KR940000670B1 - Controlled release pharmaceutical compositions formulating films after application - Google Patents

Abstract

Controlled-release solution type plaster composition obtained by mixing anti-inflammatory analgesic drug with polymer composition used as film-forming agent which is composed of wafer soluble polyvinylalcohol (PVA) 0.1-3 wt. parts, water 7-9.4 wt. parts, add water soluble polyvinylpyrrolidone 0.1-0.5 wt. parts. The plaster composition uses a mixture of water and methand as a solvent and form film after applying to skin.

Description

Composition of Controlled-Release Solution-type Pars to Form a Film After Coating

Figure 1 shows the release rate of the film after applying the methyl salicylate solution to the membrane made of cellulose tri acetate and the paste composition of the present invention containing methyl salicylate ( a) and diagram (b).

FIG. 2 shows the application of methyl salicylate solution to a film made of cellulose triacetate, and the amount of elution (a) and application (b) in the coating state after application of the parsal composition containing methyl salicylate.

3 shows the application of L-Menthol to a membrane made of cellulose triacetate, and the retention capacity ratio (a) and application (b) in the coating state after applying the pars composition containing L-menrol. .

The present invention provides a method for infiltrating an anti-inflammatory analgesic drug into the affected area through the skin, wherein the post-coating film composed of water-soluble polyvinyl alcohol (PVA) -polyvinyl pyrrolidone (PVP) has been improved. It relates to a composition of controlled-release solution type paste to be formed.

Conventional medicines that are used as anti-inflammatory drugs by applying ointments, solution-type medicines, poultices, or drugs useful for cloth are used when contaminants penetrate the affected area of skin or use cloth. In order to improve these problems, the external agent for the administration of drugs by forming a film on the surface of the skin by applying the film-forming property of the polymer compound to improve such a problem. Iv), the film-forming polymer compounded with the drug is a polyvinyl acetate partial saponified product (Japanese Patent Application Laid-Open No. 57-108011) or a cellulose-based derivative (Japanese Patent Publication No. 55-49570). Rollidone or polyvinyl pyrrolidone-polyvinyl acetate copolymers (Japanese Patent Laid-Open Nos. 54-46818, 54-4681) and polyvinylacetates and plasticizers Anti-inflammatory analgesic external preparations (Japanese Patent Application Laid-Open No. 1-165521) used as a coating agent by adding other additives are known, but they are foreign substances due to the film forming ability, film strength, film stability, formulation safety, transdermal absorption, plasticizer and additives. There was a problem that penetrates the affected area and causes skin disease.

The ointment preparation according to the prior art is applied to the affected area by mixing the drug with a suitable ointment and remains sticky even after application, so that the ointment may be easily wiped to contaminate clothes or other places and may also be contaminated with the affected area. Therefore, there is inconvenience and complexity to wrap well with gauze or band after application.

On the other hand, solution-type drugs are made by dissolving or mixing drugs in a suitable solvent, which is a solution state, so it can be applied quickly and evenly to the affected area, and the initial drug penetration rate is fast (eg, “water paste”). Easily evaporated, there is a problem that the drug is lowered.

On the other hand, the adhesive method using a cloth is a method of applying a drug on a poultice or a suitable cloth and adhering to the affected area for a long time so that the drug does not wash away and its medicinal effect lasts for a long time. There is a problem that causes skin diseases, and the use of adhesive tape, etc. in the application is cumbersome and inconvenient to use, good appearance and the adhesion is also a problem.

In addition, the manufacturing method is complicated and complicated by several steps, and the use of cloth increases the burden on the consumer economically.

In addition, in the case of an anti-inflammatory analgesic external agent added with polyvinyl acetate, a plasticizer and other additives, polyvinyl acetate (Polyvinyl acetate; Because it is insoluble in water, the film itself is hard and brittle, so foreign substances such as plasticizers and other additives penetrate the affected part of the skin and cause skin diseases.

In order to solve the above problems, the present inventors have extended the support time of the drug and its medicinal effects for a long time, harmless to the human body, and have good biocompatibility. ) And polyvinyl pyrrolidone; ) Is mixed with a number of drugs that have anti-inflammatory analgesic effect to form a solution (or cream, hereinafter includes a cream) .The solution is applied to the affected area to form a thin film immediately. will be.

As it is in solution, it is easy to apply to the affected area, and by forming a film, it can protect against external contaminants from penetrating into the affected area, and the drug is preserved in the film for a long time, so that the drug is controlled by controlled release. Since it lasts for a long time, it can solve the problem of frequent application.

The resulting polymer film is transparent, excellent in biocompatibility, good adhesion to the skin, elasticity and elasticity, soft and non-sticky, and can be easily peeled off whenever it is dry. .

It is a revolutionary invention that satisfies the continuous effect of drug efficacy and convenience of solution type simplicity which is an advantage of the adhesive method using cloth.

The polymer material used in the present invention is a water-soluble polymer that is currently used in many medical applications and has a good physical property with a good biocompatibility without harming the human body.

Since PVA and PVP, which are water-soluble polymers used in the present invention, increase the bonding strength by generating hydrogen bonds between molecules, the film forming ability is higher than that of conventional PVAc, PVA, or PVP alone or when PVAc and PVP copolymers are used. It is using the increase point.

In addition, the polymers of the present invention have the advantage of excellent flexibility and do not need to add a separate plasticizer, and also can reduce the drying time of the film when combined with a high volatile solvent, ethyl alcohol.

The present invention is easily mixed with the drugs commonly used as the external coating agent of the polymer material and anti-inflammatory analgesic present, and because a stable solution phase is made, the manufacturing method is simple and economical, as well as the convenience of application, the sustainability of the drug and the sustained release. The present invention has been completed by forming a coating film by applying a polymer compound of water-soluble polyvinyl alcohol (PVA) -polyvinyl pyrrolidone (PVP), which is excellent in many aspects such as extrudability, excellent adhesion, and ease of film stripping.

Hereinafter, the present invention will be described in detail as follows.

Example 1

1.2 parts of polyvinyl alcohol (PVA), which is a water-soluble polymer, is dissolved in 8.4 parts of water, and then 0.4 parts of polyvinyl pyrrolidone (PVP) is stirred.

In 1 g of this solution, a drug having an anti-inflammatory analgesic effect, that is, 250 mg of salicylic acid methyl (pharmaceutical), pharmacological mechanism of 100 mg of L-menthol (pharmaceutical), etc., is used as an additive to prepare a film-forming solution parse composition.

In order to examine the drug release tendency of the film-forming solution-type pars composition and the drug-free application without the film-forming agent, the following experiment was conducted. Cellulose triacetate (hereinafter abbreviated as CTA) membrane was used instead of the skin to compare the degree of absorption in the body when the drug was applied to the skin.

This CTA membrane was adhered to one side of an aluminum cylinder having a cross-sectional area of 2.3 cm ² to make a drug dissolution test apparatus.

A certain amount of salicylic acid methyl is applied to the CTA membrane in combination with a polyvinyl alcohol-polyvinylpyrrolidone composition (hereinafter PVA-PVP, abbreviated as PVA-PVP) -based film forming material, and the same amount of methyl salicylate is applied to the CTA membrane to elute it. The amount was investigated.

The eluate was analyzed by UV spectrometer using an 0.1 M phosphate buffer solution (pH 7.0) and 5 ml of methyl alcohol 1: 1 mixture at 15 minute, 30 minute or 1 hour intervals. .

The experiment temperature was 37 ° C.

Applying the salicylic acid methyl solution as it was released in about 90 minutes, but [1, (1), 2 (1)] of the present invention was confirmed that the continuous release for about 300 minutes or more. . [Fig. 1 (2) and 2 (2)] In the case of L-menthol, the same amount as L-menthol mixed in the present invention is made into a solution state and applied to the CTA film to retain the capacity according to the change over time. Investigate.

In the case of PVA-PVP type film-forming paste of the present invention, 50% is retained even after 180 minutes when the film is formed, whereas only L-menthol is easily volatilized and remains only 10% even if it is present as a crystalline form on the surface of the film. . [Fig. 3 (1), (2)] From this figure, it can be seen that the present invention has the ability to hold the drug for a long time and gradually release it.

Example 2

A portion of the H ₂ O amount in Example 1 was replaced with ethyl alcohol to speed up the formation of the coating after application.

That is, 1,2 parts of PVA is dissolved in 7 parts of H ₂ O and 1.4 parts of ethyl alcohol, and then 0.4 parts of PVP is added and stirred well.

To 1 g of this solution, drugs having an anti-inflammatory analgesic effect, namely, 250 mmg of methyl salicylic acid (pharmaceutical), 100 mg of L-menthol, and the like are added to prepare a quick dry film forming solution type pars.

Claims (2)

In a polymer composition used as an anti-inflammatory analgesic film-forming agent, a water-soluble polyvinyl pyrrolidone (PVP) 0.1-0.5 in a solution composed of 0.1-3 parts by weight of water-soluble polyvinyl alcohol (PVA) and 7-9.4 parts by weight of water as a solvent. A composition of sustained-release solution type paste for forming a post-coating film, wherein the anti-inflammatory and analgesic drug is mixed with the coating-forming composition to which the weight part is added. The composition of the sustained-release solution type paste of Claim 1 which forms a film after application | coating using the mixed solvent of water and ethyl alcohol as a solvent.