Traditional Chinese medicine composition as well as forming process and quality control method thereof

Abstract

The invention discloses a traditional Chinese medicine composition and a forming process and a quality control method thereof, and belongs to the technical field of traditional Chinese medicine, the traditional Chinese medicine composition is prepared from the following traditional Chinese medicine raw materials: astragalus membranaceus, angelica sinensis, poria cocos, rhizoma atractylodis macrocephalae, liquorice, radix bupleuri, radix paeoniae alba and fructus aurantii. The effects of reinforcing qi, nourishing blood, soothing liver, strengthening spleen, regulating qi, relieving pain and the like are achieved. The forming process comprises the steps of pretreatment of traditional Chinese medicine raw materials, extraction of effective components, addition of pharmaceutically acceptable auxiliary materials or auxiliary components and preparation forming, and the forming process is easy to operate, easy to control and suitable for industrial large-scale production. The quality control method comprises three aspects of raw material quality control, production process quality control and finished product quality control, through a perfect forming process and a strict quality control method, the consistency and stability of each batch of products are ensured, the quality problems caused by raw material difference and production process fluctuation are reduced, and the product quality is improved. And the reliability and the safety of the product are improved.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine composition with specific effects, and a forming process and quality control method of the traditional Chinese medicine composition. BACKGROUND

[0002] In the field of traditional Chinese medicine, traditional Chinese medicine compositions can exert synergistic effects due to the comprehensive effects of multiple traditional Chinese medicines, and exhibit unique advantages in disease treatment and prevention. However, many traditional Chinese medicine compositions currently have unstable effects and uneven quality. On the one hand, the sources, origins, and seasons of harvest of traditional Chinese medicine raw materials differ greatly, resulting in fluctuations in the contents of effective components and affecting the effects of the final products. On the other hand, the existing forming processes and quality control methods are not perfect, and it is difficult to ensure the consistency and stability of each batch of products. For example, some forming processes may cause loss or degradation of effective components of traditional Chinese medicine, and if the quality control method lacks scientific indicators and detection means, it cannot timely discover and correct deviations in the production process, so that the quality of traditional Chinese medicine products on the market is uneven, which limits the development and popularization of traditional Chinese medicine. SUMMARY

[0003] The purpose of the present application is to provide a traditional Chinese medicine composition and its forming process and quality control method, which solve the problems of unstable effects and uneven quality of existing traditional Chinese medicine compositions, and imperfect forming processes and quality control methods, and ensure the consistency and stability of the effects of each batch of products through perfect forming processes and strict quality control methods.

[0004] To solve the above technical problems, one of the technical solutions adopted by the present application is to provide a traditional Chinese medicine composition prepared from the following weight-proportioned traditional Chinese medicine raw materials: Radix Astragali 100-150 parts; Angelica sinensis 80-120 parts; Poria cocos 70-90 parts; Atractylodes macrocephala 60-90 parts; Glycyrrhiza 30-45 parts; Bupleurum 50-75 parts; Radix Paeoniae Alba 50-75 parts; Fructus Aurantii 40-60 parts.

[0005] Radix Astragali tonifies Qi and consolidates the exterior, Angelica sinensis tonifies blood and promotes blood circulation, and the combination of the two tonifies both Qi and blood; Poria cocos benefits water and dampness, and invigorates the spleen and calms the heart, Atractylodes macrocephala invigorates the spleen and benefits Qi, and dries dampness and benefits water, and together they enhance the effect of invigorating the spleen and eliminating dampness; Glycyrrhiza harmonizes all medicines, Bupleurum soothes the liver and relieves depression, Radix Paeoniae Alba nourishes blood and regulates menstruation, and softens the liver and relieves pain, and Fructus Aurantii regulates Qi, widens the middle, and eliminates stagnation and distension, and all the medicines synergize to have the effects of tonifying Qi and nourishing blood, soothing the liver and invigorating the spleen, regulating Qi and relieving pain, and can be used for the treatment of various symptoms caused by deficiency of Qi and blood and stagnation of the liver and deficiency of the spleen, such as sallow complexion, fatigue and weakness, distending pain in the lateral costal region, and loss of appetite.

[0006] Preferably, the Atractylodes macrocephala is fried with bran Atractylodes, which is weaker than general Atractylodes in dryness, has better effects of invigorating the spleen and eliminating dampness, can reduce the stimulation on the gastrointestinal tract, and is suitable for people with weak spleen and stomach.

[0007] Preferably, the Bupleurum is vinegar-fried Bupleurum, which is a commonly used drug for relieving superficies, can relieve superficies and interior, soothe the liver and relieve depression, and has enhanced effects of soothing the liver and relieving depression and relieving inflammation and promoting bile secretion compared with Bupleurum.

[0008] Preferably, the traditional Chinese medicine composition is prepared into a clinically acceptable dosage form by adding pharmaceutically acceptable excipients or auxiliary ingredients to the traditional Chinese medicine extract obtained by water extraction or organic solvent extraction.

[0009] Preferably, the dosage form is a decoction, a powder, a paste, a granule, a pill or a capsule.

[0010] To solve the above technical problems, the second technical solution adopted by the present application is to provide a forming process of the traditional Chinese medicine composition, which comprises the following steps: Raw material pretreatment: Each batch of traditional Chinese medicine raw materials is strictly inspected, including origin traceability, appearance inspection, impurity content detection and the like, and qualified traditional Chinese medicine raw materials are screened out. The screened traditional Chinese medicine raw materials are manually selected to remove impurities and non-medicinal parts, so as to ensure the purity of the traditional Chinese medicine raw materials. The selected traditional Chinese medicine raw materials are cleaned and dried. For Atractylodes and Bupleurum that need to be processed, they are strictly processed according to the traditional processing process to enhance the efficacy and reduce the toxicity. Extraction of active ingredients: The pretreated traditional Chinese medicine raw materials are crushed into coarse powder, and the active ingredients in the traditional Chinese medicine raw materials are extracted by water extraction or organic solvent extraction method and concentrated to obtain traditional Chinese medicine extract. Preparation of dosage form: According to the needs of the dosage form, pharmaceutically acceptable excipients or auxiliary ingredients are added to the traditional Chinese medicine extract to prepare a clinically acceptable dosage form. For example, if the prepared dosage form is a pill, the extracted traditional Chinese medicine extract is uniformly mixed with appropriate excipients (starch, dextrin, coconut oil, bee wax and the like) to prepare a soft material, which is then processed into a pill of a certain specification by a pill-making machine, and then dried, coated and the like. If the prepared dosage form is a tablet, the traditional Chinese medicine extract is uniformly mixed with excipients (fillers, disintegrants, lubricants and the like), and then granulated by a wet granulation method or a dry granulation method to prepare a granule, which is then compressed into a tablet, and finally coated and packaged. If the prepared dosage form is a capsule, the traditional Chinese medicine extract is prepared into a granule or a powder, which is then filled into a capsule shell and packaged.

[0011] Preferably, the water extraction method is as follows: adding 8-10 times of water of the weight of the traditional Chinese medicine raw material to the traditional Chinese medicine raw material, decocting 3-4 times at 95-100 DEG C for 1.5-2.5 hours each time, filtering, combining the decocting liquid, and concentrating under reduced pressure to relative density of 1.15-1.25 to obtain the traditional Chinese medicine extract.

[0012] Preferably, the organic solvent extraction method is as follows: adding 6-8 times of 60-80% ethanol of the weight of the pretreated traditional Chinese medicine raw material to the pretreated traditional Chinese medicine raw material, refluxing and extracting 2-3 times for 1-2 hours each time, filtering, combining the filtrate, and concentrating the filtrate to the traditional Chinese medicine extract with relative density of 1.20-1.30 at 60 DEG C.

[0013] To solve the above technical problems, the third technical solution of the present application provides a quality control method of the traditional Chinese medicine composition, comprising the following steps: Raw material quality control: establishing the quality standard of the traditional Chinese medicine raw material, strictly testing each batch of raw material according to the quality standard, and only the raw material meeting the standard can be put into production, wherein the quality standard of the traditional Chinese medicine raw material includes appearance identification, heavy metal and harmful element limit, pesticide residue limit, and effective component content determination, wherein the appearance identification is based on the description of the appearance of each traditional Chinese medicinal material in the Chinese Pharmacopoeia, and the appearance of the medicinal material is ensured to meet the standard through visual observation and simple measurement; the heavy metal and harmful element limit is determined by inductively coupled plasma mass spectrometry to ensure that it meets the limit standard specified in the Chinese Pharmacopoeia; the pesticide residue limit is detected by gas chromatography-mass spectrometer to ensure that the pesticide residue is lower than the specified limit; and the effective component content determination is determined by high performance liquid chromatography to ensure that the content of each effective component is within the specified range; Production process quality control: monitoring each key link in the production process and cleaning, maintaining and verifying the production equipment regularly to ensure the normal operation of the equipment and the hygiene of the production environment; specifically, in the extraction process, a temperature sensor is used to monitor the extraction temperature in real time, a time relay is used to control the extraction time, and a flow sensor is used to monitor the solvent consumption to ensure the stability of the extraction parameters; in the forming process, an electronic scale is used to accurately weigh the amount of excipients with an error of less than ±0.5%; and a mixing uniformity detector is used to detect the mixing uniformity to ensure that the content uniformity of the mixed material meets the specified requirements; Finished product quality control: establishing the quality standard of the finished product, visually observing, judging by senses, microscopically identifying, and thin layer chromatographically identifying each batch of finished product to ensure that the properties (including the appearance, color, odor, etc. of the finished product, such as the roundness, uniformity, and color consistency of the pills; the integrity, smoothness, and uniform color of the tablets) and the effective component content of the finished product meet the specified requirements; and establishing a product sample reservation system to observe each batch of product, and regularly checking the stability and quality change of the product. Beneficial effects

[0014] Precise efficacy: Through scientific formula design, this Chinese medicine composition makes the medicinal effects of multiple Chinese medicinal raw materials synergistic with each other, and has the effects of invigorating qi and nourishing blood, soothing the liver and strengthening the spleen, regulating qi and relieving pain, etc. It can effectively improve patients' symptoms and improve their quality of life.

[0015] Stable quality: Through perfect molding technology and strict quality control methods, the consistency and stability of each batch of products are ensured, reducing quality problems caused by raw material differences and production process fluctuations, and improving product reliability and safety.

[0016] The process is feasible: the molding process is simple to operate and easy to control, suitable for industrial large-scale production, can meet the market demand for this traditional Chinese medicine product, and provide technical support for the industrial development of traditional Chinese medicine. DETAILED DESCRIPTION

[0017] The present invention will be further described below in conjunction with specific embodiments.

[0018] Example 1: This embodiment provides a traditional Chinese medicine composition, which is prepared from the following traditional Chinese medicine raw materials: 100 g of Astragalus, 80 g of Angelica, 60 g of Poria, 60 g of Atractylodes, 30 g of Licorice, 50 g of Bupleurum, 50 g of White Peony Root, and 40 g of Citrus aurantium.

[0019] The pill forming process comprises the following steps: Raw material pretreatment: weigh the Chinese medicinal raw materials according to the formula, clean and dry them, stir-fry Atractylodes macrocephala with bran, and roast Bupleurum chinense with vinegar; Extraction of active ingredients: Grind the pretreated Chinese medicinal materials into coarse powder, add 8 times the amount of water, decoct for 3 times, 2 hours each time, combine the decoctions, filter, and concentrate under reduced pressure to a Chinese medicinal paste with a relative density of 1.20 (60°C); Preparation molding: Appropriate amounts of starch, dextrin, and coconut oil (mass ratio of 1:1:0.5) were added to the traditional Chinese medicine paste as excipients and mixed evenly to form a soft material. The soft material was made into pills with a diameter of 3 mm using a pill-making machine, dried at 60°C to a moisture content of less than 10%, and finally coated to form traditional Chinese medicine pills.

[0020] Quality Control: Appearance, thin-layer chromatography, and active ingredient content determination of the TCM raw materials all met quality standards. During the production process, extraction temperature, time, and excipient dosage were monitored to ensure parameter stability. The finished product was tested for properties, moisture content, disintegration time, and content. The results showed a moisture content of 8%, a disintegration time of less than 30 minutes, and active ingredient content within the specified range.

[0021] Example 2 The present example provides a traditional Chinese medicine composition, which is prepared from the following traditional Chinese medicine raw materials: Radix Astragali 150 g, Angelica sinensis 120 g, Poria cocos 90 g, Atractylodes 90 g, Glycyrrhiza 45 g, Bupleurum 75 g, Radix Paeoniae Alba 75 g, Fructus Aurantii 60 g.

[0022] The tablet forming process includes the following steps: Raw material pretreatment: the traditional Chinese medicine raw materials are weighed according to the prescription, and the traditional Chinese medicine raw materials are washed and dried. The Atractylodes is prepared by bran-frying, and the Bupleurum is prepared by vinegar-frying. Extraction of active ingredients: the pretreated traditional Chinese medicine raw materials are crushed into coarse powder, and 70% ethanol is used for reflux extraction for 3 times, 1.5 hours each time. After recovering the ethanol, the traditional Chinese medicine extract is concentrated to a relative density of 1.30 (60°C); Formulation: the traditional Chinese medicine extract is mixed with an appropriate amount of lactose, microcrystalline cellulose, sodium carboxymethyl starch (as a disintegrant) and magnesium stearate (as a lubricant) to form granules. The granules are dried at 70°C, and then tableted to form the traditional Chinese medicine tablets.

[0023] Quality control: The raw materials are put into production after passing the inspection. The mixing uniformity and particle size distribution are monitored during the production process. The finished product is detected, and the properties meet the requirements. The disintegration time is within 15 minutes, the dissolution is more than 80% within 30 minutes, and the content of active ingredients meets the requirements.

[0024] Example 3 The present example provides a traditional Chinese medicine composition, which is prepared from the following traditional Chinese medicine raw materials: Radix Astragali 120 g, Angelica sinensis 100 g, Poria cocos 70 g, Atractylodes 70 g, Glycyrrhiza 35 g, Bupleurum 60 g, Radix Paeoniae Alba 60 g, Fructus Aurantii 50 g.

[0025] The capsule forming process includes the following steps: Raw material pretreatment: the traditional Chinese medicine raw materials are weighed according to the prescription, and the traditional Chinese medicine raw materials are washed and dried. The Atractylodes is prepared by bran-frying, and the Bupleurum is prepared by vinegar-frying. Extraction of active ingredients: the pretreated traditional Chinese medicine raw materials are crushed into coarse powder. First, water is used for decoction extraction for 2 times, 2.5 hours each time, and the water extract is combined. Then, the residues are extracted with 60% ethanol for 2 times, 1 hour each time, and the alcohol extract is combined. The water extract and the alcohol extract are combined, and the traditional Chinese medicine extract is concentrated to a relative density of 1.25 (60°C) under reduced pressure. Formulation: the traditional Chinese medicine extract is mixed with an appropriate amount of starch and microcrystalline cellulose to form granules. After drying, the granules are filled into the capsule shells to form the traditional Chinese medicine capsules.

[0026] Quality control: The raw materials and production process are strictly in accordance with the quality control standards. The finished product is detected, the moisture content is less than 9%, the loading difference meets the requirements, and the effective ingredient content is within the qualified range.

[0027] Animal experiment: Experimental design: 30 clean Kunming mice weighing 18-22 g were selected and randomly divided into blank control group, model control group, traditional Chinese medicine composition low dose group, traditional Chinese medicine composition medium dose group and traditional Chinese medicine composition high dose group, 6 mice in each group. Except the blank control group, the rest of the mice in each group were established into animal models of deficiency of qi and blood and liver stagnation and spleen deficiency by chronic unpredictable mild stress (CUMS) combined with intraperitoneal injection of reserpine. After the modeling was successful, the traditional Chinese medicine composition low, medium and high dose groups were given corresponding doses (low dose was 0.5 times of the clinical equivalent dose, medium dose was the clinical equivalent dose, and high dose was 2 times of the clinical equivalent dose) of the traditional Chinese medicine composition (capsule traditional Chinese medicine composition of example 3 was adjusted into a suspension with appropriate amount of water) by gavage, and the blank control group and the model control group were given the same volume of normal saline by gavage, once a day, for 14 days of continuous administration.

[0028] Observation index: General behavior observation: The general conditions such as mental state, activity amount, diet, and fur color of the mice were observed every day.

[0029] Body weight change: The body weight of the mice was weighed every week, and the body weight change was recorded.

[0030] Serum biochemical index detection: After the administration was completed, the mice were fasted for 12 hours without water, the blood was taken from the eye socket, the serum was separated, and the indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), and hemoglobin (Hb) in the serum were detected by using a fully automatic biochemical analyzer.

[0031] Visceral index determination: After blood was taken, the mice were sacrificed by cervical dislocation, the liver, spleen and thymus were quickly taken out, washed with normal saline, and the water was absorbed with filter paper, weighed, and the visceral index was calculated (visceral index = organ weight / body weight x 100%).

[0032] Histopathological examination: The liver, spleen and thymus tissues were fixed with 10% formaldehyde solution, routinely embedded with paraffin, sliced, HE stained, and the histopathological changes were observed under a light microscope.

[0033] Experimental results: General behavior: The mice in the model control group were listless, with reduced activity and decreased food intake, and the fur was yellow and dry; the mental state, activity, diet and fur color of the mice in the traditional Chinese medicine composition groups were improved to different degrees, and the improvement in the medium and high dose groups was more obvious.

[0034] Body weight change: the body weight of the model control group mice increased slowly, and the difference was significant compared with the blank control group (P<0.05); the body weight of the mice in each dose group of the traditional Chinese medicine composition increased significantly, and the difference was significant in the medium and high dose groups compared with the model control group (P<0.05).

[0035] Serum biochemical indicators: the serum ALT and AST levels of the model control group mice were significantly increased, and the TP, ALB and Hb levels were significantly decreased, and the difference was significant compared with the blank control group (P<0.05); the ALT level of the mice in each dose group of the traditional Chinese medicine composition was decreased, and the TP, ALB and Hb levels were increased, and the difference was significant in the medium and high dose groups compared with the model control group (P<0.05).

[0036] Organ index: the liver, spleen and thymus indexes of the model control group mice were significantly lower than those of the blank control group (P<0.05); the liver, spleen and thymus indexes of the mice in each dose group of the traditional Chinese medicine composition were increased, and the difference was significant in the medium and high dose groups compared with the model control group (P<0.05).

[0037] Histopathology: the liver cells of the model control group mice appeared different degrees of edema and fatty degeneration, and the spleen and thymus tissues had reduced lymphocytes; the histopathological damage of the liver, spleen and thymus tissues of the mice in each dose group of the traditional Chinese medicine composition was reduced to different degrees, and the improvement in the medium dose group was more obvious.

[0038] The above examples are only used to illustrate the technical solutions of the present application, but not to limit them; those skilled in the art should understand that the technical solutions recorded in the foregoing examples can still be modified, or some technical features can be replaced by equivalents; and these modifications or replacements will not make the essence of the corresponding technical solutions deviate from the protection scope of the present application.

Claims

1. A Chinese medicine composition, characterized in that It is prepared from Chinese medicinal raw materials in the following weight ratios: 100-150 parts of Astragalus; 80-120 parts of Chinese Angelica sinensis; 70-90 parts of Poria cocos; 60-90 parts of Atractylodes macrocephala; 30-45 parts of licorice; 50-75 parts of Bupleurum root; 50-75 parts of white peony root; 40-60 parts of Citrus aurantium.

2. The Chinese medicine composition according to claim 1, characterized in that: The Atractylodes macrocephala is stir-fried Atractylodes macrocephala.

3. The Chinese medicine composition according to claim 2, characterized in that: The radix bupleuri is vinegar-fried radix bupleuri.

4. The Chinese medicine composition according to claim 3, characterized in that: The Chinese medicine composition is prepared into a clinically acceptable dosage form by using the Chinese medicine extract obtained by water extraction or organic solvent extraction of the Chinese medicine raw material as the active ingredient and adding pharmaceutically acceptable excipients or auxiliary ingredients.

5. The Chinese medicine composition according to claim 4, characterized in that: The dosage form is decoction, powder, paste, granule, pill or capsule.

6. The molding process of the Chinese medicine composition according to any one of claims 1 to 5, characterized in that: The following steps are involved: Raw material pretreatment: weigh the Chinese medicinal raw materials in the appropriate weight ratio, and clean and dry them; Extraction of active ingredients: crush the pretreated Chinese medicine raw materials into coarse powder, extract the active ingredients in the Chinese medicine raw materials using water extraction or organic solvent extraction and concentrate them to obtain Chinese medicine extract; Preparation molding: According to the dosage form requirements, pharmaceutically acceptable excipients or auxiliary ingredients are added to the traditional Chinese medicine extract to prepare a clinically acceptable dosage form.

7. The molding process according to claim 6, characterized in that: The water extraction method comprises the following steps: adding water 8 to 10 times the weight of the Chinese medicinal raw materials to the Chinese medicinal raw materials, decocting the mixture 3 to 4 times at a temperature of 95 to 100° C., each time for 1.5 to 2.5 hours, filtering, combining the decoctions, and concentrating under reduced pressure to a relative density of 1.15 to 1.25 to obtain a Chinese medicinal extract.

8. The molding process according to claim 6, characterized in that: The organic solvent extraction method comprises the following steps: adding 60-80% ethanol in an amount of 6-8 times the weight of the raw material to the pretreated Chinese medicinal material, performing reflux extraction 2-3 times, each time for 1-2 hours, filtering and combining the filtrate, and concentrating the filtrate to a Chinese medicinal extract with a relative density of 1.20-1.30 at 60°C.

9. The quality control method for the Chinese medicine composition according to any one of claims 1 to 5, characterized in that: include: Raw material quality control: Establish quality standards for Chinese medicine raw materials. Each batch of raw materials is strictly inspected according to the quality standards. Only raw materials that meet the standards can be put into production. Production process quality control: During the production process, each key link is monitored and production equipment is regularly cleaned, maintained and verified to ensure the normal operation of the equipment and the hygiene of the production environment; Finished product quality control: Establish quality standards for finished products, conduct visual observation, sensory judgment, microscopic identification, and thin-layer chromatography identification on each batch of finished products to ensure that the properties and active ingredient content of the finished products meet the requirements; at the same time, establish a product sample retention system, retain samples for observation on each batch of products, and regularly check their stability and quality changes.

10. The quality control method according to claim 9, characterized in that: Step (2) is as follows: During the extraction process, a temperature sensor is used to monitor the extraction temperature in real time, a time relay is used to control the extraction time, and a flow sensor is used to monitor the solvent usage to ensure stable extraction parameters. During the molding process, an electronic scale is used to accurately weigh the amount of auxiliary materials, with the error controlled within ±0.5%; a mixing uniformity tester is used to test the mixing uniformity to ensure that the content uniformity of the mixed materials meets the requirements.