KR100592513B1 - Pharmaceutical composition or health food having antioxidizing activity comprising polyphosphate as active ingredient - Google Patents

Abstract

The present invention relates to a pharmaceutical composition or health food for antioxidants containing the phosphorus as an active ingredient, and more particularly to a pharmaceutical composition or health food for antioxidants containing the phosphorus represented by the formula (1) as an active ingredient It is about. Since the inpolymer may effectively buffer free radicals generated by ultraviolet light and oxidize DNA, the composition of the present invention including the same may be usefully used as an antioxidant pharmaceutical composition or health food.

<Formula 1>

In the above, n is as described in the specification.

Description

Pharmaceutical composition or health food having antioxidizing activity comprising polyphosphate as active ingredient}             

1 is a diagram showing a state that the DNA and the polymer is ionic bond by Ca ²⁺ pier,

Figure 2 is a three-dimensional illustration of the binding state between the molecule and the in vivo polymer in general, including DNA,

3 is a graph showing the degree of colony formation according to the presence or absence of UV irradiation when 30 μl of 5% inpolymer was added.

4 is a graph showing the degree of colony formation according to the presence or absence of UV irradiation when 40 μl of 5% inpolymer was added.

5 is a graph showing the degree of colony formation according to the presence or absence of UV irradiation when 50 μl of 5% inpolymer was added.

6 is a graph showing the degree of colony formation according to the presence or absence of UV irradiation when 60 μl of 5% inpolymer was added.

The present invention relates to a pharmaceutical composition or health food for antioxidant, and more particularly, to a pharmaceutical composition or health food for antioxidant containing a phosphorus as an active ingredient.

Oxides, such as free radicals, are produced in the body by external stress, ultraviolet rays, smoking, drugs, and free radicals, and cause non-selective and irreversible destruction of cellular components such as lipids, proteins, sugars, and DNA. Aging, as well as cancer, stroke, Parkinson's disease, such as brain diseases, heart disease, ischemia, arteriosclerosis, skin diseases, digestive diseases, inflammation, rheumatism, autoimmune diseases are known to cause various diseases. Therefore, if the damage caused by these oxides can be reduced, the oxidation and aging of the cells will be reduced and the lifespan can be extended.

In the late 1960s, the research on antioxidants was discovered in earnest with the discovery of SOD, an enzyme that eliminates superoxide radicals. (Halliwell, B., and JMC Gutteridge., The chemistry of oxygen radicals and other oxygen-derived species.In: Free Radicals in Biology and Medicine., New York: Oxford University Press, 1985, pp 20-64). In recent years, research on the development of antioxidants as food additives has revealed that active oxygen and peroxides are directly responsible for various diseases and aging, and the antioxidant research has been shifted to the search for antioxidants as anti-aging and disease treatment agents. There is a situation.

Antioxidants that have been developed and used so far include synthetic antioxidants such as tert-butylhydroxytoluene (BHT) and tert-butylhydroxyanisol (BHA), natural antioxidants such as α-tocopherol, vitamin C, carotenoids, flavonoids, tannins, and antioxidants such as SOD. The situation is limited to enzymes. However, these antioxidants are limited to use due to various problems such as toxicity, low activity and limit of use. Therefore, research is being actively conducted to search for safer and stronger antioxidants from natural or microbial metabolites. Antioxidants to be studied include lipid peroxideation inhibitors, free radical scavengers or free radicals that directly eliminate free radicals that directly cause oxidative damage in vivo. It has been extended to more active antioxidants, such as preventive antioxidants such as xanthine oxidase inhibitors that inhibit the reaction of reactive oxygen production itself. It is focused on this large, safe, low molecular weight natural antioxidant.

Meanwhile, polyphosphate refers to a linear polymer of phosphates in which two or more phosphates are connected to dozens or hundreds of phosphates to form orthophosphate (Pi). phosphoanhydride). The chain ends of these inpolymers are attacked by AMP, ADP, glucose or water, respectively, by the catalysis of P-AMP phosphotransferase, inpolymer kinase, inpolymer glucokinase and exopolyphosphatase, and internally. Is attacked by endopolyphosphatase.

Since these inpolymer molecules have a high anion state, they can bind firmly to polyvalent cations such as cobalt, copper, magnesium, calcium, iron, and zinc. Due to this property, substances to be taken through normal microbial metabolism can be stably bound. It is known that it can eventually inhibit the growth of microorganisms. Phosphorus polymers are used in food and cheese color promoters and additives, canned milk curds, various carbonated water additives, hemorrhoids and gastrointestinal drugs, and have been certified as harmless to the human body by the US FDA and the Department of Agriculture. Although inpolymers have been found in animal cells, their function has not yet been clarified. To date, only a few studies of antimicrobial activity have been reported (Kornberg A., Rao NN., Ault-Riche D., Annu. Rev.). Biochem. , 68.89-125, 1999; Eisenstadt, E., BC Carlton, and BJ Brown, "Gene mutation", pp 222-239, "Gene Transfer" pp 243-250, In P Gerhardt, RGE Murray, WA Wood. , and NR Krieg (eds.), Mannual of Methods for General and Molecular Bacteriology.ASM, Washington. DC 1994).

Accordingly, the present inventors have studied the above-described phosphors, and as a result, it is confirmed that the phosphors have an excellent antioxidant action, and thus, the phosphorus can be usefully used in antioxidant pharmaceutical compositions or health foods. The invention has been completed.

An object of the present invention is to provide an antioxidant pharmaceutical composition or health food containing an inpolymer as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for antioxidant containing an inpolymer as an active ingredient.

The present invention also provides an antioxidant health food containing the phosphorus as an active ingredient.

The present invention also provides a cosmetic for antioxidant containing the phosphor as an active ingredient.

Hereinafter, the present invention will be described in detail.

The present invention provides a pharmaceutical composition containing the inpolymer represented by the following formula (1) as an active ingredient.

In the above, n is 20 to 100.

DNA is an anionic polymer and an inpolymer is also an anionic polymer. Since the anionic polymers cannot bind to each other, a cation molecule such as Ca ²⁺ can be used as a bridge to enable biomolecules such as DNA to ionically bond with the inpolymer (see FIG. 1). As such, when the inpolymer is bound to the DNA, an oxide such as free radicals cannot attack the DNA, thereby oxidizing the DNA and thus preventing or inhibiting bioaging. Figure 2 shows a general model of molecules in vivo, by binding the inpolymer to these molecules in vivo can be prevented from oxidation by oxidizing material can be prevented from aging by oxidation.

As a preferred embodiment, the present inventors examined how to protect against UV-induced strains and wild-type strains from UV-induced damage when coated with inpolymers. The number of colonies increased in the order of 65 chain length inpolymer and 75 chain length inpolymer. This means that 75 polymers have a higher protective effect from UV than 65 chains.

For wild type strains, the colony number increased in the order of control, 65 chain length inpolymer, and 75 chain length inpolymer. Colonies could not be observed in the control group, indicating that all strains were killed by UV irradiation. Compared with no UV irradiation, wild type or mutant strains had the highest number of colonies in the control group, and the number of colonies was higher in 75 cases than in 65 chain lengths (see Table 1 and FIGS. 3 to 6). ). The results indicate that the 75-chain inpolymer has a greater effect on the growth of the strain in any sense than the 65-polymer inpolymer.

In addition, the present inventors, as a preferred embodiment, by coating the Ca ²⁺ and the polymer directly on the DNA and the degree of nucleotide sequence change according to the formation of TT dimer when UV irradiation, the inpolymer is in the incidence of mutation The impact was confirmed. This provides direct data on the protective effect of the polymers against DNA damage. As a result, when comparing the formation rate of DNA TT dimer according to the case of direct UV irradiation to the DNA and the treatment of the polymer to the DNA after UV irradiation, when the UV irradiation was performed by adding the polymer to the DNA It was confirmed that the formation of TT dimer was almost completely suppressed (see Table 2). In the above experiments, it was also confirmed that the 75-chain length of the inpolymer has a greater protection against DNA than the 65-chain length of the polymer.

Therefore, it can be seen from the above results that the inpolymer of the present invention can be usefully used for the prevention or treatment of various diseases caused by aging or free radicals.

The pharmaceutical composition for antioxidant containing the inpolymer of the present invention as an active ingredient can be usefully used for the treatment or prevention of diseases caused by oxidation of cellular components by active oxygen. Such diseases include, for example, cancer, aging, coronary heart disease, hyperlipidemia, arteriosclerosis, multiple sclerosis, autoimmune encephalomyelitis, stroke, Alzheimer's disease and enteritis, but are not necessarily limited thereto.

The pharmaceutical composition containing the inpolymer of the present invention as an active ingredient may further include excipients, disintegrants, sweeteners, lubricants, flavoring agents, and the like, which are commonly used, and may be tablets, capsules, and powders by conventional methods. , Granules, suspensions, emulsions, syrups, and other liquids. Specifically, the pharmaceutical composition containing the inpolymer of the present invention as an active ingredient may be formulated for oral administration such as tablets, troches, lozenges, aqueous or oily suspensions, prepared powders or granules, Formulated as emulsions, hard or soft capsules, syrups or elixirs. Lactose, saccharose, sorbitol, mannitol, starch, amylopectin, binders such as cellulose or gelatin, excipients such as dicalcium phosphate, disintegrants such as corn starch or sweet potato starch, magnesium stearate, for formulation into formulations such as tablets and capsules Lubricants such as calcium stearate, sodium stearyl fumarate or polyethylene glycol wax. Capsules contain liquid carriers, such as fatty oils, in addition to the substances mentioned above.

In addition, the pharmaceutical composition containing the inpolymer of the present invention as an active ingredient can be administered parenterally, and parenteral administration is by subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection. To formulate into parenteral dosage forms, the inpolymers are mixed in water with stabilizers or buffers to prepare solutions or suspensions, which are formulated in unit dosage forms of ampoules or vials.

The dosage of the inpolymer as an active ingredient of the pharmaceutical composition of the present invention is appropriately selected depending on the absorption rate, inactivation rate and excretion rate of the inpolymer in the body, the age, sex and condition of the patient, the severity of the disease to be treated, In the case of an oral dosage form, an adult may be administered to the adult one time the inpolymer per kg of body weight in an amount of 80 mg, and divided into two doses of 40 mg.

In addition, the present invention provides a health food for antioxidant containing the inpolymer represented by the formula (1) as an active ingredient.

Since the phosphor polymer of the present invention has high antioxidant activity due to its excellent peroxidation inhibitory activity and radical scavenging activity, it can be usefully used for health food for antioxidant.

When the inpolymer is used as a food additive, the inpolymer may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method. The blending amount of the active ingredient can be suitably determined according to the purpose of its use (prevention, health or therapeutic treatment). Generally, in the preparation of foods or beverages, the inpolymer is added in an amount of 0.1 to 15% by weight, preferably 0.2 to 10% by weight relative to the raw material. However, in the case of long-term intake for health and hygiene or health control, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety. Is sure.

There is no particular limitation on the kind of food. Examples of foods to which the above substances can be added include dairy products, including drinks, meat, sausages, breads, chocolates, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, beverages, alcoholic beverages. And vitamin complexes and the like, and include all of the functional foods in the conventional sense.

In addition, the present invention provides an anti-oxidant cosmetic containing the phosphorus represented by the formula (1) as an active ingredient.

Vitamin C, vitamin E, and the like, which are commonly used as antioxidants, have limitations such as discoloration due to water or light in various formulations, and their amount of use has been extremely limited. Phosphorus polymers can be usefully used in various antioxidant cosmetics because they can overcome the limitations of the formulations of the conventional antioxidants.

In the cosmetic of the present invention, the phosphor is excellent in the antioxidant activity and the radical scavenging activity and has a high antioxidant activity, it can be usefully used for the prevention of peroxidation of the skin. Therefore, the inpolymer may be used as a cosmetic sample for inhibiting skin aging, maintaining skin elasticity or improving wrinkles, and is preferably used as a basic cosmetic sample of softening cream, nutrient cream, nourishing cream, essence, pack or bath powder. Can be.

In the cosmetics containing the polymer of the present invention as an active ingredient, the polymer is usually added to the cosmetic composition contained in an amount of 0.0001 to 10% by weight, preferably 0.001 to 1% by weight.

In the pharmaceutical composition, health food or cosmetic of the present invention, the number of the length of the inpolymer chain is preferably 25 to 80, more preferably 65 to 75.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following Examples are merely to illustrate the invention, the present invention is not limited to the following Examples.

Example 1 Measurement of UV Protective Effect by Inpolymers According to Strain and Chain Length

The inventors have identified how well protected against UV damage when coated with inpolymers against highly sensitive and wild type strains. For this purpose, Salmonella typhimurium LT2 was used as a wild type strain, and Salmonella typhimurium TA98 (KCTC 2053: hisD3052 rfa-uvrB) was used as a mutant strain, all from the Korea Institute of Bioscience and Biotechnology Gene Bank. I was sold. The Salmonella typhimurium TA98 strain is a strain commonly used for the detection of mutagen, and has a characteristic of not growing in a minimal medium lacking histidine as a nutritional requirement for histidine and biotin. However, reverse mutation of His + by the mutant causes growth in minimal media lacking histidine. Using the same principle as above, only a very small amount of histidine is added to the semi-solid medium inoculating the culture medium to distinguish between colony of reverse mutation and mutation and non-occurrence, and how much it is protected from UV when coated with inpolymer. It was confirmed.

As the medium, TSB medium (Tryptone, Soyton), TSA medium (Tryptone, Soyton, agar), Ames minimal medium and Soft Top agar were used, and the buffer was 0.65 M or 0.75 M. CaCl ₂ buffer was used. In the above, TSB medium was prepared by dissolving 30 g of Tryptic Soy Broth (DB) in 1 L of water, and TSA medium was prepared with 30 g of Tryptic Soy Broth (DB) and 15 g of Bacto Agar (DB). It was prepared by dissolving in water. Ames minimum medium was prepared by dissolving 200 ml of 50X VB Salts, 200 ml of 10% glucose, and 20 g of Bacto Agar in a total of 1 liter of distilled water, where 50X VB Salts consisted of 1 g of MgSO ₄ · 7H ₂ O (Sigma) and citric acid. 1 g of H ₂ O (Sigma), 50 g of K ₂ HPO ₄ (Sigma), and 17.5 g of sodium ammonium phosphate (Sigma) were prepared by dissolving in 670 ml of distilled water at about 45 ° C. In addition, the soft top agar was prepared by dissolving 1 g of NaCl and 1.2 g of Bacto Agar in 200 ml of distilled water and then adding 20 ml of a small amount of histidine-biotin solution, wherein the histidine-biotin solution was D-biotin (Sigma) 0.0124. It was prepared by dissolving g and 0.0096 g of L-histidine (Sigma) in 100 ml of distilled water. For the polymer, 5% of the inpolymer solution having 65 or 75 chain length was used for the experiment.

First, Salmonella typhimurium LT2 or Salmonella typhimurium TA98 strain was inoculated in 50 ml of TSB medium for 24 hours after inoculation. After 24 hours of incubation, strains of 3 × 10 ⁸ cells, Ca ²⁺ buffer, inpolymer solution and SDW were mixed. In this case, 10 μl and 100 μl of cells and Ca ²⁺ buffers were used, respectively, and the polymers were 30, 40, 50, or 60 μl at 5% concentration of the polymer having 65 or 75 chain lengths, respectively. Used. Salmonella typhimurium LT2 and Salmonella typhimurium TA98 strains were respectively dispensed on a plate and irradiated with UV at a wavelength of 254 nm at a distance of 20 cm for 2 minutes. Used. After UV irradiation, 100 μl of each strain was inoculated into 5 ml of soft top agar, quickly voltexed, and then plated in TSA medium and Ames minimal medium. When all of the soft tops were dried, the dish was turned upside down and incubated in a 36 ° C. incubator for 48-72 hours, after which colonies were observed. At this time, when the number of strains spread is large, the strain forms a small colony on the surface of at least agar medium due to the limited amount of histidine contained in the medium, but the reverse mutated strains are not affected by the concentration of histidine in the medium. Because of this, they form relatively large colonies. That is, the UV irradiation after addition of the inpolymer should show the number of colonies between the non UV irradiation and the control UV irradiation after addition. In other words, the control group without UV irradiation and UV irradiation after the addition of the inpolymer produced the most colonies and the control UV irradiation should be the least colonies.

UV irradiation UV irradiation UV irradiated Experiment One 2 3 4 One 2 3 4 D.W (TSA) 0 0 0 0 0 0 0 0 D.W 0 0 0 0 0 0 0 0 -4C 810 1290 1276 1180 1112 1860 2608 2157 -5C 660 550 487 358 470 918 682 690 -4 65 Ca 3 34 286 184 0 434 166 16 -5 65 Ca One 2 31 14 0 9 58 30 -4 75 Ca 0 18 118 20 0 262 224 8 -5 75 Ca 0 2 7 3 0 4 13 8 -4 65 P 0 0 11 One 0 15 16 26 -5 65 P 0 0 0 5 0 3 4 8 -4 75 P 0 0 6 0 0 4 8 6 -5 75 P 0 0 One 0 0 One 3 2

In the above, 1, 2, 3 and 4 The experiment shows the case with each of 30, 40, 50 or 60 ㎕ the philtrum copolymer at a concentration of 5%, -4 and -5 are each shown as the dilution factor 10 ^- Dilution multiples of ⁴ and ^10-5 .

As a result, Salmonella typhimurium TA98 strain was found to increase the number of colonies in the order of the control group, 65 chain length inpolymer, 75 chain length inpolymer when UV irradiation (control group was only 10 Only colonies observed). This means that 75 polymers have a higher protective effect from UV than 65 chains. In addition, the wild type Salmonella typhimurium LT2 strain was not a significant difference, but it was confirmed that the number of colonies increased in the order of the control group, the inpolymer having 65 chain length, the inpolymer having 75 chain length. Colonies could not be observed in the control group, indicating that all strains were killed by UV irradiation. Compared with no UV irradiation, Salmonella typhimurium TA98 and Salmonella typhimurium LT2 strains had the highest number of colonies in the control group, and the number of colonies was higher in 75 cases than in 65 chains ( Table 1 and FIGS. 3-6). The results indicate that the 75-chain inpolymer has a greater effect on the growth of the strain in any sense than the 65-polymer inpolymer.

Example 2 Investigation of the Effect of UV Irradiation on the Change of Base Sequence

The inventors confirmed the effect of the inpolymer on the incidence of mutations by examining the degree of change in the nucleotide sequence when UV was irradiated after coating Ca ²⁺ and the polymer directly on the DNA. This provides direct data on the protective effect of the polymers against DNA damage.

<2-1> UV irradiation

First, DNA was isolated using a DNA separation kit (Qiagen) using E. coli strain HB 101 (ATCC 33694) containing a pUC19 plasmid. After confirming the amount of DNA separated through electrophoresis, a mixture of DNA and the polymer was prepared in the following composition.

1) 20 μl DNA + 10 μl CaCl ₂ + 10 μl inpolymer, 10 μl CaCl ₂ buffer

2) 20 μl DNA + 10 μl distilled water + 10 μl inpolymer, 10 μl CaCl ₂ buffer

3) 20 μl DNA + 10 μl CaCl ₂ + 10 μl distilled water, 10 μl CaCl ₂ buffer

4) 20 μl DNA + 20 μl distilled water-(positive control)

5) 20 μl DNA + 20 μl distilled water-(negative control)

In the above, the polymer was used at a concentration of 5%, and 10 μl of CaCl ₂ buffer of 0.65 M and 0.75 M, respectively, was added at the length of 65 and 75 chains by chain length. The inpolymer mixtures were prepared with the composition as described above, whereby each buffer was added and allowed to stand at room temperature for 5 minutes to give sufficient time to be coated. The mixture prepared above was irradiated with UV for 2 minutes at a wavelength of 254 nm at a distance of 20 cm except for the negative control.

<2-2> Isolation and Sequencing of Pure DNA

40 μl of the DNA mixture of Example 2 and 460 μl of 0.5 M EDTA solution were mixed well, followed by centrifugation at 15,000 rpm for 15 minutes. Only the supernatant was recovered well, mixed with 1 ml of cold (iso) cold isopropanol and incubated at -70 ° C for 30 minutes. After obtaining the DNA pellet (peltet) by centrifugation, the DNA pellet was washed well with 1 ml of cooled 70% ethanol, and then centrifuged twice at 12,000 rpm for 15 minutes and dried. DNA pellet was well dissolved in 11 E buffer (Bioneer, DNA PreMate ^™ II, Cat. No. K 3011), and then the amount of DNA was determined from the absorbance values using electrophoresis or UV spectrophotometer. The formation rate of was analyzed. The formation rate of TT dimer was calculated in% using the experimental value / control x 100 (%).

 Solution treatment rate T-T dimer I Ⅱ Control 28 28 65 CaCl ₂ 19 17 75 CaCl ₂ 17 12 65 Inpolymer 11 11 75 inpolymer 8 9 65 CaCl ₂ + Inpolymer 4 4 75 CaCl ₂ + Inpolymer One 0

In the above, I is a case where 20 μl of DNA + 10 μl of CaCl ₂ + 10 μl of 5% inpolymer is mixed, and II is 20 μl of DNA + 20 μl of CaCl _2. 20 μl of a + 5% inpolymer was mixed.

As a result, when comparing the formation rate of DNA TT dimer according to the case of direct UV irradiation with DNA and the polymer after treating the polymer with DNA, the TT dimer was found to be 28 In the case of the calcium solution treatment, the decrease was 9-11 at the 0.65 M concentration and 11-16 at the 0.75 M concentration. In addition, in the case of adding only the polymer, 17 chains decreased by 65 chain lengths, and about 19-20 in the 75 chain lengths, and 65 chain lengths when the calcium solution and the phosphorus were added together. In the case of 24 and 75 chain lengths, about 27-28 were reduced, and almost no TT dimer was formed (Table 2). From the above results, it can be seen that the 75-chain length inpolymer has a greater protection against DNA than the 65-chain length polymer.

Preparation Example 1 Preparation of Food Containing an In-Polymer

The present inventors prepared the food containing the inpolymer as an active ingredient as follows.

<1-1> Beverage Production

522 mg of honey

Chioctosanamide 5 mg

Nicotinamide 10 mg

Riboflavin Sodium Hydrochloride 3 mg

Pyridoxine hydrochloride 2 mg

Inositol 30 mg

Orthoic acid 50 mg

Inpolymer 0.48-1.28 mg

200 ml of water

With the above composition and content, drinks were prepared using conventional methods.

<1-2> Preparation of Chewing Gum

Gum base 20%

Sugar 76.36-76.76%

Inpolymer 0.24-0.64%

1% fruit flavor

Water 2%

Chewing gum was prepared using conventional methods using the above composition and content.

<1-3> Preparation of Candy

50 to 60% sugar

Starch syrup 39.26-49.66%

Inpolymer 0.24-0.64%

Orange flavor 0.1%

Candy was prepared using conventional methods with the above composition and content.

<1-4> Preparation of Biscuits

Force Class 1 88 kg

Gravity First Class 76.4 ㎏

16.5 kg per white

2.5 kg of salt

2.7 kg of glucose

Palm shortening 40.5 kg

5.3 kg of ammo

Medium kg 0.6 kg

0.55 kg sodium bisulfite

Rice flour 5.0 kg

Vitamin B1 0.003 kg

0.003 kg of vitamin B2

Milk Flavor 0.16 ㎏

71.1 kg of water

Whole milk powder 4 kg

Substitute powder 1 kg

0.1 kg of calcium phosphate

Spray salt 1 kg

25 kg of spray oil

Inpolymer 0.2-0.5 kg

Biscuits were prepared using conventional methods with the above composition and content.

<1-5> Preparation of Ice Cream

Milkfat 10.0%

Non-fat solids 10.8%

167 sugar 12.0%

Starch syrup 3.0%

Emulsifying stabilizer (span) 0.5%

Spices (Strawberries) 0.15%

Water 63.31-62.91%

Inpolymer 0.24-0.64%

Ice cream was prepared using conventional methods using the above composition and content.

<1-6> Preparation of Chocolate

Sugar 34.36-34.76%

Cocoa Butter 34%

Cocoa Mass 15%

Cocoa Powder 15%

Lecithin 0.5%

0.5% vanilla

Inpolymer 0.24-0.64%

With the above composition and content, chocolate was prepared using conventional methods.

Preparation Example 2 Preparation of Antioxidant Pharmaceutical Composition

The present inventors prepared the antioxidant pharmaceutical composition containing the phosphorus as an active ingredient as follows.

<2-1> Manufacturing method of syrup

Syrup containing 2% (weight / volume) as an active ingredient is prepared by the following method.

Inpolymer, saccharin and sugars were dissolved in 80 g of warm water. After the solution was cooled, a solution consisting of glycerin, saccharin, spices, ethanol, sorbic acid and distilled water was prepared and mixed thereto. Water was added to this mixture to make 100 mL (Table 3).

Raw material name Quantity (g) Inpolymer 2 saccharin 0.8 Party 25.4 glycerin 8.0 Spice 0.04 ethanol 4.0 Sorbic acid 0.4 Distilled water dose

<2-2> Manufacturing method of tablet

A tablet containing 15 mg of active ingredient is prepared by the following method.

It was mixed with 250 g of inpolymer, 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid. 10% gelatin solution was added to the mixture, which was then ground and passed through a 14 mesh sieve. It was dried and the mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into a tablet (Table 4).

Raw material name Quantity (g) Inpolymer 250 Lactose 175.9 Potato starch 180 Colloidal silicic acid 32 Gelatin solution 10% Potato starch 160 talc 50 Magnesium stearate 5

As described above, since the phosphorus has a high antioxidant activity, a pharmaceutical composition containing it as an active ingredient may be used for the treatment and prevention of diseases related to peroxidation.

Preparation Example 3 Preparation of Softening Cosmetic Water Containing Phosphor Polymer

Composition of Softener Longevity Containing Inpolymer or Antioxidant Preparation Example <3-1> Preparation Example <3-2> Preparation Example <3-3> Comparative Example 1 Comparative Example 2 1. Purified water 88.369 91.17 82.17 91.17 91.67 2. Glycerin 3 3 3 3 3 3. 1,3-butylene glycol 2 2 2 2 2 4. Hyaluronic Acid One One One One One 5. Inpolymer 0.001 One 10 - - 6. Vitamin C - - - One - 7. Ethanol (95%) 5 1.2 1.2 1.2 1.2 8. Preservative 0.1 0.1 0.1 0.1 0.1 9. Solubilizer 0.4 0.4 0.4 0.4 0.4 10. Incense 0.13 0.13 0.13 0.13 0.13 11.Vitamin E - - - - 0.5

The present inventors first mixed and completely dissolved the raw materials 1 to 6 of Table 5 in order to prepare the flexible cosmetics containing the phosphor. Next, 8 to 11 raw materials were heated to 30 ° C., mixed and introduced into 7 raw materials, and then solubilized while gradually added to the mixed solution of the above 1 to 6 raw materials to prepare flexible softener.

Preparation Example 4 Preparation of Emulsion-Type Cosmetic Water Containing Inpolymer

The present inventors prepared the emulsifier-type lotion with the following composition.

number Raw material name Preparation Example <4-1> Preparation Example <4-2> Preparation Example <4-3> 10 STEARIC ACID 0.3 0.3 0.3 20 CETANOL-K One One One 30 GMS # 105 0.5 0.5 0.5 40 WECOBEE SS 0.5 0.5 0.5 50 ARL # 165 0.8 0.8 0.8 60 ARL # 60 0.2 0.2 0.2 70 D-M 0.2 0.2 0.2 80 D-P 0.05 0.05 0.05 90 PHYTOSQUALANE One One One 100 CEH 2 2 2 110 MDF 0.5 0.5 0.5 120 MANGO BUTTER 0.1 0.1 0.1 130 TWEEN # 60 One One One 140 DC 200 0.5 0.5 0.5 150 DI-WATER to 100 to 100 to 100 160 GLYCERINE 3 3 3 170 1,3-BG One One One 180 25 chain inpolymers 5 0 0 190 65 chain inpolymers 0 5 0 200 75 chain inpolymers 0 0 5 200 EDTA-2NA 0.02 0.02 0.02 210 TEA 0.13 0.13 0.13 220 CARBOPOL # 941 (1%) 12 12 12 230 BIO-HE One One One 240 GERMALL 115 0.2 0.2 0.2 250 PERFUME 0.15 0.15 0.15

Experimental Example 1 Stability Measurement of Soft Cosmetics

In order to measure the stability of the flexible cosmetics prepared above, the present inventors evaluated the discoloration of the flexible cosmetics, the overall feeling of use and storage stability.

<1-1> Measurement of discoloration

Discoloration was observed after incubation for 1 week in a 30 ° C constant temperature bath in Examples 1 to 3 and Comparative Example 1 and Comparative Example 2 put in a transparent container, the results are shown in Table 7.

Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Discoloration X X X O O

As can be seen in Table 7, the flexible cosmetics containing the inpolymer had no discoloration in appearance, while the flexible cosmetics containing the vitamin C or vitamin E were yellow.

<1-2> feeling test

Twenty women aged 20 to 30 years were asked to apply the softening lotion on the face, and then the spreadability, stickiness, moisturizing effect and the feeling of skin application were evaluated and the results are shown in Table 8. In this case, the evaluation criteria are 1: very bad, 2: bad, 3: normal, 4: good and 5: very good.

Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Spreadability 4 4 3 4 4 Sticky 4 4 3 4 4 Moisturizing 3 4 5 4 4 Feeling when applying skin 4 4 3 4 4

From the results of Table 8, it was confirmed that the formulation containing the inpolymer does not inhibit the overall feeling in general softening longevity, it is possible to improve the moisturizing power when used in an appropriate amount.

<1-3> storage stability

The present inventors investigated the stability according to the change of temperature in order to confirm the stability of the flexible cosmetics. Specifically, each sample was placed in a thermostat at -5, 5, 30, 37, 45 ° C. and observed for three months in appearance change, that is, phase separation and change in suspension degree, and the results are shown in Table 9.

Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 -5 ℃ 1 week 1 month 3 months ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ 5 ℃ 1 week 1 month 3 months ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ △ ◎ ◎ △ 30 ℃ 1 week 1 month 3 months ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ △ △ X △ △ X 37 ℃ 1 week 1 month 3 months ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ △ X X △ X X 45 ℃ 1 week 1 month 3 months ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ △ X X △ X X

◎; Very good, Δ; Discoloration, X; detach

From the results of Table 9, it was confirmed that the flexible longevity containing the inpolymer of the present invention has excellent stability in the water-soluble formulation. Similar results were also obtained in the emulsifier type.

Hereinafter, specific diseases to which the pharmaceutical composition including the inpolymer of the present invention may be applied will be described.

However, the following application examples are only for illustrating the present invention, and the content of the present invention is not limited to the following application examples.

<Application example 1> Cancer

It is caused by a myriad of cancers, but the most fundamental cause is the destruction of cells by the free radicals and their inability to repair them, leading to impairment of cell function, which progresses to cancer (Ames, BN, Science , 1983 , 221). , 1256-1264). On the other hand, the effects of phenolic acid in fruits on liver cancer (Sun J et al ., J Agric Food Chem , 2002 , 4; 50 (25), 7449-7454), and the effect of lycopene on tomatoes on breast cancer (Hadley CW et al ., Exp Biol Med , 2002 , 227 (10), 869-80), effect of isoverbascoside on gastric cancer (Chen RC et al ., Acta Pharmacol Sin , 2002 , 23 ( 11), 997-1001) and several known antioxidants are also effective against other cancers. Therefore, it can be seen that the antioxidant can be effectively used for the treatment and prevention of various types of cancer, the antioxidant pharmaceutical composition of the present invention excellent in antioxidant activity can be effectively used for the treatment and prevention of cancer.

Application Example 2 Aging

Free radicals, which are generated by the metabolic process in the normal course of metabolism, cause oxidative damage by non-selective and irreversible destruction of cell components such as lipids, proteins, sugars, or DNA. Harman, D, Free radical theory of aging , 1986 , 3-49). In addition, it has been observed that lifespan is extended by reducing basal metabolic rate, ie oxygen consumption, such as by limiting diet or reducing exercise by varying experimental conditions (Medvedev, ZA, Biol Rev. , 1990 , 65, 375-398; Loe , J. et al ., J. Biol. Chem ., 1971 , 32, 103-121; Sohal, RS, Aging , 1982 , 5, 21-24). In other words, the removal of free radicals is a way to delay aging and there are many antioxidants are currently developed to remove free radicals. Therefore, the antioxidant pharmaceutical composition of the present invention excellent in antioxidant activity may delay aging.

<Application Example 3> Coronary heart disease, hyperlipidemia and arteriosclerosis

Treatment of cholesterol biosynthetic enzyme inhibitors in patients with coronary heart disease and hypercholesterolemia reduces cholesterol content in low-density fats, but inhibits the biosynthesis of ubiquinone Q10 for peroxidation by free radicals, thereby reducing low-density lipoproteins. The protective effect was not effective in the treatment of the disease, and the administration of the antioxidant cerivastatin or probucol to the patients resulted in a sharp decrease in the content of low density lipoproteins (Lankin VZ et al ., Bull Exp Biol Med , 2002 , 134 (1), 39-42). In addition, in clinical trials in which the antioxidant dihydropyridine calcium antagonist lacidipine was administered to atherosclerosis patients, the size of atherosclerotic lesions was reduced by lowering blood pressure and lowering cholesterol levels in the blood vessel walls (Haller). H et al ., Drugs RD , 2002 , 3 (5), 311-23). That is, the antioxidant substance can be seen that it is an excellent substance in the treatment and prevention of vascular diseases related to cholesterol, such as coronary heart disease, hyperlipidemia and arteriosclerosis, the antioxidant pharmaceutical composition of the present invention excellent in antioxidant activity is coronary heart disease It can be used for the treatment or prevention of vascular diseases such as hyperlipidemia, arteriosclerosis.

Application Example 4 Multiple Sclerosis and Autoimmune Encephalomyelitis

In patients with multiple sclerosis and autoimmune encephalomyelitis disease models, a weakness was observed in clinical trials in which ALA (alpha lipoic acid), a type of antioxidant, was administered to mice. In other words, oxidative stress is a major cause of multiple sclerosis and autoimmune encephalomyelitis, and antioxidants can be used to treat such neurological disorders (Marracci GH et al ., J Neuroimmunol , 2002 , 131 (1-2)). , 104-14). Therefore, the antioxidant pharmaceutical composition of the present invention having excellent antioxidant activity can be used for the treatment or prevention of neurological diseases such as multiple sclerosis and autoimmune encephalomyelitis.

Application Example 5 Stroke and Alzheimer's Disease

Oxidative stress, or free radicals, oxidizes the components of cells, leading to their dysfunction, and their dysfunction also impairs the function of nerve cells. This neuronal dysfunction causes stroke, shock, and the like. However, if these symptoms are not treated and given constant oxidative stress, serious brain diseases such as stroke and Alzheimer's disease will occur. In addition, antioxidants that can remove free radicals can be used to treat brain diseases such as stroke and Alzheimer's disease (Perry G et al ., Comp Biochem Physiol C Toxicol Phaarmacol , 2002 , 133 (4), 507-13; Cecchi C et al ., Free Radic Biol Med , 2002 , 15:33 (10), 1372-9; Smith MA et al ., Free Radic Biol Med , 2002 , 1:33 (9), 1194-9). Therefore, the antioxidant pharmaceutical composition of the present invention excellent in antioxidant activity can be used for the treatment or prevention of brain diseases such as stroke and Alzheimer's disease.

<Application Example 6> Enteritis

Excess peroxide by-products accumulate in leukocytes of enteritis patients, and cell damage by accumulated peroxide by-products is the cause of primary or secondary pathological mechanisms in the intestinal infection. That is, oxidative stress is a major cause of inflammatory enteritis by inducing intestinal infection (Kruidenier L et al ., Aliment Pharmacol Ther , 2002 , 16 (12), 1997-2015). Therefore, the antioxidant pharmaceutical composition of the present invention excellent in antioxidant activity can be used for the treatment or prevention of diseases related to inflammation such as inflammatory enteritis.

As discussed above, unlike synthetic antioxidants, the phosphor is harmless to the human body and excellent in activity compared to other natural antioxidants, and thus, a pharmaceutical composition or health for the prevention or treatment of diseases caused by aging or free radicals. It can be usefully used as a food.

Claims (12)

delete delete delete delete delete delete delete delete Cosmetics characterized in that it has an effect of inhibiting skin aging, maintaining skin elasticity or improving wrinkles, which contains the inpolymer represented by Formula 1 as an active ingredient: <Formula 1>

In the above, n is 65 to 75. 10. The cosmetic according to claim 9, wherein the cosmetic is selected from the group consisting of soft cosmetics, nourishing cosmetics, nourishing creams, essences, packs, and basic cosmetics of bath powder. delete delete

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