Chuanxiong rhizome composition as well as preparation method and application thereof

Abstract

The invention provides a rhizoma chuanxiong composition and a preparation method and application thereof, and relates to the technical field of traditional Chinese medicine, the preparation method comprises the following steps: mixing rhizoma chuanxiong powder with water, adding a compound enzyme I, and performing enzymolysis to obtain rhizoma chuanxiong enzymatic hydrolysate; mixing the gastrodia elata powder with water, adding a compound enzyme II, and performing enzymolysis to obtain gastrodia elata enzymatic hydrolysate; inoculating the compound bacteria solution into a mixed solution of the ligusticum wallichii enzymatic hydrolysate and the gastrodia elata enzymatic hydrolysate, fermenting, performing ultraviolet sterilization, heating and extracting, filtering to take filtrate, and concentrating to obtain the large ligusticum wallichii composition; the release of effective active ingredients is accelerated, the content of polysaccharide and water-soluble protein in the gastrodia elata and the content of gastrodin are increased, so that the absorption degree of medicinal ingredients of ligusticum wallichii is improved, and the peculiar smell of the gastrodia elata can be removed; meanwhile, the ligusticum wallichii can be promoted to generate more ligustrazine in the fermentation process, and the medicine effect of the ligusticum wallichii is improved. And the fermented mixed solution is subjected to water extraction, so that active substances inside and outside the cells can be fully extracted.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicines, and in particular to a large chuanxiong rhizome composition, a preparation method and an application thereof. Background Art

[0002] Headache is a disease with chronic paroxysmal headache as the main manifestation. Western medicine believes that headache is a vascular headache and muscle tension headache. The main drugs used by Western medicine to treat this disease are: aspirin, ibuprofen, indomethacin, ergotamine preparations, etc. Although these drugs have a certain effect on headache, the use of these drugs is not only ineffective, but also has great side effects, and is not suitable for long-term use. For example, ergotamine preparations are effective vasoconstrictors, but their vasoconstrictive effect lasts for a long time, and they are not selective for cerebral blood vessels, and have a significant contraction effect on head blood vessels. Overdose can easily cause ergotamine poisoning, and the oral bioavailability is only 2%, which is easy to cause drug dependence, etc. Therefore, it is rarely used clinically at present.

[0003] Traditional Chinese medicine believes that the best Chinese medicine for treating headache and congestion headache is large Chuanxiong, and the raw materials of large Chuanxiong include Chuanxiong and Gastrodia. Because Chuanxiong has the effects of regulating blood circulation, promoting qi and removing blood stasis, modern research shows that Chuanxiong contains volatile oils, alkaloids (such as ligustrazine, etc.), phenolic substances (such as ferulic acid, etc.), as well as visfatin, vitamin A, folic acid, sterols, sucrose fatty oil, etc. Ligustrazine can inhibit the contraction of vascular smooth muscle, dilate coronary arteries, increase coronary blood flow, improve myocardial ischemia and mesenteric microcirculation, and can reduce myocardial oxygen consumption, increase brain and limb blood flow, and reduce peripheral vascular resistance; it can reduce platelet surface activity, inhibit platelet aggregation, and prevent the formation of thrombus; Gastrodia has the effects of calming the liver and suppressing yang, and removing wind and dampness. Modern research shows that Gastrodia also has the effects of reducing peripheral and coronary vascular resistance, lowering blood pressure, slowing heart rate and analgesia. The above two Chinese herbal medicines are both in the liver meridian, and their pharmacological effects complement each other, which is consistent with the conclusion of traditional Chinese medicine that headache is caused by liver deficiency and qi stagnation, and a large number of clinical trials have also confirmed the significant therapeutic effect of these two Chinese herbal medicines for the treatment of headache. In traditional Chinese medicine, large Chuanxiong is made into tablets, pills or powders. Although these types of large Chuanxiong preparations have certain therapeutic effects, they are difficult to swallow and the active ingredients in large Chuanxiong are not easily absorbed by the human body, which affects their efficacy. At present, water extraction is mostly used to extract the active ingredients in large Chuanxiong, but clinical findings show that the active ingredients in it cannot be fully extracted, which affects its efficacy.

[0004] In view of this, the present invention is proposed. Summary of the invention

[0005] One of the purposes of the present invention is to provide a method for preparing a large Chuanxiong composition, so as to solve the technical problem in the prior art that water extraction cannot fully extract the active ingredients of the Chinese medicinal materials in the large Chuanxiong preparation, thereby reducing the efficacy.

[0006] The second object of the present invention is to provide a large Chuanxiong composition.

[0007] The third object of the present invention is to provide the use of the above-mentioned large Chuanxiong composition in the preparation of a medicine for treating head wind and / or congestion type headache.

[0008] A fourth object of the present invention is to provide a medicine for treating head wind and / or congestion type headache.

[0009] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are particularly adopted:

[0010] In a first aspect, the present invention provides a method for preparing a large Chuanxiong composition, comprising the following steps:

[0011] A. Mixing Chuanxiong powder with water of 8 to 11 times the mass of the Chuanxiong powder, and then adding 2.4% to 4.7% of the mass of the Chuanxiong powder as complex enzyme I, enzymolysis to obtain Chuanxiong enzymolysis solution; mixing Gastrodia elata powder with water of 8 to 11 times the mass of the Gastrodia elata powder, and then adding 1.5% to 3.5% of the mass of the Chuanxiong powder as complex enzyme II, enzymolysis to obtain Gastrodia elata enzymolysis solution;

[0012] B. Inoculating the composite bacterial liquid into the mixed solution of Chuanxiong enzymatic hydrolyzate and Gastrodia elata enzymatic hydrolyzate at an inoculation rate of 2% to 4%, fermenting, sterilizing with ultraviolet light, heating and extracting at 100° C. for 1 to 2 hours, filtering and collecting the filtrate, and concentrating to obtain a large Chuanxiong composite;

[0013] The weight ratio of Chuanxiong and Gastrodia elata is 3:1 to 1:1;

[0014] The composite bacteria include Bacillus subtilis and Lactobacillus acidophilus;

[0015] The complex enzyme I comprises cellulase, pectinase and amylase in a mass ratio of 1:(0.9-1.1):(0.2-0.3);

[0016] The complex enzyme II comprises cellulase, pectinase and hemicellulase in a mass ratio of (1.8-2.2):(0.9-1.1):1.

[0017] Further, the fermentation conditions include shaking culture at 37°C for 24 to 48 hours;

[0018] Preferably, step B also includes a second extraction, which includes adding 6 to 9 times the total mass of water to the solid obtained after filtration, mixing, heating at 100°C for 1 to 2 hours, filtering, mixing with the filtrate of the first extraction, and concentrating to obtain a large Chuanxiong composition.

[0019] Furthermore, the preparation method of the composite bacterial liquid comprises mixing and diluting the activated cultured Bacillus subtilis seed liquid and Lactobacillus acidophilus seed liquid to obtain the composite bacterial liquid;

[0020] Preferably, the concentration of the composite bacterial solution is (2-6)×10 12 CFU / mL;

[0021] Preferably, the ratio of the number of viable bacteria of Streptococcus thermophilus to that of Bacillus subtilis in the composite bacterial liquid is 1:(1-3).

[0022] Furthermore, the dilution multiple is 50 to 150 times.

[0023] Furthermore, the conditions for the enzymatic hydrolysis include a pH of 5.0 to 7.0, a temperature of 50 to 55° C., and an enzymatic hydrolysis time of 1.5 to 2 hours.

[0024] Furthermore, the enzymatic hydrolysis also includes inactivation of the enzyme;

[0025] Preferably, the enzyme inactivation conditions include keeping the mixture at 90° C. for 30 min.

[0026] Furthermore, after the concentration, the method further includes adding 2.5 to 4 times the mass of ethanol to the concentrated solution, stirring evenly and then standing for 40 to 60 hours, taking the supernatant and adding sodium benzoate, stirring evenly, diluting, filtering and taking the filtrate to obtain a large Chuanxiong composition.

[0027] In a second aspect, the present invention provides a large Chuanxiong composition, which is prepared by the above-mentioned preparation method.

[0028] In a third aspect, the present invention provides the use of the above-mentioned Rhizoma Chuanxiong composition in the preparation of a medicine for treating headache caused by head wind or / and congestion type headache.

[0029] In a fourth aspect, the present invention provides a medicine for treating head wind and / or congestion type headache, comprising the above-mentioned large Chuanxiong composition;

[0030] Preferably, the dosage form of the drug includes oral solution, tablet, capsule, powder, pill or granule.

[0031] The invention provides a preparation method of a large Chuanxiong composition, wherein the composite enzyme is used to enzymolyze Chuanxiong and Gastrodia elata respectively, the release of effective active ingredients is accelerated, and different composite enzymes are set for different raw materials, composite enzyme I is used to enzymolyze Chuanxiong, and composite enzyme II is used to enzymolyze Gastrodia elata, so as to improve the enzymolysis efficiency; after enzymolysis, a composite bacterial liquid composed of Bacillus subtilis and Lactobacillus acidophilus is directly added for fermentation, the polysaccharide and water-soluble protein content in Gastrodia elata, and the content of gastrodin are increased, so as to improve the absorption degree of the medicinal ingredients of Chuanxiong, and the peculiar smell of Gastrodia elata can be removed; at the same time, during the fermentation process, Chuanxiong can be prompted to produce more ligustrazine, so as to improve the efficacy of Chuanxiong. The mixed solution after fermentation is then subjected to water extraction, and the active substances inside and outside the cells can be fully extracted, which solves the technical problem that the water extraction in the prior art cannot fully extract the active ingredients of the Chinese medicinal materials of large Chuanxiong preparations, and the efficacy is reduced. DETAILED DESCRIPTION

[0032] Unless otherwise defined herein, scientific and technical terms used in conjunction with the present invention shall have the meanings commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear, however, in the case of any potential ambiguity, the definitions provided herein take precedence over any dictionary or external definitions. In this application, unless otherwise stated, the use of "or" means "and / or". In addition, the use of the term "including" and other forms is non-limiting.

[0033] The methods and techniques of the present invention are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated.

[0034] In one aspect, the present invention provides a method for preparing a large Chuanxiong composition, comprising the following steps:

[0035] A. Mixing Chuanxiong powder with water of 8 to 11 times the mass of the Chuanxiong powder, and then adding 2.4% to 4.7% of the mass of the Chuanxiong powder as complex enzyme I, enzymolysis to obtain Chuanxiong enzymolysis solution; mixing Gastrodia elata powder with water of 8 to 11 times the mass of the Gastrodia elata powder, and then adding 1.5% to 3.5% of the mass of the Chuanxiong powder as complex enzyme II, enzymolysis to obtain Gastrodia elata enzymolysis solution;

[0036] B. Inoculating the composite bacterial liquid into the mixed solution of Chuanxiong enzymatic hydrolyzate and Gastrodia elata enzymatic hydrolyzate at an inoculation rate of 2% to 4%, fermenting, sterilizing with ultraviolet light, heating and extracting at 100° C. for 1 to 2 hours, filtering and collecting the filtrate, and concentrating to obtain a large Chuanxiong composite;

[0037] The weight ratio of Chuanxiong and Gastrodia elata is 3:1 to 1:1;

[0038] The composite bacteria include Bacillus subtilis and Lactobacillus acidophilus;

[0039] The complex enzyme I comprises cellulase, pectinase and amylase in a mass ratio of 1:(0.9-1.1):(0.2-0.3);

[0040] The complex enzyme II comprises cellulase, pectinase and hemicellulase in a mass ratio of (1.8-2.2):(0.9-1.1):1.

[0041] The composite enzymes are used to hydrolyze Chuanxiong and Gastrodia elata respectively, accelerating the release of effective active ingredients, and different composite enzymes are set for different raw materials, using composite enzyme I to hydrolyze Chuanxiong and composite enzyme II to hydrolyze Gastrodia elata, thereby improving the efficiency of enzymolysis; after enzymolysis, a composite bacterial liquid composed of Bacillus subtilis and Lactobacillus acidophilus is directly added for fermentation, increasing the content of polysaccharides and water-soluble proteins in Gastrodia elata, as well as the content of gastrodin, so as to improve the absorption degree of the medicinal ingredients of Chuanxiong, and remove the peculiar smell of Gastrodia elata; at the same time, during the fermentation process, Chuanxiong can be prompted to produce more ligustrazine, thereby improving the efficacy of Chuanxiong. The mixed solution after fermentation is then subjected to water extraction, which can fully extract the active substances inside and outside the cells, thereby solving the technical problem that the water extraction in the prior art cannot fully extract the active ingredients of the Chinese medicinal materials of the large Chuanxiong preparation, and the efficacy is reduced.

[0042] In some specific embodiments, the fermentation conditions include shaking culture at 37° C. for 24 to 48 hours.

[0043] In order to fully extract the effective active ingredients in the raw materials, in some specific embodiments, the step B also includes a second extraction, and the second extraction includes adding 6 to 9 times the total mass of water to the solid obtained after filtration, mixing it, heating it at 100°C for 1 to 2 hours, filtering it, mixing it with the filtrate of the first extraction, and concentrating it to obtain a large Chuanxiong composition.

[0044] In some specific embodiments, the method for preparing the composite bacterial liquid comprises mixing and diluting activated cultured Bacillus subtilis seed liquid and Lactobacillus acidophilus seed liquid to obtain the composite bacterial liquid.

[0045] The activation culture conditions can be set to culture at 35-40°C.

[0046] In some specific embodiments, the concentration of the composite bacterial solution is (2-6)×10 12 In order to further give full play to the fermentation effect of the two strains, in some specific embodiments, the ratio of the number of viable bacteria of thermophilic Streptococcus to that of Bacillus subtilis in the composite bacterial liquid is 1:(1-3).

[0047] In some specific embodiments, the enzymatic hydrolysis conditions include pH 5.0-7.0, temperature 50-55° C., and enzymatic hydrolysis for 1.5-2 h.

[0048] In some specific embodiments, the enzymatic hydrolysis further includes inactivating the enzyme;

[0049] In some specific embodiments, the enzyme inactivation conditions include keeping the temperature at 90° C. for 30 min.

[0050] The concentrated solution after water extraction and filtration will carry some water-soluble impurities, which need to be removed. In some specific embodiments, after the concentration, 2.5 to 4 times the mass of ethanol is added to the concentrated solution, stirred evenly and then allowed to stand for 40 to 60 hours, the supernatant is added with sodium benzoate and stirred evenly, diluted, filtered and the filtrate is obtained to obtain a large Chuanxiong composition. Unnecessary components are removed by precipitation, the effective components of the drug are retained, and the purity is improved.

[0051] According to another aspect of the present invention, a large Chuanxiong composition is also provided, which is prepared by the above-mentioned preparation method.

[0052] According to another aspect of the present invention, there is also provided the use of the above-mentioned Rhizoma Chuanxiong composition in the preparation of a medicine for treating headache caused by head wind or / and congestion-type headache.

[0053] According to another aspect of the present invention, a medicine for treating head wind and / or congestion type headache is provided, comprising the above-mentioned large Chuanxiong composition.

[0054] In some specific embodiments, the dosage form of the drug includes oral solution, tablet, capsule, powder, pill or granule.

[0055] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0056] Preparation of complex enzyme I: Mix cellulase, pectinase and amylase in a mass ratio of 1:1:0.3.

[0057] Preparation of complex enzyme II: Mix cellulase, pectinase and hemicellulase in a mass ratio of 2:1:1.

[0058] Bacillus subtilis seed culture medium: LB medium, peptone 10 g, yeast extract 5 g, glucose 5 g, sodium chloride 10 g, water 1000 mL, pH 7.2.

[0059] Lactobacillus acidophilus seed culture medium: MRS culture medium, maltose 20g / L, yeast extract powder FM50220g / L, soy peptone FP403 20g / L, buffer salt diammonium hydrogen citrate 2g / L, dipotassium hydrogen phosphate 2g / L, magnesium sulfate 0.58g / L, manganese sulfate 0.25g / L.

[0060] Bacillus subtilis CICC 10732 and Lactobacillus acidophilus CICC 20248 were purchased from China Industrial Microbiological Culture Collection Center.

[0061] Pretreatment of Chuanxiong and Gastrodia elata: Grind Chuanxiong and Gastrodia elata into powder respectively to obtain Chuanxiong powder and Gastrodia elata powder for later use.

[0062] Example 1

[0063] A large Chuanxiong composition, wherein the weight ratio of Chuanxiong and Gastrodia elata is 2.5:1 (total weight 1750g), is prepared according to the following steps:

[0064] 1) Mixing Chuanxiong powder with water of 9.5 times the weight of the Chuanxiong powder, adding 3% of the weight of the Chuanxiong powder compound enzyme I, adjusting the pH to 5.5, performing enzymolysis at 55° C. for 1.5 hours, and incubating at 90° C. for 30 minutes to inactivate the enzyme to obtain a Chuanxiong enzymolysis solution; mixing Gastrodia elata powder with water of 9.5 times the weight of the Gastrodia elata powder, adding 2.5% of the weight of the Gastrodia elata powder compound enzyme II, adjusting the pH to 6.0, performing enzymolysis at 55° C. for 1.5 hours, and incubating at 90° C. for 30 minutes to inactivate the enzyme to obtain a Gastrodia elata enzymolysis solution;

[0065] 2) After the enzymatic hydrolyzate of Chuanxiong and the enzymatic hydrolyzate of Gastrodia elata are mixed, a 3% composite bacterial liquid by volume is added, and the mixture is shaken and fermented at 37° C. for 36 h. After ultraviolet sterilization, the mixture is heated and extracted at 100° C. for 2 h. After filtration, the solid obtained after filtration is added with 7 times the total mass of water (i.e., the amount of water is 7 times the mass of the solid) and mixed, and then heated at 100° C. for 2 h. After filtration, the mixture is mixed with the filtrate of the first extraction and concentrated. The relative density of the concentrate is 1.23-1.24 (detected at 60° C.). 3.5 times the amount of ethanol is added to the concentrate, the mixture is stirred evenly, and then allowed to stand for 50 hours. The supernatant is added with 0.4% sodium benzoate by mass of Gastrodia elata, stirred evenly, and then diluted to 1000 mL with water. The filtrate is filtered and concentrated to obtain a large Chuanxiong composition.

[0066] The composite bacterial solution was obtained by mixing Bacillus subtilis seed solution and Lactobacillus acidophilus seed solution after activation and culture at 37°C for 16 hours and diluting them 100 times. The ratio of the number of viable bacteria of thermophilic Streptococcus to Bacillus subtilis was 1:1.57, and the concentration of the composite bacterial solution was 5.34×10 12 CFU / mL.

[0067] Example 2

[0068] A large Chuanxiong composition, wherein the weight ratio of Chuanxiong and Gastrodia elata is 2:1 (total weight 1750g), is prepared according to the following steps:

[0069] 1) Mixing Chuanxiong powder with water 11 times the weight of Chuanxiong powder, adding 4.7% of the weight of Chuanxiong powder compound enzyme I, adjusting the pH to 5.5, performing enzymolysis at 55°C for 2 hours, and incubating at 90°C for 30 minutes to inactivate the enzyme to obtain a Chuanxiong enzymolysis solution; mixing Gastrodia elata powder with water 11 times the weight of Gastrodia elata powder, adding 3.5% of the weight of Gastrodia elata powder compound enzyme II, adjusting the pH to 6.0, performing enzymolysis at 55°C for 2 hours, and incubating at 90°C for 30 minutes to inactivate the enzyme to obtain a Gastrodia elata enzymolysis solution;

[0070] 2) After the enzymatic hydrolyzate of Chuanxiong and the enzymatic hydrolyzate of Gastrodia elata are mixed, a 4% composite bacterial solution by volume is added, and the mixture is shaken and fermented at 37° C. for 24 h. After ultraviolet sterilization, the mixture is heated and extracted at 100° C. for 2 h. After filtration, the solid obtained after filtration is added with 6 times the total mass of water and mixed, and heated at 100° C. for 2 h. After filtration, the solid is mixed with the filtrate of the first extraction and concentrated. The relative density of the concentrate is 1.23-1.24 (detected at 60° C.). 2.5 times the ethanol is added to the concentrate, and the mixture is stirred evenly and allowed to stand for 40 hours. The supernatant is added with 0.4% sodium benzoate by mass of Gastrodia elata and stirred evenly, and then diluted with water to 1000 mL. The filtrate is filtered and concentrated to obtain a large Chuanxiong composition.

[0071] The composite bacterial liquid used is the same as that in Example 1.

[0072] Example 3

[0073] A large Chuanxiong composition, wherein the weight ratio of Chuanxiong and Gastrodia elata is 1:1 (total weight 1750g), is prepared according to the following steps:

[0074] 1) Mixing Chuanxiong powder with water 8 times the mass of Chuanxiong powder, adding 2.4% of the mass of complex enzyme I of Chuanxiong powder, adjusting the pH to 5.5, performing enzymolysis at 55°C for 2 hours, and incubating at 90°C for 30 minutes to inactivate the enzyme to obtain Chuanxiong enzymolysis solution; mixing Gastrodia elata powder with water 8 times the mass of Gastrodia elata powder, adding 1.5% of the mass of complex enzyme II of Gastrodia elata powder, adjusting the pH to 6.0, performing enzymolysis at 55°C for 2 hours, and incubating at 90°C for 30 minutes to inactivate the enzyme to obtain Gastrodia elata enzymolysis solution;

[0075] 2) After the enzymatic hydrolyzate of Chuanxiong and the enzymatic hydrolyzate of Gastrodia elata are mixed, a 2% composite bacterial solution by volume is added, and the mixture is shaken and fermented at 37° C. for 48 h. After ultraviolet sterilization, the mixture is heated and extracted at 100° C. for 2 h. After filtration, the solid obtained after filtration is added with 9 times the total mass of water and mixed, and heated at 100° C. for 2 h. After filtration, the solid is mixed with the filtrate of the first extraction and concentrated. The relative density of the concentrate is 1.23-1.24 (detected at 60° C.). 4 times the ethanol is added to the concentrate, and the mixture is stirred evenly and allowed to stand for 60 hours. The supernatant is added with 0.4% sodium benzoate by mass of Gastrodia elata and stirred evenly, and then diluted with water to 1000 mL. The filtrate is filtered and concentrated to obtain a large Chuanxiong composition.

[0076] The composite bacterial liquid used is the same as that in Example 1.

[0077] Comparative Example 1

[0078] The only difference from Example 1 is that in step 2), after mixing the Chuanxiong enzymatic hydrolyzate and the Gastrodia elata enzymatic hydrolyzate, the mixture is heated and extracted at 70°C for 2 hours. After filtering, the solid obtained after filtration is added with 4 times the total mass of water and mixed, and then heated at 70°C for 2 hours. After filtering, the solid is mixed with the filtrate of the first extraction and concentrated. The relative density of the concentrate is 1.23-1.24 (detected at 60°C). 3.5 times the mass of ethanol is added to the concentrate, stirred evenly and allowed to stand for 50 hours. The supernatant is added with 0.4% of the mass of Gastrodia elata sodium benzoate and stirred evenly, then diluted with water to 1000 mL, and the filtrate is filtered to obtain a large Chuanxiong composition.

[0079] Comparative Example 2

[0080] A large Chuanxiong composition, wherein the weight ratio of Chuanxiong and Gastrodia elata is 2.5:1 (total weight 1750g), is prepared according to the following steps:

[0081] 1) mixing Chuanxiong powder with water of 9.5 times the mass of the Chuanxiong powder to obtain a Chuanxiong mixed solution, and mixing Gastrodia elata powder with water of 9.5 times the mass of the Gastrodia elata powder to obtain a Gastrodia elata mixed solution;

[0082] 2) After the mixture of Chuanxiong and Gastrodia elata was mixed, a 3% composite bacterial solution by volume was added, and the mixture was shaken and fermented at 37° C. for 36 h. After ultraviolet sterilization, an equal volume of water was added and mixed, and then heated and extracted at 100° C. for 2 h. After filtering, the solid obtained after filtration was added with 7 times the total mass of water and mixed, and then heated at 100° C. for 2 h. After filtering, the solid was mixed with the filtrate of the first filtration and concentrated. The relative density of the concentrate was 1.23-1.24 (detected at 60° C.), 3.5 times the mass of ethanol was added to the concentrate, and the mixture was stirred evenly and allowed to stand for 50 hours. The supernatant was added with 0.4% sodium benzoate by mass of Gastrodia elata and stirred evenly, and then diluted with water to 1000 mL. The filtrate was filtered and concentrated to obtain a large Chuanxiong composite.

[0083] The composite bacterial liquid used is the same as that in Example 1.

[0084] Comparative Example 3

[0085] The difference from Example 1 is that the complex enzyme I used is composed of cellulase and pectinase in a mass ratio of 1:1.3.

[0086] Comparative Example 4

[0087] A large Chuanxiong composition, wherein the weight ratio of Chuanxiong and Gastrodia elata is 2.5:1 (total weight 1750g), is prepared according to the following steps:

[0088] 1) Mixing Chuanxiong powder with water of 9.5 times the weight of the Chuanxiong powder, adding a 3% composite bacterial solution by volume, fermenting at 37° C. for 36 hours under shaking culture, sterilizing with ultraviolet light, adding a 3% composite enzyme I by weight of the Chuanxiong powder, adjusting the pH to 5.5, performing enzymolysis at 55° C. for 1.5 hours, and incubating at 90° C. for 30 minutes to inactivate the enzyme to obtain a Chuanxiong fermentation hydrolyzate; mixing Gastrodia elata powder with water of 9.5 times the weight of the Gastrodia elata powder, adding a 3% composite bacterial solution by volume, fermenting at 37° C. for 36 hours under shaking culture, sterilizing with ultraviolet light, adding a 2.5% composite enzyme II by weight of the Gastrodia elata powder, adjusting the pH to 6.0, performing enzymolysis at 55° C. for 1.5 hours, and incubating at 90° C. for 30 minutes to inactivate the enzyme to obtain a Gastrodia elata fermentation hydrolyzate;

[0089] 2) After mixing the fermentation hydrolyzate of Chuanxiong and the fermentation hydrolyzate of Gastrodia elata, heat and extract at 100° C. for 2 h, filter, add 7 times the total mass of water to the solid obtained after filtration, mix, heat at 100° C. for 2 h, filter, mix with the filtrate of the first extraction and concentrate, the relative density of the concentrate is 1.23-1.24 (detected at 60° C.), add 3.5 times the mass of ethanol to the concentrate, stir evenly and let stand for 50 hours, take the supernatant, add 0.4% of the mass of Gastrodia elata sodium benzoate and stir evenly, dilute with water to 1000 mL, filter and take the filtrate to obtain a large Chuanxiong composite.

[0090] The composite bacterial liquid used is the same as that in Example 1.

[0091] Comparative Example 5

[0092] A large Chuanxiong composition, wherein the weight ratio of Chuanxiong and Gastrodia elata is 2.5:1 (total weight 1750g), is prepared according to the following steps:

[0093] 1) Put Chuanxiong powder and Gastrodia elata powder in water of 7 times the total mass, heat to 100°C and boil for 2 hours, filter to obtain a decoction, perform a second decoction according to the method of the first decoction, combine the two filtrates, filter, and concentrate to obtain a medicinal solution with a relative density of 1.23-1.24;

[0094] 2) adding 3.5 times the mass of ethanol to the liquid and stirring, stirring evenly and letting it stand for 50 hours, absorbing the supernatant, adding 0.4% sodium benzoate of the mass of Gastrodia elata to the supernatant and stirring evenly, adding distilled water to dilute to 1000 mL, and filtering to obtain the large Chuanxiong composition.

[0095] Experiment 1 Acute and chronic toxicity experiments

[0096] Thirty-six healthy Wistar female mice weighing (22±2)g were used for acute toxicology experiments, and thirty-six healthy Wistar male rats weighing (185±20)g were used for chronic toxicology experiments. Ordinary drinking water, room temperature controlled at (24±3)℃, humidity (50±10)%, and natural light were used.

[0097] 1. Acute toxicology test

[0098] 27 female mice were divided into 9 groups, 3 mice in each group, 8 of which were given the Rhizoma Chuanxiong compositions of Examples 1 to 3 and Comparative Examples 1 to 5, respectively, at a dosage of 0.5 mL / 20 g body weight by gavage; 1 group was given normal saline as a control, at a dosage of 0.5 mL / 20 g body weight by gavage; all groups were given once a day, and the experimental period was 7 days, and the activity, feeding, excretion and death of the mice were observed.

[0099] The results showed that no mice died within 7 days. After administration, the appearance, coat color and gloss of the mice were normal, and there were no abnormalities in their activity reactions, feeding and excretion.

[0100] 2. Chronic toxicology test

[0101] 27 male rats were divided into 9 groups, 3 rats in each group, 8 of which were given the Rhizoma Chuanxiong compositions of Examples 1 to 3 and Comparative Examples 1 to 5, respectively, at a dosage of 0.05 mL / 20 g body weight; 1 group was given normal saline as a control, at a dosage of 0.05 mL / 20 g body weight; all groups were given once a day, and the experimental period was 30 days, and the activity, feeding, excretion and death of the mice were observed.

[0102] The results showed that no mice died within 30 days. After administration, the appearance, coat color and gloss of the mice were normal, and there were no abnormalities in their activity reactions, feeding and excretion.

[0103] The above experimental results show that the large Chuanxiong composition of the present invention is safe for oral administration and has no obvious acute and chronic toxic side effects.

[0104] Experiment 2 Clinical Case

[0105] A clinical experiment was conducted on 160 patients with stroke precursors using the Rhizoma Chuanxiong compositions prepared by different preparation methods provided in Examples 1 to 3 and Comparative Examples 1 to 5. Stroke precursors were judged according to the clinical manifestations and symptoms of stroke precursors in the "Standards for Diagnosis and Efficacy of Diseases in Traditional Chinese Medicine".

[0106] 1. Experimental methods

[0107] 160 patients were randomly divided into 8 groups, each with 20 patients. Groups 1 to 8 were given 10 mL / person of the large Chuanxiong composition prepared by different preparation methods provided in Examples 1 to 3 and Comparative Examples 1 to 5, 3 times a day, and taken continuously for 14 days as a course of treatment, and two courses of treatment were used in succession. The results were observed, the cases were summarized, and other drugs were discontinued during the observation period.

[0108] 2. Record the symptom changes of each patient before and after treatment. The symptoms include dizziness, vertigo, headache, numbness of the upper limbs, numbness of the lower limbs, numbness of one side of the body, tongue stiffness and slurred speech, temporary hemiplegia and tongue congestion. The efficacy criteria are shown in Table 1.

[0109] Table 1 Symptom efficacy level standard

[0110]

[0111]

[0112] The symptom efficacy before and after treatment is shown in Tables 1 to 4. Effective rate = (effective number + markedly effective number + cured number) / number of cases.

[0113] Table 1

[0114]

[0115] Table 2

[0116]

[0117] Table 3

[0118]

[0119]

[0120] Table 4

[0121]

[0122] It can be seen that the efficiencies of Examples 1 to 3 are all higher than that of Comparative Example 5 of the prior art, among which Example 1 has the highest efficiency. Compared with Example 1, Comparative Example 1 is not fermented, and Comparative Example 2 is not enzymatically hydrolyzed, and its efficiency is significantly reduced; Comparative Example 3 removes amylase, and its efficiency is reduced. It can be seen that even if pectinase is added instead of amylase, the enzymatic hydrolysis effect of amylase cannot be achieved. Not all enzymatic hydrolysis can achieve the same effect. The use of amylase has a promoting effect on improving the effect of the large Chuanxiong composition. Comparative Example 4 is fermented first without enzymatic hydrolysis and then enzymatic hydrolysis, and its efficiency is reduced, indicating that the order of enzymatic hydrolysis and fermentation plays a key role in the release of effective active ingredients, and can improve the efficacy of the large Chuanxiong combination.

[0123] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a large Chuanxiong composition, characterized in that: The following steps are involved: A. Mixing Chuanxiong powder with water of 8 to 11 times the mass of the Chuanxiong powder, and then adding 2.4% to 4.7% of the mass of the Chuanxiong powder as complex enzyme I, enzymolysis to obtain Chuanxiong enzymolysis solution; mixing Gastrodia elata powder with water of 8 to 11 times the mass of the Gastrodia elata powder, and then adding 1.5% to 3.5% of the mass of the Chuanxiong powder as complex enzyme II, enzymolysis to obtain Gastrodia elata enzymolysis solution; B. Inoculating the composite bacterial liquid into the mixed solution of Chuanxiong enzymatic hydrolyzate and Gastrodia elata enzymatic hydrolyzate at an inoculation rate of 2% to 4%, fermenting, sterilizing with ultraviolet light, heating and extracting at 100° C. for 1 to 2 hours, filtering and collecting the filtrate, and concentrating to obtain a large Chuanxiong composite; The weight ratio of Chuanxiong and Gastrodia elata is 3:1 to 1:1; The composite bacteria include Bacillus subtilis and Lactobacillus acidophilus; The complex enzyme I comprises cellulase, pectinase and amylase in a mass ratio of 1:(0.9-1.1):(0.2-0.3); The complex enzyme II comprises cellulase, pectinase and hemicellulase in a mass ratio of (1.8-2.2):(0.9-1.1):

1.

2. The preparation method according to claim 1, characterized in that: The fermentation conditions include shaking culture at 37°C for 24 to 48 hours; Preferably, step B also includes a second extraction, which includes adding 6 to 9 times the total mass of water to the solid obtained after filtration, mixing, heating at 100°C for 1 to 2 hours, filtering, mixing with the filtrate of the first extraction, and concentrating to obtain a large Chuanxiong composition.

3. The preparation method according to claim 1 or 2, characterized in that: The preparation method of the composite bacterial liquid comprises mixing and diluting the activated cultured Bacillus subtilis seed liquid and the Lactobacillus acidophilus seed liquid to obtain the composite bacterial liquid; Preferably, the concentration of the composite bacterial solution is (2-6)×10 12 CFU / mL; Preferably, the ratio of the number of viable bacteria of Streptococcus thermophilus to that of Bacillus subtilis in the composite bacterial liquid is 1:(1-3).

4. The preparation method according to claim 3, characterized in that: The dilution multiple is 50 to 150 times.

5. The preparation method according to claim 1, characterized in that: The conditions of the enzymatic hydrolysis include pH 5.0-7.0, temperature 50-55° C., and enzymatic hydrolysis for 1.5-2 hours.

6. The preparation method according to claim 5, characterized in that: After enzymatic hydrolysis, the enzyme inactivation is also included; Preferably, the enzyme inactivation conditions include keeping the mixture at 90° C. for 30 min.

7. The preparation method according to any one of claims 1 to 6, characterized in that: After the concentration, the method further comprises adding 2.5 to 4 times the mass of ethanol to the concentrated solution, stirring evenly and standing for 40 to 60 hours, taking the supernatant and adding sodium benzoate, stirring evenly, diluting, filtering and taking the filtrate to obtain a large Chuanxiong composition.

8. A large Chuanxiong composition, characterized in that: The method is prepared according to any one of claims 1 to 7.

9. Use of the Rhizoma Chuanxiong composition according to claim 8 in the preparation of a medicament for treating headache caused by head wind or / and congestion type headache.

10. A medicine for treating headache caused by wind or / and congestion type headache, characterized in that: The composition comprising the Rhizoma Chuanxiong as claimed in claim 8; Preferably, the dosage form of the drug includes oral solution, tablet, capsule, powder, pill or granule.

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