New crystal form of mianserin hydrochloride, detection method and applications thereof

Abstract

The present invention provides a new crystal form of mianserin hydrochloride, a detection method and applications, and relates to a traditional Chinese medicine and Western medicine preparation for depression, especially to applications of a compound drug prepared from a Western medicine mianserin hydrochloride adopted as the main component and Chinese herbs in treatment of depression. According to the mianserin hydrochloride, benzaldehyde and ethanolamine are adopted as starting raw materials and are subjected to chemical combination to obtain an intermediate I, the intermediate I reacts with styrene oxide to obtain an intermediate II, the intermediate II and thionyl chloride are subjected to chemical combination under an alkaline condition to obtain an intermediate III, the intermediate III, o-aminobenzyl alcohol and fumaric acid are subjected to chemical combination to obtain an intermediate IV, an intermediate V is obtained from the intermediate IV under the action of concentrated sulfuric acid and sodium carbonate, the intermediate V reacts with ethyl chloroformate under an alkaline condition to obtain an intermediate VI, the intermediate VI reacts with formaldehyde and formic acid to obtain an intermediate VII, and the intermediate VII is acidified with hydrochloric acid-ethyl acetate to obtain the mianserin hydrochloride. The new crystal form of the mianserin hydrochloride of the present invention has characteristics of significant treatment effect, symptom and root cause treatment, and wide application prospets.

Description

technical field

[0001] The invention belongs to the technical field of medicine, and in particular relates to a Chinese and Western medicine preparation for depression, in particular to the application of a compound medicine made of western medicine mianserin hydrochloride and Chinese herbal medicine in treating depression. Background technique

[0002] Depression or depressive disorder is a major global mental health problem. Its etiology is very complicated and has not yet been fully elucidated. With the increasing competition in modern society, people's psychological pressure continues to increase. Emotional diseases have become the main diseases of the contemporary world. According to the World Health Organization, the biggest disease facing people in the 21st century is mental illness. WHO estimates that there are between 120 million and 200 million people worldwide suffering from depressive disorders. In 1996, a survey on the "burden of disease" published by WHO sho...

Examples

Embodiment 1

[0041] A compound mianserin hydrochloride pharmaceutical composition is characterized in that it is prepared from the following weight ratio raw materials,

[0042] 1 part of mianserin hydrochloride, 45 parts of Inulae root, 45 parts of Divine Comedy, 40 parts of Astragalus, 40 parts of Dandelion, 40 parts of Gardenia, 35 parts of Centella Asiatica, 35 parts of Scrophulariaceae, 35 parts of Ophiopogon japonicus, Huixin 35 parts of grass, 30 parts of Atractylodes macrocephala, 30 parts of Citrus aurantii, 25 parts of sea pine nuts, 25 parts of Shichangpu, 25 parts of Salvia miltiorrhiza, 20 parts of angelica, 20 parts of Chinese yam, 20 parts of forsythia, 20 parts of polygala, 15 parts of poria cocos, turmeric 15 servings.

[0043] Wherein said mianserin hydrochloride preferred preparation method is:

[0044] 1), put benzaldehyde into the reaction kettle, and add ethanolamine dropwise, the molar ratio of the two substances is 1:1, the reaction temperature is: 30-40°C, the rea...

Embodiment 2

[0060] Acute toxicity test: 40 mice, half male and half female, weighing 30-40 g, were used for acute toxicity test. The mice were randomly divided into two groups, i.e. a control group and an administration group, 20 in each group, fasted for 12 hours before the experiment, and the administration group was given the pharmaceutical composition prepared in Example 1 of the present invention dissolved in water for intragastric administration , the control group was given the same amount of normal saline, administered twice a day, with an interval of 6 hours between administrations, observed continuously for two weeks after administration, and recorded the toxicity and death of the mice. The experimental results showed that: compared with the control group, there was no significant difference in the mice after administration. The experiment was observed for two consecutive weeks, and the general condition, diet, drinking water, and weight gain of the mice were all normal. Therefo...

Embodiment 3

[0062] Embodiment 3 clinical data

[0063] Clinical data Selected 86 clinical patients and randomly divided them into two groups: 43 cases in the treatment group, including 20 males and 23 females, aged 17 to 67 years, with a course of disease of 1 to 3 years, Hamilton Depression Scale score: 26.9±3.1 43 cases in the control group, including 20 males and 23 females, aged 18-69 years, with a course of 1 to 3 years, and a score of 27.9±2.2 on the Hamilton Depression Scale; Depression scale score data, after statistical processing, no significant difference (P> 0.05), comparable.

[0064] Case selection criteria (1) patients diagnosed with depression according to the diagnostic criteria of the third edition of "Chinese Classification and Diagnostic Criteria of Mental Disorders" (CCMD-3) [2]; (2) stable vital signs, clear mind, and understanding of depression The content of the scale, with a certain expressive ability, can cooperate with the treatment; (3) Those who have not take...

technical field

[0001] The invention belongs to the technical field of medicine, and in particular relates to a Chinese and Western medicine preparation for depression, in particular to the application of a compound medicine made of western medicine mianserin hydrochloride and Chinese herbal medicine in treating depression. Background technique

[0002] Depression or depressive disorder is a major global mental health problem. Its etiology is very complicated and has not yet been fully elucidated. With the increasing competition in modern society, people's psychological pressure continues to increase. Emotional diseases have become the main diseases of the contemporary world. According to the World Health Organization, the biggest disease facing people in the 21st century is mental illness. WHO estimates that there are between 120 million and 200 million people worldwide suffering from depressive disorders. In 1996, a survey on the "burden of disease" published by WHO sho...

Examples

Embodiment 1

[0041] A compound mianserin hydrochloride pharmaceutical composition is characterized in that it is prepared from the following weight ratio raw materials,

[0042] 1 part of mianserin hydrochloride, 45 parts of Inulae root, 45 parts of Divine Comedy, 40 parts of Astragalus, 40 parts of Dandelion, 40 parts of Gardenia, 35 parts of Centella Asiatica, 35 parts of Scrophulariaceae, 35 parts of Ophiopogon japonicus, Huixin 35 parts of grass, 30 parts of Atractylodes macrocephala, 30 parts of Citrus aurantii, 25 parts of sea pine nuts, 25 parts of Shichangpu, 25 parts of Salvia miltiorrhiza, 20 parts of angelica, 20 parts of Chinese yam, 20 parts of forsythia, 20 parts of polygala, 15 parts of poria cocos, turmeric 15 servings.

[0043] Wherein said mianserin hydrochloride preferred preparation method is:

[0044] 1), put benzaldehyde into the reaction kettle, and add ethanolamine dropwise, the molar ratio of the two substances is 1:1, the reaction temperature is: 30-40°C, the rea...

Embodiment 2

[0060] Acute toxicity test: 40 mice, half male and half female, weighing 30-40 g, were used for acute toxicity test. The mice were randomly divided into two groups, i.e. a control group and an administration group, 20 in each group, fasted for 12 hours before the experiment, and the administration group was given the pharmaceutical composition prepared in Example 1 of the present invention dissolved in water for intragastric administration , the control group was given the same amount of normal saline, administered twice a day, with an interval of 6 hours between administrations, observed continuously for two weeks after administration, and recorded the toxicity and death of the mice. The experimental results showed that: compared with the control group, there was no significant difference in the mice after administration. The experiment was observed for two consecutive weeks, and the general condition, diet, drinking water, and weight gain of the mice were all normal. Therefo...

Embodiment 3

[0062] Embodiment 3 clinical data

[0063] Clinical data Selected 86 clinical patients and randomly divided them into two groups: 43 cases in the treatment group, including 20 males and 23 females, aged 17 to 67 years, with a course of disease of 1 to 3 years, Hamilton Depression Scale score: 26.9±3.1 43 cases in the control group, including 20 males and 23 females, aged 18-69 years, with a course of 1 to 3 years, and a score of 27.9±2.2 on the Hamilton Depression Scale; Depression scale score data, after statistical processing, no significant difference (P> 0.05), comparable.

[0064] Case selection criteria (1) patients diagnosed with depression according to the diagnostic criteria of the third edition of "Chinese Classification and Diagnostic Criteria of Mental Disorders" (CCMD-3) [2]; (2) stable vital signs, clear mind, and understanding of depression The content of the scale, with a certain expressive ability, can cooperate with the treatment; (3) Those who have not take...