Membrane separation and purification process of high-purity astragalus and angelica effective components and capsule preparation thereof

Abstract

The application discloses a membrane separation and purification process of high-purity effective components of Astragalus and Angelica and a capsule preparation thereof, and belongs to the technical field of traditional Chinese medicinal material processing and preparation. The application solves the technical problems of high ash residue and low capsule bioavailability in the preparation process of the existing Astragalus and Angelica capsules. The application comprises the following steps: raw material pretreatment, countercurrent extraction, coarse filtration through a ceramic microfiltration membrane, nanofiltration separation of the filtered clear filtrate into a solvent-resistant nanofiltration membrane system, and obtaining refined Astragalus and Angelica medicinal powder after elution and drying. The application realizes the precise purification goal of "only removing impurities and not removing medicine", can reduce the inorganic ash content in the extraction liquid by more than 50%, and efficiently retains core medicinal components such as astragaloside and angelica polysaccharide. The prepared Astragalus and Angelica capsules are accurate in effective component content, have small gastrointestinal irritation, and are good in storage stability.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine processing and preparation technology, specifically to a membrane separation and purification process for high-purity Astragalus membranaceus and Angelica sinensis effective components and their capsule formulation. Background Technology

[0002] Astragalus and Angelica sinensis are both traditional and commonly used Chinese medicinal herbs. When used together, they have the effects of tonifying qi and blood, regulating menstruation and relieving pain, and strengthening the spleen and lungs. They are widely used to treat symptoms such as qi and blood deficiency, sallow complexion, dizziness, palpitations, and irregular menstruation. Astragalus and Angelica sinensis capsules are a commonly used clinical dosage form with advantages such as convenient administration, easy portability, and precise dosage. However, there are still many technical challenges in their preparation process.

[0003] Ash in Chinese medicinal herbs is divided into physiological ash and exogenous ash. Physiological ash mainly consists of crystals such as calcium oxalate and calcium carbonate, which are inherent properties of Chinese medicinal herbs and cannot be completely removed without damaging the herb matrix. Furthermore, forced removal would lead to a significant loss of core active ingredients. Exogenous ash mainly consists of impurities such as mud and sand introduced during harvesting, processing, and transportation. Current preparation processes for Astragalus and Angelica capsules mostly employ traditional high-temperature decoction extraction, which not only easily causes degradation and loss of active ingredients but also makes it difficult to effectively separate inorganic ash and large molecular impurities (such as cellulose, pectin, and ineffective plant proteins), resulting in high ash residue in the final product.

[0004] High ash residue can cause many problems: First, it increases the burden on the gastrointestinal tract. Long-term use of calcium oxalate crystals in the raw medicinal materials can easily cause stomach discomfort, bloating, and even increase the risk of gallstones. Second, it reduces the content of effective ingredients. The proportion of effective ingredients in a unit mass of medicinal powder is insufficient, resulting in capsules with "insufficient efficacy" and affecting clinical efficacy. Third, it affects product stability. Moisture-absorbing inorganic salt impurities can cause capsules to absorb moisture and clump during storage, shortening the shelf life.

[0005] Currently, the purification of traditional Chinese medicinal materials mostly employs single-membrane separation technology or traditional filtration methods, which suffer from problems such as low purification precision, low yield of active ingredients, and poor ash removal, failing to meet the production requirements of high purity, high stability, and low irritation for Astragalus and Angelica capsules. Therefore, developing a novel purification process that can significantly reduce inorganic ash content while retaining the core active ingredients and is suitable for capsule dosage forms has become an urgent technical problem to be solved in this field. Summary of the Invention

[0006] The purpose of this invention is to provide a membrane separation and purification process for high-purity Astragalus and Angelica sinensis active components and their capsule formulation, solving the technical problems of high ash residue and low capsule bioavailability in existing processes, achieving precise purification of Astragalus and Angelica sinensis medicinal components, and preparing capsule formulations with stable efficacy, low irritation, and good storage properties.

[0007] The membrane separation and purification process for high-purity Astragalus and Angelica sinensis effective components includes the following steps: Step 1: Raw material pretreatment Select Astragalus and Angelica sinensis that meet the standards of the Chinese Pharmacopoeia, remove impurities, moldy parts and non-medicinal parts, wash them, slice them, and air dry them until there is no moisture on the surface for later use. Step 2: Dynamic Countercurrent Extraction Pretreated Astragalus membranaceus and Angelica sinensis slices were mixed at a mass ratio of 1 to 5:1, and 8 to 10 times the amount of purified water was added. The mixture was extracted using a countercurrent extraction device, and the extraction was performed n times. The extracts from the n extractions were then combined. Step 3: Coarse Filtration and Clarification The combined extracts were coarsely filtered through a ceramic microfiltration membrane to remove plant cell wall fragments, cellulose, inorganic mineral particles and macromolecular impurities, and the clear filtrate was collected. Step 4: Precision Nanofiltration Ash Removal The clarified filtrate is passed into a solvent-resistant nanofiltration membrane system, and a solvent-resistant nanofiltration membrane with a molecular weight cutoff of 200-500 Da is selected for nanofiltration separation. Step 5: Washing and Drying After nanofiltration, 2-3 times the amount of purified water at 60-70℃ is added to the retentate in the nanofiltration membrane for washing and elution. The elution is repeated twice, and the retentates after elution are collected and combined. The retentate is placed in a vacuum drying oven and dried to constant weight. After removal, it is pulverized and passed through an 80-100 mesh sieve to obtain a refined powder of Astragalus membranaceus and Angelica sinensis with low ash content and high content.

[0008] In step one, the Astragalus membranaceus slices are 2-3 mm thick, and the Angelica sinensis slices are 1-2 mm thick.

[0009] In step two, the extraction temperature of the countercurrent extraction equipment is controlled at 90-92℃, the extraction time is 2-3 hours, and the extraction is performed twice.

[0010] In step three, the pore size of the ceramic microfiltration membrane is controlled to be 0.1–0.5 μm, the filtration pressure is 0.2–0.3 MPa, and the filtration temperature is 25–30 °C.

[0011] In step four, the nanofiltration pressure is controlled at 0.8–1.2 MPa and the nanofiltration temperature is controlled at 30–35 °C.

[0012] In step five, the vacuum degree of the vacuum drying oven is controlled to be -0.06 to -0.08 MPa, and the drying temperature is 50-65℃.

[0013] An Astragalus and Angelica Capsule Formulation comprises Astragalus and Angelica refined powder prepared by the aforementioned process, and pharmaceutical excipients. The mass ratio of the Astragalus and Angelica refined powder to the pharmaceutical excipients is 8-10:1. After being mixed evenly, the powder is filled into empty capsules at a specification of 0.3-0.5g per capsule using a capsule filling machine. The capsules are then sealed and inspected to obtain the Astragalus and Angelica Capsules.

[0014] The pharmaceutical excipient is microcrystalline cellulose.

[0015] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are: 1. Reduces gastrointestinal burden and enhances safety. Astragalus and Angelica capsules are commonly used to replenish both qi and blood, and are suitable for long-term use. However, the physiological ash, such as calcium oxalate crystals, in the original medicinal materials can easily cause stomach discomfort, bloating, and even increase the risk of gallstones with long-term use. This process uses precise nanofiltration to remove most of the carriers of calcium oxalate crystals and inorganic salt impurities, making the capsule formulation gentler, reducing gastrointestinal irritation, and improving the safety of long-term use.

[0016] 2. Precise concentration of active ingredients ensures more stable efficacy. This process removes ash and macromolecular impurities, significantly increasing the content of core active ingredients (astragaloside A and angelica polysaccharide) per unit mass of medicinal powder. It solves the problems of insufficient efficacy and large fluctuations in the content of effective ingredients in traditional capsules, ensuring the precise and stable efficacy of each capsule and improving clinical treatment results.

[0017] 3. The product has good stability and a longer shelf life. This process removes hygroscopic inorganic salt impurities, reducing the risk of capsules absorbing moisture and clumping. At the same time, the low-temperature extraction and vacuum drying processes prevent the degradation of active ingredients, allowing the prepared Astragalus and Angelica capsules to have a shelf life of more than 24 months under normal temperature and dry conditions, thus enhancing the product's market competitiveness.

[0018] 4. Advanced technology, suitable for industrial production. This process employs multi-stage membrane separation coupled with dynamic countercurrent extraction technology, achieving physical separation throughout the entire process without the addition of chemical reagents, thus meeting the requirements for modern and green production of traditional Chinese medicine. The process steps are clear and the parameters are controllable, enabling large-scale and automated production, reducing production costs and improving production efficiency.

[0019] In summary, this invention achieves the precise purification goal of "removing only impurities, not medicinal substances," reducing the inorganic ash content in the extract by more than 50% while efficiently retaining core medicinal components such as astragaloside A and angelica polysaccharides. The resulting Astragalus and Angelica capsules exhibit precise content of active ingredients, minimal gastrointestinal irritation, and good storage stability. Detailed Implementation

[0020] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments.

[0021] Example 1 This embodiment specifically provides a membrane separation and purification process for high-purity Astragalus and Angelica sinensis effective components, including the following steps: Step 1: Raw material pretreatment Select Astragalus and Angelica sinensis that meet the standards of the Chinese Pharmacopoeia, remove impurities, moldy parts and non-medicinal parts, wash them and slice them. The Astragalus slices should be 2-3 mm thick and the Angelica sinensis slices should be 1-2 mm thick. Dry them until there is no moisture on the surface and set them aside. Step 2: Dynamic Countercurrent Extraction Pretreated Astragalus and Angelica slices were mixed at a mass ratio of 1–5:1, and 8–10 times the amount of purified water was added. The mixture was then extracted using a countercurrent extraction device at a temperature of 90–92℃ for 2–3 hours, repeated twice, with the extracts combined. This countercurrent extraction effectively prevents the degradation and loss of active ingredients. It utilizes the high solubility of water-soluble polysaccharides and organic acids in warm water to achieve efficient dissolution. Simultaneously, the dynamic countercurrent extraction process ensures thorough contact between the medicinal materials and the extract, initially removing a large amount of insoluble sand and other foreign ash, reducing the burden on subsequent purification.

[0022] Step 3: Coarse Filtration and Clarification The combined extracts are coarsely filtered through a ceramic microfiltration membrane. The pore size of the ceramic microfiltration membrane is controlled at 0.1–0.5 μm, the filtration pressure at 0.2–0.3 MPa, and the filtration temperature at 25–30 °C. This process retains plant cell wall fragments, cellulose, most inorganic mineral particles (the main carriers of physiological ash), and macromolecular impurities. The clear filtrate (clarified liquid) is collected. In this step, the ceramic microfiltration membrane removes suspended macromolecular impurities from the extract through sieving, further purifying the extract and laying the foundation for subsequent precise ash removal. At the same time, it avoids macromolecular impurities affecting the separation effect and service life of the nanofiltration membrane.

[0023] Step 4: Precision Nanofiltration Ash Removal The clarified filtrate is passed into a solvent-resistant nanofiltration membrane system. A solvent-resistant nanofiltration membrane with a molecular weight cutoff of 200–500 Da is selected, and the nanofiltration pressure is controlled at 0.8–1.2 MPa and the nanofiltration temperature at 30–35℃. Nanofiltration separation is then performed. The principle of this step is to utilize the selective permeability of the nanofiltration membrane to achieve separation based on differences in molecular size: small molecule core active substances such as astragaloside (molecular weight approximately 484 Da) and angelica polysaccharide (molecular weight 300–500 Da), whose molecular weight is greater than the molecular weight cutoff of the nanofiltration membrane, are retained inside the membrane; while inorganic salt ions (potassium, sodium, calcium, magnesium, etc.) and small molecule monosaccharides (molecular weight less than 200 Da) corresponding to inorganic ash can pass through the membrane pores and be discharged, achieving "salt washing" to remove ash. The effect of precise nanofiltration ash removal is to reduce the inorganic ash content in the extract by more than 50% without damaging the original structure of the medicinal material or losing the core medicinal components, through the "salt washing" effect. At the same time, it concentrates the effective components and increases the content of effective components per unit volume of extract.

[0024] Step 5: Washing and Drying After nanofiltration, 2-3 times the volume of purified water at 60-70℃ is added to the retentate in the nanofiltration membrane for washing and elution. The elution is repeated twice, and the retentates after elution are collected and combined. The retentate is placed in a vacuum drying oven, and the vacuum degree of the vacuum drying oven is controlled at -0.06 to -0.08 MPa, the drying temperature is 50-65℃, and the product is dried to constant weight. After drying, the product is removed, pulverized, and passed through an 80-100 mesh sieve to obtain a refined powder of Astragalus membranaceus and Angelica sinensis with low ash content and high content.

[0025] Example 2 This embodiment specifically provides an Astragalus and Angelica Capsule Formulation, comprising the refined Astragalus and Angelica powder prepared in Example 1 and pharmaceutical excipients. The pharmaceutical excipients are selected from microcrystalline cellulose. The mass ratio of the refined Astragalus and Angelica powder to the pharmaceutical excipients is 8-10:1. After being mixed evenly, the mixture is filled into empty capsules at a specification of 0.3-0.5g per capsule using a capsule filling machine. After sealing and quality inspection, the Astragalus and Angelica Capsule Formulation is obtained.

Claims

1. A membrane separation and purification process for high-purity Astragalus and Angelica sinensis effective components, characterized in that... Includes the following steps: Step 1: Raw material pretreatment Select Astragalus and Angelica sinensis that meet the standards of the Chinese Pharmacopoeia, remove impurities, moldy parts and non-medicinal parts, wash them, slice them, and air dry them until there is no moisture on the surface for later use. Step 2: Dynamic Countercurrent Extraction Pretreated Astragalus membranaceus and Angelica sinensis slices were mixed at a mass ratio of 1-5:1, and 8-10 times the amount of purified water was added. The mixture was extracted using a countercurrent extraction device, and the extraction was performed n times. The extracts from the n extractions were then combined. Step 3: Coarse Filtration and Clarification The combined extracts were coarsely filtered through a ceramic microfiltration membrane to remove plant cell wall fragments, cellulose, inorganic mineral particles and macromolecular impurities, and the clear filtrate was collected. Step 4: Precision Nanofiltration Ash Removal The clarified filtrate is passed into a solvent-resistant nanofiltration membrane system, and a solvent-resistant nanofiltration membrane with a molecular weight cutoff of 200~500 Da is selected for nanofiltration separation. Step 5: Washing and Drying After nanofiltration, 2-3 times the amount of purified water at 60-70℃ is added to the retentate in the nanofiltration membrane for washing and elution. The elution is repeated twice, and the eluted retentates are collected and combined. The retentate is placed in a vacuum drying oven and dried to constant weight. After removal, it is pulverized and passed through an 80-100 mesh sieve to obtain a refined Astragalus and Angelica powder with low ash content and high content.

2. The membrane separation and purification process for high-purity Astragalus and Angelica sinensis effective components according to claim 1, characterized in that, In step one, the Astragalus membranaceus slices are 2-3 mm thick, and the Angelica sinensis slices are 1-2 mm thick.

3. The membrane separation and purification process for high-purity Astragalus and Angelica sinensis effective components according to claim 1, characterized in that, In step two, the extraction temperature of the countercurrent extraction equipment is controlled at 90-92℃, the extraction time is 2-3 hours, and the extraction is performed twice.

4. The membrane separation and purification process for high-purity Astragalus and Angelica sinensis effective components according to claim 1, characterized in that, In step three, the pore size of the ceramic microfiltration membrane is controlled to be 0.1–0.5 μm, the filtration pressure is 0.2–0.3 MPa, and the filtration temperature is 25–30 °C.

5. The membrane separation and purification process for high-purity Astragalus and Angelica sinensis effective components according to claim 1, characterized in that, In step four, the nanofiltration pressure is controlled at 0.8–1.2 MPa and the nanofiltration temperature is controlled at 30–35 °C.

6. The membrane separation and purification process for high-purity Astragalus and Angelica sinensis effective components according to claim 1, characterized in that, In step five, the vacuum degree of the vacuum drying oven is controlled to be -0.06 to -0.08 MPa, and the drying temperature is 50 to 65℃.

7. A formulation of Astragalus and Angelica capsules, characterized in that, The product comprises Astragalus and Angelica sinensis refined powder prepared by the process described in any one of claims 1-6, and pharmaceutical excipients, wherein the mass ratio of the Astragalus and Angelica sinensis refined powder to the pharmaceutical excipients is 8-10:

1. After being mixed evenly, the powder is filled into empty capsules at a specification of 0.3-0.5g per capsule using a capsule filling machine, sealed, and quality inspected to obtain Astragalus and Angelica sinensis capsules.

8. The Astragalus and Angelica Capsule Preparation according to claim 7, characterized in that, The pharmaceutical excipient is microcrystalline cellulose silica.