CN100398138C - A traditional Chinese medicine for antidepressant and treating hypothermia - Google Patents

Abstract

The invention discloses a traditional Chinese medicine for antidepressant and treating hypothermia, which comprises polygala, turmeric, rhizoma rhizome and licorice. The traditional Chinese medicine of the invention overcomes the toxicity of chemical antidepressants, and overcomes the defect that domestic and foreign antidepressant herbal medicines have no obvious influence on the objective physiological indicators of the body. The body temperature of the mouse reserpine depression model was significantly increased, and the low, medium, and high doses could increase the body temperature by 1.69°C, 2.22°C, and 2.63°C, respectively. The content of norepinephrine, dopamine and 5-hydroxytryptamine in the brain tissue was also significantly higher than that of the reserpine depression model group. The depressive symptoms of the mice were also significantly reduced compared with the control group, and the ptosis of the upper eyelid was improved. The tail-suspension time of the mice was shortened, and the voluntary activity was enhanced. It shows that the traditional Chinese medicine preparation has obvious therapeutic effect on depression, is a clear curative effect, safe and ideal antidepressant, and has good development prospect.

Description

A traditional Chinese medicine for antidepressant and treating hypothermia

technical field

The invention relates to a traditional Chinese medicine for antidepressant and treating hypothermia

Background technique

In the early 1950s, the first generation of antidepressants monoamine oxidase inhibitors and tricyclic antidepressants began to be used clinically, but their application was severely limited due to extensive and serious side effects ^[1-13] ; in the 1960s The second-generation antidepressants developed since then are mainly heterocyclics, mainly including reversible monoamine oxidase inhibitors and selective serotonin reuptake inhibitors. Although the safety of these drugs has improved compared with the first-generation antidepressants, the curative effect has not been significantly improved, and the side effects are still relatively large, such as nausea, anxiety, decreased appetite and decreased sexual function, so there is no ideal antidepressant so far. Depressants came out. On June 2, 2004, GlaxoSmithKline, a world-renowned pharmaceutical company, was accused in New York State of the United States of producing the antidepressant Paroxetine, which was neither effective nor safe. On November 7 this year, the British "Observer" reported that the British Parliament was investigating the company. Recently, the US Food and Drug Administration (FDA) issued a comprehensive warning that the use of antidepressants (chemical drugs) in children has an increased risk of suicide. In view of the serious side effects of western medicine, many researchers have gradually lost confidence in the treatment of depression with western medicine, and turned to traditional herbal medicine to find effective therapeutic drugs. Hypericin extracted from medicinal plants by European scientists in the 1990s has been used for the treatment of depression and has been included in the national pharmacopoeias of Germany, Russia, Poland, and Switzerland ^[14] . But the same two clinical trials in the United States had no results ^[15,16] .

The traditional Chinese medicine prescription can obviously improve the symptoms of the mouse depression model, increase the body temperature of the reserpine depression model mouse, and increase the content of monoamine transmitters in the brain tissue. The LD ₅₀ could not be measured in the acute toxicity test, and no obvious toxic reaction was found in the maximum tolerated dose test. It shows that Polygala Prescription is a clear, safe and ideal antidepressant.

Contents of the invention

In order to solve the problem of large and extensive side effects of classic antidepressants, the object of the present invention is to provide an antidepressant traditional Chinese medicine with definite curative effect, obvious effect, convenient and safe use, and its dosage forms are called Jinzhi Kangdepress Tablets and Jinzhi Kangdepress Capsules.

The traditional Chinese medicine compound of the present invention has the following components: polygala, turmeric, Cyperus cyperi and licorice.

Each drug in the prescription is formulated according to the ratio of 8:5:5:1, the preparation process is determined through pharmaceutical research, and the dosage forms of tablets and capsules are made. Adults take 19g equivalent to the crude drug amount every day, and take it twice.

Three doses of antidepressants in the form of capsules were administered to Kunming mice to treat depression induced by reserpine. Observe the changes of the ptosis of the upper eyelid, the body temperature and the content of monoamine transmitters in the brain tissue of the mice.

The prescription of this traditional Chinese medicine can inhibit the drooping effect of the upper eyelid caused by reserpine, the overall P<0.01. The P value of the ratio between the low-dose group and the model group was close to 0.05, and the P value of the ratio between the middle-dose and high-dose group and the model group was <0.01.

The prescription of traditional Chinese medicine can obviously curb the drop of body temperature caused by reserpine. The P values of the ratios between the low, medium and high dose groups and the model group were all less than 0.01, and the hypothermia of the mice in each dose group was 1.69°C, 2.22°C and 2.63°C higher than that of the depression model group, respectively.

The contents of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the brain tissue of mice in each dosage group of traditional Chinese medicine were significantly higher than those in the depression model control group.

In the mouse tail suspension test, the immobility time of the mice within 4 minutes of each Chinese medicine dosage group was significantly shorter than that of the normal group (P<0.01), and there was a certain dose-effect relationship.

The traditional Chinese medicine formula conforms to the anti-depressant formula principle of traditional Chinese medicine. In addition to significantly improving the above objective indicators, it can also increase the voluntary activities of the depression model mice, enhance the compulsive biting activity, and improve the depressive symptoms of the mice. Significant improvement, its effect is comparable to imipramine antidepressant.

Detailed ways

1. Preparation process

Polygala, Curcuma Cyperi, Radix Cyperi and Glycyrrhiza were formulated according to the weight ratio of 8:5:5:1, and the preparation process was determined through pharmaceutical research as follows: the turmeric and Rhizoma Cyperi were refluxed with 70% ethanol to extract the volatile oil, and the volatile oil was extracted with β - Cyclodextrin inclusions. The above medicinal residues are mixed with polygala and licorice, decocted with 7 times of water for 2 hours, extracted twice, filtered, centrifuged at 2000 rpm, mixed with inclusions, concentrated and dried. Add auxiliary materials and flavoring agents to make sugar-coated tablets or capsules.

2. Antidepressant experiment

The experimental animals are male Kunming mice with a body weight of 20±2 g, and the depression model is reproduced by subcutaneous injection of reserpine 5 mg/kg. They were divided into normal group, model group, low-dose Chinese medicine group, middle-dose Chinese medicine group, high-dose Chinese medicine group and imipramine group, with 10 animals in each group. Gastric feeding.

In the normal group, 0.1 ml of normal saline was injected subcutaneously, and 0.5 ml of normal saline was fed into the stomach. The model group was subcutaneously injected with reserpine 5 mg/kg, and 0.5 ml of normal saline was fed into the stomach. In the low dose group of traditional Chinese medicine, 5 mg/kg of reserpine was subcutaneously injected, and the equivalent of 1 g (crude drug)/kg (about 20 mg/monkey) of traditional Chinese medicine was fed into the stomach. In the traditional Chinese medicine group, 5 mg/kg of reserpine was injected subcutaneously, and 5.5 g (crude drug)/kg (about 110 mg/monkey) of traditional Chinese medicine was fed into the stomach. In the high-dose group of traditional Chinese medicine, 5 mg/kg of reserpine was injected subcutaneously, and 11 g (crude drug)/kg (about 220 mg/monkey) of traditional Chinese medicine was fed into the stomach. In the imipramine group, 5 mg/kg reserpine was injected subcutaneously, and 20 mg/kg imipramine was fed into the stomach. Observe the following indicators:

(1) Upper blepharoptosis test: After 1 hour, the eyelids of the mice were observed for 30 seconds.

(2) Mouse body temperature drop suppression experiment: 18 hours after the administration, the corresponding drug was fed into the stomach again, and the anal temperature of the mice was measured after 1 hour.

(3) Determination of monoamine (NE, DA, 5-HT) content in mouse brain tissue: (the model is the same as above). take brain tissue,

The content of monoamine transmitters was determined by fluorescence method.

(4) Mouse tail suspension test: tail suspension for 6 minutes. The immobility time within 4min after observation.

(5) Rat swimming despair test, mouse swimming despair test.

(6) After 30 minutes, put it into a GJ-8506 mouse activity counter, and measure the number of spontaneous activities within 10 minutes.

Experimental results:

(1). Upper eyelid ptosis test: place the mouse again, observe eyelids for 30 seconds, and score eyelid ptosis, eyes closed = ++++, eyelids closed 3/4 = +++, eyelids closed 1/2 = + +, eyelids closed 1/4 = +, eyes not closed = 0. A rank sum test was performed on the observed ranking results.

Rank sum test of antidepressant traditional Chinese medicine antagonizing reserpine upper eyelid ptosis test (1 hour after administration)

Note: ++++: upper eyelid fully closed, +++: upper eyelid closed 3/4, ++: upper eyelid closed 1/2, +: upper eyelid closed 1/4, -: upper eyelid fully open

H=12/(N(N+1))∑R ² /n-3(N+1)=14.45085 c=1-∑(t ³ -t)/(N ³ -N)=0.93058 $\mathrm{Hc}=h/\sqrt{C}=14.98017$

k=4 v=k-1=3 X ² value _0.005·3 =12.48, Hc>X ² value _0.05·3· P<0.005

The prescription of this traditional Chinese medicine can inhibit the drooping effect of the upper eyelid caused by reserpine, the overall P<0.01.

Further use the t test method for pairwise comparisons:

Rank sum t-test for pairwise comparison of antidepressant traditional Chinese medicine antagonizing reserpine upper eyelid ptosis test

The P value of the ratio between the low-dose group and the model group was close to 0.05, and the P value of the ratio between the middle-dose and high-dose group and the model group was <0.001.

(2) Mouse body temperature drop suppression test:

The mouse model was prepared with reserpine, and the therapeutic drug was administered at the same time, and the therapeutic drug was given again 18 hours later, and the rectal temperature was measured 2 hours later.

Inhibition of antidepressant traditional Chinese medicine on reserpine-induced hypothermia test in mice (℃)

Note: P<0.01 for each dose group compared with the model group

High, medium and low doses can increase the hypothermia of the depression model mice by 1.69°C, 2.22°C and 2.63°C, respectively, compared with the model group.

(3) Determination of catecholamine content in mouse brain tissue:

The mouse grouping, model preparation, and administration methods were all the same as those in Experiment 3. They were killed 2 hours after the last administration, and the brain tissue was taken immediately, and processed according to the method in literature ⁽¹⁷⁾ to extract catecholamines (5-HT, DA, NE) . Determined by a modified fluorescence method.

Effects of Antidepressant Traditional Chinese Medicine on Neurotransmitter Content in Brain Tissue of Depressed Rats (ng/g wet tissue)

Note: ^** : The ratio of each drug dose group to the model group is P<0.01.

The contents of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the brain tissue were significantly higher than those in the depression model control group.

(4) Mouse tail suspension test

The mice were divided into random groups, 15 in each group, and the tails of the mice (1 cm away from the tail tip) were glued in a box of 20×25×25 cm after 1 hour of administration. The head is 5 cm from the bottom, hang upside down for 6 minutes, and record the time that the mouse does not move within 4 minutes afterward.

The immobility time (s) of antidepressant traditional Chinese medicine on mice tail suspension test within 4min

Compared with the normal group, the immobility time of the mice in each administration group was significantly shortened.

The present invention can not only obviously improve the above-mentioned objective indicators, but also increase the autonomous activities of the depression model mice, enhance the compulsive biting activity, and significantly improve the depressive symptoms of the mice. The medicine is quite.

Since this formula can not only improve the symptoms of depression models caused by drugs such as reserpine and tetrabenzine, but also improve the symptoms of depression caused by various stimuli, its effect is equivalent to that of the classic antidepressant imipramine .

The recipe was disassembled and verified with the above indicators, which proved that polygala played a key role. Traditional Chinese medicine believes that depression is caused by emotional failure, liver depression and qi stagnation, spleen failure, resulting in qi stagnation and blood stagnation, and liver qi failure. Therefore, the traditional treatment of depression is to regulate qi and relieve depression, and all depressions Hurt the mind, treat depression and calm the heart. This prescription is compatible with traditional Chinese medicines such as relieving stagnation and calming the nerves, soothing the liver and regulating qi, nourishing blood and calming the heart, and has the effects of soothing the liver and regulating qi, relieving stagnation and calming the nerves. Therefore, the special pharmacological effects of turmeric, Cyperus cyperi, and licorice were used in this prescription to strengthen the antidepressant effect and play a good therapeutic effect. Modern medicine believes that depression is not just the excessive depletion of monoamine transmitters, but the result of multiple factors, such as the excitatory amino acid (NMDA) receptor system. Traditional Chinese medicine has obvious advantages in treating diseases caused by multiple factors. According to the theory of monarch, minister, assistant and envoy, it can regulate the body as a whole. Therefore, this formula has a significant effect on treating various types of depression.

The acute toxicity test of this traditional Chinese medicine prescription could not detect the LD ₅₀ , and no obvious toxic reaction was found in the maximum tolerated dose test. It shows that this group of prescriptions is a traditional Chinese medicine group that can significantly improve the symptoms of the mouse depression model, increase the body temperature of the reserpine depression model mice, and increase the content of monoamine transmitters in the brain tissue. The LD ₅₀ could not be measured in the acute toxicity test, and no obvious toxic reaction was found in the maximum tolerated dose test. It shows that Polygala Prescription is a clear, safe and ideal antidepressant. A clear, safe and ideal antidepressant.

references

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Claims (2)

1. the Chinese medicine of antidepressant and treatment hypothermia disease is characterized in that being made by following raw material: Radix Polygalae 10-15g, Radix Curcumae 5-8g, Rhizoma Cyperi 5-8g, Herba Hyperici perforati 3-6g, Radix Glycyrrhizae 1-3g.

2. Chinese medicine according to claim 1 is characterized in that adopting conventional process to make tablet and capsule formulation.