RU2449804C2 - Pharmaceutical compositions for depression and anxiety disorder (versions) - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, particularly a pharmaceutical composition for depression and anxiety disorder (versions). Pharmaceutical composition for at least one of depression and anxiety disorder containing ginsenoside Rg1 and Rb1; a glycyrrhizic acid derivative being an acid specified in a group consisting of glycyrrhizic acid, glycyrrhetinic acid and combinations thereof; and cyclic adenosine monophosphate of jojoba (cAMP of jojoba), taken in certain amount. The pharmaceutical composition for treating at least one of depression and anxiety disorder containing ginsenoside Rg1 and Rb1; and a glycyrrhizic acid derivative being specified in a group consisting of glycyrrhizic acid, glycyrrhetinic acid and their combination taken in specific proportions.

EFFECT: compositions are effective for treating depression and anxiety disorder.

7 cl, 6 dwg, 19 tbl

Description

Field of Invention

[001] This invention relates to a pharmaceutical composition or therapeutic nutrition made from raw materials, including ginsenosides Rg1 and Rb1, glycyrrhizic acid and cyclic jujuba adenosine monophosphate (jujuba cAMP) (trans., Jujuba cAMP), for treating depression and anxiety disorder . In particular, the present invention relates to a pharmaceutical composition or therapeutic nutrition for the treatment of depression and anxiety disorder; The pharmaceutical composition has certain functions and components, an obvious therapeutic effect, fewer side effects and high safety with prolonged use.

BACKGROUND OF THE INVENTION

[002] Psychological disorders are caused by brain dysfunction, and affected individuals exhibit impaired awareness, thinking, emotions, behavior, will, intelligence, etc. Psychological disorders occupy four out of ten diseases that cause the most serious burden on society. Currently, people are paying more and more attention to psychological dysfunction in the course of social development. The medical community and society as a whole are urgently trying to find psychological medicine to combat psychological disorders. Anxiety disorder and depression are the most common psychological dysfunction, with anti-anxiety and antidepressant drugs being the main treatment.

[003] Anxiety disorder is a mental disorder that manifests itself mainly in the form of anxious emotions. The main features are outbreaks or prolonged anxious feelings, such as anxiety, catatonia, fear, etc., in combination with syndromes such as a violation of the autonomic nervous system, muscle stiffness, a violation during physical activity, etc. Since Sigmund Freud separated anxiety disorder from neurasthenia, scientists around the world have begun large-scale studies of anxiety disorder and have accumulated a large amount of data. According to modern medical research, the etiology of anxiety disorder includes defects in the anatomy of psychology, the neurotransmitter / modulator-receptor system, the neuroendocrine system, etc.

[0004] The current dominant anti-anxiety drug is benzodiazepine, whose mechanism is to modulate the activity of an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), or gamma-aminobutyric acid (GABA), to reduce and alleviate symptoms. However, benzodiazepine has many side effects, including insomnia, allergies, muscle pain, weakness, nausea, physical dysfunction, blurred vision, fatigue, mental imbalance, delirium, etc.

[0005] Depression is a common disease. The World Health Organization (WHO) published: "The incidence of depression in the world is approximately 11%. Currently, there are approximately 340 million patients with psychological depression in the world, and the number is increasing." The study found that depression will grow to become the second most common disease in the world from now to the next 20 years. "

[0006] Current dominant antidepressant drugs are Prozac, Paxil, Zoloft, etc., which relate to selective serotonin reuptake inhibitors (SSRI), serotonin, norepinephrine reuptake inhibitors (SNRI), and norepinephrine and dopamine reuptake inhibitors ( NDRI) inhibiting the uptake of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA). The mechanism by which these antidepressant drugs function is to increase the level of human neurotransmitters, such as 5-HT, to alleviate the symptoms of depression. However, antidepressant drugs sold have side effects at various levels, such as increased suicide, headache, dizziness, vertigo, insomnia, hypersomnia, tinnitus, thirst, aversion to food, orexia, increased body weight, high blood pressure, and frustration stomach, regurgitation with nausea, vomiting, dyspepsia, diarrhea, constipation, leg pain, skin rash, chills, cramps, hyperhidrosis, edema, sex drive, impotence, etc.

[0007] In recent years, antidepressant drugs, such as Prozac, etc., have become a serious social problem. In 2004, the U.S. Food and Drug Administration (FDA) further requested pharmaceutical companies to revise medical use instructions to clearly indicate side effects and warnings on 32 of the most important antidepressant drugs on the market and focused the attention of doctors and nurses on that these drugs can increase suicide in children and adolescents. However, many patients with depression who have a therapeutic condition and a therapeutic desire to stop or abandon their treatment, due to worries about side effects or inability to withstand many of the side effects of these antidepressant drugs. In the light of the current situation, the search for a new generation of drugs with fewer side effects, a high degree of safety with prolonged use and more pronounced / strong antidepressant and anti-anxiety qualities has become the focus of attention of the entire pharmaceutical world.

[0008] Therefore, an attempt was made by the authors of the application to consider the above situation, discovered in the prior art.

SUMMARY OF THE INVENTION

[0009] An object of the present invention is to provide a pharmaceutical composition or therapeutic nutrition for overcoming the deficiency of currently available methods of treating depression and anxiety disorder. The pharmaceutical composition or clinical nutrition is made from raw materials, including ginsenosides Rg and Rb1, glycyrrhizic acid and jujuba cAMP, for the treatment of depression and anxiety disorder. In particular, they provide a new technological scheme that offers precise functions and components, an obvious therapeutic effect, fewer side effects and a high degree of safety during prolonged use.

[0010] The approval scheme of a pharmaceutical preparation of the present invention is a result undertaken by the applicant in accordance with the pathological and pharmacological theories of modern medicine for the treatment of depression and anxiety disorder. The scheme, using three types of raw materials, including ginseng, licorice (per., Other names: licorice, licorice, licorice, licorice) and jujuba (per., Synonyms of the Russian name: jujuba, Chinese date), is developed on the basis of pathological and pharmacological theories of modern medicine for the treatment of anxiety; in particular, the scheme combines past research on pharmaceuticals with the latest knowledge regarding the post-receptor mechanism. Ginseng ginsenoside has adenylate cyclase (AS) activity in stimulating cAMP synthesis and inhibition of cAMP phosphodiesterase (CAPD) to reduce cAMP destruction; glycyrrhizic acid (and glycyrrhetinic acid) from licorice are potent CAPD inhibitors. In the body, ginsenosides Rg1 and Rb1 and glycyrrhizic acid, when combined and used together, additionally increase the concentration and activity of cAMP and protein kinase A (PKA), respectively. An increase in the concentration and activity of cAMP can (1) increase the synthesis and release of a neurotransmitter (trans., Neurotransmitter), such as norepinephrine, etc., (2) increase the expression of brain neurotrophic factor (BDNF) and (3) inhibit hypothalamic hyperactivity pituitary-adrenal axis (NRA) and glucocorticoid secretion to achieve significant antidepressant function. An increased concentration and activity of PKA can enhance the inhibitory function of GABA on neurons to achieve important anti-anxiety function. In addition, jujuba cAMP, being an exogenous non-hydrolyzable cAMP, can participate in the movement of cAMP in the body, mimic the function of the enzyme and enhance the expression of cAMP and PKA in the body to achieve antidepressant and anti-anxiety functions. Thus, ginsenosides Rg1 and Rb1 combine with glycyrrhizic acid and jujuba cAMP; this raw material is expected to work together to further enhance the antidepressant effect and anti-anxiety effect of the present invention. Ginseng, licorice and jujuba are commonly used raw materials for the pharmaceutical industry and food products in Chinese medicine and have been used in dietetic nutritional therapeutic nutrition for several thousand years. In this long clinical and nutritional history, the safety and effectiveness of the integrated use of ginseng, licorice and jujuba have been fully proven. A study of the inventor and experimental results showed that if these three types of pharmaceutical raw materials are only standardly infused and extracted to obtain an extract, the extract does not have significant antidepressant and anti-anxiety effects compared to the dominant antidepressant and anti-anxiety drugs of the prior art. However, upon further purification of the extract of these three types of pharmaceutical raw materials in order to increase the concentration of effective components containing ginsenosides Rg1 and Rb1, glycyrrhizic acid, jujuba cAMP, etc., as described in this invention, a pharmaceutical composition with significant antidepressant and anti-anxiety function is obtained. The experimental result proved that this invention has significant antidepressant and anti-anxiety effects compared with the dominant drugs paroxetine and diazepam for the treatment of depression and anxiety disorder, respectively. Debris obtained from these three types of pharmaceutical raw materials, after extraction and purification, was also collected and analyzed in animal experiments. Despite the fact that debris contains a trace amount of ginsenosides Rg1 and Rb1, glycyrrhizic acid and jujuba cAMP, it does not show significant antidepressant and anti-anxiety functions in animal experiments. It is important that the intake of ginseng, licorice and jujuba does not cause side effects of the widespread antidepressant and anti-anxiety drugs of the prior art. Patients will not need to worry about side effects, so they will not stop or permanently refuse pharmaceutical therapy. Thus, the inventor presents that ginsenosides Rg1 and Rb1, glycyrrhizic acid and jujuba cAMP are raw materials for the manufacture of a pharmaceutical composition or therapeutic nutrition for the treatment of depression and anxiety disorder. In particular, the new flowchart offers precise functions and components, high safety for long-term use without side effects, essentially improving the disadvantages made in the prior art.

[0011] Glycyrrhetinic acid has a higher lipid solubility than glycyrrhizic acid, and can readily enter the brain through the blood-brain barrier. Since glycyrrhizic acid is converted to glycyrrhetinic acid in the human body with almost 100% efficiency, inhibition of CAPD by glycyrrhizic acid occurs by converting glycyrrhizic acid to glycyrrhetinic acid in the body. Thus, glycyrrhizic acid or glycyrrhetinic acid may be the feedstock for the manufacture of the pharmaceutical composition of the present invention.

[0012] In accordance with one aspect of the present invention, there is provided a pharmaceutical composition for treating at least one of depression and anxiety disorder. The pharmaceutical composition includes ginsenosides Rg1 and Rb1; a glycyrrhizic acid derivative, wherein the derivative is selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, and a combination thereof; and camp jujuba.

[0013] Preferably, the pharmaceutical composition includes 2 ~ 25 mass. parts of ginsenoside, 3 ~ 46 mass. parts of a derivative of glycyrrhizic acid and 0.002 ~ 0.4 mass. parts of cAMP jujuba.

[0014] Preferably the pharmaceutical composition includes 4 ~ 12 mass. parts of ginsenoside, 5 ~ 15 mass. parts of a derivative of glycyrrhizic acid and 0.01 ~ 0.08 mass. parts of cAMP jujuba.

[0015] Preferably, ginsenoside is extracted from ginseng, a glycyrrhizic acid derivative is extracted from licorice, and jujuba cAMP is extracted from jujuba (Per. Chinese date).

[0016] Preferably, the jujuba is extracted to obtain a primary extract having a primary concentration of jujuba cAMP, the primary extract is further extracted to obtain a secondary extract having a secondary concentration of jujuba cAMP, the secondary concentration of jujuba cAMP is higher than the primary concentration of jujuba cAMP, and the secondary raw materials for the pharmaceutical composition.

[0017] In accordance with another aspect of the present invention, there is provided a pharmaceutical composition for treating at least one of depression and anxiety disorder. The pharmaceutical composition includes ginsenoside and a glycyrrhizic acid derivative, wherein the derivative is selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, and a combination thereof.

[0018] Preferably, ginsenoside includes Rg1 and Rb1.

[0019] Preferably, the pharmaceutical composition includes 2 ~ 25 mass. parts of ginsenoside and 3 ~ 46 mass. parts of a derivative of glycyrrhizic acid.

[0020] Preferably, the pharmaceutical composition includes 4 ~ 12 mass. parts of ginsenoside and 5 ~ 15 mass. parts of a derivative of glycyrrhizic acid.

[0021] In accordance with another aspect of the present invention, there is provided a pharmaceutical composition for treating at least one of depression and anxiety disorder. The pharmaceutical composition includes ginseng, licorice and jujuba.

[0022] Preferably, the pharmaceutical composition includes 4 ~ 60 mass. parts of ginseng, 2 ~ 30 mass. parts of licorice and 2 ~ 40 mass. parts of jujuba.

[0023] Preferably, the pharmaceutical composition includes 10 ~ 28 mass. parts of ginseng, 5 ~ 14 mass. parts of licorice and 4 ~ 18 mass. parts of jujuba.

[0024] In accordance with another aspect of the present invention, there is provided a pharmaceutical composition for treating at least one of depression and anxiety disorder. The pharmaceutical composition includes ginseng and licorice.

[0025] Preferably, the pharmaceutical composition includes 4 ~ 60 mass. parts of ginseng and 2 ~ 30 mass. parts of licorice.

[0026] Preferably, the pharmaceutical composition includes 10 ~ 28 mass. parts of ginseng and 5 ~ 14 mass. parts of licorice.

[0027] Preferably, the pharmaceutical composition further includes at least one pharmacologically acceptable carrier and additive.

[0028] Preferably, the pharmaceutical composition has a dosage form selected from the group consisting of a tablet, capsule, powder, dragee, powder, solution, microcapsule, suspension, emulsion, particle, drip, and bead.

[0029] Preferably, the pharmaceutical composition is in the form of one of a nutritional supplement and a nutritional supplement.

[0030] In accordance with another aspect of the present invention, there is provided a method for preparing jujuba cAMP of a pharmaceutical composition for treating at least one of depression and anxiety disorder. The production method includes the steps of: (a) extracting jujuba to obtain a primary extract having a primary concentration of jujuba cAMP, and (b) purifying the primary extract to obtain a secondary extract having a secondary concentration of jujuba cAMP. The secondary concentration of jujuba cAMP is higher than the primary jujuba cAMP concentration.

[0031] Preferably, step (b) is performed by chromatography of the primary extract using a macroporous resin with an attached aldehyde group.

[0032] Preferably, step (b) further includes the steps of: (b1) chromatographing the primary extract using a macroporous OU-2 resin with an attached aldehyde group; and (b2) chromatography the primary extract using a macroporous resin ME-2 with an associated aldehyde group.

[0033] In accordance with another aspect of the present invention, a method for producing jujuba cAMP is provided. The method includes the steps of: (a) extracting jujuba to obtain a primary extract; and (b) chromatographing the primary extract using a macroporous resin having an aldehyde group attached thereto.

[0034] The pharmaceutical composition described in the description and claims of the present invention for the treatment of depression and anxiety disorder completes the main content of the present invention. After the publication of this invention, any specialist in this field will be able to continue the normal increase / decrease or replace with other effective components of herbal medicine (such as onjisaponin, saicosaponin and licorice coumarin, etc.) having effects / functions identical to the above medicinal means in accordance with the theory of Chinese medicine or a related theory of modern pharmacology. Substitutions of the indicated normal increase / decrease of medicine based on medicinal herbs having a similar mechanism to another identical CAPD inhibitor, AC activator, or corresponding effective components are normal activities of an ordinary person skilled in the art. Thus, substitutions are within the scope of the invention.

[0035] The above objectives and advantages of the present invention will become fully apparent to those of ordinary skill in the art after reviewing the following detailed descriptions and figures.

Brief Description of Drawings

[0036] Figure 1 is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a first preferred embodiment of the present invention.

[0037] Figure 2 is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a second preferred embodiment of the present invention.

[0038] Figure 3 is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a third preferred embodiment of the present invention.

[0039] Figure 4 is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a fourth preferred embodiment of the present invention.

[0040] Figure 5 is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a fifth preferred embodiment of the present invention.

[0041] Figure 6 is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a sixth preferred embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0042] The present invention will now be described more specifically with reference to the following options. It should be noted that the following descriptions of the preferred variants of the present invention are presented here only for purposes of illustration and description; they are not intended to be exhaustive or limited to the exact form disclosed.

[0043] In order to accomplish the purpose of the present invention, the process flows of the present invention are specifically provided as set forth below.

[0044] The present invention discloses a pharmaceutical composition for treating depression and anxiety disorder, and a pharmaceutical composition is prepared, inter alia, using the raw materials ginsenosides Rg1 and Rb1, glycyrrhizic acid and jujuba cAMP.

Example 1

[0045] A pharmaceutical composition for treating depression and anxiety disorder is made from raw materials, including ginseng and licorice.

Example 2

[0046] The pharmaceutical composition for the treatment of depression and anxiety disorder is made from raw materials, including 4 ~ 60 mass. parts of ginseng and 2 ~ 30 mass. parts of licorice.

Example 3

[0047] A pharmaceutical composition for treating depression and anxiety disorder is made from raw materials, including 10 ~ 28 mass. parts of ginseng and 5 ~ 14 mass. parts of licorice.

Example 4

[0048] A pharmaceutical composition for treating depression and anxiety disorder is made from raw materials, including ginseng, licorice and jujuba.

Example 5

[0049] A pharmaceutical composition for treating depression and anxiety disorder is made from raw materials, including 4 ~ 60 mass. parts of ginseng, 2 ~ 30 mass. parts of licorice and 2 ~ 40 mass. parts of jujuba.

Example 6

[0050] A pharmaceutical composition for treating depression and anxiety disorder is made from raw materials, including 10 ~ 28 mass. parts of ginseng, 5 ~ 14 mass. parts of licorice and 4 ~ 18 mass. parts of jujuba.

Example 7

[0051] A pharmaceutical composition for treating depression and anxiety disorder is made from raw materials, including ginsenosides Rg1 and Rb1 and glycyrrhizic acid (or glycyrrhetinic acid).

Example 8

[0052] The pharmaceutical composition of this invention is made from raw materials, including only 2 ~ 25 mass. parts of ginsenosides Rg1 and Rb1 and 3 ~ 46 mass. parts of glycyrrhizic acid (or glycyrrhetinic acid).

Example 9

[0053] The pharmaceutical composition of this invention is made from raw materials, including only 4 ~ 12 mass. parts of ginsenosides Rg1 and Rb1 and 5 ~ 15 mass. parts of glycyrrhizic acid (or glycyrrhetinic acid).

Example 10

[0054] The pharmaceutical composition of this invention is made from raw materials, including ginseng extract with the above masses. parts of ginsenosides Rg1 and Rb1 and licorice extract with the above masses. parts of glycyrrhizic acid.

Example 11

[0055] The pharmaceutical composition of the present invention is made from raw materials, including ginsenosides Rg1 and Rb1, glycyrrhizic acid (or glycyrrhetinic acid) and jujuba cAMP.

Example 12

[0056] The pharmaceutical composition of this invention is made from raw materials, including only 2 ~ 25 mass. parts of ginsenosides Rg1 and Rb1, 3 ~ 46 mass. parts of glycyrrhizic acid (or glycyrrhetinic acid) and 0.002 ~ 0.4 mass. parts of cAMP jujuba.

Example 13

[0057] The pharmaceutical composition of this invention is made from raw materials, including only 4 ~ 12 mass. parts of ginsenosides Rg1 and Rb1, 5 ~ 15 mass. parts of glycyrrhizic acid (or glycyrrhetinic acid) and 0.01 ~ 0.08 mass. parts of cAMP jujuba.

Example 14

[0058] The pharmaceutical composition of this invention is made from raw materials, including ginseng extract with the above masses. parts of ginsenosides Rg1 and Rb1, licorice extract with the above masses. parts of glycyrrhizic acid and jujub extract with the above masses. parts of cAMP jujuba.

Example 15

[0059] The pharmaceutical composition of the present invention is provided, wherein the raw materials having jujuba cAMP are a secondary extract described as described below. First, jujuba is extracted to obtain a primary extract, then the primary extract is further extracted to obtain a secondary extract, where the concentration of jujuba cAMP of the secondary extract is higher than the concentration of jujuba cAMP of the primary extract.

Example 16

[0060] A pharmaceutical composition of the present invention is provided, wherein a method for producing a raw material containing jujuba cAMP includes the steps of:

[0061] (a) extracting jujuba to obtain a primary extract and

[0062] (b) extracting the primary extract to obtain a secondary extract, and the concentration of jujuba cAMP of the secondary extract is higher than the concentration of jujuba cAMP of the primary extract.

Example 17

[0063] The above production method is provided, wherein step (b) is carried out by chromatography, absorption and separation of the jujuba cAMP of the primary extract using a macroporous resin with an attached aldehyde group.

Example 18

[0064] The above production method is provided, wherein step (b) is carried out by chromatography, absorption and separation of the jujuba cAMP of the primary extract using a macroporous OU-2 resin with an attached aldehyde group.

Example 19

[0065] The above production method is provided, where step (b) is additionally carried out by chromatography, absorption and separation of the jujuba cAMP of the primary extract using the macroporous resin ME-2 with an associated aldehyde group.

Example 20

[0066] The pharmaceutical composition of the present invention may include pharmacologically acceptable carriers, additives, and a combination thereof.

Example 21

[0067] The pharmaceutical composition of the present invention can be made into a dosage form and dosage forms selected from any of the forms of tablets, capsules, powders, dragees, powders, solutions, microcapsules, suspensions, emulsions, particles, drops, beads, and pharmacological pharmaceutical drug forms for oral administration.

Example 22

[0068] The pharmaceutical composition of the present invention can be formulated as a medicament, nutritional supplement and nutritional supplement for treating depression and anxiety disorder.

[0069] In order to achieve the objective of the present invention, methods for preparing a pharmaceutical composition are described as follows.

Method 1

[0070] The pharmaceutical composition of the present invention for the treatment of depression and anxiety disorder is produced from raw materials 4 ~ 60 mass. parts of ginseng and 2 ~ 30 mass. parts of licorice and their raw materials are extracted and purified to obtain an extract having ginsenosides Rg1 and Rb1 and glycyrrhizic acid.

Method 2

[0071] The pharmaceutical composition of the present invention for the treatment of depression and anxiety disorder is made from raw materials having 10 ~ 28 mass. parts of ginseng and 5 ~ 14 mass. parts of licorice, and their raw materials are extracted and purified to obtain an extract having ginsenosides Rg1 and Rb1 and glycyrrhizic acid.

Method 3

[0072] The pharmaceutical composition of the present invention for the treatment of depression and anxiety disorder is made from raw materials having 4 ~ 60 mass. parts of ginseng, 2 ~ 30 mass. parts of licorice and 2 ~ 40 mass. parts of jujuba and their raw materials are extracted and purified to obtain an extract having ginsenosides Rg1 and Rb1, glycyrrhizic acid and jujuba cAMP.

Method 4

[0073] The pharmaceutical composition of the present invention for the treatment of depression and anxiety disorder is made from raw materials having 10 ~ 28 mass. parts of ginseng, 5 ~ 14 mass. parts of licorice and 4 ~ 18 mass. parts of jujuba and their raw materials are extracted and purified to obtain an extract having ginsenosides Rg1 and Rb1, glycyrrhizic acid and jujuba cAMP.

Method 5

[0074] The pharmaceutical composition of the present invention for the treatment of depression and anxiety disorder is made from raw materials of an extract having ginsenosides Rg1 and Rb1, extracted and purified from ginseng, and having glycyrrhizic acid extracted and purified from licorice or from the obtained raw materials having ginsenosides and Rb1 and glycyrrhizic acid (or glycyrrhetinic acid).

Method 6

[0075] The pharmaceutical composition of this invention is made from raw materials, a total of 2 ~ 25 mass. parts of ginsenosides Rg1 and Rb1 and 3 ~ 46 mass. parts of glycyrrhizic acid (or glycyrrhetinic acid).

Method 7

[0076] The pharmaceutical composition of this invention is made from raw materials, a total of 4 ~ 12 mass. parts of ginsenosides Rg1 and Rb1 and 5 ~ 15 mass. parts of glycyrrhizic acid (or glycyrrhetinic acid).

Method 8

[0077] The pharmaceutical composition of the present invention for the treatment of depression and anxiety disorder is produced from raw materials of an extract having ginsenosides Rg1 and Rb1 extracted and purified from ginseng, glycyrrhizic acid extracted and purified from licorice and jujuba cAMP, extracted and purified from jujuba the obtained raw materials of the extract having ginsenosides Rg1 and Rb1, glycyrrhizic acid (or glycyrrhetinic acid) and jujuba cAMP.

Method 9

[0078] The pharmaceutical composition of this invention is made from raw materials, a total of 2 ~ 25 mass. parts of ginsenosides Rg1 and Rb1, 3-46 mass. parts of glycyrrhizic acid (or glycyrrhetinic acid) and 0.002 ~ 0.4 mass. parts of cAMP jujuba.

Method 10

[0079] The pharmaceutical composition of this invention is made from raw materials, a total of 4 ~ 12 mass. parts of ginsenosides Rg1 and Rb1, 5 ~ 15 mass. parts of glycyrrhizic acid (or glycyrrhetinic acid) and 0.01 ~ 0.08 mass. parts of cAMP jujuba.

Method 11

[0080] A pharmaceutical composition of the invention is provided, wherein a method for producing a raw material containing jujuba cAMP includes the steps of:

[0081] (a) extraction of jujuba to obtain a primary extract and

[0082] (b) purifying the primary extract to obtain a secondary extract, and the concentration of jujuba cAMP of the secondary extract is higher than the concentration of jujuba cAMP of the primary extract.

Method 12

[0083] The above production method is provided, wherein step (b) is carried out by chromatography, absorption and separation of the jujuba cAMP of the primary extract using a macroporous resin with an attached aldehyde group.

Method 13

[0084] The above production method is provided where step (b) is carried out by chromatography, absorption and separation of the jujuba cAMP of the primary extract using a macroporous OU-2 resin with an attached aldehyde group.

Method 14

[0085] The above production method is provided, wherein step (b) is further carried out by chromatography, absorption and separation of the jujuba cAMP of the primary extract using a macroporous resin ME-2 with an associated aldehyde group.

Method 15

[0086] The pharmaceutical composition of the present invention may include pharmacologically acceptable carriers, additives, and a combination thereof.

Method 16

[0087] The pharmaceutical composition of the present invention can be formulated and dosage forms selected from any of the forms of tablets, capsules, powders, dragees, powders, solutions, microcapsules, suspensions, emulsions, particles, droplets, beads and pharmacological pharmaceutical drug forms for oral administration.

Method 17

[0088] The pharmaceutical composition of the present invention can be formulated as a medicament, nutritional supplement, and nutritional supplement for treating depression and anxiety disorder in accordance with pharmaceutical standards of Good Manufacturing Practices (GMP) and standards for a method for producing / producing therapeutic nutrition.

Preferred Embodiment

[0089] The invention is further illustrated, as set forth below, by a combination of figures and preferred embodiments of the invention.

Option 1

[0090] Please refer to FIG. 1, which is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a first preferred embodiment of the present invention. In figure 1, after grinding 20 kg of ginseng (101), the destroyed ginseng is heated for extraction with a 70% ethanol solution. The extracted ginseng is separated and purified by column chromatography, dried, and 0.8 kg of ginseng extract is obtained having 120 g of ginsenosides Rg1 and Rb1 (102). Further, after grinding 10 kg of licorice (103), the crushed licorice is soaked at room temperature for 12 hours. The soaked licorice is extracted by digestion and precipitation with alcohol, concentrated, dried, and 2 kg of licorice extract having 200 g of glycyrrhizic acid are obtained (104). Then, 150 g of the obtained ginseng extract and 200 g of the obtained licorice extract are powdered, mixed and 350 g of the pharmaceutical composition of the present invention (105) are obtained (containing 22.5 g of ginsenosides Rg1 and Rb1 and 20 g of glycyrrhizic acid).

Option 2

[0091] Please refer to FIG. 2, which is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a second preferred embodiment of the present invention. In figure 2, after 3.96 g of the obtained glycyrrhetinic acid, having a purity of 96% (202), and 200 g of ginseng extract obtained in embodiment 1 (201) are obtained, 203.96 g of pharmaceutical compositions of the present invention (203) (containing 30 g of ginsenosides Rg1 and Rb1 and 3.8 g of glycyrrhetinic acid).

Option 3

[0092] Please refer to FIG. 3, which is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a third preferred embodiment of the present invention. In Fig. 3, after 3.4 g of the obtained ginsenoside Rg1 having a purity of 90% (301), 7.8 g of the obtained ginsenoside Rb1 having a purity of 90% (302), and 36, are mixed and mixed, 36, 8 g of glycyrrhizic acid having a 90% purity (303) give 48 g of the pharmaceutical composition of the present invention (304) (containing 10 g of ginsenosides Rg1 and Rb1 and 35 g of glycyrrhizic acid).

Option 4

[0093] Please refer to FIG. 4, which is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a fourth preferred embodiment of the present invention. In Fig. 4, 10 kg of jujuba (401) is ground and soaked in water at room temperature, then the soaked jujuba is extracted by digestion and precipitation in alcohol to obtain a jujuba extract, which is further absorbed and separated sequentially on OU-2 and ME-2 macroporous resins and dried. Obtain thirty (30) g of jujuba extract containing 0.3 g of jujuba cAMP, which are the raw material for the pharmaceutical composition of the present invention (402).

[0094] Then, after grinding into powder 150 g of ginseng extract and 200 g of licorice extract obtained in embodiment 1, and mixing with 3 g of the above jujuba extract, 353 g of the pharmaceutical composition of the present invention (403) (containing 22.5 g of Rg1 ginsenosides and Rb1, 20 g of glycyrrhizic acid and 0.03 g of jujuba cAMP).

Option 5

[0095] Please refer to FIG. 5, which is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a fifth preferred embodiment of the present invention. In figure 5, after grinding into a powder 150 g of ginseng extract (501) and 200 g of licorice extract (502) obtained in option 1, respectively, and mixing with 0.5 g of jujuba extract obtained in option 4 (503), get 350.5 g of the pharmaceutical composition of the present invention (504) (containing 22.5 g of ginsenosides Rg1 and Rb1, 20 g of glycyrrhizic acid and 0.005 g of jujuba cAMP).

Option 6

[0096] Please refer to FIG. 6, which is a flowchart showing a method for preparing a pharmaceutical composition in accordance with a sixth preferred embodiment of the present invention. 6, after grinding into powder and mixing 6.8 g of the obtained ginsenoside Rg1 having 90% purity (601), 15.6 g of the obtained ginsenoside Rg1 having 90% purity (602), 26 g of glycyrrhetinic acid having 96 % purity (603), and 10 g of jujuba extract obtained in embodiment 4 (604), 58.4 g of the pharmaceutical composition of the present invention (605) (containing 20 g of ginsenosides Rg1 and Rb1, 25 g of glycyrrhetinic acid and 0.1 g cAMP jujuba).

Experiment 1: Effect of Option 1 in a Tail Suspension Experiment

[0097] 1.1 Experimental animals: ICR mice, males, body weight 22.0 ± 2 g, secondary, provided by the Department of Experimental Animal Science of Capital Medical University, Beijing.

[0098] 1.2 Experimental Medicines: Option 1 drug provided by Beijing Wonner Biotech. Ltd. Co., and paroxetine (paxil) is a product of Zhong Mei Tianjin Smith Kline pharmaceuticals Co. Ltd.

[0099] 1.3 Experimental equipment: stopwatch.

[00100] 1.4 Dose designs: 1. High dose of option 1 (80 mg / kg / day); 2. The average dose of option 1 (40 mg / kg / day) and 3. The low dose of option 1 (20 mg / kg / day).

[00101] 1.5 Experimental method and result:

[00102] 1.5.1 Grouping and drug administration: Mice are randomly divided into groups and 10 mice are in each group. 1. A high dose of option 1 (80 mg / kg, orally (P.O.), was administered for 7 days); 2. The average dose of option 1 (40 mg / kg, P.O., was administered over 7 days); 3. a low dose of option 1 (20 mg / kg, P.O., administered within 7 days); 4. paroxetine (3 mg / kg, P.O., administered over a period of 7 days) and 5. physiological saline (P.O.). 1 hour after the last administration of the drug, an experiment was performed by hanging the mouse by the tail.

[00103] 1.5.2 Experimental method: The tail of the mouse (1 cm to the tip of the tail) is glued with adhesive tape to a wooden plank 5 cm higher than the platform, and suspended for 6 minutes. Record the time of immobility of the mouse for at least 5 minutes.

и результат эксперимента вычисляют в виде дисперсионного анализа (ANOVA) с помощью пакета программ обработки статистических данных SPSS 11.5. [00104] 1.5.3 Statistical calculation: Experimental data are presented as

and the result of the experiment is calculated as analysis of variance (ANOVA) using the SPSS 11.5 statistical software package.

[00105] 1.5.4 Experiment result: see table 1.

Table 1. The effect of option 1 on the time of immobility of the mouse Group Number of animals Immobility time (seconds) Saline solution (control) 10 113.22 ± 21.18 Paroxetine 10 75.33 ± 22.91 * High Dose Option 1 10 54.67 ± 26.38 ** The average dose of option 1 10 72.68 ± 27.06 * Low Dose Option 1 10 95.26 ± 49.91 Compared with the control group: * P <0.05 and ** P <0.01.

[00106] Conclusion: In accordance with the above experiment, it can be found that all high and medium doses of Embodiment 1 of the present invention and paroxetine shortened the immobility time after hanging by the tail of the mouse, significantly different from the saline group (control). Thus, embodiment 1 of the present invention having the antiexperimental function of depression can be extrapolated.

Experiment 2: The effect of option 1 in the experiment Resetpine-induced decrease in body temperature of mice

[00107] 2.1 Experimental animals: ICR mice, males, body weight 22.0 ± 2 g, secondary, provided by the Department of Experimental Animal Science of Capital Medical University, Beijing.

[00108] 2.2 Experimental Medicines: Option 1 drug provided by Beijing Wonner Biotech. Ltd. Co., paroxetine (paxil) is a product of Zhong Mei Tianjin Smith Kline pharmaceuticals Co. Ltd. and Resetpine is a product of Guangdong BangMin Pharmaceutical Co., Ltd.

[00109] 2.3 Experimental equipment: Electronic thermometer (model: GM222) and a stopwatch.

[00110] 2.4 Dose structures: 1. High dose of option 1 (80 mg / kg / day); 2. The average dose of option 1 (40 mg / kg / day) and 3. The low dose of option 1 (20 mg / kg / day).

[00111] 2.5 Experimental method and result:

[00112] 2.5.1 Grouping and drug administration: Mice are randomly divided into groups and 10 mice are in each group. 1. A high dose of option 1 (80 mg / kg, orally (P.O.), was administered for 7 days); 2. The average dose of option 1 (40 mg / kg, P.O., was administered over 7 days); 3. a low dose of option 1 (20 mg / kg, P.O., administered within 7 days); 4. paroxetine (3 mg / kg, P.O., administered over a period of 7 days) and 5. physiological saline (P.O.).

[00113] 2.5.2 Experimental method: 1 hour after the last drug administration, the anal temperature in mice was determined on the eighth day. Then, 2 mg of Resetpine per kilogram of body weight is given by intraperitoneal injection. 4 hours after injection of Resetpine, the anal temperature in mice was determined again. The depth and time of insertion of the thermometer into the anus of mice are identical at each temperature measurement.

и результат эксперимента вычисляют в виде дисперсионного анализа ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5. [00114] 2.5.3 Statistical calculation: Experimental data are presented as

and the experimental result is calculated as ANOVA analysis of variance using the SPSS 11.5 statistical processing software package.

[00115] 2.5.4 Experiment result: see table 2.

Table 2. Effect of Option 1 on Resetpine Induced Mouse Body Temperature Group Number of animals Temperature reduction (° C) Saline solution (control) 10 3.65 ± 0.77 Paroxetine 10 2.38 ± 0.69 ** High Dose Option 1 10 1.85 ± 1.01 ** The average dose of option 1 10 2.05 ± 1.03 ** Low Dose Option 1 10 2.35 ± 0.69 ** Compared with the control group: * P <0.05 and ** P <0.01.

[00116] Conclusion: According to the above experiment, it can be found that the high, medium, and low doses of Embodiment 1 of the present invention and Paroxetine all reduced the reduced body temperature induced by Resetpine, and this means that those antiexperimental functions of depression could be associated with monoamine neurotransmitter and affect the amount of monoamine neurotransmitter. Thus, embodiment 1 of the present invention having the antiexperimental function of depression can be extrapolated.

Experiment 3: The effect of option 1 on the movement of mice in the test dark-light chamber

[00117] 3.1 Experimental animals: Kunming (KM) mice, males, body weight 24 ~ 26 g, secondary, provided by the Department of Experimental Animals of the Capital Medical University, Beijing.

[00118] 3.2 Experimental drugs: Option 1 drug provided by Beijing Wonner Biotech. Ltd. Co., and diazepam is a product of Tianjin Jinhuei Amino Acid Co. Ltd.

[00119] 3.3 Experimental equipment: Home-made camera for moving into a dark-light compartment.

[00120] 3.4 Dose designs: 1. High dose of option 1 (80 mg / kg / day); 2. The average dose of option 1 (40 mg / kg / day) and 3. The low dose of option 1 (20 mg / kg / day).

[00121] 3.5 Experimental method and result:

[00122] 3.5.1 Grouping and drug administration: Mice are randomly divided into groups and 10 mice are in each group. 1. High dose of option 1 (80 mg / kg); 2. The average dose of option 1 (40 mg / kg); 3. low dose of option 1 (20 mg / kg); 4. diazepam (2.5 mg / kg) and 5. physiological saline (0.9% sodium chloride solution, NS). Medicines are injected into the stomach of the mouse once a day and administered to mice for the next 7 days. During the period of administration, the mouse eats and drinks abundantly, and the experiment is continued 1 hour after the last administration of the drug on the eighth day.

[00123] 3.5.2 Experimental method:

[00124] Moving the mice in the test a dark-light chamber: The dark chamber occupies one third of the space of the movement chamber from dark to light compartment (44 cm × 21 cm × 21 cm) and the top is closed. A bright camera occupies two thirds of the space and is brightly lit. A door between two cameras is provided for mouse passage. The mouse is placed in the center of the light chamber at the beginning of the test and the back of the mouse in the dark chamber. The number of times the mouse enters the dark chamber and returns to the bright chamber within 10 minutes is determined and this number of times is an indicator of the evaluation of the anti-anxiety function of the drug.

и результат эксперимента вычисляют в виде дисперсионного анализа ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5. [00125] 3.5.3 Statistical calculation: Experimental data are presented as

and the experimental result is calculated as ANOVA analysis of variance using the SPSS 11.5 statistical processing software package.

[00126] 3.5.4 Experiment result: see table 3.

Table 3. The effect of option 1 on the number of times of movement in the mouse test dark light camera Group Number of animals The number of passages from the dark chamber to the light chamber High Dose Option 1 10 11.2 ± 3.84 * The average dose of option 1 10 13.1 ± 5.38 ** Low Dose Option 1 10 13.5 ± 4.65 ** Diazepam 10 11.3 ± 4.54 * Saline solution (control) 10 6.2 ± 4.32 Compared with the control group: * P <0.05 and ** P <0.01.

[00127] 3.6 Description: The movement in the test of the dark-light camera adopted in this experiment is based on the inborn hatred of the mouse towards bright light and the free, tentative and exploratory nature of behavior in the new environmental conditions. The clinical pharmaceutical preparation (diazepam) for the treatment of anxiety in humans and option 1 have an excellent correlation regarding the improvement of the function of the free, tentative and research character of mouse behavior in this model. In accordance with the above experiment, it can be found that the high, medium and low doses of option 1 of the present invention and diazepam all significantly increase the number of mouse passages from the dark chamber to the light chamber and have statistically significant values when compared with physiological saline. The result of the experiment proved that option 1 has an anti-anxiety function.

[00128] 3.7 Conclusion: In accordance with the above experimental result, the high, medium, and low doses of option 1 of the present invention and diazepam all significantly increase the number of passages of the mouse from the dark chamber to the light chamber. The result suggests that option 1 has an anti-anxiety effect.

Experiment 4: the effect of option 2 in the experiment of hanging the mouse by the tail

[00129] 4.1 Experimental animals: ICR mice, males, body weight 22.0 ± 2 g, secondary, provided by the Department of Experimental Animals of the Capital Medical University, Beijing.

[00130] 4.2 Experimental Medicines: Option 1 drug provided by Beijing Wonner Biotech. Ltd. Co., and paroxetine (paxil) is a product of Zhong Mei Tianjin Smith Kline pharmaceuticals Co. Ltd.

[00131] 4.3 Experimental Equipment: Stopwatch.

[00132] 4.4 Dose designs: 1. High dose of option 2 (80 mg / kg / day); 2. The average dose of option 2 (40 mg / kg / day) and 3. The low dose of option 2 (20 mg / kg / day).

[00133] 4.5 Experimental method and result:

[00134] 4.5.1 Grouping and drug administration: Mice are randomly divided into groups and 10 mice are in each group. 1. A high dose of option 2 (80 mg / kg, P.O., was administered over 7 days); 2. The average dose of option 2 (40 mg / kg, P.O., was administered over 7 days); 3. a low dose of option 2 (20 mg / kg, P.O., administered over a period of 7 days); 4. paroxetine (3 mg / kg, P.O., administered over a period of 7 days) and 5. physiological saline (P.O.). 1 hour after the last administration of the drug, an experiment was performed by hanging the mouse by the tail.

[00135] 4.5.2 Experimental method: The tail of the mouse (1 cm to the tip of the tail) is glued with adhesive tape to a wooden plank 5 cm higher than the platform, and suspended for 6 minutes. Record the time of immobility of the mouse in the last 5 minutes.

и результат эксперимента вычисляют в виде ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5.[00136] 4.5.3 Statistical calculation: Experimental data are presented as

and the result of the experiment is calculated as ANOVA using the SPSS 11.5 statistical processing software package.

[00137] 4.5.4 Experimental result: see table 4.

Table 4. The effect of option 2 on the time of immobility of the mouse Group Number of animals Immobility time (seconds) Saline solution (control) 10 113.22 ± 21.18 Paroxetine 10 75.33 ± 22.91 * High Dose Option 2 10 93.27 ± 36.42 The average dose of option 2 10 76.21 ± 28.36 * Low Dose Option 2 10 107.79 ± 32.56 Compared with the control group: * P <0.05 and ** P <0.01.

[00138] Conclusion: According to the above experiment, it can be found that the average dose of option 2 of the present invention and paroxetine all reduced the immobility time after hanging the mouse by the tail, significantly different from the saline group (control). Thus, embodiment 2 of the present invention having the antiexperimental function of depression can be extrapolated.

Experiment 5: The effect of option 2 in the experiment Resetpine-induced decrease in body temperature of mice

[00139] 5.1 Experimental animals: ICR mice, males, body weight 22.0 ± 2 g, secondary, provided by the Department of Experimental Animals of the Capital Medical University, Beijing.

[00140] 5.2 Experimental Medicines: Option 1 drug provided by Beijing Wonner Biotech. Ltd. Co., paroxetine (paxil) is a product of Zhong Mei Tianjin Smith Kline pharmaceuticals Co. Ltd. and Resetpine is a product of Guangdong BangMin Pharmaceutical Co., Ltd.

[00141] 5.3 Experimental equipment: Electronic thermometer (model: GM222) and a stopwatch.

[00142] 5.4 Dose design: 1. High dose of option 2 (80 mg / kg / day); 2. The average dose of option 2 (40 mg / kg / day) and 3. The low dose of option 2 (20 mg / kg / day).

[00143] 5.5. Experimental method and result:

[00144] 5.5.1 Grouping and drug administration: Mice are randomly divided into groups and 10 mice are in each group. 1. A high dose of option 2 (80 mg / kg, orally (P.O.), was administered for 7 days); 2. The average dose of option 2 (40 mg / kg, P.O., was administered over 7 days); 3. a low dose of option 2 (20 mg / kg, P.O., administered over a period of 7 days); 4. paroxetine (3 mg / kg, P.O., administered over a period of 7 days) and 5. physiological saline (P.O.).

[00145] 5.5.2 Experimental method: 1 hour after the last drug administration, the anal temperature in mice was determined on the eighth day. Then, 2 mg of Resetpine per kilogram of body weight is given by intraperitoneal injection. 4 hours after injection of Resetpine, the anal temperature in mice was determined again. The depth and time of insertion of the thermometer into the anus of mice are identical at each temperature measurement.

и результат эксперимента вычисляют в виде дисперсионного анализа ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5. [00146] 5.5.3 Statistical calculation: Experimental data are presented as

and the experimental result is calculated as ANOVA analysis of variance using the SPSS 11.5 statistical processing software package.

[00147] 5.5.4 Experimental result: see table 5.

Table 5. The effect of option 2 on the reduced mouse body temperature induced by Resetpine Group Number of animals Temperature reduction (° C) Saline solution (control) 10 3.65 ± 0.77 Paroxetine 10 2.38 ± 0.69 ** High Dose Option 2 10 2.93 ± 0.74 * The average dose of option 2 10 2.31 ± 0.82 ** Low Dose Option 2 10 3.21 ± 0.71 Compared with the control group: * P <0.05 and ** P <0.01.

[00148] Conclusion: According to the above experiment, it can be found that the average dose of option 2 of the present invention and paroxetine all reduced the decreased body temperature induced by Resetpine, and this means that those antiexperimental functions of depression could be associated with the monoamine neurotransmitter and affect the amount monoamine neurotransmitter. Thus, embodiment 2 of the present invention having the antiexperimental function of depression can be extrapolated.

Experiment 6: Effect of Option 3 in a Tail Suspension Experiment

[00149] 6.1 Experimental animals: ICR mice, males, body weight 22.0 ± 2 g, secondary, provided by the Department of Experimental Animal Science of Capital Medical University, Beijing.

[00150] 6.2 Experimental Medicines: Option 1 drug provided by Beijing Wonner Biotech. Ltd. Co., and paroxetine (paxil) is a product of Zhong Mei Tianjin Smith Kline pharmaceuticals Co. Ltd.

[00151] 6.3 Experimental equipment: stopwatch.

[00152] 6.4 Dose designs: 1. High dose of option 3 (80 mg / kg / day); 2. The average dose of option 3 (40 mg / kg / day) and 3. The low dose of option 3 (20 mg / kg / day).

[00153] 6.5. Experimental method and result:

[00154] 6.5.1 Grouping and drug administration: Mice are randomly divided into groups and 10 mice are in each group. 1. A high dose of option 3 (80 mg / kg, P.O., was administered over 7 days); 2. The average dose of option 3 (40 mg / kg, P.O., was administered over 7 days); 3. a low dose of option 3 (20 mg / kg, P.O., administered over a period of 7 days); 4. paroxetine (3 mg / kg, P.O., administered over a period of 7 days) and 5. physiological saline (P.O.). 1 hour after the last administration of the drug, an experiment was performed by hanging the mouse by the tail.

[00155] 6.5.2 Experimental method: The tail of the mouse (1 cm to the tip of the tail) is glued with tape to a wooden plank 5 cm higher than the platform, and suspended for 6 minutes. Record the time of immobility of the mouse for at least 5 minutes.

и результат эксперимента вычисляют в виде ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5.[00156] 6.5.3 Statistical calculation: Experimental data are presented as

and the result of the experiment is calculated as ANOVA using the SPSS 11.5 statistical processing software package.

[00157] 6.5.4 Experiment result: see table 6.

Table 6. The effect of option 3 on the immobility time of mice Group Number of animals Immobility time (seconds) Saline solution (control) 10 113.22 ± 21.18 Paroxetine 10 75.33 ± 22.91 * High Dose Option 3 10 70.37 ± 28.14 * The average dose of option 3 10 76.26 ± 23.81 * Low Dose Option 3 10 90.40 ± 31.32 Compared with the control group: * P <0.05 and ** P <0.01.

[00158] Conclusion: In accordance with the above experiment, it can be found that all high and medium doses of Embodiment 3 of the present invention and paroxetine reduced immobility time after hanging the mouse by the tail, significantly different from the saline group (control). Thus, embodiment 3 of the present invention having the antiexperimental function of depression can be extrapolated.

Experiment 7: The effect of option 3 in the experiment Resetpine-induced decrease in body temperature of mice

[00159] 7.1 Experimental animals: ICR mice, males, body weight 22.0 ± 2 g, secondary, provided by the Department of Experimental Animal Science of Capital Medical University, Beijing.

[00160] 7.2 Experimental drugs: option 3 drug provided by Beijing Wonner Biotech. Ltd. Co., paroxetine (paxil) is a product of Zhong Mei Tianjin Smith Kline pharmaceuticals Co. Ltd. and Resetpine is a product of Guangdong BangMin Pharmaceutical Co., Ltd.

[00161] 7.3 Experimental equipment: electronic thermometer (model: GM222) and a stopwatch.

[00162] 7.4 Dose design: 1. High dose of option 3 (80 mg / kg / day); 2. The average dose of option 3 (40 mg / kg / day) and 3. The low dose of option 3 (20 mg / kg / day).

[00163] 7.5 Experimental method and result:

[00164] 7.5.1 Grouping and drug administration: Mice are randomly divided into groups and 10 mice are in each group. 1. A high dose of option 3 (80 mg / kg, orally (P.O.), was administered for 7 days); 2. The average dose of option 3 (40 mg / kg, P.O., was administered over 7 days); 3. a low dose of option 3 (20 mg / kg, P.O., administered over a period of 7 days); 4. paroxetine (3 mg / kg, P.O., administered over a period of 7 days) and 5. physiological saline (P.O.).

[00165] 7.5.2 Experimental method: 1 hour after the last drug administration, the anal temperature in mice was determined on the eighth day. Then, 2 mg of Resetpine per kilogram of body weight is given by intraperitoneal injection. 4 hours after injection of Resetpine, the anal temperature in mice was determined again. The depth and time of insertion of the thermometer into the anus of mice are identical at each temperature measurement.

и результат эксперимента вычисляют в виде дисперсионного анализа ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5. [00166] 7.5.3 Statistical calculation: Experimental data are presented as

and the experimental result is calculated as ANOVA analysis of variance using the SPSS 11.5 statistical processing software package.

[00167] 7.5.4 Experiment result: see table 7.

Table 7.  Effect of Option 3 on Resetpine-Induced Mouse Body Temperature Group Number of animals Temperature reduction (° C) Saline solution (control) 10 3.65 ± 0.77 Paroxetine 10 2.38 ± 0.69 ** High Dose Option 3 10 2.18 ± 0.92 ** The average dose of option 3 10 2.36 ± 0.83 ** Low Dose Option 3 10 2.97 + 0.67 * Compared with the control group: * P <0.05 and ** P <0.01.

[00168] Conclusion: According to the above experiment, it can be found that the high, medium, and low doses of Embodiment 3 of the present invention and paroxetine all reduced the reduced body temperature induced by Resetpine, and this means that those antiexperimental functions of depression could be associated with monoamine neurotransmitter and affect the amount of monoamine neurotransmitter. Thus, embodiment 3 of the present invention having the antiexperimental function of depression can be extrapolated.

Experiment 8: The effect of option 4 in the experiment on the defeat of the olfactory bulbs in mice

[00169] 8.1 Experimental animals:

[00170] Olfactory bulb lesion model: healthy male Wistar rats, secondary, body weight 330 ± 20 g, purchased from Beijing Vital River Experimental Animal Technology Ltd. Co. (quality certificate number: SCXK (JING) 2002-2003).

[00171] 7.2 Reagents and Medicines: The Option 4 drug is provided by Beijing Wonner Biotech Ltd. Co. (Lot: 060313), and paroxetine is a product of Zhong Mei Tianjin Smith Kline pharmaceuticals Co. Ltd. (Lot: 04050011). The above medications are prepared in 0.5% sodium carboxymethyl cellulose (CMC-Na) for administration to the stomach. Benzylpenicillin Sodium for Injection is a product of North China Pharmaceutical Huasheng Co. Ltd. (Lot: S0511204) and norepinephrine (NE) and 5-hydrotryptamine (5-HT) standards are products of Sigma Co. Other reagents are supplied.

[00172] 8.3 Equipment: A home-made camera for studying behavior in an open field, a step through the camera, a stereotactic instrument for rats, high performance liquid chromatography (HPLC) and a 10-channel noise-resistant counter for D-radiation (type: DFM-96).

[00173] 8.4 Experimental methods:

[00174] 8.4.1 Grouping and drug administration: Rats are randomly divided into 6 groups 1. False therapeutic group; 2. model group (control); 3. high dose of option 4 (60 mg / kg / day); 4. the average dose of option 4 (30 mg / kg / day); 5. low dose of option 4 (15 mg / kg / day) and 6. paroxetine (2 mg / kg / day). The test drugs and the positive drug are prepared with 0.5% CMC-Na for administration to the stomach once a day.

[00175] 8.4.2 Method for preparing the model: Rats are anesthetized with chloral hydrate. After anesthesia, a midline incision is made in the rat fontanel from 1 cm to the frontal fontanel to 1 cm behind the frontal fontanel and the bones of the skull are exposed. Open the windows on the skull, having a diameter of 2 mm from 8 mm in front of the frontal fontanel and 2 mm on both sides of the midline. A specially made electric soldering iron is inserted perpendicularly into the skull for 2 seconds and the olfactory bulb is destroyed. A hemostatic sponge is immersed in the windows of the skull and the skin is sutured. After treatment, 40,000 units of benzylpenicillin sodium per kilogram of body weight, performed by intraperitoneal injection for every four days, give the test drug continuously for 24 days.

[00176] 8.5 Visual Observation Index:

[00177] 8.5.1 Open-field behavior experiment: An open-field behavior study chamber (1 m × 1 m × 0.4 m) is constructed using light blue plywood and an aluminum alloy frame. The bottom of the camera is divided into 25 squares (20 cm × 20 cm for each square), the perimeter is peripheral squares (16 squares), and the rest are central squares (9 squares). The rat is placed in the center of the central squares and the number of rats crossed by the rat (the number of intersections of the adjacent square by more than three claws) and the number of standing rats (two forelimbs leaving a bottom of more than 1 cm) are counted / obtained by observation for 3 minutes.

[00178] 8.5.2 Passive avoidance experiment (stepping test): A septum through the chamber is formed between the light chamber and the dark chamber, and a passage connects the light chamber and the dark chamber to exit and enter the mouse. The lattice of the dark chamber is connected to the equipment for electric shock and there in the gap a mobile plate is installed. If the rat enters a dark chamber, the rat will be exposed to electric shock. During training, the rat is placed in a bright chamber and then back into the hole for adaptation within 5 minutes. Then the plate is removed and the rat is observed for the next 5 minutes. The time when the rat enters for the first time (electroshock latent period) is recorded and this time is the result of the study. After 24 hours, the test is repeated. The plate is removed and the dark chamber is exposed to electric shock for 5 minutes to set the time when the rat enters the dark chamber for the first time. This time is a memory record.

и результат эксперимента вычисляют в виде дисперсионного анализа ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5.[00179] 8.6 Statistical calculation: Experimental data are presented as

and the experimental result is calculated as ANOVA analysis of variance using the SPSS 11.5 statistical processing software package.

[00180] 8.7 Experimental results:

[00181] 8.7.1 The result of an experiment of behavior in a chamber is an open field: see table 8.

Table 8. The result of the model of lesion of the olfactory bulbs of rats in an experiment in open-field chamber behavior Group Number of animals Horizontal movement (number of crossed squares) Vertical movement (number of vertical posts) High Dose Option 4 eleven 49.18 ± 27.68 ** 10.91 ± 6.91 ** The average dose of option 4 eleven 54.55 ± 23.01 13.45 ± 5.72 * Low Dose Option 4 eleven 61.82 ± 21.43 15.18 ± 4.47 Paroxetine eleven 55.36 ± 25.96 * 14.36 ± 5.55 Model group (control) eleven 79.55 ± 24.33 19.09 ± 8.53 False Therapeutic Group eleven 45.36 ± 26.84 ** 10.45 ± 6.19 ** Compared with the control group: * P <0.05 and ** P <0.01.

[00182] 8.7.2 Step test result: see table 9.

Table 9. The result of the rat olfactory bulb lesion model in the step test Group Number of animals Latency of the first day (seconds) Latency of the second day (seconds) High Dose Option 4 eleven 187.00 ± 87.59 * 289.82 ± 28.59 * The average dose of option 4 eleven 191.71 ± 72.95 * 288.82 ± 37.09 * Low Dose Option 4 eleven 152.44 ± 76.81 271.18 ± 38.61 Paroxetine eleven 181.87 ± 90.54 * 265.00 ± 65.39 Model group (control) eleven 111.21 ± 82.93 236.88 ± 74.17 False Therapeutic Group eleven 211.46 ± 82.10 ** 292.82 ± 14.37 * Compared with the control group: * P <0.05 and ** P <0.01.

[00183] Conclusion: The result of experiment 8 demonstrates that a high dose of option 4 can significantly improve the growth of horizontal and vertical movements of rats caused by damage to the olfactory bulbs, and the average dose of option 4 also has a noticeable improved effect on the growth of vertical movement caused by damage to the olfactory bulbs in rats. In addition, the high and medium doses of option 4 have markedly improved effects on decreased learning and memory function in rats caused by damage to the olfactory bulbs.

Experiment 9: The effect of option 4 in an experiment of unpredictable long-term stimuli in rats

[00184] 9.1 Experimental animals:

[00185] Model of unpredictable long-term stimuli: male Health Wistar rats, secondary, 240 ~ 270 g body weight, purchased from Beijing Vital River Experimental Animal Technology Ltd. Co. (Quality Certificate Number: SCXK (JING) 2002-2003).

[00186] 9.2 Reagents and Pharmaceutical Preparations: Option 4 pharmaceutical preparation provided by Beijing Wonner Biotech Ltd. Co. (Lot: 060313) and Paroxet is a product of Zhong Mei Tianjin Smith Kline pharmaceuticals Co. Ltd. (Lot: 04050011). The above medications are prepared in 0.5% sodium carboxymethyl cellulose (CMC-Na) for administration to the stomach. Benzylpenicillin Sodium for Injection is a product of North China Pharmaceutical Huasheng Co. Ltd. (Lot: S0511204) and norepinephrine (NE) and 5-hydrotryptamine (5-HT) standards are products of Sigma Co. Other reagents are supplied.

[00187] 9.3 Equipment: A home-made camera for studying behavior in an open field, a step through the camera, a stereotactic instrument for rats, high performance liquid chromatography (HPLC) and a 10-channel noise-resistant counter for D-radiation (type: DFM-96).

[00188] 9.4 Experiment method:

[00189] 9.4.1 Grouping and drug administration: Rats are randomly divided into 6 groups 1. False therapeutic group; 2. model group (control); 3. high dose of option 4 (60 mg / kg / day); 4. the average dose of option 4 (30 mg / kg / day); 5. low dose of option 4 (15 mg / kg / day) and 6. paroxetine (2 mg / kg / day). The test drugs and the positive drug are prepared with 0.5% CMC-Na for administration to the stomach once a day.

[00190] 9.4.2 A method of obtaining a model:

[00191] Model of unpredictable long-term stimuli: Rats in the control group eat and drink normally, and there are no fulfilled stimuli. In the other 5 groups, one rat is fed in each cage, and the rat is subjected to 24-day unpredictable stress / stimulus, including 24-hour absorption 3 times, 24 hours without drinking 3 times, 24-hour wet litter 3 times (200 ml of water is poured in a rat cage), lighting all night 3 times, swimming at 4 ° C for 5 minutes 3 times, heating at 45 ° C in the oven for 5 minutes 3 times, applying clamps to the tail of the rat for 1 minute 3 times and 30 -minute high-speed shaking in the horizontal direction 3 times. One stimulus is performed arbitrarily every day and only 24 days. Each stimulus cannot be performed continuously. The pharmaceutical preparation is fed into the stomach of the rat once a day and only 24 days.

[00192] 9.5 The indicator of visual observation:

[00193] 9.5.1 Open Field Behavior Experiment: Same as above.

[00194] 9.5.2 Passive avoidance experiment: Same as above.

[00195] 9.5.3 Swimming of rats in a forced swimming test: This experiment is continued for two days after the last administration of the drug. On the first day, the experiment is performed preliminarily for 15 minutes. The water temperature in the glass tank is 25 ° C and the water depth is 25 cm. After 24 hours, the formal experiment is continued. 1 hour after drug administration, the rat is placed in the reservoir and the rat immobility time is recorded for the last 5 minutes.

[00196] 9.5.4 Measurement of body weight: Compare increasing values before and after each experiment with animals.

[00197] 9.5.5 Volumetric test for drinking sucrose: Compare the volumes of sucrose absorbed in rats. Rats in each group drink 1% sucrose for 1 hour. Drinking volumes are determined before the stimulus and after 3 weeks of the stimulus. After the rat is absent and in water for 1 hour, 1% sucrose is placed in the cage and replaced with ordinary drinking water. Measure and record the difference in weight of the bottle before and after drinking the sucrose with the rat for 1 hour and calculate the amount of sucrose consumed for each point in time. Compare the amount of sucrose absorbed for each point in time.

[00198] 9.5.6 HPLC electrochemical test: The amounts of norepinephrine and 5-hydrotryptamine in the rat cerebral cortex are measured.

и результат эксперимента вычисляют в виде дисперсионного анализа ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5.[00199] 9.6 Statistical calculation: Experimental data are presented as

and the experimental result is calculated as ANOVA analysis of variance using the SPSS 11.5 statistical processing software package.

[00200] 9.7 The result of the experiment:

[00201] 9.7.1 Volumetric test for drinking sucrose: see table 10.

Table 10. Rat sucrose uptake in an unpredictable long-term stimulus model Group Number of animals The amount of absorbed sucrose (g) High Dose Option 4 13 22.55 ± 5.03 The average dose of option 4 13 26.53 ± 4.99 ** Low Dose Option 4 13 26.97 ± 6.93 ** Paroxetine 13 26.29 ± 4.87 ** Model group (control) 13 19.42 ± 4.25 False Therapeutic Group 13 29.41 ± 3.83 ** Compared with the control group: * P <0.05 and ** P <0.01.

[00202] 9.7.2 The result of an increase in rat body weight: see table 11.

Table 11. Rat weight gain in an unpredictable long-term stimulus model Group Number of animals Immobility time (seconds) High Dose Option 4 13 86.08 ± 10.84 The average dose of option 4 13 96.00 ± 11.05 ** Low Dose Option 4 13 95.15 ± 15.46 ** Paroxetine 13 96.85 ± 9.30 ** Model group (control) 13 84.92 ± 12.61 False Therapeutic Group 13 120.54 ± 10.60 ** Compared to the control group: ** P <0.01.

[00203] 9.7.3 The time of immobility of the rat during forced swimming: see table 12.

Table 12. The immobility time in the model of unpredictable long-term stimuli in the rat forced swimming test Group Number of animals Immobility time (seconds) High Dose Option 4 13 23.28 ± 18.05 ** The average dose of option 4 13 18.95 ± 12.55 ** Low Dose Option 4 13 25.20 ± 13.60 * Paroxetine 13 31.38 ± 19.59 Model group (control) 13 39.95 ± 17.46 False Therapeutic Group 13 26.96 ± 12.76 * Compared with the control group: * P <0.05 and ** P <0.01.

[00204] 9.7.4 Result of an open field behavior experiment: see table 13.

Table 13. The result of an unpredictable long-term stimulus model in an open field behavior experiment Group Number of animals Horizontal movement (number of crossed squares) Vertical movement (number of vertical posts) High Dose Option 4 fourteen 58.31 ± 15.35 * 16.54 ± 4.24 ** The average dose of option 4 fourteen 49.15 ± 14.26 13.54 ± 4.48 Low Dose Option 4 fourteen 52.62 ± 21.83 16.15 ± 7.32 * Paroxetine fourteen 61.85 ± 21.68 ** 14.69 ± 4.2 Model group (control) fourteen 39.54 ± 16.31 11.46 ± 3.26 False Therapeutic Group fourteen 64.00 ± 11.97 ** 16.85 ± 3.18 ** Compared with the control group: * P <0.05 and ** P <0.01.

[00205] 9.7.5 The result of the experiment of passive avoidance of rats: see table 14.

Table 14. The result of an unpredictable long-term stimulus model in a rat passive avoidance experiment Group Number of animals Latency of the first day (seconds) Latency of the second day (seconds) High Dose Option 4 13 65.43 ± 31.44 259.22 ± 56.51 The average dose of option 4 13 58.18 ± 18.0 212.76 ± 77.27 Low Dose Option 4 13 75.98 ± 32.22 * 204.85 ± 94.99 Paroxetine 13 75.75 ± 46.52 * 257.46 ± 66.92 Model group (control) 13 50.01 ± 15.7 189.25 ± 111.99 False Therapeutic Group 13 80.00 ± 39.17 * 263.38 ± 59.68 Compared with the control group: * P <0.05 and ** P <0.01.

[00206] 9.7.6 The result of the content of NE and 5-HT in the rat cerebral cortex: see table 14.

Table 14. The result of the content of NE and 5-HT in the rat cerebral cortex in a model of unpredictable long-term stimuli

Group Number of animals 5-HT (nmol / L brain tissue extract) NE (nmol / L brain tissue extract) High Dose Option 4 12 230.4157 ± 47.78554 * 269.5409 ± 58.86389 ** The average dose of option 4 12 303.4418 ± 70.31711 ** 227.2976 ± 28.95101 ** Low Dose Option 4 12 332.7343 ± 76.25168 ** 201.8688 ± 29.80775 ** Paroxetine 12 227.0637 ± 46.53838 * 220.5419 ± 38.31681 ** Model group (control) 12 179.3866 ± 20.49374 57.6671 ± 77.66958 False Therapeutic Group 12 228.1478 ± 28.40397 * 132.8598 ± 20.84756 ** Compared with the control group: * P <0.05 and ** P <0.01.

[00207] Conclusion: The results of experiment 9 are shown as follows. Medium and low doses of option 4 can significantly increase the reduced drinking volume of sucrose and reduce body weight in unpredictable long-term stress / stimuli. High, medium and low doses of option 4 all significantly increase the immobility time in the rat forced swimming test. The high dose of option 4 can significantly improve the reduced horizontal and vertical rat motions caused by unpredictable long-term stress / stimuli. The low dose of option 4 also has a notable function of improving the reduced vertical movement of rats caused by unpredictable long-term stress / stimuli. The low dose of option 4 has the function of improving the reduced learning ability of rats caused by unpredictable long-term stress / stimuli. High, medium, and low doses of option 4 all markedly increase the content of NE and 5-HT in the rat cerebral cortex.

Experiment 10: The effect of option 4 in the experiment, the movements of mice from light to dark compartment

[00208] 10.1 Experimental animals: Kunming (KM) mice, males, body weight 24 ~ 26 g, secondary, provided by the Department of Experimental Animal Science of Capital Medical University, Beijing.

[00209] 10.2 Experimental drugs: Option 1 drug provided by Beijing Wonner Biotech. Ltd. Co., and paroxetine (paxil) is a product of the company and diazepam is a product of Tianjin Jinhuei Amino Acid Co. Ltd.

[00210] 10.3 Experimental equipment: Home-made chamber for moving mice from light to dark compartment.

[00211] 10.4 Dose designs: 1. High dose of option 4 (80 mg / kg / day); 2. The average dose of option 4 (40 mg / kg / day) and 3. The low dose of option 4 (20 mg / kg / day).

[00212] 10.5 Experimental method and result:

[00213] 10.5.1 Grouping and drug administration: Mice are randomly divided into 5 groups and 10 mice are in each group. 1. High dose of option 4 (80 mg / kg); 2. The average dose of option 4 (40 mg / kg); 3. low dose of option 4 (20 mg / kg); 4. diazepam (2.5 mg / kg) and 5. physiological saline (0.9% sodium chloride solution, NS). Medicines are injected into the stomach of the mouse once a day and administered to mice for the next 7 days. During the period of administration, the mouse eats and drinks abundantly, and the experiment is continued 1 hour after the last administration of the drug on the eighth day.

[00214] 10.5.2 The experimental method:

[00215] Moving the mice in the test a dark-light chamber: A dark chamber occupies one third of the space of the movement chamber from dark to light compartment (44 cm × 21 cm × 21 cm) and the top is closed. The light chamber occupies two-thirds of the space and is brightly lit. A door between two cameras is provided for mouse passage. The mouse is placed in the center of the light chamber at the beginning of the test and the back of the mouse in the dark chamber. The number of times that the mouse enters the dark chamber and returns to the bright chamber within 10 minutes is determined and this number of times is an indicator of the evaluation of the anti-anxiety function of drugs.

и результат эксперимента вычисляют в виде дисперсионного анализа ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5.[00216] 10.5.3 Statistical calculation: Experimental data are presented as

and the experimental result is calculated as ANOVA analysis of variance using the SPSS 11.5 statistical processing software package.

[00217] 10.5.4 Experiment result: see table 16.

Table 16. The effect of option 4 on the number of times of movement in the mouse test dark light camera Group Number of animals The number of passages from the dark chamber to the light chamber High Dose Option 4 10 11.6 ± 4.53 * The average dose of option 4 10 13.9 ± 3.76 ** Low Dose Option 4 10 13.4 ± 4.12 ** Diazepam 10 11.7 ± 4.47 * Saline solution (control) 10 6.8 ± 3.85 Compared with the control group: * P <0.05 and ** P <0.01.

[00218] 10.6 Description: The movement in the experiment of the dark-light camera adopted in this experiment is based on the inborn hatred of the mouse towards bright light and the free, tentative and exploratory nature of behavior in the new environmental conditions. The clinical pharmaceutical preparation (diazepam) for the treatment of anxiety in humans and option 4 have an excellent correlation regarding the improvement of the function of the free, tentative and research character of mouse behavior in this model. In accordance with the above experiment, it can be found that the high, medium and low doses of option 4 of the present invention and diazepam all significantly increase the number of mouse passages from the dark chamber to the light chamber and have statistically significant values when compared with physiological saline. The result of the experiment proved that option 4 has an anti-anxiety effect.

[00219] 10.7 Conclusion: In accordance with the above experimental result, the high, medium and low doses of option 4 of the present invention and diazepam all significantly increase the number of passages of the mouse from the dark chamber to the bright chamber. The result is that option 4 has an anti-anxiety property.

Experiment 11: Effect of Option 5 in a Tail Suspension Experiment

[00220] 11.1 Experimental Medicines: Option 5 pharmaceutical preparation provided by Beijing Wonner Biotech. Ltd. Co. (an experimental storage product) and paroxetine is a product of Zhong Mei Tianjin Smith Kline pharmaceuticals Co. Ltd (Lot: 05070384). The above pharmaceutical preparations are prepared with saline for delivery to the stomach.

[00221] 11.2 Experimental animals: ICR mice, males, body weight 20.0 ± 1 g, secondary, provided by the Department of Experimental Animals of the Capital Medical University, Beijing. The mouse quality certificate number is SCXK (JING) 2006-2008.

[00222] 11.3 Experimental Equipment: Stopwatch.

[00223] 11.4 Method: Seventy (70) mice are randomly divided into 5 groups: physiological saline (NS) group, paroxetine (3 mg / kg / day), high dose of option 5 (80 mg / kg / day), average dose option 5 (40 mg / kg / day) and a low dose of option 5 (20 mg / kg / day). Drugs are injected into the mouse’s stomach once a day. 1 hour after the last injection of the drug on the eighth day, the mouse tail (1 cm to the tip of the tail) is glued with adhesive tape to a horizontal support in an open chamber, and the mouse is in an inverted hanging position. The mouse head is approximately 10 cm below the bottom of the open chamber, and the mouse is suspended for 6 minutes. The immobility of the mouse is recorded over the last 5 minutes.

и результат эксперимента вычисляют в виде однонаправленного ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5.[00224] 11.5 Statistical calculation: Experimental data are presented as

and the result of the experiment is calculated as a unidirectional ANOVA using the SPSS 11.5 statistical processing software package.

[00225] 11.6 Experiment Result: The result of the immobility time in the experiment by hanging the mouse by the tail: see table 17.

Table 17. The effect of option 5 on the total time of immobility of the mouse Group Number of animals Dose (mg / kg / day) Immobility time (seconds) High Dose Option 5 fourteen 80 64.75 ± 42.22 ** The average dose of option 5 fourteen 40 55.41 ± 33.83 ** Low Dose Option 5 fourteen twenty 62.75 ± 26.61 ** Paroxetine fourteen 3 53.27 ± 20.02 ** Saline Group (NS) fourteen 113.59 ± 36.11 Compared to the NS group: * P <0.05 and ** P <0.01.

[00226] Conclusion: The result of the study demonstrates that the high, medium, and low doses of option 5 and the clinically effective antidepressant drug, paroxetine, all significantly reduce the total time of immobility of the mouse suspended by the tail. The result shows that option 5 of the present invention has an antidepressant ability in the experiment.

Experiment 12: The effect of option 5 in the experiment forced swimming mice

[00227] 12.1 Experimental Medicines: Option 5 pharmaceutical preparation provided by Beijing Wonner Biotech. Ltd. Co. (an experimental storage product) and paroxetine is a product of Zhong Mei Tianjin Smith Kline pharmaceuticals Co. Ltd (Lot: 05070384). The above pharmaceutical preparations are prepared with saline for delivery to the stomach.

[00228] 12.2 Experimental animals: ICR mice, males, body weight 20.0 ± 1 g, secondary, provided by the Department of Experimental Animal Science of Capital Medical University, Beijing. The mouse quality certificate number is SCXK (JING) 2006-2008.

[00229] 12.3 Experimental Equipment: Stopwatch.

[00230] 12.4 Experiment Method: The mouse groups and drug administration are the same as in the experiment by hanging the mouse by the tail. In each group of test mice, the experiment is continued 1 hour after drug administration. Mice are taught swimming for 15 minutes before the experiment and on the eighth day. The experiment is performed in 24 hours. Mice are placed in water at 25 ° C. in a glass tank having a water depth of 10 cm and a diameter of 14 cm. The total immobility time for the last 5 minutes is recorded.

и результат эксперимента вычисляют в виде однонаправленного ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5.[00231] 12.5 Statistical calculation: Experimental data are presented as

and the result of the experiment is calculated as a unidirectional ANOVA using the SPSS 11.5 statistical processing software package.

[00232] 12.6 Experimental result: Forced swimming of mice: see table 18.

Table 18. The effect of option 5 on the forced swimming time of mice in the test Group Number of animals Dose (mg / kg / day) Immobility time (seconds) High Dose Option 5 fourteen 80 88.35 ± 51.64 * The average dose of option 5 fourteen 40 65.87 ± 38.96 ** Low Dose Option 5 fourteen twenty 88.12 ± 38.57 * Paroxetine fourteen 3 57.80 ± 38.07 ** Saline Group (NS) fourteen 132,47140,64 Compared to the NS group: * P <0.05 and ** P <0.01.

[00233] Conclusion: The result of the experiment shows that the high, medium and low doses of option 5 and the clinically effective antidepressant drug paroxetine all significantly reduce the total immobility time of mice in the forced swimming test. The result shows that option 5 of the present invention has an antidepressant ability in the experiment.

Experiment 13:

[00234] Nine (9) kg of remaining ginseng debris and 7 kg of remaining licorice debris, extracted from option 1 and option 4, are collected, dried, pulverized and mixed well to obtain a debris mixture containing trace amounts of ginsenosides Rg1 and Rb1, glycyrrhizin acids and cAMP jujuba. Conduct a control experiment influence in the experiment of hanging the mouse by the tail.

[00235] 13.1 Experimental animals: ICR mice, males, body weight 22.0 ± 2 g, secondary, provided by the Department of Experimental Animals of the Capital Medical University, Beijing.

[00236] 13.2 Experimental Medicines: A mixture of debris was provided by Beijing Wonner Biotech. Ltd. With. and paroxetine (paxil) is a product of Zhong Mei Tianjin Smith Kline pharmaceuticals Co. Ltd.

[00237] 13.3 Experimental Equipment: Stopwatch.

[00238] 13.4 Dose designs: 1. High dose debris mixture (160 mg / kg / day); 2. The average dose of a mixture of debris (80 mg / kg / day) and 3. The low dose of a mixture of debris (40 mg / kg / day).

[00239] 13.5 Experimental method and result:

[00240] 13.5.1 Division into groups and drug administration: Mice are randomly distributed, 10 mice are in each group. 1. A high dose of a mixture of debris (160 mg / kg, P.O., administered within 7 days); 2. the average dose of a mixture of debris (80 mg / kg, P.O., administered within 7 days); 3. a low dose of a mixture of debris (40 mg / kg, P.O., administered within 7 days); 4. paroxetine (3 mg / kg, P.O., administered over a period of 7 days) and 5. physiological saline (P.O.). 1 hour after the last injection of the drug, an experiment is performed by hanging the mouse by the tail.

[00241] 13.5.2 Experimental method: The tail of the mouse (1 cm to the tip of the tail) is glued with adhesive tape to a wooden plank 5 cm higher than the platform, and suspended for 6 minutes. Record the time of immobility of the mouse in the last 5 minutes.

и результат эксперимента вычисляют в виде однонаправленного ANOVA с помощью пакета программ обработки статистических данных SPSS 11.5. [00242] 13.5.3 Statistical calculation: Experimental data are presented as

and the result of the experiment is calculated as a unidirectional ANOVA using the SPSS 11.5 statistical processing software package.

[00243] 13.5.4 Experiment result: see table 19.

Table 19. The effect of a mixture of debris on the immobility time of mice Group Number of animals Immobility time (seconds) Saline solution (control) 10 82.03 ± 43.01 Paroxetine 10 38.37 ± 20.76 * High dose debris mix 10 76.91 ± 31.09 The average dose of a mixture of debris 10 78.89 ± 48.18 Low dose debris mix 10 81.31 ± 58.68 Compared with the control group: * P <0.05 and ** P <0.01.

[00244] Conclusion: In accordance with the above experiment, it can be found that although a high, medium, and low dose of a debris mixture can reduce the time of immobility of a mouse suspended by the tail, these three groups have no statistical significance compared with saline (control). Thus, a mixture of debris can be extrapolated as devoid of antidepressant function in the experiment.

Industrial suitability

[00245] The scope of the pharmaceutical composition of this invention for the treatment of depression and anxiety disorder is that:

[00246] 1. The described pharmaceutical composition of the present invention for the treatment of depression and anxiety disorder may include pharmacologically acceptable additives;

[00247] 2. The described pharmaceutical composition of the present invention for the treatment of depression and anxiety disorder can be formulated in known dosage forms, such as a powder, capsule and tablet, etc .; and

[00248] 3. The described pharmaceutical composition of the present invention for the treatment of depression and anxiety disorder can be formulated as a therapeutic nutrition for the treatment of depression and anxiety disorder.

[00249] While the invention has been described in the context of what is currently believed to be the most practical and preferred embodiments of the invention, it should be understood that the invention should not be limited by the disclosed embodiments. On the contrary, the invention is intended to cover various modifications and similar compositions included within the spirit and scope of the appended claims, which should be consistent with the broadest interpretation so as to encompass all such modifications and similar structures.

Claims (7)

1. A pharmaceutical composition for treating at least one of depression and anxiety disorder, comprising:
2-25 parts by weight ginsenoside Rg1 and Rb1;
3-46 parts by weight a glycyrrhizic acid derivative, being an acid selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, and a combination thereof; and
0.002-0.4 parts by weight cyclic jujuba adenosine monophosphate (jujuba cAMP). 2. The pharmaceutical composition according to claim 1, containing 4-12 parts by weight ginsenoside, 5-15 parts by weight derivative of glycyrrhizic acid and 0.01-0.08 wt.h. cAMP jujuba. 3. The pharmaceutical composition of claim 1, wherein the ginsenoside is extracted from ginseng, the glycyrrhizic acid derivative is extracted from licorice, and jujuba cAMP is extracted from jujuba. 4. The pharmaceutical composition according to claim 3, where the jujuba is extracted to obtain a primary extract having a primary concentration of jujuba cAMP, the primary extract is further extracted to obtain a secondary extract having a secondary concentration of jujuba cAMP, the secondary concentration of jujuba cAMP is higher than the primary concentration of jujuba cAMP and wherein the secondary extract is a feedstock for the pharmaceutical composition. 5. A pharmaceutical composition for treating at least one of depression and anxiety disorder, comprising:
2-25 parts by weight ginsenoside Rg1 and Rb1; and
3-46 parts by weight a glycyrrhizic acid derivative, being an acid selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, and a combination thereof. 6. The pharmaceutical composition according to claim 5, containing 4-12 parts by weight of ginsenoside and 5-15 parts by weight glycyrrhizic acid derivative. 7. The pharmaceutical composition according to claim 1, produced in the form of one of the food products in the field of health and additives.

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