KR20070016417A - A pharmaceutical composition for the prevention and treatment of obesity or diabetes mellitus comprising an extract of a puffer - Google Patents

Abstract

The present invention provides a composition for the prevention or treatment of obesity or diabetic disease, including the water extract of the puffer fish obtained by distilling the puffer fish.

Pufferfish extract, obesity, diabetic

Description

A pharmaceutical composition for the prevention and treatment of obesity or diabetes mellitus comprising an extract of a puffer}

1 is a view showing the results of Western blot analysis of the fatty acid synthase (FAS) from the liver was extracted from the mice to which the pufferfish extract was administered for 23 weeks, as a sample.

2 is a view showing the results of observing the change in weight by administering the blowfish extract of the present invention to the mouse for 30 weeks and measuring the weight every week.

The present invention relates to a pharmaceutical composition for the prevention or treatment of obesity or diabetic disease comprising a blowfish extract.

Diabetes mellitus is when the physiological function of insulin released by β cells of the Langerhans islet in the pancreas is poor or the number of insulin-receptors is low, resulting in insufficient insulin physiological function. It is a symptom of hyperglycemia that occurs when urine has sugar detected. When diabetes is induced, the secretion state of insulin and glucagon is disturbed, causing abnormal metabolic control functions such as protein and lipid metabolism as well as carbohydrates, resulting in various metabolic diseases. Thickening of epithelial cell membranes causes many complications such as the circulatory system.

Diabetes mellitus is characterized by two types, type 1 diabetes mellitus, which is caused by a lack of secretion of insulin, a glucose-regulating hormone in the blood, mainly younger people in their 10s to 20s. It is also called juvenile diabetes because it occurs in women. Type 2 diabetes mellitus occurs mainly after the age of 40 and accounts for most of the diabetic patients in Korea. Unlike type 1, it is called adult-type diabetes and the cause of the disease is not clear yet, but it is known to be caused by genetic factors and environmental factors. The type 2 diabetes is a cause of pancreatic beta cells. Both disorders and defects in insulin action (insulin resistance) in target cells are observed.

The most important goal in the treatment of diabetes is to control blood glucose levels as close to normal as possible, and therapies include pharmacotherapy, diet and exercise therapy. Oral hypoglycemic agents currently used in patients with type 1 and type 2 diabetes include α-glucosidase inhibitors, sulfonylurea preparations, and biguanide preparations. Cidase inhibitors have a therapeutic effect on diabetes by delaying the digestion and absorption of carbohydrates in the ingested diet, thereby reducing the elevation of postprandial blood sugar and blood insulin. α-glucosidase inhibitors promote the secretion of glucagon-like peptide-1 in the small intestine that promotes insulin secretion and inhibits glucagon secretion without causing hyperinsulinemia or hypoglycemia Have advantages (Mooradian, AD, Thurman, JE, Drugs, 57, pp 19-29, 1999; Baron, AD Diabetes Research and Clinical Practice, 40, ppS54-S55, 1998). Currently used in clinical practice include acarbose, acarboose, voglibose and miglitol, but long-term use of α-glycosidase inhibitors can cause side effects such as bloating and diarrhea in some patients. And its use may be limited (Hanefeld M., Journal of Diabetes and its Complications, 12, pp228-237, 1998).

To date, there is no cure for diabetes, and there are many researches to search for diabetes drugs from natural products due to the side effects of drug treatments, and WHO (1990) is effective for diabetes and has fewer side effects. The use of natural products is highly recommended (Grover JK, Vats. V., Rathi. SS, Journal of Ethnopharmacology, 73, pp 461-470, 2000).

In addition, the causes of obesity include the lack of exercise and other endocrine or pathophysiological abnormalities caused by the development of civilization in pursuit of high-fat, high-calorie diet and convenience according to environmental and social changes. In addition, the genetic factor of obesity is an important cause of the fact that obesity is related to households, and in addition to environmental factors, genetic factors affect at least 30-50% of the occurrence of obesity. Known.

Treatment and prevention of obesity has been actively studied in various countries in various ways, currently being practiced to reduce the consumption of food by reducing the consumption of energy, diet to exercise energy to exercise energy, organ Surgery therapy such as ablation or liposuction, and drug therapy using energy metabolism accelerators, appetite suppressants, and digestive absorption inhibitors. However, until now, there is no complete method of treating obesity, and when these methods are discontinued, there are various side effects such as weight loss, yo-yo phenomenon, nutritional imbalance caused by dietary restriction, and infection caused by reduced immunity. In the case of drug therapy, various side effects such as depression, insomnia, and digestive disorders have been reported. Therefore, there is an urgent need to develop effective and safe methods for promoting weight loss in addition to these traditional methods.

Blowfish is useful as a diet food containing low calorie, high protein, low fat and various minerals and vitamins, and Korean Patent Publication No. 2002-91641 discloses breast cancer, stomach cancer, lung cancer, liver cancer and ovarian cancer using aqueous extracts of puffer fish eggs. Pharmaceutical compositions capable of treating cancer have been disclosed. However, there is no disclosure as to whether such compositions have anti-obesity or anti-diabetic activity.

The present inventors have been researching to develop a natural extract useful for the prevention and treatment of diabetes and obesity. Surprisingly, the present inventors have found that the water extract of the admired puffer fish, which does not contain blowfish poison, functions to inhibit obesity and lower blood sugar. Invented the invention.

An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of obesity having an anti-obesity activity, including a blowfish extract.

Another object of the present invention to provide a pharmaceutical composition for the prevention or treatment of diabetic diseases comprising a blowfish extract.

The present invention provides a composition for the prevention or treatment of obesity, including the water extract of puffer fish obtained by distilling the puffer fish.

The present invention also provides a pharmaceutical composition for the prevention and treatment of diabetic diseases, including the water extract of puffer fish obtained by distilling the admired puffer fish.

In one embodiment of the invention, the diabetic disease is chronic hyperglycemia, atherosclerosis, microangiopathy, kidney disease, heart disease, diabetic retinopathy and other ophthalmic diseases One or more of them are included.

The puffer fish used in the present invention may use any taxonomically known puffer fish, for example, bokbokdae, firefish. You can use all of the puffer fish belonging to the turtle suit, thorn suit and the like. As a blowfish belonging to the bokbok family, the blowfish inhabiting the waters of Korea are known as 19 species including 18 species such as cock, sword, magpie, and 1 species of thorn. Blowfish are particularly toxic, including black robes, cocks and magpies.

In the present invention, "adventured blowfish" refers to a blowfish that has been removed a neurotoxin called tetradotoxin contained in the liver, gonad, digestive tract, skin, etc. of the blowfish, and usually removes the fins, gills, and eyes of the blowfish Remove pufferfish, puffer fish, and blood and wash in running water for 1 hour to detoxify.

The distillation method of "water extract of puffer fish" used in the present invention can be carried out according to a conventional distillation method (for example, simple distillation), preferably in a batch distillation column, the temperature of 100 ℃ to 150 ℃, pressure 1 By distillation at 2 to 7 hours at 5 kgF / cm ² , more preferably at a temperature of 125 ℃ to 135 ℃, 5 to 7 hours at a pressure of 2.8 to 3.2 kgF / cm ² , it is possible to extract the useful components effectively. The amount of blowfish contained in the water in the distillation process is a large amount, preferably in an amount of 500 to 1,500 g per 1 L of water.

Since the water extract used in the present invention is distilled from a mixture containing a large amount of deodorized puffer fish in the amount of 500 to 1,500 g per liter of water, it is possible to separate the useful components, particularly proteins and peptides contained in the puffer fish, in liquid and solid phase. Make sure In particular, active ingredients in pufferfish (e.g., useful peptides, widows, new technology fusion projects 2003: see "Discovery, Information and Application of Useful Peptide Ligands") are present in very small quantities and are useful in small amounts of puffer fish. Since it is difficult to obtain the ingredients, it is intended to obtain a highly concentrated active ingredient by using a large amount of blowfish.

Compositions of the present invention may include pharmaceutically acceptable additives. The additives may optionally be used one or two or more of conventional excipients, disintegrants, binders, lubricants, suspending agents and the like. For example, when the composition of the present invention is prepared in a solid form such as tablets or hard capsules, microcrystalline cellulose, lactose, low-substituted hydroxycellulose and the like can be used as excipients, sodium starch glycolate, anhydrous as a disintegrant. Calcium monohydrogen phosphate may be used. As the binder, polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose and the like can be used. The lubricant can be selected from magnesium stearate, silicon dioxide, talc and the like. In addition, as the suspending agent, surfactants (eg, sorbitan esters, polysorbates, etc.) commonly used in the pharmaceutical field may be used.

The compositions of the present invention can be formulated in a variety of forms, including solid and liquid forms, which include tablets, capsules (hard or soft), solutions, suspensions, emulsions, syrups and the like. It may preferably have liquid formulations such as liquids, suspensions, emulsions, and syrups, and may also be prepared as a functional food.

The composition of the present invention may be administered by various methods of administration, including oral or parenteral, and may be preferably administered orally. The composition of the present invention can be administered to a person in need of prevention or treatment of obesity, or prevention or treatment of diabetic disease in the range of 0.1 to 1,000 mg / kg per day. However, the dosage may be adjusted to an appropriate amount depending on the condition such as age, age and sex and the severity of the disease, such dosage is easy for those skilled in the art clinically engaged in the treatment or prevention of patients. I can adjust it.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, this embodiment is for illustrative purposes only and the scope of the present invention is not limited to this embodiment.

Example 1

The fins, gills, and eyes of the abalone ( Fugu rubripes rubripes ) were removed, and the abdominal glands, puffer fish, and blood were removed, washed in running water for 1 hour, and detoxified. 30 kg of decontaminated blowfish was added to 20 L of water. The mixture was injected into a cylindrical batch distillation column (55 L capacity). Next, distillation was performed for about 6 hours at the temperature of 130 degreeC and the pressure of 3 kgF / cm <^2> .

As a result, 30 L of the liquid extract containing the effective protein of the puffer fish, peptides, etc. were obtained on the tower, and 20 kg of the remaining solid material was obtained at the bottom of the tower.

Thus, the liquid extract obtained from the tower phase was investigated whether there is anti-obesity and anti-diabetic activity.

Example 2 Confirmation of Anti-Obesity or Anti-Diabetes Activity of Pufferfish Extract

In this example, the puffer fish extract prepared in Example 1 was administered to mice with high fat diet for 5 months, and the change in body weight was observed to determine whether obesity diabetes was induced.

(1) Effect of puffer fish extract on the induction of obesity and obesity diabetes

Six-week-old mice, C57BL / 6 (male), were divided into two groups of 7 to 8 animals per group, pre-treated with a high-fat diet for 8 weeks, and then given the following foods for 20 weeks. The diet was replaced with a normal diet.

Group 1: High-fat food (rodent diet consisting of 60 kcal% fat, 20 kcal% protein, 20 kcal% carbohydrates) + Pufferfish extract 25cc / g / d

Group 2: High fat foods (rodent diet consisting of 60 kcal% fat, 20 kcal% protein, 20 kcal% carbohydrates)

The diet consumed about 2.2 grams per day per animal. This is calculated by feeding 100g a week and measuring the remaining food weight.

High fat food refers to food consisting of 60% by weight of the total weight. Food as described above was provided, and in the case of the first group was blowfish oral administration once a day.

Mice were weighed every week after administration. Table 1 is a table showing the results of observing the change in weight by administering the blowfish extract of the present invention to the mice and measuring the weight every week.

Table 1.

Table 1 (continued)

Table 1 (continued)

As shown in Table 1, when a high fat diet containing blowfish extract was administered to mice, body weight was relatively decreased. This means that the blowfish extract of the present invention has an obesity prevention or treatment effect.

(2) Effect of puffer fish extract on blood sugar

In this section, as observed in paragraph (1) above, when the puffer fish extract of the present invention is administered to mice with normal food, to determine whether the effect of inhibiting the weight gain of mice is associated with obesity diabetes Blood glucose levels were measured in the mice to which the puffer fish extract was administered.

Specifically, each group of mice was fasted 12 hours before the start of the experiment, and the plasma glucose concentrations were measured.

Table 2.

As shown in Table 2, there was no difference in blood glucose at the beginning of the blowfish extract administration, but began to change slightly at 16 weeks, and after 20 weeks, the plasma glucose concentration of the group where the blowfish extract was administered together was administered with water. It was about 20% lower than the group.

1 is a diagram showing the results of Western blot analysis of FAS (fatty acid synthase) using a sample obtained by extracting the liver from the mice to which the pufferfish extract was administered for 23 weeks. Tubulin is a protein that is continuously expressed in vivo, and used to determine whether the same amount of protein was used, that is, to confirm the accuracy of the experiment. FAS is an enzyme that acts at the early stage of fatty acid synthesis in the liver, and it seems that fatty acid synthesis is suppressed by the puffer fish extract, which indicates that the expression of FAS in the experimental group is markedly decreased, which is believed to reduce fat storage in the body. Dietaryly regulated FAS is an enzyme involved in fatty acid synthesis in the liver. In the group fed the blowfish extract, the expression of FAS (basal level) was significantly lowered, and the fatty acid synthesis seems to be inhibited by the blowfish extract, which seems to reduce the accumulation of fat in the body.

Example 3 Inhibitory Effect of Blowfish Extract on Weight Gain

In this example, the puffer fish extract prepared in Example 1 was administered to mice with a high fat normal diet for 6 months, and the change in body weight was observed to determine whether obesity diabetes was induced.

(1) Effect of Pufferfish Extract on Body Weight

Six-week-old mice C57BL / 6 (male) were divided into two groups consisting of 7 to 8 animals per group, followed by a normal diet for 30 weeks.

Group 1: Normal Diet + Blowfish Extract 25cc / g / d

Group 2: Normal Diet

The diet consumed about 2.2 grams per day per animal. This is calculated by feeding 100g a week and measuring the remaining food weight.

Mice were weighed every week after administration. Table 3 is a table showing the results of observing the change in weight by administering the blowfish extract of the present invention to the mouse for 30 weeks and measuring the weight every week. 2 shows the result of Table 3 by drawing.

Table 3.

As shown in Table 3, the comparison of the weight change while feeding the puffer fish extract for 30 weeks while ingesting the normal diet in the mice, confirmed that the weight gain is suppressed by about 14% compared to the control group It was. Therefore, it can be seen that the puffer fish extract of the present invention is effective in suppressing weight gain.

According to the composition for preventing or treating obesity, the obesity of an individual can be prevented or treated.

According to the pharmaceutical composition for the prevention and treatment of diabetic diseases of the present invention, diabetes can be prevented or treated.

Claims (5)

A composition for the prevention or treatment of obesity, comprising a water extract of puffer fish obtained by distilling detoxified puffer fish. The composition of claim 1, wherein the distillation is performed by distillation in a batch distillation column at a temperature of 100 ° C. to 150 ° C. at a pressure of 1 to 5 kgF / cm ² for 2 to 7 hours. A pharmaceutical composition for the prevention and treatment of diabetic diseases comprising the water extract of puffer fish obtained by distilling detoxified puffer fish. 4. The diabetic disease of claim 3, wherein the diabetic disease is one of chronic hyperglycemia, atherosclerosis, microangiopathy, kidney disease, heart disease, diabetic retinopathy and other eye diseases. The pharmaceutical composition will contain the above. The composition of claim 3, wherein the distillation is performed by distillation in a batch distillation column at a temperature of 100 ° C to 150 ° C and a pressure of 1 to 5 kgF / cm ² for 2 to 7 hours.

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