JP5426844B2 - Biological collagen synthesis promoter - Google Patents

Description

  The present invention relates to a collagen synthesis promoter containing a pine bark extract and collagen and enhancing the ability of promoting collagen synthesis in vivo.

  Collagen is the main structural protein of the biological skeleton that occupies about 30% of the biological protein, plays an important role in maintaining the structure as a supporting tissue of the living body, and also exists in many tissues to protect cells and protect intercellular factors. It plays important physiological roles such as cell binding. In this way, collagen, which has an important role in the living body, also decreases with the decline in metabolism due to aging, and various disorders, diseases, and diseases associated with aging changes such as progress of aging and delayed recovery of diseases and chronic diseases. It is thought to cause etc. In particular, skin aging is likely to progress, and signs of aging are likely to be observed. Wrinkles and tarmi, which symbolize skin aging, are caused by a decrease in skin elasticity and flexibility, and such skin aging is based on a decrease in collagen.

  In addition, when a tissue is injured, a repair reaction takes place in vivo, and in the case of skin ulcers, granulation is formed, and in the case of fracture, tissue reconstruction such as callus formation occurs. These reconstructions are also deteriorated in the state of decreased metabolism, and by activating metabolism in the body and enhancing the process of tissue reconstruction, intractable skin diseases such as pressure sores, diabetic vascular ulcers or senile It can promote healing of fractures and bone defects.

  Furthermore, collagen is also important as a component constituting bone together with calcium, and it has been recognized that collagen synthesis needs to be active in order to form strong bone, and is also important for prevention of osteoporosis.

  Under such circumstances, compositions having a collagen production enhancing action have been proposed (for example, Patent Documents 1 and 2). Moreover, the present inventors have already found that the amount of collagen in the skin is enhanced by orally ingesting the pine bark extract (for example, Patent Document 3).

JP-T-60-500095 JP-A-7-2699 JP 2003-146899 A

  An object of the present invention is to provide a living body collagen synthesis promoter capable of enhancing the ability of in vivo collagen synthesis.

As a result of intensive studies to solve the above problems, the present invention contains pine bark extract and collagen in a weight ratio of 1:10 to 1: 200 , and further contains CaHPO ₄ .2H ₂ O, NaCl, MgO. , and found a synthesis promoting effect of the biological collagen by containing ZnCO _3.

  According to the present invention, it is possible to promote in vivo collagen synthesis, improve tissue synthesis ability, and improve functional deterioration such as tissue damage, disease, fatigue and the like with aging. Furthermore, it can be expected to be effective for various skin acne such as pressure sores, osteoporosis and the like.

  Hereinafter, embodiments of the present invention will be described. In addition, this invention should not be limited and interpreted by description of the following embodiment, A various change is possible within the range of description in a claim.

  The biological collagen synthesis promoter of the present invention contains a pine bark extract and collagen, and at least one selected from calcium or a compound thereof, sodium or a compound thereof, magnesium or a compound thereof, zinc or a compound thereof It is characterized by containing these components.

(Composition of pine bark extract)
The pine bark extract used in the present invention contains proanthocyanidins as one of the main active ingredients. Proanthocyanidins refer to a group of compounds consisting of a condensation polymer having a degree of polymerization of 2 or more, with flavan-3-ol and / or flavan-3,4-diol as a structural unit. It is a powerful antioxidant produced by plants and is intensively contained in plant leaves, bark, fruit peel and seeds. This proanthocyanidin is a substance that cannot be produced in the human body.

When a pine bark extract containing this proanthocyanidin is ingested, an excellent effect of improving lipid metabolism is obtained. The pine bark extract contains a condensed polymer having a polymerization degree of 2 or more as proanthocyanidins, and further contains catechin and the like. In particular, proanthocyanidins containing a large amount of a condensation polymer having a low degree of polymerization are preferably used. The condensation polymer having a low polymerization degree is preferably a condensation polymer having a polymerization degree of 2 to 30 (2 to 30 mer), more preferably a condensation polymer having a polymerization degree of 2 to 10 (2 to 10 mer). Further, a condensation polymer (2 to 4 mer) having a polymerization degree of 2 to 4 is more preferable. Proanthocyanidins that are condensation polymers having a degree of polymerization of 2 to 4 (2 to 4 mer) are particularly easily absorbed into the body. In the present specification, the polymer having a degree of polymerization of 2 to 4 is referred to as oligomeric proanthocyanidin (hereinafter referred to as “OPC”).

  Moreover, as a pine bark extract, 15% by mass, preferably 20% by mass or more, and more preferably 30% by mass of a condensation polymer having a degree of polymerization of 2 to 4 (2 to 4 mer; that is, OPC). An extract containing a pentamer or more proanthocyanidins in a proportion of 10% by mass or more, preferably 15% by mass or more is preferable.

  The pine bark extract may further contain catechins, and these catechins are preferably contained in a proportion of 5% by mass or more, more preferably 10% by mass or more. Catechin can be extracted together with proanthocyanidins (OPC) by the above extraction method. Catechin is a general term for polyhydroxyflavan-3-ol. As catechins, (+)-catechin (referred to as catechin in a narrow sense), (−)-epicatechin, (+)-gallocatechin, (−)-epigallocatechin, epigallocatechin gallate, epicatechin gallate, and afzelechin Etc. are known. In addition to the above (+)-catechin, gallocatechin, afzelekin, and (+)-catechin or 3-galloyl derivatives of gallocatechin have been isolated from the pine bark extract. Catechins are known to have a carcinogenic inhibitory effect, an active oxygen and free radical scavenging effect, and an antioxidant effect. In addition, catechins are known to have an antidiabetic effect that suppresses an increase in blood sugar. Catechins are poor in water solubility by themselves and have low physiological activity, but in the presence of OPC, catechins have the property of being activated at the same time as water solubility increases. Therefore, catechins work effectively when ingested with OPC.

  The catechins are preferably contained in the pine bark extract in an amount of 5% by mass or more. More preferably, the pine bark extract containing 20% by mass or more of OPC and 10% by mass or more of a pentamer or more of proanthocyanidins preferably contains 5% by mass or more of catechins. For example, when the catechin content of the pine bark extract is less than 5% by mass, the catechins may be added so that the content is 5% by mass or more. It is most preferable to use a pine bark extract containing 5% by mass or more of catechins, 20% by mass or more of OPC, and 10% by mass or more of proanthocyanidins of 5 or more.

(Pine bark extract)
Pine bark extracts used in the present invention include Pinus Martina, larch, Japanese black pine, Japanese red pine, Japanese pine, Japanese pine, Korean pine, Japanese pine, Ryukyu pine, Utsukushima, Japanese pine, white pine, Canadian Quebec region A bark extract such as Aneda is preferably used. Among these, a bark extract of French coastal pine is preferably used.

  French coastal pine is a marine pine that grows on the Atlantic coast of southern France. The bark of this French coastal pine contains organic acids and other physiologically active components in addition to containing proanthocyanidins, which are flavonoids, as main components. This main component, proanthocyanidins, is known to have a strong antioxidant action to remove active oxygen.

  The pine bark extract is obtained by extracting the pine bark with water or an organic solvent. When water is used, warm water or hot water is used. As an organic solvent used for extraction, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, butane, acetone, hexane, cyclohexane, propylene glycol, hydrous ethanol, hydrous propylene glycol, ethyl methyl ketone, Organic solvents that are acceptable for the production of food or drugs such as glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane, edible oils and fats, 1,1,1,2-tetrafluoroethane, 1,1,2-trichloroethene Preferably used. These water and organic solvents may be used alone or in combination. In particular, hot water, hydrous ethanol, hydrous propylene glycol and the like are preferably used.

  The extraction method from pine bark is not particularly limited, and for example, a warm extraction method, a supercritical fluid extraction method, or the like is used.

  The supercritical fluid extraction method is a method of performing extraction using a supercritical fluid that is a fluid that exceeds the critical point (critical temperature, critical pressure) of a gas-liquid substance. As the supercritical fluid, carbon dioxide, ethylene, propane, nitrous oxide (laughing gas) or the like is used, and carbon dioxide is preferably used.

  In the supercritical fluid extraction method, an extraction process for extracting a target component with a supercritical fluid and a separation process for separating the target component and the supercritical fluid are performed. In the separation step, any one of extraction separation by pressure change, extraction separation by temperature change, and extraction separation using an adsorbent / absorbent may be performed.

  Moreover, you may perform supercritical fluid extraction by the entrainer addition method. In this method, for example, ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, and ketones are added to the extraction fluid in an amount of 2 to 20 W / V. Add about% and perform supercritical fluid extraction using this fluid to dramatically increase the solubility of the target extract, such as OPC and catechins, in the extraction solvent, or enhance the selectivity of the separation. This is a method for obtaining an efficient pine bark extract.

  Since the supercritical fluid extraction method can be operated at a relatively low temperature, it can be applied to substances that are altered or decomposed at high temperatures, the advantage that the extraction fluid does not remain, and the recycling of the solvent is possible. There is an advantage that the process can be omitted and the process becomes simple.

  Extraction from pine bark may be performed by a liquid carbon dioxide batch method, a liquid carbon dioxide reflux method, a supercritical carbon dioxide reflux method, or the like other than the above extraction method.

  For extraction from pine bark, a plurality of extraction methods may be combined. By combining a plurality of extraction methods, it becomes possible to obtain pine bark extracts having various compositions.

  The pine bark extract obtained by the above extraction is safe to be purified by ultrafiltration or a column method or a batch method using an adsorptive carrier (Diaion HP-20, Sephadex-LH20, chitin, etc.). From the viewpoint of

  Specifically, the pine bark extract used in the biological collagen synthesis promoter of the present invention is prepared by the following method, but this is illustrative and is not limited to this method.

  1 kg of French coastal pine bark is placed in 3 L of a saturated aqueous solution of sodium chloride and extracted at 100 ° C. for 30 minutes to obtain an extract (extraction process). Thereafter, the extract is filtered, and the resulting insoluble matter is washed with 500 mL of a saturated solution of sodium chloride to obtain a washing solution (washing step). The extract and washing solution are combined to obtain a crude extract of pine bark.

  Next, 250 mL of ethyl acetate is added to the crude extract and the phases are separated, and the process of recovering the ethyl acetate layer is repeated 5 times. The collected ethyl acetate solutions are combined and added directly to 200 g of anhydrous sodium sulfate for dehydration. Thereafter, the ethyl acetate solution is filtered, and the filtrate is concentrated under reduced pressure until the original volume is reduced to 1/5. The concentrated ethyl acetate solution is poured into 2 L of chloroform, and the resulting precipitate is collected by filtration. Thereafter, the precipitate is dissolved in 100 mL of ethyl acetate, and then added again to 1 L of chloroform and precipitated for washing twice. By this method, for example, about 5 g of pine bark extract containing 20% by mass or more of proanthocyanidins having a degree of polymerization of 2 to 4 and 5% by mass or more of catechins is obtained. Here, the content of the specific component in the extract is a value based on the dry mass of the extract. The same applies hereinafter.

(collagen)
Collagen as referred to in the present invention is a generic term for fibrous hard proteins constituting the living body of animals and includes soluble proteins obtained by hydrolyzing them, and the base animal is a land animal. Regardless of aquatic animals. Specific examples of animals that can be used as a source include terrestrial animals such as cattle, pigs, and sheep, and aquatic animals such as fish. Preferred examples include those obtained by extracting the skeletal proteins of these animals with an aqueous carrier or hydrolyzing with a protease or the like and then extracting the soluble portion. Particularly preferred are those based on fish, hydrolyzed and solubilized. Moreover, a preferable molecular weight is 10,000 or less as an average molecular weight, More preferably, it is 5000 or less. This is because if the average molecular weight is too large, the mouth-solubility is inhibited and it may be difficult to swallow. In order to obtain collagen having such an average molecular weight, it is preferable to reduce the molecular size by hydrolysis and adjust the molecular weight distribution by ultrafiltration or the like as desired. Since such collagen already exists for food and is commercially available, it can also be used.

(Biogenic collagen synthesis promoter of the present invention)
The biological collagen synthesis promoter of the present invention contains a pine bark extract and collagen, and the proportion thereof is 10 to 250 parts by weight, preferably 10 to 200 parts by weight, with respect to 1 part by weight of the pine bark extract. Parts, more preferably 10 to 100 parts by weight.
Further, at least one component selected from calcium or a compound thereof, sodium or a compound thereof, magnesium or a compound thereof, zinc or a compound thereof is blended.

  The amount of the pine bark extract in the preparation of the present invention is not particularly limited, but is usually 0.001 to 0.5% by weight, preferably 0.01 to 0.1% by weight, based on the whole preparation. .

  The amount of collagen in the preparation of the present invention is not particularly limited, but is usually 0.1 to 20% by weight, preferably 0.5 to 10% by weight, based on the whole preparation.

  The biological collagen synthesis promoter of the present invention can be appropriately prepared by known methods in the form of solids or solutions such as tablets, pills, capsules, granules, powders, powders, softeners, gels, gels, and liquids. . That is, a solid preparation or a liquid preparation useful as the preparation of the present invention is produced by mixing a pine bark extract and collagen and, if desired, an additive and using a well-known well-known preparation method. . Examples of additives include excipients, pH adjusting agents, cooling agents, suspending agents, diluents, antifoaming agents, thickeners, solubilizers, disintegrating agents, binders, lubricants, antioxidants. Agents, coating agents, coloring agents, flavoring agents, surfactants, plasticizers or fragrances.

    Examples of the excipient include sugar alcohols such as D-sorbitol, D-mannitol or xylitol, sugars such as glucose, sucrose, lactose or fructose, crystalline cellulose, carmellose sodium, calcium hydrogen phosphate, wheat starch, rice Examples thereof include starch, corn starch, potato starch, dextrin, β-cyclodextrin, light anhydrous silicic acid, titanium oxide, and magnesium aluminate metasilicate.

  Examples of the pH adjuster include citric acid, malic acid, sodium hydrogen phosphate, and dipotassium phosphate.

  Examples of the refreshing agent include l-menthol or mint water.

  Examples of the suspending agent include kaolin, carmellose sodium, xanthan gum, methylcellulose, and tragacanth.

  Examples of the diluent include purified water, ethanol, vegetable oil, and emulsifier.

  Examples of the antifoaming agent include dimethylpolysiloxane or silicon antifoaming agent.

  Examples of the thickener include xanthan gum, tragacanth, methylcellulose, and dextrin.

  Examples of the solubilizer include ethanol, sucrose fatty acid ester, and macrogol.

  Examples of the disintegrant include low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, hydroxypropyl starch, or partially pregelatinized starch.

  Examples of the binder include methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethylcellulose, polyvinyl alcohol, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, or propylene glycol alginate. Can be mentioned.

  Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax and white beeswax.

  Examples of the antioxidant include ascorbic acid, dibutylhydroxytoluene (BHT), propyl gallate, butylhydroxyanisole (BHA), and citric acid.

  Examples of the coating agent include hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer. , Hydroxypropyl methylcellulose acetate succinate, methacrylic acid copolymer, polyvinyl acetate diethylaminoacetate or shellac.

  Examples of the colorant include turmeric extract, riboflavin, and titanium oxide.

  Examples of the flavoring agent include citric acid, adipic acid, fructose, D-sorbitol, glucose, sodium saccharin, simple syrup, sucrose, honey, amacha, licorice, citric acid, adipic acid, orange oil, spruce tincture, fennel oil, mint Or menthol.

  Examples of the surfactant include polyoxyethylene hydrogenated castor oil, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene polyoxypropylene, polysorbates, sodium lauryl sulfate, macrogol or sucrose. Examples include fatty acid esters.

  Examples of the plasticizer include triethyl citrate, polyethylene glycol, triacetin, and cetanol.

  As said fragrance | flavor, synthetic fragrance | flavors, such as natural fragrance | flavors, such as an animal fragrance | flavor or a vegetable fragrance | flavor, or an isolated fragrance | flavor etc. are mentioned, for example.

Hereinafter, the present invention will be described with reference to examples, but it goes without saying that the present invention is not limited to these examples. Of the following Examples 1 to 7, Examples 1 and 4 to 7 are reference examples and are outside the scope of the present invention.

(Tissue synthesis ability recovery experiment)
In the present invention, a measurement experiment was conducted on the recovery effect of tissue repair ability and collagen synthesis ability by the formalin filter paper method (FFP method: A. Tanaka et al, Endocrinol, Japan. 1960 (4) 357-364). The present invention is based on the report of Rao et al. (Rao et al, Heater Science, Vol. 33 (1) 1986, 1-7). The influence of the biological collagen synthesis promoter of the present invention is examined.
(1) Experimental animals Wistar male rats of 5 weeks old were used as 5 to 9 animals per group after preliminary breeding for 8 to 9 days.
(2) Feed The feed and drinking water shown in Table 1 were freely ingested. The mixed vitamins in Table 1 are the mixtures in Table 2. The sample solution was forcibly orally administered once a day using a stomach tube until the end of the experiment.

(Table 1)

(Table 2)

(3) Evaluation of FFP method Three weeks from the start of the experiment, under a ether anesthesia, filter paper (filter paper No. 26, manufactured by Toyo Roshi Kaisha, Ltd.) with a diameter of 6 mm and a weight of 10 mg soaked with 20 μL of 7% formalin was applied to the back of the rat. It was buried in 4 subcutaneous sites. After breeding for 1 week, ether was lethal, and granulation tissue immediately surrounding the filter paper was removed, and the granulation weight was measured, which was used as an index of collagen synthesis ability and rat tissue repair ability.
The results of the above experiment are shown in Tables 3 and 4.
According to Tables 3 and 4, the pine bark extract and collagen are combined at 1:10 to 1: 250, and at least one component selected from a calcium compound, sodium compound, magnesium compound, and zinc compound is administered. However, the effect of promoting granulation was observed.

(Table 3)

(Table 4)

INDUSTRIAL APPLICABILITY The present invention can provide a biological collagen synthesis promoter that can dramatically improve the ability to synthesize collagen in a living body.

Claims (2)

Containing a pine bark extract and collagen in a weight ratio of 1:10 to 1: 200 ,
_{Furthermore, CaHPO 4 · 2H 2 O,} NaCl, MgO, and, characterized in that it contains a ZnCO _3, the biological collagen synthesis promoter.   The bio-collagen synthesis promoter according to claim 1, comprising a pine bark extract and collagen in a weight ratio of 1:10 to 1: 100.