阅读说明：本技术 黄连配方颗粒及其制备方法和用途 (Coptis prescription granule and preparation method and application thereof ) 是由 王伯綸 于 2018-08-30 设计创作，主要内容包括：本发明属于中药配方领域,公开了黄连配方颗粒及其制备方法和用途。黄连配方颗粒包含活性成分黄连和药学上可接受的辅料,其中黄连的含量为250～800mg/g,黄连配方颗粒中的小檗碱含量为6.0～8.0wt％,表小檗碱、黄连碱和巴马汀的总量为3.0～5.0wt％。其由黄连配方颗粒中间体与辅料混匀、制粒,制备得到。本发明采用喷雾干燥、干法制粒工艺,严格控制工艺步骤参数,提升了黄连饮片的出膏率,制成的配方颗粒中有效成分含量高。颗粒成品质量优异,产品质量符合《中国药典》规定。(The invention belongs to the field of traditional Chinese medicine formulas, and discloses coptis formula granules as well as a preparation method and application thereof. The coptis prescription granule contains an active ingredient coptis and pharmaceutically acceptable auxiliary materials, wherein the content of the coptis is 250-800 mg/g, the content of berberine in the coptis prescription granule is 6.0-8.0 wt%, and the total amount of epiberberine, berberine and palmatine is 3.0-5.0 wt%. The rhizoma coptidis granule intermediate is uniformly mixed with auxiliary materials and granulated to prepare the rhizoma coptidis granule. The invention adopts spray drying and dry granulation processes, strictly controls the process step parameters, improves the paste yield of the coptis decoction pieces, and has high content of effective components in the prepared formula granules. The quality of the finished granular product is excellent, and the product quality conforms to the regulation of Chinese pharmacopoeia.)

1. The coptis chinensis formula particle comprises an active ingredient coptis chinensis and pharmaceutically acceptable auxiliary materials, wherein the content of the coptis chinensis is 250-800 mg/g; preferably, the pharmaceutically acceptable excipient comprises one, two or more fillers.

2. The coptis chinensis formula particle according to claim 1, wherein berberine (C) in the coptis chinensis formula particle₂₀H₁₈ClNO₄) The content is 6.0-8.0 wt%;

preferably, epiberberine (C) in the coptis formulation granules₂₀H₁₇NO₄) Coptisine (C)₁₉H₁₃NO₄) And palmatine (C)₂₁H₂₁NO₄) The total amount of (A) is 3.0-5.0 wt%;

preferably, the content of water in the coptis chinensis formula particles is 5.5-8.0 wt%;

preferably, the content of alcohol-soluble extract of the coptis formulation granule is not less than 31.0 wt%;

preferably, the granularity of the coptis chinensis formula particles is 10-100 meshes.

3. The coptis formulation granule according to claim 1, further comprising a packaging bag or a box containing the granule;

preferably, the coptis chinensis formula particle is equivalent to 2g of coptis chinensis decoction pieces per 1g of formula particle.

4. A method for preparing the coptis formulation granule according to any one of claims 1 to 3, comprising: mixing the rhizoma Coptidis formula granule intermediate with adjuvants, and granulating to obtain rhizoma Coptidis formula granule;

preferably, the preparation method of the coptis chinensis formula particle specifically comprises the following steps:

(1) preparing an intermediate of the coptis chinensis formula granules: soaking Coptidis rhizoma decoction pieces, decocting, filtering, concentrating the filtrate to obtain fluid extract, adding adjuvants into the fluid extract, mixing, and spray drying to obtain Coptidis rhizoma granule intermediate;

(2) preparing the coptis chinensis formula granules: and mixing the intermediate and auxiliary materials uniformly, and performing dry granulation to obtain a finished product.

5. The preparation method according to claim 4, wherein in the step (1), the coptis chinensis decoction pieces are added into water during soaking, and the mass ratio of the coptis chinensis decoction pieces to the water is 1 (8-15); the soaking time is 20-40 minutes;

preferably, the relative density of the clear paste is 1.05-1.25;

preferably, the mass ratio of the clear paste to the auxiliary materials is 1 (1-3);

preferably, the temperature of the spray drying is: the air inlet temperature is 115-130 ℃, and the air outlet temperature is 80-95 ℃.

6. The method according to claim 4 or 5, wherein berberine (C) is contained in the intermediate of the Coptis chinensis Franch granules₂₀H₁₈ClNO₄) The content is 9.0-11.0 wt%;

preferably, epiberberine (C) in the coptis formulation granules₂₀H₁₇NO₄) Coptisine (C)₁₉H₁₃NO₄) And palmatine (C)₂₁H₂₁NO₄) The total amount of (A) is 5.0-6.5 wt%;

preferably, the moisture content of the coptis chinensis formula granule intermediate is not more than 6.0 wt%;

preferably, the content of alcohol-soluble extract of the coptis chinensis granule intermediate is not less than 38.0 wt%.

7. The preparation method according to any one of claims 4 to 6, characterized in that in the step (2), the mass ratio of the intermediate to the auxiliary materials is (1-4): 1;

preferably, the dry granulation is performed by rolling, continuously compacting the material blocks, granulating and sieving to obtain finished granules;

preferably, the operating conditions of the dry granulation are: the roller pressure is 2-3 MPa, the tabletting frequency is 16-25 Hz, and the feeding frequency is 12-18 Hz.

8. The preparation method according to any one of claims 4 to 7, further comprising the step (3) of preparing a coptis chinensis standard decoction: soaking, decocting and filtering rhizoma Coptidis decoction pieces, concentrating the filtrate, and freeze drying to obtain lyophilized powder as standard decoction;

preferably, the method further comprises the step (4) of packaging: and (3) sealing and packaging the coptis chinensis formula particles obtained in the step (2).

9. A formulation comprising the coptis formulation granules as claimed in any one of claims 1 to 3.

10. Use of the coptis formulation granules according to any one of claims 1 to 3 for preparing a compound medicine.

Technical Field

The invention belongs to the technical field of traditional Chinese medicine formula granules, and particularly relates to a coptis formula granule as well as a preparation method and application thereof.

Background

The Coptidis rhizoma is dry rhizome of Coptis chinensis Franch of Ranunculaceae, and is called as "Weilian". The processing should meet the related regulations of Huanglian tablets in the section of "Chinese pharmacopoeia" 2015 edition. The coptis root clears heat and dries dampness, and purges fire and detoxifies; can be used for treating damp-heat distention and fullness, emesis, acid regurgitation, dysentery, jaundice, hyperpyrexia, excessive heart-fire, vexation, insomnia, palpitation, blood heat, deep mandrill, conjunctival congestion, toothache, diabetes, carbuncle, swelling, and furuncle; it is used externally to treat eczema, eczema and purulent ear canal.

The traditional Chinese medicine formula granule is prepared by taking traditional Chinese medicine decoction pieces processed according to specifications as raw materials under the guidance of traditional Chinese medicine theory. The Chinese medicinal composition can be clinically and flexibly prepared and taken after being mixed with water, can also be used as an industrial raw material of a Chinese medicinal preparation, and provides a new way for clinical medication of Chinese medicaments. Compared with the traditional Chinese medicine decoction, the formula granules can be directly used for blending the traditional Chinese medicine clinical prescription, and the patient can directly take the formula granules with water according to the prescribed dosage of the prescription, so that the traditional Chinese medicine decoction is convenient to take, small in dosage, controllable in quality, easy to store and convenient to carry.

Disclosure of Invention

The invention provides a coptis chinensis formula particle which comprises an active ingredient coptis chinensis and pharmaceutically acceptable auxiliary materials, wherein the content of the coptis chinensis is 250-800 mg/g, preferably 300-700 mg/g, and more preferably 300-600 mg/g.

According to the invention, berberine (C) in the coptis formulation granules₂₀H₁₈ClNO₄) The content is 6.0 to 8.0 wt%, for example, the content is 6.5 to 7.5 wt%; illustratively, the content is 6.6 wt%, 6.7 wt%, 7.1 wt%.

According to the invention, the epiberberine (C) in the coptis formulation granules₂₀H₁₇NO₄) Coptisine (C)₁₉H₁₃NO₄) And palmatine (C)₂₁H₂₁NO₄) The total amount of (A) is 3.0 to 5.0 wt%, for example 3.5 to 4.5 wt%; illustratively, the total amount is 3.6 wt%, 3.8 wt%, 3.9 wt%, 4.0 wt%, 4.1 wt%, 4.2 wt%.

According to the invention, the content of water in the coptis formula granules is 5.5-8.0 wt%, for example, the content is 5.9-7.2 wt%; illustratively, the content is 5.9 wt%, 6.3 wt%, 6.9 wt%.

According to the present invention, the content of alcohol-soluble extract of the coptis formulation granule is not less than 31.0 wt%, for example not less than 31.5 wt%, such as 31.6-33.9 wt%.

According to the present invention, the pharmaceutically acceptable excipients include one, two or more fillers, for example, at least one selected from the group consisting of starch, dextrin, sucrose, lactose, mannitol, xylitol and a bifidobacterium; preferably, the filler is selected from starch, dextrin, sucrose or lactose; illustratively, the filler is selected from dextrins.

According to the invention, the granularity of the coptis chinensis formula particles is 10-100 meshes, such as 10-80 meshes and 30-50 meshes. Preferably, the total amount of the yam formula particles which can not pass through a No. 1 sieve (10 meshes) and can pass through a No. 5 sieve (80 meshes) does not exceed 15 percent of the test amount; e.g., no more than 10%, 5%; preferably, between 3.2 and 4.6%.

According to the present invention, the coptis chinensis formula granule further comprises a packaging bag or a packaging box, such as a composite film bag, for containing the granule; illustratively, the composite film bag may be selected from composite aluminum foil bags.

According to the invention, the specification of the coptis chinensis formula particle is that every 1g of formula particle is equivalent to 2g of coptis chinensis decoction pieces.

According to the present invention, the packaging specification of the coptis formulation granule can have various specifications, such as 1-20 g, and exemplarily, the specification is 1g, 1.5g, 2g, 3g, 5g, 10g, 15g, 20 g.

Further, the invention also provides a preparation method of the coptis chinensis formula granules, which comprises the following steps: and mixing the rhizoma coptidis formula granule intermediate with auxiliary materials, and granulating to obtain the rhizoma coptidis formula granule.

According to the preparation method, the coptis chinensis formula granule intermediate is obtained through the following steps: adding adjuvants into the fluid extract, mixing, and spray drying to obtain Coptidis rhizoma granule intermediate.

According to the preparation method of the invention, the clear paste is obtained by the following steps: the coptis decoction pieces are soaked, decocted and filtered, and the filtrate is concentrated to obtain clear paste.

According to an embodiment of the present invention, the method for preparing the coptis chinensis formula granules specifically comprises the following steps:

(1) preparing an intermediate of the coptis chinensis formula granules: soaking Coptidis rhizoma decoction pieces, decocting, filtering, concentrating the filtrate to obtain fluid extract, adding adjuvants into the fluid extract, mixing, and spray drying to obtain Coptidis rhizoma granule intermediate;

(2) preparing the coptis chinensis formula granules: and mixing the intermediate and auxiliary materials uniformly, and performing dry granulation to obtain a finished product.

According to the preparation method, in the step (1), the coptis chinensis decoction pieces are added into water during soaking, and the mass ratio of the coptis chinensis decoction pieces to the water is 1 (8-15); preferably, the mass ratio is 1 (8-12); illustratively, the mass ratio is 1: 10;

the soaking time is 20-40 minutes, preferably 25-35 minutes, and exemplarily 30 minutes;

the water is preferably purified water, such as distilled water, deionized water or pharmaceutical water prepared by reverse osmosis.

According to the preparation method of the present invention, in the step (1), the decoction and filtration are performed at least twice cyclically, for example, twice, three times or more cyclically; before decocting, heating water to boil, and then decocting with slow fire;

illustratively, when the decoction and filtration are circularly operated twice, the first decoction is carried out for 20-40 minutes, preferably 25-35 minutes, illustratively 30 minutes, and then filtration is carried out to obtain a filtrate I and a residue I; in the second decoction, water is added into the residue I, wherein the amount of the water is 7-10 times, for example 8 times, the weight of the coptis chinensis decoction pieces, the decoction is carried out for 20-40 minutes, preferably 25-35 minutes, for example 30 minutes, and then the decoction is filtered to obtain filtrate II and residue II.

According to the preparation method, in the step (1), the hot filtering is carried out, preferably, the hot filtering is carried out by using a 80-120-mesh sieve, for example, a 80-mesh sieve, a 100-mesh sieve and a 120-mesh sieve.

According to the preparation method of the invention, in the step (1), the filtrate is a combination of filtrates obtained by multiple times of filtration, for example, a combination of filtrate one and filtrate two.

According to the preparation method of the invention, in the step (1), the concentration mode preferably adopts reduced pressure concentration. Preferably, the relative density of the clear paste is 1.05-1.25, preferably, the relative density is 1.05-1.10, such as 1.05, 1.08, 1.10; the relative density of the clear paste is measured at the temperature of 60-70 ℃, preferably at the temperature of 65 ℃.

According to the preparation method, in the step (1), the mass ratio of the clear paste to the auxiliary materials is 1 (1-3), such as 1:1, 1:2 and 1: 3.

According to the preparation method of the invention, in the step (1), the temperature of the spray drying is as follows: the air inlet temperature is 115-130 ℃, and the air outlet temperature is 80-95 ℃; preferably, the air inlet temperature is 120-130 ℃, and the air outlet temperature is 85-95 ℃; illustratively, the inlet air temperature is 127 ℃ and the outlet air temperature is 90 ℃.

According to the preparation method of the invention, berberine (C) in the intermediate of the coptis prescription granule₂₀H₁₈ClNO₄) 9.0 to 11.0 wt%, for example, 95 to 10.5 wt%; illustratively, the content is 9.6 wt%, 10.2 wt%, 10.4 wt%.

According to the preparation method of the invention, the epiberberine (C) in the rhizoma coptidis formula granule intermediate₂₀H₁₇NO₄) Coptisine (C)₁₉H₁₃NO₄) And palmatine (C)₂₁H₂₁NO₄) The total amount of (A) is 5.0-6.5 wt%, for example 5.3-6.0 wt%; illustratively, the total amount is 5.5 wt%, 5.6 wt%, 5.7 wt%, 5.8 wt%, 6.0 wt%.

According to the preparation method of the invention, the moisture content of the coptis chinensis formula granule intermediate is not more than 6.0 wt%, for example, the content is not more than 5.0 wt%; preferably, the content is 3.1 to 3.6 wt%.

According to the preparation method of the invention, the alcohol-soluble extract content of the rhizoma coptidis formula granule intermediate is not less than 38.0 wt%, for example not less than 40.0 wt%, such as 41.9-44.1 wt%.

According to the preparation method, in the step (2), the mass ratio of the intermediate to the auxiliary materials is (1-4) to 1, such as (1.5-4) to 1; exemplarily, the mass ratio is 2:1, 3:1 and 4: 1.

According to the preparation method of the invention, in the step (2), the uniformly mixed clear paste and the auxiliary materials are sieved before spray drying, preferably, the sieved clear paste and the auxiliary materials are sieved by a sieve of 80-120 meshes, for example, a sieve of 80 meshes, a sieve of 100 meshes and a sieve of 120 meshes.

According to the preparation method of the invention, in the step (2), the dry granulation can adopt the conventional operation in the field, firstly, the material block is continuously compacted by rolling, and the finished product of the granules is obtained after the material block is sized and sieved;

wherein, the operation conditions of the dry granulation are as follows: the roller pressure is 2-3 MPa, the tabletting frequency is 16-25 Hz, and the feeding frequency is 12-18 Hz. For example, the roller pressure is 2.3-2.7 MPa, the tabletting frequency is 18-22 Hz, and the feeding frequency is 13-16 Hz. Illustratively, the roll pressure is 2.5MPa, the sheeting frequency is 20Hz, and the feed frequency is 15 Hz.

Wherein the sieving is to sieve by a sieve of 10-30 meshes; preferably through a 20 mesh screen.

According to the preparation method of the invention, the method also comprises the step (3) of preparing the coptis chinensis standard decoction.

The step (3) specifically comprises the following operations: soaking, decocting and filtering rhizoma Coptidis decoction pieces, concentrating the filtrate, and freeze drying to obtain lyophilized powder as standard decoction;

wherein the operations of soaking, decocting and filtering are the same as the operations in the step (1);

wherein the filtrate is concentrated to a relative density of 1.10-1.25; preferably, the relative density is 1.12-1.15, 1.20-1.25, such as 1.11, 1.13, 1.15; the relative density is measured at a temperature of 60 to 70 ℃, preferably at a temperature of 65 ℃.

Preferably, the concentration is performed by low-temperature reduced pressure concentration.

Wherein the freeze-drying conditions are as follows: the temperature is-50-45 ℃, and the vacuum degree is 5-50 Pa; preferably, the temperature is-40 to 15 ℃, and the vacuum degree is 10 to 30 Pa; illustratively, the temperature is-25 ℃ and the vacuum is 10 Pa.

According to the preparation method of the invention, the method further comprises the following steps (4) of packaging: sealing and packaging the coptis chinensis formula particles obtained in the step (2); preferably, the packaging may use a packaging bag or box, such as a composite film bag; illustratively, the composite film bag may be selected from composite aluminum foil bags.

Furthermore, the invention also provides the coptis chinensis formula granules prepared by the preparation method.

Furthermore, the invention also provides a preparation which comprises the coptis chinensis formula granules.

Furthermore, the invention also provides application of the coptis chinensis formula granules in preparation of composite medicines.

The invention has the beneficial effects that:

1. the spray drying and dry granulation processes are adopted, the process step parameters are strictly controlled, the cream yield of the coptis chinensis decoction pieces and the transfer rate and content of berberine hydrochloride, epiberberine, coptisine and palmatine are improved, and the prepared formula granules have high content of effective components and small dosage.

2. The finished product quality of the coptis prescription granule is excellent, and the product quality accords with the regulation of Chinese pharmacopoeia, which is specifically shown in the following steps: the granule has uniform particle size, high alcohol-soluble extract content, low content of impurities and fungi (aerobic bacteria, fungi and saccharomycetes, Escherichia coli, etc.), high product stability, and easy storage.

3. The method has simple and reasonable process and is suitable for popularization to large-scale production.

Drawings

FIG. 1 is a flow chart of the preparation process of the Coptis formulation granule according to example 1 of the present invention.

Detailed Description

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are only for illustrating the present invention and are not intended to limit the scope of the present invention. After reading the disclosure of the present invention, one skilled in the art can make various changes or modifications to the invention, and such equivalents fall within the scope of the invention.

Unless otherwise indicated, the starting materials, substrates or reagents in the following examples are all commercially available products. They may, if appropriate, also be prepared by methods known in the art.

Instrument information:

bamboo Shuixi FT-30H type full-automatic decocting pot (Shenzhen Zhengyun science and technology Limited);

RE-5205 rotary evaporator (Shanghai Yangrong Biochemical Instrument factory);

SCIENTZ-50F lyophilizer (Ningbo Xinzhi Biotech Co., Ltd.);

a multifunctional extraction testing machine (Hangzhou Chunjiang automation research institute);

LPG-8 spray dryer (okay drying equipment ltd, yozhou);

JSG-20 dry granulator (Wuyi gold stone pharmaceutical machinery Co., Ltd.).

Preparation example 1 preparation and measurement of coptis chinensis standard decoction

Preparing a coptis chinensis standard decoction: weighing three batches of coptis chinensis traditional Chinese medicine decoction pieces, respectively weighing 200g of each coptis chinensis traditional Chinese medicine decoction piece, adding 10 times of water, soaking for 30 minutes, heating to boiling, decocting for 30 minutes, filtering while hot (No. 6 sieve, 100 meshes), adding 8 times of water into decoction dregs, decocting for 30 minutes after boiling, filtering while hot (No. 6 sieve, 100 meshes), combining two filtrates (determining the paste rate), concentrating at low temperature under reduced pressure to obtain clear paste with the relative density of 1.20-1.25 (65 ℃), freeze-drying the clear paste (the temperature is-50-45 ℃ and the vacuum degree is 10Pa) to prepare freeze-dried powder serving as standard decoction samples (the batches are marked as 1, 2 and 3) for later use.

(1) And (3) measuring the cream yield of the standard decoction: precisely sucking 10ml of each of the three batches of standard decoction samples, drying in an evaporation dish after constant weight in a water bath, drying at 105 ℃ for 3 hours, placing in a dryer for cooling for 30 minutes, precisely weighing, calculating the cream yield and the standard deviation according to the formula (I), and determining the cream yield range of the coptis standard decoction according to 70-130% of the average cream yield. The test results are shown in Table 1-1.

In the formula (I), W is called the net weight (g) of the clear paste, V is the volume (ml) of the clear paste, 10 is the amount (ml) of the liquid medicine, W is the amount of the liquid medicine₁-dosage of decoction pieces (g).

TABLE 1-1. determination of the cream yield of the Coptidis rhizoma Standard decoction

(2) Yield of standard decoction lyophilized powder: weighing the weight of the freeze-dried powder of the standard decoction obtained by freeze drying, and calculating the yield according to a formula (II). The test results are shown in tables 1-2.

In formula (II), W represents the weight (g) of the lyophilized powder, W represents₁-dosage of decoction pieces (g).

TABLE 1-2. yield of lyophilized powder of Coptidis rhizoma standard decoction

(3) Transfer rate of berberine hydrochloride, epiberberine, coptisine and palmatine in standard decoction

According to the method of the item of the first coptis chinensis of the edition of 'Chinese pharmacopoeia' 2015, the content of berberine hydrochloride and the total amount of epiberberine, coptisine and palmatine are measured on a coptis chinensis standard decoction sample and corresponding coptis chinensis decoction pieces, and the transfer rate is calculated. The test results are shown in tables 1-3 and tables 1-4.

TABLE 1-3. test results of berberine hydrochloride transfer rate of Coptidis rhizoma standard decoction

TABLE 1-4. test results of transfer rates of Berberine, coptisine and palmatine in Coptidis rhizoma standard decoction