JP2003146902A - Lipase activity enhancer, skin care preparation, skin care preparation for slimming and bath medicine for slimming comprising the same lipase activity enhancer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a lipase activity enhancer composed of a crude drug, a skin care preparation, a skin care preparation for slimming and a bath medicine for slimming comprising the lipase activity enhancer. SOLUTION: This lipase activity enhancer comprises one or more kinds of crude drugs selected from the whole herb of Pogostemon cablin Benth. except the root, a tuberous root of Polygonum multiflorum Thunb., a sap of Boswellia carterii Birdwood or a rhizome of Dioscorea tokoro Makino. The skin care preparation, skin care preparation for slimming and bath medicine for slimming comprise the lipase activity enhancer. Fatty tissues such as subcutaneous fats can be reduced and obesity can be ameliorated for slimming by percutaneously administering the lipase activity enhancer.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a lipase activity activator capable of directly increasing the triglyceride degrading activity of lipase which functions as a neutral lipolytic enzyme in the living body. Furthermore, the present invention relates to a skin external preparation, a slimming skin external preparation, and a slimming bath preparation containing the lipase activity activating agent.

[0002]

2. Description of the Related Art In the modern lifestyle, there are many opportunities for overeating and less exercise. Further, various factors such as disorder of hormone balance, aging, and stress do not allow fat metabolism in the body to be performed properly, resulting in abnormal accumulation of neutral fat, leading to overweight and obesity. Obesity, which is a case where a large amount of neutral fat is accumulated as body fat, causes various diseases such as arteriosclerosis, and thus prompt improvement is required. In addition, due to the recent increasing interest in health and beauty, an increasing number of people, regardless of age or sex, desire to keep their body healthy and slim. I am very interested.

[0003] Therefore, many people are in the trend of slimming down by dieting. Examples of the treatment for obesity include a strict diet method, a slimming method such as liposuction, aerobic general exercise such as aerobics, and fat burning promotion by components such as Gymnema. In addition, cosmetics and the like containing xanthine derivatives such as caffeine and capsaicin, dihydrocapsaicin, nordihydrocapsaicin and the like contained in capsicum as active ingredients have been developed.

Furthermore, various bath agents for the purpose of sweating, promoting metabolism, moisturizing, recovering from fatigue, etc. are known, and bath agents which allow one to easily enjoy a hot spring mood are also well known. In general, the effects of bathing include cleansing the skin, dilating blood vessels, promoting blood circulation, increasing substance metabolism,
Examples include hyperactivity of various organs, relaxation of muscles and joints, removal of stiffness and pain, decomposition or absorption of pathological products, and bath agents are also used to enhance these effects.

However, although various methods and drugs have been proposed so far, the effects obtained are very different among individuals and have satisfactory effects of suppressing or reducing neutral fat and the like. Has not been found.

[0006] On the other hand, extracts extracted from various plants have been studied in terms of various effects and functions and applied in various industrial fields. However, an extract that directly activates lipase activity has not been found so far.

[0007]

Various studies have been conducted so far on various extracts, but the action of activating lipase, which is one of the triglyceride degrading enzymes, has not been examined. Therefore, the object of the present invention is to find out a crude drug having an action of directly increasing lipase activity.

Furthermore, the localized distribution of fat in the body can cause inferiority, stress, and adult diseases, so that reduction of fat in the body and suppression of abnormal accumulation are very important problems. The present invention, which can be used in humans and other animals, promotes systemic or local fat loss, improves or suppresses obesity constitution, improves fat localization, or prevents fat increase. It is an object of the present invention to provide various effective external skin preparations such as new cosmetics and quasi drugs, and a bath preparation that can be effectively slimmed down by taking a bath.

[0009]

Means for Solving the Problems The inventors of the present invention have conducted extensive studies on the above problems, and have investigated materials that directly activate lipase activity. As a result, herbal medicines Kakukou, Kashi, Nukou, and Hikai have the above-mentioned effects,
A skin external preparation and a bath preparation containing these crude drugs promote decomposition of neutral fat accumulated in adipose tissue, improve or suppress obesity constitution, improve localization of fat, or prevent fat increase The present invention has been completed by discovering that it is effective for.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The lipase activity activating agent of the present invention is
It contains one or more kinds of herbal medicines selected from Kakukou, Kashi, Nukou and Hikai. The kakukou used in the present invention refers to the whole plant excluding the root of patchouli of the Lamiaceae plant, but a plant of the same genus can also be used. Kash refers to the tuberous root of Polygonaceae, a plant of the Polygonaceae family, but a plant of the same genus can also be used. Nyukou refers to a sap obtained from a frankincense tree of a citrus family plant, but a plant of the same genus can be used. What is Hikai?
It refers to the rhizome of Onidocho, which is a plant belonging to the family Yasmine.

In the present invention, as various herbal medicines for Kakukou, Kashi, Nyukou, and Hikai, the above-mentioned various parts are used as they are, after being undried or after being dried, or after being crushed or crushed before being used. You can
Further, an extract obtained by extracting these with a solvent and a non-volatile component obtained by evaporating or freeze-drying the extraction solvent from the extract can be used.

As the extraction solvent, water, alcohols (eg, methanol, ethanol, ethylene glycol,
Propylene glycol, 1,3-butylene glycol, etc.), ketones such as acetone, various solvents such as ethers such as diethyl ether, etc. can be used alone or in combination of two or more kinds. .

The crude drug used in the present invention is generally used as a component of medicines or folk medicines, foods and cosmetics, and its safety has been confirmed. The lipase activator of the present invention includes cosmetics,
It can be added to quasi drugs and bath agents.

The external preparation for skin and the external preparation for slimming of the present invention contain the above-mentioned lipase activator, that is, one or more kinds selected from the above herbal medicines. The total amount of crude drug mixed varies depending on the dosage form, but as a non-volatile component of the extract, 0.001 to 5 in the skin external preparation and slimming skin external preparation.
It is preferably 0% by weight. The amount of the external skin preparation and the external skin slimming agent of the present invention is not particularly limited, and can be appropriately adjusted according to the preference of the user.

Further, in the slimming bath agent of the present invention,
The above lipase activator, that is, one or more selected from the above herbal medicines can be used, and the total compounding amount thereof varies depending on the dosage form, but as a nonvolatile content of the extract, it is 0 in the bath agent. It is preferably 0.01 to 50% by weight.

The external preparation for skin, external preparation for slimming and bath preparation for slimming of the present invention include, in addition to the above-mentioned various herbal medicines, known functional ingredients used in ordinary external preparations, such as moisturizers and emollients. A blood circulation promoter, a cell activating agent, an antioxidant, an anti-inflammatory agent, an antibacterial agent, a whitening agent, a peroxide inhibitor, an astringent and the like can be added. For example, humectants such as glycerin, butylene glycol, urea and amino acids; emollients such as squalane, macadamia nut oil, jojoba oil; blood circulation promoters such as vitamin Es, capsicum tincture, ginkgo biloba extract; cell activating agents such as nucleic acids; Antioxidants such as dibutylhydroxytoluene (BHT), dibutylhydroxyanisole (BHA), tocopherol acetate and ascorbic acid; glycyrrhizin,
Allantoin, Scutellaria extract, Hypericum extract,
Anti-inflammatory agents such as pearl oyster extract, ginkgo biloba extract, comfrey extract; antibacterial agents such as hinokitiol, benzalkonium chloride, chlorhexidine salt; whitening agents such as ascorbic acid, arbutin, kojic acid; superoxide dismutase (SOD), etc. Peroxide inhibitors,
Astringents such as armchair extract, aloe extract, agets extract, chinkok extract, peony extract; and β-adrenergic acting substances such as butopamine and isoproterenol; α2-adrenergic action inhibitors such as yohimbine and ergotoxin; cafe Known substances having an action of reducing or suppressing adipocytes such as xanthine derivatives such as inn and theophylline can be added. In addition, placenta extract, lactic acid bacteria culture extract and other animals, plants,
Various extracts derived from microorganisms can be freely added and used.

The dosage form of the external preparation for skin or the external preparation for slimming of the present invention is not particularly limited as long as it can be applied externally.
Examples thereof include pastes, creams, ointments, lotions, emulsions, packs, powders and poultices. The dosage form of the slimming bath agent of the present invention means any dosage form applicable for bathing, and examples thereof include solid preparations such as powder and granules, liquid preparations such as emulsion and paste.

The external preparation for skin or the external preparation for slimming of the present invention comprises a base component such as a surfactant and oils and fats and, if necessary, a known thickening agent for formulation. , Various additives such as antiseptics, tonicity agents, antioxidants, ultraviolet absorbers, chelating agents, fragrances, and coloring agents can be used in combination.

The above-mentioned surfactants are not limited, and general nonionic surfactants, anionic surfactants, cationic surfactants and amphoteric surfactants are used. be able to. For example, alkylene oxide adducts of higher alkyl amines, alkylene oxide adducts of higher fatty acid amides, fatty acid esters of polyhydric alcohols, alkylene oxide adducts of hydrogenated castor oil, polyethylene glycol sorbitan alkyl esters, alkylene oxide adducts of sterols, etc. Nonionic surfactants; anionic surfactants such as sodium alkylsulfate, sodium alkyloylmethyltaurine, sodium α-olefinsulfonate, sodium polyoxyalkylene alkyl ether sulfate; alkylpyridinium chloride, distearyldimethylammonium chloride, etc. Cationic surfactants; amphoteric surfactants such as sodium alkylaminopropionate and alkylpolyaminoethylglycine. One or more of these can be selected and used.

The base component usable in the present invention is not limited, and examples thereof include olive oil, camellia oil, jojoba oil, avocado oil, macadamia nut oil,
Commonly known fats and oils such as squalane, squalene and horse oil can be mentioned. Examples of the thickener include, but are not limited to, polyvinyl alcohol, polyacrylamide, polyethylene glycol, and various derivatives thereof; celluloses such as hydroxyalkyl cellulose and derivatives thereof; dextran, gelatin,
Gums such as gum arabic and tragacanth; water-soluble polymers such as carboxyvinyl polymer.

Examples of preservatives include, but are not limited to, parahydroxybenzoic acid ester, alkylpyridinium chloride, benzalkonium chloride, chlorhexidine salt, hinokitiol and the like. Examples of the tonicity agent include, but are not limited to, inorganic salts such as sodium chloride, potassium chloride, calcium chloride and the like.

Examples of the ultraviolet absorber are not limited, and include, for example, para-aminobenzoic acid, benzofuphenone-based ultraviolet absorber, benzotriazole-based ultraviolet absorber and the like. Examples of the chelating agent include, but are not limited to, ethylenediaminetetraacetic acid, phytic acid, citric acid, and water-soluble salts thereof.

[0023]

EXAMPLES Examples will be given below for specifically explaining the present invention, but the present invention is not limited to these examples.

Evaluation of lipase activity activation The general lipase activity measurement method was partially modified and evaluated according to the following method. (Chemicals to be used) PVA solution: 18 g of Kuraray Poval (manufactured by Kuraray Co., Ltd.) 117 and 2 g of Kuraray Poval 215 were suspended in about 800 mL of water, heated with stirring, and dissolved until completely dissolved.
Hold at 5-80 ° C. After cooling to room temperature, water was added to make 1000 mL. Olive oil emulsion: 75 mL of the above PVA solution and 22.9 g of olive oil (Japanese Pharmacopoeia) using a homomixer,
It was emulsified at 000 rpm for 10 minutes. Lipase solution: L. P. L "Amano" 80 (manufactured by Amano Pharmaceutical Co., Ltd.) was adjusted to about 150 U / g with distilled water. Stop solution: Acetone-ethanol (1: 1 (v / v)) mixed solution 0.02 × 10 ⁻³ mol / m ³ sodium hydroxide aqueous solution

(Operation) Olive oil emulsion 5 mL, distilled water 4 mL
And 0.03 g of the extract (in terms of non-volatile content) were placed in a 100 mL stoppered Erlenmeyer flask, mixed well, and preheated in a constant temperature water bath at 37 ° C. for 10 minutes. 1 mL of the lipase solution was accurately added, mixed for about 15 seconds, and reacted at 37 ° C. Exactly 15 minutes after adding the lipase solution, 40 mL of stop solution
It was poured and titrated with 0.02 × 10 ⁻³ mol / m ³ aqueous sodium hydroxide solution using an automatic titrator. At this time, the required amount of the sodium hydroxide aqueous solution is AmL.

Olive oil emulsion 5mL and distilled water 4mL 100
The mixture was placed in a mL stoppered Erlenmeyer flask, mixed well, and preheated in a constant temperature water bath at 37 ° C. for 10 minutes. 1 mL of the lipase solution was accurately added, mixed for about 15 seconds, and reacted at 37 ° C. Exactly 15 minutes after adding the lipase solution, pour 40 mL of the stop solution and use an automatic titrator to obtain 0.02 × 10 ^-3 m 2.
Titrated with an ol / m ³ aqueous solution of sodium hydroxide. At this time, the required amount of the sodium hydroxide aqueous solution is BmL.

Olive oil emulsion 5mL and distilled water 4mL 100
The mixture was placed in a mL stoppered Erlenmeyer flask, mixed well, and preheated in a constant temperature water bath at 37 ° C. for 10 minutes. Then, stop solution 40
mL was poured and mixed for about 15 seconds, and after 15 minutes, 1 mL of the lipase solution was accurately added. 0.02 using an automatic titrator
Titration was performed with a 10 ⁻³ mol / m ³ aqueous sodium hydroxide solution. The required amount of sodium hydroxide aqueous solution at this time is CmL
And

Distilled water (9 mL) and extract (0.03 g, calculated as nonvolatile content) were placed in a 100 mL stoppered Erlenmeyer flask, mixed well and preheated in a constant temperature water bath at 37 ° C. for 10 minutes. Accurately add 1 mL of lipase solution and mix for about 15 seconds.
The reaction was carried out at ° C. Exactly 15 after adding the lipase solution
After a minute, 40 mL of the stop solution was poured, and an automatic titrator was used to bring the volume to 0.
Titration was performed with a 02 × 10 ⁻³ mol / m ³ aqueous solution of sodium hydroxide. The required amount of aqueous sodium hydroxide solution at this time is D
Set to mL. From the above A, B, C and D values, the lipase activity activation rate was calculated by the following formula. Lipase activity activation rate (%) = [(A-D) x 100 /
(BC)]

Examples 1 to 4 Kakkou (dry matter of whole plant except root of patchouli of Lamiaceae plant), Kashu (dried product of tuberous root of Polygonaceae of Polygonaceae plant), Nyukou (obtained from frankincense tree of Orchidaceae plant) 50 g of sap), and a piece of dried squid (dried matter of Rhizoma chinensis of the Japanese yam family).
Immerse in 300 mL of 0% ethanol aqueous solution and let it stand at room temperature
Extraction was performed over time to obtain each plant extract. Each of the obtained extracts was evaluated for the above lipase activity activating action. The non-volatile components of each extract were placed in a petri dish (5 g) and placed in a drier (Perfect Oven PV-210, Tabai Espec Co., Ltd.) at 105 ° C.
It was calculated from the residual weight ratio after standing for a period of time.

[0030]

[Table 1]

As shown in Table 1, the extracts of Examples 1 to 4 exhibited a lipase activity activating action. From this, it was found that the extract of the present invention significantly activates the activity of lipase, and was found to be effective in reducing and suppressing neutral adipose tissue such as subcutaneous fat. In Table 1, the value of Comparative Example 1 is the value when the extract is not added. Next, formulation examples of the skin external preparation of the present invention will be shown, but these do not limit the present invention at all.

Prescription of external preparation for skin (prescription examples 1 to 23)

[Table 2]

[0033]

[Table 3]

A skin external preparation having the composition shown in Table 2 was prepared.
The preparation method is as follows. First, the a component is about 70 to 8
Heated to 0 ° C. About 80% of the component c is used to heat and dissolve the component b at about 70 to 80 ° C.
It was gradually added to the component a at 80 ° C. with stirring. Then it is cooled to room temperature, the components d and e are added,
Mix until uniform.

In Table 2, polyoxyethylene (10) hydrogenated castor oil, polyoxyethylene (1
2) Sorbitan monooleate, polyoxyethylene (3
The number in parentheses of 0) cholesterol indicates the number of moles of ethylene oxide added. The “appropriate amount” of the component c means an amount for adjusting the total amount of the external preparation for skin to 100 g.
Carbopol 980 (manufactured by BF Good rich) was used as the carboxyvinyl polymer as the component d. Further, as the various extracts of the component e, 1% by weight non-volatile solutions of the various extracts obtained in Examples 1 to 4 (distilled water was used as a solvent) were used. All other ingredients used were those specified by the cosmetic raw material standards.

Examples 5 to 13 and Comparative Example 2 Formulation Examples 5, 6, 7, 8, 14, 15, 16, 17 of Table 2
For 20 and 18, 20 men and 20 women suffering from a fat layer around the waist and abdomen were monitored to examine whether the fat layer increased or decreased. Divided into 10 groups of 2 people each, the first group is Prescription Example 5
(Example 5), the second group was Prescription Example 6 (Example 6), the third group was Prescription Example 7 (Example 7), and the fourth group was Prescription Example 8 (Example 8). Prescription example 14 is for group 5 (Example 9), prescription example 15 is for group 6 (Example 10), and prescription example 1 is for group 7
6 (Example 11) and the eighth group was Prescription Example 17 (Example 1).
2), the ninth group used Formulation Example 18 (Example 13).
The 10th group used the external preparation for skin prepared by using distilled water in place of Kakukou extract in Preparation Example 5 (Comparative Example 2). As for the method of using the external preparation for skin, each external preparation was taken in a large amount of 500 yen coins on the palm after bathing, and a normal life was maintained except for rubbing while massaging, and this was continued for one month. The slimming effect was evaluated by measuring the waist and abdominal dimensions before and after the test. The measurement results are shown in Table 3.

[0037]

[Table 4]

With the extract having a lipase activity-activating effect, that is, the external preparation for skin of Comparative Example 2 to which the lipase-activity-activating agent of the present invention was not added, the waist and abdominal circumference were substantially unchanged. Since the external preparations for skin containing the lipase activator all have a reduced size, a slimming effect is recognized, and it is understood that they are useful as external skin preparations for slimming. Further, even if the extract has a low rate of lipase activity activation, its slimming effect is sufficient when it is used in the form of a dosage form. Therefore, it can be seen that those that are effective in the in vitro test can be expected to have a sufficient slimming effect in vivo.

Prescription of bath agent (prescription examples 24-36)

[Table 5]

A bath agent having the composition shown in Table 4 was prepared. Each of the f component and the g component was mixed until they became uniform, and then the f component and the g component were mixed, and further mixed until they became uniform to obtain a bath agent. Here, 1% by weight of the nonvolatile content of the various extracts obtained in Examples 1 to 18 is included in the various extracts in Table 4.
An aqueous solution (distilled water was used as a solvent) was used. The ingredients used in this formulation were all those specified by the cosmetic raw material standards.

Examples 19 to 23 and Comparative Example 3 With respect to the prescription examples 29, 30, 31, 32 and 36 in Table 4, 12 men and 12 women suffering from fat layer were monitored to find the feeling of use. Did. Each group was divided into 6 groups of 2 persons, and the first group was prescribed Example 29 (Example 1).
9), the second group is the prescription example 30 (Example 20), the third group is the prescription example 31 (Example 21), the fourth group is the prescription example 32 (Example 22), and the fifth group is the prescription. Example 36 (Example 23)
It was used. Group 6 used bath agents prepared by using distilled water instead of various extracts in Formulation Example 29. To use it, dissolve 30 g of bath agent in a 150 L bath, mix well, and take a normal life, except take a bath,
This continued for one month. One month later, the usability of each part of the upper arm, waist, abdomen and calf was evaluated according to the following three grades. The evaluation is shown in Table 5. ○: Feels tighter △; Feels slightly tighter ×: Does not change

[0042]

[Table 6]

All the subjects who used the bath preparation of the present invention felt firm, and it was found that they were particularly effective for slimming applications.

[0044]

EFFECTS OF THE INVENTION Herbal medicines of Kakukou, Kashi, Nyukou and Hikai have an action of directly activating the lipase activity and are useful as a lipase activity activating agent. The lipase activity activating agent of the present invention can be incorporated into cosmetics, quasi drugs, and bath agents. In particular, it can be used as a slimming skin external preparation and a slimming bath preparation to promote the reduction of neutral fat in the whole body or locally, and to improve and suppress or prevent obesity.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61P 43/00 111 A61P 43/00 111 F term (reference) 4C083 AA111 AA112 AA122 AB312 AB332 AB352 AC022 AC122 AC422 AC432 AC442 AC482 AC612 AC742 AC852 AD042 AD092 AD492 AD532 AD662 BB51 CC02 CC25 EE13 EE41 4C088 AB12 AB38 AB43 AB84 AC01 AC11 AC13 MA07 MA63 NA14 ZA70 ZC19

Claims (4)

[Claims] 1. A lipase activity activator containing one or more crude drugs selected from Kakukou, Kashi, Nyukou and Hikai. 2. A skin external preparation containing the lipase activator according to claim 1. 3. A slimming skin external preparation containing the lipase activator according to claim 1. 4. A slimming bath preparation containing the lipase activator according to claim 1.