Herba clinopodii oral liquid and preparation method thereof

Abstract

The invention discloses a clinopodium polycephalum oral liquid and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine preparation. The technical scheme is as follows: the oral liquid is prepared by combining enzymolysis, ultra-filtration and stabilizer regulation and specifically comprises the following steps: taking a clinopodium polycephalum medicinal material, cutting off, adding water for reflux extraction, filtering, concentrating filtrate under reduced pressure to obtain concentrated liquid medicine, adding enzyme into the concentrated liquid medicine for enzymolysis reaction, ultra-filtration, adding a stabilizer into the filtrate, regulating the pH value, sterilizing and canning to obtain the clinopodium polycephalum oral liquid. The clarity of the clinopodium polycephalum oral solution in the re-storage period can be improved, and the phenomenon that insoluble or indissolvable micromolecular particles generate a slow aggregation effect precipitation phenomenon in the storage period of the product is effectively prevented; the effective components in the medicinal materials can be more effectively reserved, the efficacy of the product during the storage period of the medicine is ensured, and the taking effectiveness of a patient is ensured.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine pharmaceutical preparation, and particularly relates to a blood-breaking oral liquid and a preparation method thereof. Background Art

[0002] Duanxueliu is the dried aerial part of Lanterna or Pinus chinensis of the Lamiaceae family, which has the effect of astringency and hemostasis. It is used to treat metrorrhagia, hematuria, epistaxis, root bleeding, traumatic bleeding, etc. The medicinal plants Pinus chinensis and Yinfenglun of Duanxueliu contain saponins, flavonoids, amino acids, polysaccharides, phenolic substances and volatile oils, among which saponins and flavonoids are the main active ingredients for Duanxueliu to stop bleeding and fight inflammation.

[0003] The clarity of Chinese medicine oral liquid is an important standard. The General Rules 0181 of Part IV of the 2020 edition of the Chinese Pharmacopoeia states that "unless otherwise specified, the mixture should be clarified. During storage, there should be no mold, rancidity, foreign matter, discoloration, gas production or other deterioration phenomena. A small amount of precipitation that is easily dispersed by shaking is allowed." There are many dosage forms of Duanxueliu on the market, such as tablets, granules, capsules, oral liquids, etc. Duanxueliu oral liquid, as a commonly used Chinese medicine preparation, has the advantages of being easy to take and easy to absorb, and has significant effects in the treatment of related diseases. However, the traditional preparation method is generally a water extraction and alcohol precipitation method, and the clarity is often difficult to achieve the ideal state, and precipitation is very easy to occur during the storage process, affecting the quality of the product and the efficacy of the drug. After water extraction, the blood-breaking medicinal materials mainly contain chemical components such as flavonoids, saponins, terpenes, organic acids, tannins, polysaccharides, proteins, resins, volatile oils, etc. Some water-soluble macromolecular products of primary metabolism will form micelle-like structures with protein end as the core and polysaccharide end as the shell. The sizes range from nanometers to micrometers and are soluble in water. However, due to the differences in polarity and solubility of each component, the insoluble components in some small molecule products of secondary metabolism will be solubilized in the micelles. During storage, these insoluble or insoluble small molecule particles will slowly aggregate due to the mutual influence of factors such as van der Waals forces, hydrogen bonds, and hydrophobic forces, resulting in unqualified clarity or even precipitation.

[0004] In addition, the water extraction process of blood-breaking herbs may also be accompanied by a series of complex physical and chemical reactions, such as changes in pH, redox reactions, and enzymatic reactions, which further affect the stability and solubility of its chemical components. In the extract, flavonoids are often well soluble in the water phase due to their unique molecular structure and strong polarity, but over time, the interaction between these molecules may also change, resulting in reduced solubility and further precipitation.

[0005] In addition, it is worth noting that as a traditional Chinese medicinal material, the efficacy of Bronchodilator is often closely related to the synergistic effect of multiple components. Therefore, in the process of extraction and purification, it is necessary to maintain the integrity and proportion of its original components as much as possible to ensure that the efficacy of the final product is not affected. Patent CN101468086A points out that the clarity of the solution can be improved by placing the liquid medicine in a static refrigerated manner, which solves the clarity problem in the production process of the liquid medicine, but the process energy consumption cost is high, and it is impossible to solve the problem of unqualified clarity caused by precipitation of the preparation during storage. The document "Technical Research on Extraction of Bronchodilator Saponins by Cellulase" points out the process conditions for extracting total saponins from Bronchodilator by cellulase enzymolysis. The enzymolysis technology can specifically destroy the plant cell wall, making it easier to release the effective ingredients in the cell, thereby improving the extraction efficiency. The use of cellulase can increase the content of Bronchodilator Saponin A to a certain extent, but it does not mention the effect of using cellulase alone on the aggregation of particles and unqualified clarity of oral solution during storage. Therefore, it is urgent to develop a production process that can not only retain the content of active ingredients but also solve the problems of precipitation and unqualified clarity of oral liquid. Summary of the invention

[0006] The invention provides an oral liquid for stopping bleeding and a preparation method thereof, which solves the problem of poor clarity of the oral liquid for stopping bleeding and ensures the content of effective components.

[0007] The technical solution of the present invention is: In a first aspect, a method for preparing an oral liquid for stopping blood flow is provided, which is prepared by a combination of enzymatic hydrolysis, ultrafiltration and stabilizer adjustment, specifically: taking a medicinal material for stopping blood flow, cutting it, adding water to reflux for extraction, filtering, decompressing and concentrating the filtrate to obtain a concentrated medicinal liquid, adding an enzyme to the concentrated medicinal liquid for enzymatic hydrolysis, ultrafiltration, adding a stabilizer to the filtrate, adjusting the pH, sterilizing, and canning to obtain the oral liquid for stopping blood flow.

[0008] Preferably, the enzymes are cellulase and pectinase, the added amount of cellulase is 0.3% to 0.8% by weight of the concentrated liquid, and the added amount of pectinase is 0.2% to 0.5% by weight of the concentrated liquid.

[0009] Preferably, the stabilizers are polyvinyl pyrrolidone K30 and hydroxypropyl methylcellulose, wherein the amount of polyvinyl pyrrolidone added is 0.05% to 0.20% by weight of the concentrated liquid, and the amount of hydroxypropyl methylcellulose added is 0.1% to 0.3% by weight of the concentrated liquid.

[0010] Preferably, the preparation method comprises the following steps: 1) Pretreatment of medicinal materials: Take the medicinal materials with blood flow cut off, remove impurities, wash and dry them, and then cut them; 2) Extraction and concentration: add water to reflux for extraction, filter, and concentrate the filtrate under reduced pressure to obtain a concentrated drug solution; 3) Enzymatic hydrolysis: Add enzyme to the concentrated liquid, stir, and perform enzymatic hydrolysis; 4) Ultra-fine filtration: Filter the liquid after enzymatic hydrolysis through a microporous filtration membrane; 5) Preparation: Add stabilizer to the filtrate and adjust the pH; 6) Sterilization and filling: The prepared liquid medicine is sterilized instantaneously at high temperature; the sterilized liquid medicine is filled and sealed in a sterile environment to obtain the finished product of blood flow interruption oral liquid.

[0011] Preferably, the weight of water added in step 2) is 6 to 8 times the weight of the medicinal material, the temperature of reflux extraction is 100°C, reflux extraction is performed 2 to 3 times, each reflux time is 3 to 4 hours, the extracts are combined, filtered through a 150 to 200 mesh stainless steel sieve, and the filtrate is collected.

[0012] Preferably, in step 2), the concentration is performed to a relative density of 1.10-1.15 g / cm 3 .

[0013] Preferably, in step 3), the enzymatic hydrolysis reaction temperature is 50-60° C. and the reaction time is 3 h.

[0014] Preferably, in step 4), the pore size of the ultra-microfiltration membrane is 0.18-0.22 μm, the operating pressure is controlled at 0.1-0.3 MPa, and the filtration temperature is maintained at 20-30°C.

[0015] Preferably, in step 5), sodium hydroxide solution is used to adjust the pH, and the pH value is adjusted in the range of 5.0 to 6.0.

[0016] In a second aspect, the invention discloses the blood-stopping oral liquid prepared by the method for preparing the blood-stopping oral liquid.

[0017] The enzymatic hydrolysis technology of the present invention can destroy macromolecular substances in a targeted manner, so that effective ingredients can be released more easily, and the aggregation of macromolecular substances during storage can also be reduced. However, the use of cellulase alone cannot completely solve the problems of particle aggregation and unqualified clarity of oral solution during storage. The compound pectinase can partially dissolve the insoluble particles and micelle components in the system in advance. Polyvinylpyrrolidone K30 has good hydrophilicity and viscosity, can wrap the particles, reduce their surface free energy, and prevent aggregation. Hydroxypropyl methylcellulose can increase the viscosity of the solution and hinder the movement of the particles. The enzyme and the stabilizer cooperate with each other to reduce the surface energy and increase the viscosity to prevent the aggregation and precipitation of the components, and stabilize the oral liquid system.

[0018] However, Duanxueliu contains chemical components such as flavonoids, saponins, and terpenes. Some water-soluble macromolecular products may form micelle-like structures with protein ends as cores and polysaccharide ends as shells, ranging in size from nanometers to micrometers, and are soluble in water. Due to differences in polarity and solubility of the components, the insoluble components will be solubilized in the micelles. During storage, due to the mutual influence of factors such as van der Waals forces, hydrogen bonds, and hydrophobic forces, the particles will slowly aggregate, resulting in unqualified clarity and even precipitation. Therefore, the ingredients of Duanxueliu oral solution are complex and changeable, and the types and combined proportions of the cellulase and pectinase, polyvinyl pyrrolidone, and hydroxypropyl methylcellulose cannot be obtained through a simple limited number of combination screening tests.

[0019] In addition, when the pH of the prepared final product solution is within the range of 5.0 to 6.0, the clarity of the solution can be better stabilized during storage, while ensuring that the effective ingredients are stable and controllable. This is mainly because when the pH is too acidic, the hydroxyl groups of flavonoid phenols are easily protonated to cause structural changes, and when the alkalinity is too strong, the saponin glycosidic bonds may be hydrolyzed. Therefore, controlling the system in a certain pH environment and coordinating with factors such as the stabilizer described in the present invention may reduce the chemical reaction activity of the entire system and maintain the stability of the chemical components and the stabilizer colloid system.

[0020] Compared with the prior art, the present invention has the following beneficial effects: 1. The present invention adds a specific ratio of cellulase and pectinase combination, combines ultrafine filtration technology, adds a certain ratio of polyvinyl pyrrolidone and hydroxypropyl methylcellulose as stabilizers, and controls the final solution in a certain pH range to improve the clarity of the blood flow interruption oral solution during storage, effectively preventing the slow aggregation effect of insoluble or poorly soluble small molecule particles of the product from precipitating during storage; can more effectively retain the effective ingredients in the medicinal materials, ensure the efficacy of the product during drug storage, and help ensure the effectiveness of patients taking the medicine.

[0021] 2. The present invention also brings significant economic and environmental benefits. On the one hand, due to the use of more efficient extraction and purification processes, by adopting specific proportions of formulas, parameters and other processes, the high energy consumption caused by the use of refrigeration and other methods is avoided, thereby achieving significant savings in production costs. On the other hand, since the generation and discharge of waste caused by defective products is reduced, it is beneficial to environmental protection. DETAILED DESCRIPTION

[0022] In order to enable those skilled in the art to better understand the technical solutions in the present invention, the technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not 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 should fall within the scope of protection of the present invention.

[0023] Example 1 The preparation method of the blood-breaking oral liquid, the prescription of which is shown in Table 1: Table 1

[0024] The preparation method is as follows: 1) Pretreatment of medicinal materials: Take the medicinal materials with blood flow cut off, remove impurities, wash and dry them, and then cut them; 2) Extraction and concentration: Add 8 times the weight of the medicinal material in deionized water, heat and reflux to extract twice, 4 hours each time, temperature 100°C. Combine the extracts, filter through a 200-mesh stainless steel sieve, collect the filtrate; decompress and concentrate the filtrate, control the temperature at 80°C, steam pressure at 0.25Mpa, vacuum at -0.06Mpa; concentrate to a relative density of 1.15g / cm 3 (80℃); 3) Enzymatic treatment: Add 0.3% cellulase and 0.2% pectinase to the concentrated solution, adjust the pH value of the solution to 4.5 with acetic acid-sodium acetate buffer solution, and perform enzymatic reaction at 55°C for 3 hours. The stirring speed should be 30r / min during the enzymatic reaction to ensure sufficient contact between the enzyme and the solution; 4) Ultrafine filtration: After the enzymatic hydrolysis reaction is completed, the drug solution is filtered through a ceramic membrane filtration device. The pore size of the ultrafine filtration membrane is selected to be 0.22μm, the operating pressure is controlled at 0.3MPa, and the filtration temperature is maintained at 25℃; 5) Preparation: Add 0.05% of the weight of the concentrated solution in step 2) of polyvinyl pyrrolidone K30 and 0.1% of hydroxypropyl methylcellulose to the filtered solution; add appropriate amount of water to make the prepared solution 1000 mL, and adjust the pH to 5.0 with 10% sodium hydroxide solution; 6) Sterilization and filling: The prepared liquid medicine is sterilized instantaneously at high temperature; the sterilized liquid medicine is filled and sealed in a sterile environment to obtain the finished product of blood flow interruption oral liquid.

[0025] Example 2 The preparation method of the blood-breaking oral liquid, the prescription of which is shown in Table 2: Table 2

[0026] The difference from Example 1 is that step 3) is enzymatic hydrolysis: 0.5% of cellulase and 0.3% of pectinase by weight of the concentrated liquid medicine are added to the liquid medicine, the pH value of the liquid medicine is adjusted to 5.5 with acetic acid-sodium acetate buffer solution, and the enzymatic hydrolysis reaction is carried out at a temperature of 55° C. for 3 hours. During the enzymatic hydrolysis process, the stirring speed is required to be 30 r / min to ensure that the enzyme is fully in contact with the liquid medicine, and the remaining preparation methods and steps are the same as those in Example 1.

[0027] Example 3 The preparation method of the blood-breaking oral liquid, the prescription of which is shown in Table 3: Table 3

[0028] The difference from Example 1 is that in step 3), 0.8% of cellulase and 0.5% of pectinase by weight of the concentrated liquid medicine are added to the concentrated liquid medicine; in step 5), the amount of polyvinyl pyrrolidone K30 is 0.1% of the mass of the liquid medicine, the amount of hydroxypropyl methylcellulose is 0.2% of the mass of the liquid medicine, and the pH is adjusted to 6.0. The remaining preparation methods and steps are the same as those in Example 1.

[0029] Example 4 The preparation method of the blood-breaking oral liquid, the prescription of which is shown in Table 4: Table 4

[0030] The difference from Example 1 is that in step 3), 0.8% of cellulase and 0.5% of pectinase by weight of the concentrated liquid medicine are added to the concentrated liquid medicine; in step 5), the amount of polyvinyl pyrrolidone K30 is 0.2% of the mass of the concentrated liquid medicine, the amount of hydroxypropyl methylcellulose is 0.3% of the mass of the concentrated liquid medicine, and the pH is adjusted to 5.5. The remaining preparation methods and steps are the same as those in Example 1.

[0031] Comparative Example 1 The preparation method of the blood-breaking oral liquid comprises the following steps: 1) Pretreatment of medicinal materials: Take the blood-cut medicinal materials, remove impurities, wash and dry them, and then crush them; 2) Extraction and concentration: Add 8 times the weight of the medicinal material in deionized water, heat and reflux to extract twice, 4 hours each time, temperature 100°C. Combine the extracts, filter through a 200-mesh stainless steel sieve, collect the filtrate; decompress and concentrate the filtrate, control the temperature at 80°C, steam pressure at 0.25Mpa, vacuum at -0.06Mpa; to a relative density of 1.15g / cm 3 (80℃); 3) Alcohol precipitation: add ethanol twice the weight of the concentrate, stir thoroughly, refrigerate and let stand for 24 hours, take the supernatant and concentrate under reduced pressure to a relative density of 1.15 (25°C), continue to add 1.5 times the weight of water, stir thoroughly, let stand for 24 hours, filter, 4) pH adjustment: Add appropriate amount of water to the prepared solution to make up to 1000 mL, and adjust the pH to 6.0 with 10% sodium hydroxide solution.

[0032] 5) Sterilization and filling: The prepared liquid medicine is sterilized instantaneously at high temperature; the sterilized liquid medicine is filled and sealed in a sterile environment to obtain the finished product of blood flow interruption oral liquid.

[0033] Comparative Example 2 Different from Example 1, in this comparative example, the phrase "adding 0.3% cellulase by weight of the concentrated medicinal solution and 0.2% pectinase by weight of the medicinal solution" in step 3) enzymatic hydrolysis treatment is replaced by "adding 0.5% cellulase by weight of the medicinal solution", and the rest of the preparation methods and steps are the same as those in Example 1.

[0034] Comparative Example 3 Different from Example 1, in this comparative example, the step 5) of "adding 0.05% polyvinyl pyrrolidone K30 and 0.1% hydroxypropyl methylcellulose equivalent to the weight of the concentrated drug solution in step 2) to the filtered drug solution" is replaced by "adding 0.15% polyvinyl pyrrolidone K30 equivalent to the weight of the concentrated drug solution in step 2) to the filtered drug solution", and the rest of the preparation methods and steps are the same as those in Example 1.

[0035] Comparative Example 4 Different from Example 1, polyvinyl pyrrolidone K30 and hydroxypropyl methylcellulose are not added in step 5) of this comparative example, and the remaining preparation methods and steps are the same as those of Example 1.

[0036] Comparative Example 5 The difference from Example 1 is that in this comparative example, the phrase "adding 0.3% cellulase and 0.2% pectinase by weight of the concentrated medicinal solution to the concentrated medicinal solution" in step 3) enzymatic hydrolysis treatment is replaced by "adding 0.25% cellulase and 0.15% pectinase by weight of the medicinal solution to the concentrated medicinal solution", and the remaining preparation methods and steps are the same as those in Example 1.

[0037] Comparative Example 6 Different from Example 1, in this comparative example, the phrase "adding 0.3% cellulase and 0.2% pectinase by weight of the concentrated medicinal solution to the concentrated medicinal solution" in step 3) enzymatic hydrolysis treatment is replaced by "adding 0.85% cellulase and 0.55% pectinase by weight of the medicinal solution to the concentrated medicinal solution", and the remaining preparation methods and steps are the same as those in Example 1.

[0038] Comparative Example 7 The difference from Example 1 is that in step 5) of this comparative example, "add 0.05% polyvinyl pyrrolidone K30 and 0.1% hydroxypropyl methylcellulose equivalent to the weight of the concentrated drug solution in step 2) to the filtered drug solution" is replaced by "add 0.04% polyvinyl pyrrolidone K30 and 0.07% hydroxypropyl methylcellulose equivalent to the weight of the concentrated drug solution in step 2) to the filtered drug solution", and the rest of the preparation method and steps are the same as those in Example 1.

[0039] Comparative Example 8 The difference from Example 1 is that in step 5) of this comparative example, "add 0.05% polyvinyl pyrrolidone K30 and 0.1% hydroxypropyl methylcellulose equivalent to the weight of the concentrated drug solution in step 2) to the filtered drug solution" is replaced by "add 0.25% polyvinyl pyrrolidone K30 and 0.35% hydroxypropyl methylcellulose equivalent to the weight of the concentrated drug solution in step 2) to the filtered drug solution", and the rest of the preparation method and steps are the same as those in Example 1.

[0040] Comparative Example 9 The difference from Example 1 is that in step 5) of this comparative example, 10% sodium hydroxide solution is used to adjust the pH to 4.7, and the remaining preparation methods and steps are the same as those of Example 1.

[0041] Comparative Example 10 The difference from Example 1 is that in step 5) of this comparative example, 10% sodium hydroxide solution is used to adjust the pH to 6.5, and the remaining preparation methods and steps are the same as those of Example 1.

[0042] The oral liquids prepared in the above examples and comparative examples were subjected to clarity test. Specifically, the above solutions were placed in a UV-visible spectrophotometer, with the cylindrical axis parallel to the slit, ensuring that the light beam was perpendicular to the surface of the sample, and with air as a reference, measuring the transmittance in the spectral range of 290-450nm with an interval of no more than 20nm. The test results are shown in Table 5.

[0043] Table 5 Comparison of clarity between examples and comparative examples during stability period

[0044] It should be noted that, at present, there are no clear legal requirements for transmittance when testing clarity. Generally, when the transmittance is greater than 90%, the solution clarity is considered to be good. In Examples 1-4, there was no significant change in the solution transmittance from 0 days of preparation to long-term storage. When Comparative Examples 1-2 adopted static refrigeration and the cellulase enzymatic hydrolysis process alone, the clarity of the samples decreased significantly after 6 months of acceleration and 36 months of long-term storage; Comparative Example 3 used a single stabilizer and Comparative Example 4 did not add a stabilizer. Although the clarity at 0 days was good, it was speculated that the clarity decreased significantly during storage due to the reduced suspending ability. The amount of enzyme added in Comparative Example 5 was less than the normal range, mainly because the decomposition ability of the enzyme was reduced, resulting in the sample's 0-day clarity being slightly worse than that of the example, and it decreased significantly during storage; the amount of enzyme added in Comparative Example 6 was greater than the normal range. The amount of enzyme added in Comparative Example 6 was greater than the normal range, and the 0-day clarity was comparable to that of the example, but there was also a downward trend in clarity during storage. It is speculated that the amount of enzyme used may be too large. On the one hand Enzyme protein residues precipitate as impurities during storage. On the other hand, the enzymes over-decompose the Chinese medicine ingredients, disrupting the solution balance, causing the originally dissolved or stable ingredients to precipitate or flocculate, and reducing the clarity. The amount of stabilizer added in Comparative Example 7 is less than the normal range. It is speculated that the clarity is significantly reduced due to the reduced suspending ability. The amount of stabilizer added in Comparative Example 8 is greater than the normal range. It is speculated that the amount of stabilizer added in Comparative Example 8 is greater than the normal range. It is speculated that the high viscosity of the stabilizer causes the system to produce a Tyndall effect. When the pH value in the preparation process of Comparative Examples 9 and 10 exceeds the range of 5.0~6.0, the performance of the stabilizer is reduced due to the change in the acidity and alkalinity environment of the system, and the insoluble particles in the solution are more likely to aggregate, causing the clarity to change significantly during storage.

[0045] The content of the effective ingredient buddleja saponin IVb in the oral liquid prepared in the above examples and comparative examples was determined by liquid chromatography as follows: Chromatographic conditions and system suitability test: octadecylsilane bonded silica gel was used as filler, methanol-water (75:25) was used as mobile phase, and the detection wavelength was 250nm. The theoretical plate number calculated based on the buddleja saponin IVb peak should be no less than 3000.

[0046] Preparation of reference solution: Accurately weigh an appropriate amount of buddleja saponin IVb reference substance and add methanol to prepare a reference solution containing 10 μg of buddleja saponin IVb per 1 mL.

[0047] Preparation of test solution: Accurately measure 1 mL of the oral solution prepared in the examples and comparative examples, put it into a 25 mL volumetric flask, dilute it with water and make it up to the mark, shake it well, transfer it to a separatory funnel, add water-saturated n-butanol and shake it for 4 times, 20 mL each time, combine the n-butanol solutions, wash them with 30 mL of ammonia test solution saturated with n-butanol, and then wash them twice with water saturated with n-butanol, 30 mL each time, evaporate the n-butanol, dissolve the residue with methanol, transfer it to a 50 mL volumetric flask, add methanol to the mark, shake it well, filter it, and take the filtrate to obtain the product.

[0048] Determination method: Accurately pipette 20 μL of reference solution and test solution respectively, inject into liquid chromatograph, and determine. The test results are shown in Table 6.

[0049] Table 6 Comparison of content determination of examples and comparative examples during stability

[0050] It should be noted that the quality standard of Duanxueliu oral solution stipulates that "each vial contains Duanxueliu with buddleja saponin IVb (C 48 H 78 O 18 ) should be no less than 5.5 mg". The effective ingredient extraction amount of Examples 1-4 was high at 0 days of preparation, and was stable without significant changes during storage. The effective ingredient content of Comparative Examples 1-10 was lower than that of the Examples at 0 days of preparation, and decreased significantly during storage, which did not meet the quality standard requirements, and was consistent with the trend of the clarity test result.

[0051] Compared with the traditional method, the method of the present invention has obvious improvements in clarity, stability and active ingredient content. The above data show that the process method of the present invention has good feasibility and practicality.

Claims

1. A method for preparing a blood-breaking oral liquid, characterized in that: The preparation method is prepared by combining enzymatic hydrolysis, ultrafine filtration and stabilizer adjustment, specifically, taking blood-breaking medicinal materials, cutting them, adding water to reflux for extraction, filtering, decompressing and concentrating the filtrate to obtain a concentrated medicinal solution, adding an enzyme to the concentrated medicinal solution for enzymatic hydrolysis, ultrafine filtering, adding a stabilizer to the filtrate, adjusting the pH, sterilizing, and canning to obtain the blood-breaking oral liquid.

2. The method for preparing the blood-stopping oral liquid according to claim 1, characterized in that: The enzymes are cellulase and pectinase. The added amount of cellulase is 0.3% to 0.8% of the weight of the concentrated liquid, and the added amount of pectinase is 0.2% to 0.5% of the weight of the concentrated liquid.

3. The method for preparing the blood-stopping oral liquid according to claim 1, characterized in that: The stabilizers are polyvinyl pyrrolidone and hydroxypropyl methylcellulose, wherein the amount of polyvinyl pyrrolidone added is 0.05% to 0.20% by weight of the concentrated solution, and the amount of hydroxypropyl methylcellulose added is 0.1% to 0.3% by weight of the concentrated solution.

4. The method for preparing the blood-stopping oral liquid according to claim 1, characterized in that: The specific steps include: 1) Pretreatment of medicinal materials: Take the blood-cut medicinal materials, remove impurities, wash and dry them, and then cut them; 2) Extraction and concentration: add water to reflux for extraction, filter, and concentrate the filtrate under reduced pressure to obtain a concentrated drug solution; 3) Enzymatic hydrolysis: Add enzyme to the concentrated liquid medicine, stir, and perform enzymatic hydrolysis reaction; 4) Ultra-fine filtration: Filter the liquid after enzymatic hydrolysis through a microporous filtration membrane; 5) Preparation: Add stabilizer to the filtrate and adjust the pH; 6) Sterilization and filling: The prepared liquid medicine is sterilized instantaneously at high temperature; the sterilized liquid medicine is filled and sealed in a sterile environment to obtain the finished product of blood flow interruption oral liquid.

5. The method for preparing the blood-breaking oral liquid according to claim 4, characterized in that: Step 2) The weight of water added is 6 to 8 times the weight of the medicinal material, the temperature of reflux extraction is 100°C, reflux extraction is performed 2 to 3 times, and the reflux time each time is 3 to 4 hours. The extracts are combined, filtered through a 150 to 200 mesh stainless steel sieve, and the filtrate is collected.

6. The method for preparing the blood-stopping oral liquid according to claim 4, characterized in that: Step 2) Concentrate to a relative density of 1.10~1.15g / cm 3 .

7. The method for preparing the blood-stopping oral liquid according to claim 4, characterized in that: In step 3), the enzymatic hydrolysis reaction temperature is 50-60°C and the reaction time is 1-3h.

8. The method for preparing the blood-stopping oral liquid according to claim 4, characterized in that: In step 4), the pore size of the ultra-microfiltration membrane is 0.18-0.22 μm, the operating pressure is controlled at 0.1-0.3 MPa, and the filtration temperature is maintained at 20-30°C.

9. The method for preparing the blood-stopping oral liquid according to claim 4, characterized in that: In step 5), sodium hydroxide solution is used to adjust the pH, and the pH value is adjusted in the range of 5.0 to 6.

0.

10. The blood-stopping oral liquid prepared by the method for preparing the blood-stopping oral liquid according to any one of claims 1 to 9.

Images