An anti-fatigue traditional Chinese medicine composition with both medicinal and edible properties, its preparation method and uses

Abstract

The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a homologous medicine and food traditional Chinese medicine composition with anti-fatigue effect, its preparation method and uses. The traditional Chinese medicine composition is processed from the following raw materials by weight: 10-30 parts of wine-processed polygonatum sibiricum, 10-20 parts of Chinese yam, 10-20 parts of green tea, 5-10 parts of mint, and 5-10 parts of pogostemon cablin. The preparation method is also disclosed, and it is made into granules. The medicine of the present invention is derived from traditional Chinese medicine that is both medicine and food, has both effectiveness and no toxic and side effects, is used for the prevention and improvement of qi deficiency and blood deficiency symptoms caused by fatigue, can effectively improve the fatigue state, and the preparation process of the present invention is reliable, has good reproducibility, and a high granule forming rate.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a homologous Chinese medicine composition for both medicine and food with anti-fatigue effect, its preparation method and uses. Background Art

[0002] In recent years, with the changes in lifestyle and living environment, fatigue has become a common sub-healthy state among modern people. Its symptoms include tiredness, inattention, muscle soreness, weakness, headache, memory decline, etc. Fatigue can be divided into physical fatigue and mental fatigue. Physical fatigue comes from muscle fatigue caused by excessive physical load, and mental fatigue is a brain fatigue state caused by mental load. Physical and mental fatigue are interrelated. The long-term accumulation of fatigue can also lead to illness and secondary diseases, which will then affect people's normal life. Therefore, the prevention and relief of fatigue are particularly important. However, since this sub-healthy state of fatigue has not reached the disease stage, there is no specific diagnostic standard. Traditional Chinese and Western medicine have different understandings and treatment methods for fatigue.

[0003] Western medicine treats fatigue mainly by regulating the body's metabolism and functions to restore physical strength. Common treatment methods include drug treatment, nutritional supplementation, exercise, and psychotherapy, etc. Drug treatment can use some drugs that regulate the nervous system and metabolism, such as stimulants and antidepressants. Nutritional supplementation can improve physical strength and immunity by supplementing vitamins, minerals, and proteins, etc. Appropriate exercise can increase the body's endurance and energy consumption, and improve the sense of fatigue. Psychotherapy can relieve fatigue and anxiety through relaxation training, cognitive behavioral therapy, etc. However, the side effects of Western medicine in treating fatigue are more obvious compared with traditional Chinese medicine.

[0004] Traditional Chinese medicine treats fatigue mainly by regulating the body's yin-yang balance and qi-blood circulation to restore physical strength. Common treatment methods include traditional Chinese medicine conditioning, acupuncture, massage, and traditional Chinese medicine health preservation, etc. Acupuncture and massage can stimulate meridians and acupoints, promote qi-blood circulation, and relieve fatigue and pain. Traditional Chinese medicine health preservation includes regulating diet, work and rest, and mental state, etc., which can help restore physical strength and improve resistance.

[0005] In traditional Chinese medicine treatment, traditional Chinese medicine conditioning is particularly important. Among traditional Chinese medicines, there are Chinese medicines homologous for both medicine and food, which can be used as both food and medicine, ensuring their safety while having certain effects, and can be eaten for a long time to relieve the sub-healthy state. The present invention uses Chinese medicines homologous for both medicine and food as raw materials to provide a traditional Chinese medicine composition with anti-fatigue effect. Summary of the Invention

[0006] The purpose of the present invention is to solve the technical problems existing in the prior art to a certain extent at least. The present invention provides an anti-fatigue granule for enhancing the physical fitness of sub-healthy people and a preparation method thereof, the granule has the effect of improving qi deficiency and blood deficiency, the preparation method of the granule is simple in process, good in reproducibility, and high in particle forming qualified rate.

[0007] Specifically, the present invention is realized from the following technical contents:

[0008] In the first aspect, the present invention provides a traditional Chinese medicine composition with anti-fatigue effect, which is made from the following traditional Chinese medicine raw materials in parts by weight: 10-30 parts of Polygonatum odoratum, 10-30 parts of yam, 10-30 parts of green tea, 5-10 parts of mint, and 5-10 parts of patchouli.

[0009] As a further improvement of the present invention, the invention is prepared from the following Chinese medicinal raw materials in parts by weight: 20 parts of polygonatum odoratum, 12 parts of yam, 15 parts of green tea, 6 parts of mint, and 6 parts of patchouli.

[0010] The present invention further protects the above-mentioned Chinese medicine composition, which also includes necessary auxiliary materials.

[0011] As a further improvement of the present invention, in the above technical solution, the auxiliary material is selected from one or more of dextrin, β-cyclodextrin, sucrose, and soluble starch.

[0012] Preferably, the auxiliary material is soluble starch.

[0013] In a second aspect, the present invention further protects a method for preparing a Chinese medicine composition having an anti-fatigue effect, comprising the following steps:

[0014] Preparation of dry paste powder: weigh the medicinal materials according to the prescription ratio, add 6-18 times the amount of water to extract 1-3 times, each time for 1-2 hours, combine the extracts, concentrate, dry at 90℃ under normal pressure, crush, and pass through an 80-mesh sieve to obtain;

[0015] Granule preparation: Accurately weigh the dry paste powder and auxiliary materials, mix them thoroughly, spray them with an appropriate amount of ethanol as a wetting agent, make them into a soft material, and then granulate them with a 14-mesh sieve, dry them at 60°C under normal pressure for 2h, and granulate them to obtain anti-fatigue granules.

[0016] As a further improvement of the present invention, the weight ratio of the dry paste powder to the auxiliary material is 1:1, the ethanol concentration is 84%, and the added amount is 29%.

[0017] In the third aspect, the present invention provides use of the Chinese medicine composition described in the first aspect or the Chinese medicine composition prepared by the preparation method described in the second aspect in preparing a product for improving qi deficiency and blood deficiency caused by fatigue.

[0018] As an alternative, in the above uses, the product is a drug, a health product or a functional food.

[0019] As an alternative, in the above uses, the dosage form of the product includes traditional dosage forms and modern dosage forms.

[0020] As an alternative, in the above uses, the traditional dosage forms are selected from pills, powders, plasters or pills, and the modern dosage forms are selected from granule agents, tablets, oral liquids or capsule agents.

[0021] The present invention has the following beneficial effects:

[0022] The granule agent in the present invention is composed of polygonatum sibiricum redolent, Chinese yam, green tea, mint and pogostemon cablin, which regulates essence, qi, blood, etc. of the human body and has the effects of improving fatigue and enhancing immunity. Pharmacodynamic experiments prove that the granule agent has the effects of relieving fatigue and improving immunity. In addition, the raw materials used in the preparation method in the present invention are few in variety, common and easily available, appropriate excipients are selected, the preparation process is reliable, the reproducibility is good, and the qualified rate of granules in the forming process is high. Description of the Drawings

[0023] Figure 1 To extract the effect diagram of single factor on the extract yield.

[0024] Figure 2 To extract the response surface 3D diagram of the interaction of various factors in the extraction process on the total solids.

[0025] Figure 3 To extract the response surface 3D diagram of the interaction of various factors in the extraction process on the polysaccharide.

[0026] Figure 4 To extract the response surface 3D diagram of the interaction of various factors in the forming process on the comprehensive score.

[0027] Figure 5 To extract the effect of the anti-fatigue granule on the area of red blood cells in the heart of blood-deficient zebrafish. Among them, a. blank control group, b. model control group, c. example group, d. control example group. **** Compared with the blank group, p < 0.0001; #### Compared with the model group, p < 0.0001, ### Compared with the model group, p < 0.001, ## Compared with the model group, p < 0.001.

[0028] Figure 6 To extract the effect of the anti-fatigue granule on the number of neutrophils in qi-deficient zebrafish. Among them, a. blank control group, b. model control group, c. example group, d. control example group. **** Compared with the blank group, p < 0.0001; #### Compared with the model group, p < 0.0001,### Compared with the model group, p<0.001. Specific implementation methods

[0029] The medicinal properties and effects of the Chinese medicinal raw materials used in the present invention are as follows:

[0030] Huangjing with wine: sweet, neutral. Enters the spleen, lung and kidney meridians. Replenishes qi and nourishes yin, strengthens the spleen, moistens the lungs and benefits the kidneys. Used for dampness and turbidity blocking the middle, abdominal distension and vomiting, summer-dampness and superficial symptoms, initial onset of damp-heat, fever and fatigue, chest tightness and discomfort, cold-dampness and summer heat, abdominal pain, vomiting and diarrhea, and sinusitis and headache.

[0031] Chinese Yam: sweet, neutral. Enters the spleen, lung, and kidney meridians. Nourishes the spleen and stomach, promotes the production of body fluids and benefits the lungs, and nourishes the kidneys and astringes semen. Used for spleen deficiency, poor appetite, chronic diarrhea, asthma and cough due to lung deficiency, spermatorrhea due to kidney deficiency, leucorrhea, frequent urination, and thirst due to deficiency heat.

[0032] Green tea: bitter, sweet, slightly cold. Enters the heart, lung, and stomach meridians. Astringent, diuretic, and refreshing. Used for fatigue, sleepiness, headache, dizziness, thirst, urinary problems, alcoholism, etc.

[0033] Patchouli: pungent, slightly warm. Enters the spleen, stomach, and lung meridians. Aromatic and turbid, harmonizes the middle and stops vomiting, and releases heat. Used for dampness and turbidity blocking the middle, abdominal distension and vomiting, summer heat, fever and fatigue, chest tightness and discomfort, cold and dampness blocking the heat, abdominal pain, vomiting and diarrhea, and sinusitis and headache.

[0034] Peppermint: pungent, cool. Enters the lung and liver meridians. Disperses wind-heat, clears the head and eyes, relieves sore throat, clears rashes, soothes the liver and promotes qi. Used for wind-heat cold, initial onset of wind-heat, headache, red eyes, throat paralysis, mouth sores, rubella, measles, chest and flank distension.

[0035] The formula analysis of the Chinese medicine composition of the present invention is as follows:

[0036] In traditional Chinese medicine, fatigue is a general term for a variety of weak symptoms with deficiency of the five internal organs as the main clinical manifestations. It is also said that spleen deficiency, kidney essence deficiency, liver qi stagnation, etc. are its basic pathogenesis. Among them, the spleen is the "foundation of acquired constitution" and the source of qi and blood production. Food and water depend on the spleen's transportation and transformation function, which is transformed into fine substances to nourish the whole body and provide energy for the normal operation of the body. If the spleen is weak and not functioning, the energy supply required for daily activities of the human body is insufficient, resulting in fatigue, inattention, muscle soreness, fatigue, etc. In addition, the spleen fails to function properly, water metabolism is disordered, dampness stagnates in the body, blocking the qi and stagnating the meridians, which can also lead to heaviness of the head and body, and soreness of the limbs. In the formula, Huangjing (Polygonatum odoratum) is the main ingredient, which is sweet and mild in nature. It is mainly used for tonic, replenishing qi and strengthening the spleen, benefiting the kidney and nourishing yin. The auxiliary ingredient is yam, which is also a sweet tonic and belongs to the spleen, lung and kidney meridians. The two complement each other and work together to achieve the effects of replenishing qi and nourishing yin, strengthening the spleen and moistening the lungs, benefiting the kidney and producing essence. The spleen likes dryness and hates dampness, so it is assisted by Patchouli to aromatically resolve turbidity, clear the dampness in the middle burner, eliminate dampness, and make the spleen's transportation and transformation unobstructed. At the same time, it is assisted by mint and green tea, whose pungent and dispersing power can lift the mind, clear the head, soothe the liver and promote qi circulation, so as to vent bad emotions and relieve mental fatigue.

[0037] The specific embodiments of the present invention will be described in detail, but it should be understood that the protection scope of the present invention is not limited by the specific embodiments.

[0038] 1. Optimization of the extraction process

[0039] 1.1 Raw material composition

[0040] Polygonatum sibiricum Red. var. giraldii (Regel) Hsiao & K. M. Feng 20 parts, green tea 15 parts, Chinese yam 12 parts, mint 6 parts, Pogostemon cablin (Blanco) Benth. 6 parts by weight.

[0041] 1.2 Investigation of single-factor experiments

[0042] Weigh the medicinal materials according to the prescription ratio, decoct them, combine the decoction liquids, filter, make up the volume, and investigate the extract yield. Five parallel samples are taken to investigate the effect of adding 6 - 30 times water on the extract yield; five parallel samples are taken to investigate the effect of extraction times from 1 to 5 times on the extract yield; five parallel samples are taken to investigate the effect of extraction time from 0.5 to 2.5 h on the extract yield. The results of the single-factor experiments are as Figure 1 . The results show that after multiple experiments, the extract yield shows a gentle increasing trend. Finally, the first three levels of each factor are selected as the three levels of factors for the subsequent response surface experiments.

[0043] 1.3 Box-Behnken response surface experimental design

[0044] According to the optimization results of the single-factor experiments, based on the Box-Behnken Design experimental design principle, the total polysaccharide content and the extract yield are used as response values for response surface optimization to obtain the optimal water extraction process. The factor level table of the extraction process response surface experiment is shown in Table 1.

[0045] Table 1 Factor level table of the extraction process response surface experiment

[0046]

[0047] Use Design-Expert 10.0 software to conduct response surface analysis on the 17 experimental points designed, among which 12 are factorial points and the rest are regional center points, repeated 5 times to estimate the experimental error. The response surface experimental design and results are shown in Table 2.

[0048] Table 2 Response surface experimental design and results of the extraction process

[0049]

[0050]

[0051] Table 3 Analysis of variance table of the extraction process response surface test - R1

[0052]

[0053] Analysis of Variance Table for Response Surface Experiment of Extraction Process - R2

[0054]

[0055]

[0056] As can be seen from Table 3 and Table 4, the binomial fitting models are all significant (P < 0.05), indicating that the model prediction fits well with the actual experiment. The binomial fitting equations are as follows:

[0057] R1 = 30.96 + 4.62*A - 0.41*B + 1.83*C - 1.26*AB - 2.79*AC - 1.23*BC - 2.88*A 2 -0.74*

[0058] B 2 -4.35*C 2

[0059] R2 = 17.75 + 1.57*A - 0.25*B + 2.79*C - 1.35*AB - 3.35*AC + 0.43*BC - 1.99*A 2 -1.03*

[0060] B 2 -2.86*C 2

[0061] According to the above quadratic polynomial fitting model, by fixing one independent variable at the intermediate value respectively, three-dimensional effect surface diagrams and two-dimensional contour diagrams of the dependent variable changing with the independent variable are drawn, as shown in Figure 2 、 Figure 3 . The optimal process predicted by the model is: the amount of added water is 12.625, the extraction time is 0.764 h, and the extraction is 2.572 times. Considering the production cost and actual operability comprehensively, the optimized extraction process is as follows: extract with 13 times the amount of water 2 times, 1 h each time.

[0062] 2. Optimization of Forming Process

[0063] 2.1 Raw Material Composition

[0064] 20 parts of processed polygonatum sibiricum, 15 parts of green tea, 12 parts of Chinese yam, 6 parts of mint, 6 parts of pogostemon cablin and appropriate amount of excipients by weight, and the excipients are selected from one or more of dextrin, soluble starch, β-cyclodextrin, and sucrose.

[0065] 2.2 Preparation Method

[0066] (1) Preparation of dry extract powder: Weigh the medicinal materials according to the prescription ratio, extract according to the optimal extraction process, concentrate under normal pressure, dry at 90 °C under normal pressure for 24 h, pulverize, and pass through an 80-mesh sieve to obtain.

[0067] (2) Particle preparation: Weigh the dry extract powder and excipients precisely, mix them thoroughly, spray an appropriate amount of ethanol as a wetting agent, make a soft material, granulate it through a 14-mesh sieve, dry it at 60 °C under normal pressure for 2 h, and size the granules to obtain the particles.

[0068] 2.3 Single-factor investigation of excipient types

[0069] After multiple preliminary tests, a weight ratio of dry extract powder to excipient of 1:1 was selected for the excipient type screening test. Weigh dextrin, soluble starch, β-cyclodextrin, and sucrose separately according to the ratio, add them to the dry extract powder, add 85% ethanol to make a soft material, granulate it through a 14-mesh sieve, record the granulation situation, and measure the granule forming rate and dissolution rate. The results are shown in Table 5.

[0070] Table 5 Screening of excipient types

[0071]

[0072] As can be seen from the table, the soluble starch has the best granule forming rate and dissolution property, and the soft material situation is good. Considering comprehensively, soluble starch is selected as the excipient.

[0073] 2.4 Screening of excipient ratio

[0074] After multiple preliminary tests, add excipients in different ratios according to the following table. After mixing, use 85% ethanol as the binder, mix and granulate, record the granulation situation, measure the granule forming rate, and screen the optimal excipient ratio. The results are shown in Table 6.

[0075] Table 6 Screening of excipient ratio

[0076]

[0077] As can be seen from the table, when the ratio of dry extract powder to soluble starch is 1:1, the soft material state is better, and other ratios are too sticky or too loose. Considering comprehensively, 1:1 is the optimal excipient ratio.

[0078] 2.5 Screening of binder concentration

[0079] After multiple preliminary tests, mix according to the ratio of dry extract powder: soluble starch 1:1, select 80%, 82%, 85%, 88%, and 90% ethanol as binders respectively, and use a single-factor test to screen the optimal binder concentration. Record the granulation situation and measure the granule forming rate. The results are shown in Table 7.

[0080] Table 7 Binder screening

[0081]

[0082] As can be seen from the table, when the ethanol concentration is 85%, the soft material state and the granule forming rate are the best, and 85% is the optimal concentration.

[0083] 2.6 Screening of the dosage of the binder

[0084] After multiple preliminary tests, the dry extract powder and soluble starch were mixed at a ratio of 1:1, 85% ethanol was selected as the binder, and the optimal dosage of the binder was screened. The granulation situation was recorded, and the granule forming rate was measured. The results are shown in Table 8.

[0085] Table 8 Screening of the dosage of the binder

[0086]

[0087] As can be seen from the table, when the dosage is 30%, the state of the soft material is better and the forming rate is higher. Therefore, the dosage of 30% is the optimal one.

[0088] 2.7 Response surface experiment indexes of the forming process and their determination methods

[0089] 2.7.1 Formability was determined by the forming rate of the granules

[0090] The determination was carried out according to the method under General Principles (0982) of Volume IV of the Chinese Pharmacopoeia (2020 Edition). The qualified granules were those passing through No. 1 sieve and not passing through No. 5 sieve.

[0091] Qualified granule rate (%) = mass of qualified granules / total mass of granules × 100%

[0092] 2.7.2 Hygroscopicity was determined by the percentage hygroscopicity of the granules

[0093] According to the reference literature, an appropriate amount of qualified granules was accurately measured and placed in a desiccator with a constant humidity (RH) of 75% (25 °C) and an ammonium chloride supersaturated solution placed at the bottom. After 48 hours, it was weighed, and its change was observed and weighed again to calculate the percentage hygroscopicity.

[0094] Percentage hygroscopicity (%) = (weight of granules after hygroscopicity - weight of granules before hygroscopicity) / weight of granules before hygroscopicity × 100%.

[0095] 2.7.3 Determination of solubility

[0096] According to the reference literature, about 1 g of qualified granule sample was taken and placed in a 50 mL dry centrifuge tube. 20 mL of hot water was added, stirred for 5 min, centrifuged at 3000 r / min for 15 min, and the supernatant was discarded. The residue was dried to a constant weight at 80 °C, and the solubility rate was accurately weighed and calculated.

[0097]

[0098] 2.7.4 Flowability was determined by the angle of repose of the granules

[0099] According to references, the fixed funnel method was used to determine the fluidity of the dry extract powder. The bottom of the funnel was kept 3.5 cm away from the coordinate paper, and the extract powder was poured along the wall of the funnel until the top of the cone formed by the extract powder touched the funnel mouth. The radius R and height H of the bottom of the cone were measured. This was repeated three times, and the angle of repose (tgα) was calculated. The formula was: tgα=H / R.

[0100] 2.7.5 Soft material status

[0101] According to the references, the soft materials are scored according to their state. The scoring rules are as follows:

[0102] Soft materials are relatively sticky ≤ 5 points; soft materials are slightly sticky and form particles 10-15 points; soft materials are not sticky and form particles 15-20 points; soft materials are not sticky and have more fine powder 5-10 points.

[0103] 2.8 Comprehensive score calculation

[0104] Formability, solubility, hygroscopicity, fluidity, and soft material state are selected as the evaluation indicators, and the CRITIC weight method is selected to determine the weight of each indicator. First, the data is normalized, in which the forming rate, solubility, and soft material state are positively processed and expressed by dmax, and the hygroscopicity and solubility are reversely processed and expressed by dmin. As a result, the weight coefficients of the indicators of formability (dmax1), solubility (dmax2), hygroscopicity (dmin1), fluidity (dmin2), and soft material state (dmax3) are 15.30%, 12.63%, 27.08%, 19.62%, and 25.36%, respectively. The formula is as follows:

[0105] Forward Normalization: (X Min Indicates the minimum value X Max Indicates the maximum value)

[0106] Negative normalization: (X Min Indicates the minimum value X Max Indicates the maximum value)

[0107] Comprehensive scoring formula:

[0108] R=0.1530*dmax1+0.1263dmax2+0.2708*dmin1+0.1962*dmin2+0.2536*dmax3

[0109] 2.9 Box-Behnken response surface design of molding process

[0110] On the basis of single-factor experiments, taking the excipient ratio, ethanol concentration, and ethanol dosage as the investigation factors, a response surface experiment with three factors and three levels was carried out. The factor level coding is shown in Table 9. Weigh 17 portions of dry extract powder, each about 5 g. Weigh appropriate excipients according to the experimental arrangement and mix them with the dry extract powder. After mixing evenly, prepare soft materials with ethanol of the corresponding volume fraction, pass through a 14-mesh sieve to make granules, dry them in an oven at 60 °C for 2 h, and screen them through No. 1 and No. 5 sieves to obtain the final product. The response surface test design and results of the forming process are shown in Table 10.

[0111] Table 9 Factor level table of response surface experiment for forming process

[0112]

[0113] Table 10 Response surface test design and results of forming process

[0114] Serial number Ethanol concentration Ethanol dosage Drug: excipient ratio Comprehensive score 1 82 25 0.55 0.73 2 88 20 0.5 0.3 3 88 25 0.45 0.61 4 82 20 0.5 0.39 5 85 30 0.55 0.8 6 88 30 0.5 0.47 7 82 30 0.5 0.61 8 85 20 0.55 0.48 9 88 25 0.55 0.32 10 82 25 0.45 0.57 11 85 30 0.45 0.63 12 85 20 0.45 0.6 13-17 85 25 0.5 0.62±0.06

[0115] Table 11 ANOVA table of response surface experiment

[0116]

[0117]

[0118] As can be seen from Table 11, the binomial fitting models are all significant (P < 0.05), indicating that the model prediction fits well with the actual experiment. The binomial fitting equation is as follows:

[0119] R1 = -120.43 + 2.6875*A - 0.019*B + 31.8*C - 0.75*AC + 0.29*BC - 0.01375A 2 -2.15×

[0120] 10 -3 *B 2 +24.5*C 2

[0121] According to the above quadratic polynomial fitting model, fix one independent variable as the intermediate value respectively, and draw the three-dimensional effect surface diagram and two-dimensional contour diagram of the dependent variable changing with the independent variable, as shown in Figure 4 . The optimal process given by the model prediction is: ethanol concentration 84.082%, ethanol dosage 28.865, excipient ratio 0.5. Considering the production cost and actual operability comprehensively, the optimized extraction process is as follows: ethanol concentration 84%, ethanol dosage 29, excipient ratio 0.5.

[0122] Unless otherwise specified, the experimental methods in the following examples are all conventional methods. Unless otherwise specified, the test materials used in the following examples are all commercially available products.

[0123] Preparation Example 1

[0124] An anti-fatigue granule with the effect of improving qi deficiency and blood deficiency, comprising raw materials and excipients. The raw materials are composed of the following components by weight: 20 g of wine-processed polygonatum sibiricum, 12 g of Chinese yam, 15 g of green tea, 6 g of mint, and 6 g of pogostemon cablin. The preparation method of the traditional Chinese medicine composition includes the following steps:

[0125] (1) Preparation of dry extract powder: Weigh the medicinal materials according to the prescription ratio, add 6 - 18 times the amount of water for extraction 1 - 3 times, each time for 1 - 2 h, combine the extraction solutions, concentrate, dry at normal pressure at 90 °C, pulverize, and pass through an 80 - mesh sieve to obtain the dry extract powder.

[0126] (2) Granule preparation process: Accurately weigh the dry extract powder and excipients in a mass ratio of 1:1, mix well, spray 29% by mass of ethanol with a volume fraction of 84% as a wetting agent, make into soft materials, granulate through a 14 - mesh sieve, dry at normal pressure at 60 °C for 2 h, and screen through a 14 - mesh sieve to obtain the anti - fatigue granules.

[0127] Preparation Example 2

[0128] The difference between this preparation example and Preparation Example 1 is that the raw materials of the granule are composed of the following components by weight: 15 g of wine - processed polygonatum sibiricum, 20 g of Chinese yam, 10 g of green tea, 10 g of mint, and 10 g of pogostemon cablin. Other components, production steps, and condition parameters are the same as those in Preparation Example 1.

[0129] Preparation Example 3

[0130] The difference between this preparation example and Preparation Example 1 is that the raw materials of the granule are composed of the following components by weight: 30 g of wine - processed polygonatum sibiricum, 10 g of Chinese yam, 15 g of green tea, 5 g of mint, and 5 g of pogostemon cablin. Other components, production steps, and condition parameters are the same as those in Preparation Example 1.

[0131] Comparative Example 1

[0132] The difference between this comparative example and Preparation Example 1 is that the raw materials of the granule are composed of the following components by weight: 32 g of Chinese yam, 15 g of green tea, 6 g of mint, and 6 g of pogostemon cablin. Other components, production steps, and condition parameters are the same as those in Preparation Example 1.

[0133] Comparative Example 2

[0134] The difference between this comparative example and Preparation Example 1 is that the raw materials of the granule are composed of the following components by weight: 32 g of wine - processed polygonatum sibiricum, 15 g of green tea, 6 g of mint, and 6 g of pogostemon cablin. Other components, production steps, and condition parameters are the same as those in Preparation Example 1.

[0135] Comparative Example 3

[0136] The difference between this comparative example and Preparation Example 1 is that the raw materials of the granule are composed of the following components by weight: 20 g of processed polygonatum sibiricum, 12 g of atractylodes macrocephala, 15 g of green tea, 6 g of mint, and 6 g of pogostemon cablin. Other components, production steps, and condition parameters are the same as those in Preparation Example 1.

[0137] Comparative Example 4

[0138] The difference between this comparative example and Preparation Example 1 is that the raw materials of the granule are composed of the following components by weight: 35 g of processed polygonatum sibiricum, 18 g of Chinese yam, and 6 g of pogostemon cablin. Other components, production steps, and condition parameters are the same as those in Preparation Example 1.

[0139] Effect Example 1

[0140] 1. Experimental purpose

[0141] To investigate the improvement effect of the traditional Chinese medicine composition (Preparation Examples 1 - 3) of the present invention on phenylhydrazine-induced blood deficiency zebrafish

[0142] 2. Experimental materials

[0143] 2.1 Experimental animals: Wild-type AB strain zebrafish at 3 days post fertilization (3dpf)

[0144] 2.2 Experimental drugs

[0145] ① Zebrafish culture solution: Weigh 1462.5 mg of sodium chloride, 242.583 mg of calcium chloride, 63.325 mg of potassium chloride, and 198 mg of magnesium sulfate, dissolve in deionized water, sonicate for 20 min, transfer to a 500 mL volumetric flask after complete dissolution, make up the volume, and dilute ten times for use.

[0146] ② Anti-fatigue granule solution: Weigh an appropriate amount of anti-fatigue granules, dissolve them by sonication with zebrafish culture solution as the solvent, and prepare a solution with a concentration of 2 mg / mL.

[0147] ③ Modeling drug: Accurately weigh the phenylhydrazine solution, dilute it with zebrafish culture solution as the solvent to a phenylhydrazine solution with a concentration of 10 -2 μg / mL.

[0148] ④ Positive control drug: Accurately weigh the powder of ferrous sulfate tablets, and prepare a 1 mg / mL ferrous sulfate tablet solution with zebrafish culture solution as the solvent.

[0149] ⑤ o-Dianisidine dye: Accurately weigh 178.65 mg of o-dianisidine and 85.05 mg of sodium acetate, place them in a 50 mL volumetric flask, add 2.5 mL of 30% hydrogen peroxide solution, then make up the volume with 50% ethanol, shake well, store in the dark, and prepare for use immediately.

[0150] 3. Experimental method

[0151] 3.1 Zebrafish Embryo Culture Conditions

[0152] The culture was carried out with reference to the relevant regulations of the National Zebrafish Resource Center. The embryonic development temperature of AB wild-type zebrafish was 28.5 °C, the dark time: light time was 10 h:14 h, the light intensity was 54 - 324 lux, the culture medium was changed daily, and the shed fetal membranes or dead embryos were removed.

[0153] 3.2 Establishment of the phenylhydrazine-induced zebrafish blood deficiency model and administration

[0154] Normal 3-dpf zebrafish embryos were selected, 10 embryos per well were randomly transferred into a 12-well plate, and 3 wells were set up in parallel for each experimental group. A blank group, a model group, a positive drug group, and an anti-fatigue granule group (Preparation Examples 1 - 3, Comparative Examples 1 - 4) were set up. Except for the blank group, each well was given 2 - 3 mL of phenylhydrazine solution for modeling. After being placed in the zebrafish incubator for 24 h, they were taken out, washed 3 times with the culture medium, and except for the blank group, the rest were given the anti-fatigue granule solution and placed in the incubator for 12 h.

[0155] 3.3 Collection of the area of cardiac red blood cells

[0156] After the zebrafish culture medium after administration was washed 3 times, it was stained with o-dianisidine dye in the dark for 15 min, then washed 3 times with DMSO solution, and placed under a fluorescence microscope to collect images.

[0157] 4. Experimental Results

[0158] The Image J image processing software was used to process the stained area of cardiac red blood cells. One-way ANOVA was used for comparison among multiple groups of data, and the t-test was used for comparison between two groups. P < 0.05 indicated that the difference was statistically significant. The results were as follows:

[0159] According to the results (see Figure 5 ), compared with the blank group, there were significant differences in the model group, indicating that the blood deficiency model was successfully established; compared with the model group, there were significant differences in the example groups, indicating that the drug groups had a significant effect on improving zebrafish blood deficiency. Among them, the difference in the Preparation Example 1 group was the most obvious, which was the optimal condition; there were no significant differences between the comparative examples and the model group.

[0160] Effect Example 2

[0161] 1. Experimental Purpose

[0162] To investigate the preventive effect of the traditional Chinese medicine composition (Preparation Examples 1 - 3) of the present invention on vinorelbine-induced qi deficiency in zebrafish

[0163] 2. Experimental Materials

[0164] 2.1 Experimental animals: Tg(mpx:EGFP) neutrophil green fluorescence transgenic zebrafish

[0165] 2.2 Experimental Drugs

[0166] ① Zebrafish culture medium: Weigh 1462.5 mg of sodium chloride, 242.583 mg of calcium chloride, 63.325 mg of potassium chloride, and 198 mg of magnesium sulfate. Dissolve them in deionized water, sonicate for 20 min, and transfer to a 500 mL volumetric flask after complete dissolution. Make up the volume and dilute tenfold for use.

[0167] ② Anti-fatigue granule solution: Weigh an appropriate amount of anti-fatigue granules, dissolve them by sonication using zebrafish culture medium as the solvent to prepare a solution with a dosing concentration of 1 mg / mL.

[0168] ③ 0.1% DMSO solvent: Add DMSO solution to zebrafish culture medium to prepare a solvent containing 0.1% DMSO.

[0169] ④ Modeling drug: Weigh vinorelbine reference standard precisely, dilute it with the solvent, dissolve it by sonication, and the dosing concentration is 100 μg / mL.

[0170] ⑤ Positive control drug: Weigh Buzhong Yiqi Pills powder precisely, dilute it with the solvent, dissolve it by sonication, and the dosing concentration is 1 mg / mL.

[0171] ⑥ Anesthetic: 0.05% mass concentration of yuaian solution.

[0172] 3. Experimental Methods

[0173] 3.1 The culture conditions of zebrafish embryos are the same as those in Effect Example 1

[0174] 3.2 Establishment of a zebrafish qi deficiency model induced by vinorelbine and drug administration

[0175] Select normal 3 dpf zebrafish embryos, randomly transfer 10 embryos per well into a 12-well plate, set up 3 parallel wells for each experimental group, and set up blank group, model group, positive drug group, and anti-fatigue granule group (Preparation Examples 1 - 3, Comparative Examples 1 - 4). Except for the blank group, add vinorelbine solution and anti-fatigue granule solution to each well simultaneously. Administer drugs while establishing the model. After 24 h in a zebrafish incubator, take them out, wash 3 times with the culture medium, and use for subsequent experiments.

[0176] 3.3 Collection of neutrophil count

[0177] After drug administration, wash the zebrafish 3 times with the culture medium and then anesthetize them with anesthetic for 5 min. Place them under a fluorescence microscope and collect images. The image effects of each group are as Figure 6 .

[0178] 4. Experimental Results

[0179] The neutrophil count was collected using Image J image processing software. One-way analysis of variance was used for comparison among multiple groups of data, and the t-test was used for comparison between two groups. P < 0.05 indicated a statistically significant difference. The results are as follows:

[0180] According to the results (see Figure 6 ), compared with the blank group, there were significant differences in the model group, indicating that the qi deficiency model was successfully established; compared with the model group, there were significant differences in the example group, indicating that the drug group had a significant effect on preventing zebrafish qi deficiency. Among them, the difference in the preparation example 1 group was the most obvious, which was the optimal condition; there was no significant difference between the comparative example and the model group.

[0181] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention is also intended to include these modifications and variations.

Claims

1. A traditional Chinese medicine composition with the function of improving qi deficiency and blood deficiency caused by fatigue, characterized in that, It is made from the following traditional Chinese medicine raw materials by weight: 10 - 30 parts of processed polygonatum sibiricum, 10 - 20 parts of Chinese yam, 10 - 20 parts of green tea, 5 - 10 parts of mint, 5 - 10 parts of pogostemon cablin. The preparation method of the traditional Chinese medicine composition includes the following preparation steps: (1) Preparation of dry extract powder: Weigh the medicinal materials according to the prescription ratio, add 6 - 18 times the amount of water and extract 1 - 3 times, each time for 1 - 2 h. Combine the extraction liquids, concentrate, dry under normal pressure at 90 °C, pulverize, and pass through an 80 - mesh sieve to obtain it; (2) Granule preparation process: Precisely weigh the dry extract powder and soluble starch in a mass ratio of 1:1, mix well, spray 29% of ethanol with a volume fraction of 84% as a wetting agent, make it into soft materials, granulate through a 14 - mesh sieve, dry under normal pressure at 60 °C for 2 h, and screen with a 14 - mesh sieve to obtain anti - fatigue granules.

2. The traditional Chinese medicine composition according to claim 1, wherein It is made from the following traditional Chinese medicine raw materials by weight: 20 parts of processed polygonatum sibiricum, 12 parts of Chinese yam, 15 parts of green tea, 6 parts of mint, 6 parts of pogostemon cablin.

3. The preparation method of the traditional Chinese medicine composition according to claim 1 or claim 2, characterized in that, It includes the following preparation steps: (1) Preparation of dry extract powder: Weigh the medicinal materials according to the prescription ratio, add 6 - 18 times the amount of water and extract 1 - 3 times, each time for 1 - 2 h. Combine the extraction liquids, concentrate, dry under normal pressure at 90 °C, pulverize, and pass through an 80 - mesh sieve to obtain it; (2) Granule preparation process: Precisely weigh the dry extract powder and soluble starch in a mass ratio of 1:1, mix well, spray 29% of ethanol with a volume fraction of 84% as a wetting agent, make it into soft materials, granulate through a 14 - mesh sieve, dry under normal pressure at 60 °C for 2 h, and screen with a 14 - mesh sieve to obtain anti - fatigue granules.

4. The preparation method according to claim 3, characterized in that, In step (1), the amount of added water is 13 times, and the extraction is carried out twice, each time for 48 min.

5. Use of the traditional Chinese medicine composition described in claim 1 or claim 2 or the traditional Chinese medicine composition prepared by using the preparation method described in claim 3 or claim 4 in the preparation of drugs or health products for improving qi deficiency and blood deficiency caused by fatigue.

6. The use according to claim 5, wherein, The dosage form of the drug or health product is granule.

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