CN102641236A - Expandable biological adhesive sustained and controlled release preparation for preventing and curing oral diseases and preparation method thereof - Google Patents
Expandable biological adhesive sustained and controlled release preparation for preventing and curing oral diseases and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an expandable biological adhesive sustained and controlled release preparation for preventing and curing oral diseases, which consists of a water phase, a surfactant and an oil phase. Active ingredients for preventing and curing the oral diseases exist in the water phase and/or the oil phase, wherein the water phase is an inner phase, the oil phase is an outer phase, the boundary of the water phase and the oil phase is constructed and maintained by the surfactant, and the water phase and the oil phase are in a uniform and fully osculatory state. The invention also discloses a preparation method of the biological adhesive sustained and controlled release preparation. Through the preparation, a drug sustained and controlled release mode is formed, a product is lasting and effective, the frequency of usage of the product is reduced, the compliance of the product is increased, and the use cost is reduced; and the release preparation exists at drug administration target positions in a plastic physical form, so that the active ingredients in the product effectively cover the drug administration target positions, even the drug administration target positions with complex physiological structures, such as teeth in an oral cavity and periodontal pocket between gingivae.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of bioadhesion sustained-release preparation, relate in particular to a kind of expansiveness bioadhesion sustained-release preparation of preventing and treating oral disease and preparation method thereof; The present invention can be applied to include but not limited to: the administration of topical, non local form, hole filling or tissue repairing and its surface-treated medical apparatus and instruments.
Background technology
Emulsion is generally by two immiscible phase compositions, and wherein one is scattered in another phase equably with trickle particle shape.According to which as decentralized photo (inner phase) or which as continuous phase (extroversion), can be divided into two kinds of fundamental types of oil-in-water and Water-In-Oil roughly.The constructed system of the present invention is the latter.At present, when using the Water-In-Oil system in the industry, the difficulty that is run into mainly is a complex manufacturing, and product stability is poor.
Be used at present treat or the reducing human oral cavity in the method for symptom of tract relevant disease comprise physical method and chemical method.Physical method generally needs doctor or professional to be undertaken by instrument, and needs the patient through adhering to using toothbrush, dental floss or toothpick partner treatment.But this method usually can be difficult to touch the dead angle in some deeps because of the restriction of the anatomical structure of tooth, and especially in antibiotic means, chemical method is still the most effectively way (like antibiotic use).Chemical method comprises available in the market polytype preparation, like solid preparation (patch, tablet, suppository etc.), and liquid preparation (like foam, lotion, liniment etc.) and semi-solid preparation (emulsifiable paste, gel, cream etc.).Generally speaking, solid preparation like buccal tablet, on the one hand is to be difficult to reach needed slow release effect (several hours or more of a specified duration) when medication, and a large amount of on the other hand medicines does not contact with lesions position but along with saliva is swallowed; The second, the administration shape can not be satisfactory, even some preparations can produce discomfort or make troubles to the patient when administration, for example mouth paster; The liquid form of medication maybe be more acceptant for the patient comparatively speaking, but be difficult to reach the purpose of slow release: because lotion generally is difficult in the enough medicines of the long-time reservation of lesions position; So all there is an identical defective in solid with the liquid drug-supplying system, be exactly all to be difficult to reach the deep layer position of needs treatment and keep the sufficiently long time.
In order to overcome the above problems, the someone has developed multiple topical therapeutic scheme; For example (patent No. is: US5599553) disclosed diformazan tetracycline hydrochloride and PCL are with the pharmaceutical preparation of strips composition, and said preparation can continue release 7 days at the periodontal pocket position for United States Patent (USP).But, in drug release process, still be difficult to preparation is filled up periodontal pocket fully, and need pharmaceutical base be removed after seven days, because its decomposition in vivo is very slowly difficult.(patent No. is United States Patent (USP): US4913882) disclose the pharmaceutical preparation that a kind of polymer particle can be scattered in water-soluble decentralized photo; Advantage is can independently discharge medicine patient is felt bad; But need frequent drug administration, because its release has only 6 hours.(number of patent application is: in fact 03116412.9) disclosed a kind of mouth paster applies it in the periodontal medical science space and remains inconvenient one Chinese patent application.One Chinese patent application (number of patent application is: 91105673.4) disclosed chewing gum method for preparing, and still undesirable on sustained release performance.
Summary of the invention
One of technical problem that the present invention will solve provides a kind of expansiveness bioadhesion sustained-release preparation of preventing and treating oral disease, and it forms slow controlled release medicine pattern, makes the lasting onset of product, reduces the frequency of usage of product, increases the product compliance, reduces use cost; Because the release dosage form is to occur with plastic physical aspect at the administration target position; Therefore can make the active component in the product effectively cover the administration target position; Even comprise administration target position with complex physiologic structure, such as the periodontal pocket between oral cavity inner teeth gear and gums or the like.
Two of the technical problem that the present invention will solve provides the method for preparing of this bioadhesion sustained-release preparation.
The present invention relates to one type of expandable emulsifiable paste system based on water and oil mixture or substrate.This system can be attached to biological mucosa or skin surface for a long time, and can discharge the active component that is contained according to the mode of the slow release of predetermined design or controlled release and reach the purpose of long-acting.The key feature of this type of preparation is that product form has plasticity because of expansiveness, thereby the prepared preparation product can form the plastic shape that is complementary with administration target position physiological make-up or can realize filling automatically at the administration target position in application.
A kind of expansiveness biologic adhesion preparation of realizing slow controlled release involved in the present invention has good stable property, is applicable to the slow release of bioactive substances in the biological tract, and realizes filling automatically.This preparation is a kind of by oil phase, surfactant, water and the common water-in-oil emulsion that makes up of auxiliary adjuvant; The controlled capability of its dilatancy, adhesiveness and active component is all relevant with constructed oil phase and the interface energy of water (also become surface energy, both increased system surface area energy needed or merit).And the kind and the ratio of the influence factor of interface energy and decentralized photo, temperature, dispersed phase drop size and particle size distribution, the rerum natura and the oil-water interfaces characteristic of oil, water, the character of emulsifying agent and content, factors such as production technology are relevant.
In order to solve the problems of the technologies described above, the present invention provides a kind of expansiveness bioadhesion sustained-release preparation of preventing and treating oral disease, and said preparation is made up of water, surfactant, oil phase; The active component of preventing and treating oral disease is present in water and/or the oil phase; Wherein, water is an inner phase, and oil phase is the foreign minister, and the interface of oil phase and water is made up and kept by surfactant, makes biphase homogeneous and the complete state of contact of being in.
Said bioadhesion sustained-release preparation can be the system of a kind of semisolid or liquid.This system has certain secular relatively bioadhesive, depends on the interface energy in this system and stick the length of time.This system administering mode can local or non local administration.The route of administration that this system is comprised in the topical mode mainly is the oral cavity.Said topical mode is to be used for periodontal pocket, gingiva, tissue, dental caries hole, tooth body, oral cavity inwall at all, perhaps medically acceptable hole.
Said active component can dissolve or be suspended in water and/or the oil phase.
Preferably, when said active component was suspended in water and/or the oil phase, it was micronized, was present in water and/or the oil phase to guarantee its stable uniform ground.
Said active component can be used as surfactant or cosurfactant.
Said active component comprises antibacterial, antiinflammatory, hemorrhage, osteoporosis agent, tissue repair agent, nutrient, analgesic.
The viscosity of this bioadhesion sustained-release preparation should be greater than 1PaS, and preferred, the viscosity of this bioadhesion sustained-release preparation should be greater than 3PaS.
The release characteristic of the viscosity of the semi-solid or liquid of said bioadhesion sustained-release preparation, stability, active component can be adjusted through adding excipient effectively.Employed excipient comprises one or several of correctives, pH regulator agent, stabilizing agent, solvent, osmotic pressure regulator, diluent, surfactant, thickening agent, delay releasing agent, antiseptic and inhibiting bacteria function agent, chelating agen, adsorbent, softening agent, wetting agent, antioxidant, aromatic, coloring agent, lucifuge agent.Said excipient is selected from: any one or a few in mannitol, sorbitol, propylene glycol, sucrose, Mel, glycerol, maltose alcohol, xylitol, xanthan gum, carrageenin, carboxymethyl cellulose (sodium), polyvidone, hypromellose, boric acid, borate, carbomer, titanium dioxide, hydrophobic ultrafine silica powder, spermaceti, paraffin, vaseline, the Cera Flava.
Said oil phase is selected from: any one in mineral oil, vegetable oil, the fatty acid (alcohol, ester, ether) be several kinds mixture perhaps; Be preferably: mineral oil, olive oil, Oleum Ricini, Oleum sesami, soybean oil, almond oil, Oleum Gossypii semen, glyceryl monostearate, medium chain length fatty acid triglyceride, hexadecanol, silicone oil, isostearic acid isopropyl ester, stearic acid gather one or several mixture of ring third Ethylene Oxide-15 ether.
Employed surfactant is one or several in nonionic surfactant, natural surfactant, the part ion type surfactant.Be preferably: one or several in polysiloxane alcohols EVA, polyglyceryl fatty acid ester, cithrol/alcohol ester, polyoxyethylene aliphatic alcohol ether, polyoxyethylene ether wax, Myrj 45, tristerin, polyethers organosilicon wax, succinic acid sulphonic acid ester salt, oxirane and expoxy propane EVA, the Span.
In the said bioadhesion sustained-release preparation, the percentage by weight of oil phase is 1 ~ 40%; The percentage by weight of surfactant is 0.5 ~ 35%; The percentage by weight of water is 25 ~ 98.5%.
In addition, the present invention also provides the preparation process of above-mentioned bioadhesion sustained-release preparation.A kind of semi-solid perhaps system of being made up of water and oil phase of liquid of the present invention, the oil-water boundary is made up and is kept by surfactant (emulsifying agent), makes biphase homogeneous and the complete state of contact of being in.This system has certain secular relatively bioadhesive, depends on the interface energy in the system and stick the length of time.Active component can be distributed in a phase or biphase wherein, and can from formulation system, diffuse out according to release profiles, emission levels and the persistent period of design.Its preparation method comprises the steps:
A) select oil phase and surfactant, if solid, fusion perhaps adds solvent and assists it, and stirs;
B) preparation water;
C) under stirring, water is slowly added oil phase until end, make emulsifiable paste, promptly get according to the dosage packing;
In step a) and/or step b), add and prevent and treat the active component of oral disease, stir;
The order of step a) and step b) is interchangeable.
In step a) and/or step b), can also add excipient.
Scheme 1:
The aqueous solution or the suspension that at first prepare the carrying active composition, the viscosity of the liquid that forms and dissolubility can be adjusted through adding excipient effectively; The excipient that adds includes but not limited to: glycerol, sorbitol, propylene glycol, sucrose, Mel, mannitol, maltose alcohol, xylitol, xanthan gum, carrageenin, carboxymethyl cellulose (sodium), polyvidone, hypromellose etc.Use surfactant and needed excipient to be dissolved in mineral oil or the vegetable oil then and process oil phase, described excipient can be hydrophobic ultrafine silica powder, paraffin, vaseline etc.At last water that makes and oil phase are at room temperature mixed, stir and make stable components and uniform Emulsion.
Scheme 1Concrete steps are following:
A) select oil phase and surfactant, if solid, fusion perhaps adds solvent and assists it, adds excipient (optional), and stirs;
B) preparation water: active component is dispersed in the water, and adds excipient (optional), stir;
C) under stirring, water is slowly added oil phase until end, make emulsifiable paste, promptly get according to the dosage packing;
The order of step a) and step b) can be exchanged.
Scheme 2:
According to method for preparing oil phase and water, active component is joined in the oil phase.In emulsion process, different active ingredient can be retained in respectively relatively independent biphase in, can also interpenetrate through oil-water interfaces.After product was used, each active component in mutually disengaged and plays a role.According to the pharmacokinetics drug release characteristic of active component self, design sustained release pattern is to realize the needed effect of preparation.
Scheme 2Concrete steps are following:
A) select oil phase and surfactant, if solid, fusion perhaps adds solvent and assists it, adds active component and excipient (optional), and stirs;
B) preparation water: this water is made up of water and optional excipient;
C) under stirring, water is slowly added oil phase until end, make emulsifiable paste, promptly get according to the dosage packing;
The order of step a) and step b) can be exchanged.
Scheme 3:
According to method for preparing oil phase and water, some compositions of a plurality of active component in the compound preparation are joined in the oil phase, remaining active component is added to water.In emulsion process, different active ingredient can be retained in respectively relatively independent biphase in, can also interpenetrate through oil-water interfaces.After product was used, each active component in mutually disengaged combined effect respectively.According to the pharmacokinetics drug release characteristic of each active component self, design sustained release pattern is to realize the needed synergism of compound preparation.
Scheme 3Concrete steps are following:
A) select oil phase and surfactant, if solid, fusion perhaps adds solvent and assists it, adds active component and excipient (optional), and stirs;
B) preparation water: water-soluble active ingredient is dispersed in the water, and adds excipient (optional), stir;
C) under stirring, water is slowly added oil phase until end, make emulsifiable paste, promptly get according to the dosage packing;
The order of step a) and step b) can be exchanged.
In addition, also bioadhesion sustained-release preparation of the present invention is carried out release property and dilatancy experiment:
A. the release of active component
Generally speaking, medicine must discharge from preparation and just can bring into play necessary curative effect.Through measuring the release conditions of medicine, with release conditions in the body of aids drug in external different time sections.
B. dilatancy experiment
When the Emulsion sample places water, can keep a complete body; Along with change of time, its volume can obviously increase, and continues to expand to all directions.Through the final volume of measuring samples initial sum, and calculate its ratio, can obtain this sample expansile evaluation index over a period to come: the coefficient of expansion, and then can obtain the quantitative criteria of this sample in the effective covering power of target position.
The present invention compared with prior art; Following beneficial effect is arranged: the effect that the present invention reached is that active component is delivered to lesions position effectively according to predetermined administering mode; And according to the speed release that designs; Preparation fully contacts with lesions position in expansion process, and the advantage of this improved drug delivery system comprises:
1. preparation of the present invention has good bioadhesive and slow release effect, can long term in the part, release is slow, reduces the administration access times, reduces toxic and side effects; And administering mode is flexible, and self-help is strong; Have certain viscosity, bioadhesive is good, can not produce water clock after the medication, has secular stability;
2. the dilatancy that preparation of the present invention had can be filled up biological space automatically; Fully contact with the lesions position surface; Need only injecting in a small amount during application, medicament makes it be full of the biological space that needs filling voluntarily; More fully contact with targeting moiety, its soft plasticity not only makes things convenient for administration, and is easier to accepted than solid preparation;
3. preparation of the present invention can be widely used in treating the exploitation of the novel product of dental disorder, personal healthcare.Related product can comprise single-activity composition or compound recipe (in containing, Western medicine), both can belong to pharmacy or medical instruments field, also can be used as hygienic article and uses;
4. prescription and technology involved in the present invention are simple, with low cost.
Description of drawings
Fig. 1 is the sustained release performance experimental result sketch map of prepared emulsifiable paste among the embodiment 1-4.
The specific embodiment
Following instance further specifies the present invention, but the present invention is not limited to following listed embodiment:
Embodiment 1-1
Method for preparing:
A) with oil phase and surfactant mix homogeneously;
B) each component of water is mixed with active component, continue to stir to guarantee that each composition is uniformly dispersed;
C) (200 ~ 600rpm) slowly add oil phase, and the limit edged stirs until end, and then high-speed stirred (more than the 1000rpm) 2min, obtain the cream preparation of the about 4PaS of viscosity, and packing promptly gets under stirring condition with the water for preparing.
Embodiment 1-2
Method for preparing is with embodiment 1-1, the about 68PaS of emulsifiable paste viscosity that obtains.
Embodiment 1-3
Method for preparing is with embodiment 1-1, the about 230PaS of emulsifiable paste viscosity that obtains.
Embodiment 1-4
A) sustained release performance of prepared emulsifiable paste test:
Testing conditions: the 5g sample spreads upon in the surface plate that diameter is 6cm equably, and the surface plate of coating places 500ml water, adopts the slurry method of Chinese Pharmacopoeia standard digestion instrument; Rotating speed 50rpm; 32 ℃ of water-baths, at the content (ultraviolet method) of sampling of different time point and mensuration pigment, the cumulative release effect is as shown in Figure 1; Can foresee significantly by Fig. 1, can be through regulating prescription to regulate release rate of drugs and level effectively.
B) expansion performance experiment of prepared emulsifiable paste:
Method of testing: get about 1.0g sample and place the graduated cylinder that 40ml water is housed under the room temperature; The liquid volume of reading is sample volume V1; During later on each mensuration original liquid is carefully poured out, added quantitative liquid again, can obtain the volume V2 after sample expands after a period of time; Sample is at the coefficient of expansion C=V2/V1 of this time period, and the result sees table 1:
The coefficient of expansion of sample in water of table 1 preparation
Embodiment 2
Method for preparing is with embodiment 1-1, and the active component chlorhexidine acetate among this embodiment can be used as surfactant.
Expansion performance experiment: method is with embodiment 1-4, and the coefficient of expansion of three days (72h) is greater than 1.4.
The sustained release performance test: method is with embodiment 1-4, and active component discharges in 72h and is less than 40%.
Embodiment 3
Method for preparing:
A) each component of oil phase (active component) is mixed with surfactant, and dispersed with stirring is even;
B) each component of water is mixed, continue to stir to guarantee that each composition is uniformly dispersed;
C) (200 ~ 600rpm) slowly add oil phase, and the limit edged stirs until end, and then high-speed stirred (more than the 1000rpm) 2min, obtain the cream preparation of the about 1700PaS of viscosity, and packing promptly gets under stirring condition with the water for preparing.
Expansion performance experiment: method is with embodiment 1-4, and the coefficient of expansion of three days (72h) is greater than 1.5.
The sustained release performance test: method is with embodiment 1-4, and active component discharges in 72h and is less than 40%.
Embodiment 4
Method for preparing:
A) oil phase is mixed with surfactant, and dispersed with stirring is even, add Oleum Caryophylli, Borneolum Syntheticum, Fructus Piperis Longi extract isoreactivity composition then after, and fully mix;
B) each component of water is mixed with micronized metronidazole, chlorhexidine acetate, continue to stir to guarantee that each composition is uniformly dispersed;
C) (200 ~ 600rpm) slowly add oil phase, and the limit edged stirs until end, and then high-speed stirred (more than the 1000rpm) 2min, obtain the cream preparation of the about 810PaS of viscosity, and packing promptly gets under stirring condition with the water for preparing.
Expansion performance experiment: method is with embodiment 1-4, and the coefficient of expansion of three days (72h) is greater than 1.7.
The sustained release performance test: method is with embodiment 1-4, and active component discharges in 72h and is less than 35%.
Claims (20)
1. an expansiveness bioadhesion sustained-release preparation of preventing and treating oral disease is characterized in that, is made up of water, surfactant, oil phase; The active component of preventing and treating oral disease is present in water and/or the oil phase; Wherein, water is an inner phase, and oil phase is the foreign minister, and the interface of oil phase and water is made up and kept by surfactant, makes biphase homogeneous and the complete state of contact of being in.
2. by the described bioadhesion sustained-release preparation of claim 1, it is characterized in that said bioadhesion sustained-release preparation is the system of a kind of semisolid or liquid.
3. by the described bioadhesion sustained-release preparation of claim 1, it is characterized in that said active component dissolves or is suspended in water and/or the oil phase.
4. by the described bioadhesion sustained-release preparation of claim 3, it is characterized in that when said active component was suspended in water and/or the oil phase, it was micronized, be present in water and/or the oil phase to guarantee its stable uniform ground.
5. by the described bioadhesion sustained-release preparation of claim 1, it is characterized in that said active component is as surfactant or cosurfactant.
6. by the described bioadhesion sustained-release preparation of claim 1, it is characterized in that said active component comprises antibacterial, antiinflammatory, hemorrhage, osteoporosis agent, tissue repair agent, nutrient, analgesic.
7. by the described bioadhesion sustained-release preparation of claim 2, it is characterized in that this system has certain secular relatively bioadhesive, depends on the interface energy in this system and stick the length of time.
8. by the described bioadhesion sustained-release preparation of claim 2, it is characterized in that this system administering mode can local or non local administration.
9. by the described bioadhesion sustained-release preparation of claim 8, it is characterized in that the route of administration that this system is comprised mainly is the oral cavity in the topical mode.
10. by the described bioadhesion sustained-release preparation of claim 9, it is characterized in that said topical mode is to be used for periodontal pocket, gingiva, tissue, dental caries hole, tooth body, oral cavity inwall at all, perhaps medically acceptable hole.
11., it is characterized in that the viscosity of this bioadhesion sustained-release preparation should be greater than 1PaS by the described bioadhesion sustained-release preparation of claim 1.
12., it is characterized in that the viscosity of this bioadhesion sustained-release preparation should be greater than 3PaS by the described bioadhesion sustained-release preparation of claim 11.
13., it is characterized in that the release characteristic of the viscosity of said semisolid or liquid, stability, active component can be adjusted through adding excipient effectively by the described bioadhesion sustained-release preparation of claim 2.
14. by the described bioadhesion sustained-release preparation of claim 13; It is characterized in that employed excipient comprises one or several of correctives, pH regulator agent, stabilizing agent, solvent, osmotic pressure regulator, diluent, surfactant, thickening agent, delay releasing agent, antiseptic and inhibiting bacteria function agent, chelating agen, adsorbent, softening agent, wetting agent, antioxidant, aromatic, coloring agent, lucifuge agent.
15. by the described bioadhesion sustained-release preparation of claim 14; It is characterized in that said excipient is selected from: any one or a few in mannitol, sorbitol, propylene glycol, sucrose, Mel, glycerol, maltose alcohol, xylitol, xanthan gum, carrageenin, carboxymethyl cellulose (sodium), polyvidone, hypromellose, boric acid, borate, carbomer, titanium dioxide, hydrophobic ultrafine silica powder, spermaceti, paraffin, vaseline, the Cera Flava.
16. by the described bioadhesion sustained-release preparation of claim 1, it is characterized in that said oil phase is selected from: any one in mineral oil, vegetable oil, the fatty acid (alcohol, ester, ether) be several kinds mixture perhaps; Employed surfactant is one or several in nonionic surfactant, natural surfactant, the part ion type surfactant.
17. by the described bioadhesion sustained-release preparation of claim 16; It is characterized in that said oil phase is selected from: mineral oil, olive oil, Oleum Ricini, Oleum sesami, soybean oil, almond oil, Oleum Gossypii semen, glyceryl monostearate, medium chain length fatty acid triglyceride, hexadecanol, silicone oil, isostearic acid isopropyl ester, stearic acid gather one or several mixture of ring third Ethylene Oxide-15 ether; Said surfactant is selected from one or several in polysiloxane alcohols EVA, polyglyceryl fatty acid ester, cithrol/alcohol ester, polyoxyethylene aliphatic alcohol ether, polyoxyethylene ether wax, Myrj 45, tristerin, polyethers organosilicon wax, succinic acid sulphonic acid ester salt, oxirane and expoxy propane EVA, the Span.
18., it is characterized in that in the said bioadhesion sustained-release preparation, the percentage by weight of oil phase is 1 ~ 40% by the described bioadhesion sustained-release preparation of claim 1; The percentage by weight of surfactant is 0.5 ~ 35%; The percentage by weight of water is 25 ~ 98.5%.
19. the method for preparing by the described bioadhesion sustained-release preparation of claim 1 is characterized in that, comprises the steps:
A) select oil phase and surfactant, if solid, fusion perhaps adds solvent and assists it, and stirs;
B) preparation water;
C) under stirring, water is slowly added oil phase until end, make emulsifiable paste, promptly get according to the dosage packing;
In step a) and/or step b), add and prevent and treat the active component of oral disease, stir;
The order of step a) and step b) is interchangeable.
20. the method for preparing by the described bioadhesion sustained-release preparation of claim 19 is characterized in that, in step a) and/or step b), adds excipient.
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| CN113713113A (en) * | 2021-09-28 | 2021-11-30 | 四川大学 | Composition for treating oral mucosa diseases and preparation method thereof |
| CN115227603A (en) * | 2022-08-02 | 2022-10-25 | 上海佩格医院管理有限公司 | Edible oral sustained-release matrix and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107998401A (en) * | 2017-12-11 | 2018-05-08 | 广州立白企业集团有限公司 | A kind of oral medicine preparation with slow release effect and preparation method thereof |
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| CN113713113A (en) * | 2021-09-28 | 2021-11-30 | 四川大学 | Composition for treating oral mucosa diseases and preparation method thereof |
| CN113713113B (en) * | 2021-09-28 | 2023-09-19 | 四川护家卫士生物医药科技有限公司 | Composition for treating oral mucosa diseases and preparation method thereof |
| CN115227603A (en) * | 2022-08-02 | 2022-10-25 | 上海佩格医院管理有限公司 | Edible oral sustained-release matrix and preparation method and application thereof |
| CN115227603B (en) * | 2022-08-02 | 2024-03-12 | 上海佩格医院管理有限公司 | Edible oral cavity slow-release matrix and preparation method and application thereof |
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