JPH07223949A - Antiphlogistic analgetic for external use - Google Patents

Abstract

PURPOSE:To obtain an indomethacin-containing antiphlogistic analgetic for external use, having an antiphlogistic and analgetic effect equal to that in oral administration and free from skin stimulation. CONSTITUTION:This anatiphlogistic analgetic for external use contains a powder of Gardenia jasminoides Ellis or an extract thereof and indomethacin in combination. This medicine for external use is prepared preferably by blending the powder of Gardenia jasminoides Ellis or the extract thereof in an amount of 0.1 to 10 pts.wt., preferably 0.5 to 5 pts.wt. based on 1 pts.wt. indomethacin with a cataplasm or a plaster.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a topical anti-inflammatory and analgesic preparation containing indomethacin, which has the same anti-inflammatory and analgesic effect as when it is orally administered and does not cause skin irritation.

[0002]

2. Description of the Related Art Yamajiko is an agent for increasing the oxygen diffusivity at the oxygen deficient site due to the oxygen transport function of blood, an antitumor effect,
Various effects such as arthritis-induced inhibition are known (JJ
SHP, Vol.26, No.5, 1990), for external use, it is used as a compress for swollen affected areas to treat bruising, sprains and contusions.

Indomethacin is an excellent non-steroidal anti-inflammatory drug and is commonly used in the orthopedic field. However, oral administration of indomethacin causes gastrointestinal disorders, and therefore transdermal preparations such as ointments, lotions, and poultices have been developed in order to reduce the side effects thereof. However, when indomethacin is transdermally administered, the transdermal absorption is not sufficient, so that a satisfactory drug effect is not exhibited. Therefore, these transdermal preparations contain fatty acid esters, alcohols, terpenes and the like as percutaneous absorption promoters of indomethacin in order to obtain the same pharmacological effect as that of oral preparations (JP-A 2-14).
2727, and JP-A-2-196718).

[0004]

Generally, these absorption promoters of indomethacin have skin irritation because they reduce the barrier properties of the skin, and the higher the transdermal absorption promotion effect, the higher the skin irritation. However, in the present circumstances, there are still problems in practical use, such as the need to add a large amount of a percutaneous absorption enhancer in order to obtain a pharmacological effect comparable to that of an oral preparation. Therefore, there is a demand for the development of a formulation that exhibits a sufficient drug effect even by transdermal administration.

[0005]

Means for Solving the Problems As a result of intensive studies for solving the above-mentioned problems, the present inventors have found that if indomethacin and Yamabuko powder or extract are administered transdermally, each of them can be administered alone. The present invention has been completed by finding that it exerts a far better analgesic and anti-inflammatory action than that used in No. 1, and there is no skin irritation.

[0006] That is, the present invention is an anti-inflammatory analgesic external preparation characterized by containing indomethacin and Yamaboshi powder or extract.

The Yamajiko used in the present invention is gardenia (Gard
enia jasminoides Ellis) or other homologous plant fruit powder, or an extract (dry extract or soft extract) produced by heating and leaching with an extract thereof (mixed solution of water, alcohol, etc.) can be used. . The blending ratio of the powder or extract of Yamaboshi to be used varies depending on the dosage form, but is usually 0.1 to 10 parts by weight, preferably 0.5 to 5 parts by weight, relative to 1 part by weight of indomethacin.

The dosage form of the anti-inflammatory analgesic external preparation of the present invention is as follows:
Formulations such as lotions, ointments, poultices, plasters and the like can be mentioned, with preference given to poultices and plasters. These may contain known pharmaceutically acceptable bases and compounding ingredients depending on the dosage form.

For example, a poultice is formed by using an adhesive, a plasticizer, a cross-linking agent, a moisturizer, an excipient, a surfactant, water and the like. As the adhesive, water-soluble polymer compounds such as polyacrylic acid, sodium polyacrylate, gelatin, gum arabic, polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethyl cellulose, sodium alginate, xanthan gum and natural rubber and SBR (styrene butadiene rubber), Synthetic rubbers such as SIS (styrene isoprene block copolymer rubber), polyisobutylene rubber, and polyisoprene rubber can be used as plasticizers such as myristic acid, lauric acid, oleic acid and other fatty acids, isopropyl myristate, diisopropyl adipate, sebacic acid. Fatty acid esters such as diethyl, lanolin, liquid paraffin, polybutylene and the like are used as the cross-linking agent, aluminum hydroxide, aluminum glycinate, magnesium aluminate silicate, meta Magnesium aluminate, etc., glycerin, propylene glycol, butylene glycol, etc. as moisturizers, kaolin, bentonite, zinc oxide, titanium oxide, silicic acid anhydride, etc. as excipients, and polyoxylic acid as surfactants. Ethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene glycerin fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene glycol ether, sorbitan fatty acid ester, Examples thereof include glycerin fatty acid ester.

Further, the plaster forms a plaster using an adhesive, a tackifier, an excipient, a plasticizer and the like. As the adhesive, natural rubber, SBR, SIS, polyisobutylene rubber,
Synthetic rubbers such as polyisoprene rubber, acrylic adhesives such as acrylic acid ester and methacrylic acid ester, silicone adhesives such as silicone rubber and resin, etc.
As a tackifier, a rosin ester, an alicyclic hydrocarbon resin, etc., as an excipient, kaolin, bentonite, zinc oxide, titanium oxide, silicic acid anhydride, etc., and as a plasticizer, myristic acid, lauric acid, oleic acid. Fatty acids such as isopropyl myristate, diisopropyl adipate, and fatty acid esters such as diethyl sebacate, lanolin, liquid paraffin, and polybutylene.

In addition to the above components, salicylates such as methyl salicylate and glycol salicylate,
Pepper powder, capsicum extract, nonyl vanillyl amide, various adjuvants such as camphor, menthol, peppermint oil, vitamin E acetate, yellow oak, Yangmei peel, etc. as pH adjusters such as citric acid, malic acid, tartaric acid, lactic acid, etc.
As the stabilizer, dibutylhydroxytoluene, butylhydroxyanisole, disodium ethylenediaminetetraacetate, sodium sulfite and the like can be blended.

[0012]

EFFECTS OF THE INVENTION The antiphlogistic / analgesic external pharmaceutical composition obtained according to the present invention is more effective than the case of indomethacin or Yamabuko alone for target diseases such as bruise, sprain, muscle aches, stiff shoulders and back pain. It is possible to provide an antiphlogistic / analgesic external preparation that is high and has no skin irritation.

[0013]

EXAMPLES The present invention will be specifically described below with reference to examples and test examples.

Example 1 To 5.0 parts by weight of polyacrylic acid and 6.0 parts by weight of sodium polyacrylate, 0.5 parts by weight of silicic acid anhydride was added, and then 7.0 parts by weight of propylene glycol were added to homogenize the mixture. Disperse and disodium ethylenediaminetetraacetic acid 0.0
65.0 parts by weight of purified water in which 3 parts by weight was previously dissolved was added and uniformly dissolved. Nikkor TS-10 0.3
Parts by weight, 0.5 parts by weight of 1-menthol, 1.0 parts by weight of Vitamin E acetate, 0.1 parts by weight of BHT after heating and dissolving, 0.5 parts by weight of Yamaboshi extract, 0.5 parts by weight of indomethacin, aluminum grease A solution in which 0.3 parts by weight of nate was evenly dispersed was added and mixed uniformly, and water was added to make 100 parts by weight, and further mixed to obtain a poultice plaster. A non-woven fabric was coated with this plaster at a coating amount of 100 g / 700 cm ^{2 to} a uniform thickness, and then a liner was attached and cut to give a poultice.

Example 2 Natural rubber 30.0 parts by weight, polyisobutylene 30.0 parts by weight, polybutylene 10.0 parts by weight, titanium oxide 6.0
Parts by weight, silicic anhydride 15.0 parts by weight, hydrogenated rosin 35.
0 parts by weight and 4.0 parts by weight of lanolin were uniformly mixed. Separately, 12.0 parts by weight of dl-menthol, 3.0 parts by weight of vitamin E acetate, 3.0 parts by weight of BHT and 5.0 parts by weight of glycol salicylate were dissolved by heating, and then 8.5 parts by weight of Yamajiko extract and 8. parts of indomethacin. A liquid in which 5 parts by weight was uniformly dispersed was added and mixed uniformly to obtain a plaster base.
This plaster was applied to a cloth at a coating amount of 170 g / m ^{2 to} a uniform thickness, and then a liner was attached and cut to give a plaster.

Example 3 Natural rubber 44.0 parts by weight, polyisobutylene 44.0 parts by weight, polybutylene 13.0 parts by weight, titanium oxide 6.0
Parts by weight, silicic anhydride 15.0 parts by weight, hydrogenated rosin 35.
0 parts by weight and 4.0 parts by weight of lanolin were uniformly mixed. Separately, 1.7 parts by weight of dl-menthol, 1.7 parts by weight of vitamin E acetate, 3.0 parts by weight of BHT, and 0.017 parts by weight of nonyl acid vanillylamide were dissolved by heating, and then 1.7 parts by weight of Yamaboshi extract and 0 parts of indomethacin. A liquid having 0.85 parts by weight uniformly dispersed therein was added and uniformly mixed to obtain a plaster plaster. This plaster is applied to a cloth with a coating amount of 170 g / m ^{2 to} a uniform thickness, and then a liner is stuck and cut,
It was a plaster.

Comparative Example 1 A poultice was prepared in the same manner as in Example 1 except that the Yamajiko extract was removed.

Comparative Example 2 A poultice was prepared in the same manner as in Example 1 except for indomethacin.

Comparative Example 3 A poultice was prepared in the same manner as in Example 2, except that the Yamajiko extract was removed.

Comparative Example 4 A poultice was prepared in the same manner as in Example 2 except for indomethacin.

Test Example 1 Example 1 and Comparative Examples 1 and 2 and Example 2 and Comparative Examples 3 and 4
Oxyhemoglobin in blood was measured using the preparation obtained in 1. as a sample. The measurement was carried out using a non-invasive oxygen monitor (manufactured by Shimadzu Corporation) by fixing the above sample prepared in a size of 10 × 14 cm and the probe of the measuring machine to the upper shoulder of an adult male. The results are shown in FIGS. 1 and 2, and Examples 1 and 2 are Comparative Examples 1 and 2, respectively.
And oxyhemoglobin in blood was increased more than in Comparative Examples 3 and 4.

Test Example 2 Example 1 and Comparative Examples 1 and 2 and Example 2 and Comparative Examples 3 and 4
Using the formulation obtained in 1 above as a sample, an ultraviolet erythema inhibition test was carried out using 8 Wistar male rats. The test was carried out by removing the hair from the back of the rat and applying the above sample prepared to a size of 2.5 × 2.5 cm for 4 hours before and 2 hours after the ultraviolet irradiation. The degree of erythema 2 hours after ultraviolet irradiation was visually confirmed according to the following criteria. (Judgment Criteria) 0: No erythema 1: Slight erythema is observed 2: Erythema is present, but border is unclear 3: Strong erythema is present, border is clear The results are shown in FIGS. In Examples 1 and 2, the erythema caused by ultraviolet rays was reduced more than in Comparative Examples 1 and 2 and Comparative Examples 3 and 4, respectively.

Test Example 3 Example 1 and Comparative Examples 1 and 2 and Example 2 and Comparative Examples 3 and 4
Wistar using the formulation obtained in
A carrageenin dorsal edema inhibitory inhibition test was carried out using 8 male rats of the strain. The test was carried out by subcutaneously injecting 0.05 ml of 2% carrageenin into a rat whose hair was removed from the back, and applying the above sample prepared in a size of 2.5 × 2.5 cm to the site where inflammation was induced. . Peel off the skin after 6 hours 15
The punching weight was measured in the size of mmφ, and the edema rate was calculated by the following formula. In addition, the same amount of physiological saline was injected as a control, which was used as a control.

[0024]

[Equation 1]

The results are shown in FIGS. 5 and 6. In Examples 1 and 2, carrageenin-induced edema was suppressed more than in Comparative Examples 1 and 2 and Comparative Examples 3 and 4, respectively.

[Brief description of drawings]

1 and 2 show the measurement results of oxyhemoglobin in blood of Test Example 1. 3 and 4 show the measurement results of the ultraviolet erythema suppression test of Test Example 2. 5 and 6
Shows the measurement results of the carrageenin dorsal edema inhibition test of Test Example 3.

1 is a test result of blood oxyhemoglobin measurement using the poultices obtained in Example 1, Comparative Example 1 and Comparative Example 2. FIG.

2 is a test result of blood oxyhemoglobin measurement performed using the plasters obtained in Example 2, Comparative Example 3 and Comparative Example 4. FIG.

FIG. 3 is a result of an ultraviolet erythema suppression test conducted using the poultices obtained in Example 1, Comparative Example 1 and Comparative Example 2.

FIG. 4 is a result of an ultraviolet erythema suppression test conducted using the plasters obtained in Example 2, Comparative Example 3 and Comparative Example 4.

5 is a result of a carrageenin dorsal edema inhibitory test conducted using the poultices obtained in Example 1, Comparative Example 1 and Comparative Example 2. FIG.

FIG. 6 is a result of a carrageenin back edema inhibition test carried out using the plasters obtained in Example 2, Comparative Example 3 and Comparative Example 4.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Masato Nara 3-24-1, Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Inventor Ikki Omata 3-24-1, Takada, Toshima-ku, Tokyo Taisho Inside Pharmaceutical Co., Ltd.

Claims (1)

[Claims] 1. An anti-inflammatory and analgesic external preparation containing indomethacin and Sanjo powder or an extract.