JP2007099714A - Urosolic acid derivative showing collagen-increasing action, food preparation, cosmetic and antiinflammatory agent therefrom - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an urosolic acid derivative that has excellent collagen-increasing action with weak side effect and provide food preparation, cosmetics and antiinflammatory agent therefrom. <P>SOLUTION: The urosolic derivatives are prepared by allowing urosolic acid to combine through an ester linkage to at least one selected from the following compounds consisting of betaine, γ-aminobutyric acid, gallic acid, eicosapentanoic acid, cinnamic acid, p-coumaric acid. The urosolic derivatives also can be obtained by allowing pulverized persimmon leaf to react with betaine, γ-aminobutanoic acid and gallic acid in the presence of a lipase as a transesterification catalyst followed by alkaline reduction. Further, the urosolic derivative can be obtained by allowing pulverized rosemary, betaine and pulverized soybean powder to be fermented by using Bacillus natto and the product is subjected to alkaline reduction. The food preparation, cosmetics and the antiinflammatory agent each include the urosolic acid derivative. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

The present invention relates to an ursoic acid derivative having an inflammation-improving effect or a preventive effect, and a wrinkle-improving effect, and exhibiting a collagen-increasing effect, a ursolic acid derivative obtained by fermenting rosemary or transesterifying a bamboo leaf, and The present invention relates to food preparations, cosmetics and anti-inflammatory agents.

Collagen is a protein present in skin, bone, cartilage, blood vessels, and membrane tissues in various tissues. The number of types of collagen is 10 or more, and its function is based on the structure of the skeleton of the parenchyma, bone, and inflammation. Such as prevention of cancer invasion and prevention of metastasis.

Fibroblasts produce collagen, and the production involves fibroblast proliferation stimulation and growth factors, and activation of transcription factors induces collagen production at the gene level (see, for example, Non-Patent Document 1). ).

The living body is decomposed by an enzyme that degrades collagen, collagenase, or matrix metalloprotease to become a peptide or amino acid, and its function disappears. This collagenase is induced and activated by inflammation and cancer cells.

Further, even with arthritis, collagenase is produced by inflammatory cells such as inflammatory tissue and neutrophils produced around cartilage sites and muscles, and collagen is degraded and disappeared, resulting in disordered tissue construction (for example, non-patent literature) 2).

As a method of increasing collagen, there are a method of increasing collagen production of fibroblasts and inhibition of collagenase activity or suppression of induction, etc. It is preferable to use both methods in combination. Research and development of extraction methods are underway.

Methods for increasing collagen, drugs, foods, and cosmetics include cancer cell metastasis, suppression of angiogenesis related to cancer metastasis, suppression of cancer cell proliferation, suppression of arthritis, improvement of inflammation, suppression of osteoporosis, suppression of cellulite, Since it is effective in improving, preventing and preventing wrinkles and talmi, methods for increasing collagen have been studied.

Plants and herbs contain active ingredients that increase collagen, and these active ingredients are being isolated and purified (for example, see Non-Patent Document 3).

Anti-inflammatory agents such as fenbuchen, indomethacin, and ipflofen are known as chemically synthesized collagenase inhibitors, but side effects such as dry cough and gastrointestinal tract have been reported for each, and ingredients and formulations with fewer side effects (For example, refer nonpatent literature 4).

As an invention for increasing collagen, there is a composition containing a phenol compound derived from mimosa, and the composition comprising an effective amount of a biologically active phenol compound-containing extract or its active fraction obtained from white mulberry (For example, refer to Patent Document 1).

As an invention of a substance that inhibits collagenase, there is a collagenase activity inhibitor containing at least one of magnolol and honokiol as an active ingredient. Here, honoki leaves, bark (shoku), trunk material, root bark, etc. And the component contained in these is utilized (for example, refer patent document 2).

In addition, as terpenes derived from herbs and plants, there is an invention concerning the use of at least one of saponin or sapogenol that is cosmetically acceptable as a cosmetic agent for increasing collagen in the dermis-epidermal junction (for example, (See Patent Document 3).

However, all the inventions are caused by either the enhancement of collagen production or the inhibition of collagenase, the effects thereof are limited, and the industrial use is limited.
Japanese Patent No. 3626727 Japanese Patent No. 2886623 Special table 2002-516837 Booth B et al., Biochim Biophys Acta, 607, 145-160, 1980. Peel N et al., Bayliers Clin Rheumatol, 6, 351-372, 1992. Niizawa A et al., Clin. Exp. Rheumatol, 21, 57-62, 2003. Crossley R, Am. J. et al. Med, 75, 84-90, 1983.

As described above, a chemically synthesized anti-inflammatory agent exhibiting a collagenase inhibitory action has a problem that side effects such as dry cough and gastrointestinal tract disorders occur.

On the other hand, there is a problem that although the safety of a naturally derived substance is high, its effect is mild. Therefore, a natural product-derived substance that has weak side effects and exhibits an excellent collagen-increasing action with an anti-inflammatory effect is desired.

The present invention has been made paying attention to the problems existing in the prior art as described above. The object is to provide a ursoic acid derivative which has weak side effects and exhibits an excellent collagen increasing action.

It is to provide a ursoic acid derivative exhibiting excellent collagen-increasing action with low side effects obtained by alkali reduction of fermented product obtained by adding fermented fermented product with fermented fermented product of rosemary ground product, betaine, soybean ground material and natto. .

Provided is a ursoic acid derivative that exhibits an excellent collagen-increasing action with low side effects obtained by alkali reduction of a reaction product obtained by adding betaine to pulverized bamboo leaves and adding lipase for transesterification to heat That is.

Ursic acid derivative with low side effects obtained by adding alkali-reduced reaction product by adding gamma-aminobutyric acid to pulverized bamboo leaf, adding lipase for transesterification reaction, and exhibiting excellent collagen increasing action Is to provide.

Providing ursoic acid derivatives with low side effects obtained by adding gallic acid to pulverized bamboo leaf and adding lipase for transesterification to reduce the temperature of the reaction mixture with alkali, and exhibiting excellent collagen-increasing action It is to be.

Addition of 1 weight ursic acid derivative exhibiting collagen-increasing action, 0.3-3 weight glucosamine, 0.2-2 weight chondroitin sulfate, stir, and heat, and the side effect of the composition obtained is weak and excellent It is to provide a food formulation.

Side effects consisting of a composition obtained by adding 1 weight of a uric acid derivative exhibiting an action of increasing collagen, 0.01 to 0.1 weight of vitamin C, and 0.2 to 2 weight of fermented soybean extract, stirring, and heating are weak. Is to provide excellent cosmetics.

It is an object of the present invention to provide an excellent anti-inflammatory agent having a weak side effect comprising a ursoic acid derivative exhibiting a collagen increasing action.

In order to achieve the above object, the invention described in claim 1 relates to a ursoic acid derivative exhibiting a collagen increasing action represented by the following formula (1).

Ｘは、ベタイン、ガンマ−アミノ酪酸、没食子酸、エイコサペンタエン酸、ケイヒ酸、パラ−クマル酸のいずれから選択される一つ。

X is one selected from betaine, gamma-aminobutyric acid, gallic acid, eicosapentaenoic acid, cinnamic acid, and para-coumaric acid.

The invention according to claim 2 is obtained by adding the betaine to the pulverized product of bamboo leaves, adding the lipase for transesterification reaction, and subjecting the heated reaction product to alkali reduction. Among them, the present invention relates to a ursoic acid derivative exhibiting a collagen increasing action represented by the following formula (2), wherein X is betaine.

The invention described in claim 3 is obtained by adding gamma-aminobutyric acid to the pulverized product of bamboo leaves, adding lipase for transesterification reaction, and subjecting the heated reaction product to alkali reduction. Among these derivatives, the present invention relates to a ursoic acid derivative exhibiting a collagen increasing action represented by the following formula (3), wherein X is gamma-aminobutyric acid.

The invention according to claim 4 is the derivative according to claim 1 obtained by alkali reduction of a reaction product obtained by adding gallic acid to a pulverized bamboo leaf and adding lipase for transesterification. Of these, X is gallic acid, and relates to a ursoic acid derivative exhibiting a collagen increasing action represented by the following formula (4).

The invention according to claim 5 is obtained by alkali reduction of a fermented product obtained by adding a fermented product of rosemary pulverized product, betaine, soybean pulverized product and natto bacteria. Alternatively, the present invention relates to a ursoic acid derivative exhibiting a collagen increasing action according to claim 4.

The invention according to claim 6 comprises 1 weight of a uric acid derivative exhibiting a collagen increasing action according to claim 1 or claim 2 or claim 3 or claim 4 or claim 5, 0.3 to 3 weight of glucosamine, The present invention relates to a food preparation comprising a composition obtained by adding 0.2 to 2 weight of chondroitin sulfate, stirring and heating.

The invention according to claim 7 is characterized in that 1 weight of ursoic acid derivative exhibiting the collagen increasing action according to claim 1 or claim 2 or claim 3 or claim 4 or claim 5, and vitamin C 0.01 to 0.1. It is related with the cosmetics which consist of a composition obtained by adding 0.2-2 weight of weight and soybean fermented extract, stirring, and heating.

Invention of Claim 8 is related with the anti-inflammatory agent which consists of a ursoic acid derivative which exhibits the collagen increase effect | action of Claim 1 or Claim 2 or Claim 3 or Claim 4 or Claim 5.

Since this invention is comprised as mentioned above, there exist the following effects. According to the ursoic acid derivative exhibiting the collagen increasing action according to claim 1 or claim 2 or claim 3 or claim 4 or claim 5, side effects are weak and an excellent anti-inflammatory effect is exhibited.

According to the food preparation of claim 6, the side effects are weak and an excellent anti-inflammatory effect is exhibited.

According to the cosmetic of claim 7, the side effect is weak and an excellent wrinkle improving effect is exhibited.

According to the anti-inflammatory agent of claim 8, side effects are weak and an excellent anti-inflammatory effect is exhibited.

Hereinafter, the best mode for carrying out the present invention will be described in detail.

First, the ursoic acid derivative exhibiting the collagen increasing action of the present embodiment is represented by the following formula (1).

Ｘは、ベタイン、ガンマ−アミノ酪酸、没食子酸、エイコサペンタエン酸、ケイヒ酸、パラ−クマル酸のいずれから選択される一つ。

X is one selected from betaine, gamma-aminobutyric acid, gallic acid, eicosapentaenoic acid, cinnamic acid, and para-coumaric acid.

The basic structure of ursoic acid derivatives that increase collagen is the triterpene ursanoic acid hydroxyl group and betaine, gamma-aminobutyric acid, gallic acid, eicosapentaenoic acid, cinnamic acid, and para-coumaric acid. A carboxyl group is an ester bond.

Ursoic acid is a naturally occurring terpenoid, the chemical name of (3beta) -3-hydroxy-12-ene-28-euic acid, and also a natural substance sometimes referred to as ursol, prunol, micromenol, malol It is.

Betaine, gamma-aminobutyric acid, gallic acid, eicosapentaenoic acid, cinnamic acid, and para-coumaric acid are also abundant in nature, and their safety has been confirmed. This ursoic acid derivative is highly safe.

The aforementioned ursoic acid derivative has the property that the triterpene moiety of ursoic acid acts on the active center of collagenase to inhibit collagenase. In particular, it is excellent in the action of inhibiting collagenase that degrades type 1, type 2, type 3, and type 4 collagen.

In the above ursoic acid derivatives, the organic acid moieties of betaine, gamma-aminobutyric acid, gallic acid, eicosapentaenoic acid, cinnamic acid and para-coumaric acid bound to ursoic acid act in the vicinity of the fibroblast growth factor receptor. It has the advantage of growing fibroblasts by increasing receptor activity and giving a stronger stimulus as a fibroblast growth factor.

Since the ursoic acid derivative has high fat solubility, it is incorporated into fibroblasts and has the advantage of activating an intracellular signal transduction pathway that constructs a collagen synthesis system.

The aforementioned ursoic acid derivative acts on monocytes and macrophages and blocks intracellular signal transduction pathways caused by bacteria and viruses, thereby suppressing the production of inflammatory cytokines such as interleukin 1 alpha and interleukin 6 It has the feature of exerting inflammatory action.

Among the ursoic acid derivatives, when X is betaine, the resulting ursoic acid derivative is ursoic acid betainate. In this ursoic acid betainate, the quaternary ammonium salt of betaine maintains the structure of the ursoic acid derivative electrically stable.

Among the above ursoic acid derivatives, when X is gamma-aminobutyric acid, the resulting ursoic acid derivative is ursoic acid gamma-aminobutyrate. Ursanoic acid gamma-aminobutyrate is expected to have a synergistic effect because gamma-aminobutyric acid functions to adjust immune function by improving nerve function in the brain.

Among the ursoic acid derivatives, when X is gallic acid, the resulting ursoic acid derivative is ursoic acid galonate. In this uronic acid galonate, the inflammatory reaction is suppressed by the strong antioxidant power of gallic acid, and the anti-inflammatory action is synergistically increased.

Among the ursoic acid derivatives, when X is eicosapentaenoic acid, the resulting ursoic acid derivative is uric acid eicosapentaate. In this eurosapentaurate, the side chain of eicosapentaenoic acid acts on blood vessels to improve blood flow, so that the distribution of ursoic acid derivatives is improved.

Among the ursoic acid derivatives, when X is cinnamic acid, the resulting ursoic acid derivative is urnate cinnamate. This cinnamate ursoate has a synergistic increase in anti-inflammatory action because the cinnamate side chain exhibits anti-inflammatory action.

Among the ursoic acid derivatives, when X is para-coumaric acid, the resulting ursoic acid derivative is ursoic acid para-coumaronate. This ursoic acid para-coumaronate is synergistically increased in anti-inflammatory action because the side chain of para-coumaric acid exhibits anti-inflammatory action.

When the ursoic acid derivative is ingested in excess, it is decomposed by a lipolytic enzyme in the liver to produce ursoic acid and other parts. Therefore, this ursoic acid derivative is highly safe because it does not accumulate excessively in the body.

The safety of both the ursoic acid and other parts has been confirmed, and the experience with food and medicines is also abundant. Therefore, the safety of ursoic acid derivatives is high.

The ursoic acid derivative can be chemically synthesized. In the case of chemical synthesis, ursoic acid and betaine, gamma-aminobutyric acid, gallic acid, eicosapentaenoic acid, cinnamic acid, para-coumaric acid, solvent, dicyclohexylcarbodiimide, 4-dimethylaminopyridine are added, and 10 Stir at ~ 30 ° C for 6-24 hours to obtain the reaction product.

The obtained reaction solution is subjected to silica gel chromatography, and the target ursoic acid derivative is separated using n-hexane as a solvent.

Ursoic acid is extracted from bamboo leaves with n-hexane and ethyl acetate, and the extract is subjected to silica gel chromatography and eluted with n-hexane and ethyl acetate.

As betaine, one extracted from natural sugarcane has high safety, and Nittenbetaine manufactured by Nippon Sugar Sugar Co., Ltd. is preferable because of its low cost and high quality.

As gamma-aminobutyric acid, products obtained from fermented rice and rice bran are highly safe. For example, a product made by Oriza Oil is preferred.

As gallic acid, those used as raw materials for antioxidants and antioxidant preparations have high safety and high quality. For example, gallic acid manufactured by Iwate Chemical Co., Ltd. is preferable because of its extensive use.

Eicosapentaenoic acid, cinnamic acid, and para-coumaric acid are all widely used as foods, and their safety has been confirmed. It is preferable to use a high-quality product provided by Nissui Pharmaceutical Co., Ltd., Nippon Biocon Co., Ltd. or STEC Co.

Moreover, the target ursoic acid derivative can be enzymatically produced using ursoic acid and betaine, gamma-aminobutyric acid, gallic acid, eicosapentaenoic acid, cinnamic acid, and para-coumaric acid as raw materials.

The above ursoic acid and betaine, gamma-aminobutyric acid, gallic acid, eicosapentaenoic acid, cinnamic acid, para-coumaric acid, lipase for ester conversion reaction or an enzyme that causes ester bond reaction, such as lipase AY “Amano manufactured by Amano Enzyme” 30G, lipase G “Amano” 50, lipase F-AP15, neurase F3G, and the like are reacted with each other to form an ester bond to produce the desired ursoic acid derivative.

These raw materials are put in a reaction tank and a reaction is performed together with a solvent. In addition, it is preferable that the reaction product is obtained as a crude product by removing the solvent because the cost required for purification can be reduced.

Furthermore, it is preferable because the raw material is safe. On the other hand, it is preferable to purify the target ursoic acid derivative from the above reaction product because it can reduce the intake per time as a highly pure substance. .

As a purification method, it is preferable to use a purification operation such as a separation resin.

That is, it is separated and separated by a separation carrier or resin. As the separation carrier or resin, porous polysaccharide, silicon oxide compound, polyacrylamide, polystyrene, polypropylene, styrene-vinylbenzene copolymer, etc. whose surface is coated as described later are used. Those having a particle size of 0.1 to 300 μm are preferred. The finer the particle size, the higher the accuracy of the separation, but the longer the separation time.

For example, a reverse phase carrier or a resin whose surface is coated with a hydrophobic compound is used for separation of a highly hydrophobic substance. Those coated with a cationic substance are suitable for the separation of anionically charged substances.

Also, those coated with an anionic substance are suitable for separating a cationically charged substance. When a specific antibody is coated, it is used as an affinity carrier or resin for separating only a specific substance.

The affinity carrier or resin is used for specific preparation of an antigen using an antigen-antibody reaction. A dispersible carrier or resin is used for isolation of substances such as silica gel (manufactured by Merck) if there is a difference in the distribution coefficient between the substances and the solvent for separation.

Among these, an adsorbent carrier or resin, a dispersible carrier or resin, a molecular sieve carrier or resin, and an ion exchange carrier or resin are preferable from the viewpoint of reducing production costs. Furthermore, the reverse phase carrier or resin and the dispersible carrier or resin are more preferable because the difference in the distribution coefficient with respect to the separation solvent is large.

When an organic solvent is used as the separation solvent, a carrier or resin having resistance to the organic solvent is used. Moreover, the carrier or resin utilized for pharmaceutical manufacture or food manufacture is preferable.

From these points, Diaion (Mitsubishi Chemical Corporation) and XAD-2 or XAD-4 (Rohm and Haas) are used as the adsorptive carrier, and Sephadex LH-20 (Amersham Pharmacia) is used as the molecular sieve carrier. Silica gel as the distribution carrier, IRA-410 (Rohm and Haas) as the ion exchange carrier, and DM1020T (Fuji Silysia) as the reverse phase carrier are more preferable. Of these, Diaion, Sephadex LH-20 and DM1020T are more preferred.

The obtained extract is dissolved in a solvent for swelling the carrier for separation or the resin before separation. The amount is preferably 1 to 50 times, more preferably 3 to 20 times the weight of the extract from the viewpoint of separation efficiency. The separation temperature is preferably 4 to 30 ° C., more preferably 10 to 25 ° C. from the viewpoint of the stability of the substance.

As the separation solvent, water or a lower alcohol containing water, a hydrophilic solvent, or a lipophilic solvent is used. As the lower alcohol, methanol, ethanol, propanol and butanol are used, and ethanol used for food is preferable.

When Sephadex LH-20 is used, a lower alcohol is preferable as the separation solvent. When silica gel is used, the separation solvent is preferably chloroform, methanol, acetic acid or a mixture thereof.

When Diaion and DM1020T are used, the separation solvent is preferably a lower alcohol such as methanol or ethanol or a mixed solution of lower alcohol and water.

After the collection, it is preferable to remove the solvent by drying or vacuum drying to obtain the desired conjugate as a powder or a concentrated liquid because the influence of the solvent can be excluded.

It can also be obtained by extracting or purifying the target ursoic acid derivative from a natural material. Natural materials include plants, seaweed, mushrooms, edible animals, edible fish, mollusks, insects, and crustaceans. In particular, bamboo leaves and fermented soybeans are characterized by being easy to extract.

Bamboo leaves are discarded and not used effectively except for being used as humus. Extracting or purifying this bamboo leaf as a raw material is preferable because it effectively uses waste and reduces the amount of waste.

It is preferable to obtain the above-mentioned ursoic acid derivative by fermentation using microorganisms or yeasts because food safety is confirmed and food experience is abundant. In this case, the microorganisms used include natto, lactic acid bacteria, red yeast, and Bacillus subtilis, and the yeast includes beer yeast and alcoholic yeast. It is preferable because the property is also secured.

The fermentation is performed using a fermentation tank by adding the microorganism or yeast to a fermentation raw material such as soybean or milk. After the fermentation, the desired ursoic acid derivative can be obtained from the reaction product. Further, fish oil, fish meat, green tea, coffee, dandelion, barley young leaves, kuzu no hana, chili pepper, royal jelly, propolis and the like can be added and fermented as described above to obtain the desired ursolic acid derivative.

In addition, the above ursoic acid derivative can be fermented together with bamboo leaves, ginger garlic, onion, garlic and alkali reduced. For example, it is possible to obtain fermented products obtained by adding fermented fermented with bamboo leaves, garlic garlic, onion or garlic, edible fish pulverized, soybean pulverized natto, and fermented fermented natto. It is preferable because leaves, fish heads and internal organs can be used effectively.

When extracting from plants, bamboo leaves, garlic garlic, onion, garlic, soybeans, scallops, licorice, vermicelli, hanai kada, barley young leaves, kuzu flower, red pepper, oysters, pears, chestnuts, green tea, cod, wasabi, bracken, rice , Wheat, corn, radish, rape blossoms, cherry, pine, aoki, akane, akamegashiwa, akebi, amachazuru, amadokoroko, aloe, licorice, itado, inocazuchi, ibutsukikousou, mugwort, weevil, udo, ume, vulgaris Psyllium, Okela, Okra, Hypericum, Hypericum, Salamander, Ominaeshi, Oyster Oyster, Calla Lily, Callas Bisaku, Kawaretsumeme, Kawaranadeshiko, Kannaoi, Jerusalem artichokes, Yellow-spotted, Yellowfin, Yellow-spotted Ko, Kuboke, Kudzu, Gardenia, Kohone, Kobushi, Sai Kachi, Sabonso, Sartorii Rose Bucket, Sanshuyu, Janusu, Silane, Honeysuckle, Seri, Assembler, Taranoki, Dandelion, Chigaya, Tsuruganeninjin, Tsuwabuki, Ninja Toki, Ninja Toshi Nanten, Neubara, Octopus, Hazel, Hakogusa, Hikikoshi, Hishi, Hitsuba, Biwa, Fuki, Fukujusou, Fuji, Matabi, Mejijiki, Yamanoimo, Yukinoshita, Mugwort, Gentian, Forsythia, Wintersweet, Walnut, Root, Flower or Root It is preferable because it is easy to do.

When extracting from algae, Aosa, Aonori, Amanori, Alame, Iwanori, Egonori, Ogonori, Kawanori, Enagaonikombu, Gagomecombu, Nagacombu, Hosomecombu, Maconbu, Mitsuishikonbu, Rishibune, Azalea, Azalea The leaves, stems, or roots of squirrels, squirrels, Okinawa mozuku, mozuku, wakame, kukiwa kame, mekabuwakame are preferred because they are easily available.

The ursoic acid derivative thus obtained is obtained as a liquid or a powder. The obtained ursoic acid derivative is used for pharmaceuticals, food preparations or cosmetics. As a pharmaceutical, it is used as an anti-inflammatory agent, an anti-arteriosclerotic agent, a cancer metastasis inhibitor, a wrinkle removing agent, and the like.

As a food preparation, it is used for the purpose of suppressing or preventing inflammation for the purpose of increasing collagen.

As a cosmetic, it is used for the purpose of improving or preventing wrinkles, tarmi and double jaws due to the decrease in collagen.

Next, the following formula in which X is betaine among the derivatives obtained by adding betaine to the pulverized bamboo leaf, adding the lipase for transesterification reaction, and alkali-reducing the reaction product. The ursoic acid derivative exhibiting the collagen increasing action shown in (2) will be described.

As used herein, the term “ursoic acid derivative” refers to one in which X is betaine among the above ursoic acid derivatives, that is, ursoic acid betainate.

Ursoic acid betainate has the property that the triterpene part of ursoic acid acts on the active center of collagenase to inhibit collagenase. In particular, it is excellent in the action of inhibiting collagenase that degrades type 1, type 2, type 3, and type 4 collagen.

Ursoic acid betainate works with fibroblasts by the organic acid moiety of ursoic acid acting in the vicinity of the fibroblast growth factor receptor, increasing receptor activity and providing a stronger stimulus as a fibroblast growth factor. It has the feature to proliferate.

Ursoic acid betainate has the feature of being incorporated into fibroblasts due to its high lipid solubility and activating the intracellular signal transduction pathway that builds the collagen synthesis system.

Ursoic acid betainate acts on monocytes and macrophages and blocks intracellular signal transduction pathways by bacterial and viral stimulation, thereby suppressing the production of inflammatory cytokines such as interleukin 1 alpha and interleukin 6 and has anti-inflammatory action It has the feature that demonstrates.

In the ursoic acid betainate, the quaternary ammonium salt of betaine makes the structure of the ursoic acid derivative electrically stable.

When ursoic acid betaineate is ingested in excess, it is degraded by lipolytic enzymes in the liver to produce ursoic acid and betaine. Therefore, since ursoic acid betainate does not accumulate excessively in the body, its safety is high and its toxicity is mild.

The ursoic acid derivative can be obtained by adding betaine to a pulverized product of bamboo leaf, adding a lipase for transesterification reaction, and subjecting the heated reaction product to alkaline reduction.

As the pulverized product of bamboo leaf, any bamboo leaf made in Japan, China, America, or Africa is used.

The cocoon referred to here may be any of the genus Fuyuri, Jiro, Hiramu Mutsu, Koshu Hyakume, Shizomi, and Dogami Bee.

It is preferable that the pulverized product of bamboo leaves is pulverized by a pulverizer after drying because the reaction can be carried out effectively. CD dryers manufactured by Nishimura Corporation as dryers, Vibrons and funnels manufactured by Okawara Manufacturing Co., Ltd., swirling air dryers manufactured by Nara Machinery Co., Ltd., tornesh dryers, fluidized bed dryers, and crushers Nara Machinery Free Mill, Super Free Mill, Sample Mill, Goblin, Super Clean Mill, Micros, Toyo Riko's Small Vacuum Dryer as Vacuum Dryer, Matsui's Small Vacuum Heat Transfer Dryer DPTH -40, clean dry VD-7, VD-20, etc. manufactured by AKM Kyushu Technos Co., Ltd. are used.

The betaine used here is of high quality used for food. For example, a product extracted from natural sugarcane is preferable because it is highly safe and Nittenbetaine manufactured by Nippon Sugar Sugar Co., Ltd. is inexpensive and has high quality.

The lipase for transesterification is a naturally occurring enzyme that esterifies a carboxyl group such as a fatty acid and a hydroxyl group of an alcohol. The desired hydroxyl group derivative is produced by ester-linking the hydroxyl group at the 3-position of ursoic acid and the carboxyl group of betaine.

Examples of the lipase for transesterification include, for example, lipozyme and Novozyme 435 manufactured by Novozyme, lipase PL and lipase QLM manufactured by Meito Sangyo Co., Ltd., lipase AY “Amano” 30G manufactured by Amano Enzyme, and Lipase G “Amano” 50, lipase F-AP15, neurase F3G, and the like are high in quality and are confirmed to be safe.

The betaine is preferably 0.05 to 0.15 weight, and the transesterification lipase is preferably 0.005 to 0.02 weight with respect to 1 weight of the pulverized bamboo leaf described above.

When the betaine weight is less than 0.05 weight with respect to 1 weight of the kneaded pulverized product described above, the amount of betaine is insufficient, and there is a possibility that a ursoic acid derivative cannot be obtained sufficiently.

When the betaine weight is more than 0.15 weight with respect to 1 weight of the pulverized bamboo leaf described above, the amount of ursoic acid may be insufficient and a ursoic acid derivative may not be obtained sufficiently.

If the weight of the lipase for transesterification is less than 0.005 weight with respect to 1 weight of the pulverized product of bamboo leaves described above, the enzyme reaction may be insufficient and the ursoic acid derivative may not be sufficiently obtained. .

When the lipase weight for transesterification exceeds 0.02 weight with respect to 1 weight of the pulverized product of bamboo leaves described above, the amount of ursoic acid is insufficient due to the reverse esterification reaction. Therefore, there is a risk that a ursoic acid derivative cannot be obtained sufficiently.

The pulverized bamboo leaf, betaine, and lipase for transesterification are heated. Heating is preferred because the aqueous solution is mixed to increase the reactivity.

As said temperature of heating, 10-30 degreeC is preferable and 15-26 degreeC is more preferable.

The warming time is preferably 1 to 24 hours, more preferably 3 to 13 hours.

The heating is preferably performed while stirring, and a rate of 19 to 90 times per minute is preferable.

Cooling after heating is preferable because it facilitates the subsequent alkali reduction.

The warmed reaction product is alkali reduced.

Here, alkali reduction is performed in order to stabilize the bond between ursoic acid and betaine. The ester bond is reduced by alkali reduction to exhibit a stable structure.

As the alkali reduction device, Cellix, Aquastera, Alivio, TI-700 type, TI-800 type, etc., manufactured by Zenon Co., Ltd. are used.

The reactant is obtained by flowing it through a pipe and subjecting it to an alkali reduction device. The target ursoic acid betainate is obtained as a liquid.

The alkali-reduced ursoic acid betainate obtained as described above is subjected to a freeze-drying apparatus, for example, a lyophilizer manufactured by Nippon FD Co., Ltd., a freeze dryer manufactured by Yusima Co., Ltd., TGD-250LF2 manufactured by Toyo Giken, and the like. Is obtained as a powder.

It is preferable to purify the target ursoic acid betainate from the above reaction product because the intake can be reduced as a highly pure substance. As a purification method, it is preferable to use a purification operation such as a separation resin.

The ursoic acid betainate thus obtained is obtained as a liquid or a powder. The obtained ursoic acid betainate is used for pharmaceuticals, food preparations or cosmetics. As a pharmaceutical, it is used as an anti-inflammatory agent, an anti-arteriosclerotic agent, a cancer metastasis inhibitor, a wrinkle removing agent, and the like.

As a food preparation, it is used for the purpose of suppressing or preventing inflammation for the purpose of increasing collagen.

As a cosmetic, it is used for the purpose of improving or preventing wrinkles, tarmi and double jaws due to the decrease in collagen.

Next, among the above-mentioned derivatives obtained by adding gamma-aminobutyric acid to the pulverized product of bamboo leaves, adding lipase for transesterification reaction, and heating the reaction product with alkali, X is gamma-amino. The ursoic acid derivative exhibiting the collagen increasing action represented by the following formula (3), which is butyric acid, will be described.

The term “ursoic acid derivative” as used herein refers to a compound in which X is a gamma-aminobutyric acid among the ursoic acid derivatives, that is, gamma-aminobutyrate ursoate.

Ursoic acid gamma-aminobutyrate has the property that the triterpene part of ursonic acid acts on the active center of collagenase to inhibit collagenase. In particular, it is excellent in the action of inhibiting collagenase that degrades type 1, type 2, type 3, and type 4 collagen.

Ursoic acid gamma-aminobutyrate has an organic acid moiety of gamma-aminobutyric acid that works in the vicinity of the fibroblast growth factor receptor, increases receptor activity, and gives a stronger stimulus as a fibroblast growth factor. Thus, it has the feature of growing fibroblasts.

Ursoic acid gamma-aminobutyrate has a feature of activating intracellular signal transduction pathways that are taken into fibroblasts and construct a collagen synthesis system because of its high lipid solubility.

Ursoic acid gamma-aminobutyrate works on monocytes and macrophages and blocks the production of inflammatory cytokines such as interleukin 1 alpha and interleukin 6 by blocking intracellular signal transduction pathways caused by bacteria and viruses. And has an anti-inflammatory effect.

Ursoic acid gamma-aminobutyrate exhibits a synergistic effect because gamma-aminobutyric acid has a function of adjusting immune function by improving nerve function in the brain.

When ursic acid gamma-aminobutyrate is ingested in excess, it is degraded by lipolytic enzymes in the liver to produce ursic acid and gamma-aminobutyric acid.

Therefore, ursic acid gamma-aminobutyrate does not accumulate excessively in the body, so its safety is high and its toxicity is mild.

The ursoic acid derivative can be obtained by adding betaine to a pulverized product of bamboo leaf, adding a lipase for transesterification reaction, and subjecting the heated reaction product to alkaline reduction.

As the pulverized product of bamboo leaf, any bamboo leaf made in Japan, China, America, or Africa is used.

The cocoon referred to here may be any of the genus Fuyuri, Jiro, Hiramu Mutsu, Koshu Hyakume, Shizomi, and Dogami Bee.

It is preferable that the pulverized product of bamboo leaves is pulverized by a pulverizer after drying because the reaction can be carried out effectively.

The high quality gamma-aminobutyric acid used here is used for food. For example, products obtained from fermented rice and rice bran are highly safe. For example, a product made from Oriza oil refined from rice is preferred.

The lipase for transesterification is a naturally occurring enzyme that esterifies a carboxyl group such as a fatty acid and a hydroxyl group of an alcohol. The desired hydroxyl group derivative is formed by ester-bonding the hydroxyl group at the 3-position of ursoic acid and the carboxyl group of gamma-aminobutyric acid.

Examples of lipases for transesterification include Lipozyme and Novozyme 435 manufactured by Novozyme, Lipase PL and Lipase QLM manufactured by Meisho Sangyo, Lipase AY “Amano” 30G, Lipase G “Amano” 50 manufactured by Amano Enzyme, It is preferable because lipase F-AP15, neurase F3G and the like have high quality and safety has been confirmed.

The gamma-aminobutyric acid is preferably 0.04 to 0.16 weight with respect to 1 weight of the kneaded pulverized product described above, and the transesterification lipase is 0.004 to 0.03 weight. Is preferred.

When the weight of the gamma-aminobutyric acid is less than 0.04 weight with respect to 1 weight of the kneaded pulverized product described above, the amount of gamma-aminobutyric acid may be insufficient and a ursoic acid derivative may not be obtained sufficiently. There is.

When the weight of the gamma-aminobutyric acid is more than 0.16 weight with respect to 1 weight of the pulverized bamboo leaf described above, there is a risk that the amount of ursoic acid is insufficient and the ursoic acid derivative cannot be obtained sufficiently. .

When the weight of the lipase for transesterification is less than 0.004 weight with respect to 1 weight of the pulverized bamboo leaf described above, the enzyme reaction may be insufficient and the ursoic acid derivative may not be obtained sufficiently. .

When the lipase weight for transesterification exceeds 0.03 weight with respect to 1 weight of the pulverized product of bamboo leaves described above, the amount of ursoic acid is insufficient due to the reverse esterification reaction. Therefore, there is a risk that a ursoic acid derivative cannot be obtained sufficiently.

The pulverized bamboo leaf, gamma-aminobutyric acid, lipase for transesterification are heated. Heating is preferred because the aqueous solution is mixed to increase the reactivity.

As said temperature of heating, 10-30 degreeC is preferable and 13-27 degreeC is more preferable.

The heating time is preferably 1 to 24 hours, more preferably 2 to 14 hours.

The heating is preferably performed while stirring, and a rate of 8 to 120 times per minute is preferable.

Cooling after heating is preferable because it facilitates the subsequent alkali reduction.

The warmed reaction product is alkali reduced.

Here, alkali reduction is performed in order to stabilize the bond between ursoic acid and gamma-aminobutyric acid. The ester bond is reduced by alkali reduction to exhibit a stable structure.

As the alkali reduction device, Cellix, Aquastera, Alivio, TI-700 type, TI-800 type, etc., manufactured by Zenon Co., Ltd. are used.

The reactant is obtained by flowing it through a pipe and subjecting it to an alkali reduction device. The intended uric acid gamma-aminobutyrate is obtained as a liquid.

The alkali-reduced uric acid gamma-aminobutyrate obtained as described above is subjected to a freeze-drying apparatus, such as a freeze dryer manufactured by Nippon FD, a freeze dryer manufactured by Yusima Co., Ltd., or TGD-250LF2 manufactured by Toyo Giken. Ursanoic acid gamma-aminobutyrate is obtained as a powder.

It is preferable to purify the target uric acid gamma-aminobutyrate from the reaction product from the viewpoint that the intake can be reduced as a highly pure substance. As a purification method, it is preferable to use a purification operation such as a separation resin.

The ursoic acid gamma-aminobutyrate thus obtained is obtained as a liquid or powder. The obtained uric acid gamma-aminobutyrate is used for pharmaceuticals, food preparations or cosmetics. As a pharmaceutical, it is used as an anti-inflammatory agent, an anti-arteriosclerotic agent, a cancer metastasis inhibitor, a wrinkle removing agent, and the like.

As a food preparation, it is used for the purpose of suppressing or preventing inflammation for the purpose of increasing collagen.

As a cosmetic, it is used for the purpose of improving or preventing wrinkles, tarmi and double jaws due to the decrease in collagen.

Next, among the above-mentioned derivatives obtained by adding gallic acid to the pulverized product of bamboo leaves, adding the lipase for transesterification reaction and heating the reaction product with alkali, X is gallic acid The ursoic acid derivative exhibiting the collagen increasing action represented by the formula (4) will be described.

As used herein, the term “ursoic acid derivative” refers to a compound in which X is composed of gallic acid among the above ursoic acid derivatives, that is, uronic acid galonate.

Ursoic acid galonate has the property that the triterpene part of ursoic acid acts on the active center of collagenase to inhibit collagenase. In particular, it is excellent in the action of suppressing collagenase that degrades type 1, type 2, type 3, and type 4 collagen.

Ursoic acid galonate works by increasing the activity of the organic acid moiety of gallic acid in the vicinity of the fibroblast growth factor receptor, increasing the receptor activity and providing a stronger stimulus as a fibroblast growth factor. It has the feature to proliferate.

Ursoic acid galonate has the feature that it is taken into fibroblasts due to its high fat solubility and activates the intracellular signal transduction pathway that constructs the collagen synthesis system.

Ursonic acid galonate acts on monocytes and macrophages and blocks intracellular signal transduction pathways caused by bacteria and viruses, thereby suppressing the production of inflammatory cytokines such as interleukin 1 alpha and interleukin 6 and has anti-inflammatory action It has the feature that demonstrates.

Ursoic acid galonate suppresses the inflammatory reaction by the strong antioxidant power of gallic acid, and synergistically increases the anti-inflammatory effect.

When ursoic acid galonate is ingested in excess, it is degraded by lipolytic enzymes in the liver to produce ursoic acid and gallic acid. Therefore, ursoic acid galonate is not highly accumulated in the body, so its safety is high and its toxicity is mild.

The ursoic acid derivative can be obtained by adding betaine to a pulverized product of bamboo leaf, adding a lipase for transesterification reaction, and subjecting the heated reaction product to alkaline reduction.

As the pulverized product of bamboo leaf, any bamboo leaf made in Japan, China, America, or Africa is used.

The cocoon referred to here may be any of the genus Fuyuri, Jiro, Hiramu Mutsu, Koshu Hyakume, Shizomi, and Dogami Bee.

It is preferable that the pulverized product of bamboo leaves is pulverized by a pulverizer after drying because the reaction can be carried out effectively.

As gallic acid used here, those used as raw materials for antioxidants and antioxidant preparations have high safety and high quality. For example, gallic acid manufactured by Iwate Chemical Co., Ltd. is preferable because of its extensive use.

The lipase for transesterification is a naturally occurring enzyme that esterifies a carboxyl group such as a fatty acid and a hydroxyl group of an alcohol. The target hydroxyl group derivative is formed by ester-bonding the hydroxyl group at position 3 of ursoic acid to the carboxyl group of gallic acid.

Examples of lipases for transesterification include Lipozyme and Novozyme 435 manufactured by Novozyme, Lipase PL and Lipase QLM manufactured by Meisho Sangyo, Lipase AY “Amano” 30G, Lipase G “Amano” 50 manufactured by Amano Enzyme, It is preferable because lipase F-AP15, neurase F3G and the like have high quality and safety has been confirmed.

The weight of the gallic acid is preferably 0.05 to 0.15 weight and the amount of the transesterification lipase is preferably 0.005 to 0.02 weight with respect to 1 weight of the pulverized product of bamboo leaves described above. .

When the weight of the gallic acid is less than 0.05 weight with respect to 1 weight of the pulverized product of bamboo leaves described above, the amount of gallic acid is insufficient and there is a possibility that the ursoic acid derivative cannot be obtained sufficiently.

When the weight of the gallic acid is more than 0.15 weight with respect to 1 weight of the pulverized bamboo leaf described above, there is a risk that the amount of ursoic acid is insufficient and a ursoic acid derivative cannot be obtained sufficiently.

If the weight of the lipase for transesterification is less than 0.005 weight with respect to 1 weight of the pulverized product of bamboo leaves described above, the enzyme reaction may be insufficient and the ursoic acid derivative may not be sufficiently obtained. .

When the lipase weight for transesterification exceeds 0.02 weight with respect to 1 weight of the pulverized product of bamboo leaves described above, the amount of ursoic acid is insufficient due to the reverse esterification reaction. Therefore, there is a risk that a ursoic acid derivative cannot be obtained sufficiently.

The pulverized material of persimmon leaves, gallic acid, and lipase for transesterification are heated. Heating is preferred because the aqueous solution is mixed to increase the reactivity.

The heating temperature is preferably 5 to 37 ° C, more preferably 15 to 25 ° C.

The warming time is preferably 1 to 24 hours, more preferably 3 to 16 hours.

The heating is preferably performed while stirring, and a rate of 6 to 120 times per minute is preferable.

Cooling after heating is preferable because it facilitates the subsequent alkali reduction.

The warmed reaction product is alkali reduced.

Here, it is alkali-reduced in order to stabilize the bond between ursoic acid and gallic acid.

The ester bond is reduced by alkali reduction to exhibit a stable structure.

As the alkali reduction device, Cellix, Aquastera, Alivio, TI-700 type, TI-800 type, etc., manufactured by Zenon Co., Ltd. are used.

The reactant is obtained by flowing it through a pipe and subjecting it to an alkali reduction device.

Thereby, the intended uronic acid galonate is obtained as a liquid.

The alkali-reduced ursoic acid galonate obtained as described above is subjected to a freeze-drying apparatus, for example, a lyophilizer manufactured by Nippon FD Co., Ltd., a freeze dryer manufactured by Yusima Co., Ltd., TGD-250LF2 manufactured by Toyo Giken, and the like. Is obtained as a powder.

It is preferable to purify the intended uronic acid galonate from the reaction product from the viewpoint that the intake can be reduced as a highly pure substance.

As a purification method, it is preferable to use a purification operation such as a separation resin.

The ursoic acid galonate thus obtained is obtained as a liquid or a powder.

The obtained uronic acid galonate is used for pharmaceuticals, food preparations or cosmetics. As a pharmaceutical, it is used as an anti-inflammatory agent, an anti-arteriosclerotic agent, a cancer metastasis inhibitor, a wrinkle removing agent, and the like.

As a food preparation, it is used for the purpose of suppressing or preventing inflammation for the purpose of increasing collagen.

As a cosmetic, it is used for the purpose of improving or preventing wrinkles, tarmi and double jaws due to the decrease in collagen.

Next, the ursoic acid derivative exhibiting a collagen increasing action obtained by alkali reduction of a fermented product obtained by adding fermented fermented product with a crushed product of rosemary, betaine, soybean crushed product and natto bacteria will be described.

The crushed product of rosemary to be used is obtained by drying and pulverizing rosemary.

The rosemary used here may be any of Japanese, European, American and Chinese.

The betaine used is of high quality used for food. For example, a product extracted from natural sugarcane is highly safe, and Nittenbetaine manufactured by Nippon Sugar Sugar Co., Ltd. is preferable because of its low cost and high quality.

The soybean pulverized product to be used may be any of overseas products such as Japanese products, Chinese products and American products. After washing and drying, the mixture is heated and further pulverized with a mixer.

It is preferable that this soybean ground product is heat-treated by steaming or boiling after washing the soybean, since fermentation can be carried out efficiently.

The Bacillus natto used here is a kind of Bacillus subtilis, a useful bacterium that has been involved in Japanese diet since ancient times, and its safety is also guaranteed.

Particularly preferred are those used for food processing. For example, natto bacteria made by Natto Motopo are preferred because they are stable in quality.

Betaine is 0.01 to 0.1 weight, soy ground is 3 to 20 weight, and Bacillus natto is 0.005 to 0.03 weight with respect to 1 weight of rosemary ground.

When the weight of betaine is less than 0.01 weight with respect to 1 weight of crushed rosemary, the amount of betaine may be insufficient and the desired ursoic acid derivative may not be obtained sufficiently.

When the weight of betaine exceeds 0.1 weight with respect to 1 weight of crushed rosemary, the amount of ursoic acid is insufficient, and the target ursoic acid derivative may not be sufficiently obtained.

When the weight of the pulverized soybean is less than 3 weights per 1 weight of the crushed rosemary, the fermentation does not proceed sufficiently and the target ursoic acid derivative may not be sufficiently obtained.

When the weight of the soybean ground product is more than 20 weights per 1 weight of the rosemary ground product, the amount of ursoic acid is insufficient and the target ursoic acid derivative may not be sufficiently obtained.

When the weight of Bacillus natto is less than 0.005 weight relative to 1 weight of the pulverized product of rosemary, the fermentation does not proceed sufficiently and the target ursoic acid derivative may not be sufficiently obtained.

When the weight of natto bacteria exceeds 0.03 weight with respect to 1 weight of the pulverized product of rosemary, the fermentation proceeds so much that the target ursoic acid derivative may be decomposed and the ursoic acid derivative may not be sufficiently obtained. .

Rosemary pulverized product, betaine, soybean pulverized product and Bacillus natto are added and fermented.

As temperature of the said fermentation, 10-40 degreeC is preferable and 20-37 degreeC is more preferable.

The fermentation time is preferably 24 to 96 hours, more preferably 30 to 60 hours.

The fermentation is preferably performed while stirring, and a rate of 12 to 120 times per minute is preferable.

Cooling after fermentation is preferable because it facilitates the subsequent alkali reduction.

Next, the fermented fermented product is subjected to alkali reduction.

Here, it is alkali-reduced in order to stabilize the ester bond of the ursoic acid derivative.

The ester bond is reduced by alkali reduction to exhibit a stable structure.

As the alkali reduction device, Cellix, Aquastera, Alivio, TI-700 type, TI-800 type, etc., manufactured by Zenon Co., Ltd. are used.

The reactant is obtained by flowing it through a pipe and subjecting it to an alkali reduction device.

The target ursoic acid derivative is obtained as a liquid.

The alkali-reduced ursoic acid derivative obtained as described above is subjected to a lyophilization apparatus, for example, a lyophilizer manufactured by Nippon FD Co., Ltd., a lyophilizer manufactured by Yusima Co., Ltd., TGD-250LF2 manufactured by Toyo Giken, and the like. Is obtained as a powder.

It is preferable to purify the target ursoic acid derivative from the reaction product from the viewpoint that the intake can be reduced as a highly pure substance. As a purification method, it is preferable to use a purification operation such as a separation resin.

The ursoic acid derivative thus obtained is obtained as a liquid or a powder. The obtained ursoic acid derivative is used for pharmaceuticals, food preparations or cosmetics. As a pharmaceutical, it is used as an anti-inflammatory agent, an anti-arteriosclerotic agent, a cancer metastasis inhibitor, a wrinkle removing agent, and the like.

As a food preparation, it is used for the purpose of suppressing or preventing inflammation for the purpose of increasing collagen.

As a cosmetic, it is used for the purpose of improving or preventing wrinkles, tarmi and double jaws due to the decrease in collagen.

Next, from the composition obtained by adding 1 weight of ursonic acid derivative, 0.3-3 weight of glucosamine, and 0.2-2 weight of chondroitin sulfate exhibiting the collagen increasing action described above, stirring and heating. The food formulation will be described.

The ursoic acid derivative exhibiting the collagen increasing action here is one selected from any of the above-described ursoic acid and betaine, gamma-aminobutyric acid, gallic acid, eicosapentaenoic acid, cinnamic acid, and para-coumaric acid. One is an ester bond and has an effect of increasing collagen.

The ursoic acid derivative may be any of a crude product, a mixture, a synthesized product, and a highly purified substance extracted and purified.

Glucosamine is an amino sugar obtained by decomposing chitosan extracted from crab and shrimp shells. Glucosamine has a synergistic action with ursanoic acid derivatives because it has a joint and cartilage enhancing action and an anti-inflammatory action, thereby enhancing the anti-inflammatory action.

For example, glucosamine manufactured by Yaizu Suisan Chemical Industry is preferred because it is naturally derived and has high quality.

Chondroitin sulfate is a sulfated sugar that forms the synovium of bone and cartilage, and is extracted from shark cartilage. Chondroitin sulfate has a function of promoting bone formation and improving or preventing inflammation such as arthritis, neuritis and myositis.

For example, chondroitin sulfate manufactured by Seikagaku Corporation is preferable because it is naturally derived and has high quality as a pharmaceutical raw material.

The ursonic acid derivative, glucosamine and chondroitin sulfate form a composition as a complex in which the carboxyl group bonded to the 17-position of ursonic acid and the amino group of glucosamine are further bonded to the sulfate group of chondroitin sulfate. Each function is demonstrated synergistically.

Ursoic acid derivatives, glucosamine, and chondroitin sulfate all exhibit anti-inflammatory effects with different mechanisms of action, and thus have an inhibitory effect on various inflammations with different onset causes. This composition is excellent in anti-inflammatory action.

The weight of glucosamine is 0.3 to 3 weights with respect to 1 weight of the ursoic acid derivative.

When the weight of glucosamine is less than 0.3 weight with respect to 1 weight of the ursoic acid derivative, glucosamine may be insufficient and composition formation may not be sufficiently performed.

When the weight of glucosamine is more than 3 weights with respect to 1 weight of the ursoic acid derivative, there is a risk that the ursanoic acid derivative is insufficient and composition formation is not sufficiently performed.

The weight of chondroitin sulfate is 0.2-2 weight with respect to 1 weight of the ursoic acid derivative.

When the weight of the chondroitin sulfate is less than 0.2 weight with respect to 1 weight of the ursoic acid derivative, the chondroitin sulfate may be insufficient and the composition may not be sufficiently formed.

When the weight of chondroitin sulfate exceeds 2 weights with respect to 1 weight of the ursoic acid derivative, there is a possibility that the ursoic acid derivative is insufficient and the composition formation is not sufficiently performed.

Ursoic acid derivatives, glucosamine and chondroitin sulfate are stirred and heated.

This stirring is performed using a mixer, and the stirring speed is preferably 10 to 100 times per minute.

This heating is preferably 7 to 40 ° C., more preferably 15 to 25 ° C. as the heating temperature.

The warming time is preferably 1 to 24 hours, and more preferably 3 to 12 hours.

Further, the composition is processed together with other raw materials to form a food preparation. In this case, by adding to various food materials or beverage materials, for example, it can be made into a food preparation in the form of powder, tablet, liquid (drink, etc.), capsule or the like. Moreover, you may add a base material, an excipient | filler, an additive, a subsidiary material, a bulking agent, etc. suitably.

The food preparation is taken orally in several divided doses per day. The daily intake is preferably 0.2 to 10 g, more preferably 0.3 to 6 g, and even more preferably 0.5 to 4 g. When the daily intake is less than 0.2 g, there is a possibility that sufficient collagen increasing action is not exhibited. If the daily intake exceeds 10 g, the cost may increase. In addition to the above, it can be used in the form of rice cake, rice crackers, cookies, beverages and the like.

The food preparation referred to here is a health functional food, health supplement food, general food, hospital food used in a hospital, animal feed, pet supplement, or pet food.

These food preparations are used for the purpose of preventing or improving inflammation such as arthritis, myositis, and neuritis, and for the purpose of preventing or improving wrinkles and tarmi.

Next, a cosmetic product comprising a composition obtained by adding 1 weight of the above-mentioned ursolic acid derivative, 0.01 to 0.1 weight of vitamin C and 0.2 to 2 weight of soybean fermented extract, stirring and heating. Will be described.

The ursoic acid derivative exhibiting the collagen increasing action here is one selected from any of the above-described ursoic acid and betaine, gamma-aminobutyric acid, gallic acid, eicosapentaenoic acid, cinnamic acid, and para-coumaric acid. One is an ester bond and has an effect of increasing collagen.

The ursoic acid derivative may be any of a crude product, a mixture, a synthesized product, and a highly purified substance extracted and purified.

Vitamin C is preferred because the product of Takeda Pharmaceutical Company Limited is of high quality. Vitamin C is the dermis and periosteum and promotes the production of collagen as an extracellular matrix outside the fibroblasts.

Since the ursoic acid derivative has a function of protecting and maintaining collagen produced by vitamin C through collagenase inhibitory action, the combination of the ursoic acid derivative and vitamin C is effective for increasing collagen.

Soybean fermented extract cleaves soy protein with a protease produced in the fermentation process to produce amino acids. The resulting amino acids are dermal fibroblasts that are used as a raw material for producing collagen.

For example, fermented soybean extract is preferably manufactured by Toyo Fermentation because of its good quality.

Mixing soybean fermented extract and vitamin C increases the amount of collagen produced by the amino acid raw material for collagen synthesis in fibroblasts and the promoting action of collagen production.

Mixing the ursoic acid derivative, fermented soybean extract and vitamin C has the advantage that the amount of collagen increases because the ursoic acid derivative protects the produced collagen from degradation through the collagenase inhibitory action.

The increase in collagen suppresses inflammation of the dermis of the skin, increases firmness and elasticity, and forms beautiful skin.

The weight of vitamin C is 0.01 to 0.1 weight with respect to 1 weight of the ursoic acid derivative.

When the weight of vitamin C is less than 0.01 weight with respect to 1 weight of ursoic acid derivative, the amount of collagen produced by fibroblasts may be reduced.

When the weight of vitamin C exceeds 0.1 weight with respect to 1 weight of the ursoic acid derivative, collagen produced by fibroblasts may be degraded by collagenase.

The weight of the fermented soybean extract is 0.2 to 2 weights per 1 weight of the ursoic acid derivative.

When the weight of the fermented soybean extract is less than 0.2 weight relative to 1 weight of the ursoic acid derivative, there is a risk that the amount of collagen produced by fibroblasts is reduced due to lack of amino acids.

When the weight of the soy fermented extract exceeds 2 weights with respect to 1 weight of the ursoic acid derivative, the collagen produced by the fibroblasts may be decomposed by the excessive fermented product.

Ursoic acid derivative, vitamin C, and fermented soybean extract are stirred and heated.

This stirring is performed using a mixer, and the stirring speed is preferably 10 to 100 times per minute.

As for this heating, 10-20 degreeC is preferable as heating temperature, and 12-18 degreeC is more preferable.

The heating time is preferably 1 to 18 hours, and more preferably 2 to 10 hours.

Subsequently, the composition is processed together with other raw materials as a cosmetic. Thereafter, it can be used together with oils, surfactants, vitamins, ultraviolet absorbers, thickeners, moisturizers, auxiliary materials and the like in accordance with conventional methods.

It can be in the form of lotion, cream, ointment, lotion, milky lotion, pack, oil, soap, face wash, fragrance, audi cologne, bath preparation, shampoo, rinse and the like. The form of the cosmetic preparation is arbitrary, and can be used as a solution, cream, paste, gel, gel, solid, or powder.

As a cosmetic, it is applied to the skin several times a day. The daily coating amount is preferably 0.01 to 10 g, more preferably 0.05 to 3 g, and further preferably 0.1 to 2 g. If the daily application amount is less than 0.01 g, the treatment or prevention effect of wrinkles and tarmi may not be exhibited. When the application amount per day exceeds 10 g, the cost may increase.

The cosmetics referred to here are basic cosmetics, whitening cosmetics, hair cleansing agents, treatment agents, dyeing agents, hair restorers, hair nourishing agents, body wash, quasi-drugs, which are cosmetics used for humans. In addition, it is a skin improvement agent used for animals, a shampoo for pets, and a body wash.

This cosmetic prevents and improves wrinkles and tarmi by increasing collagen.

Next, an anti-inflammatory agent composed of a ursoic acid derivative will be described.

The term “ursoic acid derivative” as used herein refers to a ursoic acid derivative that exhibits the collagen-increasing action described above. The ursoic acid derivative may be a mixture produced, a high-purity substance extracted and purified, or a substance synthesized by an enzymatic reaction.

When used as a pharmaceutical, it is necessary to remove the influence of impurities, and therefore it is preferable to use a uric acid derivative having the structure described above, which is synthesized by an enzymatic reaction and has little solvent residue.

It is used as a pharmaceutical orally or parenterally, and as a quasi-drug, it is used by blending with tablets, capsules, drinks, soaps, toothpastes and the like.

Examples of oral preparations include tablets, capsules, powders, syrups, and drinks. When mixed with the above-mentioned tablets and capsules, it can be used together with a binder, excipient, swelling agent, lubricant, sweetener, flavoring agent and the like. The tablets can also be coated with shellac or sugar.

Moreover, in the case of the said capsule, liquid carriers, such as fats and oils, can be further contained in said material. In the case of the above syrup and drink, sweeteners, preservatives, pigment flavoring agents and the like can be contained.

Examples of parenteral preparations include injections in addition to external preparations such as ointments, creams, and liquids. As the base material of the external preparation used here, petrolatum, paraffin, fats and oils, lanolin, macro gold and the like are used, and an ointment, a cream and the like can be obtained by a usual method. Injections include liquids, and other lyophilization agents. This is used aseptically dissolved in distilled water for injection or physiological saline at the time of use.

The term “anti-inflammatory agent” as used herein refers to a pharmaceutical product or a quasi-drug preparation intended to improve or prevent various diseases associated with inflammation. Inflammation occurs in various parts of the body, dermatitis and atopic dermatitis in the skin, sinusitis in the oronasal cavity, rhinitis, hay fever and allergic rhinitis, otitis media and internal otitis in the nasal nose, neuritis and encephalitis in the nerve Myositis in muscle, hepatitis in liver, nephritis in kidney, cystitis in bladder, pneumonia in lung, bronchitis, etc.

The above-mentioned anti-inflammatory agent comprising the ursoic acid derivative is the dermatitis, atopic dermatitis, sinusitis, rhinitis, hay fever, allergic rhinitis, otitis media, inner ear inflammation, neuritis, encephalitis, myositis, hepatitis, It is used as a drug for treating or preventing nephritis, cystitis, pneumonia and bronchitis.

In addition, it can be used as a veterinary medicine for the purpose of treating and preventing inflammation in livestock and pets.

Hereinafter, the embodiment will be specifically described with reference to examples and test examples. However, the following description is an example and can be implemented by changing the form.

In the following, ursoic acid betainate, which is an ursoic acid derivative obtained enzymatically, will be described.

Obtain 10kg of bamboo leaves to be discarded at a farm in Japan from Gifu Prefecture (Gifu Prefecture), dry it with a dryer (made by Nishimura Kako, CD dryer), and crush it (free from Nara Machinery Co., Ltd.) And 4 kg of pulverized bamboo leaf was obtained.

4 kg of this kneaded pulverized product was put into a cylinder, and 400 g of Nitten Betaine made by Nippon Sugar Sugar Co., Ltd. was added together with 10 L of purified water. 40 g of Neurase F3G manufactured by Amano Enzyme was dissolved in purified water and added as a lipase for transesterification.

A warming machine was installed, and the mixture was stirred at a temperature of 20 ° C. for 6 hours at a stirring speed of 50 times per minute using a stirring device (manufactured by Yamato Kagaku, Lab Stirrer LR500).

After heating, the mixture was cooled with water and filtered through filter paper to obtain a filtrate. This filtrate was applied to TI-700 type manufactured by Nippon Trim Co., Ltd. to obtain an alkali-reduced solution.

This solution was freeze-dried by a freeze dryer manufactured by Nippon FD Co., to obtain 940 g of ursoic acid betainate, which is a ursoic acid derivative.

Hereinafter, ursic acid gamma-aminobutyrate, which is an ursic acid derivative obtained enzymatically, will be described.

Obtain 9 kg of bamboo leaves to be discarded at a farm in Japan from Gifu Prefecture (Gifu Prefecture), dry it with a dryer (Vibron manufactured by Okawara Manufacturing Co., Ltd.), and crush it (manufactured by Nara Machinery Co., Ltd.). It was pulverized with goblin to obtain 4.5 kg of crushed bamboo leaves.

4.5 kg of this koji leaf pulverized product was put into a cylinder, and 450 g of gamma-amino dairy produced by Oriza Oil Chemical Co., Ltd. was added together with 10 L of purified water. To this, 45 g of lipase PL manufactured by Meikatsu Sangyo Co., Ltd. as a lipase for transesterification was dissolved in purified water and added.

A heating machine (manufactured by Fuji Mac, cast heater) was installed therein, and the mixture was stirred at a temperature of 25 ° C. for 6 hours at a stirring speed of 50 times per minute using a stirring device.

After heating, the mixture was cooled with water and filtered through filter paper to obtain a filtrate. This filtrate was applied to TI-700 type manufactured by Nippon Trim Co., Ltd. to obtain an alkali-reduced solution.

This solution was freeze-dried by a freeze dryer manufactured by Nippon FD Co., Ltd., to obtain 649 g of ursoic acid derivative ursoic acid gamma-aminobutyrate.

Below, the ursoic acid galonate which is a ursonic acid derivative obtained enzymatically will be described.

Obtained 11 kg of bamboo leaves to be discarded at a farm in Japan from Gifu Prefecture (Gifu Prefecture), dried it with a dryer (Vibron manufactured by Okawara Seisakusho Co., Ltd.), and pulverized by Nara Machinery Co., Ltd. It was pulverized with goblin to obtain 5 kg of pulverized bamboo leaves.

5 kg of this kneaded pulverized product was put into a cylinder, and 500 g of gallic acid manufactured by Iwate Chemical Co., Ltd. was added together with 10 L of purified water. To this, 50 g of lipase F-AP15 manufactured by Amano Enzyme Co., Ltd. as a lipase for transesterification was dissolved in purified water and added.

This was equipped with a heating machine (manufactured by Fuji Mac, cast heater), and stirred at a temperature of 20 ° C. for 6 hours at a stirring speed of 45 times per minute using a stirring device.

After heating, the mixture was cooled with water and filtered through filter paper to obtain a filtrate. This filtrate was applied to TI-700 type manufactured by Nippon Trim Co., Ltd. to obtain an alkali-reduced solution.

This solution was lyophilized with a freeze dryer manufactured by Nippon FD Co., Ltd., to obtain 778 g of ursoic acid derivative ursoic acid galonate as a powder.

Hereinafter, the purification of ursoic acid betainate will be described.

  20 g of ursoic acid betainate powder obtained in Example 1 was dissolved in 200 mL of 10% ethanol. Diaion (manufactured by Mitsubishi Chemical) suspended in 10% ethanol in advance was packed in a glass column.

The column was supplied with an ursoic acid betainate solution and flushed with 1 L of 10% ethanol. Furthermore, 1 L of 30% ethanol solution was flowed.

Subsequently, 1 L of 50% ethanol solution was flowed, and this fraction was collected.

This fraction was subjected to a vacuum dryer (manufactured by Toyo Riko Co., Ltd.) and dried to obtain 1.3 g of purified ursoic acid betainate as a powder. This was used as the sample of Example 4.

Hereinafter, purification of ursoic acid gamma-aminobutyrate will be described.

  20 g of the powder of gamma-aminobutyrate ursolate obtained in Example 2 was dissolved in 200 mL of 20% ethanol. Diaion (manufactured by Mitsubishi Chemical) suspended in 20% ethanol in advance was packed into a glass column.

This column was supplied with the above-described uric acid gamma-aminobutyrate solution and flushed with 1 L of 20% ethanol. Furthermore, 1 L of 30% ethanol solution was flowed.

Next, 1 L of 50% ethanol solution was flowed. 1 L of 70% ethanol solution was flowed, and this fraction was collected.

This fraction was subjected to a vacuum dryer (manufactured by Toyo Riko) and dried to obtain 2.1 g of ursoic acid gamma-aminobutyrate as a powder. This was used as the sample of Example 5.

Hereinafter, purification of ursoic acid galonate will be described.

  20 g of ursoic acid galonate powder obtained in Example 3 was dissolved in 200 mL of 20% ethanol. Diaion (manufactured by Mitsubishi Chemical) suspended in 20% ethanol in advance was packed into a glass column.

The column was supplied with a uronic acid galonate solution and flushed with 1 L of 20% ethanol. Further, 1 L of a 30% ethanol solution was flowed, and this fraction was collected.

This fraction was subjected to a vacuum dryer (manufactured by Toyo Riko) and dried to obtain 2.4 g of ursoic acid galonate as a powder. This was used as the sample of Example 6.

Below, the identification test of a ursoic acid derivative is demonstrated.
(Test Example 1)

The samples of Examples 1, 2, 3, 4, 5, and 6 obtained as described above were dissolved in purified ethanol, and a high performance liquid chromatography equipped with a mass spectrometer (HPLC, Shimadzu) And further analyzed with a nuclear magnetic resonance apparatus (NMR, manufactured by Bruker, AC-250).

As a result, from the sample of Example 1, ursoic acid betainate was identified as the ursoic acid derivative, and the content thereof was 23.1%.

Moreover, from the sample of Example 2, ursoic acid gamma-aminobutyrate was identified as the ursoic acid derivative, and the content thereof was 28.9%.

From the specimen of Example 3, ursoic acid galonate was identified as the ursoic acid derivative, and its content was 29.2%.

From the specimen of Example 4, ursoic acid betainate was identified as the ursoic acid derivative, and the content thereof was 79.3%.

From the sample of Example 5, ursoic acid gamma-aminobutyrate was identified as the ursoic acid derivative, and its content was 81.3%.

From the specimen of Example 6, ursoic acid galonate was identified as the ursoic acid derivative, and its content was 80.7%.

Below, the ursic acid derivative obtained by fermentation of rosemary, betaine, soybean ground material, and Bacillus natto will be described.

After obtaining rosemary cultivated in the United States in a fresh state, it is dried with a dryer (manufactured by Kawasaki Kiko, shelf type dryer), and further pulverized with a crusher (manufactured by Nara Machinery Co., Ltd., Super Free Mill). 1 kg of crushed rosemary was obtained. This was heated to 25 ° C., 1 kg of this rosemary pulverized product was added to the cylinder to which 10 L of purified water was added, and 50 g of Nitten Betaine made by Nippon Sugar Sugar Co., Ltd. was added.

To this was added 5 kg of soybean pulverized soybeans pulverized with a soybean crusher (manufactured by Nara Machinery Co., Ltd., Super Free Mill), and 10 g of natto bacteria from Natto Motopo was added. Stir.

This was equipped with a warmer, and stirred at a temperature of 32 ° C. for 48 hours at a stirring speed of 30 times per minute using a stirring device.

After heating, the mixture was cooled with water and filtered through filter paper to obtain a filtrate. The obtained filtrate was subjected to TI-700 type manufactured by Nippon Trim Co., Ltd. to obtain an alkali reduced solution.

This solution was freeze-dried by a freeze dryer manufactured by Nippon FD Co., Ltd., to obtain 59 g of ursanoic acid derivative as a powder.

Hereinafter, the purification of the ursoic acid derivative will be described.

  10 g of the ursoic acid derivative powder obtained in Example 7 was dissolved in 100 mL of 10% ethanol. Diaion (manufactured by Mitsubishi Chemical) suspended in 10% ethanol in advance was packed in a glass column.

The column was supplied with a gamma-aminobutyrate ursoate solution and flushed with 1 L of 10% ethanol. Furthermore, 1 L of 30% ethanol solution was flowed.

Next, 1 L of 50% ethanol solution was flowed. 1 L of 70% ethanol solution was flowed, and each fraction was collected.

Each fraction was subjected to a vacuum dryer (manufactured by Toyo Riko), dried, 10% ethanol fraction from ursoic acid betainate and ursoic acid cinnamate, 30% ethanol fraction from ursoic acid galonate and ursoic acid para-coumaronate, In addition, ursoic acid gamma-aminobutyrate and uric acid eicosapentaate were obtained from the 70% ethanol fraction.

Below, the identification test of a ursoic acid derivative is demonstrated.
(Test Example 2)

The samples of Examples 7 and 8 obtained as described above were dissolved in purified ethanol, analyzed by high performance liquid chromatography with a mass spectrometer (HPLC, Shimadzu Corporation), and further a nuclear magnetic resonance apparatus (NMR, Bruker). Manufactured by AC-250).

As a result, from the sample of Example 7, ursoic acid betainate, ursoic acid cinnamate, ursoic acid gamma-aminobutyrate, ursoic acid para-coumaronate, ursoic acid eicosapentaate and ursoic acid galonate were identified from the specimen of Example 7. It was. The respective contents were 8.3%, 3.4%, 8.1%, 4.4%, 0.9% and 6.7%.

From the 10% ethanol fraction purified from the specimen of Example 8, ursoic acid betainate and ursoic acid cinnamate were identified, and the respective contents were 64.7% and 12.8%.

From the 30% ethanol fraction purified from the specimen of Example 8, ursoic acid galonate and ursoic acid para-coumaronate were identified, and the contents were 66.1% and 9.3%, respectively.

Ursic acid gamma-aminobutyrate and uric acid eicosapentaate were identified from the 70% ethanol fraction purified from the specimen of Example 8, and the respective contents were 67.1% and 3.4. %Met.

Hereinafter, experiments using human skin-derived fibroblasts will be described. This is a test method for evaluating the activation effect by using fibroblasts derived from human skin.
(Test Example 3)

Normal human adult dermal fibroblasts (Fibrocell NHDF (AD), manufactured by Kurabo Corp.) were cultured in a dedicated culture solution, and were used in Example 1, Example 2, Example 3, Example 4, Example 5, and Example. 6 and the sample obtained in Example 7 were dissolved in dimethyl sulfoxide (manufactured by Wako Pure Chemical Industries, Ltd.), 0.1 mg of each was added, and cultured at 37 ° C. for 48 hours.

Dimethyl sulfoxide was used as a solvent control. As a positive control, fibroblast growth factor (FGF, manufactured by Cosmo Bio) was dissolved in purified water and 0.1 mg was added. The number of cells was counted, and the amount of collagen was further observed by an antibody method (manufactured by Chondrex).

As a result, regarding the cell number, the value of 0.1 mg of the sample of Example 1, Example 2, Example 3, Example 4, Example 5, Example 6, and Example 7 with respect to the value of the solvent control is 176%, 167%, 170%, 283%, 264%, 288% and 176%, respectively, and all specimens showed fibroblast proliferation.

Since the addition of 0.1 mg of the positive control FGF was 159% with respect to the value of the solvent control, Example 1, Example 2, Example 3, Example 4, Example 5, Example The samples of 6 and Example 7 were found to exhibit fibroblast proliferation stronger than FGF.

Regarding the amount of collagen, the value of 0.1 mg of the sample of Example 1, Example 2, Example 3, Example 4, Example 5, Example 6, and Example 7 with respect to the solvent control value is 201, respectively. %, 218%, 206%, 320%, 317%, 308%, and 244%, and all specimens showed an increasing action of collagen.

Since the addition of 0.1 mg of the positive control FGF was 187% with respect to the value of the solvent control, Example 1, Example 2, Example 3, Example 4, Example 5, Example It was found that the samples of 6 and Example 7 showed a stronger collagen increasing action than FGF.

Below, the food formulation which consists of a ursoic acid derivative is demonstrated.

10 L of purified water was added to a clean cylinder and heated to 20 ° C. To this, 1 kg of the specimen obtained in Example 7 was added, and further 1 kg of glucosamine manufactured by Yaizu Suisan Chemical Industry and 1 kg of chondroitin sulfate manufactured by Seikagaku Corporation were added. This was stirred at a rate of 10 times / minute and heated to 20 ° C. for 6 hours. This was cooled and subjected to a dryer to obtain 2.8 kg of a composition.

Mixer for food (NV type, manufactured by Nishimura Seisakusho) 1 kg of the above composition, 10 g of green tea extract, 30 g of stevia powder (manufactured by Daiei Work), 1.8 kg of edible cellulose (manufactured by Asahi Kasei), ascorbic acid (manufactured by Takeda Foods) ) 0.1 g was added and mixed.

This was filled into 300 mg each of porcine gelatin-derived No. 1 capsules (manufactured by Capsugel) by a conventional method to obtain a food preparation. This was designated as the food preparation of Example 9.

Below, the test of the food formulation which consists of a ursoic acid derivative is demonstrated.
(Test Example 4)
Five males presenting scabs and honeyworms with cedar pollens aged 40 to 60 years were fed with 2 g of the food preparation obtained in Example 9 once a day for 14 days. The reactivity with cedar pollen was observed before feeding and on the 14th day of feeding. Furthermore, blood was collected before feeding and on the 14th day of feeding, and the IgE amount and blood interleukin 6 amount were measured by an immunoantibody method.

As a result, after eating the food preparation of Example 9, the number of expression of scabs and catfish by cedar pollen was 40% on average compared to before feeding, and a reactive phenomenon was observed. Furthermore, the amount of IgE in the blood was 45% on average as compared to that before feeding, and a decrease in the amount of IgE was observed.

Further, the amount of interleukin 6 in the blood was 67% after ingestion of the food preparation of Example 8 and before ingestion, and a decrease in the amount of interleukin 6 was observed.

As a result of these, the intake of the food preparation of Example 9 caused mild symptoms of hay fever, and the amount of IgE and interleukin 6 as an index of inflammation also decreased. Therefore, the food preparation of Example 9 was It was found to exhibit an anti-inflammatory effect and a hay fever suppression effect.

There was no change in the physical condition due to the intake of food preparations, and no side effects were observed in the blood test, other blood biochemical tests, and urinalysis.

Next, cosmetics composed of ursoic acid derivatives will be described.

1 kg of natural laboratories coconut oil was added to a clean stainless steel cylinder, and 100 g of the ursoic acid derivative obtained in Example 7 was added thereto. Furthermore, 5 g of vitamin C manufactured by Takeda Pharmaceutical Co., Ltd. and 100 g of soybean fermented extract manufactured by Toyo Fermentation were added. This was heated to 16 ° C., stirred at a rate of 20 times per minute for 6 hours, and dried under reduced pressure to obtain 1.8 kg of a composition containing a ursonic acid derivative.

In a small mixer (made by Hosokawa powder), 10 g of polyethylene glycol monostearate, 10 g of lipophilic glyceryl monostearate, 20 g of horse oil ester and 30 g of oleic acid were heated and dissolved. To the obtained solution, 200 g of the above-mentioned composition containing the ursoic acid derivative, 20 g of propylene glycol, 1 g of dipotassium glycyrrhizinate, 1 g of α-tocopherol and 700 g of purified water were added. These were dissolved and then cooled to obtain a cosmetic liquid.

On the other hand, a cosmetic liquid consisting only of a base material excluding the composition containing the above ursoic acid derivative was produced and prepared as a control sample.

Below, the test of the cosmetics which consist of a ursoic acid derivative is demonstrated.
(Test Example 5)
Using the cosmetic solution obtained in Example 10, wrinkle improvement and inflammation improvement tests for ultraviolet rays were conducted on 6 women aged 41 to 68 years. That is, the cosmetic liquid of Example 10 was applied to the face portion at a rate of 1 g per day for 7 days.

Further, the woman was exposed to sunlight from 13:00 to 14:00. Before use and 7 days after use, the skin surface horny layer moisture content measuring device (IBBS, SKICON200) is used, and the skin elasticity and wrinkle length per unit area are measured using a elasticity meter (Cutometer). Was measured. Furthermore, the amount of prostaglandin E2, which is an inflammatory substance contained in sweat, was measured by an immunoenzymatic method (manufactured by Cayman).

As a result, compared to sunlight irradiation before use, after use of Example 10, the skin surface horny layer moisture content was 189% after use of Example 10.

Further, the elasticity of the elasticity meter was 176% after using Example 10 as compared to before using.

Furthermore, the length of the wrinkles was 70% as compared with that before use, and wrinkle reduction was observed.

In addition, the amount of prostaglandin E2 was reduced to 78% compared to before use.

On the other hand, there was no particular problem with the feeling of use.

As a result, the cosmetic liquid obtained in Example 10 was found to have an anti-inflammatory action, a water increasing action, a wrinkle improving effect, and an inflammatory substance suppressing action.

In addition, in the cosmetic liquid comprising only the base material excluding the composition containing the ursoic acid derivative, none of the anti-inflammatory action, the water increasing action, the wrinkle improving effect, and the inflammatory substance suppressing action were observed.

Next, an anti-inflammatory agent composed of a ursoic acid derivative will be described.

To a clean stainless steel dissolution tank, 50 g of the ursoic acid derivative obtained in Example 4 above, 300 g of lanolin, 200 g of macro gold, 20 g of beeswax and 30 g of ozokerite were added and dissolved for 1 hour. This was supplied to a kneader and mixed. This was dissolved again in a dissolution tank, heated, and deaerated with a deaerator to obtain the desired anti-inflammatory agent as an ointment.

  As a control, a control sample obtained by replacing the ursoic acid derivative obtained in Example 4 with lanolin was obtained as a control sample.

Below, the test of the anti-inflammatory agent which consists of a ursoic acid derivative is demonstrated.
(Test Example 6)
The anti-inflammatory agent obtained in the above-mentioned Example 11 was applied to the 21-year-old male with 48-73 years old chronic arthritis at 2 g once a day for 14 days. Prior to application and on the 14th day of application, the condition of the joints was observed. Furthermore, blood was collected before application and on the 14th day of application, and the amount of interleukin 6 in the blood was measured by an immunoantibody method.

As a result, after applying the anti-inflammatory agent of Example 11 for 14 days, the arthritis symptom became mild in 17 of 21 cases, and the improvement rate was 81%.

In the base material group consisting of only the base materials, the improvement rate was 0%.

Further, the amount of interleukin 6 in the blood was 56% after applying the anti-inflammatory agent of Example 11 and before application, and a decrease in the amount of interleukin 6 was observed. In addition, in the base material group which consists only of base materials, it is 95% of the value before application | coating, and the change was not recognized.

As a result, the application of the anti-inflammatory agent of Example 11 reduced the arthritis symptoms and decreased interleukin 6 as an inflammatory cytokine. Therefore, the anti-inflammatory agent of Example 11 exhibits a strong anti-inflammatory effect. It has been found.

There was no secondary change in physical condition due to the use of this anti-inflammatory agent, and no side effects were observed in the blood test, other blood biochemical tests, and urinalysis.

Ursolic acid derivatives exhibiting a collagen-increasing action according to the present invention exhibit a collagen-increasing action by a complex mechanism of increasing collagen, stimulating fibroblast proliferation, and inhibiting collagenase. Yes, it is used in various areas.

In addition, the ursoic acid derivative exhibiting the collagen-increasing action of the present invention exhibits an excellent anti-inflammatory action with weak side effects, so it is used in foods that increase collagen, cosmetics that prevent wrinkles, medical fields that suppress inflammation, etc. It is expected to contribute to the development of food, cosmetics and medical fields.

The ursoic acid derivative exhibiting the collagen-increasing action of the present invention effectively uses bamboo leaves disposed as industrial waste, and reduces the waste to nurture a new industry that produces useful substances. Can also contribute.

Food preparations composed of ursoic acid derivatives that increase collagen activity are highly safe for humans, animals, and pets, and can improve or develop arthritis, rhinitis, hay fever, bronchitis, colds, etc. It contributes to the improvement of the quality of people's lives.

Furthermore, cosmetics composed of ursoic acid derivatives exhibiting a collagen-increasing action show an effect of improving or preventing wrinkles by increasing the amount of collagen, and improve the quality of life of women, particularly elderly people.

In addition, according to the anti-inflammatory agent composed of a ursoic acid derivative exhibiting an action of increasing collagen, various inflammations can be improved or prevented, and the national life is improved.

Claims (8)

Ursoic acid derivative exhibiting collagen increasing action represented by the following formula (1).

X is one selected from betaine, gamma-aminobutyric acid, gallic acid, eicosapentaenoic acid, cinnamic acid, and para-coumaric acid. 2. The derivative according to claim 1, wherein betaine is added to the pulverized product of bamboo leaves, and the reaction product obtained by alkali reduction of the reaction product added with lipase for transesterification is heated to the following: Ursoic acid derivative exhibiting collagen increasing action represented by formula (2).

The derivative according to claim 1, wherein gamma-aminobutyric acid is added to the pulverized bamboo leaf, and the reaction product heated by adding lipase for transesterification is reduced with alkali. A ursoic acid derivative which exhibits an increase in collagen activity represented by the following formula (3), which is aminobutyric acid.

2. The derivative according to claim 1, wherein X is gallic acid obtained by adding gallic acid to the pulverized bamboo leaf and adding the lipase for transesterification to heat the reaction product. Ursoic acid derivative exhibiting collagen increasing action represented by the following formula (4).

The collagen increase according to claim 1, claim 2, claim 3, or claim 4 obtained by alkali reduction of a fermented product obtained by adding a fermented product of fermented crushed product of rosemary, betaine, crushed soybean and natto. Ursoic acid derivative that exhibits action. Claim 1 or claim 2 or claim 3 or claim 4 or claim 5 ursanoic acid derivative exhibiting collagen increasing action 1 weight, glucosamine 0.3 to 3 weight, chondroitin sulfate 0.2 to 2 weight. A food preparation comprising a composition obtained by adding, stirring and heating. Claim 1 or claim 2 or claim 3 or claim 4 or claim 5 ursanoic acid derivative exhibiting collagen increasing action 1 weight, vitamin C 0.01 to 0.1 weight, soybean fermented extract 0.2 to A cosmetic comprising a composition obtained by adding 2% by weight, stirring and heating. The anti-inflammatory agent which consists of a ursoic acid derivative which exhibits the collagen increase effect | action of Claim 1 or Claim 2 or Claim 3 or Claim 4 or Claim 5.