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WO2008083561A1 - Composition pharmaceutique orale de glycyrrhizine ou ses sels et son procédé de préparation - Google Patents

Composition pharmaceutique orale de glycyrrhizine ou ses sels et son procédé de préparation Download PDF

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Publication number
WO2008083561A1
WO2008083561A1 PCT/CN2007/003950 CN2007003950W WO2008083561A1 WO 2008083561 A1 WO2008083561 A1 WO 2008083561A1 CN 2007003950 W CN2007003950 W CN 2007003950W WO 2008083561 A1 WO2008083561 A1 WO 2008083561A1
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WO
WIPO (PCT)
Prior art keywords
salt
glycyrrhizic acid
enteric
composition
pellets
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2007/003950
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English (en)
Chinese (zh)
Inventor
Ping Dong
Cheng Zuo
Chunguang Xia
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chia Tai Tianqing Pharmaceutical Group Co Ltd
Original Assignee
Jiangsu Chia Tai Tianqing Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jiangsu Chia Tai Tianqing Pharmaceutical Co Ltd filed Critical Jiangsu Chia Tai Tianqing Pharmaceutical Co Ltd
Priority to CN200780048410.1A priority Critical patent/CN101600439B/zh
Publication of WO2008083561A1 publication Critical patent/WO2008083561A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4891—Coated capsules; Multilayered drug free capsule shells
    • 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
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses

Definitions

  • the present invention relates to an oral pharmaceutical composition of glycyrrhizic acid or a salt thereof and a process for the preparation thereof, specifically, an oral enteric pharmaceutical composition containing glycyrrhizic acid or a salt thereof.
  • Glycyrrhiza is a commonly used medicinal plant whose main active ingredient is a glycyrrhizic acid shield, namely glycyrrhizic acid in the 18- ⁇ configuration and glycyrrhizic acid (also known as isoglycyrrhizic acid) in the 18- ⁇ configuration.
  • Pharmacological, biochemical and structure-activity relationship analysis studies have shown that glycyrrhizic acid or its salt has a strong anti-inflammatory, protective effect on liver cells and an improvement in liver function (see Chinese Patent Publication No. CN1381462A and CN1569005A).
  • glycyrrhizic acid or its salt have the problem of low oral bioavailability, because glycyrrhizic acid or its salt is a highly polar, hydrophilic macromolecular substance, which is poorly absorbed in the gastrointestinal tract, and Glycyrrhizic acid or a salt thereof easily forms a molecular polymer in an acidic environment in the stomach. Therefore, it is urgent to develop a glycyrrhizic oral preparation having high bioavailability.
  • the Chinese Patent Application Publication No. WO1569005A discloses an enteric preparation of glycyrrhizic acid and a salt thereof, and the use of an enteric preparation forms a problem in which a glycyrrhizic acid preparation forms a polymer in the stomach.
  • Cispheral Patent Application Publication No. CN1594332A discloses a phospholipid complex of glycyrrhizic acid and a salt thereof, which combines glycyrrhizic acid with a phospholipid to promote in vivo absorption of glycyrrhizic acid.
  • the drug is concentrated in the small intestine.
  • the phospholipid complex of glycyrrhizic acid or its salt can easily form a gel-like mass in the intestinal fluid environment, affecting the full contact of the drug and the small intestinal wall and ultimately affecting the absorption of the drug.
  • the absorption of glycyrrhizic acid in the small intestine may be related to the carrier, there is saturation, when the drug is released intensively The resulting absorbance will be much lower than the absorbance obtained when the drug is uniformly dispersed.
  • the oral enteric pharmaceutical composition of glycyrrhizic acid or a salt thereof of the present invention solves the above-mentioned defects in the licorice preparation by an appropriate preparation form, and solves the problem of low bioavailability.
  • One aspect of the present invention is to provide an oral enteric pharmaceutical composition of glycyrrhizic acid or a salt thereof.
  • the oral enteric pharmaceutical composition of the glycyrrhizic acid or a salt thereof according to the present invention is a dose-dispersed preparation comprising a plurality of units, each unit comprising a content and an enteric coating composition encapsulating the content,
  • the contents may be in the form of pellets or granules, preferably pellets, and the contents contain glycyrrhizic acid or a salt thereof, which is isolated from the environment by an enteric coating layer.
  • the orally enteric pharmaceutical composition of glycyrrhizic acid or a salt thereof according to the present invention wherein the weight ratio of the content to the enteric coating is 1: 0.15 to 0.45, preferably 1:0.2 to 0.4, more preferably 1:0.25 to 0.35.
  • Oral enteric pharmaceutical composition of glycyrrhizic acid or a salt thereof according to the present invention wherein the maximum diameter of each unit is not more than 2 mm, preferably 0.5 nm! Between 1.5 mm, more preferably between 0.7 mm and 1.2 mm.
  • a plurality of the units constitute the composition of the present invention, each composition containing 1-500 mg of glycyrrhizic acid or a salt thereof, preferably 25-150 mg of glycyrrhizic acid or a salt thereof, more preferably 40-100 mg of glycyrrhizic acid or a salt thereof .
  • the enteric coating material of the present invention is selected from conventional enteric coating materials suitable for coating pills or granules, such as: cellulose acetate phthalate, shellac, acrylic or hypromellose. As the phthalate ester or the like, an acrylic resin enteric coating material is preferred.
  • the content of the present invention contains glycyrrhizic acid or a salt thereof and at least one intestinal absorption enhancer, and the intestinal absorption enhancer refers to enhancing intestinal permeability of the drug, promoting drug absorption, and improving bioavailability of the drug. substance.
  • the intestinal absorption enhancer used in the present invention may be any intestinal absorption enhancer which is pharmaceutically suitable for oral use, including but not limited to: phospholipids; chitosan and its derivatives, polyvinylpyrrolidone, carbomer, etc. Affinity polymer; amino acid derivative; natural bile, deoxycholic acid, sodium deoxycholate, sodium glycocholate, sodium taurocholate and other cholic acid shields and salts thereof; sodium octanoate, strontium Fatty acids and salts thereof such as sodium, sodium laurate and sodium oleate; surfactants such as sodium lauryl sulfate, polyoxyethylene ethers, esters, sorbitan esters and the like.
  • the preferred intestinal absorption enhancer is Phospholipids.
  • the content of the present invention contains a phospholipid complex of glycyrrhizic acid or a salt thereof prepared from glycyrrhizic acid or a salt thereof and an anthraquinone substance.
  • the phospholipid complex of glycyrrhizic acid or a salt thereof is formed by complexing glycyrrhizic acid or a salt thereof and a phospholipid substance, wherein a weight ratio of glycyrrhizic acid or a salt thereof to a phospholipid substance is 1:0.3-2, and a preferred weight ratio It is 1:0.5 ⁇ 1.5.
  • the glycyrrhizic acid or a salt thereof according to the present invention may be 18- ⁇ glycyrrhizic acid or a salt thereof, or may be 18- ⁇ glycyrrhizic acid or a salt thereof, preferably 18- ⁇ glycyrrhizic acid or a salt thereof.
  • the glycyrrhizinate of the present invention includes, but is not limited to, an ammonium salt, a magnesium salt, a sodium salt, a potassium salt, a zinc salt, a calcium salt, a barium salt or a silver salt of glycyrrhizic acid, preferably a magnesium salt and an ammonium salt of glycyrrhizic acid. Most preferred is the magnesium salt of glycyrrhizic acid.
  • the phospholipid substance according to the present invention is a lecithin-based shield, a cephalin-based substance, an inositol phospholipid substance or a phosphatidic acid substance, preferably a lecithin-based substance, more preferably a polyene phosphatidylcholine or a phosphatidylcholine. .
  • the contents may further contain other intestinal absorption enhancers and other conventional excipients.
  • the excipient may be a blank pellet core, a filler (diluent), a wetting agent, a binder, a disintegrant, a lubricant, a glidant, and the like.
  • the blank pellet core is a carrier of the pellets, but the present invention has no special requirement for the selected blank pellet core, as long as it does not react with the active ingredient and other auxiliary materials, does not affect the detection of the active component, and has a round shape and is easy to carry out the pellet.
  • the core medicine can be used.
  • the filler is an auxiliary material required for preparing the drug-containing pellets or granules
  • the filler selected in the invention may be selected from the group consisting of starch, pregelatinized starch, dextrin, microcrystalline cellulose, lactose, sucrose, One or more of glucose, mannitol, sorbitol, xylitol, dextran, fructose, calcium sulfate, calcium hydrogen phosphate, calcium phosphate, carbonic acid, and micronized silica gel.
  • Wetting agents suitable for use in the present invention may be distilled water, absolute ethanol or aqueous solutions of various concentrations.
  • Suitable binders for use in the present invention are selected from the group consisting of mercaptocellulose, ethylcellulose, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, hydroxypropylcellulose, sucrose, sucrose One or more of starch syrup, gelatin, and gum arabic.
  • the disintegrant is a substance or a mixture of the substances which facilitates the disintegration and dissolution of the composition in the intestinal tract in the present invention, and the disintegrant is selected from the group consisting of starch, sodium carboxymethyl starch, and croscarmylmethyl.
  • the disintegrant is selected from the group consisting of starch, sodium carboxymethyl starch, and croscarmylmethyl.
  • the lubricant and glidant are selected from the group consisting of talc, magnesium stearate, calcium stearate, zinc stearate, liquid paraffin, polyethylene glycol, magnesium lauryl sulfate, sodium lauryl sulfate.
  • additives such as coloring agents, fragrances, flavoring agents, and antioxidants may be used as necessary.
  • the orally enteric pharmaceutical composition of the glycyrrhizic acid or a salt thereof according to the present invention may be formulated into a form suitable for oral administration such as capsules, tablets and granules and the like.
  • the capsule may be in the form of any capsule other than the intestinal sol shell; the tablet may or may not be coated, and the coating layer may be in any coating form other than the enteric coating.
  • Each capsule or tablet contains 25-150 mg, preferably 40-100 mg of glycyrrhizic acid or a salt thereof, and the orally enteric pharmaceutical composition of the glycyrrhizic acid of the present invention or a salt thereof is preferably administered after being filled into a common capsule.
  • Another aspect of the present invention is a method for producing an oral enteric pharmaceutical composition which provides glycyrrhizic acid or a salt thereof.
  • the orally enteric pharmaceutical composition of glycyrrhizic acid or a salt thereof is obtained by the following steps:
  • glycyrrhizic acid or a salt thereof and an intestinal absorption enhancer and/or other excipients are prepared into pellets or granules in a conventional manner; and then the obtained pellets or granules are enteric coated with an enteric coating material to obtain Composition unit; a plurality of the composition units are mixed to constitute the composition.
  • glycyrrhizic acid or a salt thereof and a phospholipid substance are compounded to obtain a phospholipid complex of glycyrrhizic acid or a salt thereof; and then the phospholipid complex of glycyrrhizic acid or a salt thereof is combined with or
  • the other excipients are prepared into pellets or granules; the obtained pellets or granules are then enteric coated with an enteric coating material to obtain a composition unit; finally, a plurality of the composition units are mixed to constitute the invention. combination.
  • the weight ratio of the obtained pellets or granules to the enteric coating material is 1:0.15-1:0.45, preferably 1:0.2-1:0.4, more preferably 1:0.25. -1: 0.35.
  • glycyrrhizic acid or a salt thereof and a phospholipid substance are compounded at a weight ratio of 1:0.3 to 2, preferably a weight ratio of 1:0.5-1.5.
  • the process for preparing the drug-containing pellets may employ an extrusion spheronization process, a pan-pill process, and a pellet core process.
  • the drug-containing pellets are prepared by a pellet core drug process.
  • Another aspect of the present invention is to provide a method of treating hepatitis comprising the licorice of the present invention
  • An oral enteric pharmaceutical composition of an acid or a salt thereof is administered to an individual in need of such treatment.
  • Another aspect of the present invention is to provide a method for improving abnormal liver function in an individual comprising administering to the individual an oral enteric pharmaceutical composition of glycyrrhizic acid or a salt thereof according to the present invention.
  • a further aspect of the invention is the use of an oral enteric drug composition for providing glycyrrhizic acid or a salt thereof according to the invention for the preparation of a medicament for the treatment of hepatitis.
  • a further aspect of the present invention provides a use of an oral enteric drug composition for providing glycyrrhizic acid or a salt thereof according to the present invention for the preparation of a medicament for improving liver function abnormality.
  • the glycyrrhizic acid or a salt thereof is administered simultaneously with the intestinal absorption enhancer, thereby improving the bioavailability of the drug, especially by combining glycyrrhizic acid or a salt thereof with the phospholipid substance.
  • the phospholipid complex prepared as glycyrrhizic acid or a salt thereof improves the hydrophilicity and lipophilicity of glycyrrhizic acid or a salt thereof, thereby promoting the absorption of the active ingredient in the intestinal tract.
  • the medicament is made into a dose-dispersible enteric preparation, each preparation consists of a plurality of units, and the quality of the unit, such as the particle size, the weight ratio of the contents and the enteric coating, is controlled to further improve the drug. bioavailability.
  • the particle size of the enteric pellets By controlling the particle size of the enteric pellets, the drug is uniformly dispersed into the intestinal tract, and the contact area between the drug and the intestine is enlarged, so that the drug is uniformly dispersed and fully contacted with the small intestine wall, and it is difficult to form a gel-like mass forming adhesion. , thereby promoting the absorption of drugs.
  • the enteric coating of the enteric pellets By effectively controlling the weight ratio of the contents to the enteric coating, it is possible to prevent the enteric coating of the enteric pellets from rupturing under the strong pressure of gastric peristalsis, thereby causing the glycyrrhizic acid or its salt to form a polymer in a gastric acid environment. It is also possible to ensure that the drug in the form of enteric pellets is rapidly released completely in the intestinal tract. Alternatively, the rate of drug release in the intestinal tract can be controlled by controlling the weight ratio of the contents to the enteric coating.
  • Glycyrrhizic acid or its salt is absorbed reliably, smoothly and effectively in the intestine, which not only improves the bioavailability of glycyrrhizic acid or its salt, but also improves the efficacy of oral preparation of glycyrrhizic acid or its salt, and reduces its adverse reactions.
  • the medication is safe and convenient.
  • Fig. 1 is a graph showing the in vitro release rate of 18- ⁇ -Glycyrrhizic acid enteric pellets prepared in Example 1. detailed description
  • Pill prescription
  • the component obtained by the item 11 is dispersed and dispersed in distilled distilled water and added to the prescription amount of polyethylene polyethylene. Alcohol 66000000 and the slip talc powder powder, stir and mix evenly;
  • the Ou Baba will be added to the appropriate amount of water, and formulated into a coating liquid
  • the liquid of the coating and clothing prepared by the item 44 is slowly sprayed into the straight diameter diameter. 00..55mmmm ⁇ ..22mmmm intestinal enteric micro-pill pills;;
  • Group component name 18- ⁇ -diammonium glycyrrhizinate 50 (based on C 42 H 68 N 2 0 16 ) polyene phosphatidylcholine 25
  • microcrystalline cellulose, low-substituted hydroxypropylcellulose, and talc powder are uniformly mixed, and soft material is made of 15% alcohol aqueous solution, and 0.6 mm is used.
  • soft material is made of 15% alcohol aqueous solution, and 0.6 mm is used.
  • the screen is extruded and rolled into a drug-containing pellet;
  • the drug-containing pellets are dried in a fluidized bed at 40 ° C;
  • the coating liquid prepared in item 5 is slowly sprayed into the intestines: pill having a diameter of 0.5 mm to 1.2 mm;
  • Pill prescription
  • enteric pellets having a diameter of 0.5 mm to 1.5 mm were prepared by using the various components described in the above prescription using the production process described in Preparation Example 2, and then the drug content of the enteric pellets was measured and then poured. Packed with plastic bottles.
  • Preparation Example 4 18- ⁇ zinc glycyrrhizinate enteric pellets capsule
  • Pill prescription
  • Component name 1000 capsules (g) 18- ⁇ zinc glycyrrhizinate 50 (calculated as C 42 H 6() Zn0 16 )
  • Pharmaceutical blank pellet core (sucrose type) 110
  • Pill prescription
  • Microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and talc powder are pulverized and sieved through an 80-mesh sieve;
  • the drug-containing pellets are dried in a fluidized bed at 40 ° C;
  • Pill prescription
  • Pill prescription
  • Preparation Example 9 18- ⁇ -diammonium glycyrrhizinate enteric-coated pellets
  • the granules are dried in a fluidized bed at 50 ° C, sieved with a 20 mesh sieve, and passed through a 40 mesh sieve to remove fine particles and placed in a fluidized bed;
  • the coating liquid prepared in item 3 is slowly sprayed into an enteric granule having a diameter of 0.5 mm to 2.0 mm;
  • Preparation Example 12 In addition to the use of carbomer instead of sodium lauryl sulfate as an intestinal absorption enhancer, the production process described in Preparation Example 12 was used, and the diameter of 0.5 mn was prepared using the various components of the prescription described in the above prescription! ⁇ 2.0mm enteric granules, then the enteric granules are filled into common capsules.
  • Pill prescription
  • Formulation of enteric coating solution Component name per 1000g pellets (g) Eudragit (L30D-55) 1000
  • Preparation Example 1 In addition to the use of deoxycholic acid instead of soy lecithin as an intestinal absorption enhancer, the production process described in Preparation Example 1 was used to prepare a diameter of 0.5 mm to 1.2 using the various components of the prescribed amount described in the above prescription. Mm enteric pellets, then enter the enteric ⁇ : pill into the capsule. Animal Experimental Example: Oral relative bioavailability of 18-alpha magnesium glycyrrhizinate enteric pellets in Beagle dogs
  • the enteric drug composition of glycyrrhizic acid or a salt thereof according to the present invention is exemplified by an animal experiment as a pharmaceutical preparation for treating chronic viral hepatitis with a low toxic side effect and improving liver function abnormality.
  • the enteric pharmaceutical composition of glycyrrhizic acid or a salt thereof of the present invention has a markedly improved bioavailability as compared with the conventional intestinal sol of glycyrrhizic acid or a salt thereof.
  • Test drug 18- ⁇ magnesium glycyrrhizinate (referred to as magnesium isoglycyrrhizinate) enteric pellets capsule, each capsule contains 50 mg of magnesium isoglycyrrhizinate, and prepared according to the method in Example 1 of the present application; 18- ⁇ magnesium glycyrrhizinate common intestinal sol (in which 18- ⁇ -glycyrrhizinate and phosphatidylcholine are prepared into a complex at a weight ratio of 1:1, microcrystalline cellulose and talc are added as an auxiliary material, and the intestinal sol is used to prepare a common intestine according to a conventional method. Sol ⁇ ) contains 50 mg of magnesium isoglycyrrhizinate per capsule.
  • Test animals Beagle dogs, 11.7 ⁇ 1.2 kg, $ half, a total of 6. Provided by Nanjing Yadong Experimental Animal Research Center.
  • 18- ⁇ -glycyrrhizinate was determined by HPLC-UV method.
  • the analytical method is specific, sensitive, reliable, and has a wide linear range, which can fully meet the analytical requirements of biological samples in the study.
  • Beagle dogs were randomly divided into 18- ⁇ -Glycyrrhizic acid enteric-coated pellets 32 mg/kg group and 18- ⁇ -glycyrrhizinate common intestinal sol-gel 32 mg/kg, 3 in each group.
  • the formulation used in this study is 50mg/particle
  • Beagle dogs with a body weight close to 12.5kg are selected.
  • the doses of the two dogs in each group are 400mg, that is, 8 tablets of oral test preparation and reference preparation respectively.
  • Dog test Day fasting can not help but water for 12 hours, intravenous blood 2 ⁇ 2.5ml in the heparin anticoagulation tube.
  • the dog After taking the blood, the dog was orally administered with the oral test preparation and the reference preparation according to the set dose, and the blood was taken by the same method at different time points after the administration, and the collected blood was centrifuged at 3000 r/min for 10 min. 1 ml of the upper plasma was placed in an EP tube and stored at -20 ° C for testing. Plasma samples were taken at the time of the measurement, thawed, and the concentration of magnesium isoglycyrrhizinate in the plasma was measured.
  • the 18- ⁇ -Glycyrrhizinate enteric-coated pellets 32 mg/kg group and the 18- ⁇ -glycyrrhizinate common intestinal sol-gel group 32 mg/kg group were crossed, and the same method was used to take blood. , measurement.
  • Stability test example 18- ⁇ magnesium glycyrrhizinate enteric pellets capsule (Example 1) stability test 03950 18-o glycyrrhizic acid enteric pellets (batch number: 050516, 050518, 050522) according to the commercial packaging (using aluminum foil and PVC hard sheet packaging) at 40 ° C ⁇ 2 ° C, relative humidity of 75 Accelerated test for 6 months (1, 2, 3, 6 months) under conditions of 5% soil %; long-term test for 18 months at 25 °C ⁇ 2 °C, relative humidity 60% ⁇ 10% ( 0, 3, 6, 9, 12, 18 months sampling).
  • Small pill small pill, small pill, small pill, small pill, small pill, small pill, small pill, small pill, small pill, small pill, small pill, small pill
  • Small pill small pill, small pill, small pill, small pill, small pill, small pill, small pill, small pill, small pill, small pill, small pill, small pill

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Virology (AREA)
  • Molecular Biology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Composition pharmaceutique orale entérique de glycyrrhizine ou son sel et son procédé de préparation. Cette composition est constituée de parties multiples. Chacune de ces parties comprend un revêtement entérique externe et un contenu. Ce contenu est composé de glycyrrhizine ou d'un de ses sels et d'au moins un agent optimisant l'absorption intestinale.
PCT/CN2007/003950 2006-12-29 2007-12-29 Composition pharmaceutique orale de glycyrrhizine ou ses sels et son procédé de préparation Ceased WO2008083561A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN200780048410.1A CN101600439B (zh) 2006-12-29 2007-12-29 甘草酸或其盐的口服药物组合物及其制备方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200610161637.4 2006-12-29
CN200610161637 2006-12-29

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Publication Number Publication Date
WO2008083561A1 true WO2008083561A1 (fr) 2008-07-17

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102018659A (zh) * 2010-11-04 2011-04-20 武汉华纳联合药业有限公司 甘草酸、甘草次酸及其盐的肠定位制剂及其制备方法和用途
CN102188404A (zh) * 2010-03-11 2011-09-21 江苏润邦药业有限公司 甘草酸二铵胶囊及其制备方法
CN104288108A (zh) * 2014-10-18 2015-01-21 山东世博金都药业有限公司 一种甘草酸二铵肠溶缓释微丸及其制备方法

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* Cited by examiner, † Cited by third party
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CN102525943B (zh) * 2012-01-05 2014-07-16 金陵药业股份有限公司 一种微丸及其制备方法
CN103242391B (zh) * 2012-02-13 2016-04-13 南京华狮化工有限公司 一种制备甘草酸锶化合物的方法及其产品和应用
CN103301074B (zh) * 2013-06-20 2015-04-22 成都华神集团股份有限公司 一种甘草酸二铵肠溶微丸及其制备方法和制剂
CN111067877A (zh) * 2020-01-19 2020-04-28 安徽省先锋制药有限公司 一种甘草酸二铵肠溶片及其制备方法

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CN1569005A (zh) * 2003-07-18 2005-01-26 江苏正大天晴药业股份有限公司 甘草酸及其盐的肠溶制剂和制备方法
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