KR100977475B1 - uridine and uridine derivatives of enhancing biosynthesis of hyaluronic acid, glycosaminoglycan and/or collagen - Google Patents

Abstract

The present invention relates to uridine and uridine represented by the following Chemical Formula 1 which induces the promotion of the synthesis of hyaluronic acid, glycosaminoglycan and collagen in animals and human cells, animals and the human body. Preventive and therapeutic compositions for arthritis, discs (intervertebral disc protrusion), skin aging and wrinkles, dry eye, wound healing, scar removal, vaginal dryness, gum disease, atopic dermatitis and dry skin containing active ingredients of uridine derivatives It is about.

Active ingredients of uridine and uridine derivatives, arthritis, skin aging, dry eye, wound healing, scar removal and dry skin treatment and prevention, hyaluronic acid, glycosaminoglycans, collagen

Description

Uridine and uridine derivatives of enhancing biosynthesis of hyaluronic acid, glycosaminoglycan and / or collagen}, which promotes biosynthesis of hyaluronic acid, glycosaminoglycans and / or collagen             

1 is a graph illustrating the proliferation effect of chondrocytes by uridine.

Figure 2 is a graph of the degree of synthesis of hyaluronic acid in chondrocytes by uridine.

3 is a graph illustrating the degree of GAG synthesis in chondrocytes by uridine.

4 is a graph illustrating the degree of synthesis of hyaluronic acid of fibroblasts by uridine.

Figure 5 is a graph of the degree of collagen synthesis in the fibroblasts by uridine.

Figure 6 is a graph of the degree of synthesis of hyaluronic acid in the synovial cells by uridine.

7 is a graph illustrating the degree of collagen synthesis in synovial cells by uridine.

8 is a graph illustrating the proliferation effect in chondrocytes by UMP.

9 is a graph illustrating the degree of hyaluronic acid synthesis in chondrocytes by UMP.

10 is a graph illustrating the degree of GAG synthesis in chondrocytes by UMP.

11 is a graph illustrating the degree of synthesis of hyaluronic acid in fibroblasts by UMP.

12 is a graph illustrating the degree of collagen synthesis in fibroblasts by UMP.

FIG. 13 is a graph illustrating the degree of hyaluronic acid synthesis in synovial cells by UMP. FIG.

14 is a graph illustrating the degree of collagen synthesis in synovial cells by UMP.

The present invention is an arthritis, disc (intervertebral disc prolapse), skin aging and wrinkles, dry eye, wound healing, scar removal, vaginal dryness, gum disease, atopic dermatitis and dry skin containing uridine and uridine derivatives as an active ingredient And to a therapeutic composition, and more particularly, to uridine and urine represented by the following Chemical Formula 1, which shows excellent activity in promoting biosynthesis of hyaluronic acid, glycosaminoglycan and collagen in animals and human cells, animals and humans. Preventive and therapeutic compositions for arthritis, discs (intervertebral disc prolapse), dry skin and wrinkles, dry eye, wound healing, scar removal, vaginal dryness, gum disease, atopic dermatitis and dry skin containing uridine derivatives as an active ingredient It is about.

Here, glycosaminoglycan refers to polysaccharides containing amino sugars, including hyaluronic acid, chondroitin sulfate, keratan sulfate, heparin, heparan sulfate, and dermatan. Sulfuric acid (dermatan sulfate) and the like.

Hyaluronic acid and glycosaminoglycans are biopolymer polysaccharides present in all living organisms, and the human body is distributed in 56% of skin, 35% of muscle tissue, and 9% of joint synovial fluid and spinal fluid. As a substance, 1 molecule of hyaluronic acid polysaccharide combines with 218 water molecules to have both physical viscosity and elasticity, and performs various functions such as shock absorption and lubrication in muscles and joints of the skin. In addition, hyaluronic acid is an important body polysaccharide that binds to receptors of various cells such as CD44, RHAMM, and regulates life phenomena through cell differentiation, proliferation and cell signaling.

In our bodies, hyaluronic acid and glycosaminoglycans are broken down in the process of removing harmful oxygen caused by ultraviolet rays or inflammation every day, and more than 3g per day is maintained by a fast metabolism process, which is maintained again, but with age Gradually, the amount produced decreases. As the amount produced is less than the amount to be degraded, the skin loses its elasticity, wrinkles begin to form, and in the joints, shock absorption and lubrication are not performed properly, and the causes of degenerative diseases that gradually destroy cartilage and wear are continuously worsened. A vicious cycle occurs.

Until now, the development of medicines using hyaluronic acid and glycosaminoglycan has been mainly used as a surgical aid for maintaining eye shape during cataract surgery, anti-adhesion after surgery, anti-wrinkle injection, wound healing agent, sustained-release agent, and cell therapy, dry eye syndrome. As a skin moisturizer for therapeutic eye drops and tissue engineering (Scafford) and cosmetics, various products are safely used by utilizing the physicochemical properties of hyaluronic acid and glycosaminoglycan.

Hyaluronic acid and glycosaminoglycans are synthesized through the biosynthesis of mucopolysaccharides in the biosynthetic pathway of amino sugars. Hyaluronic acid and glycosaminoglycan are synthesized through a series of metabolic processes using glucose or glycogen as a raw material. One molecule of UTP is used in the synthetic route, and it is known to play an important role in the biosynthesis of UTP sugar derivatives.

It was determined that uracil, uridine, UMP, UDP and uridine derivatives could be used as a source of UTP synthesis to increase mucopolysaccharide synthesis.

Uridine is one of the four ribonucleosides necessary for constructing RNA and is widely distributed in nature. The molecular weight is 244.20 and the molecular formula is C9H12N2O6.

The pharmacological action of uridine, known to date, is useful for enzyme deficiency, pyrimidine nucleotide deficiency, and nucleic acid synthesis deficiency by converting uridine into uridine 5'-phosphate by uridine kinase enzyme catalysis. Has been reported to be used as a medicament to reduce ortic aciduria (MATINDALE, 1989, 1627). Urindine related data is registered as a therapeutic agent for collagen arthritis (Registration No.1994-0008033) in the Green Cross.

Uridine has been used in medicine to date, and it has been used as a combination drug with other drugs, vascular brain disease, hepatoprotective, peripheral neuropathy, and tissue hypoxia.

As a result of toxicity test for uridine, uridine was administered to 0.01, 0.1, 10, and 100 mg / Kg in healthy rats and mice, and observed for more than one week.

The present inventors are the first to demonstrate that uridine and uridine derivatives are effective in promoting the biosynthesis of hyaluronic acid, glycosaminoglycans and collagen in chondrocyte cells, fibroblast cells, synovial cells, and the like. It confirmed and completed this invention.

 The present inventors completed the present invention for the first time to confirm that uridine and uridine derivatives are effective in promoting biosynthesis of hyaluronic acid, glycosaminoglycan and collagen in chondrocytes, synovial membrane cells, fibroblasts, and the like. Therefore, an object of the present invention is arthritis, discs (intervertebral discs), skin aging and the like comprising an active ingredient of uridine and uridine derivatives that promote the promotion of hyaluronic acid and glycosaminoglycan synthesis in animals and human cells, animals and humans. Wrinkles, dry eye, wound healing, scar removal, vaginal dryness, gum disease, atopic dermatitis and dry skin preventive and therapeutic composition.

The present invention includes arthritis, disc (intervertebral disc protrusion), skin aging and wrinkles, dry eye, wound healing, containing uridine and uridine derivatives represented by the following formula (1) and a pharmaceutically acceptable carrier: , Scar removal, vaginal dryness, gum disease atopic dermatitis and dry skin preventive and therapeutic composition.

Hereinafter, the present invention will be described in detail.

The present invention is a composition effective for the prevention and treatment of arthritis, disc (intervertebral disc prolapse), skin aging and wrinkles, dry eye, wound healing, scar removal, vaginal dryness, gum disease, atopic dermatitis and dry skin, especially intracellular hyaluronic acid, Arthritis, disc (intervertebral disc protrusion), skin aging and wrinkles, dry eye, wound healing, scar removal, vaginal dryness, containing glycosaminoglycans and uridine and uridine derivatives showing the synthetic effect of collagen as active ingredients It relates to a composition for preventing and treating gum disease atopic dermatitis and dry skin.

Uridine and uridine derivatives promote the production of hyaluronic acid, glycosaminoglycans and collagen in cells, resulting in arthritis, discs (intervertebral disc prolapse), skin aging and wrinkles, dry eye, wound healing, scar removal, dryness, gums Disease Atopic dermatitis and dry skin will be treated.

Uridine and uridine derivatives used in the present invention can be extracted from nature or prepared using synthetic methods.

    Thus, in the present invention, the in vivo synthesis of hyaluronic acid, glycosaminoglycans and collagen in chondrocytes, fibroblasts, and synovial membrane cells for uridine and uridine derivatives to which physiological activity is given was measured. It was confirmed that the excellent activity.

The present invention is easy to absorb into the cell based on the fact that the cellular self-synthesis capacity can be restored for a certain period of time through the injection of external hyaluronic acid, the decrease in the production capacity of hyaluronic acid and glycosaminoglycans of the cells generated during the aging process It relates to new therapeutic substances that promote biosynthetic mechanisms through uridine and uridine derivatives.

Here, existing studies on hyaluronic acid and glycosaminoglycan biosynthesis mechanisms include rate-determining steps in the intracellular synthesis process, and the activity of the enzymes involved in this biosynthesis reaction step determines the amount of biosynthesis of hyaluronic acid. Promoting substances increase the amount of hyaluronic acid and glycosaminoglycans in the body artificially and in a short time, resulting in decreased production and functioning of hyaluronic acid and glycosaminoglycans. ), Skin aging and wrinkles, dry eye, wound healing, scar removal, vaginal dryness, gum disease atopic dermatitis and dry skin disease treatment.

Here, arthritis refers to degenerative joints and osteoarthritis due to aging, and refers to joint diseases due to lack of production or low molecular weight of hyaluronic acid and glycosaminoglycan in the joint cavity.

The efficacy of hyaluronic acid in degenerative arthritis has been improved by pain relief, inflammation removal, prevention of cartilage tissue destruction, lubrication, and recent reports. Molecular effects of hyaluronic acid injections have been demonstrated, and mechanisms that inhibit inflammation and pain, gene expression and activity of cartilage degrading enzymes, chondrocyte differentiation and proliferation, and increased biosynthesis of matrix materials have been identified.

However, the externally injected hyaluronic acid does not directly exert its half-life in the body for about 12 hours, but stimulates Type B synovial cells of the synovial joint of the synovial membrane by increasing the biosynthesis of hyaluronic acid through five intra-articular injections at weekly intervals. The amount of hyaluronic acid changes to a healthy joint condition, which shows a therapeutic effect. The production of hyaluronic acid gradually decreases within one year after the treatment, and the symptoms of arthritis recur again. It has been found to be directly related to disease treatment.

 Long-term administration of diseases caused by decreased production and hypofunction of hyaluronic acid and glycosaminoglycan is inevitable. Fundamental solution is the development of effective drugs that can be taken in the long term without side effects. When hyaluronic acid is used directly, it has limited efficacy that can only be seen as a local effect, but uridine and uridine derivatives have various routes of administration, and thus, as a rapid effect and safe treatment method, arthritis due to the increase of hyaluronic acid and glycosaminoglycans in the whole body, It can be developed for various uses such as disc (intervertebral disc protrusion), skin aging and wrinkles, dry eye, wound healing, scar removal, vaginal dryness, gum disease atopic dermatitis and dry skin prevention and treatment.

  Uridine and derivatives of uridine may include the following.

Uridine derivatives include uracil, uridine monophosphate, uridine diphosphate, triacetyl uridine, tribenzoyl uridine, 5-ethyl uridine, 2-deoxyuridine, and isopropylidene uridine.

Therefore, arthritis, disc (intervertebral disc prolapse), skin aging and wrinkles, dry eye, wound treatment oil, scar removal, vaginal dryness, gum disease atopy containing uridine and uridine derivatives represented by Formula 1 as active ingredients The composition for the prevention and treatment of dermatitis and dry skin is based on the rate-determining step of sugar amino acid synthesis, arthritis, disc (intervertebral disc prolapse), skin aging and wrinkles, dry eye, wound healing, scar removal, vaginal dryness, gum disease Due to its ability to prevent and treat atopic dermatitis and dry skin, it may be possible to develop various drugs for various diseases related to hyaluronic acid and glycosaminoglycan. The disease prevention and treatment composition related to hyaluronic acid and glycosaminoglycan by uridine and uridine derivatives according to the present invention contains uridine and uridine derivatives represented by Formula 1 as active ingredients, It can be prepared as a preventive and therapeutic agent for arthritis, disc (intervertebral disc prolapse), skin aging and wrinkles, dry eye, wound healing, scar removal, vaginal dryness, gum disease, atopic dermatitis and dry skin as needed with acceptable carriers. have.

Suitable dosages of the pharmaceutical compositions of the present invention may vary depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, condition of food, time of administration, route of administration, rate of excretion and response to response of the patient. Can be. The pharmaceutical composition of the above-mentioned prophylactic and therapeutic agents related to hyaluronic acid and glycosaminoglycan of the present invention contains the uridine and uridine derivatives as active ingredients. The uridine and uridine derivatives can be administered orally or parenterally during clinical administration and can be used in the form of general pharmaceutical formulations. That is, the uridine and uridine derivatives of the present invention can be administered in various oral and parenteral formulations during actual clinical administration, and when formulated, commonly used fillers, extenders, binders, wetting agents, disintegrating agents and surfactants. It is prepared using diluents or excipients. Solid preparations for oral administration include tablets, pills, powders, granules, and capsules, and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose in uridine and uridine derivatives. And gelatin etc. are mixed and prepared. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions and syrups, and may include various excipients such as wetting agents, sweeteners, fragrances and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol and gelatin may be used.

Dosage units may contain, for example, one, two, three or four times the individual dosage, or they may contain 1/2, 1/3 or 1/4 times. The individual dosage preferably contains an amount in which the effective drug is administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dose. The effective dose of uridine and uridine derivatives is concentration dependent but is preferably 0.1 mg to 1 g / kg, more preferably 0.4 to 200 mg / kg, and may be administered 1-6 times a day.

In addition, the present invention is an arthritis, disc (intervertebral disc protrusion), skin aging and wrinkles, dry eye, wound healing, scar removal, dry mouth, gum disease atopic dermatitis and dry skin containing uridine and uridine derivatives as an active ingredient Provides a therapeutic health food composition. In the present specification, the health food is a food that improves the function of the general food by adding uridine and uridine derivatives to the general food, and the uridine and uridine derivatives are added to the general food, or manufactured by encapsulation, powdering, and suspension. can do. When ingested, it brings a specific effect on health, and unlike the general medicine because it is made of food as a raw material has the advantage that there is no side effect that can occur when taking long-term use of the drug.

When the uridine and uridine derivatives of the present invention are used as food additives, the uridine and uridine derivatives may be added as they are or used together with other food or food ingredients, and may be appropriately used according to conventional methods. The mixed amount of the active ingredient can be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment). In general, uridine and uridine derivatives may be added in amounts of 0.0001 to 10% by weight, preferably 0.1 to 5% by weight, based on the raw materials in the manufacture of food or beverage. However, in the case of prolonged ingestion for health and hygiene purposes or for health control purposes, the amount can be adjusted below the above range. In addition, when the health food of the present invention is used in the pharmaceutical composition, it is preferable to contain uridine and uridine derivatives within the measured toxicity range.

There is no particular limitation on the kind of food. Examples of foods to which the uridine and uridine derivatives may be added include meat, sausage, bread, chocolate, candy, snacks, confectionary, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages Water, tea, drink, alcoholic beverages, and vitamin complexes. Specifically, health foods containing uridine and uridine derivatives include health foods and favorite products such as juice, tea, jelly, juice, etc., which have uridine and uridine derivatives as main ingredients.

Hereinafter, the present invention will be described in more detail based on the following examples, but the scope of the present invention is not limited only to the following examples.

Example 1 Uridine Proliferation Effect in Chondrocytes

The cells were transferred to 3x10 ³ cells / well in a 96-well plate, and the cells were attached and replaced with 1% FBS-DMEM medium (minimizing the effects on FBS), followed by incubation for 48 hours with uridine. The degree of cell proliferation against uridine was compared with the control group using the Cell Proliferation Kit (XTT, Roche). The simple method of using KIT is to mix XTT labeling reagent and Electron coupling reagent in the same well, and then incubate for 5 hours at 5% CO ₂ , 37 ^o C and read with ELISA reader at 490nm wavelength. See FIG. 1 for the results.

Example 2 Hyaluronic Acid Synthesis in Uridine Chondrocytes

 1. Chondrocyte Separation

The cartilage tissue was isolated from the rabbits at 3 to 4 weeks of age and then treated with 0.2% collagenase type II at 37 ° C. for 4 hours to obtain cartilage cells by filtering with a 100? M filter. Cells were replaced every 2 days with chondrocytes (DMEM / F12, 10% FBS, Insulin, Nonessential amino acid, Ascorbic acid, penicillin, Gibco BRL products) at 37 ° C and 5% CO ₂ .

2. make bead

Chondrocytes were mixed with 1.5% alginate solution to 2X10 ⁶ cell / ml, and then dropped into each drop of 102mM CaCl ₂ solution (pH7.4) using a syringe to make chondrocyte-bead, and finally washed with 0.15M NaCl. . Beads were changed every 2 days before the experiment by adding cartilage culture medium (DMEM / F12, Nonessential amino acid, Ascorbic acid, Penicillin, Gibco BRL products) and uridine at 37 ℃ and 5% CO2.

3. Content of Hyaluronic Acid in Bead

3-1. Bead acquisition

Beads were cultured for 2 weeks by adding chondrocyte culture medium and uridine and washed with PBS. The beads were collected and treated in 55mM sodium citrate, 30mM EDTA, 150mM sodium chloride (pH6.8) solution at 4 ℃ for 10-15min, followed by Papain 20ug / ml in 0.1M sodium acetate, 50mM sodium EDTA, 5mM L-cyctein hydrochloride (pH5.53) was made to react overnight at 56-60 degreeC. For enzyme inhibition, the sample obtained after heating for 10 minutes was stored at -20 ℃ until the assay.

3-2. HA assay

One day prior to assay, HA-binding protein (HABP) was coated in a 96 well plate at 4 ° C overnight and blocked with 1% BSA. After binding the samples for 60 minutes at 37 ℃ washed with 0.5% PBST. After biotin-HABP was bound for 60 minutes at RT, extra-avidin alkaline phosphatase was added and then developed with p-nitrophenyl-phosphate (PNPP). This reaction is inhibited with 3N-NaOH and the absorbance is read at 405nm wavelength. See FIG. 2 for the results.

Example 3 GAG Synthesis in Uridine Chondrocytes

The absorbance is read at 540nm wavelength by mixing the sample well with 96well and DMB (dimethylmethylene blue) dye (in formate solution). See FIG. 3 for the results.

Example 4 Hyaluronic Acid Synthesis in Uridine Fibroblasts

Rabbit fibroblasts were cultured in Dulbecco's Modified Eagle's Medium (DMEM) medium containing 10% FBS (fetal bovine serum), and subcultured by adding 2 × 10 ⁴ cells / well to a ²⁴ well plate. The next day, uridine was added to DMEM medium containing 5% FBS and incubated at 37 ° C. for 3 days. After 3 days of culture, the total amount of hyaluronic acid in the medium was measured by the sandwich ELIZA method of HA-binding protein (HABP) and HA-binding protein-biotin. Hyaluronic acid (SIGMA H) was used as a standard. See FIG. 4 for the results.

Example 5 Collagen Synthesis in Uridine Fibroblasts

The total collagen amount in the culture solution obtained by the same method as Experimental Example 4) was confirmed by Sircol red dye bind assay. The collagen bound with Dye was down by centrifugation, and the result was read at 540 nm by adding Alkali reagent. See FIG. 5 for the results.

Example 6 Hyaluronic Acid Production in Urindine Synovial Cells

Human synovial cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) medium containing 10% FBS (fetal bovine serum), and subcultured by adding 2 × 10 ⁴ cells / well to a 24well-plate. The next day, the cells were changed to DMEM medium containing 5% FBS and incubated at 37 ° C. for 3 days with the addition of uridine. After 3 days of culture, the total amount of hyaluronic acid in the medium was measured by the sandwich ELIZA method of HA-binding protein (HABP) and HA-binding protein-biotin. Hyaluronic acid (SIGMA H) was used as a standard. See FIG. 6 for the results.

Example 7 Uridine Collagen Production in Synovial Cells

The total collagen amount in the culture obtained by the same method as Experimental Example 6) was confirmed by Sircol red dye bind assay. The collagen bound with Dye was down by centrifugation, and the result was read at 540 nm by adding Alkali reagent. See FIG. 7 for the results.

Example 8 Proliferation Effect of UMP in Chondrocytes

The cells were transferred to 3x10 ³ cells / well in a 96-well plate, and the cells were attached and replaced with 1% FBS-DMEM medium (minimizing the effects on FBS) and incubated for 48 hours with the addition of UMP. The degree of cell proliferation for UMP was compared with the control group using the Cell Proliferation Kit (XTT, Roche). The simple method of using KIT is to mix XTT labeling reagent and Electron coupling reagent in the same well, and then incubate for 5 hours at 5% CO ₂ , 37 ^o C and read with ELISA reader at 490nm wavelength. See FIG. 8 for the results.

Example 9 Synthesis of Hyaluronic Acid from UMP Chondrocytes

One day prior to assay, HA-binding protein (HABP) was coated in a 96 well plate at 4 ° C overnight and blocked with 1% BSA. After binding the samples for 60 minutes at 37 ℃ washed with 0.5% PBST. After biotin-HABP was bound for 60 minutes at RT, extra-avidin alkaline phosphatase was added and then developed with p-nitrophenyl-phosphate (PNPP). This reaction is inhibited with 3N-NaOH and the absorbance is read at 405nm wavelength. See FIG. 9 for the results.

Example 10 GAG Synthesis in UMP Chondrocytes

The absorbance is read at 540nm wavelength by mixing the sample well with 96well and DMB (dimethylmethylene blue) dye (in formate solution). See FIG. 10 for the results.

Example 11 Synthesis of Hyaluronic Acid from Fibroblasts of UMP

Rabbit fibroblasts were cultured in Dulbecco's Modified Eagle's Medium (DMEM) medium containing 10% FBS (fetal bovine serum), and subcultured by adding 2 × 10 ⁴ cells / well to a ²⁴ well plate. The next day, UMP was added to DMEM medium containing 5% FBS and incubated at 37 ° C. for 3 days. After 3 days of culture, the total amount of hyaluronic acid in the medium was measured by the sandwich ELIZA method of HA-binding protein (HABP) and HA-binding protein-biotin. Hyaluronic acid (SIGMA H) was used as a standard. See FIG. 11 for the results.

Example 12 Collagen Synthesis in Fibroblasts of UMP

The total collagen amount in the culture obtained by the same method as Experimental Example 11) was confirmed by Sircol red dye bind assay. The collagen bound with Dye was down by centrifugation, and the result was read at 540 nm by adding Alkali reagent. See FIG. 12 for the results.

Example 13 Hyaluronic Acid Production in Synovial Cells of UMP

Human synovial cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) medium containing 10% FBS (fetal bovine serum), and subcultured by adding 2 × 10 ⁴ cells / well to a 24well-plate. The next day, the cells were changed to DMEM medium containing 5% FBS and incubated at 37 ° C. for 3 days with the addition of UMP. After 3 days of culture, the total amount of hyaluronic acid in the medium was measured by the sandwich ELIZA method of HA-binding protein (HABP) and HA-binding protein-biotin. Hyaluronic acid (SIGMA H) was used as a standard. See FIG. 13 for the results.

Example 14 Collagen Production in Synovial Cells of UMPs

The total collagen amount in the culture obtained by the same method as Experimental Example 13) was confirmed by the Sircol red dye bind assay method. The collagen bound with Dye was down by centrifugation, and the result was read at 540 nm by adding Alkali reagent. See FIG. 14 for the results.

The present invention provides arthritis, disc (intervertebral disc protrusion), skin aging and wrinkles, dry eye with an active ingredient of uridine and uridine derivatives that induce the promotion of hyaluronic acid and glycosaminoglycan synthesis in animals and human cells, animals and human body It can be used for the prevention and treatment of wound healing, scar removal, vaginal dryness, gum disease, atopic dermatitis and dry skin.

Claims (12)

The active ingredient comprises one or more selected from the group consisting of uridine, triacetyl uridine and tribenzoyl uridine and one or more pharmaceutically acceptable carriers or excipients, Osteoarthritis, disc (intervertebral disc protrusion), cosmetic support for wrinkle removal, anti-adhesion after surgery, artificial skin, wound healing, scar removal, vaginal dryness, cataract assistive effect, gum disease and atopic dermatitis treatment A biosynthesis promoting composition, which exhibits a further effect and promotes biosynthesis of hyaluronic acid, glycosaminoglycan, or collagen. delete delete delete According to claim 1, wherein the content of the active ingredient biosynthesis promoting composition, characterized in that administered in the range of 0.1 ~ 6,000 mg / day per 1Kg of adult body weight. The biosynthetic promoting composition according to claim 1 or 5, comprising degenerative joint and osteoarthritis, disc (intervertebral disc prolapse), cosmetic aid for wrinkle removal, prevention of adhesion after surgery, artificial skin, wound healing, scar removal, vaginal dryness, cataract surgery Formulations for use in one or more uses selected from the group consisting of adjuvant and atopic dermatitis treatment. delete The biosynthesis promoting composition according to claim 1, wherein the carrier is one or more selected from the group consisting of a solid carrier, a liquid carrier and an oil carrier. 7. The formulation of claim 6 wherein the formulation is a powder, granule, liquid, pill, troche, suspension, emulsion, syrup , tablet, hard or soft capsule, suspension, injectable formulation, emulsion, parenteral. A formulation characterized in that the unit dosage form or several dosage forms for administration. As an active ingredient, one or more selected from the group consisting of uridine, triacetyl uridine, and tribenzoyl uridine, and a food-acceptable excipient, and biosynthesis of hyaluronic acid, glycosaminoglycan, or collagen Food composition, characterized in that to promote. The food composition of claim 10, wherein the content of the active ingredient in the composition is in a range of 0.0001 to 10% by weight based on the total weight of the composition. The method of claim 8, wherein the solid carrier is selected from the group consisting of starch and lactose; The liquid carrier is selected from the group consisting of propylene glycol and polyethylene glycol; The oily carrier is a biosynthesis promoting composition, characterized in that selected from the group consisting of various vegetable oils and paraffin.

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