TW201636037A - Composition comprising ginseng berry extracts for improved ovarian aging - Google Patents

Abstract

Disclosed is a composition comprising ginseng berry extracts for improved ovarian aging which has a particular effect on suppressing ovarian aging by increasing follicular number. The composition of the present invention inhibits the exhaustion of follicular by aging, thus can be used for preventing premature ovarian failure and delaying menopause.

Description

Composition comprising ginseng fruit extract for improving ovarian aging

The present invention relates to a composition comprising ginseng fruit extract for improving ovarian aging, and more particularly to a method for improving ovarian aging to delay menopause and prevent early amenorrhea by increasing the number of ovarian ovarian cells by ginseng fruit ingredients. A composition comprising a ginseng fruit extract.

Ginseng is a perennial semi-negative medicinal food belonging to the Panax family of Araliaceae. In 1843, the Russian botanist CAMeyer synthesized the Greek word "Pan" in the meaning of "treatment of all diseases". (All) and "Axos (medicine, treatment)" and named "Panax ginseng CA Meyer". The roots of ginseng are mainly used for medicinal purposes or as natural health foods, and their demand for medicines and functional foods is increasing.

The efficacy of ginseng mainly comes from ginsenoside (Saponin), which is Ginsenoside. Ginseng contains various ginsenosides. Ginsenosides of ginseng include protopanaxadiol (PD), protopanaxatriol (PT), and oleanane. In addition to ginsenosides, carbohydrates such as starch are included. Antioxidant aromatic compound of polyacetylene, Gomisin NA which protects the liver, and acidic peptide which acts like insulin.

The main pharmacological action of ginsenosides is to influence the endocrine system, the immune system, and the metabolic system represented by the central nervous system, and to exert various effects on the body regulating function. In addition, ginsenosides are known to have the following effects: strong fat decomposition, help absorb and digest nutrients, promote metabolism by activating enzymes in cells, increase energy and restore vitality, and improve fatigue and fatigue. Loss of appetite and promote serum protein synthesis.

On the other hand, ginseng fruit not only has the same composition as ginseng root, but also has been reported as a triptere (Triperpene) which does not exist in ginseng root but only exists in ginseng fruit. Reference: Arch Pharm Res., 35 , 647-651), Isoconiferoside (reference: Molecules, 16, 6577-6581), ginseng triacondione (Panaxadione, reference: Chem Pharm Bull (Tokyo), 57, 283-287), ginseng alkaloids (Ginsenine, reference: J Asian Nat Prod Res., 8, 605-608), ginsenoside-Rh3 (Isoginsenoside-Rh3, reference: J Asian Nat Prod Res., 6, 289-293), hydroxyprotopanaxadiol (25-hydroxyprotopanaxadiol, see: Eur J Drug Metab Pharmacokinet., 35, 109-113) and other ingredients, and it is known to contain a large amount of ginsenoside Re compared to ginseng root (Ginsenoside Re, see: Nat Prod Commun., 4 , 903-906; Diabetes, 51, 1851-1858). Therefore, there is a high possibility that ginseng fruit and ginseng root have differences in pharmacological action mechanism. It has been reported that ginseng fruit extract has the effect of improving male sexual function (Korean registered patent 1,481,778), and ginseng fruit extract has the effect of improving the overall body function of women. And effects of menopausal symptoms (Korean registered patent 2014-0120280), and the effect of directly applying ginseng fruit extract to improve menstrual ovarian aging to delay menopause and prevent early amenorrhea is not disclosed or taught.

On the other hand, even increasing the number of eggs in the ovaries can not necessarily improve infertility. There are many factors for the cause of infertility, especially the ovulation disorder in which the ovaries are unable to ovulate normally, which is the most important factor accounting for about 40% of the causes of female infertility. "PCOS: Polycystic Ovary Syndrome" is a condition in which the ovary or the adrenal gland of a woman produces a male hormone of a normal value or more, and the egg is not mature and ovulated normally. Since there are multiple cysts in the form of oocytes, even if ovulation is performed, the genital egg cannot be discharged, or even if the normal egg is discharged, the uterus condition for implantation of the fertilized egg cannot be formed and becomes a factor of infertility [Acta Radiol. 2014 Mar 55(2): 248-56]. [Previous Technical Literature]

Korean Open Patent Gazette No. 2014-0120280 "Composition of ginseng fruit extract for improving women's health and quality of life"

[Question to be Solved by the Invention] A woman has 1 to 2 million oocytes at birth, 300,000 to 400,000 oocytes at the time of menarche, and then one oocyte matures into an egg during each menstrual period, thereby being discharged. The egg cells disappeared, and the number decreased by more than a thousand during amenorrhea. Oocytes can produce and secrete female hormones, so estrogen is also reduced during menopause with a sudden decrease in the number of eggs. At the time of menopause, it is more likely to suffer from cardiovascular diseases, neurological diseases, neurological diseases, and various degenerative diseases including osteoporosis due to the reduction of female hormones. In particular, amenorrhea caused by loss of ovarian function before the age of 40 is "early amenorrhea". Although the underlying cause has not been determined so far, it is a symptom caused by a decrease in the number of eggs due to aging or degeneration of the ovary.

The inventors of the present invention conducted long-term research and obtained the following findings to complete the present invention: ginseng fruit extract increases the number of oocytes in the ovary, which is not necessarily effective for infertility, but at least improves ovarian aging and prevents early amenorrhea or delay Menopause.

Accordingly, it is an object of the present invention to provide a composition for improving aging of an ovary comprising an ginseng fruit extract as an active ingredient, which can delay menopause and prevent early amenorrhea by increasing the number of eggs to inhibit ovarian aging. [Means for solving the problem]

In order to solve the above problems, the present invention provides a composition for improving aging of ovaries comprising ginseng fruit extract having ginsenosides, minerals and vitamins as an active ingredient to delay menopause and prevent early amenorrhea in women.

The composition for improving ovarian aging comprising the ginseng fruit extract as an active ingredient of the present invention can be selected from the group consisting of an oral tablet, a pill, a granule, a fine granule, a powder, a powder, a soft capsule, and a hard capsule. The dosage form in the group of emulsions, syrups and oral liquids may also be a pharmaceutical composition or a food composition. [Effect of the invention]

The composition comprising the ginseng fruit extract as an active ingredient of the present invention increases the number of egg cells in the ovary to a significant value, thereby suppressing aging of the ovary in the female, thereby having the effect of delaying menopause in women and preventing early amenorrhea.

The present invention relates to a ginseng fruit extract for improving ovarian aging, and more particularly to a composition comprising a ginseng fruit extract having an effect of increasing the number of eggs and improving ovarian aging. The composition comprising the ginseng fruit extract as an active ingredient of the present invention increases the number of egg cells to a significant value, thereby suppressing depletion due to aging of the egg cells, thereby being useful for delaying menopause and preventing early amenorrhea in women.

In the present specification, the ginseng fruit and the ginseng usually have different composition and content of the components contained in the ginseng root. In the present specification, the ginseng fruit contains minerals and vitamin components represented by ginsenosides which are more than ginseng roots, and the composition of the ginsenosides contained therein is different. Therefore, the ginseng fruit of the present invention differs from the usual ginseng root in the effects and pharmacological action mechanisms.

Further, the method for obtaining the ginseng fruit used in the present specification is not limited, and it can be cultivated and used, and can also be used by a commercially available person. That is, the range is not limited as long as it is a raw material suitable for extracting the form of the active ingredient of ginseng fruit. In the present specification, raw ginseng fruit refers to ginseng fruit which has not been subjected to drying and the like after harvesting ginseng fruit.

In the present specification, the broad concept of ginseng fruit extract is as follows: all substances obtained by extracting ginseng fruit components, irrespective of the extraction method, the extraction solvent, the extracted components or the form of the extract, are not only included in the extraction of the components thereof. The material obtained by the extraction method including the treatment using heat, acid, alkali, enzyme, etc., also includes a material obtained by processing or treating the extract of the ginseng fruit component by an additional method. As a specific example of the above processing or treatment, the ginseng fruit extract may be fermented or subjected to enzymatic treatment.

In the present specification, the ginseng fruit extract may be raw ginseng fruit, dried ginseng fruit or other ginseng fruit processed material (for example, mash, dry pulverized material, etc.), and the composition thereof may be similar or identical to each other. Therefore, raw ginseng fruits, dried ginseng fruits or other ginseng fruit processed materials having the same or the same composition described above can exhibit the same effects and uses as the ginseng fruit extracts disclosed in the present specification.

The ginseng fruit extraction method of the present invention is preferably selected from the group consisting of reflux extraction, hot water extraction, high pressure extraction, and microwave extraction. As an embodiment of the present invention, after the ginseng fruit is dried, the ginseng fruit extract can be obtained by reflux extraction using water, an organic solvent or a combination thereof, and the ginseng fruit extract can be further removed by extracting and concentrating the fat-soluble component from the ginseng fruit extract. A step of.

Further, the organic solvent used to obtain the ginseng fruit extract of the present invention may be selected from the group consisting of alcohols having a carbon number of 1 to 20, acetone, ether, ethyl acetate, diethyl ether, ethyl methyl ketone, and chloroform. The solvent in the medium is not limited thereto, and one or more selected from the group consisting of methanol, ethanol, propanol, butanol, and pentanol can be preferably used.

Saponin, which is a component of ginseng fruit extract, is often called "Ginsenoside". Ginsenoside is a glycoside (Glycoside) isolated from ginseng to distinguish it from other plant saponins. The meaning of the name to be named. The reason why ginseng has pharmacological activity different from other plants containing saponin is the ginsenoside component. The ginsenoside contains the protopanaxadiol (PD) ginsenoside of the following chemical formula 1 and the protopanaxatriol (PT) ginsenoside of the following chemical formula 2 as one of the effective saponins.

[Chemical Formula 1]

[Chemical Formula 2]

The ginsenosides Rb1, Rb2, Rc, and Rd belong to the above-mentioned protopanaxadiol (PD)-based ginsenosides, and the ginsenosides Re, Rg1, and Rg2 are classified into the original ginseng triol (PT) ginsenosides. According to previous studies, not only the amount of ginseng diol (PD) ginsenosides and ginseng triol (PT) ginsenosides is important, but also the original ginseng diol (PD) ginsenosides and protosan ginseng glycerol ( The composition of PT) ginsenosides exhibits superior pharmacological effects in the body when it is uniform without being excessively biased toward one.

As an embodiment of the present invention, the ginseng saponin content of the ginseng fruit extract may be 20% by weight or more based on the total weight of the ginseng fruit extract, and the protopanaxadiol (PD) ginsenoside is relative to the original ginseng triol ( The weight ratio (PD/PT) of the PT) ginsenoside may be from 0.5 to 1.5.

As an embodiment of the present invention, the ginseng fruit extract may comprise ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1 and Rg2, in particular, based on the total weight of the ginseng fruit extract, the ginseng saponin Re of the ginseng fruit extract The content may be from 8% by weight to 20% by weight. The structure of ginsenoside Re is as shown in the following Chemical Formula 3.

[Chemical Formula 3]

The composition comprising the ginseng fruit extract of the present invention can be applied in an oral dosage form, and the form thereof can be selected from the group consisting of tablets, pills, granules, fine granules, powders, powders, soft capsules, hard capsules, emulsions, syrups. And the group of oral liquids. In addition to the active ingredient, the composition of the dosage form can be appropriately selected from the ingredients commonly used in the technical field according to the dosage form or the purpose of use, and a synergistic effect is produced when applied simultaneously with other raw materials. Further, the above composition may be a pharmaceutical composition or a food composition.

The composition for improving ovarian aging of the present invention may comprise ginseng fruit extract as an active ingredient alone or more than one or more active ingredients for inhibiting ovarian aging, and may be in addition to the above-mentioned active ingredients, depending on the form of the dosage form, the method of use, and The use purpose further includes an additional component selected from one or more of a pharmaceutically acceptable or nutritionally acceptable carrier, excipient, diluent, and accessory component.

More specifically, in addition to the above active ingredients, it may further comprise a nutrient, a vitamin, an electrolyte, a flavoring agent, a coloring agent, a promoter, a pectic acid and a salt thereof, a brown alginic acid and a salt thereof, an organic acid, and a protective colloid. A thickener, a pH adjuster, a stabilizer, a preservative, a glycerin, an alcohol, a carbonated agent used in carbonated drinks, and the like. Further, the above carrier, excipient or diluent may be selected from the group consisting of lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, seaweed Glue, gelatin, calcium phosphate, calcium citrate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl paraben, propyl paraben, talc, stearic acid One or more of the group of magnesium acid, mineral oil, dextrin, calcium carbonate, propylene glycol, liquid paraffin, and physiological saline, but is not limited thereto, and all usual carriers, excipients or diluents can be used.

Hereinafter, the present invention will be described in detail based on specific examples. However, the present invention is not limited to the embodiments described below, and it is obvious to those skilled in the art that various modifications and changes can be made within the scope of the technical idea of the present invention. Further, the technical terms and scientific terms used in the present specification, unless otherwise defined, are meanings commonly understood by those of ordinary skill in the art to which the present invention pertains. Therefore, a repetitive description of the same technical configurations and effects as those of the prior art will be omitted.

Example 1 : Preparation of ginseng fruit extract (1) Pretreatment of ginseng fruit The ginseng (Panax ginseng CAMeyer) fruit was harvested and the seeds were separated and removed, and then the pulp and peel of the ginseng fruit were dried in the sun or hot air to prepare a ginseng dried raw material. (2) Preparation of ginseng fruit extract 3 liters of 70% alcohol was added to 1 kg of ginseng dried fruit, and the mixture was filtered under reflux for 4 hours at 70°, and then concentrated under reduced pressure at 45 to obtain ginseng fruit extract 300. g.

Comparative Example 1 : Preparation of ginseng root extract A ginseng root extract was prepared by the same method as in Example 1 except that ginseng root was used instead of ginseng root.

Experimental Example 1 : Component Analysis (1) Analysis of ginsenoside components of ginseng fruit extract and ginseng root extract The ginseng fruit extract and ginseng root extract were separately prepared by the above preparation procedure, and the extract was treated with ether to remove fat solubility. After the components were extracted and concentrated with butanol, the ginsenoside component analysis was carried out by high performance liquid chromatography (HPLC), and the results are shown in Table 1 below and FIG. [Table 1] As shown in the results of Table 1, the content of crude saponin (ginsenoside) of ginseng fruit extract was about 2 times that of the ginseng root extract prepared in Comparative Example 1, and the original ginseng diol (PD) ginsenoside Rb1 was used. When the ratio of Rb2, Rc, Rd" to "original ginseng triol (PT) ginsenoside Re, Rg1, Rg2", ie, PD/PT, distinguishes ginsenoside, the PD/PT values of ginseng fruit extract and ginseng root extract are respectively It is 0.73 and 3.23, and the composition and content of "proto-ginsengdiol (PD) ginsenoside Rb1, Rb2, Rc, Rd" and "original ginseng triol (PT) ginsenoside Re, Rg1, Rg2" are obvious. difference. Fig. 1 shows the results of analysis of ginseng fruit extract and ginseng root extract according to each ginsenoside component, and it was confirmed that the contents of the components of the two extracts were different, especially the ginsenoside Re content of the ginseng fruit extract was remarkable. Higher than ginseng root extract. Therefore, it can be known that the total content of ginsenosides of ginseng fruit extract is about twice that of ginseng root extract, especially a large amount of ginsenoside Re, and the content is not biased to one and uniformly contains protopanaxadiol (PD). ) and the original ginseng triol (PT). (2) Analysis of components other than ginseng saponin of ginseng fruit extract The ginseng fruit extract prepared in Example 1 was analyzed for minerals and vitamin components, and the results are shown in Table 2 below. [Table 2]

According to the results of Experimental Example 1, it was found that the ginseng fruit extract of the present invention contains ginsenosides which are more than ginseng roots, and the fruits other than ginseng roots are rich in minerals and 16 kinds of vitamins. As described above, the composition and content of the ginseng fruit extract are different from those of the ginseng root extract, so that the efficacy and pharmacological mechanism are also different.

Experimental Example 2 : Confirmation of improvement of ovarian aging effect (1) Composition of experimental group (8 per group) 40-week-old C57/BL6 female mice were grouped according to the experimental group and the control group as described below, each of which contained Eight of the above female mice were orally administered for two weeks at a frequency of five times per week, and at the age of 52 weeks, the mice were sacrificed and analyzed as described below. Group 1: 40 weeks old / control group (saline) Group 2: 40 weeks old / ginseng fruit extract 100 mg / kg Group 3: 40 weeks old / ginseng fruit extract 300 mg / kg Group 4: 40 weeks old / ginseng root Extract 300 mg/kg Group 5: 10 weeks old/no treatment group (2) Anti-Mullerian Hormone in the blood was analyzed after sacrifice in mice from the orbital vein layer. Serum was separated from the blood, and the anti-Mullerian hormone concentration as an indicator of the number of oocytes in the ovary was measured by Enzyme Linked Immunosorbent Assay (ELISA) (USCN Life Science Inc.). As a result, as shown in Fig. 2, the anti-Mullerian hormone concentration of the group 3 ingesting the ginseng fruit extract of 300 mg/kg was remarkably improved as compared with the group 1 as the control group. If the anti-Mullerian hormone concentration of group 2 ingesting ginseng fruit extract 100 mg/kg and group 3 ingesting ginseng fruit extract 300 mg/kg is compared, it is known that anti-Mullerian hormone concentration is associated with ginseng fruit extract. The amount of intake increases, so that the amount of increase in the number of eggs in the ovary can be adjusted by the intake of the ginseng fruit extract. On the contrary, when the group 4 in which the ginseng root extract was taken up at 300 mg/kg was compared with the control group, it was found that there was no significant difference, which was considered to be due to the effect and pharmacological mechanism of the difference in the composition of ginseng fruit and ginseng root. The difference. (3) Determination of the number of oocysts in the ovary In order to directly confirm the number of ovarian ovarian cells estimated to be the above-mentioned anti-Mullerian hormone concentration, the ovary was removed from the self-sacrificing mouse, and fixed with 10% neutral buffered formalin solution. After 16 hours, it was washed with distilled water. One side of each individual ovary was subjected to tissue treatment using an automatic tissue processing machine (Thermo Shandon, Citadel 1000, USA), and then embedded in paraffin to prepare tissue sections. Tissue sections were stained with hematoxylin-eosin (H&E: Hematoxylin and Eosin) and observed by light microscopy while counting the number of eggs. As a result, as shown in Fig. 3 and Fig. 4, the number of oocytes in the group 3 ingesting the ginseng fruit extract 300 mg/kg was higher than that in the control group, that is, the group 1. (4) Judging the amount of human oral administration, if the body surface area conversion factor from mouse to human body is 3/37, 300 mg/kg is converted into 24.3 mg/kg, which is converted into adult weight of 60 kg. 1.46 g/day. It has been confirmed by human trials that there is no safety problem when ingesting 1.4 g of ginseng per day (Int J Impot Res. 2013 Mar-Apr; 25(2): 45-50.), in this experiment, it was confirmed in mice. The concentration of 300 mg/kg is the amount that can be applied to the human body.

The present invention provides a composition comprising an ginseng fruit extract as an active ingredient, which increases the number of egg cells to a significant value, thereby suppressing depletion of cytoplasm due to aging, thereby being useful for delaying menopause and preventing early amenorrhea in women. However, an increase in the number of oocytes does not necessarily improve infertility [Acta Radiol. 2014 Mar; 55(2): 248-56], the present invention can be used indirectly to improve infertility, but does not directly treat infertility Effect.

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Fig. 1 is a result of analyzing the components of the ginseng fruit extract of the present invention by high performance liquid chromatography (HPLC). Fig. 2 shows the results of analyzing the values of anti-Mullerian hormone (AMH) in the blood of experimental mice of the experimental group and the control group of the present invention. Fig. 3 is a graph showing the results of measuring the number of ovarian ovaries in the experimental mice of the experimental group and the control group of the present invention. Fig. 4 is an image comparing ovarian tissues of experimental mice of the experimental group and the control group of the present invention.

Claims (14)

A composition for improving aging of an ovary comprising a ginseng fruit extract as an active ingredient. The composition for improving ovarian aging according to claim 1, wherein the ginseng fruit extract increases the number of egg cells in the ovary. The composition for improving ovarian aging according to claim 1, wherein the ginseng fruit extract delays menopause of a woman. The composition for improving ovarian aging according to claim 1, wherein the ginseng fruit extract prevents early amenorrhea in a woman. The composition for improving ovarian aging according to the first aspect of the invention, wherein the ginseng fruit extract is obtained by extracting and concentrating an organic solvent after removing the fat-soluble component from the ginseng fruit. The composition for improving ovarian aging according to the fifth aspect of the invention, wherein the total content of the ginsenoside of the ginseng fruit extract is 20% by weight or more based on the total weight of the ginseng fruit extract. The composition for improving ovarian aging according to claim 5, wherein the ginseng fruit extract has protopanaxadiol (PD) ginsenoside relative to protopanaxatriol (PT). The weight ratio of ginsenosides (PD/PT) is from 0.5 to 1.5. The composition for improving ovarian aging according to claim 5, wherein the ginseng fruit extract comprises ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1 and Rg2. The composition for improving ovarian aging according to claim 5, wherein the ginsenoside extract has a ginsenoside Re content of 8 wt% to 20 wt% based on the total weight of the ginseng fruit extract. %. The composition for improving ovarian aging according to claim 5, wherein the ginseng fruit extract comprises minerals and vitamins. The composition for improving ovarian aging according to any one of claims 1 to 10, wherein the composition for improving aging of the ovary is a composition of an oral dosage form. The composition for improving ovarian aging according to claim 11, wherein the oral dosage form is selected from the group consisting of a tablet, a pill, a granule, a fine granule, a powder, a powder, a soft capsule, and a hard capsule. A dosage form of a group consisting of an emulsion, a syrup, and an oral solution. The composition for improving ovarian aging according to any one of claims 1 to 10, wherein the composition for improving aging of the ovary is a pharmaceutical composition. The composition for improving ovarian aging according to any one of claims 1 to 10, wherein the composition for improving aging of the ovary is a food composition.