CN106729406B

CN106729406B - Preparation method of premenstrual ease preparation

Info

Publication number: CN106729406B
Application number: CN201611228007.4A
Authority: CN
Inventors: 林凡儒; 王世礼; 薛颖; 高聪杰; 刘超
Original assignee: Xiangyu Pharmaceutical Co ltd
Current assignee: Xiangyu Pharmaceutical Co ltd
Priority date: 2016-12-27
Filing date: 2016-12-27
Publication date: 2020-06-02
Anticipated expiration: 2036-12-27
Also published as: CN106729406A

Abstract

The invention belongs to the technical field of medicine extraction, and discloses a preparation method of a premenstrual tension preparation, which comprises the following steps: step 1) taking raw materials, step 2) preparing a radix bupleuri and fructus aurantii extract, step 3) distilling, decocting and extracting with alcohol, and step 4) granulating, tabletting and coating. The premenstrual ease preparation prepared by the invention has better effect than the prior art, has no toxicity, and can be used for further clinical trial research.

Description

Preparation method of premenstrual ease preparation

Technical Field

The invention belongs to the technical field of medicine extraction, and particularly relates to a preparation method of a premenstrual tension preparation.

Background

The premenstrual ease is mainly prepared from raw materials such as radix bupleuri, fructus aurantii, cortex albiziae, radix curcumae, rhizoma cyperi, pericarpium citri reticulatae viride, fructus liquidambaris, semen citri reticulatae, angelica sinensis, radix paeoniae alba, ligusticum wallichii, poria cocos, pericarpium arecae, liquorice and the like, and is an effective medicine for treating premenstrual tension; the product is film coated tablet, and the coating is removed to show brown color; fragrant smell, bitter and slightly pungent taste. The functional indications are as follows: soothing liver, regulating qi, promoting blood circulation and removing obstruction in channels. The traditional Chinese medicine composition is mainly used for premenstrual tension of women and traditional Chinese medicine syndrome differentiation belonging to people with liver depression and qi stagnation, and has the symptoms of premenstrual emotional agitation, dysphoria, testiness, low mood, melancholy, breast distending pain, chest and hypochondrium distending pain, hypogastric pain or headache, or edema with different degrees, more or less menstrual flow, dark color, dark tongue quality and wiry pulse. The approval date of the Qian' an tablet is 2010-3-26, and the production unit is Shandong Xiangyu health pharmaceutical Co. The invention relates to a preparation process and a detection method of a Jingqian' an tablet in the previous invention patent of the applicant, which improves the drug effect by adding raw material medicines, but has the defects of complex formula, higher raw material cost and the like.

The applicant finds that the extraction method of the medicine raw materials is relatively single in the pharmaceutical process, and the defect of loss of effective components exists when the same extraction process is adopted for various raw materials; moreover, the improvement of the known medicine can save the early development cost of enterprises, and is a hot spot of enterprise research in recent years.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention provides a preparation method of a Qianjian preparation, which is simple and feasible, extracts the effective components of the raw materials to the maximum extent, improves the drug effect and reduces the dosage of the drug.

The invention is realized by the following technical scheme:

the preparation method of the premenstrual ease preparation comprises the following steps: step 1) taking raw materials, step 2) preparing a radix bupleuri and fructus aurantii extract, step 3) distilling, decocting and extracting with alcohol, and step 4) granulating, tabletting and coating.

Specifically, the step 1) is to take raw materials:

radix bupleuri 400g fructus Aurantii 400g cortex Albizziae 320g radix Curcumae 320g

320g of nutgrass galingale rhizome, 240g of green tangerine peel, 240g of beautiful sweetgum fruit, 280g of tangerine seed and 240g of sweetgum fruit

320g of angelica, 320g of white peony root, 320g of szechuan lovage rhizome, 240g of poria cocos, 240g of rhizoma ligustici wallichii

Pericarpium arecae 240g licorice root 120 g;

specifically, the step 2) is to prepare the extract of the bupleurum and fructus aurantii: pulverizing bupleuri radix and fructus Aurantii in pulverizer, sieving with 200 mesh sieve, spreading into 3mm flat layer, and placing at intensity of 3000uW/cm²Irradiating with ultraviolet ray for 30min, collecting powder, placing in a container, adding 70% (v/v) ethanol twice the weight of the powder, heating to 40 deg.C, stirring and extracting at 300rpm, wherein the microwave power is controlled at 500W during extraction, and the extraction time is 60 min; standing for 12 hr, filtering, collecting filtrate, rotary evaporating at low temperature to recover ethanol, and freeze drying to obtain bupleuri radix and fructus Aurantii extract.

specifically, the step 3) of distilling, decocting and extracting alcohol comprises the steps of mixing radix curcumae, rhizoma cyperi, pericarpium citri reticulatae viride, angelica sinensis and ligusticum wallichii, extracting volatile oil by a distillation method, keeping the medicine residues for later use, preparing the volatile oil into a beta-cyclodextrin inclusion compound by β -cyclodextrin for later use, adding 8 times of water by weight into the medicine residues, decocting for 2 times, 1 hour for the first time and 0.5 hour for the second time, merging decoction, filtering, collecting filtrate A, mixing the rest raw materials, adding water, decocting for 2 times, adding 10 times of water by weight for the first time, decocting for 2 hours, adding 8 times of water by weight for the second time, merging decoction, filtering, collecting filtrate B, merging filtrate A and B, concentrating the filtrate under reduced pressure to obtain an extract with the density of 1.20-1.25g/mL, cooling, adding ethanol to ensure that the ethanol content is 55% (v/v), standing for 24 hours, filtering, washing precipitates by using 55% (v/v) ethanol, merging the filtrates, recovering the ethanol, concentrating the reduced pressure to obtain an extract with the density of 1.20-1.25 g.

specifically, the step 4) of granulating, tabletting and coating comprises the steps of adding β -cyclodextrin inclusion compound obtained in the step 3) and the radix bupleuri and fructus aurantii extract obtained in the step 2) into the dry powder obtained in the step 3), uniformly mixing, granulating, drying, adding proper amounts of auxiliary materials of carboxymethyl starch and magnesium stearate, uniformly mixing, tabletting into 1000 tablets, and coating with a film coating.

The features of the present invention with respect to the prior art mainly include, but are not limited to, the following aspects:

the premenstrual ease preparation prepared by the invention has better effect than the existing preparation, and the dosage is correspondingly reduced; the preparation method is simple and feasible, different traditional Chinese medicine components are treated by different technologies, the effective components of the raw materials are improved, the drug effect is increased, and the waste of the raw materials is reduced; the saikosaponin and the bupleurum polysaccharide are main effective components in bupleurum, the extraction usually adopts a water extraction and alcohol precipitation method, the saikosaponin is easy to generate chemical change during the extraction and separation, and the extraction rate of bupleurum polysaccharide components is low; when the fructus aurantii is extracted, a decoction mode is adopted, so that the decomposition of ketone substances is easily caused; according to the invention, the leaching rate of effective components can be improved by adopting smaller particle size, and a higher extraction rate can be obtained by adopting a mode of ultraviolet irradiation and microwave alcohol extraction, so that the loss of components and the waste of raw materials are avoided; animal experiments suggest that the tablet prepared by the invention has better effect than the prior art, has no toxicity and can be used for further clinical trial research.

Detailed Description

In order to make those skilled in the art better understand the technical solutions in the present application, the present invention will be described more clearly and completely below with reference to specific embodiments of the present application, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

The preparation method of the premenstrual ease preparation comprises the following steps:

weighing the following raw materials for later use:

Pericarpium arecae 240g licorice root 120 g;

pulverizing bupleuri radix and fructus Aurantii in pulverizer, sieving with 200 mesh sieve, spreading into 3mm flat layer, and placing at intensity of 3000uW/cm²Irradiating with ultraviolet ray for 30min, collecting powder, placing in a container, adding 70% (v/v) ethanol twice the weight of the powder, heating to 40 deg.C, stirring and extracting at 300rpm, wherein the microwave power is controlled at 500W during extraction, and the extraction time is 60 min; standing for 12 hr, filtering, collecting filtrate, rotary evaporating at low temperature to recover ethanol, and freeze drying to obtain bupleuri radix and fructus Aurantii extract; the total yield of the bupleurum polysaccharide detected by an absorbance method is 6.73 percent, the total yield of the saikosaponin detected by an HPLC method is 5.62 percent, and the total yield of the bitter orange neohesperidin and the naringin is 12.6 percent;

mixing radix Curcumae, rhizoma Cyperi, pericarpium Citri Reticulatae viride, radix Angelicae sinensis and rhizoma Ligustici Chuanxiong, extracting volatile oil by distillation, collecting the residue, preparing the volatile oil into clathrate with β -cyclodextrin, decocting the residue with 8 times of water for 2 times, the first time for 1 hr and the second time for 0.5 hr, mixing decoctions, filtering, collecting filtrate A, mixing the rest raw materials (cortex Albizziae, fructus Lipuidambaris, semen Citri Reticulatae, radix Paeoniae alba, Poria, pericarpium Arecae and Glycyrrhrizae radix), decocting with water for 2 times, the first time for 2 hr with 10 times of water, the second time for 1 hr with 8 times of water, mixing the decoctions, filtering, collecting filtrate B, mixing filtrate A and filtrate B, concentrating under reduced pressure to obtain extract with density of 1.20-1.25g/mL, cooling, adding ethanol to obtain ethanol content of 55% (v/v), standing for 24 hr, filtering, precipitating, washing precipitate with 55% (v/v) ethanol, mixing the filtrates, recovering ethanol, concentrating under reduced pressure to obtain extract with density of 1.20-1.25g/mL, spray drying, adding β -cyclodextrin, spray drying, mixing with starch, and coating to obtain magnesium stearate.

The tablet prepared by the above preparation method is film coated tablet, and is brown after removing coating; fragrant smell, bitter and slightly pungent taste.

[ Specification ] weight of each tablet is 0.37g (film-coated tablet)

[ STORAGE ] sealing and standing in a cool and dry place.

Comparative example 1

Jingqian' an tablet:

Areca peel 240g and licorice root 120g

extracting volatile oil from the fourteen raw materials by a distillation method, preparing the volatile oil into an inclusion compound by β -cyclodextrin for later use, adding 8 times of water into medicine residues for decoction for 2 times, adding 8 times of water for decoction for 1 hour for the first time and 0.5 hour for the second time, merging decoction, filtering, adding water into the other seven raw materials such as cortex albiziae and the like for decoction for 2 times, adding 10 times of water for decoction for 2 hours for the first time and adding 8 times of water for decoction for 1 hour for the second time, merging decoction, filtering, merging the filtrate, concentrating the filtrate under reduced pressure to obtain an extract with the density of 1.20-1.25g/mL, cooling, adding ethanol until the alcohol content is 55%, standing for 24 hours, filtering, washing a precipitate by 55% of ethanol, filtering, merging the filtrate, recovering the ethanol, concentrating the extract under reduced pressure to obtain an extract with the density of 1.20-1.25g/mL, spray drying, adding the volatile oil β -cyclodextrin, uniformly mixing, preparing into granules, drying, adding an auxiliary material carboxymethyl starch, magnesium stearate, uniformly mixing, pressing into 1000 tablets, and coating to.

The total yield of bupleurum polysaccharide detected by absorbance method is 3.98%, the total yield of saikosaponin detected by HPLC method is 4.03%, and the total yield of fructus Aurantii neohesperidin and naringin is 8.2%.

The product is film coated tablet, and is brown after removing coating; fragrant smell, bitter and slightly pungent taste.

[ DOSAGE AND ADMINISTRATION ] administered orally. 5 tablets at a time, 2 times a day. The medicine is taken 14 days before menstruation, and is stopped when menstruation comes, and a menstruation period of 3 months is a treatment course.

[ Specification ] weight of each tablet is 0.37g (film-coated tablet)

[ STORAGE ] sealing and standing in a cool and dry place.

Example 2

Toxicity test in animals

60 healthy Kunming strain mice with half male and female parts and weight of 19.5 +/-1.7 g are randomly divided into two groups, wherein each group is half male and female, 30 mice are control groups, and normal water is filled in the groups; an additional 30 mice were given the formulation prepared in example 1 at a dose of 200mg/kg three times a day, and toxicity experiments using the mice showed that: compared with a control group, the mice have no obvious difference after administration, and the mice have normal general condition, food intake, water drinking and weight increase after continuous observation for three weeks in experiments. On the day of administration and within three weeks after administration, no death of animals is observed, which indicates that the medicine has low toxicity and safe clinical administration.

Example 3

Firstly, an analgesic test:

90 female Kunming mice are selected, the weight range is 21 +/-2 g, the mice are healthy and disease-free, and the mice are bred in the experimental animal center of the company. The groups were randomly divided into 3 groups, namely, a normal saline group, an example 1 group (preparation prepared in example 1), and a control 1 group (preparation prepared in control 1); the administration was performed twice a day at a dose of 200mg/kg (the group of example 1 and the group of control example 1 were administered with the drugs, respectively, and the group of normal saline was administered with the normal saline of the same weight), and the administration was performed by continuous gavage for 3 days, and after 1 hour of the last gavage, 0.2 ml/mouse was intraperitoneally injected with 0.6% glacial acetic acid, and the number of writhing of the mice was observed within 30min, and the results are shown in Table 1.

TABLE 1

Group of	Number of mice	Number of wriggling within 30min
			Physiological saline group	30	33.9±11.8
Comparative example 1 group	30	8.2±2.9
			EXAMPLE 1 group	30	6.1±2.1

II, sedation test:

60 female Kunming mice are selected, the weight range is 21 +/-2 g, the mice are healthy and disease-free, and the mice are bred in the experimental animal center of the company. The group was randomly divided into 3 groups, namely, a physiological saline group, an example 1 group (preparation prepared in example 1), and a control 1 group; the administration is carried out twice a day, the dose is 200mg/kg (the group of example 1 and the group of control example 1 are respectively administered with drugs, and the group of normal saline is administered with normal saline with the same weight), the continuous gavage administration is carried out for 3 days, and after the last gavage administration is carried out for 30min, 50mg/kg of pentobarbital sodium is respectively injected into the abdominal cavity of the mouse. The disappearance and recovery of the turnover reflex are taken as sleep indexes, and the sleep time of the mouse after injection is recorded. Specific results are shown in table 2:

TABLE 2

Group of	Number of mice	Sleep time (min)
			Physiological saline group	20	51.8±20.4
Comparative example 1 group	20	73.6±29.6
			EXAMPLE 1 group	20	82.3±21.8

And (4) conclusion: animal experiments indicate that the medicament prepared in the embodiment 1 of the invention has good analgesic and sedative effects and is superior to the existing preparation.

The foregoing list is only illustrative of the preferred embodiments of the present invention. It is obvious that the invention is not limited to the above embodiments, but that many variations are possible. All modifications which can be derived or suggested by a person skilled in the art from the disclosure of the present invention are to be considered within the scope of the invention.

Claims

1. The preparation method of the premenstrual ease preparation comprises the following steps: step 1) taking raw materials, step 2) preparing a radix bupleuri and fructus aurantii extract, step 3) distilling, decocting and extracting with alcohol, and step 4) granulating, tabletting and coating;

the step 1) is to take raw materials:

Pericarpium arecae 240g licorice root 120 g;

the step 2) is to prepare the extract of the bupleurum and the bitter orange: pulverizing bupleuri radix and fructus Aurantii in pulverizer, sieving with 200 mesh sieve, spreading into 3mm flat layer, and placing at intensity of 3000uW/cm²Irradiating with ultraviolet ray for 30min, collecting powder, placing in a container, adding 70% v/v ethanol twice the weight of the powder, heating to 40 deg.C, stirring and extracting at 300rpm, wherein the microwave power is controlled at 500W during extraction, and the extraction time is 60 min; standing for 12 hr, filtering, collecting filtrate, rotary evaporating at low temperature to recover ethanol, and freeze drying to obtain bupleuri radix and fructus Aurantii extract;

the step 3) distillation, decoction and alcohol extraction, wherein curcuma aromatica, cyperus rotundus, pericarpium citri reticulatae viride, angelica and ligusticum wallichii are mixed, volatile oil is extracted by a distillation method, medicine dregs are reserved, the volatile oil is prepared into a β -cyclodextrin inclusion compound by β -cyclodextrin for later use, the medicine dregs are added with 8 times of water by weight and decocted for 2 times, the first time is 1 hour, the second time is 0.5 hour, decoction liquids are combined and filtered, filtrate A is collected, the rest raw materials are mixed, water is added and decocted for 2 times, 10 times of water by weight is added for the first time and decocted for 2 hours, 8 times of water by weight is added for the second time and decocted for 1 hour, the decoction liquids are combined and filtered, filtrate B is collected, filtrate A and filtrate B are combined and concentrated under reduced pressure to extract with the density of 1.20-1.25g/mL, the extract is cooled, ethanol is added to ensure that the alcohol content is 55% v/v, the mixture is stood for 24 hours, the filtration, precipitates are washed by 55% of the ethanol, the filtrate A and the filtrate B is;

and 4) granulating, tabletting and coating, namely adding the β -cyclodextrin inclusion compound obtained in the step 3) and the radix bupleuri and fructus aurantii extract obtained in the step 2) into the dry powder obtained in the step 3), uniformly mixing, granulating, drying, adding proper amount of auxiliary materials of carboxymethyl starch and magnesium stearate, uniformly mixing, tabletting into 1000 tablets, and coating to obtain the Chinese medicinal composition.