阅读说明：本技术 白术配方颗粒及其制备方法和用途 (Bighead atractylodes rhizome 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,公开了白术配方颗粒及其制备方法和用途。白术配方颗粒,其包含活性成分白术和药学上可接受的辅料,其中白术的含量为250～800mg/g。所述白术配方颗粒由白术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,提升了白术饮片的出膏率,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,具体表现在：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 a bighead atractylodes rhizome formula granule, and a preparation method and application thereof. The bighead atractylodes rhizome formula particle comprises an active ingredient bighead atractylodes rhizome and pharmaceutically acceptable auxiliary materials, wherein the content of the bighead atractylodes rhizome is 250-800 mg/g. The bighead atractylodes rhizome formula particle is prepared by uniformly mixing and granulating a bighead atractylodes rhizome formula particle intermediate and auxiliary materials. The invention adopts spray drying and dry granulation processes, strictly controls the process step parameters, improves the cream yield of the largehead atractylodes rhizome decoction pieces, and has high content of effective components and small dosage 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, which is specifically represented by 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.)

1. A bighead atractylodes rhizome formula particle comprises an active ingredient bighead atractylodes rhizome and pharmaceutically acceptable auxiliary materials, wherein the content of the bighead atractylodes rhizome is 250-800 mg/g;

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

2. The Atractylodis rhizoma formulated particle of claim 1, wherein the size of the Atractylodis rhizoma formulated particle is between 10-100 mesh;

preferably, the water content of the bighead atractylodes rhizome formula particles is 3.5-6.0 wt%;

preferably, the alcohol soluble extract of the largehead atractylodes rhizome formula particle is not less than 12.0 wt%;

preferably, the specification of the bighead atractylodes rhizome formula particle is that every 1g of formula particle is equivalent to 1g of bighead atractylodes rhizome decoction pieces.

3. The Atractylodis rhizoma granule according to claim 1 or 2, further comprising a packaging bag or a pack containing said granule.

4. A method of preparing an atractylis ovata formulation as claimed in any of claims 1 to 3, which comprises: mixing the intermediate of the rhizoma Atractylodis Macrocephalae formula granule with adjuvants, and granulating to obtain rhizoma Atractylodis Macrocephalae formula granule;

preferably, the preparation method of the bighead atractylodes rhizome formula particle specifically comprises the following steps:

(1) preparation of an intermediate of the bighead atractylodes rhizome formula particle: soaking Atractylodis rhizoma decoction pieces, decocting, filtering, concentrating the filtrate to obtain fluid extract, adding adjuvants into the fluid extract, mixing, and spray drying to obtain Atractylodis rhizoma granule intermediate;

(2) preparing the bighead atractylodes rhizome formula particles: 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 Atractylodis rhizoma decoction pieces are added into water during soaking, the mass ratio of the Atractylodis rhizoma decoction pieces to the water is 1 (8-15), and the soaking time is 20-40 minutes;

preferably, the decoction and the filtration are operated at least twice circularly, and the hot filtration is carried out;

preferably, the relative density of the clear paste is 1.05-1.25 (measured at the temperature of 60-70 ℃);

preferably, the mass ratio of the clear paste to the auxiliary materials is 1: 1-1: 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 1: 1-3: 1; sieving the mixed fluid extract and adjuvants before spray drying;

the dry granulation can adopt the conventional operation in the field, and the finished product of granules can be obtained by rolling, continuously compacting material blocks, granulating and sieving.

7. The preparation method according to any one of claims 4 to 6, further comprising the step (3) of preparing a standard decoction of Atractylodis rhizoma: soaking Atractylodis rhizoma decoction pieces, decocting, filtering, concentrating the filtrate, and freeze drying 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) sealing and packaging the bighead atractylodes rhizome formula particles obtained in the step (2).

9. A formulation comprising the atractylodes macrocephala koidz formulation granule as claimed in any one of claims 1 to 3.

10. Use of the Atractylodis rhizoma formulated particles 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 a bighead atractylodes rhizome formula granule as well as a preparation method and application thereof.

Background

Atractylodis rhizoma is dried rhizome of Atractylodes macrocephala Koidz of Compositae. In winter, the lower leaves are withered and yellow, and the upper leaves are brittle, picked and dug, sand and sand are removed, and then the leaves are dried or dried in the sun, and fibrous roots are removed. The processing should meet the relevant regulations under the item of "processing" in the first part of the 2015 pharmacopoeia. The largehead atractylodes rhizome has the effects of tonifying spleen and qi, eliminating dampness and promoting diuresis, stopping sweating and preventing miscarriage; can be used for treating spleen deficiency, anorexia, abdominal distention, diarrhea, phlegm retention, dizziness, palpitation, edema, spontaneous perspiration, and threatened abortion.

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 an bighead atractylodes rhizome formula particle, which comprises an active ingredient bighead atractylodes rhizome and pharmaceutically acceptable auxiliary materials, wherein the content of the bighead atractylodes rhizome 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 bighead atractylodes rhizome 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 water content of the bighead atractylodes rhizome formula particles is 3.5-6.0 wt%; for example, 3.9 to 5.6 wt%, 4.2 to 5.0 wt%.

According to the invention, the alcohol-soluble extract of the largehead atractylodes rhizome formula particle is not less than 12.0 wt%; for example, not less than 13.0 wt%, not less than 14.0 wt%, not less than 15.0 wt%.

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

According to the invention, the specification of the bighead atractylodes rhizome formula particle is that every 1g of formula particle is equivalent to 1g of bighead atractylodes rhizome decoction pieces.

According to the invention, the packaging specification of the rhizoma atractylodis macrocephalae formula particle can have various specifications, such as 1-20 g, and exemplarily, the specifications are 1g, 2g, 3g, 5g, 6g, 10g, 12g, 15g and 20 g.

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

According to the preparation method, the intermediate of the bighead atractylodes rhizome formula particle is obtained by the following steps: adding adjuvants into the fluid extract, mixing, and spray drying to obtain Atractylodis rhizoma granule intermediate.

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

According to an embodiment of the present invention, the preparation method of the atractylodes macrocephala formula granule specifically comprises the following steps:

(1) preparation of an intermediate of the bighead atractylodes rhizome formula particle: soaking Atractylodis rhizoma decoction pieces, decocting, filtering, concentrating the filtrate to obtain fluid extract, adding adjuvants into the fluid extract, mixing, and spray drying to obtain Atractylodis rhizoma granule intermediate;

(2) preparing the bighead atractylodes rhizome formula particles: 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), during soaking, the bighead atractylodes rhizome decoction pieces are added into water, and the mass ratio of the bighead atractylodes rhizome 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 rhizoma atractylodis macrocephalae 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 filtrate II and a 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, in the step (1), the concentration mode preferably adopts reduced pressure concentration, for example, the reduced pressure concentration is carried out until the relative density of the clear paste is 1.05-1.25; preferably, the relative density is 1.10-1.15, 1.20-1.25, 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: 1-1: 2; for example 1:1.2, 1: 1.6.

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 intermediate of the bighead atractylodes rhizome formula particle is not more than 8.0 wt%, for example not more than 5.0 wt%, for example not more than 3.5 wt%, such as 2.4-2.8 wt%.

According to the preparation method, the alcohol-soluble extract of the intermediate of the largehead atractylodes rhizome formula particle is not less than 12.0 wt%; for example, not less than 13.0 wt%, for example, 13.0 to 15.7 wt%.

According to the preparation method, in the step (2), the mass ratio of the intermediate to the auxiliary materials is 1: 1-3: 1; for example 2:1, 2.5: 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 standard decoction of the white atractylodes rhizome.

The step (3) specifically comprises the following operations: soaking Atractylodis rhizoma decoction pieces, decocting, filtering, 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 can 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 bighead atractylodes rhizome 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 bighead atractylodes rhizome formula granules prepared by the preparation method.

Furthermore, the invention also provides a preparation which comprises the bighead atractylodes rhizome formula particles.

Furthermore, the invention also provides application of the bighead atractylodes rhizome formula particle in preparation of compound 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 largehead atractylodes rhizome 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 bighead atractylodes rhizome formula particle is excellent, and the product quality accords with the regulation of Chinese pharmacopoeia, and is specifically represented as follows: 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 preparation process of the rhizoma atractylodis macrocephalae formula granules in example 1 of the 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 standard decoction of Atractylodis rhizoma

Preparation of standard decoction of white atractylodes rhizome: weighing three batches of bighead atractylodes rhizome traditional Chinese medicine decoction pieces, respectively weighing 200g, 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 (measured at 65 ℃), freeze-drying the clear paste (the temperature is-50-45 ℃ and the vacuum degree is 10Pa), and preparing freeze-dried powder as a standard decoction sample (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, drying the three batches of standard decoction samples for 3 hours at 105 ℃, placing the three batches of standard decoction samples in a dryer for cooling for 30 minutes, precisely weighing the three batches of standard decoction samples, calculating the cream yield and the standard deviation according to a formula (1), and determining the cream yield range of the white atractylodes rhizome 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 the cream yield of the standard decoction of Atractylodis rhizoma

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 Freeze-dried powder yield of standard decoction of Atractylodis rhizoma