JP2001181591A - Block copolymer adhesive and medical adhesive tape and percutaneous absorption pharmaceutical preparation using this and preparation method of block copolymer adhesive - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an adhesive suitable for a medical adhesive tape and a percutaneous absorption pharmaceutical preparation which has appropriate adhesion and cohesion to skins without the need of copolymerization of functional monomers or external crosslinking and which can stably hold a medicine susceptible to functional groups and which requires only a minimum amount of a crosslinking agent even when a crosslinking agent is used. SOLUTION: A block copolymer which comprises a hard segment comprising one or two or more of a styrene-based homopolymer, a polyamide-based polymer and an acyl acid-based polymer with a glass transition temperature of 60 deg.C or higher and a soft segment comprising an acrylic polymer with a glass transition temperature of -20 deg.C or lower is prepared to obtain the adhesive. Furthermore, the adhesive is crosslinked or an organic liquid component such as a glycerol fatty acid ester which works as a plasticizer is added to the adhesive as necessary.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a block copolymer pressure-sensitive adhesive, a medical pressure-sensitive adhesive tape using the same, a percutaneous absorption preparation, and a method for producing a block copolymer pressure-sensitive adhesive. More specifically, the present invention relates to a pressure-sensitive adhesive used for medical pressure-sensitive adhesive tapes, transdermal preparations, and the like, which can stably hold a drug that is easily affected by a functional group.

[0002]

2. Description of the Related Art In recent years, various products using an adhesive such as a percutaneous absorption preparation for administering a drug through the skin and a bandage (medical adhesive tape) have been developed. These are very excellent from the viewpoint of ease of continuous administration and protection of wounds, but are greatly restricted in properties due to the properties of the contained drug, etc. In some cases, it may be necessary to add a substance that may cause skin irritation, such as a skin or cross-linking agent.

For example, in conventional acrylic pressure-sensitive adhesives, a monomer having a carboxyl group or a hydroxyl group is usually copolymerized in order to secure the cohesive strength of the pressure-sensitive adhesive, but depending on the drug, these monomers are affected by these functional groups. Thus, the content of the drug is apparently reduced, or the reaction of a crosslinking agent added to compensate for plasticization by various additives or drugs or cohesive failure is inhibited.

As a countermeasure against this, various attempts have heretofore been made, for example, by copolymerizing a nonfunctional monomer having a high glass transition point or blending an inorganic filler in place of the functional monomer. It has been very difficult to achieve both adhesiveness and cohesiveness and to avoid the influence of drugs only by random copolymerization using a functional monomer or blending a filler.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a drug which has appropriate adhesiveness and cohesiveness to the skin and which is susceptible to a functional group without relying on copolymerization or external crosslinking of a functional monomer. However, an object of the present invention is to provide a pressure-sensitive adhesive that stably holds, a medical pressure-sensitive adhesive tape using the pressure-sensitive adhesive, and a transdermal absorption preparation.

The inventors of the present invention have conducted studies to solve the above problems, and as a result, have found that a block comprising a hard segment having a glass transition point of 60 ° C. or higher and a soft segment having a glass transition point of −20 ° C. or lower. In a copolymer, the hard segment is a styrene-based homopolymer or a polyamide or an acyl acid-based polymer, and the soft segment is an adhesive made of an acrylic polymer, without relying on copolymerization or external crosslinking of a functional monomer. , Has a suitable adhesiveness to the skin, has cohesiveness, and can stably hold even a drug that is easily affected by a functional group.Also, even when using a cross-linking agent, the amount of use is very small. They have found that it is possible to suppress them, and have completed the present invention.

[0007]

That is, the pressure-sensitive adhesive according to the present invention comprises a block copolymer comprising a hard segment having a glass transition point of 60 ° C. or higher and a soft segment having a glass transition point of −20 ° C. or lower. A block copolymer pressure-sensitive adhesive, wherein the hard segment is one or more of a styrene homopolymer, a polyamide polymer, and an acyl acid polymer, and the soft segment is an acrylic polymer. Features.

The pressure-sensitive adhesive in the present invention is a block copolymer comprising two types of segments, and comprises a hard segment having a glass transition point of 60 ° C. or higher and a soft segment having a glass transition point of −20 ° C. or lower. It is mainly composed of a block copolymer.

The cohesiveness of the adhesive according to the present invention is influenced by the molecular weight of the hard segment and the glass transition point (Tg).
The higher the molecular weight and the higher the Tg, the higher the cohesive force. At this time, the preferable number average molecular weight is 5,000 to 30,000 in terms of polystyrene, and the preferable glass transition point is 90 to 200 ° C. If the number average molecular weight or the glass transition point is smaller (lower) than this, sufficient cohesive strength cannot be obtained, which causes cohesive failure. Further, if the number average molecular weight or the glass transition point is higher (higher) than this, it becomes difficult to handle in terms of synthesis, or, as described later, it is unsuitable as a polymerization initiator at the time of block copolymerization. There is a possibility that. In the present invention, the number average molecular weight means a value converted into polystyrene using gel permeation chromatography (GPC method).

This hard segment has a glass transition point T
g is 60 ° C. or higher, and among them, styrene homopolymer, polyamide polymer and acyl acid polymer are preferably used. The monomers constituting these styrene-based homopolymers, polyamide-based polymers, and acyl-acid-based polymers are not particularly limited. For example, styrene, α-methylstyrene, and vinyltoluene are each used as monomers. Styrene-based homopolymer, polyamide-based polymer composed of dibasic acid such as adipic acid, azelaic acid, sebacic acid, dodecanoic acid and diamine such as ethylenediamine, hexamethylenediamine, isophoronediamine, meta-xylylenediamine, or ε-caprolactam , 11-aminoundecanoic acid, ω-laurolactam, 12-amidododecanoic acid, etc., polyamide-based polymers, adipic acid, azelaic acid, sebacic acid, dodecanoic acid and other dibasic acids and triethylene glycol and propylene glycol and the like. Alcohol An acyl acid polymer made of. Further, as the above-mentioned polyamide-based polymer, those using a polyamide azo polymer containing an azo compound as a monomer as a polymerization initiator are also preferably used.

The hard segments may be not only of the same kind but also of any combination such as styrene homopolymer and polyamide polymer, styrene homopolymer and acyl acid polymer, and polyamide polymer and acyl acid homopolymer. Also, the combination of the soft segments may be random.

It is the soft segment that determines the adhesiveness of the adhesive according to the present invention. This segment is-
It is an essential condition to have a glass transition point of 20 ° C. or lower, and the composition of the other is not particularly limited as long as it can exhibit tackiness,
Considering the copolymerizability with the polymerization initiator, a polymer containing alkyl acrylate as a main component is suitable.

As the polymer composition, it is preferable to use an alkyl (meth) acrylate having an alkyl group having 4 or more carbon atoms. Specifically, the alkyl group is butyl, pentyl, hexyl, heptyl, octyl,
Alkyl (meth) acrylates having a straight-chain alkyl group or a branched alkyl group having 4 to 13 carbon atoms, such as nonyl, decyl, undecyl, dodecyl, and tridecyl, can be used, and these may be used alone or in combination of two or more. Can be.

The above-mentioned alkyl (meth) acrylate is not limited to the above-mentioned ones. If the effects of the present invention can be exerted, esterified compounds other than the alkyl group or those having 1 to 3 carbon atoms may be used. It goes without saying that a (meth) acrylic acid alkyl ester having an alkyl group and an (meth) acrylic acid alkyl ester having an alkyl group having 14 or more carbon atoms may be used in combination.

Further, the following copolymerizable monomers may be copolymerized. For example, an acrylic monomer or a vinyl monomer having an amino group, an alkylamino group, a pyrrolidone group, a pyridine group, an imidazole group, or the like in a side chain, and more specifically, aminoethyl (meth)
Acrylate, dimethylaminoethyl (meth) acrylate, trimethylammoniumethyl (meth) acrylate, dimethylaminopropyl (meth) acrylate,
Mono- or dialkylamino (meth) acrylates having an alkyl group having 1 to 4 carbon atoms, such as dimethylaminobutyl (meth) acrylate, N-vinyl-2-pyrrolidone, vinylpyridine, vinylimidazole and the like can be mentioned. Of course, even among these monomers, one or more of them can be copolymerized.

Further, depending on the type of drug, when a functional monomer may be contained or when further crosslinking is required,
For example, a carboxyl group ((meth) acrylic acid, itaconic acid, maleic acid, maleic anhydride, etc.), a hydroxyl group ((meth) acrylic acid hydroxyl ethyl ester, (meth) acrylic acid hydroxypropyl ester, etc.), a sulfoxyl group ( For example, styrenesulfonic acid, allylsulfonic acid, sulfopropyl (meth) acrylate, (meth) acryloyloxynaphthalenesulfonic acid, acrylamidomethylpropanesulfonic acid, etc.),
Amino group (for example, (meth) acrylic acid aminoethyl ester, (meth) acrylic acid dimethylaminoethyl ester, (meth) acrylic acid tert-butylaminoethyl ester, etc.), amide group (for example, (meth) acrylamide, dimethyl (meth) Acrylamide, N-butylacrylamide, N-methylol (meth) acrylamide, N-methylolpropane (meth) acrylamide, etc., alkoxyl group (for example, methoxyethyl (meth) acrylate, ethoxyethyl (meth) acrylate, (meth) ) Acrylic acid methoxyethylene glycol ester, (meth) acrylic acid methoxydiethylene glycol ester, (meth) acrylic acid methoxypolyethylene glycol ester, (meth) acrylic acid methoxypolypropylene Glycol esters include monomers having a functional group such as the side chain (meth) acrylic acid tetrahydrofurfuryl ester).

The block copolymer according to the present invention is prepared in advance by preparing a peroxide of an acyl acid polymer or a polyamide azo polymer, and using such a polymer as a polymerization initiator to prepare an appropriate polymer such as toluene, benzene or xylene. It is obtained by copolymerizing with a monomer monomer constituting the soft segment in a solvent. When a styrene homopolymer is used as a hard segment, a styrene homopolymer is prepared in advance, and a monomer monomer constituting the soft segment is copolymerized with the styrene homopolymer. The monomer of the soft segment and the styrene monomer may be copolymerized using a peroxide of an acid-based polymer as a polymerization initiator.

Examples of the peroxide of the acyl acid polymer serving as a polymerization initiator include, for example, the above-mentioned dibasic acid peroxides such as an acyl acid polymer peroxide derived from a condensate of adipic acid chloride and triethylene glycol. And an acyl acid-based polymer composed of a polyhydric alcohol or the like and treated by an appropriate method.

In the present invention, when crosslinking is performed,
The obtained block copolymer solution is preferably subjected to a crosslinking treatment with an external crosslinking agent to obtain a so-called gel state. By performing the crosslinking treatment in this manner, it is possible to prevent the contained organic liquid component from flowing out as described later, and to impart cohesive force to the pressure-sensitive adhesive layer. Specifically, a chemical crosslinking treatment using a crosslinking agent such as a polyisocyanate compound, an organic peroxide, an organic metal salt, a metal alcoholate, a metal chelate compound, and a polyfunctional compound is used. Among these crosslinking agents, trifunctional isocyanates and aluminum chelate compounds are preferred from the viewpoint of crosslinking reactivity and handleability. These crosslinking agents do not cause a solution thickening phenomenon until coating and drying, and are extremely excellent in workability.
In this case, the compounding amount of the crosslinking agent is about 0.01 to 2 parts by weight based on 100 parts by weight of the block copolymer (solid content).

The block copolymer thus obtained (or a crosslinked product thereof) has an adhesive force by itself. Therefore, not only can it be used as a pressure-sensitive adhesive solution as it is, but in the present invention, various additives can be blended in order to control the tackiness and the drug release. For example, as an additive having a plasticizing effect, an organic liquid component for plasticizing a crosslinked pressure-sensitive adhesive to form a gel and imparting a soft feeling can be given. This organic liquid component has compatibility with the above-mentioned block copolymer and is uniformly dissolved and dispersed in the pressure-sensitive adhesive layer. In other words, by containing such an organic liquid component, the pressure-sensitive adhesive layer can have flexibility, and when peeled from the skin surface, it can reduce pain and skin irritation caused by adhesion (skin adhesion). . Furthermore, since the pressure-sensitive adhesive layer is plasticized, when the preparation is used as a transdermal preparation, the free diffusion property of the contained drug is improved, and the release onto the skin surface (skin transferability) is also improved. Become.

As such a component, any substance having a plasticizing effect on the pressure-sensitive adhesive may be used, but when applied as a transdermal absorption preparation, the transdermal absorption May be used that have an absorption promoting action to improve the absorption. Specifically, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, polyethylene glycol, glycols such as polypropylene glycol, olive oil, castor oil, squalene, oils and fats such as lanolin, ethyl acetate,
Organic solvents such as ethyl alcohol, dimethyldecylsulfoxide, methyloctylsulfoxide, dimethylsulfoxide, dimethylformamide, dimethylacetamide, dodecylpyrrolidone and isosorbitol, liquid surfactants, phthalic acid esters, diethylsebacate, triethyl citrate, acetylcitrate Plasticizers such as tributyl, hydrocarbons such as liquid paraffin, ethoxylated stearyl alcohol, glycerin fatty acid ester, isopropyl myristate, isotridecyl myristate,
Examples thereof include ethyl laurate, N-methylpyrrolidone, ethyl oleate, oleic acid, diisopropyl adipate, isopropyl palmitate, and 1,3-butanediol. One or more of these can be used in combination.

Among these organic liquid components, preferred organic liquid components include fatty acid esters and glycerin fatty acid esters (particularly, fatty acid monoglycerides). However, these fatty acid esters and glycerin fatty acid esters may be any as long as they exert an action of plasticizing the pressure-sensitive adhesive. There is a danger that the compatibility with the compound may worsen or that the compound may be volatilized in the heating step in preparing the preparation. In addition, fatty acids having a double bond in the molecule may cause oxidative decomposition and the like, which may cause a problem in storage stability. Furthermore, in the case of a percutaneous absorption preparation, if the content of the percutaneous absorption drug per unit area is large, a drug having a saturation solubility or higher is precipitated in the preparation, but the type of fatty acid ester or glycerin fatty acid ester to be added is determined. Depending on the case, the crystal precipitation of the drug may be inhibited or the deposition rate may be slowed down, resulting in poor appearance of the obtained preparation or adversely affecting the storage stability.

Therefore, the fatty acid esters used include:
Preferably the carbon number is 12-16, more preferably 12-
A fatty acid ester comprising 14 higher fatty acids and a lower monohydric alcohol having 1 to 4 carbon atoms is employed. Such higher fatty acids are preferably lauric acid (C12),
These are myristic acid (C14) and palmitic acid (C16), and it is particularly preferable to use myristic acid. Examples of the lower monohydric alcohol include methyl alcohol, ethyl alcohol, propyl alcohol, and butyl alcohol. These are not limited to linear alcohols, and may be branched alcohols. Preferably, isopropyl alcohol is used. Thus, the most preferred fatty acid ester is isopropyl myristate.

On the other hand, the glycerin fatty acid ester is preferably a glyceride with a higher fatty acid having 8 to 10 carbon atoms. Such higher fatty acids are preferably caprylic acid (octanoic acid, C8), pelargonic acid (nonanoic acid, C9), capric acid (decanoic acid, C10),
Particularly, caprylic acid monoglyceride, diglyceride and triglyceride using caprylic acid are used.

These organic liquid components are used in an amount of 40 to 15 parts by weight per 100 parts by weight of the block copolymer constituting the adhesive.
0 parts by weight, preferably 80 to 150 parts by weight. When the content is out of this range, practical skin adhesion and low skin irritation cannot be obtained, and the release of the drug for transdermal absorption (skin transferability) is not sufficient. Absent. Such a problem becomes more conspicuous as the size (area) of a product as a skin patch preparation is smaller.

In addition, other additives, for example, fillers such as talc, fragrances, and the like, within a range that does not affect the stability of the drug for transdermal absorption or a range that does not adversely affect skin irritation. , A colorant or the like may be added.

The pressure-sensitive adhesive thus obtained is provided as a medical pressure-sensitive adhesive tape by directly applying it on a support, or separately applying it on a separator to form a pressure-sensitive adhesive layer and then transferring this onto the support. In the present invention, a transdermal drug is blended in the pressure-sensitive adhesive layer and is suitably used for a transdermal preparation. The drug for percutaneous absorption can be arbitrarily selected depending on the purpose of the treatment, and examples thereof include corticosteroids, analgesics and anti-inflammatory agents, hypnotics and sedatives, tranquilizers, antihypertensives, antihypertensives, and antibiotics. Various drugs such as anesthetics, antibacterials, antifungals, vitamins, coronary vasodilators, antihistamines, antitussives, sex hormones, antidepressants, cerebral circulation improvers, antiemetic agents, antitumor agents, biopharmaceuticals, etc. However, a transdermally absorbable drug that does not stay on the skin surface but penetrates subcutaneously or into the blood to exert a local action or a systemic action can be used. These drugs may be used in combination of two or more as necessary.
In addition, from the viewpoint of uniform dispersibility in the pressure-sensitive adhesive layer and transdermal absorbability, a fat-soluble drug (dissolved amount of 0.4
g or less / 100 ml of water, at ordinary temperature). Of course, not limited to transdermally absorbed drugs,
It goes without saying that a drug that directly acts on the wound of the skin may be contained.

The content of the drug for transdermal absorption can be appropriately set according to the kind of the drug and the purpose of administration, but is usually 1 to 40% by weight, preferably 3 to 30% by weight in the adhesive. Range. If the content is less than 1% by weight, release of an effective amount for treatment or prevention may not be expected, and if it exceeds 40% by weight, the effect of increasing the amount cannot be expected, so that it is not economical. Not only is it disadvantageous, but it also tends to have poor adhesion to the skin. In the present invention, the above-mentioned drug does not need to be completely dissolved in the pressure-sensitive adhesive, but may contain a drug having a solubility equal to or higher than the solubility in the pressure-sensitive adhesive, and may contain an undissolved drug.
In this case, the drug in an undissolved state needs to be uniformly dispersed in the transdermal absorption preparation so that the content does not vary.

However, from the viewpoint of providing sustained release over a long period of time, increasing the content per unit area to increase the release amount, and reducing the size of the preparation to reduce skin irritation. Needless to say, they may be blended beyond the above range of the content.

The pressure-sensitive adhesive containing these components is applied, for example, on a suitable support to form a pressure-sensitive adhesive layer.
As the support, it is preferable that the block copolymer or the organic liquid component contained in the pressure-sensitive adhesive layer, a drug for percutaneous absorption or the like is not lost from the back surface through the support and causes a decrease in the content. . Specifically, it is possible to use a single film such as polyester, nylon, Saran, polyethylene, polypropylene, polyvinyl chloride, ethylene-ethyl acrylate copolymer, polytetrafluoroethylene, Surlyn, metal foil, or a laminated film thereof, or the like. it can. Among these, in order to improve the adhesive force (anchoring force) between the support and the pressure-sensitive adhesive layer, it is preferable that the support be a laminated film of a nonporous plastic film and a porous film made of the above-mentioned materials. In this case, it is preferable to form the pressure-sensitive adhesive layer on the porous film side.

As such a porous film, a film having an improved anchoring force with the pressure-sensitive adhesive layer is used. Specifically, paper, woven fabric, non-woven fabric, knitted fabric, or mechanically perforated. Among them, paper, woven fabric and non-woven fabric are particularly preferable from the viewpoint of handleability and the like. The porous film is 10 to 200 μm in terms of improving anchoring power, flexibility and sticking operability of the whole adhesive tape or transdermal absorption preparation.
m, in the case of a thin preparation such as a plaster type or an adhesive tape type, a range of 10 to 100 μm is employed.

When a woven or nonwoven fabric is used as the porous film, the basis weight is preferably 5 to 30 g / m ² , and more preferably 6 to 15 g / m ² . The most preferable support in the present invention is a laminated film of a polyester film having a thickness of 1.5 to 6 μm and a polyester nonwoven fabric having a basis weight of 6 to 12 g / m ² .

[0033]

Next, the present invention will be described in more detail with reference to the following examples. 1. Preparation of Polymerization Initiator (1) Acyl acid-based polymer peroxide (PA) Take 72.3 g of adipic acid chloride in a flask, add dropwise 29.7 g of triethylene glycol while stirring at 50 ° C. under a nitrogen stream, and lightly add. The reaction was performed for 3 hours while reducing the pressure and removing hydrogen chloride. Condensate 2 of this acid chloride
A solution consisting of 2.2 g and 2.3 g of methyl ethyl ketone was added to 5.0 g of sodium hydroxide, 4.3 g of 50% aqueous hydrogen peroxide and 0.22 g of dioctyl phosphate in water 1
20 g while stirring at 5 ° C.
Dropped over minutes. After further reacting for 20 minutes, the precipitate was filtered and washed and filtered repeatedly to obtain 40 g of a water-containing product. This was further washed three times with water and methanol, respectively, and then dried under vacuum to obtain an acyl-acid-based polymer peroxide. Its molecular weight was about 7,000 (GPC method, calculated as polystyrene).

(2) Aliphatic azo polymer (PAZ) 12.7 g of 4,4'-azobis (4-cyanopentanoic acid chloride) and 36.2 adipic acid dichloride were placed in a flask.
g and dissolve by adding 500 ml of nitrobenzene. In another flask, 35.0 g of hexamethylenediamine
And 1.6 g of sodium hydroxide, and 750 ml of water is added and dissolved. In a flask containing nitrobenzene,
An alkaline aqueous solution of hexamethylenediamine was gently poured and reacted at the interface between the aqueous phase and the organic phase. The polyamide thin film formed at this interface was continuously taken out in a rope shape and continued until the thin film could not be taken. The product was washed several times with dilute hydrochloric acid, washed with water, neutralized with a weak alkaline aqueous solution, washed again with water, finally washed several times with a 50% aqueous ethanol solution, and dried under vacuum to obtain an aliphatic azopolymer. The aliphatic azo polymer was dissolved in meta-cresol before use, purified by reprecipitation in ether, and used. Its molecular weight was about 26,000 (GPC method, calculated as polystyrene).

2. Preparation of pressure-sensitive adhesive (Example 1) In toluene, 10 parts by weight of the above-mentioned acyl acid-based polymer peroxide and 2-ethylhexyl acrylate (2-
EHA) was charged to a total of 60% by weight, and the mixture was stirred and reacted at 60 ° C. for 12 hours and further at 80 ° C. for 12 hours in an inert gas (N ₂ ) atmosphere. ) Got. This solution has a thickness of 300 after drying.
μm, apply on polyester liner,
The adhesive was dried at 40 ° C. for 20 minutes, then at 60 ° C. for 20 minutes, and further at 100 ° C. for 10 minutes. The pressure-sensitive adhesive was recovered and subjected to thermal analysis.
g was observed at about 80 ° C. as Tg based on PA.

Example 2 Toluene was charged with 4 parts by weight of the above-mentioned acyl acid-based polymer peroxide and 90 parts by weight of 2-ethylhexyl acrylate (2-EHA) so that the total was 60% by weight, and an inert gas (N ₂ ) 4 at 60 ° C under atmosphere
After stirring and reacting for a time, 6 parts by weight of styrene (ST) were added, and the temperature was raised to 70 ° C. and reacted for 5 hours.
The temperature was further raised to 80 ° C. and the mixture was heated for 6 hours to obtain a pressure-sensitive adhesive solution (pressure-sensitive adhesive PA). An adhesive was obtained from this solution in the same manner as in Example 1. When this adhesive was recovered and subjected to thermal analysis, it was not clear at about 80 ° C. and about 90 ° C., but the Tg based on PA and poly ST oligomer was about -40 ° C., and the Tg of poly 2-EHA was about Was observed.

Example 3 In toluene, 3 parts by weight of the above-mentioned acyl acid-based polymer peroxide, 92 parts by weight of 2-ethylhexyl acrylate (2-EHA), and acrylic acid (AA) 2
Parts by weight to a total of 60 wt%, and stirred and reacted at 60 ° C. for 4 hours in an inert gas (N ₂ ) atmosphere.
Next, 6 parts by weight of styrene (ST) was added, and the temperature was raised to 70 ° C. and reacted for 5 hours. The temperature was further raised to 80 ° C. and the mixture was heated for 6 hours to obtain a pressure-sensitive adhesive solution (pressure-sensitive adhesive PA).
An adhesive was obtained from this solution in the same manner as in Example 1. The adhesive was recovered and subjected to thermal analysis.
And Tg based on PA and poly ST oligomer, which is not clear at about 90 ° C, is about 2--30 ° C at about -30 ° C.
A, Tg based on the AA copolymer was observed.

Example 4 10 parts by weight of the above-mentioned aliphatic azo polymer (as a 50% purified DMF solution) and 90 parts by weight of 2-EHA were charged into ethyl acetate so that the total was 60% by weight, and inert gas (N ₂ ) was used. The mixture was stirred and reacted at 60 ° C. for 6 hours in an atmosphere, and further heated at 75 ° C. and heated for 6 hours to obtain a pressure-sensitive adhesive solution (pressure-sensitive adhesive PAZ). An adhesive was obtained from this solution in the same manner as in Example 1. This adhesive was recovered and subjected to thermal analysis. As a result, Tg based on polyamide was observed at about 65 ° C., and Tg of poly-2-EHA was observed at about −42 ° C.

Example 5 5 parts by weight of the above aliphatic azo polymer (as a 50% purified DMF solution) and 2 parts
-93 parts by weight of EHA and 2 parts by weight of acrylic acid (AA) were charged so as to be a total of 60 wt%, and inert gas (N ₂ ) was used.
The mixture was stirred and reacted at 60 ° C. for 6 hours in an atmosphere, and then heated at 75 ° C. and heated for 6 hours to form a pressure-sensitive adhesive solution (pressure-sensitive adhesive PA).
Z) was obtained. An adhesive was obtained from this solution in the same manner as in Example 1. The pressure-sensitive adhesive was recovered and subjected to a thermal analysis. As a result, the Tg based on the polyamide was found to be about −65 ° C. at about 65 ° C.
At 28 ° C., a Tg based on the 2-EHA, AA copolymer was observed.

COMPARATIVE EXAMPLE 1 Under an inert gas (N ₂ ) atmosphere, 95 parts by weight of 2-ethylhexyl acrylate and 5 parts by weight of acrylic acid were charged into ethyl acetate so as to be a total of 60% by weight, and benzoyl peroxide was added. The copolymer was copolymerized at 60 ° C. in the presence to obtain an adhesive solution (comparative adhesive).

3. Preparation of medical adhesive tape 2 μm thick polyester sheet and 8 g / m ² as support
Using a polyester non-woven fabric laminate (lamination of the pressure-sensitive adhesive layer on the non-woven fabric side) and a 75 μm-thick polyester sheet (silicon-treated on the lamination surface) for the liner, the pressure-sensitive adhesive layer after drying has a thickness of about 60 μm. According to the pressure-sensitive adhesive composition of Table 1, coating was performed according to a conventional method to obtain a medical pressure-sensitive adhesive tape (or transdermal absorption preparation). In the pressure-sensitive adhesive composition, a solvent such as ethyl acetate, toluene, or THF was appropriately used, and drying was performed at 100 ° C. for 5 minutes (in a circulating hot air dryer).

[0042]

[Table 1]

4. Evaluation Test Next, using each of the medical pressure-sensitive adhesive tapes, the measurement of the adhesive strength, the sticking sensory test, and the drug stability test were evaluated as described below.

(Measurement of Adhesive Strength)
Each of the band-shaped adhesive tapes cut to a thickness of 30 mm was applied, and the load was 30
After the roller of 0 g was reciprocated once and adhered closely, peeling was performed at a speed of 300 m / min in the direction of 180 degrees, and the peeling force at that time was measured.

(Sticking Sensory Test)
^They were cut into 0 cm ² and applied to the chest of three healthy panelists. Peeled 24 hours after application, pain and the like at that time were comprehensively evaluated according to the following criteria. ◎: Applied well and peeled with little pain at the time of peeling. ：: Sufficiently attached and slightly painful at the time of peeling. Δ: Partially peeled off. Or it was stuck well, but it hurt when peeled. ×: Dropped. Or, it was stuck well, but it was very painful at the time of peeling, and I thought that I did not want to stick it again.

(Drug stability test) The obtained adhesive tape was cut into 20 cm ² , and the drug was extracted with methanol.
The amount of drug in the adhesive was measured using high performance liquid chromatography. This content was used as the initial value. The separately cut pressure-sensitive adhesive tape was hermetically packaged with a packaging material made of a heat-sealing film laminated with polyethylene, and stored at 40 ° C. for 3 months. Using this preserved product, the amount of drug in the adhesive was measured in the same manner as in the initial value measurement, and the remaining amount was calculated from the following equation. Residual amount = {drug content after storage (g) / initial value (g)} ×
100%

(Evaluation Results) Table 2 shows the results of various tests. Comparative tape 2 could not be tested due to cohesive failure. Further, Comparative Tape 1 was poor in drug stability, painful in peeling, and poor in sticking feeling. On the other hand, although each of the practice tapes was found to have a slightly strong adhesive force and some discomfort in peeling, the adhesive force was generally within a range of 40 to 200 g, which is considered to be good. The feeling of sticking was also good. The stability of the drug was also good. In addition, in the sensory test, there was no major defect such as dropout in all cases.

[0048]

[Table 2]

[0049]

According to the present invention, appropriate adhesiveness to skin can be achieved without depending on copolymerization or external crosslinking of a functional monomer.
It is possible to provide a pressure-sensitive adhesive which has cohesiveness and can stably hold a drug which is easily affected by a functional group. Therefore, by using this pressure-sensitive adhesive, it is possible to provide a percutaneous absorption preparation holding various drugs such as a medical pressure-sensitive adhesive tape capable of maintaining appropriate sticking properties and drug stability, and a drug for percutaneous absorption. .

Even when a cross-linking agent is used, the amount of the cross-linking agent can be minimized, so that skin irritation caused by the cross-linking agent can be eliminated.

Continued on the front page F term (reference) 4C076 AA74 BB31 CC12 DD45 EE03A EE10A EE24A EE26A EE45A EE49A FF63 FF70 4C081 AA03 AA12 BB04 CA031 CA081 CA161 CA231 CB011 CC02 CC05 CE07 4J004 AA07 CA01 CC04 DM001 EE022 EF191 HB07 HB09 HB10 HB15 HB24 HB31 HB41 HC11 HC21 HD15 HD43 JA09 JB09 KA12 KA16 KA23 KA31 KA38 KA41 LA01 LA02 MA15 NA02

Claims (9)

[Claims] 1. An adhesive comprising a block copolymer comprising a hard segment having a glass transition point of 60 ° C. or higher and a soft segment having a glass transition point of −20 ° C. or lower, wherein the hard segment is a styrene homopolymer. A block copolymer pressure-sensitive adhesive, which is one or more of a polymer, a polyamide polymer, and an acyl acid polymer, and wherein the soft segment is an acrylic polymer. 2. The block copolymer pressure-sensitive adhesive according to claim 1, wherein the number average molecular weight of the hard segment is 5,000 to 30,000. 3. The block copolymer pressure-sensitive adhesive according to claim 1, wherein the soft segment comprises a copolymer containing an alkyl acrylate as a main component. 4. The block copolymer pressure-sensitive adhesive according to claim 3, wherein the acrylic acid alkyl ester-based copolymer has no functional group. 5. The block copolymer pressure-sensitive adhesive according to claim 3, wherein the acrylic acid alkyl ester-based copolymer has a functional group and is further subjected to external crosslinking. 6. The block copolymer pressure-sensitive adhesive according to claim 1, further comprising an additive having a plasticizing action. 7. A medical pressure-sensitive adhesive tape having a pressure-sensitive adhesive layer on a sheet or tape-like substrate, wherein the pressure-sensitive adhesive layer is formed from the block copolymer pressure-sensitive adhesive according to any one of claims 1 to 6. A medical adhesive tape, comprising: 8. A transdermal preparation having a pressure-sensitive adhesive layer containing a drug for transdermal absorption, wherein the pressure-sensitive adhesive layer comprises the block copolymer pressure-sensitive adhesive according to any one of claims 1 to 6. A transdermal absorption preparation characterized by the following. 9. The method for producing a block copolymer pressure-sensitive adhesive according to claim 1, wherein an acyl acid-based polymer peroxide or a polyamide azo polymer is used as a polymerization initiator. Of producing a block copolymer pressure-sensitive adhesive.