CN106728080B

CN106728080B - Preparation process of compound medicine for treating chronic nephritis

Info

Publication number: CN106728080B
Application number: CN201611227108.XA
Authority: CN
Inventors: 林凡友; 郭增光; 张海雷; 王文天; 秦承盟
Original assignee: Xiang Yu Pharmaceutical Ltd Co
Current assignee: Xiang Yu Pharmaceutical Ltd Co
Priority date: 2016-12-27
Filing date: 2016-12-27
Publication date: 2020-02-21
Anticipated expiration: 2036-12-27
Also published as: CN106728080A

Abstract

The invention belongs to the technical field of Chinese herbal medicine extraction, and discloses a preparation process of a compound medicine for treating chronic nephritis, which comprises the following steps: step 1) weighing, step 2) preparing a component A, step 3) preparing a component B, step 4) preparing a component C, step 5) preparing a component D, and step 6) uniformly mixing, crushing and granulating. The preparation method is an improvement of the existing preparation method of Cordyceps, radix astragali and radix Ginseng capsule, and has improved extraction rate of effective components of raw materials and improved drug effect.

Description

Preparation process of compound medicine for treating chronic nephritis

Technical Field

The invention belongs to the technical field of Chinese herbal medicine extraction, and particularly relates to a preparation process of a compound medicine for treating chronic nephritis.

Background

Chronic nephritis is also called chronic glomerulonephritis, is a group of glomerular diseases with diverse etiology, different pathological forms and similar clinical manifestations, is a systemic disease mainly caused by renal diseases, and clinically takes edema and proteinuria as main symptoms, accompanied by renal hypofunction of different degrees, frequently repeated attacks, difficult recovery, anemia, retinopathy and uremia at the later stage, and even endangers life. The main table of the method comprises: (1) edema; (2) hypertension; (3) pain in the renal area and renal colic; (4) urinary tract irritation (i.e., urgency, pain, frequency); (5) abnormal urination (including urine volume reduction, proteinuria, hematuria, cylindruria, leucocyturia, purulent urine, bacteriuria, positive renal function tests and the like, incomplete data statistics of data arrays show that the prevalence rate of chronic glomerular diseases in China is about 1-2%, and the incidence rate of renal diseases also tends to rise continuously in recent years.

The cordyceps sinensis, astragalus and ginseng capsule is a medicine for effectively treating chronic nephritis, has relatively simple raw material components, good effect and small toxic and side effect, and is popular with patients. The applicant finds that the preparation method of the medicine is single in the pharmaceutical process, the defect of loss of effective components exists when multiple raw materials are subjected to the same extraction process, and the cordyceps sinensis-astragalus-ginseng capsule needs to be taken for 4 granules every time, three times every day, the dosage is too large, so that part of patients are difficult to accept, and the rejection mood is easy to appear. How to utilize raw materials to the maximum extent and improve the drug effect by improving the process is a problem which needs to be researched.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention provides a preparation process of a compound medicine for treating chronic nephritis, which is improved by the existing preparation process of cordyceps sinensis, astragalus and ginseng capsules, so that the leaching rate of active ingredients of raw materials is improved, the medicine effect is improved, and the dosage of the medicine is reduced.

The invention is realized by the following technical scheme:

a preparation process of a compound medicine for treating chronic nephritis comprises the following steps: step 1) weighing, step 2) preparing a component A, step 3) preparing a component B, step 4) preparing a component C, step 5) preparing a component D, and step 6) uniformly mixing, crushing and granulating.

Specifically, the step 1) comprises the following steps of weighing: weighing the raw materials according to the parts by weight for later use, wherein the raw materials comprise 80g of cordyceps sinensis, 1200g of astragalus membranaceus, 600g of salvia miltiorrhiza, 600g of safflower and 320g of spina date seeds.

Specifically, the step 2) is to prepare a component A: pulverizing Cordyceps into fine powder to obtain component A.

Specifically, the step 3) is to prepare a component B: pulverizing radix astragali, sieving with 200 mesh sieve, placing in a container, adding 85% ethanol three times the weight of radix astragali, stirring and extracting at 300rpm, controlling microwave power at 500W during extraction process, and extracting for 90 min; then placing at 4 ℃ for 12h, filtering, and keeping filter residues for later use; evaporating the filtrate under reduced pressure to recover ethanol, and concentrating the filtrate to obtain extract 1 with density of 1.2 g/ml; adding water with twice weight of the filter residue, stirring uniformly, adding neutral protease, performing enzymolysis at 37 ℃ for 90min, boiling for 5min, adding absolute ethanol with twice weight of the filter residue, stirring at 300rpm for 8min, standing for 12h, removing supernatant, collecting precipitate, dissolving in water, standing at-20 ℃ for 6h, centrifuging at 3000rpm for 3min, filtering to remove precipitate, and concentrating the filtrate under reduced pressure to obtain extract 2 with density of 1.2 g/ml; and mixing the extract 1 and the extract 2 to obtain a component B.

Specifically, the step 4) is to prepare a component C: pulverizing Saviae Miltiorrhizae radix, sieving with 100 mesh sieve, spreading into flat layer with thickness of 3mm, irradiating under ultraviolet for 20min, and collecting powder; mixing Carthami flos with the above powder, placing into a container, adding 75% ethanol with weight twice of the powder, stirring and extracting at 300rpm, controlling microwave power at 600W during extraction process, and extracting for 30 min; filtering, collecting filtrate, recovering ethanol under reduced pressure, and concentrating to obtain extract of 1.3g/ml to obtain component C.

Specifically, the step 5) is to prepare a component D: decocting semen Ziziphi Spinosae in water twice, adding 8 times of water for the first time, decocting for 2 hr, and filtering to obtain filtrate and residue; adding 5 times of water into the residue, decocting for 1.5 hr, and filtering to obtain filtrate; mixing the above two filtrates, concentrating into fluid extract with density of 1.1g/ml, cooling, adding ethanol to make ethanol content reach 70% (volume fraction), standing for 24 hr, filtering, collecting supernatant, recovering ethanol under reduced pressure, and concentrating into extract with density of 1.3g/ml to obtain component D.

Specifically, the step 6) of uniformly mixing, crushing and granulating: mixing component B, component C and component D, oven drying at 60 deg.C, pulverizing, adding component A, mixing, drying, adding adjuvants, and making into capsule.

Compared with the preparation process of the cordyceps sinensis, astragalus and ginseng capsules in the prior art, the preparation process of the invention has the following advantages and effects:

the preparation process is simple and feasible, different traditional Chinese medicine components are treated by different technologies, the effective components of the raw materials are improved, the drug effect is increased, and the waste of the raw materials is reduced; when the salvia miltiorrhiza is extracted, a decoction mode is adopted, so that phenolic acid and ketone substances are easily decomposed; the leaching rate of the effective components of the astragalus membranaceus can be improved due to the small particle size, and glycosides and polysaccharides can be obtained by matching with microwave alcohol extraction and the like, so that the loss of the components is avoided; the extraction process of the salvia miltiorrhiza adopts the ultraviolet rays with proper intensity, improves the dissolution rate of the effective ingredients, adopts the microwave-assisted water extraction, has short time, improves the extraction efficiency and reduces the energy consumption; acid substances such as chlorogenic acid and phenolic active substances in the safflower are not easy to decoct, and the invention adopts alcohol extraction and reserves active ingredients; the capsule preparation prepared by the invention has high effective component and good effect, and animal experiments suggest that the effect is superior to that of the existing capsule preparation, and the capsule preparation can be used for further clinical trial research. The applicant also tries to slightly improve the proportion of the raw materials of the known cordyceps sinensis-astragalus-ginseng capsule, and the pharmacodynamic result shows that no obvious difference exists, but the cost reduction of the cordyceps sinensis can reduce the cost of the raw materials of the medicine and improve the profit of enterprises.

Detailed Description

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

Example 1

A preparation process of a compound medicine for treating chronic nephritis comprises the following steps:

1) weighing: weighing the raw materials according to the parts by weight for later use, wherein the raw materials comprise 80g of cordyceps sinensis, 1200g of astragalus membranaceus, 600g of salvia miltiorrhiza, 600g of safflower and 320g of spina date seeds;

2) preparation of component A: pulverizing Cordyceps into fine powder to obtain component A;

3) preparation of component B: pulverizing radix astragali, sieving with 200 mesh sieve, placing in a container, adding 85% (v/v) ethanol three times the weight of radix astragali, stirring and extracting at 300rpm, controlling microwave power at 500W during extraction process, and extracting for 90 min; then placing at 4 ℃ for 12h, filtering, and keeping filter residues for later use; evaporating the filtrate under reduced pressure to recover ethanol, and concentrating the filtrate to obtain extract 1 with density of 1.2 g/ml; testing the content of astragaloside in the extract 1 to be 1.33mg/ml by adopting a high performance liquid chromatography;

adding water with twice weight of the filter residue, stirring uniformly, adding 0.5wt% of neutral protease (20 ten thousand U/g), performing enzymolysis at 37 ℃ for 90min, boiling for 5min, adding absolute ethanol with twice weight of the filter residue, stirring at 300rpm for 8min, standing for 12h, removing supernatant, collecting precipitate, dissolving in water, standing at-20 ℃ for 6h, centrifuging at 3000rpm for 3min, filtering to remove precipitate, and concentrating the filtrate under reduced pressure to obtain extract 2 with density of 1.2 g/ml; mixing the extract 1 and the extract 2 to obtain a component B; measuring the mass of the astragalus polysaccharide in the extract B by adopting gel chromatography, wherein the mass of the astragalus polysaccharide is 20000-40000 and accounts for more than 70% of the total sugar;

4) preparation of component C: pulverizing Saviae Miltiorrhizae radix, sieving with 100 mesh sieve, spreading into flat layer with thickness of 3mm, irradiating under ultraviolet for 20min, and collecting powder; mixing Carthami flos with the above powder, placing into a container, adding 75% (volume parts) ethanol twice the weight of the powder, stirring and extracting at 300rpm, controlling microwave power at 600W during extraction process, and extracting for 30 min; filtering, collecting filtrate, recovering ethanol under reduced pressure, and concentrating to obtain extract of 1.3g/ml to obtain component C; the ultraviolet intensity is 3000uW/cm²；

5) Preparation of component D: decocting semen Ziziphi Spinosae in water twice, adding 8 times of water for the first time, decocting for 2 hr, and filtering to obtain filtrate and residue; adding 5 times of water into the residue, decocting for 1.5 hr, and filtering to obtain filtrate; mixing the above two filtrates, concentrating into fluid extract with density of 1.1g/ml, cooling, adding ethanol to make ethanol content reach 70% (volume fraction), standing for 24 hr, filtering, collecting supernatant, recovering ethanol under reduced pressure, and concentrating into extract with density of 1.3g/ml to obtain component D;

6) mixing, crushing and granulating: mixing component B, component C and component D, oven drying at 60 deg.C, pulverizing, adding component A, mixing, drying, adding adjuvants, and making into 1000 capsules.

The usage and dosage are as follows: orally administered 3 capsules at a time, 0.45 g/capsule, 3 times a day.

Comparative example 1

A Chinese caterpillar fungus, astragalus and ginseng capsule for treating chronic nephritis is prepared from the following raw materials by weight: 80g of cordyceps sinensis, 1200g of astragalus membranaceus, 600g of salvia miltiorrhiza, 600g of safflower and 320g of spina date seeds;

the production method of the cordyceps sinensis, astragalus and ginseng capsule comprises the following steps: weighing the raw materials by weight for later use;

(1) pulverizing Cordyceps into fine powder;

(2) decocting radix astragali, Saviae Miltiorrhizae radix, Carthami flos and semen Ziziphi Spinosae in water twice, adding 8 times of water for the first time, decocting for 2 hr, and filtering to obtain filtrate and residue;

(3) adding 5 times of water into the dregs obtained in the step (2), decocting for 1.5 hours, and filtering to obtain filtrate;

(4) mixing the filtrates of step (2) and step (3), concentrating into fluid extract with relative density of 1.16, cooling, adding ethanol to make ethanol content reach 70% (volume fraction), standing for 24 hr, filtering, collecting supernatant, recovering ethanol under reduced pressure, concentrating into dry extract with density of 1.38g/ml, pulverizing, adding the fine powder prepared in step (1), mixing, drying, adding adjuvants, and making into 1000 granules.

The usage and dosage are as follows: orally administered 4 capsules at a time, 0.45 g/capsule, 3 times a day.

Example 2

Toxicity test in animals

60 healthy Kunming strain mice with half male and female parts and the weight of 18.9 +/-2.6 g are randomly divided into two groups, wherein each group is half male and female, 30 of the mice are control groups, and normal water is filled in the groups; an additional 30 mice were given the formulation prepared in example 1 at a dose of 200mg/kg three times a day, and toxicity experiments using the mice showed that: compared with a control group, the mice have no obvious difference after administration, and the mice have normal general condition, food intake, water drinking and weight increase after continuous observation for two weeks in experiments. On the day of administration and within two weeks after administration, no death of animals is found, which indicates that the medicine has low toxicity and is safe for clinical administration.

Example 3

Comparative test of drug efficacy

Animals: 120 SD male rats with the body weight of 221 +/-19 g and the health and cleanness grade are raised in the experimental animal center of the company.

Grouping processing: 120 SD male rats, 30 SD male rats were randomly selected as blank control groups according to no significant difference in body weight, and the rest 90 SD male rats were subjected to doxorubicin nephropathy model preparation. The model rats were randomly divided into a model control group (gavage physiological saline, dose 100 mg/kg), an example 1 group (preparation produced in gavage example 1, dose 100 mg/kg), a control example 1 group (preparation produced in gavage control example 1, dose 100 mg/kg), and 30 rats per group. The administration is carried out once a day for one month. The rats in each group were left to take 24h urine volume at the beginning and end of the experiment to measure 24h urine protein quantification (sulfosalicylic acid method).

Observation indexes are as follows: including food intake, body hair, stool, mental state, weight, edema and other conditions of the rat.

As a result: the rats in the model control group had poor mental performance, reduced food intake, weight loss, fluffy body hair, and significant edema starting from the third week. The rats in the example 1 group and the control 1 group had better mental performance, more food intake, heavier weight than the model control group, and less edema, while the rats in the example 1 group had better weight, mental performance, food intake, and edema than the rats in the control 1 group. The comparison of the quantitative dynamic changes of urine protein of rats in each group is shown in Table 1.

TABLE 1

Group of	Start time detection result	End time detection result
			Blank control group	26.32±4.13	25.69±5.03
Model control group	223.39±54.47	359.73±68.96
			EXAMPLE 1 group	226.09±43.18	196.72±51.92
Comparative example 1 group	219.21±53.49	258.37±61.45

And (4) conclusion: the compound medicine prepared in the embodiment 1 of the invention has better treatment effect on the chronic nephritis of mice, the effect is obviously better than that of the comparative example 1, and simultaneously, the compound medicine is also obviously better than the cordyceps, astragalus and ginseng capsule product sold in the company.

Finally, it is also noted that the above-mentioned lists merely illustrate a few specific embodiments of the invention. It is obvious that the invention is not limited to the above embodiments, but that many variations are possible. All modifications which can be derived or suggested by a person skilled in the art from the disclosure of the present invention are to be considered within the scope of the invention.

Claims

1. A preparation process of a compound medicine for treating chronic nephritis comprises the following steps

Step 1) weighing: weighing the raw materials according to the parts by weight for later use, wherein the raw materials comprise 80g of cordyceps sinensis, 1200g of astragalus membranaceus, 600g of salvia miltiorrhiza, 600g of safflower and 320g of spina date seeds;

step 2) preparation of component a: pulverizing Cordyceps into fine powder to obtain component A;

step 3) preparation of component B: pulverizing radix astragali, sieving with 200 mesh sieve, placing in a container, adding 85% ethanol three times the weight of radix astragali, stirring and extracting at 300rpm, controlling microwave power at 500W during extraction process, and extracting for 90 min; then placing at 4 ℃ for 12h, filtering, and keeping filter residues for later use; evaporating the filtrate under reduced pressure to recover ethanol, and concentrating the filtrate to obtain extract 1 with density of 1.2 g/ml; adding water with twice weight of the filter residue, stirring uniformly, adding neutral protease, performing enzymolysis at 37 ℃ for 90min, boiling for 5min, adding absolute ethanol with twice weight of the filter residue, stirring at 300rpm for 8min, standing for 12h, removing supernatant, collecting precipitate, dissolving in water, standing at-20 ℃ for 6h, centrifuging at 3000rpm for 3min, filtering to remove precipitate, and concentrating the filtrate under reduced pressure to obtain extract 2 with density of 1.2 g/ml; mixing the extract 1 and the extract 2 to obtain a component B;

step 4) preparation of component C: pulverizing Saviae Miltiorrhizae radix, sieving with 100 mesh sieve, spreading into flat layer with thickness of 3mm, irradiating under ultraviolet for 20min, and collecting powder; mixing Carthami flos with the above powder, placing into a container, adding 75% ethanol with weight twice of the powder, stirring and extracting at 300rpm, controlling microwave power at 600W during extraction process, and extracting for 30 min; filtering, collecting filtrate, recovering ethanol under reduced pressure, and concentrating to obtain extract of 1.3g/ml to obtain component C;

step 5) preparation of component D: decocting semen Ziziphi Spinosae in water twice, adding 8 times of water for the first time, decocting for 2 hr, and filtering to obtain filtrate and residue; adding 5 times of water into the residue, decocting for 1.5 hr, and filtering to obtain filtrate; mixing the above two filtrates, concentrating into fluid extract with density of 1.1g/ml, cooling, adding ethanol to make ethanol content reach 70%, standing for 24 hr, filtering, collecting supernatant, recovering ethanol under reduced pressure, and concentrating to obtain extract with density of 1.3g/ml to obtain component D;

step 6), mixing, crushing and granulating: mixing component B, component C and component D, oven drying at 60 deg.C, pulverizing, adding component A, mixing, drying, adding adjuvants, and making into capsule.