JPH054916A - Plaster - Google Patents

Abstract

PURPOSE:To obtain a plaster, having a support, hardly causing reduction in a medicine content and deterioration such as coloring or a change in shape, etc., of a pharmaceutical and satisfying both the application stability and the applicability CONSTITUTION:A plaster is obtained by providing a tacky plaster layer containing 1-30wt.% medicine or additive, having a solubility parameter within the range of 7-11 and relatively improved in fat solubility on one surface of a support (preferably having 30-150mum, especially 40-100mum thickness) composed of a uniaxially stretched or unstretched low-density polyethylene having 1-8 melt index. The aforementioned support is composed of a low-density polyethylene film formed by a melt molding method such as a T-die method and its deformation, etc., are within the range of + or -10% in the longitudinal direction and <=0.5% in the width direction under conditions of 100 deg.C and 20 min.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a patch having an adhesive plaster layer containing a drug or the like on one surface of a flexible support, and more specifically, stability as a preparation and patchability. Relating to an excellent patch.

[0002]

2. Description of the Related Art As a dosage form used for transdermal administration of drugs, ointments, lotions, plasters and the like have been used for a long time, but in recent years, patches called tapes or patches. Is getting attention. The patch is formed by forming an adhesive plaster layer containing a drug or an additive on one surface of a support made of a flexible material such as a synthetic resin film or a non-woven fabric.

When an adhesive patch is used, the drug or the like can be continuously administered, and the administration can be easily stopped by peeling off the adhesive patch as needed. Therefore,
It has advantages that the dose of the drug intended for systemic action can be easily controlled, side effects due to rapid drug absorption can be reduced, and the number of drug administrations can be reduced. In addition, the patch is easier to handle than an ointment, and stains or the like of clothes during application are less likely to occur.

In the adhesive patch having various advantages as described above, the support is required to satisfy the following conditions in order to make full use of these advantages. First, the support is required to be able to stably maintain the drugs and additives in the adhesive plaster layer. Further, it is desirable that the support itself does not change its shape or discolor. Further, those having sufficient flexibility are required. Even if it is excellent in stability, if it is inflexible, it may give a patient a feeling of discomfort during application, or the adhesion to the skin may be impaired, resulting in insufficient drug administration. Also,
It is necessary to select an appropriate support according to the compound such as drug or additive.

Conventionally, a flexible material such as a synthetic resin film or a non-woven fabric has been used as a support for forming a patch. As the synthetic resin film, one made of polyethylene, polypropylene, polyethylene terephthalate or the like is used. Further, in JP-A-62-82967, a support formed from a resin composition comprising a hydrocarbon-based elastomer and a polyolefin, and in JP-A-62-153215, a vinyl chloride-ethylene copolymer and ethylene- A support formed from a resin composition comprising a carbon monoxide-vinyl acetate copolymer and a hydrous aluminosilicate, JP-A-1-224313.
In Japanese Patent Application Laid-Open No. 1-249719, a support formed by adhering a vinyl chloride resin film and a polyethylene terephthalate film to a support formed from a resin composition comprising a vinyl chloride polymer and an ethylene-vinyl acetate copolymer. JP-A-2-247118 also discloses a support in which polyethylene terephthalate is adhered to a flexible polyurethane-polyvinyl chloride graft copolymer film. However, none of the supports used in the conventional patches have sufficiently satisfied the above various conditions.

[0006]

DISCLOSURE OF THE INVENTION The object of the present invention is to prevent a decrease in drug content even when various drugs are contained, to prevent deterioration of the preparation such as coloring or shape change, and An object of the present invention is to provide a patch having a support capable of satisfying both stability and patchability.

[0007]

Means for Solving the Problems As a result of studying various materials, the inventors of the present invention can stably hold a drug by using uniaxially stretched or unstretched low density polyethylene as a support. Moreover, they have found that a support having less change in shape and discoloration of the preparation can be obtained, and completed the present invention.

That is, the patch of the present invention has a melt index of 1 to 8, a support made of uniaxially stretched or non-stretched low density polyethylene, and a support provided on one side of the support, and has a dissolution parameter. Is in the range of 7 to 11, and an adhesive plaster layer containing a drug or an additive. The details of the configuration of the present invention will be described below.

Support In the patch of the present invention, uniaxially stretched or unstretched low density polyethylene is used as a support. This is because in uniaxially stretched or non-stretched polyethylene, the shape change caused by stress relaxation over time is at most one direction, and therefore wrinkles and slack due to strain are less likely to occur. Further, since it is uniaxially stretched or non-stretched, it is also excellent in flexibility and rarely gives a patient a feeling of discomfort during application. That is, it is possible to form a support having good adhesiveness.

The support made of uniaxially stretched or unstretched low density polyethylene as described above can be constituted by a low density polyethylene film molded by a melt molding method such as a T-die method. The melting temperature is usually 1
The temperature is 30 to 200 ° C., and after being extruded during melt molding, the film is rapidly cooled to room temperature or lower to obtain a transparent and flexible film.

The biaxially stretched low density polyethylene film is produced, for example, by the inflation method. When such a biaxially stretched polyethylene film is used as a support, the solubility parameter is 7-11.
When an adhesive plaster layer containing a drug or an additive in the range is formed, wrinkles and slack are likely to occur due to residual stress.

The deformation rate of the uniaxially stretched or unstretched low density polyethylene film used in the present invention is ± 10% or less in the length direction and ± 0.5% in the width direction under the conditions of 100 ° C. and 20 minutes. The range is as follows. Although the thickness of the support varies depending on the type of the adhesive plaster layer and the required feeling of use, it is usually in the range of 30 to 150 μm, and preferably in the range of 40 to 100 μm.

The low-density polyethylene used may be uniaxially stretched or unstretched, and JIS K
It is necessary that the melt index as measured by the 6760 polyethylene test method be in the range of 1-8. When the melt index is less than 1, it is difficult to form a smooth film, and when the melt index exceeds 8, the chemical resistance deteriorates.

Adhesive plaster layer In the present invention, the adhesive plaster layer provided on the lower surface of the support contains a drug or an additive having a solubility parameter in the range of 7 to 11. This solubility parameter is
Solubility Parameters / All
an F. M. Barton; Chemical Re
views, Vol. 75, no. 6p731- (19
75), and specifically, A
Method for Estimating Bot
h the SolubilityParameter
s and Mollar Volumes of Li
quids / Robert F. Fedors; POL
YMER ENGINEERING AND SCIE
NCE, FEBRUARY, 1974, Vol. 14,
No. 2 It is calculated according to the calculation method described in p147-.

As described above, the solubility parameter is 7 to 11
The drug or additive having a relatively high lipophilicity is contained in the drug or additive having a solubility parameter of more than 11, originally, the interaction with the support is small and the deterioration phenomenon of the preparation occurs. Because there is no difficulty. On the other hand, in the case of a drug or additive having a solubility parameter of 7 to 11,
When a conventional support is used, penetration of a drug or an additive and dissolution in the support are likely to occur, which tends to cause deterioration of the formulation, whereas when the support of the present invention is used in combination. This is because such deterioration hardly occurs and the effect of the present invention can be obtained.

In the present invention, examples of the drug contained in the adhesive plaster layer include anti-inflammatory agents, analgesics, antihistamines, hormones, vasodilators, antihypertensive agents, antibiotics, antibacterial agents, muscle relaxants. , Antidepressants, anesthetics, vitamins and the like. Specific examples include glycyrrhetinic acid, aminopyrine, diphenhydramine, pentaerythritol tetranitrate, and mianserin. These drugs are blended in the adhesive plaster layer in the range of 1 to 30% by weight. This is because if it is less than 1% by weight, the effect of adding the drug cannot be obtained, and if it exceeds 30% by weight, the sticking property is adversely affected.

The additives include solubilizers, plasticizers,
As the absorption promoter or stabilizer, higher fatty acid, higher alcohol, fatty acid ester, alkylamine, etc. are contained. Specifically, stearic acid, myristic acid,
Examples thereof include oleic acid, linolenic acid, behenyl alcohol, oleyl alcohol, lauryl alcohol, cetyl acetate, isopropyl myristate, octyldodecyl myristate, sorbitan (mono) laurate, glycerin (mono) oleate, and diisopropylamine. These additives are blended in the adhesive plaster layer in the range of 1 to 50% by weight. This is because if it is less than 1% by weight, the effect of adding the additive cannot be obtained, and if it exceeds 50% by weight, the effect due to the addition of the additive is saturated, while the functions such as sticking property are deteriorated. Is.

In the adhesive plaster layer, a liquid drug or additive having a relatively high lipophilicity and a solubility parameter in the range of 7 to 11 is dissolved or dispersed in the adhesive base. As the adhesive base, one made of an appropriate material that has been conventionally used to form a patch can be used. Examples of such an adhesive base include an acrylic adhesive, a urethane adhesive or a rubber adhesive.

Formulation composition to which the present invention is applied The composition of the patch of the present invention other than the support is not particularly limited as long as it enables effective supply of the drug into the body through the skin. Not done. For example, a single adhesive plaster layer system in which a drug is dispersed or dissolved in an adhesive base, a system in which a drug is encapsulated in microparticles and dispersed in an adhesive base, a release control film in a drug storage layer, and Examples thereof include a multi-layer system in which an adhesive base layer is combined as necessary, a system in which the surface contacting with the skin is divided into a drug storage area and an adhesive area.

In addition to the drug, a solubilizer, a plasticizer, an absorption enhancer, a stabilizer and the like may be blended with the drug as required, or may be arranged as a layer different from the drug. Usually, the surface of the adhesive plaster layer opposite to the surface in contact with the support is treated with a release paper for the purpose of protecting the adhesive plaster layer until it is applied to the skin. Are pasted together.

If necessary, a primer layer may be provided between the support and the adhesive plaster layer to enhance the adhesion between the adhesive plaster layer and the support. .. The primer can be made of any material as long as it has an affinity for both the support and the adhesive plaster layer and does not impair the stability of the preparation, and such a primer can be used. Examples of the material include acrylic polymers, rubber polymers, urethane polymers, epoxy resins, and the like.

Production Method The patch of the present invention can be obtained by coating one side of the above-mentioned support with an adhesive base solution or dispersion in which a drug or the like is dissolved or dispersed, and drying. Also,
On another base member, an adhesive base solution or dispersion containing a drug or the like is applied to form an adhesive plaster layer,
You may comprise by transferring the said adhesive plaster layer on the said support body.

In addition to the above solvent coating method, hot melt coating method can be used for coating.

[0024]

In the patch of the present invention, the melt index is 1
8 to 8, and since the support made of uniaxially stretched or unstretched low density polyethylene is used, the drug can be stably held, and the shape change and discoloration of the preparation hardly occur. Further, since it is uniaxially stretched or unstretched low density polyethylene, the shape change due to stress relaxation is at most unidirectional, and thus wrinkles and slack are less likely to occur. further,
The uniaxially stretched or non-stretched low density polyethylene is excellent in flexibility, so that it does not give a patient an uncomfortable feeling when applied.

Therefore, even when a drug or an additive having a dissolution parameter of 7 to 11 which easily causes the deterioration of the preparation is contained in the adhesive plaster layer, it hardly penetrates or dissolves into the support, and It is possible to form a patch that is less likely to cause deterioration of the preparation.

[0026]

EXAMPLES The present invention will be clarified further by describing examples of the present invention. First, the following materials were prepared in order to prepare patches of Examples and Comparative Examples described later.

[0027] As a material constituting the support substrate, was prepared film consisting of seven synthetic resin below. Low-density polyethylene manufactured by T-die: thickness 50 μm, melt index 2. The deformation rate is -4.8% in the length direction and + 0.1% in the width direction. Polyethylene terephthalate with a thickness of 15 μm and a thickness of 2
Laminated film made of 0 μm polyvinyl chloride ...
An adhesive plaster layer was provided on the polyethylene terephthalate side. Laminate film composed of polyvinyl chloride having a thickness of 30 μm and polyvinylidene fluoride having a thickness of 20 μm ... An adhesive plaster layer was provided on the surface on the polyvinyl chloride side. Stretched nylon ... 50 μm thick. Polyethylene terephthalate ... 15 μm thick. Ethylene-vinyl acetate copolymer ... Thickness 60μ
m. Inflation made low density polyethylene ... thickness 50μ
m. The deformation rate is -3.1% in the length direction and +1.
5%.

In the above, the deformation rate indicates each change rate with respect to the lengthwise or widthwise dimension before heating at 100 ° C. and 20 minutes.

Adhesive plaster layer As the adhesive plaster layer, the following two types were prepared. Adhesive plaster layer A ... 2-ethylhexyl methacrylate 1
80 g, 60 g of 2-ethylhexyl acrylate and 100 g of ethyl acetate are put into 1 liter of Kolben,
After heating to 0 ° C., 0.2 g of lauroyl peroxide dissolved in 100 g of cyclohexane was added over 6 hours to carry out polymerization. As a result, a weight average molecular weight of 105
An adhesive solution having a solid content of 58% was obtained.

An adhesive solution prepared as described above,
Indomethacin as a drug (solubility parameter: 1
2.9) and isopropyl myristate (dissolution parameter: 8.5) as a plasticizer were mixed so as to contain 80% by weight of an adhesive, 5% by weight of indomethacin and 15% by weight of isopropyl myristate after drying. After adjusting the non-volatile concentration to 30% by weight with ethyl acetate, the mixture was stirred and mixed with a mixer to uniformly dissolve the composition to obtain an adhesive plaster layer A solution.

Adhesive plaster layer B ... The same acrylic adhesive solution used to form the adhesive plaster layer A, and pentaerythritol tetranitrate as a drug (dissolution parameter: 10.0) And octyldodecyl myristate as a plasticizer (solubility parameter: 8.6) so that after drying, 75% by weight of an adhesive, 15% by weight of pentaerythritol tetranitrate and 10% by weight of octyldodecyl myristate are contained. After mixing and adjusting the non-volatile content to 30% by weight with ethyl acetate, the mixture was stirred and mixed with a mixer to uniformly dissolve the composition, to give a solution of adhesive plaster layer B.

Production of adhesive patch The solution of the adhesive plaster layer A or the solution of the adhesive plaster layer B prepared as described above is uniformly applied onto a polyester film having a thickness of 50 μm and subjected to a release treatment. Then, the adhesive plaster layer A or the adhesive plaster layer B having a thickness of 80 μm was formed by drying. Next, Examples 1 and 2 shown in Table 1 below are prepared by laminating the above-mentioned supports on the adhesive plaster layer A or the adhesive plaster layer B.
And each patch of Comparative Examples 1-9 was obtained.

[0033]

[Table 1]

With respect to the patches of Examples and Comparative Examples obtained as described above, the appearance observation during the following severe test and the drug content stability during the severe test were evaluated.

Observation of Appearance During Severe Test Each of the patches of Examples 1 and 2 and Comparative Examples 1 to 9 was 6
It was cut into a size of 6 cm ² , put in an aluminum packaging material, and heat-sealed. Next, after being stored at 60 ° C. for 2 weeks, the package was opened and the appearance of the stored patch was visually observed. The results are shown in Table 2 below.

Stability of drug content during severe test Regarding the patches of Examples 1 and 2 and Comparative Examples 2 and 4, each patch was 2 cm immediately after preparation of the patch and after storage at 60 ° C. for 2 weeks. Punched into a circular shape, peel off the release body (polyester film that has been released),
Next, after extraction with methanol, the amount of drug was measured using a liquid chromatograph. The weight of the adhesive plaster layer was calculated from the weight of the patch before extraction and the total weight of the support and the peeled body after extraction to calculate the drug content. The results are shown in Table 3 below.

[0037]

[Table 2]

[0038]

[Table 3]

As is clear from Table 2, the patches of Examples 1 and 2 showed no coloring or change in shape even when left at a relatively high temperature of 60 ° C. for 2 weeks. On the other hand, it is found that the patches of Comparative Examples 1 to 9 cause coloring such as yellowing and wrinkles. In Comparative Example 4, the back surface, that is, the surface of the support opposite to the side where the adhesive plaster layer was provided was sticky, and in Comparative Example 5, there was an interlayer between the adhesive plaster layer and the support. Peeling had occurred.

Further, as is clear from Table 3, the drug contents in Examples 1 and 2 hardly decreased, whereas the drug contents after storage in Comparative Examples 2 and 4 decreased at a considerable ratio. You can see that

[0041]

As described above, according to the present invention, an adhesive plaster containing a drug or an additive on one surface of a support made of uniaxially stretched or unstretched low density polyethylene having a melt index of 1 to 8 Since the patch is constituted by providing the layer, it is possible to provide the patch in which the drug content is unlikely to decrease and the formulation is less likely to be deteriorated due to coloring, shape change and the like. In particular, even when the adhesive parameter contains a drug or an additive having a dissolution parameter of 7 to 11 and easily penetrating or dissolving into a support and thereby causing deterioration of the preparation, Since the patch of the invention uses the above-mentioned support, the above-mentioned deterioration of the preparation hardly occurs. Further, since the support is composed of uniaxially stretched or non-stretched low density polyethylene, it is excellent in flexibility and therefore does not give a patient a feeling of discomfort during application.

Therefore, according to the present invention, it is possible to provide a patch excellent in stability of drug content, stability as a preparation and patchability.

Claims (1)

Claim: What is claimed is: 1. A support comprising a uniaxially stretched or unstretched low density polyethylene having a melt index of 1 to 8, and a support provided on one side of the support and having a solubility parameter. An adhesive patch comprising a pressure-sensitive adhesive plaster layer containing a drug or an additive in the range of 7 to 11.