Preparation method of herba siegesbeckiae luoda capsule

Abstract

The invention provides a preparation method of a herba siegesbeckiae luoda capsule. The preparation method comprises the following steps: step 1, weighing raw traditional Chinese medicinal materials according to a prescription amount; step 2, crushing gastrodia elata into fine powder, then mixing with borneol and calculus bovis factitius, grinding into fine powder, sieving, and uniformly mixing for later use; step 3, carrying out reflux extraction on ligusticum wallichii for 2-3 times by using ethanol, filtering, combining filtrates, and recovering ethanol to obtain a ligusticum wallichii extracting solution; step 4, mixing herba siegesbeckiae, leech, ginger processed pinellia, gentiana macrophylla, pseudo-ginseng, safflower, peach kernel, salvia miltiorrhiza and arisaema cum bile, adding water for decoction, filtering after decoction, and combining filtrate; step five, soaking musk and ground beetles in water for 1-2 hours, then performing microwave radiation treatment, separating filter residues and filtrate after microwave radiation, drying the filter residues, and crushing the dried filter residues into fine powder; and step 6, combining the ligusticum wallichii extracting solution in the step 3, the filtrate in the step 4 and the filtrate in the step 5, performing vacuum concentration to obtain thick paste with the relative density of 1.30-1.40, performing vacuum drying, crushing the obtained dried substance into fine powder, uniformly mixing the fine powder with the fine powder in the step 2 and the fine powder in the step 5, and preparing the capsule with a pharmaceutically acceptable carrier or excipient. The musk and the ground beetles are treated together, the special fragrance of the musk is used for covering the bad smell of the ground beetles, the fishy smell of the ground beetles is effectively weakened, and the medicine taking compliance of a user is improved.

Description

Technical Field

[0001] The invention relates to the technical field of medicines, and in particular to a preparation method of Xizhiluoda capsules. Background Art

[0002] Acute cerebral infarction is one of the common cerebrovascular diseases, with a high incidence, disability and mortality rate. With the acceleration of the aging process in my country, its incidence rate is on the rise, and it has become a social public health problem that threatens people's lives. Traditional Chinese medicine believes that cerebral infarction belongs to the category of "stroke" and emphasizes syndrome differentiation and treatment. Wind-phlegm blood stasis and obstruction of the meridians is a common syndrome of stroke. Xizhiluoda Capsule has the clinical efficacy of resolving phlegm, activating blood circulation, extinguishing wind and unblocking meridians. It is a Chinese patent medicine developed for acute stage wind-phlegm blood stasis and obstruction of the meridians.

[0003] Xizhiluoda Capsule is made of 15 kinds of Chinese medicinal materials, among which Xiqiancao is the main medicine, which can dispel wind and dampness, promote the qi of the large intestine, benefit the vital energy, treat liver and kidney wind, and paralysis of the limbs. Nanxing is cool in nature, bitter in taste, flat in qi, can rise or fall, and specializes in meridians. It is a guide for treating paralysis caused by stroke and the thick disease of falling and speechlessness caused by stroke; Pinellia is pungent in taste, slightly bitter, flat in qi, sinking and descending, but it can disperse and still has the function of internal defense. With the help of Nanxing, it can break the source of the disease; Danshen is bitter in taste, slightly cold, clears heat, activates blood circulation and removes blood stasis. It is good at promoting blood circulation and cooling blood, and can also nourish blood and calm the mind. The combination of the three medicines can reduce wind and phlegm, calm heat, activate blood, and wake up stroke coma. It is supplemented with Gastrodia elata, Panax notoginseng, safflower, peach kernel, Chuanxiong and other blood circulation, blood circulation and blood stasis, wind extinguishing and collateral dredging products. Musk, borneol, and artificial bezoar are used together, and the fragrance spreads, refreshing the brain and opening the mind. Musk has a strong fragrance that reaches from the inside to the outside, opens the orifices, and opens the hair and joints, leading the evil out. Borneol has a pungent fragrance that spreads everywhere, so that the wind does not stay inside and leads the fire to go out. Artificial bezoar is bitter and cool, and can clear the heart, resolve phlegm, open the mind, and wake up the mind. The three medicines are used together, and the effect is remarkable.

[0004] The Chinese earthworm is the dried body of the female Chinese earthworm or Chinese earthworm of the family Blattidae. After being caught, it is put into boiling water and scalded to death, and then dried in the sun or in an oven. It has a fishy smell and a slightly salty taste. The Chinese earthworm likes to eat bran, rice bran, cornmeal, broken grains, soybean meal, miscellaneous fish, meat, various grass and vegetable leaves, melon and fruit peels, chicken, cow dung and other coarse materials, and lives in dark, humid, humus-rich loose soil for a long time. The unique ecological habits make the Chinese earthworm have a strong "fishy smell". This fishy smell makes people feel nauseous and difficult to swallow, and it can't be dissipated for a long time. Therefore, the Chinese earthworm is the main source of the fishy smell of the finished product of Xizhiluoda Capsule, which seriously affects the taste of the medicine.

[0005] Therefore, covering up the unpleasant smell of earthworms and improving the compliance of users with medication are issues that need to be urgently addressed. Summary of the invention

[0006] In view of this, the present invention aims to provide a preparation method of Xizhiluoda Capsules to solve the problem that the Xizhiluoda Capsules have a bad taste and affect patients' taking the medicine.

[0007] In order to solve the above technical problems, the technical solution adopted by the present invention is:

[0008] A method for preparing Xizhiluoda capsules comprises the following steps:

[0009] Step 1, weighing the raw Chinese medicinal materials of the prescribed amount;

[0010] Step 2, crushing the Gastrodia elata into fine powder, then mixing it with borneol and artificial bezoar, grinding it into fine powder, sieving it, mixing it evenly and setting it aside;

[0011] Step 3, extracting Chuanxiong with ethanol by refluxing for 2 to 3 times, filtering and combining the filtrates, and recovering the ethanol to obtain a Chuanxiong extract;

[0012] Step 4, mixing Siegesbeckia sibiricum, Hirudo, Pinellia ternata, Gentiana macrophylla, Panax notoginseng, Carthamus tinctorius, Semen persicae, Salvia miltiorrhiza, and Arisaema cinerea, adding water to boil, filtering after boiling, and combining the filtrate;

[0013] Step 5, soaking musk and earthworm in water for 1 to 2 hours, and then subjecting them to microwave radiation treatment, separating the filter residue and the filtrate after microwave radiation, and drying and crushing the filter residue into fine powder;

[0014] Step six, combining the Chuanxiong extract of step three, the filtrate of step four and the filtrate of step five, concentrating under reduced pressure to a thick paste with a relative density of 1.30 to 1.40, vacuum drying, crushing the obtained dry matter into fine powder, and then mixing it evenly with the fine powder in step two and the fine powder in step five, and preparing it into capsules with a pharmaceutically acceptable carrier or excipient.

[0015] Furthermore, the prescription composition includes the following raw Chinese medicinal materials by weight: 60-1000 parts of Siegesbeckia, 25-400 parts of Leech, 30-500 parts of Pinellia, 20-300 parts of Gentiana macrophylla, 25-400 parts of Gastrodia elata, 15-240 parts of Eupolyphaga sinensis, 20-350 parts of Panax notoginseng, 9-150 parts of Chuanxiong, 20-300 parts of Carthamus tinctorius, 3-50 parts of Borneolum, 15-245 parts of peach kernel, 1.6-25 parts of Musk, 30-250 parts of Salvia miltiorrhiza, 4-75 parts of artificial bezoar, and 30-250 parts of Arisaema cinerea.

[0016] Furthermore, in the step 5, the amount of water used for soaking is 1 to 2 times the amount of the raw medicinal materials of musk and earthworm.

[0017] Furthermore, in the step five, the intensity of microwave radiation is 2000-3000 MHz, and the time of microwave radiation is 20-30 min.

[0018] Furthermore, in the step three, the Chuanxiong is extracted by reflux with an ethanol aqueous solution having a volume concentration of 50 to 80%.

[0019] Furthermore, in step three, the extraction temperature is 40-80° C., and each extraction lasts 2-4 hours.

[0020] Furthermore, in the step three, the amount of the ethanol aqueous solution is 5 to 18 times the amount of the raw drug of Chuanxiong.

[0021] Furthermore, in step 4, water is added and boiled for 2 to 3 times, each time for 2 to 4 hours.

[0022] Furthermore, in the step six, the filtrate of step four and the filtrate of step five are combined and concentrated under reduced pressure to a thick paste with a relative density of 1.10 to 1.20, and 0.2 to 0.3 times the weight of microcrystalline cellulose is added to the thick paste while stirring and continuing to stir evenly; the Chuanxiong extract of step three is concentrated under reduced pressure to a thick paste with a relative density of 1.10 to 1.20, and 0.2 to 0.3 times the weight of microcrystalline cellulose is added to the thick paste while stirring and continuing to stir evenly; the two parts of the thick paste with microcrystalline cellulose added are mixed evenly, vacuum dried, and the obtained dry matter is crushed into fine powder, which is then mixed evenly with the fine powder in step two and the fine powder in step five, and prepared into capsules with a pharmaceutically acceptable carrier or excipient.

[0023] Compared with the prior art, the preparation method of Xizhiluoda capsules of the present invention has the following advantages:

[0024] (1) Musk and Chinese earthworm are processed together, and the special aroma of musk is used to cover the bad smell of Chinese earthworm, effectively reducing the fishy smell of Chinese earthworm, and emitting the soft fragrance of musk, thereby improving the compliance of users to take the medicine;

[0025] (2) It can maximize the extraction rate of effective ingredients in raw Chinese medicinal materials, thereby better exerting their efficacy. DETAILED DESCRIPTION

[0026] The present invention will be further described below in conjunction with specific embodiments. It should be noted that the data in the following experimental examples are obtained by the inventor through a large number of experiments. Due to space limitations, only a part of them is shown in the specification, and those of ordinary skill in the art can understand and implement the present invention under these data. These embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these changes or modifications also fall within the scope protected by the present application.

[0027] The invention provides a preparation method of Xizhiluoda capsules. The prescription composition comprises the following raw Chinese medicinal materials by weight: 60-1000 parts of Siegesbeckia sibiricum, 25-400 parts of leeches, 30-500 parts of ginger pinellia tuber, 20-300 parts of gentiana macrophylla, 25-400 parts of gastrodia elata, 15-240 parts of earthworm, 20-350 parts of notoginseng, 9-150 parts of chuanxiong, 20-300 parts of safflower, 3-50 parts of borneol, 15-245 parts of peach kernel, 1.6-25 parts of musk, 30-250 parts of salvia miltiorrhiza, 4-75 parts of artificial bezoar, and 30-250 parts of arisaema cinerea.

[0028] The preparation method comprises the following steps:

[0029] Step 1, weighing the raw Chinese medicinal materials of the prescribed amount;

[0030] Step 2, crushing the Gastrodia elata into fine powder, then mixing it with borneol and artificial bezoar, grinding it into fine powder, sieving it, mixing it evenly and setting it aside;

[0031] Step 3, extracting Chuanxiong with ethanol by refluxing for 2 to 3 times, filtering and combining the filtrates, and recovering the ethanol to obtain a Chuanxiong extract;

[0032] In step 3, chuanxiong is extracted by refluxing with an ethanol aqueous solution having a volume concentration of 50 to 80%.

[0033] In step 3, the extraction temperature is 40-80° C., and each extraction lasts 2-4 hours.

[0034] In step 3, the amount of ethanol aqueous solution used is 5 to 18 times the amount of Chuanxiong crude drug.

[0035] Step 4, mixing Siegesbeckia sibiricum, Hirudo, Pinellia ternata, Gentiana macrophylla, Panax notoginseng, Carthamus tinctorius, Semen persicae, Salvia miltiorrhiza, and Arisaema cinerea, adding water to boil, filtering after boiling, and combining the filtrate;

[0036] In step 4, add water and boil 2 to 3 times, each time for 2 to 4 hours.

[0037] Step 5, soaking musk and earthworm in water for 1 to 2 hours, and then subjecting them to microwave radiation treatment, separating the filter residue and the filtrate after microwave radiation, and drying and crushing the filter residue into fine powder;

[0038] In step 5, the amount of water used for soaking is 1 to 2 times the amount of the raw medicinal materials of musk and earthworm, the intensity of microwave radiation is 2000 to 3000 MHz, and the time of microwave radiation is 20 to 30 minutes.

[0039] Step six, combining the Chuanxiong extract of step three, the filtrate of step four and the filtrate of step five, concentrating under reduced pressure to a thick paste with a relative density of 1.30 to 1.40, vacuum drying, crushing the obtained dry matter into fine powder, and then mixing it evenly with the fine powder in step two and the fine powder in step five, and preparing it into capsules with a pharmaceutically acceptable carrier or excipient.

[0040] Example 1

[0041] The prescription consists of: 1000 parts of Siegesbeckia, 400 parts of Leech, 500 parts of Pinellia, 300 parts of Gentiana macrophylla, 400 parts of Gastrodia elata, 240 parts of Eupolyphaga sinensis, 350 parts of Panax notoginseng, 150 parts of Ligusticum chuanxiong, 300 parts of Carthamus tinctorius, 50 parts of Borneolum, 245 parts of Peach Kernel, 25 parts of Musk, 250 parts of Salvia miltiorrhiza, 75 parts of artificial Bezoar, and 250 parts of Arisaema cinerea.

[0042] Step 1, weigh the raw Chinese medicinal materials according to the above amount;

[0043] Step 2, crushing the Gastrodia elata into fine powder, then mixing it with borneol and artificial bezoar, grinding it into fine powder, sieving it, mixing it evenly and setting it aside;

[0044] Step 3, placing Chuanxiong in a reflux extraction device, adding 70% ethanol aqueous solution by volume for reflux extraction twice, the amount of ethanol aqueous solution used is 10 times the amount of Chuanxiong crude drug, the extraction temperature is 80°C, the extraction time is 2h and 1.5h respectively, filtering after each extraction, combining the filtrate, recovering ethanol, and obtaining Chuanxiong extract;

[0045] Step 4: mix Siegesbeckia sibiricum, Hirudo, Pinellia ternata, Gentiana macrophylla, Panax notoginseng, Safflower, Semen persicae, Salvia miltiorrhiza, and Arisaema cinerea, add water and boil twice, the time being 2 hours and 2 hours respectively, filter after each boiling, and combine the filtrate;

[0046] Step 5, soaking musk and earthworm in water for 1 hour, and then subjecting to microwave radiation treatment, wherein the amount of water used for soaking is 1 times the amount of the musk and earthworm raw drugs, the intensity of microwave radiation is 2000 MHz, and the microwave radiation time is 20 minutes. After microwave radiation, the filter residue and the filtrate are separated, and the filter residue is dried and crushed into fine powder;

[0047] Step six, combining the Chuanxiong extract of step three, the filtrate of step four and the filtrate of step five, concentrating under reduced pressure to a thick paste with a relative density of 1.30 to 1.40, and vacuum drying the obtained dried product into fine powder, which is then evenly mixed with the fine powder in step two and the fine powder in step five, and loaded into a hard capsule shell to prepare the Xizhiluoda capsule of the present invention.

[0048] Example 2

[0049] The prescription consists of: 1000 parts of Siegesbeckia, 400 parts of Leech, 500 parts of Pinellia, 300 parts of Gentiana macrophylla, 400 parts of Gastrodia elata, 240 parts of Eupolyphaga sinensis, 350 parts of Panax notoginseng, 150 parts of Ligusticum chuanxiong, 300 parts of Carthamus tinctorius, 50 parts of Borneolum, 245 parts of Peach Kernel, 25 parts of Musk, 250 parts of Salvia miltiorrhiza, 75 parts of artificial Bezoar, and 250 parts of Arisaema cinerea.

[0050] Step 1, weigh the raw Chinese medicinal materials according to the above amount;

[0051] Step 2, crushing the Gastrodia elata into fine powder, then mixing it with borneol and artificial bezoar, grinding it into fine powder, sieving it, mixing it evenly and setting it aside;

[0052] Step 3, placing Chuanxiong in a reflux extraction device, adding 80% ethanol aqueous solution by volume for reflux extraction 3 times, the amount of ethanol aqueous solution used is 5 times the amount of Chuanxiong crude drug, the extraction temperature is 40°C, the extraction time is 2h and 4h respectively, filtering after each extraction, combining the filtrate, recovering ethanol, and obtaining Chuanxiong extract;

[0053] Step 4: mix Siegesbeckia sibiricum, Hirudo, Pinellia ternata, Gentiana macrophylla, Panax notoginseng, Safflower, Semen persicae, Salvia miltiorrhiza, and Arisaema cinerea, add water and boil twice, the time being 2 hours and 3 hours respectively, filter after each boiling, and combine the filtrate;

[0054] Step 5, soaking musk and earthworm in water for 2 hours, and then subjecting to microwave radiation treatment, wherein the amount of water used for soaking is twice the amount of the musk and earthworm raw drugs, the intensity of microwave radiation is 3000 MHz, and the microwave radiation time is 30 minutes. After microwave radiation, the filter residue and the filtrate are separated, and the filter residue is dried and crushed into fine powder;

[0055] Step six, combining the Chuanxiong extract of step three, the filtrate of step four and the filtrate of step five, concentrating under reduced pressure to a thick paste with a relative density of 1.30 to 1.40, and vacuum drying the obtained dried product into fine powder, which is then evenly mixed with the fine powder in step two and the fine powder in step five, and loaded into a hard capsule shell to prepare the Xizhiluoda capsule of the present invention.

[0056] Example 3

[0057] The prescription consists of: 1000 parts of Siegesbeckia, 400 parts of Leech, 500 parts of Pinellia, 300 parts of Gentiana macrophylla, 400 parts of Gastrodia elata, 240 parts of Eupolyphaga sinensis, 350 parts of Panax notoginseng, 150 parts of Ligusticum chuanxiong, 300 parts of Carthamus tinctorius, 50 parts of Borneolum, 245 parts of Peach Kernel, 25 parts of Musk, 250 parts of Salvia miltiorrhiza, 75 parts of artificial Bezoar, and 250 parts of Arisaema cinerea.

[0058] Step 1, weigh the raw Chinese medicinal materials according to the above amount;

[0059] Step 2: Grind the Gastrodia elata, borneol and artificial bezoar into fine powder, add 5 times the amount of water, heat at 40° C. for 3 h, and then put them into a freeze dryer for freeze drying. After freeze drying, ultrafine grinding is performed at -20° C. to obtain fine powder;

[0060] Step 3, placing Chuanxiong in a reflux extraction device, adding 70% ethanol aqueous solution by volume for reflux extraction twice, the amount of ethanol aqueous solution used is 10 times the amount of Chuanxiong crude drug, the extraction temperature is 80°C, the extraction time is 2h and 1.5h respectively, filtering after each extraction, combining the filtrate, recovering ethanol, and obtaining Chuanxiong extract;

[0061] Step 4: mix Siegesbeckia sibiricum, Hirudo, Pinellia ternata, Gentiana macrophylla, Panax notoginseng, Safflower, Semen persicae, Salvia miltiorrhiza, and Arisaema cinerea, add water and boil twice, the time being 2 hours and 2 hours respectively, filter after each boiling, and combine the filtrate;

[0062] Step 5, soaking musk and earthworm in water for 1 hour, and then subjecting to microwave radiation treatment, wherein the amount of water used for soaking is 1 times the amount of the musk and earthworm raw drugs, the intensity of microwave radiation is 2000 MHz, and the microwave radiation time is 20 minutes. After microwave radiation, the filter residue and the filtrate are separated, and the filter residue is dried and crushed into fine powder;

[0063] Step six, combining the Chuanxiong extract of step three, the filtrate of step four and the filtrate of step five, concentrating under reduced pressure to a thick paste with a relative density of 1.30 to 1.40, and vacuum drying the obtained dried product into fine powder, which is then evenly mixed with the fine powder in step two and the fine powder in step five, and loaded into a hard capsule shell to prepare the Xizhiluoda capsule of the present invention.

[0064] Example 4

[0065] The prescription consists of: 1000 parts of Siegesbeckia, 400 parts of Leech, 500 parts of Pinellia, 300 parts of Gentiana macrophylla, 400 parts of Gastrodia elata, 240 parts of Eupolyphaga sinensis, 350 parts of Panax notoginseng, 150 parts of Ligusticum chuanxiong, 300 parts of Carthamus tinctorius, 50 parts of Borneolum, 245 parts of Peach Kernel, 25 parts of Musk, 250 parts of Salvia miltiorrhiza, 75 parts of artificial Bezoar, and 250 parts of Arisaema cinerea.

[0066] Step 1, weigh the raw Chinese medicinal materials according to the above amount;

[0067] Step 2: Grind the Gastrodia elata, borneol and artificial bezoar into fine powder, add 5 times the amount of water, heat at 40° C. for 1 hour, and then put them into a freeze dryer for freeze drying. After freeze drying, ultrafine grinding is performed at -20° C. to obtain fine powder;

[0068] Step 3, placing Chuanxiong in a reflux extraction device, adding 70% ethanol aqueous solution by volume for reflux extraction twice, the amount of ethanol aqueous solution used is 10 times the amount of Chuanxiong crude drug, the extraction temperature is 80°C, the extraction time is 2h and 1.5h respectively, filtering after each extraction, combining the filtrate, recovering ethanol, and obtaining Chuanxiong extract;

[0069] Step 4: mix Siegesbeckia sibiricum, Hirudo, Pinellia ternata, Gentiana macrophylla, Panax notoginseng, Safflower, Semen persicae, Salvia miltiorrhiza, and Arisaema cinerea, add water and boil twice, the time being 2 hours and 2 hours respectively, filter after each boiling, and combine the filtrate;

[0070] Step 5, soaking musk and earthworm in water for 1 hour, and then subjecting to microwave radiation treatment, wherein the amount of water used for soaking is 1 times the amount of the musk and earthworm raw drugs, the intensity of microwave radiation is 2000 MHz, and the microwave radiation time is 20 minutes. After microwave radiation, the filter residue and the filtrate are separated, and the filter residue is dried and crushed into fine powder;

[0071] Step six, combining the filtrate of step four and the filtrate of step five, concentrating under reduced pressure to a thick paste with a relative density of 1.10 to 1.20, adding 0.2 times the weight of microcrystalline cellulose to the thick paste while stirring until it is evenly mixed; concentrating the Chuanxiong extract of step three under reduced pressure to a thick paste with a relative density of 1.10 to 1.20, adding 0.2 times the weight of microcrystalline cellulose to the thick paste while stirring until it is evenly mixed; mixing the two parts of the thick paste with microcrystalline cellulose evenly, after vacuum drying, crushing the obtained dry matter into fine powder, and then mixing it evenly with the fine powder in step two and the fine powder in step five, filling it into a hard capsule shell to prepare the Xizhiluoda Capsule of the present invention.

[0072] Example 5

[0073] The prescription consists of: 1000 parts of Siegesbeckia, 400 parts of Leech, 500 parts of Pinellia, 300 parts of Gentiana macrophylla, 400 parts of Gastrodia elata, 240 parts of Eupolyphaga sinensis, 350 parts of Panax notoginseng, 150 parts of Ligusticum chuanxiong, 300 parts of Carthamus tinctorius, 50 parts of Borneolum, 245 parts of Peach Kernel, 25 parts of Musk, 250 parts of Salvia miltiorrhiza, 75 parts of artificial Bezoar, and 250 parts of Arisaema cinerea.

[0074] Step 1, weigh the raw Chinese medicinal materials according to the above amount;

[0075] Step 2: Grind the Gastrodia elata, borneol and artificial bezoar into fine powder, add 10 times the amount of water, heat at 50° C. for 1 hour, and then put them into a freeze dryer for freeze drying. After freeze drying, ultrafine grinding is performed at -10° C. to obtain fine powder;

[0076] Step 3, placing Chuanxiong in a reflux extraction device, adding 70% ethanol aqueous solution by volume for reflux extraction twice, the amount of ethanol aqueous solution used is 10 times the amount of Chuanxiong crude drug, the extraction temperature is 80°C, the extraction time is 2h and 1.5h respectively, filtering after each extraction, combining the filtrate, recovering ethanol, and obtaining Chuanxiong extract;

[0077] Step 4: mix Siegesbeckia sibiricum, Hirudo, Pinellia ternata, Gentiana macrophylla, Panax notoginseng, Safflower, Semen persicae, Salvia miltiorrhiza, and Arisaema cinerea, add water and boil twice, the time being 2 hours and 2 hours respectively, filter after each boiling, and combine the filtrate;

[0078] Step 5, soaking musk and earthworm in water for 1 hour, and then subjecting to microwave radiation treatment, wherein the amount of water used for soaking is 1 times the amount of the musk and earthworm raw drugs, the intensity of microwave radiation is 2000 MHz, and the microwave radiation time is 20 minutes. After microwave radiation, the filter residue and the filtrate are separated, and the filter residue is dried and crushed into fine powder;

[0079] Step six, combining the filtrate of step four and the filtrate of step five, concentrating under reduced pressure to a thick paste with a relative density of 1.10 to 1.20, adding 0.3 times the weight of microcrystalline cellulose to the thick paste while stirring until it is evenly mixed; concentrating the Chuanxiong extract of step three under reduced pressure to a thick paste with a relative density of 1.10 to 1.20, adding 0.3 times the weight of microcrystalline cellulose to the thick paste while stirring until it is evenly mixed; mixing the two parts of the thick paste with microcrystalline cellulose evenly, after vacuum drying, crushing the obtained dry matter into fine powder, and then mixing it evenly with the fine powder in step two and the fine powder in step five, filling it into a hard capsule shell to prepare the Xizhiluoda Capsule of the present invention.

[0080] Example 6

[0081] The prescription consists of: 60 parts of Siegesbeckia herb, 25 parts of Leech, 30 parts of Pinellia ternata, 20 parts of Gentiana macrophylla, 25 parts of Gastrodia elata, 15 parts of Eupolyphaga sinensis, 20 parts of Panax notoginseng, 9 parts of Ligusticum chuanxiong, 20 parts of Carthamus tinctorius, 3 parts of Borneolum, 15 parts of Peach Kernel, 1.6 parts of Musk, 30 parts of Salvia miltiorrhiza, 4 parts of artificial Bezoar, and 30 parts of Arisaema cinerea.

[0082] Step 1, weigh the raw Chinese medicinal materials according to the above amount;

[0083] Step 2: Grind the Gastrodia elata, Borneol and artificial bezoar into fine powder, add 8 times the amount of water, heat at 50° C. for 2 h, and then put them into a freeze dryer for freeze drying. After freeze drying, ultrafine grinding is performed at -10° C. to obtain fine powder;

[0084] Step 3, placing Chuanxiong in a reflux extraction device, adding 50% ethanol aqueous solution by volume for reflux extraction twice, the amount of ethanol aqueous solution used is 10 times the amount of Chuanxiong crude drug, the extraction temperature is 60°C, the extraction time is 2h and 1.5h respectively, filtering after each extraction, combining the filtrate, recovering ethanol, and obtaining Chuanxiong extract;

[0085] Step 4: mix Siegesbeckia sibiricum, Hirudo, Pinellia ternata, Gentiana macrophylla, Panax notoginseng, Safflower, Semen persicae, Salvia miltiorrhiza, and Arisaema cinerea, add water and boil for 3 times, the time being 2h, 2h and 4h respectively, filter after each boiling, and combine the filtrate;

[0086] Step 5, soaking musk and earthworm in water for 1 hour, and then subjecting to microwave radiation treatment, wherein the amount of water used for soaking is 1 times the amount of the musk and earthworm raw drugs, the intensity of microwave radiation is 2000 MHz, and the microwave radiation time is 20 minutes. After microwave radiation, the filter residue and the filtrate are separated, and the filter residue is dried and crushed into fine powder;

[0087] Step six, combining the filtrate of step four and the filtrate of step five, concentrating under reduced pressure to a thick paste with a relative density of 1.10 to 1.20, adding 0.3 times the weight of microcrystalline cellulose to the thick paste while stirring until it is evenly mixed; concentrating the Chuanxiong extract of step three under reduced pressure to a thick paste with a relative density of 1.10 to 1.20, adding 0.3 times the weight of microcrystalline cellulose to the thick paste while stirring until it is evenly mixed; mixing the two parts of the thick paste with microcrystalline cellulose evenly, after vacuum drying, crushing the obtained dry matter into fine powder, and then mixing it evenly with the fine powder in step two and the fine powder in step five, filling it into a hard capsule shell to prepare the Xizhiluoda Capsule of the present invention.

[0088] Example 7

[0089] The prescription consists of: 470 parts of Siegesbeckia herb, 188 parts of Leech, 235 parts of Pinellia ternata, 140 parts of Gentiana macrophylla, 188 parts of Gastrodia elata, 112 parts of Eupolyphaga sinensis, 165 parts of Panax notoginseng, 70 parts of Ligusticum chuanxiong, 140 parts of Carthamus tinctorius, 24 parts of Borneol, 115 parts of Peach Kernel, 11.7 parts of Musk, 110 parts of Salvia miltiorrhiza, 35 parts of artificial Bezoar, and 110 parts of Arisaema consanguineum.

[0090] Step 1, weigh the raw Chinese medicinal materials according to the above amount;

[0091] Step 2: Grind the Gastrodia elata, borneol and artificial bezoar into fine powder, add 8 times the amount of water, heat at 45° C. for 3 hours, and then put them into a freeze dryer for freeze drying. After freeze drying, ultrafine grinding is performed at -10° C. to obtain fine powder;

[0092] Step 3, placing Chuanxiong in a reflux extraction device, adding 80% ethanol aqueous solution by volume for reflux extraction 3 times, the amount of ethanol aqueous solution used is 18 times the amount of Chuanxiong crude drug, the extraction temperature is 40°C, the extraction time is 2h, 1.5h and 4h respectively, filtering after each extraction, combining the filtrate, recovering ethanol, and obtaining Chuanxiong extract;

[0093] Step 4: mix Siegesbeckia sibiricum, Hirudo, Pinellia ternata, Gentiana macrophylla, Panax notoginseng, Safflower, Semen persicae, Salvia miltiorrhiza, and Arisaema cinerea, add water and boil for 3 times, the time being 2h, 2h and 4h respectively, filter after each boiling, and combine the filtrate;

[0094] Step 5, soaking musk and earthworm in water for 1 hour, and then subjecting to microwave radiation treatment, wherein the amount of water used for soaking is 1 times the amount of the musk and earthworm raw drugs, the intensity of microwave radiation is 2000 MHz, and the microwave radiation time is 20 minutes. After microwave radiation, the filter residue and the filtrate are separated, and the filter residue is dried and crushed into fine powder;

[0095] Step six, combining the filtrate of step four and the filtrate of step five, concentrating under reduced pressure to a thick paste with a relative density of 1.10 to 1.20, adding 0.3 times the weight of microcrystalline cellulose to the thick paste while stirring until it is evenly mixed; concentrating the Chuanxiong extract of step three under reduced pressure to a thick paste with a relative density of 1.10 to 1.20, adding 0.3 times the weight of microcrystalline cellulose to the thick paste while stirring until it is evenly mixed; mixing the two parts of the thick paste with microcrystalline cellulose evenly, after vacuum drying, crushing the obtained dry matter into fine powder, and then mixing it evenly with the fine powder in step two and the fine powder in step five, filling it into a hard capsule shell to prepare the Xizhiluoda Capsule of the present invention.

[0096] Compared with Examples 1 to 2, Examples 3 to 7 further improve step 2, and the specific operations are as follows: in step 2, Gastrodia elata, borneol, and artificial bezoar are ground into fine powder, water is added, heated at 40 to 50° C. for 1 to 3 hours, and then sent to a freeze dryer for freeze drying. After freeze drying, low-temperature ultrafine grinding is performed to obtain fine powder.

[0097] Furthermore, the amount of water added is 5 to 10 times the amount of Gastrodia elata, Borneol, and artificial bezoar. The temperature of low-temperature crushing is -20 to -10°C. The parameters of freeze drying can be set according to the amount of raw medicine and the experience of technicians in this field. Specifically, the parameters of freeze drying are as follows: freezing: temperature -40 to -30°C, setting time 30 to 50min, duration 2 to 3h; drying: first stage, -20°C, 0.1mbar, setting time: 50 to 90min, duration 3 to 5h; second stage, 25 to 35°C, 0.1mbar, setting time: 40 to 60min, duration 1 to 1.5h.

[0098] Comparative Example 1

[0099] The prescription composition and preparation method of Comparative Example 1 are the same as those of Example 1 in CN1284589C.

[0100] Comparative Example 2

[0101] The prescription consists of: 1000 parts of Siegesbeckia, 400 parts of Leech, 500 parts of Pinellia, 300 parts of Gentiana macrophylla, 400 parts of Gastrodia elata, 240 parts of Eupolyphaga sinensis, 350 parts of Panax notoginseng, 150 parts of Ligusticum chuanxiong, 300 parts of Carthamus tinctorius, 50 parts of Borneolum, 245 parts of Peach Kernel, 25 parts of Musk, 250 parts of Salvia miltiorrhiza, 75 parts of artificial Bezoar, and 250 parts of Arisaema cinerea.

[0102] Step 1, weigh the raw Chinese medicinal materials according to the above amount;

[0103] Step 2: Grind the Gastrodia elata, borneol and artificial bezoar into fine powder, add 5 times the amount of water, heat at 40° C. for 1 hour, and then put them into a freeze dryer for freeze drying. After freeze drying, ultrafine grinding is performed at -20° C. to obtain fine powder;

[0104] Step 3, placing Chuanxiong in a reflux extraction device, adding 70% ethanol aqueous solution by volume for reflux extraction twice, the amount of ethanol aqueous solution used is 10 times the amount of Chuanxiong crude drug, the extraction temperature is 80°C, the extraction time is 2h and 1.5h respectively, filtering after each extraction, combining the filtrate, recovering ethanol, and obtaining Chuanxiong extract;

[0105] Step 4: mix Siegesbeckia sibiricum, Hirudo, Pinellia ternata, Gentiana macrophylla, Panax notoginseng, Safflower, Semen persicae, Salvia miltiorrhiza, and Arisaema cinerea, add water and boil twice, the time being 2 hours and 2 hours respectively, filter after each boiling, and combine the filtrate;

[0106] Step 5, soaking musk and earthworm in water for 1 hour, and then subjecting to microwave radiation treatment, wherein the amount of water used for soaking is 1 times the amount of the musk and earthworm raw drugs, the intensity of microwave radiation is 2000 MHz, and the microwave radiation time is 20 minutes. After microwave radiation, the filter residue and the filtrate are separated, and the filter residue is dried and crushed into fine powder;

[0107] Step six, combining the Chuanxiong extract of step three, the filtrate of step four and the filtrate of step five, concentrating under reduced pressure to a thick paste with a relative density of 1.30 to 1.40, adding 0.2 times the weight of microcrystalline cellulose to the thick paste while stirring until it is evenly stirred, and after vacuum drying, crushing the obtained dry matter into fine powder, and then mixing it evenly with the fine powder in step two and the fine powder in step five, and filling it into a hard capsule shell to prepare the Xizhiluoda capsule of the present invention.

[0108] The Xizhiluoda capsule prepared in the present application contains Chinese earthworms, which have a fishy smell and are difficult to swallow. Therefore, the present invention attempts to cover the smell of Chinese earthworms. By changing the order of adding the raw Chinese medicinal materials in the original preparation method, musk and Chinese earthworms are processed together, and the special fragrance of musk is used to cover the bad smell of Chinese earthworms. Musk and Chinese earthworms are mixed and treated, and microwave radiation is used. Musk and Chinese earthworms are soaked in water. Under the action of microwaves, the pressure generated by the vaporization of liquid water causes the cell structure of Chinese earthworms to rupture, accelerating the dissolution of the effective ingredients of Chinese earthworms into water. In addition, the high temperature generated by the microwave action makes the fragrance of musk better stimulated and penetrates into the Chinese earthworms with ruptured cell structures, playing a role in covering the fishy smell of Chinese earthworms.

[0109] Sensory evaluation test

[0110] 50 assessors were recruited. After training and screening, 20 assessors who were healthy, had no rhinitis, normal sense of smell, and had no bad habits were selected to form an assessment team to conduct sensory evaluation on the Xizhiluoda capsules prepared in Examples 1 to 5 and Comparative Examples 1 to 2. The fishy odor evaluation adopted a 5-point system, 0 points: no fishy odor; 1 point: slightly fishy odor; 2 points: weak fishy odor; 3 points: obvious fishy odor; 4: heavy fishy odor; 5 points: extremely heavy fishy odor. Take 1 capsule of Xizhiluoda capsule prepared in Examples 1 to 5 and Comparative Examples 1 to 2 respectively and put it into an EP tube, seal it for 30 minutes, and then rest for 10 minutes after the sample evaluation is completed before evaluating the next sample. The average score is taken as the evaluation result, and the specific results are shown in Table 1.

[0111] As shown in Table 1, the Xizhiluoda capsule of Comparative Example 1 has a distinct fishy odor, which easily causes difficulty in swallowing for the user. The Xizhiluoda capsules of Examples 1 to 5 prepared by the preparation method of the present invention can reduce the score to 1, effectively reduce the fishy odor of the earthworm, and emit a soft musky fragrance, thereby improving the user's compliance with the medication.

[0112] Bilirubin content test

[0113] The bilirubin content in Xizhiluoda Capsules was determined by HPLC. The specific determination method is as follows: Wang Zhiping, Zhang Yanyan. Determination of bilirubin content in Xizhiluoda Capsules by HPLC [J]. Chinese Pharmaceutical Affairs, 2011, 025(006): 598-599, 602. The determination results are shown in Table 1.

[0114] It can be seen from Table 1 that the Xizhiluoda capsules prepared in Examples 3 to 5 and Comparative Example 2 contain more bilirubin. In Example 3, Gastrodia elata, Borneol and artificial bezoar are treated by freeze drying after heating. During the process of adding water and heating, the volume of the Chinese medicinal materials expands under the action of swelling. The solvent is removed by freeze drying, so that the soluble components of the fine powder of the Chinese medicinal materials form a loose and porous hole structure, which is conducive to the extraction of effective ingredients, thereby improving the efficacy. In Examples 4 and 5, microcrystalline cellulose is added in batches to the thick paste obtained in step six. Due to its high viscosity, the thick paste is prone to violent boiling during the drying process, resulting in the loss of effective ingredients. The addition of microcrystalline cellulose can reduce the viscosity of the paste, reduce the loss of effective ingredients during the drying process, and is conducive to the loose structure of the thick paste, which is convenient for the extraction of effective ingredients. Therefore, compared with Examples 1 to 3, Examples 4 to 5 can extract more bilirubin.

[0115] But the timing of adding microcrystalline cellulose is also very important. Although microcrystalline cellulose is also added in Comparative Example 2, the content of bilirubin is not as good as that in Examples 4 to 5. In Comparative Example 2, microcrystalline cellulose is directly added to the thick paste formed after the chuanxiong extract of step three, the filtrate of step four and the filtrate of step five are concentrated. Under the action of stirring, microcrystalline cellulose is more likely to wrap the thick paste of step four and the thick paste of step five containing a small amount of water, and less participation and the effect of the thick paste of step three are not conducive to reducing the viscosity of the thick paste of step three and forming a loose structure. In Examples 4 to 5, microcrystalline cellulose is added separately, one part is mixed with the thick paste of step three and embedded therein to reduce viscosity and increase looseness, and the other part is mixed with the thick paste of step four and the thick paste of step five and plays a role, which is conducive to better play the role of microcrystalline cellulose in reducing the viscosity of the paste.

[0116] Table 1

[0117]

[0118]

[0119] Effects on experimental thrombosis

[0120] Experimental animals: Wistar rats 240±SD20g, half male and half female.

[0121] For specific test methods, please refer to CN1284589C Test Example 2.

[0122] Effects of arteriovenous bypass on experimental thrombosis in rats

[0123] 70 rats were randomly divided into 7 groups. Except for the control group, the other groups were continuously administered for 6 days, and the dosage was 3.6g / kg. One hour after the last administration, the rats were anesthetized with 1% sodium pentobarbital according to the arteriovenous bypass blood circulation experiment method, and heparin-filled saline was taken, and a siliconized plastic tube with a 4.5cm surgical silk thread was placed inside. One end of the tube was inserted into the right common carotid artery and the other end was inserted into the left common jugular vein. The blood flow was opened for 15 minutes, and platelet plugs were formed on the silk thread. The silk thread was taken out and weighed. The results are shown in Table 2.

[0124] Effects on in vitro thrombosis

[0125] 70 rats were randomly divided into 7 groups. Except for the control group, the other groups were continuously administered for 6 days, and the dosage was 3.6g / kg. 1 hour after the last administration, 1.8mL of blood was collected from the abdominal aorta of the rats, placed in a siliconized rubber tube, and rotated at 3.7n / min for 15min at 37℃ using an XSN-RⅡ in vitro thrombosis platelet adhesion dual-purpose instrument to form platelet thrombus. The thrombus length and dry weight were measured. The results are shown in Table 2.

[0126] Table 2

[0127]

[0128]

[0129] Note: *P<0.05 compared with the control group, **P<0.01 compared with the control group.

[0130] As shown in Table 2, the Xizhiluoda capsules of Examples 1 to 5 prepared by the preparation method of the present invention have a significant inhibitory effect on experimental thrombosis of dynamic and static bypass circulation, and have a significant inhibitory effect on the formation of thrombi in vitro. And the inhibitory effect of Examples 4 to 5 is the best. The possible reason is that the preparation method of Examples 4-5 can extract more effective ingredients, so that the finished Xizhiluoda capsules can better exert their efficacy.

[0131] Clinical efficacy trials

[0132] The specific test method is referred to in Test Example 5 of CN1284589C, which will not be described here due to space limitations. The drug group of the present invention selected Xizhiluoda Capsule of Example 5. The results of the comparison of clinical efficacy between the two groups are shown in Table 3, n=300.

[0133] Table 3

[0134] Recovery rate (%) Efficiency(%) Effectiveness (%) Inefficiency (%) Total Effectiveness Example 5 30.20 50.61 17.32 1.87 98.13 Comparative Example 1 20.31 53.78 22.99 2.92 97.08

[0135] It can be seen from Table 3 that the total effective rate of Example 5 of the present invention reaches 98.13%, which is higher than 97.08% of Comparative Example 1. And the cure rate of Example 5 of the present invention is 30.20%, which is higher than 20.31% of Comparative Example 1. The curative effect of Xizhiluoda Capsule prepared by the preparation method of the present invention is better than that of Comparative Example 1. The possible reason is that the present invention obtains the effective ingredients of the raw Chinese medicinal materials to the greatest extent, so that the drug can play a better role, thereby improving the efficacy.

[0136] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing Xizhiluoda capsules, characterized in that: The steps include: Step 1, weighing the raw Chinese medicinal materials of the prescribed amount; Step 2, crushing the Gastrodia elata into fine powder, then mixing it with borneol and artificial bezoar, grinding it into fine powder, sieving it, mixing it evenly and setting it aside; Step 3, extracting Chuanxiong with ethanol by refluxing for 2 to 3 times, filtering and combining the filtrates, and recovering the ethanol to obtain a Chuanxiong extract; Step 4, mixing Siegesbeckia sibiricum, Hirudo, Pinellia ternata, Gentiana macrophylla, Panax notoginseng, Carthamus tinctorius, Semen persicae, Salvia miltiorrhiza, and Arisaema cinerea, adding water to boil, filtering after boiling, and combining the filtrate; Step 5, soaking musk and earthworm in water for 1 to 2 hours, and then subjecting them to microwave radiation treatment, separating the filter residue and the filtrate after microwave radiation, and drying and crushing the filter residue into fine powder; Step six, combining the Chuanxiong extract of step three, the filtrate of step four and the filtrate of step five, concentrating under reduced pressure to a thick paste with a relative density of 1.30 to 1.40, vacuum drying, crushing the obtained dry matter into fine powder, and then mixing it evenly with the fine powder in step two and the fine powder in step five, and preparing it into capsules with a pharmaceutically acceptable carrier or excipient.

2. The method for preparing Xizhiluoda capsule according to claim 1, characterized in that: The prescription composition includes the following raw Chinese medicinal materials by weight: 60-1000 parts of Siegesbeckia, 25-400 parts of Leech, 30-500 parts of Pinellia, 20-300 parts of Gentiana macrophylla, 25-400 parts of Gastrodia elata, 15-240 parts of Eupolyphaga sinensis, 20-350 parts of Panax notoginseng, 9-150 parts of Chuanxiong, 20-300 parts of Safflower, 3-50 parts of Borneolum, 15-245 parts of peach kernel, 1.6-25 parts of Musk, 30-250 parts of Salvia miltiorrhiza, 4-75 parts of artificial bezoar, and 30-250 parts of Arisaema cinerea.

3. The method for preparing Xizhiluoda capsule according to claim 1, characterized in that: In the step 5, the amount of water used for soaking is 1 to 2 times the amount of the raw medicinal materials of musk and earthworm.

4. The method for preparing Xizhiluoda capsule according to claim 1, characterized in that: In the step 5, the intensity of microwave radiation is 2000-3000 MHz, and the time of microwave radiation is 20-30 minutes.

5. The method for preparing Xizhiluoda capsule according to claim 1, characterized in that: In the step 3, chuanxiong is extracted by refluxing with an ethanol aqueous solution having a volume concentration of 50 to 80%.

6. The method for preparing Xizhiluoda capsule according to claim 1, characterized in that: In the step 3, the extraction temperature is 40-80° C., and each extraction takes 2-4 hours.

7. The method for preparing Xizhiluoda capsule according to claim 1, characterized in that: In the step 3, the amount of the ethanol aqueous solution is 5 to 18 times the amount of the crude drug of Chuanxiong.

8. The method for preparing Xizhiluoda capsule according to claim 1, characterized in that: In the step 4, add water and boil for 2 to 3 times, each time for 2 to 4 hours.

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