JP3157082B2 - Base for medical pack-type preparation and pack-type preparation for medical use - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical pack-type preparation base, and more particularly, to a medical pack which adheres to the skin for a long time and can be easily removed without washing with water. A base for a mold preparation.

[0002]

2. Description of the Related Art As medical coating agents, those containing polyvinyl alcohol, resin latex emulsion, polyhydric alcohol and the like as essential components have been often used. For example, Japanese Patent Publication No. 46-23277 discloses an excipient for a medical coating agent containing a polyvinylpyrrolidone acetate resin, a thixotropic agent containing 1,2-hydroxystearic acid triglyceride and a plasticizer for the resin. .
This excipient is characterized in that it can be easily applied in a very short time, but since it needs to be dissolved with running water or washed off with water, it can be easily removed from the skin without water. It had a disadvantage that it could not be peeled off. Further, there is a pack cosmetic for forming a similar film. For example, Japanese Patent Publication No. 3-77166 discloses a pack cosmetic comprising a pack containing polyvinyl alcohol, a resin latex emulsion, powder and water as essential components and a polysaccharide produced by a specific bacterium. Further, Japanese Patent Publication No. 5-21081 discloses that at least one kind of a water-soluble natural polysaccharide such as a microorganism natural polysaccharide, a vegetable polysaccharide or a mucopolysaccharide or a salt thereof, at least one kind of a protein or a salt thereof, and A pack cosmetic characterized by comprising a phase component is disclosed, and hyaluronic acid is disclosed as an example of a water-soluble natural polysaccharide. However, any of these pack cosmetics lacks the flexibility to follow the skin and peels off in a short time, so that it was practically impossible to use it as a base for pharmaceutical preparations for medical use.

[0003]

As described above, both the conventional medical coating agent and the pack cosmetic have a problem that the film lacks flexibility. In view of this, and from the viewpoint of the adhesiveness of the pack cosmetics, there have been problems in using them as bases for medical preparations. An object of the present invention is to provide a medical pack-type preparation base which can adhere to the skin for a long time and can be easily removed without washing with water.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, have found that a certain proportion of a polyhydric alcohol and a film-forming agent as water retention components is used for medical use. It has been found that by adding hyaluronic acid to a pharmaceutical base, a medical pack-type pharmaceutical base excellent in releasability and adhesion can be obtained, and the present invention has been completed. Again, the base for medical pack-type preparations of the present invention has excellent peelability and adhesiveness because it is obtained by mixing hyaluronic acid in addition to polyhydric alcohol as a water retention component. In fact, such advantages cannot be obtained with polyhydric alcohol alone or hyaluronic acid alone. The present invention provides at least one
It is intended to provide a base for a medical pack-type preparation, characterized by comprising at least one kind of polyhydric alcohol, at least one kind of film-forming agent, hyaluronic acid and a solvent. The details are described below.

[0005] The polyhydric alcohol in the present invention acts as a water-retaining component, and may be a substance used in a usual base for pack-type preparations. Examples of these substances include, but are not particularly limited to, polyhydric alcohols having a molecular weight of 200 to 4000, such as polyethylene glycol, propylene glycol, glycerin, sorbitol, and mannitol. In addition, two or more polyhydric alcohols can be used in appropriate combination. Among them, molecular weight 2
Polyethylene glycol and propylene glycol of 00 to 4000 are preferred, and more preferably they are used in combination. The amount of the polyhydric alcohol varies depending on the nature of the polyhydric alcohol and the nature of the film-forming agent, but is generally about 0.01 to about 50% of the total amount of the pharmaceutical base.
%, Preferably about 6 to about 15.5% by weight.

The film-forming agent in the present invention may be any resin suitable for forming a film, and uses many natural or synthetic resins which can be dissolved in one or more of water and alcohol. be able to. Examples of the film-forming agent include polyvinyl alcohol, polyvinyl acetate, methylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, sodium polyacrylate, polyvinylacetal diethylaminoacetate, pullulan, aminoalkyl methacrylate copolymer, methacrylic acid copolymer and the like. However, the present invention is not particularly limited to these. Also, two or more kinds of film forming agents can be used in appropriate combination. Among these, polyvinyl alcohol and polyvinyl acetate are preferred, and more preferably they are used in combination. The amount of the film-forming agent varies depending on its properties, but is generally about 1 to about 5 of the total amount of the preparation base.
0% by weight, preferably about 6 to about 25% by weight.

The hyaluronic acid used in the present invention is used as a water retention component, and preferably has a molecular weight in the range of about 50,000 to about 3,000,000. Hyaluronic acid can be added in the form of a salt such as sodium hyaluronate and calcium hyaluronate. The amount of hyaluronic acid varies depending on the characteristics and amounts of other water-retaining components and film-forming agents, but it is about 0.0001 to about 4% by weight, preferably about 0.01 to about 4% by weight of the total amount of the formulation base. 2% by weight. As described above, in the base for a medical pack-type preparation of the present invention, polyhydric alcohol and hyaluronic acid act as water retention components, but the type of polyhydric alcohol can be appropriately selected here. On the other hand, it should be noted that hyaluronic acid is contained as an essential component. As a solvent, water, ethanol or the like is usually used, and for example, benzyl alcohol or the like can be used as a solvent for dissolving the drug.

[0008] The base for a medical pack-type preparation of the present invention can contain a desired drug in addition to the above essential components.
These drugs need only be absorbed percutaneously when used and exert pharmacological effects. Examples of agents that can be used in the present invention include general anesthetics, hypnotics, sedatives, antiepileptics, antipyretic analgesics and anti-inflammatory agents, stimulants, agents for psychoneural nerves, local anesthetics, skeletal muscle relaxants, autonomic agents , Analgesics, ophthalmic agents, otolaryngological agents, antidiarrheals, cardiotonic agents, arrhythmic agents, diuretics, antihypertensive agents, vascular reinforcing agents, vasoconstrictors, vasodilators, hyperlipidemic agents Respiratory stimulants, antitussives,
Expectorant, intestinal suppressant, peptic ulcer, stomachic, antacid, laxative, bile, hormonal, urinary, reproductive, uterine contractile, germicidal disinfectant, Wound protectants,
Drugs for purulent diseases, analgesic / pruritic, astringent / anti-inflammatory drugs, drugs for parasitic skin diseases, vitamins, nourishing tonics, hemostats, anticoagulants, drugs for liver diseases, antidote, gout remedies, enzymes Examples include, but are not limited to, preparations, diabetes agents, chlorophyll preparations, antihistamines, stimulants, sulfa drugs, antituberculous drugs, antiprotozoal drugs, anthelmintics, preservatives, and the like.

[0009] The base for a medical pack-type preparation of the present invention may contain, as necessary, an antioxidant, a preservative or a preservative, a pH adjuster, a cooling agent, a stabilizer and the like in addition to the above-mentioned components. can do. As the antioxidant, sodium pyrosulfite, sodium bisulfite, dried sodium sulfite, butylhydroxytoluene, butylhydroxyanisole and the like can be used. Further, as a stabilizer, sodium edetate or the like can be used. As a preservative or preservative, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate and the like can be used. As a pH adjuster, diisopropanolamine, diethanolamine, monoethanolamine,
Ethylene diamine and the like can be used. As a freshener,
l-menthol and the like can be used. Further, a certain amount of a partially saponified carboxyvinyl polymer can be added to adjust the viscosity and improve the dispersion stability.

[0010]

EXAMPLES Next, the present invention will be described in more detail by way of examples, but these do not limit the present invention.

Table 1: Treatment of Examples 1-2 and Comparative Example 1
Square component Example 1 Example 2 Comparative Example 1 Sodium edetate (mg) 50.0 50.0 50.0 sodium pyrosulfite (mg) 50.0 50.0 50.0 Polyvinyl alcohol (g) 2.5 2.5 2.5 Water (ml) 20 20 20 Propylene glycol (ml) 1.5 1.5 1.5 Polyethylene glycol 400 (ml) 1.5 1.5 1.5 Polyvinyl acetate emulsion (g) 5.0 5.0 5.0 Indomethacin (g) 0.5 0.5 0.5 Benzyl alcohol (ml) 2.5 2.5 2.5 1-Menthol (mg) 250 250 250 Ethanol (ml) 15 15 15 Diisopropanolamine (drops) 25 25 25 Carboxyvinyl polymer (g) 0.3 0.3 0.3 Sodium hyaluronate (mg) 50.0 5.0 −

Preparation method 50 mg of sodium edetate, 50 mg of sodium pyrosulfite and 2.5 mg of polyvinyl alcohol were added to 20
Add to ml of purified water, warm to about 70 ° C. in a water bath and dissolve completely. After cooling, 50.0 mg (Example 1) or 5.0 mg (Example 2) of sodium hyaluronate (weight average molecular weight 1,100,000) was added (in the comparative example, no sodium hyaluronate was added), mixed, and mixed. Leave to stand overnight. After confirming dissolution of sodium hyaluronate, 1.5 ml of propylene glycol and 1.5 ml
ml of polyethylene glycol 400 and 5 g of polyvinyl acetate emulsion (trade name: Vinibulan GV-56)
51, manufactured by Nissin Chemical Industry Co., Ltd.) and mixed (this is referred to as solution A). Separately, 0.3 g of a carboxyvinyl polymer (trade name: Hibiswako 105, manufactured by Wako Pure Chemical Industries, Ltd.) is dissolved in 15 ml of ethanol. After complete dissolution, 0.5 g of indomethacin, 2.5 g
Of benzyl alcohol and 250 mg of l-menthol are added and dissolved (this is referred to as solution B). Solution A and solution B are mixed, and the pH is adjusted to 6.0 to 6.0 with diisopropanolamine.
Adjust to 7.0.

Evaluation Test Results The bases of Examples 1 and 2 and Comparative Example 1 were subjected to evaluation tests for hardness, flexibility, quick-drying, releasability and adhesion as follows. Hardness refers to the degree to which the base of the present invention does not sag when applied to the skin at any position of the body or joints, and was measured according to the following method: 0.5 ml of the sample is placed, a glass plate is placed thereon, and a weight is further placed. The total weight of the glass plate and the weight is 120 g. The diameter of the spread sample was measured from different 90 ° directions, and the average value of the length was defined as hardness. The smaller the average value of the measured lengths, the harder the sample.

Fast drying is the rate at which a sample dries after application and is measured according to the following method: 0.2 ml of a sample is placed on a glass plate on a thermostat at 32 ° C.
Spread to a uniform thickness with a glass rod. The drying time is then measured by observing the coating surface. Softness refers to the degree of softness of a film formed after a base is applied to the skin and dried. Peelability refers to the degree to which the dried coating can be easily peeled off the skin. Adhesiveness refers to the area (%) of the film adhering to the skin after a certain period of time from application. The flexibility, peelability and adhesion were tested by applying samples to the arms of 20 healthy men and women. The presence or absence of flexibility and releasability was judged based on the subject's subjectivity, and the adhesion was expressed as an average of the area of adhesion 4 hours after application in%.

The results of the evaluation test are shown in Table 2 below.

Table 2 Example 1 Example 2 Comparative Example 1 Hardness (cm) 5.39 5.42 5.49 Flexibility (human) ○ ○ ○ Quick drying (min) 8.58 7.40 7.98 Peelability (human) ○ ○ ○ Adhesion ( %, 4hr, human) 80.2 70.2 57.8 Note: ○ indicates good flexibility or peelability.

As is clear from the results in Table 2, the bases of Examples containing hyaluronic acid are excellent in both peelability and adhesion. On the other hand, the base of the comparative example containing no hyaluronic acid was inferior to that of the example in terms of adhesiveness and was not preferred. From these results, it can be seen that by adding hyaluronic acid to the film-forming agent, a base for a pack-type preparation excellent in both peelability and adhesiveness can be obtained.

[0016]

The base for a medical pack-type preparation according to the present invention has the flexibility to follow the skin, keeps adhering to the skin for a long time, dries in a short time, and is easily removed without washing with water. It has an excellent effect of being able to do so.

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int. Cl. ⁷ , DB name) A61K 9/70, 7/00

Claims (12)

(57) [Claims] Claims: 1. At least one polyhydric alcohol, poly
Do not combine vinyl alcohol and polyvinyl acetate.
That film-forming agents, medical packed pharmaceutical base agent characterized in that it comprises a hyaluronic acid and a solvent. 2. The base for a medical pack-type preparation according to claim 1, wherein the polyhydric alcohol is propylene glycol and / or polyethylene glycol. 3. The polyethylene glycol having a molecular weight of 20.
The base for a medical pack-type preparation according to claim 2, wherein the base is from 0 to 4,000. 4. A polyhydric alcohol content of 0.01 to 5
The base for a medical pack-type preparation according to any one of claims 1 to 3, which is 0% by weight. 5. A polyhydric alcohol content of 6 to 15.5.
5. The base for a medical pack-type preparation according to claim 4, which is contained in% by weight. 6. The medical packed pharmaceutical base according to any one of claims 1 to 5 content is 1 to 50% by weight of the film-forming agent. 7. The content of the film-forming agent is a medical packed pharmaceutical base according to claim 6, wherein a 6-25% by weight. 8. The medical packed pharmaceutical base according to any one of claims 1 to 7, hyaluronic acid is supplied from the sodium hyaluronate. 9. The molecular weight of sodium hyaluronate is 5
9. The base for a medical pack-type preparation according to claim 8 , which is in a range of from 000 to 3,000,000. 10. The hyaluronic acid content is 0.0001.
The base for a medical pack-type preparation according to any one of claims 1 to 9 , which is from 4 to 4% by weight. 11. The content of hyaluronic acid is 0.01 to 2
The base for a medical pack-type preparation according to claim 10, which is in a percentage by weight. 12. A medical packed preparation according to any one of claims 1 to 11 further comprising a drug.