JPS61277613A - Gelatinous drug composition for external use - Google Patents

Abstract

PURPOSE:The titled composition having improved shape retention and endermic absorption of drug, obtained by blending a gelatinous base composition consisting of a polyvinyl alcohol, a dispersion medium, a sulfoxide compound as an endermic absorption promoter and a specific liquid substance with an endermic absorption drug. CONSTITUTION:A gelatinous base composition containing (ii) a sulfoxide compound as a dispersion medium and an endermic absorption promoter and (iii) one or more specific liquid substances selected from 8-22C saturated or unsaturated monohydric alcohol, 5-30C hydrocarbon which may contain a halogen, 11-26C fatty carboxylic acid alcohol ester, 10-14C mono--diether, and 11-15C ketone, etc., in (i) a gel skeleton consisting of a polyvinyl alcohol or a modified polyvinyl alcohol is blended with an endermic absorption drug, to give the titled composition having improved diffusion and migration of drug, releasability of the drug to the skin to be applied, and absorption properties of the drug form the skin, capable of providing various properties by regulating the amounts of the above-mentioned components.

Description

[Detailed Description of the Invention] <Industrial Application Field> The present invention relates to a gel-like external pharmaceutical composition for treating or preventing diseases by administering transdermally absorbable drugs into living bodies through the skin. .

<Conventional technology> Traditionally, drugs administered to the integument have mainly been locally active drugs for sterilization, disinfection, and analgesic effects, but in recent years, drugs that have systemic effects have been administered orally, by injection, etc. In addition, attempts have been made to administer the drug to the outer skin, a so-called transdermal administration method. When drugs, especially drugs that exhibit systemic effects, are administered transdermally, it is easy to maintain their pharmacological effects and it is easy to control the absorption rate of the drug, so side effects can occur due to excessive administration. It is possible to suppress the expression of
It has the advantage that it is less susceptible to metabolism due to the effects of cancer, allowing effective use of drugs, and that even drugs that cause gastrointestinal disorders when administered orally, such as indomethacin, can be administered safely.

However, normal skin has a protective effect on the body against external foreign substances, and generally has a property that makes it difficult for drugs to be absorbed or penetrated. Therefore, drugs cannot be administered in the form of conventional ointments, lotions, etc. However, it is difficult for the body to absorb enough drugs to exert a sufficient pharmacological effect, and to improve this problem, various promoters are being researched to promote transdermal absorption of drugs.

Among these transdermal absorption enhancers, alkyl sulfoxides such as dimethyl sulfoxide have been reported to have excellent effects, and their use is by applying them to the skin together with drugs in the form of ointments, creams, and lotions. (U.S. Pat. No. 3,551,554, U.S. Pat. No. 4)
353896, Japanese Patent Publication No. 53-31222, Japanese Patent Publication No. 55-94316).

On the other hand, in addition to the above-mentioned preparations for transdermal administration, there are tape preparations, gel preparations, etc., but gel preparations in particular are attracting attention because they have unique and excellent properties such as flexibility and drug diffusion mobility. ing.

In general, gel-like materials whose dispersion medium is water are called hydrogels, and those whose dispersion medium is organic solvent are called lyogels.In general, research on hydrogels is actively conducted in the medical field, but little research has been done on lyogels. This has not been done yet, and only some products using rubber-based polymer materials have been considered in the field of sanitary materials.

<Problems to be Solved by the Invention> As mentioned above, although alkyl sulfoxides such as dimethyl sulfoxide may exhibit excellent effects, when used as a skin liniment such as a cream, the amount of drug administered may be uneven. However, gel-like pharmaceutical preparations have not yet been developed to overcome these drawbacks and effectively exert the transdermal absorption promoting effect of sulfoxide compounds. There wasn't.

In addition, since the main component of the dispersion medium in ordinary hydrogels is water, it is not possible to contain a sufficient amount of sulfoxide compound as a transdermal absorption enhancer, and tape formulations induce plasticization of the polymeric material used. Therefore, it is not possible to increase the content of a sulfoxide compound, and therefore there is a demand for the development of a lyogel-type gel-like pharmaceutical preparation with good shape retention using a sulfoxide compound as a dispersion medium.

Means for Solving Problems〉 In view of the above-mentioned conventional techniques, the present inventors have conducted extensive studies on lyogel containing a sulfoxide compound as a dispersion medium as a transdermal absorption enhancer, and found that a hydrophilic polymer When polyvinyl alcohols, which are a type of polyvinyl alcohol, are used, a gel-like base composition that retains a large amount of a sulfoxide compound and a specific liquid substance can be obtained, and when a transdermally absorbable drug is added to the gel, it has excellent shape retention. Furthermore, it has been found that a completely new external pharmaceutical composition can be obtained in which the transdermal absorption of the drug is significantly improved.

That is, the present invention includes a sulfoxide compound as a dispersion medium of the gel and a transdermal absorption enhancer, and the following (a) to (g) in the skeleton of a gel made of polyvinyl alcohol or a modified product thereof.
An object of the present invention is to provide a gel-like external pharmaceutical composition comprising a gel-like base composition containing at least one liquid substance selected from the following, and a transdermally absorbable drug.

(a) A saturated or unsaturated monohydric alcohol having 8 to 22 carbon atoms.

(b) A hydrocarbon having 5 to 30 carbon atoms (however, it may be partially substituted with a halogen atom).

(c) Alcohol ester of aliphatic carboxylic acid having a total of 11 to 26 carbon atoms.

(dl Mono- or diether having 10 to 24 carbon atoms.

(e) Ketone having 11 to 15 carbon atoms.

(f) 2-pyrrolidonecarboxylic acid and an alcohol ester having 5 to 20 carbon atoms.

(Alcohol ester of gl Nicotine M and Charcoal SR4-20.

Polyvinyl alcohol or a modified product thereof (hereinafter referred to as polyvinyl alcohols), which is a component of the gel-like external pharmaceutical composition of the present invention, forms the skeleton of the external pharmaceutical composition of the present invention in a gel state, and sulfoxide It contains and retains a compound, a liquid substance described below, and a transdermal absorbable drug, and therefore, it can be used regardless of whether it is a chain polymer that is uncrosslinked or intramolecularly or intermolecularly crosslinked.

In addition, "polyvinyl alcohol or its modified product" as used in the present invention refers to fully saponified polyvinyl alcohol, partially saponified polyvinyl acetate, and poly(vinyl alcohol/modified product).
It also includes copolymerizable monomers).

The mechanical strength of the above-mentioned polyvinyl alcohols can be easily changed from weak to strong by changing the blending ratio and the degree of saponification and polymerization of the polyvinyl alcohol. These polyvinyl alcohols have a saponification degree of 95 mol% or more, preferably 97 mol% or more, in order to maintain practical shape retention during the production of the external pharmaceutical composition or when applied to the skin. It is better to do so.

In addition, when the degree of polymerization of polyvinyl alcohol is set to a viscosity average degree of polymerization of 1000 or more, preferably 1500 to 3300, the composition has excellent shape retention and moldability when formed into a gel. can do. On the other hand, if the viscosity average degree of polymerization is less than 1,000, especially if it is less than 900, it will become a highly viscous or fluid gel-like material that will have poor shape retention, and will not stick to the skin surface when applied to the skin. There is a possibility that the gel-like substance remains.

The sulfoxide compound used in the present invention serves as a gel dispersion medium and a transdermal absorption enhancer by dissolving a specific liquid substance that is liquid at room temperature and the polyvinyl alcohol. These sulfoxide compounds are aprotic polar solvents that dissolve polyvinyl alcohol extremely well. Examples include dimethyl sulfoxide, methyl ethyl sulfoxide, diethyl sulfoxide, dipropylsulfoxide, and dioctyl sulfoxide. 45-9 in external pharmaceutical compositions
It is blended in a range of 5% by weight. Among these sulfoxide compounds, dimethyl sulfoxide (hereinafter referred to as DMSO), which has relatively low acute toxicity and a high flash point, is preferable from the viewpoint of safety when in contact with the skin of a living body. It is also desirable in terms of safety during the manufacturing process.

The specific liquid substance used in the present invention is intended to improve the transdermal absorption of the drug contained therein and to exhibit pharmacological effects effective in treating diseases, and includes at least one of the following liquid substances.

(a) Saturated or unsaturated monohydric alcohol having 8 to 22 carbon atoms (2) The alcohol includes linear or branched alcohols, such as octyl alcohol, lauryl alcohol,
Examples include so-stearyl alcohol, oleyl alcohol, linalyl alcohol, and the like.

(b) Hydrocarbon having 5 to 30 carbon atoms (however, 1. may be partially substituted with halogen atoms): The hydrocarbon is
It may be linear, branched or cyclic.

As the halogen atom as a substituent, bromine and chloro are preferred.

The hydrocarbon is preferably an alkyl group having 5 to 30 (preferably 6 to 24) carbon atoms or having 1 or 2 unsaturated bonds in the case of a chain, and a monocyclic or 2-carbon alkyl group in the case of a chain. A ring is preferred. The number of carbon atoms in a monocyclic ring is 6
~10, preferably one or more methyl,
It may be substituted with a saturated or unsaturated alkyl having 1 to 3 carbon atoms, such as C(cHs) =CHt. Alternatively, two or more monocycles may be bonded via an alkylene.

In the case of two rings, the number of carbon atoms is preferably 10 to 12, which is
For example, it may be substituted with one or more lower alkyl such as methyl. Specifically, n-pentane, n-hexane, n-hebutane, n-octane, n-nonane, n-decane, n-undecamine, n-octadecane, 2-methylpentane, 2-methylhexane, 2,3 -dimethylhexane, 2-methylnonane, 2,6-cyclooctane, 2゜2.4.4.6,8.8-heptamethylnonane, pristane, squalane, light liquid paraffin, paramethane,
Limonene, hydrogenated product of limonene dimer, cyclohexane, 1,3-dimethylcyclohexane, cyclooctane, isobutylcyclohexane, cyclododecane, methyldecalin, decalin, octyl bromide, decyl bromide, dodecyl bromide, hexadecyl bromide, dodecyl chloride, dibromide Examples include dodecane.

(c) Alcohol ester of aliphatic carboxylic acid having a total number of carbon atoms of 11 to 26: the alcohol moiety is methyl alcohol, ethyl alcohol, n-propyl alcohol, 1s
o-propyl alcohol, n-butyl alcohol, 1s
o-butyl alcohol, 5ec-butyl alcohol, t
-butyl alcohol, n-amyl alcohol, tso-
Monohydric alcohols having 1 to 6 carbon atoms such as amyl alcohol and n-hexyl alcohol are listed as preferred. In addition, the carboxylic acid moiety has 10 to 20 carbon atoms.
Among these fatty acids, saturated fatty acids having 12 to 18 carbon atoms are preferred.

Specific examples of the ester include methyl laurate, ethyl laurate, hexyl laurate, isopropyl myristate, isopropyl palmitate, methyl stearate, and butyl stearate.

(d) Mono- or diether having 10 to 24 carbon atoms: Specifically, alkyl monoethers such as dioctyl ether, dioctyl ether, dioctyl ether, didodecyl ether, methoxydodecane, ethoxydodecane, ethylene glycol diptyl ether, ethylene glycol di Examples include alkyl diethers such as propyl ether and ethylene glycol dioctyl ether.

Its preferable carbon number is 10-15.

(e) Ketone with 11 to 150 carbon atoms: Aliphatic ketones are preferred, specifically 2-undecanone, 3-undecanone, 4-undecanone, 5-undecanone, 6-undecanone, 3-dodecanone, 4-dodecanone, 5-undecanone, Examples include dodecanone, 2-tridecanone, 3-tridecanone, 7-tridecanone, 8-pentadecanone, and 3-hexadecanone.

(f) 2-pyrrolidonecarboxylic acid and alcohol ester having 5 to 20 carbon atoms: Specifically, 2-pyrrolidonecarboxylic acid n-pentyl ester, 2-pyrrolidonecarboxylic acid n-dodecyl ester, 2-pyrrolidonecarboxylic acid n-
Eicosyl ester, 2-pyrrolidonecarboxylic acid 2-ethylhexyl ester, 2-pyrrolidonecarboxylic acid3.
Examples include 7-dimethyloctyl ester, 2-pyrrolidonecarboxylic acid 2-cyclohexylethyl ester, 2-pyrrolidonecarboxylic acid oleyl ester, and 2-pyrrolidonecarboxylic acid geranyl ester.

(g) Nicotinic acid and alcohol ester having 4 to 20 carbon atoms: Specifically, nicotinic acid n-pentyl ester, nicotinic acid n-dotesyl ester, nicotine fin-eicosyl ester, nicotinic acid 2-ethylhexyl ester, nicotinic acid Examples include acid 3,7-dimethyloctyl ester, nicotinic acid cyclobutyl ester, and nicotinic acid sulfuryl ester.

The concentration of the polyvinyl alcohol in the gel-like external pharmaceutical composition of the present invention is not particularly limited, and can be arbitrarily changed depending on the shape retention and mechanical strength of the target composition and the amount of the sulfoxide compound to be contained. However, it is not rated 5 in terms of controllability of gelation rate and shape retention of the resulting composition.
It is desirable that the content be in the range of ~35% by weight, preferably 10-25% by weight. A gel-like substance can be obtained by gelation even at a concentration exceeding 35% by weight, but the viscosity of the solution before the gelation reaction increases, and the viscosity may increase during storage in the solution state or a gelation reaction may occur spontaneously. It is difficult to handle (
It may happen. In addition, if the amount is less than 5% by weight, the solution viscosity will be low, so the polyvinyl alcohol may not be able to sufficiently retain the sulfoxide compound even after the gelation reaction is completed, resulting in a soft gel-like product with slightly poor shape retention. There is a risk that

The transdermal drug contained in the gel-like base composition is not particularly limited as long as it can be administered to the skin, and if it is a drug with local action, the drug is intended to penetrate deep into the subcutaneous layer, Furthermore, in the case of a drug that acts on the systemic system, a gel-like external pharmaceutical composition is provided for the purpose of rapidly transferring the drug into the blood.

Local drugs include local anesthetics (e.g., procaine hydrochloride, tetrahydrochloride, dibucaine hydrochloride, lidocaine, lidocaine hydrochloride, piperocaine acetate, etc.), antihistamines (e.g., diphenhydramine hydrochloride, chlorpheniramine maleate, maleic acid) Prompheniramine, diphenylimidazole, clemizole hydrochloride, etc.],
Antibiotics [e.g., lincomycin, penicillin G, erythromycin, tetracycline hydrochloride, clindama, icin, kanamycin, oxytetracycline, chloramphenicol, fradiomycin, nystatin, grami hydrochloride, sydin, bacitracin, etc.], antifungal agents [e.g.,
Griseofulvin, N-methyl-N-(3-lyl)thiocarbamic acid-2-naphthyl ester, siametazole hydrochloride, oriothricin, trifumycin, virolnitrile, 5-fluorocytosine, etc.].

Specifically, as systemic drugs, benzodiazepines [
e.g., diazepam, nitrazepam, fludiazepam, lorazepam, prazepam, fludiazepam, clonazepam, etc.], diuretics (e.g., thiazides (e.g., pendroflumethiazide, polythiazide, metoclotiazide, trichlormethiazide, cyclopenthiazide, pentyl) hydrochlorothiazide, hydrochlorothiazide, bumetanide, etc.), antihypertensive agents (e.g., clonidine hydrochloride, clonidine, etc.)
, antihistamines [e.g., aminoethers (e.g., diphenhydramine, carbinoxamine, diphenylbilarin, etc.), ethylenediamines (e.g., fenbenzamine, etc.), monoamines (e.g., chlorpheniramine, etc.)
], non-steroidal anti-inflammatory drugs [e.g., indomethacin, ibuprofen, ibufenac, alclofenac, diclofenac, diclofenac sodium, mefenamic acid, flurbiprofen, flufenamic acid, ketoprofen, etc.], anti-tumor agents [e.g., 5 -Fluorouracil, 1-(2-tetrahydrofuryl)5-fluorouracil, cytarabine, proxuridine, etc.], steroidal anti-inflammatory agents (e.g., cortisone, hydrocortisone, prednisolone, triamcinolone, dexamethacin, betamesazoshi, etc.), antiepileptic agents (e.g., ethosuximide) etc.], antiarrhythmia agents [e.g., ajmaline, brassimarin, pindolol, propranolol, quinidine, etc.],
Neuropsychiatric agents [e.g., clofluperidol, trifluperidol, haloperidol, moperon, scopolamines (
(e.g., methylscopolamine, butylscopolamine, scopolamine hydrobromide, etc.), chloropromacine, atrobins (e.g., methylatropine bromide, methylanisotropin bromide, etc.)], vasodilators (e.g., isosorbide dinitrate, nitroglycerate, etc.) , phosphorus, pentaerythritol tetranitrate, propyl nitrate, dipyridamole, etc.],
Examples include antibiotics [eg, tetracyclines (eg, tetracycline, oxytetracycline, methacycline, doxycycline, methacycline, etc.), chloramphenicols, erythromycins], and the like.

The content of the above drug may be sufficient as long as it has the desired pharmacological effect, and varies depending on the type of drug used, patient's weight, symptoms, etc. Depending on these conditions, one or more of the above drugs may be used. What is necessary is just to select suitably by combining two or more types. In the gel-like external pharmaceutical composition of the present invention, it is usually 0.01 to 20% by weight, especially 0.2 to 20% by weight based on the total amount.
Preferably it is 10% by weight. Incidentally, the amount of the drug used can be adjusted by increasing or decreasing the area to which the composition is applied or the thickness of the gel-like material, so it is not necessarily limited to the above-mentioned amount.

An example of a method for producing a gel-like base composition is a method in which a predetermined amount of polyvinyl alcohol is dissolved in DMSO to obtain a solution state, and then the liquid substance is added and gelated after thorough mixing. Another example is a method in which the liquid substance is made into a solution and then gelled in the same manner as described above, and then the liquid substance is absorbed and retained.

The gelling means used in producing the composition of the present invention is as follows: (a) For example, the solution is heated to a temperature of about 75° C. to form a uniform solution, and then allowed to stand at room temperature while being allowed to cool.

(b) Gradually air dry the solution.

(c) Irradiating the solution with radiation such as electron beams or T-rays.

(d) Adding a gelling agent such as boric acid or borax (or an aqueous solution thereof) to the solution.

(e) Freeze the solution at a low temperature of -15°C or lower, shape it, and then re-thaw it, or freeze and shape it and then perform a vacuum drying process and then thaw it, or repeat freezing and thawing several times.

Examples include.

A gel-like base composition can be obtained using such a gelling method, but the gelling method may be applied after injecting a solution into a mold for forming the final object, A solution prepared to an appropriate viscosity is applied onto a film or sheet made of paper, woven fabric, non-woven fabric, metal foil, or a combination thereof and then gelled, or once gelled into a molded object of an appropriate shape. It may be later formed into a desired shape by means such as slicing.

The shape of these molded bodies may be granular, film-like, block-like, plate-like, cylindrical, or any other shape depending on the purpose.

In the gel-like base composition, it is also possible to make the skeleton made of polyvinyl alcohols porous by selecting the above-mentioned gelling means, and by making it a porous body, mechanical strength, shape retention, and content can be improved. It is also possible to control the diffusion mobility of transdermal drugs during cleavage.

In addition, in order to incorporate a transdermal absorbable drug into the gel-like base composition as a gel-like external pharmaceutical composition, it may be added at the same time when the base composition is manufactured; The drug may then be absorbed and retained as a drug solution dissolved in an appropriate solvent.

In the present invention, polyvinyl alcohol is used as a gelling component, and a gel-like base composition or transdermal drug containing a specific liquid substance and a sulfoxide compound that is liquid at room temperature is contained therein. Provided is a gel-like external pharmaceutical composition that retains the gel strength, but various fillers and reinforcing materials such as silicon compounds, calcium carbonate, clays, and glass fibers may be included in the composition for the purpose of improving gel strength. You can also do it. In addition, for the purpose of improving the solubility and release properties of the transdermally absorbable drug contained in the gel-form external pharmaceutical composition of the present invention, methyl alcohol, ethyl alcohol, propyl alcohol, etc., which can be optionally mixed with a sulfoxide compound, are also used. Auxiliary agents such as lower alcohols, glycols, and water can also be added as appropriate.

The content of each of the above substances can be arbitrarily selected depending on the purpose of use and the type of each substance. part, the filler is 0.1 to 200 parts by weight, and the auxiliary agent is 0.1 part by weight.
A range of 100 parts by weight is desirable since it does not adversely affect the properties of the composition itself.

<Effects of the Invention> As described above, the gel-like external pharmaceutical composition of the present invention contains polyvinyl alcohol, which is a hydrophilic polymer, or a modified product thereof, a specific liquid substance, and a sulfoxide compound as a transdermal absorption enhancer. By adjusting the amount of the sulfoxide compound contained, the mechanical strength of the composition can be changed, ranging from elastic and strong to soft and jelly-like. It is possible to obtain products with various characteristics. In addition, unlike ordinary hydrogels, the sulfoxide compound contained as a dispersion medium has the effect of promoting transdermal absorption of drugs, and the base composition exhibits a wet state due to this compound, so it has a dense structure. Unlike those in a solid state, the transdermal drug contained in the external pharmaceutical composition comprising the base composition has diffusion mobility, release properties to the skin surface to which it is applied, and absorption properties of the drug from the skin surface. It is highly effective in treating or preventing diseases.

<Examples> Examples of the present invention will be shown below and explained in more detail, but the present invention is not limited to these in any way, and various modifications can be made without departing from the technical idea. .

Example 1 31.6 g of polyvinyl alcohol (aqueous solution viscosity 22 centipoise/20°C with saponification degree 99.0 mol% and viscosity average degree of polymerization 1500.4% by weight) (water content 5% by weight) was dissolved in dimethyl sulfoxide (DMSO). 90 g under heating at 80°C to make a solution with a solid content concentration of 25.0% by weight. After adding 9.0 g of lauryl alcohol and 1.3 g of hydrocortisone acetate and thoroughly mixing and dissolving, a solution with a thickness of 2 The mixture was placed in a petri dish so as to form a crane and left to stand at a temperature of 20° C. for 48 hours to obtain a gel-like external pharmaceutical composition of the present invention.

Example 2 13.0 g (water content 5 wt%) of powder of polyvinyl alcohol (saponification degree 99.4 mol%, viscosity average degree of polymerization 2600.4 wt% aqueous solution viscosity 66 centipoise/20°C) was added to DMSO 93.5 g at 75% After melting under heating at ℃ to make a solution with a solid content concentration of 11.3% by weight, 10 g of octyl nicotinate and 2.3 g of diclofenac sodium were added, thoroughly mixed and dissolved, and the solution was made to a thickness of 1111 mm. The mixture was placed in a petri dish and air-dried at room temperature for 72 hours to obtain a gel-like external pharmaceutical composition of the present invention.

Example 3 Polyvinyl alcohol, coal powder 21 used in Example 1
．． 1g (water content 5% by weight) in 78.9g of DMSO at 80%
After melting under heating at ℃ to make a solution with a solid content concentration of 20.0% by weight, add isopropyl myristate trog and 1.1 g of propranolol hydrochloride, mix thoroughly, and dissolve, resulting in a thickness of 2 cranes. Put it in a petri dish for 20 minutes.
Example 4 Aqueous solution of polyvinyl alcohol (saponification degree 97.0 mol%, viscosity average degree of polymerization 1800.4% by weight, viscosity 28 centiboise) /20°C) powder 21.5g (moisture content 7% by weight)
was dissolved in 078.5 g of DMS under heating at 80°C to make a solution with a solid content concentration of 20.0% by weight, and then N-methylpyrrolidone io, Og, 8.0 g of linalyl alcohol, and 4.0 g of diazepam were added. After thoroughly mixing and dissolving, the gel-like external pharmaceutical composition of the present invention was prepared by placing the gel in a petri dish to a thickness of 1 square inch, freezing at -40°C, and thawing at 20°C four times. Obtained.

Examples 5 to 8 Limonene, ethylene glycol dioctyl ether, 3-dodecanone, and 2-pyrrolidonecarboxylic acid n-dodecyl ester were added in place of lauryl alcohol to the solution obtained in Example 1, mixed, and the mixture was placed in a glass beaker. The procedure of freezing at -20'C and thawing at 20C was repeated four times to obtain a bulk gel-like external pharmaceutical composition.

Experimental Example 1 The gel-like external pharmaceutical compositions obtained in Examples 1 and 5 to 8 were punched out to a diameter of 12w1, and applied to the pressure side of the forearm of a healthy adult male using surgical adhesive tape, and peeled off after 8 hours. After removal, the drug remaining on the skin surface was gently wiped off with soapy water. As a result of determining the presence of pallor due to vasoconstriction 1, 4, and 8 hours after removal, significant pallor was observed even after 8 hours.

Experimental Example 2 Table 1 shows the results of testing the inhibitory effect of the gel-like external pharmaceutical composition obtained in Example 2 on carrageenan foot edema.

The test method was to use Wistar male rats (body weight approx. 200g).
) were used as a group of 10 rats, and after measuring the right hind paw volume of each rat, a sample piece with a diameter of about 2 cm and a thickness of 211 mm was applied to the right hind paw, and after 2 hours, it was removed and a 0.
Inject 0.05 ml of 5% carrageenan saline subcutaneously,
Three hours later, the volume of the right hind paw was measured, and the difference between the volume before and after applying the sample piece was defined as the paw edema volume.

Vc-Vt Carrageenin foot edema suppression rate = X100c However, Vc and Vt indicate the average foot edema volume of the control group and the sample piece applied group, respectively.

Table 1 Experimental Example 3 The gel-like external pharmaceutical composition obtained in Example 3 was
11, and punched into Wistar male rats (body weight approx.
00 g) on the pricked area of the chest using surgical adhesive tape, and the caudal artery pressure was measured over time to examine the blood pressure lowering effect. Table 2 shows a comparison with the case without treatment.

Table 2 Experimental Example 4 The gel-like external pharmaceutical composition obtained in Example 4 was
A red-haired monkey (weighing approximately 15 kg) cut into 4 cm pieces and with pricked hair.
The blood concentration of diazepam in the blood was measured by applying surgical adhesive tape to the chest of the patient and collecting blood over time.

The results are shown in Table 3.

As is clear from the results in Table 3 and above, the gel-like external pharmaceutical composition of the present invention had good release of transdermally absorbable drugs, and its pharmacological effects were very remarkable.

Claims (4)

[Claims] (1) In the skeleton of a gel made of polyvinyl alcohol or a modified product thereof, a sulfoxide compound as a dispersion medium of the gel and a transdermal absorption enhancer, and at least one type of liquid substance selected from the following liquid substances (a) to (g) are added. A gel-like external pharmaceutical composition comprising a gel-like base composition containing a transdermally absorbable drug. (a) A saturated or unsaturated monohydric alcohol having 8 to 22 carbon atoms. (b) A hydrocarbon having 5 to 30 carbon atoms (however, it may be partially substituted with a halogen atom). (c) Alcohol ester of aliphatic carboxylic acid having a total of 11 to 26 carbon atoms. (d) Mono- or diether having 10 to 24 carbon atoms. (e) Ketone having 11 to 15 carbon atoms. (f) 2-pyrrolidonecarboxylic acid and an alcohol ester having 5 to 20 carbon atoms. (g) Nicotinic acid and alcohol ester having 4 to 20 carbon atoms. (2) The gel-like pharmaceutical composition for external use according to claim 1, wherein the polyvinyl alcohol has a degree of saponification of 95 mol% or more. (3) The viscosity average degree of polymerization of polyvinyl alcohol is 100
3. The gel-like external pharmaceutical composition according to claim 1 or 2, wherein the gel composition is 0 or more. (4) The gel-like external pharmaceutical composition according to claim 1, wherein the sulfoxide compound is dimethyl sulfoxide.