KR20110052952A - A pharmaceutical composition and food additive containing a persimmon fruit juice - Google Patents

Abstract

PURPOSE: A composition containing persimmon juice is provided to promote nicotine metabolism and to enhance blood antioxidative vitamin and ubiquinone. CONSTITUTION: A composition with a function of detoxifying tobacco toxicity due to smoking contains persimmon juice as an active ingredient. A composition for enhancing blood ubiquinone concentration contains persimmon juice as an active ingredient. A medical composition for preventing or treating disease caused by smoking contains persimmon juice as an active ingredient. The persimmon juice is prepared by pulverizing-juicing, double boiling, steaming, hot water extraction, and high pressure extraction.

Description

Pharmaceutical composition and food additive containing a Persimmon fruit juice

The present invention relates to a composition comprising the juice of persimmon, and relates to a composition that lowers the toxicity of tobacco during smoking and is useful for the prevention or treatment of diseases related to smoking.

The research for the present invention was partially supported by the Agriculture, Forestry, and Fisheries Department of Agriculture, Forestry and Technology Development Project [Task No .: 608007-05-1-SB210 Task Name: Development of Functional Search and Promotion Technique of Sweet Persimmon].

In recent years, the seriousness of smoking has increased, and not only direct smoking but also indirect smoking has increased its damage. Nicotine absorption due to smoking does not immediately reach fatality, but it causes many diseases that involve direct and indirect pain, which interferes with daily life and poses a risk for life. In particular, smoking by the mother causes many harms to the fetus and even severe malformations. As is well known, smoking is an important factor in respiratory diseases including lung cancer, various gastrointestinal diseases, various circulatory diseases including atherosclerosis, and promoting aging.

Tobacco smoke contains about 4,000 chemicals. Tar is a powerful carcinogen that can kill animals or insects in small amounts. In addition, all of the gaseous components of tobacco smoke, such as carbon monoxide, which is a main component of briquette gas, have a detrimental effect. Nicotine, which contains 2 mg per dog, is delivered to the brain in seven seconds of smoking, which is harmful to the heart, blood vessels and digestive system, and is completely excreted in vitro after three days. About 90% of nicotine is metabolized to cotinine by C-oxidation and excreted in vitro by urine. Nicotine is increased not only by smoking but also by secondhand smoke. When nicotine is absorbed into the body, it consumes 25 mg of vitamin C per cigarette and excites sympathetic nerves to constrict blood vessels, which leads to increased blood pressure, increased respiratory rate, changes in lipid metabolism, platelet aggregation, and hypercoagulation. May contribute to the development of cardiovascular disease. Nicotine also produces a lot of elastase and destroys alveolar structures, contributing to the development of emphysema. Therefore, there is an urgent need to develop a method of promoting the metabolism of nicotine to be quickly removed from the body.

Smoking increases the risk of developing cancer due to DNA damage, and is also an important cause of lung cancer, oral cancer, laryngeal cancer, esophageal cancer, kidney cancer, bladder cancer, pancreatic cancer and cervical cancer. Smokers also have a higher risk of morbidity and mortality than nonsmokers, including changes in serum lipid and lipoprotein levels and plasma antioxidant vitamin status.

Ubiquinone (coenzyme Q10) is known to play various roles in maintaining homeostasis in the body. Coenzyme Q10 also acts as an important antioxidant in mitochondria and lipid membranes in the form of ubiquinol in addition to its role as coenzyme of electron transport system in mitochondria, preventing damage of biofilm by free radicals, minimizing DNA oxidation, and functioning by aging It is known to prevent deterioration and to serve as a supplemental vitamin for the prevention and treatment of many diseases. Coenzyme Q10 is synthesized from lower ubiquinones such as Q6 or Q8 in younger people, but older and unhealthy people are not able to synthesize it sufficiently, so they need to be administered externally like vitamins. widely used as a dietary supplement). Pharmaceutical or nutritional supplements containing ubiquinone may be used for mitochondrial related diseases or metabolic diseases. Ubiquinone has also been reported to be effective for migraines. Recent studies have shown that ubiquinone is effective in maintaining a healthy heart or improving heart disease, such as increasing survival after cardiac arrest, preventing neurodegenerative diseases such as Parkinson's disease, and lowering systolic blood pressure in hypertensive patients. Has been reported. U.S. Patent No. 5,011,858 also describes that coenzyme Q10 is effective in the treatment of diseases caused by retroviruses such as AIDS. Coenzyme Q10 is also effective in maintaining healthy gums and teeth. Therefore, there is a greater demand to increase the level of coenzyme in the body by taking ubiquinone (coenzyme Q10).

Persimmon ( Diospyros kaki ) is a fruit with increasing cultivation area in Korea and is one of fruits with excellent nutritional value.It is a composition for treating immune-related diseases such as atopy and asthma containing persimmon extract (Patent Publication 10-2009- 0084159), an anti-obesity food containing immature persimmon (Patent Publication No. 10-2009-0025033) has been applied for a patent. However, the effects of detoxifying tobacco toxicity by nicotine and the like, and the enhancing effect of blood ubiquinone have not been studied.

The technical problem to be achieved by the present invention is to find a composition having a detoxifying effect of tobacco toxicity due to smoking. It is an object of the present invention to provide a composition useful for promoting the metabolism and removal of nicotine. It is another object of the present invention to provide a composition for inhibiting DNA damage. Another object of the present invention is to provide a composition for increasing the concentration of ubiquinone in the blood.

The present invention to solve the above problems provides a composition comprising a juice of persimmon as an active ingredient.

The pharmaceutical composition or food composition of the present invention containing persimmon juice as an active ingredient has an effect of promoting the metabolism and removal of nicotine in vivo. In addition, the composition of the present invention has the effect of inhibiting DNA damage and increases blood ubiquinone and antioxidants. The composition of the present invention can be used as a composition for deciphering the toxicity of tobacco caused by smoking, and thus can be used for the prevention, amelioration or treatment of diseases caused by smoking.

The present invention relates to a pharmaceutical composition or a food composition comprising persimmon juice as an active ingredient.

The inventors of the present invention, in the clinical trials of adult male smokers, ingesting the juice of sweet persimmon promotes the metabolism of nicotine into cotinine, which increases the amount of cotinine excreted in the urine, DNA damage is reduced, blood ubiquinone, It has been found that the concentrations of alpha-tocopherol and retinol are increased to complete the present invention.

Based on the test results, the present invention provides a composition comprising, in one aspect, the juice of persimmon as an active ingredient and having a function of detoxifying the toxicity of tobacco by smoking. In another aspect, the present invention comprises a persimmon juice as an active ingredient, and provides a composition characterized in promoting the metabolism or removal of nicotine in the body. In another aspect, the present invention includes a juice of persimmon as an active ingredient, and provides a composition characterized in that it inhibits DNA damage. In another aspect, the present invention comprises a persimmon juice as an active ingredient, provides a composition characterized in that to increase the concentration of ubiquinone in the blood. The composition of the present invention can be used as a pharmaceutical composition or food composition for preventing or treating diseases caused by smoking, including the juice of persimmon as an active ingredient.

The juice of the persimmons used in the compositions of the present invention can be prepared using various forms of persimmons, such as mature persimmons, immature persimmons, sweet persimmons, red persimmons, hongsi.

The juice of persimmons used in the present invention may be prepared by, for example, grinding-juice, water bath, steaming, hot water extraction, high pressure extraction, but is not limited thereto. The extracted persimmon juice can be used as it is, can be used to make a powder by a method such as concentrated or lyophilization, spray drying.

Smoking-related diseases that can be prevented, improved or treated by the composition of the present invention include lung cancer, respiratory diseases, various gastrointestinal diseases, various circulatory diseases including arteriosclerosis, aging, blood pressure increase, respiratory rate increase, lipid metabolism Changes, platelet aggregation, hypercoagulation, emphysema, lung cancer, oral cancer, laryngeal cancer, esophageal cancer, kidney cancer, bladder cancer, pancreatic cancer, cervical cancer, and the like.

Diseases associated with deficiency of ubiquinone that can be prevented, ameliorated or treated by the composition of the present invention include mitochondrial related diseases, metabolic diseases, migraines, heart diseases, neurodegenerative diseases such as Parkinson's disease, hypertension, acquired immunodeficiency syndrome (AIDS) Diseases such as retroviruses, and the like, but are not limited thereto.

Preparation of a medicament comprising the composition of the present invention can be carried out according to methods known in the art, and auxiliaries and further suitable carriers or diluents generally known and used may be used. The pharmaceutical compositions of the present invention may be used in the form of solids, solutions, emulsions, dispersants, micelles, liposomes and the like, wherein the composition obtained is used as an active ingredient with an organic or inorganic carrier or excipient suitable for enteral or parenteral application. Contains persimmon juice. The active ingredient may be mixed with pharmaceutically acceptable carriers which are generally nontoxic for, for example, tablets, pellets, capsules, suppositories, solutions, emulsions, suspensions and any other form suitable for use. have. Carriers which can be used include solid, semisolid or liquid glucose, lactose, gum arabic, gelatin, mannitol, starch paste, magnesium trisilicate salt, talc, corn starch, keratin, colloidal silica, potato starch, urea , Triglycerides of medium chain length, dextran, and other carriers suitable for use in the preparation of the formulations. In addition, auxiliaries, stabilizers, thickeners and coloring and flavoring agents can be used.

Because each subject has varying degrees of manifestation and each agent has unique therapeutic properties, it is up to the expert to determine the subject's response to the treatment and to change the dosage accordingly. Typical daily dosages of the compositions of the present invention are generally as persimmon juices. It is in the range of about 10 to 1000 ml / day (based on 60kg adult man), preferably about 50 ml to about 500 ml, but can be adjusted depending on the situation.

The composition of the present invention can be used as a food composition. The food composition comprising the juice of the persimmon of the present invention may be appropriately used alone or in combination with other foods or food ingredients according to a conventional method, and may also be used as a food additive. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use thereof. In general, the juice of persimmon may be added in an amount of 0.01 to 100% by weight, preferably 0.1 to 50% by weight, based on the content of the juice of persimmon, with respect to the raw materials, respectively, in the manufacture of food or beverage, but the amount added may be You can adjust as much as you want. The food composition is not particularly limited, and may be in any form such as powder, capsules, tablets, pills, liquids, etc. Examples of specific foods include meat, sausage, bread, chocolate, candy, snacks, confectionary, pizza, ramen, other noodles, Dairy products, including gum and ice cream, various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes, but is not limited thereto.

Hereinafter, the present invention will be described with reference to specific examples. However, these examples are only intended to illustrate the present invention, it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as limited by these examples.

Example

Example 1 Preparation of Persimmon Juice

After washing the purchased / harvested persimmons, they were crushed, water was added to 10% of the persimmon weight in the autoclave, followed by a water bath at 2 atm and 121 ° C. for 3 hours.

Example 2 Influence of Sweet Persimmon Juice on Nicotine Metabolism and Elimination of Adult Male Smokers

Subjects were 20 to 25 year old healthy males who selected 20 to 25 cigarettes per day through a preliminary smoking survey, and four per day persimmons (fruit juice, 320ml) were supplied in the form of sweet persimmon juice for 4 days. In addition, the diet was instructed to maintain the previous diet during the sweet persimmon intake period. Blood and urine were collected on an empty stomach before administration of sweet persimmon juice, and blood and urine were taken on an empty stomach the morning after 4 days of feeding persimmon juice. In addition, urine was collected for 24 hours from the day before the administration of sweet persimmon and juice to the morning of the persimmon juice administration, and urine was collected for 24 hours from the last day of the persimmon juice administration to the morning of the end of the persimmon juice administration. Keep fasting until the end. Blood and urine samples were stored frozen at −80 ° C. until analysis.

 Cortinine Analysis in Urine

Urine was collected for 24 hours for comparison before and after intake of persimmon juice. The urine sample was collected for 24 hours from the day before administration of the persimmon juice to the morning of the administration of persimmon juice. Urine was collected for 24 hours until the morning of the end of the juice, and the stomach was kept on an empty stomach until the end of the next morning. The collected 24-hour urine samples were stored at -80 ^o C, dissolved at room temperature, and measured using a cotinine assay reagent (Cotinine Direct ELISA kit, Bio-Quant Inc.). Urine was mixed with a cotinine enzyme conjugate and reacted with an anti-cotinine antibody in a micro-plate well, and then the absorbance at 450 nm was measured by ELISA for the color intensity indicated by the addition of a chromogenic substrate. The concentration was calculated using a standard curve.

When nicotine detoxification was measured before and after intake of sweet persimmon juice, the concentration of cotinine, a metabolite of tobacco nicotine, was 6019.82 ± 123.22ng / ml at 5724.69 ± 103.05 ng / ml after sweet persimmon juice intake than before persimmon juice intake. 0.01), which proved the detoxification ability of sweet persimmon against nicotine, one of the carcinogens of tobacco.

Example 3 Intake of Sweet Persimmon Juice in Adult Male Smokers DNA  Impact on damage

In order to investigate the protective effect of sweet persimmon against oxidative DNA damage in smokers, 200 μL of whole blood before and after ingestion of sweet persimmon obtained in Example 2 was added to 200 μL of 800 μL phosphate buffer solution (PBS) and Picol (Histopaque 1077). The leukocytes were isolated by treatment, and the prepared leukocytes were treated with 200 μM H ₂ O ₂ to induce oxidative stress. After the reaction, the white blood cells were evenly suspended in 0.7% low melting agarose gel (LMA) and fixed on a slide coated with 1% agarose. The fixed slides were lysed by immersion in cold alkaline lysis buffer (2.5 M NaCl, 100 mM Na ₂ EDTA, 10 mM tris, 1% Triton X-100) in dark conditions for 1 hour. After dissolving, the slides were unwinded by treatment with cold electrophoretic buffer (300 mM NaOH, 10 mM Na ₂ EDTA, pH> 13) for 20 minutes under dark conditions, and electrophoresis was performed at 25 V / 300 ± 3 mA for 20 minutes. It was. The electrophoretic slides were washed three times with 0.4 M Tris buffer (pH 7.4) and dried. Cells on the slides were stained with ethidium bromide and observed with a fluorescence microscope (Leica, Germany). Each cell image sent through a CCD camera (Nikon, Japan) was installed on a computer equipped with a Komet 5.0 comet image analyzing system (Kinetic Imaging, UK). Analyze on the phase. DNA damage caused by H ₂ O ₂ in leukocytes was shown by measuring the DNA content (Tail Intensity) in the tail portion that moved away from the nucleus and fell to the tail portion (Duthie SJ, Ma A, Ross MA, Collins AR. Cancer Res 56 1996, Molller P. Loft S. Am J Clin Nutr 76: 303-310. 2002).

Before ingesting sweet persimmon juice, the tail DNA intensity (%), which is the DNA content in the tail that moved from the nucleus to the tail, was 24%, but significantly decreased to 13% ( p <0.01) after ingestion. DNA damage was significantly lower than that of persimmon juice intake. This indicates that persimmon juice has a DNA damaging effect.

Example 4 Effect of Sweet Persimmon Juice Intake on Blood Concentrations of Antioxidant Vitamins and Ubiquinone in Adult Male Smokers

To investigate the effects of sweet persimmon juice on the blood concentrations of smoker's antioxidant vitamins and ubiquinones, retinol, alpha-tocopherol and Ubiquinone (Coenzyme Q10) content was analyzed using reversed phase HPLC (Genser D, Kang MH, Vogelsang H, Elmadfa I. Eur J Clin Nutr 53: 675-679. 1999). In other words, frozen plasma was dissolved at room temperature to precipitate proteins with ethanol and lipid components were extracted with n-hexane. After evaporating n-hexane, the remaining part was dissolved in eluent mixed with dichloromethane and methanol at a ratio of 15:85, 150 μL was taken into the guard-column of HPLC, and HPLC with UV detector. Analyzed. After reading the absorbance at 325 nm for retinol, 295 nm for alpha-tocopherol, and 270 nm for ubiquinone, the concentration of each nutrient was calculated from the area under the curve using an external calibration curve.

Retinol, an antioxidant that removes free radicals in the blood after sweet persimmon juice intake, was measured from 67.05 ± 5.43 μg / dl to 83 ± 4.66 μg / dl, respectively. <0.05), alpha-tocopherol from 650.39 ± 61.16μg / dl to 832.23 ± 54.82μg / dl (p <0.05), and ubiquinone (Coenzyme Q10) from 67.02 ± 9.22μg / dl to 100.25 ± 28.49μg / dl, respectively. significantly increased (p <0.001) (FIGS. 3 and 4).

Figure 1 shows the nicotine metabolism and elimination effect by sweet persimmon juice intake in smokers, compared to the urine cotinine content before and after intake of sweet juice (**, p <0.01). Figure 2 shows the protective effect of oxidative DNA damage by sweet persimmon juice intake smokers compared the DNA damage when H ₂ O ₂ induced oxidative stress in isolated white blood cells before and after the single persimmon intake (** , p <0.01).

Figure 3 shows the effect on the concentration of antioxidant vitamins in blood by sweet persimmon intake in smokers compared blood (a) retinol and (b) alpha-tocopherol content before and after sweet persimmon intake (*, p <0.05) .

Figure 4 compared the ubiquinone (coenzyme Q10) content in blood before and after sweet persimmon and juice intake in smokers (***, p <0.001).

Claims (6)

Comprising the juice of persimmon as an active ingredient, a composition characterized in that it has the action of detoxifying the toxicity of tobacco by smoking. The composition of claim 1 which promotes metabolism or removal of nicotine in the body. The composition of claim 1, wherein the composition inhibits DNA damage. Comprising a juice of persimmon as an active ingredient, a composition comprising increasing the concentration of ubiquinone in the blood. A pharmaceutical composition for preventing or treating diseases caused by smoking, comprising persimmon juice as an active ingredient. Food composition for preventing or ameliorating diseases caused by smoking, including persimmon juice as an active ingredient.

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