful part The skin of the outer area is bonded to fix the preparation layer on the skin and completely seal the preparation layer between the covering film (such as a medical covering film) and the human body tissue at the painful part In a closed space composed of surfaces;

Preferably, the area and shape of the preparation layer can cover most or all of the human body tissue surface of the painful part.

Preferably, the edge area adheres to the skin of the skin area around the human body tissue surface at the painful site where there is no pain.

In this treatment method, "the length or distance of the outer edge of the covering film (for example, the medical covering film) from the outer edge of the preparation layer", "the thickness of the preparation layer", "maintain the preparation layer and the "The time that the covering film is on the surface of the human body tissue", "The preparation layer is completely enclosed in the enclosed space", and in the preferred embodiment, "The pharmaceutical preparation contains a substance that can be crosslinked Glue, and the cover film (for example, a medical cover film) contains a cross-linking agent corresponding to the cross-linkable substance glue," which is consistent with one of the aforementioned treatment methods.

When the pain to be treated is neuroma pain, phantom limb pain, joint pain, osteoarthritis pain, back pain, pain caused by gout, or pain caused by soft tissue injury, the treatment method is the same as one of the treatment methods Or bis; where,

When the pain is phantom limb pain, the human body tissue surface at the painful part is the skin of the painful part or the skin surface of the severed limb;

When the pain is joint pain, the human body tissue surface at the painful part is the skin outside or around the joint;

When the pain is back pain, the human body tissue surface at the painful part is back skin.

When the pain to be treated is neuroma pain, phantom limb pain, joint pain, osteoarthritis pain, back pain, pain caused by gout, or pain caused by soft tissue injury, the treatment method preferably includes the following steps: The covering film (for example, medical covering film) defined in the aforementioned system is covered on all areas coated with the preparation layer formed by the pharmaceutical preparation in such a way that the net-like glue layer faces the human body tissue surface of the painful part. The surface of the human body tissue at the painful part, the central area of the reticulum layer is in contact with the preparation layer, and the edge area of the reticulum layer is in contact with the skin outside the human body tissue surface at the painful part Adhesive to fix the preparation layer on the skin outside the surface of human body tissue at the painful part, and completely seal the preparation layer on the covering film (for example, medical covering film) and the pain The part of the human body tissue surface consists of a closed space.

When the pain to be treated is post-operative incision pain, the treatment method preferably includes the following steps: applying the pharmaceutical preparation on the sutured surgical incision, so that the surgical incision is covered with a layer of more than 1 mm thickness. The pharmaceutical preparation is covered by the preparation layer formed by the object, and the time for keeping the pharmaceutical preparation on the surgical incision is more than 3 hours. More preferably, the preparation layer formed by the pharmaceutical preparation is used in the same or similar method as described above to be completely enclosed by the covering film (for example, the medical covering film) defined in the aforementioned system, the surgical incision and the skin on both sides thereof. In the enclosed space formed.

Or, when the pain to be treated is post-operative incision pain, the treatment method preferably includes the following steps: before the surgical incision is sutured, a hydrogel pharmaceutical preparation is placed into the incision tissue; wherein, the hydrogel pharmaceutical The formulation contains 0.2wt%-4wt% sodium phosphate, a pH buffer pair, a local anesthetic and water; the pH buffer pair is dissolved in the water in the pharmaceutical preparation; the local anesthetic in the pharmaceutical preparation includes a dissolved local Anesthetics and undissolved local anesthetics; the pH buffer pair is a buffer composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; the local anesthetic is lidocaine or bupivacaine; the hydrogel drug The pH of the preparation is 7.8-8.8; the concentration of the dissolved local anesthetic in the hydrogel pharmaceutical preparation is less than 5 mg/ml, and the local anesthetic in the hydrogel pharmaceutical preparation is in the water The concentration in the gel drug preparation is 20 mg/ml or more; the amount of the hydrogel drug preparation put into the incision tissue is 0.1 g/cm incision length-1 g/cm incision length.

Wherein, more preferably, the concentration of the local anesthetic in the hydrogel pharmaceutical preparation in the hydrogel pharmaceutical preparation is more than 40 mg/ml.

Wherein, more preferably, the treatment method further includes the following steps: smear the aforementioned pharmaceutical preparation on the sutured surgical incision, so that the surgical incision is formed by a layer of the pharmaceutical preparation with a thickness of 1 mm or more. The time for which the drug preparation is covered by and keeps the drug preparation on the surgical incision is more than 3 hours.

More preferably, the preparation layer formed by the pharmaceutical preparation is completely enclosed in the covering film (for example, the medical covering film) and the surgical incision and the skin on both sides thereof as defined in the aforementioned system by the same or similar method as above. In the closed space formed; or, the preparation layer formed by the pharmaceutical preparation is completely enclosed in the closed space formed by the covering film (such as medical covering film) defined in the aforementioned system and the surface of the human body tissue Inside.

When the pain to be treated is postoperative incision pain, the treatment method preferably includes the following steps: before the surgical incision is sutured, the pharmaceutical preparation is placed in the incision tissue; the pharmaceutical preparation is placed in the incision tissue The amount is 0.1-2 grams per cm of incision length.

When the pain to be treated is burn pain or pain during burn scab removal, the treatment method preferably includes the following steps: apply the pharmaceutical preparation to the burn or the burn surface (wound surface) that needs to be scabbed to form a covered wound surface Layer of pharmaceutical preparations. And keeping the drug preparation layer on the wound surface or the burn surface for more than 5 minutes. The drug preparation layer can be covered with the above-mentioned covering film, or can be covered with coverings commonly used for treating wounds. More preferably, the preparation layer formed by the pharmaceutical preparation is completely enclosed in a closed space formed by a covering film (such as a medical covering film) defined in the aforementioned system and the surface of the human body tissue.

In the present invention, the central area refers to the area on the net-like glue layer that does not contact the outer edge of the net-like glue layer, and the edge area refers to the non-all areas on the net-like glue layer. The other areas of the central area.

In the present invention, intact skin means that the main barrier (stratum corneum) to foreign bodies is intact skin.

In the present invention, the human body tissue surface may be a complete or incomplete skin surface, a complete or incomplete mucosal surface, or an open human tissue surface. Open body tissue surfaces include burn wounds, surgical incision surfaces, and damaged skin surfaces caused by diseases or trauma.

In the present invention, "skin" includes skin covered by the stratum corneum and mucous membranes not covered by the stratum corneum.

In the present invention, the components in the pharmaceutical preparation are uniformly mixed.

In the present invention, the term "long-term" in terms such as "long-term analgesia" refers to a time longer than 6 hours, 12 hours, or even 24 hours or longer.

In the present invention, words such as "can anesthetize intact skin within 120 minutes" means that most people's skin will be anesthetized within the stated time after applying the pharmaceutical preparation at normal room temperature, which is understood from a medical perspective, Those skilled in the art know that the description of such words does not necessarily mean that everyone's skin will be anesthetized within the stated time.

On the basis of not violating common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain preferred embodiments of the present invention.

The positive and progressive effects of the present invention are:

The pharmaceutical preparation of the present invention and the system containing it are mainly applied to the human body surface (intact skin or open human body surface) that needs analgesia, and can obtain 6, 12, 18, 24, 36, 48 hours or even longer Continuous analgesic effect, and easy to use.

In analgesic applications, the pharmaceutical preparation of the present invention can replace the traditionally used central nervous system anesthetics, thereby avoiding the serious side effects caused by the central nervous system anesthetics.

Description of the drawings

Figure 1 is a schematic diagram of the structure of each layer of the medical covering film used in the embodiment;

Figure 2 is a schematic view of the structure of the medical covering film used in the embodiment;

Figure 3 is a top view of a covering film coated with a preparation layer formed by the pharmaceutical preparation;

Figure 4 is a cross-sectional view of the medical covering film and the pharmaceutical preparation in use.

Fig. 5 is a schematic diagram of the structure of the cover film.

Description of reference signs:

Barrier film 10

Adsorption layer 20

Non-woven fabric layer containing sodium borate 201

Mesh glue layer 30

No glue area 31

Area with glue 32

Preparation layer 40

detailed description

The present invention will be further explained by way of examples below, but the present invention is not limited to the scope of the described examples. In the following examples, the experimental methods without specific conditions are selected according to conventional methods and conditions, or according to the product specification.

The pharmaceutical preparations used in the following effect examples are all the pharmaceutical preparations of the examples that have been left for more than 14 days.

For the pharmaceutical preparations in the following examples, when the pharmaceutical preparations contain lidocaine and xanthan gum, it is observed after 14 days that there are no visible lidocaine crystals; when the pharmaceutical preparations contain lidocaine Therefore, when it does not contain xanthan gum, it is observed after 14 days that there are visible lidocaine crystals.

Example 1

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
利多卡因Lidocaine	5％5%
磷酸氢二钠Disodium phosphate	0.094mol/L0.094mol/L
磷酸二氢钠Sodium dihydrogen phosphate	0.006mol/L0.006mol/L
黄原胶Xanthan gum	4％4%
氢氧化钠Sodium hydroxide	0.08％0.08%
水water	补足至100％Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

Add sodium hydroxide, disodium hydrogen phosphate, sodium dihydrogen phosphate and xanthan gum into the water and stir until a uniform viscous liquid is obtained. Then, add lidocaine and heat to 80°C, stir quickly, and cool to room temperature to get it.

In this pharmaceutical preparation, the pH buffer pair is composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; xanthan gum is a thickening agent and a suspending agent.

Effect data: The obtained pharmaceutical preparation is marked as pharmaceutical preparation A, and the obtained pharmaceutical preparation is a viscous solution containing dissolved lidocaine and undissolved lidocaine, in which the undissolved lidocaine exists in the form of suspended crystals. In a stagnant solution; the pH value of drug formulation A is about 8; each gram of drug formulation A contains a total of 50 mg of lidocaine, of which: about 3 mg is dissolved lidocaine and about 47 mg is undissolved suspended lidocaine Because of crystals.

Example 2

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
利多卡因Lidocaine	8％8%
磷酸氢二钠Disodium phosphate	0.094mol/L0.094mol/L
磷酸二氢钠Sodium dihydrogen phosphate	0.006mol/L0.006mol/L
Pemulen TR2Pemulen TR2	0.24％0.24%
氢氧化钠Sodium hydroxide	0.2％0.2%
羟乙基纤维素Hydroxyethyl cellulose	3％3%
甘油glycerin	15％15%
水water	补足至100％Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

Add sodium hydroxide, disodium hydrogen phosphate, sodium dihydrogen phosphate, Pemulen TR-2 and hydroxyethyl cellulose into water and stir until a uniform viscous liquid is obtained. Then, add lidocaine and glycerin and heat to 80°C, stir quickly, and cool to room temperature to get it.

In this pharmaceutical preparation, the pH buffer pair is composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; sodium hydroxide is used to adjust the pH value and participates in the pH buffer pair; Pemulen TR2 is a suspending agent; hydroxyethyl cellulose is a thickening agent and Suspending agent.

Effect data: The obtained pharmaceutical preparation is marked as pharmaceutical preparation B. The obtained pharmaceutical preparation is a viscous solution containing dissolved lidocaine and undissolved lidocaine, in which the undissolved lidocaine is present in the form of suspended crystals. In a stagnant solution; the pH value of the obtained pharmaceutical preparation is about 8; the dissolved lidocaine in each gram of pharmaceutical preparation B is less than 5 mg, and the rest of the lidocaine exists in the form of undissolved suspended crystals.

Example 3

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
利多卡因Lidocaine	8％8%
磷酸氢二钠Disodium phosphate	0.28mol/L0.28mol/L
磷酸二氢钠Sodium dihydrogen phosphate	0.02mol/L0.02mol/L
Pemulen TR2Pemulen TR2	0.24％0.24%
氢氧化钠Sodium hydroxide	0.2％0.2%
羟乙基纤维素Hydroxyethyl cellulose	3％3%
甘油glycerin	15％15%
水water	补足至100％Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

Add sodium hydroxide, disodium hydrogen phosphate, sodium dihydrogen phosphate, Pemulen TR-2 and hydroxyethyl cellulose into the water and stir until a uniform viscous liquid is obtained. Then, add lidocaine and glycerin and heat to 80°C, stir quickly, and cool to room temperature to get it.

Effect data: The obtained pharmaceutical preparation is marked as pharmaceutical preparation C. The obtained pharmaceutical preparation is a viscous solution containing dissolved lidocaine and undissolved lidocaine, in which the undissolved lidocaine is present in the form of suspended crystals. In a stagnant solution; the pH value of the obtained pharmaceutical preparation is about 8; the dissolved lidocaine in each gram of pharmaceutical preparation C is less than 5 mg, and the remaining lidocaine exists in the form of undissolved suspended crystals.

Example 4

A pharmaceutical preparation with the following ingredients

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration

利多卡因Lidocaine	10％10%
四硼酸钠Sodium tetraborate	0.03mol/L0.03mol/L
氢氧化钠Sodium hydroxide	0.06％0.06%
羟乙基纤维素Hydroxyethyl cellulose	3％3%
甘油glycerin	5％5%
水water	补足至100％Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

Add sodium hydroxide, sodium tetraborate and hydroxyethyl cellulose into water and stir until a uniform viscous liquid is obtained. Then, add lidocaine and glycerin and heat to 80°C, stir quickly, and cool to room temperature to get it.

In this pharmaceutical preparation, the pH buffer pair is composed of sodium tetraborate and sodium hydroxide; hydroxyethyl cellulose is a suspending agent and thickening agent.

Effect data: The obtained pharmaceutical preparation is marked as pharmaceutical preparation D. The obtained pharmaceutical preparation is a viscous solution containing dissolved lidocaine and undissolved lidocaine, in which the undissolved lidocaine exists in the form of suspended crystals. In a stagnant solution; the pH value of the obtained drug preparation is higher than 8; each gram of drug preparation D contains 100 mg of lidocaine, of which: the dissolved lidocaine is below 5 mg, and the undissolved suspended lidocaine crystals are at 95 More than milligrams.

Example 5

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
布比卡因Bupivacaine	8％8%
磷酸氢二钠Disodium phosphate	0.094mol/L0.094mol/L
磷酸二氢钠Sodium dihydrogen phosphate	0.006mol/L0.006mol/L
氢氧化钠Sodium hydroxide	0.08％0.08%
羟乙基纤维素Hydroxyethyl cellulose	3％3%
甘油glycerin	15％15%
水water	补足至100％Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

Add sodium hydroxide, disodium hydrogen phosphate, sodium dihydrogen phosphate, glycerin and hydroxyethyl cellulose to water, and stir until a uniform viscous liquid is obtained. Then, add bupivacaine and glycerin and heat to 80°C, stir quickly, and cool to room temperature to get it.

In this pharmaceutical preparation, the pH buffer pair is composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; hydroxyethyl cellulose is a suspending agent and thickening agent.

Effect data: The obtained pharmaceutical preparation is marked as pharmaceutical preparation E, the obtained pharmaceutical preparation is a viscous solution containing dissolved bupivacaine and undissolved bupivacaine, in which the undissolved bupivacaine is in the form of suspended crystals Exist in viscous solution; the pH value of the obtained pharmaceutical preparation is about 8; most of the bupivacaine exists in the form of undissolved suspended crystals.

Example 6

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
利多卡因Lidocaine	8％8%
磷酸氢二钠Disodium phosphate	0.28mol/L0.28mol/L
磷酸二氢钠Sodium dihydrogen phosphate	0.02mol/L0.02mol/L
黄原胶Xanthan gum	2.0％2.0%
水water	补足至100％Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

Mix disodium hydrogen phosphate, sodium dihydrogen phosphate, xanthan gum and water until a uniform viscous liquid is obtained. Then, add lidocaine and heat to 80°C, stir quickly, and cool to room temperature to get it.

In this pharmaceutical preparation, the pH buffer pair is composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; xanthan gum is a thickening and suspending agent.

Effect data: The obtained pharmaceutical preparation is marked as pharmaceutical preparation F, the obtained pharmaceutical preparation is a viscous solution containing dissolved lidocaine and undissolved lidocaine, wherein the undissolved lidocaine is present in the form of suspended crystals In the stagnant solution; the pH value of the obtained pharmaceutical preparation is about 8; the dissolved lidocaine in each gram of the pharmaceutical preparation F is less than 5 mg, and the remaining lidocaine exists in the form of undissolved suspended crystals.

Example 7

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
利多卡因Lidocaine	8％8%
磷酸氢二钠Disodium phosphate	0.28mol/L0.28mol/L
磷酸二氢钠Sodium dihydrogen phosphate	0.02mol/L0.02mol/L
质酸钠Sodium Sodium	2.0％2.0%

water

Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

Mix disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium phosphate and water until a uniform viscous liquid is obtained. Then, add lidocaine and heat to 80°C, stir quickly, and cool to room temperature to get it.

In this pharmaceutical preparation, the pH buffer pair is composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; sodium phosphate is a thickener and suspending agent.

Effect data: The obtained pharmaceutical preparation is designated as pharmaceutical preparation G, which is a pharmaceutical preparation in the form of a hydrogel, containing dissolved lidocaine and undissolved lidocaine. The undissolved lidocaine exists in the hydrogel in the form of suspended crystals; the pH value of the obtained pharmaceutical preparation is about 8; the dissolved lidocaine in each gram of pharmaceutical preparation G is less than 5 mg, and the rest of the lidocaine In the form of undissolved suspended crystals.

Example 8

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
利多卡因Lidocaine	5％5%
95％乙醇95% ethanol	2.5％2.5%
甘油glycerin	4％4%
白色凡士林White vaseline	10％10%
聚乙烯醇Polyvinyl alcohol	7.5％7.5%
氢氧化钠Sodium hydroxide	0.64％0.64%
磷酸氢钙Dicalcium Phosphate	8％8%
黄原胶Xanthan gum	1.6％1.6%
水water	补足至100％Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

Dissolve lidocaine in 95% ethanol solution, add xanthan gum, stir until evenly distributed, add glycerin, and stir. Add white petroleum jelly and stir. Add calcium hydrogen phosphate and stir. Add the polyvinyl alcohol aqueous solution prepared in advance and stir. Add 10% sodium hydroxide solution and stir. Immediately.

In this formulation, polyvinyl alcohol is a glue and a substance that can be crosslinked, and it is also a crosslinkable glue. 95% ethanol is used to help initially dissolve lidocaine. White petroleum jelly makes the preparation soft.

This formulation contains dissolved lidocaine and undissolved lidocaine. The undissolved lidocaine is present in the hydrogel in the form of suspended crystals; the pH value of the obtained pharmaceutical preparation is about 8; the dissolved lidocaine in each gram of the pharmaceutical preparation is about 5 mg or less, and the rest of the lidocaine Because it exists in the form of undissolved suspended crystals.

Example 9

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
利多卡因Lidocaine	8％8%
磷酸氢二钠Disodium phosphate	0.28mol/L0.28mol/L
磷酸二氢钠Sodium dihydrogen phosphate	0.02mol/L0.02mol/L
质酸钠Sodium Sodium	2.0％2.0%
黄原胶Xanthan gum	0.2％0.2%
水water	补足至100％Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

Stir the disodium hydrogen phosphate, sodium dihydrogen phosphate, xanthan gum, sodium phosphate and water until a uniform viscous liquid is obtained. Then, add lidocaine and heat to 80°C, stir quickly, and cool to room temperature to get it.

In this pharmaceutical preparation, the pH buffer pair is composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; sodium phosphate and xanthan gum are both thickening and suspending agents.

Effect data: The obtained pharmaceutical preparation is designated as pharmaceutical preparation H, which is a pharmaceutical preparation in the form of a hydrogel, containing dissolved lidocaine and undissolved lidocaine. The undissolved lidocaine exists in the hydrogel in the form of suspended crystals; the pH value of the obtained pharmaceutical preparation is about 8; the dissolved lidocaine in each gram of pharmaceutical preparation H is less than 5 mg, and the rest is lidocaine In the form of undissolved suspended crystals.

Example 10

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration

利多卡因Lidocaine	20％20%
磷酸氢二钠Disodium phosphate	0.28mol/L0.28mol/L
磷酸二氢钠Sodium dihydrogen phosphate	0.02mol/L0.02mol/L
质酸钠Sodium Sodium	2.0％2.0%
黄原胶Xanthan gum	0.2％0.2%
水water	补足至100％Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

In this pharmaceutical preparation, the pH buffer pair is composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; sodium phosphate and xanthan gum are thickening and suspending agents.

Effect data: The obtained pharmaceutical preparation is marked as pharmaceutical preparation J, which is a pharmaceutical preparation in the form of a hydrogel, containing dissolved lidocaine and undissolved lidocaine. The undissolved lidocaine exists in the hydrogel in the form of suspended crystals; the pH value of the obtained pharmaceutical preparation is about 8; the dissolved lidocaine in each gram of pharmaceutical preparation J is less than 5 mg, and the rest of the lidocaine In the form of undissolved suspended crystals.

Example 11

A pharmaceutical preparation used to control surgical incision pain. Its components are:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
质酸钠Sodium Sodium	2.5％2.5%
磷酸二氢钠Sodium dihydrogen phosphate	0.01mol/L0.01mol/L
磷酸氢二钠Disodium phosphate	0.19mol/L0.19mol/L
利多卡因Lidocaine	5％5%
水water	补足100％Make up 100%

The preparation method of the pharmaceutical preparation is as follows:

Put sodium dihydrogen phosphate and disodium hydrogen phosphate into water and dissolve them, add sodium sulfate and stir until completely dissolved; add lidocaine, heat to 70°C and stir for 10 minutes, and cool to room temperature to obtain.

In this pharmaceutical preparation, the pH buffer pair is composed of disodium hydrogen phosphate and sodium dihydrogen phosphate, and sodium phosphate is a gel forming agent that is safely absorbed by body tissues.

Effect data: The obtained pharmaceutical preparation is marked as pharmaceutical preparation K, which is a pharmaceutical preparation in the form of a hydrogel, containing dissolved lidocaine and undissolved lidocaine. The undissolved lidocaine exists in the hydrogel in the form of suspended crystals; the pH value of the obtained pharmaceutical preparation is about 8; the dissolved lidocaine in each gram of pharmaceutical preparation K is less than 5 mg, and the rest of the lidocaine In the form of undissolved suspended crystals.

Example 12

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
羧化壳聚糖Carboxylated chitosan	4％4%
磷酸二氢钠Sodium dihydrogen phosphate	0.01mol/L0.01mol/L
磷酸氢二钠Disodium phosphate	0.19mol/L0.19mol/L
布比卡因Bupivacaine	4％4%
水water	补足100％Make up 100%

The preparation method of the pharmaceutical preparation is as follows:

Put sodium dihydrogen phosphate and disodium hydrogen phosphate into water and dissolve them, add carboxylated chitosan and stir until completely dissolved; add bupivacaine, heat to 70°C and stir for 10 minutes, and cool to room temperature. Immediately.

In this pharmaceutical preparation, the pH buffer pair is composed of disodium hydrogen phosphate and sodium dihydrogen phosphate, and carboxylated chitosan is a gel forming agent that is safely absorbed by body tissues.

Effect data: The obtained pharmaceutical preparation is marked as pharmaceutical preparation L, which is a pharmaceutical preparation in the form of a hydrogel, containing dissolved bupivacaine and undissolved bupivacaine. The undissolved bupivacaine exists in the hydrogel in the form of suspended crystals; the pH value of the obtained drug preparation is about 8; the dissolved bupivacaine in each gram of drug preparation L is below 5 mg, and the rest of the cloth Bicaine exists in the form of undissolved suspended crystals.

Example 13-24

The local anesthetics in Example 1 were used tetracaine, articaine, cinchocaine, dibucaine, eticaine, levobupivacaine, mepivacaine, prilocaine, and ropivare respectively. Substitution of caine, trimocaine, benzocaine or procaine to obtain Examples 13-24.

Examples 25-30

The medical cover film as shown in Figures 1 and 2, the medical cover film includes a barrier film layer 10, an adsorption layer 20 and a network glue layer 30. The adsorption layer 20 is compounded on the barrier film layer 10, and the network glue layer 30 is compounded on On the adsorption layer 20.

The mesh adhesive layer 30 is composed of a set of parallel warp threads and a set of parallel weft threads. The warp threads and the weft threads are arranged perpendicularly, and the distance between two adjacent warp threads is equal to the distance between two adjacent weft threads. The warp and weft threads on the net-like glue layer 30 constitute a glue area 32, and the other areas on the net-like glue layer 30 except for the warp and weft constitute a glue-free area 31.

Wherein, the adsorption layer 20 is adhered to the barrier film layer 10 by glue, and the network glue layer 30 is adhered to the adsorption layer 20 by spraying.

Among them, the material of the barrier film layer 10 and the material of the adsorption layer 20, the type of glue of the net-like glue layer 30, the thickness of the net-like glue layer 30, and the area of the glue-free area 31 of the net-like glue layer 30 account for the net glue layer The ratio of 30 total area is shown in Table 1.

Table 1 The material and structural parameters of the medical covering films of Examples 25-30

In Table 1, the side length a refers to the side length of each square constituting the glue-free area 31; the ratio b refers to the ratio of the area of the glue-free area 31 to the total area of the network adhesive layer 30.

Example 31

A cover film

The cover film consists of a layer of plastic film (1525L film from 3M) and a layer of non-woven fabric (50g/m ² ) bonded on the film. The non-woven fabric layer contains 0.2 mg sodium borate, 1 mg glycerin, and 1 mg maltodextrin per square centimeter.

Example 32

A cover film

This covering film consists of a layer of plastic film (1525L film from 3M), a layer of non-woven fabric (50g/m ² ) bonded on the film, and a mesh bonded on the other side of the non-woven fabric Adhesive layer composition. The non-woven fabric layer contains 0.2 mg sodium borate, 1 mg glycerin, and 1 mg maltodextrin per square centimeter. The net-shaped adhesive layer is composed of a net formed by crossed pressure-sensitive adhesive strips (a pattern like a screen). The width of each strip is 1 mm, and the gap between the strip and the adjacent strip is 9 mm. This covering film is referred to as a medical covering film 32.

Example 33

Seven formulations containing dissolved and undissolved lidocaine were made with the ingredients listed in the table below.

Among the above 7 preparations, the combination of xanthan gum, hydroxypropyl cellulose, hydroxyethyl cellulose, starch, Pemulen TR-2 and sodium hydroxide is a suspending agent and also functions as a thickening agent; dihydrogen phosphate The combination of sodium and disodium hydrogen phosphate is a pH buffer pair. In the 7 preparations, the mass percentage of dissolved lidocaine is about 0.5% or less, and the rest of the lidocaine exists in the form of undissolved particles.

When making each of the above formulations, put all the ingredients of the formulation together and stir until the suspending agent is completely dissolved, then heat the formulation to 80 degrees Celsius and stir quickly, after cooling, store at room temperature. Observation after 14 days revealed that there were no visible lidocaine crystals in Xanthan gum-free Formulation 3, Formulation 4, Formulation 5, and Formulation 6, but no visible lidocaine crystals in Xanthan gum-containing Formulation 1, Formulation 2, and Formulation 7 Lidocaine crystals.

This unexpected discovery shows that xanthan gum has the effect of inhibiting the growth of lidocaine crystals, which in turn makes the distribution of lidocaine in preparations containing xanthan gum more uniform, and the contact with the skin during use will be better.

Example 34

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
利多卡因Lidocaine	5％5%
聚乙烯醇Polyvinyl alcohol	5％5%
氢氧化钠Sodium hydroxide	0.5％0.5%
磷酸氢钙Dicalcium Phosphate	8％8%
黄原胶Xanthan gum	2％2%
水water	补足至100％Make up to 100%

In this preparation, both xanthan gum and polyvinyl alcohol are suspending agents, glues, and have the function of thickening agent; polyvinyl alcohol is also a crosslinkable glue. Sodium hydroxide is used to adjust the pH of the preparation. Calcium hydrogen phosphate has a weak function of adjusting the pH value. In this preparation, the mass percentage of dissolved lidocaine is about 0.5% or less, and the remaining lidocaine exists in the form of undissolved particles.

Example 35

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration
利多卡因Lidocaine	8％8%
磷酸氢二钠Disodium phosphate	0.28mol/L0.28mol/L
磷酸二氢钠Sodium dihydrogen phosphate	0.02mol/L0.02mol/L
聚乙烯醇Polyvinyl alcohol	2.0％2.0%
水water	补足至100％Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

Mix disodium hydrogen phosphate, sodium dihydrogen phosphate, polyvinyl alcohol and water until a uniform viscous liquid is obtained. Then, add lidocaine and heat to 80°C, stir quickly, and cool to room temperature to get it.

In this pharmaceutical preparation, the pH buffer pair is composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; polyvinyl alcohol is a thickening agent and suspending agent, a gel forming agent, and also a gel agent.

Effect data: The obtained pharmaceutical preparation is marked as pharmaceutical preparation S, which is a pharmaceutical preparation in the form of a hydrogel, containing dissolved lidocaine and undissolved lidocaine. The undissolved lidocaine exists in the hydrogel in the form of suspended crystals; the pH value of the obtained pharmaceutical preparation is about 8; the dissolved lidocaine in each gram of pharmaceutical preparation S is less than 5 mg, and the rest of the lidocaine In the form of undissolved suspended crystals.

Example 36

A pharmaceutical preparation, its ingredients are shown in the following table:

成分ingredient	质量百分比或摩尔浓度Mass percentage or molar concentration

利多卡因Lidocaine	20％20%
磷酸氢二钠Disodium phosphate	0.28mol/L0.28mol/L
磷酸二氢钠Sodium dihydrogen phosphate	0.02mol/L0.02mol/L
聚乙烯醇Polyvinyl alcohol	2.0％2.0%
黄原胶Xanthan gum	0.2％0.2%
水water	补足至100％Make up to 100%

The preparation method of the pharmaceutical preparation is as follows:

Mix disodium hydrogen phosphate, sodium dihydrogen phosphate, xanthan gum, polyvinyl alcohol and water until a uniform viscous liquid is obtained. Then, add lidocaine and heat to 80°C, stir quickly, and cool to room temperature to get it.

In this pharmaceutical preparation, the pH buffer pair is composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; polyvinyl alcohol and xanthan gum are thickeners, glues, and suspending agents. Polyvinyl alcohol is also a crosslinkable substance or a crosslinkable glue.

Effect data: The obtained pharmaceutical preparation is marked as pharmaceutical preparation T, which is a pharmaceutical preparation in the form of a hydrogel, containing dissolved lidocaine and undissolved lidocaine. The undissolved lidocaine is present in the hydrogel in the form of suspended crystals; the pH value of the obtained pharmaceutical preparation is about 8; the dissolved lidocaine in each gram of the pharmaceutical preparation T is less than 5 mg, and the rest of the lidocaine In the form of undissolved suspended crystals.

Example 37-42

The cover film as shown in Figures 1 and 2, the cover film includes a barrier film layer 10, an adsorption layer 20, and a network adhesive layer 30. The adsorption layer 20 is composited on the barrier film layer 10, and the network gel layer 30 is composited on the adsorption layer. 20 on.

Table 1 The material and structural parameters of the medical covering films of Examples 37-38

Example 40

Among the above 7 preparations, the combination of xanthan gum, hydroxyethyl cellulose, starch, Pemulen TR-2 and sodium hydroxide are all suspending agents and also functions as a thickening agent; sodium dihydrogen phosphate and disodium hydrogen phosphate The combination of is a pH buffer pair. Polyvinyl alcohol is a comparator, and it is also a crosslinkable substance and a crosslinkable glue. In the 7 preparations, the mass percentage of dissolved lidocaine is about 0.5% or less, and the rest of the lidocaine exists in the form of undissolved particles.

When making each of the above formulations, put all the ingredients of the formulation together and stir until the suspending agent is completely dissolved, then heat the formulation to 80 degrees Celsius and stir quickly, after cooling, store at room temperature. Observation after 14 days revealed that there were no visible lidocaine crystals in xanthan gum-free formulations 3, 4, and 6, but there were no visible lidocaine crystals in xanthan gum-containing formulations 1, 2 and 7 Because of crystals.

Effect Example 1

As shown in Fig. 3, a layer of 2 mm thick pharmaceutical preparation A is applied to a 10 cm×10 cm piece of the mesh glue layer 30 of the medical covering film of Example 29, and the pharmaceutical preparation A covers the mesh glue layer 30 The central area is an area of 6 cm x 6 cm. This medical covering film with drug preparation A was affixed to the back skin of a human subject. The 2 cm wide edge area around the drug preparation A and the mesh adhesive layer 30 directly touched the skin. The edge area and the skin together form a flat square closed space, and the middle 6×6 cm drug preparation A layer (that is, the preparation layer 40 shown in Figure 4) is enclosed in this closed space, forming Figure 4 The status shown. Part of the pharmaceutical preparation A in the closed space is absorbed by the non-woven fabric layer through the glue-free area 31 of the net-like glue layer 30, thereby being fixed in place.

The skin covered by the drug preparation A was anesthetized about 90 minutes later, and 24 hours after the start of the medication, the drug preparation A was removed from the skin; the skin covered by the drug preparation A was removed when the drug preparation A was removed After an hour, they were still under anesthesia.

The system composed of the medical covering film and the drug preparation A can well fix the drug preparation A on the above skin during the above use period, and can well maintain the moisture in the drug preparation A, and the drug preparation during the above use period The pH value of A has been maintained at around 8.

Effect Example 2

A patient’s back skin has been suffering from neuralgia after shingles for more than 8 years. The skin of the affected area is about 15 cm × 30 cm rectangle. Cut 35 cm length from a roll of 20 cm wide and 200 cm long medical covering film (as in Example 29) to obtain a 20 cm x 35 cm medical covering film. The drug preparation B was smeared on the 16 cm x 31 cm area in the middle of the reticulated glue layer to form a 1 mm thick layer. Cover the skin of the affected area with the medical covering film with drug preparation B, so that the skin of the affected area is completely covered by the layer of drug preparation B. The 2 cm wide edge area around the net-like glue layer directly contacts the skin and forms a flat square enclosed space with the skin, and the middle 16 cm × 31 cm drug preparation layer B (that is, the preparation shown in Figure 4 The layer 40) is enclosed in this enclosed space and forms the state shown in FIG. 4. Part of the pharmaceutical preparation B in the closed space is absorbed by the non-woven fabric layer in the middle of the glue-free area of the net-like glue layer, thereby being fixed in place.

After about 90 minutes, the patient's pain began to decrease significantly. The patient maintained the drug preparation B and the medical covering film on the skin for 18 hours. Her daily activities and sleeping did not make the drug preparation B leave the original application place, because most of the drug preparations of the drug preparation B were layered with non-woven fabric Adsorbed to the original application. In the following months, she repeatedly used the drug formulation B-L in the same way, and achieved similar satisfactory results.

A system composed of a medical covering film and a pharmaceutical preparation B can well fix the pharmaceutical preparation B on the skin of the affected area during the above use period, and can well maintain the moisture in the pharmaceutical preparation B, and the pharmaceutical preparation B during the above use period The pH value has been maintained at around 8.

Effect Example 3

A patient’s abdominal skin has been suffering from neuralgia after shingles. The skin of the affected area is about 10 cm × 20 cm rectangle. The patient applied the drug preparation described in Example 8 to the affected area to form a drug preparation layer about 1 mm thick (the content of polyvinyl alcohol was 7.5%). The patient then covered the drug preparation layer with a cover film similar to the drug preparation layer but slightly larger as described in Example 31 (covering film containing 0.2 mg of sodium borate per square centimeter), and the non-woven fabric surface of the cover film contacted the drug Preparation layer. Due to the adhesiveness of the pharmaceutical preparation (mainly provided by the adhesive polyvinyl alcohol in the preparation), the covering film can be stuck on the pharmaceutical preparation layer without being fixed by another method. After the cover film comes into contact with the drug preparation layer, the sodium borate in the cover film begins to diffuse into the drug preparation layer and begin to cross-link the polyvinyl alcohol. After enough sodium borate enters the drug formulation layer, enough polyvinyl alcohol is cross-linked so that the drug formulation layer solidifies soft and solid.

After about 90 minutes, the patient's pain began to decrease significantly. After the patient maintained the pharmaceutical preparation and medical covering film on the skin for 18 hours, the covering film was removed. Since the drug preparation layer has been cured and attached to the cover film before, the cured drug preparation layer is also removed when the cover film is removed. No residual pharmaceutical preparations remain on the skin. The analgesic effect of this patient continued for about 2 hours after the covering film and the drug preparation layer were removed.

Effect Example 4

In order to alleviate the pain of the surgical incision of a cesarean section patient, the medical staff covered the sutured surgical incision with a 3 mm thick and 1.5 cm wide drug preparation C (the length of the drug preparation C layer is slightly longer than the length of the surgical incision), and used The medical covering film of Example 30 covers the pharmaceutical preparation C, and the pharmaceutical preparation C is enclosed in a closed space composed of the medical covering film and the skin, forming a state as shown in FIG. 4. The lidocaine molecules in the drug preparation C immediately began to penetrate the incision and surrounding tissues. Since the concentration of lidocaine dissolved in the pharmaceutical preparation C is below 0.5%, the lidocaine in the pharmaceutical preparation C penetrates into the incision tissue in a slow-release form.

The pH buffer pair in the pharmaceutical preparation C helps to keep the pH of the pharmaceutical preparation C at about 8, thereby enhancing the sustained release function of the pharmaceutical preparation C (see related discussion in the content of the invention). The patient's surgical incision pain began to be significantly reduced within 15 minutes, and the satisfactory analgesic effect lasted for more than 12 hours. When the patient felt pain again, the medical staff removed the drug preparation C and the medical cover film, and then used the new drug preparation C and the medical cover film in the same operation. In the future, whenever the patient needs analgesia, the medical staff will use the pharmaceutical preparation C and the medical covering film in the same operation method, and the same technical effect can be achieved.

The system composed of the medical covering film and the drug preparation C can well fix the drug preparation C on the skin of the affected area during the above use period, and can well maintain the moisture in the drug preparation C, and the drug preparation C during the above use period The pH value has been maintained at around 8.

After using the medical covering film of Example 28, the effect was the same.

Effect Example 5

The entire right leg and part of the pelvis of a patient were removed due to bone cancer. After the resection, she felt severe pain in the skin on the incision surface (the incision surface was covered by the patient's own skin left during the operation). Doctors believe that the pain is caused by nerve damage caused by surgery. In addition, she also felt severe phantom limb pain in her non-existent right calf (phantom limb pain is a kind of pain that amputees often feel in a non-existent limb). In order to alleviate these two kinds of pain, the medical staff applied the drug preparation D about 1 mm thick on the skin of the affected area, and covered the drug preparation D with the medical covering film of Example 30, and sealed the drug preparation D in the medical covering film and the skin. In the enclosed space, the state shown in Figure 4 is formed.

After an hour, her skin pain and phantom limb pain basically disappeared. She kept the drug formulation D on the skin for 24 hours. The effective analgesic effect is maintained for about 24 hours after the drug preparation D is removed. This patient repeated the above medication every two days for many weeks. The analgesic effect is so satisfactory that she does not need oral pain medication most of the time.

The system composed of the medical covering film and the pharmaceutical preparation D can well fix the pharmaceutical preparation D on the skin of the affected area during the above use period, and can well maintain the moisture in the pharmaceutical preparation D, and the pharmaceutical preparation D during the above use period The pH value has been maintained at around 8.

After using the medical covering film of Example 25, the effect was the same.

Effect Example 6

A patient with 30cm×30cm skin on the back and 15cm×15cm skin on the chest suffered from severe herpes zoster neuralgia for about 8 years. All the treatments used are not ideal. The drug preparation C with a thickness of about 2 mm and the medical covering film of Example 30 were covered on the skin of the affected area, and the drug preparation C was enclosed in a closed space composed of the medical covering film and the skin, forming a state as shown in FIG. 4.

One hour later, the patient's pain began to decrease significantly. The pharmaceutical preparation C and the medical covering film were removed after being kept on the skin for 36 hours. Except for the first hour, during these 36 hours, the analgesic effect was very satisfactory.

After using the medical covering film of Example 26, the effect was the same.

Effect Example 7

In order to alleviate the pain of the surgical incision of a patient with gallbladder removal, the medical staff covered the surgical incision with a thickness of 3 mm on the sutured surgical incision, and covered the pharmaceutical preparation E with the method in Example 4 with similar effect. The preparation E is enclosed in the closed space formed by the medical covering film and the skin, and forms the state shown in FIG. 4. The bupivacaine molecules in the drug preparation E immediately began to penetrate the incision and surrounding tissues.

Since the concentration of the dissolved bupivacaine in the drug formulation E is below 0.5%, the bupivacaine in the drug formulation E penetrates into the incision tissue in a slow-release form. The pH buffer pair in the pharmaceutical preparation E helps to keep the pH of the pharmaceutical preparation E at around 8, thereby enhancing the sustained release function of the pharmaceutical preparation E (see the relevant discussion in the content of the invention). The patient’s surgical incision pain began to be significantly reduced within 15 minutes. The satisfactory analgesic effect lasted more than 12 hours. In the future, whenever the patient needs analgesia, the medical staff will use the combination of the pharmaceutical preparation E and the medical covering film in the same way.

The system composed of the medical covering film and the drug preparation E can well fix the drug preparation E on the skin of the affected area during the above use period, and can well maintain the moisture in the drug preparation E, and the drug preparation E during the above use period The pH value has been maintained at around 8.

Effect Example 8

A patient suffers from pain caused by frozen shoulders in both shoulders. Apply a layer of pharmaceutical preparation F with a thickness of 1-2 mm on the skin of the patient's shoulders and cover it with the medical covering film shown in Example 29, and seal the pharmaceutical preparation F in the closed space formed by the medical covering film and the skin Inside, the state shown in Figure 4 is formed.

Three hours later, the pain in the patient's shoulders basically disappeared. This satisfactory analgesic effect lasted 8 hours on one shoulder joint and more than 18 hours on the other shoulder joint.

The system composed of the medical covering film and the pharmaceutical preparation F can well fix the pharmaceutical preparation F on the skin of the affected area during the above use period, and can well maintain the water in the pharmaceutical preparation F, and the pharmaceutical preparation F during the above use period The pH value has been maintained at around 8.

Effect Example 9

The pharmaceutical preparation G is applied to a layer that has covered a burn wound, and the pharmaceutical preparation G is enclosed in the closed space formed by the medical covering film 26 and the skin, forming a state as shown in FIG. 4.

The drug preparation G immediately began to deliver lidocaine into the wound tissue, and the pain of the wound was therefore greatly reduced. Because of the slow-release function of pharmaceutical preparation G, lidocaine penetrates into the wound in a slow-release manner, so the analgesic effect lasts for many hours and the concentration of lidocaine in the blood circulation is much lower than the concentration that will cause cardiac side effects. After that, when analgesia is needed, repeat the above method.

The same method mentioned above is used to control the pain caused in the process of scab removal of burn wounds, and the same technical effect is also achieved.

The system composed of the medical covering film 26 and the pharmaceutical preparation G can well fix the pharmaceutical preparation G on the skin of the affected area during the above use period, and can well maintain the moisture in the pharmaceutical preparation G, and the pharmaceutical preparation during the above use period The pH value of G has been maintained at around 8.

Effect Example 10

A patient suffers from pain caused by osteoarthritis in his knee joint. Apply a layer of drug preparation H with a thickness of about 1 mm on the skin of the entire knee joint, and cover the drug preparation H layer with the medical covering film of Example 30, and seal the drug preparation H in the closed space formed by the medical covering film and the skin Inside, the state shown in Figure 4 is formed.

The patient kept the drug preparation H on the knee joint for 18 hours and then removed it, and repeated the same operation every day. The patient's pain was greatly reduced as a result.

The system composed of the medical covering film and the pharmaceutical preparation H can well fix the pharmaceutical preparation H on the skin of the affected area during the above use period, and can well maintain the moisture in the pharmaceutical preparation H, and the pharmaceutical preparation H during the above use period The pH value has been maintained at around 8.

Effect Example 11

A patient suffers from pain caused by gout in the ankle joint. Using the method similar to that of Example 10, the pharmaceutical preparation is enclosed in the closed space composed of the medical covering film and the skin, forming the state shown in FIG. 4.

The patient's pain was greatly reduced as a result. The system consisting of the medical covering film and the pharmaceutical preparation can well fix the pharmaceutical preparation on the skin of the affected area during the above use period, and can well maintain the moisture in the pharmaceutical preparation, and during the above use period The pH value of the pharmaceutical preparation has been maintained at around 8.

Effect Example 12

A patient suffers from back pain. Using the method of Example 10, the pharmaceutical preparation C is applied, and the pharmaceutical preparation C is enclosed in the closed space composed of the medical covering film and the skin, and the state shown in FIG. 4 is formed.

The patient's pain was greatly reduced as a result. The system composed of the medical covering film and the drug preparation C can well fix the drug preparation C on the skin of the affected area during the above use period, and can well maintain the moisture in the drug preparation C, and the drug preparation C during the above use period The pH value has been maintained at around 8.

Effect Example 13

In order to alleviate the pain of the surgical incision of a cesarean section patient, the medical staff used the medical covering film of Example 30 to cover and fix the drug preparation B on the sutured surgical incision, and the drug preparation B was sealed in the seal composed of the medical cover film and the skin In the space, the state shown in Figure 4 is formed.

The lidocaine molecules in the drug preparation B immediately began to penetrate the incision and surrounding tissues, and entered the tissues in a slow-release manner for 12 hours. The patient's surgical incision pain began to be significantly reduced within 15 minutes, and the satisfactory analgesic effect lasted for more than 12 hours. In the future, whenever the patient needs analgesia, the medical staff will use the pharmaceutical preparation B and the medical covering film in the same way.

During the analgesia, the patient had daily actions such as turning over and lying on his side. The system composed of the medical covering film and the drug preparation B can well fix the drug preparation B on the skin of the affected area during the above use period, and can maintain it well. The water in the pharmaceutical preparation B, and the pH value of the pharmaceutical preparation B has been maintained at about 8 during the above use period.

Effect Example 14

The medicinal preparations of Examples 1-32 and the medical covering films of Examples 25-32 are used to treat the herpes pain of herpes zoster and the postherpetic neuralgia of herpes zoster by adopting the method of the similar effects in Examples 1-13. , Neuroma pain, phantom limb pain, diabetic peripheral neuralgia, arthralgia, including osteoarthritis pain, soft tissue injury, gout, surgical incision pain, burn pain or burn pain during scab removal, the pharmaceutical preparations can all play 12-30 hours continuous analgesic effect.

The system composed of the above-mentioned medical covering film and the above-mentioned pharmaceutical preparation can well fix the pharmaceutical preparation on the skin of the affected area during the above-mentioned use period, and can well maintain the moisture in the pharmaceutical preparation, and during the above-mentioned use period The pH value of the pharmaceutical preparation has been maintained at about 8.

Effect Example 15

In order to relieve the pain of the surgical incision of an abdominal surgery patient, the medical staff put the drug preparation H into the surgical incision before the final suture. The amount of the pharmaceutical preparation H put in is 0.2 grams of the pharmaceutical preparation H per cm of the incision length. After the drug preparation H was placed, the incision was sutured normally.

After being put into the incision, the dissolved lidocaine molecules in the drug preparation H begin to diffuse out of the drug preparation in the form of a hydrogel and enter the incision and surrounding tissues. Because only a small part of the lidocaine in the pharmaceutical preparation H is in a dissolved state, and only the dissolved lidocaine molecules can diffuse out of the hydrogel form of the pharmaceutical preparation and enter into contact with the hydrogel form of the pharmaceutical preparation Most of the lidocaine in the pharmaceutical preparation H exists in the pharmaceutical preparation H in the form of particles and cannot enter the human tissue. As the dissolved lidocaine leaves the hydrogel-form pharmaceutical formulation through a diffusion process, the undissolved lidocaine particles will gradually dissolve to maintain the concentration of lidocaine in the hydrogel-form pharmaceutical formulation at a saturated concentration.

The lidocaine in the pharmaceutical preparation H enters the surgical incision tissue in a sustained-release manner for more than 24 hours, and provides patients with satisfactory analgesia for more than 24 hours.

Effect Example 16

In order to relieve the pain of the surgical incision of a cesarean section patient, the medical staff put the drug preparation J into the surgical incision before the final suture.

The amount of the pharmaceutical preparation J put in is 0.2 g of the pharmaceutical preparation J per cm of the incision length. After drug preparation J was put in, the incision was sutured normally. After being put into the incision, the dissolved lidocaine molecules in the pharmaceutical preparation J begin to diffuse out of the pharmaceutical preparation in the form of a hydrogel and enter the incision and surrounding tissues. Because only a small part of the lidocaine in the pharmaceutical preparation J is in a dissolved state, and only the dissolved lidocaine molecules can diffuse out of the hydrogel form of the pharmaceutical preparation and enter into contact with the hydrogel form of the pharmaceutical preparation Most of the lidocaine in the pharmaceutical preparation J is present in the pharmaceutical preparation J in the form of particles and cannot enter the human tissue. As the dissolved lidocaine leaves the hydrogel form of the pharmaceutical formulation through a diffusion process, the undissolved lidocaine particles will gradually dissolve to maintain the concentration of lidocaine in the hydrogel form of the pharmaceutical formulation at a saturated concentration.

The lidocaine in the pharmaceutical preparation J enters the surgical incision tissue in a sustained-release manner for more than 48 hours, and provides patients with satisfactory analgesia for more than 48 hours.

Effect Example 17

In order to relieve the pain of the surgical incision of an abdominal surgery patient, the medical staff put the drug preparation J into the surgical incision before the final suture. The amount of the pharmaceutical preparation J put in is 0.2 g of the pharmaceutical preparation J per cm of the incision length. After drug preparation J was put in, the incision was sutured normally. In addition, the medical staff also applied the pharmaceutical preparation J to the sutured incision (the method and the medical covering film are the same as the effect example 14).

After being put into the incision, the dissolved lidocaine molecules in the pharmaceutical preparation J begin to diffuse out of the pharmaceutical preparation in the form of a hydrogel and enter the incision and surrounding tissues. Because only a small part of the lidocaine in the pharmaceutical preparation J is in a dissolved state, and only the dissolved lidocaine molecules can diffuse out of the hydrogel form of the pharmaceutical preparation and enter into contact with the hydrogel form of the pharmaceutical preparation Most of the lidocaine in the pharmaceutical preparation J is present in the pharmaceutical preparation J in the form of particles and cannot enter the human tissue. As the dissolved lidocaine leaves the hydrogel-form pharmaceutical formulation through a diffusion process, the undissolved lidocaine particles will gradually dissolve to maintain the concentration of lidocaine in the hydrogel-form pharmaceutical formulation at a saturated concentration.

The lidocaine in the pharmaceutical preparation J enters the surgical incision tissue in a sustained-release manner for more than 48 hours, and provides patients with satisfactory analgesia for more than 48 hours. In addition, the lidocaine molecules in the J layer of the pharmaceutical preparation applied to the sutured incision will diffuse into the incision tissue in a slow-release manner, providing additional long-term analgesic effects to the patient.

Effect Example 18

Before suturing a patient's cesarean section surgical incision, the doctor extruded the drug preparation K stored in a syringe into a cylindrical strip with a diameter of about 5 mm and placed it into the surgical incision (approximately 0.2 grams of drug per cm of incision tissue length) Preparation K), and then suture the surgical incision by conventional methods.

Due to the certain internal cohesion of sodium phosphate, it will not flow into the body tissues very quickly, but will only be slowly absorbed, so it will stay in the incision tissue for a long time. During this retention time, only a small part of the lidocaine in the drug preparation K that is sutured in the incision tissue is in dissolved form, and the dissolved lidocaine concentration in the drug preparation K is below 5 mg/ml , The rest of lidocaine exists in the form of undissolved particles. Since only the dissolved lidocaine can enter the surrounding tissues through the diffusion process, and play an analgesic effect, the undissolved lidocaine particles in this pharmaceutical preparation K do not directly participate in the diffusion process, but with the dissolution Lidocaine is slowly dissolved when it is absorbed by human tissues to keep the dissolved lidocaine concentration at a saturated concentration until all particles are dissolved. Since the process of slowly dissolving undissolved lidocaine is a very slow process, the process of lidocaine leaving the pharmaceutical preparation K into human tissue is a slow-release process.

The pharmaceutical preparation K of Example 11 has a relatively long analgesic effective time (longer than 12 hours). The pH buffering pair of phosphate in the pharmaceutical preparation K can help reduce the change of pH, thereby reducing the change of the saturated concentration of lidocaine, thereby achieving the effect of supporting the sustained-release function.

Effect Example 19

Before suturing a patient's cesarean section surgical incision, the doctor extruded the pharmaceutical preparation L stored in a syringe into a cylindrical strip with a diameter of about 4 mm and placed it into the surgical incision (approximately the length of the incision per cm 0.13 grams of pharmaceutical preparation L), and then suture the surgical incision by conventional methods.

Due to the certain internal cohesion of sodium phosphate, it will not flow into the body tissues very quickly, but will only be slowly absorbed, so it will stay in the incision tissue for a long time. During this retention time, only a small part of the bupivacaine in the drug preparation L sutured in the incision tissue is in dissolved form, and the concentration of the dissolved bupivacaine in the drug preparation L is 5 mg/ Below milliliter, the rest of bupivacaine exists in the form of undissolved particles. Since only the dissolved bupivacaine can enter the surrounding tissues through the diffusion process and play an analgesic effect, the undissolved bupivacaine particles in this pharmaceutical preparation L do not directly participate in the diffusion process, but follow The dissolved bupivacaine is slowly dissolved when it is absorbed by human tissues to keep the dissolved bupivacaine concentration at a saturated concentration until all particles are dissolved. Since the process of slowly dissolving undissolved bupivacaine is a very slow process, the process of leaving the drug formulation L into human tissues is a slow-release process.

The pharmaceutical preparation L of Example 12 has a relatively long analgesic effective time (longer than 12 hours). The phosphate pH buffer pair in the pharmaceutical preparation L can help reduce the change of pH, thus reducing the change of the saturated concentration of bupivacaine, thereby achieving the effect of supporting the sustained-release function.

Effect Example 20

A patient suffered from shingles on the waist skin. During the herpes stage, it was very painful. The skin of the affected area is about 10 cm × 20 cm rectangle. From a roll of 20 cm wide and 200 cm long cover film containing sodium borate (such as the cover film in Example 32), a 16 cm x 26 cm cover film is cut out. The pharmaceutical preparation (pharmaceutical preparation S) in Example 35 was smeared on the 12 cm x 22 cm area in the middle of the reticulated glue layer to form a 1 mm thick layer. Cover the skin of the affected area with the covering film with the drug preparation, so that the skin of the affected area is completely covered by the layer of the drug preparation. The edge area around the mesh glue layer that is not in contact with the drug preparation directly contacts the skin and forms a flat rectangular enclosed space with the skin, while the middle drug preparation layer (that is, the preparation layer 40 shown in Figure 4) is closed In this closed space, the state shown in Figure 4 is formed. Part of the pharmaceutical preparations in the closed space are absorbed by the middle non-woven fabric layer through the non-adhesive area of the reticulated glue layer, thereby being fixed in place. After the cover film contacts the drug preparation layer, the sodium borate contained in the adsorption layer of the cover film diffuses into the drug preparation layer, and cross-links with the polyvinyl alcohol in the drug preparation layer, thereby curing the drug preparation layer.

After about 90 minutes, the patient's pain began to decrease significantly. The patient took the drug formulation and cover film on the skin for 18 hours and then removed it. The drug preparation layer has been cured before removal and the cured drug preparation layer adheres to the cover film. Therefore, when the patient removes the covering film, the cured drug preparation layer attached to it is also removed together, and there is no residual drug preparation on the skin. In this way, the operation of washing the residual pharmaceutical preparations on the skin is avoided.

The system composed of the covering film and the pharmaceutical preparation can well fix the pharmaceutical preparation on the skin of the affected area during the above use period, and can well maintain the moisture in the pharmaceutical preparation.

Effect Example 21

A patient suffers from pain caused by osteoarthritis in his knee joint. A layer of the pharmaceutical preparation of Example 34 with a thickness of about 1 mm was applied to the entire knee joint skin, and the medical covering film of Example 30 was used to cover the pharmaceutical preparation layer. Due to the glue (polyvinyl alcohol) in the pharmaceutical preparation, the covering film is stuck on the pharmaceutical preparation layer. Therefore, the fixation of the cover film does not completely depend on the adhesiveness of the reticulated glue layer at the edge that does not touch the pharmaceutical preparation and the skin. Such a dual fixation method is very important to reliably fix the drug preparation layer and the covering film on the knee joint with a lot of movement.

The patient kept the drug preparation on the knee joint for 18 hours and then removed it, and repeated the same operation every day. The patient's pain was greatly reduced as a result.

The system composed of the medical covering film and the pharmaceutical preparation can well fix the pharmaceutical preparation on the skin of the affected area during the above-mentioned use period, and can well maintain the moisture in the pharmaceutical preparation layer, and the medicine during the above-mentioned use period The pH of the formulation has been maintained at around 8.

Effect Example 22

A patient suffers from back pain. Using the method of Example 10 with the effect of applying the pharmaceutical preparation in Example 36 (pharmaceutical preparation T), the pharmaceutical preparation was enclosed in a closed space composed of the medical covering film 32 (the covering film in Example 32) and the skin to form The state shown in Figure 4.

The patient's pain was greatly reduced as a result. The system composed of the medical covering film and the pharmaceutical preparation can well fix the pharmaceutical preparation layer on the skin of the affected area during the above use period, and can well maintain the moisture in the pharmaceutical preparation layer, and is The pH value of pharmaceutical preparation C has been maintained at about 8 during use. During use, the cross-linking agent sodium borate in the covering film diffuses into the drug preparation layer, and cross-linking reaction with the cross-linkable substance polyvinyl alcohol inside, solidifies and adheres the drug preparation layer On the cover film, when the patient removes the cover film after use, the cured drug preparation layer is removed at the same time. There are no residual pharmaceutical preparations on the skin.

Although the specific embodiments of the present invention have been described above, those skilled in the art should understand that this is only an example, and the protection scope of the present invention is defined by the appended claims. Those skilled in the art can make various changes or modifications to these embodiments without departing from the principle and essence of the present invention, but these changes and modifications all fall within the protection scope of the present invention.

Claims

A pharmaceutical preparation, characterized in that the pharmaceutical preparation includes water and a local anesthetic; the local anesthetic in the pharmaceutical preparation includes a dissolved local anesthetic and an undissolved local anesthetic; the local anesthetic in the pharmaceutical preparation The mass percentage of the anesthetic in the pharmaceutical preparation is more than 2% and not 100%; the mass percentage of the dissolved local anesthetic in the pharmaceutical preparation is less than 1% and is not 0; The local anesthetics in the pharmaceutical preparations are lidocaine, tetracaine, bupivacaine, articaine, cinchocaine, dibucaine, eticaine, levobupivacaine, mepivacaine, Prilocaine, ropivacaine, trimecaine, benzocaine or procaine; the total mass percentage of each component in the pharmaceutical preparation is 100%.
The pharmaceutical preparation according to claim 1, wherein the pharmaceutical preparation further contains a pH buffering pair; the pH buffering pair is dissolved in the water in the pharmaceutical preparation and forms a pH buffering solution; the pH buffering solution makes The mass percentage of the dissolved local anesthetic in the pharmaceutical preparation is less than 1% and is not 0;

Wherein, the pH buffer pair is a pH buffer pair that can effectively resist changes in the pH value of the pharmaceutical preparation in the range of pH 7-13, preferably a pH buffer composed of disodium hydrogen phosphate and sodium dihydrogen phosphate Yes, a pH buffer pair composed of dipotassium hydrogen phosphate and potassium dihydrogen phosphate, a pH buffer pair composed of sodium tetraborate and sodium hydroxide or a pH buffer pair composed of tris and HCl, more preferably hydrogen phosphate A pH buffer pair composed of disodium and sodium dihydrogen phosphate or a pH buffer pair composed of sodium tetraborate and sodium hydroxide, and more preferably a pH buffer pair composed of disodium hydrogen phosphate and sodium dihydrogen phosphate;

Wherein, when the pH buffer pair is a pH buffer pair composed of disodium hydrogen phosphate and sodium dihydrogen phosphate, the molar concentration of the pH buffer pair in the pharmaceutical preparation is preferably 0.02-0.4 mol/L, It is more preferably 0.05-0.3 mol/L or 0.1-0.3 mol/L, and still more preferably 0.08-0.22 mol/L; wherein the molar concentration of sodium dihydrogen phosphate and the molar concentration of disodium hydrogen phosphate in the pharmaceutical preparation The molar concentration ratio is preferably 14:1-19:1.
The pharmaceutical preparation according to claim 1 or 2, wherein the pH of the pharmaceutical preparation is 7-13, 7-11 or 7.5-9.5; preferably, when the pharmaceutical preparation is prepared, the selected The pH buffer pair controls the pH value of the pharmaceutical preparation within the range of the pH value; more preferably, during the preparation of the pharmaceutical preparation, before adding the pH buffer pair, an alkaline substance is used to The pH value of the system is adjusted to the range of the pH value, and then the pH buffer pair that can form a pH buffer solution corresponding to the pH value is added; the alkaline substance is preferably sodium tripolyphosphate, sodium bicarbonate , One or more of sodium hydroxide and potassium hydroxide, more preferably sodium hydroxide and/or potassium hydroxide, further more preferably sodium hydroxide;

And/or, the mass percentage of the local anesthetic in the pharmaceutical preparation in the pharmaceutical preparation is 3% or more, 4% or more, 5% or more, 8% or more or 10% or more, preferably 3%- 15%, 4%-10% or 5%-8%;

And/or, the mass percentage of the dissolved local anesthetic in the pharmaceutical preparation is less than 0.7%, 0.5%-0.7% or less than 0.5%;

And/or, the local anesthetic in the pharmaceutical preparation is lidocaine, tetracaine or bupivacaine, preferably lidocaine or tetracaine, more preferably lidocaine.
The pharmaceutical preparation according to any one of claims 1 to 3, wherein the pharmaceutical preparation comprises a suspending agent, the suspending agent is preferably carbomer, and the type of the suspending agent is preferably Pemulen TR-2 or Carbopol 971; the mass percentage of the suspension in the pharmaceutical preparation is preferably 0.10%-0.50%;

And/or, the pharmaceutical preparation includes a thickening agent, and the thickening agent is preferably one or more of xanthan gum, starch, carbomer and cellulose, more preferably xanthan gum, One or more of starch, hydroxyethyl cellulose and hydroxypropyl cellulose; the mass percentage of the thickening agent in the pharmaceutical preparation is preferably 0.2%-8%, more preferably 1 %-6%, more preferably 2%-5%;

And/or, the pharmaceutical preparation includes glycerin and/or propylene glycol; the mass percentage of the glycerin and/or propylene glycol in the pharmaceutical preparation is preferably 2%-25%;

And/or, the pharmaceutical preparation includes a gel-forming agent, and the mass percentage of the gel-forming agent in the pharmaceutical preparation is 0.2%-10%, preferably 0.2%-5%, more preferably 0.5% -4%, more preferably 1.0% -3.0%;

Among them, the gel forming agent is preferably one or more of xanthan gum, uronic acid and uronic acid salt, more preferably xanthan gum, uronic acid or uronic acid salt, and further more preferably xanthan A mixture of native gum and acid or a mixture of xanthan gum and sodium sulfate;

Among them, the salt of salt is preferably sodium salt;

Wherein, more than 95% by weight of the qualitative acid in the qualitative acid is preferably non-crosslinked plasmonic acid, and more preferably 98% to 100% by weight of the qualitative acid is non-crosslinked plasmonic acid;

Wherein, preferably more than 95% by weight of the sodium arginate is non-cross-linked sodium acrylate, and more preferably 98% by weight to 100% by weight of the sodium argonate is non-cross-linked sodium;

And/or, the pharmaceutical preparation contains a glue, and the glue is used to make the pharmaceutical preparation sticky; preferably, the glue is xanthan gum, polyvinyl alcohol or polyvinylpyrrolidone; the glue The mass percentage of the agent in the pharmaceutical preparation is preferably 0.1-30%, more preferably 0.5-15%, or 1%-5%;

And/or, the pharmaceutical preparation contains a substance that can be crosslinked; the mass percentage of the substance that can be crosslinked in the pharmaceutical preparation is preferably 0.1-30%, more preferably 0.5-15% , Or 1%-5%;

Preferably, the cross-linkable substance is polyvinyl alcohol or polyvinyl pyrrolidone; more preferably, the cross-linkable substance is polyvinyl alcohol; more preferably, the polyvinyl alcohol is in the The mass percentage in the pharmaceutical preparation is preferably 0.1-30%, more preferably 0.5-15%, or 1%-5%;

And/or, the pharmaceutical preparation is semi-solid, and preferably has immobility; or the pharmaceutical preparation has immobility, which means that the pharmaceutical preparation in a container is being stirred During the next 12 hours of standing, its surface will not flow into a horizontal plane;

And/or, the local anesthetic is tetracaine, the mass percentage of tetracaine in the pharmaceutical preparation in the pharmaceutical preparation is more than 0.5%, and the tetracaine dissolved in the pharmaceutical preparation is The mass percentage in the pharmaceutical preparation is 0.1% or less; or, the local anesthetic is lidocaine, and the mass percentage of lidocaine in the pharmaceutical preparation is 2% or more or 3% or more, The mass percentage of lidocaine dissolved in the pharmaceutical preparation in the pharmaceutical preparation is less than 1%.
The pharmaceutical preparation according to any one of claims 1 to 4, wherein the pharmaceutical preparation does not contain lipid substances; the lipid substances are preferably animal fat, vegetable fat and other fatty substances One or more of;

And/or, the concentration of the dissolved local anesthetic in the pharmaceutical preparation is 10 mg/ml or less, preferably 5 mg/ml or less;

And/or, the concentration of the local anesthetic in the pharmaceutical preparation in the pharmaceutical preparation is 20 mg/ml or more, preferably 40 mg/ml or more, more preferably 60 mg/ml or more;

And/or, the undissolved local anesthetic in the pharmaceutical preparation accounts for more than 80% of the local anesthetic in the pharmaceutical preparation;

And/or, the pH of the pharmaceutical preparation is 7.4-9.2, preferably 7.4-9.0, more preferably 7.8-8.8, still more preferably 7.9-8.4;

And/or, the pharmaceutical preparation further contains a gel-forming agent, and the mass percentage of the gel-forming agent in the pharmaceutical preparation is 0.2%-5%; the mass percentage of the gel-forming agent in the pharmaceutical preparation Preferably it is 0.5%-4%, more preferably 1.0%-3.0%;

Among them, the gel forming agent is preferably one or more of xanthan gum, uronic acid and uronic acid salt, more preferably xanthan gum, uronic acid or uronic acid salt, and further more preferably xanthan A mixture of native gum and acid or a mixture of xanthan gum and sodium sulfate;

Wherein, more than 95% by weight of the qualitative acid in the qualitative acid is preferably non-crosslinked plasmonic acid, and more preferably 98% to 100% by weight of the qualitative acid is non-crosslinked plasmonic acid;

Among them, preferably more than 95% by weight of the sodium arginate is non-cross-linked sodium acrylate, and more preferably 98% by weight to 100% by weight is non-cross-linked sodium acrylate.
The pharmaceutical preparation according to any one of claims 1 to 5, wherein the gel-forming agent is sodium sulfate, and the mass percentage of the gel-forming agent in the pharmaceutical preparation is 0.2%-4 %, the pH buffer pair is a pH buffer pair composed of disodium hydrogen phosphate and sodium dihydrogen phosphate, the local anesthetic is lidocaine or bupivacaine, and the pH of the pharmaceutical preparation is 7.8-8.8; The concentration of the local anesthetic in the pharmaceutical preparation in the pharmaceutical preparation is more than 20 mg/ml or more than 40 mg/ml; the concentration of the dissolved local anesthetic in the pharmaceutical preparation is 5 mg/ml the following;

Alternatively, the gel-forming agent is a sulfonic acid or a salt of a sulfonic acid, and the mass percentage of the gel-forming agent in the pharmaceutical preparation is 0.2%-10%, preferably 0.2-5%, and the pH buffer is The formed pH buffer solution makes the pH value of the pharmaceutical preparation 7.8-8.8, the concentration of the dissolved local anesthetic in the pharmaceutical preparation is less than 5 mg/ml, and the local anesthetic of the pharmaceutical preparation The concentration in the pharmaceutical preparation is 20 mg/ml or more; wherein the mass percentage of the gel forming agent in the pharmaceutical preparation is preferably 0.3%-3%; the pH buffer pair is preferably The pH buffer pair composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; the local anesthetic is preferably lidocaine or bupivacaine; the salt of the qualitative acid is preferably sodium phosphate, and the qualitative acid Preferably, more than 95% by weight of sodium arginate in sodium is non-cross-linked sodium alginate, and more preferably 98% by weight to 100% by weight is non-cross-linked sodium argonate; the pH value of the pharmaceutical preparation is preferably It is 7.8-8.5; the concentration of the local anesthetic in the pharmaceutical preparation in the pharmaceutical preparation is preferably more than 40 mg/ml.
A pharmaceutical preparation, the pharmaceutical preparation is a preparation containing lidocaine, characterized in that the preparation containing lidocaine contains lidocaine, xanthan gum and water, and the preparation containing lidocaine The lidocaine includes dissolved lidocaine and undissolved lidocaine; the sum of the mass percentages of the components in the lidocaine-containing preparation is 100%;

Alternatively, the pharmaceutical preparation is a lidocaine-containing preparation, the lidocaine-containing preparation contains lidocaine, xanthan gum, polyvinyl alcohol, and water, and the lidocaine in the lidocaine-containing preparation It includes dissolved lidocaine and undissolved lidocaine; the sum of the mass percentages of the components in the lidocaine-containing preparation is 100%.
The pharmaceutical preparation according to claim 7, wherein the mass of the sum of dissolved lidocaine and undissolved lidocaine in the lidocaine-containing preparation is The percentage is 2% or more and not 100%; the mass percentage of the dissolved lidocaine in the lidocaine-containing preparation is 1% or less, and not 0; more preferably, the dissolved lidocaine The mass percentage of lidocaine in the lidocaine-containing preparation is 0.1%-1%;

And/or, the lidocaine-containing preparation contains a pH buffer pair composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; wherein, preferably, the disodium hydrogen phosphate is contained in the lidocaine-containing The mass percentage in the preparation is 0.1%, and the mass percentage of the sodium dihydrogen phosphate in the lidocaine-containing preparation is 4%;

And/or, the mass percentage of lidocaine in the lidocaine-containing preparation is greater than 1.5%, and not 100%; preferably 2%-8%, such as 5%;

And/or, the mass percentage of the dissolved lidocaine in the lidocaine-containing preparation is 1% or less or 0.5% or less, and is not 0;

And/or, the mass percentage of xanthan gum in the lidocaine-containing preparation is greater than 0.1%, and not 100%; preferably 0.2%-10%, further preferably 0.5%-6% or 1-6%, such as 1% or 3%;

And/or, the lidocaine-containing preparation further contains hydroxypropyl cellulose; the mass percentage of the hydroxypropyl cellulose in the lidocaine-containing preparation is preferably more than 1%, and no 100%, more preferably 1% to 5%, for example, 3%;

And/or, the lidocaine-containing preparation further contains polyvinyl alcohol; the mass percentage of the polyvinyl alcohol in the lidocaine-containing preparation is preferably 0.1-30%, more preferably 0.5 -15%; more preferably 1%-5%;

Preferably, the lidocaine-containing preparation comprises the following components (or consists of the following components) lidocaine, xanthan gum and water; the mass percentage of lidocaine in the lidocaine-containing preparation 2%-8%; the mass percentage of the dissolved lidocaine in the lidocaine-containing preparation is 1% or less, and is not 0, preferably 0.6% or less or 0.5% or less, and Not 0, more preferably 0.1%-1%; the mass percentage of the xanthan gum in the lidocaine-containing preparation is greater than 0.1%, preferably 0.2%-10%, more preferably 1%-6%; water is the balance;

Preferably, the lidocaine-containing preparation includes the following components (or consists of the following components) lidocaine, polyvinyl alcohol and water; the mass percentage of lidocaine in the lidocaine-containing preparation is 2%-8%; the mass percentage of the dissolved lidocaine in the lidocaine-containing preparation is 1% or less, and not 0, preferably 0.6% or less or 0.5%, and not It is 0, such as 0.1%-1%; the mass percentage of the polyvinyl alcohol in the lidocaine-containing preparation is greater than 0.1%, preferably 0.2%-10%, more preferably 1% -6％; water is the balance;

Preferably, the lidocaine-containing preparation includes the following components (or consists of the following components) lidocaine, xanthan gum, polyvinyl alcohol and water; the lidocaine in the lidocaine-containing preparation The mass percentage of the dissolved lidocaine is 2%-8%; the mass percentage of the dissolved lidocaine in the lidocaine-containing preparation is 1% or less, and is not 0, preferably 0.6% or less or 0.5% Below, and not 0, more preferably 0.1%-1%; the mass percentage of the xanthan gum in the lidocaine-containing preparation is greater than 0.1%, preferably 0.2%-10%, and more Preferably it is 1%-6%; the mass percentage of the polyvinyl alcohol in the lidocaine-containing preparation is greater than 0.1%, preferably 0.2%-10%, more preferably 1%-6% ; Water is the balance.
A cover film, characterized in that the cover film includes a barrier film layer and an adsorption layer;

Wherein, the covering film is preferably a medical covering film;

And/or, the material of the barrier film of the barrier film layer is preferably a polyethylene film, an ethylene-vinyl acetate copolymer film or a polyurethane film;

And/or, the adsorption layer is preferably a non-woven fabric; the adsorption layer preferably further contains a crosslinking agent, and the crosslinking agent is preferably dispersed in the material of the adsorption layer; more preferably , The crosslinking agent is a boron-containing substance, such as sodium borate, or N,N'-methylene bisamide amide, or glutaraldehyde, glyoxal, maleic acid, citric acid, trimetaphosphoric acid Trisodium, sodium hexametaphosphate, dianhydride, succinic acid or sulfosuccinic acid; the covering film contains a crosslinking agent higher than 0.01 mg/per square centimeter, preferably higher than 0.1 mg/per square centimeter, Or 0.01mg-100mg/per square centimeter, more preferably 0.02-0.2mg/per square centimeter;

And/or, one side of the adsorption layer is bonded to the barrier film layer by glue, or one side of the adsorption layer is composited on the barrier film layer by hot pressing;

And/or, the cover film preferably further includes a net-like glue layer, one side of the adsorption layer is compounded on the barrier film layer, and the net-like glue layer is compounded on the other side of the adsorption layer; The area of the glue-free area of the net-like glue layer accounts for more than 10% of the total area of the net-like glue layer, and not 100%; the net-like glue layer is used to fix the pharmaceutical preparation on the human body The tissue surface is more preferably completely enclosed in a closed space formed by the covering film (such as a medical covering film) and the surface of the human body tissue.
The cover film according to claim 9, wherein the net-like glue layer is preferably a glue net composed of curves and/or straight lines; the net-like glue layer is more preferably a set of parallel to each other A glue net composed of warp threads and a set of weft threads parallel to each other; further preferably, the warp threads and the weft threads are arranged perpendicularly; still more preferably, the distance between two adjacent warp threads and the distance between two adjacent weft threads equal;

And/or, the thickness of the reticulated adhesive layer is preferably 0.01mm-0.75mm, more preferably 0.05mm-0.75mm, still more preferably 0.25mm-0.75mm;

And/or, the glue of the net-like glue layer is preferably a medical pressure-sensitive glue that is insoluble in water, more preferably an organic silica gel and/or acrylic glue;

And/or, preferably, the area of the glue-free area of the network glue layer accounts for more than 30% of the total area of the network glue layer; more preferably, the area of the glue-free area of the network glue layer It occupies more than 50% of the total area of the reticulated adhesive layer; more preferably, the area of the non-adhesive area of the reticulated adhesive layer accounts for more than 70% of the total area of the reticulated adhesive layer, and still more preferably , The area of the glue-free area of the network adhesive layer accounts for 70%-90% of the total area of the network adhesive layer;

And/or, preferably, the length stretch rate of the cover film in all directions is more than 10%, more preferably 10%-30%.
A system for fixing a pharmaceutical preparation on the skin, characterized in that the system comprises the pharmaceutical preparation according to any one of claims 1-8 and the covering film according to claim 9 or 10. The covering film is used to cover the pharmaceutical preparation applied on the surface of human body tissue, or to completely enclose the pharmaceutical preparation in a closed space formed by the covering film and the surface of the human body tissue; or through the covering The cross-linking agent contained in the film cross-links the cross-linkable substances in the covered pharmaceutical preparation and solidifies the pharmaceutical preparation;

Or; the system includes the pharmaceutical preparation according to any one of claims 1-8 and the medical covering film according to claim 9 or 10, the medical covering film is used to cover the surface of human body tissue The pharmaceutical preparation is either used to completely enclose the pharmaceutical preparation in a closed space formed by the medical covering film and the surface of human body tissue; or it is covered by the crosslinking agent contained in the medical covering film The substance in the drug formulation can be cross-linked and solidify the drug formulation.
The system for fixing a pharmaceutical preparation on the skin according to claim 11, wherein the surface of the human body tissue is the surface of intact skin or the surface of open human tissue or the surface of incomplete skin. The surface of is preferably a burn surface or a surgical incision surface, and the open human tissue surface is a burn and scald wound, surgical incision surface, or the surface of damaged skin caused by disease or trauma;

And/or, when the pharmaceutical preparation contains a substance that can be crosslinked, the covering film contains a corresponding crosslinking agent; or, when the pharmaceutical preparation contains a substance that can be crosslinked, the medical covering film Contains the corresponding cross-linking agent;

Wherein, the cross-linking agent is preferably a substance containing boron-containing elements, more preferably sodium borate;

Wherein, when the pharmaceutical preparation contains polyvinyl alcohol, the covering film preferably contains boron-containing substances, such as sodium borate, or glutaraldehyde, glyoxal, maleic acid, citric acid, trimetaphosphoric acid Trisodium, sodium hexametaphosphate, dianhydride, succinic acid or sulfosuccinic acid;

Or, when the pharmaceutical preparation contains polyvinyl alcohol, the medical covering film preferably contains a boron-containing substance, such as sodium borate, or glutaraldehyde, glyoxal, maleic acid, citric acid, trimethylene Trisodium phosphate, sodium hexametaphosphate, dianhydride, succinic acid or sulfosuccinic acid;

Wherein, when the pharmaceutical preparation contains polyvinylpyrrolidone, the cover film preferably contains N,N'-methylenebisamide amide;

Or, when the pharmaceutical preparation contains polyvinylpyrrolidone, the medical covering film preferably contains N,N'-methylenebisamide amide;

And/or, the length of the outer edge of the covering film or the medical covering film away from the outer edge of the preparation layer formed by the pharmaceutical preparation is more than 5 mm, for example, may be 2-4 cm.
A system for fixing a pharmaceutical preparation on the skin, characterized in that the pharmaceutical preparation is the pharmaceutical preparation according to any one of claims 1-8, and the pharmaceutical preparation contains a substance that can be crosslinked The pharmaceutical preparation; the covering film is the covering film according to claim 9 or 10, the covering film is a covering film containing a crosslinking agent; and/or, the covering film is a medical covering film; wherein, more Preferably, the pharmaceutical preparation is the pharmaceutical preparation according to claim 7 or 8.
A system for fixing a pharmaceutical preparation on the skin, characterized in that the pharmaceutical preparation is the pharmaceutical preparation according to any one of claims 1-8, and the pharmaceutical preparation contains a substance that can be crosslinked The pharmaceutical preparation; the covering film is the covering film as claimed in claim 9 or 10, the covering film is a covering film containing a crosslinking agent; and/or, the covering film is a medical covering film; but not Contains reticulated glue layer.
A method of using a system for fixing a pharmaceutical preparation on the skin, comprising the following steps: it comprises the following steps: applying the pharmaceutical preparation as claimed in any one of claims 1 to 8 and covering the surface of the human tissue in need of treatment To form a pharmaceutical preparation layer, and then cover the pharmaceutical preparation layer with the covering film as claimed in claim 9 or 10; or, apply the pharmaceutical preparation as claimed in any one of claims 1 to 8 to the pharmaceutical preparation layer as claimed in claim 9 or 10. The adsorption layer or the net-like glue layer of the covering film is used to form a drug preparation layer, and then the drug preparation layer is covered on the surface of the human tissue to be treated.
A method for preparing a pharmaceutical preparation according to any one of claims 1-8, characterized in that, the preparation method comprises the following steps: mixing the components of the pharmaceutical preparation uniformly; The preparation method preferably includes the following steps: (1) mixing the remaining components in the pharmaceutical preparation except the local anesthetic to obtain a mixed solution; (2) combining the mixed solution with the local anesthetic After mixing the anesthetics, heat it and cool it down to room temperature;

Wherein, in step (2), the heating temperature is preferably 75-85°C, more preferably 80°C;

Wherein, in step (2), the heating is preferably performed under stirring.
An application of the pharmaceutical preparation as described in any one of claims 1-8 or the system for fixing the pharmaceutical preparation on the skin as described in any one of claims 11-14 in the preparation of a medicine for treating pain; The pain is pain during herpes zoster, post-herpetic nerve damage pain, neuroma pain, phantom limb pain, diabetic peripheral neuralgia, joint pain, osteoarthritis pain, back pain, pain caused by gout , Pain caused by soft tissue injury, pain from incision after surgery, pain from skin breakage caused by disease or trauma, pain from burns, or pain during burn removal.
An application of the system for fixing a pharmaceutical preparation on the skin as described in any one of claims 11-14 in the preparation of a medical device or a medical device/drug combination product for treating pain; the pain is in a band shape Herpes pain, post-herpetic nerve damage pain, neuroma pain, phantom limb pain, diabetic peripheral neuralgia, joint pain, osteoarthritis pain, back pain, pain caused by gout, pain caused by soft tissue injury , Post-operative incision pain, skin break pain caused by disease or trauma, burn pain, or burn pain during scab removal.
A treatment method using the pharmaceutical preparation as described in any one of claims 1-8 or the system for fixing the pharmaceutical preparation on the skin as described in any one of claims 11-14 to treat pain;

The treatment method includes the following steps: the preparation layer formed by the pharmaceutical preparation is completely enclosed in a closed space formed by the covering film or medical covering film and the surface of human body tissue;

The pain is pain in herpes zoster stage, pain caused by nerve damage after herpes zoster, neuroma pain, phantom limb pain, diabetic peripheral neuralgia, joint pain, osteoarthritis pain, back pain, and pain caused by gout , Pain caused by soft tissue injury, postoperative incision pain, burn pain or burn pain during scab removal, pain caused by skin breakage caused by disease or trauma;

Preferably, the treatment method includes the following steps: smearing the pharmaceutical preparation on the covering film or the medical covering film, and then fixing the preparation layer formed by the pharmaceutical preparation on the covering film or the covering film. In the enclosed space formed by the medical covering film and the surface of the human body tissue;

Alternatively, preferably, the treatment method includes the following steps: smearing the pharmaceutical preparation on the surface of the human body tissue to form a preparation layer, and then covering the preparation layer with a covering film or a medical covering film, and applying the The preparation layer is fixed in a closed space formed by the covering film or the medical covering film and the surface of the human body tissue;

Wherein, preferably, the covering film or the medical covering film is the covering film or the medical covering film according to claim 9;

Wherein, preferably, the length of the outer edge of the covering film or the medical covering film away from the outer edge of the preparation layer formed by the pharmaceutical preparation is more than 5 mm, more preferably 2-4 cm;

Or, preferably, when the pharmaceutical preparation is applied to intact skin or close to intact skin, the time for keeping the pharmaceutical preparation on the surface of the human body tissue is more than 6 hours, more than 8 hours, more than 12 hours, or more than 18 hours. More than, 24 hours or more, or more than 30 hours; when the pharmaceutical preparation is applied to burn pain or burn pain during scab removal, the time for keeping the pharmaceutical preparation on the surface of the human body tissue is 5 min-50 min, or 3 Hours or more, 6 hours or more, 8 hours or more, 12 hours or more, 18 hours or more, 24 hours or more, or 30 hours or more; when the pharmaceutical preparation is applied to the postoperative incision, the pharmaceutical preparation is maintained in the human body tissue The surface time is 2 hours or more, preferably 2 hours to 48 hours, more preferably 6 hours to 24 hours;

Or, preferably, the thickness of the pharmaceutical preparation on the surface of the human body tissue is maintained at 0.1 mm or more, 0.2 mm or more, 0.5 mm or more, 1 mm or more, or 2 mm or more.
The method of treatment according to claim 19, wherein:

When the pain to be treated is herpes zoster pain, postherpetic neuralgia or diabetic peripheral neuralgia, one of the treatment methods preferably includes the following steps: applying the pharmaceutical preparation to the The central area of the covering film (for example, medical covering film) (when there is a net-like glue layer, it is the central area of the net-like glue layer) so that the edge area of the net-like glue layer is not coated by the drug formulation To obtain a cover film with a preparation layer (for example, a medical cover film); then cover the cover film with a preparation layer (for example, a medical cover film) on the surface of the human body tissue at the painful part, and make The preparation layer is in contact with the human body tissue surface at the painful part, or the preparation layer is in contact with and covers the human body tissue surface at the painful part, and the edge area is in contact with the human body at the painful part The skin outside the tissue surface area is bonded to fix the preparation layer on the surface of the human body tissue at the painful part and completely seal the preparation layer on the covering film (for example, medical covering film) and the The painful part is in a closed space composed of the surface of human body tissue; wherein the length or distance of the outer edge of the covering film (such as the medical covering film) from the outer edge of the preparation layer is more than 5 mm; the preparation The thickness of the layer is 0.1 mm or more, preferably 0.5 mm or more; the time for keeping the preparation layer and the covering film (such as the medical covering film) on the surface of the human body tissue is more than 6 hours; preferably , The area and shape of the preparation layer can cover most or all of the human body tissue surface of the painful part;

Or, when the pain to be treated is herpes zoster pain, postherpetic neuralgia or diabetic peripheral neuralgia, the second treatment method preferably includes the following steps: coating the pharmaceutical preparation on A preparation layer is formed on the surface of the human body tissue at the painful part; and then a covering film (such as a medical covering film) as described above that is larger than the preparation layer is covered with the preparation layer, and the center of the covering film The area (when there is a net-like glue layer, the central area of the net-like glue layer) covers the preparation layer and the edge area does not touch the preparation layer, and the edge area is the surface area of the human body tissue at the painful part Adhesive outside the skin to fix the preparation layer on the skin and completely seal the preparation layer on the covering film (such as a medical covering film) and the human body tissue at the painful part In a closed space composed of a surface; preferably, the area and shape of the preparation layer can cover most or all of the human body tissue surface of the painful part;

Alternatively, when the pain to be treated is neuroma pain, phantom limb pain, joint pain, osteoarthritis pain, back pain, pain caused by gout, or pain caused by soft tissue injury, the treatment method is the treatment method One or two; wherein, when the pain is phantom limb pain, the human body tissue surface at the painful part is the skin of the painful part or the skin surface of the severed limb; when the pain is joint pain, the pain The human body tissue surface at the part of is the skin outside or around the joint; when the pain is back pain, the human body tissue surface at the painful part is the back skin;

Alternatively, when the pain to be treated is neuroma pain, phantom limb pain, joint pain, osteoarthritis pain, back pain, pain caused by gout, or pain caused by soft tissue injury, the treatment method preferably includes the following Step: Cover the covering film (such as medical covering film) as defined in the aforementioned system on the preparation layer coated with the pharmaceutical preparation in a manner that the mesh glue layer faces the surface of the human body tissue of the painful part The surface of the human body tissue at the painful part, the central area of the reticulum layer is in contact with the preparation layer, and the edge area of the reticulum layer is outside the surface of the human body tissue at the painful part The skin adhesion to fix the preparation layer on the skin outside the human body tissue surface at the painful part, and to completely seal the preparation layer on the covering film (for example, medical covering film) and the skin The painful part of the human body tissue surface constitutes a closed space; preferably, the preparation layer covers all the painful human body tissue surface and the edge area of the covering film sticks to the skin of the skin area without pain Together

Alternatively, when the pain to be treated is post-operative incision pain, the treatment method preferably includes the following steps: applying the pharmaceutical preparation on the sutured surgical incision so that the surgical incision is covered by a layer of 1 mm The above thickness of the pharmaceutical preparation is covered by the preparation layer formed by the object, and the time for keeping the pharmaceutical preparation on the surgical incision is more than 3 hours; more preferably, the preparation layer formed by the pharmaceutical preparation is used The same or similar method as above is completely enclosed in the closed space formed by the covering film (such as the medical covering film) and the surgical incision and the skin on both sides defined in the aforementioned system;

Or, when the pain to be treated is post-operative incision pain, the treatment method preferably includes the following steps: before the surgical incision is sutured, a hydrogel pharmaceutical preparation is placed into the incision tissue; wherein, the hydrogel pharmaceutical The formulation contains 0.2wt%-4wt% sodium phosphate, a pH buffer pair, a local anesthetic and water; the pH buffer pair is dissolved in the water in the pharmaceutical preparation; the local anesthetic in the pharmaceutical preparation includes a dissolved local Anesthetics and undissolved local anesthetics; the pH buffer pair is a buffer composed of disodium hydrogen phosphate and sodium dihydrogen phosphate; the local anesthetic is lidocaine or bupivacaine; the hydrogel drug The pH of the preparation is 7.8-8.8; the concentration of the dissolved local anesthetic in the hydrogel pharmaceutical preparation is less than 5 mg/ml, and the local anesthetic in the hydrogel pharmaceutical preparation is in the water The concentration in the gel drug preparation is 20 mg/ml or more; the amount of the hydrogel drug preparation put into the incision tissue is 0.1 g/cm incision length-1 g/cm incision length;

Wherein, more preferably, the concentration of the local anesthetic in the hydrogel pharmaceutical preparation in the hydrogel pharmaceutical preparation is 40 mg/ml or more;

Wherein, more preferably, the treatment method further includes the following steps: smear the aforementioned pharmaceutical preparation on the sutured surgical incision, so that the surgical incision is formed by a layer of the pharmaceutical preparation with a thickness of 1 mm or more. Covered by the layer and keep the pharmaceutical preparation on the surgical incision for more than 3 hours;

Alternatively, when the pain to be treated is post-operative incision pain, the treatment method preferably includes the following steps: putting the pharmaceutical preparation into the incision tissue before suturing the surgical incision; putting the medicine into the incision tissue The amount of preparation is 0.1-2 grams per cm of incision length;

Alternatively, when the pain to be treated is burn pain or pain during burn scab removal, the treatment method preferably includes the following steps: apply the pharmaceutical preparation to the burn or the burn surface (wound surface) that requires scab removal to form A drug preparation layer covering the wound surface; and keeping the drug preparation layer on the wound surface or the burn surface for more than 5 minutes.