JPH04244019A - Patch for medical application - Google Patents

Abstract

PURPOSE:To obtain a patch for medical application, transferring a medicine to organisms as rapidly as possible, successively maintaining effective medicine concentration in blood for a long period of time, having extremely low irritation to skin face applied. CONSTITUTION:A tacky polymer substance layer 1 containing a medicine for percutaneous absorption is laminated to one side of a substrate 2 having high moisture permeability and a covering material 3 having low moisture permeability is laminated to the other side in a readily peelable state. A substance to change color by moisture absorption is preferably contained to readily recognize a release period of the covering material.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical patch, and more particularly to a medical patch that can efficiently absorb drugs transdermally while reducing skin irritation when applied to the skin.

0002

BACKGROUND OF THE INVENTION In recent years, various transdermal absorption preparations have been developed as preparations for administering drugs into living bodies, and among these, patches have attracted attention from the viewpoint of ease of handling and strict control of dosage. One of the superior features of patches compared to other preparations is that the blood concentration of the drug can be maintained within the effective therapeutic range for a long period of time (durability of effect). In addition, in drug therapy, an important characteristic required is that the blood concentration quickly reach the effective therapeutic range (fast-acting), but there are only a few developed patches that have both the above-mentioned long-lasting and quick-acting properties. is the reality.

[0003] The basic structure of the above-mentioned patch is usually a laminate of a moisture-impermeable support and an adhesive polymer layer containing a drug, and occlusive dressing therapy (ODT) is achieved by laminating the support.
This improves the transdermal absorption of drugs. However, ODT is a therapy that loosens the stratum corneum of the skin by making the skin stuffy, so it tends to irritate the skin, and although the transdermal absorption of the drug is good, it tends to cause skin irritation. have a problem

On the other hand, preparations that suppress skin irritation by using a support with high moisture permeability have been proposed, but ODT may not be able to be performed sufficiently, and quick effects may not be expected, and sometimes effective treatment may not be possible. The blood concentration of the drug within the range may not be reached.

[0005]

SUMMARY OF THE INVENTION Therefore, the present invention solves the above-mentioned drawbacks of conventional patches for transdermal absorption of drugs, and allows drugs to be transferred into the body as quickly as possible to maintain a sustained state over a long period of time. An object of the present invention is to provide a medical patch that can maintain an effective blood concentration of a drug and suppress irritation to the skin.

[0006]

[Means for Solving the Problems] Therefore, the present inventors have made extensive studies to achieve the above object, and as a result, have developed an adhesive polymer material layer containing a drug on a support having a moisture permeability above a specific level. The inventors have discovered that the above object can be achieved by laminating a cover material with low moisture permeability on the other surface of the support in an easily peelable state, and have completed the present invention.

That is, in the present invention, an adhesive polymer material layer containing a drug for transdermal absorption is laminated on one side of a support having high moisture permeability, and the other side has a moisture permeability of 250 g/m2/24 h.
The present invention provides a medical patch characterized in that the following low moisture permeability cover material is laminated in an easily peelable state.

[0008] The support used in the present invention has relatively high moisture permeability, and is preferably flexible in terms of its ability to follow the movement of the skin surface. Examples of the material for such a support include polyolefin, polyester, polyvinyl alcohol, polyurethane, polyvinyl chloride, polyvinylidene chloride, polyamide, polytetrafluoroethylene, etc.; It is used in the form of These supports may be a single layer or a laminate, or may be a metal vapor deposited body. Note that if the material of the support itself does not have high moisture permeability, perforation treatment may be performed to impart moisture permeability to the support. In addition, the thickness of the support is not particularly limited as long as it has high moisture permeability, but it is usually 5 to 10
It is set to about 00 μm.

The adhesive polymer material layer formed on one side of the support contains and retains a drug for transdermal absorption to be administered into a living body, and has the function of storing and retaining the drug;
It has both the function of releasing drugs to the skin surface and the function of adhesion to the skin surface. Examples of the polymeric substances forming this layer include silicone rubber, polyisobutylene rubber, polyisoprene rubber, styrene-isoprene (or butadiene)-styrene block copolymer rubber, acrylic rubber,
Synthetic rubbers such as gum arabic and natural rubbers, (meth)
Adhesives such as acrylic adhesives, vinyl ether adhesives, silicone adhesives, etc., which are polymerized using an acrylic acid alkyl ester as a main monomer can be used. Furthermore, measures such as adding various liquid substances to these adhesives or subjecting them to crosslinking treatment may be taken in order to adjust the cohesive force.

[0010] Drugs for transdermal absorption are drugs that are administered transdermally into living bodies to exert therapeutic or preventive effects on various diseases, and are not limited to the type. Examples of pharmacological effects include corticosteroids, anti-inflammatory analgesics,
Hypnosedatives, tranquilizers, antihypertensives, antihypertensive diuretics, antibiotics, anesthetics, antifungals, vitamins, antiepileptics, coronary vasodilators, antihistamines, antitussives, sex hormones, antidepressants, brain Circulation improvers, antiemetics, antitumor agents, enzyme inhibitors, biomedicines (polypeptides), and the like can be used. The content of these drugs in the polymeric material layer can be arbitrarily set depending on the pharmacological effect and purpose of use.

[0011] In the medical patch of the present invention, the patch in which an adhesive polymer material layer containing a drug for transdermal absorption is laminated on one side of the support has high moisture permeability and does not cause skin irritation. plays an important role in suppressing The moisture permeability of a patch with this configuration is preferably 350 g/m2/
24 hours or more, more preferably 500g/m2/24
It is preferable to set it to h or more in order to reduce skin irritation when it is attached to the skin surface for a long time.

The medical patch of the present invention has a moisture permeability of 250 g/m2/24h on the other side of the patch support having the above structure.
It is made by laminating the following low moisture permeability cover materials in an easily peelable state. In other words, by providing a low moisture permeable cover material on the other surface of the support, that is, on the back surface, when the medical patch of the present invention is first applied to the skin surface, the OD
T can be performed to loosen the stratum corneum on the applied skin surface. Therefore, drugs for transdermal absorption can be absorbed transdermally in a short period of time, and rapid efficacy can be expected. However, if this condition continues for a long period of time, skin irritation will occur, so in the present invention, the covering material is peeled off at an appropriate time after application to the skin surface, giving moisture permeability to the patch and preventing skin irritation. In addition to reducing the effects of the drug, efforts are made to maintain the pharmacological effect.

[0013] In order to perform ODT, such a cover material should have a moisture permeability value of 250 g/m2/24 h or less and a thickness of about 5 to 1000 μm, and should have a low permeability. The material is not particularly limited as long as it has humidity, and the materials exemplified for the support can be used. In addition, such a cover material is laminated to the support in a releasable state, but it must be adhered to the support with at least an adhesive force that is smaller than the adhesive force between the adhesive polymer material layer and the support. . Specific methods for removably laminating include a method in which the back surface of the support is subjected to a release treatment and a cover material is laminated via an adhesive, a method in which a weakly adhesive adhesive layer is interposed, and a cover material is laminated. Examples include a method of laminating with rubber latex particles interposed therebetween, a method of laminating by thermocompression bonding, and the like.

[0014] It is preferable that the above-mentioned cover material is peeled off when sufficient ODT is applied, but the transpiration of moisture from the skin surface varies from person to person, and even in the same individual, for example, diurnal fluctuations and seasonal fluctuations occur. Furthermore, the amount of hydration in the skin is large after taking a bath, and the ODT effect appears relatively early. Therefore, in order to peel off the cover material when a certain ODT effect appears, for example, if the medical patch of the present invention contains a substance that changes color due to changes in humidity, it is possible to Easy to recognize. Although the content is not particularly limited, it is usually 0.1 to 20% by weight, preferably 1% by weight based on the total weight of the layer containing the color-changing substance.
~10% by weight.

[0015] Examples of such substances include cobalt ions. Cobalt ions have a blue color when not absorbing moisture, and change to a red color when they absorb moisture. Therefore, since cobalt ions evaporate from the skin surface and change color due to water (moisture) absorbed into the patch, the effect of the present invention can be maximized by peeling off the cover material after the color change occurs.

The above-mentioned color-changing substance may be contained in at least one of the support, the adhesive polymer layer, and the cover material constituting the medical patch of the present invention, but preferably in the support or the cover material, More preferably, it is contained in the cover material. However, when incorporating it into the cover material, it is necessary to prevent it from being affected by atmospheric moisture that penetrates from the back side of the cover material, so it must be overcoated with a non-moisture-permeable film or treated to make it non-moisture-permeable. is preferred. Further, it is preferable that the cover material contains a discoloration substance, since the degree of discoloration can be easily recognized by whitening the support.

[0017] Furthermore, the color-changing substance does not necessarily have to be contained in the above-mentioned layer, but may be contained in a medical patch; for example, it can be contained in a water-soluble polymer and placed between the cover material and the support, or between the support and the adhesive. It can also be interposed between a polymer material layer and a polymer material layer. By using a water-soluble polymer, water absorbed from the skin surface quickly reaches the color-changing substance, so a color change reaction (response) occurs sensitively. Water-soluble polymers include highly saponified polyvinyl alcohol, polyalkylene oxide, crystalline water-soluble polymers such as cellulose, polyvinylpyrrolidone, polyalkylene oxide, or polyalkyl ether crosslinked products, polyhydroxyethyl methacrylate, gelatin crosslinked products, Water-soluble polymer crosslinked products such as polyacrylic acid crosslinked products can be preferably used.

[0018]

[Example] The medical patch of the present invention will be explained in detail with reference to Examples below.

Example 1 A sticky polymer material obtained by copolymerizing 95 parts by weight of acrylic acid 2-ethylhexyl ester and 5 parts by weight of acrylic acid was added with isosorbide dinitrate (20% by weight). (hereinafter abbreviated as ISDN) to form an adhesive polymer material layer (40 μm thick) containing a drug for transdermal absorption.

Next, the above polymer was applied to the EVA side of a laminated support consisting of a 9 μm thick polyethylene terephthalate (hereinafter abbreviated as PET) film and a 30 μm thick ethylene/vinyl acetate copolymer (hereinafter abbreviated as EVA) film. The material layers were laminated to form a patch. This patch has a moisture permeability of 350g/m2/24 by perforating the support.
It was adjusted so that it was more than h. The PET film used had its back surface treated with silicone.

On the other hand, the adhesive polymer material copolymerized above is laminated to a thickness of 10 μm on the same PET film as above, and this is used as an adhesive sheet-like low moisture permeable cover material (moisture permeability 70
g/m2/24h) and adhered to the support surface of the patch prepared above to obtain a medical patch of the present invention as shown in FIG.

[0022] This medical patch was cut into pieces of 30 mm in diameter and applied to the chest skin of five subjects for 3 hours, and then the cover material was peeled off and the application was continued. The effective blood concentration was maintained for 48 hours, confirming the pharmacological effect. Furthermore, no skin irritation (rash) was observed.

Example 2 On the other hand, the degree of saponification was 99.5 mol%, the average degree of polymerization was about 1700
A color-changing substance-containing layer (20 μm thick) prepared from 15 parts by weight of polyvinyl alcohol (hereinafter abbreviated as PVA) and 1 part by weight of cobalt chloride was placed on a porous support made of polytetrafluoroethylene (hereinafter abbreviated as PTFE). Body (60
(μm thickness, moisture permeability 4000g/m2/24h) by a casting method. Note that the support and the color-changing substance-containing layer were laminated in such a manner that they could be easily peeled off.

Next, the low moisture permeability cover material used in Example 1 was adhered to the discoloration substance-containing layer side of the laminate, and the same ISDN-containing adhesive polymer as used in Example 1 was then applied. A material layer was attached to the support side of the laminate to obtain a medical patch of the present invention as shown in FIG. The moisture permeability of the laminate of the support and the adhesive polymer material layer is 1400.
g/m2/24h.

[0025] When this medical patch was cut into 45 mm diameter pieces and applied to the chest skin of five subjects, the entire surface of the patch, which was blue before application, gradually changed color, with an average of about 2.
After some time, the entire surface turned pink. Thereafter, when the cover material was peeled off and the application was continued, ISDN quickly reached the effective blood concentration range, and the effective blood concentration was maintained for 48 hours, confirming the pharmacological effect. Also,
No skin irritation (rash) was observed.

Example 3 A sticky polymer substance obtained by copolymerizing 55 parts by weight of 2-ethylhexyl acrylate, 25 parts by weight of 2-methoxyethyl acrylate, and 20 parts by weight of vinyl acetate contained Theophylline was contained in an amount of 20% by weight to form an adhesive polymer material layer (80 μm thick) containing a drug for transdermal absorption.

Next, the above-mentioned polymer material layer was laminated on one side of a 12 μm thick polyethylene porous support (moisture permeability 3000 g/m 2 /24 h) to prepare a patch. The back surface of this support was treated with silicone.

On the other hand, the low moisture permeability cover material used in Example 1 was adhered to the support surface of the patch prepared above to obtain a medical patch of the present invention.

[0029] This medical patch was cut into 30 mm diameter pieces and applied to the chest skin of five subjects for 2 hours, and then the cover material was peeled off and the application continued. As a result, theophylline quickly reached the effective blood concentration range. The effective blood concentration was maintained for 24 hours, confirming the pharmacological effect. Furthermore, no skin irritation (rash) was observed.

[0030]

Effects of the Invention As described above, the medical patch of the present invention has a drug-containing adhesive polymer material layer formed on a support having a moisture permeability above a specific level, and a transparent adhesive layer on the other side of the support. Because it has a structure in which a backing member with low moisture content is laminated in a state that is easy to peel off, the drug contained therein is quickly transferred into the body, and the effective blood concentration of the drug can be continuously maintained over a long period of time. It is something that can be demonstrated.

[Brief explanation of the drawing]

FIG. 1 is a cross-sectional view showing the medical patch of the present invention obtained in Example 1.

FIG. 2 is a cross-sectional view showing the medical patch of the present invention obtained in Example 2.

[Explanation of symbols]

1 Adhesive polymer material layer containing drug for transdermal absorption 2
Support 3 Low moisture permeability cover material 4 Color-changing substance-containing layer

Claims (3)

[Claims] Claim 1: An adhesive polymer material layer containing a drug for transdermal absorption is laminated on one side of a support having high moisture permeability,
A medical patch characterized in that a low moisture permeable cover material having a moisture permeability of 250 g/m2/24 h or less is laminated on the other side in an easily peelable state. 2. The medical patch according to claim 1, wherein the support and the adhesive polymer material layer have a moisture permeability of 350 g/m2/24 h or more in a laminated state. 3. The medical patch according to claim 1, wherein the medical patch contains a substance that visibly changes color due to changes in humidity.