JP2002053480A - Production-inducing agent for tumor necrosis factor, skin care preparation and health food - Google Patents

Abstract

PROBLEM TO BE SOLVED: To discover a safe and new production-inducing agent for tumor necrosis from a medical plant used from old times, and supposed that the safety is established, and further to provide a skin care preparation and a health food by utilizing the production-inducing agent for the tumor necrosis. SOLUTION: This production-inducing agent for the tumor necrosis is obtained by extracting one or more kinds selected from Scutellariae Radix, Phellodendri Cortex, Caryophylli Flos, Lithospermi Radix and Gentianae Radix with a water- based solvent such as water, ethanol and methanol. The skin care preparation and the health food are produced by using the production-inducing agent for the tumor necrosis.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an agent for inducing tumor necrosis factor production, an external preparation for skin, and a health food. Specifically, TNF-a, which has a strong apoptotic effect on tumors,
The present invention relates to a medicinal plant-derived tumor necrosis factor production inducer excellent in safety for inducing lpha, an external preparation for skin containing the tumor necrosis factor production inducer, and a health food.

[0002]

2. Description of the Related Art TNF became old (LJOl) in 1975.
d) etc., animals such as rabbits and mice
Sensitizes with a primary stimulant such as CG or anaerobic corynebacterium (C. parvum), and further administers a secondary stimulant such as lipopolysaccharide (hereinafter referred to as "LPS"). Was found to cause hemorrhagic necrosis in tumor cells (Carswell EA et al., Pro
c. Natl. Acad. Sci. USA, 72, 3666 (1975)). TN
F is a tumor-inducing factor produced by macrophages, and its antitumor activity has been confirmed by many studies since its discovery in 1975 (Gresser I, et al., Int.
J. Cancer. 38, 771 (1986); Regenass U, et al., Int.
J. Cancer. 39, 266 (1987); Marquet RL et al., Int.
J. Cancer. 40, 550 (1987)).

On the other hand, recently, there has been a demand for the development of a primary stimulant which is inexpensive and easily available as a primary stimulant and which can be administered to the human body with low toxicity.

[0004]

DISCLOSURE OF THE INVENTION The present invention has been made to provide a primary stimulant which can be easily obtained at a low cost and which can be administered to the human body with low toxicity. From a plant that has been used for a long time and whose safety is considered to be established, we have worked diligently to provide a safe and novel inducer of tumor necrosis factor production. The present inventors have found that the extract of gentian has a significant tumor necrosis factor production-inducing action, and have completed the present invention.

[0005]

The tumor necrosis factor production inducer according to the present invention (hereinafter, referred to as "TNF production inducer" in the present invention) is a group consisting of gongon, oakaku, clove, sicon and gentian. Or one or more extracts selected from the group consisting of:

[0006] The external preparation for skin according to the present invention is characterized by containing the above-mentioned TNF production inducer according to the present invention.

Further, a health food according to the present invention is characterized by containing the above-mentioned TNF production inducer according to the present invention.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The TNF production inducer according to the present invention is selected from Scutellariae Radix and Phellod.
endri Cortex), Clove (Caryophylli Flos), Sicon
(Lithospermi Radix) and one or more extracts selected from the group consisting of Gentianae (Gentianae Radix). Ougon is a dried root of Scutellaria baicalensis Georgi belonging to the family Lamiaceae, Scutellaria spp. In addition, yellowtail (Phellodendron amurense Ru) belongs to the citrus family Asteraceae.
precht) and other bark of the same genus plant except for the bark. The butterfly is Syzygium aromaticum Merrill et Perry, which belongs to the genus Adek in the family Myrtaceae.
The flower pattern of the bud was removed and dried. Sicon,
Purple (Lithospermum offinala L)
inn.var.erythrorhizon Maxim.) and other closely related plants. Gentian is also obtained by drying the roots and rhizomes of Gentian (Gentiana Linn.) Belonging to the Gentian family. All of these have been used as crude drugs widely since ancient times as medicinal plants,
Its safety is sufficiently appreciated. The TNF production inducer of the present invention can be used to convert these medicinal plants into various aqueous solvents such as water, hydrophilic solvents such as methanol, ethanol, isopropanol and ethyl ether, or a mixture of these hydrophilic solvents and water, Extracted using water from the height of, and contains a substance having a TNF production-inducing effect, but the details thereof are unknown.

In the present invention, the above-mentioned medicinal plants can be obtained individually or in a mixture of two or more by various known extraction methods. However, the above-mentioned medicinal plants are generally crude from the viewpoint of extraction efficiency. It is pulverized by various methods such as cutting and shredding.

[0010] The extraction is carried out at room temperature or by heating at a temperature which does not affect the TNF production inducing action. , A medicinal plant is added thereto, and the mixture is stirred as needed. The extraction time also varies depending on the extraction solvent and the medicinal plant used, but is generally about 2-3 hours to 24 hours. Thereafter, the extraction residue is removed by liquid-solid separation to obtain an extract.

The extract can be used as it is as the TNF production inducer according to the present invention. However, since the TNF production inducing effect may be low in some cases, the extract is concentrated as necessary to obtain a concentrated extract, It can be made into a so-called dense extract, or it can be made into a solid by a method such as spray drying.

Further, the obtained extract may give off an unpleasant odor peculiar to medicinal plants or may be colored. Therefore, in order to remove these unpleasant odors and coloring, the TNF production inducing action is not significantly reduced. Thus, an activated carbon treatment or a resin adsorption treatment can be performed.

[0013] The TNF production inducer of the present invention includes T
Any excipient, for example, a solid substance such as lactose or starch, or a solvent that does not affect the human body such as ethanol or water can be added to the extent that the NF production-inducing action is not affected.

The TNF production inducer thus obtained is provided together with the above-mentioned excipients or with the addition of other preservatives. The shape is not particularly limited, and it is provided in the form of a liquid, a powder, a granule, a tablet, or the like.

The TNF production inducer can of course be used by taking it as a pharmaceutical or health food, but can also be applied as various skin external preparations for medical use or cosmetics. The amount of these additives is approximately 0.1 to 1000 mg per day when drinking, and 0.1 to 1000 mg when used as an external preparation.
It is used to be about 20 w / w%.

The health food of the present invention is provided, for example, as liquids such as so-called soft drinks or as various types of foods and drinks such as solids such as candy and semi-solids such as jelly. It is also added to various Japanese and Western sweets, dairy products, processed marine products, and processed agricultural products. Further, as the external preparation for skin of the present invention, emulsions, lotions, creams,
It is provided as a pack or the like.

In these cases, similar to those used for ordinary processed foods and skin external preparations, various vitamins and other pigments, coloring agents, surfactants and the like are used as long as they do not interfere with the TNF production inducing action. It goes without saying that various additives such as stabilizers, ultraviolet absorbers, antioxidants, preservatives and other fragrances can be added.

[0018]

EXAMPLES Next, TNF production inducers as examples of the present invention, skin external preparations and health foods as formulation examples of the present invention will be shown, and the present invention will be described in more detail.

(Example of production of TNF production inducer)
Oubak, clove, sicon, and gentian are each finely chopped, and 50 g thereof is taken.
Time decocted. After that, the extract was filtered and freeze-dried to obtain 6.5 g of powdered extract of pentagon and extract of pentagram.
g, clove extract 8.4 g, siconium extract 4.5 g,
6.3 g of gentian extract was obtained.

(TNF production inducing action) The extract of the pentagon, the extract of oak, the extract of clove,
The TNF production-inducing effect of the siconium extract and the Gentian extract was examined. The test consisted of a group of 5 ICR female mice (7-8
Weekly), each extract (1 mg / (animal / day) and 10 mg / (animal / da)
y)) was orally administered for 9 days, and then LP as a secondary stimulant
S was administered. Two hours later, blood was collected from each mouse, and serum was separated by a standard method, and TNF activity was measured. For the measurement of TNF activity, an enzyme antibody immunoreaction (E
LISA method). Specifically, a sample serum was added to a 96-well microplate coated with an anti-mouse TNF antibody, and incubated at room temperature for 2 hours. Then, the microplate was washed, reacted with a labeled anti-mouse TNF antibody, and then developed, and the absorbance at 450 nm was measured. Was measured. A similar reaction was performed using mouse TNF as a standard, and a calibration curve was prepared.
The amount of F was quantified. Further, the TNF amount was similarly measured for the control group to which water was administered. Table 1 shows the results.

[0021]

[Table 1]

As can be seen from Table 1, it was confirmed that each extract had a significant TNF production inducing effect. In addition, in the administration group of Ogon and Obak 10 mg, sufficient production inducing action could not be confirmed.

Next, various health foods and skin external preparations of the present invention were produced using the TNF production inducer of the present invention.
A good formulation could be obtained without any problems.

(Preparation example 1) 5 g of the gogon extract in 100 g of candy 95 g of starch syrup 95 g of the above components were kneaded to obtain a candy by a conventional method.

(Preparation Example 2) Oleum extract 1 g in soft drink 100 ml Sucrose 5 g Water balance The above components were mixed and dissolved to obtain soft drink.

(Formulation Example 3) Tablets (of 10 tablets) Gentian extract (Production Example 1) 2 g Lactose 8 g Magnesium stearate 0.1 g The above components were mixed and stirred to obtain tablets by a conventional method.

Formulation Example 4 Cream (in 100 g) Squalane 8.0 g Octyldodecyl myristate 1.0 g Bacyl alcohol 5.0 g Polyoxyethylene (10EO) hydrogenated castor oil 1.0 g Sorbitan monostearate 0 0.5 g Preservatives Appropriate amount 1,3-butylene glycol 5.0 g Purified water residue Silicone extract 0.5 g Mix the above squalane to preservative and heat and dissolve at 75 ° C to make oil phase. Separately, purified water and 1,3-
An aqueous phase in which butylene glycol and a sicon extract were mixed was added and emulsified. Thereafter, the mixture is cooled to 30 ° C. while stirring,
I got a cream.

(Preparation Example 5) Lotion Loquat extract 0.3 g Ethanol 10.0 g Polyoxyethylene nonylphenyl ether (10EO) 0.1 g Glycerin 2.0 g Preservatives Appropriate amount Purified water residual amount Polyoxyethylene nonylphenyl ether was mixed from the extract at room temperature, and glycerin to purified water was mixed and dissolved to obtain a lotion.

(Formulation Example 6) Emulsion Stearic acid 2.0 g Cetanol 1.5 g Squalane 5.0 g Self-emulsifying glyceryl monostearate 2.0 g Glycerin 2.0 g 1,3-butylene glycol 6.0 g Sodium hydroxide 0.0 g 03 g Preservatives Appropriate amount Purified water residual amount Gentian extract 0.1 g The above stearic acid to self-emulsifying glyceryl monostearate are mixed, and heated and dissolved at 70 ° C. to form an oil phase. Separately, glycerin to gentian extract were mixed and dissolved, and the oil phase was added to an aqueous phase heated to 70 ° C., followed by uniform emulsification with a homomixer. Thereafter, the mixture was cooled to 30 ° C. with stirring to obtain an emulsion.

[0030]

According to the present invention, a novel and highly safe 1
It is possible to provide a TNF production inducer, which is a secondary agent, and to provide a skin external preparation or a health food which leads to tumor treatment and prevention of tumor occurrence.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 7/48 A61K 7/48 A61P 43/00 111 A61P 43/00 111 (72) Inventor Miki Nakayama Osaka 2-6-11 Nishihonmachi, Nishi-ku, Osaka-shi Inside Club Cosmetics Co., Ltd. (72) Inventor Keika Kato 2-6-111 Nishihonmachi, Nishi-ku, Osaka-shi, Osaka F-term in Club Cosmetics Co., Ltd. 4B018 MD48 MD61 ME08 4C083 AA111 AA112 AB032 AC022 AC072 AC102 AC122 AC182 AC242 AC342 AC422 AC432 AC442 CC04 CC05 DD27 DD33 EE13 4C088 AB12 AB38 AB57 AB62 AB67 AC03 AC06 AC11 AC13 ZA89 ZB21

Claims (3)

[Claims] 1. One or two members selected from the group consisting of a giant gourd, a ginkgo biloba, a clove, a sicon and a gentian
An agent for inducing tumor necrosis factor production, comprising an extract of at least one species. 2. An external preparation for skin, comprising the agent for inducing tumor necrosis factor production according to claim 1. 3. A health food comprising the tumor necrosis factor production inducer according to claim 1.