WO2012064158A2 - Composition comprenant des herbes médicinales fermentées pour le traitement du syndrome du côlon irritable - Google Patents

Composition comprenant des herbes médicinales fermentées pour le traitement du syndrome du côlon irritable Download PDF

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WO2012064158A2
WO2012064158A2 PCT/KR2011/008643 KR2011008643W WO2012064158A2 WO 2012064158 A2 WO2012064158 A2 WO 2012064158A2 KR 2011008643 W KR2011008643 W KR 2011008643W WO 2012064158 A2 WO2012064158 A2 WO 2012064158A2
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fermented
mixture
baekchul
fermentation
formal
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WO2012064158A3 (fr
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김호준
김영수
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동국대학교 산학협력단
한국보건산업진흥원
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/284—Atractylodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes

Definitions

  • the present invention relates to a formal pharmaceutical composition and health functional food comprising a mixture of herbal medicines containing fermented Baekchul, Singok and Baekpok. More specifically, the present invention relates to a formal pharmaceutical composition and a dietary supplement comprising a mixture of herbal medicines containing fermented baekchul, singok and baekryeom as optimal fermentation conditions for maximizing the efficacy of functional bowel disease.
  • IBS Irritable bowel syndrome
  • IBS disease is more common in people who are nervous or stressed, have a weak stomach, have a lack of exercise, and are meticulous and timid. For example, it is necessary to develop treatment and prevention techniques for various diseases such as office workers, examinees, young housewives, job drivers, postpartum or postoperative weakness, irregular smokers and drinkers.
  • Irritable bowel syndrome has many causes, but it is closely related to the imbalance of the intestinal microorganisms, that is, the lack of beneficial bacteria and the excessive number of harmful bacteria that adversely affect metabolism, so in the West, many probiotic agents called probiotics It is utilized.
  • the present inventors produce a component having an improved yield yield and improved toxin reduction efficacy of the natural-derived formal component in the mixed fermentation tablet by using the fermented natural product resources, and has a formal effect through the mixed fermentation of beneficial bacteria of the formal intestinal efficacy verified.
  • the present invention has been completed by maximizing the development of a high functional material having an effect on chronic irritable bowel disease and stomach ailment, food intolerance, and developing a composition that can be utilized for health promotion of all the people based on the material.
  • the present invention provides a formal composition comprising a mixture of fermented Baekchul, Singok and Baekdudu.
  • the fermentation of the baekchul is preferably fermented with Bacillus licheniformis (Bacillus licheniformis) as a fermentation strain of 1 to 3% glucose.
  • Bacillus licheniformis Bacillus licheniformis
  • the fermentation of the new song is preferably fermented with 1% to 3% glucose as a fermentation strain of Leuconostoc mesenteroides.
  • the fermentation of the white migraine is preferably fermented with 1% to 3% LB broth as Bacillus rickeniformis as a fermentation strain.
  • the ratio of fermented baekchul, new song, and white bean contained in the mixture is preferably in the range of 0.5 to 2 parts by weight of fermented new song and 0.5 to 2 parts by weight of fermented white bean, based on 1 part by weight of fermented baekchul. More preferably, the weight ratio of the white out, the new song, and the white bean is 1: 1: 1.
  • the mixture may be administered to the subject in an amount of 50 to 200 mg / kg, preferably administered to the subject in an amount of 50 to 100 mg / kg.
  • the present invention provides a dietary supplement for dietary supplement comprising a mixture of fermented Baekchul, Singok and Baekpok.
  • the ratio of fermented baekchul, new song, and white bean contained in the mixture is preferably in the range of 0.5 to 2 parts by weight of fermented new song and 0.5 to 2 parts by weight of fermented white bean, based on 1 part by weight of fermented baekchul. More preferably, the weight ratio of the white out, the new song, and the white bean is 1: 1: 1.
  • composition of the present invention can be used as a medicine and health food by using it because it has excellent suitability effect, has no absorption rate and no toxicity or side effects in vivo, and excellent stability.
  • C is a graph showing the effect of various concentrations of fermented or non-fermented herbal medicines on RAW264.7 cells on cell viability.
  • C represents a control group.
  • Figure 2 is a graph related to the protective action of fermented and non-fermented herbal medicine against LPS-induced cytotoxicity.
  • C represents the control group and a, b represent significant differences from the control and LPS treated groups, respectively (p ⁇ 0.05).
  • Figure 3 is a graph showing the effect of the herbal medicine on the gene expression of iNOS expressed in RAW264.7 cells.
  • C represents the control group and a represents the significant difference from the LPS treated group (p ⁇ 0.05).
  • Figure 4 is a graph showing the effect of the herbal medicine on COX-2 expression in LPS induced RAW264.7 cells.
  • C represents the control group and a represents the significant difference from the LPS treated group (p ⁇ 0.05).
  • FIG. 5 is a graph showing the inhibitory effect of fermented herbal and non-fermented herbal medicines on NO produced from RAW264.7 cells by LPS.
  • C represents the control group and a represents the significant difference from the LPS treated group (p ⁇ 0.05).
  • FIG. 6 is a graph showing the effect on LPS-induced endotoxin levels of mixed fermented and unfermented or colostrum. a shows a significant difference from the group treated with LPS (p ⁇ 0.05).
  • FIG. 8 is a graph showing the lactulose / mannitol ratio following the injection of mixed fermented or unfermented or colostrum in rats treated with LPS. a shows a significant difference from the group treated with LPS (p ⁇ 0.05).
  • 9 is a graph of the water content of feces following injection of mixed fermented or unfermented or probiotics in rats treated with neomycin. a shows significant difference from the group treated with neomycin (p ⁇ 0.05).
  • FIG. 10 is a graph of CRP levels following infusion of fermented or unfermented or probiotics in rats treated with neomycin. a shows significant difference from the group treated with neomycin (p ⁇ 0.05).
  • FIG. 11 is a graph of interferon- ⁇ following injection of mixed fermented or unfermented or probiotics in rats treated with neomycin. a shows significant difference from the group treated with neomycin (p ⁇ 0.05).
  • FIG. 12 is a micrograph of colon tissue following administration of mixed fermented or unfermented or probiotics in rats treated with neomycin.
  • antibiotic-induced diarrhea intestinal membrane damage, infiltration of inflammatory cells, edema and discontinuity of lower tissues were observed, but pathologic findings were clearly improved in the intestinal mucosa of fermented herbs.
  • FIG. 13 is a graph showing Lactobacillus proliferation following injection of mixed fermented or unfermented or colostrum in rats treated with LPS. It can be seen that the microorganisms of the genus Lactobacillus significantly increased in the fermented herbal medicine group compared to the control group.
  • FIG. 14 is a graph showing the intestinal beneficial bacteria (Bifidobacterium) proliferation following injection of mixed fermented or unfermented or colostrum in rats treated with LPS. Compared to the control group, the fermented Chinese herbal medicine group showed significantly increased Bifidobacterium genus.
  • the present invention provides a formal pharmaceutical composition comprising a mixture of fermented baekchul, singok and baekryeom.
  • the pharmaceutical composition of the present invention includes fermented medicinal herb containing fermented Baekchul, Singok and Baekdudu at optimum fermentation conditions for maximizing the efficacy of functional bowel disease, and Baekchul, Singok contained in the mixture of the herbal medicine ,
  • the ratio of Baekdudu is preferably in the range of 0.5-2 parts by weight of fermented new song and 0.5-2 parts by weight of fermented Baengdu with respect to 1 part by weight of fermented Baekchul. It is more preferable that it is a weight ratio of: 1.
  • Atractylodis Rhizoma alba belongs to the Asteraceae, and its components are known as Atractylone, Atractylenolide, Beta-Eudesmol and Heynesol. Exudation acts as a diuretic and sweating effect on the abnormality of water metabolism in the digestive tract and subcutaneous tissue, and it is effective in pain and gastroenteritis.
  • new song in the present invention is a medicinal herb made by mixing fermented flour, bran, spear juice, fermented juice, cheongho juice, hanginni, red bean, etc., is used as a drying agent and a fire extinguishing agent.
  • white flakes (Latin name Dolichos Semen, scientific name Dolichoris lablab L., scientific name Leguminosae) is a white, dried seed, round egg shape. It strengthens the stomach, harmonizes the middle and lowers the heat, has the effect of reducing moisture, and cures the loss of appetite due to vomiting and diarrhea.
  • the taste is sweet and the properties are slightly warm. It contains 0.227% protein, 0.018% fat, 0.57% carbohydrate, calcium, phosphorus, zinc and iron, and has trypsin inhibitor, amylase inhibitor, hemagglutinin A and B Contains.
  • Preferred fermentation conditions for maximizing the efficacy of functional intestinal diseases of the respective herbs are as follows.
  • baekchul in case of baekchul, it can be dissolved in autoclaved Milli-Q water and fermented. It is preferred to inject 1-3% LB broth or 1-3% glucose as the medium during fermentation, more preferably 2% glucose. After the mixture is cooled by autoclaving, bacterial inoculum can be injected and fermented.
  • the bacterial inoculum is preferably Bacillus rickeniformis, Lactobacillus acidophilus or Leukonostock mesenteroides, and more preferably Bacillus rickeniformis as a fermentation strain. .
  • bacterial inoculum can be injected and fermented.
  • the bacterial inoculum is preferably Bacillus rickeniformis, Lactobacillus ashidophilus or Leukonostock mesenteroides, and more preferably Bacillus rickeniformis as a fermentation strain.
  • the new song can be fermented by dissolving in autoclaved Milli-Q water. It is preferred to inject 1-3% LB broth or 1-3% glucose as the medium during fermentation, more preferably 2% glucose.
  • the mixture may be cooled by autoclaving and then fermented by injecting bacterial inoculum.
  • the bacterial inoculum is preferably Bacillus rickeniformis, Lactobacillus ashidophyllus or Leukonostock mesenteroides as the fermentation strain, and more preferably using Leukonostock mesenteroides.
  • the formal pharmaceutical composition of the present invention may further include a pharmaceutically acceptable additive.
  • the additives may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
  • compositions of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds, as well as in any suitable collection.
  • compositions according to the invention can each be in the form of tablets, pills, capsules, powders, suspensions, granules or extracts in the form of oral formulations, external preparations, suppositories and sterile injectable solutions according to conventional methods. Can be formulated and used.
  • Carriers, excipients and diluents that may be included in the pharmaceutical formulation comprising the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium Phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may comprise at least one excipient in the composition, for example starch, calcium carbonate, sucrose or lactose, gelatin The mixture is prepared.
  • lubricants such as magnesium stearate and talc are also used.
  • Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • the non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used.
  • utopsol macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • the fermentation mixture may be administered to the subject in an amount of 50 to 200 mg / kg, preferably administered to the subject in an amount of 50 to 100 mg / kg. Administration may be administered once a day or may be divided several times.
  • composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
  • the present invention provides a dietary supplement for dietary supplement comprising a mixture of fermented Baekchul, Singok and Baekpok.
  • Formal health functional food of the present invention is characterized in that it comprises the fermentation mixture as an active ingredient showing the efficacy of the prevention and treatment of functional bowel disease.
  • foods to which the fermented products of the herb may be added include, but are not limited to, various foods, powders, granules, tablets, capsules, syrups, beverages, gums, teas, vitamin complexes, and health functional foods. no.
  • the fermentation mixture may be added to food or beverage for the purpose of preventing the functional bowel disease.
  • the amount of the fermented product in the food or beverage may be added to 0.01 to 15% by weight of the total food weight
  • the health beverage composition may be added in a ratio of 0.02 to 5g, preferably 0.3 to 1g based on 100ml. .
  • the health functional beverage composition of the present invention is not particularly limited to other ingredients except the fermented product as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
  • natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents such as, tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
  • the proportion of natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
  • the fermented products of the present invention include various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavoring agents, colorants and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and Salts, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
  • the fermented products of the present invention may contain fruit flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is usually chosen in the range of 0 to about 20 parts by weight per 100 parts by weight of the fermentation of the invention.
  • the non-fermented preparation of each herb was carried out in a similar manner as above, but 2% (v / v) sterile bacterial medium was used in place of the bacterial inoculum.
  • non-fermented products of individual herbals were sterilized (sterilized non-fermented products) to kill bacteria, and the experimental group was used without sterilization.
  • the rodent macrophage cell line, RAW264.7 cells was cultured in DMEM using 10% heat inactivated fetal calf serum, 2 mM L-glutamine, 100 U / ml penicillin, and 100 mcg / ml streptomycin. Incubated at 37 ° C., 5% CO 2 incubator. RAW264.7 cells were dispensed in 24-well plates at 2 ⁇ 10 5 cells / well and then incubated overnight in incubator. Thereafter, 10 mcg / ml of LPS (Pseudomonas aeruginosa 10, Sigma, St.
  • Reduction of reaction was induced by incubating for 3 hours after adding MTT, and medium was carefully removed from each well and DMSO solution was added to completely dissolve formazan crystal byproduct.
  • the absorbance of each well was measured at 570 nm using a microplate reader (Spectramax Plus, Molecular Devices, Sunnyvale, Calif., USA) and cell viability was expressed as OD value.
  • RAW264.7 cells were dispensed into 6-well plates at 8 ⁇ 10 5 cells / well and incubated overnight in incubator. Thereafter, 5% and 10% fermented herbal and non-fermented Chinese herbs were administered or not treated with 10 mcg / ml LPS was incubated for 24 hours. RNA was then extracted from the cells using Trizol® reagent (Invitrogen, Carsbad, CA, USA) and 2 ⁇ g RNA was extracted from the cDNA synthesis kit (SprintTM RT Complete Oligo- (dT) 18, Clontech, Mountain View, CA, USA ) Was reverse transcribed to obtain the first chain cDNA.
  • Trizol® reagent Invitrogen, Carsbad, CA, USA
  • 2 ⁇ g RNA was extracted from the cDNA synthesis kit (SprintTM RT Complete Oligo- (dT) 18, Clontech, Mountain View, CA, USA ) was reverse transcribed to obtain the first chain cDNA.
  • RT-PCR was performed to investigate the effect of the drug on gene expression of iNOS and COX-2 expressed in RAW264.7 cells.
  • RAW264.7 cells were dispensed in 6-well plates at 8 ⁇ 10 5 cells / well and incubated overnight in incubator. Since 5% and 10% fermented herbal or non-fermented Chinese medicine was administered or not treated with 10mcg / ml LPS was incubated for 24 hours.
  • RNA was then extracted from the cells using Trizol® (Invitrogen, Carsbad, CA, USA), reverse transcription of 2mcg RNA, followed by cDNA synthesis kit (SprintTM RT Complete Oligo- (dT) 18, Clontech, Mountain View, CA , USA) to obtain the first-chain cDNA.
  • PCR amplification was performed as follows: COX-2 (40 amplifications after 95 ° C. 10 min incubation step, 95 ° C. 10 sec denaturation, 53 ° C. 10 sec annealing, and 72 ° C. 15 sec extension): GAPDH (55 amplifications) , 94 ° C. 3 min incubation, 94 ° C. 30 sec denaturation, 56 ° C. 30 sec annealing, 72 ° C. 90 sec extension): and PCR parameters for iNOS were identical to the PCR parameters of GAPDH except for 55 times amplification of GAPDH. .
  • iNOS expression was significantly increased after LPS treatment (17,750 fold over control, FIG. 3). Except for the 3-2 experimental group treated with 10%, iNOS expression was significantly suppressed in the fermented or non-fermented herbal groups (p ⁇ 0.05). In the 1-2 experimental group, iNOS expression was more suppressed than in the 1-1 experimental group. In the 1-2 experimental group, 70% of the iNOS expression was suppressed compared to the LPS-induced iNOS expression. Appeared to inhibit. In addition, the 5% treatment group of the 3-2 sample was inhibited by 48% compared to LPS-induced iNOS expression.
  • RAW264.7 cells were dispensed into 6-well plates at 8 ⁇ 10 5 cells / well and incubated overnight in incubator. Thereafter, 5% and 10% fermented herbal and non-fermented Chinese herbs were administered or not treated with 10 mcg / ml LPS was incubated for 24 hours. NO generated from the cell line was measured using colorimetric analysis using Griess reagent (Promega, Madison, WI, USA). 100mcL of culture medium and 100mcL of Griess reagent were mixed, incubated at room temperature for 10 minutes, and the absorbance was measured at 540 nm. The concentration of NO was estimated using the prepared sodium nitrite standard curve.
  • the concentration of NO in the cell culture by LPS was increased by about 16 times than when only the cells were cultured.
  • LPS-induced NO production was significantly inhibited in all fermented and non-fermented herbs (p ⁇ 0.05).
  • the 2-1 experimental group and the 2-3 experimental group were found to most inhibit LPS-induced NO production (FIG. 5).
  • Example 2 In the in vitro experiment of Example 2, the animal experiment was performed by selecting a pair showing the most significant anti-inflammatory effect in each herbal-microbial combination.
  • Ryukonostoke Mesenteroidesu of the new song Bacillus rickenformis in fermented products, leachate and white migraine The fermented products were mixed and used for the experiment.
  • the weight ratio of the mixed new song, Baekchul, Baekdu fermentation was 1: 1: 1.
  • LPS from Escherichia coli 055: B5, Sigma, St. Louis, MO, USA was dissolved in physiological saline and administered in an amount of 1 mg / kg from group 2 to group 6, and group 1 was physiological without LPS. Saline was administered.
  • Administered On the other hand, rats belonging to groups 1 and 6 were administered water and colostrum (Diatech Korea, Seoul, Korea; dose: 1ml / rat using 10% v / v solution) instead of the herbal medicine according to the plan.
  • rats were transferred to their respective metabolic cages, after which no food was consumed except for 12 hours. Twenty four hours after LPS administration, 1 ml aqueous test solution containing 66 mg / ml lactulose and 50 mg / ml mannitol was administered orally to each rat by intubation. In this situation, rats were maintained for 24 hours with only water allowed, followed by urine and blood tests for further analysis.
  • Serum endotoxin levels were measured using a Limulus Ameobocyte Lyasate (LAL) -based kit (Diatech Korea, Seoul, Korea) with an Endo-Check TM analyzer (Diatech Korea, Seoul, Korea). Serum CRP was analyzed by ELISA using rat-specific kits available from BD Biosciences (San Diego, CA, USA) and Thermo Scientific (Rockford, IL, USA). LPS is known to cause endotoxin shock as an extracellular membrane component of Gram-negative bacteria.
  • LAL Limulus Ameobocyte Lyasate
  • TM analyzer Diatech Korea, Seoul, Korea
  • Serum CRP was analyzed by ELISA using rat-specific kits available from BD Biosciences (San Diego, CA, USA) and Thermo Scientific (Rockford, IL, USA).
  • LPS is known to cause endotoxin shock as an extracellular membrane component of Gram-negative bacteria.
  • the endotoxin level was increased by 300 times compared to the control by LPS administration (300 fold over control, Figure 6).
  • LPS-induced endotoxin levels in the group administered LPS and oral colostrum for 5 days after oral administration of mixed fermented herbal medicines 300 mg / kg, 600 mg / kg) for 5 days
  • the group receiving mixed fermented herbal medicine 600 mg / kg
  • the group receiving mixed fermented herbal medicine reduced LPS-induced endotoxin levels by 65%
  • the group receiving mixed fermented herbal medicine 300 mg / kg
  • the colostrum group was reduced by 62%.
  • Mixed non-fermented herbal and sterile fermented herbal groups did not significantly reduce LPS-induced endotoxin levels (p> 0.05) (FIG. 6).
  • CRP was measured using a kit for rats from BD Biosciences (San Diego, CA, USA).
  • Increased gut permeability is also known as leaky gut syndrome, and microbial toxins such as endotoxins, food toxins, etc. may be systemic if the integrity of the intestinal mucosa decreases due to stress, drugs, and alcohol. Entering the bloodstream circulatory system causes systemic inflammation and is known to cause various chronic diseases. Lactulose, a large molecule, should not normally be excreted from urine, while mannitol, a small molecule, is detected in urine. This ratio can be used to measure the integrity and intestinal permeability of the intestinal mucosa.
  • Urine lactulose and mannitol levels were measured using the K-Lactul and K-Manol kit purchased from Megazyme (Bray, Co. Wicklow, Ireland). Assays were performed according to the kit manufacturer's instructions. Urine lactulose and mannitol levels were determined by the percentage recovered through ingestion and calculated the L / M ratio.
  • the mixed fermented Chinese herbal medicine significantly reduced the ratio of lactulose / mannitol (p ⁇ 0.05) depending on the dose
  • the group containing the mixed non-fermented Chinese medicine and the steamed Chinese herbal medicine and the colostrum-treated group did not significantly reduce the ratio of lactose / mannitol (p> 0.05) (FIG. 8).
  • mice Male sprag-dolly (200 ⁇ 20 g, 6 weeks) rats were maintained at controlled temperature and humidity. The rats were kept in a 12-hour day / night cycle environment with randomly ingested food and water, and the experiment was conducted under the prior permission of Dongguk University Animal Ethics Committee in accordance with the Animal Breeding Guidelines of the National Institutes of Health.
  • Neomycin was used to cause diarrhea in rats after taking antibiotics. Animals adapted to this were randomly divided into six groups as follows: (1) control group, (2) neomycin injection group, (3) mixed fermentation herbal and neomycin injection group, (4) mixed non-fermentation Herbal medicine and neomycin injection group, (5) mixed non-fermented sterilized herbal medicine and neomycin injection group, (6) probiotics and neomycin injection group.
  • Neomycin product of La Jolla Calbiochem / EMD Biosciences, Calif.
  • animals in groups 2-6 were injected 800 mg / kg orally once a day for 7 consecutive days. In contrast, only sterile purified water was injected into group 1.
  • Rats in groups 3, 4, and 5 correspond to 600 mg / kg of the fermented mixture, the non-fermented mixture, and the non-fermented autoclaved materials 1-2, 2-3 and 3-1, respectively, for the herbal medicine.
  • the dose was given once a day for 8 consecutive days (from the day before initiating neomycin).
  • animals belonging to Group 1 and Group 6 were treated with water and probiotics (Lactobacillus ashdophyllus, 1.0 ⁇ 10 11 CFU / g, manufactured by CellBiotech, respectively. / Kg). After this diet, blood and feces were collected for further analysis.
  • the feces of each rat collected were weighed and recorded immediately. It was then centrifuged for 2 hours and weighed again in the dry state. The water content of the feces was calculated through the following formula.
  • Moisture Content (%) ((Original Moisture Weight (g)-Dry Weight (g)) / Original Moisture Weight (g)) ⁇ 100
  • the stool began to appear semisolid between days 2 and 3 of neomycin injection. Injection of the herbal medicines or probiotics mentioned above did not change the amount of stool compared to neomycin. However, a marked increase in stool moisture content is evidence of neomycin infusion by indicating the onset of diarrhea symptoms. However, the water content of the stool did not show a clear change according to the herbal medicine and probiotics injection mentioned above (Fig. 9).
  • Endotoxin levels in serum were measured using an Endo-Check TM analyzer (Diatech, South Korea) provided by Diatech using a kit based on the Mycobacterium toxin test (Limulus Ameobocyte Lyasate).
  • Serum CRP and interferon- ⁇ levels were measured by ELISA (enzyme-linked immunosorbent assay) using BD commercial kits from BD Biosciences (San Diego, Calif.) And Thermo Scientific (Rockford, Ill., USA), respectively.
  • ELISA enzyme-linked immunosorbent assay
  • Tissue paraffin processing was as follows: 1 hour in 70% methanol, 1 hour in 90% methanol, 1 hour in 95% methanol, 1 hour in 100% methanol, 1 hour in 100% ethanol, 1 in xylene Time (2 Changes), 30 minutes in paraffin (65 ° C.).
  • paraffin blocks of tissues were prepared. Each block was made using a thin slicer to make 4 ⁇ M tissue sections, soaked in a water bath, and fixed on a clean glass slide. The glass slide was heated in a 65 ° C. oven for 20 minutes to secure the tissue to the glass slide.
  • the glass slides were rehydrated with deparaffins in the following steps: 2 minutes in xylene (3 changes); 100% ethanol (2 changes); 95% ethanol; 80% ethanol; water.
  • Hematoxylin & Eosin (H & E) tissue staining was performed as follows: 2 minutes in hematoxylin; Rinsing with running water; Hydrochloric acid alcohol (76.6% ethanol and 1/300 (v / v) concentrated HCl); water; Ammonia solution (0.084% (w / v) NH 4 OH); Rinsing with running water for 5 minutes; 80% ethanol; Eosin 15 seconds; 95% ethanol (2 changes); 100% ethanol (2 changes).
  • the prepared slides were observed under a microscope and each image was captured.
  • Neomycin-administered rats were observed with cecal tissue lesions such as loss of epithelial integrity, inflammatory symptoms including edema and loss of crypts.
  • cecal tissue profile in the neomycin dose group exposed to fermented non-sterile herbal medicine material was similar to that of the control group, suggesting that the herbal material is protective against neomycin dosed tissue damage and gut inflammation.
  • treatment of non-fermented (sterile / non-sterile) herbal mixtures showed only modest effects on neomycin administered tissue lesions in the cecum of rats.

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Abstract

La présente invention concerne une composition pharmaceutique et un aliment santé fonctionnel pour le traitement du syndrome du côlon irritable, comprenant un mélange d'herbes médicinales fermentées, le mélange contenant Atractylodis Rhizoma Alba fermenté, Massa Medicata Fermentata et Semen Dolichoris fermenté. Plus particulièrement, la présente invention concerne une composition pharmaceutique et un aliment santé fonctionnel pour le traitement du syndrome du côlon irritable, comprenant un mélange d'herbes médicinales fermentées, le mélange contenant Atractylodis Rhizoma Alba, Massa Medicata Fermentata et Semen Dolichoris, qui sont fermentés dans des conditions de fermentation optimales pour rendre maximaux les effets de ceux-ci dans le traitement de troubles gastro-intestinaux fonctionnels.
PCT/KR2011/008643 2010-11-12 2011-11-11 Composition comprenant des herbes médicinales fermentées pour le traitement du syndrome du côlon irritable WO2012064158A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2010-0112814 2010-11-12
KR1020100112814A KR101088004B1 (ko) 2010-11-12 2010-11-12 발효된 한약재를 이용한 정장용 조성물

Publications (2)

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WO2012064158A2 true WO2012064158A2 (fr) 2012-05-18
WO2012064158A3 WO2012064158A3 (fr) 2012-08-23

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112877257A (zh) * 2021-03-18 2021-06-01 昆明理工大学 一株地衣芽孢杆菌及其应用

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014175651A1 (fr) 2013-04-24 2014-10-30 경희대학교 산학협력단 Composition pharmaceutique
CN104042742B (zh) * 2014-06-19 2016-08-24 上海浦东高星生物技术研究所 内服外敷治疗胰腺炎
WO2016060426A1 (fr) * 2014-10-13 2016-04-21 한국 한의학 연구원 Composition contenant un extrait de dolichos lablab l. comme principe actif pour prévenir ou soulager une stéatose hépatique non alcoolique

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100331885B1 (ko) * 1999-03-31 2002-04-09 유민수 숯분말 함유 약제의 제조방법
KR20050050291A (ko) * 2003-11-25 2005-05-31 이광현 한약 치료제
KR100972116B1 (ko) * 2009-10-29 2010-07-23 (주)한국파비스 알엔디 생약 발효물의 제조 방법, 이에 의해 제조된 생약 발효물 및 이를 포함하는 식품
KR20100106788A (ko) * 2009-03-24 2010-10-04 최재훈 정장제용 한약 분말 및 이를 이용한 환

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100331885B1 (ko) * 1999-03-31 2002-04-09 유민수 숯분말 함유 약제의 제조방법
KR20050050291A (ko) * 2003-11-25 2005-05-31 이광현 한약 치료제
KR20100106788A (ko) * 2009-03-24 2010-10-04 최재훈 정장제용 한약 분말 및 이를 이용한 환
KR100972116B1 (ko) * 2009-10-29 2010-07-23 (주)한국파비스 알엔디 생약 발효물의 제조 방법, 이에 의해 제조된 생약 발효물 및 이를 포함하는 식품

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112877257A (zh) * 2021-03-18 2021-06-01 昆明理工大学 一株地衣芽孢杆菌及其应用

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KR101088004B1 (ko) 2011-12-01
WO2012064158A3 (fr) 2012-08-23

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