JPH0751702B2 - Medical adhesive base - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Use) The present invention has good adhesiveness when applied to the skin,
The present invention relates to a medical adhesive base that can significantly reduce the adhesiveness during storage and peeling from the skin.

(Prior Art) Adhesives in which a medicinal component (hereinafter referred to as a drug) contained in an adhesive base is provided in layers on the surface of a backing support have been used for many types of patches. Has been proposed and put into practical use. It is said that the effective temperature range having adhesiveness of the adhesive base used in the patch is preferably as wide as possible (particularly low temperature range), and such an adhesive base has been used.

For example, when the patch is applied to the skin, it is sufficient if it has sufficient tackiness at about 30 ° C, but in reality, it gives a large tackiness even at a temperature of 5 to 10 ° C or lower. Adhesive bases having properties are used or proposed.

Conventionally, the following is considered as the reason why such an adhesive base is used.

There has been a general idea that the wider the operating temperature range of an adhesive (especially on the lower temperature side), the higher the practical value of the adhesive.

Actually, the adhesive having the conventional composition (regardless of the presence or absence of the drug) has a higher adhesiveness to the skin of the human body and is well adapted to the bending and stretching of the skin as it adheres well at low temperature.

(Problems to be Solved by the Invention) However, when a patch is prepared using a conventional adhesive base, there are the following drawbacks.

As the tackiness of the adhesive base increases, the dissipation of the drug present in the adhesive plaster increases, and therefore the drug dissipates to the backing support or surface protective paper and to the outer layer through them during storage of the patch. Tend to do.

The reason for this is presumed that as the adhesiveness of the adhesive base increases, the microscopic molecular movement of the base molecule becomes active, which promotes the dissipation of the drug.

Similarly to the above, as the adhesive base becomes softer, the drug contained in the adhesive plaster is more likely to deteriorate during storage.

For the purpose of improving the drug utilization efficiency of the patch and obtaining the rapid effect of the drug, the drug was produced in a high concentration only near the surface of the adhesive plaster layer, and the drug concentration was diluted to a deeper portion. For patches, the temperature during storage (for example, 10 to 25
In the case of an adhesive having a high adhesiveness at (.degree. C.), the micromolecular motion of the adhesive base is relatively large, so that the drug uniformly diffuses throughout the plaster layer during storage.

After peeling, when peeling the patch from the skin,
It is painful because of its high adhesive strength.

The present invention is to solve the above-mentioned drawbacks, and an object thereof is to have sufficient adhesiveness at the temperature at which the patch is applied, while maintaining good retention of the drug contained in the adhesive base. In addition, the deterioration of the drug can be reduced, and the drug can be made to exist in a high concentration only near the surface of the adhesive plaster layer, and the pain when peeling the patch from the skin can be reduced. To provide a viscous base material.

(Means for Solving the Problem) For example, a patch having an adhesive plaster layer containing a drug provided on the surface of a backing support is stored at a low temperature at which the adhesiveness is significantly reduced or disappears. It has been observed from time to time that the dissipation and degeneration of drugs becomes very slow. However, conventional pressure-sensitive adhesives, especially pressure-sensitive adhesives containing a polymer having a (meth) acrylic acid ester as a main monomer component, which is suitable for medical purposes, have a considerably low temperature at which deterioration of the drug can be prevented (for example, 0 ° C.). Since the following), it was difficult to apply to a patch stored at room temperature.

However, the present inventor, by using as a main component a polymer having a composition as described in the following essential constitution, while exhibiting sufficient adhesiveness at a temperature for application and pasting, it becomes a conventional adhesive at a temperature below that. By virtue of the fact that the adhesiveness was significantly lowered, the adhesive base material capable of exhibiting the above-mentioned effects was obtained, and the present invention was completed.

That is, the medical adhesive base of the present invention, at least 35
A medical adhesive base having adhesiveness at a temperature of ℃ or more, which mainly comprises acrylic acid ester and / or methacrylic acid ester having a linear alkyl group having 16 or more carbon atoms as its ester residue. It is characterized by containing a polymer as a main component, whereby the above object is achieved.

In addition, another medical adhesive base of the present invention is an acrylic ester and / or methacrylic acid ester having a linear alkyl group having a carbon number of 16 or more as its ester residue of 20 to 80.
A polymer containing, as a main component, wt% and 80 to 20 wt% of an acrylic acid ester and / or a methacrylic acid ester whose ester residue is an alkyl group having an average carbon number of 8 to 2 is contained as a main component. The above object is achieved by that. It is preferable that the medical adhesive base further contains a plasticizer.

The polymer contained in the medical adhesive base of the present invention has the following A
The component monomer and the component B monomer are obtained as constituent components. A component is 20-80% by weight in all monomers
It is preferable that the B component is contained in a proportion of 80 to 20% by weight based on the total monomers.

(Component A) An acrylic acid ester and / or a methacrylic acid ester having a linear alkyl group having 16 or more carbon atoms as its ester residue.

For example, octadecyl acrylate, octadecyl methacrylate, hexadecyl acrylate, hexadecyl methacrylate, etc. may be mentioned, and these may be used alone or in combination of two or more. The proportion of component A in all monomers is preferably 20 to 80% by weight.

(Component B) 60% by weight or more of the component B is an acrylic acid ester having an alkyl group (linear and / or non-linear) having an average carbon number of 8 to 2 as its ester residue, and / or Alternatively, methacrylic acid ester (hereinafter referred to as (meth) acrylic acid ester) is preferably used. Examples thereof include 2-ethylhexyl (meth) acrylate, (meth)
Octyl acrylate, heptyl (meth) acrylate,
Hexyl (meth) acrylate, butyl (meth) acrylate, isobutyl (meth) acrylate, t-butyl (meth) acrylate, ethyl (meth) acrylate, methyl (meth) acrylate and the like can be mentioned.

Of the monomers in component B, most (60% or more) of the components are preferably the above-mentioned (meth) acrylic acid ester, but as an example of possible monomers (40% or less) other than (meth) acrylic acid ester. Examples of the monomer include

Acrylic acid, methacrylic acid, vinyl acetate, diethyl acrylamide, (meth) acrylic acid diethylaminoethyl ester, (meth) acrylic acid butoxyethyl ester, diacetone acrylamide, vinylpyrrolidone,
Nn-butoxymethylacrylamide and the like.

Further, in addition to the above-mentioned essential components, a plasticizer, a tackifier, a filler, a stabilizer and the like can be appropriately added to the adhesive base of the present invention. In particular, it is the plasticizer that has the greatest effect on the primary physical properties of the adhesive base, such as temperature sensitivity and adhesiveness. In many cases, the plasticizer corrects and corrects the properties of the adhesive base. Used.

Examples of such plasticizers include the following.

Dioctyl phthalate, dibutyl phthalate, etc. Phthalate type dibutyl sebacate, dioctyl sebacate, etc. sebacate ester type Dioctyl adipate, etc. adipic acid ester type tributyl phosphate, etc. Phosphate ester type Castor oil, olive oil, cottonseed oil, etc. vegetable oil Liquid paraffin Etc.Aliphatic or alicyclic HC oil Other general plasticizers such as isopropyl myristate, glycerin triacetate, triethyl citrate, etc.Low polymerization degree polymers or oligomers that are liquid at room temperature, for example, liquid polyurethane, poly Isobutylene,
Polyvinyl alkyl ether, polyvinyl alkyl ester, etc. The above tackifier is also used together with the plasticizer to modify its tackiness and temperature sensitivity. Examples of tackifiers include rosin derivatives such as ester gum, polyterpene resins, and petroleum fraction (C4 to C6) polymer resins.

<Synthesis Method of Main Polymer> Generally, it can be most suitably obtained by a usual polymerization method in which an acrylic ester-based pressure-sensitive adhesive is synthesized. The radical polymerization reaction is most suitable in terms of its polymerization mechanism, and the external appearance can be any of solution polymerization, emulsion polymerization, suspension polymerization, bulk polymerization, etc., but especially solution polymerization is easy to control and quality is stable. It is preferable because it is easy to carry out and all the processes including the subsequent processing flow smoothly.

<Blending of adhesive base> When the adhesive base is prepared only by the main polymer, it can be used in the form of its polymerization (solution, emulsion, etc.). When the tacky base is prepared by mixing the post-additives, it is preferably carried out in a solution system. In that case, the polymer solution and other additives are mixed in a common solution, and if necessary, adjusted to a concentration and viscosity suitable for use, aged, and then used. Often suitable solvents for this are ethyl acetate, butyl acetate, n-hexane, cyclohexane, n-heptane, toluene, tetrahydrofuran, petroleum ether and the like. In addition, necessary chemicals, auxiliary agents therefor, stabilizers and the like are also added in this step.

<Post-processing such as preparation of patch> By using a prepared polymer solution or the like, by a conventional coating means or the like, for example, continuous coating, for each sheet, on the surface of the backing support serving as a base material Is applied to form a dried coating film of the adhesive base or plaster. When a layer containing only the adhesive base containing no drug is formed, the required drug is sprayed with the drug or the drug solution,
It is incorporated into an adhesive base by various methods such as coating and transfer (dried as necessary), and after further processing, finally processed into a patch.

In the patch obtained in this manner, the pressure-sensitive adhesive layer has a pressure-sensitive adhesive property of at least 35 ° C. or higher so that it can be applied to the skin of the human body, and a temperature lower than that.
For example, at a temperature of 15 ° C or lower, the tackiness decreases or disappears to such an extent that it cannot be sensed with a finger touch, and the temperature-sensitive tackiness has a property that is significantly different from that of a conventional tackiness agent. .

When the blending ratio of the component A is less than 20% by weight, the special effect with respect to the temperature-sensitive adhesiveness is lost, and the temperature-sensitivity of ordinary pressure-sensitive adhesives is the same. Also,
If it exceeds 80% by weight, the temperature range where the non-to low-adhesive region changes to the adhesive region shifts to a direction higher than the target temperature of around 35 ° C, which is not suitable. Therefore, in the target temperature range (30 ~ 40 ℃) gives a large change in the adhesiveness,
Alternatively, the proportion of the component A which may be given is in the range of 20 to 80% by weight.

In addition, as for the B component, it is not possible to say unequivocally because a large number of types are possible depending on the usage (including auxiliary means such as addition of a plasticizer or a tackifier). For example, it gives a very hard polymer when it becomes a homopolymer such as (meth) acrylic acid, vinyl acetate, dimethyl acrylamide, diacetone acrylamide, or the glass transition point of the polymer is about 50 ° C. When a highly polar monomer that gives the above is used, it is desirable that the content is in a low content range (for example, 50% by weight or less in the component B or 30% by weight or less in all the monomer components), and conversely, an alkyl group is contained. In the case of (meth) acrylic acid having a side chain, it is possible to use up to the above-mentioned high content, and in particular, its glass transition point is low in the case of its homopolymer. More it can be used up to a higher content.

Furthermore, the size of the molecular weight of the obtained polymer also affects the temperature dependence of the tackiness. For example, if the content of A component is the same, the smaller the molecular weight of the polymer is, the lower the sticking-non-sticking transition temperature becomes. Therefore, it is not necessary to use a plasticizer. It is possible to increase.

With respect to plasticizers, it is used to reduce the temperature range in which tackiness is restored. Therefore, when the tackiness recovery temperature of the polymer alone is higher than the target temperature, the temperature range can be effectively lowered by adding an appropriate amount of the plasticizer. The addition amount of the plasticizer can be changed as necessary, but it is preferably 30% by weight or less in the adhesive base.

Regarding tackifiers, it depends on the softening temperature, but for those with a softening temperature of at least 50 ° C or higher, on the contrary, it has the function of raising the adhesive recovery temperature range and at the same time the effect of increasing the adhesive strength after recovery. Have The content of tackifier is also preferably less than 30% by weight in the adhesive base.

As described above, the main factor that is dominant in the temperature range in which the low (or non-) adhesive state is sensitively and largely changes from the low (or non-) adhesive state to the present invention is that the components A and B in the polymer are The ratio and the composition of the components, the added plasticizer and the tackifier, and the like, which have a wide range of arbitrary selections, can be combined to obtain the performance suitable for the purpose.

With regard to the component A, if the content ratio is the same, the acrylic acid ester type can make the adhesive recovery temperature range of the obtained polymer higher than that of the methacrylic acid ester type, and the ester residue The larger the carbon number is, the higher the adhesive recovery temperature is. Therefore, when selecting and determining the composition of the adhesive base of the present invention, it should be determined in consideration of their relationship.

In the present invention, the temperature dependence of the sharp tackiness mainly caused by the component A is presumed to be due to the following reason. That is, the linear alkyl group having 16 or more carbon atoms, which is the side chain of the component A, is in a crystallized state between the side chains below a specific temperature range, which brings about a non-adhesive appearance. When the temperature exceeds the temperature range, the crystallized state is rapidly released, which enables free micromotion of side chain molecules, and as a result, a sharp adhesive recovery phenomenon is shown. This leads to the effect of the adhesive base of the present invention, but the transition temperature from the crystallized state to the non-crystallized state (or in the opposite direction) has a specific composition of the A component and the B component and It is also possible to modify with a plasticizer and other added components.

(Example) Below, this invention is demonstrated based on an Example.

Example 1 Octadecyl methacrylate (component A) 60 parts by weight 2-ethylhexyl acrylate (component B-1) 20 parts by weight Butyl acrylate (component B-2) 20 parts by weight 1,6-hexanediol dimethacrylate (component B) −
3) 0.02 parts by weight The total amount of the above monomers was charged in a reaction vessel together with a solvent to carry out polymerization. As the solvent, a mixed solvent of ethyl acetate and n-heptane in a ratio of 2: 1 (weight ratio) was used, and an amount such that the entire monomer had a concentration of 62% by weight was added. Polymerization was carried out using lauroyl peroxide as a radical polymerization catalyst in a stream of N ₂ at 60 ° C. for 8 hours at 70 ° C.
The temperature was elevated to 8 ° C. for 8 hours, and the system boiling point (about 77 ° C.) for 12 hours. The total amount of the catalyst was 1.2% by weight based on the total amount of the monomers, and this was added in 10 batches, and the polymerization was completed 8 hours after the final addition of the catalyst.
During that time, the viscosity gradually increased as the polymerization proceeded and stirring became difficult, so the viscosity was adjusted while the solvent having the above composition was dividedly added as necessary.

After the polymerization was completed, a viscous polymer solution was obtained. The concentration of the polymer component in the obtained polymer solution is 38% by weight.
Met. The weight average molecular weight of this polymer (which was measured by the GPC method, the same applies hereinafter) was about 680,000.

Using the above polymer solution, the surface of the backing support was cast, dried, etc. to form a pressure-sensitive adhesive layer to prepare a patch. This pressure-sensitive adhesive layer had a good pressure-sensitive adhesive property at about 35 ° C. or higher, and substantially lost the pressure-sensitive adhesive property at 20 ° C. or lower, exhibiting the properties meeting the object of the present invention.

Example 2 Octadecyl acrylate (component A) 40 parts by weight 2-ethylhexyl methacrylate (component B-1) 40 parts by weight Butyl acrylate (component B-2) 20 parts by weight 1,6-hexanediol dimethacrylate (component B) −
3) 0.02 parts by weight Polymerization was carried out according to the same method and conditions as in Example 1 except that the monomer having the above composition was used and the concentration of all the monomers at the time of charging was 58% by weight. A different solution was obtained. The weight average molecular weight of the obtained polymer was about 520,000.

Further, the temperature at which the obtained polymer transitioned from the non-adhesive state to the adhesive state was about 45 to 55 ° C. Therefore, the transition region temperature was lowered by adding a small amount of a plasticizer as shown below.

<Preparation of adhesive base> Polymer solution (44% by weight concentration) 100 parts by weight Dioctyl phthalate 12 parts by weight The above composition was stirred and mixed by a mixer to obtain a final adhesive base solution. This solution was cast on the surface of the backing substrate and dried to form a pressure-sensitive adhesive layer to prepare a patch.

This adhesive layer has good adhesiveness at about 35 ° C and above,
Below 0 ° C, the tackiness was so low that it did not show tackiness by touch with the fingers.

Example 3 Octadecyl methacrylate (A component-1) 30 parts by weight Octadecyl acrylate (A component-2) 20 parts by weight Hexadecyl acrylate (A component-3) 20 parts by weight Ethyl acrylate (B component-1) 20 parts by weight Part Vinyl acetate (B component-2) 10 parts by weight Using the monomers having the above composition, the concentration of all the monomers at the time of charging was 55% by weight, and the solvent composition used was 3: 1 (weight ratio) of ethyl acetate to cyclohexane. Polymerization was performed according to the same method and conditions as in Example 1 except that the mixed solvent was used to obtain a viscous solution having a polymer concentration of 48% by weight. The weight average molecular weight of the obtained polymer was about 450,000.

Further, the temperature at which the obtained polymer transitioned from the non-adhesive state to the adhesive state was about 45 to 55 ° C. Therefore, the transition region temperature was lowered by adding a small amount of a plasticizer as shown below.

<Preparation of Adhesive Base> Polymer solution (48% by weight concentration) 100 parts by weight Olive oil 10 parts by weight The above composition was stirred and mixed by a mixer to obtain a final adhesive base solution. This solution was cast on the surface of the backing substrate and dried to form a pressure-sensitive adhesive layer to prepare a patch.

This adhesive layer has good adhesion at about 30 ° C or higher,
At ~ 20 ° C, it did not have tackiness due to the feel of the finger.

Example 4 Octadecyl methacrylate (A component-1) 50 parts by weight Octadecyl acrylate (A component-2) 10 parts by weight Acrylic acid (B component-1) 4 parts by weight Butyl methacrylate (B component-2) 36 parts by weight Polymerization was carried out according to the same method and conditions as in Example 1 except that the monomer having the above composition was used to obtain a viscous solution having a polymer concentration of 42% by weight. The weight average molecular weight of the obtained polymer was about 560,000.

Further, since the temperature at which the obtained polymer transitioned from the non-adhesive state to the adhesive state was higher than the temperature range of the object of the present invention, the transition region temperature was lowered by the following composition.

<Preparation of adhesive base> Polymer solution (42% by weight concentration) 100 parts by weight Dioctyl phthalate 8 parts by weight Ester gum 10 parts by weight The above composition was stirred and mixed by a mixer to obtain a final adhesive base solution. This solution was cast on the surface of the backing substrate and dried to form a pressure-sensitive adhesive layer to prepare a patch.

This pressure-sensitive adhesive layer had good tackiness at 25 to 30 ° C or higher, and did not have tackiness at a temperature below 25 ° C.

Comparative Example 1 2-Ethylhexyl Acrylate 50 parts by weight Butyl Acrylate 30 parts by weight Butyl Methacrylate 16 parts by weight Acrylic Acid 4 parts by weight A monomer concentration at the time of charging was set to 50 by using the monomer of the above composition.
Polymerization was carried out according to the same method and conditions as in Example 1 except that the concentration was 35% by weight to obtain a viscous solution having a polymer concentration of 35% by weight. The weight average molecular weight of the obtained polymer was about 430,000.

Further, the solution of the obtained polymer was cast on the surface of the backing substrate and dried to form a pressure-sensitive adhesive layer to prepare a patch.

This adhesive layer has strong adhesiveness up to around 10 ° C,
The tackiness did not suddenly disappear even at a temperature of ℃ or lower, and the temperature at which the tackiness gradually diminished and the tackiness by the substantial feel of the finger disappeared was about -15 ℃.

(Effects of the Invention) Since the adhesive base of the present invention is configured as described above, it has the following effects.

Since it has adhesiveness in the temperature range where it is applied to the skin, the patch prepared using the adhesive base can be applied to the skin without any trouble.

At temperatures below the transition temperature region, the adhesiveness of the adhesive base is greatly reduced, so that the drug contained in the adhesive base is kept more stable, for example, backing support layer, surface peeling. The drug does not migrate or exude to the protective paper sheet or the packaging paper layer or the like via the protective paper sheet. In addition, alteration of the drug itself is unlikely to occur.

For the same reason as above, it is possible to greatly reduce the exudation to the periphery due to the flow phenomenon of the adhesive bio-base or plaster layer during storage, resulting in stain and deterioration of usability.

For example, in the product composition, when the drug is aimed at a specific effect by making the drug ubiquitous in a specific portion (eg, near the surface layer, near the deep layer) in the adhesive plaster layer, If the adhesive is a storage agent, the drug diffuses into all the layers evenly even during storage, and it is very quick to homogenize, while the adhesive base of the present invention keeps its original state for a very long time. Can be maintained.

Even when it is peeled off from the skin, its tackiness can be reduced by, for example, slight local cooling (for example, cooling with a cooling tool), so that it can be peeled off from the skin without pain. This can prevent skin damage due to peeling of the patch for delicate skin such as women and young children.

The adhesive base can be produced inexpensively without using a special raw material, is non-irritating, and can be particularly widely used as an adhesive base for medical use.

Claims (3)

[Claims] 1. A medical adhesive base having an adhesive property at least at 35 ° C. or higher, which is an acrylic ester and / or methacrylic acid having a linear alkyl group having 16 or more carbon atoms as its ester residue. A medical adhesive base comprising a polymer mainly comprising an ester as a main component. 2. An alkyl having an average carbon number of 8 to 2 with 20 to 80% by weight of an acrylate ester and / or a methacrylic acid ester whose ester residue is a linear alkyl group having 16 or more carbon atoms. A medical adhesive base comprising as a main component a polymer containing 80 to 20% by weight of an acrylic acid ester and / or a methacrylic acid ester having a group as an ester residue. 3. The method according to claim 1, further comprising a plasticizer.
The medical adhesive base described.