JPH10158179A - Skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin preparation for external use having excellent substance P antagonist activities especially for skin, and further having high safety, and useful for improving symptom of various kinds of dermatosis by including a specific plant or an extract thereof. SOLUTION: This skin preparation for external use includes one or more kinds of plants selected from among Eucommia ulmoides, Eclipta prostrata and leaf of Phyllostachys nigra, or an extract thereof. The extract is preferably a water fraction obtained by extracting the plant with water and/or water-soluble organic solvent and fractionating the extract with water and ethyl acetate. A daily dose of the objective skin preparation for external use is preferably 10-5,000mg per adult in terms of the dried weight of the extract and administered by dividing to 1-4 times.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an external preparation for skin,
More specifically, the present invention relates to a skin external preparation having a substance P antagonistic effect and having an excellent effect of suppressing itching and pain.

[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 diseases, but in particular, Huntington's disease, carcinoid syndrome, chronic pain, and cutaneous vascular penetration. It is considered to be deeply involved in hypersexuality 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 been developed as external skin preparations from the viewpoint of safety. Not in. Accordingly, an object of the present invention is to provide an external preparation for skin having excellent substance P antagonistic activity, high safety, and effective for ameliorating symptoms of various skin diseases.

[0006]

Means for Solving the Problems The present inventors have studied the pharmacological action of plant extracts widely in order to solve the above-mentioned problems. Alternatively, they have found that an extract thereof has an excellent substance P antagonistic action particularly in the skin and is useful as an external preparation, and have completed the present invention.

That is, the present invention provides an external preparation for skin containing one or more plants selected from Eucommia, Takasaburo and bamboo leaves, or an extract thereof.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The plant used in the present invention refers to one or more of the whole plant or its leaves, stems, roots, fruits, seeds, and flowers (hereinafter referred to as "protozoa"). ) Or dried and crushed, and the plant extract is
Various solvent extracts obtained by drying the raw material or pulverizing without drying, extracting with a solvent at room temperature or under heating, or using an extraction device such as a Soxhlet extractor, and diluents thereof , Its concentrated liquid, or its dried powder. In the present invention, it is preferable to use bark for eucommia, whole plant for takasaburo, and dried leaf or extract for tan bamboo leaf. In the present invention, one or more of these plants or extracts thereof can be used.

[0009] Extraction from these plants 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-
Examples thereof include butylene glycol, and among them, 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 to 20.
It is preferable to make the weight times.

[0010] On the other hand, it is preferable that the plant as a raw material is coarse powder or powder, rather than used for extraction as it is.
The plant may be immersed in the above-mentioned extraction solvent and extraction may be performed by a conventional method. However, if necessary, the plant 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.

[0011] The above-mentioned plant or its extract has the effect of suppressing the increase in cutaneous vascular permeability caused by substance P.
Therefore, the external preparation for skin of the present invention containing the plant or the extract thereof is useful as a therapeutic agent for various inflammatory conditions in skin and a skin cosmetic.

The external preparation for skin of the present invention may be in any form as long as it contains the above-mentioned plant or its extract.
It can be used as a cream, lotion, gel and the like. To make these preparations, the above-mentioned plant or its extract and excipients, fillers, binders, wetting agents, disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, fragrances It can be manufactured by formulating these in an appropriate combination.

The amount of the external preparation for skin of the present invention varies depending on the symptoms and the like, but is generally 10 to 5,000 mg, especially 50 to 50 mg as the above plant extract (dry weight) for adults.
It is preferable to use 2,000 mg usually in 1 to 4 divided doses per day.

[0014]

The external preparation for skin of the present invention has high safety,
And substance P antagonistic action is strong, so substance P
It is useful as an external preparation for skin for treating and preventing itching / pain and skin inflammatory symptoms associated with.

[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 Eucommia extract Eucommia ulmoides bark was cut into small pieces , and 10 g of the bark was mixed with 100 ml of a mixture of water and ethanol (50:50).
Was added and immersed. This was filtered to obtain a eucommia extract.

Production Example 2 Takasaburo Extract Whole grass of Takasaburo ( Eclipta prostrata ) was cut into pieces,
A mixture of water and ethanol (70:30)
0 ml was added and immersed. This was filtered to obtain a Takasaburo extract.

Production Example 3 Pale bamboo leaf extract Leaves of L. crustacea ( Lophatherum gracile ) are cut into small pieces , and 10 g of the leaves are mixed with 100 ml of a mixture of water and ethanol (50:50).
Was added and immersed. This was filtered to obtain a fresh bamboo leaf 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 is found that the plant extract of the present invention suppresses the vascular permeability-enhancing effect of substance P.

[0020]

[Table 1]

Test Example 2 Inhibitory Effect of Plant Extract on Itching 7 to 10-week-old female WBN / ILA-HT hairless rats were placed in individual cages, allowed to acclimate to the environment for one hour, and then the plant extract ( 500 μg (weight of solid content) /
ml) or physiological saline (solvent) was applied at 50 μl / site. No treatment was performed on the left back. After 6 hours, the evaluation plant extract (500 μg /
ml: 50 μl / site) and intradermal administration of a pruritic substance (substance P10-5M: 50 μl / site)
The images were taken with an 8 mm video camera for 90 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 plant extract of the present invention had an excellent itch suppressing effect.

[0022]

[Table 2]

Test Example 3 Pain Suppressing Effect of Plant Extract The plant extract of the present invention was evaluated by the Randall-Selitto method. That is, a 5-week-old DS male rat was subjected to Mycobacterium butyricum 0.6 mg / 0.1 ml suspended in liquid paraffin in the sole of the left hind paw under ether anesthesia.
/ Head (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 plant extract of the present invention had an excellent pain-suppressing effect.

[0024]

[Table 3]

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

Example 2 (Ointment) The following components were uniformly mixed to obtain an ointment. (Components) (g) Takasaburo extract (Production Example 2) 10 Squalane 20 Glycerin 20 Cetyl alcohol 5 Magnesium stearate 3 Propylene glycol 5 Water 20 Ethanol 7 Total 90

Example 3 (Cream) The following ingredients were uniformly mixed to obtain a cream. (Components) (g) Bamboo leaf extract (Production Example 3) 1 Cholesterol 0.5 Cholesteryl isostearate 1 Polyether-modified silicone 1.5 Cyclic silicone 20 Methylphenylpolysiloxane 2 Methylpolysiloxane 2 Magnesium sulfate 0.555 % Ethanol 5 Carboxymethyl chitin 0.5 Purified water 66 Total 100

Example 4 (Skin Lotion) (Components) (g) Eucommia Extract (Production Example 1) 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

Continued on the front page (72) Inventor Satoshi Kanazawa 2606, Akabane, Kaga-cho, Haga-gun, Tochigi Prefecture Inside the Kao Corporation Research Institute

Claims (3)

[Claims] 1. An external preparation for skin containing one or more plants selected from Eucommia, Takasaburo and bamboo leaves, or an extract thereof. 2. The external preparation for skin according to claim 1, wherein the plant extract is an extract extracted from the plant using water and / or a water-soluble organic solvent. 3. The external preparation for skin according to claim 1, wherein the plant extract is a water fraction obtained by fractionating water and / or a water-soluble organic solvent and extracting with water and ethyl acetate. .