WO2009070923A1 - A pharmaceutical composition for treating melancholy and preparation method thereof - Google Patents

A pharmaceutical composition for treating melancholy and preparation method thereof Download PDF

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Publication number
WO2009070923A1
WO2009070923A1 PCT/CN2007/003399 CN2007003399W WO2009070923A1 WO 2009070923 A1 WO2009070923 A1 WO 2009070923A1 CN 2007003399 W CN2007003399 W CN 2007003399W WO 2009070923 A1 WO2009070923 A1 WO 2009070923A1
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Prior art keywords
extract
jujube
pharmaceutical composition
ginseng
weight
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PCT/CN2007/003399
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French (fr)
Chinese (zh)
Inventor
Zuoguang Zhang
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Chi, Yu-Fen
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Priority to PCT/CN2007/003399 priority Critical patent/WO2009070923A1/en
Publication of WO2009070923A1 publication Critical patent/WO2009070923A1/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)
    • A61K36/25Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258Panax (ginseng)
    • 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 pharmaceutical composition for treating depression caused by ginseng and jujube, which can be used as a medicine, a nutrient and a health food.
  • the present invention also relates to a method of preparing the above pharmaceutical composition for treating depression. Background technique
  • 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.
  • the anti-depressant drugs that have been asked have different degrees of side effects, such as increased suicide rate, headache, dizziness, dizziness, insomnia, lethargy, deafness, dry mouth, anorexia, increased appetite, weight gain, and increased 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 asked the 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 ginseng 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 the treatment of depression or a method for preparing a health food prepared by using the above-mentioned ginseng and jujube as raw materials.
  • 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: Ginsenoside contains adenylate cyclase (AC) to stimulate adenosine and contains cAMP phosphodiesterase (CAPD) inhibitor; jujube cAMP can increase the expression of cAMP in human body, and the content of jujube is extremely small.
  • AC adenylate cyclase
  • CAD cAMP phosphodiesterase
  • jujube cAMP can increase the expression of cAMP in human body, and the content of jujube is extremely small.
  • BDNF brain-derived neurotrophic factor
  • HPA axis hyperthalamic-pituitary-adrenal axis
  • glucocorticoids glucocorticoids
  • the present invention discloses a pharmaceutical composition for treating depression, which is made from a raw material including ginseng and jujube.
  • the pharmaceutical composition of the present invention is prepared from a raw material comprising 4 to 62 parts by weight of ginseng and 2 to 42 parts by weight of jujube.
  • the pharmaceutical composition of the present invention is prepared from a raw material comprising 10 to 30 parts by weight of ginseng and 4 to 20 parts by weight of jujube.
  • the present invention discloses a pharmaceutical composition for treating depression, which is prepared from a raw material including ginseng and jujube extract extract.
  • the pharmaceutical composition of the present invention comprises an extract of ginseng comprising 4 to 62 parts by weight of ginsenosides (Rgl + Rbl ) and an extract of jujube extract containing 0.01-0.2 parts by weight of jujube cyclic adenosine monophosphate. Made of raw materials.
  • the pharmaceutical composition of the present invention is a raw material comprising a ginseng extract containing 12-36 parts by weight of ginsenosides (Rgl + Rbl ) and a jujube extract containing 0.024-0.12 parts by weight of jujube cyclic adenosine monophosphate. Made.
  • the jujube extract used in the pharmaceutical composition of the present invention is the following second extract: first extracting the jujube to obtain the extract, and then purifying the first extract to obtain the second extract;
  • the concentration of the cyclic adenosine monophosphate (jujube cAMP) of the second extract in the second extract is higher than the concentration of the cyclic adenosine monophosphate of the first extract.
  • the present invention discloses a method of 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 selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a microclay, a suspension, an emulsion, a granule, and a drip.
  • a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a microclay, a suspension, an emulsion, a granule, and a drip.
  • a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a microclay, a suspension, an emulsion, a granule, and a drip.
  • the pharmaceutical compositions of the invention may comprise a pharmaceutically acceptable carrier or additive.
  • the pharmaceutical compositions of the invention are also useful in the manufacture of health foods and nutraceuticals.
  • the above pharmaceutical composition is a core formulation for achieving the object of the present invention, and after the present invention is disclosed, those skilled in the art can routinely add and subtract the above-mentioned pharmaceutical composition according to the theory of traditional Chinese medicine or related modern pharmacological theory. Such conventional addition and subtraction is a general technical activity of those skilled in the art, and any general technical additions and subtractions made on the basis of the formulation of the pharmaceutical composition of the present invention are 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 schematic flow chart of a method for preparing a medicament of Example 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 using methods well known to those skilled in the art.
  • the following examples are for illustrative purposes only 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 from a raw material including ginseng and jujube.
  • the pharmaceutical composition for treating depression of the present invention is prepared from a raw material comprising 4 to 62 parts by weight of ginseng and 2 to 42 parts by weight of jujube.
  • the pharmaceutical composition for treating depression of the present invention is prepared from a raw material comprising 10 to 30 parts by weight of ginseng and 4 to 20 parts by weight of jujube.
  • the pharmaceutical composition for treating depression of the present invention is prepared from a raw material comprising ginseng extract and jujube extract.
  • the medicament for treating depression of the present invention is prepared from a raw material comprising a ginseng extract containing 4-62 parts by weight of ginsenosides (Rgl + Rbl ) and a jujube extract containing 0.01-0.2 parts by weight of jujube cyclic adenosine monophosphate. combination.
  • a raw material comprising a ginseng extract containing 4-62 parts by weight of ginsenosides (Rgl + Rbl ) and a jujube extract containing 0.01-0.2 parts by weight of jujube cyclic adenosine monophosphate. combination.
  • Option six is
  • the pharmaceutical composition for treating depression is prepared from a raw material comprising a ginseng extract containing 12 36 parts by weight of ginsenosides (Rgl + Rbl ) and a jujube extract containing 0.024-0.12 parts by weight of jujube cyclic adenosine monophosphate. Things.
  • the jujube extract according to the fourth aspect of the present invention is the 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 substance 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 first extract After crushing 4-62 parts by weight of ginseng, the first extract is obtained by heating with ethanol solution or water, and the first extract is separated and purified by column chromatography to obtain a second extract, wherein The concentration of ginsenoside (Rgl + Rbl ) of the second extract is higher than the concentration of ginsenoside (Rgl + Rbl ) of the first extract
  • the pharmaceutical composition of the present invention can be processed into a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a micro-dip, a suspension, an emulsion, a granule, a pill, and a pill. And one of the pharmacy oral pharmaceutical dosage forms.
  • a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a micro-dip, a suspension, an emulsion, a granule, a pill, and a pill.
  • a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a micro-dip, a suspension, an emulsion, a granule, a pill, and a pill.
  • compositions of the invention may include a pharmaceutically acceptable carrier or additive.
  • compositions of the invention may also be used to formulate health foods and nutrients.
  • Raw materials including ginseng and jujube are processed into a pharmaceutical composition for treating depression in the present invention.
  • a raw material comprising 4 to 62 parts by weight of ginseng and 2 to 42 parts by weight of jujube is processed to prepare a pharmaceutical composition for treating depression in the present invention.
  • a raw material comprising 10 30 parts by weight of ginseng and 4-20 parts by weight of jujube is processed to prepare a pharmaceutical composition for treating depression in the present invention.
  • a raw material including ginseng extract and jujube extract is processed to prepare a pharmaceutical composition for treating depression in the present invention.
  • ginseng extract containing 12 ⁇ 36 parts by weight of ginsenosides (Rgl + Rbl ) and
  • the raw material of the jujube extract of 0.024-0.12 parts by weight of jujube cyclic adenosine monophosphate is processed to prepare a pharmaceutical composition for treating depression in the present invention.
  • 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 is The concentration of cyclic adenosine monophosphate in jujube is higher than the concentration of adenosine monophosphate in the first extract.
  • composition of the invention for treating depression is prepared by a preparation method comprising the following steps:
  • Method nine The pharmaceutical composition of the present invention is processed into a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, an elixir, a suspension, an emulsion, a granule, a pill, and a pill. And one of the pharmacy oral pharmaceutical dosage forms.
  • compositions of the 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 drug of the embodiment 1 of the present invention.
  • Fig. 1 10 kg of ginseng was crushed, and the ginseng extract was extracted with 70% ethanol solution, and the ginseng extract was separated and purified by column chromatography, and dried to obtain 0.4 kg of ginseng extract (including 60).
  • FIG. 2 is a schematic flow chart of a method for preparing the drug of Example 2 of the present invention.
  • 1.2 g of ginsenoside Rgl having a purity of 90% and 2.8 g of ginsenoside Rbl having a purity of 90% are directly mixed with 0.8 g of a large amount of 0.8 mg of jujube cAMP.
  • Uniform that is, 4.8 g of the drug extract composition of the present invention.
  • 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.
  • Example 1 High dose of 60 mg/kg/d, medium dose of 30 mg/kg/d and low dose of 15 mg/kg/d
  • mice were randomized into groups of 10: 1. Example 1 high dose group (60 mg/kg, PO, 7d administration); 2. Example 1 dose group (30 mg/kg, PO, administration) 7d); 3. Example 1 low dose group (15 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 glued to the wooden strip with a head height of 5 cm.
  • Example 1 Effect of Example 1 on immobility time in mice Number of animals in the group (only) Immobility time (seconds) Physiological benefit water group (model group) 10 122.18 ⁇ 45.78 Paroxetine group 10 67.59 ⁇ 32.09**
  • Example 1 High dose group 10 106.92 ⁇ 36.89 Example 1 medium dose group 10 59.57 ⁇ 37.63**
  • the high, medium and low dose groups and the paroxetine group of the present invention can reduce the immobility time of the mice after the tail suspension, the middle dose and the low dose group and the saline group (model group). Compared with the significant difference, it can be inferred that the first embodiment of the present invention has anti-experimental depression work.
  • 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.
  • Example 1 High dose is 60 mg/kg/d, medium dose is 30 mg/kg d and low dose is I 5
  • mice were randomized into groups of 10: 1. Example 1 high dose group (60 mg/kg, PO, 7d administration); 2. Example 1 dose group (30 mg/kg, PO, administration) 7d); 3. Example 1 low dose group (15 mg / kg, PO, 7d administration); 4. Paroxetine group (3 mg kg, PO, 7d administration); 5. Saline group (PO). A forced swimming test was performed 1 hour after the last administration.
  • mice were placed in a glass jar with a water depth of 10 cm and a diameter of 14 cm, and the water temperature was 25 ° C. The cumulative immobility time of the mice in the water was recorded for 5 minutes.
  • Example 1 Low dose group 10 88.96 ⁇ 38.76 Note: Compared with the model group * P ⁇ 0.05 * ⁇ 0.01
  • the high, medium and low dose groups and the paroxetine group of the present invention can significantly shorten the cumulative immobility time of the forced swimming in the mice, the middle dose group and the high dose group and the saline group (model) There is a significant difference compared to the group), so it can be inferred that the embodiment 1 of the present invention has anti-reality Depressive depression.
  • the oral drug for treating depression according to the present invention may contain a pharmaceutically acceptable additive
  • the oral medicament for treating depression according to the present invention can be processed into various known dosage forms such as powders, capsules, tablets, and the like;
  • the oral medicament for treating depression according to the present invention can be formulated into a health food for treating depression.

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Abstract

A pharmaceutical composition for treating melancholy and preparation method thereof, said pharmaceutical composition is prepared by using ginseng and jujube as raw materials.

Description

一种治疗忧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
本发明涉及以人参、 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、营养剂和保健食品使用。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。 背景技术  The present invention relates to a pharmaceutical composition for treating depression caused by ginseng and jujube, which can be used as a medicine, a nutrient and a health food. The present invention also relates to a method of preparing the above pharmaceutical composition for treating depression. 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、 赛乐特、 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、 头暈、 暈眩、 失眠、 嗜睡、耳呜、 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 )更于 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 能增加儿童及青少年自杀的机率。 其中, 赛乐特更是早在 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 性隐瞒了服用 赛乐特与"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。 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、 E、 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, 临床试验表明其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。 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, deafness, dry mouth, anorexia, increased appetite, weight gain, and increased 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 asked the 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, Celite 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 concealing a study related to the use of Celet and "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-depressant effects has become a concern of the global pharmaceutical community. 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 with 5-HT, E, and DA reuptake inhibition, adjustment can be adopted. The post-receptor 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 post-receptor mechanism of action drug 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.
综上所述, 申请人在了解了公知技术中所具有的局限性后, 经过悉心研 究与探索, 并本着锲而不舍的精神, 终于发现了本发明的 "以甘草、 大枣为 原料的治疗忧郁症的药物组合物及其制法,, , 以下为本发明的筒要说明。 发明内容  In summary, after understanding the limitations of the known technology, the applicant has carefully studied and explored, and in the spirit of perseverance, finally discovered the treatment of melancholy and jujube as the raw material for the treatment of depression. The pharmaceutical composition of the disease and the preparation method thereof, the following is a description of the cartridge of the present 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人参、 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 ginseng 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人参、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 the treatment of depression or a method for preparing a health food prepared by using the above-mentioned ginseng and jujube as raw materials.
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: 人参皂甙含有腺苷酸环化酶(adenylate cyclase, AC )刺激腺苷, 并含有 cAMP磷酸二酯酶(CAPD )的抑制成份; 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的大枣提取物来进行抗试猃性 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; 人参皂甙、 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, E ) 等神经递质的合成与释放, 增强脑源性神经营养因子 ( brain-derived neurotrophic factor, BDNF ) 的表达, 抑制下丘脑-垂体-肾上腺轴 ( hypothalamic-pituitary-adrenal axis, HPA轴)的亢进和糖皮质激素的分泌, 从而达到显著的抗忧郁功能。人参、 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, 已充分证明人参、 大枣 二者配伍的安全性, 而服用人参及大枣不会发生强烈呕吐等副作用,故发明 人提出以人参及大枣为原料, 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 技术方案以改进公知技术中所具有的不足之处。 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: Ginsenoside contains adenylate cyclase (AC) to stimulate adenosine and contains cAMP phosphodiesterase (CAPD) inhibitor; jujube cAMP can increase the expression of cAMP in human body, and the content of jujube is extremely small. (About 1 in 10,000) of jujube cAMP extracted and purified into jujube extract containing 1% jujube cAMP for anti-test depressive effect animal test results show that it has obvious anti-test depression function, and Jujube extract containing normal jujube cAMP does not have obvious anti-test depression function; ginsenoside, Jujube cAMP compatibility, synergistic effect, can further improve the utilization and activity of cAMP, and the concentration and activity of cAMP can increase the synthesis and release of neurotransmitters such as norepinephrine (E). The expression of brain-derived neurotrophic factor (BDNF) inhibits the hyperthalamic-pituitary-adrenal axis (HPA axis) and the secretion of glucocorticoids, thereby achieving significant Anti-depressant function. Ginseng and jujube are commonly used medicines 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 ginseng and jujube has been fully proved, and ginseng and large ginseng are used. Jujube does not cause side effects such as strong vomiting. Therefore, the inventors propose to use ginseng and jujube as raw materials to prepare oral or health foods for the treatment of depression. In particular, the efficacy ingredients are clear, and long-term safety is high, and will not cause New technical solutions for side effects such as strong vomiting to improve the deficiencies in the known art.
为了完成本发明的目的, 特提出以下技术方案。  In order to accomplish the object of the present invention, the following technical solutions are proposed.
本发明揭露了一种用于治疗忧郁症的药物组合物,所述药物组合物是由 包括人参、 大枣的原料所制成。  The present invention discloses a pharmaceutical composition for treating depression, which is made from a raw material including ginseng and jujube.
优选地, 本发明的药物组合物, 是由包括 4~62重量份的人参及 2〜42 重量份的大枣的原料所制成。  Preferably, the pharmaceutical composition of the present invention is prepared from a raw material comprising 4 to 62 parts by weight of ginseng and 2 to 42 parts by weight of jujube.
优选地, 本发明的药物组合物, 是由包括 10~30重量份的人参及 4~20 重量份的大枣的原料所制成。  Preferably, the pharmaceutical composition of the present invention is prepared from a raw material comprising 10 to 30 parts by weight of ginseng and 4 to 20 parts by weight of jujube.
才艮据本发明的另一概念,本发明揭露了一种用于治疗忧郁症的药物組合 物, 所述药物组合物是由包括人参、 大枣提取提取物的原料所制成。  According to another concept of the present invention, the present invention discloses a pharmaceutical composition for treating depression, which is prepared from a raw material including ginseng and jujube extract extract.
优选地,本发明的药物组合物,是由包括含 4~62重量份人参皂甙(Rgl + Rbl )的人参提取提取物及含 0.01-0.2重量份大枣环腺苷酸的大枣提取提 取物的原料所制成。  Preferably, the pharmaceutical composition of the present invention comprises an extract of ginseng comprising 4 to 62 parts by weight of ginsenosides (Rgl + Rbl ) and an extract of jujube extract containing 0.01-0.2 parts by weight of jujube cyclic adenosine monophosphate. Made of raw materials.
优选地,本发明的药物组合物,是由包括含 12-36重量份人参皂甙(Rgl + Rbl )的人参提取物及含 0.024-0.12重量份大枣环磷酸腺苷的大枣提取物 的原料所制成。  Preferably, the pharmaceutical composition of the present invention is a raw material comprising a ginseng extract containing 12-36 parts by weight of ginsenosides (Rgl + Rbl ) and a jujube extract containing 0.024-0.12 parts by weight of jujube cyclic adenosine monophosphate. Made.
优选地, 本发明的药物组合物中所用的大枣提取物是下述的第二提取 物: 先提取大枣获得笫一提取物, 再纯化所述第一提取物得第二提取物; 其 中所述第二提取物的大枣环磷酸腺苷 (大枣 cyclic adenosine monophosphate, 大枣 cAMP )浓度高于所述第一提取物的大枣环磷酸腺苷浓度。 Preferably, the jujube extract used in the pharmaceutical composition of the present invention is the following second extract: first extracting the jujube to obtain the extract, and then purifying the first extract to obtain the second extract; The concentration of the cyclic adenosine monophosphate (jujube cAMP) of the second extract in the second extract is higher than the concentration of the cyclic adenosine monophosphate of the first extract.
根据本发明的另一概念,本发明揭露了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 discloses a method of preparing a pharmaceutical composition for treating depression, comprising the steps of:
(a)将 4〜62 重量份的人参破碎后用乙醇溶液或水加温提取得第一提取 物,将所述第一提取物上柱层析分离纯化后得第二提取物, 其中所迷第二提 取物的人参皂甙(Rgl + Rbl )浓度高于所述第一提取物的人参皂甙(Rgl + Rbl )浓度;  (a) 4 to 62 parts by weight of ginseng is crushed and then extracted with an ethanol solution or 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 ginsenoside (Rgl + Rbl ) of the second extract is higher than the concentration of ginsenoside (Rgl + Rbl ) of the first extract;
(b)将 2〜42重量份的大枣破碎后用水加温提取得第一提取物, 将所述第 —提取物上柱层析分离纯化后得第二提取物,其中所述第二提取物的大枣环 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; 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 first extract;
(c)将步驟 (a)及步骤 (b)所得的人参第二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 ginseng second extract obtained in the steps (a) and (b) and the jujube second extract are mixed and pulverized to obtain the pharmaceutical composition of the present invention.
优选地, 本发明的药物组合物可以加工制成剂型, 该剂型选自锭剂、胶 嚢剂、 散剂、 片剂、 粉剂、 溶液剂、 微嚢剂、 混悬剂、 乳剂、 颗粒剂、 滴丸 剂、 丸剂及药剂学上的口服药物剂型之一。  Preferably, the pharmaceutical composition of the present invention can be processed into a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a microclay, a suspension, an emulsion, a granule, and a drip. One of the oral pharmaceutical dosage forms of pills, pills and pharmaceutics.
优选地, 本发明的药物组合物可以包括药学上可接受的载体或添加剂。 优选地, 本发明的药物组合物还可用来制成保健食品和营养剂。  Preferably, the pharmaceutical compositions of the invention may comprise a pharmaceutically acceptable carrier or additive. Preferably, the pharmaceutical compositions of the invention are also useful in the manufacture of health foods and nutraceuticals.
上述的药物组合物是实现本发明目的的核心配方,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础上所进行的一般性技术加 减, 均在本发明的保护范围之内。  The above pharmaceutical composition is a core formulation for achieving the object of the present invention, and after the present invention is disclosed, those skilled in the art can routinely add and subtract the above-mentioned pharmaceutical composition according to the theory of traditional Chinese medicine or related modern pharmacological theory. Such conventional addition and subtraction is a general technical activity of those skilled in the art, and any general technical additions and subtractions made on the basis of the formulation of the pharmaceutical composition of the present invention are within the scope of the present invention.
通过参阅附图及伴细说明可以更好地了解本发明。 附图概述  The invention may be better understood by reference to the drawings and accompanying drawings. 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 2 is a schematic flow chart of a method for preparing a medicament of Example 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 技术人员公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 仅仅是为了说明, 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 using methods well known to those skilled in the art. The following examples are for illustrative purposes only 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的技术方案。  In order to accomplish the object of the present invention, the present invention particularly proposes the following technical solutions.
方案一: Option One:
以包括人参、 大枣的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 from a raw material including ginseng and jujube.
方案二: Option II:
以包括 4~62重量份的人参及 2〜42重量份的大枣的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 from a raw material comprising 4 to 62 parts by weight of ginseng and 2 to 42 parts by weight of jujube.
方案三: third solution:
以包括 10~30重量份的人参及 4-20重量份的大枣的原料制成本发明用 于治疗忧郁症的药物組合物。  The pharmaceutical composition for treating depression of the present invention is prepared from a raw material comprising 10 to 30 parts by weight of ginseng and 4 to 20 parts by weight of jujube.
方案四: Option 4:
以包括人参提取物及大枣提取物的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 from a raw material comprising ginseng extract and jujube extract.
方案五: Option 5:
以包括含 4-62重量份人参皂甙( Rgl + Rbl )的人参提取物及含 0.01-0.2 重量份大枣环磷酸腺苷的大枣提取物的原料制成本发明用于治疗忧郁症的 药物組合物。 方案六: The medicament for treating depression of the present invention is prepared from a raw material comprising a ginseng extract containing 4-62 parts by weight of ginsenosides (Rgl + Rbl ) and a jujube extract containing 0.01-0.2 parts by weight of jujube cyclic adenosine monophosphate. combination. Option six:
以包括含 12 36 重量份人参皂甙 (Rgl + Rbl ) 的人参提取物及含 0.024-0.12 重量份大枣环磷酸腺苷的大枣提取物的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 from a raw material comprising a ginseng extract containing 12 36 parts by weight of ginsenosides (Rgl + Rbl ) and a jujube extract containing 0.024-0.12 parts by weight of jujube cyclic adenosine monophosphate. Things.
方案七: Option seven:
本发明方案四所述的大枣提取物是下述的第二提取物:先提取大枣获得 第一提取物,再纯化所述第一提取物得第二提取物; 其中所述第二提取物的 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 jujube extract according to the fourth aspect of the present invention is the 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 substance 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 4-62重量份的人参破碎后, 以乙醇溶液或水加温提取得第一提取 物,将所述第一提取物上柱层析分离纯化后得第二提取物,其中所述第二提 取物的人参皂甙(Rgl + Rbl ) 浓度高于所述第一提取物的人参皂甙(Rgl + Rbl )浓度  (a) After crushing 4-62 parts by weight of ginseng, the first extract is obtained by heating with ethanol solution or water, and the first extract is separated and purified by column chromatography to obtain a second extract, wherein The concentration of ginsenoside (Rgl + Rbl ) of the second extract is higher than the concentration of ginsenoside (Rgl + Rbl ) of the first extract
' (b)将 2~42重量份的大枣破碎后, 以水加温提取得笫一提取物, 将所述 笫一提取物上柱层析分离纯化后得第二提取物,其中所述第二提取物的大枣 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; 及  (b) after crushing 2 to 42 parts by weight of jujube, extracting the extract with water and heating, and separating and purifying the extract of the same extract by column chromatography to obtain a second extract, wherein The concentration of the adenine cyclic adenosine monophosphate of the second extract is higher than the concentration of the adenosine adenosine monophosphate of the first extract;
(c)将步骤 (a)及步骤 (b)所得的人参第二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 ginseng second extract obtained in the steps (a) and (b) and the jujube second extract 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剂型, 该剂型选自锭剂、胶嚢剂、散 剂、 片剂、 粉剂、 溶液剂、 微嚢剂、 混悬剂、 乳剂、 颗粒剂、 滴丸剂、 丸剂 及药剂学上的口服药物剂型之一。 方案十: The pharmaceutical composition of the present invention can be processed into a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a micro-dip, a suspension, an emulsion, a granule, a pill, and a pill. And one of the pharmacy oral pharmaceutical dosage forms. Option 10:
本发明的药物组合物可以包括药学上可接受的载体或添加剂。  The pharmaceutical compositions of the invention may include a pharmaceutically acceptable carrier or additive.
方案十一: Option 11:
本发明的药物组合物还可用来制成保健食品和营养剂。  The pharmaceutical compositions of the invention may also be used to formulate health foods and nutrients.
为了完成本发明的目的, 特提出以下的药物制备方法。 In order to accomplish the object of the present invention, the following pharmaceutical preparation methods are specifically proposed.
方法一: method one:
将包括人参、 大枣的原料,加工制成本发明用于治疗忧郁症的药物组合 物。  Raw materials including ginseng and jujube are processed into a pharmaceutical composition for treating depression in the present invention.
方法二: Method Two:
将包括 4~62重量份的人参及 2-42重量份的大枣的原料,加工制成本发 明用于治疗忧郁症的药物組合物。  A raw material comprising 4 to 62 parts by weight of ginseng and 2 to 42 parts by weight of jujube is processed to prepare a pharmaceutical composition for treating depression in the present invention.
方法三: Method three:
将包括 10 30重量份的人参及 4-20重量份的大枣的原料, 加工制成本 发明用于治疗忧郁症的药物组合物。  A raw material comprising 10 30 parts by weight of ginseng and 4-20 parts by weight of jujube is processed to prepare a pharmaceutical composition for treating depression in the present invention.
方法四: Method four:
将包括人参提取物及大枣提取物的原料,加工制成本发明用于治疗忧郁 症的药物组合物。  A raw material including ginseng extract and jujube extract is processed to prepare a pharmaceutical composition for treating depression in the present invention.
方法五: Method five:
将包括含 4-62重量份人参皂甙( Rgl + Rbl )的人^ ^取物及含 0.01-0.2 重量份大枣环磷酸腺苷的大枣提取物的原料,加工制成本发明用于治疗忧郁 症的药物组合物。 Will include 4-62 parts by weight of ginsenosides (Rgl + Rbl) and contain 0.01-0.2 The raw material of the jujube extract of the jujube cyclic adenosine monophosphate is processed to prepare a pharmaceutical composition for treating depression in the present invention.
方法六: Method six:
将包括含 12~36 重量份人参皂甙(Rgl + Rbl ) 的人参提取物及含 It will include ginseng extract containing 12~36 parts by weight of ginsenosides (Rgl + Rbl ) and
0.024-0.12重量份大枣环磷酸腺苷的大枣提取物的原料, 加工制成本发明用 于治疗忧郁症的药物组合物。 The raw material of the jujube extract of 0.024-0.12 parts by weight of jujube cyclic adenosine monophosphate is processed to prepare a pharmaceutical composition for treating depression in the present invention.
方法七: Method seven:
方法四所述的大枣提取物是下述的第二提取物:先提取大枣获得第一提 取物,再纯化所述第一提取物得第二提取物; 其中所述第二提取物的大枣环 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 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 is The concentration of cyclic adenosine monophosphate in jujube is higher than the concentration of 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 4~62 重量份的人参破碎后用乙醇溶液或水加温提取得第一提取 物,将所述第一提取物上柱层析分离纯化后得第二提取物, 其中所述第二提 取物的人参皂甙(Rgl + Rbl )浓度高于所述第一提取物的人参皂武 ( Rgl + Rbl )浓度;  (a) 4 to 62 parts by weight of ginseng is crushed and then extracted with an ethanol solution or water to obtain a first extract, and the first extract is subjected to column chromatography separation and purification to obtain a second extract, wherein The concentration of ginsenoside (Rgl + Rbl ) of the second extract is higher than the concentration of ginsenoside (Rgl + Rbl ) of the first extract;
(b)将 2-42重量份的大枣破碎后用水加温提取得第一提取物, 将所述第 一提取物上柱层析分离纯化后得第二提取物,其中所述第二提取物的大枣环 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; 及  (b) 22-4 parts by weight of 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 The concentration of the adenosine monophosphate of the jujube is higher than the concentration of the adenosine monophosphate of the first extract;
(c)将步骤 (a)及步骤 (b)所得的人参第二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 ginseng second extract obtained in the steps (a) and (b) and the jujube second extract are mixed and pulverized to obtain the pharmaceutical composition of the present invention.
方法九: 将本发明的药物组合物加工制成剂型,该剂型选自锭剂、胶嚢剂、散剂、 片剂、 粉剂、 溶液剂、 敫嚢剂、 混悬剂、 乳剂、 颗粒剂、 滴丸剂、 丸剂及药 剂学上的口服药物剂型之一。 Method nine: The pharmaceutical composition of the present invention is processed into a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, an elixir, a suspension, an emulsion, a granule, a pill, and a pill. And one of the pharmacy oral pharmaceutical dosage forms.
方法十: Method ten:
将本发明的药物组合物加工制成包括药学上可接受的载体或添加剂。  The pharmaceutical compositions of the 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.
具体实施例 Specific embodiment
以下将结合附图和具体实施例进一步说明本发明。  The invention will be further illustrated by the following figures and specific examples.
实施例 1 Example 1
请参阅图 1, 其为制备本发明实施例 1药物的方法流程示意图。 在图 1 中, 将 10 kg的人参破碎, 以 70%乙醇溶液加温提取得人参提取物, 再将该 人参提取物上柱层析分离纯化, 干燥, 得 0.4 kg的人参提取物 (含 60 g人 参皂甙 Rgl + Rbl ) ; 将 2 kg大枣破碎后加水常温浸泡, 再以水提醇沉法提 取获得大枣提取物,再将该提取物用大孔树脂 OU-2、 ME-2两柱先后连续上 柱吸附分离、 干燥, 得 6 g的大枣提取物(含 0.06 g大枣 cAMP ) , 将上述 步骤所得提取物混合粉碎均匀, 即得 406 g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 drug of the embodiment 1 of the present invention. In Fig. 1, 10 kg of ginseng was crushed, and the ginseng extract was extracted with 70% ethanol solution, and the ginseng extract was separated and purified by column chromatography, and dried to obtain 0.4 kg of ginseng extract (including 60). g ginsenoside Rgl + Rbl ); 2 kg jujube is crushed, soaked in water at room temperature, and extracted with water and alcohol precipitation to obtain jujube extract, and then the extract is made of macroporous resin OU-2, ME-2 The column was successively adsorbed and separated by a column, and dried to obtain 6 g of jujube extract (containing 0.06 g of jujube cAMP). The extract obtained in the above step was mixed and pulverized uniformly to obtain 406 g of the pharmaceutical composition of the present invention.
实施例 2 Example 2
请参阅图 2, 其为制备本发明实施例 2药物的方法流程示意图。 在图 2 中,直接将已制备成純度为 90%的 1.2 g的人参皂甙 Rgl及纯度为 90%的 2.8 g的人参皂甙 Rbl与含 8 mg大枣 cAMP的大^是取物 0.8 g混合粉碎均匀, 即得 4.8 g本发明药物提取物组合物。 实验例 1 实施例 1对小鼠悬尾实验的影响 Please refer to FIG. 2 , which is a schematic flow chart of a method for preparing the drug of Example 2 of the present invention. In Fig. 2, 1.2 g of ginsenoside Rgl having a purity of 90% and 2.8 g of ginsenoside Rbl having a purity of 90% are directly mixed with 0.8 g of a large amount of 0.8 mg of jujube cAMP. Uniform, that is, 4.8 g of the drug extract composition of the present invention. Experimental Example 1 Effect of Example 1 on Mouse Suspension Experiment
1.1 实 动物 1.1 Real animal
' 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.
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 实验仪器  1.3 Experimental instruments
秒表。  Stopwatch.
1.4 剂量设计 1.4 Dose design
实施例 1 高剂量为 60 mg/kg/d、 中剂量为 30 mg/kg/d及低剂量为 15 mg/kg/d„  Example 1 High dose of 60 mg/kg/d, medium dose of 30 mg/kg/d and low dose of 15 mg/kg/d
1.5 实验方法及结果  1.5 Experimental methods and results
1.5.1 分組给药 1.5.1 Group administration
将小鼠随机分组, 每组 10只: 1.实施例 1高剂量组(60 mg/kg, PO, 给药 7d ); 2.实施例 1中剂量组(30 mg/kg, PO, 给药 7d ); 3.实施例 1低 剂量组(15 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 high dose group (60 mg/kg, PO, 7d administration); 2. Example 1 dose group (30 mg/kg, PO, administration) 7d); 3. Example 1 low dose group (15 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 实验方法  1.5.2 Experimental 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 The tail of the mouse (1 cm from the tip of the tail) was glued to the wooden strip with a head height of 5 cm.
6分钟, 记录后 5分钟内小鼠的不动时间。 6 minutes, the immobility time of the mice within 5 minutes after recording.
1.5.3 统计学处理  1.5.3 Statistical processing
实验数据用 ±SD表示,实验结果用 SPSS 11.5统计软件进行方差分析。 1.5.4 实验结果  The experimental data were expressed by ±SD, and the experimental results were analyzed by SPSS 11.5 statistical software for analysis of variance. 1.5.4 Experimental 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 组 别 动物数(只) 不动时间 (秒) 生理益水組(模型組) 10 122.18±45.78 帕罗西汀组 10 67.59±32.09** 实施例 1高剂量組 10 106.92±36.89 实施例 1中剂量组 10 59.57±37.63** 实施例 1低剂量組 10 82.83±29.40* 注: 与模型组比较 * P<0.05 **P<0.01 Table 1. Effect of Example 1 on immobility time in mice Number of animals in the group (only) Immobility time (seconds) Physiological benefit water group (model group) 10 122.18±45.78 Paroxetine group 10 67.59±32.09** Example 1 High dose group 10 106.92±36.89 Example 1 medium dose group 10 59.57±37.63** Example 1 Low dose group 10 82.83±29.40* 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高、 中、低剂量组和帕罗西汀 组均可减少小鼠悬尾后的不动时间, 中剂量和低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 According to the above experiment, it can be seen that the high, medium and low dose groups and the paroxetine group of the present invention can reduce the immobility time of the mice after the tail suspension, the middle dose and the low dose group and the saline group (model group). Compared with the significant difference, it can be inferred that the first embodiment of the present invention has anti-experimental depression work.
At, At,
实验例 2 实施例 1对小鼠强迫游泳实验的影响 Experimental Example 2 Example 1 Effect on forced swimming test in mice
2.1 实睑动物 2.1 Real 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 实睑药品  2.2 Real 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 实验仪器 2.3 Experimental instruments
秒表。  Stopwatch.
2.4剂量设计  2.4 dose design
实施例 1 高剂量为 60 mg/kg/d, 中剂量为 30 mg/kg d及低剂量为 I5
Figure imgf000013_0001
Example 1 High dose is 60 mg/kg/d, medium dose is 30 mg/kg d and low dose is I 5
Figure imgf000013_0001
2.5.实验方法及结果 2.5.1 分組给药 2.5. Experimental methods and results 2.5.1 Group administration
将小鼠随机分组, 每组 10只: 1.实施例 1高剂量组(60 mg/kg, PO, 给药 7d ); 2.实施例 1中剂量组(30 mg/kg, PO, 给药 7d ); 3.实施例 1低 剂量组( 15 mg/kg, PO,给药 7d ); 4.帕罗西汀组( 3 mg kg, PO,给药 7d ); 5.生理盐水組(PO ) 。 最后一次给药 1小时后进行强迫游泳实验。  Mice were randomized into groups of 10: 1. Example 1 high dose group (60 mg/kg, PO, 7d administration); 2. Example 1 dose group (30 mg/kg, PO, administration) 7d); 3. Example 1 low dose group (15 mg / kg, PO, 7d administration); 4. Paroxetine group (3 mg kg, PO, 7d administration); 5. Saline group (PO). A forced swimming test was performed 1 hour after the last administration.
2.5.2 实验方法  2.5.2 Experimental methods
将小鼠分别放入水深 10 cm、 直径 14 cm的玻璃缸中, 水温 25°C , 观察 5分钟记录小鼠在水中的累计不动时间。  The mice were placed in a glass jar with a water depth of 10 cm and a diameter of 14 cm, and the water temperature was 25 ° C. The cumulative immobility time of the mice in the water was recorded for 5 minutes.
2.5.3 统计学处理  2.5.3 Statistical processing
实验数据用 土 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 was expressed in soil, and the experimental results were analyzed by SPSS 11.5 statistical software for analysis of variance. 2.5.4 Experimental results
实验结果请参阅表 2。  See Table 2 for the experimental results.
表 2、 实施例 1对小鼠不动时间的影响  Table 2. Example 1 Effect on immobility time of mice
组 别 动物数(只) 不动时间(秒) 生理盐水组(模型组) 10 114.83±40.59 帕 罗 西 汀 组 10 Group Number of animals (only) Immobility time (seconds) Saline group (model group) 10 114.83±40.59 Paroxetine group 10
76.58±45.04* 76.58±45.04*
实施例 1高剂量组 10 73.27±42.30* 实 施 例 1 中 剂 量 组 10 Example 1 High dose group 10 73.27±42.30* Example 1 Medium dosage group 10
64.33±35.82** 64.33±35.82**
实施例 1低剂量组 10 88.96±38.76 注: 与模型组比较 * P<0.05 *叩<0.01  Example 1 Low dose group 10 88.96±38.76 Note: Compared with the model group * P<0.05 *叩<0.01
结论: in conclusion:
根据以上实睑, 可以看出本发明实施例 1高、 中、 低剂量组和帕罗西汀 组均可明显缩短小鼠强迫游泳累计不动时间,中剂量組和高剂量组与生理盐 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, it can be seen that the high, medium and low dose groups and the paroxetine group of the present invention can significantly shorten the cumulative immobility time of the forced swimming in the mice, the middle dose group and the high dose group and the saline group (model) There is a significant difference compared to the group), so it can be inferred that the embodiment 1 of the present invention has anti-reality Depressive depression.
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. 本发明所述的用于治疗忧郁症的口服药物中, 可以含有药物学上可 接受的添加剂;  1. The oral drug for treating depression according to the present invention may contain a pharmaceutically acceptable additive;
. 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、 等各种已知的剂型; 以及  2. The oral medicament for treating depression according to the present invention can be processed into various known 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成用于治疗忧郁症 的保健食品。  3. The oral medicament for treating depression according to the present invention can be formulated into a health food for treating depression.
本领域技术人员可以对本发明做出各种改进,而不脱离如所附权利要求 的保护范围。  A person skilled in the art can make various modifications to the invention without departing from the scope of the appended claims.

Claims

权 利 要 求 书 Claim
1. 一种治疗忧郁症的药物组合物, 其由包括人参及大枣的原料制成。A pharmaceutical composition for treating depression, which is prepared from a raw material comprising ginseng and jujube.
2. 如权利要求 1 所述的药物组合物, 其中所述药物組合物进一步由包 括 4 ~ 62重量份的人参及 2 ~ 42重量份的大枣的原料制成。 The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is further prepared from a raw material comprising 4 to 62 parts by weight of ginseng and 2 to 42 parts by weight of jujube.
3. 如权利要求 2所述的药物组合物, 其中所述药物组合物进一步由包 括 10 ~ 30重量份的人参及 4 ~ 20重量份的大枣的原料制成。  The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition is further prepared from a raw material comprising 10 to 30 parts by weight of ginseng and 4 to 20 parts by weight of jujube.
4. 如权利要求 1所述的药物组合物, 其中所述药物含有选自药学上可 接受的载体、 添加剂及其组合。  4. The pharmaceutical composition according to claim 1, wherein the medicament comprises a carrier selected from the group consisting of pharmaceutically acceptable carriers, additives, and combinations 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剂型, 该剂型选自锭剂、 胶嚢剂、 散剂、 片剂、 粉剂、 溶液剂、 微嚢剂、 混悬剂、 乳剂、 颗粒剂、 滴丸剂、 丸剂及药剂学上的口服药物剂型之一。  The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is in a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a micro-tank, and a suspension. One of the oral pharmaceutical dosage forms of the agent, emulsion, granule, pill, pill and pharmacy.
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保健食 品或营养剂。  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, 其由包括人参提取物及大枣提取物 的原料制成。  A pharmaceutical composition for treating depression, which is prepared from a raw material comprising ginseng extract and jujube extract.
8. 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 4-62 重量份人参皂甙( Rgl + bl )的所述人参提取物及含 0.01-0.2重量份大枣 环磷酸腺苷的所述大枣提取物。  The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition comprises the ginseng extract containing 4 to 62 parts by weight of ginsenoside (Rgl + bl ) and 0.01 to 0.2 parts by weight of jujube cyclophosphate The jujube extract of adenosine.
9. 如权利要求 8所述的药物组合物, 其中所述药物組合物进一步包括 含 12~36重量份人参皂甙( Rgl + Rbl )的所述人参提取物及含 0.024-0.12 重量份大枣环磷酸腺苷的所迷大枣提取物。  The pharmaceutical composition according to claim 8, wherein the pharmaceutical composition further comprises the ginseng extract containing 12 to 36 parts by weight of ginsenoside (Rgl + Rbl ) and 0.04-10.12 parts by weight of jujube ring Jujube extract of adenosine phosphate.
10.如权利要求 7所述的药物组合物, 其中所述含大枣环磷酸腺苷的原 料是下述的第二提取物: 先提取大枣获得第一提取物,再纯化所述第一提取 物得所述第二提取物,其中所述第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碌酸腺苷浓度。  The pharmaceutical composition according to claim 7, wherein the raw material containing jujube cyclic adenosine monophosphate is the following second extract: first extracting jujube to obtain a first extract, and then purifying the first extract The 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 succinate adenosine of the first 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含有选自药 学上可接受的载体、 添加剂及其組合。 The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition contains a drug selected from the group consisting of Acceptable carriers, additives, and combinations thereof.
• 12. 如权利要求 7所述的药物组合物, 其中所述药物組合物制成剂型, 该剂型选自锭剂、 胶嚢剂、 散剂、 片剂、 粉剂、 溶液剂、 微嚢剂、 混悬剂、 乳剂、 颗粒剂、 滴丸剂、 丸剂及药剂学上的口服药物剂型之一。  The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition is in a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, a solution, a micro-tank, and a mixture. Suspension, emulsion, granules, pills, pills, and one of the pharmaceutically acceptable oral dosage forms.
13. 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保健食 品及营养剂。  13. The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition is formulated into a health food and a nutrient.
14.一种治疗忧郁症的药物组合物的制备方法, 包括以下步骤:  14. A method of preparing a pharmaceutical composition for treating depression comprising the steps of:
(a)提取 4 ~ 62重量份的人参, 得第一人参提取物;  (a) extracting 4 to 62 parts by weight of ginseng to obtain a first ginseng extract;
(b)提取 2 ~ 42重量份的大枣, 得第一大枣提取物;  (b) extracting 2 to 42 parts by weight of jujube to obtain the first jujube extract;
(c)纯化所述第一大枣提取物得第二大枣提取物; 及  (c) purifying the first jujube extract to obtain a second jujube extract;
(d)混合所述第一人参提取物及所述第二大枣提取物, 得该药物组合物, 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 ginseng extract and the second jujube extract to obtain the pharmaceutical composition, wherein the second jujube extract has a higher concentration of cyclic adenosine monophosphate than the first Jujube extract adenosine monophosphate concentration in jujube extract.
15.如权利要求 14所述的制备方法, 其中步骤 (a)进一步包括:  The preparation method according to claim 14, wherein the step (a) further comprises:
(al)纯化所述第一人参提取物, 得第二人参提取物,  (al) purifying the first ginseng extract to obtain a second ginseng extract,
其中所述第二人参提取物的人参皂甙(Rgl + Rbl )浓度高于所述第一 人参提取物的人参皂甙(Rgl + RM )浓度。  Wherein the concentration of ginsenoside (Rgl + Rbl ) of the second ginseng extract is higher than the concentration of ginsenoside (Rgl + RM ) of the first ginseng extract.
16. 如权利要求 14所述的制备方法, 其中步骤 (c)选用含 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 14, wherein the step (c) adsorbs and separates the jujube cyclic adenosine monophosphate in the first jujube extract by using a matrix-containing macroporous resin column.
17. 如权利要求 16所述的制备方法, 其中步骤 (c)选用含醒基的大孔树 脂 OU-2上柱吸附分离所述笫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 carried out by using a macroporous resin OU-2 containing a waking group to adsorb and separate the jujube cyclic adenosine monophosphate in the extract of the jujube.
18. 如权利要求 14所述的制备方法, 其中步骤 (c)再以大孔树脂 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 14, wherein the step (c) further separates the jujube cyclic adenosine monophosphate in the first jujube extract with a macroporous resin ME-2 column.
PCT/CN2007/003399 2007-11-30 2007-11-30 A pharmaceutical composition for treating melancholy and preparation method thereof WO2009070923A1 (en)

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Publication number Priority date Publication date Assignee Title
CN103704712A (en) * 2014-01-07 2014-04-09 威海环翠楼红参科技有限公司 Preparation method of Korean red ginseng buccal tablets
CN103704712B (en) * 2014-01-07 2015-06-17 威海环翠楼红参科技有限公司 Preparation method of Korean red ginseng buccal tablets

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