JP2010083824A - Analgesic composition for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a preparation that exhibits persistent analgesic effects without restricting a movable range of a joint portion. <P>SOLUTION: The analgesic composition for external use comprises 6-11 wt.% of a cool feeling-imparting component and 40-90 wt.% of a polyhydric alcohol based on 100 wt.% of the composition, and comprises 0.001-0.02 pt.wt. of nonanoic acids based on 1 pt.wt. of the cool feeling-imparting component. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

TECHNICAL FIELD OF THE INVENTION

  The present invention relates to an external analgesic composition. More specifically, the present invention relates to an external analgesic composition excellent in the sustained analgesic effect of joint pain without limiting the range of motion of the joint site.

Conventional technology

  A joint is a connection site between bones and exists throughout the body including knees, elbows, shoulders, hips, and the like. The bones separated from each other are in contact with each other through articular cartilage, and are composed of muscles and ligaments.

  Since the joint repeatedly bends and stretches when it moves, the burden on the joint is very large. Therefore, the articular cartilage is worn out, muscle weakness, blood circulation disorder, etc. occur, and various pains are felt. It is a symptom called joint pain in a broad sense.

  For the purpose of improving this symptom, supplementation of worn cartilage is considered effective, but first of all, improvement of inflammation and pain is the top priority. Inflammation and pain result in a lack of balance during operation, leading to further enlargement of the affected area and worsening of symptoms. To deal with these symptoms, external use of analgesics has been carried out, but the effect is transient and anxiety is felt when walking or going out, or the range of motion is restricted depending on the dosage form, so it is uncomfortable. In addition, there were problems such as being unable to deal with on a daily basis.

  Japanese Patent Application Laid-Open No. 7-228537 (Patent Document 1) describes that a patch capable of maintaining a moderate warmth irritation can be obtained by blending a red pepper extract. In the case of a disease involving, it was insufficient to show a sustained analgesic effect. In addition, since the patch limits the range of motion of the joint part, it is difficult to deal with it on a daily basis.

Therefore, there has been a demand for a preparation capable of obtaining a sustained analgesic effect without limiting the range of motion of the joint site, particularly a gel having a low shape retention.
Japanese Unexamined Patent Publication No. 7-228537

  The present invention does not limit the range of motion of the joint part, provides continuous warming to relieve pain of joint pain, and also has the effect of removing inflammation and promoting blood circulation, improving the metabolism of the affected area, An object of the present invention is to provide an external analgesic composition excellent in the treatment of joint pain that can be expected to have a repair effect.

  As a result of intensive studies in view of the above-mentioned problems of the prior art, the present inventor becomes an excellent external analgesic composition by blending nonanoic acids, cooling components and polyhydric alcohols into an external preparation. As a result, the present invention has been completed.

That is, the present invention provides the following external analgesic composition.
(1) In 100% by weight of the composition, 6 to 11% by weight of a cooling component and 40 to 90% by weight of a polyhydric alcohol are blended, and nonanoic acids are added in an amount of 0.001 to 0.001% with respect to 1 part by weight of the cooling component. An external analgesic composition comprising 02 parts by weight.
(2) The external analgesic composition as described in (1) above, which does not contain a volatile lower alcohol.
(3) The external analgesic organism according to (1) or (2) above, which is a gel.
(4) The external analgesic composition according to any one of (1) to (3), which is a preparation for application.

[Embodiment of the Invention]
Nonanoic acids to be blended in the external analgesic composition of the present invention are compounds having the following structure and having a blood circulation promoting action.

(In the formula, n is 7 to 10, and m is 15 to 20)
Nonanoic acids include capsaicin, dihydrocapsaicin, norcapsaicin, homocapsaicin, octanoic acid vanillylamide, nonanoic acid vanillylamide and the like. Preferred nonanoic acids are capsaicin and nonanoic acid vanillylamide.

  In the present invention, nonanoic acids are preferably 0.001% by weight or more, more preferably 0.008 to 0.2% by weight, and further preferably 0.012 to 0.2% by weight in 100% by weight of the external analgesic composition. .

  The refreshing component is a component that imparts a refreshing sensation, such as p-menthane such as limonene, terpinolene, menthane, terpinene, and terpene hydrocarbon compounds such as monocyclic monoterpene hydrocarbon compounds derived therefrom, l-menthol , Isopulegol, 3,1-menthoxypropane-1,2-diol, 1- (2-hydroxydiphenyl) -4- (3-nitrophenyl) -1,2,3,6-tetrahydroxypyrimidin-2-one And menthol-related compounds such as ethylmenthane carboxamide, p-menthane-3,8-diol, 3,8-dihydroxy-p-menthane-3-9-diol, and trialkyl-substituted cyclohexanecarboxyamide. These can use only 1 type or can also be used in combination of 2 or more type. A preferred cooling component is l-menthol.

  In the present invention, the refreshing agent is preferably 6 to 11% by weight in 100% by weight of the external analgesic composition. Furthermore, in the external analgesic composition of this invention, it is preferable that nonanoic acids are 0.001-0.02 weight part with respect to 1 weight part of cooling components, and is 0.002-0.018 weight part. More preferably, the amount is 0.002 to 0.016 parts by weight. By setting it as such a range, the thermal effect of nonanoic acid can be maintained while giving an appropriate cooling feeling to an affected part, and pain can be relieved effectively.

  Polyhydric alcohol is a component known as a solvent and a solubilizing agent, and propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, glycerin, sorbitol, xylitol, etc. are preferable, and propylene glycol and polypropylene glycol are particularly preferable. preferable. The compounding quantity of a polyhydric alcohol is 40 to 90 weight% in 100 weight% of external analgesic compositions, Preferably it is 40 to 70 weight%.

  In addition to the polyhydric alcohol, the external analgesic composition of the present invention can contain a solvent such as water or a lower alcohol such as ethanol, methanol, and propanol. In the present invention, it is preferable not to contain a volatile lower alcohol from the viewpoint of thermal durability.

  The external analgesic composition of the present invention can be prepared by the usual method of each preparation by adding appropriate components according to the dosage form as other optional components. Since the external analgesic composition of the present invention is applied to joints and the like, it is a gel, liquid, or cream that is a preparation that does not limit the range of motion of the joint site and can obtain a continuous analgesic effect of joint pain. It is preferable to use a preparation for application such as an agent or an ointment, and it is particularly preferable to use a gel having a low shape retention.

  The external analgesic composition of the present invention can be blended with a thickening agent to form a gel having a low shape retention. The thickening agent is preferably an aqueous thickening agent, particularly polyacrylic acid, polyacrylate, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl pyrrolidone / vinyl acetate copolymer, carboxyvinyl copolymer, methylcellulose, carboxymethylcellulose, carboxy. One or more water-soluble polymers such as methyl cellulose salt, carboxyethyl cellulose, carboxyethyl cellulose salt, hydroxypropyl cellulose, sodium alginate, gelatin, pectin, polyethylene oxide, methyl vinyl ether / maleic anhydride copolymer, carboxymethyl starch Substances can be used, and cellulose-based polymers such as hydroxypropylcellulose are particularly preferable. The blending amount of the thickening agent is 0.3 to 30% by weight, preferably 0.75 to 20.75% by weight, in 100% by weight of the external analgesic composition.

  Moreover, when manufacturing the external analgesic composition of this invention as a gel agent, the stickiness of an agent can be suppressed and a usability | use_condition can be improved by mix | blending powders. Powders are generally called powders and are solid at room temperature. Examples of the inorganic powder include layered silicate minerals such as talc, kaolin, bentonite, and aluminum magnesium silicate, titanium oxide, and zinc oxide. Examples of the organic powder include spherical powders such as nylon, silica, and polymethyl methacrylate, polyethylene beads, cellulose powder, corn starch, and a superabsorbent polymer (such as polyacrylate starch). Corn starch, synthetic aluminum silicate, light anhydrous silicic acid and the like are particularly preferable.

  The external analgesic composition of the present invention becomes a preferable gel agent by adding a cellulosic polymer such as hydroxypropyl cellulose as a thickening agent, but in addition to this, a gelling agent such as glycerin monooleate is added. When preparing a gel, it can be produced by a conventional method. For example, the above components other than the gelling agent are sequentially added and dissolved in the above solvent, and then the gelling agent is added to be gelled. Can be prepared.

  In the case of an ointment, glycols, surfactants, water-soluble polymer compounds and the like can be blended as a base. Specifically, for example, lanolin, hydrogenated oil, lecithin, plastibase, liquid paraffin, beeswax, paraffin Wax, microcrystalline wax, silicone oil, etc., as glycols such as glycerin, propylene glycol, polyethylene glycol, polypropylene glycol, etc., as water-soluble polymer compounds such as carboxyvinyl polymer, sodium carboxymethylcellulose, polyvinyl alcohol, methylcellulose, hydroxyethylcellulose Hydroxypropylcellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, polyacrylic acid and the like can be blended.

When it is prepared as an ointment, it can be produced by a conventional method. For example, it can be prepared by sequentially adding the above components to the above solvent and kneading for an appropriate time.
When the external analgesic composition of the present invention is prepared as a solution, it can be prepared by a usual method for preparing a solution. For example, it can prepare by adding each component to alkylene glycol and polyalkylene glycol, heating as needed, and melt | dissolving.

  The external analgesic composition of the present invention may contain other medicinal ingredients and various additives (humectant, pigment, fragrance, surfactant, pH adjuster, antioxidant, etc.) in addition to the above components. good. These components are blended within a range that does not hinder the effects of the present invention.

  Examples of other medicinal ingredients include non-steroidal anti-inflammatory agents such as flurbiprofen, felbinac, piroxicam, indomethacin, glycol salicylate, local anesthetics such as procaine hydrochloride and lidocaine, penicillins, cephalosporins, aminoglycosides , Macrolides and other antibiotics, griseofulvin, amphotericin B and other antifungal agents, hydrocortisone and brendonizolone and other steroidal anti-inflammatory agents, chlorpheniramine and oxatomide and other antiallergic and antihistamines, clonidine and captopril and other antihypertensive agents Coronary vasodilators such as nitroglycerin and isosorbite nitrate, calcium antagonists such as nifedipine and nicardipine, β-blockers such as pindolol and propranol, deophylline and hydro Antihypertensive drugs such as Iazide, cardiotonic drugs such as dopamine hydrochloride and diquitaris, antiepileptic drugs such as sodium valproate and phenytoin, anti-vertigo drugs such as scopolamine, antipsychotics such as haloperidol, sleep regulators such as flurazepam hydrochloride and phenobarbital , 5-fluorouracil, mitomycin C, antineoplastic agents such as bleomycin, hormonal agents such as estradiol and insulin, vitamins such as vitamin E, and the like.

  Other additives include layered silicate minerals such as talc, kaolin, bentonite and aluminum magnesium silicate, spherical powders such as titanium oxide, zinc oxide, nylon, silica, polymethyl methacrylate, polyethylene beads, cellulose powder, Corn starch, powders such as superabsorbent polymers (such as starch polyacrylate), humectants such as sodium pyrrolidonecarboxylate and sodium lactate, sorbitan fatty acid esters (eg sorbitan monostearate, sorbitan sesquioleate), glycerin Fatty acid esters (eg, glyceryl monostearate, glyceryl isooctanoate, glyceryl monomyristate), polyglyceryl fatty acid esters (eg, diglyceryl monooleate, tetraglyceryl monostearate) ), Propylene glycol fatty acid esters (eg, propylene glycol monostearate), polyoxyethylene hydrogenated castor oil (eg, polyoxyethylene (5) hydrogenated castor oil, polyoxyethylene (10) hydrogenated castor oil) And pH adjusters such as monoethanolamine, diethanolamine, diisopropanolamine, triethanolamine, sodium hydroxide, citric acid and hydrochloric acid.

  ADVANTAGE OF THE INVENTION According to this invention, it can be set as the external use analgesic composition excellent in the analgesic effect by mix | blending nonanoic acids, a cooling component, and a polyhydric alcohol to make an external preparation.

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.
Preparation of composition for external use Formulations (Examples 1 to 29 and Comparative Examples 1 to 10) were prepared by the following method at the ratios shown in Tables 1 to 6 below.
(1) Nonanoic acids and l-menthol are dissolved in water, polyhydric alcohol and / or absolute ethanol.
(2) Add hydroxypropylcellulose to the dissolved material and stir for 1 hour.
(3) Disperse the powders and stir.

In addition, the numerical value of each component in each table is parts by weight, nonanoic acid vanillylamide and l-menthol are Nagaoka Kogyo Co., Ltd., capsaicin is Alps Pharmaceutical, propylene glycol is ADEKA, and 1,3-butylene glycol is Kyowa. Fermentation Chemical Co., Ltd., Polyethylene Glycol 200 and Polyethylene Glycol 400 are Sanyo Chemical Industries, Polypropylene Glycol 400 is Pure Chemical Co., Ltd. Anhydrous ethanol is Konishi Co., Ltd., Synthetic Aluminum Silicate (heavy) is Kyowa Chemical Industry Co., Ltd., Corn starch was purchased from Nissho Chemical Co., Ltd., light silicic acid was purchased from Fuji Silysia Chemical Co., Ltd., and hydroxypropyl cellulose was purchased from Shin-Etsu Chemical Co., Ltd.
Evaluator The analgesic effect was evaluated by applying the preparation of each example to 10 subjects having pain in the knee joint.
Evaluation of analgesic effect The analgesic effect up to 1 hour after application is evaluated in 5 stages (maximum 5 points, minimum 1 point), 35 points or more ◎, 30 points to less than 34 points ○, less than 30 points × As evaluated.

  As shown in Tables 1 to 3, the composition of Comparative Examples 1 to 3 lacking any of nonanoic acids, cooling components and polyhydric alcohols, and the cooling component in the composition of 100% by weight is 6 to 11% by weight. The compositions of Comparative Examples 4 and 5 that are outside the range, the composition of Comparative Example 6 that is outside the range of 40 to 90% by weight of the polyhydric alcohol in the composition, and the nonanoic acids / cooling component in the composition No suitable analgesic effect was obtained with the compositions of Comparative Examples 7 and 9 having a N value of less than 0.001 and the compositions of Comparative Examples 8 and 10 with a nonanoic acid / cooling component of greater than 0.02.

  On the other hand, the analgesic effect was suitable for the compositions of Examples 1 to 14 which contained all the above three components and the ratio of nonanoic acids / cooling component in the composition was 0.001 to 0.02. . Moreover, since Example 1 does not contain a lower alcohol, the analgesic effect was superior to Example 14 containing a lower alcohol.

  Moreover, in Examples 1-13, although the difference of an effect was not seen by the quantity of purified water, about the feeling of use, such as stickiness, the composition of Examples 6 and 8 containing polyhydric alcohol 75weight% or more The compositions of Examples 1 to 5, 7, and 9 to 13 were superior to the product.

Furthermore, when the external use analgesic composition of Examples 15-29 was manufactured according to Tables 4-6, the effect excellent in Examples 1-4 was recognized about the analgesic effect.
A prescription example is shown below.
Formulation Examples 1-11: according to the formulation examples described liquid Table 7, were prepared liquid was prepared a conventional manner.

Formulation examples 12 to 16: Gelling agent According to the formulation examples described in Table 8, gel agents were prepared by a conventional method.
Formulation Example 17: Ointment According to the formulation example described in Table 8, an ointment was prepared in the usual manner.

Claims (4)

In 100% by weight of the composition, 6 to 11% by weight of a cooling component and 40 to 90% by weight of a polyhydric alcohol are blended, and 0.001 to 0.02 part by weight of nonanoic acid is added to 1 part by weight of the cooling component. An analgesic composition for external use characterized by being formulated. The analgesic composition for external use according to claim 1, which does not contain a volatile lower alcohol. The external analgesic composition according to claim 1 or 2, which is a gel. The external analgesic composition according to any one of claims 1 to 3, which is a preparation for application.