WO2009070917A1

WO2009070917A1 - An oral pharmaceutical composition for treating barythymia

Info

Publication number: WO2009070917A1
Application number: PCT/CN2007/003388
Authority: WO
Inventors: Zuoguang Zhang
Original assignee: Chi, Yu-Fen
Priority date: 2007-11-30
Filing date: 2007-11-30
Publication date: 2009-06-11

Abstract

An oral pharmaceutical composition or health food for treating barythymia prepared by using glycyrrhizinic acid or glycyrrhetinic acid as raw material.

Description

Oral medication for treating sorrow

Technical field

The invention relates to an oral medicine for treating depression caused by glycyrrhizic acid or glycyrrhetic acid, in particular to prevent side effects such as strong vomiting. A drug or health food that treats 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.

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.

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, blood pressure rise, Gastrointestinal discomfort, nausea, nausea, vomiting, indigestion, diarrhea, constipation, lower extremity 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, Selot was found to have potential safety hazards as early as 1996. Since 2001, it has been recalled from the market. In June 2004, the US Attorney General of New York accused the British GlaxoSmithKline of fraudulently concealing a study related to the use of Celote 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-depression effects has become a full The issues of concern to the ball medical 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 by 5-HT, NE, and DA reuptake inhibition, it is possible to adopt regulation. The post-posterior mechanism of action is used to treat depression, and it has become a research and development hotspot for antidepressants in the pharmaceutical industry due to the advent of the drug-restricting mechanism Rolipram. Rollipura is an inhibitor of phosphodiesterase type 4 (PDE4). Clinical trials have shown that it has significant antidepressant effects, but it is forced to terminate R&D due to strong vomiting. However, it has developed a new generation of "receptor-poster mechanism antidepressant drugs" research and development ideas.

Therefore, in view of the shortcomings in the prior art, the applicant has carefully studied and explored, and has conceived the "orally-administered oral medication for treating depression" of the present invention. The following is a brief description of the invention. Summary of the invention

In order to overcome the deficiencies of the prior art, an object of the present invention is to provide an oral drug for treating depression caused by a raw material containing glycyrrhizic acid or glycyrrhetic acid, in particular, a new technique which does not cause side effects such as strong vomiting. Program.

The solution of the medicament of the invention is the scar of the research and exploration by the inventors, and the anti-depressant medicine is prepared by using glycyrrhizic acid or glycyrrhetinic acid as raw materials according to the pathology and pharmacological mechanism and experiment of modern medical treatment of depression, after animal experiment. Proven to have significant anti-depressant function. Licorice is a medicinal material commonly used in traditional Chinese medicine and dietary supplement diets for thousands of years. In the long-term clinical treatment of traditional Chinese medicine and daily human consumption, there has not been a case of vomiting caused by taking licorice, so the inventor proposed glycyrrhizic acid. Or glycyrrhetinic acid is used as a raw material to make new technical solutions for treating depression drugs to improve the defects produced in the prior art.

The drug of the present invention differs from the conventional antidepressant drug rolita, which is a post-receptor mechanism of action, in that it can simultaneously initiate cyclic adenosine monophosphate by inhibiting cAMP phosphodiesterase (CAPD). cAMP), in order to achieve anti-') effect, can avoid side effects such as strong vomiting caused by taking loliprazol. Glycyrrhizinate:

Chemical name: α-D-glucopyranosiduronic acid, (3β, 20β)- 20-carboxy- 11 -οχο-30-norolean- 12-3-yl,

2-0- -D-glucopyranosyl)- Synonyms: licorice, glycyrrhizin, Glycyrrhetinic acid, Glycoside, Glycyrrhizinic acid

English name: Glycyrrhizic acid, Glycyrrhizin.

Structure:

Molecular formula and relative molecular weight: C _{42 2} 0 ₁₆ , 822.92.

Biological activity: Inhibition of cAMP citrate diesterase (CAPD) with a median effective dose (ED50) of 1.9 10 ^-4 .

Since the conversion rate of glycyrrhizic acid into glycyrrhetinic acid in the human body is almost 100%, and the glycyrrhetinic acid which is more fat-soluble than glycyrrhizic acid can enter the brain through the blood-brain barrier, glycyrrhizic acid inhibits CAPD and has anti-depression effect. It is carried out by in vivo conversion to glycyrrhetinic acid, and therefore, the medicament of the present invention can be processed by using glycyrrhizic acid or glycyrrhetinic acid as a raw material.

The present invention is an oral drug for treating depression which is made of a raw material comprising glycyrrhizic acid or glycyrrhetinic acid. Preferably, the oral medicament of the present invention can be processed into a tablet, a capsule, a powder, a tablet, a powder, a solution, a micro-dip, a suspension, an emulsion, a granule, a pill, a pill, etc. Oral pharmaceutical dosage forms well known in pharmacy.

Preferably, the dosage form of the oral administration of the present invention once a day is prepared from a raw material comprising 6 to 240 mg of glycyrrhizic acid or glycyrrhetinic acid; more preferably, it comprises 12 to 120 mg of glycyrrhizic acid. Or made of raw materials of glycyrrhetinic acid.

Preferably, the oral dosage form of the oral administration of the present invention is prepared from a raw material comprising 3 to 120 mg of glycyrrhizic acid or glycyrrhetinic acid; more preferably, it comprises 6 to 80 mg of licorice. Made from raw materials of acid or glycyrrhetinic acid.

Preferably, the dosage form of the oral drug of the present invention taken three times a day is made of a raw material comprising 2 to 80 mg of glycyrrhizic acid or glycyrrhetinic acid; more preferably, it comprises 4 - 60 mg of glycyrrhizic acid. Or made of raw materials of glycyrrhetinic acid.

Preferably, the oral dosage form of the present invention is administered four times a day, and is prepared from a raw material comprising 1.5 - 60 mg of glycyrrhizic acid or glycyrrhetinic acid; more preferably, it comprises 3 to 40 mg of licorice. Made from raw materials of acid or glycyrrhetinic acid.

Preferably, the oral medicament of the present invention comprises a pharmaceutically acceptable carrier or additive.

Preferably, the invention further comprises a health food and a nutrient.

The oral medication for treating depression as described in the specification and the scope of the present application is the core of the object of the present invention. After the disclosure of the present invention, those skilled in the art can according to the theory of traditional Chinese medicine or related modern pharmacology. In theory, the above drugs are routinely added or subtracted or replaced with other traditional Chinese medicine active ingredients (such as Polygala, Bupleurum, Licorice coumarin, etc.). Such conventional addition and subtraction cultivation and replacement of the traditional Chinese medicines of other CAPD inhibitors having similar or identical mechanism of action or corresponding active ingredients are common technical activities of those skilled in the art, and thus all of them are in the present invention. Within the scope of protection.

A better understanding of the present invention can be obtained by referring to the figures and the detailed description.

1 is a schematic flow chart of a method for preparing a medicament of Example 1 of the present invention.

Fig. 2 is a flow chart showing the process of preparing the medicament of the embodiment 2 of the present invention.

Fig. 3 is a schematic flow chart showing the process of preparing the drug of the third embodiment of the present invention.

Fig. 4 is a flow chart showing the process of preparing the drug of the fourth embodiment of the present invention.

Fig. 5 is a flow chart showing the process of preparing the drug of the fifth embodiment of the present invention.

Fig. 6 is a flow chart showing the process of preparing the drug of the sixth embodiment of the present invention. Preferred embodiment of the invention

The invention will be further illustrated by the following figures and examples. The present invention is primarily directed to the preparation of the medicaments of the present invention in combination with the features of the present invention by methods well known to those skilled in the art. The following examples are merely illustrative of the invention and are not intended to limit the invention.

In order to accomplish the object of the present invention, the present invention particularly proposes the following technical solutions.

Option One:

The raw material for treating depression is treated by the raw material containing glycyrrhizic acid or glycyrrhetinic acid.

Option II:

The invention comprises the raw material containing glycyrrhizic acid or glycyrrhetinic acid, and is processed into the tablet, the capsule, the powder, the tablet, the powder, the solution, the microcapsule, the suspension, the emulsion and the granule for treating depression. Any of the pharmaceutically acceptable oral dosage forms, such as agents, pills, pills, and the like.

third solution:

The preparation of the invention is prepared by using a raw material containing 6 to 240 mg of glycyrrhizic acid or glycyrrhetinic acid in a daily dosage form; more preferably, it is made of a raw material containing 12 to 120 mg of glycyrrhizic acid or glycyrrhetinic acid. The medicament of the present invention is administered in a dosage form once a day.

Option 4:

The medicine of the present invention is prepared by using a raw material containing 3 to 120 mg of glycyrrhizic acid or glycyrrhetinic acid twice daily; more preferably, it is made of a raw material containing 6 - 80 mg of glycyrrhizic acid or glycyrrhetinic acid. The medicament of the present invention is administered in a dosage form twice daily. Option 5:

The preparation of the invention is prepared by using a raw material containing 2 to 80 mg of glycyrrhizic acid or glycyrrhetinic acid in a dosage form which is taken three times a day; more preferably, it is made of a raw material containing 4 to 60 mg of glycyrrhizic acid or glycyrrhetinic acid. A medicament of the invention in a dosage form taken three times a day.

Option six:

The preparation of the invention is prepared by using a raw material containing 1.5 - 60 mg of glycyrrhizic acid or glycyrrhetinic acid in a dosage form of four times a day; more preferably, it is made of a raw material containing 3 to 40 mg of glycyrrhizic acid or glycyrrhetinic acid. The drug of the present invention is administered in a dosage form that is taken four times a day.

Option seven:

The oral medicament of the present invention may contain a pharmaceutically acceptable carrier or additive.

Option eight:

The invention described in the present invention can also be used to make health foods and nutrients.

In order to accomplish the object of the present invention, a method of producing the following drugs is specifically proposed.

method one:

According to the Good Manufacturing Practice (GMP) pharmaceutical standard method, glycyrrhizic acid is extracted from licorice as raw material, or directly prepared by using glycyrrhizic acid or glycyrrhetinic acid as raw material, and processed into the present invention for treating depression Oral medication.

Method Two:

According to the GMP pharmaceutical standard method, the raw material containing glycyrrhizic acid or glycyrrhetinic acid is processed into a tablet, a capsule, a powder, a tablet, a powder, a solution, a micro-tank, and the like for treating depression in the present invention. Any of the pharmaceutically acceptable oral pharmaceutical dosage forms such as suspensions, emulsions, granules, pills, pills, and the like.

Method Two:

According to the GMP pharmaceutical standard method, a raw material containing 6 to 240 mg of glycyrrhizic acid or glycyrrhetinic acid is processed into a dosage form of the present invention; more preferably, it contains 12 to 120 mg of glycyrrhizic acid or The raw material of glycyrrhetinic acid is prepared into a medicament of the present invention in a dosage form which is taken once a day.

Method four: According to the GMP pharmaceutical standard method, a raw material containing 3 to 120 mg of glycyrrhizic acid or glycyrrhetinic acid is processed into a dosage form of the present invention which is administered twice a day; more preferably, it contains 6 to 80 mg of glycyrrhizic acid. Or a raw material of glycyrrhetinic acid, which is prepared into a medicament of the present invention in a dosage form which is administered twice a day.

Method five:

According to the GMP pharmaceutical standard method, a raw material containing 2 to 80 mg of glycyrrhizic acid or glycyrrhetinic acid is processed into a dosage form of the present invention which is administered three times a day; more preferably, it contains 4 to 60 mg of glycyrrhizic acid or The raw material of glycyrrhetinic acid is prepared into a medicament of the present invention in a dosage form which is administered three times a day.

Method six two

According to the GMP pharmaceutical standard method, a raw material containing 1.5 to 60 mg of glycyrrhizic acid or glycyrrhetinic acid is processed into a dosage form of the present invention which is administered four times a day; more preferably, it contains 3 to 40 mg of licorice. The raw material of acid or glycyrrhetinic acid is prepared into a medicament of the present invention in a dosage form taken four times a day.

Method seven:

According to the method of the GMP pharmaceutical standard, the medicament of the present invention may contain a raw material such as a pharmaceutically acceptable carrier or an additive, and is processed into an oral medicament for treating depression in the present invention.

Method eight:

The raw material according to the present invention is processed into a health food for treating depression according to the method for producing and manufacturing a health food.

Specific embodiment

The invention will be further described below in conjunction with the drawings and specific embodiments.

Example 1

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, according to the GMP pharmaceutical standard method, 100 g of glycyrrhizic acid having a purity of 90% is prepared as a raw material, and 170 g of starch, lactose, silica, magnesium stearate and the like are added. After the agent was uniformly mixed, it was processed into a 9,000 capsule form (30 mg/granule containing 10 mg of glycyrrhizic acid). The first embodiment of the present invention is for treating an oral or health food for depression.

Example 2

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 Figure 2, According to the GMP pharmaceutical standard method, 10 kg of licorice is crushed, firstly immersed in water at room temperature, extracted by water extraction and alcohol precipitation, and then the extracted supernatant is concentrated and dried to obtain 2.1 kg of glycyrrhizic acid-containing extract. The raw material containing the medicament of the present invention containing 0.23 kg of glycyrrhizic acid (the purity of glycyrrhizic acid in the extract is 11%) is detected by a high performance liquid chromatography instrument, and 2.5 kg of an auxiliary material such as starch, lactose and silica is added and mixed with the extract. After homogenization, the second embodiment of the present invention, which is processed into a 11,500 capsule dosage form (400 mg capsule containing 20 mg of glycyrrhizic acid), is used for the treatment of oral medication or health food for depression.

Example 3

Please refer to FIG. 3, which is a schematic flow chart of a method for preparing the drug of the embodiment 3 of the present invention. In Fig. 3, according to the GMP pharmaceutical standard method, 200 g of glycyrrhizic acid having a purity of 96% is prepared as a raw material, and 280 g of an auxiliary material such as starch, lactose, silica, magnesium stearate, and the like are added. The preparation is processed into an 8,000 tablet dosage form (60 mg/granule containing 24 mg of glycyrrhizic acid). The third embodiment of the present invention is an oral medicine or health food for treating depression.

Example 4

Please refer to FIG. 4, which is a schematic flow chart of a method for preparing the drug of the fourth embodiment of the present invention. In Figure 4, 100 g of glycyrrhetinic acid having a purity of 96% is prepared according to GMP pharmaceutical standards, and 140 g of starch, lactose, silica, strontium stearate and other excipients and excipients are added. , processed into a 8,000 tablet dosage form (30 mg / granule containing 12 mg of glycyrrhetinic acid). The fourth embodiment of the invention is used for treating oral or health food for depression.

Example 5

Please refer to FIG. 5, which is a schematic flow chart of a method for preparing the drug of Example 5 of the present invention. In Fig. 5, according to the GMP pharmaceutical standard method, 100 g of glycyrrhizic acid having a purity of 96% is prepared as a raw material, and 260 g of an auxiliary material such as starch, lactose, silica, magnesium stearate, and the like are added. The preparation is processed into a 12,000 tablet dosage form (30 mg/granule containing 8 mg of glycyrrhizic acid). The fifth embodiment of the present invention is an oral medicine or health food for treating depression.

Example 6

Please refer to FIG. 6 , which is a schematic flow chart of a method for preparing the drug of Example 6 of the present invention. In Fig. 6, according to the GMP pharmaceutical standard method, 50 g of glycyrrhetinic acid having a purity of 96% is prepared as a raw material, and 190 g of starch, lactose, silica, magnesium stearate and the like are added. Shape agent, processed 8,000 tablet dosage form (30 mg/granule containing 6 mg of glycyrrhetinic acid). The sixth embodiment of the present invention is an oral or health food for treating depression.

Experimental Example 1 Example 3 Effect on Mouse Suspension Experiment

1.1 Experimental animals

ICR mice, male, weighing 22.0 ± 2 g, secondary, provided by the Department of Laboratory Animal Science, Capital Medical University, Beijing.

1.2 Real-risk drugs

Example 3: Provided by Beijing O'Neill Bioengineering Technology Co., Ltd.

Paroxetine (Selite): Sino-US Tianjin Shike Pharmaceutical Co., Ltd. products.

1.3 Real face instrument

Stopwatch.

1.4 Dose design

Example 3 Large dose: 16 mg/kg/d, medium dose: 8 mg/kg/d and small dose: 4 mg/kg/d.

1.5 Experimental methods and results

1.5.1 Group administration

Mice were randomized into groups of 10: 1 Example 3 high dose group (16 mg/kg, PO, 7d); 2 Example 3 medium dose group (8 mg/kg, PO, 7d) 3 Example 3 Low-dose group (4 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 Experimental method

The tail of the mouse (1 cm from the tip of the tail) was adhered to the 5 cm wooden strip with a tape on the head for 6 minutes, and the immobility time of the mouse within 5 minutes after the recording was recorded.

1.5.3 Statistical processing

The experimental data were expressed as ±, and the experimental results were analyzed by SPSS 11.5 statistical software for analysis of variance. 1.5.4 Experimental results

See Table 1 for the experimental results. Table 1. Effect of Example 3 on immobility time in mice

Group other 'j number of animals (only) immobility time (seconds) saline group (model group) 10 113.22 ± 21.18 paroxetine group 10 75.33 ± 22.91 * Example 3 high dose group 10 54.67 ± 26.38** Example 3 Dosage group 10 61.60±49.84** Example 3 low dose group 10 103.26±49.91 Note: Compared with the model group * P<0.05 **P<0.01

in conclusion:

According to the above experiment, it can be seen that the large, medium-dose group and the paroxetine group of the present invention can reduce the immobility time of the mice after the tail suspension, and the high-dose and middle-dose groups are compared with the saline group (model group). There is a significant difference, so that it can be inferred that Example 3 of the present invention has an anti-experimental depression function.

Experimental Example 2 Example 3 Effect of reserpine induced hypothermia in mice

2.1 Experimental animals

ICR mice, male, weighing 22.0±2 g, secondary, provided by the Department of Laboratory Animal Science, Capital Medical University, Beijing.

2.2 Experimental drugs

Example 3: Provided by Beijing O'Neill Bioengineering Technology Co., Ltd.

Paroxetine (Selite): Sino-US Tianjin Shike Pharmaceutical Co., Ltd. products.

Reserpine: Guangdong Bangmin Pharmaceutical Factory Co., Ltd.

2.3 Experimental instruments

GM222 type electronic thermometer, stopwatch.

2.4 Dose design

2.5 Experimental methods and results 2.5.1 Group administration

The mice were randomly divided into groups of 10: 1 Example 3 large dose group (16 mg kg, PO, 7d); 2 Example 3 medium dose group (8 mg/kg, PO, 7d); 3 Example 3 Small dose group (4 mg / kg, PO, 7d administration); 4 paroxetine group (3 mg / kg, PO, 7d administration); 5 saline group (PO).

2.5.2 Experimental methods

The anus temperature of the mice was measured 1 hour after the administration on the 8th day, and then the reserpine 2 mg/kg was intraperitoneally injected, and the anal temperature of the mice was measured 4 hours after the injection of reserpine. The depth and time of insertion of the thermometer into the anus of the mouse were consistent at each temperature measurement.

2.5.3 Statistical processing

The experimental data were expressed and the experimental results were analyzed by SPSS 11.5 statistical software. 2.5.4 Experimental results

See Table 2 for the experimental results.

Table 2. Example 3 Effect of reserpine induced hypothermia in mice

Group Number of animals (only) Temperature drop value

( °C ) saline group (model group) 10 3.65 soil 0.77 paroxetine group 10

2.38±0.69**

Example 3 Large dose group 10 1.85±1.01** Example 3 Medium dose group 10 2.05±1.03** Example 3 Low dose group 10 3.30±0.69 Note: Compared with the model group * P<0.05 **P<0.01

in conclusion:

According to the above experiment, it can be seen that the large, medium-dose group and the paroxetine group of the embodiment 3 of the invention can significantly reduce the hypothermia-induced hypothermia, indicating that the anti-experimental depression effect and the influence list The amine transmitter content is related, so that it can be inferred that Example 3 of the present invention has an anti-experimental depression function. Experimental Example 3 Effect of Example 4 on Mouse Suspension Experiment

3.1 Experimental animals

3.2 Experimental drugs

Example 4: Provided by Beijing O'Neill Bioengineering Technology Co., Ltd.

Paroxetine (Selite): Sino-US Tianjin Shike Pharmaceutical Co., Ltd. products.

3.3 Experimental instruments

Stopwatch.

3.4 dose design

Example 4 Large dose: 10 mg/kg/d, medium dose: 5 mg/kg/d and small dose: 2.5 mg/kg/d.

3.5 Experimental methods and results

3.5.1 Group administration

The mice were randomly divided into groups of 10: 1 Example 4 large dose group (10 mg/kg, PO, 7d); 2 Example 4 dose group (5 mg / kg, PO, 7d) 3 Example 4 Low-dose group (2.5 mg/kg, PO, 7d); 4 paroxetine group (3 mg kg, PO, 7d); 5 saline group (PO). A tail suspension experiment was performed 1 hour after the last administration.

3.5.2 Experimental method

The tail of the mouse (1 cm from the tip of the tail) was adhered to a 5 cm-long wooden strip with a tape on the head for 6 minutes, and the immobility time of the mouse within 5 minutes after the recording was recorded.

3.5.3 Statistical processing

The experimental data were expressed as ±, and the experimental results were analyzed by SPSS 11.5 statistical software for analysis of variance. 3.5.4 Experimental results

See Table 3 for the experimental results.

Table 3. Effect of Example 4 on immobility time in mice Group animals (only) Immobility time (seconds) Saline group (model group) 10 101.64±37.20 Paroxetine group 10 60.32±29.13** Example 4 high dose group 10 62.48±30.65** Example 4 dose Group 10 70.11±28.90* Example 4 Low-dose group 10 99.82±41.38 Note: Compared with model group * P<0.05 **P<0.01

in conclusion:

According to the above experiment, it can be seen that the large, medium-dose group and the paroxetine group of the present invention can reduce the immobility time of the mice after the tail suspension, and the high-dose and middle-dose groups are compared with the saline group (model group). There is a significant difference, so that it can be inferred that Example 4 of the present invention has an anti-experimental depression function.

Experimental Example 4 Example 4 Effect of Reserpine Inducing Temperature Drop in Mice

4.1 Real-睑 animals

4.2 Real-risk drugs

Example 4: Provided by Beijing O'Neill Bioengineering Technology Co., Ltd.

Paroxetine (Selite): Sino-US Tianjin Shike Pharmaceutical Co., Ltd. products.

Reserpine: Guangdong Bangmin Pharmaceutical Factory Co., Ltd.

4.3 Experimental instruments

GM222 type electronic thermometer, stopwatch.

4.4 Dose design

Example 4 Large dose: 10 mg/kg d, medium dose: 5 mg/kg/d, small dose: 2.5 mg/kg/d „ 4.5 Experimental methods and results

4.5.1 Group administration The mice were randomized into groups of 10: 1 Example 4 large dose group (10 mg/kg, PO, 7d); 2 Example 4 medium dose group (5 mg/kg, PO, 7d) 3 Example 4 Low-dose group (2.5 mg/kg, PO, 7d); 4 paroxetine group (3 mg/kg, PO, 7d); 5 saline group (PO).

4.5.2 Experimental method

4.5 Statistical processing

The experimental data were expressed and the experimental results were analyzed by SPSS 11.5 statistical software.

4.5.4 Experimental results

See Table 4 for the experimental results.

Table 4, Example 4 The effect of reserpine induced hypothermia in mice

Group other ij number of animals (only) body temperature drop (°C) saline group (model group) 10 2.63±0.68 paroxetine group 10 1.12±0.73** Example 4 high dose group 10 1.39±0.50** Example 4 Medium dose group 10 1.96±0.66* Example 4 low dose group 10 2.11±0.98 compared with model group * P<0.05 ** P<0.01

in conclusion:

According to the above experiment, it can be seen that the large, medium-dose group and the paroxetine group of the present invention can significantly reduce the decrease of body temperature induced by reserpine, indicating that the anti-test depression effect may affect the monoamine neurotransmitter content. Relatedly, it can be inferred that Example 4 of the present invention has an anti-experimental depression function. Modifications, equivalent changes and modifications are still within the scope of the technical solutions of the present invention. Industrial applicability

The scope of application of the oral medicament of the present invention for treating depression:

1. The oral drug for treating depression according to the present invention may contain a pharmaceutically acceptable additive;

2. The oral medicament for treating depression according to the present invention can be processed into various conventionally known dosage forms such as powders, capsules, tablets, and the like;

3. The oral medicament for treating depression according to the present invention can be used for the treatment of health food for depression.

Claims

Claim

A medicament for treating depression, which is an oral drug selected from the group consisting of a glycyrrhizic acid, a glycyrrhetinic acid or a combination thereof.

The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is formulated into a dosage form selected from the group consisting of a tablet, a capsule, a powder, a tablet, a powder, and a dosage form. Any one of a solution, a microcapsule, a suspension, an emulsion, a granule, a pill, a pill, and a pharmaceutically acceptable oral pharmaceutical dosage form.

3. The medicament according to claim 2, which is a dosage form prepared once a day, wherein the dosage form is a raw material selected from the group consisting of 6 to 240 mg of the glycyrrhizic acid, the glycyrrhetic acid or a combination thereof. Made.

The drug according to claim 3, wherein the dosage form is further prepared from a raw material selected from the group consisting of 12 to 120 mg of the glycyrrhizic acid, the glycyrrhetic acid or a combination thereof.

5. The medicament according to claim 2, which is a dosage form prepared twice daily, wherein the dosage form is selected from the group consisting of 3 to 120 mg of the glycyrrhizic acid, the glycyrrhetic acid or a combination thereof. Made from raw materials.

The drug according to claim 5, wherein the dosage form is further prepared from a raw material selected from the group consisting of 6 to 80 mg of the glycyrrhizic acid, the glycyrrhetic acid or a combination thereof.

7. The medicament according to claim 2, which is a dosage form prepared three times a day, wherein the dosage form is a material selected from the group consisting of 2 to 80 mg of the glycyrrhizic acid, the glycyrrhetic acid or a combination thereof. Made.

The drug according to claim 7, wherein the dosage form is further prepared from a raw material selected from the group consisting of 4 to 60 mg of the glycyrrhizic acid, the glycyrrhetic acid, and or a combination thereof.

9. The medicament according to claim 2, which is a dosage form prepared four times a day, wherein the dosage form is selected from the group consisting of 1.5 to 60 mg of the glycyrrhizic acid, the glycyrrhetic acid or a combination thereof. Made from raw materials.

10. The medicament according to claim 9, wherein the dosage form is further prepared from a raw material selected from the group consisting of 3 to 40 mg of the glycyrrhizic acid, the glycyrrhetinic acid, and or a combination thereof.

The medicament according to claim 1, wherein the medicament contains a carrier selected from a pharmaceutically acceptable carrier, an additive, or a combination thereof.

The medicament according to claim 1, wherein the medicament is a health food or a nutrient.