KR101561139B1 - COMPOSOTIONS COMPRISING α-LIPOIC ACID AND N-ACETYLCYSTEINE FOR PREVENTING OR TREATING OBESITY - Google Patents

Abstract

The present invention relates to a composition comprising α-lipoic acid and N-acetylcysteine as active ingredients. The mixed composition of α-lipoic acid and N-acetylcysteine of the present invention can reduce a risk of side effects due to drugs with synergistic effects due to merge administration of two drugs, and can be usefully used for preventing or treating obesity with excellent effects in inhibiting weight gain in comparison with each single composition comprising α-lipoic acid or N-acetylcysteine.

Description

[0001] The present invention relates to a composition for prevention or treatment of obesity comprising alpha-lipoic acid and N-acetylcysteine as active ingredients,

The present invention relates to a composition for preventing or treating obesity comprising alpha-lipoic acid and N-acetylcysteine as an active ingredient.

Obesity is the accumulation of excess fat in the body, and the World Health Organization (WHO) says that because of the increase in obesity around the world, vitamin, minerals and other micronutrients are low and energy intensive foods are consumed frequently , And the means of transport are the main reasons for the decrease in physical activity. In other words, the underlying cause of obesity is the calorie consumed is more energy than the calories burned. In particular, obesity increases the risk of developing type 2 diabetes, arteriosclerosis, and increases the risk of cardiovascular diseases by inducing cardiovascular disease. The remaining fat is accumulated in the liver and causes fatty liver, gallstone disease, cirrhosis . Excessive weight gain also affects both the bones and joints, resulting in skeletal abnormalities and limiting activity. This results in a vicious cycle in which obesity is further intensified.

As such, obesity is one of the symptoms but it is accompanied by many metabolic diseases. Therefore, it is urgent to develop therapeutic agents that are focused on and easy to use.

To date, obesity treatments are classified as appetite suppressants, fat absorption inhibitors, and energy consumption stimulants. Among the major obesity treatment drugs approved for long-term use are orlistat (trade name: XENICAL) and sibutramine : REDUCTIL). Orlistat is a lipase inhibitor, a lipase inhibitor secreted by the pancreas and the digestive system. It inhibits the lipase secreted from the pancreas and digestive system to prevent the absorption of fat. Sibutramine is an appetite suppressant that inhibits norepinephrine and serotonin Reduce reabsorption. However, orlistat causes fat-soluble vitamin absorption reduction, intestinal seizures, gas-induced stomach bloating, and oil-filled stools, and sibutramine causes side effects such as headache, dry mouth (severe thirst), insomnia and constipation. Recently, attention has focused on obesity treatment without side effects.

On the other hand, alpha-lipoic acid (C ₈ H ₁₄ O ₂ S ₂ ) has various names such as thioctic acid, 6,8-dithioctanoic acid, and 1,2-diethylene-3-pentanoic acid. Alpha-lipoic acid has emerged as a new vitamin because it is known that the unknown trace elements in liver and yeast extracts are lactic acid bacteria. In 1951, LJ Reed et al. First crystallized this trace component in the liver and named it alpha-lipoic acid, and then the structure was established by synthesis. Alpha-lipoic acid physiologically acts as a coenzyme closely related to thiamine in the complete oxidative decarboxylation of pyruvic acid or alpha-ketoglutaric acid. It is recognized as essential for metabolism, but it is not known what is required for food intake of higher animals, and the lack of lipoic acid in animals has not yet been fully tested. In recent years, it has been known that alpha-lipoic acid and its reduced form, DHLA (dihydrolipoic acid), have a function as an antioxidant, including peroxide radicals, hydroxyl radicals, peroxy radicals, and singlet oxygen ) With reactive oxygen species. In addition, it has a function of protecting the cell membrane by reacting with vitamin C or glutathione, and it has been reported that it acts effectively on oxidative stress when alpha-lipoic acid is administered.

In addition, N-acetylcysteine has been developed about 50 years ago and is mainly used as an expectorant agent or an antioxidant for the treatment of acetaminophen poisoning. N-acetylcysteine can be directly or indirectly reduced by oxidizing glutathione by indirectly reacting with peroxides, hydrogen peroxide and hydroxyl radicals to reduce oxidative stress or by providing cysteine as a source of glutathione biosynthesis. Which is known to exhibit an oxidative effect. N-acetylcysteine has been used for decades in various clinical fields such as treatment of acute respiratory distress syndrome, treatment of acute lung oxygen toxicity and prevention of acute renal failure by contrast agent, and is known as a safe drug which does not cause side effects.

On the other hand, the present inventors have previously confirmed that alpha-lipoic acid has a pronounced effect of inhibiting appetite in mice (Kim MS et al., Nat Med. 2004), and that N-acetylcysteine inhibits significant weight gain in rats (Korean Registered Patent No. 10-2003-0030302). However, there was a risk of side effects due to the drug when the single administration of each of the above ingredients was performed only at a high concentration. Thus, the inventors of the present invention confirmed that synergistic effect is exhibited when a combination of alpha-lipoic acid and N-acetylcysteine is administered in comparison with a single administration of each ingredient, and that an anti-obesity effect remarkably excellent even at a low concentration, Thereby completing the present invention.

It is an object of the present invention to provide a pharmaceutical composition for preventing or treating obesity comprising alpha-lipoic acid and N-acetylcysteine as an active ingredient.

It is still another object of the present invention to provide a food composition for preventing or ameliorating obesity comprising alpha-lipoic acid and N-acetylcysteine as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating obesity comprising alpha-lipoic acid and N-acetylcysteine as an active ingredient.

The present invention also provides a food composition for preventing or ameliorating obesity comprising alpha-lipoic acid and N-acetylcysteine as an active ingredient.

The mixed composition of alpha-lipoic acid and N-acetylcysteine of the present invention reduces the risk of side effects due to the drug due to the synergistic effect due to the combined administration of the two drugs and reduces the production of alpha-lipoic acid or N-acetylcysteine The composition of the present invention can be effectively used for prevention or treatment of obesity.

Fig. 1 shows the effect of suppressing weight gain when a single administration of alpha-lipoic acid or N-acetylcysteine is administered.
FIG. 2 is a graph comparing the effect of suppressing weight gain when alpha-lipoic acid or N-acetylcysteine is administered singly and when alpha-lipoic acid and N-acetylcysteine are administered in combination.

The present invention provides a composition for preventing or treating obesity comprising alpha-lipoic acid and N-acetylcysteine as an active ingredient.

The composition comprises a pharmaceutical composition or a food composition.

The alpha-lipoic acid or N-acetyl cysteine of the present invention can be synthesized by a conventional organic synthesis method or purchased commercially available reagents.

The alpha-lipoic acid contained in the composition of the present invention is not limited thereto, but it is a racemic form or an R-isomer, preferably an R-isomer.

The alpha-lipoic acid and N-acetyl cysteine of the present invention are remarkably excellent in the effect of suppressing weight gain compared with the case of administration of the two components together, N-acetylcysteine may be useful for the prevention or treatment of obesity. Alpha-lipoic acid and N-acetylcysteine, which have an appetite-suppressing effect and increase energy metabolism, are more effective when the two drugs are administered in combination, ) Synergistic effect, which is a more significant effect than the effect. This synergistic effect can result in a strong weight loss effect while reducing the side effects of high doses of the single drug.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions. In addition, it can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral formulations such as syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to a conventional method. Suitable formulations known in the art are preferably those as disclosed in Remington ' s Pharmaceutical Science, recently, Mack Publishing Company, Easton PA. Examples of carriers, excipients and diluents which may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. When the composition is formulated, it is prepared using a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant, which is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances and preservatives have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.

The term "administering" as used herein is meant to provide any desired composition of the invention to a subject in any suitable manner.

The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the individual, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. For a desired effect, the mixture of alpha-lipoic acid and N-acetylcysteine of the present invention may be administered in an amount of 0.1 mg / kg to 1000 mg / kg per day, and may be administered once or several times a day have.

The pharmaceutical composition of the present invention may be administered in various ways in an individual. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.

The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers for the prevention and treatment of obesity.

In the present invention, the term "health functional food" refers to a food having a biological control function such as prevention and improvement of disease, bio-defense, immunity, recovery after disease and aging inhibition.

The composition of the present invention can be added to a health functional food for the purpose of preventing or improving obesity. When alpha-lipoic acid and N-acetylcysteine of the present invention are used as a food additive, the alpha-lipoic acid and N-acetyl cysteine can be added intact, used together with other food or food ingredients, Can be used. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). Generally, the alpha-lipoic acid and N-acetyl cysteine of the present invention are added to the raw material in an amount of not more than 15% by weight, preferably not more than 10% by weight in the production of food or beverage. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

There is no particular limitation on the kind of the food. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, rice noodles, other noodles, gums, dairy products including ice cream, various soups, , An alcoholic beverage and a vitamin complex, and includes all the health foods in a conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. The above-mentioned natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may comprise flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of these additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, preferred embodiments and examples of the present invention will be described in order to facilitate understanding of the present invention. However, the following experimental examples and preparative examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the experimental examples and formulation examples.

Experimental Example 1. Confirmation of effect of inhibiting weight gain by the combination of alpha-lipoic acid and N-acetylcysteine

The following experiments were carried out in order to confirm that the effect of inhibiting weight gain by combination administration of alpha-lipoic acid and N-acetylcysteine is significantly superior to that of alpha-lipoic acid or N-acetylcysteine.

Specifically, 7 week old C57 / BL6J male mice were divided into a control group, an alpha-lipoic acid group, an N-acetylcysteine group, a combination of alpha-lipoic acid and N- % Carbohydrates were fed unrestrictedly. At the same time, alpha-lipoic acid was added to the diet for a period of 3 weeks, and alpha-lipoic acid was added to the diet at concentrations of 0.05%, 0.1% and 0.2% , And N-acetylcysteine was added at a concentration of 2 g / L, which was then ingested for 3 weeks in a negative manner, and the degree of weight gain was measured. The results are shown in Fig.

In addition, mice belonging to the group administered with alpha-lipoic acid and N-acetylcysteine were fed a diet supplemented with alpha-lipoic acid at a concentration of 0.2% and a diet containing N-acetylcysteine at a concentration of 2 g / L for 3 weeks And the weight gain of each group was measured. The results are shown in Fig.

As shown in Figs. 1 and 2, the weight gain of an animal group to which alpha-lipoic acid and N-acetylcysteine were administered in combination was significantly inhibited compared to the animal group to which each of alpha-lipoic acid or N-acetylcysteine was administered , Confirming the synergistic effect between the drugs.

Hereinafter, a pharmaceutical composition for prevention or treatment of obesity containing the alpha-lipoic acid and N-acetylcysteine of the present invention as an active ingredient and a preparation example of a food composition for preventing or improving are described below, but the present invention is not limited thereto It is just a specific description.

Formulation Example 1. Preparation of pharmaceutical composition

1-1. Manufacture of Powder

Mixture of alpha-lipoic acid and N-acetylcysteine 20 mg

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

1-2. Manufacture of tablets

Mixture of alpha-lipoic acid and N-acetylcysteine 10 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

1-3. Preparation of capsules

Mixture of alpha-lipoic acid and N-acetylcysteine 10 mg

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

1-4. Injection preparation

Mixture of alpha-lipoic acid and N-acetylcysteine 10 mg

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na ₂ HPO ₄ .2H ₂ O 26 mg

(2 ml) per 1 ampoule in accordance with the usual injection preparation method.

1-5. Manufacture of liquid agent

Mixture of alpha-lipoic acid and N-acetylcysteine 20 mg

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

Formulation Example 2. Preparation of Food Composition

2-1. Manufacture of health food

Mixture of alpha-lipoic acid and N-acetylcysteine 100 mg

Vitamin mixture quantity

Vitamin A acetate 70 μg

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

Vitamin B12 0.2μg

Vitamin C 10 mg

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 μg of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

2-2. Manufacture of health drinks

Mixture of alpha-lipoic acid and N-acetylcysteine 100 mg

Vitamin C 15 g

Vitamin E (powder) 100 g

19.75 g of ferrous lactate

3.5 g of zinc oxide

Nicotinic acid amide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3 g

Water quantification

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The resulting solution was filtered and sterilized in a sterilized 2 L container, ≪ / RTI >

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (4)

Alpha-lipoic acid and N-acetylcysteine as an active ingredient.
The pharmaceutical composition for preventing or treating obesity according to claim 1, wherein the alpha-lipoic acid is a racemate or an R-isomer.
Alpha-lipoic acid and N-acetylcysteine as an active ingredient.
4. The food composition for preventing or improving obesity according to claim 3, wherein the alpha-lipoic acid is a racemate or an R-isomer.

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