JP2008273856A - Material containing starfish essence as active ingredient - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To utilize an essence extracted from a starfish, the utility value of which has been low, as an antiobestic material and anti-hyperlipemia material. <P>SOLUTION: The antiobestic material and the anti-hyperlipemia material contain the essence obtained by extracting the starfish as an active ingredient. The amount of cadmium contained in the starfish of a raw material from which the starfish essence is extracted is preferably ≤20 ppm per one starfish, and the amount of arsenic is preferably ≤20 ppm per one starfish. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a substance containing a starfish extract as an active ingredient.

  In Japan, there is no example of starfish being a regular diet. In the Amakusa region, there is a custom of eating the starfish ovary, but this is limited to a period of early summer. In China, Itoki starfish has been used for medicinal purposes for a long time, and this was mainly intended for use in response to renal emptiness in Chinese medicine, that is, to increase vitality, cool the legs, and improve pain.

  However, China does not recommend long-term intake of starfish. This is because the starfish contains steroid saponins that are hemolytic to fish, and there is a concern that the intake of starfish may adversely affect mammals. This is the reason why the use of starfish as a food has been hindered.

  In this way, starfish have hardly been used so far, but rather, there is a problem of eating and destroying cultured scallops, and the damage to fishermen has been enormous. Even if it is captured, the starfish is used only for fertilizer, and it is currently disposed of, and the labor and cost for capturing and disposal are great. Therefore, if diversion of starfish to food becomes possible, it will be a great gospel for many fishermen.

  In recent years, treatment using a combination of Chinese medicine and Western medicine, which are said to be non-disease medicine, has been widely taken up. This is a medical treatment for semi-healthy people who are in the boundary between normal and sick, especially for the symptoms such as obesity, diabetes and hypertension, using various Chinese medicines, dim sum, etc. It is intended to maintain or improve the health of healthy people, or to recover.

  At present, the number of diabetic patients in Japan is increasing remarkably, and the number is said to be 2 million or millions including untreated persons. As is well known, diabetes causes various complications such as vascular disorders such as arteriosclerosis, retinopathy, nephropathy or neuropathy. Therefore, prevention, recovery and maintenance of medical conditions are one of the important issues for diabetic patients. Diabetes is delayed in the transition to complications due to blood glucose control, and it is possible to prevent the onset of diabetes.

Looking at the knowledge about the blood glucose lowering effect using Kampo medicine, there are many reports such as research on the ox cart kidney kagemaru extract. Oxshajinkigan is a Chinese herbal medicine aimed at improving renal emptiness in Chinese medicine. Renal collapse is a malfunction of the autonomic nervous system or endocrine system resulting from aging. The present inventor thought that starfish, which is an animal herbal medicine that has been used for renal failure since ancient times, may have the same effect.
Japanese Patent No. 3245138

  The present inventor has conducted research on the toxicity of starfish and found that some starfish have low toxicity. This low-toxic starfish extract showed neither acute nor subacute toxicity, and it was confirmed that the starfish extract is highly safe. Furthermore, it has been found that the extract extracted from starfish has an anti-obesity action and an anti-high fat action.

  The present invention is an anti-obesity substance and an anti-hyperlipidemic substance containing as an active ingredient an extract obtained by extraction from such a starfish extract. Further, the amount of cadmium contained in the starfish as a raw material for extracting the starfish extract is preferably 20 ppm or less per starfish, and the amount of arsenic is preferably 20 ppm or less per starfish.

  A starfish extract was extracted using an alcohol (ethanol) extraction method. The following experiment was performed using the starfish extract extracted by this method. By using alcohol extraction, heavy metals that are harmful substances such as cadmium and arsenic contained in starfish can be removed. As the starfish for extraction, a starfish having a heavy metal content of 20 ppm or less, particularly cadmium and arsenic content of 20 ppm or less was used. This is because if heavy metals such as cadmium and arsenic are contained more than this, even if alcohol extraction is performed, the heavy metals may not be completely removed to the safe value specified by the Food Sanitation Law. Such a starfish corresponds to, for example, a starfish produced in Nemuro, Hokkaido. Thus, the starfish extract obtained by subjecting a starfish with a cadmium content of 20 ppm or less and an arsenic content of 20 ppm or less to an alcoholic extract is preferably 0.8 ppm or less as defined in the Food Sanitation Law. Can be suppressed to 0.2 ppm or less, and the arsenic content can be suppressed to 15 ppm or less, preferably 5 ppm or less as defined by the Food Sanitation Law.

  Extraction of the extract can also be performed using an ion exchange resin as described in Japanese Patent No. 3245138, for example. However, this method is expensive and time-consuming, and is not suitable for food processing.

Experiment 1-Acute toxicity of starfish extract The present inventor confirmed the acute toxicity of a starfish extract extracted by the alcohol extraction method as described above by using an experiment with rats. That is, a starfish extract corresponding to 100 times the normal human dose was given to rats for 10 days, and the effects on blood biochemical values and blood coagulation function were investigated. In addition, changes in liver tissue and kidney tissue were observed.

Experimental Method Wistar male rats 4 weeks old were preliminarily raised for 3 weeks, and the body weight was about 80 g. These rats were allowed to eat a diet containing 10000 ppm of starfish extract extracted with alcohol (the composition is shown in Table 1) freely for 10 days, blood was collected under Nembutal anesthesia, and the organs were removed. Plasma was separated from blood collected directly from the heart, ALT, AST and γ-GTP as indicators of liver function were measured, PT time of blood coagulation index, thrombotest, and T4 (thyroxine) were measured. The extracted liver and kidney were fixed with a neutral formalin solution to prepare a specimen, and histological examination was performed.

Experimental Results 200 mg / day / 250 g starfish extract equivalent to 100 times the normal human dose (extract 400 mg / day / 50 kg) was given to rats. Both feed intake and water consumption (Table 2) were given in the control group. There was no particular difference. In addition, the starfish extract did not affect the body weight (Table 3), biochemical test value and blood coagulation function (Table 4) of rats. Furthermore, there was no significant difference in the weights of the liver and kidney (Table 5), and no abnormal findings were found in either the liver tissue or the kidney tissue. From the above experimental results, it is considered that the safety of starfish extract is high.

  Since starfish extract contains steroid saponins, hematological findings were observed. However, no effect was observed on thrombotest and PT, and GOT (ALT), GPT (AST), γ- There was no change in GTP. From these results, it became clear that the short-term intake of starfish extract has no harmful effect on the living body.

Experiment 2-Subacute toxicity of starfish extract The present inventor further confirmed the subacute toxicity of starfish extract through experiments using rats. A starfish extract equivalent to 100 times the normal human dose was given to rats for 4 weeks to measure liver function, blood coagulation function and blood biochemical value, and to observe the effect on liver tissue and kidney tissue.

Experimental Method Wistar male rats immediately after weaning were preliminarily raised for 3 weeks, and the body weight was about 80 g. These rats were allowed to freely feed a diet containing 10,000 ppm of starfish extract extracted with alcohol (shown in Table 1) for 4 weeks, and then blood was collected under Nembutal anesthesia to remove the organ. Plasma was separated from blood collected directly from the heart, ALT, AST and γ-GTP as indicators of liver function were measured, and PT time, thrombotest, and T4 of blood coagulation indicators were measured. The extracted liver and kidney were fixed with a neutral formalin solution to prepare a specimen, and histological examination was performed.

Experimental Results The feed intake of rats was as shown in Table 6. Many rats ingested starfish extract showed a tendency to suppress weight gain (Table 7), but no significant difference was observed between the control group and the control group. There was also no difference in organ weights of kidney and liver (Table 8). Starfish extract did not affect blood biochemical test values or blood coagulation function of rats (Table 9). Furthermore, no abnormal findings were found in either liver tissue or kidney tissue. From the above experimental results, it is considered that the safety of starfish extract is high in terms of subacute toxicity. Regarding the tendency to suppress body weight gain, no change was observed in the T4 (thyroxine) value. It is assumed that it is not due to enhancement.

  A long-term (4 weeks) intake of starfish extract showed a tendency to suppress weight gain, but there was no difference between the experimental group and the control group in the amount of feed intake. An increase was speculated.

Experiment 3-Obesity inhibitory action of starfish extract In Experiment 1 and Experiment 2, no acute toxicity and subacute toxicity of starfish extract to rats were observed, and it was confirmed that the safety of starfish extract is high. In subacute toxicity experiments, it has been suggested that starfish extract has a tendency to suppress obesity. In this experiment, a high-calorie diet supplemented with starfish extract was given to white rats, and the effects on body fat, T-CHO, TG, β-lipoprotein levels and other serum lipids were examined. Rats were confirmed for the effects of lipemia and anti-obesity.

Experimental method (1) Experimental animal A Wistar white rat with a weight of around 110 g, 6 weeks old, was used.
(2) Feed composition For the control group (Group A), a high-calorie feed of 20% gazein as a protein source, 5.0% fiber and 15% soybean oil was given. For the experimental group (Group B), fiber 5% is 4.9%, starfish extract 0.1% is added, and calorie is not different from the feed given to the control group (Group A). A conditioned high-calorie diet was provided. Detailed feed composition is shown in Table 10.
(3) Breeding method, period The feed of Table 10 was freely fed with white water together with water. The breeding period was 30 days. The breeding room was kept in a separate cage while keeping the room temperature at 21 ° C. and the humidity around 50%. Body weight and food intake were measured daily.
(4) Blood collection method Blood samples were collected from white rats by cardiac puncture and used as biochemical test samples.

Experimental Results (1) Weight gain A white rat that weighed about 116 g on average at the beginning of the experiment grew to over 300 g after 30 days of breeding. Table 11 shows the weight gain on day 30 of both groups. As expected, a tendency for the weight gain of Group B to decrease significantly was observed.
(2) Feed intake The feed intake was measured in order to investigate the cause of the difference in body weight between the two groups. As apparent from Table 12, there was no clear difference in the feed intake between the two groups, and it was found that the appearance of the difference in body weight was not related to the feed intake.
(3) Visceral weight At the time of slaughter, the liver and kidney of a rat were removed and their weights were measured. The results are as shown in Table 13, and there was no significant difference between the two groups.
(4) Biochemical test values in serum Tables 14, 15, and 16 show biochemical test values in serum of white rats. Group B has lower values of total cholesterol, neutral fat, and β lipoprotein protein than Group A.

Discussion When the experimental group (B) and the control group (A) are compared, it can be seen that the weight gain of the experimental group B is significantly suppressed. Total cholesterol, neutral fat, and β-lipoprotein protein are also low in the method of the experimental group (B), and the anti-obesity effect of starfish extract is clear. In an experiment on subacute toxicity (Experiment 2), it has been found that the anti-obesity effect is not mediated by T4. Therefore, it is considered that steroid saponin in starfish extract affects lipid metabolism.

Experiment 4-Effect of starfish extract on hypoglycemic action of streptozotocin (STZ) diabetic white rat To confirm the hypoglycemic effect of starfish extract, powdered starfish extract extracted with alcohol from black starfish was administered to white rat, and anti-diabetic effect was observed. investigated. Streptozotocin is known to induce hyperglycemia by reducing the insulin secretory function of the islets of Langehans in the pancreas, and how the administration of starfish extract to streptozotocin diabetic white mice suppresses the blood glucose level during glucose load. An experiment was conducted to observe this.

Experimental Method (1) Experimental Animal A Wistar strain male male mouse having a weight of about 260 g, 10 weeks old, was used.
(2) Feed composition A feed prepared according to the composition of AIN was used. That is, feed containing fiber was prepared using casein (20%) as a protein source. However, the fiber blending amount of the control (Group B and Group C) was 5.0%, the fiber blending amount of the starfish extract experimental group (Group A) was 4.9%, and 0.1% starfish extract was added. . Table 17 shows the details of the feed composition.
(3) Breeding method, period The feed described in Table 17 was fed freely with water to each group of rats. The breeding period was 15 days. Group C was bred for 15 days without administration of streptozotocin (hereinafter STZ). Groups A and B were injected intraperitoneally with STZ on day 1. For the dosage, literature values from the New Drug Development Laboratory were adopted. That is. A dose of 50 mg / kg STZ dissolved in 0.05 mol / 1 citrate buffer (pH 4.5) was administered as 10 mg / head in consideration of the body weight of white mice. On day 5 after administration of STZ, the urine of a white rat was examined using new urease Ga to examine an increase in blood glucose level. Then, from the sixth day, group A was fed with a starfish extract, and group B was fed the same feed as group C, ie, a feed containing no starfish extract. The room was kept at 21 ° C. and the humidity around 50%, and was raised with individual gauges. The rats' body weight and food intake were measured daily. Table 18 shows the history of the experiment.
(4) Glucose tolerance test and blood sampling method Glucose loading was about 75 g / 60 kg as in humans. That is, since the body weight of the rat is about 1/200 of that of a human, 750 mg / ml / 1 glucose was administered to the rat with a Komagome pipette. Blood was collected from a white rat by cardiac puncture and biochemical examination was performed.

Experimental Results (1) Change in body weight Table 19 shows the weight of a white rat with a normal mood of about 250 g. By STZ intraperitoneal injection, the group A and group B tended to lose weight at first, but the group A recovered from the 6th day and showed the same growth as the group C after 15 days of breeding. On the other hand, Group B suffered from malnutrition, slowed growth and showed end stage symptoms of diabetes.
(2) Feed intake Table 20 shows the feed intake for 5 days before slaughter. No clear difference was observed in each group.
(3) Visceral weight At the time of slaughter, the liver and kidney of a rat were removed and their weights were measured. The results are as shown in Table 21, and almost no difference was observed in each group.
(3) Results of the load test Blood glucose levels were compared at a value of 1 hour after glucose loading at 0 hours (fasting). The results are shown in Table 22. A blood glucose lowering effect was observed by administration of starfish extract.
(4) Discussion As described above, when a glucose tolerance test of STZ-induced diabetic white rats was attempted, hypoglycemia was observed in the experimental group fed with starfish extract-added diet, and the same growth curve as in the group not administered with STZ was gotten. The onset mechanism of diabetes mellitus due to STZ is considered to be because insulin secretion is lowered and blood glucose level information is obtained by breaking the DNA chain of pancreatic islets of Langerhans. As a result, when urine sugar increases, weight loss is a phenomenon frequently seen in advanced diabetic patients. In this experiment, we found that the starfish extract shows the repair function of Langehans Island.

Experiment 5-Clinical experiment on improvement of blood glucose level for diabetic patients with starfish extract and improvement of obesity As described above, extract extracted from starfish with ethanol proved to have anti-obesity and anti-hyperlipidemic effects In addition, the safety of oral administration of starfish extract was also confirmed. Therefore, an extract obtained by extracting alcohol (ethanol) from starfish captured in the sea near Nemuro, Hokkaido, was used as a test agent and administered to adult diabetic patients. Changes in fasting blood glucose level, serum neutral fat Increases and decreases, and changes in body weight were examined.

Test Method (1) Subjects Five adult (non-insulin dependent) input disease patients whose fasting blood glucose level was around 180 mg / dl to around 240 mg / dl were subjects. All subjects were obese with hyperlipidemia. The breakdown of the subjects is three men and two women aged 38 to 55 years.
(2) Test agent, administration method Alcohol-extracted powdered starfish extract (dry material: extract = 5: 1) was used as a test agent. 3 g per day, 1 g after morning and dinner, 2 g per day. The dosing period was 60 days.
(3) Concomitant medications Drugs that were used by subjects were allowed to continue to be used as they were so that they could continue living as before. However, it was forbidden to take additional drugs.
(4) Outline of the test The test agent was taken every day for 60 days, and during that period, the blood glucose level and the triglyceride level during fasting were measured about every 15 days, depending on the convenience of the subject. The body weight was measured every other month.
(5) Determination method The fasting blood glucose level before administration of the test agent, the neutral fat, the fasting blood glucose level on the 60th day after administration of the test agent, and the neutral fat were compared. The efficacy and antihyperlipidemic effect were determined. In consideration of errors, an increase or decrease of less than 20% compared to the blood glucose level or neutral fat before taking the test agent was regarded as unchanged, and an increase or decrease of 20% or more was used as a criterion for determining validity or deterioration. Regarding the body weight, an increase / decrease of less than 2 kg was made nonflammable, and an increase / decrease of 2 kg or more was used as a criterion for determining validity or deterioration.
(6) Measurement of side effects When clinically unexpected symptoms were observed, these were considered as side effects, and their relevance to the test agent was examined.

Test results As shown in Table 23, blood glucose levels in 5 cases decreased among 5 cases, but there were 3 effective cases in which blood glucose levels decreased with a difference of 20% or more. There was one worsening case in which the blood glucose level increased with a difference of 20% or more, and one unchanged case in which the decrease or increase was less than 20%. Therefore, the effective example was 60%. However, the worsened item was the amount of alcohol consumed due to workplace stress, and the calorie intake was significantly increased compared to before taking the test agent. As shown in Table 24, the number of effective cases in which the neutral fat value decreased was 4 out of 5 cases. Regarding body weight, as shown in Table 25, effective cases were observed in 4 out of 5 cases. Regarding side effects, there was nothing special to mention, but three subjects reported that stool became loose. However, while continuing to take starfish extract, I received a report that it was reduced for a while and returned to normal flights in about a week.

Discussion Although the number of cases is small, the blood glucose level of refractory diabetic patients who do not respond to drugs has been improved, it is speculated that starfish extract has an anti-diabetic effect. Since there were many cases where the body fat was also reduced in neutral fat, it is presumed that it also has an anti-obesity effect. Three of the subjects had a maximum blood pressure of 150 mmHg or higher, but all of them had fallen within the normal range of around 130 mmHg after taking the extract, so starfish extract is anti-diabetic and anti-high. It is considered to have combined effects such as lipemia, anti-obesity, anti-hypertension. Therefore, these effects are unlikely to be simply the effects of steroid saponins. Since starfish are shellfish, they may contain a large amount of taurine.

  In the experiments described above, the starfish extract used was an extract obtained by extracting alcohol from a starfish produced in Nemuro, Hokkaido. The place of production does not matter. As for the type of starfish, it is most preferable to use a starfish.

  Furthermore, it is thought that steroid saponins contained in herbal medicines such as ginseng and yucca also have the effect of lowering serum lipids and suppressing obesity, and these herbal medicines are used by mixing them with starfish extract. May be. Such herbal medicines include tougan, oysters, mulberry leaves, leek, netherlands view, cinnamon, sanshuyu, yam, psyllium, ketsumeishi, honeysuckle, yellow spirit, turmeric, capsicum (capsaicin), and amadochoro.

  As described above, the substance containing the starfish extract according to the present invention as an active ingredient has anti-obesity action, anti-hyperlipidemia, anti-diabetic action, and anti-hypertensive action.

Claims (5)

An anti-obesity substance characterized by comprising an extract obtained by extraction from starfish as an active ingredient. An antihyperlipidemic substance characterized by comprising an extract obtained by extraction from starfish as an active ingredient. The anti-obesity substance according to claim 1 further comprises togan, oyster, mulberry leaves, leek, Dutch view, cinnamon, sanshuyu, yam, plantain, ketsumeishi, honeysuckle, yellow spirit, turmeric, capsicum (capsaicin), and amadokororo. An anti-obesity substance comprising at least one extract obtained by extraction from a material selected from a group. The anti-hyperlipidemic substance according to claim 2 further comprises Togan, Oyster, Mulberry leaves, leek, Dutch view, cinnamon, sanshuyu, yamaha, plantain, ketsumeishi, honeysuckle, yellow spirit, turmeric, capsicum (capsaicin), and amadokoro An antihyperlipidemic substance comprising at least one extract obtained by extraction from a material selected from the group consisting of: The substance according to any one of claims 1 to 4, wherein the amount of cadmium contained in the starfish is 20 ppm or less per starfish and the amount of arsenic is 20 ppm or less per starfish.