CN102579869A - Preparation method of traditional Tibetan medicine composition for treating liver diseases - Google Patents

Abstract

The invention relates to a preparation method of a Tibetan medicine composition preparation for treating liver diseases. The method includes the steps of volatile oil extraction and inclusion, ethanol extraction, medicinal material fine powder crushing, preparation molding and the like. Compared with traditional preparations, the patient's medication compliance will be significantly improved; the pharmaceutical preparation prepared by the method of the present invention can achieve fast absorption under the premise of retaining the efficacy of the original preparation, and the active ingredients can reach the lesion in a concentrated manner. The utilization degree is high; the curative effect of the obtained pharmaceutical preparation is good.

Description

A kind of preparation method of Tibetan medicine composition for treating liver diseases

technical field

The invention relates to a preparation method of a Tibetan medicine composition, in particular to a preparation method of a Tibetan medicine composition for treating liver diseases, and belongs to the field of Tibetan medicine preparations.

Background technique

The liver is the metabolic center of the human body. It is one of the important organs for maintaining life. Its functional status is closely related to the health of the human body. If the liver cells are damaged, the function of the liver will be damaged, which may cause a series of inadaptable symptoms of the body. Hepatitis belongs to the category of "liver disease" in traditional Chinese medicine. Liver disease is mostly caused by feeling the poison of dampness and turbidity during epidemics; or improper diet, which damages the spleen and stomach, resulting in abnormal movement and transformation of water and grain qi, internal resistance of dampness and turbidity, stagnant steaming heat and mixing of dampness and heat, spleen and stomach Obstruction, stagnation of liver qi, inability to ventilate; or internal injury of the seven emotions, failure of liver circulation; or stagnation of qi into fire, stagnation of liver collaterals; or deficiency of yin and blood, hyperactivity of liver yang, and accumulation of damp heat, cold stagnation of the liver The disease is caused by the pulse; or the heat forces the bile to leak out; or the stagnation of liver qi, which damages the collaterals and blood stasis for a long time, causes poor bile excretion, bile leaks, and overflows on the skin as jaundice. The main clinical manifestations are pain in the right rib, pressing, loss of appetite, weakness of limbs, vomiting, headache, dizziness, tinnitus, red eyes, irritability, yellowing of the whole body, and enlarged liver. According to statistics, the number of people carrying hepatitis B surface antigen in the world exceeds 280 million. my country is a big country with hepatitis. At present, 8-10% of the population in our country are carriers of hepatitis B virus, and there are still a considerable number of new patients every year.

Ganchang Capsule is an exclusive product of Jinhe Tibetan Medicine Co., Ltd., which is recorded in the national standard part of the local standard of Chinese patent medicine, standard number: WS-10927(ZD-0927)-2002. Ganchang capsule preparation is made of the following medicinal materials in the following weight ratio: turquoise 20.1g, Tianzhuhuang 20.1g, safflower 40.0g, saffron 8.0g, Meconopsis 59.6g, Ganqing Qinglan 40.1g, Saibei purple Viola 40.1g, Rock Extract 40.1g, Clove 20.1g, Artificial Bezoar 4.0g, Indian Swertia 20.1g, Melon Seed 12.0g, Woody Aristolochia 12.0g, Stone Flower 4.0g, Musk 1.6g, Vermillion 1.7g.

Due to the good effect of Ganchang Capsule and the comprehensive consideration of the patient's physiological and pathological characteristics, it has been clinically verified that the curative effect is remarkable. However, the preparation methods of Ganchang drugs in the prior art all adopt simple physical treatment of crushing and mixing the raw materials, and the active ingredients of the raw materials are released slowly, which seriously affects the absorption and utilization of the active ingredients of the drug. It is urgent to introduce modern preparation methods. Provide fast dissolution, onset of effect, and better absorption and utilization of Ganchang preparations.

Contents of the invention

Aiming at the deficiencies of the prior art, the invention provides a preparation method of a Tibetan medicine composition preparation for treating liver diseases.

Technical scheme of the present invention is as follows:

A preparation method of a Tibetan medicine composition preparation for treating liver diseases, the raw material drug composition of the pharmaceutical composition consists of: 10-30 parts of turquoise, 10-30 parts of Tianzhuhuang, 20-60 parts of safflower, and saffron 4-10 parts, Meconopsis 25-75 parts, Ganqing Qinglan 15-50 parts, Corydalis 15-50 parts, Rock Extract 15-50 parts, Clove 10-30 parts, Artificial Bezoar 2-5 parts, 10-30 parts of Indian Swertia, 5-15 parts of Boling melon seeds, 2-5 parts of stone flowers, 1-3 parts of artificial musk; including the following steps:

(1) Get cloves according to the proportioning ratio of raw material medicine, add water 4-10 times the weight, adopt steam distillation method, extract volatile oil for 3-6h, collect volatile oil, and filter the medicinal liquid to obtain extract A' and medicinal residue A;

Add the collected volatile oil into a saturated aqueous solution of 3-4% by weight and volume of β-cyclodextrin, the volume-to-weight ratio of the volatile oil to β-cyclodextrin is 1ml: 3-5g, and keep the temperature at 40°C-60°C under stirring conditions , stirred for 3 to 4 hours, refrigerated overnight at -4°C-4°C, filtered with suction, precipitated, and vacuum-dried at 40°C-60°C to obtain the clathrate of volatile oil;

(2) According to the composition ratio of the raw materials, seven medicinal materials including sweet orchid, safflower, meconopsis, Corydalis sylvestris, Indian water swert, melon seeds, and stone flowers are taken, and the medicinal materials after extracting the volatile oil in step (1) are used. Mix the slag A, add ethanol solution B with a volume concentration of 30% to 100% to extract 2-3 times, the temperature is 50°C-100°C, and the amount of ethanol solution B added each time is the total weight of the 7 herbs and the dregs A 8-10 times, extract for 2-3 hours, filter, combine with the extract A' after extracting the volatile oil in step (1), concentrate under reduced pressure, and concentrate to a medicinal solution with a relative density of 1.06-1.12 at 25°C or 60°C A liquid extract with a relative density of 1.20-1.40 under certain conditions; or,

According to the composition ratio of the raw materials, seven medicinal materials including Ganqing Qinglan, safflower, Meconopsis, Corydalis sylvestris, Indian Swertia, Boling melon seeds, and Shihua were taken, mixed evenly, and crushed into 0.5mm-2mm fine powder, and mixed with Mix the medicinal dregs A after extracting the volatile oil from cloves, add ethanol solution B with a volume concentration of 30% to 100%, soak for 6-12 hours, and use ethanol solution B to percolate and extract. The amount used is the total weight of the 7 herbs and medicinal residues A 10-30 times of that, collect the percolation medicinal solution, combine with the extract A' after extracting the volatile oil from cloves, and concentrate under reduced pressure at a temperature lower than 60°C, until concentrated to a drug with a relative density of 1.06-1.12 at 25°C Liquid or liquid extract with a relative density of 1.20-1.40 at 60°C; or,

According to the composition ratio of raw materials, seven medicinal materials including Ganqing Qinglan, safflower, Meconopsis, Corydalis saber, Indian water swertia, porin melon seeds, and stone flower are mixed with the medicinal residue A after extracting the volatile oil in step (1). , add water to extract 2-3 times, the temperature is 50°C-100°C, the amount of water added each time is 8-10 times the total weight of the 7 herbs and medicinal residues A, extract for 2-3h, filter, and step ( 1) The extracts A' after extracting the volatile oil are combined, concentrated under reduced pressure, and concentrated to a medicinal solution with a relative density of 1.06-1.12 at 25°C or a liquid extract with a relative density of 1.20-1.40 at 60°C;

(3) Take the liquid extract obtained in step (2) with a relative density of 1.20-1.40 at 60°C, and dry it to obtain ethanol extract C; or,

Take the medicinal solution with a relative density of 1.06-1.12 at 25°C obtained in step (2), filter it, and absorb it with a macroporous resin with a volume of 0.2 to 1 times the medicinal solution for 2 to 12 hours, and then use a macroporous resin with a volume of 2 to 8 times the amount of water for elution, and then sequentially eluted with ethanol of different concentrations that are 2 to 8 times the volume of the macroporous resin. , 95% ethanol for elution, collect the eluents separately, combine them for later use, concentrate the combined eluents under reduced pressure to recover ethanol, collect and concentrate the liquid extracts with a relative density of 1.20-1.40 at 60°C, dry them, and obtain macropores Resin purification extract D;

(4) Take turquoise, Tianzhuhuang, saffron, rock essence ointment, artificial bezoar, and artificial musk according to the composition ratio of the raw materials, and grind them into 1-200 μm to obtain fine powder of medicinal materials; or,

Take turquoise, Tianzhuhuang, saffron, rock essence paste, artificial bezoar, and artificial musk according to the composition ratio of the raw materials, and add a total of 6 medicinal materials, add ethanol solution B with a volume concentration of 30% to 100%, soak for 6-12h, and use Percolation extraction of ethanol solution B, the amount used is 10-30 times the total weight of the six medicinal materials, the percolation liquid is collected, the temperature is lower than 60°C, concentrated under reduced pressure, and dried to obtain extract E; or,

Take turquoise, Tianzhuhuang, saffron, Yanjing ointment, artificial bezoar, and artificial musk according to the composition ratio of the raw materials, and a total of 6 medicinal materials are added to ethanol solution B with a volume concentration of 30% to 100% to extract 2-3 times. 50°C-100°C, the amount of ethanol solution B added each time is 8-10 times the total weight of the six medicinal materials, extract for 2-3 hours, filter, concentrate the medicinal solution under reduced pressure, and dry to obtain extract F;

(5) The volatile oil clathrate obtained in the above step (1), the ethanol extract C or the macroporous resin purified extract D obtained in the step (3), and the medicinal material fine powder or extract obtained in the step (4) E or the extract F is mixed evenly, added with conventional excipients, and prepared into any pharmaceutically acceptable dosage form according to the conventional process.

The macroporous resin for adsorption in the above step (3) is preferably HPD600, LSA-21, LSA-40, DM130 type.

Preferably according to the present invention, the raw material drug of the pharmaceutical composition is composed of: 15-20 parts of turquoise, 15-20 parts of geranium, 42-47 parts of safflower, 4-7 parts of saffron, and meconopsis 50-55 parts, 30-37 parts of Ganqing Qinglan, 30-37 parts of Saibei Viola, 30-39 parts of Yanjing Paste, 10-18 parts of cloves, 2-3.5 parts of artificial bezoar, 15-18 parts of Indian Swertia , 5-11 parts of watermelon seeds, 2-3.5 parts of stone flower, 1-1.5 parts of artificial musk.

Further preferably, the raw material drug composition of the pharmaceutical composition consists of 17.6 parts by weight of turquoise, 17.6 parts of geranium, 43.7 parts of safflower, 7 parts of saffron, 52 parts of Meconopsis, 35 parts of Ganqing Qinglan, Saibei 35 parts of Corydalis, 38.2 parts of rock extract, 17.6 parts of clove, 3.5 parts of artificial bezoar, 17.6 parts of Indian water swerve, 10.5 parts of melon seeds, 3.5 parts of stone flower, and 1.4 parts of artificial musk.

Preferably according to the present invention, the preparation method of the Tibetan medicine composition capsule for the treatment of liver disease of the present invention comprises the following steps:

(1) Get cloves according to the proportioning ratio of the raw material medicine, add water to 6 times the weight, adopt steam distillation, extract the volatile oil for 4 hours, collect the volatile oil to obtain the volatile oil, filter the medicinal liquid, and obtain the extract A' and the medicinal residue A;

Add the collected volatile oil into 4% by volume percent β-cyclodextrin saturated aqueous solution, the volume-to-weight ratio of volatile oil to β-cyclodextrin is 1ml:4g, under stirring conditions, keep the temperature at 50°C, stir for 4h, -4°C Refrigerate overnight, filter with suction, precipitate, and vacuum-dry at 5°C to obtain volatile oil clathrate;

(2) According to the composition ratio of the raw materials, take 7 kinds of medicinal materials including sweet orchid, safflower, meconopsis, Corydalis sylvestris, Indian swertia, melon seeds, and stone flower, mix them evenly, and grind them into 200 μm fine powder, and mix them with Mix the dregs A after extracting the volatile oil from cloves, add ethanol solution B with a volume concentration of 50%, soak for 8 hours, and extract by percolation with ethanol solution B. The amount used is 25 times the total weight of the 7 medicinal materials and dregs A, and collected Percolating the medicinal solution, combining with the extract A' obtained from the extraction of volatile oil from cloves, concentrating under reduced pressure at a temperature lower than 60°C, and concentrating to a medicinal solution with a relative density of 1.10 at 25°C;

(3) get the liquid medicine that relative density is 1.10 under the condition of 25 ℃ of step (2) gained, filter, absorb 6h with HPD600 type macroporous resin of 1/3 times of the weight of medicine liquid, then use HPD600 type macroporous resin volume 5 times the amount of water for elution, and then sequentially eluted with ethanol at different concentrations of 5 times the volume of the HPD600 macroporous resin. % ethanol and 95% ethanol were eluted, the eluents were collected separately, combined, the combined eluents were concentrated under reduced pressure to recover ethanol, and the liquid extract concentrated to a relative density of 1.20 at 60°C was collected and dried to obtain a macroporous resin Purified extract D;

(4): Take turquoise, Tianzhuhuang, saffron, Yanjing ointment, artificial bezoar, and artificial musk according to the composition ratio of the raw materials, a total of 6 medicinal materials, grind them into 50 μm fine powder, and add ethanol solution B with a volume concentration of 80% , soaked for 12 hours, extracted by percolation with ethanol solution B, the amount used is 30 times the total weight of the six medicinal materials, collected the percolation liquid, concentrated under reduced pressure at a temperature lower than 60°C, and dried to obtain extract E ;

(5): Mix the volatile oil clathrate prepared in the above step (1), the macroporous resin purified extract D prepared in the step (3), and the extract E prepared in the step (4), and add conventional auxiliary materials, It is prepared into capsules according to conventional techniques.

The relationship between parts by weight and parts by volume in the present invention is g/ml or kg/l.

The present invention has the following advantages:

1. The characteristics of the present invention are based on the phytochemical components as the material basis, guided by the efficacy and activity, fully considering the properties of the drug components, the needs of clinical symptoms, and the physiological conditions of the drug subjects, etc., and adopting a new extraction and preparation method to prepare the As a result, compared with traditional preparations, the pharmaceutical composition prepared by the method of the present invention can realize rapid dissolution and absorption of active ingredients, and concentrate on the lesion site under the premise of retaining the efficacy of the original preparation, thereby improving the utilization. For details, see the data description of the test case.

2. The present invention extracts and protects the volatile oil components of prescription medicinal materials, and adopts the β-cyclodextrin inclusion process to effectively ensure the stability of the volatile oil medicinal components. For details, see the data description of the test case.

3. The preparation method of percolation extraction adopted in the present invention can effectively protect thermally unstable components.

4. The ultrafine pulverization preparation method adopted in the present invention, such as turquoise, geranium, saffron, rock extract, artificial bezoar, artificial musk, etc., can realize rapid dissolution of medicinal ingredients and fully absorb and utilize them. For details, see the data description of the test case.

5. The preparation method of the macroporous resin used in the present invention to purify the medicinal ingredients can realize the effective enrichment of the active ingredients, increase the concentration of the drug, and make the medicinal ingredients convenient to quickly concentrate and reach the lesion site. For details, see the data description of the test case.

6. The pharmaceutical composition prepared by the present invention overcomes the shortcomings of the prior art that the original medicinal materials are pulverized into medicine and is not suitable for modern dosage forms. The pharmaceutical composition obtained by modern technology can be used for capsules, granules, oral liquids, dripping pills, dispersed Tablets and other modern dosage forms.

Detailed ways

The following examples and experimental examples are used to further illustrate but not limit the present invention. The Ganchang composition used in the experimental examples is the pharmaceutical composition for treating liver diseases prepared by the method of the present invention.

The proportioning by weight of the crude drug of the embodiment 1-5 pharmaceutical composition is as follows:

17.6 parts of turquoise, 17.6 parts of geranium, 43.7 parts of safflower, 7 parts of saffron, 52 parts of Meconopsis, 35 parts of Ganqing Qinglan, 35 parts of Corydalis viridifera, 38.2 parts of rock extract, 17.6 parts of clove, artificial bezoar 3.5 parts, Indian Swertia 17.6 parts, Pollen melon seeds 10.5 parts, stone flower 3.5 parts, artificial musk 1.4 parts.

The original commercially available Ganchang Capsules used for comparison was the product of Jinhe Tibetan Medicine Pharmaceutical Co., Ltd.

The Ganchang pharmaceutical composition used in Experimental Example 1 is the pharmaceutical composition prepared in Examples 1-5.

The DM130 type resins used in the examples and experimental examples are available from Anhui Sanxing Resin Technology Co., Ltd.; HPD600, YWD-01 type resins are available from Cangzhou Baoen Chemical Co., Ltd.; X-5, NKA, ADS-F8, LS-300 , D101 type resin Nankai University Chemical Plant is available; LSA-21LSA-40 type resin Xi'an Lanxiao Technology Co., Ltd. is available for sale.

Embodiment 1, the preparation of a kind of pharmaceutical composition capsule for the treatment of liver disease

(1) Get cloves according to the proportioning ratio of the raw material medicine, add water to 6 times the weight, adopt steam distillation, extract the volatile oil for 4 hours, collect the volatile oil to obtain the volatile oil, filter the medicinal liquid, and obtain the extract A' and the medicinal residue A;

Add the collected volatile oil into 4% by volume percent β-cyclodextrin saturated aqueous solution, the volume-to-weight ratio of volatile oil to β-cyclodextrin is 1ml:4g, under stirring conditions, keep the temperature at 50°C, stir for 4h, -4°C Refrigerate overnight, filter with suction, precipitate, and vacuum-dry at 5°C to obtain volatile oil clathrate;

(2) According to the composition ratio of the raw materials, take 7 kinds of medicinal materials including sweet orchid, safflower, meconopsis, Corydalis sylvestris, Indian swertia, melon seeds, and stone flower, mix them evenly, and grind them into 200 μm fine powder, and mix them with Mix the dregs A after extracting the volatile oil from cloves, add ethanol solution B with a volume concentration of 50%, soak for 8 hours, and extract by percolation with ethanol solution B. The amount used is 25 times the total weight of the 7 medicinal materials and dregs A, and collected Percolating the medicinal solution, combining with the extract A' obtained from the extraction of volatile oil from cloves, concentrating under reduced pressure at a temperature lower than 60°C, and concentrating to a medicinal solution with a relative density of 1.10 at 25°C;

(3) get the liquid medicine that relative density is 1.10 under the condition of 25 ℃ of step (2) gained, filter, absorb 6h with HPD600 type macroporous resin of 1/3 times of the weight of medicine liquid, then use HPD600 type macroporous resin volume 5 times the amount of water for elution, and then sequentially eluted with ethanol at different concentrations of 5 times the volume of the HPD600 macroporous resin. % ethanol and 95% ethanol for elution, collect the eluents separately, combine them, concentrate the combined eluents under reduced pressure to recover ethanol, collect and concentrate the fluid extract with a relative density of 1.3 at 60°C, and dry to obtain macropores Resin purification extract D;

(4) Take turquoise, Tianzhuhuang, saffron, Yanjing ointment, artificial bezoar, and artificial musk according to the composition ratio of the raw materials, and altogether 6 medicinal materials are crushed into 50 μm fine powder, and then added into ethanol solution B with a volume concentration of 80%, Soak for 12 hours, use ethanol solution B for percolation extraction, the amount used is 30 times the total weight of the six medicinal materials, collect the percolation liquid, concentrate under reduced pressure at a temperature lower than 60°C, and dry to obtain extract E;

(5) Mix the volatile oil clathrate obtained in the above step (1), the macroporous resin purified extract D obtained in the step (3), and the extract E obtained in the step (4), and add conventional auxiliary materials, according to Prepared into capsules by conventional techniques.

Embodiment 2, the preparation of a kind of pharmaceutical composition granule for the treatment of liver disease

(1) Take cloves according to the proportioning ratio of the raw material medicine, add water to 8 times the weight, adopt steam distillation, extract the volatile oil for 6 hours, collect the volatile oil to obtain the volatile oil, filter the medicinal liquid, and obtain the extract A' and the medicinal residue A;

Add the collected volatile oil into a saturated aqueous solution of 3% by weight and volume of β-cyclodextrin, the volume-to-weight ratio of volatile oil to β-cyclodextrin is 1ml:5g, under stirring conditions, keep the temperature at 60°C, stir for 4h, and -4°C Refrigerate overnight, filter with suction, precipitate, and dry under vacuum at 40°C to obtain inclusion complex of volatile oil;

(2) According to the composition ratio of the raw materials, seven medicinal materials including sweet orchid, safflower, meconopsis, Corydalis sylvestris, Indian water swert, melon seeds, and stone flowers are taken, and the medicinal materials after extracting the volatile oil in step (1) are used. Mix dregs A, add ethanol solution B with a volume concentration of 80% to extract 3 times, the temperature is 80°C, the amount of ethanol solution B added each time is 8 times the total weight of the 7 herbs and dregs A, extract for 3 hours, filter , combined with the extract A' after extracting the volatile oil in step (1), concentrated under reduced pressure, and concentrated to a fluid extract with a relative density of 1.40 at 60°C;

(3) Take the liquid extract obtained in step (2) with a relative density of 1.40 at 60°C, and dry it to obtain ethanol extract C;

(4) Take turquoise, Tianzhuhuang, saffron, Yanjing ointment, artificial bezoar, and artificial musk according to the composition ratio of the raw materials, and altogether 6 medicinal materials are crushed into 0.5mm fine powder, and added to ethanol solution B with a volume concentration of 80%. , soaked for 8 hours, extracted by percolation with ethanol solution B, the amount used is 30 times the total weight of the six medicinal materials, the percolation liquid was collected, concentrated under reduced pressure at a temperature lower than 60°C, and dried to obtain extract E ;

(5) Mix the volatile oil clathrate obtained in the above step (1), the ethanol extract C obtained in the step (3), and the extract E obtained in the step (4), add conventional auxiliary materials, and prepare according to the conventional process into granules. Embodiment 3, the preparation of a kind of pharmaceutical composition tablet for the treatment of liver disease

(1) Take cloves according to the proportioning ratio of the raw material medicine, add water to 5 times the weight, adopt steam distillation, extract the volatile oil for 3 hours, collect the volatile oil to obtain the volatile oil, filter the medicinal liquid, and obtain the extract A' and the medicinal residue A;

Add the collected volatile oil into a saturated aqueous solution of 3% by weight and volume of β-cyclodextrin, the volume-to-weight ratio of volatile oil to β-cyclodextrin is 1ml:4g, under stirring conditions, keep the temperature at 60°C, stir for 4h, and refrigerate at 4°C Overnight, suction filtration, precipitation, vacuum drying at 60°C to obtain inclusion complex of volatile oil;

(2) According to the composition ratio of the raw materials, seven medicinal materials including sweet orchid, safflower, meconopsis, Corydalis sylvestris, Indian water swert, melon seeds, and stone flowers are taken, and the medicinal materials after extracting the volatile oil in step (1) are used. Mix dregs A, add water to reflux and extract 3 times, the amount of water added each time is 10 times the total weight of the 7 herbs and dregs A, extract for 2 hours, filter, and extract the volatile oil in step (1) A' are combined, concentrated under reduced pressure, and concentrated to a medicinal solution with a relative density of 1.10 at 25°C;

(3) Take the medicinal solution with a relative density of 1.10 under the condition of 25°C obtained in step (2), filter it, and absorb it with LSA-21 type macroporous resin with 1/6 times the weight of the medicinal solution for 8 hours, and then use LSA-21 type 8 times the volume of the macroporous resin for elution, followed by elution with ethanol at different concentrations of 8 times the volume of the LSA-21 type macroporous resin. Elute with 50% ethanol, 70% ethanol, and 95% ethanol, collect the eluents separately, combine them for later use, concentrate the combined eluents under reduced pressure to recover ethanol, collect and concentrate the liquid extracts with a relative density of 1.40 at 60°C , dried to obtain macroporous resin purified extract D;

(4) Take turquoise, Tianzhuhuang, saffron, Yanjing ointment, artificial bezoar, and artificial musk according to the composition ratio of the raw materials, a total of 6 medicinal materials, and grind them into 50 μm to obtain medicinal powder;

(5) Mix the volatile oil clathrate obtained in the above step (1), the purified macroporous resin extract D obtained in the step (3), and the fine powder of medicinal materials obtained in the step (4), add conventional auxiliary materials, and follow the Tablets are prepared by conventional techniques.

Embodiment 4, the preparation of a kind of pharmaceutical composition pill for the treatment of liver disease

(1) Get cloves according to the proportioning ratio of the raw material medicine, add water to 6 times the weight, adopt steam distillation, extract the volatile oil for 4 hours, collect the volatile oil to obtain the volatile oil, filter the medicinal liquid, and obtain the extract A' and the medicinal residue A;

Add the collected volatile oil into 4% by volume percent β-cyclodextrin saturated aqueous solution, the volume-to-weight ratio of volatile oil to β-cyclodextrin is 1ml:4g, under stirring conditions, keep the temperature at 50°C, stir for 4h, -4°C Refrigerate overnight, filter with suction, precipitate, and vacuum-dry at 50°C to obtain volatile oil clathrate;

(2) According to the composition ratio of the raw materials, seven medicinal materials including sweet orchid, safflower, meconopsis, Corydalis sylvestris, Indian water swert, melon seeds, and stone flowers are taken, and the medicinal materials after extracting the volatile oil in step (1) are used. Mix the dregs A, add ethanol solution B with a volume concentration of 60% to reflux for extraction 3 times, add 60% ethanol solution B each time to 10 times the total weight of the 7 herbs and dregs A, extract for 2 hours, filter, Combine with the extract A' after extracting the volatile oil in step (1), concentrate under reduced pressure, and concentrate the medicinal solution with a relative density of 1.10 at 25°C;

(3) Take the medicinal solution with a relative density of 1.10 at 25°C obtained in step (2), filter it, and use 1/3 times the weight of the DM130 type macroporous resin to adsorb for 6 hours, and then use the DM-130 type macroporous resin to volume 8 times the amount of water for elution, and then sequentially eluted with ethanol at different concentrations that are 8 times the volume of DM130 macroporous resin. ethanol and 95% ethanol were eluted, the eluents were collected separately, combined for later use, the combined eluents were concentrated under reduced pressure to recover ethanol, and the liquid extract concentrated to a relative density of 1.20-1.40 at 60°C was collected and dried to obtain Different concentrations of ethanol extract D after purification by macroporous resin;

(4) Take turquoise, Tianzhuhuang, saffron, Yanjing ointment, artificial bezoar, and artificial musk according to the proportioning ratio of the raw materials, and grind them into 1.4mm fine powder, and add ethanol solution B with a volume concentration of 90%. , soaked for 12 hours, extracted by percolation with ethanol solution B, the amount used is 30 times the total weight of the six medicinal materials, collected the percolation liquid, concentrated under reduced pressure at a temperature lower than 60°C, and dried to obtain extract E .

(5) Mix the volatile oil clathrate obtained in the above step (1), the macroporous resin purified extract D obtained in the step (3), and the extract E obtained in the step (4), and add conventional auxiliary materials, according to The conventional process is prepared into pills.

Embodiment 5, the preparation of a kind of pharmaceutical composition drop pill for the treatment of liver disease

(1) Get cloves according to the proportioning ratio of the raw material medicine, add water to 6 times the weight, adopt steam distillation, extract the volatile oil for 4 hours, collect the volatile oil to obtain the volatile oil, filter the medicinal liquid, and obtain the extract A' and the medicinal residue A;

Add the collected volatile oil into 4% by volume percent β-cyclodextrin saturated aqueous solution, the volume-to-weight ratio of volatile oil to β-cyclodextrin is 1ml:4g, under stirring conditions, keep the temperature at 50°C, stir for 4h, -4°C Refrigerate overnight, filter with suction, precipitate, and vacuum-dry at 50°C to obtain volatile oil clathrate;

(2) According to the composition ratio of the raw materials, seven medicinal materials including sweet orchid, safflower, meconopsis, Corydalis sylvestris, Indian water swert, melon seeds, and stone flowers are taken, and the medicinal materials after extracting the volatile oil in step (1) are used. Mix the dregs A, add ethanol solution B with a volume concentration of 60% to reflux for extraction 3 times, add 60% ethanol solution B each time to 10 times the total weight of the 7 herbs and dregs A, extract for 2 hours, filter, Combine with the extract A' after extracting the volatile oil in step (1), concentrate under reduced pressure, and concentrate the liquid extract with a relative density of 1.3 at 60°C;

(3) Take the liquid extract obtained in step (2) with a relative density of 1.3 at 60°C, and dry it to obtain ethanol extract C;

(4) Get turquoise, Tianzhuhuang, saffron, rock extract paste, artificial bezoar, and artificial musk according to the proportioning ratio of the raw material medicines, a total of 6 medicinal materials, add ethanol solution B with a volume concentration of 80%, and add 80% volume concentration Extract with ethanol solution B for 2-3 times at a temperature of 60°C, add ethanol solution B each time with an amount 10 times the total weight of the 6 medicinal materials, extract for 3 hours, filter, concentrate the medicinal solution under reduced pressure, and dry to obtain the extract F.

(5) Mix the volatile oil clathrate obtained in the above step (1), the different ethanol extracts C obtained in the step (3), and the extract F obtained in the step (4), add conventional auxiliary materials, and follow the conventional process Prepared into drop pills.

Experimental example 1. Taking the anti-hepatitis B virus effect as the target, the pharmacological effect of the Ganchang pharmaceutical composition was observed by using the duck hepatitis B model.

Animal model preparation: 1-day-old male shelduck duck, weighing 40-50g, was injected with duck DHBV-DNA strong positive serum through the tibial vein of the leg, 0.2ml/piece, and raised until 2 weeks old as a duck hepatitis B experimental animal model.

Test method: 140 ducks congenitally infected with DHBV were randomly divided into 7 groups, 20 in each group: positive control group, virus control group, Ganchang composition 1-5. The Ganchang pharmaceutical composition of the administration group, the dose is 100mg/kg/d, the starch solution is used in the virus control group, and the Ganchang capsule is used in the positive control group, and the dosage is 100mg/kg/d; One day is a course of treatment. Blood was collected from the external jugular vein before and 10 days after the administration, and the separated serum was stored at -20°C for testing. Take the above duck blood samples, dot the membranes at the same time for each batch, use P to label the DHBV-DNA probe, and do duck blood spot hybridization, autoradiography membrane spots, measure the OD value (490nm) on a microplate reader, and calculate the serum DHBV-DNA density. The results are shown in Table 1.

Table 1 The inhibitory effect of body Ganchang pharmaceutical composition on DHBV-DNA

(Note: Compared with this group before medication, *P<0.01)

The results show that in the in vivo anti-duck hepatitis B virus test, Ganchang pharmaceutical composition 1-5 can significantly reduce DHBV-infected duck serum DHBV-DNA levels, and is better than the Ganchang capsule control group, suggesting that Ganchang pharmaceutical composition has an anti-hepatitis B effect. The effect is better than that of the original Ganchang capsule preparation, and Ganchang pharmaceutical composition 1 has the best effect.

Experimental example 2, stability test

Taking the volatile oil of clove as an index, the advantages of β-cyclodextrin inclusion technology of volatile oil were investigated.

Extract volatile oil according to the method of Example 1, and inclusion, prepare Ganchang composition capsule simultaneously; Prepare Ganchang capsule by the preparation method of former Ganchang capsule; Place 0, 1, 2, 3, 6 months under the same condition, The volatile oil content was detected, and the results are shown in Table 2.

Table 2 The results of investigation on the stability of volatile oil by inclusion of β-cyclodextrin

The results show that the stability of the clove volatile oil in the preparation can be improved after inclusion inclusion of clove volatile oil with β-cyclodextrin.

Experimental example 3, dissolution test

Taking the dissolution rate of hydroxysafflower yellow A, crocin I and glucoside II, muskone, eugenol, swertiamarin and other medicinal ingredients as indicators, the advantages of Ganchang pharmaceutical composition were investigated. The results are shown in Table 3.

Table 3 Dissolution results of Ganchang pharmaceutical composition

The results showed that the dissolution rates of active ingredients such as 1-5-hydroxysafflower yellow A, crocin I and glucoside II, muscone, eugenol, and swertiamarin in Ganchang pharmaceutical composition were better than those of Ganchang. Chang capsule control group.

Experimental Example 4: Process Screening Test

Taking the content of total flavonoids and swertiamarin as indicators, the effects of different types of resins on the enrichment and purification of the active ingredients of the Ganchang composition were investigated. The results are shown in Table 4 and Table 5.

Table 4 Screening results of different types of resins

The results showed that the HPD600 macroporous resin had the highest adsorption of total flavonoids and swertiamarin, and the smallest dead adsorption loss.

Table 5 Results of macroporous resin enrichment and purification of active ingredients

craft Total flavonoid content (mg/g) Hydroxysafflower yellow A (mg/g) Indian swertiamarin (mg/g) Before HPD600 purification 35.6 1.5 0.21 After HPD600 purification 400.8 21.5 2.53

The results show that after purification by the macroporous resin, the effective components are effectively enriched and the concentration of the active components is increased.

Claims (5)

1. A preparation method of a Tibetan medicine composition preparation for treating liver diseases comprises the following raw material medicines in parts by weight: 10-30 parts of turquoise, 10-30 parts of tabasheer, 20-60 parts of safflower, 4-10 parts of saffron, 25-75 parts of artemisia virginiana, 15-50 parts of dracocephalum tanguticum, 15-50 parts of corydalis impatiens, 15-50 parts of rock essence paste, 10-30 parts of clove, 2-5 parts of artificial bezoar, 10-30 parts of India swertia, 5-15 parts of herpetospermum pedunculosum seeds, 2-5 parts of lithospermum and 1-3 parts of artificial musk; the method is characterized by comprising the following steps:

(1) taking clove according to the composition ratio of the raw materials, adding 4-10 times of water by weight, extracting volatile oil for 36 hours by adopting a steam distillation method, collecting the volatile oil, and filtering liquid medicine to obtain an extracting solution A' and medicine dregs A;

adding the collected volatile oil into a beta cyclodextrin saturated aqueous solution with the weight volume percentage of 3-4%, wherein the volume weight ratio of the volatile oil to the beta cyclodextrin is 1 ml: 3-5g, stirring, keeping the temperature at 40-60 ℃, stirring for 3-4 h, refrigerating overnight at-4 ℃, performing suction filtration, precipitating, and performing vacuum drying at 40-60 ℃ to obtain a volatile oil inclusion compound;

(2) mixing 7 medicinal materials of dracocephalum tanguticum, safflower, artemisia rupestris, corydalis impatiens, swertia indica, herpetospermum pedunculosa and lithospermum, which are taken according to the composition ratio of the raw materials, with the dregs A after the volatile oil is extracted in the step (1), adding an ethanol solution B with the volume concentration of 30-100% for extraction for 2-3 times, at the temperature of 50-100 ℃, wherein the amount of the ethanol solution B added each time is 8-10 times of the total weight of the 7 medicinal materials and the dregs A, extracting for 2-3h, filtering, combining with the extracting solution A' after the volatile oil is extracted in the step (1), concentrating under reduced pressure to obtain a liquid medicine with the relative density of 1.06-1.12 under the condition of 25 ℃ or a fluid extract with the relative density of 1.20-1.40 under the condition of; or,

taking 7 medicinal materials of dracocephalum tanguticum, safflower, artemisia rupestris, corydalis impatiens, swertia davidi, herpetospermum pedunculosa seeds and lithospermum, mixing uniformly, crushing into fine powder of 0.5-2 mm, mixing with decoction dregs A obtained after volatile oil extraction of clove, adding an ethanol solution B with the volume concentration of 30-100%, soaking for 6-12h, percolating and extracting with the ethanol solution B, wherein the dosage is 10-30 times of the total weight of the 7 medicinal materials and the decoction dregs A, collecting percolate liquid medicine, mixing with an extracting solution A' obtained after volatile oil extraction of clove, concentrating under reduced pressure at the temperature of less than 60 ℃, and concentrating to liquid medicine with the relative density of 1.06-1.12 at the temperature of 25 ℃ or fluid extract with the relative density of 1.20-1.40 at the temperature of 60 ℃; or,

mixing 7 medicinal materials of dracocephalum tanguticum, safflower, artemisia rupestris, corydalis impatiens, swertia indica, herpetospermum pedunculosa and lithospermum, which are taken according to the composition ratio of the raw materials, with the decoction dregs A after the volatile oil is extracted in the step (1), adding water for 2-3 times at the temperature of 50-100 ℃, wherein the amount of water added for each time is 8-10 times of the total weight of the 7 medicinal materials and the decoction dregs A, extracting for 2-3h, filtering, combining with the extracting solution A' after the volatile oil is extracted in the step (1), concentrating under reduced pressure to liquid medicine with the relative density of 1.06-1.12 under the condition of 25 ℃ or fluid extract with the relative density of 1.20-1.40 under the condition of 60 ℃;

(3) taking the fluid extract with the relative density of 1.20-1.40 at the temperature of 60 ℃ obtained in the step (2), and drying to obtain an ethanol extract C; or,

taking the liquid medicine with the relative density of 1.06-1.12 at 25 ℃ obtained in the step (2), filtering, adsorbing for 2-12 h by using macroporous resin with the weight of 0.2-1 time of the liquid medicine, eluting by using water with the volume of 2-8 times of that of the macroporous resin, sequentially eluting by using ethanol with different concentrations of 2-8 times of that of the macroporous resin, eluting by using ethanol with the volume concentrations of 10% ethanol, 30% ethanol, 50% ethanol, 70% ethanol and 95% ethanol, respectively collecting the eluates, merging for later use, concentrating the merged eluates under reduced pressure to recover ethanol, collecting fluid extract with the relative density of 1.20-1.40 at 60 ℃, and drying to obtain a macroporous resin purified extract D;

(4) taking 6 kinds of medicinal materials including pine needle, concretio silicea Bambusae seu Schizostachyi, stigma croci, rock extract, artificial bezoar and artificial musk according to the composition ratio of the raw materials, and crushing the medicinal materials into 1-200 mu m to obtain medicinal material fine powder; or,

taking 6 medicinal materials of pinitol, tabasheer, saffron, rock extract, artificial bezoar and artificial musk according to the composition ratio of the raw medicinal materials, adding an ethanol solution B with the volume concentration of 30-100%, soaking for 6-12h, percolating and extracting by using the ethanol solution B, wherein the using amount is 10-30 times of the total weight of the 6 medicinal materials, collecting percolate, concentrating under reduced pressure at the temperature of lower than 60 ℃, and drying to obtain an extract E; or,

taking 6 medicinal materials of pine needle, tabasheer, saffron, rock extract, artificial bezoar and artificial musk according to the composition ratio of the raw materials, adding an ethanol solution B with the volume concentration of 30-100% for extraction for 2-3 times at the temperature of 50-100 ℃, wherein the amount of the ethanol solution B added each time is 8-10 times of the total weight of the 6 medicinal materials, extracting for 2-3 hours, filtering, concentrating the liquid medicine under reduced pressure, and drying to obtain an extract F;

(5) mixing the volatile oil clathrate prepared in step (1), ethanol extract C or macroporous resin purified extract D prepared in step (3), and medicinal material fine powder or extract E or extract F prepared in step (4), adding conventional adjuvants, and making into pharmaceutically acceptable dosage forms according to conventional process.

2. The preparation method of a Tibetan medicinal composition for treating liver diseases according to claim 1, wherein the macroporous resin for adsorption in step (3) is HPD600, LSA-21, LSA-40 or DM130 type.

3. The preparation method of the Tibetan medicine composition preparation for treating liver diseases as claimed in claim 1, wherein the raw material medicines of the medicine composition comprise the following components in parts by weight: 15-20 parts of turquoise, 15-20 parts of tabasheer, 42-47 parts of safflower, 4-7 parts of saffron, 50-55 parts of artemisia virginiana, 30-37 parts of dracocephalum tanguticum, 30-37 parts of corydalis impatiens, 30-39 parts of rock essence paste, 10-18 parts of clove, 2-3.5 parts of artificial bezoar, 15-18 parts of India swertia, 5-11 parts of herpetospermum pedunculosum seeds, 2-3.5 parts of lithospermum and 1-1.5 parts of artificial musk.

4. The preparation method of the Tibetan medicine composition preparation for treating liver diseases as claimed in claim 3, wherein the raw material medicines of the medicine composition comprise the following components in parts by weight: 17.6 parts of turquoise, 17.6 parts of tabasheer, 43.7 parts of safflower, 7 parts of saffron, 52 parts of artemisia selengensis, 35 parts of dracocephalum tanguticum, 35 parts of corydalis impatiens, 38.2 parts of rock essence paste, 17.6 parts of clove, 3.5 parts of artificial bezoar, 17.6 parts of India swertia, 10.5 parts of herpetospermum pedunculosum seeds, 3.5 parts of lithospermum and 1.4 parts of artificial musk.

5. The preparation method of the Tibetan medicinal composition preparation for treating liver diseases as claimed in claim 4, which comprises the following steps:

(1) mixing flos Caryophylli with 6 times of water, extracting volatile oil for 4 hr by steam distillation, collecting volatile oil to obtain volatile oil, and filtering medicinal liquid to obtain extractive solution A' and residue A;

adding the collected volatile oil into a beta-cyclodextrin saturated aqueous solution with the weight volume percentage of 4%, wherein the volume weight ratio of the volatile oil to the beta-cyclodextrin is 1 ml: 4g, stirring at 50 ℃, refrigerating at-4 ℃ for 4h overnight under stirring, performing suction filtration, precipitating, and performing vacuum drying at 5 ℃ to obtain a volatile oil inclusion compound;

(2) taking 7 medicinal materials of dracocephalum tanguticum, safflower, artemisia rupestris, corydalis impatiens, swertia indica, herpetospermum pedunculosa and lithospermum, uniformly mixing, crushing into fine powder of 200 mu m, mixing with decoction dregs A obtained after volatile oil extraction of clove, adding an ethanol solution B with the volume concentration of 50%, soaking for 8h, percolating and extracting with the ethanol solution B, wherein the using amount of the ethanol solution B is 25 times of the total weight of the 7 medicinal materials and the decoction dregs A, collecting percolate liquid medicine, mixing with an extracting solution A' obtained after volatile oil extraction of clove, concentrating under reduced pressure at the temperature of below 60 ℃, and concentrating to liquid medicine with the relative density of 1.10 at the temperature of 25 ℃;

(3) taking the liquid medicine with the relative density of 1.10 obtained in the step (2) at 25 ℃, filtering, adsorbing for 6 hours by using HPD600 type macroporous resin with the weight of 1/3 times of the liquid medicine, eluting by using water with the volume 5 times of that of the HPD600 type macroporous resin, sequentially eluting by using ethanol with different concentrations 5 times of that of the HPD600 type macroporous resin, wherein the volume concentrations of the ethanol for elution are respectively 10% ethanol, 30% ethanol, 50% ethanol, 70% ethanol and 95% ethanol, respectively collecting the eluates, merging for later use, concentrating the merged eluates under reduced pressure to recover ethanol, collecting fluid extract concentrated to the relative density of 1.3 at 60 ℃, and drying to obtain a macroporous resin purified extract D;

(4) taking 6 medicinal materials of pinitol, tabasheer, saffron, rock extract, artificial bezoar and artificial musk according to the composition ratio of the raw medicinal materials, crushing the medicinal materials into 50 mu m fine powder, adding an ethanol solution B with the volume concentration of 80%, soaking for 12h, percolating and extracting by using the ethanol solution B, wherein the using amount is 30 times of the total weight of the 6 medicinal materials, collecting percolate, concentrating under reduced pressure at the temperature of lower than 60 ℃, and drying to obtain an extract E;

(5) mixing the volatile oil clathrate prepared in step (1), the macroporous resin purified extract D prepared in step (3) and the extract E prepared in step (4), adding conventional adjuvants, and making into capsule according to conventional process.