JPH0474118A - Plaster - Google Patents

Abstract

PURPOSE:To obtain a plaster scarcely generating rash of skin, causing little staining of the skin even after sticking to the skin over a long period, resistant to peeling off and having excellent handleability by laminating a tacky adhesive layer containing a drug having transcutaneous absorbability to one surface of a film having a specific shape. CONSTITUTION:The objective plaster is composed of (A) a film layer consisting of a film having a thickness of 0.5-4.9mum, an elongation of 30-150% in each of two essentially perpendicularly crossing directions, an elongation ratio of 1.5-5.0 in the above directions and a strength of preferably 8-85 g/cm in two perpendicularly crossing directions and (B) a tacky adhesive layer composed of a tacky adhesive having a thickness of 260mum, laminated to one surface of the above film and containing a drug having transcutaneous absorbability (e.g. isosorbide nitrate and nitroglycerin). The film is preferably polyethylene terephthalate film containing 0.01-1 wt.% of fine solid particles having an average particle diameter of 0.01-1mum and not larger than 1.5 times the film thickness.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a patch that can be used for the treatment of various diseases.

<Prior art and problems to be solved by the invention> Oral administration and injection have traditionally been the administration routes for pharmaceuticals.

In addition to rectal administration, ointments and the like have been frequently used for local administration. Furthermore, in recent years, advances have been made in the development of techniques for longitudinally administering drugs that act on the whole body, and several types of drugs have actually come to be used clinically.

By administering drugs orally, for example, the first-pass effect that drugs undergo in the liver when administered orally can be avoided, thus maintaining a much more stable blood concentration of the drug compared to oral or injection administration. It has been found that orally administered preparations offer many advantages, such as long drug duration, ease of drug removal when serious drug-induced side effects occur, and the like.

Taking note of these advantages, many pharmaceuticals are being considered to change from conventional formulations to orally administered formulations.

However, as the clinical application of drugs for orally administered preparations advances, the difficulties of the orally administered route.

Problems have also become clear.

Some of them are as follows.

(1) The biggest problem with orally administered preparations is local irritation and skin irritation. According to some statistics, the incidence of skin irritation due to sealed meridian preparations is 20 to 50%.
%.

However, because of the advantages of orally administered preparations, patients often have no choice but to use irritating preparations even if skin irritation occurs.

(2) In general, many of the drugs currently in clinical use are difficult to absorb longitudinally, and even if they are absorbed longitudinally, the area of the patch must be large in order to absorb the clinically effective amount. It is necessary to use auxiliary agents.

However, increasing the application area or using an absorption enhancer often results in an increase in the area of skin irritation and worsening of the degree of skin irritation.

Therefore, there is a need for an orally administered preparation that can absorb a clinically effective amount of a drug while suppressing the occurrence of skin irritation.

(3) Conventionally, when orally administered preparations are applied for a long period of time, they not only become dirty, but also tend to peel off naturally, especially when taking a bath during that period.

However, changing the adhesive each time is not only troublesome, but also makes it difficult to control the dosage, does not provide sufficient medicinal efficacy, and poses problems in terms of appearance and hygiene.

Therefore, an orally administered preparation has been developed that is resistant to contamination and resistant to peeling off even when applied for a long period of time.

(4) Orally administered preparations are long-lasting preparations and are particularly effective for dominant diseases or diseases requiring long-term treatment.

A large proportion of patients with such diseases are elderly people who live in high places.

However, -a, elderly people are not good at handling things that require complicated explanations.

Therefore, there is a need for a orally administered preparation that is not only satisfactory in terms of absorbability and the like, but also has excellent handling properties for patients.

Means for Solving the Problems> The present inventors have developed a method that takes advantage of conventional orally administered preparations, reduces skin irritation, and allows even drugs that are difficult to be absorbed longitudinally to be absorbed in as much clinically effective amount as possible. The present invention has been arrived at as a result of extensive research into ways to create a formulation that is both easy to handle and easy to handle.

That is, the present invention has the following features: (1) The thickness is 0.5 to 4.9 μm, the elongation in two substantially perpendicular directions is 30 to 150%, and the ratio of the elongation in the two directions is 1.0. ~5.0 (however, if each elongation is not the same, the smaller elongation is used as the denominator), (the thickness of the film layer laminated on one side is 2 ~ This is a patch consisting of an adhesive layer having a thickness of 60 μm and containing a longitudinally absorbable drug.

The adhesive patch of the present invention has a specific film as one of its components. In order to reduce skin irritation, it is first important to reduce the physical irritation of the formulation. The thickness of the film used as the backing for the patch is important for this purpose. The smaller the thickness, the less stimulation there will be, so 4
．． The thickness is preferably 9 μm or less, and particularly preferably 4.0 μm or less because this tendency becomes remarkable. However, since patches are used by being applied to human skin, they need to be able to follow the expansion and contraction movements of human skin to some extent as a result of human activities. If the film is too thin, it may break, or if it barely follows the surface, it may cause severe skin irritation. Even if the thickness is reduced to 1.0 μm or less, not only the physical irritation does not change much, but also the inconveniences such as inconvenience in manufacturing increase. .

The purpose of attaching a film as a backing to a patch is to improve the sealing of the patch area and promote absorption, and to cover the licked adhesive surface, which can stick to clothes or skin if exposed, causing problems in management. It is for things such as doing. However, the thickness of the film and the material of the film are also related to this sealing performance, and the smaller the film thickness, the lower the sealing performance. In fact, when the thickness of the film is 5 μm or more, it is almost the same, and when it is less than 5 μm, especially 4 μm or less, the sealing performance tends to decrease in correlation with the thickness. Therefore, if the film thickness is less than 0.5 μm, it will be difficult to obtain sufficient sealing performance as a patch.

In addition, regarding the strength of the film, if the strength in two substantially orthogonal directions is 85 g/■ or more in each direction, the physical irritation will not be sufficiently small no matter how thin the film is.
/ cm or less, the preparation is likely to be damaged during application or use after application, making it difficult to use with confidence.

Regarding the elongation of the film, if the elongation in two directions substantially perpendicular to each other exceeds 150%, handling is poor;
If the elongation is less than 30%, physical irritation will be large and breakage will easily occur during application.

Furthermore, according to the study results of the present inventor, the ratio of the elongations in the two directions is 1.0 to 5.0 (however, if the elongations are the same, the smaller elongation is used as the denominator), In particular, when a film with a ratio of 1.0 to 3.0 is used, the adhesion feeling is good, but films with this ratio exceeding 5.0, that is, films with extremely low elongation in a certain direction. When using a film, the problem is that the film can sufficiently follow the expansion and contraction of the skin in that direction, resulting in a feeling of stiffness, making it uncomfortable to apply, and making it easy to peel off or break. This is likely to occur and is not appropriate.

Therefore, the film of the present invention has a thickness of 0.5 to 4.
9 μm, and the elongation in two substantially orthogonal directions is 3 in each direction.
0 to 150%, and the elongation ratio in the two directions is 1.0 to 150%.
5.0 (however, if the elongations are not the same, the smaller elongation is used as the denominator).

Further, it is preferable that the film of the present invention has a strength of 8 to 85 g/σ in each of two substantially orthogonal directions.

Strength as used in the present invention refers to the maximum load obtained until cutting according to the tensile strength measurement method of the Japanese Pharmacopoeia for "adhesive plasters" and converted into a load per unit liter, and elongation refers to the elongation at the time of cutting. shows.

In the present invention, it is further desirable that such a film has good stability over time and is highly safe, such as being unlikely to cause an allergic reaction when applied to human skin. As such a film, films made of polyolefins such as polyethylene and polypropylene; polyesters such as polyethylene terephthalate and polyethylene naphthalate; polyamides such as nylon 6 and nylon 66; ethylene-vinyl acetate copolymers, etc. can be used. These films may be used alone, or may be used in combination or in a laminated manner.

Among these films, films made of polyester, particularly polyethylene terephthalate, are preferred. Polyester film has good stability against heat and light for boat fishing, has little adsorption or interaction with drugs, and is highly safe for humans. Furthermore, even if the film has the above-mentioned specific thickness, it has appropriate sealing properties, meaning that the moisture permeability is appropriate and the moisture content of the stratum corneum of the skin at the site where the patch is applied helps the longitudinal absorption of the drug. This is preferable because the amount is sufficient for

In particular, the film thickness is 3.5 μm or less and the strength is 8.
When using an ultrathin film with a thickness of ~85 g/cm and an elongation of 45 to 150% in two substantially orthogonal directions, it can be stuck stably for a long time even if the adhesive thickness is 30 μm or less. This is a preferred embodiment.

Furthermore, the thickness is 1.0~2.0μm and the strength is 8~85t/
an, and the elongation in two substantially orthogonal directions is 45 to 45, respectively.
It is surprising that when a thinner film of 150% is used, it can be applied to human skin with sufficient stability even when the thickness of the adhesive layer is 2 to 15 μm, especially 10 μm or less. .

For example, a film with a thickness of 10 μm
It is possible to make a patch with a μm adhesive attached.

However, the adhesion to human skin and its stability are surprisingly different between this case and the case of the present invention in which a 10 μm adhesive layer is attached to an ultra-thin film with a thickness of 1.0 to 2.0 μm. This film is significantly better.

One reason for this is that human skin has unevenness when viewed microscopically, and a film of normal thickness does not follow the unevenness of the skin, whereas the film of the present invention does not follow the unevenness of the skin. It is also speculated that even a very small amount of adhesive layer can exhibit sufficient adhesive strength.

The adhesive patch of the present invention has an adhesive layer laminated on one side of the film layer, the adhesive layer having a thickness of 2 to 60 μm and containing a longitudinally absorbable drug.

-i, the thickness of the adhesive layer is preferably as small as possible so long as it can maintain the necessary amount of meridically absorbable drug such as crude drug and stably apply the patch to human skin. The smaller the size, the less the amount of adhesive used, which is more economical. What is even more important is that in order to reduce the residual amount of various solvents used to create the adhesive layer, which causes skin irritation, the smaller the adhesive layer thickness is 60 μm or less, the more important it is. be advantageous to

In the present invention, since a film having a specific elongation is used as the film layer, peeling of the patch during application can be extremely reduced even if the thickness of the adhesive layer is small.

The objects of the present invention are (1) a patch that can suppress the occurrence of skin irritation, (2) a patch that can suppress skin irritation and absorb a clinically effective amount of a drug, and (3) a patch that can be applied for a long period of time. The objective is to provide a patch that is difficult to peel off, and the measures to achieve this objective are as described above.

Another object of the present invention is to provide a patch with excellent handling properties. In particular, as mentioned above, the goal of reducing skin rash is to use an ultra-thin film layer and an ultra-thin adhesive layer; However, since it has an adhesive layer, the adhesive layers tend to stick together, making it difficult to use it stably.

In the present invention, (a) the thickness is 0.5 to 4.9 μm, the elongation in two substantially orthogonal directions is 30 to 150%, and the ratio of the elongation in the two directions is 1.0. ~5. O (however, if the elongations are not the same, the smaller elongation will be used as the denominator). an adhesive layer consisting of an adhesive containing an absorbable drug; and (1) a surface state attached to part or all of the surface of the film layer opposite to the surface on which the adhesive layer is laminated. a support, and the adhesive force between the planar support and the film layer is smaller than the adhesive force between the film layer and the adhesive layer. It has been found that the above-mentioned problems can be overcome by this method.

Such a support is, in principle, used to first apply the patch of the present invention to human skin and then remove it, leaving only the film layer and adhesive layer.

By doing this, when handling the patch, the patch will not curl or tear due to the support, and the patient can easily apply it to the patient's private area.

Since this planar support is removed after application to a private area, the characteristics of the film layer are fully exhibited during application, and several benefits such as reducing skin irritation are achieved.

As a measure for the same purpose, for example,
One such measure has been proposed as shown in Japanese Patent No. 260. However, no detailed study has been made on the structure of the patch body as in the present invention.

Since an extremely thin film is used in the present invention,
The adhesion between the support and the film layer is important. If the adhesion between the support and the film layer is too strong, problems such as the film layer being torn when the support is removed from the film layer or the formulation peeling off from the skin tend to occur. According to the study results of the present inventors, it is important that the adhesive force between the support and the film layer is smaller than the adhesive force between the film layer and the adhesive layer.

More specifically, the adhesive force between the support and the film layer is 2Lr.
If it exceeds /12an, the film layer will be more likely to break when the support is removed from the film layer. Theoretically, when the strength of the film is 8 to 85 g/(7), the adhesion force is greater than 3 to 20 g/12 an, for example 24 g/12
It is thought that the film will not tear even if the adhesive strength exceeds 2C1g/12cm, that is, 8g per 1α unit width, but in actual preparations, if the adhesive strength exceeds 2C1g/12 countries, the film will break frequently, and the patch will not be suitable for humans. It may peel off from the skin. Moreover, if it is less than 3 g/12 an, the layer between the support and the film layer will peel off during manufacturing, storage, or handling, making it impossible to achieve the desired purpose. Therefore, the preferred adhesion is between 3ir/12cx and 20g/12aa.

Adhesion in the present invention refers to cutting a film layer and a support attached to the film layer preferably through a suitable adhesive into a slit shape with a width of 12an, and cutting the support or film in a 90° direction. It refers to the load (gr) when peeling off at a speed of 30c++/min. When the film and the support are partially attached in the form of slits or dots, measure the load (gr) when peeling off the attached part, and calculate that value as a width of 1.
The value is converted to 2aa equivalent.

In the present invention, a more preferable formulation can be obtained by adjusting the stiffness of the planar support.

The stiffness of the planar support is determined by, for example, JIS P-8143.
The stiffness can be determined by the stiffness test method (■3/100), but preferably the stiffness is 0.0.
It is 8 or more, more preferably 0.27 or more.

The base material for the planar support is polyethylene.

Polyolefins such as polypropylene; Polyesters such as polyethylene terephthalate and polyethylene naphthalate; Polyamides such as nylon 6 and nylon 66; Ethylene-vinyl acetate copolymers; Films, non-woven fabrics, paper-like materials, woven and knitted fabrics such as polyvinyl alcohol etc. can be used. Also, natural or recycled ordinary woven or knitted fabrics for clothing, such as cotton or acetate, can also be used.

The adhesion of the film layer to the base material of a planar support made of such a film, nonwoven fabric, #li knitted fabric, etc. can be achieved by heating either or both of the base material of the support and the film layer as necessary. Pressing can be carried out by using an adhesive substance such as a pressure-sensitive adhesive or a glue between the two-sided support and the film layer.

Particularly good results are obtained when a woven or knitted fabric is used as the base material of the planar support and an adhesive substance such as polyvinyl alcohol, vinyl acetate, polyvinylpyrrolidone, acrylic copolymer, sorbitol, or starch is used as the adhesive substance. Cheap.

That is, the planar support is attached to the film layer during handling of the patch, and is removed as necessary after the patch is applied to human skin. However, the patch
During storage, keep it sealed in an aluminum bag, etc. If methanol, ethyl acetate, water, etc., which are the solvents used for the adhesive used to attach the planar support to the film layer, remain, these may During storage of the patch, the residual solvent tends to migrate and diffuse into the drug-containing adhesive layer. This may lead to the occurrence of skin irritation and a decrease in the stability of the drug over time.

In order to eliminate such inconveniences, it is necessary to ensure that the solvent used to attach the planar support and the film layer does not remain. However, if the planar support consists of a film layer, it is necessary to prevent the solvent, etc. It is difficult to completely remove it and requires special ingenuity in production methods. In this case, since the adhesive patch of the present invention uses a specific film as a backing, if the process is complicated,
The film tends to break or wrinkle, reducing production efficiency. However, when the planar support is a woven or knitted material, the vapor of the solvent etc. easily escapes from the weaving or knitting opening, so that the solvent etc. can be removed extremely easily, which is a preferred embodiment.

In particular, by combining a planar support made of a woven or knitted fabric with a film, adding an adhesive solution over the woven or knitted fabric, and then heating, the planar support and film can be bonded together without worrying about residual solvent. Can be attached. Alternatively, a method is adopted in which an adhesive substance is attached in advance to a planar support made of woven or knitted fabric, and after drying or as it is attached to the film layer, heating or air drying is performed to remove residual solvent as necessary. can. The adhesive layer containing the drug can be attached to the film layer before or after attaching the planar support, but since drugs are generally unstable to heat, the adhesive layer containing the drug can be attached to the film layer and the planar support in advance. It is preferable to keep the body attached.

In the present invention, the adhesive surface between the planar support and the film layer may be the entire surface or a part of the film layer, but even if the adhesive force between the planar support and the film layer is small, the adhesive patch can be When trying to remove only the planar support after pasting, the problem tends to occur that the extremely thin film is also peeled off. In order to prevent this, instead of having the surface of the planar support and the surface of the film layer completely adhered, it is also possible to create a part where both sides are not attached, that is, they are simply overlapped. This is a desirable aspect. The patient can more easily remove the planar support from this unattached portion. In order to create a surface where part of the surface of the planar support and the surface of the film layer are not attached, it is also useful to place, for example, a film, paper, cloth, etc. with a thickness of 5 to 100 μm between the two surfaces. be.

It has been found that the patient can remove the planar support very easily, especially when the non-adherent portion of the surface of the planar support and the surface of the film layer is at the edge of the patch. Moreover, the patient can only hold the planar support from this end by, for example, 90' or 18'.
Since the patch is removed by pulling in the 0° direction, the risk of the patch peeling off from the human skin and the risk of the film layer breaking is reduced.

Particularly preferred is the patch of the present invention, which uses an ultra-thin, low-strength film that causes less skin irritation to patients, and which uses a thin adhesive layer.

Examples of the drug of the present invention include isosorbide nitrate, nitroglycerin, and buprenorphine hydrochloride.

Morphine, estradiol, progesterone.

Ketotifen, vinpocetine, nicotine, their derivatives, and other known meridian-absorbing drugs are blended together, and the content is, for example, 0.1 to 20% relative to the adhesive.
% can be used.

In particular, the present invention is suitable for drugs that are expensive, used in excessive amounts, or have some type of skin defect that may cause serious problems if abnormal skin absorption occurs. The use of an adhesive layer is preferable because the amount of drug used can be extremely reduced. Examples of such drugs include fermentable analgesics such as buprenorphine hydrochloride and morphine, and hormonal agents such as estradiol and progesterone derivatives.

In the present invention, it is preferable to use a polyester film as the above-mentioned film layer. Normally, a small proportion of solid fine particles are present in a polyester film for the purpose of improving its slipperiness, but what kind of influence does such solid fine particles have on a patch like the present invention? There was not enough knowledge.

As a result of intensive study on this point, the present inventor found that the amount of solid fine particles present in the polyester film layer is 0.01 to
It has been found that it is important that the average particle size is 1% by weight, that the average particle size is 0.01 to 1 μm, and that the average particle size does not substantially exceed 1.5 times the thickness of the polyester film.

Examples of the solid fine particles include: (1) silicon dioxide, (2) alumina, (2) silicates and aluminosilicate compounds containing 30% by weight or more of silicon dioxide, (4) magnesium, zinc,
Oxides of one or more metals selected from zirconium and titanium, ■ Sulfates of one or more metals selected from calcium and barium, ■ Phosphates of one or more metals selected from lithium, sodium, and calcium, ■ Calcium, barium , zinc, terephthalate of one or more metals selected from manganese, ■magnesium, calcium.

Titanates of one or more metals selected from barium, iron, cobalt, manganese, nickel, etc., one selected from calcium and magnesium, 0 carbon, O glass, and inorganic or organic solid fine particles such as crosslinked polystyrene. I can give an example. Of course, these may be used alone or in combination of two or more.

If the amount of such fine particles is less than 0.01% by weight, it is not preferable because the slipperiness tends to be insufficient.
In addition, if the amount exceeds 1% by weight, the longitudinal absorbability of the drug may not be sufficiently satisfied, which may be undesirable as a pharmaceutical preparation.

In addition, if the average particle size is less than 0.01 μm, the slip properties may be insufficient and the handling property may not be fully satisfied, and if the average particle size is more than 1 μm or more than 1.5 times the thickness of the film. If it falls within this range, the meridional absorbability of the drug may not be fully satisfied, as described above. This may be because in such cases, water evaporation and air permeability become too large due to voids between the particles and the film layer.

As described in detail above, the patch of the present invention is a patch that is easy to handle and has low skin irritation.

<Example> The present invention will be explained in further detail by referring to Reference Examples and Examples below. Parts in Examples indicate parts by weight.

The characteristics appearing in the examples were measured by the following methods.

Reference example (1) Adhesive solution (1) 2-ethylhexyl acrylate 97.4 parts, methacrylic acid 2.5 parts, polyethylene glycol (polymerization degree 14
) Dimethacrylate 0.1 part, benzoyl peroxide 1.0
100 parts of ethyl acetate were charged into a reaction vessel equipped with a reflux condenser and a stirrer, and polymerization was continued for 9 hours under a nitrogen atmosphere [70°C with slow stirring. Polymerization conversion rate is 9
It was 9.5%.

500 parts of ethyl acetate was added to the obtained polymer solution to adjust the solid content concentration to about 20%.

+21BN blood concentration measurement method After separating plasma from 1 ml of collected blood,
urnal of chromatography,
338 (1985) 89-98) by the GC-MS method.

(3) Progesterone blood concentration measurement method After separating serum from 1 ml of collected blood, it was analyzed by radioimmunoassay.

Example 1 After adding 8.8 parts of progesterone to 500 parts of an adhesive solution with a solid content concentration of 20% +1, the thickness of the adhesive layer after drying was 1 on a silicone-coated release film.
Coat to a thickness of 5 μm and heat at 70'C for 3 minutes at 110°C.
The soot was closed and dried for 3 minutes. The remaining amount of ethyl acetate in the resulting adhesive layer was 18 ppm, and the progesterone content was 1.3.
It was t/rd.

On the other hand, a polyester fabric with a basis weight of 32 g/rrP was impregnated with a 10% aqueous solution of polyvinyl alcohol (degree of polymerization 500), so that after drying, the polyvinyl alcohol amounted to 25% by weight based on the fabric. Stiffness of the fabric containing the polyvinyl alcohol (cm3/100)
was 6.2.

The fabric impregnated with polyvinyl alcohol and dried was wetted with water and pressed onto a polyethylene terephthalate film having a thickness of 1.3 μm, strength and elongation in two orthogonal directions of 22 and 32 g/α, respectively, and 75 to 35%. Drying at °C yielded a bonded laminate.

The adhesion force between the film and the fabric of the adhesive laminate is 5f/12
It was cx. Mana stiffness (an' /100) 4.
It was 8. A thickness of 1 containing 1.3 t/rd of progesterone on the free side of the film of the adhered laminate.
A 5 μm adhesive layer was pressure-bonded.

The original fabric of the patch obtained was cut to a size of 3α×3α and applied to the back of a dehaired rat weighing 180 g, and then the fabric serving as the planar support was peeled off. Substantially no polyvinyl alcohol remained on the surface of the film. Subsequently, blood was collected at a predetermined time, and the progesterone level in the serum was measured by radioimmunoassay. The results and the condition of the rat skin after 24 hours of application are shown in Table 1.

Examples 2 to 4 and Comparative Examples 1 to 2 Ten gesterone patches were obtained in exactly the same manner as in Example 1 using the films listed in Table 1, and a rat patch test was conducted. The results are shown in Table 1. .

Test Example 1 A pressure-sensitive adhesive solution (1) having a solid content of 20% was applied onto a silicone-coated release film to obtain pressure-sensitive adhesive layers of different thicknesses. The drying conditions after coating were 70℃ for 3 minutes, 1
The temperature was kept at 10° C. for 3 minutes, and the amount of ethyl acetate remaining in the resulting adhesive layer was measured by gas chromatography.

On the other hand, a woven fabric made of polyester and having a basis weight of 32irlrd was impregnated with a 10% aqueous solution of polyvinyl alcohol (degree of polymerization 500) to produce planar supports containing different amounts of polyvinyl alcohol relative to the dried woven fabric.

The dry planar support and polyethylene terephthalate films of different thicknesses were pressure-bonded in the same manner as in Example 1 to obtain an adhered laminate, and the adhesion force between the film and the fabric of the adhered laminate was measured.

The previously obtained adhesive layer was combined and pressure-bonded to the free surface of the film of the adhered laminate as shown in Table 2.

The original fabric of the resulting drug-free placebo patch was cut to a size of 3α x 3af+ and placed on the backs of five healthy male adults (age 22-45, weight 55-82). Apply the preparation to 12 sheets in total, 1 sheet at a time, and check the feeling of use and 4
Evaluate the condition of skin irritation after applying for 8 hours. Judgment is based on the sum of the scores of 5 people, with no response being 0, slight erythema being 1, obvious erythema being 2, and papules, etc. occurring being 3.

The test conditions and results of this test are summarized in Table 2.

These results show that skin irritation suddenly increases when the film thickness exceeds approximately 5 μm, and that even if an adhesive layer of the same thickness and adhesive strength is used, the backing film thickness is approximately 5 μm.
It can be seen that when it exceeds m, it suddenly decreases. It is also found that when the elongation of the film is less than about 30%, the film is easily torn during application to humans or handling of the preparation. In addition, when the adhesive force between the planar support and the film increases, even if you carefully remove only the planar support from the film, the film is a weak material and will easily tear, and the thickness of the adhesive layer It can be seen that the larger the value, the larger the skin rash.

Example 5 Buprenorphine hydrochloride was prepared in exactly the same manner as in Example 1, except that buprenorphine hydrochloride was used instead of progesterone in Example 1, and the thickness of the adhesive layer containing buprenorphine hydrochloride after drying was 7 μm. 0.5
A patch containing 6irlrd was obtained, size 3 an
The sample was applied to the back of a 3 cm hair-removed rat (n=3), and blood was collected before and 2,8, and 24 hours after the application to measure the concentration of buprenorphine in the serum, which was 0.4j,
6.0.5.8 (ng/ml), indicating a good analgesic effect. There was no skin rash at all on the skin area after the drug was removed.

In addition, despite using an extremely thin adhesive layer of 7 μm, which is not seen in conventional patches, it has sufficient adhesion to the skin, and the amount of expensive bubrenorphine hydrochloride used can be greatly reduced. could be reduced.

Example 6 A patch was prepared in exactly the same manner as in Example 5 except that nicotine was contained instead of bubrenorphine hydrochloride.

This patch was applied to the backs of rats, and it was confirmed that no skin irritation occurred.

Example 7 A patch was prepared in exactly the same manner as in Example 5 except that estradiol was contained instead of buprenorphine hydrochloride. This patch was applied to the backs of rats, and it was confirmed that no skin irritation occurred.

Procedure Supplement ■January 93, 1991 To the Director General of the Japan Patent Office 1, Indication of the Case Patent Application No. 187092 Patch (1) The following parts of the specification■ Page 17, No. 2nd line, 5th line, 6th line, 8th line, 10th line, 7th line from the bottom (there are 2 locations), and 4th line from the bottom, ■ Page 18, No. 2nd line, ■ Page 27, 3rd line from the bottom, and ■ Page 32, ``Table 2,'' 3rd to 4th lines, ``Adhesive force'' column, unit display: '12cm.'' I corrected it to "r12mm".

that's all

Claims (1)

[Claims] 1. (a) The thickness is 0.5 to 4.9 μm, and the elongation in two substantially orthogonal directions is 30 to 150%, and the ratio of the elongation in the two directions is 30 to 150%. is 1.0 to 5.0 (however, if each elongation is not the same, the smaller elongation is used as the denominator), (a) laminated on one side of the film layer; The thickness is 2
A patch comprising an adhesive layer comprising an adhesive having a length of ~60 μm and containing a longitudinally absorbable drug. 2. (A) The thickness is 0.5 to 4.9 μm, the elongation in two substantially orthogonal directions is 30 to 150%, and the ratio of the elongation in the two directions is 1.0 to 5. .0 (however, if each elongation is not the same, the smaller elongation is used as the denominator), (a) a film layer laminated on one side with a thickness of 2
A pressure-sensitive adhesive layer consisting of a pressure-sensitive adhesive containing a longitudinally absorbable drug with a diameter of ~60 μm; and (c) adhered to part or all of the surface of the film layer opposite to the surface on which the pressure-sensitive adhesive layer is laminated. and a planar support, characterized in that the adhesive force between the planar support and the film layer is smaller than the adhesive force between the film layer and the adhesive layer. patch. 3. The adhesive patch according to claim 2, wherein the support is a fabric made of a nonwoven fabric, a paper-like material, and/or a woven or knitted fabric. 4. The adhesive patch according to claim 1 or 2, wherein the film layer and the adhesive layer are attached to a part or the entire surface of these layers. 5. The elongation of the film layer in two substantially perpendicular directions is 30 to 150%, and the ratio of the two directions is 1.0 to 3.0.
(However, if each elongation is not the same, the lower elongation is used as the denominator). 6. Claim 1, wherein the film is a polyester film.
5. The adhesive patch according to any one of 5 to 5. 7. The polyester film has an amount of solid fine particles present in the film layer of 0.01 to 1% by weight, and an average particle diameter of 0.01%.
7. The adhesive patch according to claim 6, which is a polyester film having a particle diameter of 1 μm and an average particle diameter substantially not exceeding 1.5 times the thickness of the polyester film. 8. The patch according to any one of claims 1 to 7, wherein the adhesive is an acrylic resin adhesive. 9. The drug is isosorbide nitrate, nitroglycerin, buprenorphine, estradiol, progesterone,
The patch according to any one of claims 1 to 8, which is one or more drugs selected from ketotifen, vinpocetine, nicotine, and derivatives thereof.