阅读说明：本技术 一种用作基准物质的黄芪桂枝五物汤冻干粉及其制备方法 (Radix astragali and cassia twig five-material decoction freeze-dried powder used as reference substance and preparation method thereof ) 是由 朱立彬 黄志军 陈骞 曾庆恢 李霞 翟莉 李蓉芝 于 2019-11-11 设计创作，主要内容包括：本发明公开了一种用作基准物质的黄芪桂枝五物汤冻干粉的制备方法,该方法通过严格控制提取条件,并针对黄芪桂枝五物汤化学成分不稳定的特点,通过采取冷冻干燥以及使用多种辅料,减少了成分在制剂成型过程中以及贮存期间的氧化、降解,使提取物中的成分种类更多,含量更高,更能全面反映黄芪桂枝五物汤的内在质量,从而能准确地控制和指导黄芪桂枝五物汤及其制剂的生产。(The invention discloses a method for preparing astragalus and cassia twig five-substance decoction freeze-dried powder used as a reference substance, which reduces the oxidation and degradation of components in the preparation forming process and the storage period by strictly controlling the extraction conditions and aiming at the characteristic of unstable chemical components of the astragalus and cassia twig five-substance decoction, so that the components in the extract have more types and higher content, and the internal quality of the astragalus and cassia twig five-substance decoction can be comprehensively reflected, thereby accurately controlling and guiding the production of the astragalus and cassia twig five-substance decoction and a preparation thereof.)

1. A preparation method of astragalus mongholicus and cassia twig five-ingredient decoction freeze-dried powder used as a reference substance is characterized by comprising the following steps:

1) soaking decoction pieces of radix astragali and ramulus Cinnamomi, radix astragali, radix Paeoniae alba, ramulus Cinnamomi, rhizoma Zingiberis recens, and fructus Jujubae in small amount of water for 10-60min, decocting with 3-10 times of water for 1-3 times (each for 1-3 hr), mixing decoctions, standing, and settling to obtain supernatant;

2) adding 20-50% of lyophilized protectant, 0.5-5% of antioxidant, and 1-10% of stabilizer into the supernatant, mixing, freeze-drying under vacuum to obtain lyophilized powder,

the freeze-drying protective agent is selected from one or more of mannitol, lactose and glucose;

the antioxidant is selected from one or more of sodium thiosulfate, vitamin C, vitamin E and tea polyphenol;

the stabilizing agent is selected from one or more of povidone K30, gelatin, cyclodextrin and silicon dioxide.

2. The method for preparing the astragalus mongholicus and cassia twig five-ingredient decoction freeze-dried powder used as the reference substance according to claim 1, which is characterized in that: the weight ratio of the astragalus to the white paeony root to the cassia twig to the ginger to the Chinese date is 1:1:1:2: 1.

3. The method for preparing the astragalus mongholicus and cassia twig five-ingredient decoction freeze-dried powder used as the reference substance according to claim 1, which is characterized in that: the stabilizer is a combination of povidone K30, cyclodextrin and silicon dioxide, and the dosage of the stabilizer is 0.5-3%, 2-5% and 1-3% of the weight of the supernatant respectively.

4. The method for preparing the astragalus mongholicus and cassia twig five-ingredient decoction freeze-dried powder used as the reference substance according to claim 1, wherein the freeze vacuum drying comprises three steps of pre-freezing, sublimation drying and resolution drying, and the specific procedures of the steps are as follows:

pre-freezing: directly and rapidly cooling the uniformly mixed material to-30 to-60 ℃, and keeping for 1 to 5 hours;

sublimation drying: controlling the vacuum degree below 20 Pa, raising the temperature of the material to-10-5 ℃ and preserving the heat for 10-15 hours;

and (3) resolving and drying: controlling the vacuum degree below 20 Pa, raising the temperature of the material to 15-35 ℃, and preserving the heat for 2-5 hours.

5. The method for preparing the astragalus mongholicus and cassia twig five-ingredient decoction freeze-dried powder used as the reference substance according to claim 6, which is characterized in that the specific procedures of the steps are as follows:

pre-freezing: directly and rapidly cooling the uniformly mixed materials to-50 ℃ and keeping the temperature for 3 hours;

sublimation drying: controlling the vacuum degree below 20 Pa, raising the temperature of the material to-5 ℃ and keeping the temperature for 12 hours;

and (3) resolving and drying: controlling the vacuum degree below 20 Pa, raising the temperature of the materials to 25 ℃, and preserving the temperature for 3 hours.

Technical Field

The invention relates to a preparation method of astragalus mongholicus and cassia twig five-ingredient decoction freeze-dried powder serving as a reference substance.

Background

The astragalus and cassia twig five-ingredient decoction is a classic and famous formula of traditional Chinese medicine, is an interior-warming agent, and has the effects of tonifying qi, warming channels and activating blood and relieving arthralgia. Clinically, the traditional Chinese medicine is usually used for treating diseases such as dermatitis, peripheral neuritis, apoplexy sequelae and the like, and a large amount of Chinese patent medicines are developed on the basis of the prescription at present.

Since the establishment and implementation of the traditional Chinese medicine law in 2016, in order to encourage and standardize the development of the traditional Chinese medicine of the classic famous prescription, the state starts to establish the substance standard of the classic famous prescription, namely, the quality information of the traditional Chinese medicine can be comprehensively reflected by the standard for preparing the traditional Chinese medicine medicinal substance based on the preparation method of the ancient classic famous prescription recorded in the ancient medical books.

The astragalus and cassia twig five-component decoction is complex in components, the material standard is used for inspecting the quantity value transfer rule of each component from a medicinal material, a decoction liquid and a finished product in the classical famous formula research, and comprises various links in the process, such as extraction, concentration, drying, purification, forming and the like, so the initial components and the proportion of each component in the decoction liquid are very important, and in addition, the components in the standard material cannot be oxidized and degraded during the preparation forming, storage and transportation, and must have very high stability.

Disclosure of Invention

The invention aims to provide a preparation method of astragalus and cassia twig five-substance decoction freeze-dried powder serving as a reference substance, which can more comprehensively reflect the internal quality information of traditional Chinese medicines and more accurately control and guide the production quality of the astragalus and cassia twig five-substance decoction and a preparation thereof.

The preparation method provided by the invention comprises the following steps:

1) soaking decoction pieces of radix astragali and ramulus Cinnamomi, radix astragali, radix Paeoniae alba, ramulus Cinnamomi, rhizoma Zingiberis recens, and fructus Jujubae in small amount of water for 10-60min, decocting with 3-10 times of water for 1-3 times (each for 1-3 hr), mixing decoctions, standing, and settling to obtain supernatant;

2) adding 20-50% of lyophilized protectant, 0.5-5% of antioxidant, and 1-10% of stabilizer into the supernatant, mixing, freeze-drying under vacuum to obtain lyophilized powder,

the freeze-drying protective agent is selected from one or more of mannitol, lactose and glucose;

the antioxidant is selected from one or more of sodium thiosulfate, vitamin C, vitamin E and tea polyphenol;

the stabilizing agent is selected from one or more of povidone K30, gelatin, cyclodextrin and silicon dioxide.

Preferably, the weight ratio of the astragalus to the white paeony root to the cassia twig to the ginger to the Chinese date is 1:1:1:2: 1.

Preferably, the stabilizer is povidone K30, cyclodextrin and silicon dioxide combination, and the dosage is 0.5-3%, 2-5% and 1-3% of the weight of the supernatant respectively.

Preferably, the freeze vacuum drying comprises three steps of pre-freezing, sublimation drying and resolution drying, and the specific procedures of the steps are as follows:

pre-freezing: directly and rapidly cooling the uniformly mixed material to-30 to-60 ℃, and keeping for 1 to 5 hours;

sublimation drying: controlling the vacuum degree below 20 Pa, raising the temperature of the material to-10-5 ℃ and preserving the heat for 10-15 hours;

and (3) resolving and drying: controlling the vacuum degree below 20 Pa, raising the temperature of the material to 15-35 ℃, and preserving the heat for 2-5 hours.

Further preferably, the specific procedures of the steps of the freeze vacuum drying are as follows:

pre-freezing: directly and rapidly cooling the uniformly mixed materials to-50 ℃ and keeping the temperature for 3 hours;

sublimation drying: controlling the vacuum degree below 20 Pa, raising the temperature of the material to-5 ℃ and keeping the temperature for 12 hours;

and (3) resolving and drying: controlling the vacuum degree below 20 Pa, raising the temperature of the materials to 25 ℃, and preserving the temperature for 3 hours.

According to one embodiment of the present invention, the reference substance is optimally prepared as follows:

1) soaking the decoction pieces of the five-material decoction of astragalus and cassia twig, namely astragalus, white paeony root, cassia twig, ginger and Chinese date with a small amount of water for 30min, then adding 6 times of water for decocting for 2 times, 2 hours for the first time and 1 hour for the second time, combining the decoctions, standing and settling for 12 hours, and taking supernatant, wherein the weight ratio of the astragalus to the white paeony root to the cassia twig to the ginger to the Chinese date is 1:1:1:2: 1;

2) adding 30% of mannitol, 2% of sodium thiosulfate, 1% of povidone K30, 3% of betacyclodextrin and 2% of silicon dioxide into the supernatant according to the weight, uniformly mixing, and performing freeze vacuum drying, wherein the procedure is as follows:

pre-freezing: directly and rapidly cooling the uniformly mixed materials to-50 ℃ and keeping the temperature for 3 hours;

sublimation drying: controlling the vacuum degree below 20 Pa, raising the temperature of the material to-5 ℃ and keeping the temperature for 12 hours;

and (3) resolving and drying: controlling the vacuum degree below 20 Pa, raising the temperature of the materials to 25 ℃, and preserving the temperature for 3 hours.

The reference substance prepared by the optimal process has the advantages of abundant components reflecting the internal quality of the traditional Chinese medicine, relatively high content and better stability.

The invention has the beneficial effects that:

1) the invention strictly controls the extraction conditions, has more component types and higher content in the extract, and can more comprehensively reflect the internal quality of the astragalus-cassia twig five-ingredient decoction.

2) Aiming at the characteristic of unstable chemical components of the astragalus-cassia twig five-component decoction, the invention reduces the oxidation and degradation of the components in the process of forming the preparation and during the storage by adopting freeze drying and strictly controlling the drying conditions and using various auxiliary materials, further improves the product quality, prolongs the storage period and can more accurately control and guide the production quality of the astragalus-cassia twig five-component decoction and the preparation thereof.

Drawings

FIG. 1 is a fingerprint of the reference substance of example 1.

FIG. 2 is a fingerprint of a reference substance for comparative example.

Detailed Description

The present invention will be described in detail below with reference to specific examples.