阅读说明：本技术 调胃承气汤在制备防治精神***症患者服用奥氮平引起的代谢综合症的药物中的应用 (Application of stomach-regulating qi-supporting decoction in preparation of medicine for preventing and treating metabolic syndrome caused by olanzapine taken by schizophrenia patient ) 是由 朱丽萍 龙彬 赵静 张建明 陆颖 陈妍 于 2020-07-01 设计创作，主要内容包括：本发明涉及调胃承气汤在制备防治精神分裂症患者服用奥氮平引起的代谢综合症的药物中的应用。本发明通过临床实验评价了调胃承气汤治疗精神分裂症患者服用奥氮平引起代谢综合症的疗效和安全性,结果表明,与二甲双胍相比,调胃承气汤可以更好地改善精神分裂症患者服用奥氮平引起的体重及腰围的增加、降低糖化血红蛋白,副反应更少；调胃承气汤对服用奥氮平后引起的血脂各项指标紊乱有预防作用。本发明为临床精神分裂症患者服用奥氮平引起代谢综合症的防治提供了一种新的有效手段。(The invention relates to application of stomach regulating and qi supporting decoction in preparing a medicine for preventing and treating metabolic syndrome caused by olanzapine taken by a patient with schizophrenia. The curative effect and the safety of the stomach-regulating qi-supporting decoction for treating metabolic syndrome caused by olanzapine taken by patients with schizophrenia are evaluated through clinical experiments, and the results show that compared with metformin, the stomach-regulating qi-supporting decoction can better improve the weight and waistline increase caused by olanzapine taken by patients with schizophrenia, reduce glycosylated hemoglobin and has fewer side reactions; the stomach-regulating qi-supporting decoction has a prevention effect on various index disorders of blood fat caused by olanzapine taking. The invention provides a new effective means for preventing and treating metabolic syndrome caused by olanzapine taken by patients with clinical schizophrenia.)

1. The application of a traditional Chinese medicine composition in preparing a medicine for preventing and treating metabolic syndrome caused by olanzapine taken by a patient with schizophrenia is characterized in that the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 8-10 g of rhubarb, 5-7 g of liquorice and 5-7 g of mango.

2. The application of claim 1, wherein the raw material medicines are in parts by weight as follows: rhubarb horsetails 9 g, licorice root 6g, and mango juice 6 g.

3. Use according to claim 1 or 2, wherein the medicament is in an oral dosage form.

4. The use according to claim 3, wherein the oral dosage form is a decoction, a granule, a tablet, a capsule or a mixture.

5. The use according to claim 1 or 2, wherein the medicament further comprises a pharmaceutically acceptable carrier.

6. Use according to claim 5, wherein the pharmaceutically acceptable carrier is selected from the group consisting of emulsifiers, excipients, fillers, binders, humectants, disintegrants, absorption enhancers, flavourings, colourings and cosolvents.

Technical Field

The invention relates to the field of traditional Chinese medicine compositions, in particular to application of stomach-regulating qi-supporting decoction in preparing a medicine for preventing and treating metabolic syndrome caused by olanzapine taken by a patient with schizophrenia.

Background

Antipsychotics are the primary treatment of schizophrenic patients, but most of them, especially the second generation antipsychotics, often cause weight gain, glycolipid metabolic disorders, etc., leading to the development of metabolic syndrome. About one third of schizophrenic patients have metabolic syndrome, accounting for 69% of chronic patients^[1]. The prevalence of obesity, type 2 diabetes and hypercholesterolemia in schizophrenic patients is estimated to be 3-5 times that of the general population^[2]. Compared to the general population, schizophrenic patients are twice as likely to be diagnosed with heart disease and die as the general population^[3]. The mortality gap between schizophrenic patients and the general population is expanding^[4]. Metabolic syndrome is an independent predictor of cardiovascular disease and a major public health problem requiring urgent countermeasures^[5]。

Psychologists recommend a healthy lifestyle for the metabolic syndrome caused by taking antipsychotic drugs. If lifestyle changes fail, the patient needs to receive a pharmaceutical intervention. It is contemplated to switch to antipsychotics which are less metabolically risky, but this may lead to repeated disease or other adverse effects of the drug. It is also contemplated that drugs (e.g., metformin, etc.) may be added to reduce the risk of weight gain and metabolic abnormalities caused by antipsychotics. It has been shown that metformin reverses the weight gain and metabolic disturbances associated with olanzapine treatment^[6]Meta-analysis also indicates that metformin can manage antipsychotic-associated metabolic disorders^[7]. However, metformin also has some adverse reactions which cannot be tolerated by patients, such as nausea, vomiting, diarrhea, abdominal pain, abdominal distension, dyspepsia, hypodynamia and the like. It has also been reported that metformin causes spermatozoaWorsening of mental symptoms^[8]. Therefore, scholars at home and abroad are still striving to explore other treatment means capable of improving metabolic syndrome.

The existing research shows that the Chinese herbal medicine has obvious effect on treating the metabolic syndrome caused by the antipsychotic drugs. For example, the phlegm-eliminating and lipid-lowering decoction can remarkably improve the clinical effect of metformin on treating obesity caused by antipsychotics, and the phlegm-eliminating and lipid-lowering decoction comprises the following components: poria cocos, white atractylodes rhizome, pinellia tuber, dried orange peel each 15g, oriental water plantain rhizome, cape jasmine fruit, coptis root each 10g, polygala root, curcuma root, finger citron, Sichuan reed each 12g, licorice root 10g^[9]. The weight-reducing and fat-reducing decoction is combined with the metformin hydrochloride enteric-coated tablet to treat obesity caused by antipsychotics, can effectively reduce the weight of a human body and has few adverse reactions, and the weight-reducing and fat-reducing decoction comprises the following medicinal components: 15g of ginger processed pinellia tuber, 12g of dried orange peel, 12g of bighead atractylodes rhizome, 10g of rhubarb, 12g of hawthorn, 12g of tuckahoe, 12g of rhizoma alismatis and 6g of liquorice tablets, and the following are added: os Draconis and Concha Ostreae for patients with delusions and severe insomnia; radix aucklandiae and rhizoma Zingiberis recens for treating abdominal distention and fullness; rhizoma Dioscoreae, radix astragali, and fructus evodiae can be added for patients with soreness of waist and knees and listlessness; for halitosis, food hunger, thirst, and constipation, Coptidis rhizoma may be added^[10]. The Liu Yu Tang can effectively improve the glycolipid metabolism of a patient suffering from metabolic syndrome of schizophrenia caused by olanzapine, effectively regulate the blood pressure of the patient and improve the mental symptoms of the patient, and the Liu Yu Tang comprises the following components: rhizoma Ligustici Chuanxiong, Poria, fructus Amomi 15g each, rhizoma Pinelliae, fructus Gardeniae, fructus Aurantii Immaturus, rhizoma Cyperi, rhizoma Atractylodis, pericarpium Citri Tangerinae, cortex Magnolia officinalis 12g each, and Glycyrrhrizae radix 6g^[11]. The metformin-combined self-made Shugandingzhi decoction can relieve the adverse effects of the increase of physical quality and the disturbance of glycolipid metabolism of patients with schizophrenia caused by olanzapine and is beneficial to improving the clinical curative effect, and the Shugandingzhi decoction comprises the following components: 15g of radix bupleuri, 30g of snakegourd fruit, 15g of cape jasmine fruit, 15g of immature bitter orange, 15g of white paeony root, 12g of radix curcumae, 10g of arisaema cum bile, 12g of ginger processed pinellia tuber, 10g of coptis chinensis, 10g of rhizoma acori graminei, 30g of raw dragon and oyster respectively, and 6g of honey-fried licorice root; radix et rhizoma Rhei and Natrii sulfas can be added for patients with constipation and abdominal distention and pain; cinnabaris and Succinum can be added for patients with severe insomnia; for those who are thirsty and drinking pleasure, ginger-processed pinellia tuber is removed, and trichosanthes root and rhizoma anemarrhenae are added; rhizoma Ligustici Chuanxiong and fructus Vitics Simplicifoliae can be added for patients with headache; gypsum Fibrosum can be added for patients with sweating and fever^[12]. The lipid glucose-eliminating granule for treating schizophrenia with metabolic syndrome has the effects of reducing blood sugar, reducing weight, reducing triglyceride and regulatingThe function of cholesterol and the control of hypertension, and the lipid sugar eliminating granule medicine comprises the following components: summer 1 bag, pericarpium Citri Tangerinae 1 bag, Poria 1 bag, Glycyrrhrizae radix 1 bag, bupleuri radix 1 bag, Saviae Miltiorrhizae radix 2 bag, radix Puerariae 2 bag, and Trichosanthis radix 2 bag^[13]。

The stomach-regulating Chengqi decoction in Zhang Zhongjing Shang Han Lun is a proved recipe used for thousands of years and has been widely used clinically. The stomach-regulating qi-supporting decoction comprises 9 g of rhubarb (peeled and washed by sake), 6g of liquorice (roasted) and 6g of mango, and has the functions of treating slow-descending heat accumulation, main yangming disease gastrointestinal dryness-heat, thirst and constipation, abdominal fullness and tenderness, yellow tongue coating and smooth and rapid pulse; in the formula, rhubarb is bitter and cold in taste, the fire-purging and knot-dredging function is taken as a monarch, the mango is salty and cold in taste, the hard lump is softened and the dryness is moistened as a minister, the liquorice is sweet and moderate, the qi is benefited and the stomach is nourished, the bitter of the yellow is slowly relieved, and the potency of the guiding drug is slowly released to act as an assistant. The dryness-heat is relieved and the stomach-qi is self-harmonized, so it is called as stomach-regulating and qi-supporting decoction.

At present, no report on the application of stomach-regulating qi-supporting decoction in preventing and treating metabolic syndrome caused by olanzapine taken by schizophrenia patients is found.

Disclosure of Invention

The invention provides an application of a traditional Chinese medicine composition in preparing a medicine for preventing and treating metabolic syndrome caused by olanzapine taken by a patient with schizophrenia aiming at the defects in the prior art, wherein the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 8-10 g of rhubarb, 5-7 g of liquorice and 5-7 g of mango.

As a preferred example, the weight parts of the raw materials are as follows: rhubarb horsetails 9 g, licorice root 6g, and mango juice 6 g.

As another preferred example, the dosage form of the drug is an oral dosage form.

More preferably, the oral dosage form is decoction, granules, tablets, capsules or mixture.

As another preferred example, the medicament further comprises a pharmaceutically acceptable carrier.

More preferably, the pharmaceutically acceptable carrier is selected from the group consisting of emulsifiers, excipients, fillers, binders, humectants, disintegrants, absorption enhancers, flavoring agents, coloring agents and co-solvents.

The invention has the advantages that:

1. the inventor believes that the atypical antipsychotic olanzapine causes dysfunction of the spleen and the stomach, causes dryness-heat in the stomach and the intestine, polyphagia, hunger, dry stool or constipation, red tongue with yellow and dry fur and forceful pulse. According to the syndrome differentiation and treatment of the traditional Chinese medicine, the excessive stomach heat causes the appetite to be enhanced, the excessive food intake amount and the accumulation of green fat to form the metabolic syndrome. Therefore, the stomach-regulating and qi-supporting decoction is used for treating the adverse reaction of the metabolic syndrome caused by olanzapine and carrying out related clinical research to evaluate the curative effect and safety of the olanzapine.

2. In clinical studies, the method: 72 patients were randomly assigned to the modified stomach Chengqi decoction group (study group) and the metformin group (control group) for 8 weeks. Blood pressure, body weight, body mass index, waist circumference, hip circumference, waist-to-hip ratio measurements were performed on the patients at baseline and at the end of weeks 4 and 8, while triglyceride, total cholesterol, high density lipoprotein, low density lipoprotein, apolipoprotein-a, apolipoprotein-B, fasting glucose, glycated hemoglobin were measured before and after treatment to assess the change in the adverse reactions of the metabolic syndrome in the patients. As a result: (1) repeated measures analysis of variance, main effects analysis: the time-major effect of waist circumference after intervention was statistically significant (P <0.05), individual effect analysis: the body weights of the study groups differed at different time points before and after treatment (P <0.01), while the body weights of the control groups did not differ before and after treatment (P > 0.05); the differences between the time points before and after waist circumference treatment in the study group were statistically significant (P <0.05), while no significant difference was observed between the time points before and after waist circumference treatment in the control group (P > 0.05). (2) The time-major effect of triglycerides after intervention was statistically significant (P <0.05) using repeated measures of anova. After the study group had a decrease in total cholesterol (P ═ 0.059), an increase in HDL, a decrease in LDL, and a decrease in apolipoprotein-B at each time point, but the differences were not statistically significant (P > 0.05). (3) After dry prognosis, the change before and after glycated hemoglobin treatment (baseline phase-8 weeks after treatment) between groups was statistically significant (Z-2.378, P0.017), and the change before and after fasting glucose treatment was not statistically significant (P > 0.05). (4) Analysis of repeated measures of variance, analysis of main effects: after intervention, the Chinese medicine syndrome scale score has statistical significance (P <0.05) for comparing the main effect among groups, and the time main effect has statistical significance (P < 0.001). The effect analysis alone shows that the difference between the study group and the control group before and after treatment in the aspect of Chinese medicine symptom scale score has statistical significance (P is less than 0.01). (5) After the dry prognosis, the two groups of patients have the adverse reactions of tremor, akathisia, hypoactivity, constipation, salivation, blurred vision, insomnia, abnormal electrocardiogram and the like, and the incidence rate of the adverse reactions of the treatment group in the aspects of dry mouth, nausea, vomiting and diarrhea is obviously reduced compared with that of the control group (P is less than 0.05). And (4) conclusion: compared with metformin, the stomach-regulating qi-supporting decoction can better improve the increase of body weight and waist circumference of a schizophrenic patient caused by olanzapine taking, reduce glycosylated hemoglobin and has fewer side effects. The stomach-regulating qi-supporting decoction has a prevention effect on various index disorders of blood fat caused by olanzapine taking.

3. In the early stage of research, clinical diagnosis and treatment experience shows that the stomach-regulating and qi-supporting decoction has a remarkably better prevention and treatment effect on metabolic syndrome caused by olanzapine taken by schizophrenia patients than other formulas.

4. The stomach-regulating qi-supporting decoction can prevent and treat metabolic syndrome caused by olanzapine taken by schizophrenia patients, and has early curative effect.

5. Compared with other formulas, the stomach-regulating qi-supporting decoction has the advantages of less medicinal ingredients, convenience in preparation and low cost.

Drawings

FIG. 1: the body weight and waist circumference before and after treatment in the two groups were compared.

Detailed Description

The following detailed description of the present invention will be made with reference to the accompanying drawings.