JP5619363B2 - Transdermal absorption enhancer, skin treatment preparation containing the same, and transdermal absorption preparation - Google Patents

Description

  The present invention relates to a transdermal absorption enhancer, and more particularly to a transdermal absorption enhancer comprising triglyceride in which at least one fatty acid is a higher fatty acid having 14 or more carbon atoms. The present invention also relates to a skin treatment preparation and a transdermal absorption preparation containing the transdermal absorption enhancer.

  Since transdermal administration of a drug can absorb the drug directly from the capillaries on the skin surface, the first-pass effect in the liver can be avoided. Further, since transdermal administration releases a drug continuously, side effects due to absorption of a large amount of drug in a short time can be reduced. For this reason, transdermal administration is one of the effective methods of drug administration.

  However, since the skin functions as a barrier to prevent the invasion of foreign substances from the outside, even if a drug is simply applied or pasted to the skin, a necessary and sufficient amount of the drug can be delivered into the body. Is difficult. Therefore, in general, a drug intended to promote skin permeation of a drug is mixed with the drug to exert the effect of the drug.

  Ethanol, crotamiton, medium chain fatty acid triglycerides and the like are known as substances having such a transdermal absorption promoting effect, but ethanol and crotamiton have problems such as skin irritation.

  Medium-chain fatty acid triglycerides are used in transdermal preparations because they have poor affinity with the components that make up the support and are not easily absorbed by the support, but are compatible with the adhesive component. .

  For example, Patent Document 1 discloses a medical percutaneous absorption tape preparation using a triglyceride of caprylic acid, which is a medium chain fatty acid having 8 carbon atoms, as a drug percutaneous absorption enhancer. Moreover, the external preparation which consists of C8-10 medium-chain fatty acid triglycerides, water, γ-aminobutyric acid and / or diisopropylamine dichloroacetate has the effect of promoting transdermal absorption of a carboxyl group-containing water-soluble compound. There is a report to the effect (see Patent Document 2).

  However, the percutaneous absorption promoting action by the medium chain fatty acid triglyceride described above is still not satisfactory.

  In addition, the skin to which the drug is administered transdermally varies depending on race, age, site, skin tissue condition, etc., and the transdermal absorbability of the drug may vary. Was not well controlled. Furthermore, there has been a conventional way of incorporating a transdermal absorption enhancer into a drug-containing transdermal preparation, but there was no concept of applying a transdermal absorption enhancer to the skin before the application of the drug.

WO2004 / 112760 pamphlet Japanese Patent Laid-Open No. 11-80029

  An object of the present invention is to provide a percutaneous absorption enhancer, a skin treatment preparation and a transdermal absorption preparation which promote the percutaneous absorption of a drug and are less irritating to the skin and excellent in safety. .

The inventors have paid attention to the fact that most of the fatty acids constituting triglycerides contained in human sebum components are higher fatty acids, and as a result of extensive research, they have obtained excellent transdermal absorption of unsaturated higher fatty acid triglycerides. The knowledge that it has a promoting action was obtained.

Further, from another viewpoint, by applying an unsaturated higher fatty acid triglyceride to the skin before the drug is applied and incorporating the triglyceride into the skin, the drug transdermal absorbability is improved, and the race, age, The present inventors have found that the drug transdermal absorbability of different skins can be controlled depending on the site / tissue state and the like, and have completed the present invention. Specifically, the present invention provides the following.

  The transdermal absorption enhancer of the present invention is characterized in that at least one fatty acid is a triglyceride which is a higher fatty acid having 14 or more carbon atoms.

The percutaneous absorption enhancer of the present invention, a higher fatty acid is an unsaturated fatty der Rukoto also features.

  In the transdermal absorption enhancer of the present invention, the unsaturated fatty acid is preferably oleic acid.

  The skin treatment preparation of the present invention contains the percutaneous absorption enhancer according to claim 1 and is used before applying the drug.

  In the preparation for skin treatment of the present invention, the dosage form is preferably a patch, solution, ointment, cream, lotion, aerosol or spray.

  A transdermal absorption preparation according to the present invention is characterized by containing the percutaneous absorption enhancer according to claim 1 and a drug.

  The transdermal absorption type patch of the present invention comprises a support and a layer containing the percutaneous absorption enhancer and the drug according to claim 1 formed on the support.

Since the transdermal absorption enhancer of the present invention comprises triglyceride, which is an unsaturated higher fatty acid having 14 or more carbon atoms, constituting at least one fatty acid component of human sebum, it has excellent drug transdermal absorbability and skin irritation. It is estimated that there are few and it is excellent also in safety.
Further, when the preparation for skin treatment of the present invention is used before drug application, it can transfer and contain triglyceride in the applied skin part, and then when the drug-containing transdermal preparation is applied, the drug is transdermally absorbed. Sexuality can be promoted.
Furthermore, since the transdermal preparation and transdermal patch of the present invention contain the transdermal absorption enhancer of the present invention and a drug, the triglyceride improves the skin permeability of the drug, It is presumed to promote transdermal absorption.

It is a microscope picture (upper stage A: magnification 150, lower stage B: magnification 800) which shows the keratinocyte lipid lamellar liquid crystal structure of human skin. It is a microscope picture (upper A: magnification 150, lower B: magnification 800) which shows the stratum corneum lipid lamellar liquid crystal structure of hairless rat skin. It is a HPTLC chromatogram (S: internal standard, A: human, B: hairless rat) showing the composition of skin surface lipids of hairless rats and human skin. It is a figure which shows the tulobuterol permeability | transmittance to the human skin from which the triglyceride was removed. It is a figure which shows the influence (cumulative permeability | transmittance) on the permeability | transmittance of tulobuterol by application | coating of a triglyceride in a hairless rat. It is a figure which shows the influence (permeation rate of a skin) on the permeability | transmittance of tulobuterol by application | coating of a triglyceride in a hairless rat.

  Hereinafter, the present invention will be described more specifically.

  The transdermal absorption enhancer of the present invention means a substance that enhances the drug permeability of the skin when applied to the skin, or enhances the absorbability by dissolving a crystalline drug or the like. The application of the transdermal absorption enhancer may be performed before or after the drug is applied, and can be appropriately selected depending on the properties such as solubility and stability of the drug to be applied. The transdermal absorption enhancer of the present invention can be applied to, for example, pharmaceuticals and cosmetics. Furthermore, the transdermal absorption enhancer of the present invention can also be applied to drug screening methods. That is, by evaluating the solubility of the drug in the percutaneous absorption enhancer of the present invention and / or the permeability of the drug to the skin to which the percutaneous absorption enhancer of the present invention is applied, the transdermal absorbability of the drug is evaluated. Since it can be evaluated, it is considered possible to screen for drugs using this.

The higher fatty acid of the present invention is not particularly limited as long as it has 14 or more carbon atoms, but preferably has 14 to 20 carbon atoms, and is particularly preferable in that a large amount of 16 to 18 carbon atoms is contained in human sebum components. Further, higher fatty acid is a perspective of the drug solubility or et unsaturated fatty acids.

The higher fatty acid of the present invention, O maleic acid, palmitoleic acid, palmitic acid, and linoleic acid are preferable, oleic acid having 18 carbon atoms are particularly preferable in terms of percutaneous absorption-promoting and safety. Since oleic acid is a main component constituting the sebum of human skin, it is considered to be particularly low in skin irritation and excellent in safety compared to other fatty acids.

  The triglyceride of the present invention contains at least one of the above-mentioned higher fatty acids and may be composed of the same type of higher fatty acid or different types. For example, triglyceride has a structure in which three fatty acids are ester-bonded to glycerin, but 1) oleic acid, 2) linoleic acid, and 3) palmitic acid may be bonded to glycerin. A structure in which oleic acid is bonded may be used.

  Further, at least one of the fatty acids bonded to glycerin may be a higher fatty acid, and both higher fatty acids and medium chain fatty acids (intermediate fatty acids) may be bonded to glycerin, but preferably three fatty acids. All are higher fatty acid triglycerides.

  The triglyceride of the present invention can be obtained by various production methods and is not particularly limited. For example, fats and oils originating from natural plants and animals, specifically, sasanqua oil, camellia oil, avocado oil, almond oil, olive oil, sesame oil, safflower oil, soybean oil, corn oil, rapeseed oil, permanent oil, It can be obtained from castor oil, cottonseed oil, peanut oil, palm oil, palm oil, cacao butter and other vegetable oils, mink oil, egg yolk oil, beef tallow, pork fat, etc. It can be separated and purified and used in the present invention. Moreover, it is also possible to use for this invention the chemical synthesis product obtained by ester-bonding a higher fatty acid and glycerol by a normal method.

  The preparation for skin treatment of the present invention means a product for treating the applied skin part into a state suitable for percutaneous absorption of the drug before applying the drug. The use time of the preparation for skin treatment is not particularly limited as long as it is before application of the drug, but is preferably about 12 hours before application of the drug and immediately before application. This is because it is presumed that the preparation for skin treatment stays on the applied skin part and the effect of promoting percutaneous absorption of the drug is obtained.

  The dosage form of the skin treatment preparation can be arbitrarily selected according to the purpose as long as it is a dosage form that can be easily applied to the skin. Examples include patches, liquids, ointments, creams, lotions, aerosols, sprays, and the like. The patch means all preparations to be applied to the skin, and includes tapes, poultices, plasters and the like.

  In addition to the transdermal absorption enhancer of the present invention, the skin treatment preparation of the present invention includes various components used in pharmaceuticals and cosmetics, that is, antiseptics, as long as the effects of the present invention are not impaired as necessary. An agent, an antioxidant, a pH adjuster, a chelating agent, a fragrance, a colorant and the like can be appropriately contained.

  The percutaneous absorption type preparation of the present invention is a percutaneous absorption type preparation containing the percutaneous absorption enhancer of the present invention, and the dosage form is not limited. For example, a patch, solution, ointment, cream, lotion Agents, aerosols, sprays, and the like. Among these, transdermal patches are preferable. The patch means all preparations to be applied to the skin, and includes tapes, poultices, plasters and the like. Further, the transdermally absorbable preparation of the present invention is not limited to those described in the general rules of preparation of the Japanese Pharmacopoeia.

  In addition to the transdermal absorption enhancer of the present invention, the percutaneous absorption preparation of the present invention includes active ingredients such as drugs and, if necessary, pharmaceuticals and cosmetics as long as the effects of the present invention are not impaired. Various components used, that is, preservatives, antioxidants, pH adjusters, chelating agents, fragrances, coloring agents, and the like can be appropriately contained.

  Examples of the form of the transdermal absorption patch of the present invention include those in which an adhesive layer in which the transdermal absorption accelerator of the present invention and a drug are mixed is formed on a support. This form is preferred in that it is presumed that triglycerides of higher fatty acids improve the skin permeability of the drug and promote the transdermal absorbability of the drug.

  As another form of the transdermal absorption patch of the present invention, there may be mentioned one in which the transdermal absorption promoter of the present invention and the drug form a concentration gradient in the adhesive layer on the support. This form is preferable in that it is presumed that the skin permeability of the drug can be controlled by adjusting the concentration of the percutaneous absorption enhancer in the part close to the skin, and thus the percutaneous absorption of the drug can be controlled.

  As another form of the transdermal absorption patch of the present invention, a pressure-sensitive adhesive layer containing a drug and a pressure-sensitive adhesive layer containing the transdermal absorption enhancer of the present invention are formed on a support. Things. For example, a release sheet or the like may be provided between the pressure-sensitive adhesive layer containing the drug and the pressure-sensitive adhesive layer containing the transdermal absorption enhancer of the present invention so that they do not contact each other. By providing a release sheet or the like, the layer containing the transdermal absorption enhancer of the present invention is in contact only with the skin surface and not with the layer containing the drug. Thus, the drug permeability of the skin is first increased, and then the layers are in contact with each other by removing the release sheet or the like between the drug-containing layer and the layer containing the transdermal absorption enhancer of the present invention. Therefore, since the drug gradually moves to a layer containing a higher fatty acid triglyceride, and the drug is dissolved by the higher fatty acid triglyceride, it is presumed that the absorbability to the skin is further increased, and thus this form is preferable. . In addition, this form is particularly preferable for a transdermal patch containing an unstable drug that decomposes by long-term contact with a higher fatty acid triglyceride.

  Here, the release sheet protects the pressure-sensitive adhesive layer containing the drug and / or the pressure-sensitive adhesive layer containing the transdermal absorption promoter of the present invention. The material is a material that can be easily removed from the adhesive layer containing the drug and / or the adhesive layer containing the percutaneous absorption enhancer of the present invention. Any material that is permeable can be used. Examples thereof include a single layer film selected from materials such as plastic films such as polyethylene, polyester, polyvinyl chloride, and polypropylene, and metal films, or a laminate of two or more materials. Those obtained by treating the surface of these films with silicon can also be used.

  The support of the present invention is more preferably a stretchable support, but it may be non-stretchable as long as it is flexible and can be used as long as it is a drug-impermeable material. Even if it is a support body of a structure, the support body of the structure where several raw materials were laminated | stacked may be sufficient. In the case of a single-layer structure support, plastic films such as polyethylene, polyester, polypropylene, polyvinyl chloride, polycarbonate, polyurethane, or metal films are preferably used, and the surface of the film should be siliconized. Is also possible. The support may be colorless and transparent, or may be white or skin-colored, and the white or skin-colored may be coated with a pigment on the surface of the support, It may be one in which a dye or a pigment is uniformly kneaded in the support. When using a support having a laminated structure, it is sufficient that at least one layer is a drug-impermeable film. Non-woven fabrics such as polyethylene, polyester, polyurethane, and polypropylene, woven fabrics, and knitted fabrics are used as the support film having a single layer structure. A laminated film obtained by laminating one or more materials selected from paper, metal film and the like can be used.

  The drug of the present invention is not particularly limited, and can be arbitrarily selected according to its therapeutic purpose. For example, steroid hormones, non-steroidal analgesic anti-inflammatory agents, tranquilizers, antihypertensive agents, ischemic heart Disease treatment, antihistamine, anti-asthma, anti-parkinsonian, cerebral circulation remedy, antiemetic, antidepressant, anti-dementia, Sjögren's syndrome, antiarrhythmic, anticoagulant, antigout, anti Fungal drugs, narcotic analgesics, beta blockers, β1 agonists, β2 agonists, antitumor drugs, diuretics, antithrombotics, local anesthetics, histamine H1 receptor antagonists, histamine H2 receptor antagonists, antiallergic drugs , Serotonin receptor antagonists, anti-high cholesterol drugs, smoking cessation aids, etc., which do not stay on the skin surface, penetrate subcutaneously or into the blood and have local effects Alternatively, any drug capable of transdermal absorption that exhibits systemic action can be used. These drugs can be used in combination of two or more drugs as required. Moreover, the compounding quantity of these drugs can be suitably set according to the kind of drug, drug efficacy, and administration purpose.

  In addition, the drug according to the present invention is preferably one that is dissolved or compatible with the percutaneous absorption enhancer of the present invention, and specifically, is a selective stimulant (β2 agonist) of the β2 receptor of the exchange nerve. Tulobuterol, isosorbide nitrate, lidocaine, a local anesthetic, and fervinac, indomethacin, ketoprofen, diclofenac sodium, non-steroidal analgesic anti-inflammatory agents.

  Furthermore, the drug according to the present invention may be a dissolution type preparation or a crystal type preparation, but the drug in the preparation is effective in that the effect of the percutaneous absorption enhancer of the present invention is remarkably exhibited. Is more preferably a crystalline preparation in which a part thereof is present in a crystalline form.

  EXAMPLES Hereinafter, although this invention is demonstrated in more detail according to an Example, it cannot be overemphasized that the scope of the present invention is not limited to these Examples. The skin permeability test method is as follows.

<Skin permeability test (1): Hairless rat and human isolated skin>
0.05 mol / L McIlvaine buffer (pH 7.4) is placed on the dermis side (reciever side) of the isolated skin attached to the vertical diffusion cell, and the tulobuterol-containing patch (product name: Hokunarin) is placed on the stratum corneum side (donor side). Tape, manufactured by Abbott Japan Co., Ltd., and a crystal-type preparation (drug is partially present in the preparation) was applied. After sampling 0.6 mL of the receiver solution at each time point, 0.05 mol / L McIlvine buffer (pH 7.4) was added in the same amount. The drug concentration in the sampling solution was measured by HPLC, and the steady state skin permeation rate was calculated from the cumulative permeation amount and the slope portion of the time curve. The sampling time was 2, 4, 6, 8, 10, 12, and 24 hours, the temperature was constant at 32 ° C., and the number of repetitions was 6-12.

<Skin permeability test (2): Hairless rat>
0.05 mol / L McIlvine buffer (pH 7.4) was placed on the dermis side (receiver side) of the isolated skin attached to the vertical diffusion cell, and the drug-containing patch was applied to the stratum corneum side (donor side). The drugs include lidocaine (product name: Penless Tape, manufactured by Nitto Denko Corporation), isosorbide nitrate (product name: Nitras Tape, manufactured by Daikyo Pharmaceutical Co., Ltd.), ketoprofen (product name: Moras Tape, manufactured by Hisamitsu Pharmaceutical Co., Ltd.), diclofenac Sodium (see Production Method 1) was used. After sampling 0.6 mL of the receiver solution at each time point, 0.05 mol / L McIlvine buffer (pH 7.4) was added in the same amount. The drug concentration in the sampling solution was measured by HPLC, and the cumulative permeation amount was calculated. The sampling time was 3, 6 and 9 hours, the temperature was constant at 32 ° C., and the number of repetitions was 6-12.

[Production Example 1]
In a Henschel mixer (registered trademark), liquid paraffin, rosin ester resin (trade name: KE-100, manufactured by Arakawa Chemical Industries), dibutylhydroxytoluene, hydrogenated oil (K-3 wax 200, manufactured by Kawaken Fine Chemical Co., Ltd.) In addition, the mixture was stirred. A styrene-isoprene-styrene block copolymer (D-KX401CS, manufactured by Kraton Polymer Japan) is added to the obtained mixture, and 1-menthol, N-methyl-2-pyrrolidone, diclofenac sodium, and citric acid are further added. The paste was prepared by mixing and stirring. The prepared plaster was spread on a support (100 g / m ² basis weight knitted fabric (made of polyester)), and a patch was prepared by laminating a release liner film on the plaster. The recipe is shown in Table 1.

[Test 1]
The human isolated skin surface was peeled off with a tape, and observed with a microscope (KEYENCE digital HF microscope VH-8000). The results are shown in FIG. 1 (A: magnification 150, B: magnification 800).

[Test 2]
In the same manner as in Test 1, the hairless rat-extracted skin surface was observed with a microscope. The results are shown in FIG.

  In human skin, there was a lamellar liquid crystal structure part and a white lump in part, and a state covering the lamellar liquid crystal structure was observed, whereas in hairless rat skin, the lamellar liquid crystal structure of intercellular lipids was It was observed relatively uniformly. From this, it became clear that there is a difference in the surface condition of the skin between humans and hairless rats.

[Test 3]
Skin surface lipids were extracted from the surface of human isolated skin with chloroform / methanol (2: 1), developed by HPTLC, and the composition was examined. The result is shown in FIG.

[Test 4]
In the same manner as in Test 3, the skin surface lipid composition of hairless rats was examined. The result is shown in FIG.

  Humans characteristically contain oleic acid triglyceride, the main component of sebum derived from sebaceous glands, whereas hairless rats characteristically contain cholesterol esters, which differ in the composition of skin surface lipids. It was recognized that there was. Since sebum is known to exist as a sebum film on the skin surface, the white mass (FIG. 2) observed on the human isolated skin surface was considered to be oleic acid triglyceride.

[Test 5]
After wiping the surface of the human isolated skin with chloroform, the surface of the human isolated skin was peeled off with a tape and observed with a microscope. A decrease in white mass covering the structure was confirmed. Moreover, when the skin surface lipid was measured, triglyceride was selectively reduced. From this, it was considered that the white lump was mainly triglyceride.

[Test 6]
Skin permeability was evaluated using human isolated skin from which triglycerides were removed with chloroform. The test followed the method described in the skin permeability test (1). The result is shown in FIG. It was revealed that the skin permeability of tulobuterol was reduced in the skin from which triglycerides were removed.

[Comparative Example 1]
Using the skin of hairless rats, the skin permeability of tulobuterol was evaluated. The test followed the method described in the skin permeability test (1). FIG. 5 shows the change in the accumulated permeation amount, and FIG. 6 shows the skin permeation speed.

[Example 1]
Using the skin of hairless rats, the skin permeability of tulobuterol was evaluated. The test followed the method described in the skin permeability test (1). Oleic acid triglyceride (product number: T7140 (manufactured by Sigma)) as a skin treatment preparation was applied to the isolated skin of a hairless rat (10 mg per 4.52 cm ^{2 of the} extracted skin sample), and a tulobuterol-containing patch after about 10 minutes had elapsed. Applied. FIG. 5 shows the change in the accumulated permeation amount, and FIG. 6 shows the skin permeation speed.

  By applying oleic acid triglyceride before applying the tulobuterol-containing patch, the permeability of tulobuterol was improved by 2 times or more as compared with the case of not applying (Comparative Example 1) (Example 1).

[Comparative Example 2]
The skin permeability of lidocaine was evaluated using the isolated skin of hairless rats. The test followed the method described in the skin permeability test (2). Table 2 shows changes in the accumulated transmission amount.

[Comparative Example 3]
The skin permeability of isosorbide nitrate was evaluated using the skin of hairless rats. The same procedure as in Comparative Example 2 was performed except that isosorbide nitrate was used as the drug. Table 2 shows changes in the accumulated transmission amount.

[Comparative Example 4]
The skin permeability of ketoprofen was evaluated using isolated skin of hairless rats. The same procedure as in Comparative Example 2 was performed except that ketoprofen was used as the drug. Table 2 shows changes in the accumulated transmission amount.

[Comparative Example 5]
The skin permeability of diclofenac sodium was evaluated using the skin of hairless rats. The same procedure as in Comparative Example 2 was performed except that diclofenac sodium was used as the drug. Table 2 shows changes in the accumulated transmission amount.

[Example 2]
The skin permeability of lidocaine was evaluated using the isolated skin of hairless rats. The test followed the method described in the skin permeability test (2). As a preparation for skin treatment, oleic acid triglyceride (product number: T7140 (manufactured by Sigma)) was applied to the isolated skin of hairless rats (10 mg per 4.52 cm ^{2 of the} extracted skin sample), and about 10 minutes later, the lidocaine-containing patch Applied. Table 2 shows changes in the accumulated transmission amount.

[Example 3]
The skin permeability of isosorbide nitrate was evaluated using the skin of hairless rats. The same procedure as in Example 2 was performed except that isosorbide nitrate was used as the drug. Table 2 shows changes in the accumulated transmission amount.

[Example 4]
The skin permeability of ketoprofen was evaluated using isolated skin of hairless rats. The same procedure as in Example 2 was performed except that ketoprofen was used as the drug. Table 2 shows changes in the accumulated transmission amount.

[Example 5]
The skin permeability of diclofenac sodium was evaluated using the skin of hairless rats. The same procedure as in Example 2 was performed except that diclofenac sodium was used as the drug. Table 2 shows changes in the accumulated transmission amount.

  In any drug-containing patches, drug permeability was improved by applying oleic acid triglyceride as a liquid before application (Comparative Examples 2 to 5) compared to those not applied (Comparative Examples 2 to 5). .

[Example 6]
Using the skin of hairless rats, the skin permeability of tulobuterol (crystal form) was evaluated. The test followed the method described in the skin permeability test (1) except that the sampling time was 4, 8 and 12 hours. As a preparation for skin treatment, palmitoleic acid triglyceride (product number: T2630, manufactured by Sigma) was applied to the isolated skin of hairless rats (10 mg per 4.52 cm ^{2 of the} extracted skin sample), and the tulobuterol-containing patch was applied after about 10 minutes. Applied. Table 3 shows changes in the accumulated transmission amount.

  Before applying the tulobuterol-containing patch, the permeability of tulobuterol was improved by applying palmitoleic acid triglyceride (Example 6).

[Comparative Example 6]
Using the skin of hairless rats, the skin permeability of tulobuterol (crystal form) was evaluated. The test followed the method described in the skin permeability test (1) except that the sampling time was 4, 8 and 12 hours. Tri (caprylic acid / capric acid) glyceride (product number: Triester F810 (manufactured by Nikko Chemical Co., Ltd.)) was applied to the isolated skin of hairless rats (10 mg for 4.52 cm ^{2 of the} extracted skin sample) as a skin treatment preparation, The tulobuterol-containing patch was applied after about 10 minutes. Table 4 shows changes in the accumulated transmission amount.

  Before applying the tulobuterol-containing patch, the one applied with tri (caprylic acid / capric acid) glyceride (Comparative Example 6) showed the same cumulative permeation amount as the one not applied (Comparative Example 1). There was no improvement.

[Example 7]
After applying oleic acid triglyceride (product number: T7140 (manufactured by Sigma)) to the surface of the hairless rat's isolated skin (10 mg for 4.52 cm ^{2 of the} extracted skin sample), the surface of the hairless rat's isolated skin was peeled off with tape, When observed with a microscope, a white portion that was thought to be triglyceride was observed.

1 Squalane 2 Cholesterol ester 3 Oleic acid triglyceride 4 Fatty acid 5 Cholesterol / ceramide I
6 Ceramide II
7 Ceramide III
8 Ceramide VI
9 Cholesterol sulfate 10 Phospholipid

Claims (5)

  A skin treatment preparation comprising a transdermal absorption enhancer comprising a triglyceride, wherein at least one fatty acid is an unsaturated higher fatty acid having 14 or more carbon atoms, and is used before applying the drug.   The preparation for skin treatment according to claim 1, wherein the higher fatty acid is oleic acid.   The preparation for skin treatment according to claim 1 or 2, wherein the dosage form is a patch, solution, ointment, cream, lotion, aerosol or spray. A support, and a layer containing a transdermal absorption enhancer and a drug composed of a triglyceride, which is an unsaturated higher fatty acid having at least one fatty acid having 14 or more carbon atoms, formed on the support, Between the layer containing the drug and the layer containing the transdermal absorption enhancer, there is provided a release sheet that is removed after the layer containing the transdermal absorption enhancer contacts the skin . Skin-absorbing patch. The transdermal patch according to claim 4 , wherein the higher fatty acid is oleic acid.