JPH02145512A - External preparation of film forming type - Google Patents

Abstract

PURPOSE:To obtain an external preparation of film forming type having excellent durability of medicinal effects, not damaging normal physiological action of skin, having a good feeling in use by blending a volatile cyclic silicone oil with a triorganosilyl group-containing polymer. CONSTITUTION:A cyclic organopolysiloxane shown by formula I (m and n are 0-8 and 3<=m+n<=8) and at least one film-forming polymer selected from a triorganosilyl group-containing polyvinyl alcohol shown by formula II (R1-R3 are 1-8C polymer), a water-soluble nonionic natural polysaccharide (e.g., starch) and a derivative thereof are stirred at room temperature under heating and dissolved. The solution is properly blended with drugs such as antibiotic, agent for chemotherapy, vitamin agent, enzyme preparation, remedy for keratinization, adrenal cortex hormone agent or anti-inflammatory analgesic to prepare the aimed substance. The external preparation is applied in a liquid and/or gelatinous state and forms a film by drying.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention provides a film-forming external preparation, which has excellent long-lasting medicinal efficacy, has no risk of interfering with the normal physiological functions of the skin, and is suitable for use on the skin after application. The present invention relates to a film-forming external preparation that can form a film that has excellent water resistance and strong affinity for the skin, and is also comfortable to use.

(Prior Art) Medical transdermal and transmucosal preparations include, for example, ointments, plasters such as tapes and patch preparations, and poultices. However, when ointments are applied to the affected area, they tend to adhere to surfaces other than the affected area, such as skin or clothing. As a result, it stains contact objects such as clothes, and decreases the effectiveness and durability of the drug's efficacy due to a decrease in the active ingredient of the drug. Moreover,
Because the affected area is exposed, it is difficult to prevent bacteria from entering (
, which is not sanitary. Plates and poultices do not synchronize with the expansion and contraction of the skin, so they may be painful to apply or may fall off after application. In addition, side effects such as rashes and rashes occur as skin disorders due to inhibition of skin breathing due to covering the skin by pasting, and skin damage when peeled off. Poultices have low adhesive properties and tend to peel off even if they are fixed with a bandage or the like.

To solve these drawbacks, a film-forming external preparation that is liquid at the time of application and forms a film by drying after application has been proposed. A polymeric dressing composition comprising a coalescing agent and a plasticizer is disclosed.

However, since this composition is based on an acrylic copolymer, it lacks water resistance, and when used under high temperature and high humidity conditions such as in the summer, the adhesiveness deteriorates due to excessive sweating on the skin surface. . In addition, in JP-A-52-79018, a composition in which polyvinyl alcohol and a coating film-forming waterproofing aid are combined is proposed in order to improve the above-mentioned drawbacks, but this composition has good water resistance. However, it lacks flexibility. Therefore, the film formed by applying this to the skin and drying it easily peels off due to expansion and contraction of the skin. In addition, the above-mentioned film-forming external preparations have a problem in use in that they are sticky and uncomfortable when applied.

On the other hand, solvents used in conventional transdermal and transmucosal preparations are mainly alcohols and other solvents that are irritating to the skin. These formulations are viewed as problematic because they are formulations that come into direct contact with the skin.

(Problems to be Solved by the Invention) The present invention solves the problems of the prior art described above, and its purpose is to provide excellent water resistance, sweat resistance, skin adhesion, and oxygen permeability, and to prevent contact with objects when applied. The object of the present invention is to provide a film-forming external preparation that does not adhere to the skin, has very little skin irritation compared to conventional products, and uses a non-biotoxic solvent.

(Means for Solving the Problems) The present invention is a liquid and/or gel-like film-forming external preparation made by blending a volatile cyclic silicone oil and a polymer having a triorganosilyl group in its side chain. After that, the above object is achieved by forming a film by drying.

That is, the gist of the present invention is a) general formula % formula % () (in the formula, m and n are 0 or an integer from 1 to 8, and 3≦m
+n≦8) cyclic organopolysiloxane)
Polyvinyl alcohol or water-soluble polyvinyl alcohol having a triorganosilyl group represented by the general formula (R, , R, and ``in the formula may be the same or different and are hydrocarbon groups having 1 to 6 carbon atoms.'') The present invention is a film-forming external preparation consisting of a small amount (and at least one kind of film-forming polymer c) selected from nonionic natural polysaccharides and their derivatives having the following properties.

The cyclic organopolysiloxane that is the first component used in the present invention is a cyclic silicone oil represented by general formula (I). Such cyclic silicone oils include, for example, hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, tetradecamethylcycloheptasiloxane, hexadecamethylcyclooctasiloxane, and the like. Cyclic dimethylpolysiloxane, tetramethylcyclotetrasiloxane, pentamethylcyclopentasiloxane, hexamethylcyclotetrasiloxane, heptamethylcyclotetrasiloxane, hexamethylcyclopentasiloxane, octamethylcyclopentasiloxane, heptamethylcyclopentasiloxane, nonamethylcyclo Examples include cyclic dimethylmethylhydrodiene polysiloxanes such as pentasiloxane, and methylhydrodiene polysiloxanes, and mixtures of two or more thereof can also be used.
Particularly preferred among these is cyclic dimethylpolysiloxane. If the amount of this product in the formulation of the present invention is less than 10% by weight, the amount of other ingredients will increase, and the expected effects of light extensibility, prevention of stickiness, and prevention of skin irritation will be poor. If it exceeds 99% by weight, the content of the film-forming material will be too small to form a sufficient film. Therefore, the blending amount is required to be in the range of 99 to 10% by weight, and the preferred range is 90 to 30% by weight.

Next, the film forming material, which is the second component used in the present invention, is a polymer having a triorganosilyl group represented by the general formula (II) in its side chain. Polyvinyl alcohol, polyvinyl alcohol derivatives, water-soluble nonionic natural polysaccharides, and their polysaccharide derivatives used as raw materials for this film-forming material all have triorganosilyl groups introduced to form silyl ether bonds. It is a polymer with hydroxyl groups that can be formed. Here, examples of polyvinyl alcohol derivatives include vinyl ether/vinyl alcohol copolymers, ethylene/vinyl alcohol copolymers, and vinyl acetate/vinyl alcohol copolymers. The content of these hydroxyl groups is not particularly limited, but it is preferably 30 mol% or more. If the hydroxyl group content is less than this, it becomes impossible to increase the 1 content of triorganosilyl groups, and the compatibility with the cyclic silicone oil represented by the above general formula (I) may be poor. Examples of water-soluble nonionic natural polysaccharides include starch, pullulan, guar gum, and locust bean gum, and derivatives thereof include alkyl groups such as methyl, ethyl, and propyl. , partial ether compounds substituted by hydroxyalkyl groups such as hydroxyethyl, hydroxypropyl, hydroxybutyl, and/or carboxyalkyl groups such as carboxymethyl, carboxyethyl, and aliphatic acyl groups such as acetyl, propionyl, butyryl. Examples include partial ester compounds.

The degree of substitution of these derivatives is not particularly limited, but is preferably 1 or less for alkyl groups, carboxyalkyl groups, and aliphatic acyl groups. When the degree of substitution increases, the number of active hydroxyl groups in the repeating units of the polysaccharide decreases, making it impossible to increase the content of triorganosilyl groups (which makes it difficult to combine with the cyclic silicone oil represented by general formula (I) above). Compatibility may be poor.

As a polysaccharide, it is considered nonionic because nonionic polysaccharides have about 3 hydroxyl groups in their repeating units, whereas ionic polysaccharides (e.g., alginic acid, chitin, etc.) have about 2 hydroxyl groups. This is because the triorganosilyl group content cannot be increased, and it is not soluble in the cyclic silicone oil represented by the above general formula (I). In addition, triorganosilyl derivatives of cellulose that are not water-soluble are not used because they do not dissolve in the cyclic silicone oil shown in general formula (1) above, perhaps because the cellulose used as the raw material is highly crystalline and substituents cannot be uniformly introduced. I can't. The hydrocarbon group having 1 to 6 carbon atoms in the triorganosilyl group represented by the general formula (II) that is present in the side chain of the polymer used as a film forming material in the present invention is a straight chain or a branched chain. an alkyl group,
For example, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, hexyl, etc.; cycloalkyl groups, such as cyclopentyl, cyclohexyl, etc.; straight-chain or branched alkenyl groups, such as vinyl, allyl, isopropenyl, l-butenyl,
Examples include l-pentenyl and 1-hexenyl, but as the number of carbon atoms in these hydrocarbon groups increases, the hydrocarbon groups become bulky and difficult to effectively introduce into polymers. Therefore, the above-mentioned alkyl groups, especially methyl, ethyl, propyl, tert-
Butyl is preferred. Specific examples of the triorganosilyl group of general formula (Il) having such a hydrocarbon group include:
Examples include trimethylsilyl group, triethylsilyl group, tripropylsilyl group, dimethylpropylsilyl group, butyldimethylsilyl group, tert-butyldimethylsilyl group, and cyclohexyldimethylsilyl group. The triorganosilyl group of general formula (n) is preferably contained in an average of 40% by weight or more in the polymer used. Average content of triorganosilyl group is 40% by weight
If it is less than 1, the solubility of the obtained polymer having a triorganosilyl group in the cyclic silicone oil represented by the above general formula (I) will be significantly poor. The polymer used in the present invention by introducing the triorganosilyl group of general formula (II) into a raw material polymer may be produced by a known method of silylating a hydroxyl group. However, in the present invention, the manufacturing method is not particularly limited.

The amount of the polymer having the triorganosilyl group as a substituent in the side chain in the film-forming external preparation of the present invention can be arbitrarily selected, but is preferably 1% by weight or more. If it is less than 1% by weight, a sufficient film cannot be formed.

Next, the drug which is the third component used in the present invention is not particularly limited as long as it can penetrate the skin and mucous membranes and exert its medicinal effect, and is appropriately selected depending on the purpose. Examples of drugs used include antibiotics, chemotherapeutic agents, vitamin preparations, enzyme preparations, keratosis treatment agents, adrenocortical hormone agents, anti-inflammatory analgesics, antispasmodics, antirheumatic agents, antigout agents, antihistamines, cardiac Examples include vascular agents, vasodilators, antihypertensive agents, arteriosclerotic agents, ulcer treatment agents, bactericidal agents, and veterinary drugs.

The present composition may be prepared by simply mixing the drug as the third component with the first and second components, but the drug may not be dissolved in this system and may be in a dispersed state.

It may be used in this state, but in order to improve dispersibility, a solvent that dissolves the drug and is compatible with the cyclic silicone oil represented by the above general formula (I) and a carbon number of 10 to 2.
A polysaccharide derivative having 0 saturated fatty acid ester groups as a substituent may also be added.

Examples of solvents that dissolve drugs and are compatible with the cyclic silicone oil represented by the above general formula (1) include ethyl acetate, impropyl myristate, neopentyl glycol di-2-ethylhexanoate, jojoba oil, and squalane. Examples of polysaccharide derivatives having a saturated fatty acid ester group having 10 to 20 carbon atoms as a substituent include dextrin fatty acid ester, hydroxypropyl stearate, laurate, and the like.

The film-forming external preparation of the present invention can be obtained by mixing a drug into a solution obtained by stirring and dissolving a polymer having the above-mentioned triorganosilyl group as a substituent in the side chain in the above-mentioned silicone oil at room temperature or under heating. However, the order of compounding may be changed arbitrarily. In addition, various organic and inorganic powders and pigment dispersants, plasticizers, fibers, fragrances, preservatives, antioxidants, ultraviolet absorbers, various thickeners such as organic bentonite, drugs, and pigments are added as necessary. Dispersion stabilizers and other diluents can be mixed.

(Effects of the Invention) The film-forming external preparation according to the present invention is liquid and/or gel-like when applied, and forms a film by drying after application.
The drug adsorbed and/or encapsulated in the formed film,
It provides a type of preparation that is absorbed transdermally through the contact surface between the skin and the coating.

According to the present invention, since the cyclic organopolysiloxane used has low viscosity and volatility, it has good spreadability during application and provides a light feel when applied. In addition, cyclic organopolysiloxanes are not biotoxic or skin irritating, making them ideal for such formulations. In addition, the polymer used in the present invention having a triorganosilyl group as a substituent in its side chain has high oxygen permeability, so it may cause dermatitis such as a rash or impede the skin's ability to breathe normally. There is no risk of inhibiting physiological effects. In addition, it forms a film that has high affinity for the skin, is strong, and has excellent water resistance, so it has excellent long-lasting medicinal effects. It also forms a very transparent film, so when applied to the skin, the appearance does not change.

(Synthesis Example) Synthesis Example 1 Polyvinyl alcohol (C-25 manufactured by Shin-Etsu Chemical Co., Ltd.)
) was dispersed in 1320 g of pyridine and ter
904g of t-butyldimethylchlorosilane to 88g of toluene
60g was added and stirred at 120°C for 6 hours.

After cooling, the reaction solution was diluted with 800 g of toluene, stirred, and then poured into methanol to precipitate a polymer, which was collected by filtration.

The obtained polymer was further dissolved in toluene, precipitated with methanol, and filtered twice.
After vacuum drying at 'C', 300 g of tert-butyldimethylsilyl polyvinyl alcohol was obtained. The Si content of the obtained polymer was 15.4% by weight (tert-butyldimethylsilyl group: 63% by weight in the polymer).
)Met.

Synthesis Example 2 Pullulan (Zaiatsu Shoji Co., Ltd.; PF-10) 20
．． After dissolving 0g in 100g of N-methylpyrrolidone at 100°C, 75°3g of N,0-bistrimethylsilylacetamide and 100g of toluene were added and heated.
The mixture was stirred and reacted at 0'C for 5 hours. Thereafter, it was purified and dried in the same manner as in Synthesis Example 1 to obtain 36.9 g of trimethylsilyl pullulan. The Si content of the obtained polymer is
21°8% by weight (trimethylsilyl group in polymer; 57
weight%).

Synthesis Example 3 Hydroxypropyl guar gum (Mishima Co., Ltd., JAGU
ARHP-60) 100g N-methylpyrrolidone 10
00g, and further added 395g of N,O-bistrimethylsilylacetamide, heated, and reacted at 140°C for 6 hours with stirring. After cooling, purification and drying were performed in the same manner as in Synthesis Example 1 to obtain 175 g of trimethylsilylhydroxypropyl guar gum. The Si content of the obtained polymer was 19.5% by weight (trimethylsilyl group in the polymer, 5% by weight).
It was 1% by weight.

(Example) Example 1 A: Indomethacin...0.50% by weight Ethyl acetate...45°00% by weight B: Octamethylcyclotetrasiloxane (Shin-Etsu Chemical Co., Ltd. ) made,
KF994)...38.25% by weight ・Decamethylcyclopentasiloxane (manufactured by Shin-Etsu Chemical Co., Ltd.; KF995)...
...6.75% by weight ・Tert-butyldimethylsilyl polyvinyl alcohol (Synthesis Example 1) ...9.50% by weight Dissolve the mixture A at room temperature and the mixture B under heating, respectively. did. Next, the solutions A and B were mixed at room temperature to obtain a uniform liquid external preparation. The obtained liquid external preparation formed an inconspicuous and non-sticky thin film in about 3 minutes after being applied to the skin. The feel during application was also good with no irritation. Furthermore, the obtained thin film did not fall off due to washing with water or sweating, and remained in close contact with the skin.

(Example 2) A: Indomethacin...0.50% by weight Isopropyl myristate...28.35% by weight B; Octamethylcyclotetrasiloxane (Shin-Etsu Chemical Co., Ltd.) Manufacturer: KF994)...43.
48% by weight ・Decamethylcyclopentasiloxane (manufactured by Shin-Etsu Chemical Co., Ltd., KF995)...
・・7.67% by weight ・Trimethylsilylpullulan (Synthesis Example 2)・・・・・・
...5.00% by weight C:-Dextrin fatty acid ester (manufactured by Chiba Flour Milling Co., Ltd.; Leopard K E)...
...15.00% by weight of the mixture was dissolved at room temperature, and the mixture of B was dissolved under heating. Next, each solution of A and B and C were mixed at room temperature, stirred under heating, and then cooled to obtain a gel-like external preparation. The resulting gel ointment, unlike conventional ones, had a light texture and was not sticky, and adhered closely to the skin after application.

(Example 3) A; Indomethacin...0.50% by weight Isopropyl myristate 28.35% by weight B; Octamethylcyclotetrasiloxane (Shin-Etsu Chemical Co., Ltd. ); KF994)...56.
23% by weight ・Decamethylcyclopentasiloxane (manufactured by Shin-Etsu Chemical Co., Ltd.: KF995)...
9.92% by weight Trimethylsilylhydroxypropyl guar gum (Synthesis Example 3) 5.00% by weight The mixture A was dissolved at room temperature and the mixture B was dissolved under heating. Next, the solutions A and B were stirred and mixed at room temperature to obtain a uniform gel-like external preparation. The resulting gel ointment is
An inconspicuous, non-sticky thin film was formed on the skin approximately 3 minutes after application. The feel during application was also good with no irritation. Furthermore, the obtained thin film did not fall off due to washing with water or sweating, and remained in close contact with the skin.

Patent applicant: Shin-Etsu Chemical Co., Ltd.

Claims (1)

[Claims] 1. A) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・・・・
・(I) (m and n in the formula are 0 or integers from 1 to 8, and 3≦m+
Cyclic organopolysiloxane represented by n≦8) General formula ▲ Numerical formulas, chemical formulas, tables, etc. are available▼・・・・・・・・・(
II) Polyvinyl alcohol having a triorganosilyl group represented by (R_1, R_2 and R_3 in the formula may be the same or different and are hydrocarbon groups having 1 to 6 carbon atoms) or water-soluble A film-forming external preparation consisting of at least one film-forming polymer selected from nonionic natural polysaccharides and their derivatives, c) a drug, and the above drugs a), b), and c). 2. The film-forming external preparation according to claim 1, wherein the cyclic polysiloxane is a cyclic dimethylpolysiloxane. 3. The film-forming external preparation according to claim 1, wherein the triorganosilyl group content of the polymer (b) is 40% by weight or more. 4. Triorganosilyl group (II) of the polymer of (b) above
The film-forming external preparation according to claim 1, wherein R_1, R_2, and R_3 are alkyl groups having 1 to 6 carbon atoms.