KR20180040906A - A composition comprising poly-gamma glutamic acid for protecting and treating vaginosis disease and the use thereof - Google Patents

Abstract

The present invention relates to a composition comprising poly-gamma glutamic acid salt, sugar, and polygamma glutamic acid (PGA), which exhibit a vaginal cleansing effect in women. In more detail, a combination composition of the salt, sugar, and PGA according to the present invention inhibits the proliferation of bacteria to maintain the vaginal cleansing state of women, thereby being used as a composition for parenteral administration which is effective and safe for prevention and treatment of the vaginosis disease.

Description

TECHNICAL FIELD The present invention relates to a polygamma glutamic acid-containing composition for preventing and treating vaginitis,

The present invention provides an effective and safe composition for prevention and treatment of vaginal inflammation containing salt, sugar and polygamat glutamic acid combination as an active ingredient.

[Document 1] Sujatha Srinivasan and David N. Fredricks, Review Article, The Human Vaginal Bacterial Biota and Bacterial Vaginosis. Interdisciplinary Perspectives on Infectious Diseases, Vol. 2008, Article ID 750479, 22p

[Patent Document 2] Korean Patent Registration No. 10-0485727

[Patent Document 3] Korean Patent Application No. 1997-0003404

[Patent Document 4] Korean Patent Application No. 1997-0067605

[Literature 5] Korean Patent Application No. 2001-0106025

[Literature 6] Korean Patent Application No. 2001-0001481

[Patent Document 7] Korean Patent Publication No. 10-2013-0131268

[Literature 8] Orrhge, K. et al., 2000, Bifidobacteria and lactobacilli in human health, Drugs Exptl. Clin. Res., 26, 95-111

[Literature 9] Fuller, K., 1989, Probiotics in man and animals, J. Appl. Bacteriol., 66, 365-378

[Patent Document 10] Korean Patent Publication No. 10-2015-0075447

[Document 11] Korean Patent Registration No. 10-1133723 B1

[Document 12] PCT / WO2011 / 049327 A1

[Literature 13] Korean Patent Application No. 10-2016-115716

The present invention relates to a composition containing an effective and safe parenteral composition for prevention and treatment of vaginitis containing salt, sugar and glutamic acid combination as an active ingredient. More particularly, the present invention relates to a salt, It is possible to use the composition as an effective and safe detergent composition for prevention and treatment of vaginitis by inhibiting the proliferation of bacteria in the vagina and maintaining the cleanliness of the vagina in vagina.

On the other hand, more than 90% of the vaginitis in fertile women is bacterial vaginosis, Candida vaginitis, Trichomonas vaginitis, and the bacterial vaginosis accounts for 40-50%. These germs can not multiply when the vaginal inside of the woman is normal pH, but they can easily infiltrate when the condition is not normal due to overeating, stress, contraceptive medication, etc. and increase the postoperative complications such as infection, Because of complications such as early labor, attention should be paid and effective treatment should be done.

The quality of women is naturally colonized by various bacteria, yeasts and microorganisms. For example, normal women's vagina usually contains more than about 10 ⁴ Lactobacillus spp. Per milliliter of vaginal material. Under normal conditions, vinegars provide a weak acidic environment that helps protect against invasion by pathogenic microorganisms.

However, under normal conditions as described above, vaginal bacteria, i.e., vaginal equilibrium, can be easily overturned by various external factors that ultimately induce vaginal infection. Vaginal infection is a clinical syndrome. Bacterial vaginosis, Candida vaginitis and Trichomonas vaginitis are the most common vaginitis. Bacterial vaginitis is the most common vaginitis.

The bacterial vaginosis has been reported to be caused mainly by an increase in the number of anaerobic organisms accompanied by a decrease in lactic acid bacteria in the vagina. In addition, bacterial vaginosis can also be caused by bacterial or viral infection, antibiotic use, contraceptive use, . The reduction in the number of lactic acid bacteria in the vagina reduces competition for nutrients, decreases the amount of lactic acid present and increases the pH, and increases the proliferation of opportunistic pathogens whose growth is normally suppressed in the vagina And the onset of the disease.

The normal vaginal pH is 4.5 to 5.1. The reason why the inside of the vagina is acidic is that vaginal bacteria and vaginal epithelial cells produce lactic acid by using glycogen and glucose. Lactic acid bacteria that live in the vagina play a useful role in suppressing the growth of harmful bacteria by maintaining the pH by producing lactic acid.

Bacterial vaginosis is the most common cause of vaginal irritation, and it is not clear whether it is transmitted through sexual intercourse. However, bacterial vaginitis has been reported to be associated with sexually transmitted diseases such as gonorrhea and chlamydia. Bacterial vaginitis is caused by the proliferation of lactic acid bacteria in the vagina within the vagina, resulting in the proliferation of anaerobic bacteria in vaginal bacteria. Genitourinary pathogens that cause vaginitis include Trichomonas vaginalis, Gardnerella vaginalis, Candida albicans, Group B Streptococcus Agaracs (Trichomonas vaginalis), Candida albicans, Streptococcus agalactiae, Staphylococcus aureus, Neisseria gonorrore, E. coli and the like. Most of these infections originate from urinary tract infections (Reid, G., Jass, J., Sebulsky, T., and MaCormick, JK 2003. Potential uses of probiotics in clinical practice. Clinical Microbiology Reviews 16: 658-672). Typical symptoms include an increase in vaginal discharge and a color of the secretions (white or pale yellow, green, gray, etc.). Characteristic odor is caused by aromatic amines produced by overgrown bacteria. (Sujatha Srinivasan and David N. Fredricks, Review Article, The Human Vaginal Bacterial Biota and Bacterial Vaginosis. Interdisciplinary Perspectives on Infectious Diseases, Vol. 2008, Article ID 750479, 22p).

Many methods for treating vaginitis for preventing and treating vaginitis have been studied. Recently, as a treatment for vaginal bacterial infection, a method of administering a therapeutic agent for vaginitis such as metronidazole orally in a cream form is generally used. Such use of a broad spectrum antibiotic such as metronidazole not only poses a problem of antibiotic resistance but also the use of such an antibiotic is undesirable because it can kill a wide range of normal bacterial flora in the vagina containing beneficial lactic acid bacteria .

On the other hand, the death of normal flora in vagina including lactic acid bacteria has been reported to cause secondary complications. In other words, the reduction of lactic acid bacteria, which inhibit various opportunistic pathogens in the vagina, increases the pH in the vagina, making it difficult to maintain the acidic environment, which may cause further infection by accelerating the infection by anaerobic microbial growth. In addition, long-term use of antibiotics has been reported to cause systemic toxicity due to absorption of antibiotics through the vagina.

       Poly-gamma-glutamic acid (PGA) is a polymer in which D, L-glutamic acid is bound to gamma-glutamyl and is a mucilage substance. PGA is produced from Bacillus sp. Strain isolated from Korean traditional soybean fermented food, Chungkookjang using rice straw, Natto, a traditional soybean fermented food in Japan, and Kinema, a traditional soybean fermented food in Nepal. PGA, produced from Bacillus subtilis strain, is an edible, water-soluble, anionic, biodegradable polymer material and can be used as a raw material for moisture absorbers, moisturizers and cosmetics. In recent years, research on the production and use of PGA has been actively carried out in advanced countries with regard to the development of heat-resistant plastics by replacing refractory polymers, esterification reactions, and water-soluble fibers and membranes. 10-0485727)

On the other hand, in Korea, the basic researches such as efficient production of PGA (Korean Patent Application No. 1997-0003404, Korean Patent Application No. 1997-0067605) and improvement of physical properties, and production method of high concentration PGA (Korean Patent Application No. 2001-0106025) ; A salt resistant Bacillus subtilis Chungkukjang strain producing high molecular weight PGA (Korean Patent Application No. 2001-0001481); And a composition for preventing or treating a Th17 mediated disease comprising polygamma glutamic acid (Korean Patent Laid-Open No. 10-2013-0131268) has also been reported

On the other hand, lactic acid bacteria are widely used as probiotic bacteria. They are widely found in nature and are easily found in the intestines and fermented foods of humans and animals. Food and Drug Administration (Orrhge, K. et al., 2000, Bifidobacteria and lactobacilli in human health, Drugs Expt. Clin. Res., 26, 95-111). Lactic acid bacteria attach to the intestinal epithelial cells and become parasitic, thereby improving the properties of intestinal microflora. Thus, the intestinal microflora such as the stabilization of intestinal microflora, the reduction of the formation of decay products due to the inhibition of harmful bacteria and the prevention of disease, immune activation, It helps a lot. Lactic acid bacteria have several metabolic characteristics that inhibit the growth of various pathogenic microorganisms and pathogenic microorganisms because lactic acid bacteria produce organic acid, hydrogen peroxide, reuterin, diacetyl, acetaldehyde, bacteriocin, etc. as metabolic products (Fuller, K., 1989, Probiotics in man and animals, J. Appl. Bacteriol., 66, 365-378; Korean Patent Publication No. 10-2015-0075447)

Therefore, it is urgent to develop a safe vaginitis preventive or therapeutic composition that does not cause side effects that can effectively inhibit and / or treat vaginal infection.

Meanwhile, the inventors of the present invention found that a composition containing salt and a compounding composition of the present invention as an active ingredient exhibits an excellent inhibitory effect on the antimicrobial activity, particularly Gardnerella vaginalis (Korea Patent No. 10- 1133723 B1) and the PCT application (PCT / WO2011 / 049327 A1); As a follow-up study, Korean Patent Application No. 10-2016-115716 (2016.09.08) filed for the treatment of yeast infection of salt, sugar and lactic acid bacteria combination.

The inventors of the present invention have further found that the combination of polygamma glutamic acid (PGA) and optionally probiotic lactic acid bacterium as disclosed in the prior inventions of the present inventors is capable of inhibiting the growth inhibitory effect on vaginosis causing bacteria Confirming that the compounding composition of the present invention exhibits the effects of an unprecedented effect of lowering the pH, increasing the lactic acid concentration, and inhibiting the vaginosis-causing bacteria, which are unexpected to those skilled in the art than the conventional inhibitory activity of the group treated with polygamma glutamic acid or lactic acid bacteria, .

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing and treating vaginitis containing salt, sugar and a polygamma glutamic acid (PGA) combination as an active ingredient.

In addition, the present invention provides a use for producing a composition comprising, as an active ingredient, a salt, a sugar and a polygamma glutamic acid (PGA) combination for the prevention and treatment of vaginitis.

The invention also provides a method of treating vaginitis in a mammal comprising administering a salt, a sugar, and a polygamma glutamic acid (PGA) combination to a mammal, including a human.

The present invention also provides a health functional food for prevention and improvement of vaginitis containing salt, sugar, and a polygamma glutamic acid (PGA) combination as an active ingredient.

The present invention also provides a health supplement or food additive for prevention and improvement of vaginitis containing salt, sugar and polygamma glutamic acid (PGA) combination as an active ingredient.

The present invention also provides a composition for parenteral use for prevention and improvement of vaginitis containing salt, sugar, and a polygamma glutamic acid (PGA) combination as an active ingredient.

The present invention also provides a detergent composition for prevention and improvement of vaginitis containing salt, sugar and polygamma glutamic acid (PGA) combination as an active ingredient.

In addition, the present invention can further comprise lactic acid bacteria in the salt, sugar and polygamma glutamic acid (PGA) formulations.

Salts as defined herein include, but are not limited to, sea salt, salt salts such as rock salt, processed salts, or purified salts; Preferably a processed salt such as a refined salt or molten salt such as bamboo salt; More preferably, the refined salt or molten salt, most preferably the refined salt or the domestic seawater salt is heated at a heating temperature of 200 to 2000 ° C, preferably 800 to 1200 ° C for 2 to 7 days, preferably 12 to 48 hours Lt; RTI ID = 0.0 > molten < / RTI >

Poly-gamma-glutamic acid (PGA), as defined herein, is a polymer in which D, L-glutamic acid is coupled to gamma-glutamyl as a mucilage material, co. Ltd.) is produced from Bacillus sp. isolates which are commercially available and are separated from Korean traditional soybean fermented food using rice straw, Chungkookjang, traditional soybean fermented food, Natto, and traditional soybean fermented food, do.

The lactic acid bacterium as defined herein is a typical bacterium widely used as a probiotic well known in the art. Preferably, it is any lactic acid bacterium widely used as probiotics. Specifically, lactic acid bacteria belonging to the genus Lactobacillus A microorganism of Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus; Preferably Bifidobacterium, Lactobacillus or Streptococcus, more preferably Bifidobacterium or Streptococcus; More preferably Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium animalis spp., Bifidobacterium spp., Bifidobacterium spp., Bifidobacterium spp. lactis, Bifidobacterium adolescentis, Bifidobacterium pseudocatenulatum, Bifidobacterium catenulatum or Bifidobacterium infantis, and the like. Bifidobacteria, such as B. thermophilum; Bifidobacterium sp .; Lactobacillus plantus, Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus casei, Lactobacillus casei ssp. Paracasei, Lactobacillus rhamnosus, Lactobacillus spp. Lactobacillus delbrueckii ssp. Lactobacillus delbrueckii ssp. Bulgaricus, Lactobacillus delbrueckii ssp. Lactobacillus delbrueckii ssp., Lactobacillus delbrueckii ssp., Lactobacillus delbrueckii ssp. Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus reuteri, L. brevis, L. cellobiosus, Lactobacillus spp., Lactobacillus spp., Lactobacillus spp. , Lactobacillus crispatus, Lactobacillus support (Lb. GG), Lactobacillus Loose zone soniyi (Lb. johnsonii), Lactobacillus lactis (Lb. lactis), Lactobacillus flow Terry (Lb. reuteri), Lactobacillus spp, including Lactobacillus salivarius (Lb. salivarius) species; Bacillus subtilis strains such as Bacillus cereus toyoi or Bacillus cereus strains; Leuconostoc species, such as Leuconostoc citreum and Leuconostoc mesenteroides; Pediococcus species such as Pediococcus acidilactici and Pediococcus pentosaceus; Pediococcus species such as Pediococcus pentosaceus; Propionibacterium species such as Propionibacterium acidifaciens, Propionibacterium acidipropionici, etc .; Streptococcus thermophilus, S. < RTI ID = 0.0 > S. cremoris, S. < RTI ID = 0.0 > S. infantarius, S. et al. S. intermedius, S. < RTI ID = 0.0 > S. lactis, S. Streptococcus species such as S. salivarius subsp. Thermophilus strains; Enterococcus species such as Enterococcus faecalis and E. faecium; Enterococcus species such as Enterococcus faecalis and E. faecium; Saccharomyces species such as Saccharomyces cerevisiae and Saccharomyces boulardii, preferably strains belonging to the genus Bifidobacterium or Bifidobacterium, strains belonging to the genus Bifidobacterium, most preferably, Lactobacillus ash FIG filler's (Lactobacillus acidophilus, KCTC No.3164), Bacillus cereus (Bacillus cereus, KCTC No.13123), Bifidobacterium ronggum (Bifidobacterium longum sub sp. longum , KCTC No. 3128) or Streptococcus sp. (KCTC No. 564).

The sugars as defined herein may be monosaccharides, disaccharides, oligosaccharides, and polysaccharides, which can be used as prebiotics well known in the art, xylose and arabinose; monosaccharides including hexoses such as glucose, mannose, fructose, galactose and the like; Disaccharides such as lactulose, lactitol, sucrose, lactose, maltose and trehalose; disaccharides such as lactose, lactitol, sucrose, lactose, maltose and trehalose; Oligosaccharides such as fructo-oligosaccharide, raffinose, stachyose, and maltodextrin; Polysaccharides such as amylose, amylopectin, starch, cellulose, and pectin; More preferably, a sugar compound such as glucose, fructose, galactose, sucrose, lactose, fructo-oligosaccharide and the like is more preferable Preferably includes glucose, fructose, lactulose, lactitol, or fructo-oligosaccharide. The term " fructose-oligosaccharide "

In the case of the salt, sugar and polygamma glutamic acid (PGA) blend, a blend weight ratio of 1: 100 to 0.01: 100 to 0.01, preferably 1: 50 to 0.5: 50 to 0.5, , A blend weight ratio of 1: 10 to 0.1: 10 to 0.1, more preferably 1: 5 to 1: 5 to 1; Preferably 1:50 to 0.5:50 to 0.5: 50 to 0.5 (parts by weight), based on the weight of the active ingredient, salt, sugar, lactic acid bacteria and polygamaric acid (PGA) , More preferably 1: 10 to 0.1: 10 to 0.1: 10 to 0.1, even more preferably 1: 5 to 1: 5 to 1: 5 to 1 ≪ / RTI >

The diseases of vagina (vaginosis) defined herein may be any one selected from the group consisting of bacterial vaginosis, fungal vaginitis and Tricomonas vaginitis, preferably bacterial vaginitis And more preferably Trichomonas vaginalis, Gardnerella vaginalis, Candida albicans, Group B Streptococcus agalactiae, and the like, more preferably Trichomonas vaginalis, Candida albicans, Group B Streptococcus agalactiae, Staphylococcus aureus, Staphylococcus aureus, Neisseria gonorrore, E. coli Enterobacter cloacae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus aureus, (Pseudomonas aeruginosa), Salmonella typhimurium (Salomella typhimurium), bacteriophage id infrastructure-less tired (Bacteroid fragilis , and Candida albicans, more preferably vaginitis caused by infection of Gadnerella vaginalis or Bacteroid fragilis , .

Hereinafter, the present invention will be described in detail.

For example, domestic and foreign processed salts, sun salts, or refined salts of the present invention may be treated at 200-2000 캜, preferably at refining salt or heating temperature of 800-1200 캜 for 2 hours to 7 days, preferably 12 hours to 48 hours A first step of heating to obtain molten molten salt; Sugar, such as glucose, fructose, or sugar, preferably glucose, polygamma glutamic acid (PGA) and / or Bifidobacterium species; Lactobacillus species; Bacillus species; The present invention relates to a method for producing a microorganism belonging to the genus Leuconostoc, which comprises a strain of Leuconostoc, a species of Pediococcus, a strain of Propionibacterium species, a species of Streptococcus, a strain of Enterococcus in the case of salt, sugar and polygamma glutamic acid (PGA) blended in a ratio of 1: 100 to 0.01: 100 to 0.01, preferably 1: , More preferably from 1: 10 to 0.1: 10 to 0.1, and even more preferably from 1: 5 to 1: 5 to 1 A blend weight ratio of 1: 100 to 0.01: 100 to 0.01: 100 to 0.01, preferably 1: 50 to 0.5: 50 to 0.5: 50, in terms of weight of salt, sugar, lactic acid bacteria and polygamaric acid (PGA) More preferably 1: 5 to 1: 5 to 1: 5 to 1: 5, and even more preferably 1: 10 to 0.1: 10 to 0.1: 1 to obtain a combination formulated with the compounding portion at a temperature of 0 to 100 DEG C, preferably 10 to 80 DEG C, a relative humidity of 50 to 90%, preferably 60 to 80% relative At a temperature of 20 to 100 째 C, preferably at a temperature of 20 to 100 째 C, for 1 to 7 days, preferably for 6 to 3 days, more preferably for 12 to 24 hours, And a fourth step of adding a proper amount of purified water, buffer or other isotonic solution applicable to the skin to the dried compounding composition in addition to the above-mentioned effective ingredient, at a drying temperature of 50 ° C to 80 ° C. It is possible to prepare the composition of the present invention.

In addition, in addition to the third step, at least one additive selected from an appropriate amount of coloring matter, perfume, etc. may be added in an amount of about 0 to 10% by weight based on the total weight of the composition.

Thus, the present invention is directed to a method for producing a fused product by heating domestic and foreign salt, preferably domestic salt, at a heating temperature of 200 to 2000 ° C, preferably 800 to 1200 ° C, for 2 to 7 days, preferably 12 to 48 hours A first step of obtaining a molten salt; Sugars such as glucose, fructose, or sugar, preferably glucose, polygamma glutamic acid (PGA) and / or Bifidobacterium species, commercially available for the salt; Lactobacillus species; Bacillus species; The present invention relates to a method for producing a microorganism belonging to the genus Leuconostoc, which comprises a strain of Leuconostoc, a species of Pediococcus, a strain of Propionibacterium species, a species of Streptococcus, a strain of Enterococcus in the case of salt, sugar and polygamma glutamic acid (PGA) blended in a ratio of 1: 100 to 0.01: 100 to 0.01, preferably 1: , More preferably from 1: 10 to 0.1: 10 to 0.1, and even more preferably from 1: 5 to 1: 5 to 1 A blend weight ratio of 1: 100 to 0.01: 100 to 0.01: 100 to 0.01, preferably 1: 50 to 0.5: 50 to 0.5: 50, in terms of weight of salt, sugar, lactic acid bacteria and polygamaric acid (PGA) More preferably 1:10 to 0.1: 10 to 0.1: 10 to 0.1, even more preferably 1: 5 to 1: 5 to 1: 5 To about 1 to about 1% by weight of the composition, and the mixture is cultivated at a culture temperature of from 0 to 100 캜, preferably from 10 to 80 캜, at a relative humidity of from 50 to 90%, preferably from 60 to 80% At a relative humidity of 1 hour to 7 days, preferably 6 hours to 3 days, more preferably 12 hours to 24 hours to produce a culture; and culturing the culture at 20 to 100 ° C, preferably A third step of drying at a drying temperature of 50 ° C to 80 ° C, and a fourth step of adding an appropriate amount of purified water, buffer solution or other isotonic solution applicable to the skin to the dried compounding composition in addition to the active ingredient A process for producing the composition of the present invention is provided.

Accordingly, the present invention provides a composition containing salt, sugar and a polygamma glutamic acid (PGA) combination, which is effective for prevention and treatment of vaginal inflammation produced by the above production method, as an active ingredient.

In addition, the composition of the present invention is a medicinal substance that has been used for a long time as an edible or herbal medicine, and the composition of the present invention is also free from problems such as toxicity and side effects.

The pharmaceutical composition of the present invention contains 0.1 to 50% by weight of the above-described components based on the total weight of the composition.

The pharmaceutical compositions comprising the ingredients of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The compositions containing the components of the present invention may be formulated in the form of powders, granules, tablets, capsules, oral preparations such as suspensions, emulsions, syrups and aerosols, external preparations, suppositories and sterile injection solutions, Can be used.

More specifically, when formulating the composition, it can be prepared using a diluent or an excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like. Solid formulations for oral administration include tablets, pills, powders, granules and capsules, which may contain at least one excipient such as starch, calcium carbonate, sucrose, ), Lactose, gelatin and the like.

In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral use include suspensions, solutions, emulsions and syrups. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances and preservatives may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol and vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a suppository base, witepsol, macrogol, tween 61, cacao paper, laurin, and glycerol gelatin can be used.

The preferred dosage of the components of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the administration route and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the components of the present invention can be administered in an amount of (0.0001-100) mg / kg, preferably (0.001-100) mg / kg, once or several times a day. In the composition, the components of the present invention may be formulated in an amount of (0.0001 to 50) wt% based on the total weight of the total composition.

The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine and intracerebroventricular injections.

The present invention also provides a health functional food for prevention and improvement of vaginitis comprising salt, sugar and polygamma glutamic acid (PGA) combination as an active ingredient.

&Quot; Health functional food "as defined herein means food prepared and processed using raw materials or ingredients having functionality useful to the human body in accordance with Law No. 6727 on Health Functional Foods." Functional " Structure and function of the nutrient to control or physiological effects, such as to obtain a beneficial effect for health is intended to eat.

The health functional food of the present invention contains 0.01 to 95% by weight, preferably 1 to 80% by weight, of the above-described ingredients based on the total weight of the composition.

For the purpose of preventing or ameliorating the disease of the present invention, for the purpose of preventing or ameliorating the disease, a pharmaceutical dosage form such as a powder, a granule, a tablet, a capsule, a pill, a suspension, an emulsion or a syrup, Can be manufactured and processed.

The present invention also provides a health supplement or food additive for preventing and improving vaginitis comprising salt, sugar and a polygamma glutamic acid (PGA) combination as an active ingredient.

In addition, the above health functional foods may further include food additives, and whether or not they are suitable as "food additives" may be added to the relevant items in accordance with the general provisions of the Food Additives Ordinance approved by the Food and Drug Administration Shall be determined according to the relevant standards and standards.

Examples of the products available in the above-mentioned "food additives" include natural products such as ketones, chemical products such as glycine, potassium citrate, nicotinic acid and cinnamic acid, coloring matter, licorice extract, crystalline cellulose and guar gum, sodium L- A mixed preparation such as a preparation, a noodle-added alkali agent, a preservative preparation, a tar coloring agent, and the like.

Examples of the functional food containing the ingredient of the present invention include confectionery ice creams such as bread, rice cake, dried fruit, candy, chocolate, chewing gum and confectionery, ice cream products such as ice cream, ice cream powder, low fat milk, Processed products such as processed oil, goat milk, fermented oil, butter oil, concentrated oil, yogurt cream, butter oil, natural cheese, processed cheese, milk powder, milk products, meat products such as hamburger meat products, ham Such as processed fish products such as sausages, bacon and the like fish products such as ramen noodles, dried noodles, fresh noodles, noodle noodles, luxury noodles, improved noodles, frozen noodles, noodles such as pasta, fruit drinks, Seasonings such as beverages such as beverages, miso, red pepper paste, chunks, chonggukjang, mixed berries, vinegar, sauces, tomato ketchup, curry, dressing , It is not but be a shortening and pizza, limited.

The health functional beverage composition of the present invention has no particular limitation on other components other than those containing the above components as essential components in the indicated ratios and may contain various flavors or natural carbohydrates as additional components such as ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides (e.g., glucose, fructose, etc.); Disaccharide, (e.g., maltose, sucrose, etc.); And polysaccharides (for example, dextrin, cyclodextrin and the like), and sugar alcohols such as xylitol, sorbitol and erythritol. As natural flavors other than those described above, natural flavors (such as tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin)) and synthetic flavors (saccharin, aspartame, etc.) have. The ratio of the natural carbohydrate is generally about (1 to 20) g, preferably about (5 to 12) g per 100 mL of the composition of the present invention.

In addition to the above, the composition of the present invention may further contain various additives such as flavoring agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants, pectic acid and its salts, alginic acid and its salts, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

In addition, the components of the present invention can be added to foods or beverages for the purpose of preventing the desired diseases. At this time, the amount of the ingredient in the food or drink may be 0.01 to 15% by weight of the total food, and the health drink composition may be added in a proportion of 0.02 to 5 g, preferably 0.3 to 1 g, .

The ingredients according to the present invention, which are added to foods containing beverages in the course of manufacturing the health functional food, can be appropriately added or decreased as needed.

The present invention also provides a detergent composition for prevention and improvement of vaginitis comprising salt, sugar and polygamma glutamic acid (PGA) combination as an active ingredient.

In addition, the detergent composition proposed by the present invention may further contain at least one additive selected from the group consisting of antimicrobial agents, coloring matters, perfumes, etc. in addition to the above-mentioned effective ingredients in an amount of 0.1 to 20 parts by weight per 100 parts by weight of the composition. It is also possible to select different usage amounts as needed.

Since the detergent composition according to the present invention is made of a material having the above-mentioned action and effect, it is judged that there is an excellent effect in suppressing the propagation of bacteria by the action of the mixed combination thereof.

The combination compositions of salt, sugar and polygamma glutamic acid (PGA) combinations according to the present invention are further formulated with the polygamma glutamic acid (PGA) and optionally probiotic acting lactic acid bacteria disclosed in the prior art Experiments were conducted to determine the effect of growth inhibition on the causative bacteria of vaginitis causing changes in pH and lactic acid concentration (Experimental Example 1); ( Experimental Example 2) and simple clinical experiments, it was found that the compound composition of the present invention is superior to the conventional inhibitory activity of the group treated with polygamma glutamic acid or lactic acid bacteria, Lactate concentration increase activity, and inhibitory activity of vaginosis induced bacteria.

Accordingly, the present invention provides a composition for prevention and treatment of vaginitis comprising, as an active ingredient, a salt, a sugar and a polygamma glutamic acid (PGA) combination obtained by the above-described manufacturing process. The formulations may be formulated for parenteral administration and may be in the form of, for example, a topical dosage form such as a liquid, a gel, a cleansing composition, a vaginal insert, a suppository, cream, ointment, dressing, spray, Liquid formulations such as solutions, suspensions, emulsions and the like and may be in the form of sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, creams, ointments, jellies, The present invention is not limited to the use of a liquid external preparation such as a liquid preparation, a gel composition, a cleaning composition and a tablet for intravaginal insertion, more preferably a liquid preparation, a gel gel preparations, cleansing compositions, external preparation for vaginal insertion, and the like. The formulation can be prepared, for example, by adding a solubilizer, an emulsifying agent, a buffering agent for pH control, etc. to the sterilized water.

Examples of the non-aqueous solvent or suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like.

Witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like may be used as the left side.

More specifically, the composition for vaginal cleaning may further comprise a carrier for formulation thereof in addition to the antimicrobial composition. The carrier may be a binder, a lubricant, a suspending agent, a solubilizer, a buffer, a preservative, a lubricant, an isotonic agent, an excipient, a stabilizer, a dispersant, a suspending agent,

Furthermore, the compositions for the prevention or treatment of vaginitis of the present invention may be prepared using methods known in the art or as disclosed in Remington ' s Pharmaceutical Sciences (recent edition), Mack Publishing Company, Easton PA And the like.

The composition of the present invention is used in an amount of 0.001 to 99.99% by weight, preferably 0.1 to 99% by weight, more preferably 1 to 30% by weight, and even more preferably 5 to 10% by weight, based on the total weight of the composition, The content of the active ingredient may be appropriately controlled depending on the method of use and the intended use of the composition.

The preferred dosage of the combination of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art.

The dosage of the composition for the prevention or treatment of vaginitis according to the present invention can be suitably selected by those skilled in the art in view of the administration method, the age, sex, and weight of the recipient, severity of the disease, and the like. For example, the composition for the prevention or treatment of vaginitis according to the present invention may be administered at a dose of 0.0001 mg / kg to 1000 mg / kg based on the composition and 0.01 mg / kg to 100 mg / kg to be more effective. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.

In addition, the composition for preventing or treating vaginitis according to the present invention may further comprise a compound having a known vaginosis inhibitory activity or a plant extract in addition to the antimicrobial composition, and may be contained in an amount of 5 to 20 parts by weight per 100 parts by weight of the antimicrobial composition .

The composition for preventing or treating vaginitis of the present invention can be directly applied to animals including humans. The animal is a biological group corresponding to a plant. It mainly consumes organic matter as nutrients, and has digestion or excretion and differentiation of the respiratory organs. Preferably, it may be a vertebrate, more preferably a mammal. The mammal may preferably be a human.

The present invention also provides a composition for vaginal cleaning comprising the salt, the sugar and the polygamma glutamic acid (PGA) combination as an active ingredient.

The combined composition of the salt, sugar and polygamma glutamic acid (PGA) blend according to the present invention may further comprise a polygamma glutamic acid (PGA) as described in the preceding inventions and optionally a lactic acid bacterium acting as a probiotic, Experimental Example 1: Measurement of pH change and lactic acid concentration change by growth inhibition effect on causative bacteria ( Experimental Example 2) and simple clinical experiments, it was found that the compound composition of the present invention is superior to the conventional inhibitory activity of the group treated with polygamma glutamic acid or lactic acid bacteria, Lactate concentration-increasing activity, and inhibitory activity against vaginosis-causing bacteria, and thus can be used as an effective and safe composition for preventing and treating vaginitis.

Hereinafter, the present invention will be described in detail with reference to the following examples and experimental examples.

However, the following examples and experimental examples are illustrative of the present invention, and the content of the present invention is not limited by the following examples and experimental examples.

Example 1. Preparation of formulations

1-1. Preparation of salt

1-1-1. Manufacture of molten salt

400 mg of melted salt (Chunsan acid gold salt) obtained by heating the domestic salt (Shinan silver salt) at a heating temperature of 850 to 1000 캜 for 24 hours was obtained.

1-1-2. Manufacture of refined salt

400 mg of purified salt (Ducksan Pharm NaCl F.W.58.44) was obtained.

1-1-3. Manufacture of sun salt

400 mg of a salt of the sun (salt of salt as a salt of sun) was obtained.

1-2. Sugar preparation

1-2-1. Production of glucose

Glucose was purchased from company (D (+) - Glucose, Cat no. Jb01, JT Baker) 800mg.

1-2-2. Preparation of fructo-oligosaccharides

800 mg of fructooligosaccharide was purchased from the company (chicory-derived, Cat No. F8052050 g, Sigma).

1-2-3. Production of lactulose

800 mg of lactulose was purchased from Lactulose (wako, 126-03732).

1-2-4. Manufacture of fructose

Fructose was purchased from the company (Fructose, junsei, 64505-0410) at 800 mg.

1-2-5. Manufacture of fructose

Lactitol was purchased from the company (Lactitol, cat no. Sc488686, santa cruz) at 800 mg.

One- 3. Polygamma glutamic acid (PGA)  Preparation of

800 mg of polygamma glutamic acid (PGA; CAS No: 25513-46-6) was purchased from a company (P4033-10MG, mol wt 15,000-50,000, Sigma-Aldrich Co. LLC).

Preparation and culture of lactic acid bacteria

1-4-1. Preparation of lactic acid bacteria

The lactic acid bacteria used in this experiment were purchased from the international depository institution (Korea Research Institute of Bioscience and Biotechnology, KCTC) as shown in Table 1 below and used in this experiment.

1-4-2. Cultivation of lactic acid bacteria

Lactobacillus acidophilus ( KCTCNo.3164), which is a facultative anaerobic, an anaerobic and microaerophilic bacterium used in this experiment, and Streptococcus sp. ; KCTCNo.5644), Bifidobacterium spp ronggum ronggum (Bifidobacterium longum subsp longum;. KCTCNo.3128 ), bakteriohyi des plastic jilriseu (Bacteroides fragilis ; KCTCNo.5013), Gardnerella vaginalis ; KCTCNo.5097) was used, and (2) Bacillus cereus ( KCTCNo.13123), an aerobic bacterium, was used.

Bacteroides fragilis ; KCTCNo.5013), Gardnerella vaginalis ; The medium used for the culture of KCTCNo.5097) was casmans medium containing 5% sheep blood (12 g of Tryptone, 5 g of Meat peptone, 5 g of sodium chloride, 3 g of Yeast extract, 3 g of Beef extract, 1 g of Starch casein, 0.5 g of D- , Nicotinamide 0.05g, p-aminobenzoic acid 0.005g, Distilled water 1L, pH 7.3) was used.

Lactobacillus acidophilus ( KCTCNo.3164), Streptococcus sp . (KCTCNo.5644), Bifidobacterium longum ( Bifidobacterium spp. longum subsp . longum; KCTCNo.3128) was prepared by adding MRS Medium (Proteose peptone 10 g, Beef extract 10 g, Yeast extract 5 g, D-glucose 20 g, Tween 80 1 ml, K ₂ HPO ₄ 2 g of sodium acetate, 2 g of diammonium hydrogencitrate, 0.2 g of MgSO ₄ 7H ₂ O, 0.2 g of MnSO ₄ H ₂ O, 1 L of distilled water, pH 6.2-6.5) and cultured at 37 ° C with shaking at 150 rpm.

(1) Lactobacillus acidophilus (KCTCNo.3164), which is facultative anaerobic, anaerobic and microaerophilic bacteria, Streptococcus sp (KCTCNo.5644), Bifidobacterium longum subsp . longum (KCTCNo. 3128), Bacteroides fragile (KCTCNo.5013), Gardnerella vaginalis Shaking incubation was performed at 150 rpm using a GasPak ( ^TM) EZ Pouch System (BD, Cat # 26083, USA) for anaerobic cultivation of the culture medium (KCTCNo.5097).

1-5. Preparation of formulations

The salts, saccharides and lactic acid bacteria were dried and blended with the composition shown in Table 2 below and used as a preparation sample in the following experiment.

Clinical Examples 1. Clinical Experimental Examples (1)

The effect of the purified tablet composition for PC1 vaginal penetration prepared in the above example on 100 women (35 patients with vaginitis, 65 normal persons, 20 to 50 years old Korean women living in Jeonbuk area) was investigated.

The purified tablet composition for vaginal insertion prepared in the above-described example was allowed to be used for 100 days for 5 days (once a day, once at a dose of 1200 mg), and the effect of suppressing unpleasant odor, the degree of refreshing, (2) Satisfaction, (3) Normal, and (4) Dissatisfied. The results are shown in Table 3 below.

As can be seen from the above Table 3, 97% of the unpleasant odor suppressing effect was satisfied, and 81% of the respondents answered that they were very satisfied. (The questionnaire was selected mainly for people who had an unpleasant smell in advance. ) Considering the difference in individual differences and constitution, it was confirmed that the present invention has an excellent effect in suppressing unpleasant odor.

In addition, 93% of the mood after washing using the present invention was satisfied, and 77% was particularly satisfied. In view of the individual difference and the difference in constitution, the present invention was found to be clean It was confirmed that the effect of keeping the mood for a long time was confirmed.

In addition, 94% of the skin irritation-relieving effect of the present invention is satisfied, and especially 679% is very satisfactory. Considering individual differences or differences in constitution, it is confirmed that the present invention is effective for relieving skin itching .

Clinical cases 2. Examples of clinical trials (2)

The PSL1 combination cleaning composition prepared in the above example was applied to 100 women (42 patients with vaginitis, 58 normal persons, 20 to 50 years old Korean women living in Jeonbuk area), and their effects were investigated.

The compounded cleaning composition prepared in the above-described example was used for 100 days for 5 days (once a day, once for 200ml), and the vaginal acidity was measured with a pH meter / MP-103 , www.yuyuinst.co.kr), and the vaginal acidity after the experiment was measured, and the results are shown in Table 4 below.

Before the experiment, it was found that the pH of the experimental group was 85% or more, and the percentage of those who had an acidity of 6.0 or more reached 68%, indicating that the alkalization was proceeding considerably.

As shown in Table 4, the acidity of the vagina rapidly increased after the experiment. In the experimental group, 90% belonged to the normal acidity group, and the normal acidity in the vinegar group reached 4.5%.

Therefore, it has been confirmed that the present invention greatly contributes to the acidification of the vagina in consideration of the individual differences and differences in the constitution of the detergent composition of the present invention.

Formulation examples of compositions comprising a combination of the present invention are described, but the present invention is not intended to be limited thereto but is only specifically described.

Preparation Example 1. Preparation of powder

PC1 ------------------------------------------------- 20 mg

Lactose ----------------------------------------------- 100 mg

Talc ------------------------------------------------ 10 mg

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

Formulation Example 2. Preparation of tablets

PLL3 ------------------------------------------------ 10 mg

Corn starch ----------------------------------------- 100 mg

Lactose ----------------------------------------------- 100 mg

Magnesium stearate ---------------------------------- 2 mg

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

Formulation example  3. Preparation of capsules

PB1 ------------------------------------------------- - 10 mg

Crystalline cellulose - 3 mg

Lactose ------------------------------------------- 14.8 mg

Magnesium Stearate ------------------------------- 0.2 mg

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

Formulation Example 4. Preparation of injection

PF4 ------------------------------------------------ 10 mg

Mannitol -------------------------------------------- 180 mg

Sterile sterilized distilled water for injection ------------------------------ 2974 mg

Na ₂ HPO ₄ 12H ₂ O ---------------------------------------- 26 mg

(2) The above components are prepared per ampoule according to the usual injection preparation method.

Formulation Example 5. Preparation of a liquid preparation

PSL1 ----------------------------------------------- 10 mg

Isolation Party --------------------------------------------- 10 g

Mannitol ------------------------------------------------ 5 g

Purified water -----------------------------------------------

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and then purified water was added thereto to adjust the whole volume to 100. The solution was filled in a brown bottle and sterilized to prepare a liquid preparation do.

Formulation Example 6. Preparation of Healthy Foods

PS5 ---------------------------------------------- 1000 mg

Vitamin mixture ---------------------------------------

Vitamin A acetate -------------------------------- 70 μg

Vitamin E ------------------------------------------ 1.0 mg

Vitamin B1 ---------------------------------------- 0.13 mg

Vitamin B2 ---------------------------------------- 0.15 mg

Vitamin B6 ----------------------------------------- 0.5 mg

Vitamin B12 ---------------------------------------- 0.2 μg

Vitamin C ------------------------------------------- 10 mg

Biotin --------------------------------------------- 10 μg

Nicotinic acid amide 1.7 mg

Folic acid ----------------------------------------------- 50 μg

Calcium pantothenate ------------------------------------- 0.5 mg

Inorganic mixture ---------------------------------------

Ferrous sulfate ---------------------------------------- 1.75 mg

Zinc oxide ----------------------------------------- 0.82 mg

Magnesium carbonate ------------------------------------- 25.3 mg

Potassium phosphate monohydrate 15 mg

Secondary calcium phosphate ---------------------------------------- 55 mg

Potassium citrate ----------------------------------------- 90 mg

Calcium carbonate ------------------------------------------ 100 mg

Magnesium chloride ------------------------------------- 24.8 mg

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

Formulation Example 7. Preparation of health drink

PC1 --------------------------------------------- 1000 mg

Citric acid ------------------------------------------ 1000 mg

Oligosaccharide ------------------------------------------ 100 g

Plum concentrate ------------------------------------------ 2 g

Taurine ---------------------------------------------- 1 g

Add purified water ----------------------------- Total 900 mL

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The resulting solution was filtered to obtain a sterilized container, which was sealed and sterilized, Used in the manufacture of health beverage compositions.

Claims (21)

A pharmaceutical composition for the prevention and treatment of vaginitis containing salt, sugar and polygamma glutamic acid (PGA) combination as an active ingredient. The method according to claim 1,
Wherein the salt, sugar and polygamma glutamic acid (PGA) combination further comprises lactic acid bacteria. 3. The method according to claim 1 or 2,
Wherein the salt is at least one selected from the group consisting of sun salt, salt, and salt. 3. The method of claim 2,
The lactic acid bacterium is Bifidobacterium sp .; A strain of the genus Lactobacillus; Bacillus sp .; Leuconostoc species;); Pediococcus species; Propionibacterium species; Streptococcus species; Enterococcus species; Or a strain selected from Saccharomyces species. 5. The method of claim 4,
Wherein the lactic acid bacterium is a Bifidobacterium sp. Strain or a Bifidobacterium sp. Strain. 3. The method according to claim 1 or 2,
Wherein the sugar is selected from the group consisting of monosaccharides, disaccharides, oligosaccharides, and polysaccharides. The method according to claim 6,
The sugar may be selected from the group consisting of xylose, arabinose, glucose, mannose, fructose, galactose, lactulose, lactitol, sucrose, lactose, maltose, trehalose, fructo-oligosaccharide, raffinose, stachyose, maltodextrin, amylose, Wherein the sugar is selected from the group consisting of amylopectin, starch, cellulose, and pectin. 3. The method according to claim 1 or 2,
(PGA) formulation in the case of the above salt, sugar, and polygamma glutamic acid (PGA) formulation in a weight ratio of 1: 100 to 0.01: 100 to 0.01, 1: 100 to 0.01: 100 to 0.01: 100 to 0.01. 3. The method according to claim 1 or 2,
Wherein the vaginitis is any one selected from the group consisting of bacterial vaginitis, fungus vaginitis, and trichomoniasis vaginitis. A health functional food for preventing and improving vaginitis containing salt, sugar, and polygamma glutamic acid (PGA) combination as an active ingredient. 11. The method of claim 10,
Characterized in that the salt, sugar and polygamma glutamic acid (PGA) combination further comprises lactic acid bacteria. The method according to claim 10 or 11,
The health functional food is in the form of a powder, a granule, a tablet, a capsule, a pill, a suspension, an emulsion, a syrup, a tea bag, an oiled tea, or a health drink. A health supplement for the prevention and improvement of vaginitis containing salt, sugar and polygamma glutamic acid (PGA) combination as an active ingredient. 14. The method of claim 13,
Characterized in that the salt, sugar and polygamma glutamic acid (PGA) combination further comprises lactic acid bacteria. A composition for parenteral use for prevention and improvement of vaginitis containing salt, sugar, and polygamma glutamic acid (PGA) combination as an active ingredient. 16. The method of claim 15,
Wherein the salt, sugar and polygamma glutamic acid (PGA) combination further comprises a lactic acid bacterium. 17. The method according to claim 15 or 16,
The composition may be in the form of a liquid, a gel, a cleaning composition, a vaginal insert, a suppository, a cream, an ointment, a dressing solution, a spray, a coating agent, a solution, a suspension, an emulsion, a sterilized aqueous solution, Freeze-dried preparation, suppository, cream, ointment, jelly, foam, detergent or vaginal insert. 18. The method of claim 17,
The composition is used for application of sanitary articles such as tampons, sanitary napkins, diapers, shorts or the like, or for direct application to the skin. A detergent composition for preventing and improving vaginitis containing salt, sugar and polygamma glutamic acid (PGA) combination as an active ingredient. 20. The method of claim 19,
Characterized in that the salt, sugar and polygamma glutamic acid (PGA) combination further comprises lactic acid bacteria. 21. The method according to claim 19 or 20,
The composition may be in the form of a liquid, a gel, a cleaning composition, a vaginal insert, a suppository, a cream, an ointment, a dressing solution, a spray, a coating agent, a solution, a suspension, an emulsion, a sterilized aqueous solution, Wherein the detergent composition is an emulsion, an emulsion, a lyophilized preparation, a suppository, a cream, an ointment, a jelly, a foam, a detergent or a vaginal insert.