JPH10158177A - Itching and / or pain inhibitor - Google Patents

Abstract

(57) Abstract: An agent for suppressing itch and / or pain, comprising one or more natural products selected from chondrogenic fat, rhubarb, silk, Kumasa and mulberry, or an extract thereof. [Effect] Strong substance P antagonism and high safety.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a pruritus and / or pain inhibitor having a substance P antagonistic action.

[0002]

2. Description of the Related Art Substance P is a peptide consisting of 11 amino acids which is known to have an ileal contraction action, a saliva secretion promoting action, a pain stimulating action and the like. This substance P has recently been positioned as a kind of tachykinins.

[0003] This substance P is known to act in a wide range of diseases such as digestive diseases, nervous system diseases, and circulatory system diseases. In particular, Huntington's disease, carcinoid syndrome, chronic pain, and cutaneous blood vessels It is thought to be deeply involved in permeability enhancement and the like.

[0004] Various substance P antagonists have been reported for the purpose of developing therapeutic agents for these diseases involving substance P (MM Chang, SE Leeman, HD Nia).
ll, Nature New Biol., 232, 86 (1971), Hugan RM et
al, Br. J. Pharmacol., 99 (Suppl.), 62P (1990)).

[0005]

However, since these conventional substance P antagonists are synthetic peptides and have an agonistic activity and antigenicity against humans, they have not been developed as drugs from the viewpoint of safety. ,
No drug has been developed to suppress itching and pain involving substance P. Accordingly, an object of the present invention is to provide a highly safe pruritus and / or pain inhibitor having excellent substance P antagonistic activity.

[0006]

Means for Solving the Problems The present inventors have studied the pharmacological action of plant extracts widely to solve the above-mentioned problems. Alternatively, the inventors have found that the extract has an excellent substance P antagonistic effect particularly on the skin, and have completed the present invention.

[0007] That is, the present invention provides an itch and / or pain inhibitor containing one or more natural products or extracts thereof selected from chondrogenic fat, rhubarb, silk, Kumasa and mulberry. is there.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Plants among natural products used in the present invention are plants or whole plants or one or more of leaves, stems, roots, fruits, seeds and flowers (hereinafter referred to as "primary plants"). ) Or dried and ground, and plant extracts are dried or ground without drying and then extracted with a solvent at room temperature or under heating, or by Soxhlet. Various solvent extracts obtained by extraction using an extraction device such as an extractor, a diluent thereof, a concentrate thereof,
Or it means the dry powder. In the present invention, it is preferable to use matured seeds for rheumatoid arthritis, rhizomes for rhubarb, silk fibers for silk, bark for Kumasa, and dried leaves or extracts of mulberry for mulberry. In the present invention, one or more of these natural products or extracts thereof can be used.

Extraction from these natural products requires the use of water and / or a water-soluble organic solvent in order to obtain an effective ingredient efficiently. Examples of the water-soluble organic solvent used here include methanol, ethanol, propanol, butanol, propylene glycol, 1,3
-Butylene glycol and the like, among which ethanol, butanol, propylene glycol and 1,3-butylene glycol are preferred. The water-soluble organic solvent may be used singly or as a mixture of two or more kinds, and is preferably combined with water. The amount of the solvent for the plant is 1-2.
It is preferably 0 times by weight.

On the other hand, the above-mentioned natural product as a raw material is preferably made into a coarse powder or a powder, rather than used for extraction as it is. The above-mentioned natural product may be immersed in the above-mentioned extraction solvent and may be extracted by a conventional method. However, if necessary, it may be heated to about 50 ° C. to increase the extraction efficiency. If the extract is directly or concentrated and then fractionated with a solvent, and only an effective fraction is taken out, a higher effect can be expected with a smaller amount. Here, as the solvent used for fractionation, water and ethyl acetate are preferable, and this water fraction is preferably used.

The above-mentioned natural product or its extract has an effect of suppressing the increase in cutaneous vascular permeability caused by substance P. Therefore, the agent for suppressing itch and / or pain of the present invention containing the plant or its extract is useful as a therapeutic agent for various inflammatory conditions particularly in the skin.

The pruritus suppressant of the present invention may be in any form as long as it contains the above-mentioned natural product or its extract. Oral preparations such as tablets, granules and capsules; injections;
External preparations such as ointment creams, lotions and gels; can be used as bath preparations and the like. To make these preparations,
The natural product or its extract and excipient, extender, binder,
It can be produced by appropriately combining a wetting agent, a disintegrant, a surfactant, a lubricant, a dispersant, a buffer, a preservative, a flavoring agent, a fragrance, a coating agent and the like. In addition, in order to use as a bathing agent, inorganic salts, carbon dioxide, and a carbon dioxide generator can be added to these additives.

The dosage of the pruritus and / or pain inhibitor of the present invention varies depending on symptoms, administration route, etc., but is generally 10% as the above natural product extract (dry weight) for adults.
5,000 mg, especially 50 to 2,000 mg, usually 1 day
It is preferable to administer in 4 to 4 divided doses. When used as a bathing agent, there is no particular limitation, but the extract obtained from 0.001 to 1,000 g of the above-mentioned natural product powder (raw powder) per 150 to 200 L of standard bath water is used. Preferably, the amount is an extract obtained from 0.01 to 100 g of the bulk powder.

[0014]

The itch and / or pain inhibitor of the present invention comprises
Since it is highly safe and has a strong substance P antagonistic effect, it is useful as a therapeutic agent for itch and / or pain due to a disease involving substance P, especially itch and / or pain due to skin inflammation.

[0015]

Next, the present invention will be described with reference to examples and test examples, but the present invention is not limited to these examples.

Production Example 1 Bone Bone Extract Extract Mature seeds of Dutch beaulace ( Psoralea corylifolia ) were minced, and 10 g of the mixture was mixed with water and ethanol (50: 5).
0) 100 ml was added and immersed. This was filtered to obtain an osteoclast extract.

Production Example 2 Rhubarb Extract Rhizome of rhubarb ( Rheum palmatum ) was cut into small pieces, and 10 g of the rhizome was immersed in 100 ml of a mixture of water and ethanol (58:42). This was filtered to obtain a rhubarb extract.

Production Example 3 Silk extract 10 g of silk fiber was immersed in 10 ml of 1N hydrochloric acid, 100 ml of a mixture of water and ethanol (50:50). This was filtered to obtain a silk extract.

Production Example 4 Kuma-basa extract Extract The bark of Kumazasa ( Sasa albo-marginata ) was cut into small pieces, and 10 g of the bark was mixed with 100 parts of a mixture of water and ethanol (70:30).
ml was added and immersed. This was filtered to obtain a Kumasa bamboo extract.

Production Example 5 Mulberry Extract Leaves of Morus alba were cut into small pieces, and 10 g of the leaves were immersed in 100 ml of a mixture of water and ethanol (50:50). This was filtered to obtain a mulberry extract.

Test Example 1 The back of a guinea pig was shaved, and a test extract solution (diluted with physiological saline to a concentration of 500 μg (solid content weight) / ml) 10
0 μl intradermally, and 6 hours later, Evans Blue (dissolved in physiological saline, 5 mg / ml, 0.1 mg / kg guinea pig body weight).
5 ml) was administered intravenously. Next, 50 μl of the test extract solution and 50 μl of the substance P solution (10 ⁻⁵ M) were intradermally administered to the site of intradermal administration of the test substance. 20 minutes later,
The skin on the back of the guinea pig was peeled off, and the area where the pigment (Evans blue) leaked from the back side was measured. As a result, as shown in Table 1, it can be seen that the natural product extract of the present invention suppresses the vascular permeability enhancing effect of substance P.

[0022]

[Table 1]

Test Example 2 Itching-inhibiting effect of natural product extract 7- to 10-week-old female WBN / ILA-HT hairless rats were placed in individual cages, allowed to acclimate to the environment for 1 hour, and evaluated for evaluation of natural products on the right side of the back. 500 μg (solid content weight) /
ml or physiological saline (solvent) was applied at 50 μl / site.
No treatment was performed on the left back. After 6 hours, the applied natural product extract (500 μg / ml:
50 μl / site) and pruritic substance (substance P)
10-5M: 50 μl / site) was administered intradermally, and 9
The images were taken with an 8 mm video camera for 0 minutes, and the scraping and licking times on the administration site side and the untreated side were measured. As an index of evaluation, in order to remove the effect of grooming, the time of scraping and licking of the test site (right) was
The scratching frequency was calculated by dividing by the licking time, and the efficacy was evaluated. As a result, it was confirmed that the natural product extract of the present invention had an excellent itch suppressing effect.

[0024]

[Table 2]

Test Example 3 Pain Suppressing Effect of Natural Product Extract The natural product extract of the present invention was evaluated by the Randall-Selitto method. That is, a 5-week-old male SD rat was Mycobacterium butyricum 0.6 mg / 0.1 suspended in liquid paraffin in the sole of the left hind limb under ether anesthesia.
ml / head was injected (day 0). On the 14th day, the pain level of the right hind limb was measured (using a pain level measuring device manufactured by UGO BASILE), and divided into groups so that the average value was almost uniform. The plant extract was applied to the right hind limb. On day 28, the pain crest value of the right hind limb was measured again,
The analgesic effect was evaluated based on the difference in weight at which pain was felt. As a result, it was confirmed that the natural product extract of the present invention had an excellent pain suppressing effect.

[0026]

[Table 3]

Example 1 (Tablets) Tablets having the following composition were produced by direct compression molding. Bone fat extract (Production Example 1) 100 mg Crystalline cellulose 393 mg Lactose 100 mg Hydroxypropylcellulose-L 4 mg Magnesium stearate 3 mg Total amount 500 mg

Example 2 (Granules) The following components were uniformly mixed, kneaded, granulated by an extrusion granulator, and sieved to obtain granules. (Ingredients) (g) Kuma-basa extract (Production Example 4) 10 Microcrystalline cellulose 50 10% Hydroxypropylcellulose 40 Total 100

Example 3 (Spray) A spray containing the following components in one cylinder was produced by a conventional method. (Components) (g) Rhubarb extract (Production Example 2) 1 Oleic acid 3 Freon 11 1.2 Freon 12 2.5 Freon 114 1.3 Total 9

Example 4 (Ointment) The following components were uniformly mixed to obtain an ointment. (Components) (g) Silk extract (Production Example 3) 10 Squalane 20 Glycerin 20 Cetyl alcohol 5 Magnesium stearate 3 Propylene glycol 5 Water 20 Ethanol 7 Total 90

Example 5 (Capsule) The following components were uniformly mixed to obtain a capsule. (Components) (g) Mulberry extract (Production Example 5) 100 Crystalline cellulose 100 Lactose 150 Light anhydrous silicic acid 20 Total 370

Example 6 (Cream) The following ingredients were uniformly mixed to obtain a cream. (Components) (g) Bone cartilage extract (Production Example 1) 1 Cholesterol 0.5 Cholesteryl isostearate 1 Polyether-modified silicone 1.5 Cyclic silicone 20 Methylphenylpolysiloxane 2 Methylpolysiloxane 2 Magnesium sulfate 0.5 55% ethanol 5 carboxymethyl chitin 0.5 purified water 66 total 100

Example 7 (Skin Lotion) (Components) (g) Silk Extract (Production Example 3) 2 Glycerin Monostearate 1 Ethanol 15 Propylene Glycol 4 Isopropyl Palmitate 3 Lanolin 1 Methyl Paraoxybenzoate 0.1 Ceramide 1 Perfume and pigment Trace purified water Fuel gauge 100.0

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI A61K 35/78 ADA A61K 35/78 ADAU AED AEDC (72) Inventor Satoshi Kanazawa 2606 Akabane, Kakaicho, Haga-gun, Tochigi Pref. Research by Kao Corporation (72) Inventor Yoshinori Nishizawa 2606 Akabane, Kaigamachi, Haga-gun, Tochigi Pref.

Claims (3)

[Claims] 1. An itching and / or pain suppressant comprising one or more natural products selected from chondrogenic fat, rhubarb, silk, Kumasa and mulberry, or an extract thereof. 2. The agent for suppressing itch and / or pain according to claim 1, wherein the natural product extract is an extract extracted from the natural product using water and / or a water-soluble organic solvent. 3. The itch according to claim 1, wherein the natural product extract is a water fraction obtained by fractionating water and / or a water-soluble organic solvent extracted with water and ethyl acetate. // Pain suppressants.