WO2009070916A1 - Composition pharmaceutique pour le traitement de la dépression et son procédé de préparation - Google Patents

Composition pharmaceutique pour le traitement de la dépression et son procédé de préparation Download PDF

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Publication number
WO2009070916A1
WO2009070916A1 PCT/CN2007/003387 CN2007003387W WO2009070916A1 WO 2009070916 A1 WO2009070916 A1 WO 2009070916A1 CN 2007003387 W CN2007003387 W CN 2007003387W WO 2009070916 A1 WO2009070916 A1 WO 2009070916A1
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WIPO (PCT)
Prior art keywords
jujube
extract
pharmaceutical composition
weight
licorice
Prior art date
Application number
PCT/CN2007/003387
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English (en)
Chinese (zh)
Inventor
Zuoguang Zhang
Original Assignee
Chi, Yu-Fen
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 Chi, Yu-Fen filed Critical Chi, Yu-Fen
Priority to PCT/CN2007/003387 priority Critical patent/WO2009070916A1/fr
Publication of WO2009070916A1 publication Critical patent/WO2009070916A1/fr

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Classifications

    • 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)
    • A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
    • A61K36/725—Ziziphus, e.g. jujube
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants

Definitions

  • the present invention relates to a group of pharmaceutical compositions comprising licorice and jujube which are used as raw materials for the treatment of depression, which can be used as medicines, nutrients and health foods.
  • the present invention also relates to a method of preparing the above pharmaceutical composition for treating depression.
  • Depression is a common disease. According to statistics, about 25% of women in the general population have experienced depression during their lifetime, and about 10% of men have experienced depression (Zhang Chunxing: Modern Psychology) . Data from the World Health Organization (WHO): The incidence of depression in the world is about 11%. There are currently about 340 million people with depression in the world, and this number is still on the rise. The survey found that in the next 20 years, depression It will rise to the second most common disease in the world.
  • WHO World Health Organization
  • the antidepressant drugs are mainly based on Prozac, Serote, Zoloft, etc. (SS-, SNRI, NDRI, etc. 5-HT, NE, DA reuptake inhibitors), and the mechanism of action is Increase the content of serotonin and other components in the human nervous medium to alleviate the symptoms of depression.
  • anti-depressant drugs that have been asked have different degrees of side effects, such as: increased suicide rate, headache, dizziness, dizziness, insomnia, lethargy, tinnitus, dry mouth, anorexia, increased appetite, weight gain, blood pressure, gastrointestinal Discomfort, nausea, nausea, vomiting, indigestion, diarrhea, constipation, lower limb pain, skin rash, trembling, cramps, sweating, edema, loss of libido, sexual incompetence, etc.
  • anti-depressant drugs such as Prozac have become a serious concern in the society.
  • the US Food and Drug Administration (FDA) in 2004 requested pharmaceutical companies to relabel the main 32 anti-depressants on the market.
  • FDA US Food and Drug Administration
  • the inventors have studied the pathogenesis and mechanism of action of traditional Chinese medicine for treating depression in combination with modern medical and pharmacological theories.
  • the inventors have proposed the present invention, and the object thereof is to provide A pharmaceutical composition or health food for treating depression caused by licorice and jujube as raw materials.
  • the pharmaceutical composition is characterized by a clear functional component and a mechanism of action, and the main functional component can be quantified, so that the quality is stable, the curative effect is obvious, the safety is high, and the administration is convenient.
  • Another object of the present invention is to provide a pharmaceutical composition for preparing a depression or a health food prepared by using the above-mentioned licorice or jujube as a raw material.
  • the solution of the medicament of the invention is the result of intensive research and exploration by the inventors, according to the pathology and pharmacology theory of modern medical treatment of depression, especially the anti-depression drug target research combined with the post-receptor mechanism, after a large number of animal experiments prove: Glycyrrhizic acid (glycyrrhetinic acid) is a strong inhibitor of cAMP phosphodiesterase (CAPD); jujube cAMP can increase the expression of cAMP in human body, extracting jujube cAMP with very small content (about one ten thousandth) in jujube The results of experiments with the jujube extract containing 1% jujube cAMP for anti-test depression have shown that it has obvious anti-test inhibition.
  • Glycyrrhizic acid glycyrrhetinic acid
  • CAPD cAMP phosphodiesterase
  • jujube cAMP can increase the expression of cAMP in human body, extracting juju
  • glycyrrhizic acid Since the conversion rate of glycyrrhizic acid to glycyrrhetinic acid in the human body is almost 100%, glycyrrhetinic acid, which is more fat-soluble than glycyrrhizic acid, can enter the brain through the blood-brain barrier, so glycyrrhizic acid inhibits CAPD and has anti-depression effect. It is carried out by in vivo conversion to glycyrrhetinic acid, and therefore, the pharmaceutical composition of the present invention can be processed by using glycyrrhizic acid or glycyrrhetinic acid as a raw material.
  • Licorice and jujube are the commonly used medicinal materials and foods for traditional Chinese medicine and food supplement diets for thousands of years.
  • the safety of licorice and jujube have been fully proved, while taking licorice and large Jujube does not cause side effects such as strong vomiting, so the inventor proposed to use licorice and jujube as raw materials to make oral or health foods for the treatment of depression, especially the clear functional ingredients, long-term safety is high, will not cause New technical solutions for side effects such as strong vomiting to improve the deficits produced in the prior art.
  • the present invention discloses a pharmaceutical composition for treating depression, which is prepared by using licorice and jujube as raw materials.
  • the pharmaceutical composition of the present invention is prepared by including 2 to 32 parts by weight of licorice and 2 to 42 parts by weight of jujube.
  • the pharmaceutical composition of the present invention is prepared by including 5 to 15 parts by weight of licorice and 4 to 20 parts by weight of jujube.
  • the present invention is a pharmaceutical composition for treating depression, which is prepared by using licorice and jujube extract as raw materials.
  • the pharmaceutical composition of the present invention comprises a licorice extract comprising 4 to 64 parts by weight of glycyrrhizic acid (or glycyrrhizic acid or glycyrrhetinic acid prepared) and 0.01 to 0.2 parts by weight of jujube ring gland.
  • the jujube extract of the monoglyceride monophosphate is made of a raw material.
  • the pharmaceutical composition of the present invention comprises a licorice extract containing 10 to 30 parts by weight of glycyrrhizic acid (or glycyrrhizic acid or glycyrrhetinic acid prepared) and a ring-shaped gland containing 0.024-0.12 parts by weight of jujube
  • the jujube extract of the monoglyceride monophosphate is made of a raw material.
  • the pharmaceutical composition of the present invention wherein the jujube extract used is the following second extract: first extracting jujube to obtain a first extract, and then purifying the first extract to obtain a second extract
  • concentration of the cyclic adenosine monophosphate (cAMP) of the second extract is higher than the concentration of the cyclic adenosine monophosphate of the extract of the first extract.
  • the present invention is a method for preparing a pharmaceutical composition for treating depression, comprising the steps of:
  • the pharmaceutical composition of the present invention can be processed into a dosage form comprising a lozenge, a capsule, a powder, a tablet, a powder, a solution, a tincture Any one of a suspension, an emulsion, a granule, a pill, a pill, and a pharmaceutically acceptable oral pharmaceutical dosage form.
  • compositions of the present invention comprise a pharmaceutically acceptable carrier or additive.
  • the pharmaceutical composition of the present invention further comprises a health food and a nutrient.
  • the above pharmaceutical composition is a core component for achieving the object of the present invention.
  • those skilled in the art can routinely add or subtract the above pharmaceutical composition according to the theory of traditional Chinese medicine or related modern pharmacological theory. Cut.
  • Such conventional addition and subtraction is a general technical activity of those skilled in the art, and as long as it is a general technical addition or subtraction performed on the formulation base of the pharmaceutical composition of the present invention, it is within the scope of the present invention.
  • FIG. 1 is a schematic view showing the flow of a method for preparing a medicament of Example 1 of the present invention.
  • Fig. 2 is a flow chart showing the process of preparing the medicament of the embodiment 2 of the present invention. Preferred embodiment of the invention
  • the present invention is primarily directed to the preparation of the medicaments of the present invention in combination with the features of the present invention by methods well known to those skilled in the art.
  • the following examples are merely illustrative of the invention and are not intended to limit the invention.
  • the present invention particularly proposes the following technical solutions.
  • the pharmaceutical composition for treating depression of the present invention is prepared by using licorice and jujube as raw materials.
  • Fang Zhong 2
  • the pharmaceutical composition for treating depression of the present invention is prepared by using 2 to 32 parts by weight of licorice and 2 to 42 parts by weight of jujube as raw materials.
  • the pharmaceutical composition for treating depression is prepared by using 5 to 15 parts by weight of licorice and 4 to 20 parts by weight of jujube as a raw material.
  • the pharmaceutical composition for treating depression of the present invention is prepared by using a licorice extract and a jujube extract as raw materials.
  • the invention comprises a licorice extract containing 4 to 64 parts by weight of glycyrrhizic acid (or glycyrrhizic acid or glycyrrhetinic acid prepared) and a jujube extract containing 0.01-0.2 parts by weight of jujube cyclic adenosine monophosphate.
  • a pharmaceutical composition for treating depression is invented.
  • licorice extract containing 10-30 parts by weight of glycyrrhizic acid (or glycyrrhizic acid or glycine which has been prepared)
  • a jujube extract containing 0.024-0.12 parts by weight of jujube cyclic adenosine monophosphate is used as a raw material to prepare a pharmaceutical composition for treating depression.
  • the jujube extract according to the fourth aspect of the present invention is the following second extract: first extracting jujube to obtain a first extract, and then purifying the first extract to obtain a second extract; wherein the second extract
  • the concentration of the adenosine adenosine monophosphate of the extract is higher than the concentration of the adenosine adenosine monophosphate of the first extract.
  • composition of the invention for treating depression is prepared by a preparation method comprising the following steps:
  • the pharmaceutical composition of the present invention can be processed into a dosage form comprising a tablet selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a microtane, a suspension. Any one of an emulsion, a granule, a pill, a pill, and a pharmaceutically acceptable oral pharmaceutical dosage form.
  • compositions of the present invention comprise a pharmaceutically acceptable carrier or additive.
  • compositions of the present invention also include those useful in the manufacture of health foods and nutraceuticals.
  • the raw materials including licorice, jujube and the like are processed into the pharmaceutical composition for treating depression in the present invention. Things.
  • Raw materials such as 2 to 32 parts by weight of licorice and 2 to 42 parts by weight of jujube are processed to prepare a pharmaceutical composition for treating depression in the present invention.
  • Raw materials such as 5 to 15 parts by weight of licorice and 4 to 20 parts by weight of jujube are processed to prepare a pharmaceutical composition for treating depression in the present invention.
  • Raw materials such as licorice extract and jujube extract are processed to prepare a pharmaceutical composition for treating depression in the present invention.
  • the licorice extract containing 4 to 64 parts by weight of glycyrrhizic acid (or prepared glycyrrhizic acid or glycyrrhetinic acid) and the jujube extract containing 0.01 to 0.2 parts by weight of jujube cyclic adenosine monophosphate may be processed.
  • the invention relates to a pharmaceutical composition for treating depression.
  • the licorice extract containing 10 to 30 parts by weight of glycyrrhizic acid (or prepared glycyrrhizic acid or glycyrrhetinic acid) and the jujube extract containing 0.024-0.12 parts by weight of jujube cyclic adenosine monophosphate are processed.
  • the invention relates to a pharmaceutical composition for treating depression.
  • the jujube extract according to the fourth method is the following second extract: first extracting jujube to obtain a first extract, and then purifying the first extract to obtain a second extract; wherein the second extract
  • the concentration of adenosine monophosphate in the jujube is higher than the concentration of the adenosine adenosine monophosphate in the first extract.
  • composition of the invention for treating depression is prepared by a preparation method comprising the following steps:
  • the pharmaceutical composition of the present invention is processed into a dosage form comprising a tablet selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a microtane, a suspension. , an emulsion, a granule, a pill, a pill, and any one of a pharmaceutically acceptable pharmaceutical dosage form.
  • compositions of the present invention are processed to include a pharmaceutically acceptable carrier or additive.
  • the pharmaceutical composition of the present invention is processed into a health food and a nutrient.
  • FIG. 1 is a schematic flow chart of a method for preparing the pharmaceutical composition of Example 1 of the present invention.
  • Fig. 1 4 kg of licorice is crushed, infiltrated with water for 12 hours, then extracted by warming, alcohol precipitation, and dried to obtain 0.8 kg of licorice extract containing 10% glycyrrhizic acid; 2 kg of jujube is broken, and water is added at room temperature. Then, it is extracted by water extraction and alcohol precipitation method, and the jujube extract is obtained. Then, the macroporous resin OU-2 and ME-2 are successively adsorbed and separated by two columns, and dried to obtain 6 g of jujube containing 1% jujube cAMP. Extract; The extract obtained in the above step is mixed and pulverized uniformly to obtain the pharmaceutical composition of the present invention.
  • FIG. 2 is a schematic flow chart of a method for preparing the pharmaceutical composition of Example 2 of the present invention.
  • the prepared 4 g of glycyrrhetinic acid and 1 g of jujube extract containing 10 mg of jujube cAMP were directly mixed and pulverized to obtain the pharmaceutical composition of the present invention.
  • Example 1 Provided by Beijing O'Neill Bioengineering Technology Co., Ltd.
  • Example 1 The large dose was 20 mg/kg/d, the medium dose was 10 mg/kg/d, and the small dose was 5 mg/kg/d.
  • mice were randomized into groups of 10: 1 Example 1 large dose group (20 mg/kg, PO, 7d); 2 Example 1 dose group (10 mg/kg, PO, 7d) 3 Example 1 Low-dose group (5 mg/kg, PO, 7d); 4 paroxetine group (3 mg/kg, PO, 7d); 5 saline group (PO).
  • a tail suspension experiment was performed 1 hour after the last administration.
  • the tail of the mouse (1 cm from the tip of the tail) was adhered to the 5 cm wooden strip with a tape on the head for 6 minutes, and the immobility time of the mouse within 5 minutes after the recording was recorded.
  • the experimental data were expressed by ⁇ SI>, and the experimental results were analyzed by SPSS 11.5 statistical software for analysis of variance.
  • Example 1 of the present invention has an anti-experimental depression function.
  • ICR mice male, weighing 22.0 ⁇ 2 g, secondary, provided by the Department of Laboratory Animal Science, Capital Medical University, Beijing.
  • Example 1 Provided by Beijing O'Neill Bioengineering Technology Co., Ltd.
  • thermometer GM222 type electronic thermometer, stopwatch.
  • Example 1 The large dose is 20 mg/kg/d, the medium dose is 10 mg/kg/d, and the small dose is 5
  • mice were randomized into groups of 10: 1 Example 1 high dose group (20 mg/kg, PO, 7d); 2 Example 1 dose group (10 mg / kg, PO, 7d); 3 Example 1 low dose group (5 mg / kg, PO, 7d); 4 paroxetine group ( 3 mg/kg, PO, 7d); 5 saline group (PO). 2.5.2 Experimental methods
  • the anus temperature of the mice was measured 1 hour after the administration on the 8th day, and then the reserpine 2 mg/kg was intraperitoneally injected, and the anal temperature of the mice was measured 4 hours after the injection of reserpine.
  • the depth and time of insertion of the thermometer into the anus of the mouse were consistent at each temperature measurement.
  • mice body temperature drop value ( °C ) saline group (model group) 10 3.65 ⁇ 0.77
  • the large, medium and small dose groups and the paroxetine group of the present invention can reduce the decrease of body temperature induced by reserpine in the high dose group and the middle dose group and the saline group.
  • the oral drug for treating depression according to the present invention may comprise a pharmaceutically acceptable Additive P agent
  • the oral medicament for treating depression according to the present invention can be processed into various conventional dosage forms such as powders, capsules, tablets, and the like;
  • the oral medicament for treating depression according to the present invention can be used for the treatment of health foods and nutrients for depression.

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Alternative & Traditional Medicine (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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  • Pain & Pain Management (AREA)
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  • Neurology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une composition pharmaceutique pour le traitement de la dépression qui comprend du Fructus Jujubae et du glycyrrhiza uralensis en tant que matières premières, ainsi que le procédé de préparation de ladite composition.
PCT/CN2007/003387 2007-11-30 2007-11-30 Composition pharmaceutique pour le traitement de la dépression et son procédé de préparation WO2009070916A1 (fr)

Priority Applications (1)

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PCT/CN2007/003387 WO2009070916A1 (fr) 2007-11-30 2007-11-30 Composition pharmaceutique pour le traitement de la dépression et son procédé de préparation

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Application Number Priority Date Filing Date Title
PCT/CN2007/003387 WO2009070916A1 (fr) 2007-11-30 2007-11-30 Composition pharmaceutique pour le traitement de la dépression et son procédé de préparation

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WO2009070916A1 true WO2009070916A1 (fr) 2009-06-11

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1836687A (zh) * 2005-03-25 2006-09-27 北京欧纳尔生物工程技术有限公司 治疗抑郁症的药物组合物及其制法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1836687A (zh) * 2005-03-25 2006-09-27 北京欧纳尔生物工程技术有限公司 治疗抑郁症的药物组合物及其制法

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