JP2008074767A - Cyclic amp phosphodiesterase inhibiting agent and slimming agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To find a substance having cyclic AMP phosphodiesterae inhibiting action from natural substances and provide a cyclic AMP phosphodiesterase inhibiting agent or a slimming agent containing the substance as an active component. <P>SOLUTION: The agent is produced by using the finding that extract of Himalayan raspberry has cyclic AMP phosphodiesterase inhibiting action and slimming action. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a slimming agent and a cyclic AMP phosphodiesterase inhibitor that inhibit the action of cyclic AMP phosphodiesterase that degrades cyclic AMP, which is an important signal transmitter in vivo, and thus reduce body fat.

  In recent years, body fat has increased due to lifestyle habits such as satiety and lack of exercise, thereby increasing adult diseases with obesity. Obesity is a cause of adult diseases such as hyperlipidemia and arteriosclerosis, which is not only a cosmetic problem but also a major problem in health. In order to prevent adult diseases such as hyperlipidemia and arteriosclerosis associated with obesity due to excessive intake of animal fat, fat metabolism may be promoted and fat accumulated excessively in the living body may be used as energy. In order to break down fat in the living body, the role of cyclic AMP is important. Cyclic AMP activates triglyceride lipase present in the living body, and fat is broken down into fatty acid and glycerol by the activated lipase. However, when cyclic AMP phosphodiesterase is activated, degradation of cyclic AMP is induced and activation of triglyceride lipase is inhibited.

  Therefore, it is considered that by inhibiting the activity of cyclic AMP phosphodiesterase, the amount of cyclic AMP in the cell can be increased and the decomposition of fat can be promoted. Therefore, if the action of cyclic AMP phosphodiesterase, which is a cyclic AMP degrading enzyme, is suppressed to prevent a decrease in the cyclic AMP concentration, fat accumulated in the living body should be able to be further used as energy.

Based on such an idea, the present applicants already have a cyclic AMP phosphodiesterase inhibitory action, and are extracted from monopods, Kojiro and Psycho (see Patent Document 1), peanut astringent skin extract (patent Document 2), ginger family mango ginger extract (see Patent Document 3), tubeyside I (see Patent Document 4), and the like.
JP 2003-261457 A JP 2004-26719 A JP 2005-104886 A JP 2006-56855 A

  An object of the present invention is to find a substance having a cyclic AMP phosphodiesterase inhibitory action from highly safe natural products, and to provide a cyclic AMP phosphodiesterase inhibitor or slimming agent containing the substance as an active ingredient.

  In order to solve the above problems, the cyclic AMP phosphodiesterase inhibitor or slimming agent of the present invention is characterized by containing a Himalayan raspberry extract as an active ingredient.

  According to the present invention, a cyclic AMP phosphodiesterase inhibitor or slimming agent containing a Himalayan raspberry extract as an active ingredient and excellent in safety can be provided.

  The cyclic AMP phosphodiesterase inhibitor or slimming agent of the present invention contains an extract of Himalayan raspberry as an active ingredient.

  In the present invention, the “extract” includes an extract obtained from an extraction raw material by an extraction process, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or these Either a crude product or a purified product is included.

  The Himalayan raspberry (scientific name: Rubus ellipticus, also known as: Oni strawberry, Chinese name: truncated coconut) belongs to the family Rosaceae, and fresh fruits are fragrant and edible. Himalayan raspberries are grown or grown in the Southeast Asia and Southeast China from the Himalayas and can be easily obtained from these regions.

  The component part of Himalayan raspberry used as an extraction raw material is not particularly limited, and for example, a leaf part, a stem part, a flower part, a bark, a root part, a seed coat, a fruit, a fruit core or a mixed part thereof is used as an extraction raw material. Among these, it is preferable to use the root as an extraction raw material.

  Although the details of the substance having a cyclic AMP phosphodiesterase inhibitory action or slimming action contained in the Himalayan raspberry extract are unknown, the cyclic AMP phosphodiesterase inhibitory action from Himalayan raspberry by an extraction method generally used for plant extraction Alternatively, an extract having a slimming action can be obtained.

  For example, it can be obtained by drying the Himalayan raspberry and pulverizing it as it is or using a crusher and using it as an extraction solvent. Drying may be performed in the sun or using a commonly used dryer. The Himalayan raspberry may be used as a raw material for extraction after pretreatment such as degreasing with a nonpolar solvent such as hexane or benzene. By performing pretreatment such as degreasing, extraction with a polar solvent can be performed efficiently.

  As the solvent used for the extraction, it is preferable to use water, a hydrophilic organic solvent, or a mixture thereof at room temperature or a temperature not higher than the boiling point of the solvent.

  Examples of water that can be used as the extraction solvent include pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, as well as water that has been subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, and the like. Therefore, the water that can be used as the extraction solvent in the present invention includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.

  Examples of the hydrophilic organic solvent include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; 1,3-butylene glycol, propylene glycol, Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as glycerin, and a mixed solvent of the hydrophilic organic solvent and water can be used.

  In addition, when using the extraction solvent of the said water and a hydrophilic organic solvent, in the case of a lower alcohol, it is 1-90 mass parts with respect to 10 mass parts of water, and in the case of a lower aliphatic ketone, it is 10 mass parts of water. It is preferable to add 1-40 mass parts with respect to it. In the case of a polyhydric alcohol, it is preferable to add 1 to 90 parts by mass with respect to 10 parts by mass of water.

  The extraction treatment is not particularly limited as long as the soluble component contained in the extraction raw material can be eluted in the extraction solvent, and can be performed according to a conventional method. Specifically, Himalayan raspberry as an extraction raw material is put into a treatment tank filled with an extraction solvent, and further, with occasional stirring as necessary, it is allowed to stand for 30 minutes to 4 hours to elute soluble components, followed by filtration. Then, the solid matter is removed, the extraction solvent is distilled off from the obtained extract, and the extract is obtained by drying. The amount of the extraction solvent is usually 5 to 15 times (mass ratio) of the extraction raw material. The extraction condition is usually about 1 to 4 hours at 50 to 95 ° C. when water is used as the extraction solvent. Moreover, when using the mixed solvent of water and ethanol as an extraction solvent, it is about 30 minutes-4 hours at 40-80 degreeC normally. The extract obtained by extraction with a solvent can be used as an active ingredient of the cyclic AMP phosphodiesterase inhibitor or slimming agent of the present invention as long as the extraction solvent is highly safe. However, it is easier to use the concentrated solution or the dried product.

  The obtained Himalayan raspberry extract is diluted, concentrated, dried and purified according to a conventional method in order to obtain a diluted or concentrated solution of the extract, a dried product of the extract, or a crude purified product or a purified product thereof. Etc. may be performed.

  Purification can be performed by, for example, activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like. The obtained extract can be used as it is as a cyclic AMP phosphodiesterase inhibitor or slimming agent, but a concentrated solution or a dried product thereof is easier to use.

  In addition, since the Himalayan raspberry extract has a peculiar odor, it can be purified for the purpose of decolorization, deodorization, etc. within a range that does not cause a decrease in its physiological activity. Since it is not used in a large amount when blended, there is no practical problem even if it is not purified.

Since the Himalayan raspberry extract obtained as described above has a cyclic AMP phosphodiesterase inhibitory action, it can be used as an active ingredient of a cyclic AMP phosphodiesterase inhibitor or a slimming agent using the action.
The cyclic AMP phosphodiesterase inhibitor or slimming agent of the present invention may consist solely of a Himalayan raspberry extract or may be a formulation of a Himalayan raspberry extract.

  Himalayan raspberry extract should be formulated into any dosage form such as powder, granule, liquid, etc. according to conventional methods using pharmaceutically acceptable carriers such as dextrin and cyclodextrin. Can do. In this case, as an auxiliary agent, for example, it can be used as an excipient, a stabilizer, a flavoring agent and the like. Himalayan raspberry extract can be used in other compositions (for example, basic cosmetics such as creams, lotions, emulsions, packs, etc.), as well as ointments, topical solutions, bath preparations, patches, etc. Can be used. In addition, the cyclic AMP phosphodiesterase inhibitor or slimming agent of this invention can mix | blend other natural extracts which have a cyclic AMP phosphodiesterase inhibitory effect or a slimming effect as needed, and can use it as an active ingredient.

  The cyclic AMP phosphodiesterase inhibitor or slimming agent of the present invention can prevent or improve skin symptoms such as sagging and swelling through the cyclic AMP phosphodiesterase inhibitory action of the Himalayan raspberry extract. However, the cyclic AMP phosphodiesterase inhibitor or slimming agent of the present invention can be used for all uses that are meaningful for exerting a cyclic AMP phosphodiesterase inhibitory action in addition to these uses.

  The cyclic AMP phosphodiesterase inhibitor or slimming agent of the present invention is preferably applied to humans, but should be applied to animals other than humans as long as each effect is exhibited. You can also.

  Examples of the present invention will be described below, but the present invention is not limited to these examples.

(Production Example 1) Production of Himalayan Raspberry Extract 100 g of a coarsely pulverized root of Himalayan raspberry was put into 1 L of 80% ethanol, and kept at 80 ° C. for 2 hours with gentle stirring. Thereafter, filtration was performed to obtain a residue. This residue was again added to 1 L of 50% ethanol, and kept at 80 ° C. for 2 hours with gentle stirring. The filtrates obtained by the two extractions were combined, concentrated at 40 ° C. under reduced pressure, and further dried with a vacuum dryer to obtain the extract. The yield of the extract was as shown in Table 1.

[Table 1]
Plant extract yield (% by mass)
Himalayan raspberry extract 9.5

(Test Example 1) Cyclic AMP phosphodiesterase inhibitory action test The Himalayan raspberry extract of Production Example 1 was tested for cyclic AMP phosphodiesterase inhibitory action by the following method.

 Add 0.1 mL of fetal serum alpmin solution and 0.1 mL of cyclic AMP phosphodiesterase solution to 0.2 mL of Tris-HCl buffer (pH 7.5) containing 5 mM magnesium chloride, and dissolve at a predetermined concentration using 50% DMSO. 0.05 mL of the prepared sample solution (Production Example 1) was added and pre-incubated at 37 ° C. for 5 minutes. Subsequently, 0.05 mL of cyclic AMP solution was added and incubated at 37 ° C. for 60 minutes. The reaction was stopped by boiling in a boiling bath for 3 minutes, and centrifuged at 3500 rpm at 4 ° C., and the reaction substrate and 5′-AMP in the supernatant were quantified by high performance liquid chromatography. The same enzyme reaction and reaction substrate were analyzed without adding the sample solution, and the cyclic AMP phosphodiesterase inhibition rate of the sample was determined from the ratio of the reactive group mass at the time of sample addition to the reactive group mass at the time of no sample addition. .

The above measurement was repeated while decreasing the sample concentration of the sample solution stepwise, and a sample concentration IC ₅₀ (μg / mL) that inhibits the activity of cyclic AMP phosphodiesterase by 50% was determined by interpolation. The results are shown in Table 2.

[Table 2]
Plant 50% inhibition sample concentration (μg / mL)
Himalayan raspberry extract 55.3

  As can be seen from the results in Table 2, it was confirmed that the Himalayan raspberry extract exhibits a good cyclic AMP phosphodiesterase activity inhibitory action.

(Test Example 2) Slimming effect test The Himalayan raspberry extract of Production Example 1 was subjected to a slimming effect test by measuring the rate of lipolysis acceleration by the following method.

  Rodbell method [Rodbell M. , J .; Biol. Chem. , 239, 375 (1964)], free adipocytes were prepared from a testicular adipose tissue of Wistar male rats (body weight 150 to 200 g) using a collagenase solution. To 90 μL of the free adipocyte suspension, 10 μL of Hank's buffer solution containing bovine serum albumin prepared so that the final sample concentration was 12.5 μg / mL was added and reacted at 37 ° C. for 90 minutes. After the reaction, the fatty acid liberated in the reaction solution was measured with NEFA C-Test Wako.

  The lipolysis acceleration rate was calculated with the value when no sample was added as 100%. The results are shown in Table 3.

[Table 3]
Plant lipolysis promotion rate (%)
Himalayan raspberry extract 114.9 ± 2.0

  As can be seen from the results in Table 3, it was confirmed that the Himalayan raspberry extract promotes the degradation of fat in fat cells.

[Formulation Example 1] Gel (blending ingredients)
3.0 g of Himalayan raspberry extract from Production Example 1
Dimethylpolysiloxane 5.0g
Glycerin 2.0g
1,3-butylene glycol 5.0 g
Polyethylene glycol 1500 3.0g
Polyethylene glycol 20000 3.0 g
Cetyl octanoate 3.0g
0.01 g of citric acid
Sodium citrate 0.1g
Sodium hexametaphosphate 0.1g
0.1g dipotassium glycyrrhizinate
Ascorbic acid glucoside 2.0g
Tocopherol acetate 0.1g
α-Linolenic acid 0.5g
Ogon Extract 0.1g
Edetate trisodium 0.1g
Xanthan gum 0.3g
Acrylic acid / alkyl methacrylate copolymer (Pemulene TR-2) 0.05 g
Agar powder 1.5g
Phenoxyethanol Appropriate amount Dibutylhydroxytoluene Appropriate amount Purified water The remainder (the total amount is 100 g)
(Manufacturing method) According to a conventional method, after producing a translucent emulsion composition, the gel was cooled to 30 ° C. or less to be gelled, and when sufficiently solidified, the gel was crushed using a disper to obtain a microgel (average particle size 70 μm). Then, it was deaerated to obtain a gel product.

[Formulation Example 2] Patch (Formulation component)
0.5 g of Himalayan raspberry extract from Production Example 1
Polyacrylic acid 4.5g
Sodium polyacrylate 1.5g
Carboxymethylcellulose sodium 4.0g
Glycerin 15.0g
1,3-propanediol 5.0g
Aluminum hydroxide 0.1g
Synthetic hydrotalcite 0.05g
Kaolin 6.0g
1-menthol 0.2g
Purified water remainder (total amount is 100 g)
(Manufacturing method) According to a conventional method, an aqueous pressure-sensitive adhesive composition is prepared by mixing and stirring with a Henschel mixer, and this is uniformly applied onto a nonwoven fabric so as to be 700 ± 100 g / m ² .
A polyethylene film was subjected to fencing to obtain a patch.

[Formulation Example 3] Tablet bath agent A tablet bath agent having the following composition was produced by a conventional method.
(Compounding ingredients)
5.0 g of Himalayan raspberry extract from Production Example 1
Sodium sulfate 45.0g
Sodium bicarbonate 15.0g
Sodium carbonate 5.0g
Citric acid 28.0g
Keihi extract 1.0g
Peonies extract 1.0g
Perfume

[Formulation Example 4] Powdery bath agent A powdery bath agent having the following composition was produced by a conventional method.
(Compounding ingredients)
5.0 g of Himalayan raspberry extract from Production Example 1
Sodium sulfate 45.0g
Sodium bicarbonate 46.0g
Borax 2.0g
Bukuryu extract 1.0g
Shobu extract 1.0g
Perfume

[Formulation Example 5] Lotion Toner lotion having the following composition was produced by a conventional method.
(Compounding ingredients)
3.0 g of Himalayan raspberry extract from Production Example 1
Ethanol 5.0g
Methyl P-oxybenzoate 0.1g
Polyoxyethylene (40) hydrogenated castor oil 0.1g
Perfume
Purified water 10.0g
1,3-butylene glycol 3.0 g
Glycerin 2.0g
Xanthan gum 0.02g
Oil soluble licorice extract 0.1g
Purified water remainder (total amount is 100 g)

[Formulation Example 6] Emulsion An emulsion having the following composition was produced by a conventional method.
(Compounding ingredients)
1.0 g of Himalayan raspberry extract from Production Example 1
1.0 g polyoxyethylene sorbitan monostearate
Tetraoleic acid polyoxyethylene sorbit 1.5g
Lipophilic glyceryl monostearate 1.0g
Stearic acid 0.5g
Behenyl alcohol 1.5g
Cetyl palmitate 0.5g
Squalane 10.0g
Methyl polysiloxane 0.5g
Ginkgo biloba extract 0.1g
Abou extract 0.1g
Jaundice extract 0.1g
Fragrance Appropriate amount Preservative (methyl paraoxybenzoate) 0.15g
1,3-butylene glycol 7.0 g
Xanthan gum 0.1g
Purified water remainder (total amount is 100 g)

[Formulation Example 7] Cream A cream having the following composition was produced by a conventional method.
(Compounding ingredients)
1.0 g of Himalayan raspberry extract from Production Example 1
Polyglyceryl monomyristate 1.0g
Polyoxyethylene hydrogenated castor oil 1.0g
Hydrogenated soybean phospholipid 0.5g
Stearic acid 4.0g
Cetanol 2.0g
Behenyl alcohol 2.0g
3.0 g paraffin
Squalane 12.0g
Jojoba oil 3.0g
0.2g of methylpolysiloxane
Preservative (Methyl paraoxybenzoate) 0.15g
Perilla extract 0.1g
Linden extract 0.1g
Jiyu extract 0.1g
Perfume appropriate amount 1,3-butylene glycol 7.0g
Xanthan gum 0.2g
Purified water remainder (total amount is 100 g)

[Formulation Example 8] Pack A pack having the following composition was produced by a conventional method.
(Compounding ingredients)
1.0 g of Himalayan raspberry extract from Production Example 1
Polyvinyl alcohol 15. 0g
Polyethylene glycol 3. 0g
Propylene glycol 7. 0g
Ethanol 10. 0g
Sage extract 0.1g
Toki extract 0.1g
Carrot extract 0.1g
0.05 g ethyl paraoxybenzoate
Fragrance 0.05g
Purified water remainder (total amount is 100 g)

[Formulation Example 9] Cleansing lotion A cleansing lotion having the following composition was produced by a conventional method.
(Compounding ingredients)
1.0 g of Himalayan raspberry extract from Production Example 1
1,3-butylene glycol 4.0 g
Glycerin 4.0g
Dipropylene glycol 2.0g
0.7 g of polyoxyethylene polyoxypropylene decyl tetradecyl ether
Ethanol 3.0g
Seaweed extract 0.1g
Kujin extract 0.1g
Jiyu extract 0.1g
Fragrance Appropriate amount Preservative (methyl paraoxybenzoate) 0.15g
Purified water remainder (total amount is 100 g)

  The cyclic AMP phosphodiesterase inhibitor or slimming agent of the present invention is effective and excellent in safety, and prevents and ameliorates skin symptoms such as sagging and swelling by decomposing fat stored in fat cells, It can be expected that the skin is cosmetically preferable.

Claims (2)

  A cyclic AMP phosphodiesterase inhibitor comprising an extract of Himalayan raspberry.   A slimming agent comprising an extract of Himalayan raspberry.