JP2002302451A - Scf binding inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an SCF binding inhibitor comprising a plant or a plant extract useful as a medicine or a cosmetic having a preventing and treating effects on allergic diseases such as asthma, hay fever, atopic dermatitis, due to inhibition of SCF binding to c-kit at cell surface. SOLUTION: This SCF binding inhibitor comprises one or more kinds of plants selected from licorice, Aspalathus linearis, Uncaria gambir, Ruscus aculeatus L., root of Lithospermum erythrorhizon, grass of Plectranthus rugosus, red pepper, Curcuma domestica, comfrey, wild rose, lily, tea, clove and camellia or their extracts.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to ck on the cell surface.
Stem cell factor for it receptor (Stem c
ell factor (hereinafter referred to as "SCF").

[0002]

2. Description of the Related Art SCF
Is a ligand for the c-kit receptor expressed on the surface of hematopoietic stem cells, and is known as a membrane-bound growth factor that promotes proliferation and differentiation of hematopoietic cells. In recent years, c-ki
t is also expressed on the surface of mast cells and germ cells in addition to hematopoietic cells. By binding of SCF to c-kit receptor on mast cells, mast cells migrate and differentiate. -Proliferation has been reported to cause immediate allergy such as asthma and atopic dermatitis (J. Immunol 1996 May 15; 156 (10), 3945-3)
951).

[0003] Therefore, if the binding between the c-kit receptor on the surface of mast cells and SCF can be specifically inhibited, it is possible to prevent and treat allergic diseases caused by the differentiation and proliferation of such cells.

[0004] However, there is no known substance that blocks the binding of SCF to the c-kit receptor on the cell surface.

[0005] An object of the present invention is to provide an SCF binding inhibitor which inhibits the binding of SCF to c-kit receptor on the cell surface, particularly mast cell surface, and is useful as a medicine or cosmetic.

[0006]

Means for Solving the Problems The present inventors have searched for a natural product that specifically inhibits the binding of SCF to the c-kit receptor on the cell surface. It has been found that it has a binding inhibitory activity and is useful as a medicine or cosmetic having a preventive / therapeutic effect on diseases caused by the differentiation / proliferation of the cell.

[0007] That is, the present invention relates to liquorice, asparagus salinearis, asenyaku, butcher bloom, sicon, enmeiso, capsicum, turmeric, comfrey,
An object of the present invention is to provide an SCF binding inhibitor comprising a plant selected from Novara, lily, tea, clove and camellia, or an extract thereof.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The SCF binding inhibitor of the present invention
It specifically inhibits the binding of SCF to the c-kit receptor on the cell surface, especially on the surface of mast cells. It has a preventive / therapeutic effect.

The licorice in the present invention is a legume (Le
guminosae) Glycyrrhiza uralensis Fischer, Glycyr
The roots and strons of rhiza glabra L. or other congeners are asparasacea linealis, and leguminous (Legumino
sae) Aspalathus linearis (NLBurm.) R. Dahlgr whole plant, and Asenyak is Uncar of Rubiaceae (Rubiaceae)
ia gambir ROXB. Dry water extract obtained from the leaves and shoots of butcher bloom is called butcher bloom, R of Liliaceae.
The rhizome of uscus aculeatus Linne, and the sicon is the purple squirrel Lithospermum erythro of the scorpion family (Boraginaceae)
Rhizon Siebold et Zuccarini roots, Emisoso is the Labiatae of the family Labiatae Isodon japonicu
s Hara foliage, Capsicum and Solanaceae (Solanaceae)
Capsicum annuum L. or its variant fruit, turmeric refers to the rhizome of Curcuma domestica Valeton of Zingiberaceae, and comfrey refers to Symphytum officina of Boragiginaceae.
Le Linne leaves, nobara, Rose of Roseaceae (Rosaceae)
The fruits of canina Linne, lily, and lily family (Liliacea
e) Lily Lilium candidum, tea is the leaves of Thea sinensis Linne of the Camellia family (Theaceae), and the butterfly is Eugenla caryophylla of the family Myrtaceae.
ta THUNB., Camellia is Camellia japoni of Camellia
ca Linne means each flower.

The above-mentioned plant in the present invention can be used as it is, or the whole plant, leaves, bark, branches, fruits or roots of the plant can be used as it is or by pulverizing it. Whole grass for Echinacea, leaves for Asenyaku, Comfrey and Cha, butchers for Butcher Bloom and Turmeric, fruits for Capsicum and Novara, bulbs for Lilies, buds for Cloves, Camellia for Camellia Preference is given to using flowers. Further, the extract in the present invention, further extracted at room temperature or under heating or extracted using an extraction device such as a Soxhlet extractor, various solvent extracts obtained by diluting the same, It means a concentrated liquid or a dried powder thereof. Here, the extract may be obtained from two or more kinds of plants.

As the extraction solvent used to obtain the plant extract of the present invention, any of a polar solvent and a non-polar solvent can be used. For example, water; alcohols such as methanol, ethanol, propanol and butanol; polyhydric alcohols such as propylene glycol and butylene glycol; ketones such as acetone and methyl ethyl ketone; esters such as methyl acetate and ethyl acetate; tetrahydrofuran and diethyl ether Chain and cyclic ethers such as polyethylene glycol; polyethers such as polyethylene glycol; hydrocarbons such as squalane, hexane, cyclohexane, petroleum ether; aromatic hydrocarbons such as toluene;
Halogenated hydrocarbons such as dichloromethane, chloroform and dichloroethane; and carbon dioxide. These can be used as a mixture.

The above-mentioned plant extract can be used as it is, but it can also be used after diluting, concentrating or freeze-drying the extract and then preparing it in powder or paste form. In addition, the above-mentioned plant extract can be used after removing inactive contaminants from the extract by a separation technique such as chromatography and liquid distribution.

These plants or extracts thereof have excellent SCF binding inhibitory activity, as shown in the Examples below. Therefore, a preparation containing this is useful as a medicine or cosmetic having a preventive / therapeutic effect on allergic diseases such as asthma, hay fever, and atopic dermatitis.

When the SCF binding inhibitor of the present invention is formulated as a medicament, oral preparations such as tablets and capsules, ointments,
External preparations such as solutions, extracts, lotions, and emulsions and injections can be used, and among them, use as external preparations is preferable.

When formulated as a cosmetic, various forms such as a water-in-oil type or oil-in-water type emulsified cosmetic,
It can be a cream, lotion, gel, foam, essence, foundation, pack, stick, powder, etc. In addition to the plant of the present invention or its extract, oils and surfactants generally used as cosmetic ingredients , UV absorbers, alcohols, chelating agents, pH
Conditioning agents, preservatives, thickeners, pigments, fragrances, various skin nutrients, and the like can be combined in any combination.

The compounding amount of the plant of the present invention or its extract in a medicine or a cosmetic is usually 0.1% of the whole composition as a dry product.
00001 to 1% by weight, particularly preferably 0.0001 to 0.1% by weight.

[0017]

The present invention will be described below in detail with reference to examples. Production Example 1 Production of Clove Extract After drying and chopping a bud of a clove, 150 g of the bud was obtained.
Then, 1500 mL of a 50% (v / v) aqueous ethanol solution was added to the mixture, and the mixture was extracted at room temperature for 7 days, followed by filtration. The solution was concentrated under reduced pressure, and 7,500 mL of water was further added thereto. The solution was concentrated under reduced pressure, and then dissolved in 1500 mL of a 50% (v / v) aqueous ethanol solution. Activated carbon (36 g) was added thereto, and the mixture was stirred at room temperature for 6 hours and then filtered to obtain a clove extract. Yield 1200
mL, evaporation residue 1.5%.

Preparation Example 2 Each plant extract shown in Table 1 below was prepared according to Preparation Example 1.

[0019]

[Table 1]

Example 1 SCF Binding Inhibitory Activity Human cultured melanocytes (Sanko Junyaku) were seeded on a 24-well plate (Iwaki Shoji) and cultured until they became confluent.
Thereafter, the melanocyte growth medium was replaced with RPMI1640 (Gibco) containing 0.05% albumin (Wako Pure Chemical Industries, Ltd.), and POD was added using IODO-GEN lodination Reagent (PIERCE).
According to the protocol shown by IERCE, human recombinant SCF (IBL) labeled with ¹²⁵ I was used at a final concentration of 1 nM in Table 2.
Were added at a final concentration of 1%.
100 times as much unlabeled SCF as ¹²⁵ I-SCF
To determine the amount of non-specific binding. After incubation for 90 minutes, the cells were washed with ice-cold RPMI1640 after the reaction to remove unbound SCF. The cells were lysed with 2M NaOH, and the binding to c-kit on melanocytes was measured using a γ-counter according to a conventional method. In each case, the value obtained by subtracting the non-specific binding amount from the total binding amount was defined as the specific binding amount of SCF / c-kit. The results are shown in Table 2.

[0021]

[Table 2]

As shown in Table 2, it was confirmed that the plant extract of the present invention had an activity of inhibiting the binding of SCF to c-kit.

[0023]

Industrial Applicability The plant or plant extract of the present invention inhibits the binding of SCF to c-kit on the cell surface, thus preventing and treating allergic diseases such as asthma, hay fever, and atopic dermatitis. It can be used as an effective medicine or cosmetic.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 35/78 A61K 35/78 V A61P 11/06 A61P 11/06 17/00 17/00 37/08 37 / 08 // A61K 7/00 A61K 7/00 K 7/48 7/48 C07G 17/00 C07G 17/00 Z (72) Inventor Atsushi Ouchi 2606 Kabane-cho, Akaba, Kaga Corporation, Haga-gun, Tochigi (72) Inventor Hiroshi Kusunoki 2606 Akabane, Kaga-cho, Haga-gun, Tochigi Pref.F-term in the Kao Corporation Research Laboratory BA09 BA10 CA05 CA06 CA08 NA14 ZA59 ZA89 ZB13 4H055 AA01 AA03 AB12 AB22 AC60 AD21 AD22 CA60 CA62 CA65

Claims (1)

[Claims] Claims: 1. A liquorice, asparagus linenalis, asenyaku, butcher bloom, sicon, emmeso, pepper, turmeric, comfrey, novara, lily,
An SCF binding inhibitor comprising a plant selected from tea, clove and camellia, or an extract thereof.