KR20130112413A

KR20130112413A - Transdermal formulation comprising lidocaine or its salt and prilocaine or its salt

Info

Publication number: KR20130112413A
Application number: KR1020120034779A
Authority: KR
Inventors: 최후균
Original assignee: 조선대학교산학협력단
Priority date: 2012-04-04
Filing date: 2012-04-04
Publication date: 2013-10-14

Abstract

PURPOSE: A transdermal formulation is provided to remarkably enhance skin permeability of lidocaine and to suppress skin permeability of prilocaine in a proper level, thereby preventing side effects caused by excessive administration of prilocaine. CONSTITUTION: A transdermal formulation contains a mixture containing lidocaine or a salt thereof and prilocaine or a salt thereof mixed in a weight ratio of 5:1-1.4:1. The mixture is an eutetic mixture of lidocaine or the salt thereof and prilocaine or the salt thereof. The transdermal formulation comprises a support layer, a drug-containing matrix layer, and a release layer. [Reference numerals] (AA) Example 6; (BB) Comparative example 2

Description

Transdermal formulation comprising lidocaine or its salt and prilocaine or its salt}

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to transdermal comprising a mixture of lidocaine or a salt thereof and a specific weight ratio of prilocaine or a salt thereof, i.e., a mixture in which the weight ratio of lidocaine or a salt thereof to a prilocaine or a salt thereof is 5: 1 to 1.4: 1. It relates to an absorbent agent.

Ideal local anesthesia / analgesics should have no systemic toxicity at effective concentrations, rapid onset of action, and pharmacological action for a period of time. Local anesthesia / analgesics should also be water soluble, stable in solution, sterile, sterilized and effective and reversible in injection or mucosal applications. However, the synthesis of compounds having all the characteristics of an ideal local anesthetic / analgesic agent is very difficult and has disadvantages in at least one part. Therefore, it is necessary to appropriately select effective local anesthetic / analgesic agents required for a specific situation and to apply them effectively and safely.

Local anesthesia / analgesic agents inhibit intracellular migration of sodium ions when shock is conducted to nerves, thereby elevating the electrical excitability threshold, inhibiting the generation of action potentials, delaying the conduction of shocks, and completely blocking conduction when drug concentrations are increased. Local anesthesia / analgesics block the instantaneous explosive increase of sodium ion due to the potential change and decrease the increase in potassium ion conduction, but the effect on sodium ion is much greater and delayed repolarization rather than blocking nerve conduction To extend.

High concentrations of local anesthetics / analgesics affect the central nervous system and the cardiovascular system. Symptoms of the central nervous system appear before cardiovascular disorders, such as instability, tremor, tinnitus and tremors, seizures at high concentrations, respiratory depression and lethargy. Cardiotoxicity mainly refers to the suppression of the electrocardiogram (ventricular block, intraventricular block) and systemic vascular relaxation, resulting in severe hypotension and heart attack. Other allergic reactions occur in procaine, and local anesthetic / analgesics of amides usually have no allergic symptoms.

Lidocaine or prilocaine, which is a local anesthetic / analgesia of amides, is widely used in clinical practice. Currently, injection and cream are commercially available as pharmaceutical preparations for the application of local anesthetic / analgesic in clinical practice. In the case of injections, however, the needle must penetrate the skin to deliver the drug to the target site, which can cause pain in another patient, which can reduce patient compliance and must be administered with the help of a healthcare professional. There was an inconvenience to receive. On the other hand, in the case of creams, it is not easy to control the exact dose, and even if the correct dose is initially administered, it is not easy to maintain the exact dose because it is easily removed by a collar or sweat. In recent years, cataplasma preparations containing lidocaine have been commercialized, but due to the low skin permeability of lidocaine, the total area of the preparation is about 140 cm 2, which reduces the patient's compliance and inadequate handling of lidocaine at 700 mg. May have serious side effects.

US Pat. Nos. 4,529,601 and 4,520,60 disclose the use of eutectic mixtures of lidocaine and prilocaine as local anesthetics. The patent discloses that the weight ratio of prilocaine and lidocaine is significantly effective when compared to the respective emulsions and placebo emulsions when the eutectic mixtures of 42:58 to 80:20 are applied topically in the form of emulsions. However, when the eutectic mixture as disclosed in the patent is applied to a transdermal absorption preparation, the expression of side effects due to prylocine cannot be avoided. That is, when preparing the eutectic mixture based on the weight ratio of the prilocaine and lidocaine disclosed in the patent, the ratio of the prilocaine than the lidocaine had to be prepared or higher. However, it is known that prilocaine cannot be used in large doses because of adverse reactions called methemoglobinaemia at adult doses of 8 mg / kg or more.

The present inventors have conducted various studies to develop a complex transdermal absorption preparation of lidocaine and prilocaine, and in particular, the skin permeability of lidocaine can be increased in the same transdermal absorption formulation, while the skin permeability of prilocaine is reduced to an appropriate level and excellent. Various studies have been conducted to develop transdermal absorbents with safety. Surprisingly, the present inventors have found that percutaneous absorption preparations containing lidocaine and prilocaine in a specific ratio range, in particular percutaneous absorption preparations containing a mixture of lidocaine and prilocaine in a specific ratio range, have a skin permeability of prilocaine. It was found that not only can the side effects caused by prilocaine be minimized by appropriate control, but also the skin permeability of lidocaine can be significantly increased.

Accordingly, an object of the present invention is to provide a transdermal absorption preparation capable of ensuring excellent safety by controlling the skin permeability of lidocaine and prilocaine in duplicate.

According to one aspect of the invention, a transdermal absorbent comprising a mixture in which the weight ratio of lidocaine or a salt thereof to a prilocaine or a salt thereof is 5: 1 to 1.4: 1, preferably a mixture of 4: 1 to 3: 1 I am provided.

In one embodiment, the transdermal absorbent preparation according to the present invention comprises an eutectic mixture of lidocaine or a salt thereof with prilocaine or a salt thereof. Specifically, the transdermal absorption preparations of the present invention comprise (a) a eutectic mixture of lidocaine or a salt thereof with prilocaine or a salt thereof; (b) a water-soluble polymer selected from the group consisting of polyacrylic acid or a salt thereof, methyl cellulose, carboxymethyl cellulose, polyvinylpyrrolidone, and polyvinyl alcohol; And (c) a drug-containing matrix layer comprising at least one polyhydric alcohol selected from the group consisting of polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerol, and sorbitol.

In another embodiment, transdermal absorption preparations according to the present invention comprise (i) lidocaine or a salt thereof and prilocaine or a salt thereof; And (ii) at least one selected from the group consisting of an acrylic pressure sensitive adhesive, a styrene-isoprene-styrene copolymer, a styrene-butadiene-styrene copolymer, a polyisobutylene, silicone, and an acrylic-rubber hybrid adhesive It may comprise a drug-containing matrix layer comprising an adhesive. The percutaneous absorption preparations, if necessary, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene alkyl ether, oleic acid, isopropyl myristate, polyglyceryl fatty acid ester, oleyl polyoxyl-6 glyceride, Lauryl polyoxyl-6 glyceride, triglyceride, polyethylene glycol fatty acid ester, propylene glycol fatty acid ester; It may further comprise an absorption enhancer selected from the group consisting of oleyl alcohol, polyethylene glycol fatty acid alcohol ether, sugar esters, terpenes, diethylene glycol monoethyl ether, propylene glycol, and glycerin.

When formulated as a transdermal absorbent using a mixture of lidocaine or a salt thereof and prilocaine or a salt thereof in a specific range of weight ratios, the skin permeability of lidocaine is significantly increased while the skin permeability of prilocaine is moderately increased. It has been found by the present invention that the present invention can be suppressed and the side effects of overdose of prilocaine can be prevented. Therefore, the transdermal absorption preparation according to the present invention can be usefully used to effectively alleviate the pain of patients suffering from shingles or postherpetic neuralgia.

1 and 2 are the results of evaluating the skin permeability with time in the hairless mouse for a transdermal absorbent preparation prepared according to the present invention and a eutectic mixture of lidocaine: prilocaine = 1: 1. 1 is a result of measuring the skin permeability of lidocaine, Figure 2 is a result of measuring the skin permeability of prilocaine.

The present invention provides a transdermal absorption preparation comprising a mixture of lidocaine or a salt thereof and a prilocaine or a salt thereof in a weight ratio of 5: 1 to 1.4: 1, preferably a mixture of 4: 1 to 3: 1.

In the transdermal absorbent according to the present invention, lidocaine or a salt thereof and prilocaine or a salt thereof can be used in therapeutically effective amounts, and are not particularly limited. In one embodiment, transdermal absorbents according to the present invention may contain from about 40 mg to about 65 mg of lidocaine or salt thereof per unit formulation and from about 20 mg to about 35 mg of prilocaine or salt thereof Although it can be carried out, if the weight ratio of lidocaine or its salt and prilocaine or its salt is in the above-mentioned range, it will not specifically limit.

In one embodiment, the transdermal absorbent preparation according to the present invention comprises an eutectic mixture of lidocaine or a salt thereof with prilocaine or a salt thereof. Specifically, the transdermal absorption preparations of the present invention comprise (a) a eutectic mixture of lidocaine or a salt thereof with prilocaine or a salt thereof; (b) a water-soluble polymer selected from the group consisting of polyacrylic acid or a salt thereof, methyl cellulose, carboxymethyl cellulose, polyvinylpyrrolidone, and polyvinyl alcohol; And (c) a drug-containing matrix layer comprising at least one polyhydric alcohol selected from the group consisting of polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerol, and sorbitol. The transdermal absorbent may be composed of a support layer, a drug-containing matrix layer, and a release layer.

The content of the eutectic mixture of lidocaine or a salt thereof with prilocaine or a salt thereof is 0.1 to 20% by weight, preferably 0.5 to 15% by weight, more preferably 1 to 10, based on the total weight of the drug-containing matrix layer. It may range in weight. The content of the water-soluble polymer serving as a gelling agent and a pressure-sensitive adhesive in the transdermal absorption agent is 1 to 30% by weight, preferably 3 to 25% by weight, more preferably 5 to 20% based on the total weight of the drug-containing matrix layer. It may range from weight percent. As described above, the drug-containing matrix layer including the water-soluble polymer is in the form of a hydrogel preparation (dry preparation) containing a small amount of solvent (for example, ethanol, water, etc.) after drying, and thus the water-soluble matrix layer. The weight of the polymer is based on a hydrogel dry formulation comprising a small amount of solvent. In addition, the content of the polyhydric alcohol which acts as an absorption enhancer and a moisturizing agent is 5 to 60% by weight, preferably 10 to the total weight of the drug-containing matrix layer (ie, the drug-containing matrix layer in the form of a hydrogel dry preparation). To 55% by weight, more preferably 20 to 50% by weight.

In another embodiment, transdermal absorption preparations according to the present invention comprise (i) lidocaine or a salt thereof and prilocaine or a salt thereof; And (ii) acrylic pressure sensitive adhesives [eg, Durotech 87-2510 ^™ (Durotak 87-2510 ^™ ), Durotech 87-2979 ^™ (Durotak 87-2979 ^™ ), Durotech 87-9301 ^™ (Durotak 87-9301) ^TM ), etc., styrene-isoprene-styrene copolymer, styrene-butadiene-styrene copolymer, polyisobutylene, silicone, and acrylic-rubber hybrid adhesive [for example, Durotech 87-502A ^TM ( Durotak 87-502A ^TM ), etc.] may comprise a drug-containing matrix layer comprising at least one pressure-sensitive adhesive. The transdermal absorbent may be composed of a support layer, a drug-containing matrix layer, and a release layer. Transdermal absorption preparations according to this embodiment are 0.1 to 20% by weight, preferably 0.5 to 15% by weight, more preferably 0.5 to 15% by weight, based on the total weight of the drug-containing matrix layer of the active ingredient, i.e. lidocaine or salt thereof and prilocaine or salt thereof. Preferably it may be contained in the range of 1 to 10 weight, the weight ratio of lidocaine or salt thereof and prilocaine or salt thereof is as described above. The content of the pressure-sensitive adhesive may be in the range of 60 to 99.5% by weight, preferably 70 to 95% by weight, more preferably 75 to 90% by weight, based on the total weight of the drug-containing matrix layer. In addition, the transdermal absorbent preparation according to the present embodiment may further include an absorption enhancer including a nonionic surfactant.

The absorption enhancing agent is a sorbitan fatty acid ester [for example, Span ^TM (Span ^TM), etc.], polyoxyethylene sorbitan fatty acid esters [e.g., Tween ^TM (Tween ^TM), etc.], polyoxyethylene alkyl ethers [for example, example, the bridge ^TM (Brij ^TM), etc.], oleic acid, isopropyl myristate, polyglyceryl fatty acid esters [for example, polyglyceryl -6 diol LES benzoate, etc.], oleyl polyoxyl -6 glycerides, La Usyl polyoxyl-6 glycerides, triglycerides (eg caprylic / capric triglycerides, etc.), polyethylene glycol fatty acid esters, propylene glycol fatty acid esters [eg propylene glycol monolaurate, etc.], fats Alcohols, polyethylene glycol fatty acid alcohol ethers, sugar esters, terpenes, diethylene glycol monoethyl ether, propylene glycol, It may be at least one selected from the group consisting of glycerin. The content of the absorption enhancer may be in the range of 5 to 10% by weight based on the total weight of the drug-containing matrix layer, but is not limited thereto.

Transdermal absorption preparations according to the present invention may be composed of a support layer, a drug-containing matrix layer, and a release layer. The transdermal absorbent preparation of the present invention composed of the support layer, the drug-containing matrix layer, and the release layer can be prepared by forming the above-described drug-containing matrix layer on the release layer and again forming the support layer thereon. The release layer may be a release liner or a laminate thereof commonly used in the field of transdermal absorbents, for example, polyethylene, polyester, polyvinyl chloride, polyvinylidene coated with silicone resin or fluorine resin. Films such as chloride, paper or laminates thereof can be used. In addition, the support layer (also referred to as a backing membrane) can also be used a drug-non-absorbing and flexible material commonly used in the field of transdermal absorbents, for example, polyolefin, polyether ( polyether, multi-layer ethylene vinyl acetate film, polyester, polyurethane and the like can be used.

Hereinafter, the present invention will be described in more detail with reference to specific examples. However, these examples are for illustrating the present invention, and the present invention is not limited to these examples.

Example 1-7. Eutectic Containing mixture Percutaneous Absorption

To prepare a transdermal absorbent formulation containing a eutectic mixture of lidocaine and prilocaine according to the ingredients and contents of Table 1 below. That is, lidocaine hydrochloride and prilocaine hydrochloride were mixed, and then heated to 32 ° C. to melt to prepare a eutectic mixture of lidocaine and prilocaine. Separately, polyacrylic acid and polyvinyl alcohol were added to a mixed solvent of ethanol and purified water, mixed at 80 ° C. for about 25 minutes, and glycerin and propylene glycol were added for 12 hours at 37 ° C. to prepare a tacky gel. . The eutectic mixture prepared above was added to the prepared tacky gel, mixed for 2 hours, coated on a release paper, dried in air for 40 minutes, and covered with a protective layer to prepare a transdermal absorbent.

ingredient Example (weight, g) One 2 3 4 5 6 7 Lidocaine Hydrochloride 0.048 0.053 0.057 0.06 0.062 0.064 0.06 Prilocaine Hydrochloride 0.032 0.027 0.023 0.02 0.018 0.016 0.02 Polyvinyl alcohol 0.145 0.145 0.145 0.145 0.145 0.145 0.145 Polyacrylic acid 0.029 0.029 0.029 0.029 0.029 0.029 0.029 Propylene glycol 0.15 0.15 0.15 0.15 0.15 0.15 0.15 glycerin 0.438 0.438 0.438 0.438 0.438 0.438 0.438 Purified water 0.868 0.868 0.868 0.868 0.868 0.868 0.868 ethanol 1.37 1.37 1.37 1.37 1.37 1.37 1.37 Formulation Thickness (μm) ^* 160 160 160 160 160 160 225

* Formulation thickness (μm): thickness of drug-containing matrix layer when dried in air for 40 minutes as described above

Example 8-10. Lidocaine Prilocaine Through melting Percutaneous Absorption

Lidocaine and prilocaine were dissolved using an organic solvent according to the ingredients and contents shown in Table 2 below, and then formulated into a transdermal absorbent. That is, after dissolving the lidocaine free base and the prilocaine free base in ethyl acetate, an absorption enhancer (span 80 ^TM or oleyl alcohol) and a pressure-sensitive adhesive [Durotec 87-2510 ^TM , Durotec 87-2287 ^™ , or Durotech 87-502A ^™ ] was added to the solution, mixed, applied onto a release paper, dried in air for 10 minutes, and further dried at 80 ° C. for 20 minutes. A transdermal absorption preparation was prepared by covering the dried matrix layer with a protective layer.

ingredient Example (weight, g) Ingredients function 8 9 10 Lidocaine Active ingredient 0.06 0.06 0.06 Prilocaine Active ingredient 0.02 0.02 0.02 Duro Tek 87-2510 ^TM Pressure Sensitive Adhesive ^* 0.75 Durotech 87-2287 ^TM Pressure Sensitive Adhesive ^* 0.75 Duro TEX ^TM 87-502A Pressure Sensitive Adhesive ^* 0.75 Span 80 ^TM Absorption enhancer 0.07 Oleyl alcohol Absorption enhancer 0.07 0.07 Ethyl acetate menstruum 2.6 2.6 2.6 Formulation Thickness (μm) ** 120 120 120

* However, the weight of a pressure-sensitive adhesive shows the weight of solid content.

** Formulation Thickness (μm): As described above, the thickness of the drug-containing matrix layer when dried for 20 minutes

Comparative Example 1. Commercially available formulations ( Lidocaine Alone)

A commercially available lidocaine transdermal absorbent "Lidoderm" (Endo laboratories, USA) was used.

Comparative Example 2. Lidocaine Prilocaine Weight ratio of 1: 1 Eutectic Percutaneous Absorbents Including Mixtures

A transdermal absorption preparation was prepared using a eutectic mixture of lidocaine and prilocaine in a weight ratio of 1: 1. That is, the percutaneous absorption preparations were prepared according to the same ingredients and contents as in Example 6, except that 0.04 g each of lidocaine and prilocaine was used.

Test Example 1. Skin Permeability Measurement

The skin permeability of the transdermal absorption preparations prepared in Examples 1 to 6 was evaluated by applying to the hairless mouse skin. Specifically, the skin of a hairless mouse (6 to 8 weeks old) was extracted immediately before the experiment, and the percutaneous absorbent preparations of Examples 1 to 5 were cut into a circle of 3 cm ² and attached to the skin, followed by a flow-through diffusion device (Flow -Clamped in Through Diffusion Cell), the isotonic phosphate buffer solution (pH 6.0) was added to the receptor and maintained at 37 ° C. The samples were taken at intervals of 4 hours with constant stirring with a magnetic stirrer and analyzed in Table 3 below. The conditions were quantified using high performance liquid chromatography. The results are shown in Table 4 below.

Analysis condition Analysis column C18 (Gemini, 10 cm, 5 μm) Mobile phase Acetonitrile / 10 mM phosphate buffer (pH 5.5) = 25/75, v / v Flow rate 1 ml / min Analysis wavelength 230 nm Temperature 30 ℃

Lidocaine Permeation (μg / cm ² / 24h) Prilocaine Permeation (μg / cm ² / 24h) Example 1 310 116 Example 2 344 100 Example 3 362 90 Example 4 396 70 Example 5 416 66 Example 6 454 61

From the results of Table 4, the transdermal absorption preparation according to the present invention shows excellent skin permeability, in particular, it can be seen that the overall flux increases as the ratio of lidocaine increases.

Test Example 2. Skin Permeability Comparison (1)

The skin permeability was evaluated in the same manner as in Test Example 1 for the transdermal absorption preparation of Example 7 and the commercial preparation of Comparative Example 1, and the results are shown in Table 5 below.

Example 7 Comparative Example 1 Formulation Thickness (μm) 225 900 Lidocaine content per unit area (mg / cm ² ) 1.05 4.05 Lidocaine permeation per unit area (㎍ / cm ² / 24h) 518 489

From the results in Table 5, it can be seen that the skin permeability of the transdermal absorbent of Example 7, which contains a relatively much smaller amount of the drug, than the transdermal absorbent of Comparative Example 1. Therefore, the transdermal absorption preparation according to the present invention can achieve excellent skin permeability of lidocaine.

Test Example 3. Skin Permeability Comparison (2)

The skin permeability was evaluated in the same manner as in Test Example 1 for the transdermal absorbent preparation of Example 6 and the transdermal absorbent preparation of Comparative Example 2, and the results are shown in FIGS. 1 and 2. 1 is a result of measuring the skin permeability of lidocaine, Figure 2 is a result of measuring the skin permeability of prilocaine.

As can be seen from the results of FIG. 1 and FIG. 2, in the case of lidocaine, the skin permeability of the transdermal absorbent preparation (Example 6) of the present invention was much higher than that of the transdermal absorbent preparation of Comparative Example 2, and in the case of prilocaine In the transdermal absorption formulation (Example 6) of the present invention, the skin permeability was much lower than that of Comparative Example 2. Therefore, when the lidocaine and the prilocaine are mixed in a specific ratio and formulated as a transdermal absorbent, the skin permeability of lidocaine is remarkably increased, while the skin permeability of the prilocaine can be suppressed to an appropriate level. The side effects of administration can be prevented.

Test Example 4. Stability Evaluation

The transdermal absorbent preparation prepared in Example 4 was stored for 1 month, 2 months and 3 months at 40 ° C./75% relative humidity, and the drug content change was measured. The results are shown in Table 6 below.

Storage period Lidocaine (wt%) Prilocaine (% by weight) 1 month 101.41 ± 2.47 97.67 ± 2.38 2 months 96.84 ± 5.65 97.71 ± 5.36 3 months 101.12 ± 8.25 96.53 ± 7.54

From the results of Table 6, the transdermal absorption preparation according to the present invention does not show a significant drug content change for three months, it can be seen that it has excellent stability.

Claims

A transdermal absorption preparation comprising a mixture of lidocaine or a salt thereof and a prilocaine or a salt thereof in a weight ratio of 5: 1 to 1.4: 1.

The transdermal absorption preparation according to claim 1, wherein the weight ratio of lidocaine or a salt thereof to prilocaine or a salt thereof is 4: 1 to 3: 1.

The transdermal absorption preparation according to claim 1 or 2, wherein the mixture is an eutectic mixture of lidocaine or a salt thereof and prilocaine or a salt thereof.

4. The method of claim 3, further comprising: (a) a eutectic mixture of lidocaine or a salt thereof with prilocaine or a salt thereof; (b) a water-soluble polymer selected from the group consisting of polyacrylic acid or a salt thereof, methyl cellulose, carboxymethyl cellulose, polyvinylpyrrolidone, and polyvinyl alcohol; And (c) a drug-containing matrix layer comprising a polyhydric alcohol selected from the group consisting of polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerol, and sorbitol.

The percutaneous absorption preparation according to claim 4, wherein the percutaneous absorption preparation consists of a support layer, a drug-containing matrix layer, and a release layer.

The transdermal absorption preparation according to claim 4, wherein the content of the eutectic mixture of lidocaine or a salt thereof and prylocine or a salt thereof is 0.1 to 20% by weight based on the total weight of the drug-containing matrix layer.

The transdermal absorption preparation according to claim 4, wherein the content of the water-soluble polymer is 1 to 30% by weight based on the total weight of the drug-containing matrix layer.

The transdermal absorption preparation according to claim 4, wherein the content of the polyhydric alcohol is 5 to 60% by weight based on the total weight of the drug-containing matrix layer.

The method of claim 1 or 2, comprising: (i) lidocaine or a salt thereof and prilocaine or a salt thereof; And (ii) at least one selected from the group consisting of an acrylic pressure sensitive adhesive, a styrene-isoprene-styrene copolymer, a styrene-butadiene-styrene copolymer, a polyisobutylene, silicone, and an acrylic-rubber hybrid adhesive A transdermal absorption preparation comprising a drug-containing matrix layer comprising an adhesive.

The transdermal absorption preparation according to claim 9, wherein the transdermal absorption preparation consists of a support layer, a drug-containing matrix layer, and a release layer.

The transdermal absorbent preparation according to claim 9, wherein the pressure-sensitive adhesive is 60 to 99.5 wt% based on the total weight of the drug-containing matrix layer.

10. The sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene alkyl ether, oleic acid, isopropyl myristate, polyglyceryl fatty acid ester, oleyl polyoxyl-6 glyceride, lauryl poly Oxyl-6 glyceride, triglyceride, polyethylene glycol fatty acid ester, propylene glycol fatty acid ester, oleyl alcohol, fatty alcohols, polyethylene glycol fatty acid alcohol ether, sugar ester, terpenes, diethylene glycol monoethyl A transdermal absorption preparation further comprising an absorption enhancer selected from the group consisting of ether, propylene glycol, and glycerin.

The transdermal absorption preparation according to claim 12, wherein the content of the absorption enhancer is 5 to 10% by weight based on the total weight of the drug-containing matrix layer.