CN115624604B

CN115624604B - Traditional Chinese medicine composition for treating climacteric depression and preparation method and application thereof

Info

Publication number: CN115624604B
Application number: CN202211099175.3A
Authority: CN
Inventors: 耿嘉玮
Original assignee: GULOU TRADITIONAL CHINESE MEDICAL HOSPITAL BEIJING
Current assignee: GULOU TRADITIONAL CHINESE MEDICAL HOSPITAL BEIJING
Priority date: 2022-09-07
Filing date: 2022-09-07
Publication date: 2023-10-24
Anticipated expiration: 2042-09-07
Also published as: CN115624604A

Abstract

The application relates to a traditional Chinese medicine composition for treating climacteric syndrome and depression, and a preparation method and application thereof, wherein the traditional Chinese medicine composition is prepared from the following raw materials: lily, glossy privet fruit, cortex albiziae, lotus plumule, eclipta alba, radix curcumae, rhizoma acori graminei, dens draconis, fructus Tritici Levis and inula flower. Making into capsule, tablet, granule, etc. according to conventional pharmaceutical method. The pharmaceutical preparation disclosed by the application can treat both symptoms and root causes of climacteric depression, has no side effect, is low in price, is simple and convenient to prepare, and has a wide application prospect.

Description

Traditional Chinese medicine composition for treating climacteric depression and preparation method and application thereof

Technical Field

The application belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating climacteric depression, and a preparation method and application thereof.

Background

The climacteric depression syndrome is a word which is continuously lifted in the current society, the high-speed development of the society brings pressure to a plurality of people, the pressure can not be released, and finally, diseases such as depression and the like are generated, and the depression is an emotional state of emotional mental disorder. Affective disorders are defined as a group of mental disorders that take a marked and persistent change in mood (high or low) as a basic clinical manifestation, accompanied by corresponding mental and behavioral abnormalities.

Climacteric syndrome (climacteric syndrome) refers to the symptoms and psychological syndromes of the various organ systems caused by changes in the mental, neuroendocrine and metabolic processes of menopause. With age, female ovarian function declines, sex hormone secretion decreases, resulting in elevated gonadotrophin levels, causing imbalance of hypothalamic-pituitary-ovarian axis, and thus endocrine and autonomic nerve dysfunction. Is characterized by irritability, easy crying, hot perspiration, dysphoria with feverish sensation in chest, dizziness, tinnitus, amnesia, palpitation, insomnia, menstrual disorder, arthralgia and the like. Men are associated with impaired testicular function and reduced testosterone levels. Other things such as genetics, environment, living habit, diet structure, individual constitution, character, whether there is mental stress and so on are closely related to them.

At present, the pathogenesis of climacteric depression is not completely elucidated and is in the exploratory stage. However, a great deal of research has shown that the decline of estrogen levels, dysfunction of the neuroendocrine axis, and release of monoamine neurotransmitters all may lead to the onset of this disease, and academic views such as "cytokine hypothesis", "hyperglucocorticoid hypothesis" have been proposed by the scholars.

The treatment of climacteric depression is focused on treating specific etiology, and a better treatment effect can be achieved only by removing the root cause of the pathogenesis. Although western medicine can alleviate clinical symptoms of patients to some extent in a short time, western medicine has many disadvantages in treating climacteric depression in the long term. For example: it has a lot of adverse reactions, potential cancerogenic risks, and physiological or psychological dependence and addiction after being taken for a period of time; the clinical recurrence rate after stopping the medicine is higher, the compliance is poor, and the like, and the use is controversial, thereby limiting the clinical application of the medicine. The current Western medicine mainly comprises the following using methods: antidepressants, hormone replacement therapy, calcium and vitamin D therapy, and behavioral therapies such as psychotherapy, aerobic exercise, etc.

Disclosure of Invention

In view of the above, the application provides a traditional Chinese medicine composition for treating climacteric depression, which has the advantages of abundant clinical experience, better treatment effect and unique advantages in treating climacteric depression. Under the guidance of the theory of traditional Chinese medicine, the syndrome differentiation is more flexible, the medication is safer, and the application prospect is wider. And also provides a preparation method and application of the traditional Chinese medicine composition.

According to the theory of traditional Chinese medicine, through continuous exploration of the inventor, the unique drug property of the traditional Chinese medicine is utilized to carefully screen the traditional Chinese medicine in the field, and a traditional Chinese medicine composition formula for treating climacteric depression is obtained, wherein the formula is as follows: lily, glossy privet fruit, cortex albiziae, lotus plumule, eclipta alba, radix curcumae, rhizoma acori graminei, dens draconis, fructus Tritici Levis and inula flower.

The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 3 to 10 parts of lily, 3 to 6 parts of glossy privet fruit, 3 to 6 parts of cortex albiziae, 1 to 1.5 parts of lotus plumule, 3 to 6 parts of eclipta alba, 3 to 5 parts of radix curcumae, 1.5 to 5 parts of grassleaf sweelflag rhizome, 7.5 to 15 parts of dens Draconis, 7.5 to 15 parts of light wheat and 1.5 to 4.5 parts of inula flower.

The traditional Chinese medicine composition is preferably selected, and the preferred weight part ratio is as follows: 10 parts of lily, 5 parts of glossy privet fruit, 5 parts of cortex albiziae, 1 part of lotus plumule, 5 parts of eclipta alba, 5 parts of radix curcumae, 5 parts of rhizoma acori graminei, 7.5 parts of dens draconis, 10 parts of fructus Tritici Levis and 2 parts of inula flower.

Wherein: the fructus Ligustri Lucidi is one of fructus Ligustri Lucidi and fructus Ligustri Lucidi.

According to the theory of traditional Chinese medicine, the pharmacological actions of the traditional Chinese medicine used in the prescription of the traditional Chinese medicine composition are as follows:

1. lily (alias: heavy Mich, atrium, heavy box, moluo)

Sweet in flavor and slightly cold in nature

Channel tropism: lung and heart returning

The main functions are as follows: has effects of nourishing yin, moistening lung, clearing heart fire and tranquilizing. It is indicated for cough due to yin deficiency and dryness, cough due to fatigue and hemoptysis, insomnia and palpitation due to yin deficiency with heat, and heart lung yin deficiency and internal heat due to lily.

2. Glossy privet fruit (alias: winter green fruit, glossy privet fruit)

Sweet, bitter and cool in nature

Channel tropism: enter liver and kidney meridians

The main functions are as follows: has effects of nourishing liver and kidney, clearing heat and improving eyesight. Is mainly used for treating soreness of waist and knees, premature graying hair, yin deficiency and internal heat, bone steaming and fatigue heat, night sweat and spermatorrhea, dizziness, dim eyesight and unknown, amnesia and tinnitus, etc.

Deficiency of liver-yin and kidney-yin: for dizziness, soreness and weakness of waist and knees, premature graying of beard and hair caused by yin deficiency of liver and kidney, it can be used singly to tonify liver and kidney, or combined with Ecliptae herba, and added with sang Gen, the efficacy is more remarkable.

3. Cortex Albiziae (alias: comatose bark, night bark, cortex Albiziae)

Sweet in flavor and neutral in nature

Channel tropism: it enters heart, liver and lung meridians

The main functions are as follows: has effects of resolving depression, tranquilizing, promoting blood circulation, and relieving swelling. Is mainly used for treating restlessness, depression, dysphoria, insomnia, traumatic injury, fracture, swelling and pain due to blood stasis, lung abscess, sore, carbuncle, and toxic swelling.

4. Plumula Nelumbinis (alias: job's tears, bitter Job's tears, lotus seeds and heart)

Bitter and cold taste

Channel tropism: enter heart and kidney meridians

The main functions are as follows: has effects of clearing heart fire, suppressing hyperactive liver fire, stopping bleeding, and stopping nocturnal emission. Is mainly used for treating coma and delirium, dysphoria, insomnia, dizziness, conjunctival congestion, hematemesis and spermatorrhea.

5. Eclipta (alias: herba Potentillae chinensis, lotus seed grass and eclipta alba)

Sweet and sour taste and cold nature

Channel tropism: enter liver and kidney meridians

The main functions are as follows: has effects of nourishing liver and kidney, cooling blood, stopping bleeding, eliminating dampness, and relieving itching. Is mainly used for treating dizziness, premature gray hair, deficiency of the kidney, odontalgia, hematemesis, hemoptysis, diabetes insipidus, pruritus vulvae, turbid urine, reddish leucorrhea, etc.

Effects on the central nervous system: the eclipta has very remarkable sedative and analgesic effects, and the total flavone has less effect than the total component

6. Radix Curcumae (alias: ma, five emperors, yellow depression and aconite)

Pungent and bitter taste and cold property

Channel tropism: liver and gallbladder invigorating

The main functions are as follows: has effects of promoting blood circulation, relieving pain, activating qi-flowing, resolving stagnation, clearing heart fire, cooling blood, promoting bile flow, and eliminating jaundice. Is used for treating pain due to qi stagnation and blood stasis, fever unconsciousness, epilepsia, phlegm stagnation, hematemesis, epistaxis, menorrhagia, hematuria, stranguria, jaundice due to damp-heat in liver and gallbladder, and cholelithiasis.

7. Rhizoma Acori Graminei (alias: sword grass, rhizoma Acori Graminei, rhizoma Acori Tatarinowii)

Pungent and bitter in flavor and warm in nature

Channel tropism: enter heart and stomach meridians

The main functions are as follows: has effects of inducing resuscitation, refreshing mind, eliminating dampness, regulating stomach function, tranquilizing mind, and nourishing mind. Mainly treats phlegm obstruction and consciousness clearing and unconsciousness; damp obstruction of middle energizer, gastric and abdominal distention and fullness, distention and pain; vomiting dysentery; amnesia, insomnia, tinnitus, deafness.

8. Dragon tooth

Sweet and astringent taste and cool nature

Channel tropism: enter heart and liver meridian

The main functions are as follows: has effects of relieving convulsion, tranquilizing, clearing heat and relieving restlessness. Is mainly used for treating convulsion, mania, palpitation, insomnia, dreaminess, fever and vexation.

9. Floating wheat (alias: floating wheat)

Sweet and cool in nature

Channel tropism: enter heart meridian

The main functions are as follows: has effects of consolidating superficial resistance, arresting sweating, invigorating qi, and removing heat. Is mainly used for treating spontaneous perspiration, night sweat, yin deficiency, fever, and bone steaming and fatigue heat.

10. Inulae flos (alias: yellow ripe flower, sunflower and calendula)

Pungent and salty taste and slightly warm nature

Channel tropism: lung-returning device

The main functions are as follows: has effects of lowering qi, eliminating phlegm, and relieving vomiting. Is mainly used for treating cough and asthma with excessive phlegm, accumulation of phlegm-fluid, chest and diaphragm distention and fullness, belching and qi, emesis, chest and hypochondrium pain, etc.

Wherein:

cortex Albiziae is matched with lily: both of them are sweet in flavor and enter heart meridian to induce tranquilization, so they are indicated for restlessness and insomnia. The albizia Pi Xing can calm liver meridian, nourish heart and tranquilize mind, sooth liver and relieve depression, activate blood and remove carbuncles, and is used for treating uneasiness, melancholy and insomnia caused by emotional injury, traumatic injury fracture, carbuncle and sore. Lily is slightly cold in lung meridian, and can clear heart and tranquilize mind, nourish yin and moisten lung, and is mainly used for treating dysphoria, insomnia, dysphoria, palpitation, dysphoria, and hemoptysis due to chronic cough, dry cough and cough due to lung deficiency caused by deficiency of yin with heat in later stage of heat disease and undelived waste heat.

The eclipta is matched with glossy privet fruit: ecliptae herba is sweet, sour and cold, and has effects of nourishing liver and kidney; fructus Ligustri Lucidi is sweet and bitter, and has effects of cooling and nourishing liver and kidney. The two herbs are combined to strengthen the action of nourishing liver and kidney. It is suitable for dizziness, blurred vision, premature gray hair, soreness of waist and knees, etc. caused by deficiency of liver-yin and kidney-yin.

Rhizoma Acori Graminei is prepared with radix Curcumae: rhizoma Acori Graminei opens orifices and ventilates qi, and is effective in relieving Yu Huashi; radix Curcumae has effects of resolving liver stagnation, clearing heart-fire, cooling blood and removing blood stasis. When the two are combined, the two are used for inducing resuscitation and resolving depression, and clearing away heart-fire and refreshing mind. It is indicated for heat disease with phlegm obstructing the heart orifices and mental confusion.

The medicine of the application can be mixed with one or more pharmaceutically acceptable carriers to prepare any clinically or pharmaceutically acceptable dosage form, preferably oral preparation. When administered orally to a patient in need of such treatment, they may be formulated into conventional solid or liquid preparations such as tablets, capsules, granules, and the like.

On the basis, the inventor also provides a preparation method of the traditional Chinese medicine composition for treating climacteric depression: the raw materials are weighed according to the proportion, and conventional auxiliary materials are added to prepare the conventional pharmaceutical preparation according to the conventional method.

Specifically: the raw materials are weighed according to the proportion, the raw materials are decocted with water for extraction, the extracting solution is decompressed and concentrated into extract, the extract is dried and crushed into fine powder, and the conventional auxiliary materials are added to prepare the conventional pharmaceutical preparation according to the conventional method.

More specifically: the raw materials are weighed according to the proportion, soaked in 8-10 times of water for 30min, then boiled for 10min by strong fire for 1.5 h, decocted for 2-3 times by slow fire, each time for 40-90 min, filtered, and the filtrate is decompressed and concentrated to extract with relative density of 1.17-1.20 under the condition of 50-60 ℃ under the condition of minus 0.06-minus 0.08Mpa, dried, crushed into fine powder, added with conventional auxiliary materials and prepared into conventional pharmaceutical preparations according to a conventional method.

The pharmaceutical preparation comprises an oral liquid preparation and an oral solid preparation, wherein the oral solid preparation comprises granules, capsules and tablets.

The oral liquid preparation is prepared by the following steps: the raw materials are weighed according to the proportion, soaked in 8-10 times of water for 30min, then boiled for 10min with strong fire for 1.5 h, decocted for 2-3 times with slow fire, each time for 40-90 min, filtered, and the filtrate is decompressed and concentrated to extract with relative density of 1.17-1.20 under the condition of 50-60 Mpa under-0.06 to-0.08 Mpa, and one or more of refined honey and sugar are added or not added for uniform mixing, and the weight ratio of the total amount of auxiliary materials to the extract is 1:4-2:1, thus obtaining the oral liquid preparation.

The granule is prepared by the following steps: the raw materials are weighed according to the proportion, soaked in 8-10 times of water for 30min, then boiled for 10min with strong fire for 1.5 h, decocted for 2-3 times with slow fire, each time for 40-90 min, filtered, concentrated to extract with relative density of 1.17-1.20 under the condition of minus 0.06-minus 0.08Mpa under the condition of minus 0.06 Mpa, dried and crushed into fine powder, silica is added, one or more of dextrin and maltodextrin is added or not added, and then evenly mixed, the weight ratio of the extract to the total amount of auxiliary materials is 1:2-2:1, dry granulation or wet granulation with ethanol is carried out, and the prepared granules can be directly used as granules.

The capsules were prepared as follows: weighing the raw materials according to the proportion, soaking the raw materials in 8-10 times of water for 30min, then boiling the raw materials with strong fire for 1.5 h, decocting the raw materials for 2-3 times with slow fire for 40-90 min each time, filtering the raw materials, concentrating the filtrate under reduced pressure to an extract with relative density of 1.17-1.20 at 50-60 ℃ under the condition of minus 0.06-minus 0.08Mpa, drying the extract, crushing the extract into fine powder, adding silicon dioxide, adding one or more of dextrin and maltodextrin or uniformly mixing the extract and the auxiliary materials, wherein the weight ratio of the extract to the total amount of the auxiliary materials is 1:2-2:1, granulating the dry method or granulating the dry method by using ethanol, drying the obtained granules, and filling the obtained granules into capsules.

The tablets were prepared as follows: weighing the raw materials according to the proportion, soaking the raw materials in 8-10 times of water for 30min, then boiling the raw materials with strong fire for 1.5 h, decocting the raw materials for 2-3 times with slow fire for 40-90 min each time, filtering the raw materials, concentrating the filtrate under reduced pressure to an extract with relative density of 1.17-1.20 at 50-60 ℃ under the condition of minus 0.06-minus 0.08Mpa, drying the extract, crushing the extract into fine powder, adding silicon dioxide, adding one or more of dextrin and maltodextrin or uniformly mixing the extract and the auxiliary materials, wherein the weight ratio of the extract to the total amount of the auxiliary materials is 1:2-2:1, granulating the mixture by a dry method or granulating the mixture by an ethanol wet method, drying the granules, tabletting the granules and preparing tablets.

The inventor also provides application of the traditional Chinese medicine composition in preparation of medicines for treating climacteric depression.

The application takes lily, glossy privet fruit, cortex albiziae, lotus plumule, eclipta, radix curcumae, rhizoma acori graminei, dens draconis, floating wheat and inula flower as main materials and auxiliary materials as auxiliary materials, and the medicines are mutually assisted, treat both principal and secondary aspects of the disease, and play roles of tonifying kidney, nourishing yin, removing dryness, soothing nerves, nourishing nest and regulating menstruation together. Researches show that the Chinese medicinal composition has the effects of increasing the secretion of estrogen, relieving irregular menstruation, flushed complexion, palpitation, insomnia, hypodynamia, depression, anxiety, unstable emotion, dysphoria, irritability or depression, difficulty in concentrating attention and other symptoms, and has a therapeutic effect on climacteric syndrome and depression caused by various reasons.

Detailed Description

The application aims to provide a traditional Chinese medicine composition which can treat both principal and secondary aspect of disease, has small side effect, is safe and convenient and has low price. The traditional Chinese medicine composition aims to solve the problems of serious toxic and side effects of western medicines, easiness in repeated stopping medicines and insignificant treatment effects in treating climacteric depression, and achieves the aim of treating both principal and secondary aspects of diseases.

Based on the defects of the existing medicines for treating the climacteric depression, the inventor collects the length of the masses through researching the traditional Chinese medicines and combining dialectical demonstration, searches an optimal treatment scheme, screens out natural Chinese medicines for tranquillizing, stabilizing, tonifying deficiency and strengthening body resistance from a national medical treasury, extracts essence according to a traditional Chinese medicine theory formula, enables the essence to exert the effects of clearing heart, relieving restlessness, nourishing yin, promoting the production of body fluid and tranquillizing and nourishing heart, adopts pure natural Chinese medicine raw materials, and combines the traditional Chinese medicine technology to carefully prepare the traditional Chinese medicine composition for treating the climacteric depression through systematic study and scientific compatibility, so that the traditional Chinese medicine composition has remarkable treatment effect on the climacteric depression.

In order to achieve the above purpose, the technical scheme adopted by the application is as follows:

a Chinese medicinal composition for treating climacteric depression comprises Bulbus Lilii, fructus Ligustri Lucidi, cortex Albiziae, plumula Nelumbinis, ecliptae herba, radix Curcumae, rhizoma Acori Graminei, dens Draconis, fructus Tritici Levis, and Inulae flos.

Specifically, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight:

3 to 10 parts of lily, 3 to 6 parts of glossy privet fruit, 3 to 6 parts of cortex albiziae, 1 to 1.5 parts of lotus plumule, 3 to 6 parts of eclipta alba, 3 to 5 parts of radix curcumae, 1.5 to 5 parts of grassleaf sweelflag rhizome, 7.5 to 15 parts of dens Draconis, 7.5 to 15 parts of light wheat and 1.5 to 4.5 parts of inula flower.

The preparation method comprises the following steps:

the raw materials are weighed according to the proportion, soaked in 8-10 times of water for 30min, then boiled for 10min by strong fire for 1.5 h, decocted for 2-3 times by slow fire, each time for 40-90 min, filtered, and the filtrate is decompressed and concentrated to extract with relative density of 1.17-1.20 under the condition of 50-60 ℃ under the condition of minus 0.06-minus 0.08Mpa, dried, crushed into fine powder, added with conventional auxiliary materials and prepared into conventional pharmaceutical preparations according to a conventional method.

Example 1

The formula comprises the following components: 20g of lily, 10g of wine glossy privet fruit, 10g of cortex albiziae, 2g of lotus plumule, 10g of eclipta alba, 10g of radix curcumae, 10g of grassleaf sweelflag rhizome, 15g of dens Draconis, 20g of floating wheat and 4g of inula flower

The process comprises the following steps: the raw materials are weighed according to the proportion, soaked in 8 times of water for 30min, then boiled for 10min with strong fire, decocted for 1.5 h with slow fire for 3 times, each time for 60min, filtered, and the filtrate is decompressed and concentrated to extract with relative density of 1.17-1.20 at 50-60 ℃ under the condition of minus 0.06-minus 0.08Mpa, dried and crushed into fine powder, silicon dioxide is added, dextrin is added and mixed uniformly, and the weight ratio of the extract to the total amount of auxiliary materials is 2:1. Wet granulating to obtain granule. The obtained granule can also be filled into capsule or pressed into tablet.

The usage amount is as follows: the medicine is taken with warm water, and 1 bag each time is taken once a day in the morning and evening

Example 2

The formula comprises the following components: 6g of lily, 6g of glossy privet fruit, 6g of cortex albiziae, 2g of lotus plumule, 6g of eclipta alba, 6g of radix curcumae, 6g of grassleaf sweelflag rhizome, 12g of dens Draconis, 10g of floating wheat and 2g of inula flower

The process comprises the following steps: the raw materials are weighed according to the proportion, soaked in 10 times of water for 30min, then boiled for 10min with strong fire, decocted for 1.5 h with slow fire for 2 times, each time for 40min, filtered, and the filtrate is decompressed and concentrated to extract with relative density of 1.17-1.20 at 50-60 ℃ under the condition of minus 0.06-minus 0.08Mpa, dried and crushed into fine powder, silicon dioxide is added, dextrin is added and mixed uniformly, and the weight ratio of the extract to the total amount of auxiliary materials is 1:2. Granulating by dry method to obtain granule. The obtained granule can also be filled into capsule or pressed into tablet.

Example 3:

the formula comprises the following components: 22g of lily, 12g of wine glossy privet fruit, 12g of cortex albiziae, 6g of lotus plumule, 12g of eclipta alba, 12g of radix curcumae, 12g of grassleaf sweelflag rhizome, 18g of dens Draconis, 30g of floating wheat and 6g of inula flower

The process comprises the following steps: the raw materials are weighed according to the proportion, soaked in 9 times of water for 30min, then boiled for 10min with strong fire, decocted for 1.5 h with slow fire for 3 times, each time for 90min, filtered, and the filtrate is decompressed and concentrated to an extract with relative density of 1.17-1.20 at 50-60 ℃ under the condition of minus 0.06-minus 0.08Mpa, and added with refined honey or sugar for even mixing, wherein the weight ratio of the refined honey or sugar to the extract is 1:3. Thus obtaining the oral liquid preparation.

The usage amount is as follows: this is measured on a daily basis and taken once a day in the morning and evening.

Example 4

The formula comprises the following components: 16g of lily, 8g of glossy privet fruit, 8g of cortex albiziae, 4g of lotus plumule, 8g of eclipta alba, 8g of radix curcumae, 8g of grassleaf sweelflag rhizome, 14g of dens Draconis, 24g of floating wheat and 3g of inula flower

The process comprises the following steps: the raw materials are weighed according to the proportion, soaked in 8 times of water for 30min, then boiled for 10min with strong fire, decocted for 1.5 h with slow fire for 3 times, each time for 70min, filtered, and the filtrate is decompressed and concentrated to extract with relative density of 1.17-1.20 at 50-60 ℃ under the condition of minus 0.06-minus 0.08Mpa, thus obtaining the oral liquid preparation.

Example 5 toxicity experiment

Acute toxicity experiment: 40 mice, each half of which is male and female, have a weight of 30-40 g, and are subjected to an acute toxicity test. The mice were randomly divided into 2 groups, namely, a control group and a dosing group (pharmaceutical preparation prepared in example 1), 20 animals per group were fasted for 12 hours before the experiment, the pharmaceutical preparation prepared in example 1 of the present application was administered by dissolution in water and gastric administration (the single administration dose for gastric administration was 50g crude drug/kg), the control group was administered with an equivalent amount of physiological saline, 2 times a day, 6 hours between administrations, 14 days after administration was continuously observed, and the toxic reaction and death number of the mice were recorded. The experimental results show that: compared with the control group, the mice have no obvious difference after administration, the experiment is continuously observed for 14 days, and the whole body condition, diet, drinking water and weight increase of the mice are normal. Therefore, the pharmaceutical preparation of the application has extremely low acute toxicity and safe clinical application.

Long-term toxicity experiments: the results of the continuous administration of the pharmaceutical preparation prepared in the embodiment 1 of the application to mice for 15 weeks and 3 weeks after stopping the administration show that: the traditional Chinese medicine has no obvious influence on indexes such as hair, behaviors, urination and defecation, body weight, organ weight, hemogram, liver and kidney functions, blood sugar, blood fat and the like of a mouse, and the viscera naked eyes do not find abnormal changes and histological examination results show that after 15 weeks of administration and 3 weeks of withdrawal, all organs of the mouse are not obviously changed. The medicine preparation has low toxicity to mice after long-term administration, has no abnormal reaction after stopping administration, and is safe to apply.

EXAMPLE 6 pharmacodynamic Studies

1. Purpose of experiment

The effect of the drug on the climacteric syndrome of rats is observed by combining the ovariectomized rats with a depression model, so as to determine the effect of the drug on improving the climacteric depression.

2. Experimental materials

2.1 laboratory animals

Healthy SD female rats, grade 200-220g, SPF, purchased from Beckland Biotechnology Co., ltd., license number: scxk (Beijing) 2019-0008.

2.2 test drug

The Chinese medicinal composition granule (prepared according to the method of the example 1) of the application is equivalent to 6.49g crude drug per gram of medicinal powder.

2.3 Positive drug

Kunbao pill, beijing Tongren Tang Co., ltd., specification: the weight of the pill is 10g per 100g, and the clinical daily dose is 10g.

2.4 reagents

Pentobarbital, MERCK, lot number: p11011.

Penicillin sodium for injection, north China pharmaceutical Co., ltd., lot number: F0092102.

3. experimental method

3.1 Process for preparing medicine

(1) The preparation method of the tested medicine comprises the following steps:

weighing 6.3g of a tested medicament, adding purified water to 90ml for dissolution, and taking the mixture as a high-dose group solution;

taking 40ml of high-dose group solution, adding purified water to 80ml, and uniformly mixing to obtain a medium-dose solution;

30ml of the medium dose group solution was taken and purified water was added to 60ml as the low dose group solution.

The administration was by gavage according to a weight of 2ml/100 g. The dosage of the high, medium and low dosage groups is 9.10g crude drug/kg, 4.55g crude drug/kg and 2.275g crude drug/kg respectively.

(2) The preparation method of the positive medicine comprises the following steps:

taking pills, grinding, adding water and dissolving into 45mg/ml solution. The administration volume was 2ml/100g body weight. The rat test dose was 0.9g/kg.

3.2 grouping, modeling and administration

70 female rats are adaptively bred for 3 days, except 10 animals in a normal group and a sham operation group, the other animals are anesthetized by intraperitoneal injection of 2% pentobarbital, the abdomen of the rat is cut, the lower oviduct (including fat) of the ovary is ligated firstly, the ovaries on two sides are removed after ligation, the uterus is sent back to the abdominal cavity in a postoperative homeopathic manner, and then wounds are sutured layer by layer. In the sham operation group, only the uterus is taken out and then put back into the abdominal cavity, and the ovary is not removed. Penicillin is continuously injected 3 days after operation, 1 time a day to prevent wound infection. One week after molding, vaginal smear observation of rats, no or only a small number of keratinocytes observed for 5 consecutive days, indicated that the ovariectomization was successful, indicating that the animals substantially met the "climacteric" manifestation, the successfully molded animals were randomly divided into model, high dose, medium dose, low dose, positive drug groups, and the unpredictable stress treatments of each group were initiated: the rats are raised in solitary mode with 1 cage, the following stimulation (1 cage inclination (45 degrees) 24h (2)4 ℃ cold water swimming 5 min; 3) wet padding 24 h; 5) tail clamping 1min (1 cm from tail) (6) fasted 24 h; 7) shaking are carried out with 7 days as one period, and one is selected randomly every day for continuous stimulation. The stimulation was initiated simultaneously with the administration of the corresponding test drug according to a mass of 20ml/kg for 4 weeks. Normal, model, sham groups were given equal volumes of distilled water.

3.3 test methods

The sugar water preference test is carried out after 21 days of continuous stimulation, 1 bottle of pure water and one bottle of water containing 1% of sucrose are placed in a cage before the test, the positions of the two bottles of water are exchanged after 12 hours, and rats drink freely for 24 hours. After 24 hours of non-fasting but water-deprivation, 150ml of pure water and 150ml of 1% sucrose water were placed in each cage, two bottles of water were exchanged after 2 hours, and the intake of pure water and sucrose water was recorded for rats over 4 hours, and the preference degree of sugar water (ratio of sugar water consumption to total liquid consumption) was calculated.

The next day after the sugar water preference test was completed, the rats were put into a cylindrical barrel having a height of 50cm and a diameter of 20cm, and the water depth was about 40cm. Forced swimming was performed for 6min, the first 2min being the adaptation time and the last 4min being the record observation time, the rest time of the rats in the water was recorded (stop struggling floating, forepaw immobilized or slight rowing keeping the body immobile).

The abdominal cavity is injected with 2% pentobarbital for anesthesia after the last administration for 1h, blood is taken, and the sea horse body is subjected to related index detection.

3.4 statistical treatment method

Data sheet is expressed as mean ± standard deviationThe SPSS21.0 software is used for checking the data, and independent samples Mann-Whitney U in non-parametric statistics are used for statistical treatment, and P is adopted for all<0.05 was statistically significant as a difference.

4. Experimental results

Effects of test drugs on sugar water intake in ovariectomized rats with climacteric depression. The results are shown in Table 1.

TABLE 1 influence of sugar water intake in ovariectomized rats with climacteric depressionn＝10)

The medium dose group was compared to the model group, P <0.05; the model group was compared to the control group, P <0.05.

The sugar water drinking rate of the model group was significantly reduced (P < 0.05) compared to the control group; the sugar water drinking rate was significantly increased in the medium dose group (P < 0.05) compared to the model group in the subject drug-dosed group.

Influence of test drugs on forced swimming time of ovariectomized rats with climacteric depression. The results are shown in Table 2.

TABLE 2 influence on forced swimming time of ovariectomized rats with climacteric depressionn＝10)

Comparing the medium dose group, the positive drug group and the model group, wherein P <0.05; the model group was compared to the control group, P <0.05.

Compared with the control group, the immobility time of the forced swimming of the rats in the model group is obviously increased (P < 0.05); compared with the model group, the time of forced swimming immobility of rats in the dose group and the positive drug group in the tested drug is obviously increased (P < 0.05).

Effects of test drugs on neurotransmitter levels in hippocampal tissue of ovariectomized rats with menopausal depression. The results are shown in Table 3.

TABLE 3 influence on the neurotransmitter content in hippocampal tissuen＝10)

HT (5-hydroxytryptamine), 5-HIAA (5-oxindole acetic acid), DA (dopamine), GABA (gamma-aminobutyric acid).

* P <0.05 compared to model group; delta is compared to control, P <0.05.

The 5-HT, 5-HIAA, DA, GABA in the hippocampus was significantly reduced (P < 0.05) in the rats of the model group compared to the control group, the 5-HT, 5-HIAA, DA, GABA in the hippocampus was significantly increased (P < 0.05) in the high dose group, the 5-HIAA, GABA in the middle dose group was significantly increased (P < 0.05), the 5-HT, GABA in the hippocampus was significantly increased (P < 0.05) in the low dose group, and the 5-HT, 5-HIAA, GABA in the hippocampus was significantly increased (P < 0.05) in the positive drug group compared to the model group.

Effects of the test drug on serum Follistatin (FSH), luteinizing Hormone (LH), and Corticosterone (CORT) levels in ovariectomized rats with menopausal depression. The results are shown in Table 4.

TABLE 4 influence of serum FSH, LH, CORT levels in ovariectomized rats with menopausal depressionn＝10)

* P <0.05 compared to model group; delta is compared to control, P <0.05.

The rats in the model group showed significantly decreased CORT (P < 0.05), the FSH and LH showed significantly increased CORT (P < 0.05) in the blood of the rats in the control group, and the serum of the high, medium and low dose groups and the positive group showed significantly increased CORT (P < 0.05) and the FSH and LH showed significantly decreased (P < 0.05) in the blood of the rats in the test group.

The research result shows that the tested medicine has the function of improving climacteric depression.

EXAMPLE 7 concrete case

King somebody, woman, 51 years old.

Complaints: low mood with insomnia and dreaminess for half a year.

The symptoms are as follows: the emotion is low throughout the day, and the feeling of spelts, responsibilities and guilts is common; insomnia, difficulty in falling asleep, dreaminess and awakening; dizziness, amnesia, weakness, soreness of waist and knees, and sweating due to heat. Poor appetite, sometimes with abdominal distension, dark complexion, and difficulty in regulating. Menstrual irregularities are near one year, and stop menstruation for 2 months. A dark red tongue with thin and yellow coating and a wiry and thready pulse.

Scale scoring: HAMD score 28 points, which is a moderate depression, kupperman score 35 points.

Western diagnosis: climacteric depression

Diagnosis of traditional Chinese medicine: perimenopausal depression with deficiency of liver-yin and kidney-yin.

The treatment method comprises the following steps: nourishing liver and kidney, resolving depression and tranquillizing.

Treatment: the traditional Chinese medicine composition granule is taken with warm water twice a day in the morning and at night, 1 bag each time and is treated for 4 weeks.

After treatment, the patient's mood is obviously improved, the feeling of spelt, responsibility and guilt disappears, the working state is good during working, and the patient is actively engaged in social activities or gathering; sleep quality is improved, and early wake is sometimes generated; the hot sweat disappears. Poor appetite, abdominal distention, dizziness, amnesia, debilitation, soreness of waist and knees, and the like. The HAMD score is reduced by 8 points, the Kupperman score is 15 points, the liver and kidney functions are not obviously abnormal, and the curative effect judgment is obvious.

Example 8 clinical trials

1. Study object

140 female climacteric depression patients in the clinic of the Drum tower traditional Chinese medicine hospital are collected and randomly grouped, and the clinical experiment of the traditional Chinese medicine composition is carried out. The selected cases all accord with the diagnosis standard of perimenopausal syndrome diagnosis in gynaecology and obstetrics (Beijing: 2008 edition of Min health Press) and the diagnosis standard of China mental disease classification and diagnosis standard (CCMD-3) and simultaneously carry out HAMD score (scale score is more than or equal to 21 minutes), and the syndrome differentiation accords with the diagnosis standard of 'depression syndrome' in Chinese medical condition diagnosis curative effect standard and the syndrome differentiation and typing standard of 'pre-menopausal and post-menopausal symptoms' formulated in Chinese medical science. General data collection is carried out on female climacteric depression patients meeting the selection criteria, including the age, the reproductive endocrine hormone level and the like of the patients, and data such as the age among groups, the HAMD score, the Kupperman score, the PSQI and the reproductive endocrine hormone level are determined, so that the data are statistically comparable.

2. Therapeutic method

According to the statement, design and implementation of medical research subject, 140 patients are randomly divided into a treatment group and a control group by a random number method, and 70 patients in each group. The control group was orally administered flupentixol melitracen tablets (standard Chinese medicine, 0.5mg:10mg x 20 tablets, denmark North pharmaceutical Co., ltd.) 1 each after noon in the morning for 4 weeks. Treatment group: the traditional Chinese medicine composition granule is taken with warm water, 150ml each time in the morning and evening, and is continuously taken for 4 weeks.

3. Effect criterion

Adopting a HAMD scale as a main index for evaluating the severity of depression before and after treatment; the improvement rate of symptom score of traditional Chinese medicine, kupperman score and PSQI score were used to evaluate the improvement of climacteric symptom as secondary evaluation criteria. The calculation formula is as follows: decrease rate = (total score before treatment-total score after treatment)/total score before treatment x 100%. According to the nationally unified level 4 standard, the following is followed:

and (3) healing: HAMD reduction rate is more than or equal to 75 percent

The effect is shown: HAMD reduction rate is more than or equal to 50 percent

The method is effective: HAMD reduction rate is more than or equal to 25 percent

Invalidation: HAMD reduction rate <25%

Total effective rate = healing + onset + effectiveness

4. Experimental results

The result of the early clinical study shows that the total effective rate of the treatment group is 84.4 percent, and the total effective rate of the control group is 59.4 percent. The differences were statistically significant (P < 0.05).

Wherein two groups of patients were compared for changes in HAMD score: the HAMD score of the treatment group was 25.09+ -2.89 min, 14.72+ -2.95 min before and after treatment, respectively; the HAMD score of the control group was 25.63+ -3.42 score and 18.53+ -3.53 score before and after treatment, respectively, and the difference was statistically significant. The difference of the t test of two samples is statistically significant by comparing the Kupperman score, the PSQI score and the traditional Chinese medicine syndrome score of the two groups of patients with the change condition before and after the integral treatment. The comparison of the serum genital hormone level change of the two groups of patients shows that the difference of E2 and FSH before and after treatment has statistical significance. No adverse reaction occurs

The traditional Chinese medicine components adopted by the application are mutually compatible, so that the synergistic disease treatment effect can be exerted, the components of the traditional Chinese medicine raw materials have the efficacy of mutual interweaving and mutual promotion and coordination, and through clinical verification, the traditional Chinese medicine raw materials have good treatment effect on climacteric depression.

It will be apparent to those skilled in the art that the details of the embodiments of the application may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are to be considered as illustrative and not restrictive, and all changes coming within the meaning and equivalency range of the claims are therefore intended to be embraced therein.

Claims

1. The traditional Chinese medicine composition for treating climacteric depression is characterized by comprising, by weight, 3-10 parts of lily, 3-6 parts of glossy privet fruit, 3-6 parts of cortex albiziae, 1-1.5 parts of lotus plumule, 3-6 parts of eclipta alba, 3-5 parts of radix curcumae, 1.5-5 parts of grassleaf sweelflag rhizome, 7.5-15 parts of dens Draconis, 7.5-15 parts of fructus Tritici Levis and 1.5-4.5 parts of inula flower.

2. The traditional Chinese medicine composition for treating climacteric depression according to claim 1, wherein the weight parts of the traditional Chinese medicine raw materials comprise 10 parts of lily, 5 parts of glossy privet fruit, 5 parts of cortex albiziae, 1 part of lotus plumule, 5 parts of eclipta alba, 5 parts of radix curcumae, 5 parts of rhizoma acori graminei, 7.5 parts of dens Draconis, 10 parts of fructus Tritici Levis and 2 parts of inula flower.

3. A Chinese medicinal composition for treating climacteric metancholia as defined in any one of claims 1 to 2, wherein said fructus ligustri lucidi is one of fructus ligustri lucidi or fructus ligustri lucidi.

4. The method for preparing the traditional Chinese medicine composition for treating climacteric depression according to any one of claims 1 to 2, wherein the raw materials are weighed according to a proportion, and conventional auxiliary materials are added to prepare the traditional Chinese medicine preparation according to a conventional method.

5. The method for preparing a Chinese medicinal composition for treating climacteric depression according to claim 4, wherein the raw materials are weighed according to a proportion, the raw materials are decocted with water and extracted, the extract is concentrated into an extract under reduced pressure, the extract is dried and crushed into fine powder, and conventional auxiliary materials are added to prepare the conventional medicinal preparation according to a conventional method.

6. The method for preparing the traditional Chinese medicine composition for treating climacteric depression according to claim 5, wherein the traditional Chinese medicine composition is characterized in that raw materials are weighed according to a proportion, soaked in 8-10 times of water for 30min, then boiled for 10min with strong fire and boiled for 1.5 hours with slow fire for 2-3 times, each time for 40-90 min, filtered, and the filtrate is concentrated to an extract with relative density of 1.17-1.20 under the condition of minus 0.06-minus 0.08Mpa under the condition of 50-60 ℃, dried, crushed into fine powder, added with conventional auxiliary materials and prepared into a conventional pharmaceutical preparation according to a conventional method.

7. The method for preparing a Chinese medicinal composition for treating climacteric syndrome of claim 6, wherein the pharmaceutical preparation comprises an oral liquid preparation and an oral solid preparation, wherein the oral solid preparation comprises granules, capsules and tablets.

8. Use of a traditional Chinese medicine composition for treating menopausal depression according to any one of claims 1 to 2, wherein the use of the traditional Chinese medicine composition for preparing a medicament for treating menopausal depression.