WO2004108112A1

WO2004108112A1 - Pressure-sensitive adhesive composition for preparation for external use on skin and pressure-sensitive adhesive sheet preparation for external use on skin

Info

Publication number: WO2004108112A1
Application number: PCT/JP2004/008285
Authority: WO
Inventors: Akio Iwama; Yuzo Sumida
Original assignee: K & I Medical Research Ltd.; Sumita Nanotechnologies, Inc.
Priority date: 2003-06-09
Filing date: 2004-06-08
Publication date: 2004-12-16
Also published as: JPWO2004108112A1

Abstract

A pressure-sensitive adhesive composition for preparations for external use on the skin which gives a pressure-sensitive adhesive layer in which a drug to be percutaneously absorbed, in particular, a sparingly soluble, amphipathic, crystalline organic drug, e.g., a ceramide, can be stably dissolved into molecules and which is satisfactory in both of skin adhesion and strippability; a pressure-sensitive adhesive composition for preparations for external use on the skin which contains, dissolved therein, the drug to be percutaneously absorbed; and a pressure-sensitive adhesive sheet preparation for external use on the skin, e.g., a cosmetic or a medicine for external use on the skin, which comprises a substrate and the composition superposed thereon. The composition for preparations for external use on the skin is obtained from an intermediate composition comprising an acrylic copolymer (ingredient (A)) which is an acrylic polymer containing no crosslinkable functional group and contains 10-40 mol% vinyl monomer units having a cyclic lactam group, an acrylic polymer (ingredient (B)) having crosslinkable functional groups, and a nonionic surfactant (ingredient (C)) having an HLB of 0.5-9.5, by crosslinking the ingredient (B) with an external crosslinking agent, the amounts of the ingredients (B) and (C) being 20-50 parts by weight and 50-300 parts by weight, respectively, per 100 parts by weight of the ingredient (A). Also provided are: a pressure-sensitive adhesive composition which contains a drug to be percutaneously absorbed and is produced mainly from that composition; and a pressure-sensitive adhesive sheet preparation for external use on the skin.

Description

Description Adhesive composition for external preparation for skin and adhesive sheet for external preparation for skin

The present invention relates to a pressure-sensitive adhesive thread and a pressure-sensitive adhesive sheet for use in a skin external preparation such as a cosmetic external preparation and the like, and relates to a textile absorbent or difficult (hereinafter referred to as a drug together), especially ceramide. Oily gel-like adhesive for skin external preparations that can stably and molecularly dissolve (disperse molecules) even at a high concentration even if the fiber U and f The present invention relates to an exfoliated substance, an adhesive exfoliated substance for external preparations for skin in which the agent for absorption is dissolved, and a occupational sheet for external application obtained by applying the same to fiber. Background art

Ceramides serve as the ^^^ component of the interstitial lipid of the sulphate, which balances water in the skin to provide a healthy moisturizing function for the skin, a skin barrier function to protect the body from external stimuli and bacteria 'Fiber © ί¾λ. Let's play a very important role. Using the characteristics of such ceramides, it has been attempted to apply the I [im ³ skin external agents, and the like. However, ceramides, etc., which have strong parental abundance and are crystallized, have poor needle life against both water and oil, making their use difficult. Accompany.

Conventionally, in order to overcome such problems, ceramides have generally been dissolved in an oil phase component at a high temperature and emulsified. At that time, in order to increase the solubility of ceramides, fatty acids and higher alcohols that are liquid at room temperature have been used together. However, these methods are not enough to stably dissolve the ceramides in the drug product and can prevent the ceramides from crystallizing over time and depositing in the drug product. What Ceramides are mixed with amphiphilic substances such as cholesterols, higher fatty acids, higher alcohols, and lipophilic surfactants in the presence of a polyhydric alcohol and a small amount of a hydrophilic surfactant to form lamellar liquid crystals. Techniques have been proposed for forming a structure to facilitate the addition to the drug product and to prevent the precipitation of crystals over time (for example, see Japanese Patent Application Laid-Open Nos. 2001-039859 and 2001-348319). ). According to this method, ceramides can be easily incorporated into the preparation, and crystallization over time can be prevented.However, applicable preparations are limited to emulsification systems, and application to solubilization systems is difficult. Met.

In the application of ceramides to external preparations for skin, it is difficult for the ceramides to penetrate into the stratum corneum unless the molecules are sufficiently dissolved, but the above-mentioned micellar-lamellar type liquid crystal containing ceramides is formed. The conventional formulation method using the emulsification method had its limitations.

Among the external preparations for skin, the adhesive sheet preparation is a form of preparation that can cover the target site with the sheet and efficiently absorb the medicinal ingredients through the skin, but because it is effectively transferred and penetrated into the skin In addition, it is desirable that the medicinal components and the like are dissolved in the adhesive layer at the highest possible concentration.

In addition, since the adhesive sheet preparation for external use is applied to the skin surface, the adhesive layer has appropriate adhesiveness to the skin, but does not damage the keratinocytes of the skin when peeled off. In addition, sufficient cohesiveness is required so that no glue remains on the skin.

Regarding the development of such a pressure-sensitive adhesive sheet preparation for external application to the skin, which has an appropriate balance of skin adhesion and exfoliation / removal, an oil-based product containing a large amount of oily liquid components in a cross-linked acryl-based pressure-sensitive adhesive layer Gel-like adhesive layer preparations have been conventionally proposed (see, for example, ^ 2000-44904, and Kyohei 6-319793).

However, the balance of skin adhesion and exfoliation was improved in these preparations. Even if successful, it is difficult to say that the solubility of a drug such as a medicinal ingredient is particularly excellent.In particular, it is not possible to molecularly dissolve the effective amount of an amphiphilic and poorly soluble drug such as the ceramides described above. It was difficult. Disclosure of the invention

The present invention provides a stable and highly concentrated drug for percutaneous absorption, particularly an amphiphilic crystalline organic drug such as ceramides, which is hardly soluble in water or oil. Pressure sensitive adhesive composition for external preparations for skin, which is capable of dissolving molecules at the same time, and both of which are suitable for both skin adhesion and peeling and removing properties, and pressure sensitive adhesive compositions for external preparations for skin, in which the drug for transdermal absorption is dissolved It is an object of the present invention to provide a pressure-sensitive adhesive sheet preparation for use in external preparations such as cosmetics and external preparations for skin, such as cosmetics and external preparations, which are laminated on a base material.

As a result of various studies conducted by the present inventors, it has been found that acryl-based copolymers containing a predetermined amount of mol% of a lactam ring-containing monomer unit and having no crosslinkable functional group (AJ¾ and HLB) 5 to 9.5 (The viscous solution obtained by mixing a nonionic surface active agent (Cj5¾) with a specified Sftt has a strong amphipathic property and is extremely difficult to dissolve. It has been found that even ceramides, which are crystalline materials, are stable and can be dissolved in molecules at high concentrations in a stable manner. As a result, it is considered that the mutual solubility with non-ionic surfactants and amphiphilic substances such as ceramides is improved.

Acrylic fi-polymer (component A) containing a predetermined amount of the above-mentioned ratatam ^ and having no functional group capable of cross-linking reaction and HLB force SO.5 to 9.5 (non-ionic interface at ¾¾H) An acrylic polymer (component B) having a functional group capable of cross-linking reaction that is completely soluble in a mixed solution with an activator (component C) eliminates adhesive residue on the skin in the adhesive composition Necessary to adjust to moderate cohesion A predetermined amount is dissolved in a mixed solution of A ^^ / C j ^. By cross-linking this with an acryl-based polymer (B component) having a functional group capable of undergoing a cross-linking reaction by adding an external cross-linking agent, it is possible to obtain the above-mentioned pressure-sensitive adhesive composition for external preparation for skin. The present invention has been completed.

That is, the present invention relates to an acrylamide polymer containing 10 to 40 mol% of a vinyl monomer unit having a ratatum ring group and having no crosslinkable functional group (component A), The B component is cross-linked by an external cross-linking agent between ^ lf and a nonionic surfactant (C fi¾ ^) whose HLB is in the range of 0.5 to 9.5 © $. The adhesive composition for an external preparation for skin comprising: 100 to 100 parts by weight of the B component, 20 to 50 parts by weight (^ leakage, C, 50 to 30 Οβ And a pressure-sensitive adhesive composition for an external preparation for skin, wherein the pressure-sensitive adhesive composition is formulated in a range of parts.

In addition, the present invention provides a pressure-sensitive adhesive composition for a skin external preparation in which a percutaneous absorption drug including an amphiphilic and sparingly soluble crystalline organic drug such as ceramides is dissolved in the base of the pressure-sensitive adhesive composition. Offer things.

Further, the present invention provides a pressure-sensitive adhesive sheet preparation for external use on skin, wherein the pressure-sensitive adhesive composition for external use on skin is laminated on a substrate.

In the oily gel-like pressure-sensitive adhesive preparation of the present invention, an acrylic copolymer containing a predetermined amount of mol% of a rat monomer unit having a ratatum ring group and having no crosslinkable functional group as a main dissolving carrier. (Α¾) and

0.5 to 9.5 (^) Use of the on-active surfactant IJ (C ゝ) in a predetermined manner and use an acrylic polymer (B component) having a crosslinkable functional group. It is cross-linked with an external cross-linking agent using only a predetermined amount necessary to adjust the cohesiveness, and as a result, the transdermal drug, especially the ceramide which is incompatible with both 7 and oil Amphiphilic crystalline organic drugs such as liposomes can be dissolved in the adhesive layer stably and at high concentrations, and both skin adhesion and exfoliation can be removed. Pressure sensitive adhesive composition for external preparation for skin, and a pressure sensitive adhesive sheet preparation for external skin preparation in which the transdermal absorption agent is dissolved and a pressure sensitive adhesive sheet composition for skin externally prepared by laminating the composition on a substrate Can be obtained. BEST MODE FOR CARRYING OUT THE INVENTION

In the present invention, an important component for stably dissolving even hardly soluble amphiphilic crystalline organic drugs such as ceramides in rice fiber is a monomer unit having a lactam ring group. Containing 10 to 40 mono% and having no bridgeable functional group »Polymerized polymer (A) and HLB of 0.5-9.5 (^ nonionic surfactant (C j ^).

The Mβ¾¾ · to the M ^ of the present invention is an acryl-based polypoly containing 10 to 40 mono / ₀ biel monomer having a lactam ring group and having no functional group capable of performing a bridge reaction. It is.

Examples of the vinylinomers having lactam Λ¾ £ include those having at least ^ lactam 分子 in the molecule, such as Ν-vinylinole-2-pyrrolidone, Ν-vienole 2-piperidone, Ν-vinyl 2 ルー ε-force prolatatatam, and the like. Can use power S. Generally, only one of these vinyl monomers is used, but if necessary, two or more of them can be used as a mixture.

In the acryl polymerized polyvinyl monomer having a lactam (a ratio of 1

When TID of mono / ₀ is TID, the amphiphilic property of the ataryl copolymer becomes insufficient, the mutual solubility with nonionic surfactants and ceramides is reduced, and 40 mono / ₀ If the ratio exceeds the above, the acryl-based copolymer becomes difficult to dissolve in the polymerization solution using ethyl acetate or the like as a solvent, solidifies and precipitates, and the desired acryl-based copolymer cannot be obtained.

In the acryl-based copolymer of the present invention, an alkyl (meth) acrylate monomer copolymerized with a vinyl monomer having a For this purpose, it is preferable to use an alkyl group having 2 to 18 carbon atoms. For example, the alkyl group may be ethyl, methoxethyl, propyl, isopropyl, pentinole, isoptinole, pentizole, hexizole, hexinole, octinole, One or more types can be selected from those such as isooctynole, 2-ethynolehexynole, nor-norre, isono-norre, lauryl, stearyl and isostearyl.

In addition, the cryl copolymer is prepared by mixing and dissolving a predetermined amount of mole% of a lactam with a vinyl / nomer and an alkyl (meth) acrylate monomer, and then performing solution polymerization using an organic solvent such as ethyl acetate. It is preferable to manufacture by.

Of the main dig! Q ^ i HLB which is ^^ ^ ^ is the on-interface translation in the column 0.5 ~ 9.5 · <^.

Say! ^ On surface activity As long as U is in the range of 0.5 to 9.5 © | marriage, there is no particular limitation, but; ^^^ 1 Saturation with a long-chain alkyl group consisting of 0 to 18 Or mono- or poly-esters of unsaturated fatty acids and di- to poly-hydric alcohols, or mono- or poly-esters having a saturated or unsaturated long-chain alkyl group having 10 to 18 carbon atoms Alkyl glyceryl ethers and the like are preferably used.

Specifically, as an ester of a saturated or unsaturated fatty acid having an alkyl group having 10 to 18 carbon atoms and fffi V rechol, glycerol Λ ^ Έ nocapto, glycerol _t ^ nosteate, Ethyleneglycono 1 ^ nostearate, propyleneglycono I ^ nostearate, glycerononorreate, propylenedaricomononorreate, sorbitan monolaut, kalebitan monopalmiate, sorbitan monosteatoto, sodium Rubitan monooleate, sorbitan distearate, sonolebita schioleate, sorbitan tristearate, sorbitan trisoleate, etc.

Examples of the monoalkyl glyceryl ether of a vertical or unsaturated alkyl group having 0 to 18 carbon atoms include stearyl glyceryl ether and isoalkyl glyceryl ether. Stearyl glyceryl ether, 'Oleiruk,' Liserinoleetheno 1

In the main excavation, these HLBs are used in the range of 0.5 to 9.5 (one of the most important fields). For the purpose of adjustment, two or more kinds may be mixed and used.

When a nonionic surfactant having a ratio of 11 1 ^ 8 of 0.5 or less is used, ceramides and the like, which are amphiphilic and hardly soluble crystalline substances having strong hydrophilicity and lipophilicity, are used as molecules. However, when a nonionic surfactant with an HLB of 9.5 or more is used, the hydrophilicity is so strong that the hydrophilic lipophilic balance for molecular dispersion of ceramides etc. It is observed that ceramides and the like are hardly dissolved, and are also hardly dissolved in an acryl-based polymer (component B) having a crosslinkable functional group.

The component B used in the pressure-sensitive adhesive composition of the present invention is an acryl-based polymer having a functional group capable of performing a cross-linking reaction.

The type of the acrylic polymer is not particularly limited as long as it is a polymer obtained by copolymerizing or homopolymerizing an acryl-based monomer including a vinyl monomer having a functional group capable of performing a cross-linking reaction. Acrylic poly ^ "obtained by copolymerizing a vinyl monomer having a functional group such as a sulfoxyl group or a hydroxyl group, and a (meth) acryloalkyl ester having 1 to 14 carbon atoms in an alkyl group. It is preferable that

Alkyl 嶽 dake ~ 14 (Meth) acrino! ^ Alkyl esters (Meth) acrinomethyl, (Meth) atari «Ethyl, (Meth) Atalipropyl, (Meth) Aclinisopropyl, (Meth) atarizo 2-methoxyethyl, (Meth) acryl / butyl, (Meth) acrino! ^ Isoptyl, (Meth) acrino I ^ ntyl, (Meth) acrinohexyl, (Meth) acrinooctyl, (Meth) acrino Isooctyl, (Meth) Atarino] ^ 2-Ethylhexyl, (meth) atalino 1-noryl, (meth) acrino isonolyl, (meth) atari / lauryl, (meth) atalino stearyl, (meth) acrino isos One or a combination of two or more such as tearyl can be mentioned.

On the other hand, as a monomer having a crosslinkable functional group, for example, a (meth) acrino having a carboxyl group and a (meth) atali having a hydroxyl group メタ 2-hydroxyethino] ^) ^ You can power S to name the combination.

The amount of the vinyl monomer having a functional group capable of undergoing a cross-linking reaction depends on Βthe amount of the vinyl monomer when polymerizing to obtain the acryl-based polymer as a component (1 to 15

It is preferable to set the value in the range of Μ%. If the amount of such a monomer is less than 1% by weight, the crosslinking becomes insufficient and the cohesive force of the adhesive as a whole is insufficient, and when the adhesive is peeled off after being used as an adhesive sheet, adhesive residue on the skin, etc. Occurs. On the other hand, if the amount of such a monomer exceeds 15% by weight, skin irritation of the adhesive sheet may be increased.

An acryl-based polymer having a functional group capable of cross-linking reaction (component (1)), which is preferably produced by solution polymerization using an organic solvent such as ethyl acetate or the like, is easily cross-linked by an external cross-linking agent. The pressure-sensitive adhesive layer of the present invention has a necessary cohesive force.

The acrylic polymer having a functional group capable of cross-linking reaction (component (1)) contains a predetermined amount of a butyl monomer unit having a ratatum ring group and has no functional group capable of performing a ^^ bridge reaction. It is preferable to include at least one monomer component identical to the copolymer (component (I)). When both polymer components contain the same monomer component, the compatibility between both polymer components is remarkably improved, so that a place where ceramides and the like can be more stably dissolved can be provided.

Further, the acrylic copolymer having a ratatum ring group and having no functional group capable of cross-linking reaction (component (II)) and the acrylic polymer having a functional group capable of cross-linking reaction (component (II)) of the present invention are: The finally obtained adhesive for external preparation for skin In order to secure the cohesion of the agent, those having a number average molecular weight in the range of 300,000 to 1,500,000 are preferably used.

In the pressure-sensitive adhesive composition for external preparations for skin of the present invention, it is important for the effects of the present invention to achieve the following prescribed mixing ratio of components A to C.

That is, the blending amount of 100 parts by weight of an acryl-based copolymer (component A) containing 10 to 40 mono% of a butyl monomer unit having a lactam ring group and having no functional group capable of performing a ^^ bridge reaction. On the other hand, an acryl-based polymer having a functional group capable of cross-linking reaction (component B) is in the range of 20 to 50 parts by weight, and the HLB is in the range of 0.5 to 9.5. It is necessary to mix the agent (C) in the range of 50 to 300 Sft part.

If the blending amount of the acrylic polymer having a functional group capable of cross-linking reaction (component B) is less than 20 parts by weight based on 100 parts by weight of component A, the cohesive force of the adhesive for external preparation for skin becomes excessive. If it is too low, adhesive residue may be left on the skin.If it exceeds 50 parts by weight, the solubility of poorly soluble drugs such as ceramides as the whole adhesive composition for external preparations for the skin will be significantly reduced. . More preferably, the amount of the component B is in the range of 20 to 45 parts by weight based on 100 parts of the component A.

Further, in the present invention, the amount of the nonionic surfactant (Q （) in which ^ 11 ^ is in the range of 0.5 to 9.5 is determined by the amount of the component A If it is less than 50 parts by weight with respect to the O Ofi * part, the adhesive composition as a whole will reduce the rate of poorly soluble drugs such as ceramides * ^ 氐. In addition, if the content is 300S *, the cohesive force of the adhesive for ^^ lt ^ agent is excessively reduced, which may cause inconvenience such as the generation of adhesive residue on the skin. , 酉 Sf A component 100-βS part, 100-250 S * part (preferably a value within the box.

A sparingly soluble amphiphilic crystal that can be suitably dissolved in molecules by the adhesive composition base for external preparation for skin of the present invention composed of components A to C In addition to ceramides, the active organic drugs (drugs) include, for example, difedipine as a drug for treating hypertension, pravastatin as a drug for treating hyperlipidemia, azelastine deemedastine as a basic antiallergic drug, and as an analgesic. Buprenorphine morphine and the like.

Of course, in the present invention, a drug for transdermal absorption which is more soluble than these poorly soluble drugs can be more easily molecularly dissolved.

In the present invention, the amount of the transdermal absorption agent such as an amphiphilic and poorly soluble crystalline organic drug varies depending on the type of the agent and the use of the pressure-sensitive adhesive composition for an external preparation for skin. 0.1 to 30% by weight with respect to the total amount of the pressure-sensitive adhesive composition for use (^ preferably within a shelf, more preferably within 0.1 to 25 charge. Skin The content of the transdermal drug in the pressure-sensitive adhesive composition for external preparation is 0.1 times

If the amount is less than *%, the drug will migrate to the skin or? ^ It will be weaker and) m will be more volatile. This is because crystals tend to precipitate in the adhesive for external preparations, which may hinder the adhesion to the skin.

The ceramides that can be formed in the present invention are not particularly limited as long as they have a ceramide structure, and have one or more long-chain linear and / or branched alkyl or alkenyl groups in the molecule. A nonionic amphiphilic substance having at least two or more hydroxyl groups and at least one amide group and / or amino group, and / or a phosphatidylcholine residue or a sugar residue in the hydroxyl group of the nonionic amphiphilic substance. A series of ceramides in which groups are combined and expressed as derivatives.

Specific examples include ceramides such as sufingosine, phytosphingosine, and their male amides such as ceramide 1, ceramide 2, ceramide 3, ceramide 3A, ceramide 3B, ceramide 4, ceramide 5, ceramide 61, and ceramide 6 II. Also, sphingomyelin and phytosphingomyelin, which are phosphorous conductors of sphingosine and phytosphingosine ^ Sphingophospholipids or their glycosides, such as selegolipid sigands such as gangliosides, can be used. In addition, N- (hexoxyhydroxypropyl) -N-hydroshethylhexamide amide (Kao Ne: ^, trade name, Sofcare Ceramide SL-E), which has been simulated by lamid, may also be mentioned.

One of these ceramides may be used alone, or a second one may be used.

In the present invention, when ceramide is frequently picked up, its compounding amount is 0.1 to 15% by weight (within 7 marriages) based on the total amount of the adhesive composition for external preparation for skin. , 0.1 ~ 10M% (^ It is more preferable to set the inside power than S. If the content of ceramides is less than 0.1 «%, the transfer of ceramides to the skin and 弱 ^ weakening This is because ^ t ^ i¾ ^ ¾ is difficult to volatilize, and when it is 15 fi *%, ceramide tends to crystallize out in the adhesive for external preparations for the skin, which may hinder the adhesion to the skin. is there.

Further, in the present invention, various additives usually used for external preparations for skin can be added to the pressure-sensitive adhesive composition for external preparations for skin, if necessary.

For example, liquid oils such as myristi isopropyl, noremicil »tyl, oley, cinnamate, esters of saturated or unsaturated higher fatty acids; keratin softeners such as urea; NMF (natural moisturizing factor), glycerin, sorbitol Natural or synthetic moisturizing ingredients such as polyethylene glycol can be added. Other,? Detergents such as salon propyl, tocopherol, and nodroquinone; squalene, wax, triglyceride, cholesterol monole, cholesteryl ester, vitamins, and epidermal lipid component regulators such as vitamins and books; ultraviolet absorbers; concealing agents; Plasticizers; coloring agents; inorganic or organic fillers; extenders and the like can be added.

In addition, the compounding amount of these additives is hardly soluble in the adhesive composition for external preparation for skin. There is no particular limitation as long as the solubility of a transdermal drug such as a degradable crystalline organic drug and the adhesiveness of the composition are hardly deteriorated. Depending on the type of the drug and the type of the additive, it cannot be said unconditionally, but usually, the total amount is 100% by weight of the acrylic polymer (component A) having a lactate and having no functional group capable of cross-linking reaction. It is desirable to keep below.

In the present invention, an intermediate composition comprising the components A to C; or an intermediate composition further containing a transdermal absorption agent such as ceramides; and various additives added as necessary. An external cross-linking agent is added to each of the intermediate compositions. By cross-linking an acryl-based poly (component B) having a functional group capable of undergoing a cross-linking reaction with an external cross-linking agent, necessary cohesive properties can be imparted to the entire pressure-sensitive adhesive composition.

Examples of the external cross-linking agent include polyvalent epoxy compounds such as ethylenedalichol diglycidyl ether and tridaridyl isocyanurate; polyvalent isocyanates as adducts of tolylene diisocyanate and hexamethylene diisocyanate. Compounds (manufactured by Nippon Polyurethane Industry Co., Ltd .: Coronate L, Coronate HL, etc.), polyvalent aziridine compounds and the like can be suitably used. The external crosslinking agent is added in an amount of 1 to 20 parts by weight based on 100 parts by weight of the acrylic polymer (component B) having a functional group capable of undergoing a crosslinking reaction.

The method for producing the pressure-sensitive adhesive composition for external preparations for skin of the present invention is not particularly limited, but is, for example, based on the following StICi (1;) to (5).

According to such a removal, an acryl-based copolymer containing a predetermined amount of a bul monomer unit having a ratatum ring group and having no functional group capable of performing a bridge reaction.

(A component) and an acrylic polymer (B component) having a possible functional group, and HLB of 0.5 to 9.5 (^^-on surface activity ij (CJ5¾3) in marriage) A stable and high-concentration molecular dissolution of transdermal drugs, especially amphiphilic crystalline organic drugs (drugs) such as ceramides The obtained pressure-sensitive adhesive composition for external preparation for skin can be efficiently obtained.

(1) Acrylic copolymer having a number average molecular weight of 300,000 to 1,500,000 containing 10 to 40 mono V% of vinyl monomer units having a lactam ring group and having no functional group capable of performing a bridge reaction Preparation process of polymer (A component)?

(2) The process of preparing a latex of ^ m ^ 10,000 ~ 15,000 acryl-based polymer (component B) with ^ ability

(3) A solution of A component, B so that S component of S component is within the range of 50 to 300 parts by weight with respect to A component l O Ofift part. Step of converting the component solution and C component to

(4) Steps of adding percutaneous absorption agents such as ceramides and various additives as necessary:

(5) a step of adding an external cross-linking agent to the intermediate composition to cross-link the acryl-based polymer having a cross-linkable functional group

The step of preparing an acrylic polymer descendant in the steps (1) and (2) is preferably carried out by solution polymerization using an organic solvent such as ethyl acetate as described above. The presence of such an organic solvent throughout the entire manufacturing process of the composition lowers the viscosity of the composition, which is advantageous for the uniform mixing of each component. (Including the application to the substrate during the production of the next PSA sheet) Handling of the system becomes easy. The organic solvent is volatilized during the production of the adhesive sheet preparation. The viscous solution of the pressure-sensitive adhesive composition for an external preparation for skin of the present invention thus produced is uniformly applied to a base material such as a plastic film such as a urethane film ^ a lyolefin film, a cloth, or a paper. By heating and drying to form a layer of the adhesive composition for external preparation for skin, a pressure-sensitive adhesive sheet for external preparation for skin can be produced.

The obtained skin external preparation adhesive sheet is cut into various suitable shapes and sizes such as tapes, rectangular sheets, and circular sheets, depending on the formulation use. Production in the form of the final formulation can be performed.

Example

Hereinafter, embodiments of the present invention will be described in detail. However, the following description illustrates the present invention by way of example, and the present invention is not limited to these descriptions.

(Example 1)

1. Production of pressure-sensitive adhesive composition for external preparation for skin and pressure-sensitive adhesive sheet for external preparation for skin:

(1) Production of an acrylic copolymer (Component A) containing a predetermined amount of a butyl monomer unit having a lactam ring group and having no functional group capable of reacting with a bridge;

N-Vienolay 2-pyrrolidone 35.0 g (0.315 mol,

: 34 mono / ₀ ) and Acryno 2-Echinino 1 ^ xinole 113.0 g (0.613 mono,,? _¾ ^ ¾ΐ · Λ ^ rate: 66 m / o) And a monomer mixed solution. Then, the obtained monomer mixture solution is equipped with a steam condensation reflux tower: a small polymerization vessel is weighed ^ f, and 0.12 g of AIBN is added, and then immersed in »at 60 ° C, Solution polymerization was initiated. The solution polymerization was carried out for about 3 hours while keeping the temperature of the polymerization reaction solution at 65 ± 5 ° C. At the stage when the exothermic reaction was almost completed, the temperature was raised to 70 ± 5 ° C and heated for about 5 hours to complete the polymerization reaction. Next, the polymerization reaction solution was taken out, and the Μ¾ of the resulting acryl-polymerized poly ^ ″ was measured by a method. As a result, it was 35,7 fift%. The solution viscosity of the obtained acrylic copolymer was also measured. (Measurement ° «: 25 ° C, using B temperature;« as ェ etino W firewood night, 以下, the following ¾). The measured value was 190 dPa'S. Gel permeation chromatography The number-average molecular weight determined by the method (GPC 00) was 840,000.

(2) Production of an acrylic polymer (component B) having a functional group capable of crosslinking reaction;

Acrylic 71 ^ 15g (10 parts by weight) Volume) and Echinore 202 g ^^

Next, the obtained monomer ^ ^ was charged into a polymerization reactor equipped with a stirrer equipped with a steam reflux tower, and after 0.25 g of azobisisobutyl mouth-trinole (AIBN) was used as a polymerization initiator, It was immersed in a valley at 58 ° C, and the descendants were combined. The solution polymerization was carried out for about 3 hours while controlling the temperature of the polymerization reaction solution at 65 ± 5 ° C. At the stage when the exothermic reaction was almost completed, the temperature was raised to 70 ± 5 ° C and heated for about 5 hours to complete the polymerization reaction. Next, the polymerization reaction solution is taken out from the polymerization reactor, and the obtained acryl-based polymer (a)) is dried to dryness.

(Measured by 150 ° 1 «, 45.8 liters /. The descendant of the obtained acrylate / polymer was determined to be 94dPa.S, ¾ ^ child volume is 750,000

(3) production of the intermediate composition;

96.6 g (acrylic acid) of an acrylic copolymer (component A) containing a predetermined amount of the obtained bier monomer unit having a ratatum ring group and having no functional group capable of crosslinking reaction 34.5 g) as a synthetic poly ^^), 25 g of an ethyl polymer solution of an acrylic polymer (component B) having a functional group capable of cross-linking reaction (11.5 g as an atalinole polymer), and sonolebitan trio Reate (Reodol SP-030V ヽ -NET HLB value: 1.8) (C 38.0 g, N- (Hex 1 ^, oxyhydroxy ^ pill) 1N-Hydroxyethino, Kanamide (Sofcare ceramide SL — E, 3.05g, fool, medium ^ chino night (medium ϋ¾Λ (D ^: 53.5Sft%) ^ f) Is calculated.

(4) Cross-linking and laminating steps with an external cross-linking agent;

86.7 _{g of the} obtained ェ etino W at night 162 _g (medium ¾) 、), 11.5 g of the acrylic poly- (B component) having F¾T? 75% of the compound @ confetti (Nichibayashi. After adding 1.4 g of necolonate HL), ethyl acetate was further added and adjusted to obtain an ethyl acetate solution of a pressure-sensitive adhesive composition for a skin external preparation having a nonvolatile residue of 50% by weight. The content of ceramides in this pressure-sensitive adhesive composition for external preparation for skin was 3.5% by weight.

Then, the obtained pressure-sensitive adhesive composition for external preparations for skin was applied to a polyurethane film (50 μm®), then heated at 110 ° C., and the thickness of the base layer was adjusted. A pressure-sensitive adhesive sheet for external use with a skin strength of 50 μm was produced.

2. Rating:

(1) Solubility of ceramides in the pressure-sensitive adhesive layer of the external skin pressure-sensitive adhesive sheet; press the resulting fe 力! Ft ^ square ^^^ into a strip (35 mm x 35 mm) to form a cap. to礴忍that there is no曰output ^s to. Next, the three sheets were stored for 30 days under the condition of (30 ° C x 75% RH) for 30 days and then taken out to remove the ceramides contained in the adhesive layer of the external adhesive sheet. The presence or absence of crystal precipitation in the agent layer was visually determined. In this case, it was confirmed that all test pieces before storage for 30 days did not have crystal precipitation, so it can be judged that the solubility of ceramides is inferior if any one crystal precipitates. . The results are shown in Table 1.

(2) Peeling adhesive strength as an adhesive sheet;

Obtained; fe ^ S! T ^ 膽ン騰 J 力力力 J 測定測定測定測定測定表測定測定表 ^ ^ ^ ^ ^ ^ ^ ^.

(3) adhesive residue;

Obtained: ^^ Paint a leg piece on short fiber ^ ^ i † (25 瞧 X 25mm) and apply it to the skin of the upper arms of the five subjects for 24 hours After attaching, adhesive residue was evaluated according to the following criteria. The results are shown in Table 1.

◎: There is no glue residue as an average of five persons.

〇: There is almost no glue residue as an average of five people. Δ: There is a little glue residue as an average of 5 people.

X: There is a noticeable glue residue as an average of five people.

(4) Measurement of recovery rate of skin moisturizing performance (moisture content of stratum corneum of skin epidermis); Measured effect of ceramides to restore skin moisturizing effect of obtained ceramide-containing skin external preparation adhesive sheet To do this, a commercially available skin moisture meter “Shitori-san” (Sekisui Chemical Co., Ltd .: Skin moisture meter based on the measurement principle based on the fact that water is different from other substances and the dielectric constant (impedance) is constant) And a measuring instrument for displaying the water content of the skin with a numerical value of 0 to 99], and the following evaluations i) to iii) were performed. The results are shown in Table 1.

i) The water content of the healthy skin inside the forearm of the healthy subject was measured and evaluated using a skin moisture meter “Moist”, and was measured as 60 to 63. Let N be the average value of 61.5.

ii) Treatment of healthy skin inside the forearm of the same healthy subject with the Imokawa method [acetone / ether (1Z1) mixed solvent for 20 minutes] (The main component is ceramide of biological origin) Elute and extract: Localized according to “Arashire ^ Utonashia”, 13 (3), 35-1-359 (1996)] By adding ¾ ^ (Z ^ return shelf IK power, the water content of the skin decreases and the skin becomes rough and rough, and the stratum corneum becomes large and small keratin pieces and peels off When the dry desquamation '14 ^ «7j ^ 4 was measured in i) and the rain, it was found to be 28-32 and 孭 symptom. Here, Z is defined as the value of this Taira Lake 30. In addition, in the state of し f ここ屑屑 'がが状態状態状態状態状態生理状態生理生理生理生理生理生理生理生理生理生理生理状態状態状態状態状態状態状態状態It turned out to be.

iii) The obtained c ^ / ft ^ 赚眯 -like, ~~ ¾S-shaped IWt (3 5 SUB X 3 5 SUB) cutting force 、, induced local generation of "^ by the above i) After 24 hours on the desquamated skin area, peel off and knead 24 days after kneading, i) T! ^ Wft¾ ^ sound! ? (Standing ^ t water ^ * was sick, and it was 58-60. ^ This flat;

Here, when the «rate (%) of the male dampness 14 ^ was calculated according to the following formula, it was found to be 92%, and the skin f dampness!“ Percentage of vital capacity (%) = [(XZ) / (NZ)] X100

(Examples 2 to 7)

As shown in Table 1, within the range stipulated by the present invention, the composition of the monomer of the component A; the type of the reactive cross-linking agent, the nonionic surfactant and the ceramide; the combination of the components in the adhesive composition A pressure-sensitive adhesive composition and a pressure-sensitive adhesive sheet were prepared and evaluated in the same manner as in Example 1 except that the ratio was changed. As a result, in each case, there is no adhesive residue while showing an appropriate peel adhesion to the skin, and the ceramides are completely dissolved in the pressure-sensitive adhesive layer. It has been found that an adhesive sheet for external preparations for skin can be obtained in which the effect of transferring and penetrating the skin into the skin is exhibited, and as a result, the skin moisturizing performance is restored.

(Comparative Example 1)

In the case of Nenne, the adhesive sheet was prepared in the same manner as in Example 1 except that ceramides were not blended, and consultation was conducted. (This example is the meaning of a comparative example as an IJI occupation sheet for external use on the skin.

It corresponds to "Example". )

As a result, as shown in Table 1, both the skin adhesiveness and the peeling-off property are suitable for skin external preparations.However, since ceramides are not added, the biological Except for the recovery amount due to the physiological recovery function, it was found that the skin external agent pressure-sensitive adhesive sheet exhibited extremely poor recoverability of the skin moisturizing performance.

(Comparative Examples 2, 3)

As shown in Table 1, in Comparative Examples 2 and 3, the monomer composition of the component A and the mixing ratio of each component in the pressure-sensitive adhesive composition were changed outside the range defined by the present invention, respectively. Based on Example 1, a pressure-sensitive adhesive composition for a skin external preparation and a pressure-sensitive adhesive sheet for a skin external preparation were prepared and evaluated.

In Comparative Example 2, the acrylyl polymerized poly ^ 4 of Aj¾¾ had a too low N-vinyl-2-pyrrolidone copolymer weight ratio ^ El ^, so that the entire pressure-sensitive adhesive composition for skin external preparations was As a result, it was found that the solubility of the ceramides was reduced and the ceramides were precipitated, and sufficient transfer permeability of the ceramides to the skin was hindered. As a result, the recoverability of the skin moisturizing performance was extremely deteriorated.

In Comparative Example 3, the amount of the nonionic surfactant of the component C was too small, so that the added and blended ceramides were not easily dissolved in the pressure-sensitive adhesive composition, and contained in the pressure-sensitive adhesive layer. It was found that the precipitation of ceramide crystals prevented sufficient migration penetration into the skin, and as a result, the recovery of skin moisturizing performance was extremely poor. Industrial applicability

The oily gel-like adhesive preparation of the present invention is stable in the adhesive layer, even for transdermally absorbable drugs, in particular, amphiphilic crystalline organic drugs such as ceramides which are hardly soluble in oils such as 7 Pressure sensitive adhesive composition for external preparations for skin, which is capable of dissolving molecules at high concentration and at a high concentration, and which is suitable for both skin adhesion and exfoliation and removability, and an external preparation for skin in which the transdermal absorption agent is dissolved Pressure sensitive adhesive composition and a pressure sensitive adhesive sheet preparation obtained by laminating the composition on a substrate for use in external preparations for skin such as cosmetics and external preparations for skin.

Claims

The scope of the claims

1.1 0-4 0 mol Bulle monomer unit having a lactam ring ^_0/0 containing by and crosslinkable Akuriru based copolymer having no functional group and (A component), a crosslinkable functional group An intermediate composition containing an acrylic polymer (B component) and a nonionic surfactant (C component) having an HLB in the range of 0.5 to 9.5 is crosslinked with an external crosslinker to crosslink the B component. A pressure-sensitive adhesive composition for an external preparation for skin, comprising 100 to 100 parts by weight of component A, 20 to 50 parts by weight of component B, and 50 to 3 parts by weight of component C. A pressure-sensitive adhesive composition for a skin external preparation, which is blended in an amount of 100 parts by weight.

2. An acrylic copolymer (Aj ^) containing 10 to 40 mono-V% of butyl monomer units having a lactam ring group and having no crosslinkable functional group, and a crosslinkable functional group Containing an acrylic polymer (component B), a nonionic surfactant (C j ^) with an HLB of 0.5 to 9.5, and a drug for transdermal absorption, · «) Is a pressure-sensitive adhesive composition for external preparation for skin prepared by cross-linking component B with a cross-linking agent, and 100 to 100 parts by weight of component A, 20 to 50 parts by weight of {β} ^ shelf, C , In a range of 50 to 30 parts.

3. The pressure-sensitive adhesive composition for an external preparation for skin according to claim 2, wherein the transdermally absorbable drug is an amphiphilic and sparingly soluble crystalline organic drug.

4. The pressure-sensitive adhesive composition according to claim 3, wherein the amphiphilic and sparingly soluble crystalline organic drug is a ceramide.

5. The content of the ceramides is 0.1 to 15 weight with respect to the total amount of the pressure-sensitive adhesive composition for external preparation for skin. /. The pressure-sensitive adhesive composition for an external preparation for skin according to claim 4, which is:

6. An external skin pressure-sensitive adhesive sheet in which the external pressure-sensitive adhesive composition according to any one of Items 2 to 5 is laminated on a base material.