JP2001139485A - Fervesceuce agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a fervesceuce agent bringing sufficient body-warming feeling, and an activating agent of a decoupling protein for capable of improving a converting efficiency of a chemical energy coupled in ATP synthesis to a thermal energy. SOLUTION: This fervesceuce agent contains a plant belonging to the genus Cirsium or its extract as an active ingredient, and an activating agent for the decoupling protein contains the plant belonging to the genus Cirsium or its extract as the active ingredient.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001] The present invention relates to a body temperature increasing agent and an uncoupling protein activator.

TECHNICAL FIELD OF THE INVENTION

[0002]

2. Description of the Related Art As means for warming a body that is cooled in summer or in winter, blood circulation is promoted by massage of limbs, or heat is absorbed into the body by ingestion of warm food and drink. And the like. Massage agents used for this purpose have also been developed. However, in these methods, blood circulation is temporarily promoted immediately after use, and a feeling of warmth of the body is obtained, but the effect is not sustained. For this reason, there has been a demand for a body temperature increasing agent that provides a sufficient feeling of warmth of the body.

[0003] Uncoupling protein (hereinafter referred to as "UCP")
Is a chemical energy that exists in mitochondria such as adipose tissue, skeletal muscle, and liver, and inhibits the energy obtained by electron transfer in oxidative phosphorylation in vivo from coupling to ATP synthesis reaction, and couples to ATP synthesis. It functions as a special proton channel protein that converts OH into heat energy. If such UCP can be activated, A
It is thought that the conversion efficiency of chemical energy conjugated to TP synthesis into thermal energy is improved.
Activators are scarcely known and their development has been sought.

[0004]

The present inventors have studied the pharmacological effects of various plants. As a result, surprisingly, thistle plants or extracts thereof have excellent body temperature increasing effects and U.S.P.
The present inventors have found that they show a CP activating effect and that they are useful as a body temperature increasing agent and a UCP activating agent if they are contained as an active ingredient, and thus completed the present invention.

[0005] The present invention provides a body temperature increasing agent comprising a thistle plant or an extract thereof as an active ingredient. The present invention also provides
Provided is a UCP activator comprising a thistle plant or an extract thereof as an active ingredient.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION As thistle plants of the present invention, for example, genus Acetylus (Cephalonoplos)
Genus), Thistle genus (Cirsium genus), and Thistle genus (Carduns)
Genus), spruce (Saussurea), fox thistle (Hemistepta), yamabokuchi (Synurus), tamurasou (Serratula), okera (Atractylodes)
Genus), plants belonging to the genus Higotai (genus Echinops) and the like. Among these, there are thistle, thistle foxtle thistle, nohara thistle, nambu thistle, silk thistle,
Yoshino Thistle, Stone Thistle, Moria Thistle, and Thistle are preferred. In the present invention, one or more of these can be used.

[0007] Thistle family plants include leaves, flower heads, seeds,
Stems, roots and whole plants can be used as raw materials, and are used as raw as juice, dry powder or solvent extract.

[0008] The solvent extract is obtained by extracting the above plant as it is or by drying and pulverizing it with a solvent at room temperature or under heating. Alternatively, the extract may be diluted, concentrated, dried, purified, sterilized, or the like.
Examples of the extraction solvent include those commonly used for extracting natural product components, for example, water; alcohols such as methanol, ethanol, propanol, and butanol; polyhydric alcohols such as ethylene glycol, propylene glycol, butylene glycol, and glycerin; acetone, methyl ethyl ketone Ketones such as methyl acetate, ethyl acetate and the like; ethers such as tetrahydrofuran, diethyl ether and polyethylene glycol; halogenated hydrocarbons such as dichloroethane and chloroform; petroleum ether;
aliphatic hydrocarbons such as n-hexane and cyclohexane;
Aromatic hydrocarbons such as toluene; pyridines; sodium chloride solution; and the like, with water, ethanol, propylene glycol and butylene glycol being particularly preferred. In the present invention, one or more of these can be used.
The extraction can be performed under ordinary conditions. For example, the above natural product may be immersed at 3 to 100 ° C. for several hours to several weeks or heated and refluxed.

The body temperature increasing agent of the present invention can be used as an external preparation for the skin, but is preferably used as an injection, an oral administration agent, a food or drink, and particularly preferably a food or drink. The form of the injection is not particularly limited, and examples thereof include intradermal injections, subcutaneous injections, intramuscular injections, and intravenous injections. The form for oral administration is not particularly limited, and examples thereof include solid preparations such as powders, granules, capsules, pills, and tablets; and liquid preparations such as solutions, suspensions, and emulsions. In the case of foods and drinks, the form is not particularly limited, and for example, beverages such as fruit juices, milk drinks, teas, etc .; breads, noodles, confectioneries, dressings, seasonings, processed meats, fish and shellfishes Foods such as processed products are included. These injections, oral preparations, and foods and drinks can be produced according to a conventional method by adding, in addition to the above-mentioned thistle plant or its extract, commonly used raw materials according to their form.

The UCP is UCP-1, UCP-2, UC
Although subtypes and variants of P-3 and UCP-4 are known, the UCP activator of the present invention is effective for activating any of them. The UCP activator of the present invention comprises an injection,
It is preferable to use it for oral administration, food and drink, and external preparation for skin. Examples of the injection, the oral administration agent and the food and drink include the same ones as described above. The external preparation for skin may be any one that can be externally applied to the body, and may be any of a medicated external preparation for skin and a cosmetic. Examples of the medicated skin external preparation include various ointments containing a medicinal ingredient such as an analgesic anti-inflammatory agent, an antipruritic agent, and a disinfectant. Examples of the cosmetics include water-in-oil type or oil-in-water type emulsified cosmetics, creams, and skin care cosmetics such as oily cosmetics. External preparations for skin include, in addition to the above thistle plant or its extract, inorganic compounds, organic acids, silicones, pigments, vitamins, fine powders, fine powders, used in ordinary cosmetics, quasi-drugs, pharmaceuticals, etc. Various optional components such as an activator may be appropriately blended and manufactured according to a conventional method. In order to facilitate the effect of increasing the body temperature of the present invention particularly in an external preparation for skin, ethanol; polyhydric alcohols such as polyethylene glycol, propylene glycol, butylene glycol, and glycerin; sodium alginate, gum arabic, and carboxyvinyl polymer in the formulation; It is preferable to use at least one water-soluble polymer such as polyvinylpyrrolidone, etc., and the compounding amount is 0.005 to 80% by weight (hereinafter simply referred to as “%”), particularly 0.1 to 70% in the external preparation. Is preferred.

The amount of the above thistle plant or its extract in the body temperature-increasing agent of the present invention depends on the form of the body temperature-increasing agent, but is 0.05% or more in terms of solid content, especially 0.1 to 50%. %
Is preferred. In addition, the amount of the above thistle plant or its extract in the UCP activator of the present invention depends on the form of the UCP activator, but is 0.05% or more in terms of solid content, particularly 0.1 to 0.1%. 50% is preferred.

The dosage of the body temperature increasing agent of the present invention is preferably 1 μg to 10 mg, particularly preferably 10 μg to 1 mg per day for an adult in the case of an injection, in terms of the solid content of the above thistle plant or its extract. In the case of an oral administration agent, food and drink, it is preferably 0.01 to 10 g, particularly preferably 0.1 to 2 g per day for an adult. The dose of the UCP activator is preferably 1 μg to 10 mg, particularly preferably 10 μg to 1 mg per day for an adult in the case of an injection, in terms of solid content of the above thistle plant or its extract. In the case of an oral administration agent, food and drink, it is preferably 0.01 to 10 g, particularly preferably 0.1 to 2 g per day for an adult. When the UCP activator is used as an external preparation for skin, preferably 1 mg to 1 g, particularly preferably 10 mg to 500 mg, is applied to the skin per adult day.

[0013]

EFFECT OF THE INVENTION By using the body temperature increasing agent of the present invention, a sufficient feeling of warming of the body can be obtained. In addition, the U of the present invention
The use of the CP activator can improve the conversion efficiency of chemical energy conjugated to ATP synthesis into heat energy.

[0014]

EXAMPLES Reference Example 1 Dried Root 1 of thistle (Cirsium oligophyllum)
00g was extracted with hot water by a conventional method, and concentrated under reduced pressure after filtration.
Subsequently, 11 g of the extract was obtained by freeze-drying.

Reference Example 2 100 g of fresh leaf of thistle (Cirsium japonicum) was extracted with a 30% aqueous ethanol solution by a conventional method, filtered, concentrated under reduced pressure, and lyophilized to obtain 9 g of an extract.

Reference Example 3 Dried Stem 10 of Nambu Thistle (Cirsium nipponicum)
0 g was extracted with hot water by a conventional method, filtered, concentrated under reduced pressure, and then freeze-dried to obtain 10 g of the extract.

Test Example 1 Using physiological saline containing 5 mg of each extract obtained in Reference Examples 1 to 3 (each extract containing 10% in terms of solid content), its body temperature increasing effect was determined by the following test method. Examined. Table 1 shows the results. (Test method) A micro temperature sensor was inserted between the subcutaneous adipose tissue of the back and the trapezius muscle of male Wistar rats (weight: 200-250 g) kept at 37 ° C under bent barbital anesthesia, and the body temperature was monitored. Add each of the above physiological saline to 50
μl was administered intravenously, and changes in body temperature before and after administration were calculated.

[0018]

[Table 1]

From Table 1, the injection of physiological saline containing the extracts of Reference Examples 1 to 3 showed an increase in the temperature of tissues in the living body, and an extract of a thistle plant increased the body temperature. Particularly, the body temperature of the physiological saline injection group containing the extract of Reference Example 3 increased remarkably.

Test Example 2 Using the aqueous solution containing 1 g of each extract obtained in Reference Examples 1 to 3 (each extract contained 1% in terms of solid content), the warming effect when drinking was determined by the following test method. Examined. Table 2 shows the results. (Test Method) Each subject drank the aqueous solution containing the extract of Reference Examples 1 to 3, and after 30 minutes, the feeling of warmth of the body was judged according to the following criteria, and indicated by the average score of five persons. The control was water without the extract. 4 points: There is a stronger feeling of warming compared to before drinking 3 points: There is a feeling of warming after drinking compared to before drinking 2 points: There is a slightly warmer feeling after drinking compared to before drinking 1 point: After drinking compared to before drinking Is also equivalent

[0021]

[Table 2]

From Table 2, it was confirmed that when the aqueous solutions containing the extracts of Reference Examples 1 to 3 were drunk, a warming feeling of the body was obtained. In particular, the sense of warmth of the body of the extract-containing aqueous solution drinking group of Reference Example 3 was remarkable.

Test Example 3 Using the extracts obtained in Reference Examples 1 to 3, skin external preparations 1 to 3 were prepared according to a conventional method with the formulations shown in Table 3. As a control, a skin external preparation not containing the extract was produced. Next, the UCP expression promoting effect of the subcutaneous tissue was examined by the following test method using each skin external preparation. Table 4 shows the results. (Test method) Shaved male Wistar rats (body weight 20)
0-250 g) between the back shoulder blades, 100 μL of the control product shown in Table 3 or 100 μL of the external preparation for skin 1-3 was applied every day. The application was performed after the back shoulder was dipped in tap water at 40 ° C. for 5 minutes. On the seventh day, the trapezius muscle under the applied site was excised, RNA was extracted by a conventional method, and then UCP-3 mRNA was analyzed by RT-PCR. In addition, mRNA
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as the internal standard, and the amount of UCP-3 mRNA was determined by UCP.
-3 mRNA / GAPDH mRNA ratio, and the average value (mean ± SD: n = 5) is shown in Table 4.

[0024]

[Table 3]

[0025]

[Table 4]

From Table 4, it can be seen that by using the extract-containing skin external preparations of Reference Examples 1 to 3, significant UCP-3 mRNA was obtained.
It was found that the expression of UCP was promoted.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 43/00 107 A23L 2/00 F (72) Inventor Tadashi Hase 2606 Akabane, Kakaicho, Haga-gun, Tochigi Kao stock Inside the Company Research Laboratory (72) Takashi Murase Inventor 2606 Kabane-cho, Akaga-cho, Haga-gun, Tochigi Prefecture Inside the Kao Corporation Research Institute Reference) 4B017 LC03 LG15 LP01 LP02 LP03 4B018 LB01 LB02 LB05 LB06 LB08 LB09 MD61 ME14 MF01 MF06 4C088 AB27 AC01 AC03 AC04 AC05 AC11 BA07 BA08 BA09 BA10 CA05 CA06 CA08 MA02 MA17 MA22 MA35 MA37 MA41 MA43 MA52 MA63 MA66 NA19

Claims (3)

[Claims] 1. A body temperature increasing agent comprising a thistle plant or an extract thereof as an active ingredient. 2. The body temperature increasing agent according to claim 1, which is used for eating and drinking. 3. An uncoupled protein activator comprising a thistle plant or an extract thereof as an active ingredient.