JP7190981B2 - gel composition - Google Patents

Description

The present invention relates to gel compositions.

As dosage forms of transdermal preparations, patches, poultices, tapes, ointments, gels, lotions, creams, aerosols, and the like are known. In particular, when a highly fluid composition such as a lotion is applied to the skin, the applied composition may drip. On the other hand, a gel contains a gelling agent in its composition and increases the viscosity of the composition, so it is generally known that the composition does not drip easily even after being applied to the skin. It is

JP-A-2003-192575 JP 2014-114273 A JP 2014-114274 A Japanese Patent Application Laid-Open No. 2001-342113 JP-A-1-305012 WO2014/050301

In a gel containing a physiologically active substance, when the gel is applied, the components contained in the gel may agglomerate to form a solid content, resulting in "twisting". “Wrinkle” generally means that when the composition is applied to the skin, the solid content contained in the composition dries and forms a scale-like (paste-like) lump. For example, in gel formulations containing carboxyvinyl polymer, solids such as ionic water-soluble polymers may aggregate due to interactions with ionic components such as physiologically active substances.

When twisting occurs, problems may occur such as the solid content easily adhering to clothes, poor appearance and feel, and insufficient medicinal effects of physiologically active substances.

Therefore, an object of the present invention is to provide hydroxypropyl cellulose (hereinafter also referred to as "HPC") and hydrophobized hydroxypropylmethyl cellulose (hereinafter also referred to as "hydrophobic HPMC") that are less prone to wrinkling when rubbed on the skin. It is to provide a gel containing and a method for producing the same.

The present inventors have found that a gel containing HPC, hydrophobized HPMC and a specific surfactant is less likely to wrinkle when applied to the skin than when each is used alone. .

That is, the present invention provides the following [1] to [16].
[1] A gel composition containing a physiologically active substance, water, HPC, hydrophobized HPMC, and a surfactant, wherein the surfactant is a polyoxyethylene unit having an average added mole number of oxyethylene units of 20 to 50. A gel composition which is an ethylene alkyl ether or a polyethylene glycol saturated fatty acid ester having an average number of added moles of oxyethylene units of 45-60.
[2] The gel composition of [1], wherein the polyoxyethylene alkyl ether is selected from the group consisting of polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether and polyoxyethylene behenyl ether. .
[3] The gel composition of [1] or [2], wherein the polyethylene glycol saturated fatty acid ester is polyoxyethylene monostearate.
[4] The gel composition according to any one of [1] to [3], wherein the surfactant has an HLB value of 18-20.
[5] The surfactant is at least one surfactant selected from the group consisting of polyoxyethylene (30) behenyl ether, polyoxyethylene (45) monostearate and polyoxyethylene (40) cetyl ether. , the gel composition according to any one of [1] to [4].
[6] The gel composition according to any one of [1] to [5], wherein the surfactant has a concentration of 0.3 to 5% by mass relative to the total mass of the gel composition.
[7] The gel composition according to any one of [1] to [6], wherein the total content of HPC and hydrophobized HPMC is 2% by mass or less relative to the mass of the entire gel composition.
[8] The content of HPC is less than 1.5% by mass relative to the total weight of the gel composition, and the content of hydrophobized HPMC is less than 1.5% by mass relative to the total weight of the gel composition. The gel composition according to any one of [1] to [7].
[9] A method for producing a gel composition according to any one of [1] to [8], which comprises mixing a physiologically active substance, water, HPC, hydrophobized HPMC and a surfactant.
[10] The method of [9], wherein the polyoxyethylene alkyl ether is selected from the group consisting of polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether and polyoxyethylene behenyl ether.
[11] The method of [9] or [10], wherein the polyethylene glycol saturated fatty acid ester is polyoxyethylene monostearate.
[12] The method according to any one of [9] to [11], wherein the HLB value of the surfactant is 18-20.
[13] The surfactant is at least one surfactant selected from the group consisting of polyoxyethylene (30) behenyl ether, polyoxyethylene (45) monostearate and polyoxyethylene (40) cetyl ether. , the method according to any one of [9] to [12].
[14] The method according to any one of [9] to [13], wherein the surfactant has a concentration of 0.3 to 5% by mass relative to the total mass of the gel composition.
[15] The method according to any one of [9] to [14], wherein the total content of HPC and hydrophobized HPMC is 2% by mass or less relative to the mass of the entire gel composition.
[16] The content of HPC is less than 1.5% by mass relative to the total weight of the gel composition, and the content of hydrophobized HPMC is less than 1.5% by mass relative to the total weight of the gel composition. The method according to any one of [9] to [15].

ADVANTAGE OF THE INVENTION According to this invention, the gel composition which can suppress generation|occurrence|production of a twist when rubbing on skin can be provided. In addition, the gel composition of the present invention can exert its physiological activity by percutaneously absorbing the physiologically active substance.

4 is a graph showing the results of Test 1; 4 is a graph showing the results of Test 2; 4 is a graph showing the results of Test 3;

The present invention is described in detail below.

A gel composition according to one embodiment of the present invention is a gel composition comprising a bioactive agent, water, HPC, hydrophobized HPMC, and a surfactant, wherein the surfactant comprises an average addition of oxyethylene units of The gel composition is a polyoxyethylene alkyl ether having a molar number of 20 to 50, or a polyethylene glycol saturated fatty acid ester having an average molar number of oxyethylene units added of 45 to 60.

The physiologically active substance is not particularly limited as long as it is known in the art to have physiological activity. Examples of physiologically active substances include antifungal agents (e.g., butenafine, terbinafine, naftifine, amorolfine, neticonazole, luliconazole, lanoconazole, oxiconazole, ketoconazole, miconazole, tioconazole, bifonazole, clotrimazole, econazole, itraconazole, fluconazole). , anti-inflammatory analgesics (e.g., indomethacin, ketoprofen, diclofenac, felbinac, flurbiprofen, loxoprofen, ibuprofen, ibuprofen piconol, guaiazulene, allantoin, piroxicam, glycyrrhizic acid, glycyrrhetinic acid, salicylic acid, methyl salicylate, ethylene glycol monosalicylate) , antihistamines (e.g., mediator release inhibitors (tranilast, cromoglycate), histamine H1 receptor antagonists ( _oxatomide , mequitazine, emedastine, ebastine, loratadine, cetirizine, desloratadine, fexofenadine, astemizole, azelastine, chlorfenidin lamin, diphenhydramine, ketotifen), histamine H2 receptor antagonists ₍ cimetidine, ranitidine, famotidine, nizatidine), histamine H3 receptor antagonists (thioperamide, _impromidine , mifentidine, _impentamine , clozapine), histamine H4 receptor antagonists, essential oils Ingredients (e.g. l-menthol, camphor, limonene, isopulegol, borneol, eugenol, eucalyptus oil, mint oil, clove oil, cinnamon oil, tea tree oil), fungicides (e.g. isopropylmethylphenol, chlorhexidine gluconate, acrinol , benzalkonium hydrochloride), local anesthetics (e.g., dibucaine, lidocaine, procaine, tetracaine, bupivacaine, propitocaine, oxybuprocaine, mepivacaine, oxethazaine), antipruritics (e.g., crotamiton, ictamol, moktal), blood circulation promotion agents (e.g. capsaicin, dihydrocapsaicin, capsanthin, nonylic acid vanillylamide, benzyl nicotinate), steroid hormones (e.g. dexamethasone valerate, dexamethasone valerate acetate, dexamethasone propionate, prednisolone acetate, prednisolone valerate acetate, prednisolone, propionate butyrate Hydrocortisone Acetate, Hydrocortisone Acetate, Butyrate acid hydrocortisone, cortisone acetate, clobetasone butyrate, triamcinolone acetonide, diflucortolone valerate, difluprednate, diflorazone acetate, betamethasone dipropionate, amcinonide, halcinonide, budesonide, alclomethasone propionate), berberine, Phellodendron bark powder, arnica tincture, tocopherol and the like. The physiologically active substance may be in the form of a free form of the corresponding compound or in the form of a pharmacologically acceptable salt. Physiologically active substances may be used singly or in combination of two or more. A preferred physiologically active substance is diclofenac or a pharmacologically acceptable salt thereof. Pharmaceutically acceptable salts include metal salts such as sodium, potassium and calcium, and ammonium salts such as ammonia, triethylamine, diethanolamine, triethanolamine and hydroxyethylpyrrolidine.

The content of the physiologically active substance may be 0.001 to 15% by mass, preferably 0.1 to 10% by mass, and 0.5 to 7% by mass, based on the mass of the entire gel composition. is more preferable.

The water content may be 20 to 60% by weight, preferably 30 to 50% by weight, more preferably 35 to 45% by weight, based on the weight of the entire gel composition. When the water content is 20% by mass or more, the gel composition has appropriate fluidity, is easy to apply to the skin, and is less likely to become sticky after application. Moreover, when the water content is 60% by mass or less, the gel composition is less likely to drip after being applied to the skin.

HPC is a nonionic cellulose ether. The HPC used in the present invention may be purchased and used as a commercial product. HPC is used as a lubricant for tablets or granules, a coating agent, a disintegrant, a binder, a suspending agent or stabilizer for syrup, a thickening agent for poultices, an ointment, a jelly base, and the like. As a food additive, it is used as a film-forming agent, protective colloid, stabilizer, dispersant, thickening agent, binder, and the like.

The content of HPC is less than 1.5% by weight, may be 0.2-1.4% by weight, and is 0.3-1.3% by weight, based on the weight of the entire gel composition. is preferred, 0.4 to 1.2 mass % is more preferred, and 0.5 to 1.0 mass % is particularly preferred.

Hydrophobized HPMC is HPMC into which a hydrophobic group has been introduced. The hydrophobic group may be an alkyl group or alkenyl group having 4 to 30 carbon atoms, an alkyl group having 12 to 24 carbon atoms such as cetyl group, lauryl group, stearyl group, oleyl group, or It may be an alkenyl group. Moreover, the hydrophobic group may optionally have an ether bond or a hydroxy group. Based on its weight, the hydrophobized HPMC may contain 0-33% by weight of methoxy groups, preferably 10-30% by weight of methoxy groups, and 21.5-30% by weight of methoxy groups. More preferably, it contains 21.5 to 24% by weight or 27 to 30% by weight of methoxy groups. Based on its weight, the hydrophobized HPMC may contain 0-20% by weight of hydroxypropyloxy groups, preferably 4-15% by weight of hydroxypropyloxy groups, and 7-11% by weight of hydroxypropyloxy groups. More preferably, it contains an oxy group. Hydrophobized HPMC may be HPMC having a stearyloxy group (stearyloxy HPMC). Stearyloxy HPMC may contain 0.3 to 4.5% by weight of stearyloxyhydroxypropyloxy groups, and may contain 0.3 to 2% by weight of stearyloxyhydroxypropyloxy groups, based on its weight. More preferably, it contains 0.3-0.6% by weight or 1-2% by weight of stearyloxyhydroxypropyloxy groups. As hydrophobized HPMC, for example, Sangelose 60L, 60M, 90L, and 90M (trade names, manufactured by Daido Kasei Kogyo Co., Ltd.) may be used.

Hydrophobized HPMC is superior in thickening effect to cellulose derivatives such as hydroxyethyl cellulose (HEC) and HPC, and is also superior in compatibility with lower alcohols. Hydrophobized HPMC easily forms a thixotropic gel, is superior in shape retention, and can further suppress stickiness after application.

The content of hydrophobized HPMC is less than 1.5% by weight, may be 0.2-1.4% by weight, and is 0.3-1.3% by weight, based on the weight of the entire gel composition. , more preferably 0.3 to 1.1% by mass, and particularly preferably 0.4 to 0.9% by mass.

The total content of HPC and hydrophobized HPMC is 2.0% by mass or less, preferably 0.5 to 2.0% by mass, preferably 1.0 to 2.0% by mass, based on the mass of the entire gel composition. 0% by mass, and particularly preferably 1.4 to 2.0% by mass. When the total content of HPC and hydrophobized HPMC is 2.0% by mass or less, the occurrence of twisting can be further suppressed.

The surfactant is a polyoxyethylene alkyl ether having an average number of added moles of oxyethylene units of 20 to 50 (hereinafter also referred to as "POE alkyl ether"), or an average number of added moles of oxyethylene units of 45 to 60 is a polyethylene glycol saturated fatty acid ester.

The alkyl group of the POE alkyl ether preferably has 10 to 24 carbon atoms, more preferably 16 to 24 carbon atoms, and even more preferably 18 to 22 carbon atoms. Preferred surfactants are POE behenyl ether, POE stearyl ether, POE lauryl ether or POE cetyl ether.

POE behenyl ether preferably has an average number of added moles of oxyethylene units of 30-50, more preferably 30-40. POE stearyl ether preferably has an average number of added moles of oxyethylene units of 20-50, more preferably 20-40. POE lauryl ether preferably has an average number of added moles of oxyethylene units of 20-50, more preferably 20-30. POE cetyl ether preferably has an average number of added moles of oxyethylene units of 23-50, more preferably 23-40.

The surfactant is preferably a nonionic surfactant with an HLB value of 18-20. The HLB value is a numerical value indicating the balance between hydrophilicity and lipophilicity of a surfactant, and is defined in the range of 0-20. The closer the HLB value to 0, the stronger the lipophilicity, and the closer the HLB value to 20, the stronger the hydrophilicity. For example, the HLB value of polyethylene glycol monolaurate (10E.O.) (trade name: NIKKOL MYL-10) is 12.5, and the HLB value of POE (15) cetyl ether (trade name: NIKKOL BC-15) is 15.5. By containing a surfactant with an HLB value of 18 to 20, it is possible to further suppress the occurrence of wrinkling when the gel composition is applied to the skin.

Examples of such surfactants include POE (30) behenyl ether, POE (20) stearyl ether, POE (21) lauryl ether, POE (25) lauryl ether, POE (23) cetyl ether, POE (25) POE alkyl ethers such as cetyl ether, POE (30) cetyl ether, POE (40) cetyl ether, polyethylene glycol monostearate (45E.O.), polyoxyethylenes such as polyethylene glycol monostearate (55E.O.) Saturated fatty acid esters can be mentioned. More specifically, NIKKOL BB-30, NIKKOL BS-20, NIKKOL BL-21, NIKKOL BL-25, NIKKOL BC-23, NIKKOL BC-25, NIKKOL BC-30, NIKKOL BC-40, NIKKOL MYS-45V , NIKKOL MYS-45MV, NIKKOL MYS-55V, and NIKKOL MYS-55MV (all trade names, manufactured by Nikko Chemicals Co., Ltd.) may be used as surfactants. In the above, the number in parentheses after POE is the average added mole number of oxyethylene units.

The HLB value can be measured by a method well known to those skilled in the art. The measurement of the HLB value is, for example, the most stable when emulsifying a standard oil (e.g., liquid paraffin) and purified water using a standard HLB-known surfactant and an HLB-unknown sample, respectively. A method of obtaining the ratio of a combination that gives an emulsion and comparing the two can be mentioned. The composition of the composition used for measurement may be 40% by weight of oil phase, 56% by weight of purified water, 4% by weight of surfactant or HLB unknown sample. For the measurement method, reference may be made to the descriptions in JP-A-2010-099017, JP-A-2005-272750, JP-A-2002-301352, and the like.

The content of the surfactant may be 0.3 to 5.0% by mass, preferably 0.5 to 3.0% by mass, based on the mass of the entire gel composition, and 1.0% by mass. More preferably, it is up to 3.0% by mass. When the content of the surfactant is 1.0% by mass or more, there is a tendency that the occurrence of twisting can be further suppressed. When the content of the surfactant is 3.0% by mass or less, the feeling of applying the gel composition to the skin is excellent, and the applied surface tends to be less sticky.

The ratio of the total content of HPC and hydrophobized HPMC to the content of surfactant may be 0.4-4, more preferably 0.63-2. When the ratio is within this range, it is easier to suppress the occurrence of twisting.

The gel composition according to the present embodiment may further contain other components as long as the effect of suppressing the occurrence of twisting is exhibited. Other ingredients include other gelling agents, lower alcohols, oily ingredients, absorption enhancers, solubilizers, stabilizers, pH adjusters, preservatives and anti-rash agents.

Other gelling agents are semi-synthetic starches such as methylhydroxypropyl starch, hydroxypropyl starch, hydroxyethylcellulose (HEC), hydroxyethylmethylcellulose, hydroxypropylmethylcellulose (HPMC), propylene glycol alginate, gum arabic, guar gum, agar, starch, locust bee gum, mannan, galactomannan, curdlan, dextran, pullulan, polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, polyacrylamide.

The content of other gelling agents may be 0.5 to 2.0% by mass, preferably 0.7 to 2.0% by mass, based on the mass of the entire gel composition. 0 to 2.0% by mass is more preferable.

A lower alcohol functions as a liquid medium for forming a gel with a water-soluble polymer in the gel base. Moreover, when a lower alcohol is contained, the drying time after application of the composition can be shortened, and the feeling of use is further improved. The lower alcohol may be a fatty alcohol having 1-6 carbon atoms, preferably a fatty alcohol having 1-3 carbon atoms. Alcohols with more carbon atoms dry more slowly after application. Lower alcohols include, for example, ethanol and isopropanol, preferably ethanol. A lower alcohol may be used individually by 1 type, and may be used in combination of 2 or more type.

The content of the lower alcohol is not particularly limited. preferably 0.8 to 1.2 times the amount. When the content of the lower alcohol is 0.5 times or more the content of water, the feeling of application can be further improved, and the drying time after application can be further shortened. When the content of the lower alcohol is not more than twice the content of water, the swelling or dissolution of the gelling agent can be further promoted, and irritation to the skin due to the lower alcohol can be further reduced.

The oily component may be any component that can form the oil phase of the gel composition. By adding an oil component, the gel composition can be emulsified, and even if the physiologically active substance has poor water solubility, the content can be easily increased. Oily ingredients include, for example, avocado oil, linseed oil, olive oil, orange oil, chamomile oil, sesame oil, wheat germ oil, rice bran oil, safflower oil, squalane (phytosqualane, olive squalane, etc.), squalene, soybean oil, Tea oil, evening primrose oil, camellia oil, turpentine oil, corn oil, rapeseed oil, palm oil, peppermint oil, castor oil, sunflower oil, jojoba oil, cottonseed oil, coconut oil, eucalyptus oil, peanut oil, lemon oil, rose oil, etc. Vegetable oil, beef tallow, squalane, squalene, turtle oil, milk fat, horse oil, mink oil, lanolin, animal oils such as egg yolk oil, cholesterols (cholesterol, phytosterols, etc.), fatty acids (capric acid, oleic acid, etc.), Fatty alcohols (oleyl alcohol, lauryl alcohol, isostearyl alcohol, etc.), fatty acid esters (diisopropyl adipate, isopropyl palmitate, etc.), paraffin oil, silicone oil and the like.

The absorption enhancer may be anything as long as it has the effect of promoting percutaneous absorption of physiologically active substances. Examples of absorption enhancers include fatty acid esters such as propylene carbonate, diethyl sebacate and diisopropyl adipate, crotamiton and propylene glycol.

Any dissolving agent used in the art can be used as long as it can dissolve the components contained in the gel composition according to the present embodiment. Examples of solubilizers include higher alcohols (e.g., cetyl alcohol, stearyl alcohol, behenyl alcohol, oleyl alcohol, octyldodecanol), fatty acid esters (e.g., isopropyl myristate, octyldodecyl myristate, cetyl myristate, myristyl myristate, diethyl sebacate, diisopropyl sebacate, diisopropyl adipate, oleyl oleate, hexyl laurate, cetyl isooctanoate, medium chain fatty acid triglyceride, propylene glycol fatty acid ester, etc.), N-methyl-2-pyrrolidone, triacetin, benzyl alcohol, l - menthyl glyceryl ether, polyhydric alcohols (glycerin, propylene glycol, polyethylene glycol, polypropylene glycol, sorbitol, 1,3-butylene glycol, dipropylene glycol, batyl alcohol (glycerin-α-monostearyl ether), etc.), dimethyl sulfoxide mentioned.

The stabilizer may be any component as long as it can suppress decomposition of the physiologically active substance by ultraviolet light or oxygen. Examples of stabilizers include ascorbic acid, ascorbyl palmitate, propyl gallate, dibutylhydroxytoluene, dibutylhydroxyanisole, tocopherol, tocopherol acetate, sodium sulfite, sodium hydrogensulfite, sodium pyrosulfite, 2-mercaptobenzimidazole, oxybenzone. etc.

The content of the stabilizer may be 0.001 to 1% by mass, preferably 0.01 to 0.5% by mass, and 0.05 to 0.5% by mass, based on the total mass of the gel composition. 0.2% by weight is more preferred.

A pH adjuster is a component added to adjust the pH of the gel composition to a pH suitable for application to the skin. Furthermore, the pH of the gel composition is preferably a pH suitable for the storage stability and percutaneous absorbability of the physiologically active substance. Examples of pH adjusters include acidifying agents such as citric acid, acetic acid, lactic acid and phosphoric acid, and alkalizing agents such as monoethanolamine, diethanolamine and triethanolamine.

The content of the pH adjuster may be 0.001 to 1% by mass, preferably 0.001 to 0.5% by mass, based on the mass of the entire gel composition. .1 mass % is more preferred.

Most preferably, the gel composition according to this embodiment does not contain an ionic polymer. However, the gel composition may contain ionic polymers such as carboxyvinyl polymer, carboxymethyl cellulose, polyacrylic acid and salts thereof as long as the effects of the present invention are not impaired. When the gel composition contains an ionic polymer, the content of the ionic polymer is preferably 1.0% by mass or less, and 0.5% by mass or less, based on the weight of the entire gel composition. is more preferable. When the gel composition contains a carboxyvinyl polymer, it interacts with a specific physiologically active substance such as diclofenac sodium, causing the ionic polymer to aggregate easily, and moreover, it tends to wrinkle when rubbed on the skin. The lower the content of the ionic polymer, the better the gel composition.

When the gel composition contains HPC and hydrophobized HPMC, aggregation as described above does not occur, the gel composition has sufficient viscosity, and dripping and wrinkling of the gel composition can be suppressed when applied to the skin. Furthermore, a gel composition containing hydrophobized HPMC is excellent in spreadability during application, and tends to cause less stickiness on the applied surface after application.

Moreover, the gel composition according to the present embodiment may not contain sucrose, sorbitol, polyethylene glycol, glycerin, (meth)acrylic polymer compound and POE hydrogenated castor oil. A (meth)acrylic polymer compound is a polymer containing a (meth)acrylic acid alkyl ester as a monomer having adhesiveness to human skin at room temperature. As used herein, the term "(meth)acryl" means an "acryloyl group", a "methacryl group", or both. The same applies to terms similar to "(meth)acryl".

The gel composition according to the present embodiment can be obtained by weighing each component and mixing by stirring or the like.

The present invention will be described in more detail below using examples and comparative examples.

A gel composition was prepared by mixing each component according to the descriptions in Tables 1 to 3. In Table 1, "Other physiologically active substances" are glycyrrhetinic acid, nonylic acid vanillylamide and L-menthol, and "Hydrophobic HPMC" is Sangelose 90L (manufactured by Daido Kasei Kogyo Co., Ltd.). The numbers in Table 1 mean "% by mass", and the "residue" is the ratio at which the mass ratio of purified water and ethanol is 1:1, and the mass of the entire gel composition is 100. means added.

The HLB values of the surfactants used in the tests are as follows.
Glyceryl monostearate: HLB=4.0
POE(5) behenyl ether: HLB=7.0
POE (60) hydrogenated castor oil: HLB = 14.0
Polysorbate 20: HLB=17.0
POE(30) behenyl ether: HLB=18.0
POE(45) monostearate: HLB=18.0
POE (40) cetyl ether: HLB = 20.0

<Evaluation method for wrinkles and stickiness>
0.5 g of the resulting gel composition was placed on the skin of the forearms of 6 test subjects (healthy adults), and the gel composition was rubbed and spread for 10 to 30 seconds so that the application area was 50 cm ² . After that, the dried composition was observed by the touch of a finger or visually to evaluate the degree of wrinkle and stickiness. The evaluation results were scored according to the following criteria, and the average value was calculated.

<Evaluation Criteria for Twist>
100: There was no twist 75: There was a slight twist 50: There was a twist (slightly)
25: There was a twist (many)
0: There was a twist (quite a lot)

<Evaluation Criteria for Stickiness>
100: No stickiness at all 75: Slight stickiness 50: Slight stickiness 25: Much stickiness 0: Very much stickiness

Tables 1 to 3 and Figures 1 to 3 show the average values of the slippage score and stickiness score of each gel composition obtained. The twist scores of Comparative Examples 1 to 11 were 16 to 42, while the twist scores of Examples 1 to 7 were 58 to 88, indicating that the occurrence of twist was suppressed.

Gel compositions (Production Examples 1 to 6) were prepared in the same manner as in Example 1, using ketoprofen, indomethacin, felbinac, flurbiprofen, butenafine hydrochloride, and terbinafine hydrochloride instead of diclofenac sodium.

Claims (7)

A gel composition containing a physiologically active substance containing diclofenac sodium , water, hydroxypropylcellulose, hydrophobized hydroxypropylmethylcellulose and a surfactant,
The surfactant is a polyoxyethylene alkyl ether having an average added mole number of oxyethylene units of 20 to 50, or a polyethylene glycol saturated fatty acid ester having an average added mole number of oxyethylene units of 45 to 60,
The total content of hydroxypropylcellulose and hydrophobized hydroxypropylmethylcellulose is 2% by mass or less with respect to the mass of the entire gel composition,
A gel composition that does not contain an ionic polymer or has an ionic polymer content of 1.0% by mass or less based on the total mass of the gel composition. 2. The gel composition of Claim 1, wherein the polyoxyethylene alkyl ether is selected from the group consisting of polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, and polyoxyethylene behenyl ether. 3. The gel composition according to claim 1 or 2, wherein the polyethylene glycol saturated fatty acid ester is polyoxyethylene monostearate. The gel composition according to any one of claims 1-3, wherein the surfactant has an HLB value of 18-20. The surfactant is at least one surfactant selected from the group consisting of polyoxyethylene (30) behenyl ether, polyoxyethylene (45) monostearate and polyoxyethylene (40) cetyl ether. 5. The gel composition according to any one of 1-4. The gel composition according to any one of claims 1 to 5, wherein the surfactant concentration is 0.3 to 5% by weight relative to the weight of the entire gel composition. The content of hydroxypropyl cellulose is less than 1.5% by mass with respect to the mass of the entire gel composition,
The gel composition according to any one of claims 1 to 6, wherein the content of hydrophobized hydroxypropylmethylcellulose is less than 1.5% by weight relative to the weight of the entire gel composition.

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