WO2014042426A1 - Composition comprenant de la saikosaponine a, de la berbérine et de la licoisoflavone b pour la prévention ou le traitement de maladies gastriques - Google Patents

Composition comprenant de la saikosaponine a, de la berbérine et de la licoisoflavone b pour la prévention ou le traitement de maladies gastriques Download PDF

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WO2014042426A1
WO2014042426A1 PCT/KR2013/008214 KR2013008214W WO2014042426A1 WO 2014042426 A1 WO2014042426 A1 WO 2014042426A1 KR 2013008214 W KR2013008214 W KR 2013008214W WO 2014042426 A1 WO2014042426 A1 WO 2014042426A1
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composition
berberine
present
reduced pressure
weight
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Korean (ko)
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박영준
권오억
조예경
김동규
성보현
여말희
최낙현
유재훈
박재홍
김세환
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씨제이제일제당 (주)
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/233—Bupleurum
    • 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)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484—Glycyrrhiza (licorice)
    • 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)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A61K36/718—Coptis (goldthread)
    • 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

Definitions

  • the present invention relates to a composition for the prevention or treatment of gastrointestinal diseases, including psychosaponin A (Saikosaponin A), berberine (Berberine) and lycoisoflavone B (Licoisoflavone B), specifically 15 mg / g to 50 mg / g, berberine 30mg / g to 100mg / g and lysoisoflavone B 0.5mg / g to 5mg / g, a pharmaceutical composition for the prevention or treatment of gastrointestinal diseases, food compositions for the prevention or improvement of gastrointestinal diseases, the composition It relates to a method for preparing and a method for treating gastrointestinal diseases using the composition.
  • gastritis and gastric ulcer are largely caused by pathological excess of attack factors such as gastric acid, pepsin, alcohol and smoking, stress and nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, and gastric mucosal cells from gastric acid attack. It may be classified into a decrease in the secretion of bicarbonate ions, a protective protective factor, a decrease in the production of prostaglandins, and a structural or morphological defect of the gastric mucosa.
  • attack factors such as gastric acid, pepsin, alcohol and smoking, stress and nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, and gastric mucosal cells from gastric acid attack. It may be classified into a decrease in the secretion of bicarbonate ions, a protective protective factor, a decrease in the production of prostaglandins, and a structural or morphological defect of the gastric mucosa.
  • gastric acid secretion In order to treat inflammation and ulcer of stomach and duodenum caused by attack factors, gastric acid secretion, mucous secretion promotion, gastric mucosal epithelial cell regeneration, proliferation of Helicobacter pylori bacteria and anti-inflammatory drugs are required.
  • H2-receptor antagonist the most representative treatment for gastritis and gastric ulcer, is cimetidine, ranitidine, famotidine, roxatidine, Although nizatidine has excellent anti-ulcer effect in clinical practice, relapse occurs frequently after discontinuation of drug administration, and in case of long-term administration, the drug continues to accumulate in the body and stop the medication. Or side effects such as thickening of the stomach wall by dosing have been reported. Therefore, the use of only H2 inhibitors and proton-pump inhibitors to suppress gastric acid secretion for the treatment of gastritis and gastric ulcers cannot suppress the recurrence of lesions that are most problematic in the treatment of peptic ulcers.
  • cimetidine is known to exhibit side effects such as neutropenia and drug interactions. Recently, the use of cimetidine has been shown to avoid its use. Recently, drugs such as ranitidine and famotidine have a significant decrease in efficacy. Was reported.
  • proton pump inhibitors include omeprazole, omeprazole, lansoprazol, and pantoprazole, which inhibit acid secretion in gastric parietal cells in the final stages, and have a strong effect of inhibiting acid secretion. It is known to represent.
  • gastric mucosal diseases such as antacid, Artemisiae argyi Folium extract, and teprenone.
  • drugs such as rebamipide.
  • Gastric mucosal protectors are known to regenerate mucosal tissue to a similar level as normal to compensate for the short-acting gastric acid secretion inhibitors (Folia Pharmacol. Japan, 92: 389, 1988) and are an important part of the treatment of gastritis. .
  • gastric mucosa protective agents have the disadvantage that they are fast-acting, high-dose, and have to be taken for a relatively long time.
  • the present inventors have investigated the active ingredient from the mixed herbal extracts having a gastrointestinal disease treatment effect, and have tried hard to determine the optimal composition ratio with excellent gastrointestinal disease effects but no side effects, and the psychosaponin A, berberine and lysoisoflavones. It was confirmed that the three B components significantly bring about the therapeutic effect of gastrointestinal diseases, and the optimal composition ratio was identified to complete the present invention.
  • One object of the present invention is 15 mg / g to 50 mg / g of Saikosaponin A, 30 mg / g to 100 mg / g of Berberine and 0.5 mg / g to 5 mg / g of Lycoisoflavone B. It includes, to provide a pharmaceutical composition for the prevention or treatment of gastrointestinal diseases.
  • Another object of the present invention is a food for preventing or ameliorating gastrointestinal diseases, including 15 mg / g to 50 mg / g of psychosaponin A, berberine 30 mg / g to 100 mg / g, and 0.5 mg / g to 5 mg / g of lysoisoflavone B. It is to provide a composition.
  • Another object of the present invention is to provide a method for preparing the composition.
  • Another object of the present invention to provide a method for treating gastrointestinal diseases using the composition.
  • Another object of the present invention is the prevention of gastrointestinal diseases of psychosaponin A 15mg / g to 50mg / g, berberine 30mg / g to 100mg / g and lysoisoflavone B 0.5mg / g to 5mg / g, or a composition comprising the same Or to provide a therapeutic use.
  • Still another object of the present invention is to provide a gastrointestinal disease of 15 mg / g to 50 mg / g, berberine 30 mg / g to 100 mg / g and lysoisoflavone B 0.5 mg / g to 5 mg / g, or a composition comprising the same.
  • composition of the present invention comprising psychosaponin A, berberine and lysoisoflavone B is composed of an optimal composition ratio with excellent therapeutic effect and fewer side effects, and can be usefully used for the prevention or treatment of gastrointestinal diseases.
  • 1 is a view showing a process for producing a solvent-specific fraction of the mixed herbal extract of the present invention.
  • Figure 2 shows the schematic diagram of the drug test method for the animal model that caused gastrointestinal diseases with alcohol.
  • Figure 3 is a diagram showing the result of confirming the inhibitory effect of the mixed herbal extract of the present invention and the solvent fractions thereof for the animal model causing the gastrointestinal disease with alcohol.
  • Figure 4 is a diagram showing the results of gastritis inhibition rate when the administration of psychosaponin A, berberine and lysoisoflavone B, which are the active ingredients of the mixed herbal extract of the present invention in an animal model causing gastrointestinal diseases with alcohol, respectively.
  • Figure 5a shows the chemical structure of psychosaponin A, an active ingredient present in the mixed herbal extract of the present invention.
  • Figure 5b shows the chemical structure of berberine which is an active ingredient present in the mixed herbal extract of the present invention.
  • Figure 5c shows the chemical structure of lycoisoflavone B as an active ingredient present in the mixed herbal extract of the present invention.
  • the present invention provides 15 mg / g to 50 mg / g of Saikosaponin A, 30 mg / g to 100 mg / g of Berberine, and 0.5 mg / g to 5 mg / g of Lycoisoflavone B. It provides a pharmaceutical composition for preventing or treating gastrointestinal diseases, comprising g.
  • the composition for preventing or treating gastrointestinal diseases of the present invention comprises psychosaponin A, berberine and lysoisoflavone B as active ingredients, and each of the psychosaponin A, berberine and lysoisoflavone B 15 mg / g to 50 mg / g, If it contains 30mg / g to 100mg / g and 0.5mg / g to 5mg / g, it has an excellent effect in the prevention or treatment of gastrointestinal diseases.
  • Said psychosaponin A, berberine, lycoisoflavone B can be obtained by extracting and separating from various plants including the compound by a commercialized compound or a known method.
  • the term "saikosaponin A” is a compound having the structure of Formula 1 below, (3beta, 4alpha, 16beta) -13,28-Epoxy-16,23-dihydroxyolean-11-en-3 It may also be named -yl-6-deoxy-3-O-beta-D-glucopyranosyl-beta-D-galactopyranoside.
  • the psychosaponin A refers to a compound having an effect in the prevention or treatment of gastrointestinal diseases.
  • berine refers to a quaternary ammonium salt belonging to the protoberberine group of the isoquinoline alkaloid, and has a structure of Formula 2 below.
  • the berberine may mean a compound which is included as an active ingredient in the composition of the present invention and may help in preventing or treating gastrointestinal diseases, but is not limited thereto.
  • Licoisoflavone B (Licoisoflavone B) refers to a compound having a structure of Formula 3 as a flavonoid-based compound.
  • Licoisoflavone B may also be named 5,7-dihydroxy-3- (5-hydroxy-2,2-dimethylchromen-6-yl) chromen-4-one.
  • the composition of the present invention may preferably comprise 15 mg / g to 50 mg / g, 30 mg / g to 100 mg / g and 0.5 mg / g to 5 mg / g, respectively, of the psychosaponin A, berberine and lycoisoflavone B .
  • the present inventors have identified 12 active ingredients from the extract of the mixed herbal medicine having a therapeutic effect of gastrointestinal diseases, 3 of the present invention showing an excellent therapeutic effect on gastrointestinal diseases among the 12 active ingredients
  • the compound of the species was identified (Experimental Example 1-3). In addition, it was confirmed that when the three compounds are included in the composition ratio, it can have an excellent therapeutic effect in gastrointestinal diseases.
  • composition of the present invention comprising the psychosaponin A, berberine and lycoisoflavone B of the present invention may be in the form of a mixed herbal extract.
  • the term "mixed herbal extract” may be in the form of an extract obtained by mixing natural products such as plants, followed by extraction with one or more solvents, or a mixture of extracts obtained by extracting each natural product with a solvent.
  • the type of the solvent for extracting the extract from the mixed herbal extract is not particularly limited as long as it extracts the psychosaponin a, berberine and lysoisoflavone B, preferably water, alcohol having 1 to 6 carbon atoms and their Can be extracted with one or more solvents selected from the group consisting of mixed solvents, but is not limited thereto.
  • 15 mg / g to 50 mg / g, 30 mg / g to 100 mg / g and 0.5 mg / g to 5 mg / g, respectively, of psychosaponin A, berberine and lysoisoflavone B in the form of a mixed herbal extract A composition was prepared.
  • composition of the present invention comprising the psychosaponin A, berberine and lysoisoflavone B can be usefully used for the prevention or treatment of gastrointestinal diseases.
  • the term "gastrointestinal disease” is a generic term for diseases of the gastrointestinal tract, the gastrointestinal disease is not particularly limited if the gastrointestinal diseases that can be treated by the composition of the present invention, for example, gastritis, gastric ulcer, Duodenal ulcer, Solinger-Elison syndrome, reflux esophagitis, postoperative ulcer, erosion of gastric mucosa, bleeding of gastric mucosa, redness of gastric mucosa or edema of gastric mucosa, but is not limited thereto.
  • the gastrointestinal disease may be characterized in that the mucous membrane damage of the stomach or duodenum caused by alcohol, smoking, stress, drugs, or a combination thereof, but is not limited thereto.
  • prevention refers to any action that inhibits or delays the onset of gastrointestinal disease by administration of the composition, and “treatment” improves or advantageously changes the symptoms caused by gastrointestinal disease by administration of the composition. It means every act to do
  • the pharmaceutical composition comprising the psychosaponin A, berberine and lycoisoflavone B may further include appropriate carriers, excipients or diluents commonly used in the manufacture of pharmaceutical compositions, and may also include tablets, pills, powders, Granules, capsules, suspensions, solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories, and may have any one oral or parenteral formulation. There may be various formulations of the spheres.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
  • Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose ( Lactose), gelatin, etc. are mixed.
  • lubricants such as magnesium stearate, talc and the like are also used.
  • Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be included.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, etc. may be used.
  • Whitepsol, macrogol, Tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • composition of the present invention may be administered in a pharmaceutically effective amount.
  • the term "administration” means introducing a pharmaceutical composition of the present invention to an individual in any suitable manner, and the route of administration of the composition is as long as possible to reach the desired tissue or through various routes of oral oral use. It may be administered, and specifically, in a conventional manner via the oral, rectal, topical, intravenous, intraperitoneal, intramuscular, intraarterial, transdermal, nasal, inhaled or intradermal routes.
  • the term "pharmaceutically effective amount” refers to an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level refers to the subject's type and severity, age, sex, and gastrointestinal disease. Can be determined according to the type of drug, activity of the drug, sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including concurrently used drugs, and other factors well known in the medical field.
  • the compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. And single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, and can be easily determined by those skilled in the art.
  • composition can be administered to a variety of mammals, such as 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 extracts of Examples 1 to 4 comprising 15 mg / g to 50 mg / g of psychosaponin A, 30 mg / g to 100 mg / g of berberine, and 0.5 mg / g to 5 mg / g of lysoisoflavone B have excellent gastric protective effect.
  • Comparative Examples 1 to 3 containing 15 mg / g or less of psychosaponin and 30 mg / g or less of berberine had a drug efficacy of 23, 13 and -3%, respectively, about 40 to 56%. Compared with Examples 1 to 4 showing the efficacy of% showed a significantly lower efficacy (Table 7).
  • Table 7 Such results indicate that the composition of the present invention comprising psychosaponin A 15 mg / g to 50 mg / g, berberine 30 mg / g to 100 mg / g, and lysoisoflavone B 0.5 mg / g to 5 mg / g efficiently contains gastritis. It can be used to treat various gastrointestinal diseases. Therefore, the composition of the present invention can be effectively used for the prevention or treatment of various gastrointestinal diseases.
  • the present invention provides a method for treating gastrointestinal disease, comprising administering the pharmaceutical composition to a suspected gastrointestinal disorder.
  • the pharmaceutical composition and gastrointestinal diseases are as described above.
  • the method of treatment of the present invention comprises administering the pharmaceutical composition in a pharmaceutically effective amount into a suspected gastrointestinal disorder.
  • the subject means an entire mammal including a dog, cow, horse, rabbit, mouse, rat, chicken or human, but the mammal of the present invention is not limited to the above examples.
  • the pharmaceutical composition may be administered orally, orally, subcutaneously, intraperitoneally, pulmonary, and intranasally, and may be administered by a suitable method including topical administration if necessary for local treatment.
  • Non-oral infusions include intramuscular, intravenous, intraarterial, intraperitoneal or subcutaneous administration.
  • Preferred dosages of the pharmaceutical compositions of the present invention vary depending on the condition and weight of the individual, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art.
  • the present invention provides for the prevention or amelioration of gastrointestinal diseases, including 15 mg / g to 50 mg / g of psychosaponin A, 30 mg / g to 100 mg / g of berberine and 0.5 mg / g to 5 mg / g of lysoisoflavone B. It provides a food composition for.
  • Said psychosaponin A, berberine, lycoisoflavone B and gastrointestinal diseases are as described above. More specifically, the psychosaponin A, berberine and lysoisoflavone B of the present invention comprises 15 mg / g to 50 mg / g, 30 mg / g to 100 mg / g and 0.5 mg / g to 5 mg / g, respectively. Or it may be added to the food composition for the purpose of improvement.
  • the compound When the psychosaponin A, berberine and lysoisoflavone B are used as food additives, the compound may be added as it is or used with other foods or ingredients, and may be appropriately used according to a conventional method.
  • Examples of foods to which the compounds may be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, dairy products including other noodles, gums, ice creams, various soups, drinks, teas, drinks, Alcoholic beverages and vitamin complexes, and the like, and may include all foods in a conventional sense, and include foods used as feed for animals.
  • the food composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols. And carbonation agents used in carbonated beverages. Others may contain pulp for the production of natural fruit juices, fruit juice drinks and vegetable drinks.
  • the food may also be prepared in the form of tablets, granules, powders, capsules, liquid solutions and pills according to known production methods. There is no particular limitation on other components except for including the compound according to the present invention as an active ingredient, and various conventional flavoring agents or natural carbohydrates may be included as additional ingredients.
  • the food composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols. And carbonation agents used in carbonated beverages. Others may contain pulp for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components can be used independently or in combination.
  • the present invention provides a method of preparing the composition.
  • the method preferably comprises (a) 10 to 30 parts by weight of Coptidis Rhizoma and 10 to 30 parts by weight of licorice ( Glycyrrhizae Radix ) based on 100 parts by weight of Bupleuri Radix in water, 1 carbon. Extracting with at least one solvent selected from the group consisting of alcohols from 6 to 6 and mixed solvents thereof; (b) concentration of the filtrate obtained in the extraction step under reduced pressure; And (c) suspending by adding alcohol to the reduced pressure concentrate of step (b), and then preparing a soft-core extract by concentrating the secondary under reduced pressure, but is not limited thereto.
  • the solvent in the step (a) is preferably used 3 to 10 times the solvent compared to the mixed herbal weight, but is not limited thereto. In one embodiment of the present invention, about 5 times the weight of the mixed herbal weight ethanol was used as the solvent.
  • the method is preferably extracted for 20 to 100 hours at an extraction temperature of 40 to 50 °C, and concentrated under reduced pressure at a temperature of 60 °C or less, but is not limited thereto.
  • the vacuum concentration may be preferably performed at a temperature of 40 ° C. to 60 ° C., but is not limited thereto.
  • Extracts prepared by the above method of a mixed herbal medicine containing 10 to 30 parts by weight of Cooptidis Rhizoma and 10 to 30 parts by weight of Glycyrrhizae Radix based on 100 parts by weight of Buleuri Radix were prepared by the following methods: psychosaponin A, berberine and lyco It was confirmed that isoflavone B contained 15 to 50 mg / g, 30 to 100 mg / g, and 0.5 mg / g to 5 mg / g, respectively, and it was confirmed that it had a therapeutic effect in gastrointestinal diseases (Tables 5 and 6).
  • the first reduced pressure concentration of step (b) of the method may be 10 to 20% by volume by drying under reduced pressure at a temperature of 500 to 700mmHg and 60 °C or less, but is not limited thereto.
  • the vacuum drying may be preferably performed at a temperature of 40 ° C. to 60 ° C., but is not limited thereto.
  • the second vacuum concentration in step (c) may be dried under reduced pressure in a soft-extract state of preferably 25 to 35% by weight, but is not limited thereto.
  • the extract of the mixed herbal medicine prepared in step (a) to (c) may be further fractionated using one or more solvents selected from the group consisting of n-hexane, ethyl acetate and saturated n-butanol.
  • the fractions of the extract include psychosaponin A, berberine and lycoisoflavones B, in particular, butanol and ethyl acetate fractions were confirmed to contain a high proportion of the components (Table 4). It was also confirmed that butanol and ethyl acetate fractions containing the above components had a high effect in gastrointestinal disease animal models (FIG. 3).
  • the composition prepared by the above method of the present invention comprises psychosaponin A, berberine and lysoisoflavone B, each containing 15 to 50 mg / g, 30 to 100 mg / g, and 0.5 mg / g to 5 mg / g, respectively. It can be used in the form of a pharmaceutical composition or food composition.
  • the present invention is a gastrointestinal disease of 15 mg / g to 50 mg / g, berberine 30 mg / g to 100 mg / g and lysoisoflavone B 0.5 mg / g to 5 mg / g, or a composition comprising the same To provide a prophylactic or therapeutic use.
  • the present invention is a gastrointestinal disease of 15 mg / g to 50 mg / g, berberine 30 mg / g to 100 mg / g and lysoisoflavone B 0.5 mg / g to 5 mg / g, or a composition comprising the same
  • a gastrointestinal disease 15 mg / g to 50 mg / g, berberine 30 mg / g to 100 mg / g and lysoisoflavone B 0.5 mg / g to 5 mg / g, or a composition comprising the same
  • Shiho 373kg, rhubarb 84kg and licorice 84kg were extracted once with 2,660L of 80% ethanol at 45 ° C. for 91 hours to obtain 2,400 L of extract, which was filtered through a filter press of 1 ⁇ m size and then at 60 ° C. or lower, at 500 mmHg.
  • the first step was concentrated under reduced pressure to obtain a 150 kg concentrate.
  • the water of the first concentrate was removed, and then the concentrate was dissolved in ethanol and concentrated under reduced pressure again to obtain 40.6 kg of the final soft extract.
  • Shiho 373kg, rhubarb 84kg and licorice 84kg were extracted once with 2,660L of 80% ethanol for 22 hours at 45 ° C. to obtain 2,000 kg of the extract, which was filtered through a filter press of 1 ⁇ m in size and then at 60 ° C. or below at 550 mmHg.
  • the first step was concentrated under reduced pressure to obtain 119 kg concentrate.
  • the water of the first concentrate was removed and the concentrate was dissolved in ethanol, and then concentrated under reduced pressure again to obtain a final soft extract 32.8 kg.
  • Shiho 650kg, rhubarb 150kg and licorice 150kg were extracted once with 48% of 4,750L of 80% ethanol at 45 ° C. for 48 hours, and the extract filtrate was filtered under a filter press of 1 ⁇ m and concentrated under reduced pressure at 60 ° C. or lower to obtain 68 kg concentrate. . After removing the water from the primary concentrate, the concentrate was dissolved in ethanol, and then concentrated under reduced pressure again to obtain 74 kg of lead extract.
  • Pre-gelatinized starch, croscarmellose sodium and magnesium stearate are added to the granules in a homogeneous manner, mixed homogeneously, and a rectangular tablet is prepared using a continuous tableting machine (Erweka, Germany) so that the total weight is 275 mg. Film coating in an appropriately sized film-coating apparatus.
  • Alcohol-induced acute gastritis animal model was used to confirm gastric mucosal protection, and the experiment was performed as follows.
  • mice Seven week old male rats were purchased and after one week of acclimatization, eight week old male rats (270g to 280g) were used for the experiment. Each group was divided into 8 groups, and each animal was orally administered with each extract at a dose of 48 hours under fast free water ingestion, and after 1 hour, rat ethanol (absolute ethanol) was weighed in rats. After oral administration of 5 mL / kg, gastric mucosal injury was induced for 1 hour. After 1 hour of anhydrous ethanol administration, rats were distal to the cervical spine and lethal, followed by extraction. The extracted stomach was infused with 2% formalin solution and fixed on ice for 1 hour. Then, the stomach was cut along the Taiwan section, spread out on a glass plate, and photographed. Gastric lesion area was measured using a photographic image to compare the degree of gastric mucosal injury to the group administered only with absolute ethanol alone.
  • the present inventors confirmed the gastric mucosa protective effect of Shiho, rhubarb and licorice mixed herbal extract obtained in Example 4 and the organic solvent fraction obtained in Example 5.
  • the fraction of Example 4 exhibited a value of 60.5%, resulting in a reduction of gastric mucosal damage, in particular the saturated n-butanol fraction and ethyl acetate.
  • the fraction treated groups showed lesion areas of 55.5 and 54.6%, respectively, resulting in a significant reduction in gastric mucosal damage induced by ethanol.
  • the hexane fraction showed a lesion area of 87.3%, which did not significantly reduce gastric mucosal damage to ethanol (FIG. 3).
  • Said 13 substances were administered to the gastritis animal model of Experimental Example 1-1 at 10 mg / kg, respectively, and 3 substances psychosaponin A (Saikosaponin A) exhibiting gastric protective effect of 50% or more as shown in Table 3 below.
  • 3 substances psychosaponin A (Saikosaponin A) exhibiting gastric protective effect of 50% or more as shown in Table 3 below.
  • Berberine and Lycoisoflavone B were selected as key active ingredients.
  • Example 5 As a result of performing the HPLC analysis, it was confirmed that even in the purification of Example 5, the content of psychosaponin A (Saikosaponin A), berberine (Berberine), and lycoisoflavone B (Licoisoflavone B) was present in a predetermined amount or more. As a result of evaluating the contents present in the active ingredient layer, it was found that most of these components were transferred to the ethyl acetate fraction and the butanol fraction. In addition, the content ratio present in the active fraction layer relative to the total extract was as shown in Table 4.
  • Examples 1 to 4 showed gastritis inhibition of 56.0, 38.0, 43.0 and 39.5%, respectively.
  • Example 1 27.54 mg / g 65.44 mg / g 1.48mg / g 56.0
  • Example 2 21.8mg / g 45.69 mg / g 0.89 mg / g 38.0
  • Example 3 21.9 mg / g 43.32mg / g 0.68 mg / g 43.0
  • Example 4 28mg / g 60.39 mg / g 1.31 mg / g 39.5
  • Table 6 shows the amount present in tablet 1T, the amount of soft lead in tablet 1T is 150 mg, and the amount shown in Table 6 in mg / g is 28 mg / g for psychosaponin A, 60 mg / g for berberine, Lycoisoflavones B are converted to 1.2 mg / g.

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Abstract

La présente invention concerne une composition comprenant de la saikosaponine A, de la berbérine et de la licoisoflavone B, destinée à prévenir ou à traiter des maladies gastriques, et concerne plus particulièrement une composition pharmaceutique destinée à prévenir ou à traiter des maladies gastriques, une composition alimentaire destinée à prévenir ou à traiter des maladies gastriques, une méthode de préparation desdites compositions, et une méthode destinée à traiter des maladies gastriques à l'aide desdites compositions, la composition pharmaceutique et la composition alimentaire présentant une teneur en saikosaponine A située dans la plage allant de 15 mg/g à 50 mg/g, une teneur en berbérine située dans la plage allant de 30 mg/g à 100 mg/g et une teneur en licoisoflavone B située dans la plage allant de 0,5 mg/g à 5 mg/g.
PCT/KR2013/008214 2012-09-11 2013-09-11 Composition comprenant de la saikosaponine a, de la berbérine et de la licoisoflavone b pour la prévention ou le traitement de maladies gastriques WO2014042426A1 (fr)

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KR101647506B1 (ko) * 2016-03-16 2016-08-10 김현민 황련 추출물의 독성 저감화 방법, 이로부터 제조된 독성이 저감화된 생약추출물, 및 그 생약추출물을 함유하는 호흡기 질환 예방 또는 치료용 조성물
KR101888845B1 (ko) 2016-06-21 2018-08-17 지엘팜텍주식회사 애엽 추출물
CN117503947B (zh) * 2024-01-04 2024-03-08 唐宁医药科技(济南)有限公司 一种用于修复和保护sh-sy5y细胞损伤的药物及其制备方法

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