JP4837896B2 - Vitality enhancer - Google Patents

Description

  The present invention relates to a composition for enhancing vigor using octopine obtained by extraction from seafood and the like.

  Maintaining a good sexual life has an important significance in living a youthful and fulfilling life forever, and leads to an improvement in so-called quality of life (QOL).

  However, in the stressful Japanese society, it is very difficult to maintain a good sexual life due to erectile dysfunction (ED) or decreased libido.

  Therefore, in order to improve the quality of life (QOL), provision of prevention and treatment to prevent physical psychological symptoms such as ED and decreased libido is desired. In addition, many people suffer from infertility, and providing such prevention and treatment to those who desire pregnancy is a particularly practical issue.

  Technically, ED is defined as “a state in which satisfactory sexual intercourse cannot be achieved because sufficient erection cannot be obtained during sexual intercourse or sufficient erection cannot be maintained”. According to statistics about 10 years ago, there were 4.2 million ED patients, but recently it has been estimated that there are more than 10 million, and it is doubling. ED is thought to occur due to psychological stress such as psychological stress or physical causes such as a decrease in male hormones with age and diabetic complications.

  In recent years, “sildenafil” has emerged and attracted attention as an ED drug whose effectiveness has been proven by oral administration. When a man is sexually stimulated, nitric oxide (NO) is synthesized in the NANC (non-adrenergic, non-cholinergic) nerves and cavernous endothelial cells of the penile corpus cavernosum. When NO penetrates into cavernous cells, activation of guanylate cyclase occurs, converting inactive GTP to active cyclic GMP (cGMP). cGMP causes erection by increasing the relaxation of the corpus cavernosum and increasing the internal pressure. The compound sildenafil is a selective inhibitor of phosphodiesterase (PDE) 5 that degrades this cGMP.

  Side effects and drug interactions have been reported for sildenafil used as a pharmaceutical, although it is transient. For example, sildenafil has an accelerated effect on the blood pressure lowering effect of nitrates such as nitroglycerin, and it has been proven by clinical pharmacology studies that blood pressure is significantly reduced, and its combined use is contraindicated. . As for the effects on the eyes, 2 out of 6 cases in the single dose (150 mg) group in the single dose (150 mg) group showed blue vision, diplopia, and red vision. Among 244 cases, there were 14 visual abnormalities such as chromia and it was reported that a dose-dependent increase in the frequency of occurrence was observed. Accordingly, sildenafil is contraindicated in patients with specific diseases (those with severe cardiovascular disorders, patients with hypotension, patients with retinitis pigmentosa, etc.) because of side effects.

  In the case of a medicine containing sildenafil as an active ingredient, a doctor's prescription is required for use, and it should not be used easily, and its use is restricted particularly for those with cardiovascular disease.

  In general, a vigorous enhancer is often taken in order to satisfy a tasteful desire in daily life, and for such purposes, it is desired that it can be used simply and safely.

  As in the example of Viagra, many of the pharmaceuticals and the like containing purified compounds as active ingredients have significant effects, but have many undesirable side effects and sometimes side effects that adversely affect the body.

  In view of the above background, there is a demand for an energy enhancing agent that can be taken more easily and without worrying about side effects and that is particularly effective in reducing libido and infertility.

  For the above purpose, for example, Patent Document 1 discloses an oral energy enhancing agent using an extract from garlic, which is a natural product.

Patent Document 2 discloses a method for improving the implantation rate after in vitro fertilization in a mammalian female using the amino acid L-arginine, for which no particularly significant side effects have been reported.
JP-A-10-306032 JP 2000-510462 A

  In Patent Document 1 above, the amount of testosterone in the testis is measured after oral administration to male rats in order to test the effectiveness of the extract from garlic as a potentiator. The rate has not been tested and it is not clear whether it is effective in reducing libido or infertility.

  Patent Document 2 discloses a method for improving the implantation rate after fertilization by maintaining the blood L-arginine concentration in female rats at or above the effective concentration, but L- in male rats is disclosed. The effect of arginine has not been examined and is not aimed at improving libido, so the number of matings has not been tested.

  As described above, although some attempts can be made, there are few known energy enhancing agents that can contribute to an improvement in the actual pregnancy rate.

  Accordingly, an object of the present invention is to provide a composition for enhancing energetics that can be taken with ease and without worrying about side effects, and that is effective in reducing libido and infertility.

  As a result of diligent research to achieve the above object, the present inventors have found that the composition extracted from an aquatic product containing octopine at a significantly high concentration has an excellent energy enhancing effect and completes the present invention. It came to.

That is, the present invention is an extract extracted from one or more aquatic products selected from fish and shellfish that are bivalves or cephalopods, and contains the extract containing at least octopine as an active ingredient. It is intended to provide a composition for enhancing vitality used for the improvement of symptoms of decreased libido , characterized by containing as follows.

The composition for enhancing vigor used for improving the symptoms of decreased libido according to the present invention is particularly useful for improving motivation for sexual activity and improving the pregnancy rate.

In addition, the composition for enhancing vigor used for improving the symptoms of decreased libido of the present invention is preferably prepared in a dosage form for oral intake.

In the present invention, the bivalves or cephalopods are preferably one or more aquatic products selected from scallops, clams, clams and squid.

Furthermore, the extract was 0.1~50,000mg / 100g content octopine, the energy reinforcement composition preferably contains the extract 0.001 mass%.

  Furthermore, the extract is most preferably extracted from scallops.

  Octopine is an imino compound having a structure in which D-alanine and L-arginine are bonded in a form that shares an amino group in terms of chemical structure. Although it is found in the body of marine invertebrates in nature, No other natural product has been found to be significantly contained, and it can be said that it is a natural component that is uniquely present in the body of marine invertebrates. Octopine is synthesized intracellularly from pyruvate and L-arginine by reductive dehydration condensation with octopine dehydrogenase. It is known that the amount of body production increases during muscle exercise in an anoxic or hypoxic environment, and the reaction of synthesizing octopine is the coenzyme NADH that results from anaerobic glycolysis associated with cellular energy production. It is considered as one of the coupling reactions for re-oxidizing NAD + and continuously supplying it.

Living organisms such as scallops, snails, clams or squid that are eaten daily as nutrients are classified as marine invertebrates, and the octopine of the compound described above is contained in a large amount in their muscle tissue. However, as far as the present inventors know, it has not been reported so far that octopine has a vigorous enhancing action for improving the symptoms of decreased libido .

Oh Kutopin, for example scallops, clams, clams, can be extracted from the bivalves or cephalopods fishery organism musculature squid, etc., there is no side effect because it is an extract from natural products, daily conveniently And can be taken safely.

Octopine content above Symbol extract composition is typically a 10~10,000mg / 100g, as in the examples described later, a significant effect in improving the improvement and pregnancy rates decreased libido symptoms octopine Assuming that the effective intake is 0.01 to 200 mg / kg body weight per day, the effective amount can be satisfied by ingesting the raw extract.

According to the present invention, daily can easily and safely ingested without worrying about the unexpected effect of such side effects, a significant effect in improving the improvement and pregnancy rates decreased libido symptoms, the amelioration of the symptoms of decreased libido It is possible to provide a composition for enhancing energy used .

In the present invention , an extract that is extracted from one or more aquatic products selected from fish and shellfish that are bivalves or cephalopods and that contains at least octopine is used. In other words, it contained significantly higher concentrations of octopine such may be a composition containing two-rugosa and cephalopods in an amount sufficient energy potentiation results for the improvement of symptoms of decreased libido octopine It may be an extract such as a concentrated extract extracted from a water product. Further, the octopine content may be increased from the extract by concentration or purification treatment.

As the aquatic product for extracting the above extract, one or more selected from among scallops, clams, clams and squids are preferably used among the bivalves or cephalopods. It is done. In particular, those muscle tissues are preferable, and scallops are most preferably used.

  The extraction method is not particularly limited, and for example, water may be added to the seafood raw material and heated and extracted at 60 to 100 ° C. for 0.5 to 3 hours. Moreover, what is necessary is just to heat-extract at 110-120 degreeC for 0.5 to 3 hours, when extracting by pressure heating.

  Further, a general food concentrate may be used as a starting material. For example, scallop extract (trade name: “scallop extract Y”) and clam extract (trade name: “Clam extract No. 626BF” used as a seasoning extract. )), Or a seafood extract (trade name: “Surume Extract No. 50BF”) or other commercially available seafood concentrate extract (all manufactured by Yaizu Suisan Chemical Co., Ltd.) may be used.

  These concentrated extracts contain arginine, taurine, glycogen, zinc and the like as other components, and these are also considered to contribute to the improvement of the energy enhancing action.

Oite this onset Ming, may be used directly above octopine-containing extract may be used after concentrating the active ingredient by membrane separation or column purification or the like. Moreover, the isolated octopine can also be mix | blended in order to improve the effectiveness.

In the case of using a concentrated active ingredient by membrane separation or column purification, it can be obtained by concentrating and purifying octopine by performing a molecular fractionation treatment using the following method. In addition, as pre-processing of a concentration / purification process, it is preferable to concentrate or dilute the said seafood extract suitably, and to adjust to Brix1-40%, and adjust to Brix5-15% from the point of operativity and efficiency. It is more preferable.

(1) Concentration / purification by membrane separation A reverse osmosis membrane or ultrafiltration membrane is a size separation membrane that can separate solute components according to their size, and by using it as a molecular fractionation means, the seafood extract described above The impurities can be removed from the octopine and the octopine content can be significantly increased.

The reverse osmosis membrane preferably has a salt blocking rate of 5 to 50% through which octopine permeates. When an ultrafiltration membrane is used, a membrane with a molecular weight cut-off of 10,000 or less, which is less permeable to polymer contaminants, is preferred. . As such a size separation membrane, for example, trade name “NTR-7410HG” (salt blocking rate of about 10%) or trade name “NTR-7450HG” (salt blocking rate of about 50%) (both manufactured by Nitto Denko Corporation) ) And the like.

  The octopine content is significantly increased by concentrating the fish extract that has been appropriately diluted or concentrated in advance to Brix 0.1-20% using the above size separation membrane and collecting the permeate. Fractions can be obtained. The selection of the size separation membrane may be appropriately set according to the conditions such as the concentration of the seafood extract as a raw material, pH, temperature, or impurities contained therein.

(2) Concentration / Purification by Ion Exchange Resin The ion exchange resin is a separation and purification resin that utilizes the difference in adsorption properties of ionic substances to the resin, and the fish extract described above is used as a molecular fractionation means. The impurities can be removed from the octopine and the octopine content can be significantly increased.

Ion exchange resins, the separation capacity, recovery efficiency, strongly acidic ion-exchange resin from the viewpoint of easy handling of the resin. Examples of such ion exchange resins include strongly acidic ion exchange resins (trade name “Amberlite 252”; manufactured by Organo Corporation).

  Using the above ion exchange resin, a fish acid extract that has been appropriately diluted or concentrated in advance so that the salt content is 1% or less and Brix 0.1 to 20%, and desalted as necessary, is converted into a proton-type strong acid in advance. After adsorbing to the ion exchange resin, washing the resin with water, elution of the adsorbed components using the eluate, and collecting the eluate, it is possible to obtain a fraction with a significantly increased octopine content. it can.

  In this case, it is sufficient to wash the resin with water in an amount of 1 to 3 times the amount of resin. The eluate is not particularly limited as long as it has an ionic strength that allows octopine to be eluted. However, for example, if it is 0.5 to 2N hydrochloric acid or 0.5 to 2N saline, it is useful for work or food. Is safe and can be used with confidence. The amount of the eluate is sufficient if it is 1 to 3 times the amount of the resin. In addition, the purification using an ion exchange resin in the present invention may be performed using either a column type in which a resin is packed in a column or a batch type in which the resin is added to a seafood extract.

  The concentration / purification methods (1) and (2) above can be appropriately selected and combined depending on the conditions such as contaminants contained in the seafood extract or the target purification degree and other purposes.

  The octopine-rich fraction obtained as described above may be subjected to steps such as desalting, deodorizing / decoloring, concentration, and drying as necessary for commercialization. Good. As the method, if it is a desalting method, resin desalting, membrane desalting, electric desalting, etc., deodorizing / decoloring method, activated carbon treatment, etc., if concentration method, membrane concentration, vacuum concentration, etc., drying method If it is, spray-drying, freeze-drying, vacuum drying, etc. are mentioned, It does not restrict | limit in particular. The product form may be liquid, paste, solid, powder or the like, and is not particularly limited.

Energy reinforcement composition used in amelioration of symptoms of decreased libido of the present invention preferably contains 0.1~100,000mg / 100g of o Kutopin, and more preferably contains 100~100,000mg / 100g .

When using the composition for enhancing energy used for improving the symptoms of decreased libido of the present invention as a pharmaceutical, functional food, etc., in addition to the above basic ingredients, excipients, minerals, vitamins, sugars, fragrances The product form includes tablets, powders, granules, solutions, capsules and the like, but is not particularly limited.

The composition for enhancing vigor used for improving the symptoms of decreased libido according to the present invention may be combined with other components within a range not impairing the effect of octopine. For example, arginine, taurine, glutamic acid, histidine, branched chain amino acids (leucine, isoleucine, valine) and the like are used as amino acids. Also, imidazole compounds such as histidine, 1-methylhistidine, 3-methylhistidine, anserine, carnosine, homocarnosine, and valenin can be used in combination. Others, octacosanol, citric acid, acetic acid, chitin dimer, chitin pentamer, chitosan hexamer, glucosamine, oligoglucosamine, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, homarine, suppon extract, viper extract, fur seal extract, reindeer Examples include horn, maca extract, guarana extract, red pepper, ginseng, zinc and selenium.

The dosage form of the composition for enhancing vigor used for improving the symptoms of decreased libido of the present invention is not particularly limited. For example, a dosage form such as a tablet, powder, granule, solution, capsule or the like is orally administered. Can be taken. At that time, although it varies depending on the food and medicine to be blended, the daily intake is preferably 0.01 to 5,000 mg, more preferably 0.1 to 200 mg in terms of octopine per kg body weight. preferable.

  Hereinafter, the present invention will be specifically described by way of examples. However, these examples are illustrative of embodiments of the present invention and are not intended to limit the scope of the present invention.

(Preparation of scallop extract from scallops)
Scallops (500 g) from the Okhotsk Sea of Hokkaido were put into 5,000 ml of deionized water and homogenized with a mixer. After heating at 70 ° C. for 30 minutes and cooling, insolubles were removed using 100 g of filter aid. The filtrate was then applied to a reverse osmosis membrane (trade name “NTR-7410HG”; manufactured by Nitto Denko Corporation) having a salt rejection rate of about 10%, and the permeate side (15 L in total) was collected while appropriately adding water. This permeate was heated and concentrated under reduced pressure to obtain 61 g of a paste-like seafood extract with a high octopine content.

(Analysis of scallop extract)
In order to measure the octopine concentration contained in the paste of the scallop extract prepared in Example 1, HPLC was performed according to the method of Kai, M. at al. [J. Chromatography, 268, 417-424 (1983)]. Analysis was performed.

  That is, in order to derivatize octopine in the paste, 0.2 ml of a suitably diluted scallop extract paste sample was placed in a glass test tube with a screw cap, and 0.1 ml of 4.0 mM benzoin (methyl cellosolve solution). 0.1 ml of a reducing agent (0.1 M β-mercaptoethanol, 0.2 M sodium sulfite) and 0.2 ml of 2 M potassium hydroxide were added, and the cap was closed and heated at 100 ° C. for 5 minutes. Next, after cooling in ice for 2 minutes, 0.2 ml of 2M hydrochloric acid (containing 0.5M Tris-HCl buffer, pH 8.5) was added for neutralization.

This neutralized solution containing derivatized octopine was filtered through a membrane having a pore size of 0.45 μm and subjected to HPLC analysis under the conditions shown in Table 1.

  As a result of HPLC analysis, it was revealed that the octopine-rich seafood extract derived from scallop prepared in Example 1 contained 10.0% by mass of octopine.

  As a result of analyzing components other than octopine contained in this octopine-rich seafood extract, the composition has a solid content of 75 mass%, a total nitrogen content of 4.4 mass%, a moisture content of 18.2 mass%, and an ash content of 6.8 mass%. It became clear. In addition, as a result of analyzing the free component with an amino acid analyzer, it is clear that taurine is contained at a concentration of 3.3% by mass, arginine is contained at a concentration of 0.83% by mass, and a branched chain amino acid is contained at a concentration of 0.3% by mass. became. The zinc content analyzed with an atomic absorption spectrometer was 28 ppm.

(Analysis of octopine contained in shellfish)
24 ml of 1N perchloric acid was added and homogenized to 8.0 g of meat of scallops, clams, clams or oysters (cultured). The supernatant obtained by centrifugation (10,000 × g, 20 minutes) was neutralized with 5N potassium hydroxide. Again, centrifugation (10,000 × g, 20 minutes) was repeated to recover the supernatant. Octopine in the supernatant was quantified by the method of Example 2 according to the method of Kai, M. at al. [J. Chromatography, 268, 417-424 (1983)].

  As a result of the analysis, the octopine content per weight of the raw material was 964 mg / 100 g for scallops, 16 mg / 100 g for clams, and 11 mg / 100 g for clams. No octopine was detected in oysters (cultured).

(Analysis of octopine content in marine products)
The octopine content of the following seasoning extract (all manufactured by Yaizu Suisan Chemical Co., Ltd.) was analyzed by HPLC in the same manner as in Example 2. As a result, the octopine content per weight of the raw material extract was 178 mg / 100 g for the scallop extract (trade name “scallop extract Y”) and 154 mg / 100 for the clam extract (trade name “Clam extract No.626 BF”), respectively. It was 197 mg / 100 g for 100 g and a shark extract (trade name “Sulume extract No. 50 BF”).

(Effects of octopine and scallop extracts on total mating frequency and pregnancy rate in rats)
During the breeding period, the animals were preliminarily raised for at least 1 week in a light / dark cycle of temperature 23 ± 1 ° C., humidity 70 ± 10%, and 12 hours. Drinking water and standard feed were ad libitum.

  36 16-week-old male Wistar rats (average body weight 460 g) were divided into 4 groups (n = 9). For each group of rats, water for injection, arginine (manufactured by Sigma), octopine (manufactured by Sigma), or scallop extract prepared in Example 1 was adjusted to a daily dose of 40 mg / kg body weight. It was orally administered twice a day for 14 days continuously to obtain a control group, an arginine administration group, an octopine administration group, or a scallop extract administration group, respectively. The administration was performed from 10 am to 5 pm. From the 8th day to the 14th day after the start of the oral administration, 6 female rats are combined with 1 male rat in the control group or the administration group, and from 5 pm to 10 am, They were reared in a transparent Plexiglas chamber. Using a 5 watt red lamp as illumination, the rat's behavior was recorded with a video camera and the number of matings performed during this time period was observed. The number of matings was measured every day from day 8 to day 14, and the total number of matings per male rat carried out during these 7 days was defined as the total number of matings.

  The measurement of the pregnancy rate of female rats was started from the day after the end of oral administration of the test substance (day 15). Skilled inspectors judged the presence or absence of pregnancy by palpation at a rate of twice a week for 2 weeks. Of the 6 females mated with 1 male, how many became pregnant was expressed as a percentage and defined as pregnancy rate (%).

  The result about the influence of the to-be-tested substance (Arginine, octopine, and a scallop extract) on the mating frequency of a male rat is shown in FIG. Data are expressed as the mean ± S.E. Of 9 male rats. The number of matings in the control group was 212 ± 59 times, and that in the arginine-administered group was 183 ± 46 times. There was no difference between the two groups, and it became clear that arginine did not affect the number of matings in rats. . On the other hand, the number of matings in the octopine-administered group was 243 ± 31, which was 1.15 times that of the control group. Furthermore, in the scallop extract administration group, it was 285 ± 47 times, and increased 1.34 times compared with the control group. From this result, it was revealed that octopine and scallop extracts have the effect of increasing the number of matings. In particular, a significant effect was observed in the scallop extract administration group.

  FIG. 2 illustrates the effect of test substances (arginine, octopine and scallop extract) on the pregnancy rate of female rats. Data are expressed as the mean ± S.E. Of 9 male rats. The pregnancy rate of the control group was 45.8 ± 7.7%, the arginine administration group was 52.1 ± 4.6%, and no difference was observed between the two groups. Arginine administration to male rats was female rats It became clear that it does not affect the pregnancy rate. On the other hand, the pregnancy rate in the octopine administration group was 68.8 ± 4.6%, which was significantly increased by 1.50 times compared to the control group. Furthermore, in the scallop extract administration group, the pregnancy rate was 75.0 ± 5.9%, which was significantly increased to 1.64 times that of the control group. From this result, it became clear that administration of octopine or scallop extract to male rats significantly increased the pregnancy rate. In particular, a significant effect was observed in the scallop extract administration group.

  As is clear from the above, no significant effect was observed in the arginine administration group, whereas octopine containing an arginine moiety in the chemical structure showed significant effects in both the number of matings and the pregnancy rate. Considering that octopus is contained in the scallop extract at a high concentration of 10.0% by mass, it was strongly suggested that the action of the scallop extract is attributable to the contained octopine.

  Here, as clarified in Example 2, the composition of the scallop extract contains components other than octopine such as branched chain amino acids and zinc. Therefore, according to this example in which administration of scallop extract containing octopine has a more significant effect than administration of isolated octopine, any component other than octopine contained in scallop extract It was also suggested that it is useful as a supplementary active ingredient of the composition for enhancing energetics that uses octopine as the main active ingredient for the purpose of improving the symptoms of decreased libido and pregnancy rate.

  Arginine and octopine are known to be substrates of nitric oxide synthase that produces nitric oxide (NO). In the method useful for the treatment of erectile dysfunction in the above-mentioned example of “sildenafil” and the improvement of the implantation rate after in vitro fertilization in the female animal in the example disclosed in Patent Document 2, the action mechanism of the effect is used. As an introduction, it has become clear that nitric oxide (NO) in the body or cells is a major factor. Therefore, it can be inferred that the change in nitric oxide (NO) concentration in the body or cells by octopine administration also contributes to the improvement of the symptoms of decreased libido and the pregnancy rate in the examples of the present invention. Arginine rapidly moves into the metabolism and biosynthetic pathways in the body and cells, and is degraded or taken into proteins, so it stays long as a substrate for producing effective substances such as nitric oxide (NO). I can't expect to do it. On the other hand, since octopine in the present invention is a derivative of arginine, it is difficult to shift to its metabolic and biosynthetic pathways, and its effective concentration in the body is maintained high, which is considered to bring about a remarkable effect.

The composition for enhancing vigor used for improving the symptoms of decreased libido according to the present invention can be used as a pharmaceutical, functional food, etc. having an effect of enhancing vigor for improving the symptoms of decreased libido and improving the pregnancy rate. it can.

It is a figure which shows the result of having investigated the influence of the oral administration of arginine, octopine, and a scallop extract on the number of mating of a male rat. It is a figure which shows the result of having investigated the influence of the oral administration of arginine, octopine, and a scallop extract on the pregnancy rate of a female rat.

Claims (7)

An extract extracted from one or more aquatic products selected from bivalves or cephalopods, comprising at least the octopine-containing extract as an active ingredient A composition for enhancing vigor used to improve symptoms of decreased libido . The composition for enhancing energy used for improving symptoms of decreased libido according to claim 1, which is useful for improving motivation for sexual activity. The composition for enhancing vigor used for improving symptoms of decreased libido according to claim 1, which is useful for improving the pregnancy rate. 4. The composition for enhancing vigor used for improving symptoms of decreased libido according to any one of claims 1 to 3, wherein the composition is prepared for oral intake. According to seafood the a bivalves or cephalopods is, any one of claims 1 to 4 is one or more aquatic organisms selected from scallops, clams, clams, in the squid A composition for enhancing vigor used to improve symptoms of decreased libido . The said extract contains 0.1-50,000 mg / 100g of octopine , and the said composition for sexual enhancement contains 0.001-100 mass% of said extract as described in any one of Claims 1-5. A composition for enhancing vigor used to improve symptoms of decreased libido described in 1. The composition for enhancing vigor used for improving symptoms of decreased libido according to claim 5 or 6 , wherein the extract is extracted from scallops.