TWI625130B - Gel base and gel preparation - Google Patents

Abstract

The present invention is a gel matrix, characterized in that it contains a group selected from 3-L-menthoxypropane-1,2-diol and 3,7-dimethyl-2,6-octadiene-1 -At least one monoterpene derivative, water-soluble polymer, talc, alcohol, and water in the group consisting of alcohol; and the content of the monoterpene derivative relative to the total mass of the gel matrix is 0.5 to 10 mass %, The content of the talc is 1.0 to 6.0% by mass relative to the total mass of the gel matrix.

Description

Gel base and gel preparation

The invention relates to a gel base and a gel preparation containing the same.

In general, as external preparations for application to the skin and the like, liquids, ointments, gels, creams, aerosols, sprays, and the like are known. Among these, gels (gel preparations) include gel bases that are made into gels by adding gelling agents such as polymer compounds, and external preparations for drugs, which are easy to apply directly to the affected area, etc. Compared with other dosage forms, it is easier to handle, and it has an excellent sense of use. As such a gel preparation, for example, in International Publication No. 94/26309 (Patent Document 1), a compounded medicinal ingredient, a lower alcohol such as 3-L-menthoxypropane-1,2-diol, ethanol, A gel preparation made of a gelling agent such as water, a carboxyvinyl polymer, and a neutralizing agent such as triethanolamine, and describes the above 3-L-menthoxypropane-1,2-diol as an active ingredient Function as a dissolving agent. Furthermore, the aforementioned 3-L-menthoxypropane-1,2-diol is generally known as a compound that has a cooling or cooling effect and has high skin safety (Japanese Patent Laid-Open Gazette No. 58-88334 (Patent Document 2) and Japanese Patent Laid-Open No. 60-25908 (Patent Document 3)).

In addition, it is known that, for the purpose of improving the usability of the gel preparation, the gel base contains powder materials such as talc to impart an excellent dryness to the coated portion of the gel preparation. However, if the gel preparation contains talc, there is a problem that after the gel preparation is applied to the skin and dried, a "white residue" in which the applied part turns white occurs. As a gel preparation for the purpose of suppressing the generation of such white residues, for example, Japanese Patent Laid-Open No. 2011-173823 (Patent Document 4) describes the inclusion of specific water-soluble polymers, Gel preparation of talc, water, aliphatic alcohol and medicine. In addition, as a substrate for the purpose of suppressing the generation of white residue caused by talc, Japanese Patent Laid-Open No. 2012-87117 (Patent Document 5) describes a liquid composition contained in a sheet-like cosmetic A liquid composition composed of a hydrophilic powder containing talc and other powders and silica powder, a specific side-chain polyester-modified polysiloxane, and ethanol at a specific ratio.

[Prior Technical Literature] [Patent Literature]

Patent Literature 1: International Publication No. 94/26309

Patent Document 2: Japanese Patent Laid-Open No. 58-88334

Patent Document 3: Japanese Patent Laid-Open No. 60-25908

Patent Document 4: Japanese Patent Laid-Open No. 2011-173823

Patent Document 5: Japanese Patent Laid-Open No. 2012-87117

However, the present inventors recognized that in the gel matrix of the previous gel formulation containing talc, it is difficult to sufficiently contain talc in order to improve the sense of use of the gel formulation and to make it contain talc at a higher concentration. Suppresses the generation of white residue. Moreover, the present inventors recognized that in the gel matrix of the previous gel formulation containing talc and a water-soluble polymer, in addition to the white residue caused by the above talc, it also has the following problem, namely, the After the adhesive preparation is applied to the skin and allowed to dry, it is easy to produce "scaly-like substances" where the dried polymer is squamously deposited on the coated part.

The present invention has been completed in view of the above-mentioned problems in the prior art, and its object is to provide a gel matrix capable of sufficiently suppressing the generation of white residue caused by talc or the formation of scale-like substances caused by water-soluble polymers , And gel preparations containing it.

In order to achieve the above purpose, the inventors of the present Now: by combining the gel base of the gel preparation with a combination of 3-L-menthoxypropane-1,2-diol and 3,7-dimethyl-2,6-octadiene-1 -At least one monoterpene derivative, water-soluble polymer, talc, alcohol, and water in the group consisting of alcohol, and then the above monoterpene derivative and the above talc are combined in such a manner as to become a specific content, even if the content of talc is The relatively high concentration can also sufficiently suppress the white residue caused by talc. Furthermore, it was found that such a gel matrix can also sufficiently suppress the generation of scale-like substances caused by water-soluble polymers.

Furthermore, the present inventors have found that by increasing the alcohol concentration contained in the gel matrix containing talc and water-soluble polymers, there is a tendency to suppress the generation of white residues or scale-like substances, but if the alcohol concentration is increased , It will cause problems such as increased skin irritation caused by alcohol. On the other hand, it was found that according to the gel matrix containing the above-mentioned monoterpene derivative, even if the alcohol concentration is relatively low, the generation of white residue or the formation of scale-like substances can be sufficiently suppressed.

In addition, Patent Documents 4 to 5 describe the same content as the above 3-L-menthoxypropane-1,2-diol and 3,7-dimethyl-2,6-octadien-1-ol 1-Menthol, a monoterpene derivative, is used as a medicine or any component. However, the present inventors found that even if 1-menthol is used instead of 3-L-menthoxypropane-1,2-diol and / or 3,7-dimethyl-2,6-octadiene- 1-Alcohol also did not exert sufficient white residue generation inhibitory effect and scale-like substance generation inhibitory effect, and these effects were exerted by the specific combination described above, thereby completing the present invention.

That is, the gel matrix of the present invention contains a composition selected from 3-L-menthoxypropane-1,2-diol and 3,7-dimethyl-2,6-octadien-1-ol At least one monoterpene derivative, water-soluble polymer, talc, alcohol and water in the group, and the content of the above monoterpene derivative is 0.5 to 10% by mass relative to the total mass of the above gel matrix. The content is 1.0 ~ 6.0 mass relative to the total mass of the above gel matrix %.

In the gel matrix of the present invention, preferably, the content of the monoterpene derivative is 0.75 to 5.0% by mass relative to the total mass of the gel matrix. Further, it is preferable that the water-soluble polymer is at least one selected from the group consisting of water-soluble cellulose derivatives and carboxyvinyl polymers.

Furthermore, in the gel matrix of the present invention, preferably, the alcohol is an alcohol having 1 to 3 carbon atoms. Moreover, it is preferable that the content of the water-soluble polymer is 0.5 to 5.0% by mass relative to the total mass of the gel matrix.

The gel preparation of the present invention contains the gel base and the drug of the present invention. As the gel preparation of the present invention, preferably, the above drug is diclofenac sodium.

According to the present invention, it is possible to provide a gel matrix capable of sufficiently suppressing the generation of white residue caused by talc or the formation of scale-like substances caused by water-soluble polymers, and a gel preparation containing the same.

FIG. 1 is a graph showing the results of white residue evaluation tests performed on the gel bases obtained in Comparative Examples 1, 3, and 4. FIG.

FIG. 2 is a graph showing the results of a scale-like substance evaluation test performed on the gel matrix obtained in Comparative Examples 1, 3, and 4. FIG.

Hereinafter, the present invention will be described in detail based on its preferred embodiments. The gel matrix of the present invention is characterized in that it contains selected from 3-L-menthoxypropane-1,2-diol and 3,7-dimethyl-2,6-octadien-1-ol At least one monoterpene derivative, water-soluble polymer, talc, alcohol and water in the group formed; and the content of the monoterpene derivative relative to the total mass of the gel matrix is 0.5 to 10 Mass%, the content of the talc is 1.0 to 6.0% by mass relative to the total mass of the gel matrix.

<Monoterpene derivatives>

The monoterpene derivative of the present invention is selected from the group consisting of 3-L-menthoxypropane-1,2-diol and 3,7-dimethyl-2,6-octadien-1-ol At least one of them. 3-L-menthoxypropane-1,2-diol is generally known as a compound having a cooling or cooling effect. In addition, 3,7-dimethyl-2,6-octadien-1-ol (geraniol) is known as a fragrance component of rose oil or geraniol. In the present invention, the gel matrix containing talc and water-soluble polymer contains these specific monoterpene derivatives. Surprisingly, this can sufficiently suppress the generation or cause of white residue caused by talc The generation of scale-like substances caused by water-soluble polymers. Furthermore, even if, for example, 1-menthol, which is another monoterpene derivative, is used instead of the monoterpene derivative of the present invention, it is difficult to sufficiently suppress the generation of white residues or the formation of scale-like substances.

As the monoterpene derivative of the present invention, it can be used alone selected from 3-L-menthoxypropane-1,2-diol and 3,7-dimethyl-2,6-octadien-1-ol Any one of the groups can be used in combination of two or more, but the viewpoint of white residue caused by talc or scale-like substances caused by water-soluble polymers is more fully suppressed In particular, it is more preferable to use 3-L-menthoxypropane-1,2-diol.

In the gel matrix of the present invention, as the content of the monoterpene derivative of the present invention (3-L-menthoxypropane-1,2-diol content and / or 3,7-dimethyl-2, The total content of 6-octadien-1-ol) must be 0.5 to 10% by mass relative to the total mass of the above gel matrix. When the content of the above-mentioned monoterpene derivative does not reach the above lower limit, it is difficult to sufficiently suppress the generation of white residue and the generation of scale-like substances. On the other hand, when the above upper limit is exceeded, a sticky feeling may occur, or dryness may be damaged by the addition of talc.

Moreover, as the content of the above-mentioned monoterpene derivative, it is particularly preferable that it is relative to the above-mentioned gel matrix The total mass is 0.75 ~ 5.0 mass%. If the content of the above-mentioned monoterpene derivative is more than the above-mentioned lower limit, there is a tendency that the generation of white residues and scale-like substances can be more fully suppressed. On the other hand, if the content of the above-mentioned monoterpene derivative exceeds the above-mentioned upper limit, there is a tendency to produce a sticky feeling and reduce the dry feeling, or the drying becomes slow.

<Water-soluble polymer>

The water-soluble polymer functions in the gel matrix as a gelling agent for forming a gel. In the present invention, as the above water-soluble polymer, even when a gel preparation is prepared by combining a drug that is a pharmaceutically acceptable salt with a gel matrix, the gel matrix gel can be made better In addition, even in the case where the total amount of the above drugs is large, there is a tendency to easily obtain a gel formulation with better flow characteristics (especially ductility, drip prevention), 2% by mass The viscosity of the aqueous solution at 20 ° C is preferably 1,000 to 280,000 mPa‧s, more preferably 1,000 to 30,000 mPa‧s. Furthermore, in the present invention, the above-mentioned viscosity is a value measured using a Brookfield viscometer in accordance with the provisions of the Japanese Pharmacopoeia.

As the water-soluble polymer of the present invention, a user who has previously used the above-mentioned gelling agent can be suitably used, and without particular limitation, the above-mentioned preferable viscosity and good thixotropy can be achieved, and the "tightness" can be sufficiently reduced From a viewpoint, it is preferably at least one selected from the group consisting of water-soluble cellulose derivatives and carboxyvinyl polymers, and more preferably at least one selected from the group consisting of water-soluble cellulose derivatives 1 kind.

Generally, when a gel matrix containing a water-soluble polymer is dried on the skin to form a skin film, the skin film shrinks during the drying process, thereby causing an uncomfortable "tightness" to the skin. At this time, if a water-soluble polymer having a large molecular weight and easy to crystallize is used, the physical strength of the water-soluble polymer constituting the film becomes greater, so a stronger sense of tightness is generated. Furthermore, the water-soluble polymer that is easily crystallized is usually linear and has high symmetry of the molecule, and a polymer having a polar functional group is a polymer with high crystallinity. In contrast, the above water-soluble cellulose derivatives and carboxyvinyl polymers Since it is a polymer with relatively low crystallinity, it tends to further reduce the tightness.

Examples of the water-soluble cellulose derivatives include hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, and hydroxypropyl methyl cellulose (hydroxypropyl cellulose). (Methyl cellulose) may be used alone or in combination of two or more. Among them, as the water-soluble cellulose derivative, either hydroxypropyl methyl cellulose or hydroxypropyl cellulose is preferably used, and hydroxypropyl cellulose is more preferably used.

The hydroxypropyl methyl cellulose (hypromellose) is obtained by partially introducing hydroxypropoxy and methoxy groups as substituents to the three hydroxyl groups of the unit sugar structure (glucose) of cellulose. These substituents are introduced irregularly to the hydroxyl group of the unit sugar structure of the cellulose. By introducing two kinds of substituents locally and irregularly in this way, the regularity of the molecular structure of the above hydroxypropyl methylcellulose is reduced and it becomes a polymer with lower crystallinity, so there is a gel matrix The strength of the film formed by drying becomes smaller, and the above-mentioned tight feeling tends to be further reduced.

As such hydroxypropyl methylcellulose, it is preferred that the degree of substitution of hydroxypropoxy is 4.0 to 32.0%, and the degree of substitution of methoxy is 16.5 to 30.0%, more preferably, hydroxypropoxy The substitution degree of the group is 4.0 ~ 12.0%, and the substitution degree of the methoxy group is 22.0 ~ 30.0%. If the degree of substitution is within this range, the flow characteristics of the gel tend to be better, and when the gel matrix contains a drug, there is a tendency to exert a better therapeutic effect of the drug.

In addition, the hydroxypropyl cellulose is obtained by partially introducing hydroxypropoxy groups as substituents to the three hydroxyl groups of the unit sugar structure (glucose) of cellulose. The substituent is introduced irregularly to the hydroxyl group of the unit sugar structure of the cellulose. By introducing substituents locally and irregularly in this way, the regularity of the molecular structure of the above hydroxypropyl cellulose is reduced to become a polymer with lower crystallinity, so the gel matrix is formed by drying The strength of the film becomes smaller, and the above-mentioned feeling of tightness tends to be reduced. As the above hydroxypropyl cellulose The substitution degree of the hydroxypropoxy group is preferably 50 to 80%. In the present invention, the viscosity at 20 ° C. of the 2% by mass aqueous solution of the hydroxypropyl cellulose is preferably 1,000 to 4,000 mPa‧s.

The carboxyvinyl polymer is a polymer having a cross-linked structure partially cross-linked with polyacrylic acid as the main chain. The above-mentioned carboxyvinyl polymer is cross-linked in this way and has a very high molecular weight, so the gel matrix can be thickened by a small amount of addition to improve the ductility, prevent dripping, and prevent the gel matrix from being coated. From the viewpoint of the formation of scale-like masses due to the solid content of the gel matrix when it is applied to the skin, that is, "caking" is preferred. In addition, since the cross-linked structure is local, the strength of the film formed by drying the gel matrix tends to decrease, and the tightness tends to be reduced.

In the case of using the above carboxyvinyl polymer, from the viewpoint of exerting higher viscosity increase by neutralizing the carboxyl group, when manufacturing the above gel matrix, it is preferable to And formulated to carry out the above neutralizing agent. The neutralizing agent is not particularly limited, but organic amines such as ammonia water, sodium hydroxide, diisopropanolamine, di (2-ethylhexyl) amine, triethanolamine, and triethylamine are preferably used.

In the present invention, the viscosity at 20 ° C of the 0.2% by mass aqueous solution (pH value 7 to 7.5) of the above carboxyvinyl polymer is preferably 5,000 mPa‧s to 29,000 mPa‧s, more preferably 5,000 mPa‧ s ~ 28,000mPa‧s, further preferably 6,000mPa‧s ~ 14,000mPa‧s

In the gel matrix of the present invention, as the content of the water-soluble polymer of the present invention (in two or more cases, the total content of each water-soluble polymer), relative to the total mass of the gel matrix, It is preferably 0.5 to 5.0% by mass, and more preferably 2.0 to 4.0% by mass. In addition, when the above water-soluble cellulose derivative is used as the water-soluble polymer of the present invention, the content thereof is preferably 0.5 to 5.0% by mass relative to the total mass of the above gel matrix, and more preferably 2.0 ~ 4.0% by mass. If the content of the water-soluble polymer is within this range, there is a tendency that the viscosity and fluidity of the gel matrix become better and sufficient To suppress dripping or agglomeration.

As the content of the water-soluble polymer of the present invention, when a water-soluble polymer having the above-mentioned viscosity characteristics is used, by formulating the relatively small amount of the above-mentioned water-soluble polymer having a relatively high viscosity, there is a tendency to dry as follows: Become faster, or can sufficiently suppress the formation of lumps.

In addition, if the above-mentioned water-soluble cellulose derivative is used as the above-mentioned water-soluble polymer, it tends to be particularly likely to produce scale-like substances. However, in the present invention, a relatively high concentration (e.g., relative to the total The mass is 3.0% by mass or more (more specifically, for example, 3.0 to 5.0% by mass)) Using such a water-soluble cellulose derivative can also sufficiently suppress the generation of scale-like substances.

<Talc>

The talc of the present invention has a function of adjusting the flow characteristics of the gel matrix, and after applying the gel matrix to the skin or the like, it can give a dry feeling to the coated part. Furthermore, it is presumed that this dry feeling is achieved by the following: the film formed by drying the gel matrix containing the water-soluble polymer on the skin is rubbed by the talc, and as a result, a large number of fragile parts are formed on the film and the film The strength becomes smaller and the above-mentioned feeling of tightness is reduced.

Examples of the talc of the present invention include natural hydrous magnesium silicate obtained by pulverizing talc (Mg ₃ Si ₄ O ₁₀ (OH) ₂ ). This type of talc is classified as a layered silicate mineral, and its crystal structure is as follows, that is, Mg (OH) ₂ octahedral is repeated between 2 layers with SiO ₄ tetrahedron as the repeating unit. The structure in which the layers of the units are laminated in a sandwich shape is regarded as the basic structure, and the basic structure is laminated in layers. Because the combination of the sandwich-shaped layers is only Van der Waals, talc has the characteristics of easy cleavage and easy disintegration, so the Mohs hardness is smaller than other minerals. Therefore, it is speculated that, compared with other minerals, the above-mentioned excellent dry feeling can be imparted.

The particle size of such talc powder is preferably 1-30 μm in terms of volume-based average particle size from the viewpoint of providing a smoother touch and being easy to adhere to the skin. Within. Furthermore, in the present invention, the volume-based average particle size is obtained from a volume-based particle size distribution obtained by using a laser diffraction particle size distribution measuring device.

In the gel matrix of the present invention, the content of talc of the present invention must be 1.0 to 6.0% by mass relative to the total mass of the gel matrix. When the content of the talc does not reach the above lower limit, the effects of imparting dryness, reducing stickiness, and making the gel matrix easy to spread, etc. cannot be fully exerted. On the other hand, when the above upper limit is exceeded, it is difficult to spread the gel matrix or produce a rough feeling. In addition, as the content of the above-mentioned talc, the effect of more adequately suppressing the stickiness, making it easier to spread, and preventing the tendency of roughness is particularly preferable to the above-mentioned gel matrix. The total mass is 3.0 ~ 5.0 mass%. In addition, if the above-mentioned talc is used, there is a tendency to produce white residues in particular, but in the present invention, even at a high concentration (for example, the total mass of the gel matrix is 4.0% by mass or more (more specifically , For example, 4.0 to 6.0% by mass)) Use of such talc can also sufficiently suppress the occurrence of white residue.

<Alcohol, water>

Alcohol and water function as a liquid medium that forms a water-soluble polymer and a gel in the gel matrix. In the present invention, the above-mentioned alcohol is not particularly limited, but from the viewpoint of increasing the number of carbons, drying tends to be slow, and alcohols having 1 to 3 carbons are preferred. Examples of the alcohols having 1 to 3 carbon atoms include ethanol and isopropanol. One of these may be used alone, or two or more of them may be used in combination.

The content of the alcohol is not particularly limited, and is preferably 30 to 95% by mass, more preferably 40 to 90% by mass, and still more preferably 60 to 85% by mass relative to the total mass of the gel matrix. If the content of the alcohol does not reach the above lower limit, drying tends to slow down or lumps easily, on the other hand, if it exceeds the above upper limit, the skin irritation caused by alcohol tends to increase. Furthermore, the present inventors have found that by increasing the concentration of alcohol contained in the gel matrix containing talc and water-soluble polymers, there is a tendency to suppress the generation of white residues or scale-like substances, but in the present invention , Even if the alcohol concentration is relatively low (eg For example, with respect to the total mass of the gel matrix being 40% by mass or less (more specifically, for example, 30 to 40% by mass), the occurrence of white residues or scale-like substances can also be sufficiently suppressed, so it is possible Provides a gel base with less skin irritation

The water is preferably water after purification such as ion exchange, distillation, and filtration, and for example, "purified water" described in the Japanese Pharmacopoeia (15th revised edition of the Japanese Pharmacopoeia) can be preferably used. The content of such water is not particularly limited, and it is preferably 1.0 to 59.5 mass%, more preferably 1.0 to 40.0 mass% relative to the total mass of the gel matrix.

As the gel matrix of the present invention, in addition to the above-mentioned monoterpene derivative, the above-mentioned water-soluble polymer, the above-mentioned talc, the above-mentioned alcohol, and the above-mentioned water, it may further contain the above-mentioned as needed within the range not hindering the effect of the present invention Powder ingredients other than talc, oil ingredients, fragrances, pigments, stabilizers, absorption accelerators and other additives.

<Medicine>

The gel preparation of the present invention is characterized by containing the above-mentioned gel matrix of the present invention and a drug. The drug that can be used in the gel preparation of the present invention is not particularly limited, and examples include butenafine hydrochloride, terbinafine hydrochloride, naftifine, amorolfine hydrochloride, neconazole hydrochloride, luliconazole , Lanoconazole, oxime konconazole nitrate, ketoconazole, miconazole nitrate, ticonazole, bifonazole, clotrimazole, canaconazole nitrate, itraconazole, fluconazole And other antifungal drugs; for example indomethacin, ketoprofen, biphenylacetic acid, flurbiprofen, diclofenac sodium, loxoprofen, ibuprofen, ibuprofen methyl ester, melon [camomile] azulene, Allantoin, glycyrrhizic acid, glycyrrhetinic acid, salicylic acid, methyl salicylate, ethylene glycol monosalicylate and other anti-inflammatory analgesics (anti-inflammatory drugs); for example, mediator free inhibitors (tranilast, color Sodium Glycinate), Histamine H1 Receptor Antagonist (Oxamid, Allergic Meguidine, Emestatin, Ebastine, Loratadine, Cetirizine, Deloratadine, Fexo Phenadine, astemizole, azelastine, clofiphenamine, diphenhydramine, codotifen), histamine H2 receptor antagonists (simetidine, ranitidine, phenmotidine , Nizatidine), histamine H3 receptor antagonists (tipamide, imprimidine, mifentidine, imatinamide, clozapine), histamine H4 receptor Antihistamines such as antagonists; for example, 1-menthol, camphor, borneol, eugenol, eucalyptus oil, peppermint oil, clove oil, cassia oil, tea tree oil and other essential oil components; for example isopropylmethylphenol, gluconate Chlorhexidine, rivanol, benzalkonium hydrochloride and other fungicides; for example, dobucaine hydrochloride, lidocaine hydrochloride, procaine hydrochloride, tetracaine hydrochloride, bupivacaine hydrochloride, prilocaine hydrochloride Local anesthetics such as caffeine, occaine hydrochloride, mepivacaine hydrochloride, oxycaine; etc .; for example, anti-itch agents such as crotamiton, tartar, Mocthammol, thymol phenolic acid; for example, pepper extract, capsaicin, nony Blood flow enhancers such as vanillyl amide; for example, dexamethasone valerate, dexamethasone valerate acetate, dexamethasone propionate, prednisolone acetate, prednisolone valerate, prednisolone, butyl Hydrocortisone Propionate, Hydrocortisone Acetate, Cortisone Butyrate, Cortisone Acetate, Clobetasone Butyrate, Triamcinolone acetonide, Difluorocortisone valerate, Difluoropregnantine Steroid hormones such as esters, diflurasone acetate, betamethasone dipropionate, ancinald, hasinaide, budesonide, aclomethasone dipropionate; and the pharmaceutically acceptable salts of these (in When the above-mentioned medicine is a salt, it is another salt) and when the above-mentioned medicine is a salt, its free substance can be used alone or in combination of two or more.

In the gel preparation of the present invention, the content of the above-mentioned drugs can be appropriately adjusted according to the type of the above-mentioned drugs and / or the purpose of administration of the gel preparation to obtain an amount with better therapeutic effect. The intended amount does not hinder the production inhibitory effect of the white residue of the gel matrix or the production inhibitory effect of scale-like substances. As the content of such a drug that can obtain a better therapeutic effect, generally, for example, an amount of 0.5 to 3.1 parts by mass relative to 100 parts by mass of the gel matrix can be mentioned. In addition, the gel preparation of the present invention can appropriately set the amount of use or the number of times of use according to the type, combination, and amount of drugs.

The method for producing the gel matrix and the gel preparation of the present invention is not particularly limited, and can be produced by appropriately adopting known methods for producing the gel matrix and the gel preparation, respectively. For example, by mixing the above-mentioned monoterpene derivative, the above-mentioned water-soluble polymer, the above-mentioned talc, the above-mentioned alcohol, the above-mentioned water, and, if necessary, the above-mentioned additives, a uniform gel can be made Gelatinous, the target gel matrix can be obtained. Furthermore, it is prepared by mixing the gel matrix with the drug, or mixing the monoterpene derivative, the water-soluble polymer, the talc, the alcohol, the water, the drug, and the additives as needed. Uniform gel form, the target gel preparation can be obtained. The manufactured gel matrix and gel preparation of the present invention are filled in tubes, plastic containers, glass containers, etc., and packaged.

[Example]

Hereinafter, the present invention will be described more specifically based on examples and comparative examples, but the present invention is not limited to the following examples. In addition, in each Example and Comparative Example, the white residue evaluation test and the scale-like substance evaluation test were performed by the methods shown below, respectively.

(White residue evaluation test)

For the gel matrix obtained in each of the examples and comparative examples, first, 500 mg of each gel matrix was applied to the lower arm of a healthy adult male (5 persons) so as to become 50 cm ² and dried. Then, for each coated part after drying, the state where the entire coated part is whitened is recorded as "1", and the state where the coated part cannot be recognized as whitened is set to "5", with 1 to 5 In the 5-stage evaluation, a sensory evaluation test was carried out, and the average value was used as the 5-stage evaluation result.

In addition, 500 mg of each gel matrix was applied to the lower arm of a healthy adult male so as to become 50 cm ² , and the coated portion after drying was also evaluated based on the following evaluation criteria, and set as a three-stage evaluation result:

A: The coated part cannot be seen as white

B: It can be seen that the area below 30% of the area of the coated part turns white

C: It can be seen that the area exceeding 30% of the area of the coated part turns white.

Further, in the healthy adult male (30) about left and right of the arm so as to be applied to each of Embodiment ² 50cm gel matrix 500mg, in another embodiment the lower arm ² of 50cm so as to be applied to the evaluation criteria become the reference formulation (containing A fixed amount of talc, a water-soluble polymer and a gel matrix of alcohol) 500 mg, and allowed to dry. For the coated part after drying, the state where the entire coated part is whitened is recorded as "20", and the state where the coated part is not recognized as whitened is recorded as "100", with 20, 40, 60, The sensory evaluation test was carried out in the 5-stage evaluation of 80 and 100. The ratio (score ratio) of the evaluation value of each gel matrix to the evaluation value of the reference preparation was obtained, and the average value was used as the result of the score evaluation.

(Evaluation Test of Scale Sample)

For the gel matrix obtained in each of the examples and comparative examples, first, 500 mg of each gel matrix was applied to the lower arm of a healthy adult male (5 persons) so as to become 50 cm ² and dried. Then, for each coated portion after drying, the state where the dried gel matrix is visually recognized as squamously remaining on the entire coated portion is denoted as "1", and the scaly remaining on the coated portion cannot be recognized The state of the dried gel matrix was recorded as "5", and the functional evaluation test was carried out in 5 stages of evaluation from 1 to 5, and the average value was taken as the evaluation result of 5 stages.

In addition, 500 mg of each gel matrix was applied to the lower arm of a healthy adult male so as to become 50 cm ² , and the coated portion after drying was also evaluated based on the following evaluation criteria, and set as a three-stage evaluation result:

A: It is not visible that the dried gel matrix remains scaly on the coated part

B: It can be seen that the dried gel matrix remains squamously within a range of 30% or less of the area of the coated part

C: It can be seen that the dried gel matrix remains scaly in a range exceeding 30% of the area of the coated part.

Further, in the healthy adult male (30) about left and right of the arm so as to be applied to each of Embodiment ² 50cm gel matrix 500mg, in another embodiment the lower arm ² of 50cm so as to be applied to the evaluation criteria become the reference formulation (containing A fixed amount of talc, a water-soluble polymer and a gel matrix of alcohol) 500 mg, and allowed to dry. For the coated part after drying, the state where the dried gel matrix can be visually recognized as squamously remaining on the entire coated part is denoted as "20", and it cannot be recognized that the dried part has squamously dried on the coated part The state of the gel matrix was recorded as "100", and the functional evaluation test was conducted in five stages of 20, 40, 60, 80, and 100. The ratio (score ratio) of the evaluation value of each gel matrix to the evaluation value of the reference preparation was obtained, and the average value was used as the result of the score evaluation.

(Example 1)

First, hydroxypropyl cellulose (water-soluble polymer / trade name: HPC-H, manufactured by Japan Soda Co., Ltd.): 3 parts by mass, talc (volume-based average particle size: 10 μm, manufactured by Matsumura Industries Co., Ltd.) : 4 parts by mass, 3-L-menthoxypropane-1,2-diol (trade name: 1-menthyl glyceryl ether, manufactured by Takasago Perfume Industry Co., Ltd.): 0.5 parts by mass, isopropyl alcohol (alcohol) : 70 parts by mass, and purified water: 22.5 parts by mass to obtain a uniform gel matrix. Furthermore, the viscosity of the 2% by mass aqueous solution of the above hydroxypropyl cellulose at 20 ° C is 2,660 mPa‧s.

(Examples 2-7, Examples 9-12, Comparative Examples 1-2, and Comparative Examples 5-6)

Each gel matrix was obtained in the same manner as in Example 1 except that the components of the gel matrix were set as the components shown in Tables 1 to 2, respectively. In addition, in Table 1, as geraniol, 2-trans-3,7-dimethyl-2,6-octadien-1-ol (trade name: GERANIOL, Takasago Perfume Industry Co., Ltd.) was used Manufacturing).

(Example 8)

First, in hydroxypropyl cellulose (water-soluble polymer / trade name: HPC-H, manufactured by Nippon Soda Co., Ltd.): 3 parts by mass, talc (volume-based average particle size: 10 μm, manufactured by Matsumura Industries Co., Ltd.) : 4 parts by mass, 3-L-menthoxypropane-1,2-diol (trade name: 1-menthyl glyceryl ether, manufactured by Takasago Perfumery Co., Ltd.): 2.5 parts by mass, isopropyl alcohol (alcohol) : 75 parts by mass, 1-menthol: 3 parts by mass, and purified water: 11.5 parts by mass mixed with diclofenac sodium: 1.0 parts by mass (1.01 parts by mass relative to 100 parts by mass of the gel matrix) to obtain a uniform gel The gel preparation.

(Comparative examples 3 to 4)

Isopropyl alcohol was set to 50 parts by mass (Comparative Example 3) and 89 parts by mass (Comparative Example 4), and the amount of purified water was adjusted so that the total amount of the gel matrix became 100 parts by mass. Each gel matrix was obtained in the same manner as in Comparative Example 1.

For the gel bases obtained in Examples 1 to 7 and Comparative Examples 1 to 2, white residue evaluation test (5-level evaluation) and scale-like substance evaluation test (5-level evaluation) were performed, and the results were compared with each gel The composition of the matrix is shown in Table 1.

As can be seen from the results shown in Table 1, it is confirmed that the gel matrix of the present invention can sufficiently suppress the generation of white residue due to talc or the generation of scale-like substances due to water-soluble polymers. In addition, the whiteness evaluation test (3-level evaluation) and scale-like substance evaluation test (3-level evaluation) of the gel preparation obtained in Example 8 were both A evaluations. On the other hand, in the gel base (Comparative Example 1) which does not contain the 3-L-menthoxypropane-1,2-diol or geraniol of the present invention, or the same as those compounds In the gel matrix (Comparative Example 2) of 1-menthol substituted for terpene derivatives, the evaluation of the white residue evaluation test and the scale-like substance evaluation test are both low, and it can be confirmed that the generation of white residue and scales are not sufficiently suppressed The generation of samples.

The results of the white residue evaluation test (score evaluation) on the gel matrix obtained in Comparative Examples 1, 3, and 4 are shown in FIG. 1, and the results of the scale-like substance evaluation test (score evaluation) are shown in FIG. 2. In addition, by using Examples 9-12 and Comparative Examples 5-6 The obtained gel matrix was subjected to a white residue evaluation test (3-stage evaluation) and scale-like substance evaluation test (3-stage evaluation). The results are shown in Table 2 together with the composition of each gel matrix. In addition, Table 2 also shows the results of the white residue evaluation test (3-level evaluation) and scale-like substance evaluation test (3-level evaluation) performed on the gel matrix obtained in Examples 4 and 5.

As can be seen from the results shown in Figures 1-2, in a gel matrix that does not contain 3-L-menthoxypropane-1,2-diol or geraniol of the present invention, if the reference formulation is Comparing the score ratios of the benchmarks with each other, it is confirmed that the lower the alcohol concentration, the lower the score ratio in the white residue evaluation test and the scale-like sample evaluation test. The tendency. In contrast, as can be seen from the results shown in Table 2, it is confirmed that the gel matrix of the present invention can sufficiently suppress the occurrence of white residue caused by talc or water solubility even if the alcohol concentration is relatively low. The generation of scale-like substances caused by the polymer can further suppress the generation of white residues or the scale-like substances compared with the case where only the alcohol concentration is set to a high concentration (Comparative Examples 5 to 6).

[Industry availability]

As described above, according to the present invention, it is possible to provide a gel matrix capable of sufficiently suppressing the generation of white residue caused by talc or the formation of scale-like substances caused by water-soluble polymers, and a gel containing the same preparation.

Claims (5)

A gel matrix which is selected from the group consisting of 3-L-menthoxypropane-1,2-diol and 3,7-dimethyl-2,6-octadien-1-ol At least one monoterpene derivative, water-soluble polymer, talc, alcohol, and water; the water-soluble polymer is selected from the group consisting of water-soluble cellulose derivatives and carboxyvinyl polymers, and the water-soluble fiber Element derivatives are at least one selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose and hydroxypropyl methyl cellulose The content of the monoterpene derivative is 0.5 to 10% by mass relative to the total mass of the gel matrix, and the content of the water-soluble polymer is 0.5 to 5.0% by mass relative to the total mass of the gel matrix. The content is 1.0 to 6.0% by mass relative to the total mass of the above gel matrix. The gel matrix according to claim 1, wherein the content of the above monoterpene derivative is 0.75 to 5.0% by mass relative to the total mass of the above gel matrix. The gel matrix according to claim 1 or 2, wherein the alcohol is an alcohol having 1 to 3 carbon atoms. A gel preparation containing the gel matrix according to any one of claims 1 to 3, and a medicine. The gel preparation according to claim 4, wherein the above drug is diclofenac sodium.