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WO2009070916A1 - A pharmaceutical composition for treating depression and a preparation process thereof - Google Patents

A pharmaceutical composition for treating depression and a preparation process thereof 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
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PCT/CN2007/003387
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French (fr)
Chinese (zh)
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Zuoguang Zhang
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Priority to PCT/CN2007/003387 priority Critical patent/WO2009070916A1/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484Glycyrrhiza (licorice)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/72Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
    • A61K36/725Ziziphus, e.g. jujube
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants

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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Abstract

A pharmaceutical composition for treating depression comprising Fructus Jujubae and glycyrrhiza uralensis as raw materials, and a preparation thereof are disclosed.

Description

治疗抑郁症的药物组合物及其制备方法  Medicine composition for treating depression and preparation method thereof

技术领域 Technical field

本发明涉及一组包括以甘草、大枣为原料制成的用于治疗忧郁症的药物 组合物, 可将其作为药物、 营养剂和保健食品。 本发明还涉及上述用于治疗 忧郁症的药物组合物的制备方法。  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.

背景技术 Background technique

忧郁症是一种常见的疾病,据统计在一般人口中大约有 25%女性在其一 生中经历过忧郁症, 男性中约有 10%左右经历过忧郁症(张春兴著: 《现代 心理学》 ) 。 世界卫生组织 (WHO )提供的数据: 忧郁症在全世界的发病 率约为 11%, 目前全球约有 3.4亿精神忧郁患者, 而且这个数字仍成上升趋 势, 调查发现在今后 20年, 忧郁症将会上升为全球第二大常见疾病。  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.

现有技术中, 抗忧郁药物以百忧解、 赛洛特、 左洛复等(SSRI、 SNRI、 NDRI等类的 5-HT、 NE、 DA再摄取抑制剂)为主, 其作用机制是通过增加 人体神经介质内 5-羟色胺等成分含量以緩解忧郁症状。  In the prior art, 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.

但是, 已问市的抗忧郁药物都有不同程度的副作用,例如:增加自杀率、 头痛、 头晕、 晕眩、 失眠、 嗜睡、 耳鸣、 口干、 厌食、 食欲增加、 体重上升、 血压上升、肠胃不适、反胃、 恶心、 呕吐、 消化不良、腹泻、便秘、 下肢痛、 皮肤出疹、 颤抖、 痉挛、 多汗、 水肿、 性欲降低、 性无能等。 近年来百忧解 等抗忧郁药物已成为社会严重关注的问题, 美国食品暨药物管理局 (Food and Drug Administration, FDA )更在 2004年要求药厂将市场上主要的 32种 抗忧郁药物重新标示其副作用和警告的部分,并对医护人员强调这些药物可 能增加孩童及青少年自杀的机率。 其中, 赛洛特-加龙省更是早在 1996年就 被发现存在有安全隐患, 自 2001年开始已陆续从市场上召回。 2004年 6月, 美国纽约州总检察长指控英国葛兰素史克公司为了获取利润 ,欺骗性隐瞒了 服用赛洛特与"增加青少年自杀倾向及行为的风险,,之间有关联的研究报告。 在这种背景下,如何研发新一代副作用低又能有明显抗忧郁作用的药物已成 为全球医药界所关注的问题。 However, the 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. In recent years, 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. Part of its side effects and warnings, and stressing to medical staff that these drugs may increase the chances of suicide in children and adolescents. Among them, the Cellot-Garonne province was found to have potential safety hazards as early as 1996, and has been recalled from the market since 2001. In June 2004, the US Attorney General of New York accused the British GlaxoSmithKline of deceptively concealing the use of Selot and the risk of increasing the risk of suicidal tendencies and behavior among adolescents in order to make a profit. In this context, how to develop a new generation of drugs with low side effects and significant anti-depression effects has become A concern for the global pharmaceutical community.

近年来,国际医药界的科学家们在忧郁症致病机理的研究方面出现了新 的突破, 发现除了以 5-HT、 NE、 DA的再摄取抑制方式治疗忧郁症之外, 更可以采取调节受体后作用机制的方式治疗忧郁症,并且由于受体后作用机 制调节类药物罗列普拉 ( Rolipram )的问世而成为医药界抗忧郁药物的研发 热点。 罗列普拉是四型磷酸二酯酶(phosphodiesterase 4, PDE4 )的抑制剂, 临床试验表明它具有明显的抗忧郁作用,但由于服用罗列普拉会出现强烈呕 吐, 故被迫终止研发, 然而罗列普拉却开拓了新一代 "受体后作用机制抗忧 郁药物" 的研发思路。  In recent years, scientists in the international medical community have made new breakthroughs in the study of the pathogenesis of depression. It has been found that in addition to the treatment of depression by 5-HT, NE, and DA reuptake inhibition, it is possible to adopt regulation. The post-posterior mechanism of action is used to treat depression, and it has become a research and development hotspot for antidepressants in the pharmaceutical industry due to the advent of the drug-restricting mechanism Rolipram. Rollipura is an inhibitor of phosphodiesterase 4 (PDE4). Clinical trials have shown that it has significant antidepressant effects, but it is forced to terminate R&D due to strong vomiting. Pula has developed a new generation of "receptor-poster mechanism anti-depression drugs" research and development ideas.

因此, 申请人鉴于习知技术中所产生的缺失, 经悉心研究与探索, 并以 锲而不舍的精神, 终构思出本发明 "以甘草、 大枣为原料的治疗忧郁症的药 物组合物及其制法" , 以下为本发明的简要说明。  Therefore, in view of the shortcomings in the prior art, the applicant has carefully studied and explored, and in the spirit of perseverance, finally conceived the pharmaceutical composition of the present invention for treating depression with licorice and jujube as raw materials. The method is as follows, which is a brief description of the invention.

发明内容 Summary of the invention

为了克服现有药物制剂的不足,发明人结合现代医学和药理学理论对传 统中药治疗忧郁症的病机和作用机理进行了研究,在此基础之上,发明人提 出本发明,其目的在于提供一种以甘草、 大枣为原料所制成的用于治疗忧郁 症的药物组合物或保健食品。这种药物组合物的特点是功效成份及作用机理 明确, 主功效成分可以量化, 因此质量稳定, 疗效明显, 安全性高, 服用方 便。  In order to overcome the deficiencies of the existing pharmaceutical preparations, 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. On the basis of this, 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.

本发明的另一目的是提供上述以甘草、大枣为原料所制成的用于治疗忧 郁症的药物组合物或保健食品的制备方法。  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.

本发明药物的解决方案是经发明人潜心研究探索的结果,依据现代医学 治疗忧郁症的病理及药理学理论,特别是结合受体后作用机制抗忧郁药靶标 研究, 经过大量的动物实验证明: 甘草酸(甘草次酸)是 cAMP磷酸二酯酶 ( CAPD )强抑制剂; 大枣 cAMP可以提高人体 cAMP的表达, 将大枣中含 量极微 (约万分之一 )的大枣 cAMP提取并纯化成含 1%大枣 cAMP的大枣 提取物进行抗试险性抑郁作用动物试验的结果显示,具有明显的抗试验性抑 郁功能,而正常含微量大枣 cAMP的大枣提取物则不具有明显的抗试验性抑 郁功能; 甘草酸(甘草次酸)、 大枣 cAMP二者配伍, 协同作用, 可以进一 步提高 cAMP的利用度和活性, 而 cAMP的浓度和活性增强, 则可增加去 甲肾上腺素( norepinephrine, NE )等神经递质的合成与释放, 从而达到显著 的抗忧郁功能。 由于甘草酸在人体内转化为甘草次酸的转化率几乎达到 100%, 而脂溶性比甘草酸强的甘草次酸能够透过血脑屏障进入脑内, 故甘 草酸抑制 CAPD起到抗忧郁功效是通过体内转化为甘草次酸来进行的, 因 此, 可以用甘草酸或甘草次酸为原料加工制成本发明的药物组合物。 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. The function of stagnation, while the jujube extract containing normal jujube cAMP does not have obvious anti-experimental depression function; the combination of glycyrrhizic acid (glycyrrhetinic acid) and jujube cAMP, synergistic effect, can further improve the utilization of cAMP Degree and activity, while the concentration and activity of cAMP are enhanced, it can increase the synthesis and release of neurotransmitters such as norepinephrine (NE), thus achieving significant anti-depression function. 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.

甘草、 大枣是几千年以来中医及食补药膳常用的药材和食品,在千百年 的食用和临床使用过程中, 已充分证明甘草、 大枣二者配伍的安全性, 而服 用甘草及大枣不会发生强烈呕吐等副作用,故发明人提出以甘草及大枣为原 料, 制成用于治疗忧郁症的口服药物或保健食品, 特别是功效成份明确, 长 期服用安全性高,不会引起强烈呕吐等副作用的新技术方案以改进习知技术 中所产生的缺失。  Licorice and jujube are the commonly used medicinal materials and foods for traditional Chinese medicine and food supplement diets for thousands of years. In the course of food and clinical use 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.

本发明是揭露一种用于治疗忧郁症的药物组合物, 它是由包括用甘草、 大枣为原料所制成。  The present invention discloses a pharmaceutical composition for treating depression, which is prepared by using licorice and jujube as raw materials.

较佳者, 本发明的药物組合物, 是由包括 2~32 重量份的甘草及 2~42 重量份的大枣为原料所制成。  Preferably, 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.

较佳者, 本发明的药物组合物, 是由包括 5~15 重量份的甘草及 4-20 重量份的大枣为原料所制成。  Preferably, 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.

根据本发明的另一概念,本发明是揭露一种用于治疗忧郁症的药物组合 物, 它是由包括用甘草、 大枣提取物为原料所制成。  According to another concept of the present invention, the present invention is a pharmaceutical composition for treating depression, which is prepared by using licorice and jujube extract as raw materials.

较佳者, 本发明的药物组合物, 是由包括含 4〜64重量份甘草酸的甘草 提取物 (或已制备成的甘草酸或甘草次酸)及含 0.01〜0.2重量份大枣环腺苷单 磷酸的大枣提取物为原料所制成。  Preferably, 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.

较佳者,本发明的药物组合物,是由包括含 10~30重量份甘草酸的甘草 提取物 (或已制备成的甘草酸或甘草次酸)及含 0.024-0.12重量份大枣环腺苷 单磷酸的大枣提取物为原料所制成。 较佳者,本发明的药物组合物, 其中所用的大枣提取物是下述的第二提 取物:先提取大枣获得一第一提取物,再纯化该第一提取物得一第二提取物; 其中该第二提取物的大枣环石舞酸腺苷 ( cyclic adenosine monophosphate, cAMP )浓度高于该笫一提取物的大枣环磷酸腺苷浓度。 Preferably, 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. Preferably, 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 The 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.

才 据本发明的另一概念,本发明是揭露一种用于治疗忧郁症的药物组合 物的制备方法, 包括下列步骤:  According to another concept of the present invention, the present invention is a method for preparing a pharmaceutical composition for treating depression, comprising the steps of:

(a)将 2~32重量份的甘草破碎后, 先加水常温浸泡, 再以水提醇沉法提 取, 再将提取的上清液浓缩干燥后, 得含甘草酸的甘草提取物;  (a) After crushing 2 to 32 parts by weight of licorice, first adding water to be immersed at room temperature, and then extracting by water extraction and alcohol precipitation, and then concentrating and drying the extracted supernatant to obtain licorice extract containing glycyrrhizic acid;

(b)将 2〜42重量份的大枣破碎后用水加温提取得一第一大枣提取物, 将 该第一大枣提取物上柱层析分离纯化后得一第二大枣提取物,其中该第二大 枣提取物的大枣环磷酸腺苷浓度高于该第一大枣提取物的大枣环磷酸腺苷 浓度; 及  (b) 2~42 parts by weight of jujube is broken and then extracted with water to obtain a first jujube extract, and the first jujube extract is separated and purified by column chromatography to obtain a second jujube extract. , wherein the concentration of the adenosine adenosine monophosphate of the second jujube extract is higher than the concentration of the adenosine adenosine monophosphate of the first jujube extract;

(c)将步骤 (a)及步骤 (b)所得的甘草提取物及第二大枣提取物混合粉碎, 即得本发明药物组合物。  (c) The licorice extract obtained in the steps (a) and (b) and the second jujube extract are mixed and pulverized to obtain the pharmaceutical composition of the present invention.

较佳者,本发明的药物组合物可以加工制成一剂型,该剂型包括选自一 锭剂、 一胶嚢剂、 一散剂、 一片剂、 一粉剂、 一溶液剂、 一^:嚢剂、 一混悬 剂、 一乳剂、 一颗粒剂、 一滴丸剂、 一丸剂及药剂学上的一口服药物剂型中 的任一种。  Preferably, 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.

较佳者,本发明的药物组合物包括可以含有药学上可接受的载体或添加 剂。  Preferably, the pharmaceutical compositions of the present invention comprise a pharmaceutically acceptable carrier or additive.

较佳者, 本发明的药物组合物还包括可用来制成保健食品和营养剂。 上述的药物组合物, 是实现本发明目的的核心组方, 在本发明公开后, 本领域的技术人员可以根据中医理论或是相关现代药理学理论,对上述药物 组合物进行常规的加减化裁。这种常规的加减化裁是本领域技术人员的一般 性技术活动,只要是在本发明药物组合物的配方基 上所进行的一般性技术 加减, 均在本发明的保护范围之内。  Preferably, 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. After the disclosure 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.

参阅附图及详细说明可对本发明获得较佳的了解。 附图概述 A better understanding of the present invention can be obtained by reference to the drawings and detailed description. BRIEF abstract

图 1为制备本发明实施例 1药物的方法流程示意图。  BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic view showing the flow of a method for preparing a medicament of Example 1 of the present invention.

图 2为制备本发明实施例 2药物的方法流程示意图。 本发明的较佳实施方式  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

以下将结合附图和实施例进一步说明本发明。本发明主要是采用本领域 技术人员习知的方法结合本发明的特征制备本发明所述的药物。以下实施例 仅仅是用以说明本发明, 并非限定本发明。  The invention will be further illustrated by the following figures and examples. 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.

为了完成本发明的目的, 本发明特别提出下面技术方案。  In order to accomplish the object of the present invention, the present invention particularly proposes the following technical solutions.

方案一:  Option One:

以包括甘草、 大枣为原料制成本发明用于治疗忧郁症的药物组合物。 方衆二:  The pharmaceutical composition for treating depression of the present invention is prepared by using licorice and jujube as raw materials. Fang Zhong 2:

以包括 2〜32重量份的甘草及 2~42重量份的大枣为原料制成本发明用于 治疗忧郁症的药物组合物。  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.

方案三:  third solution:

以包括 5〜15重量份的甘草及 4~20重量份的大枣为原料制成本发明用于 治疗忧郁症的药物组合物。  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.

方案四:  Option 4:

以包括甘草提取物及大枣提取物为原料制成本发明用于治疗忧郁症的 药物組合物。  The pharmaceutical composition for treating depression of the present invention is prepared by using a licorice extract and a jujube extract as raw materials.

. 方案五:  Option 5:

以包括含 4-64重量份甘草酸的甘草提取物(或已制备成的甘草酸或甘 草次酸)及含 0.01-0.2重量份大枣环磷酸腺苷的大枣提取物为原料制成本发 明用于治疗忧郁症的药物组合物。  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.

方案六:  Option six:

以包括含 10-30重量份甘草酸的甘草提取物(或已制备成的甘草酸或甘 草次酸)及含 0.024-0.12重量份大枣环磷酸腺苷的大枣提取物为原料制成本 发明用于治疗忧郁症的药物组合物。 To include 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.

方案七:  Option seven:

本发明方案四所述的该大枣提取物是下述的第二提取物:先提取大枣获 得一第一提取物,再純化该第一提取物得一第二提取物; 其中该第二提取物 的大枣环磷酸腺苷浓度高于该第一提取物的大枣环磷酸腺苷浓度。  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.

方案八:  Option eight:

以包括下列步驟的制备方法, 制成本发明用于治疗忧郁症的药物组合 物:  The pharmaceutical composition of the invention for treating depression is prepared by a preparation method comprising the following steps:

(a)将 2〜32重量份的甘草破碎后, 先加水常温浸泡, 再以水提醇沉法提 取, 再将提取的上清液浓缩干燥后, 得含甘草酸的甘草提取物;  (a) after crushing 2 to 32 parts by weight of licorice, first adding water at room temperature, then extracting by water extraction and alcohol precipitation, and then concentrating and drying the extracted supernatant to obtain licorice extract containing glycyrrhizic acid;

(b)将 2〜42重量份的大枣破碎后用水加温提取得一第一提取物, 将该第 一提取物上柱层析分离纯化后得一第二提取物,其中该第二提取物的大枣环 磷酸腺苷浓度高于该笫一提取物的大枣环磷酸腺苷浓度; 及  (b) 2~42 parts by weight of the jujube is broken and then extracted with water to obtain a first extract, and the first extract is separated and purified by column chromatography to obtain a second extract, wherein the second extract is obtained. The concentration of the adenosine monophosphate of the jujube is higher than the concentration of the adenosine monophosphate of the jujube extract;

(c)将步骤 (a)及步骤 (b)所得的甘草提取物及大枣第二提取物混合粉碎, 即得本发明药物组合物。  (c) The licorice extract obtained in the steps (a) and (b) and the second extract of jujube are mixed and pulverized to obtain the pharmaceutical composition of the present invention.

方案九:  Option nine:

本发明的药物组合物可以加工制成一剂型,该剂型包括选自一锭剂、一 胶嚢剂、 一散剂、 一片剂、 一粉剂、 一溶液剂、 一微嚢剂、 一混悬剂、 一乳 剂、一颗粒剂、一滴丸剂、一丸剂及药剂学上的一口服药物剂型中的任一种。  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.

方案十:  Option 10:

本发明的药物组合物包括可以含有药学上可接受的载体或添加剂。  The pharmaceutical compositions of the present invention comprise a pharmaceutically acceptable carrier or additive.

方案十一:  Option 11:

本发明的药物组合物还包括可用来制成保健食品和营养剂。  The pharmaceutical compositions of the present invention also include those useful in the manufacture of health foods and nutraceuticals.

为了完成本发明的目的, 特提出以下药物的制作方法。  In order to accomplish the object of the present invention, a method of producing the following drugs is specifically proposed.

方法一:  method one:

将包括甘草、 大枣等原料,加工制成本发明用于治疗忧郁症的药物组合 物。 The raw materials including licorice, jujube and the like are processed into the pharmaceutical composition for treating depression in the present invention. Things.

方法二:  Method Two:

将包括 2〜32重量份的甘草及 2~42重量份的大枣等原料,加工制成本发 明用于治疗忧郁症的药物组合物。  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.

方法三:  Method three:

将包括 5〜15重量份的甘草及 4〜20重量份的大枣等原料,加工制成本发 明用于治疗忧郁症的药物组合物。  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.

方法四:  Method four:

将包括甘草提取物及大枣提取物等原料,加工制成本发明用于治疗忧郁 症的药物组合物。  Raw materials such as licorice extract and jujube extract are processed to prepare a pharmaceutical composition for treating depression in the present invention.

方法五:  Method five:

将包括含 4~64重量份甘草酸的甘草提取物(或已制备成的甘草酸或甘 草次酸)及含 0.01~0.2重量份大枣环磷酸腺苷的大枣提取物等原料,加工制 成本发明用于治疗忧郁症的药物组合物。  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.

方法六:  Method six:

将包括含 10〜30重量份甘草酸的甘草提取物(或已制备成的甘草酸或甘 草次酸)及含 0.024-0.12重量份大枣环磷酸腺苷的大枣提取物等原料,加工 制成本发明用于治疗忧郁症的药物组合物。  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.

方法七:  Method seven:

方法四所述的该大枣提取物是下述的第二提取物:先提取大枣获得一第 一提取物,再纯化该第一提取物得一第二提取物; 其中该第二提取物的大枣 环磷酸腺苷浓度高于该第一提取物的大枣环磷酸腺苷浓度。  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.

方法八:  Method eight:

以包括下列步骤的制备方法, 制成本发明用于治疗忧郁症的药物组合 物:  The pharmaceutical composition of the invention for treating depression is prepared by a preparation method comprising the following steps:

(a)将 2〜32重量份的甘草破碎后, 先加水常温浸泡, 再以水提醇沉法提 取, 再将提取的上清液浓缩干燥后, 得含甘草酸的甘草提取物; (b)将 2〜42重量份的大枣破碎后用水加温提取得一第一提取物, 将该第 一提取物上柱层析分离纯化后得一第二提取物,其中该第二提取物的大枣环 磷酸腺苷浓度高于该第一提取物的大枣环磷酸腺苷浓度; 及 (a) after crushing 2 to 32 parts by weight of licorice, first adding water to be immersed at room temperature, extracting by water extraction and alcohol precipitation, and then concentrating and drying the extracted supernatant to obtain licorice extract containing glycyrrhizic acid; (b) 2~42 parts by weight of the jujube is broken and then extracted with water to obtain a first extract, and the first extract is separated and purified by column chromatography to obtain a second extract, wherein the second extract is obtained. The concentration of the adenosine monophosphate of the jujube is higher than the concentration of the adenosine monophosphate of the first extract;

(c)将步驟 (a)及步骤 (b)所得的甘草提取物及大枣第二提取物混合粉碎, 即得本发明药物组合物。  (c) The licorice extract obtained in the steps (a) and (b) and the second extract of jujube are mixed and pulverized to obtain the pharmaceutical composition of the present invention.

方法九:  Method nine:

将本发明的药物组合物加工制成一剂型,该剂型包括选自一锭剂、一胶 嚢剂、 一散剂、 一片剂、 一粉剂、一溶液剂、 一微嚢剂、 一混悬剂、 一乳剂、 一颗粒剂、 一滴丸剂、 一丸剂及药剂学上的一口^ 1良药物剂型中的任一种。  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.

方法十:  Method ten:

将本发明的药物组合物加工制成包括含有药学上可接受的载体或添加 剂。  The pharmaceutical compositions of the present invention are processed to include a pharmaceutically acceptable carrier or additive.

方法十一:  Method 11:

将本发明的药物组合物加工制成包括保健食品和营养剂。  The pharmaceutical composition of the present invention is processed into a health food and a nutrient.

实施例 1  Example 1

请参阅图 1, 为制备本发明实施例 1药物组合物的方法流程示意图。 在 1图中, 将 4 kg的甘草破碎后用水浸润 12小时后加温提取, 醇沈, 干燥, 得 0.8 kg含 10%甘草酸的甘草提取物; 将 2 kg大枣破碎后加水常温浸泡, 再以水提醇沈法提取,得大枣提取液,再用大孔树脂 OU-2、 ME-2两柱先后 连续上柱吸附分离, 干燥, 得 6 g含 1%大枣 cAMP的大枣提取物; 将上述 步骤所得提取物混合粉碎均匀, 即得本发明药物組合物。  Please refer to FIG. 1, which is a schematic flow chart of a method for preparing the pharmaceutical composition of Example 1 of the present invention. In 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.

实施例 2  Example 2

请参阅图 2, 为制备本发明实施例 2药物组合物的方法流程示意图。 在 图 2中, 直接将已制备成的 4 g甘草次酸、 1 g的含 10 mg大枣 cAMP的大 枣提取物混合粉碎, 即得本发明药物组合物。  Please refer to FIG. 2, which is a schematic flow chart of a method for preparing the pharmaceutical composition of Example 2 of the present invention. In Fig. 2, 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.

实验例 1 实施例 1对小鼠悬尾实验的影响  Experimental Example 1 Example 1 Effect on Mouse Suspension Experiment

1.1 实验动物 . ICR小鼠, 雄性, 体重 22.0±2 g, 二级, 北京首都医科大学实验动物科 学部提供。 1.1 Experimental animals ICR mice, male, weighing 22.0±2 g, secondary, provided by the Department of Laboratory Animal Science, Capital Medical University, Beijing.

1.2 实验药品  1.2 Experimental drugs

实施例 1 : 北京欧纳尔生物工程技术有限公司提供。  Example 1: Provided by Beijing O'Neill Bioengineering Technology Co., Ltd.

帕罗西汀(赛乐特) : 中美天津史克制药有限公司产品。  Paroxetine (Selite): Sino-US Tianjin Shike Pharmaceutical Co., Ltd. products.

1.3 实 仪器:  1.3 Real Instrument:

秒表。  Stopwatch.

1.4 剂量设计  1.4 Dose design

实施例 1 大剂量为 20 mg/kg/d, 中剂量为 10 mg/kg/d及小剂量为 5 mg/kg/d。  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.

1.5 实-检方法及结果  1.5 Real-test methods and results

1.5.1 分组给药  1.5.1 Group administration

将小鼠随机分组, 每组 10只: ①实施例 1大剂量组(20 mg/kg, PO, 给药 7d ) ; ②实施例 1中剂量组( 10 mg/kg, PO, 给药 7d ) ; ③实施例 1 小剂量组(5 mg/kg, PO, 给药 7d ) ; ④帕罗西汀组(3 mg/kg, PO, 给药 7d ) ; ⑤生理盐水组(PO ) 。 最后一次给药后 1小时进行悬尾实验。  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.

1.5.2 实^ r方法  1.5.2 Real ^ r method

将小鼠尾(距尾尖 1 cm处)用胶布粘在头高出台面 5 cm的木条上悬吊 6分钟, 记录后 5分钟内小鼠的不动时间。  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.

1.5.3 统计学处理  1.5.3 Statistical processing

实验资料用 ±SI>表示,实验结果用 SPSS 11.5统计软件进行方差分析。  The experimental data were expressed by ±SI>, and the experimental results were analyzed by SPSS 11.5 statistical software for analysis of variance.

1.5.4 实-险结果  1.5.4 Real-risk results

实验结果请参阅表 1。  See Table 1 for the experimental results.

表 1、 实施例 1对小鼠不动时间的影响  Table 1. Effect of Example 1 on immobility time in mice

组 别 动物数(只) 不动时间 (秒) 生理盐水组(模型组) 10 122.18±45.78 帕罗西汀組 10 67.59士 32.09** 实施例 1大剂量组 10 54.67+26.38** 实施例 1中剂量组 10 61.60±49.84** 实施例 1小剂量組 10 103.26+49.91 注: 与模型组比较 * P<0.05 * *P<0.01 Number of animals in the group (only) No time (seconds) Saline group (model group) 10 122.18±45.78 Paroxetine group 10 67.59±32.09** Example 1 high dose group 10 54.67+26.38** Example 1 medium dose group 10 61.60±49.84** Example 1 low dose group 10 103.26+49.91 Note: Compared with the model group * P<0.05 * *P<0.01

结论:  in conclusion:

才艮据以上实验, 可以看出本发明实施例 1大、 中剂量組和帕罗西汀组均 可减少小鼠悬尾后的不动时间, 大、 中剂量组与生理盐水组(模型组)相比 有显著性差异, 从而可以推断本发明实施例 1具有抗实验性抑郁功能。  According to the above experiment, it can be seen that the large and medium dose groups and the paroxetine group of the present invention can reduce the immobility time of the mice after the tail suspension, and the large and middle dose groups and the saline group (model group) There is a significant difference in the ratio, so that it can be inferred that Example 1 of the present invention has an anti-experimental depression function.

实验例 2 实施例 1对小鼠利血平诱导体温下降的影响  Experimental Example 2 Example 1 Effect of reserpine induced hypothermia in mice

2.1 实验动物  2.1 Experimental animals

ICR小鼠, 雄性, 体重 22.0±2 g, 二级, 北京首都医科大学实验动物科 学部提供。  ICR mice, male, weighing 22.0±2 g, secondary, provided by the Department of Laboratory Animal Science, Capital Medical University, Beijing.

2.2 实验药品  2.2 Experimental drugs

实施例 1: 北京欧纳尔生物工程技术有限公司提供。  Example 1: Provided by Beijing O'Neill Bioengineering Technology Co., Ltd.

帕罗西汀(赛乐特) : 中美天津史克制药有限公司产品。  Paroxetine (Selite): Sino-US Tianjin Shike Pharmaceutical Co., Ltd. products.

2.3 实验仪  2.3 Experimenter

GM222型电子温度计, 秒表。  GM222 type electronic thermometer, stopwatch.

2.4 剂量设计  2.4 Dose design

实施例 1 大剂量为 20 mg/kg/d、 中剂量为 10 mg/kg/d及小剂量为 5

Figure imgf000012_0001
Example 1 The large dose is 20 mg/kg/d, the medium dose is 10 mg/kg/d, and the small dose is 5
Figure imgf000012_0001

2.5 实验方法及结果  2.5 Experimental methods and results

2.5.1 分组给药  2.5.1 Group administration

将小鼠随机分组, 每组 10只: ①实施例 1大剂量组(20 mg/kg, PO, 给药 7d ); ②实施例 1中剂量组( 10 mg/kg, PO, 给药 7d ) ; ③实施例 1 小剂量组(5 mg/kg, PO, 给药 7d ) ; ④帕罗西汀组(3 mg/kg, PO, 给药 7d ) ; ⑤生理盐水组(PO ) 。 2.5.2 实验方法 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

在第 8天给药后 1小时测定小鼠肛温,然后经腹腔注射利血平 2 mg/kg, 在注射利血平后 4小时再测定小鼠肛温。每次测温时温度计插入小鼠肛门的 深度及时间均一致。  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.

2.5.3 统计学处理  2.5.3 Statistical processing

实验资料用 表示,实验结果用 SPSS 11.5统计软件进行方差分析。 2.5.4 实验结果  The experimental data were expressed and the experimental results were analyzed by SPSS 11.5 statistical software. 2.5.4 Experimental results

实验结果请参阅表 2。 See Table 2 for the experimental results.

Figure imgf000013_0001
Figure imgf000013_0001

组 另' J 动物数(只) 小鼠体温下降值 ( °C ) 生理盐水组(模型组) 10 3.65±0.77  Group Another 'J animal number (only) mouse body temperature drop value ( °C ) saline group (model group) 10 3.65 ± 0.77

帕罗西汀组 10 2.38+0.69**  Paroxetine group 10 2.38+0.69**

实施例 1大剂量组 10 1.85+1.01**  Example 1 High dose group 10 1.85+1.01**

实施例 1中剂量组 10 2.05+1.03**  Example 1 Medium dose group 10 2.05+1.03**

实施例 1小剂量组 10 3.30+0.69  Example 1 Low dose group 10 3.30+0.69

注: 与模型组比较 * p<0.05 * *P<0.01  Note: Compared with the model group * p<0.05 * *P<0.01

结论:  in conclusion:

根据以上实验, 可以看出本发明实施例 1大、 中、 小剂量组和帕罗西汀 组均可减少利血平诱导的小鼠体温下降,大剂量组和中剂量组与生理盐水组 According to the above experiment, it can be seen that 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.

(模型组)相比有显著性差异,从而可以推断本发明实施例 1具有抗实验性 抑郁功能( 修改、 等同变化与修饰, 均仍属于本发明技术方案的范围内 工业实用性 There is a significant difference (model group), so that it can be inferred that the embodiment 1 of the present invention has anti-experimental depression function ( modification, equivalent change and modification, all still fall within the scope of the technical scheme of the present invention. Industrial applicability

本发明用于治疗忧郁症的口服药物的应用范围:  The scope of application of the oral medicament of the present invention for treating depression:

• 1.本发明所述用于治疗忧郁症的口服药物中, 可以含有药物学上可接受 的添力 P剂;  1. The oral drug for treating depression according to the present invention may comprise a pharmaceutically acceptable Additive P agent;

2.本发明所述的用于治疗忧郁症的口服药物可以将其加工制成散剂、 胶 嚢剂、 片剂等各种习知的剂型; 以及  2. 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;

3.本发明所述的用于治疗忧郁症的口服药物可以制用于治疗忧郁症的 保健食品及营养剂。  3. The oral medicament for treating depression according to the present invention can be used for the treatment of health foods and nutrients for depression.

Claims

权 利 要 求 书 Claim 1. 一种治疗忧郁症的药物組合物, 包括由一甘草及一大枣为原料所制 成。 A pharmaceutical composition for treating depression, comprising a licorice and a jujube as a raw material. 2. 如权利要求 1所述的药物组合物,其中所述药物组合物包括由 2 ~ 32 重量份的所述甘草及 2 ~ 42重量份的所述大枣为原料所制成。 The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition comprises 2 to 32 parts by weight of the licorice and 2 to 42 parts by weight of the jujube as a raw material. . . 3.如权利要求 2所述的药物组合物,其中所述药物组合物还包括由 5 ~ 15重量份的所述甘草及 4 ~ 20重量份的所述大枣为原料所制成。 The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition further comprises 5 to 15 parts by weight of the licorice and 4 to 20 parts by weight of the jujube as a raw material. 4.如权利要求 1 所述的药物组合物, 其中所述药物组合物含有选自药 学上可接受的一载体、 一添加剂或其组合。 The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition contains a carrier selected from a pharmaceutically acceptable one, an additive, or a combination thereof. 5. 如权利要求 1所述的药物组合物, 其中所述药物组合物制成一剂型, 所述剂型包括选自一锭剂、一胶嚢剂、一散剂、一片剂、一粉剂、一溶液剂、 一微嚢剂、 一混悬剂、 一乳剂、 一颗粒剂、 一滴丸剂、 一丸剂及药剂学上的 一口服药物剂型中的任一种。 The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is formulated into a dosage form comprising a tablet, a capsule, a powder, a tablet, a powder, and a dosage form. Any one of a solution, a microinjector, a suspension, an emulsion, a granule, a pill, a pill, and a pharmaceutically acceptable oral pharmaceutical dosage form. 6. 如权利要求 1 所述的药物组合物, 其中所述药物组合物制成一保健 食品或一营养剂。 6. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is formulated into a health food or a nutrient. 7. 一种治疗忧郁症的药物组合物, 包括由一大枣提取物及一甘草酸类 为原料所制成, 其中所述甘草酸类包括选自一甘草提取物、一甘草酸、 一甘 草次酸及其组合中的任一种。 A pharmaceutical composition for treating depression, comprising a jujube extract and a glycyrrhizic acid as a raw material, wherein the glycyrrhizic acid comprises a glycyrrhizic acid extract, a glycyrrhizic acid, a licorice Any of a hypoacid and a combination thereof. 8. 如权利要求 7 所述的药物组合物, 其中所述药物组合物包括含 0.01-0.2重量份大枣环磷酸腺苷的所述大枣提取物及含 4-64重量份甘草酸 的所述甘草提取物。 The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition comprises the jujube extract containing 0.01-0.2 parts by weight of jujube cyclic adenosine monophosphate and the solution containing 4-64 parts by weight of glycyrrhizic acid. The licorice extract is described. 9. 如权利要求 7 所述的药物组合物, 其中所述药物組合物包括含 0.01-0.2重量份大枣环磷酸腺苷的所述大枣提取物及含 4 ~ 64重量份选自所 述甘草酸、 所述甘草次酸或其组合中的任一种。 The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition comprises the jujube extract containing 0.01-0.2 parts by weight of jujube cyclic adenosine monophosphate and 4 to 64 parts by weight selected from the group consisting of Any one of glycyrrhizic acid, the glycyrrhetic acid, or a combination thereof. . . 10. 如权利要求 7 所述的药物组合物, 其中所述药物组合物包括含 0.024-0.12重量份大枣环嶙酸腺苷的所述大枣提取物及含 10 - 30重量份甘 草酸的所述甘草提取物。 The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition comprises the jujube extract containing 0.024 to 0.12 parts by weight of jujube cyclamate and 10 to 30 parts by weight of glycyrrhizic acid. The licorice extract. 11. 如权利要求 7所述的药物组合物, 其中所述药物组合物还包括含 0.024-0.12重量份大枣环磷酸腺苷的所述大枣提取物及含 10-30重量份选自 所述甘草酸、 所述甘草次酸或其组合中的任一种。 The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition further comprises the jujube extract containing 0.024 to 0.12 part by weight of jujube cyclic adenosine monophosphate and 10 to 30 parts by weight of the selected Any one of glycyrrhizic acid, the glycyrrhetic acid, or a combination thereof. 12. 如权利要求 7所述的药物組合物, 其中所述含大枣环磷酸腺苷的原 料是下述的一第二提取物:先提取一大枣获得一第一提取物,再纯化所述第 一提取物得所述第二提取物,其中所述笫二提取物的大枣环磷酸腺苷浓度高 于所述第一提取物的大枣环磷酸腺苷浓度。 The pharmaceutical composition according to claim 7, wherein the raw material containing jujube cyclic adenosine monophosphate is a second extract: first extracting a large jujube to obtain a first extract, and then purifying the The first extract obtains the second extract, wherein the concentration of the jujube cyclic adenosine monophosphate of the second extract is higher than the concentration of the jujube cyclic adenosine monophosphate of the first extract. 13. 如权利要求 7所述的药物组合物, 其中所述药物组合物含有选自药 学上可接受的一载体、 一添加剂或其组合。 13. The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition comprises a carrier selected from the group consisting of a pharmaceutically acceptable carrier, an additive, or a combination thereof. 14. 如权利要求 7所述的药物组合物,其中所述药物组合物制成一剂型, 所述剂型包括选自一锭剂、一胶嚢剂、一散剂、一片剂、一粉剂、一溶液剂、 一微嚢剂、 一混悬、剂、 一乳剂、 一颗粒剂、 一滴丸剂、 一丸剂及药剂学上的 一口服药物剂型中的任一种。 The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition is formulated into a dosage form comprising a tablet selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, and a Any one of a solution, a microinjector, a suspension, an emulsion, a granule, a pill, a pill, and a pharmaceutically acceptable oral pharmaceutical dosage form. 15.如权利要求 7所述的药物组合物, 其中所述药物组合物制成一保健 食品或一营养剂。 The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition is formulated into a health food or a nutrient. 16. 一种治疗忧郁症的药物组合物的制备方法, 包括以下步驟: (a)提取 4〜64重量份的一甘草, 得一第一甘草提取物; A method for preparing a pharmaceutical composition for treating depression, comprising the steps of: (a) extracting 4 to 64 parts by weight of licorice to obtain a first licorice extract; (b)提取 2~42重量份的一大枣, 得一第一大枣提取物; (b) extracting 2 to 42 parts by weight of a large jujube, and obtaining a first jujube extract; (c)纯化所述笫一大枣提取物, 得一笫二大枣提取物; 及 (c) purifying the extract of the jujube and jujube extract, and obtaining an extract of jujube and jujube; (d)混合所述第一甘草提取物及所述第二大枣提取物, 得所述药物组合 物, 其中所述第二大枣提取物的大枣环磷酸腺苷浓度高于所述第一大枣提 取物的大枣环磷酸腺苷浓度。 (d) mixing the first licorice extract and the second jujube extract to obtain the pharmaceutical composition, The concentration of the cyclic adenosine monophosphate of the jujube extract of the second jujube extract is higher than the concentration of the cyclic adenosine monophosphate of the jujube extract of the first jujube extract. 17.如权利要求 16所述的制备方法, 其中步 (a)还包括: The preparation method according to claim 16, wherein the step (a) further comprises: (al)纯化所述第一甘草提取物, 得一第二甘草提取物, 其中所述第二甘草提取物的甘草酸浓度高于所述第一甘草提取物的甘 草酸浓度。 (al) Purifying the first licorice extract to obtain a second licorice extract, wherein the second licorice extract has a glycyrrhizic acid concentration higher than a glycyrrhizic acid concentration of the first licorice extract. 18.如权利要求 16所述的制备方法, 其中步骤 (c)是选用一含醒基的大 孔树脂上柱吸附分离所述第一大枣提取物中的大枣环磷酸腺苷。 The preparation method according to claim 16, wherein the step (c) is: adsorbing and separating the jujube cyclic adenosine monophosphate in the first jujube extract by using a macroporous resin upper column containing a waking group. 19. 如权利要求 18所述的制备方法, 其中步骤 (c)是选用一含 基的大 孔树脂 OU-2上柱吸附分离所述第一大枣提取物中的大枣环磷酸腺苷。 The preparation method according to claim 18, wherein the step (c) is carried out by adsorbing and separating the jujube cyclic adenosine monophosphate in the first jujube extract by using a matrix-containing macroporous resin OU-2. 20. 如权利要求 18所述的制备方法, 其中步骤 (c)再以一孔树脂 ME-2 上柱分离所述第一大枣提取物中的大枣环磷酸腺苷。 The preparation method according to claim 18, wherein the step (c) further separates the jujube cyclic adenosine monophosphate in the first jujube extract by a column of a resin ME-2.
PCT/CN2007/003387 2007-11-30 2007-11-30 A pharmaceutical composition for treating depression and a preparation process thereof Ceased WO2009070916A1 (en)

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CN1836687A (en) * 2005-03-25 2006-09-27 北京欧纳尔生物工程技术有限公司 Pharmaceutical composition for treating depression and its making method

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1836687A (en) * 2005-03-25 2006-09-27 北京欧纳尔生物工程技术有限公司 Pharmaceutical composition for treating depression and its making method

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