JP5313064B2 - Neutral fat accumulation promoter, breast augmentation - Google Patents

Description

  The present invention relates to a neutral fat accumulation-promoting agent and breast augmentation agent that are effective in accumulating and increasing adipose tissue by promoting neutral fat accumulation in local adipocytes.

Women's breasts are mainly composed of mammary glands and adipose tissue. It is known that the volume of the breast varies greatly depending on the increase or decrease in body weight or the like, and the volume of these breasts varies depending on the volume of adipose tissue in healthy women.
On the other hand, it has been clarified that fat cells constituting adipose tissue have different fat metabolism depending on body parts. In particular, breasts are characterized by low fat accumulation and high lipolysis compared to the lower leg, etc., and breast augmentation promotes fat accumulation in fat cells and promotes the increase of adipose tissue. Is desirable. Plant extracts extracted from diam, salamander, shiitake mushroom, salvia, cascon, saicin, tonin, and cinnamon (see Patent Document 1) Root or processed product thereof, periaceae plant, iridaceae plant, pea subfamily plant root or flax or processed product thereof, soybean, sesame, isoflavones (refer to Patent Document 2), Japanese ash, betel loaf, hubso (Patent Document 3) Almoase oil, elder oil, cypress oil, petit grain oil, and myrtol oil (see Patent Document 4) are already known.

JP-A-11-199499 JP 2000-302667 A JP 2005-126350 A JP 2005-187431 A

  Conventionally used fat accumulation promoters have not yet been sufficient in terms of stability, side effects, effects and the like, such as their fat accumulation promoting effect is not necessarily sufficient. The present invention has been made in view of such circumstances. Accordingly, an object of the present invention is to provide a neutral fat accumulation promoter and a breast augmentation agent that are effective in accumulating and increasing adipose tissue by promoting the accumulation of neutral fat in local adipocytes.

  In order to find a neutral fat accumulation-promoting agent that exhibits an excellent effect, the present inventors have studied various substances regarding the effect of promoting the accumulation of neutral fat in adipocytes. As a result, carbon dioxide is used as a supercritical extractant, and it is excellent in an extract obtained by extracting from one or more shellfishes selected from clams, clams, himezobora, Triggery, milk oysters, oyster scallops, scallops, and snails. It has been found that there is an action to promote the accumulation of sex fat, and further studies have been made to complete the present invention.

  That is, the present invention provides an extract obtained by extracting from one or more shellfishes selected from clams, clams, himezobora, tiger oysters, milk oysters, snails, scallops, and snails using carbon dioxide as a supercritical extractant. The present invention relates to a neutral fat accumulation promoter as an active ingredient.

  In addition, the present invention effectively uses an extract obtained by extracting from one or more shellfishes selected from clams, clams, himezobora, tiger oysters, milk oysters, snails, scallops and snails using carbon dioxide as a supercritical extractant. It relates to breast augmentation ingredient.

  According to the present invention, an extract obtained by extracting from one or more shellfishes selected from clams, clams, himezobora, tiger oysters, milk oysters, scallops, scallops and snails using carbon dioxide as a supercritical extractant. By making it an active ingredient, it is possible to provide a neutral fat accumulation promoter and breast augmentation agent that have excellent effects.

  Details of the present invention will be described.

  Clams used in the present invention are a general term for bivalves belonging to the genus Clamaceae, and are widely distributed to Japan, the Korean Peninsula, Taiwan, and the Philippines. It has also been introduced to the Mediterranean (Adriatic and Tyrrhenian Seas), France (Brittany), the Hawaiian Islands, and the Pacific coast of North America. It is edible and used as a tide soup, sake steamed, miso soup and soup, as well as Vongoles paghetti and clam chowder ingredients.

  The clam used in the present invention is a collective term for bivalves belonging to the genus Clamaceae, and is distributed throughout Asia. It is edible and is used for grilled clams, boiled clams and soups.

  Himezobora used in the present invention is a snail belonging to the genus Ezobora. It is edible and is used for sashimi, grilled sushi, sushi seeds, seasoned dishes, and boiled dishes.

  The mussel used in the present invention is a bivalve belonging to the genus Trichomyidae, and is distributed in Japan, the Korean peninsula, and the Chinese coast except Hokkaido. Widely used in edible sushi, sashimi, vinegared foods.

  The milk oyster used in the present invention is a bivalve belonging to the genus Tressus, and is distributed throughout Japan. It is edible and uses large water tubes for sashimi, sushi seeds, and grilled salt.

  The mussel used in the present invention is a bivalve belonging to the genus genus Uchagai and is distributed in the northern part of the Sea of Japan, the Pacific Ocean north of Ibaraki Prefecture, and the Siberian coast. In addition to sashimi and sushi seeds, cooked rice and curry are local specialties.

  The scallop used in the present invention is a bivalve belonging to the genus Scallop genus scallop and is distributed in a cold water region of 22 ° C. or less. It is used in various dishes such as sashimi, stew, butter grill, and soup. Dried scallops are used as a high-class Chinese food.

  The larva is a bivalve that belongs to the genus Amaranthaceae, and has been confirmed to have multiple siblings, including scaled and non-scaled species, and is widely distributed from Japan to the West Pacific to the Bay of Bengal. It is used for edible sashimi, sushi seeds, grilled foods, and soups.

  In this invention, the extract obtained by extracting from these shellfish using a carbon dioxide as a supercritical extractant is used.

  For extraction of shellfish in the present invention, any part of the whole, except for shellfish shells, straps, liver, scallops, etc. may be used, but shellfish shells were removed from the point of effectiveness of the present invention. The whole should be used. In the extraction, the raw material may be used as it is, but in consideration of the extraction effect, it is preferable to perform the extraction after performing treatments such as drying and pulverization. Extraction is performed by a supercritical fluid or subcritical fluid extraction method using carbon dioxide as a supercritical extractant. The extraction pressure can be appropriately selected, but it is usually preferably 3 to 70 MPa, particularly 4 to 60 MPa, preferably 5 to 50 MPa, and most preferably 10 to 40 MPa when carbon dioxide is used. Although extraction temperature can be suitably selected according to the critical temperature of the extractant to be used, it is usually preferably 10 to 700 ° C., particularly 15 to 200 ° C. when carbon dioxide is used as the extractant. Preferably it is 20-150 degreeC, Most preferably, it is 25-100 degreeC.

  The ratio of shellfish and extractant during extraction is not particularly limited, but is preferably 0.1 to 1000 times by weight of the extractant relative to shellfish 1, particularly 0.5 to 100 times by weight in terms of extraction operation and efficiency. . Moreover, although extraction time changes with extraction conditions etc., it is preferable to set it as the range of 2 hours-2 weeks.

  An entrainer can also be used to improve the solubility of the extractant. Examples of the entrainer include water, methanol, ethanol, propanol, butanol, acetone, hexane, cyclohexane, toluene, and the like, but are not particularly limited.

  Extracts of shellfish supercritical fluids can be used as they are, but concentrated and dried solids can be used by re-dissolving them in water or polar solvents, so long as these physiological effects are not impaired. It may be used after performing purification treatment such as decolorization, deodorization, and desalting, and fractionation treatment by column chromatography. The extract of shellfish and the processed product and fraction thereof can be freeze-dried after each treatment and fractionation and dissolved and used at the time of use.

  Carbon dioxide as a supercritical extractant. Neutral containing as an active ingredient an extract obtained by extracting from one or more shellfish selected from clams, clams, shimezobora, Triggery, milk oysters, scallops, scallops and snails. The fat accumulation promoter exhibits an excellent neutral fat accumulation promoting action and is also effective as a breast augmentation agent.

  An extract obtained by extracting from one or more shellfishes selected from clams, clams, himezobora, Triggery, milk oysters, scallops, scallops using carbon dioxide as a supercritical extractant is a topical skin preparation, oral It can also be used as an agent.

  A skin external preparation or an oral preparation obtained by extracting carbon dioxide as a supercritical extractant from one or more shellfish selected from clams, clams, shimezobora, Triggery, milk oysters, scallops, scallops and snails The blending amount when blended in can be adjusted according to the type of skin external preparation or oral preparation, purpose of use, etc., but in terms of effects and stability, the total amount is 0.0001 to 50.0. % By mass is preferable, and more preferably 0.001 to 20.0% by mass.

  A skin external preparation that uses carbon dioxide as a supercritical extractant and contains an extract obtained by extraction from one or more shellfish selected from clams, clams, himezobora, Triggery, milk oysters, scallops, scallops and snails The dosage form is arbitrary, and for example, it can be provided as a solubilizing system such as a lotion, an emulsifying system such as a cream or emulsion, or a dispersing system such as a calamine lotion.

  It should be noted that the topical skin preparation containing the above extract contains oily ingredients, moisturizing agents, which are usually blended in pharmaceuticals, quasi-drugs, skin cosmetics, and cleansing agents as necessary in addition to these extracts. Agents, powders, pigments, emulsifiers, solubilizers, cleaning agents, ultraviolet absorbers, thickeners, drugs, fragrances, resins, antibacterial and antifungal agents, alcohols, and the like can be appropriately blended.

  In addition, an oral preparation containing carbon dioxide as a supercritical extractant and an extract obtained by extraction from one or more shellfish selected from clams, clams, shimezobora, Triggery, milk oysters, mussels, scallops, and snails The dosage form is optional, but it can also be provided in various dosage forms such as powders, granules, capsules, liquids, etc., and if necessary, it is blended into pharmaceuticals, quasi drugs, foods, etc. , Oily ingredients, moisturizers, powders, emulsifiers, solubilizers, thickeners, drugs, fragrances, antifungal agents, alcohols, sugar, condensed milk, flour, salt, glucose, chicken eggs, butter, margarine, chickenpox , Calcium, iron, seasonings, spices, vitamin A and derivatives thereof, carotenoids, riboflavin and derivatives thereof, vitamin B and salts or derivatives thereof, ascorbic acid Beauty derivatives, cobalamin, vitamin E and derivatives thereof, vitamin K, adenosine and derivatives thereof, can be blended flavonoids and tannins.

  Hereinafter, production examples of shellfish extracts, tests for evaluating neutral fat accumulation promoting action, formulation examples as external preparations for skin and oral preparations will be described in detail, but the technical scope of the present invention is based on this. It is not limited at all.

[Extract 1]
The entire clam shell is removed and dried, pulverized, put into a pressure cell, liquefied carbon dioxide is pumped continuously with a pump, and carbon dioxide is allowed to flow under conditions of 25 MPa, 5 mL / min, and 40 ° C. for extraction. Ingredients were collected in a gas-liquid separator. The yield was 2.7%. The extract component was dissolved in ethanol to obtain Extract 1 as a 10 mg / mL ethanol solution.

[Extract 2]
The whole of the clam shell removed is dried and pulverized, put into a pressure cell, liquefied carbon dioxide is continuously poured with a pump, and carbon dioxide is allowed to flow under conditions of 25 MPa, 5 mL / min, and 40 ° C. for extraction. Ingredients were collected in a gas-liquid separator. The yield was 3.2%. The extract component was dissolved in ethanol to obtain Extract 2 as a 10 mg / mL ethanol solution.

[Extract 3]
The whole of the himeezobora shell is removed and pulverized, put into a pressure cell, liquefied carbon dioxide is continuously poured by a pump, and carbon dioxide is allowed to flow under conditions of 25 MPa, 5 mL / min, and 40 ° C. for extraction. Ingredients were collected in a gas-liquid separator. The yield was 4.7%. The extract component was dissolved in ethanol to obtain Extract 3 as a 10 mg / mL ethanol solution.

[Extract 4]
The whole with the trigger shell removed is dried and pulverized, put into a pressure cell, liquefied carbon dioxide is continuously pumped in, pumped with carbon dioxide as it is under the conditions of 25 MPa, 5 mL / min, 40 ° C., and extracted. Ingredients were collected in a gas-liquid separator. The yield was 2.9%. The extract component was dissolved in ethanol, and Extract 4 was obtained as a 10 mg / mL ethanol solution.

[Extract 5]
The whole milky shell is removed and dried, pulverized, put into a pressure cell, liquefied carbon dioxide is continuously poured with a pump, carbon dioxide is allowed to flow under conditions of 25 MPa, 5 mL / min, 40 ° C., and extracted. Ingredients were collected in a gas-liquid separator. The yield was 3.1%. The extract component was dissolved in ethanol to obtain Extract 5 as a 10 mg / mL ethanol solution.

[Extract 6]
The whole of the shell is removed and pulverized, put into a pressure cell, liquefied carbon dioxide is continuously poured with a pump, and carbon dioxide is allowed to flow under conditions of 25 MPa, 5 mL / min, and 40 ° C. for extraction. Ingredients were collected in a gas-liquid separator. The yield was 3.8%. The extract component was dissolved in ethanol to obtain extract 6 as a 10 mg / mL ethanol solution.

[Extract 7]
The whole scallop shell removed is dried and pulverized, put into a pressure cell, liquefied carbon dioxide is continuously poured with a pump, carbon dioxide is allowed to flow under conditions of 25 MPa, 5 mL / min, and 40 ° C. for extraction. Ingredients were collected in a gas-liquid separator. The yield was 4.4%. The extract component was dissolved in ethanol to obtain Extract 7 as a 10 mg / mL ethanol solution.

[Extract 8]
The whole of the rye shell removed is dried and pulverized, put into a pressure cell, and liquefied carbon dioxide is continuously poured with a pump, and carbon dioxide is allowed to flow as it is under conditions of 25 MPa, 5 mL / min, and 40 ° C. for extraction. Ingredients were collected in a gas-liquid separator. The yield was 0.5%. The extract component was dissolved in ethanol to obtain Extract 8 as a 10 mg / mL ethanol solution.

[Test Example] Neutral fat accumulation promoting action Subcutaneous fat-derived normal human preadipocytes Cryo HPRAD-SQ were seeded in a 96-well microplate so as to be 5.0 × 10 ³ per well. PGM medium (10% FBS, 2 mM L-glutamine, 100 units / mL Penicillin, containing 100 μg / mL Streptomycine) was used as the seeding medium. After culturing for 48 hours, extracts 1 to 8 were added to each medium and replaced with a PGM differentiation medium adjusted to the concentrations shown in Tables 1 and 2 (containing 10 μg / mL insulin, 1 μM Dexamethasone, 200 μM Indomethacin, 500 μM Isobutylmethylxanthine). Then, differentiation into adipocytes was induced. After initiation of differentiation induction, the cells were cultured for 10 to 14 days until the control group matured and many lipid droplets accumulated in the cells. After harvesting the cells, the cells were fixed using a 10% neutral buffered formaldehyde solution. After washing with PBS (−), 0.5 mass / volume% oil red O solution was added and cultured at 37 ° C. for 2 hours. After washing with PBS (−), methanol was added to extract the dye, and the absorbance at 550 nm was measured. At the same time, the absorbance at 650 nm was measured as turbidity, and the neutral fat accumulation promoting action was evaluated using the difference between the two measured values. The evaluation results are shown in Tables 1 and 2 as relative values when the neutral fat accumulation amount in the control with no sample added is defined as 100. About this test result, less than 5% of significance probability (P <0.05) is represented by *, and less than 1% of significance probability (P <0.01) is represented by ** with respect to the significance probability P value in t test.

  As is clear from Tables 1 and 2, extracts 1 to 8 showed a significant effect of promoting neutral accumulation of human preadipocytes. Therefore, the supercritical extract of specific shellfish has an excellent neutral fat accumulation promoting action, and it can be used as a breast augmentation agent by using such a supercritical extract of shellfish as a topical skin external preparation. It became clear that it was useful.

[Prescription Example 1] Breast augmentation emulsion (1) Squalane 10.0 (mass%)
(2) Methylphenylpolysiloxane 4.0
(3) Hydrogenated palm kernel oil 0.5
(4) Hydrogenated soybean phospholipid 0.1
(5) Polyoxyethylene monostearate
Sorbitan (20E.O.) 1.3
(6) Sorbitan monostearate 1.0
(7) Glycerin 4.0
(8) Methyl paraoxybenzoate 0.1
(9) Carboxyvinyl polymer 0.15
(10) Purified water 53.85
(11) Arginine (1% by weight aqueous solution) 20.0
(12) Extract 1 5.0
Production method: The oil phase components (1) to (6) are heated and dissolved at 80 ° C. On the other hand, the aqueous phase components (7) to (10) are dissolved by heating at 80 ° C. The oil phase component is added to this while stirring and uniformly emulsified with a homogenizer. After the emulsification, cooling is started, and (11) and (12) are sequentially added and mixed uniformly.

[Prescription Example 2] Breast augmentation lotion (1) Ethanol 15.0 (mass%)
(2) Polyoxyethylene (40E.O.) hydrogenated castor oil 0.3
(3) Fragrance 0.1
(4) Purified water 78.38
(5) Citric acid 0.02
(6) Sodium citrate 0.1
(7) Glycerin 1.0
(8) Hydroxyethyl cellulose 0.1
(9) Extract 2 5.0
Production method: (2) and (3) are dissolved in (1). After dissolution, (4) to (8) are sequentially added, and then sufficiently stirred, (9) is added and mixed uniformly.

[Prescription Example 3] Breast augmentation cream (1) Squalane 10.0 (mass%)
(2) Stearic acid 2.0
(3) Hydrogenated palm kernel oil 0.5
(4) Hydrogenated soybean phospholipid 0.1
(5) Cetanol 3.6
(6) Lipophilic glyceryl monostearate 2.0
(7) Glycerin 10.0
(8) Methyl paraoxybenzoate 0.1
(9) Arginine (20 mass% aqueous solution) 15.0
(10) Purified water 36.7
(11) Carboxyvinyl polymer (1% by weight aqueous solution) 15.0
(12) Extract 3 5.0
Production method: The oil phase components (1) to (6) are heated and dissolved at 80 ° C. On the other hand, the aqueous phase components (7) to (10) are dissolved by heating at 80 ° C. The oil phase component is added to this while stirring and uniformly emulsified with a homogenizer. (11) is added after completion | finish of emulsification, cooling is started, (12) is added at 40 degreeC, and it mixes uniformly.

[Prescription Example 4] Breast augmentation serum (1) Purified water 27.45 (mass%)
(2) Glycerin 10.0
(3) Sucrose fatty acid ester 1.3
(4) Carboxyvinyl polymer (1% by weight aqueous solution) 17.5
(5) Sodium alginate (1% by weight aqueous solution) 15.0
(6) Polyglyceryl monolaurate 1.0
(7) Macadamia nut oil fatty acid phytosteryl 3.0
(8) N-lauroyl-L-glutamic acid di (phytosteryl-2-octyldodecyl) 2.0
(9) Hardened palm oil 2.0
(10) Squalane (derived from olive) 1.0
(11) Behenyl alcohol 0.75
(12) Beeswax 1.0
(13) Jojoba oil 1.0
(14) 1,3-butylene glycol 10.0
(15) L-arginine (10% by mass aqueous solution) 2.0
(16) Extract 4 5.0
Production method: The aqueous phase components (1) to (6) are mixed and dissolved by heating at 75 ° C. On the other hand, the oil phase components (7) to (14) are mixed and dissolved by heating at 75 ° C. Next, the oil phase component is added to the aqueous phase component and preliminary emulsification is performed, followed by uniform emulsification with a homomixer. Cooling is started after completion of emulsification, and (15) is added at 50 ° C. Cool further to 40 ° C., add (16) and mix evenly.

[Formulation Example 5] Breast augmentation aqueous gel (1) Carboxyvinyl polymer 0.5 (mass%)
(2) Purified water 78.7
(3) Sodium hydroxide (10% by mass aqueous solution) 0.5
(4) Ethanol 10.0
(5) Methyl paraoxybenzoate 0.1
(6) Fragrance 0.1
(7) Extract 5 10.0
(8) Polyoxyethylene (60E.O.) hydrogenated castor oil 0.1
Manufacturing method: (1) is added to (2), and after stirring uniformly, (3) is added. After stirring uniformly, (5) previously dissolved in (4) is added. After stirring uniformly, the previously mixed (6) to (8) are added and stirred and mixed uniformly.

[Formulation Example 10] Water-in-oil emollient cream for breast augmentation (1) Liquid paraffin 30.0 (mass%)
(2) Microcrystalline wax 2.0
(3) Vaseline 5.0
(4) Diglycerin oleate 5.0
(5) Sodium chloride 1.3
(6) Potassium chloride 0.1
(7) Propylene glycol 3.0
(8) 1,3-butylene glycol 5.0
(9) Methyl paraoxybenzoate 0.1
(10) Extract 6 5.0
(11) Purified water 43.4
(12) Fragrance 0.1
Production method: Dissolve (5) and (6) in a part of (11) to 50 ° C, and gradually add to (4) heated to 50 ° C with stirring. After mixing this, it disperse | distributes uniformly to (1)-(3) heated and melt | dissolved at 70 degreeC. (7) to (10) are added to the remainder of (11) heated and dissolved at 70 ° C. with stirring, and emulsified with a homomixer. Cooling is started after completion of emulsification, and (12) is added at 40 ° C. and mixed uniformly.

[Prescription Example 11] Breast augmentation pack (1) Purified water 58.9 (mass%)
(2) Polyvinyl alcohol 12.0
(3) Ethanol 17.0
(4) Glycerin 5.0
(5) Polyethylene glycol (average molecular weight 1000) 2.0
(6) Extract 7 5.0
(7) Fragrance 0.1
Production method: (2) and (3) are mixed, heated to 80 ° C, and then dissolved in (1) heated to 80 ° C. After uniformly dissolving, add (4) and (5), and start cooling while stirring. Cool to 40 ° C, add (6) and (7) and mix uniformly.

Claims (2)

Extraction of the dried and crushed composition excluding shells from one or more shellfish selected from clams, clams, himezobora, Triggery, milk oysters, scallops, scallops and snails using carbon dioxide as a supercritical extractant The fat accumulation promoter which uses the extract obtained by this as an active ingredient. Extraction of the dried and crushed composition excluding shells from one or more shellfish selected from clams, clams, himezobora, Triggery, milk oysters, scallops, scallops and snails using carbon dioxide as a supercritical extractant A breast augmenter containing the extract obtained as an active ingredient.