阅读说明：本技术 地骨皮配方颗粒及其制备方法和用途 (Cortex lycii radicis formula particle 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颗粒技术领域,公开了地骨皮配方颗粒及其制备方法和用途。所述配方颗粒包含活性成分地骨皮和药学上可接受的辅料,其中地骨皮的含量为250～800mg/g,所述药学上可接受的辅料包括一种或多种填充剂。所述配方颗粒由地骨皮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,提升了地骨皮饮片的出膏率,制成的配方颗粒中有效成分含量高,服用量小。颗粒成品质量优异,产品质量符合《中国药典》规定：颗粒粒度均匀,醇溶性浸出物含量高,杂质及菌类(需氧菌总数、霉菌和酵母菌总数、大肠埃希菌等)含量较低,成品稳定性较高,容易保存。(The invention belongs to the technical field of traditional Chinese medicine formula granules, and discloses cortex lycii radicis formula granules as well as a preparation method and application thereof. The formula particle comprises an active ingredient cortex lycii radicis and pharmaceutically acceptable auxiliary materials, wherein the content of the cortex lycii radicis is 250-800 mg/g, and the pharmaceutically acceptable auxiliary materials comprise one or more fillers. The formula particle is prepared by uniformly mixing and granulating a cortex lycii radicis formula particle intermediate and auxiliary materials. The invention adopts spray drying and dry granulation processes, strictly controls the process step parameters, improves the paste yield of the cortex lycii radicis decoction pieces, and the prepared formula granules have high content of effective components and small dosage. The quality of the finished granular product is excellent, and the product quality conforms to the regulation of Chinese pharmacopoeia: 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.)

1. The cortex lycii radicis formula particle is characterized by comprising an active ingredient cortex lycii radicis and pharmaceutically acceptable auxiliary materials, wherein the content of the cortex lycii radicis is 250-800 mg/g;

preferably, the pharmaceutically acceptable excipient comprises one, two or more fillers.

2. The cortex lycii radicis formulation granules according to claim 1, wherein the particle size of the cortex lycii radicis formulation granules is between 10 and 100 mesh;

preferably, the water content of the cortex lycii radicis formula particles is 4.0-5.5 wt%;

preferably, the cortex lycii radicis formulation particles have an alcohol soluble extract of not less than 23.0 wt%.

According to the invention, the specification of the cortex lycii radicis formula particle is equivalent to 3g of cortex lycii radicis decoction pieces per 1g of formula particle.

3. The cortex lycii radicis formulation granulate according to claim 1 or 2, further comprising a packaging bag or a box containing the granulate.

4. A method of preparing a cortex lycii radicis formulation granulate according to any of claims 1 to 3, characterised in that it comprises: mixing the intermediate of the cortex lycii radicis formula particle with auxiliary materials, and granulating to obtain cortex lycii radicis formula particles;

preferably, the preparation method of the cortex lycii radicis formula particle specifically comprises the following steps:

(1) preparation of cortex lycii radicis formula particle intermediate: soaking cortex Lycii decoction pieces, decocting, filtering, concentrating the filtrate to obtain fluid extract, adding adjuvants into the fluid extract, mixing, and spray drying to obtain cortex Lycii granule intermediate;

(2) preparation of cortex lycii radicis formula granules: and mixing the intermediate and auxiliary materials uniformly, and performing dry granulation to obtain a finished product.

5. The method of claim 4, wherein the moisture content of the intermediate of cortex Lycii granules is no more than 8 wt%;

preferably, the content of alcohol-soluble extract of cortex lycii radicis formula particle intermediate is not less than 33.0 wt%;

preferably, in the step (1), during soaking, cortex lycii radicis decoction pieces are added into water, and the mass ratio of the cortex lycii radicis decoction pieces to the water is 1 (10-15); 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 (1-2) to (1-2);

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 preparation method according to claim 4 or 5, wherein in the step (2), the mass ratio of the intermediate to the auxiliary materials is (3-9): 1-2); and sieving the uniformly mixed clear paste and auxiliary materials before spray drying, wherein the dry granulation can adopt the conventional operation in the field, firstly rolling, continuously compacting material blocks, and granulating and sieving to obtain the finished product of granules.

7. The method according to any one of claims 4 to 6, further comprising the step of (3) preparing a standard decoction of cortex Lycii: soaking cortex Lycii decoction pieces, decocting, filtering, concentrating the filtrate, and lyophilizing to obtain lyophilized powder as standard decoction.

8. The method for preparing a cosmetic composition according to any one of claims 4 to 7, further comprising the step of (4) packaging: and (3) hermetically packaging the cortex lycii radicis formula particles obtained in the step (2).

9. A formulation comprising the cortex lycii radicis formulation particles according to any one of claims 1 to 3.

10. Use of the cortex lycii radicis formulation granules according to any one of claims 1 to 3 for the preparation of a compound medicament.

Technical Field

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

Background

Cortex Lycii is dried root bark of Lycium chinense Mill or Lycium barbarum L of Lycium barbarum of Solanaceae. Digging root in early spring or after autumn, cleaning, peeling root bark, and sun drying. Cortex Lycii has effects of cooling blood, removing heat, clearing lung-heat, and lowering fire; can be used for treating hectic fever due to yin deficiency, hectic fever, night sweat, cough due to lung heat, hemoptysis, epistaxis, internal heat, and diabetes.

The traditional Chinese medicine formula granule is a granule 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 cortex lycii radicis formula particle which comprises an active ingredient cortex lycii radicis and pharmaceutically acceptable auxiliary materials, wherein the content of the cortex lycii radicis is 250-800 mg/g, preferably 300-700 mg/g, and more preferably 300-600 mg/g.

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 cortex lycii radicis formula particles is 10-100 meshes, such as 10-80 meshes and 30-50 meshes. Preferably, the total amount of the granules 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 invention, the moisture content of the cortex lycii radicis formula particles is between 4.0 and 5.5 wt%; for example, 4.5 to 5.2 wt%, 4.7 to 5.0 wt%.

According to the invention, the alcohol-soluble extract of the cortex lycii radicis formula granules is not less than 23.0 wt%; for example, not less than 24.0 wt%, not less than 26.0 wt%; preferably, the cortex lycii radicis formula particle has an alcohol-soluble extract content of 23.5-24.6 wt%.

According to the present invention, the cortex lycii radicis formulation granules further comprise a packaging bag or box, such as a composite film bag, containing the granules; illustratively, the composite film bag may be selected from composite aluminum foil bags.

According to the invention, the specification of the cortex lycii radicis formula particle is equivalent to 3g of cortex lycii radicis decoction pieces per 1g of formula particle.

According to the invention, the packaging specification of the cortex lycii radicis formulation granules may have various specifications, for example 1-20 g, exemplarily 1g, 2g, 3g, 5g, 6g, 9g, 10g, 12g, 15g, 20 g.

Further, the invention also provides a preparation method of the cortex lycii radicis formula particle, which comprises the following steps: and mixing the intermediate of the cortex lycii radicis formula particle with auxiliary materials, and granulating to obtain the cortex lycii radicis formula particle.

According to the preparation method, the cortex lycii radicis formula particle intermediate is obtained through the following steps: adding adjuvants into the fluid extract, mixing, and spray drying to obtain cortex Lycii granule intermediate.

According to the preparation method of the invention, the clear paste is obtained by the following steps: soaking cortex Lycii decoction pieces, decocting, filtering, and concentrating the filtrate to obtain fluid extract.

According to an embodiment of the present invention, the method for preparing the cortex lycii radicis formula particle specifically comprises the following steps:

(1) preparation of cortex lycii radicis formula particle intermediate: soaking cortex Lycii decoction pieces, decocting, filtering, concentrating the filtrate to obtain fluid extract, adding adjuvants into the fluid extract, mixing, and spray drying to obtain cortex Lycii granule intermediate;

(2) preparation of cortex lycii radicis 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), cortex lycii radicis decoction pieces are added into water during soaking, and the mass ratio of the cortex lycii radicis decoction pieces to the water is 1 (10-15); preferably, the mass ratio is 1 (10-12); illustratively, the mass ratio is 1: 12;

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 first decoction dregs, wherein the amount of the water is 8-12 times, for example 10 times, of the mass of the cortex lycii radicis decoction pieces, the decoction is carried out for 20-40 minutes, preferably 25-35 minutes, for example 30 minutes, and then the filtration is carried out to obtain a second filtrate and second decoction dregs.

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 can adopt reduced pressure concentration; for example, concentrating under reduced pressure until the relative density of the fluid extract is 1.05-1.25, preferably, the relative density is 1.10-1.15, such as 1.10, 1.12, 1.15; 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 (1-2) to (1-2); for example 1:1.2, 1:1.6, 1.5: 1.

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, the moisture content of the cortex lycii radicis formula particle intermediate is not more than 8 wt%; for example, not more than 7 wt%, not more than 6 wt%; preferably, the moisture content is 4.7 to 5.7 wt%.

According to the preparation method, the content of alcohol-soluble extract of the cortex lycii radicis formula particle intermediate is not less than 33.0 wt%; for example, not less than 34.0 wt%, not less than 35.0 wt%; preferably, the content of alcohol-soluble extract of the cortex lycii radicis formula particle intermediate is 33.4-36.2%.

According to the preparation method, in the step (2), the mass ratio of the intermediate to the auxiliary materials is (3-9): (1-2); such as 4:1, 5: 2.

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.

The preparation method further comprises the step (3) of preparing a cortex lycii radicis standard decoction.

The step (3) specifically comprises the following operations: soaking cortex Lycii decoction pieces, decocting, filtering, concentrating the filtrate, and lyophilizing 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 may be performed by low-temperature reduced-pressure concentration.

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

Further, the invention also provides cortex lycii radicis formula particles obtained by the preparation method.

Further, the present invention also provides a preparation comprising the above cortex lycii radicis formulation granules.

Furthermore, the invention also provides application of the cortex lycii radicis formula particle in preparing a compound medicine.

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 paste yield of the cortex lycii radicis decoction pieces is improved, and the prepared formula granules are high in effective component content and small in dosage.

2. The finished product quality of the cortex lycii radicis formula particle is excellent, and the product quality accords with the regulation of Chinese pharmacopoeia and 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 a process for preparing a cortex lycii radicis 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 cortex Lycii Standard decoction

Preparing a cortex lycii standard decoction: weighing three batches of cortex lycii radicis traditional Chinese medicine decoction pieces 200g each, adding 12 times of water to soak for 30 minutes, heating to boil, decocting for 30 minutes, filtering while hot (No. 6 sieve, 100 meshes), adding 10 times of water into dregs of a decoction, 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 (measured at 65 ℃) to obtain clear paste, and 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 batch numbers are marked as 1, 2 and 3) for later use.

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

In the formula (1), W-is called the clear paste net weight (g), V-is the clear paste volume (ml), 10-the liquid medicine dosage (ml) is measured, W₁-dosage of decoction pieces (g).

TABLE 1 determination of cortex Lycii standard decoction cream yield

Yield of standard decoction lyophilized powder: the weight of the freeze-dried powder of the standard decoction obtained by freeze drying is weighed, and the yield is calculated according to the following formula. The test results are shown in Table 2.

In the formula (2), W is the weight (g) of the freeze-dried powder, W₁-dosage of decoction pieces (g).

TABLE 2 cortex Lycii Standard decoction lyophilized powder yield