CN106728081B - Preparation method of capsule for clearing away turbid and tonifying kidney - Google Patents

Abstract

The invention belongs to the technical field of medicine extraction and preparation, and discloses a preparation method of a capsule for clearing away turbid heat and tonifying the kidney, which comprises the following steps: step 1) weighing raw materials, step 2) preparing fine powder of the cordyceps sinensis, step 3) preparing an astragalus extract, step 4) preparing a salvia miltiorrhiza extract, step 5) preparing a safflower extract, step 6) preparing a spina date seed and dodder seed rhubarb extract, and step 7) granulating. The cure rate of the capsule for clearing away turbid heat and tonifying the kidney prepared by the preparation method is obviously higher than that of the capsule for clearing away turbid heat and tonifying the kidney in the prior art, and the dosage is reduced by one fourth.

Description

Preparation method of capsule for clearing away turbid and tonifying kidney

Technical Field

The invention belongs to the technical field of medicine extraction and preparation, and particularly relates to a preparation method of a capsule for clearing away turbid and tonifying the kidney and a quality standard inspection method.

Background

Kidney disease has now become one of the major public health hazards. And the incidence of nephropathy in our country is also rising year after year due to irregular treatment, drug abuse and bad lifestyle. Nephrotic Syndrome (NS), abbreviated as renal heddle, refers to a group of syndromes mainly caused by various causes and mainly caused by glomerular diseases such as increase of glomerular basement membrane permeability and decrease of glomerular filtration rate. Nephrotic syndrome is not an independent disease, but a group of syndromes in glomerular disease. Typical symptoms are marked by massive proteinuria, hypoalbuminemia, high edema, hyperlipidemia. Can be caused by a plurality of kidney diseases, and is generally considered to be a cell immune disease in the medical field at present. Currently, the clinical routine treatment protocols are hormone therapy, anti-platelet aggregation therapy and the application of immunosuppressive agents.

The capsule for clearing turbid and tonifying kidney is a medicine for effectively treating nephrotic syndrome, has relatively simple raw material components, good effect and small toxic and side effect, and is popular with patients. The applicant finds that the extraction method of the raw materials of the medicine is relatively single in the pharmaceutical process, the same extraction process is adopted for various raw materials, the defect of loss of effective components exists, 4 granules are required to be taken for nephrotic syndrome every time, the dosage is too large, and the medicine is difficult to be accepted by part of patients and is easy to generate rejection emotion. Moreover, the improvement of the known medicine can save the early development cost of enterprises, and is a hot spot of enterprise research in recent years. Meanwhile, the quality control of the Qingzhuoyishen capsule is also a problem which needs to be taken into account in a GMP workshop. 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 method of the capsule for clearing away the turbid and tonifying the kidney, which is simple and feasible, extracts the effective components of the raw materials to the maximum extent, improves the drug effect and reduces the dosage of the drug.

The invention also provides a quality standard test method of the capsule for clearing away turbid and tonifying the kidney.

The invention is realized by the following technical scheme:

the preparation method of the capsule for clearing away turbid and tonifying the kidney comprises the following steps: step 1) weighing raw materials, step 2) preparing fine powder of the cordyceps sinensis, step 3) preparing an astragalus extract, step 4) preparing a salvia miltiorrhiza extract, step 5) preparing a safflower extract, step 6) preparing a spina date seed and dodder seed rhubarb extract, and step 7) granulating.

Specifically, the preparation method comprises the following steps: step 1) weighing raw materials: weighing the following raw materials for later use: 100g of cordyceps sinensis, 1400g of astragalus membranaceus, 280g of salvia miltiorrhiza, 280g of safflower, 280g of spina date seeds, 500g of semen cuscutae and 100g of rheum officinale;

step 2) preparing fine winter-spring cordyceps powder: pulverizing Cordyceps into fine powder;

step 3) preparing the astragalus extract: pulverizing radix astragali, sieving with 200 mesh sieve, placing in a container, adding 85% (v/v) ethanol twice the weight of radix astragali, stirring and extracting at 300rpm, controlling microwave power at 500W during extraction process, and extracting for 60 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 A with density of 1.3 g/ml;

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 120min, boiling for 5min, adding absolute ethyl alcohol with twice weight of the filter residue, stirring at 300rpm for 5min, standing for 12h, removing supernatant, collecting precipitate, dissolving in water, standing at-20 ℃ for 12h, centrifuging at 3000rpm for 3min, filtering to remove precipitate, and concentrating the filtrate under reduced pressure to obtain extract B with density of 1.3 g/ml; mixing the extract A and the extract B to obtain an astragalus extract;

step 4), preparing the salvia miltiorrhiza extract: pulverizing Saviae Miltiorrhizae radix, sieving with 200 mesh sieve, spreading into 3mm thick flat layer, irradiating under ultraviolet for 15min, collecting powder, placing in a container, adding water twice the weight of the powder, stirring at 300rpm, extracting, controlling microwave power at 700W during extraction, and extracting for 20 min; filtering, collecting filtrate, and concentrating to obtain extract of 1.3g/ml to obtain Saviae Miltiorrhizae radix extract;

step 5) preparing a safflower extract: putting Carthami flos into ultrasonic extraction tank, adding 75% ethanol with three times weight, controlling extraction temperature at 50 deg.C, performing ultrasonic extraction at 50KHz for 30min, filtering, collecting filtrate, and concentrating to obtain extract of 1.3g/ml to obtain Carthami flos extract;

step 6) preparing the spina date seed, the dodder seed and the rhubarb extract: mixing semen Ziziphi Spinosae and semen Cuscutae to obtain mixture of semen Ziziphi Spinosae and semen Cuscutae, decocting with water twice, adding 10 times of water, decocting for 2 hr, and filtering to obtain filtrate and residue; adding rhubarb into the medicine residues, then adding water which accounts for 5 times of the weight of the mixture of the spina date seeds and the south dodder seeds, decocting for 1.5 hours, 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 semen Ziziphi Spinosae and semen Cuscutae radix et rhizoma Rhei extract;

step 7) granulation: mixing the radix astragali extract obtained in step 3), the radix Salviae Miltiorrhizae extract obtained in step 4), the flos Carthami extract obtained in step 5), the semen Ziziphi Spinosae, semen Cuscutae, radix Et rhizoma Rhei extract obtained in step 6) and the Cordyceps fine powder obtained in step 2), drying, pulverizing, adding appropriate amount of starch, mixing, and making into capsule.

Preferably, the ultraviolet intensity is 3000uW/cm²。

Quality standard test method of the capsule preparation prepared by the preparation method.

The method should detect Cordyceps, protocatechuic aldehyde and radix et rhizoma Rhei, and the content of astragaloside IV in each granule should be not less than 0.30 mg.

Compared with the prior art, the invention has the following advantages and effects:

the effect of the clear turbid kidney-tonifying capsule preparation prepared by the invention is superior to that of the existing preparation, and the dosage is correspondingly reduced; the preparation method 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; the preparation method of the invention adopts smaller grain diameter to improve the leaching rate of the effective components of the astragalus, and can obtain glycoside compounds and polysaccharides by matching with a microwave alcohol extraction mode, thereby avoiding the loss of the components; when the salvia miltiorrhiza is extracted, the phenolic acid and ketone substances are easily decomposed by adopting a decoction mode, the extraction process of the salvia miltiorrhiza adopts ultraviolet rays with proper intensity, so that the dissolution rate of the effective ingredients is improved, and simultaneously, the microwave-assisted water extraction is adopted, so that the time is short, the extraction efficiency is improved, and the energy consumption is reduced; the chlorogenic acid and other acid substances and phenolic effective substances in the safflower are not easy to decoct, and the alcohol extraction method is adopted, so that the effective components are reserved.

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

The preparation method of the capsule for clearing away turbid and tonifying the kidney comprises the following steps:

1) weighing the following raw materials for later use: 100g of cordyceps sinensis, 1400g of astragalus membranaceus, 280g of salvia miltiorrhiza, 280g of safflower, 280g of spina date seeds, 500g of semen cuscutae and 100g of rheum officinale;

2) pulverizing Cordyceps into fine powder;

3) pulverizing radix astragali, sieving with 200 mesh sieve, placing in a container, adding 85% (v/v) ethanol twice the weight of radix astragali, stirring and extracting at 300rpm, controlling microwave power at 500W during extraction process, and extracting for 60 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 A with density of 1.3 g/ml; testing the content of astragaloside in the extract A to be more than 1.2mg/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 120min, boiling for 5min, adding absolute ethyl alcohol with twice weight of the filter residue, stirring at 300rpm for 5min, standing for 12h, removing supernatant, collecting precipitate, dissolving in water, standing at-20 ℃ for 12h, centrifuging at 3000rpm for 3min, filtering to remove precipitate, and concentrating the filtrate under reduced pressure to obtain extract B with density of 1.3 g/ml; mixing the extract A and the extract B to obtain an astragalus extract; the molecular weight of the astragalus polysaccharide in the extract B is mostly distributed in 20000-40000 and accounts for more than 70 percent of the total sugar by adopting gel chromatography;

4) pulverizing Saviae Miltiorrhizae radix, sieving with 200 mesh sieve, spreading into 3mm thick flat layer, irradiating under ultraviolet for 15min, collecting powder, placing in a container, adding water twice the weight of the powder, stirring at 300rpm, extracting, controlling microwave power at 700W during extraction, and extracting for 20 min; filtering, collecting filtrate, and concentrating to obtain extract of 1.3g/ml to obtain Saviae Miltiorrhizae radix extract; the ultraviolet intensity is 3000uW/cm²；

5) Putting safflower into an ultrasonic extraction tank, adding 75% (volume parts) of ethanol with three times of weight, controlling the extraction temperature at 50 ℃, carrying out ultrasonic extraction for 30min at the frequency of 50KHz, filtering, collecting filtrate, and concentrating into 1.3g/ml extract to obtain safflower extract;

6) mixing semen Ziziphi Spinosae and semen Cuscutae to obtain mixture of semen Ziziphi Spinosae and semen Cuscutae, decocting with water twice, adding 10 times of water, decocting for 2 hr, and filtering to obtain filtrate and residue; adding rhubarb into the medicine residues, then adding water which accounts for 5 times of the weight of the mixture of the spina date seeds and the south dodder seeds, decocting for 1.5 hours, 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, concentrating into extract with density of 1.3g/ml to obtain semen Ziziphi Spinosae and semen Cuscutae radix et rhizoma Rhei extract;

7) mixing the radix astragali extract obtained in step 3), the radix salviae miltiorrhizae extract obtained in step 4), the safflower extract obtained in step 5), the spina date seed, semen cuscutae and rheum officinale extract obtained in step 6) and the cordyceps sinensis fine powder obtained in step 2), drying, crushing, adding a proper amount of starch, mixing uniformly, and encapsulating to prepare 1000 granules.

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 capsule for treating nephrotic syndrome is prepared from the following raw materials by weight: 100g of cordyceps sinensis, 1400g of astragalus membranaceus, 280g of salvia miltiorrhiza, 280g of safflower, 280g of spina date seeds, 500g of semen cuscutae and 100g of rheum officinale.

The preparation method of the capsule for clearing away turbid and tonifying the kidney comprises the following steps: weighing the raw materials according to 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 10 times of water for the first time, decocting for 1.5 hr, and filtering to obtain filtrate and residue;

(3) adding rhubarb into the dregs obtained in the step (2), adding 8 times of water into the dregs, decocting the dregs for 1 hour, and filtering the decoction to obtain filtrate

(4) Mixing the filtrates of step (2) and step (3), concentrating into fluid extract with relative density of 1.14-1.16 (80-85 deg.C), cooling, adding ethanol to make ethanol content reach 70% (volume fraction), standing for 24 hr, filtering, collecting supernatant, and recovering ethanol.

(5) Decocting semen Cuscutae in water twice, adding 10 times of water for the first time, decocting for 1.5 hr, filtering to obtain filtrate and residue, decocting the residue in 8 times of water for 1 hr, and mixing the filtrates.

(6) And (3) combining the filtrate obtained in the step (5) and the supernatant obtained in the step (4), concentrating the mixture to thick paste with the relative density of 1.30-1.35(80-85 ℃), adding the fine powder prepared in the step (1), uniformly mixing, drying, crushing, adding a proper amount of starch, uniformly mixing, and encapsulating to prepare 1000 capsules.

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

Example 2

Quality standards and inspection methods for the finished product prepared in example 1:

example 3

Animal safety test

40 healthy Kunming strain mice with the male and female halves and the body weight of 18.9 +/-2.3 g are randomly divided into two groups, wherein each group has the male and female halves, 20 of the mice are control groups, and normal water is filled in the control groups; in addition, 20 mice were administered with the drug prepared by the preparation method of example 1 at a dose of 2 mg/mouse three times a day, and acute 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. Within two weeks after administration, no animal death is found, which indicates that the medicine has low acute toxicity and safe clinical administration.

Example 4

Clinical data

Selecting 2015 3-2016 9-month-old 108 patients admitted to the hospital, wherein 61 men and 47 women are in the group, the age is 32-73 years, and the average age is 43.1 years; the course of the disease is 2 months to 28 months, patients are randomly divided into 2 groups, 54 persons in example 1 group, and 54 persons in control 1 group. Inclusion criteria and therapeutic efficacy criteria reference CN 103638135A:

the treatment method comprises the following steps:

example 1 group: the medicine prepared in example 1 is taken 3 times a day 3 times, 4 weeks are a treatment course, and 2 treatment courses are treated.

Control example 1 group: the medicines prepared in the group of the control example 1 were taken 4 capsules at a time, 3 times a day, 4 weeks as a treatment course, and 2 treatment courses were performed.

The therapeutic effects are shown in the following table 2:

TABLE 2

Group of	Cure of disease	Improvement of life	Not cured	Cure rate
					EXAMPLE 1 group	41	11	2	75.92%
Comparative example 1 group	30	18	6	55.56%

And (4) conclusion: the cure rate of the composition of example 1 is significantly higher than that of the composition of control 1, and the dosage is reduced by one fourth.

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 (2)

1. The preparation method of the capsule for clearing away turbid and tonifying the kidney comprises the following steps:

step 1) weighing raw materials: 100g of cordyceps sinensis, 1400g of astragalus membranaceus, 280g of salvia miltiorrhiza, 280g of safflower, 280g of spina date seeds, 500g of semen cuscutae and 100g of rheum officinale;

step 2) preparing fine winter-spring cordyceps powder: pulverizing Cordyceps into fine powder;

step 3) preparing the astragalus extract: pulverizing radix astragali, sieving with 200 mesh sieve, placing in a container, adding 85% v/v ethanol twice the weight of radix astragali, stirring and extracting at 300rpm, controlling microwave power at 500W during extraction process, and extracting for 60 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 A with density of 1.3 g/ml;

adding water with twice weight of the filter residue, stirring uniformly, adding 0.5wt% of neutral protease, performing enzymolysis at 37 ℃ for 120min, boiling for 5min, adding absolute ethyl alcohol with twice weight of the filter residue, stirring at 300rpm for 5min, standing for 12h, removing supernatant, collecting precipitate, dissolving with water, standing at-20 ℃ for 12h, centrifuging at 3000rpm for 3min, filtering to remove precipitate, and concentrating the filtrate under reduced pressure to obtain extract B with density of 1.3 g/ml; mixing the extract A and the extract B to obtain an astragalus extract;

step 4), preparing the salvia miltiorrhiza extract: pulverizing Saviae Miltiorrhizae radix, sieving with 200 mesh sieve, spreading into 3mm thick flat layer, irradiating under ultraviolet for 15min, collecting powder, placing in a container, adding water twice the weight of the powder, stirring at 300rpm, extracting, controlling microwave power at 700W during extraction, and extracting for 20 min; filtering, collecting filtrate, and concentrating to obtain extract of 1.3g/ml to obtain Saviae Miltiorrhizae radix extract;

step 5) preparing a safflower extract: putting Carthami flos into ultrasonic extraction tank, adding 75% ethanol with three times weight, ultrasonic extracting at 50 deg.C for 30min, filtering, collecting filtrate, and concentrating to obtain extract of 1.3g/ml to obtain Carthami flos extract;

step 6) preparing the spina date seed, the dodder seed and the rhubarb extract: mixing semen Ziziphi Spinosae and semen Cuscutae to obtain mixture of semen Ziziphi Spinosae and semen Cuscutae, decocting with water twice, adding 10 times of water, decocting for 2 hr, and filtering to obtain filtrate and residue; adding rhubarb into the medicine residues, then adding water which accounts for 5 times of the weight of the mixture of the spina date seeds and the south dodder seeds, decocting for 1.5 hours, and filtering to obtain filtrate; mixing the above two filtrates, concentrating into fluid extract with density of 1.1g/ml, cooling, adding ethanol, standing for 24 hr, filtering, collecting supernatant, recovering ethanol under reduced pressure, and concentrating into extract with density of 1.3g/ml to obtain semen Ziziphi Spinosae and semen Cuscutae radix et rhizoma Rhei extract;

step 7) granulation: mixing the radix astragali extract obtained in step 3), the radix Salviae Miltiorrhizae extract obtained in step 4), the flos Carthami extract obtained in step 5), the semen Ziziphi Spinosae, semen Cuscutae, radix Et rhizoma Rhei extract obtained in step 6) and the Cordyceps fine powder obtained in step 2), drying, pulverizing, adding appropriate amount of starch, mixing, and making into capsule.

2. The method according to claim 1, wherein the ultraviolet intensity is 3000uW/cm²。