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WO2023038350A1 - Composition pour soulager le syndrome prémenstruel, contenant des souches de lactobacillus mélangées en tant que principe actif - Google Patents

Composition pour soulager le syndrome prémenstruel, contenant des souches de lactobacillus mélangées en tant que principe actif Download PDF

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Publication number
WO2023038350A1
WO2023038350A1 PCT/KR2022/012862 KR2022012862W WO2023038350A1 WO 2023038350 A1 WO2023038350 A1 WO 2023038350A1 KR 2022012862 W KR2022012862 W KR 2022012862W WO 2023038350 A1 WO2023038350 A1 WO 2023038350A1
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Prior art keywords
strain
premenstrual syndrome
lactobacillus
present application
composition
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PCT/KR2022/012862
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English (en)
Korean (ko)
Inventor
손민
김태락
배원영
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Lactomason Co Ltd
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Lactomason Co Ltd
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina

Definitions

  • Lactobacillus gasseri Lactobacillus gasseri
  • LM1065 strain KCCM13018P
  • Lactobacillus reuteri Lactobacillus reuteri
  • KCCM12650P Lactobacillus reuteri LM1071 strain
  • PMS Premenstrual syndrome
  • dysmenorrhea is a common gynecological symptom experienced every month by women of childbearing age until they reach menopause, and is a very common symptom in the female menstrual cycle.
  • compositions for alleviating premenstrual syndrome through changes in prolactin there is a composition for improving symptoms of premenstrual syndrome containing a compound isolated from malt extract as an active ingredient (Korean Patent No. 10-2187335).
  • a compound isolated from malt extract as an active ingredient
  • the present inventors have made diligent efforts to develop an excellent composition capable of alleviating premenstrual syndrome.
  • NO, IL-6 gene expression is reduced, and prostaglandin E 1 / prostaglandin E 2 production rate and DGLA level are increased in the blood.
  • a mixed strain was developed to complete the present invention.
  • Patent Document 1 Korean Patent Registration No. 10-2187335
  • Lactobacillus gasseri Lactobacillus gasseri
  • LM1065 strain KCCM13018P
  • Lactobacillus reuteri Lactobacillus reuteri
  • KCCM12650P Lactobacillus reuteri LM1071 strain
  • the first aspect of the present application is a mixture of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P), or a culture, lysate, or extract of the mixed strain It provides a pharmaceutical composition for preventing or treating premenstrual syndrome, comprising one or more as active ingredients.
  • the second aspect of the present application is a mixture of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P), or a culture, lysate, or extract of the mixed strain It provides a food composition for alleviating dysmenorrhea, containing one or more as active ingredients.
  • the mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) reduces the amount of NO production and the expression of IL-6, iNOS and COX-2 genes in the blood, By increasing the prostaglandin E 1 /prostaglandin E 2 production rate and the levels of GLA and DGLA in blood, premenstrual syndrome can be alleviated, and the mixed strain can be applied to food compositions, health functional food compositions, pharmaceutical compositions, and the like.
  • KCCM13018P Lactobacillus gasseri LM1065 strain
  • KCCM12650P Lactobacillus reuteri LM1071 strain
  • Figure 2 examines the symptom relieving effect of a mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) for premenstrual syndrome for premenstrual syndrome according to an embodiment of the present application.
  • KCCM13018P Lactobacillus gasseri LM1065 strain
  • KCCM12650P Lactobacillus reuteri LM1071 strain
  • Figure 3 is to determine the symptom relief effect of a mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) for premenstrual syndrome for premenstrual syndrome according to an embodiment of the present application.
  • KCCM13018P Lactobacillus gasseri LM1065 strain
  • KCCM12650P Lactobacillus reuteri LM1071 strain
  • Figure 4 is to determine the symptom relief effect of a mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) for premenstrual syndrome for premenstrual syndrome according to an embodiment of the present application.
  • serum obtained by collecting blood on the last day of administration was analyzed for concentrations of GLA and DGLA in blood using LC-MS/MS (Liquid Chromatograph-Tandem Mass Spectrometer; Liquid Chromatograph-Multiple Mass Spectrometry) method.
  • LC-MS/MS Liquid Chromatograph-Tandem Mass Spectrometer; Liquid Chromatograph-Multiple Mass Spectrometry
  • step of (doing) or “step of” as used throughout the present specification does not mean “step for”.
  • the first aspect of the present application is a mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P), or a culture, lysate, or extract of the mixed strain It provides a pharmaceutical composition for preventing or treating premenstrual syndrome, comprising the above as an active ingredient.
  • the mixed strain may reduce the amount of NO production in the blood.
  • nitric oxide used throughout the present specification is called “nitric oxide” or “nitrogen monoxide” and refers to a compound in which nitrogen is oxidized. It is formed from arginine, an amino acid, within cells, and is involved in various physiological activities such as immune action, vasodilation, and signal transmission as a kind of signaling substance. It is also known to induce inflammation and pain by promoting the secretion of inflammatory cytokines such as TNF- ⁇ and IL-6 (Hu et al., 2020).
  • the mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) of the present application reduces the amount of NO production, thereby exhibiting an effect of alleviating menstrual pain.
  • the term "Griess reagent” used throughout the present specification refers to a reagent used in a Griess test to determine the presence or absence of nitrite ions NO 2 - . In general, it is prepared by mixing a solution of 0.5 g of sulfanilic acid in 150 ml of dilute acetic acid and a solution of 0.1 g of a-naphthylamine in 20 ml of water and 150 ml of acetic acid.
  • the NO production ability measurement experiment is an experiment using the above grease reagent, and through this, the expression level of NO can be measured.
  • the mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) of the present application reduces the expression of IL-6, iNOS and COX-2 genes, thereby It may have a menstrual pain relief effect.
  • IL-6 InterLeukin-6
  • TNF- ⁇ Tumor Necrosis Factor- ⁇
  • IL-6 is secreted from various cells such as T lymphocytes and macrophages to promote immune responses.
  • IL-6 is involved in inflammatory responses and causes inflammation and pain in the process of regulating high fever or acute phase proteins.
  • iNOS inducible NO synthase
  • iNOS inducible NO synthase
  • the gene expression of iNOS is closely related to the inflammatory response, and the gene is induced in cells such as macrophages, smooth muscle cells, and hepatocytes by stimulation of inflammatory cytokines to produce NO.
  • cyclooxygenase-2 (COX-2) used throughout the present specification refers to an enzyme that produces prostaglandin, and the expression level increases along with an inflammatory response.
  • LPS lipopolysaccharide
  • TLR4 Toll-like receptor 4
  • mouse caspase-11 and its human homologues caspase-4/5 are also known to induce pyroptosis and secretion of IL-1 ⁇ and IL-18, which are derived from Gram-negative bacteria. It was found to induce an inflammatory response by directly recognizing LPS (intracellular LPS) within a cell (Lee Young-soo, 2017).
  • the mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) of the present application reduces the expression of IL-6, iNOS and COX-2 genes, , it can be seen that it can be effective in relieving menstrual pain and treating or preventing premenstrual syndrome.
  • the mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) of the present application increases the production ratio of prostaglandin E 1 / prostaglandin E 2 in blood, thereby It can show the effect of alleviating menstrual cramps and premenstrual syndrome.
  • prostaglandin used throughout the present specification refers to a kind of hormone secreted during menstruation, which contracts the uterus and smoothly pushes menstrual blood out of the body when the endometrium is peeled off.
  • Prostaglandin is a process in which arachidonic acid is converted into prostaglandin using a cyclooxygenase (COX) system, and arachidonic acid is converted into prostaglandin G2 and then into prostaglandin H2, thereby producing prostaglandins with various physiological activities.
  • COX cyclooxygenase
  • prostaglandins have been reported as substances that cause inflammation and pain (Jayesh et al., 2020).
  • PGE 2 prostaglandin E 2
  • dinoprostone refers to a naturally occurring prostaglandin with oxytocin properties.
  • PGE 2 induces pain through inflammatory mediation in tissues or cells damaged by G protein bound to the PGE 2 receptor (Treutlein et al., 2018), and stimulates the central nervous system and peripheral nervous system (Gr ⁇ sch et al., 2017).
  • the mixed strain may increase the blood prostaglandin E 1 / prostaglandin E 2 ratio, and specifically, the strain may increase the production ratio of prostaglandin E 1 to prostaglandin E 2 .
  • PGE 1 prostaglandin E 1
  • alprostadil refers to a naturally occurring prostaglandin that serves to dilate blood vessels in the body, relaxes smooth muscles and reduces secretion of inflammatory cytokines. It is known that there is a pain relieving effect (Gezginci-Oktayoglu et al., 2016).
  • PGE 1 /PGE 2 The production ratio of PGE 1 /PGE 2 (PGE 2 to PGE 1 ) is a major index in the guidelines of the Ministry of Food and Drug Safety related to premenstrual syndrome in women, and if the ratio increases, it can be judged that it contains functions related to the treatment of premenstrual syndrome.
  • the mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) of the present application increases the production ratio of prostaglandin E 1 / prostaglandin E 2 in blood, which Through this, it can be seen that it can be effective in relieving menstrual pain and relieving premenstrual syndrome.
  • the mixed strain may increase the level of GLA or DGLA in blood.
  • GLA Gamma-linolenic acid
  • Prostaglandin metabolism disorders are found in women with premenstrual syndrome. Because prostaglandins are involved in central nervous system function, fluid balance, and regulation of uterine contractility, prostaglandin metabolism disorders can cause premenstrual syndrome. Therefore, it is known that allowing women with defects in the process of converting linoleic acid to gamma-linolenic acid in the prostaglandin synthesis process to take GLA can directly synthesize prostaglandin, which can help alleviate the symptoms of premenstrual syndrome.
  • DGLA Dihomo-gamma-linolenic acid
  • DGLA produces PGE 1 and 15-OH-DGLA through metabolism.
  • PGE 1 is effective in suppressing inflammation
  • 15-OH-DGL inhibits 5-lipoxygenase and 12-lipoxygenase to inhibit the production of inflammatory metabolites such as PGE 2 and LTB4 produced from arachidonic acid. interfere
  • Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) of the present application enhances the production of GLA and DGLA, thereby relieving menstrual pain. there is.
  • treatment used throughout the specification of the present application is a pharmaceutical composition comprising a mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) of the present application as an active ingredient. It refers to all actions to improve or benefit the symptoms of premenstrual syndrome by administering the composition to a subject having premenstrual syndrome.
  • the composition may be for treating or preventing premenstrual syndrome, and specifically, reduces blood NO production and IL-6, iNOS, and COX-2 gene expression, and blood prostaglandin E 1 /prostaglandin and treating or preventing premenstrual syndrome by increasing the E 2 production rate and the levels of GLA and DGLA.
  • menstrual syndrome refers to a series of symptoms characterized by emotional, behavioral, and physical symptoms that occur repeatedly before menstruation, such as edema, breast pain, digestive disorders, headache, back pain, lower abdominal pain, and abdominal pain. These include bloating, constipation, diarrhea, depression and insomnia.
  • the pharmaceutical composition is in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories or sterile injection solutions according to conventional methods, respectively. It may be formulated and used, but may not be limited thereto.
  • the pharmaceutical composition when formulating the pharmaceutical composition, it may be prepared using diluents or excipients such as generally used fillers, extenders, binders, wetting agents, disintegrants, or surfactants, but limited thereto It may not be.
  • diluents or excipients such as generally used fillers, extenders, binders, wetting agents, disintegrants, or surfactants, but limited thereto It may not be.
  • solid preparations for oral administration include tablets, pills, powders, granules, or capsules, etc., and these solid preparations include at least one excipient in the dead cells of the strain, for example, It may be prepared by mixing starch, calcium carbonate, sucrose, lactose, or gelatin.
  • lubricants such as magnesium stearate and talc may be used in addition to simple excipients, but may not be limited thereto.
  • liquid preparations for oral administration include suspensions, internal solutions, emulsions, syrups, etc., and various excipients such as wetting agents, Sweeteners, aromatics, preservatives, and the like may be included, but may not be limited thereto.
  • preparations for parenteral administration may include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories, but may not be limited thereto.
  • non-aqueous solvent or suspension propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used, but may not be limited thereto.
  • the suppository witepsol, macrogol, tween 61, cacao paper, laurin paper, glycerogelatin, etc. may be used, but may not be limited thereto.
  • the pharmaceutical composition according to one embodiment of the present application may be a pharmaceutical composition or a quasi-drug composition.
  • quasi-drugs used throughout the present specification refers to items with a milder effect than pharmaceuticals among items used for the purpose of diagnosing, treating, improving, mitigating, treating or preventing diseases of humans or animals. According to the Act, quasi-drugs are items excluding items used for pharmaceutical purposes, and include products used for the treatment or prevention of human or animal diseases, products with minor or no direct action on the human body, etc.
  • the quasi-drug composition of the present application consists of body cleanser, disinfectant cleanser, detergent, kitchen detergent, cleaning detergent, toothpaste, gargling agent, wet tissue, detergent, soap, hand wash, hair detergent, hair softener, humidifier filler, mask, ointment and filter filler It can be prepared in a formulation selected from the group, but is not limited thereto.
  • the pharmaceutical composition may be administered in a pharmaceutically effective amount
  • pharmaceutically effective amount refers to treating a disease at a reasonable benefit / risk ratio applicable to medical treatment or prevention Or means an amount sufficient to prevent, and the effective dose level is the severity of the disease, the activity of the drug, the age, weight, health, sex of the patient, the sensitivity of the patient to the drug, the administration time of the composition of the present invention used, the route of administration and excretion rate, treatment period, factors including drugs used in combination or simultaneous use with the composition of the present invention used, and other factors well known in the medical field.
  • the pharmaceutical composition of the present application may be administered alone or in combination with components known to exhibit therapeutic effects on known intestinal diseases. It is important to administer the amount that can obtain the maximum effect with the minimum amount without side effects in consideration of all the above factors.
  • the dosage of the pharmaceutical composition can be determined by a person skilled in the art in consideration of the purpose of use, the degree of addiction of the disease, the patient's age, weight, sex, history, or the type of substance used as an active ingredient.
  • the pharmaceutical composition of the present invention can be administered at about 0.1 ng to about 1,000 mg/kg, preferably 1 ng to about 100 mg/kg per adult, and the frequency of administration of the composition of the present application is particularly limited thereto. However, it can be administered once a day or divided into several doses. The dosage or frequency of administration is not intended to limit the scope of the present application in any way.
  • the pharmaceutical composition of the present application is not particularly limited thereto, but as desired, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, transdermal patch administration, oral administration, intranasal administration, intrapulmonary administration, intrarectal administration, etc. It can be administered through the route of However, when administered orally, it can be administered in an unformulated form, and since the Lactobacillus gasseri LM1065 strain and the Lactobacillus reuteri LM1071 strain can be denatured or decomposed by gastric acid, the oral composition contains an active agent. It can also be administered orally in the form of a coating or formulated to protect it from degradation in the stomach or in the form of an oral patch. In addition, the composition may be administered by any device capable of transporting active substances to target cells.
  • the second aspect of the present application is a mixture of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P), or a culture, lysate, or extract of the mixed strain It provides a food composition for alleviating dysmenorrhea, containing one or more as active ingredients. Content overlapping with the first aspect is also applied to the food composition of the second aspect.
  • relief used throughout the present specification refers to any activity in which menstrual pain is alleviated or related symptoms are improved by administration of the composition.
  • the composition may alleviate menstrual pain, and specifically, reduce the amount of NO production in the blood and the expression of IL-6, iNOS and COX-2 genes, and the blood prostaglandin E 1 / prostaglandin E 2 production ratio and relieving menstrual cramps by increasing the levels of GLA and DGLA.
  • the composition is a mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P), or its live cells, dead cells, cultures, lysates and / or its It may contain extracts.
  • the term "dead cell body” used throughout the present specification is the opposite concept of live bacteria, and means a form in which the growth of bacteria is prevented from occurring by heat treatment or the like of live bacteria and metabolites obtained through fermentation.
  • the dead cell body may include cytoplasm, cell wall, antibacterial active substances such as bacteriocin, polysaccharides, organic acids, and the like.
  • Products using the dead cells have higher stability compared to live cell products, especially have excellent heat resistance and high stability to the external environment, so they are easier to store than existing live cell products and have the advantage of extending the shelf life.
  • regulations on the use of antibiotics are being strengthened, the marketability and growth potential are very high, as there are only a handful of companies that have entered into the production of dead cell products in earnest and usable as an alternative.
  • culture refers to an object obtained by culturing the strain of the present application in a known liquid medium or solid medium, and may be used interchangeably with “culture medium”.
  • food used throughout the present specification refers to meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages, vitamin complexes, health functional foods and health foods, etc., and include all foods in a conventional sense.
  • the term "functional health food” used throughout the present specification refers to food manufactured and processed using raw materials or ingredients having functional properties useful for the human body in accordance with the Act on Health Functional Foods No. 6727, and is referred to as 'functional'. It means to obtain useful effects for health purposes, such as regulating nutrients for the structure and function of the human body or physiological functions.
  • the food of the present application can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and components commonly added in the art during the preparation.
  • the formulation of the food may also be prepared without limitation as long as the formulation is recognized as a food.
  • the composition for food of the present invention can be prepared in various types of formulations, and unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time using food as a raw material, and has excellent portability, so the present invention Of the foods can be consumed as supplements to enhance the effect of improving the intestinal environment.
  • the health food means food that has an active health maintenance or promotion effect compared to general food
  • health supplement food means food for the purpose of health supplement.
  • the terms health functional food, health food, and dietary supplement may be used interchangeably.
  • the health functional food is a mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) of the present application is added to food materials such as beverages, teas, spices, gum, confectionery, It is a food manufactured in capsules, powders, suspensions, etc., which means that it brings specific health effects when ingested.
  • the food composition of the present application can be consumed on a daily basis, a high effect on depression improvement can be expected, so it can be used very usefully.
  • the food composition may further include a physiologically acceptable carrier.
  • a physiologically acceptable carrier is not particularly limited, and any carrier commonly used in the art may be used.
  • the food composition may include additional ingredients that are commonly used in food compositions and can improve smell, taste, and vision.
  • vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid, and the like may be included.
  • minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), and chrome (Cr) may be included.
  • amino acids such as lysine, tryptophan, cysteine, and valine may be included.
  • the food composition may include preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), bactericides (bleaching powder, high bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisole (BHA), butyl hydroxy Loxytoluene (BHT), etc.), coloring agents (tar color, etc.), coloring agents (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite, etc.), seasonings (MSG sodium glutamate, etc.), sweeteners (dulcin, cyclemate, saccharin) , sodium, etc.), flavoring (vanillin, lactones, etc.), expanding agent (alum, D-potassium hydrogen stannate, etc.), strengthening agent, emulsifier, thickener (thickener), coating agent, gum base agent, foam inhibitor, solvent, improver, etc. food May contain food additives.
  • the additive may be
  • the mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) of the present application may be added as is or used together with other foods or food ingredients, and may be appropriately used according to conventional methods.
  • the mixing amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment).
  • the food composition of the present invention may be added in an amount of 50 parts by weight or less, specifically 20 parts by weight or less, based on the food or beverage when preparing food or beverage.
  • the amount below the above range may be included, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
  • the food composition of the present application may be used as a health beverage composition, and in this case, as in conventional beverages, various flavoring agents or natural carbohydrates may be included as additional ingredients.
  • the aforementioned natural carbohydrates include monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrins and cyclodextrins; It may be a sugar alcohol such as xylitol, sorbitol, or erythritol.
  • Sweeteners include natural sweeteners such as thaumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame may be used.
  • the ratio of the natural carbohydrates may be generally about 0.01 to 0.04 g, specifically about 0.02 to 0.03 g per 100 mL of the health drink composition of the present invention.
  • the health beverage composition includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, It may contain alcohol or a carbonating agent, and the like. In addition, it may contain fruit flesh for the manufacture of natural fruit juice, fruit juice beverages, or vegetable beverages. These components may be used independently or in combination. The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health beverage composition of the present invention.
  • the food composition of the present application may include a mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) of the present application in various weight% if it can exhibit an intestinal environment improvement effect.
  • a mixed strain of Lactobacillus gasseri LM1065 strain and Lactobacillus reuteri LM1071 strain may be included in 0.00001 to 100% by weight or 0.01 to 80% by weight based on the total weight of the food composition, but is not limited thereto.
  • the food composition may be a health functional food composition.
  • RAW 264.7 cells which are mouse macrophages, were inoculated into a 96 well plate at a concentration of 1x10 5 cell/well.
  • the culture plate was cultured for 24 hours in an environment of 37°C and 5% CO 2 .
  • a mixed strain of Lactobacillus gasseri LM1065 strain (KCCM13018P) and Lactobacillus reuteri LM1071 strain (KCCM12650P) was treated at a concentration of 1x10 8 CFU/ml for 2 hours cultured in an incubator.
  • Example 2 Anti-inflammatory gene expression ability measurement experiment using real-time PCR (Real-time PCR)
  • Mouse macrophage RAW 264.7 cells were inoculated into a 24 well plate at a concentration of 1x10 5 cell/well. The culture plate was cultured for 24 hours in an environment of 37°C and 5% CO 2 .
  • the mixed strain of Lactobacillus gasseri LM1065 strain and Lactobacillus reuteri LM1071 strain was treated at a concentration of 1x10 8 CFU/ml, and then cultured in an incubator for 2 hours.
  • RNA was extracted using an RNA extraction kit (RNA extraction kit [TaKaRa]), and cDNA was synthesized and synthesized using a high-capacity cDNA reverse transcription kit (Applied Biosystems). Diluted to a final concentration of 5ng/ul.
  • RNA extraction kit [TaKaRa] RNA extraction kit [TaKaRa]
  • cDNA was synthesized and synthesized using a high-capacity cDNA reverse transcription kit (Applied Biosystems). Diluted to a final concentration of 5ng/ul.
  • the rats used in this example are specific pathogen-free (SPF) rats produced and supplied by Coretech.
  • SPF pathogen-free rats produced and supplied by Coretech.
  • temperature 23 ⁇ 3 ° C temperature 23 ⁇ 3 ° C
  • relative humidity 55 ⁇ 15% relative humidity 55 ⁇ 15%
  • ventilation frequency 10-20 times / hr lighting time 1 hour (8:00 am on - pm on - 8:00 pm off) and Experiments were conducted in a laboratory set to 150 to 300 Lux.
  • test substance administration After weighing an appropriate amount of test substance, it was diluted in sterile water for injection to prepare a prescribed concentration. In the case of the administration method, oral administration was administered once/day for 4 weeks, and the amount of administration was calculated based on 10 mL/kg of body weight measured on the latest weight measurement day.
  • a vaginal cornification (smear cytology) test was performed at 4 weeks after the start of test substance administration. Blood was collected once/day for 3 days (Day26, Day27, Day28) from 3 days before the last administration of the test substance. Blood collection was performed through the jugular vein, and the collected blood was injected into a vacutainer tube containing a clot activator, left at room temperature for about 15 minutes to coagulate, and then centrifuged at 3,000 rpm for 10 minutes. Serum was separated. Serum was stored in a deep freezer set at -70 ° C or lower until analysis, and used for ELISA analysis. At each blood collection point, a portion of serum obtained by centrifugation using an ELISA kit was used to analyze PGE 1 and PGE 2 concentrations and PGE 1 /PGE 2 concentrations. Analysis was performed using a commercially available ELISA kit.
  • the concentrations of GLA and DGLA in the blood were analyzed using the LC-MS/MS method using serum collected on Day 26 from the last test substance administration day.
  • the prostaglandin E 1 /prostaglandin E 2 ratio of the mixed strain-administered group of Lactobacillus gasseri LM1065 strain and Lactobacillus reuteri LM1071 strain was significantly higher than that of the normal control group on Day 28 (p ⁇ 0.05, FIG. 3 reference).
  • the prostaglandin E 1 /prostaglandin E 2 ratio increased in the group administered with the mixed strain of Lactobacillus gasseri LM1065 strain and Lactobacillus reuteri LM1071 strain and increased blood levels of GLA and DGLA were observed. It is shown that the administration of the test substance induced an increase in PGE 1 and a decrease in PGE 2 to induce symptom improvement in the PMS model.
  • the mixed strain of Lactobacillus gasseri LM1065 strain and Lactobacillus leuteri LM1071 strain increases the PGE 1 / PGE 2 ratio and promotes the production of GLA and DGLA, which are inflammatory substances, to contribute to relieving menstrual cramps and premenstrual symptoms. I was able to confirm that there is
  • the mixed strain of the present application inhibits the production of NO, an inflammation and pain-inducing substance, and inhibits the expression of anti-inflammatory genes IL-6, iNOS and COX-2, , It was confirmed that PGE 1 /PGE 2 ratio, which is a major index related to premenstrual syndrome, was increased, and the production of GLA and DGLA, which are substances that relieve inflammation, was increased to show an effect in alleviating premenstrual syndrome.

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Abstract

Le but de la présente demande est de fournir une composition pour soulager le syndrome prémenstruel, contenant, en tant que principe actif, des souches mélangées d'une souche de Lactobacillus gasseri LM1065 (KCCM13018P) et une souche de Lactobacillus reuteri (KCCM12650P), ou un produit de culture, un lysat ou un extrait des souches mélangées. Les souches mélangées d'une souche de Lactobacillus gasseri LM1065 (KCCM13018P) et d'une souche de Lactobacillus reuteri LM1071 (KCCM12650P), selon un mode de réalisation de la présente demande, réduisent la production de NO sanguin et l'expression de IL-6, iNOS et COX-2 et augmentent le taux de production de la prostaglandine sanguine E1/prostaglandine E2 et les taux de GLA sanguin et DGLA, de sorte que le syndrome prémenstruel peut être atténué, et ainsi les souches mélangées peuvent être appliquées à des compositions alimentaires, à des compositions alimentaires fonctionnelles bénéfiques pour la santé, à des compositions pharmaceutiques et analogues.
PCT/KR2022/012862 2021-09-09 2022-08-29 Composition pour soulager le syndrome prémenstruel, contenant des souches de lactobacillus mélangées en tant que principe actif Ceased WO2023038350A1 (fr)

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KR102268128B1 (ko) * 2021-02-09 2021-06-22 주식회사 락토메이슨 모유 유래 신규한 락토바실러스 루테리 lm1071 균주, 및 상기 균주 또는 이의 배양물을 포함하는 월경전 증후군 완화용 조성물
WO2024117705A1 (fr) * 2022-11-28 2024-06-06 주식회사 엠바이옴쎄라퓨틱스 Composition pharmaceutique pour soulager ou traiter le syndrome prémenstruel comprenant la souche d'enterococcus lactis lcm001
KR20240161867A (ko) 2023-05-03 2024-11-13 주식회사 엠바이옴쎄라퓨틱스 엔테로코커스 락티스 lcm001 균주를 포함하는 생리전증후군 완화 또는 치료용 약학적 조성물
KR20240086744A (ko) 2022-11-28 2024-06-19 주식회사 엠바이옴쎄라퓨틱스 엔테로코커스 패시움 lcm001 균주를 포함하는 생리전증후군 완화 또는 치료용 약학적 조성물
WO2025143308A1 (fr) * 2023-12-28 2025-07-03 주식회사 엠바이옴쎄라퓨틱스 Composition pharmaceutique pour soulager ou traiter le syndrome prémenstruel comprenant une souche d'enterococcus faecium lcm001

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CN119776204B (zh) * 2024-12-31 2025-08-29 胃早安健康科技(山东)有限公司 一株暖宫驱寒和改善乳腺健康的干酪乳酪杆菌及其后生元

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