A traditional Chinese medicine composition for supplementing both qi and blood as well as a preparation method and application thereof

Abstract

This invention relates to the field of traditional Chinese medicine (TCM) technology, specifically to a TCM composition for replenishing both Qi and blood, its preparation method, and its application. The TCM composition of this application comprises sixteen medicinal materials: steamed Codonopsis pilosula, Angelica sinensis, processed Atractylodes macrocephala, Astragalus membranaceus, Poria cocos, Paeonia lactiflora, processed Ligusticum chuanxiong, Rehmannia glutinosa, Lycium barbarum, Polygonatum sibiricum (processed with wine), deer antler powder, cinnamon, longan pulp, jujube, tangerine peel, and processed licorice root. The combined effects of these herbs primarily replenish Qi, secondarily nourish blood, strengthen the spleen and kidneys, regulate Qi and harmonize the middle Jiao (digestive system), replenishing Qi without causing stagnation, and replenishing blood without causing greasiness. Together, they form a formula for replenishing Qi and blood, strengthening the spleen and nourishing the heart. It is suitable for symptoms such as sallow complexion, shortness of breath, fatigue, dizziness, and blurred vision caused by Qi and blood deficiency due to inherent weakness, illness, or postpartum.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition that nourishes both qi and blood, its preparation method, and its application. Background Technology

[0002] Qi and blood are the material basis for maintaining human life activities. Qi generates blood, circulates blood, and retains blood; blood carries qi and nourishes qi. When qi and blood are abundant, the internal organs are in harmony, and the body is healthy. In modern society, factors such as the fast pace of life, increased work and study pressure, irregular diet, chronic illness and physical weakness, postpartum malnutrition, and overwork can easily lead to dysfunction of the spleen and stomach, insufficient production of qi and blood, resulting in qi and blood deficiency syndrome. Qi and blood deficiency is a common deficiency syndrome in clinical practice, which can affect multiple systems and organs. Its clinical manifestations are diverse, commonly including a sallow or pale complexion, shortness of breath and reluctance to speak, fatigue, dizziness, palpitations, insomnia, numbness in the hands and feet, scanty menstruation, lower abdominal pain during or after menstruation, pale tongue with a thin white coating, and a weak pulse. It is widely present in various chronic diseases in internal medicine, gynecology, traditional Chinese medicine, and other departments, as well as in people with weak constitutions, seriously affecting patients' health and quality of life. Clinical intervention and conditioning are of great significance. Our hospital has long been committed to the treatment of deficiency syndromes with traditional Chinese medicine. The Qi-tonifying and Blood-nourishing Formula is an effective formula with many years of clinical experience. The formula takes the principles of tonifying Qi and strengthening the spleen, nourishing blood and replenishing essence, regulating Qi and harmonizing the middle Jiao as its treatment method. It targets the core pathogenesis of Qi and Blood deficiency, tonifies Qi without stagnation, and nourishes blood without being greasy. It is suitable for various symptoms of Qi and Blood deficiency caused by physical weakness, recovery period after illness, postpartum, and fatigue.

[0003] Therefore, the current key research direction is to find a formula that can effectively treat symptoms such as sallow complexion, shortness of breath, fatigue, dizziness, and blurred vision caused by physical weakness, illness, or childbirth, alleviate various symptoms caused by deficiency of both qi and blood, and has not shown adverse reactions such as internal heat, allergies, or damage to liver and kidney function. It should be safe and can be used as an effective formula for long-term conditioning of people with deficiency of both qi and blood. Summary of the Invention

[0004] To address the aforementioned technical problems in the existing technology, this invention provides a traditional Chinese medicine composition for replenishing both Qi and Blood, its preparation method, and its application. Specifically, this is achieved through the following technical solution: A traditional Chinese medicine composition for tonifying both qi and blood includes the following ingredients: steamed Codonopsis pilosula, Angelica sinensis, processed Atractylodes macrocephala, Astragalus membranaceus, Poria cocos, Paeonia lactiflora, processed Ligusticum chuanxiong, Rehmannia glutinosa, Lycium barbarum, Polygonatum sibiricum (processed with wine), deer antler powder, cinnamon, longan pulp, jujube, tangerine peel, and prepared licorice root.

[0005] Furthermore, the weight proportions of each raw material are as follows: 80-85 parts of steamed Codonopsis pilosula, 45-55 parts of Angelica sinensis, 80-85 parts of processed Atractylodes macrocephala, 80-85 parts of Astragalus membranaceus, 80-85 parts of Poria cocos, 45-55 parts of Paeonia lactiflora, 45-55 parts of processed Ligusticum chuanxiong, 65-70 parts of Rehmannia glutinosa, 80-85 parts of Lycium barbarum, 80-85 parts of Polygonatum sibiricum (processed with wine), 80-85 parts of deer antler powder, 15-20 parts of cinnamon, 30-35 parts of longan pulp, 65-70 parts of jujube, 45-55 parts of dried tangerine peel, and 30-35 parts of processed licorice root.

[0006] Furthermore, the weight proportions of each raw material are as follows: 83 parts steamed Codonopsis pilosula, 50 parts Angelica sinensis, 83 parts processed Atractylodes macrocephala, 83 parts Astragalus membranaceus, 83 parts Poria cocos, 50 parts Paeonia lactiflora, 50 parts processed Ligusticum chuanxiong, 67 parts Rehmannia glutinosa, 83 parts Lycium barbarum, 83 parts Polygonatum sibiricum (processed with wine), 83 parts deer antler powder, 17 parts Cinnamomum cassia, 33 parts longan pulp, 67 parts jujube, 50 parts dried tangerine peel, and 33 parts processed Glycyrrhiza uralensis.

[0007] The above-mentioned traditional Chinese medicine composition is used in the preparation of medicines that replenish qi and blood, enhance immunity, and combat fatigue.

[0008] Furthermore, the aforementioned qi-tonifying and blood-tonifying drugs are those that increase the levels of blood RBC, HCT, and HGB.

[0009] Furthermore, the aforementioned anti-fatigue drug is a drug that increases the activity of sodium-potassium ATPase and calcium-magnesium ATPase in rat serum.

[0010] The above-mentioned traditional Chinese medicine composition is used in the preparation of medicines for treating symptoms such as sallow complexion, shortness of breath, fatigue, dizziness, and blurred vision caused by physical weakness, illness, or childbirth.

[0011] The oral preparation is prepared using the above-mentioned traditional Chinese medicine composition.

[0012] Furthermore, the oral preparation is specifically a compound preparation.

[0013] The preparation method of this compound is as follows: take 16 ingredients in proportion, including steamed Codonopsis pilosula, Angelica sinensis, processed Atractylodes macrocephala, Astragalus membranaceus, Poria cocos, Paeonia lactiflora, processed Ligusticum chuanxiong, Rehmannia glutinosa, Lycium barbarum, Polygonatum sibiricum (processed with wine), deer antler powder, cinnamon, longan pulp, jujube, tangerine peel, and processed licorice root. Add water and decoct twice. The first time, add 8 times the amount of water and decoct for 1.5 hours. The second time, add 6 times the amount of water and decoct for 1.5 hours. Filter, combine the filtrates, concentrate the filtrate to 1000ml, let stand for 24 hours, filter, add 0.5g of ethylparaben dissolved in 50ml of boiling water, add water to adjust the total volume to 1000ml, stir well, and fill into bottles to obtain the final product.

[0014] Qi and blood are the material basis for maintaining human life activities. Qi is the commander of blood, capable of generating, circulating, and controlling blood; blood is the mother of qi, capable of carrying and nourishing qi. The two are mutually generative and complementary. Modern people often suffer from spleen and stomach weakness and insufficient qi and blood production due to irregular diet, irregular work and rest, excessive thinking and fatigue, prolonged illness, or postpartum malnutrition, resulting in qi and blood deficiency syndrome. Symptoms include sallow complexion, shortness of breath, fatigue, dizziness, and irregular menstruation. The pathogenesis is rooted in qi deficiency and manifested in blood deficiency; treatment focuses on tonifying qi and blood, strengthening the spleen and nourishing the heart, and regulating both the spleen and kidneys.

[0015] This formula is designed to address the symptoms and etiology of Qi and Blood Deficiency Syndrome. It is a modified version of the Bazhen Decoction from the *Taiping Huimin Heji Jufang* (Formulary of the Bureau of Imperial Medical Services for the Benefit of the People) and the Renshen Yangrong Decoction from the *Sanyin Jiyi Bingzheng Fanglun* (Treatise on the Three Causes of Diseases). Bazhen Decoction, also known as Bazhen Powder, is a tonifying formula composed of ginseng, atractylodes macrocephala, poria cocos, angelica sinensis, chuanxiong rhizome, white peony root, rehmannia root, and licorice root (processed). It is used to treat Qi and Blood Deficiency Syndrome, characterized by pale or sallow complexion, dizziness, fatigue, shortness of breath, palpitations, reduced appetite, pale tongue with a thin white coating, and a weak or feeble pulse. Clinically, it is often used to treat post-illness weakness, various chronic diseases, and menstrual disorders in women who are also suffering from Qi and Blood Deficiency. Renshen Yangrong Decoction is composed of peony root, angelica root, tangerine peel, astragalus root, cinnamon bark, ginseng, atractylodes rhizome, prepared licorice root, prepared rehmannia root, schisandra fruit, poria cocos, and polygala root. It is used for symptoms such as fatigue and weakness, heaviness in the limbs, shortness of breath, palpitations, lower abdominal distension, back pain, dry throat and lips. It has the functions of tonifying qi and blood, strengthening the spleen and nourishing the heart. This standardized formula has been used clinically in our hospital for many years and has evolved based on research into the main indications and symptoms. The formula consists of codonopsis root, poria cocos, prepared atractylodes rhizome, white peony root, angelica root, prepared chuanxiong rhizome, rehmannia root, wolfberry fruit, polygonatum rhizome, deer antler powder, astragalus root, cinnamon bark, longan pulp, jujube, tangerine peel, and prepared licorice root. Based on the fundamental theories of traditional Chinese medicine, such as the normal functioning of Qi and blood in the human body, the deficiency of Qi leading to blood deficiency, and the dissipation of Qi due to blood deficiency, the prescription addresses symptoms such as sallow complexion, shortness of breath, fatigue, dizziness, and blurred vision caused by inherent weakness, illness, or childbirth. The prescription uses replenishing Qi and blood as the basic treatment method to achieve the therapeutic goal of simultaneously replenishing Qi and blood, thereby alleviating various symptoms caused by deficiency of both Qi and blood.

[0016] This syndrome is caused by physical weakness, illness, or postpartum deficiency of qi and blood. The treatment should focus on replenishing qi and nourishing blood.

[0017] Chief herb: Codonopsis pilosula. Codonopsis pilosula is sweet and neutral in nature. It enters the spleen and lung meridians, replenishes qi and blood, and is an essential herb for replenishing qi and blood. It directly targets the root cause of qi deficiency and blood weakness, and governs the entire formula's function of replenishing qi and blood.

[0018] Assistant herbs: Astragalus membranaceus, processed Atractylodes macrocephala, and Poria cocos. Astragalus membranaceus is sweet and warm, tonifying Qi and raising Yang, consolidating the exterior and generating fluids, thus enhancing the Qi-tonifying effect of the principal herb; when Qi is abundant, blood is generated. Processed Atractylodes macrocephala strengthens the spleen and tonifies Qi, dries dampness and harmonizes the middle Jiao, assisting the spleen and stomach in their digestive functions to support the generation of Qi and blood. Poria cocos strengthens the spleen and eliminates dampness, calms the mind and soothes the nerves, ensuring that tonification is not stagnant. These three herbs together act as assistant herbs, assisting the principal herb in tonifying Qi and strengthening the spleen, laying the foundation for blood replenishment.

[0019] The adjuvant herbs are: Angelica sinensis, processed Ligusticum chuanxiong, Paeonia lactiflora, Rehmannia glutinosa, Lycium barbarum, Polygonatum sibiricum, deer antler powder, cinnamon, longan pulp, jujube, and dried tangerine peel. Angelica sinensis, Paeonia lactiflora, Rehmannia glutinosa, and processed Ligusticum chuanxiong nourish and harmonize the blood, nourish yin and soften the liver, ensuring that blood replenishment does not lead to stagnation. Lycium barbarum and Polygonatum sibiricum nourish the liver and kidneys, benefit essence and nourish blood, replenishing kidney essence to transform into blood. Deer antler powder warms the kidneys and assists yang, benefits essence and nourishes blood, warming and nourishing essence and blood. Cinnamon tonifies fire and assists yang, warms and unblocks blood vessels, and promotes the growth of qi and blood. Longan pulp and jujube tonify the heart and spleen, nourish blood and calm the mind, improving sallow complexion and fatigue. Dried tangerine peel regulates qi and strengthens the spleen, dries dampness and resolves phlegm, harmonizes qi and regulates the middle jiao, ensuring that the entire formula is nourishing without being cloying and nourishing without being greasy. All these herbs work together as adjuvant herbs to simultaneously replenish qi and blood, regulate the spleen and kidneys, and simultaneously nourish blood, nourish yin, warm yang, and regulate qi.

[0020] The main ingredient is roasted licorice root. Roasted licorice root is sweet and warm, and it invigorates qi, strengthens the middle jiao, and harmonizes the other ingredients, making the whole formula mild and gentle, thus achieving the effect of invigorating qi and nourishing blood.

[0021] When used together, these herbs primarily invigorate Qi, secondarily nourish blood, strengthen the spleen and kidneys, regulate Qi and harmonize the middle Jiao. They replenish Qi without causing stagnation and nourish blood without being cloying, thus forming a formula that invigorates Qi and nourishes blood, strengthens the spleen and nourishes the heart. It is suitable for symptoms such as sallow complexion, shortness of breath, fatigue, dizziness, and blurred vision caused by Qi and blood deficiency due to inherent weakness, illness, or childbirth.

[0022] Compared with the prior art, the technical effects of this invention are reflected in: The traditional Chinese medicine composition of this application consists of sixteen herbs: steamed Codonopsis pilosula, Angelica sinensis, processed Atractylodes macrocephala, Astragalus membranaceus, Poria cocos, Paeonia lactiflora, processed Ligusticum chuanxiong, Rehmannia glutinosa, Lycium barbarum, Polygonatum sibiricum (processed with wine), deer antler powder, cinnamon, longan pulp, jujube, tangerine peel, and processed licorice root. The combined effects of these herbs primarily tonify Qi, secondarily nourish blood, strengthen the spleen and kidneys, regulate Qi and harmonize the middle Jiao, tonify Qi without causing stagnation, and nourish blood without being cloying. Together, they form a formula that tonifies Qi and blood, strengthens the spleen and nourishes the heart. It is suitable for symptoms such as sallow complexion, shortness of breath, fatigue, dizziness, and blurred vision caused by Qi and blood deficiency due to inherent weakness, illness, or postpartum.

[0023] This traditional Chinese medicine composition for replenishing both Qi and Blood can improve Qi deficiency symptoms in mice with Qi and Blood deficiency, increase blood RBC, HCT, and HGB levels, improve the rate of weight change and swimming exhaustion time in mice, improve energy metabolism, increase the proportion of nucleated cells in bone marrow, and improve pathological changes in the spleen of mice. It can also increase the spleen and thymus indices, blood immune cell counts, and humoral immune function in mice with restricted food intake and Qi deficiency. Furthermore, it can increase blood RBC, HGB, and HCT levels in rats with blood loss and blood deficiency, and increase the activity of serum sodium-potassium ATPase and calcium-magnesium ATPase in rats. In summary, this Qi and Blood replenishing compound has the effects of replenishing both Qi and Blood, improving immunity, and combating fatigue.

[0024] In long-term clinical application, this formula has been found to be mild in nature, with only a very small number of patients experiencing mild stomach discomfort, which can be relieved by adjusting the method of administration. No adverse reactions such as fever, allergies, or liver and kidney damage have been observed, indicating high safety. It can be used as an effective formula for long-term conditioning of people with deficiency of both qi and blood, and has good clinical promotion value. Attached Figure Description

[0025] Figure 1 The effect of the Qi and Blood Tonifying Compound on nucleated cells in the bone marrow of mice with Qi and Blood Deficiency (×400) is shown in the following groups: A. Blank group; B. Model group; C. Compound Donkey-hide Gelatin Oral Liquid 12.33 g / kg group; D. Qi and Blood Tonifying Compound 6.17 g / kg group; E. Qi and Blood Tonifying Compound 12.33 g / kg group; F. Qi and Blood Tonifying Compound 24.66 g / kg group.

[0026] Figure 2 The study investigated the effects of a Qi and Blood Tonifying Compound on the histopathological characteristics of spleen tissue in mice with Qi and Blood Deficiency (HE staining, ×400). The groups included: A. Blank group; B. Model group; C. Compound Donkey-hide Gelatin Oral Liquid 12.33 g / kg group; D. Qi and Blood Tonifying Compound 6.17 g / kg group; E. Qi and Blood Tonifying Compound 12.33 g / kg group; F. Qi and Blood Tonifying Compound 24.66 g / kg group.

[0027] Figure 3 It is a detailed process flow diagram. Detailed Implementation

[0028] The technical solution of the present invention will be further defined below with reference to specific embodiments, but the scope of protection is not limited to the description made.

[0029] Example 1 (1) Steamed Codonopsis pilosula 83g, Angelica sinensis 50g, processed Atractylodes macrocephala 83g, Astragalus membranaceus 83g, Poria cocos 83g, Paeonia lactiflora 50g, processed Ligusticum chuanxiong 50g, Rehmannia glutinosa 67g, Lycium barbarum 83g, Polygonatum sibiricum 83g, deer antler powder 83g, Cinnamomum cassia 17g, longan pulp 33g, jujube 67g, tangerine peel 50g, prepared Glycyrrhiza uralensis 33g.

[0030] Example 2 (1)85 g of steamed Codonopsis pilosula, 45 g of Angelica sinensis, 80 g of processed Atractylodes macrocephala, 80 g of Astragalus membranaceus, 80 g of Poria cocos, 45 g of Paeonia lactiflora, 45 g of processed Ligusticum chuanxiong, 65 g of Rehmannia glutinosa, 80 g of Lycium barbarum, 80 g of processed Polygonatum sibiricum, 80 g of Cornu cervi degelatinatum, 15 g of Cinnamomum cassia, 30 g of Arillus longan, 65 g of Fructus jujubae, 45 g of Pericarpium citri reticulatae, 30 g of roasted Glycyrrhiza uralensis.

[0031] Example 3 (1)80 g of steamed Codonopsis pilosula, 45 g of Angelica sinensis, 85 g of processed Atractylodes macrocephala, 85 g of Astragalus membranaceus, 85 g of Poria cocos, 45 g of Paeonia lactiflora, 45 g of processed Ligusticum chuanxiong, 65 g of Rehmannia glutinosa, 80 g of Lycium barbarum, 80 g of processed Polygonatum sibiricum, 80 g of Cornu cervi degelatinatum, 15 g of Cinnamomum cassia, 30 g of Arillus longan, 65 g of Fructus jujubae, 45 g of Pericarpium citri reticulatae, 30 g of roasted Glycyrrhiza uralensis.

[0032] Example 4 (1)80 g of steamed Codonopsis pilosula, 55 g of Angelica sinensis, 80 g of processed Atractylodes macrocephala, 80 g of Astragalus membranaceus, 80 g of Poria cocos, 55 g of Paeonia lactiflora, 55 g of processed Ligusticum chuanxiong, 70 g of Rehmannia glutinosa, 85 g of Lycium barbarum, 85 g of processed Polygonatum sibiricum, 85 g of Cornu cervi degelatinatum, 20 g of Cinnamomum cassia, 35 g of Arillus longan, 70 g of Fructus jujubae, 55 g of Pericarpium citri reticulatae, 30 g of roasted Glycyrrhiza uralensis.

[0033] Main pharmacodynamic experiments: 1. Experimental purpose According to the functions, indications of the Qi and Blood Double-Supplement Mixture, select the experimental methods and detection indexes, investigate its effects of supplementing Qi, nourishing blood, enhancing immunity and anti-fatigue, and provide the basis for main pharmacodynamic experiments for clinical application.

[0034] 2. Experimental materials 2.1 Tested drugs Qi and Blood Double-Supplement Mixture, production batch number: 20241115, provided by Yulin Traditional Chinese Medicine Hospital, clinical usage and dosage: oral administration, 2 vials each time, 3 times a day; specification: 10 ml per vial (1.0 g of cut crude drugs per ml). Before the experiment, it was concentrated into a thick paste, bottled and stored in the refrigerator for standby.

[0035] 2.2 Test control products Normal control: Distilled water.

[0036] Positive control: Compound Ejiao Jiang, batch number: 2406022, Dong'e Ejiao Co., Ltd.

[0037] 2.3 Experimental animals and feeds KM mice, SPF grade, half male and half female, 18 - 22 g, provided by Changsha Tianqin Biotechnology Co., Ltd., license number: SCXK(Xiang)2024 - 0021.

[0038] SD rats, SPF grade, half male and half female, weighing 180 - 220 g, provided by Tianqin Biotechnology Co., Ltd. in Changsha, license number: SCXK(Xiang)2024 - 0021.

[0039] Growth and reproduction feed for mice and rats, produced by Keao Xieli (Tianjin) Feed Co., Ltd., license number: SCXK(Jin)2020 - 0004. Rearing conditions: room temperature 22 - 24°C, humidity 57 - 63%, animal use license number: SYXK(Gui)2022 - 0001.

[0040] Number of animals in each group: 10.

[0041] 2.4 Experimental reagents and instruments Cyclophosphamide, product of Sigma, batch number: PHR1404; Acetylphenylhydrazine, product of Shanghai Macklin Biochemical Co., Ltd., batch number: A800026; Mouse interleukin - 1β (IL - 1β) ELISA kit, mouse interleukin - 6 (IL - 6) ELISA kit, cyclic adenosine monophosphate (cAMP) ELISA kit, cyclic guanosine monophosphate (cGMP) ELISA kit, mouse immunoglobulin M (IgM) ELISA kit, mouse immunoglobulin G (IgG) ELISA kit, products of Wuhan Ealite Biotechnology Co., Ltd., batch numbers are: E - EL - M0037, E - EL - M0044, E - EL - 0056, E - EL - 0083, E - EL - M3036, E - EL - M0692; Wright - Giemsa compound staining solution, product of Beijing Solarbio Science & Technology Co., Ltd., batch number: G1020; Ultra - micro ATPase (Na + K +) kit, Ultra - micro ATPase (Ca2 + Mg2 +) kit, products of Nanjing Jiancheng Bioengineering Institute Co., Ltd., batch numbers: A070 - 2 - 4, A070 - 3 - 3.

[0042] BC - 5000Vet fully automatic five - classification animal blood cell analyzer, produced by Shenzhen Mindray Bio - medical Electronics Co., Ltd.; Multiskan microplate reader, produced by Thermo Fisher Scientific Inc. in the United States; RM2255 fully automatic rotary microtome, Leica DM2500 microscope, produced by Leica Microsystems in Germany.

[0043] 3. Test methods Qi - and - blood - tonifying mixture is derived from the clinical prescription of Yulin Traditional Chinese Medicine Hospital and has the effect of supplementing qi and blood. It is used for symptoms such as sallow complexion, lack of qi and shortness of breath, listlessness, dizziness and vertigo caused by congenital weakness, after illness or after childbirth. Entrusted by Yulin Traditional Chinese Medicine Hospital, according to the functions, indications of this medicine and the requirements of the guiding principles for pre - clinical research of new drugs, its main pharmacodynamic research was carried out.

[0044] 3.1 Test plan 3.1.1 Dosage Each test substance was divided into three dosage groups, and the drug dosage was expressed in g / kg (amount of medicinal slices / animal body weight). According to the "Methodology of Pharmacological Research of Traditional Chinese Medicine," dosage conversion was calculated based on body surface area ratio. Using an adult clinical dosage of 60 g / day, the equivalent dose for mice (20g body weight) to adults was 12.33 g / kg (equivalent dose = 60g (adult daily dose) ÷ 60kg (adult body weight) × 12.33 (body surface area method coefficient) = 12.33 g / kg, approximately 12 times the adult clinical daily dose); the equivalent dose for rats (200g) to adults was 5.52 g / kg (equivalent dose = 60g (adult daily dose) ÷ 60kg (adult body weight) × 6.17 (body surface area method coefficient for 150g rats) × 0.894 (correction coefficient between 200g rats and 150g standard rats) = 5.52 g / kg, approximately 5 times the adult clinical daily dose). The dosage groups were: low dose (half the equivalent dose), medium dose (equivalent dose), and high dose (twice the equivalent dose). The positive control drug dose, calculated based on body surface area ratio, was equal to the adult equivalent dose.

[0045] 3.1.2 Administration method All experiments involved gavage administration of the drugs. The dosage for mice was 20 ml / kg, and for rats it was 10 ml / kg, once daily.

[0046] 3.2 Statistical Methods Quantitative data are expressed as (x±s). SPSS 27.0 statistical software was used for t-tests between groups, and ANOVA was performed to compare differences between groups. Qualitative response data were compared using the χ² test. 2 Test. P < 0.05 indicates that the difference is statistically significant.

[0047] 3.3 Test Methods 3.3.1 Effects of Qi and Blood Tonifying Compound on Qi and Blood Deficiency in Mice Induced by Swimming Fatigue Combined with Drugs Healthy KM mice, half male and half female, were acclimatized for 3 days and then trained to swim. Ten mice were randomly selected from suitable swimming mice (those that did not sink directly or spin within 10 seconds) as the control group. The remaining mice were subjected to exhaustive swimming with a weight-bearing load (a 10% weight of lead wire was wrapped around the base of the mouse's tail, and the mice were trained to swim at 40 km / h). Mice were swam in a CM-deep water tank until exhaustion (weak limbs, upright body, head submerged for 5 seconds and unable to surface) for 10 consecutive days to create a Qi deficiency mouse model. The model was considered successfully established when mice exhibited signs such as curling up, arched back, ruffled fur, dull coat, and shortness of breath. Mice with Qi deficiency were subcutaneously injected with acetylphenylhydrazine at 20 mg / kg in the morning and intraperitoneally injected with cyclophosphamide at 40 mg / kg in the afternoon for 3 consecutive days to induce anemia. Blood was collected from the orbital sinus to measure hemoglobin levels. A significantly lower hemoglobin level than the normal group was considered a successful anemia model. Mice with both Qi and blood deficiency were divided into a model group, a compound donkey-hide gelatin oral liquid group (12.33 mL / kg), and a Qi and blood tonifying combination group (6.17, 12.33, 24.66 mL / kg, respectively). The test drug was administered in g / kg groups, with 10 mice in each group. Mice in the drug administration groups were given the corresponding test drug by gavage at a dose of 20 ml / kg, while the control group and the model group were given an equal volume of distilled water. The administration was once daily for 14 consecutive days. One hour after the last administration, the mice were put to exhaustion by swimming, and relevant indicators were measured.

[0048] Detection indicators: (1) Observe the behavior and physiological state of mice; (2) Hematological indicators: detect the red blood cell (RBC), hemoglobin (HGB) content and hematocrit (HCT) of mouse blood; (3) Calculate the change rate of mouse body weight (%): Change rate of body weight (%) = (body weight after administration - body weight before administration) ÷ body weight before administration × 100%; (4) Record the time of exhaustion of swimming in mice; (5) Blood biochemical indicators: detect the serum IL-6, IL-1β, cAMP, and cGMP levels and calculate the cAMP / cGMP ratio; (6) Stain nucleated cells of femoral head bone marrow with Wright-Giemsa composite staining solution; (7) Histopathological examination: HE staining of spleen.

[0049] 3.3.2 Effects of Qi and Blood Tonifying Compound on Immune Function in Food-Restricted Qi-Deficient Mice Healthy KM mice (half male and half female) were randomly divided into three groups (n=10 per group) after acclimatization for 3 days: a control group, a model group, a compound donkey-hide gelatin oral liquid group (12.33 g / kg), and a Qi and Blood Tonifying Mixture group (6.17, 12.33, and 24.66 g / kg). Mice in the drug-treated groups were administered the corresponding test drug by gavage at a dose of 20 ml / kg, while the control and model groups were given an equal volume of distilled water. Administration was once daily for 14 consecutive days. From day 1 to day 14 of drug administration, all mice except the control group were fed a limited diet of 100 g / kg, except for the control group which was given sufficient feed (250 g / kg). Twenty-four hours after the last drug administration, blood and organs were collected and weighed for relevant indicator testing.

[0050] Detection indicators: (1) Organ index: calculate the organ index of spleen and thymus; (2) Hematology: detect the content of white blood cells (WBC), lymphocytes (Lym) and neutrophils (Neu) in mouse blood; (3) Blood biochemical indicators: detect the content of IgM and IgG in mouse serum.

[0051] 3.3.3 Effects of Qi and Blood Tonifying Compound on Rats with Blood Loss-Induced Anemia Healthy SD rats, half male and half female, were acclimatized for 3 days and then divided into four groups: a control group, a model group, a compound donkey-hide gelatin oral liquid group (5.52 g / kg), and groups treated with a qi and blood tonic (2.76, 5.52, and 11.04 g / kg), with 10 rats in each group. Rats in the treatment groups were administered the corresponding test drug by gavage at a dose of 10 ml / kg, while the control and model groups were given an equal volume of distilled water, once daily for 14 consecutive days. On the first day of administration, except for the control group, all other groups underwent venous leukemia (5.0 mL / kg) daily for 14 consecutive days to induce hemorrhagic anemia. Twenty-four hours after the last administration, blood and organs were collected and weighed for relevant index testing.

[0052] Detection indicators: (1) Hematological indicators: detection of RBC, HGB, HCT; (2) Blood biochemical indicators: activity of ultra-micro APT enzyme (Na+K+) and ultra-micro APT enzyme (Ca2+Mg2+).

[0053] 4. Test Results 4.1 Effects of Qi and Blood Tonifying Compound on Qi and Blood Deficiency in Mice Induced by Swimming Fatigue Combined with Drugs 4.1.1 Observation of blood behavior and physiological state in mice with qi and blood deficiency The model group mice exhibited symptoms of Qi deficiency, including lethargy, listlessness, sluggishness, curling up and arching their backs, and a tendency to huddle together; physiologically, their fur was fluffy, sparse, dull, and prone to falling out; their skin was loose; their eyes were dull and squinting; their paws and tails were pale and lackluster; their stools were loose and their perianal area was soiled. The Qi and Blood Tonifying Agent was administered to mice by gavage at doses of 6.17, 12.33, and 24.66 g / kg, which improved the symptoms of Qi deficiency to varying degrees. Specifically, the symptoms were: (1) Behavioral aspects: the mice were active and agile, had a lively spirit, bright and alert eyes, erect ears, relaxed posture, and no huddling; (2) Physiological aspects: the mice had a suitable body surface temperature, smooth and shiny fur that did not easily fall out, rosy paws and tails, stable food intake, formed stools, and a clean perianal area. The results showed that the Qi and Blood Tonifying Agent could improve the symptoms of Qi deficiency in mice with both Qi and Blood deficiency and had a Qi-tonifying effect.

[0054] 4.1.2 Effects on the levels of RBC, HCT, and HGB in the blood of mice with qi and blood deficiency The results are shown in Table 1. The levels of RBC, HCT, and HGB in the blood of mice in the model group were significantly lower than those in the control group (p<0.01), indicating the successful establishment of the blood deficiency mouse model. Gavage administration of the Qi and Blood Tonifying Agent at doses of 6.17, 12.33, and 24.66 g / kg to mice increased the levels of RBC, HCT, and HGB in the blood to varying degrees. Compared with the model group, the RBC levels in the 6.17, 12.33, and 24.66 g / kg dose groups showed significant differences (p<0.05, p<0.01), and the HCT and HGB levels in the 6.17 and 24.66 g / kg dose groups showed significant differences (p<0.05, p<0.01). These results indicate that the Qi and Blood Tonifying Agent can increase the levels of RBC, HCT, and HGB in the blood of mice with Qi and Blood deficiency, demonstrating a blood-tonifying effect.

[0055] Table 1. Effects of Qi and Blood Tonifying Compound on Blood RBC, HGB, and HCT in Mice with Qi and Blood Deficiency (x±s, n=10)

[0056] Compared with the blank group, ** p <0.01; compared with the model group, △ p <0.05, △△ p <0.01 4.1.3 Effects on the rate of change in body weight and time to exhaustion during swimming in mice with qi and blood deficiency The results are shown in Table 2. The body weight change rate and swimming exhaustion time of the model mice were significantly lower than those of the control group. Compared with the control group, the body weight change rate and swimming exhaustion time showed significant differences (p<0.01), indicating that the mice with qi and blood deficiency had impaired energy metabolism and decreased exercise endurance. Gavage administration of the qi and blood tonifying agent to mice at doses of 6.17, 12.33, and 24.66 g / kg increased the body weight change rate and prolonged the swimming exhaustion time to varying degrees. Compared with the model group, the body weight change rate and swimming exhaustion time of the 12.33 and 24.66 g / kg dose groups showed significant differences (p<0.05 or p<0.01). The results indicate that the qi and blood tonifying agent can increase the body weight change rate and swimming exhaustion time of mice with qi and blood deficiency, and has the effects of enhancing physical fitness and anti-fatigue.

[0057] Table 2. Effects of the Qi and Blood Tonifying Compound on the rate of change in body weight and time to exhaustion in mice with Qi and Blood Deficiency (x±s, n=10)

[0058] Compared with the blank group, ** p <0.01; compared with the model group, △ p <0.05, △△ p <0.01 4.1.4 Effects on serum IL-1β, IL-6, cAMP, and cGMP levels in mice with qi and blood deficiency The results are shown in Table 3. The serum IL-1β, IL-6, and cAMP levels and the cAMP / cGMP ratio were significantly increased in the model group mice, while the cGMP content was decreased. These differences were statistically significant compared with the blank group (p<0.01), indicating that the mice with qi and blood deficiency had excessive inflammatory activation and energy metabolism imbalance. The Qi-Blood Tonifying Compound, administered to mice by gavage at doses of 6.17, 12.33, and 24.66 g / kg, reduced serum IL-1β, IL-6, and cAMP levels and the cAMP / cGMP ratio to varying degrees, while increasing cGMP levels. Compared with the model group, the 6.17 and 24.66 g / kg dose groups showed significant differences in IL-1β (p<0.01), the 6.17, 12.33, and 24.66 g / kg dose groups showed significant differences in IL-6 levels and the cAMP / cGMP ratio (p<0.05, p<0.01), and the 12.33 and 24.66 g / kg dose groups showed significant differences in cAMP levels (p<0.05, p<0.01). These results indicate that the Qi-Blood Tonifying Compound can reduce serum inflammatory factor levels in mice, improve energy metabolism, and has anti-inflammatory and energy metabolism balance regulating effects, thus exerting a regulatory effect of tonifying Qi and nourishing blood.

[0059] Table 3. Effects of the Qi and Blood Tonifying Compound on serum IL-1β, IL-6, cAMP, cGMP, and cAMP / cGMP levels in mice with Qi and Blood Deficiency (x±s, n=10)

[0060] Compared with the blank group, ** p <0.01; compared with the model group, △ p <0.05, △△ p <0.01 4.1.5 Effects on nucleated cells in the bone marrow of mice with qi and blood deficiency The results are shown in Table 4. Figure 1 The proportion of nucleated cells in the femoral head bone marrow of the model group mice was significantly reduced compared with the control group (p<0.01), indicating that the bone marrow hematopoietic function was suppressed in mice with qi and blood deficiency. Gavage administration of the qi and blood tonifying compound to mice at doses of 6.17, 12.33, and 24.66 g / kg increased the proportion of nucleated cells in the femoral head bone marrow to varying degrees. Compared with the model group, the proportion of nucleated cells in the bone marrow of the 12.33 and 24.66 g / kg dose groups showed significant differences (p<0.01). These results indicate that the qi and blood tonifying compound can increase the proportion of nucleated cells in the bone marrow and promote bone marrow hematopoietic function.

[0061] Table 4. Effects of the Qi and Blood Tonifying Compound on Nucleated Cells in the Bone Marrow of Mice with Qi and Blood Deficiency (x±s, n=10)

[0062] Compared with the blank group, ** p <0.01; compared with the model group, △△ p <0.01 4.1.6 Effects on the histopathology of spleen tissue in mice with qi and blood deficiency See results Figure 2 In the control group, the red and white pulp of the spleen of mice was clearly demarcated, with abundant white pulp and a large number of lymphocytes. In the model group, the red and white pulp of the spleen of mice was not clearly demarcated, the lymph nodes were atrophied, the number of lymphocytes was reduced, and a large number of red blood cells were exuded. Administering the Qi and Blood Tonifying Compound by gavage to mice at doses of 6.17, 12.33, and 24.66 g / kg reduced red blood cell exudation and increased the area of ​​white pulp and the number of lymph nodes. The results indicate that the Qi and Blood Tonifying Compound can improve the pathological changes in the spleen of mice with Qi and Blood deficiency.

[0063] 4.2 Effects of Qi and Blood Tonifying Compound on Immune Function in Food-Restricted Qi-Deficient Mice 4.2.1 Effects on spleen and thymus indices in mice with calorie restriction and qi deficiency The results are shown in Table 5. The spleen and thymus indices of the model group mice were significantly decreased compared to the control group (p<0.01), indicating atrophy of immune organs in mice with food restriction and qi deficiency. Gavage administration of the Qi and Blood Tonifying Agent at doses of 6.17, 12.33, and 24.66 g / kg to mice increased the spleen and thymus indices to varying degrees. Compared with the model group, the spleen and thymus indices of the 6.17, 12.33, and 24.66 g / kg dose groups showed significant differences (p<0.05, p<0.01). These results indicate that the Qi and Blood Tonifying Agent can increase the spleen and thymus indices in mice with food restriction and qi deficiency, and has the effects of enhancing immune function and tonifying qi.

[0064] Table 5. Effects of the Qi and Blood Tonifying Compound on Spleen Index and Thymus Index in Food-Restricted Qi-Deficient Mice (x±s, n=10)

[0065] Compared with the blank group, ** p <0.01; compared with the model group, △ p <0.05, △△ p <0.01 4.2.2 Effects on blood immune cells in mice with calorie restriction and qi deficiency The results are shown in Table 6. The number of WBCs, Neu, and Lym cells in the blood of mice in the model group was significantly reduced compared to the control group (p<0.01), indicating impaired immune function in mice with qi deficiency due to food restriction. Gavage administration of the qi and blood tonic at doses of 6.17, 12.33, and 24.66 g / kg to mice increased the number of WBCs, Neu, and Lym cells to varying degrees. Compared with the model group, the 6.17, 12.33, and 24.66 g / kg dose groups showed significant differences in the number of WBCs, Neu, and Lym cells (p<0.05, p<0.01). These results indicate that the qi and blood tonic can increase the number of immune cells in the blood of mice with qi deficiency due to food restriction, and has the effects of enhancing immune function and replenishing qi.

[0066] Table 6. Effects of the Qi and Blood Tonifying Compound on Blood Immune Cells in Food-Restricted Qi-Deficient Mice (x±s, n=10)

[0067] Compared with the blank group, * p <0.05,** p <0.01; compared with the model group, △ p <0.05, △△ p <0.01 4.2.3 Effects on serum IgG and IgM in mice with food restriction and qi deficiency The results are shown in Table 7. Serum IgG and IgM levels in the model group mice were significantly decreased compared to the control group (p<0.01), indicating impaired humoral immune function in mice with qi deficiency due to calorie restriction. Gavage administration of the qi-blood tonifying compound to mice at doses of 6.17, 12.33, and 24.66 g / kg increased serum IgG and IgM levels to varying degrees. Compared to the model group, the serum IgG and IgM levels in the 6.17, 12.33, and 24.66 g / kg dose groups showed significant differences (p<0.05, p<0.01). These results indicate that the qi-blood tonifying compound can improve humoral immune function and enhance the qi-tonifying effect.

[0068] Table 7. Effects of the Qi and Blood Tonifying Compound on IgG and IgM in mice with restricted food intake and Qi deficiency (x±s, n=10)

[0069] Compared with the blank group, ** p <0.01; compared with the model group, △ p <0.05, △△ p <0.01 4.3 Effects of Qi and Blood Tonifying Compound on Rats with Blood Loss-Induced Anemia 4.3.1 Effects on blood RBC, HGB, and HCT levels in rats with hemorrhagic anemia The results are shown in Table 8. The levels of RBC, HGB, and HCT in the model group rats were significantly lower than those in the blank group (p<0.01), indicating the successful establishment of the blood deficiency rat model. Gavage administration of the Qi-Blood Tonifying Compound to mice at doses of 2.76, 5.52, and 11.04 g / kg increased the levels of RBC, HGB, and HCT in the rat blood to varying degrees. Compared with the model group, the 5.52 and 11.04 g / kg dose groups showed significant differences in RBC, HGB, and HCT levels (p<0.05, p<0.01). These results indicate that the Qi-Blood Tonifying Compound can increase the levels of RBC, HGB, and HCT in the blood of rats with blood loss and blood deficiency, demonstrating a blood-tonifying effect.

[0070] Table 8. Effects of Qi and Blood Tonifying Compound on Blood RBC, HGB, and HCT in Rats with Blood Loss and Blood Deficiency (x±s, n=10)

[0071] Compared with the blank group, ** p <0.01; compared with the model group, △ p <0.05, △△ p <0.01 4.3.2 Effects on serum sodium-potassium ATPase and calcium-magnesium ATPase in rats with hemorrhagic anemia The results are shown in Table 9. The serum sodium-potassium ATPase and calcium-magnesium ATPase activities in the model group rats were significantly decreased compared to the control group (p<0.01), indicating that cellular energy metabolism disorders exist in rats with blood loss deficiency. The Qi-Blood Tonifying Compound administered to rats by gavage at doses of 2.76, 5.52, and 11.04 g / kg increased the serum sodium-potassium ATPase and calcium-magnesium ATPase activities to varying degrees. Compared with the model group, the serum sodium-potassium ATPase activities in the 2.76, 5.52, and 11.04 g / kg dose groups showed significant differences (p<0.01), and the serum calcium-magnesium ATPase activities in the 5.52 and 11.04 g / kg dose groups showed significant differences (p<0.01). These results indicate that the Qi-Blood Tonifying Compound can increase the serum sodium-potassium ATPase and calcium-magnesium ATPase activities in rats, improve energy metabolism disorders in rats with blood loss deficiency, and enhance the blood-tonifying effect.

[0072] Table 9. Effects of Qi and Blood Tonifying Compound on the Activities of Sodium-Potassium ATPase and Calcium-Magnesium ATPase in Rats with Blood Loss and Anemia (x±s, n=10)

[0073] Compared with the control group, ** p < 0.01; compared with the model group, △△ p < 0.01 5. Conclusion The Qi and Blood Tonifying Compound can improve the Qi deficiency symptoms in mice with both Qi and Blood deficiency, increase the levels of blood RBCs, HCTs, and HGBs, improve the rate of weight change and swimming exhaustion time, improve energy metabolism, increase the proportion of nucleated cells in bone marrow, and improve pathological changes in the spleen of mice. It can also increase the spleen and thymus indices, the number of blood immune cells, and humoral immune function in mice with restricted food intake and Qi deficiency. Furthermore, it can increase the levels of blood RBCs, HGBs, and HCTs in rats with blood loss and blood deficiency, and increase the activities of serum sodium-potassium ATPase and calcium-magnesium ATPase in rats. In summary, the Qi and Blood Tonifying Compound has the effects of simultaneously tonifying Qi and Blood, improving immunity, and combating fatigue.

[0074] Preparation process and process research data 1. Prescription Steamed Codonopsis pilosula 83g, Angelica sinensis 50g, Prepared Atractylodes macrocephala 83g, Astragalus membranaceus 83g Poria cocos 83g, Paeonia lactiflora 50g, processed Ligusticum chuanxiong 50g, Rehmannia glutinosa 67g 83g wolfberry, 83g Polygonatum sibiricum (processed with wine), 83g deer antler powder, 17g cinnamon Longan pulp 33g, jujube 67g, dried tangerine peel 50g, prepared licorice root 33g 2. Preparation method The above sixteen ingredients are decocted twice with water. The first time, add 8 times the amount of water and decoct for 1.5 hours. The second time, add 6 times the amount of water and decoct for 1.5 hours. Filter, combine the filtrates, concentrate the filtrate to 1000ml, let stand for 24 hours, filter, add 0.5g of ethylparaben dissolved in 50ml of boiling water, add water to adjust the total volume to 1000ml, stir well, and fill into bottles to obtain the final product.

[0075] 3. Process Flow See the detailed process flow diagram. Figure 3 .

[0076] 4. Preparation process research 4.1 Basis for dosage form selection The dosage form of this product is selected based on the needs of clinical treatment, the nature of the main components of the medicine, and the production equipment, conditions and technical level of the preparation of this medicine in our medical institution. This ensures that the medicine is convenient for patients to take, has no unpleasant odor, and meets the requirements of traditional Chinese medicine.

[0077] 4.1.1 Liquid Preparations Oral liquid preparations of traditional Chinese medicine include mixtures, tinctures, syrups, and fluid extracts. Oral liquid preparations have advantages such as small dosage, rapid absorption, stable quality, convenient carrying and administration, and easy storage, making them easy to take. Therefore, liquid preparations were chosen as the dosage form for this product.

[0078] 4.1.2 Pills are a traditional dosage form of Chinese medicine, but due to their low level of automation in production and difficulty in taking them, they have been gradually replaced by other dosage forms.

[0079] 4.1.3 Granules are convenient to transport, carry, and take, and have a sweet and palatable taste, making them popular with patients. However, they are prone to absorbing moisture or even deliquescence if the packaging is not airtight, and their cost is relatively high.

[0080] 4.1.4 Tablets have advantages such as convenient administration, carrying, and transportation; large production volume; low cost; and easy compliance with hygiene standards. They also offer accurate dosage, stable quality, and can effectively mask the product's unpleasant odor. However, tablets have disadvantages such as long processing time, high energy consumption, difficulty in GMP control, and high cost.

[0081] 4.1.5 Capsules: This dosage form has the characteristics of a smooth and attractive appearance, which can mask the unpleasant bitterness and odor of the drug, but it also has problems such as difficulty in swallowing.

[0082] 4.2 Basis for formulation The production process of Yiqi Rongxue Mixture is mainly based on the agreed prescription of the original medical institution preparation, which is a decoction. It is derived through experimental research, analysis and comparison based on the effective components and solubility properties of various Chinese medicinal materials in the prescription of Yiqi Rongxue Mixture, as well as many factors in production and preparation.

[0083] Decoction is currently the most important and commonly used extraction method in the production of medical preparations and traditional Chinese medicines, so water extraction is the basic production process route.

[0084] 4.3 Preparation process, technical conditions and methods of key steps 4.3.1 Raw material processing: Medicinal herbs that have passed inspection are ready for use.

[0085] 4.3.2 Steam sixteen kinds of medicinal materials, including Codonopsis pilosula, add water and decoct twice. The first time, add 8 times the amount of water and decoct for 1.5 hours. The second time, add 6 times the amount of water and decoct for 1.5 hours. Filter and combine the filtrates.

[0086] 4.3.3 Concentrate the filtrate to 1000ml and let it stand for 24 hours.

[0087] 4.3.4 After filtering the filtrate, add 0.5g of ethylparaben dissolved in 50ml of boiling water, and adjust the total volume to 1000ml with water.

[0088] 4.3.5 Stir well, fill, and select sodium-calcium glass controlled oral liquid bottles for packaging, dispensing in 10ml / bottles.

[0089] 4.3.6 The finished product shall be inspected according to the self-formulated "Standard for Internal Control of Qi-Boosting and Blood-Nourishing Compound".

[0090] 4.4 Research on water extraction technology This product was originally a standardized prescription for medical institution preparations, and its usage was to be taken by decoction in water. Therefore, it was designed to be extracted by water.

[0091] The main factors affecting water extraction were selected as follows: (A) soaking time of medicinal materials; (B) amount of extraction solvent; (C) number of extractions; and (D) extraction time. Three levels were set for soaking time: 0h, 0.5h, and 1.0h; three levels for extraction solvent amount: 8 (6) times, 10 (8) times, and 12 (10) times the amount of water added; three levels for number of extractions: 1, 2, and 3; and three levels for extraction time: 1h, 1.5h, and 2h. An orthogonal experiment was conducted using an L9 (34) orthogonal experimental design. The factor levels are shown in Table 10.

[0092] Table 10. Factor Level Table for Orthogonal Experiment of Water Extraction Process Conditions

[0093] Experimental methods and results analysis: According to the process requirements, 9 portions of medicinal materials (1 / 2 of the prescription amount) were weighed (each portion contained 41.5g of steamed Codonopsis pilosula, 25.0g of Angelica sinensis, 41.5g of processed Atractylodes macrocephala, 41.5g of Astragalus membranaceus, 41.5g of Poria cocos, 25.0g of Paeonia lactiflora, 25.0g of processed Ligusticum chuanxiong, 33.5g of Rehmannia glutinosa, 41.5g of Lycium barbarum, 41.5g of Polygonatum sibiricum (processed with wine), 41.5g of deer antler powder, 8.5g of cinnamon, and 16.5g of longan pulp). Jujube (33.5g), dried tangerine peel (25.0g), and prepared licorice root (16.5g) were used. Four factors were considered, with three levels for each factor. The experiments were conducted according to the nine experimental columns and conditions in the L9(34) orthogonal array. The extracts from each experiment were filtered, the filtrates were combined, concentrated to 500ml, allowed to stand for 24 hours, filtered again, and 0.25g of ethylparaben dissolved in 25ml of boiling water was added. Water was added to adjust the total volume to 500ml, and the mixture was bottled for later use. The total solid content of the samples extracted in each experiment was determined. The results are shown in Tables 11 and 12.

[0094] Table 11 Orthogonal Experiment L9 (3 4 Data analysis table and results

[0095] Table 12 Analysis of Variance Table for Extraction Experiments

[0096] Table 11 shows that the RC value is the largest, and the order is RC > RD > RB > RA. Table 12 shows that factor C has a significant impact on the results, while factors A, B, and D have no significant impact on the results. Based on the analysis of the k values ​​of each factor, the optimal extraction process is A1B1C2D2. Therefore, the extraction process conditions are finally determined as follows: (A) Soaking time: 0h. The k values ​​of the three factors are not significantly different. To save time, the soaking time is set to 0h. (B) Extraction solvent amount: 8 (6) times the amount. The k values ​​of the three factors are not significantly different. To save solvent, the water amount is set to 8 (6) times the amount. (C) Number of extractions: 2 times. The k value is smallest after the first extraction. The k values ​​are larger after the second and third extractions, but the difference between them is not significant. To save time and solvent, this can be disregarded for large-scale production. Therefore, the number of extractions is set to 2 times. (D) Extraction time: 1.5h. The k value is smallest after the first extraction. The k values ​​are larger after the first and second extractions, but the difference between them is not significant. To save time, the extraction time is set to 1.5h.

[0097] 4.5 Study on the setting time process This product is a mixture, and the filtrate may develop significant precipitation after prolonged standing. However, mixtures are only permitted to have a small amount of easily dispersed precipitate upon shaking. Therefore, the water-extracted filtrate needs to be allowed to stand for a period of time to remove the precipitate. Take 50 ml of the filtrate and observe it after standing for 12 h, 24 h, and 48 h respectively. Filter the filtrate, and observe it again after standing for one week. The results are shown in Table 13.

[0098] Table 13 Results of settling time

[0099] Based on the above experimental results, after standing for 12 hours, a small amount of precipitate formed. After filtration, precipitate still formed after the filtrate was left to stand for a week. After standing for 24 hours and 48 hours, precipitate formed, with the amount exceeding that after 12 hours of standing. After filtration, no obvious precipitate was observed after the filtrate was left to stand for a week. Therefore, the standing time was set at 24 hours.

[0100] 4.6 Study on the solubility of preservatives This product is a compound containing a large amount of polysaccharides. Prolonged storage can easily cause microbial growth to exceed the limit, so appropriate preservatives should be added.

[0101] After consulting the "Handbook of Pharmaceutical Excipients" (4th edition), the applicability of three types of preservatives was compared. Benzoic acid and sodium benzoate: Only the undissociated form has antibacterial activity; therefore, the activity depends on the pH of the medium. Maximum antibacterial activity is observed at pH 2.5–4.5, and almost no activity is observed above pH 5. Sorbic acid and potassium sorbate: Although sorbic acid has antibacterial properties, it is generally used as an antifungal agent. Sorbic acid and its potassium salt have strong inhibitory effects on molds, yeasts, and aerobic bacteria, but are almost ineffective against anaerobic Bacillus and Lactobacillus acidophilus. Sorbic acid has the strongest antibacterial activity at pH 4.5, and no activity is observed above pH 6. Furthermore, sorbic acid is easily oxidized, and under light conditions, it oxidizes more readily in aqueous solution than in its solid state. Ethylparaben: It has broad-spectrum antibacterial activity in the pH range of 4–8. Due to the formation of phenol salt anions, the preservative efficacy decreases with increasing pH. Ethylparaben aqueous solutions remain stable at room temperature within a pH range of 3-6, with a degradation rate of less than 10%. In summary, ethylparaben possesses broad-spectrum antibacterial activity, wide applicability to various pH conditions, and stability in aqueous solutions. Furthermore, ethylparaben is a commonly used preservative in hospital preparations, inhibiting microbial growth by disrupting microbial cell membranes. It is precisely compatible with various dosage forms, including solutions and creams, and exerts its preservative effect within safe concentrations. Therefore, ethylparaben was selected as a preservative. The Chinese Pharmacopoeia stipulates that the amount of ethylparaben added to compound preparations should not exceed 0.05%. Studies have reported that accelerated testing for 3 months and stability testing for 7 months were conducted on liquid preparations with ethylparaben concentrations of 0.01%, 0.03%, 0.04%, and 0.05%, respectively. Only 0.05% ethylparaben showed good preservative activity, ensuring the quality of the preparation; therefore, a concentration of 0.05% was chosen as the appropriate preservative dosage.

[0102] 0.5 g of ethylparaben was dissolved in 50 ml of ethanol, boiling water, hot water, and cold water, and its solubility was observed. The results are shown in Table 14.

[0103] Table 14 Preservative Dissolution Results

[0104] Take 950ml each of hot water (75℃), warm water (45℃), and room temperature water (18℃), weigh out 0.5g of ethylparaben, dissolve each in 50ml of boiling water, and quickly add each of the three different temperature waters. After mixing and allowing to stand at room temperature, observe the solubility of ethylparaben with the naked eye. The results are shown in Table 15.

[0105] Table 15 Preservative Dissolution Results

[0106] As shown in Tables 14 and 15, dissolving ethylparaben in boiling water and adding it to the sample while it is still hot ensures that ethylparaben does not precipitate. Therefore, the preservative ethylparaben should be dissolved in boiling water and added to the sample while it is still hot.

[0107] 4.7 Validation Test of the Overall Mixing Process To confirm the reliability and stability of the optimized process conditions, a total mixing process validation test was conducted using the corresponding medicinal materials according to the optimized process conditions. The results are shown in Table 16.

[0108] Table 16 Results of the Validation Test for the Overall Mixing Process

[0109] Three portions of the prescribed medicinal materials were weighed and decocted and extracted according to the optimized process conditions. The total solids content of the three batches of total mixed process verification test samples were measured to be 325.7 mg / ml, 331.2 mg / ml, and 328.5 mg / ml, respectively. This is not much different from the highest total solids content of 345.2 mg / ml obtained from the orthogonal experiment, indicating that the optimal preparation process conditions are reasonable.

[0110] 4.8 Summary of Process Research The production process of this product was derived through experimental research, analysis, and comparison, based on the clinically agreed-upon prescription usage of each medicinal material in the formula and the properties of the main effective components. During the process research, orthogonal experiments on water extraction, studies on standing time processes, studies on preservative dissolution methods, and verification experiments on the overall mixing process were conducted. The optimized preparation process obtained through these experiments is as follows: The above sixteen ingredients are decocted twice with water. The first time, add 8 times the amount of water and decoct for 1.5 hours. The second time, add 6 times the amount of water and decoct for 1.5 hours. Filter, combine the filtrates, concentrate the filtrate to 1000ml, let stand for 24 hours, filter, add 0.5g of ethylparaben dissolved in 50ml of boiling water, add water to adjust the total volume to 1000ml, stir well, and fill into bottles to obtain the final product.

[0111] 5. Preparation of three batches of small-scale test samples Three batches of pilot-scale products were prepared according to the above process (using three times the amount of the standard prescription). The three batches of samples were tested according to the internal control agent standard of Yiqi Rongxue Compound. The quality was stable and controllable. The pilot-scale test results and the finished product test results are shown in Tables 17 and 18.

[0112] Table 17 Data Table for Three Batches of Pilot Products

[0113] Table 18 Test Results of Three Batches of Small-Scale Samples

[0114] 6. Preparation status of three batches of pilot-scale samples in the workshop Three batches of pilot-scale products were prepared using the above process (using 20 times the amount of the standard prescription medicinal materials).

[0115] 1. Each batch of medicinal materials for the prescription must pass inspection and be kept on standby.

[0116] 2. Using a multi-functional Chinese medicine extraction and concentration unit (model: DTQ-1000), add water to sixteen kinds of medicinal materials, including steamed Codonopsis pilosula, and decoct twice. For the first decoction, add 8 times the amount of water and decoct for 1.5 hours. For the second decoction, add 6 times the amount of water and decoct for 1.5 hours. Combine the decoctions and filter the filtrate through a plate and frame filter (model: WBG-1). Concentrate the filtrate to 20L.

[0117] 3. Let stand for 24 hours.

[0118] 4. Filter the filtrate through a plate and frame filter (model: WBG-1), add 10.0g of ethylparaben dissolved in 1L of boiling water, and adjust the total volume to 20L with water.

[0119] 5. Stir well, and fill using the washing, drying, filling and tying line (model: DGZ8A), selecting soda-lime glass controlled oral liquid bottles for packaging, 10ml / bottle.

[0120] The specific configuration data, results, and finished product inspection results for each batch of pilot-scale testing are shown in Tables 19 and 20, and the equipment list is shown in Table 21.

[0121] Table 19 Data Table of Three Batches of Pilot Products

[0122] Table 20 Test Results of Three Batches of Pilot Products

[0123] Table 21 Detailed Equipment List

[0124] 7. Other According to the technical requirements of the "Technical Guidelines for Stability Research of Traditional Chinese Medicine and Natural Drugs" issued by the National Medical Products Administration and the investigation items for compound preparations, and following the trial standards for this product, pilot-scale products of Yiqi Rongxue Compound (batch numbers: 220407, 220408, 220409) were taken and observed at room temperature under the conditions of market-ready packaging. Testing was conducted periodically (0 months, 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months) according to the investigation items. In addition, a 6-month accelerated stability study was also required. Testing was conducted according to the methods described in the standard for Yiqi Rongxue Compound internal control preparations and the microbial limit test method in the 2020 edition of the Chinese Pharmacopoeia.

[0125] 8. Sources and quality standards of auxiliary materials Ethylparaben: Purchased from Guangxi Yizhi Pharmaceutical Excipients Co., Ltd., with quality standards conforming to the standards included in Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0126] Finally, it should be noted that the above embodiments are merely representative examples of the present invention. Obviously, the technical solution of the present invention is not limited to the above embodiments, and many variations are possible. All variations that can be directly derived or conceived by those skilled in the art from the content disclosed in this invention should be considered within the scope of protection of this invention.

Claims

1. A traditional Chinese medicine composition for simultaneously nourishing qi and blood, characterized in that, The ingredients include: steamed Codonopsis pilosula, Angelica sinensis, processed Atractylodes macrocephala, Astragalus membranaceus, Poria cocos, Paeonia lactiflora, processed Ligusticum chuanxiong, Rehmannia glutinosa, Lycium barbarum, Polygonatum sibiricum (processed with wine), deer antler powder, cinnamon, longan pulp, jujube, dried tangerine peel, and prepared licorice root.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The weight proportions of each raw material are as follows: 80-85 parts of steamed Codonopsis pilosula, 45-55 parts of Angelica sinensis, 80-85 parts of processed Atractylodes macrocephala, 80-85 parts of Astragalus membranaceus, 80-85 parts of Poria cocos, 45-55 parts of Paeonia lactiflora, 45-55 parts of processed Ligusticum chuanxiong, 65-70 parts of Rehmannia glutinosa, 80-85 parts of Lycium barbarum, 80-85 parts of Polygonatum sibiricum (processed with wine), 80-85 parts of deer antler powder, 15-20 parts of cinnamon, 30-35 parts of longan pulp, 65-70 parts of jujube, 45-55 parts of dried tangerine peel, and 30-35 parts of processed licorice root.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The weight proportions of each ingredient are as follows: 83 parts steamed Codonopsis pilosula, 50 parts Angelica sinensis, 83 parts processed Atractylodes macrocephala, 83 parts Astragalus membranaceus, 83 parts Poria cocos, 50 parts Paeonia lactiflora, 50 parts processed Ligusticum chuanxiong, 67 parts Rehmannia glutinosa, 83 parts Lycium barbarum, 83 parts Polygonatum sibiricum (processed with wine), 83 parts deer antler powder, 17 parts cinnamon, 33 parts longan pulp, 67 parts jujube, 50 parts dried tangerine peel, and 33 parts processed licorice root.

4. The application of the traditional Chinese medicine composition according to claim 1 in the preparation of medicines for replenishing qi, replenishing blood, improving immunity and relieving fatigue.

5. The application according to claim 4, characterized in that, The qi-tonifying and blood-tonifying drugs mentioned are those that increase the levels of RBC, HCT, and HGB in the blood.

6. The application according to claim 4, characterized in that, The aforementioned anti-fatigue drug is one that increases the activity of sodium-potassium ATPase and calcium-magnesium ATPase in rat serum.

7. The application of the traditional Chinese medicine composition according to claim 1 in the preparation of a medicine for treating symptoms such as sallow complexion, shortness of breath, fatigue, dizziness, and blurred vision caused by physical weakness, illness, or childbirth.

8. An oral preparation made using the traditional Chinese medicine composition according to claim 1.

9. The oral preparation according to claim 8, characterized in that, The oral preparation is specifically a compound preparation.

10. The preparation method of the compound according to claim 9 is specifically as follows: take 16 raw materials in proportion, including steamed Codonopsis pilosula, Angelica sinensis, processed Atractylodes macrocephala, Astragalus membranaceus, Poria cocos, Paeonia lactiflora, processed Ligusticum chuanxiong, Rehmannia glutinosa, Lycium barbarum, Polygonatum sibiricum, deer antler powder, cinnamon, longan pulp, jujube, tangerine peel, and processed licorice root, add water and decoct twice. The first time, add 8 times the amount of water and decoct for 1.5 hours. The second time, add 6 times the amount of water and decoct for 1.5 hours. Filter, combine the filtrates, concentrate the filtrate to 1000ml, let stand for 24 hours, filter, add 0.5g of ethylparaben dissolved in 50ml of boiling water, add water to adjust the total volume to 1000ml, stir well, and fill into bottles to obtain the final product.

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