TRADITIONAL CHINESE MEDICINE COMPOSITION FOR RECOVERY PHASE OF EXOGENOUS FEVER, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF

Abstract

A traditional Chinese medicine composition for recovery phase of exogenous fever and a preparation method therefor. The traditional Chinese medicine composition comprises the following raw materials: radix codonopsis, rhizoma atractylodis macrocephalae, poria cocos, radix ophiopogonis, schisandra chinensis, hairyvein agrimony, perilla seeds, cortex moriradicis, folium eriobotryae, radix platycodi, apricot kernels, and radix glycyrrhizae. According to the monarch, minister, assistant and guide theory of traditional Chinese medicines, the radix codonopsis is used as a monarch drug; fried rhizoma atractylodis macrocephalae, the poria cocos, the radix ophiopogonis, the schisandra chinensis, and the hairyvein agrimony are used as minister drugs; the perilla seeds, the cortex moriradicis, and the folium eriobotryae are used as assistant drugs; and the radix platycodi, the apricot kernels, and the radix glycyrrhizae are used as guide drugs. Also disclosed is use of the traditional Chinese medicine composition for rehabilitation treatment of novel coronavirus pneumonia and other exogenous fever in the recovery phase.

Claims

1. A traditional Chinese medicine composition for a recovery phase of a fever disease caused by an exogenous pathogenic factor, wherein the traditional Chinese medicine composition is made of the following raw materials: Radix Codonopsis, Rhizoma Atractylodis Macrocephalae, Poria cocos, Radix Ophiopogonis, Fructus Schisandrae Chinensis, Herba Agrimoniae, Fructus Perillae, Cortex Mori, Folium Eriobotryae, Radix Platycodonis, Semen Armeniacae Amarum and Radix Glycyrrhizae.

2. The traditional Chinese medicine composition according to claim 1, wherein the Rhizoma Atractylodis Macrocephalae is roasted Rhizoma Atractylodis Macrocephalae.

3. The traditional Chinese medicine composition according to claim 1, wherein the Folium Eriobotryae is stir-fried Folium Eriobotryae.

4. The traditional Chinese medicine composition according to claim 1, wherein the Radix Glycyrrhizae is stir-fried Radix Glycyrrhizae.

5. The traditional Chinese medicine composition according to claim 1, to wherein the traditional Chinese medicine composition is made of the following parts by weight of raw materials: 1-20 parts of Radix Codonopsis, 1-20 parts of Rhizoma Atractylodis Macrocephalae, 1-30 parts of Poria cocos, 1-20 parts of Radix Ophiopogonis, 1-10 parts of Fructus Schisandrae Chinensis, 1-30 parts of Herba Agrimoniae, 1-20 parts of Fructus Perillae, 1-20 parts of Cortex Mori, 1-25 parts of Folium Eriobotryae, 1-10 parts of Radix Platycodonis, 1-10 parts of Semen Armeniacae Amarum and 1-10 parts of Radix Glycyrrhizae.

6. The traditional Chinese medicine composition according to claim 5, wherein the traditional Chinese medicine composition is made of the following parts by weight of raw materials: 5-15 parts of Radix Codonopsis, 5-15 parts of Rhizoma Atractylodis Macrocephalae, 10-20 parts of Poria cocos, 5-15 parts of Radix Ophiopogonis, 5-8 parts of Fructus Schisandrae Chinensis, 10-20 parts of Herba Agrimoniae, 5-15 parts of Fructus Perillae, 5-15 parts of Cortex Mori, 10-15 parts of Folium Eriobotryae, 5-8 parts of Radix Platycodonis, 5-8 parts of Semen Armeniacae Amarum and 5-8 parts of Radix Glycyrrhizae.

7. A preparation method for the traditional Chinese medicine composition according to claim 1, comprising: (1) separately pulverizing Radix Codonopsis, Rhizoma Atractylodis Macrocephalae, Poria cocos, Radix Ophiopogonis, Fructus Schisandrae Chinensis, Herba Agrimoniae, Fructus Perillae, Cortex Mori, Folium Eriobotryae, Radix Platycodonis, Semen Armeniacae Amarum and Radix Glycyrrhizae, which are in formulated amounts; (2) extracting Radix Codonopsis by an ultrasonic countercurrent method to obtain an extract solution and medicine residues, and concentrating the extract solution to obtain a Radix Codonopsis extractum; (3) mixing the medicine residues with Rhizoma Atractylodis Macrocephalae, Poria cocos, Radix Ophiopogonis, Fructus Schisandrae Chinensis, Herb a Agrimoniae, Fructus Perillae, Cortex Mori, Folium Eriobotryae, Radix Platycodonis, Semen Armeniacae Amarum and Radix Glycyrrhizae and subjecting the mixture to decoction, impurity removal and concentration to obtain an aqueous extractum; and (4) mixing the aqueous extractum with the Radix Codonopsis extractum, adding a pharmaceutically acceptable excipient, formulating the mixture into granules, and dispensing the granules to obtain the traditional Chinese medicine composition.

8. The preparation method according to claim 7, wherein in step (1), each component of traditional Chinese medicine is pulverized to 200-300 meshes.

9. The preparation method according to claim 7, wherein the decoction in step (3) is three-stage decoction; wherein, the three-stage decoction comprises the following specific steps: a first stage carried out at a temperature of 60-80° C. for 5-10 min; a second stage carried out at a temperature of 90-100° C. for 6-8 min; and a third stage carried out at a temperature of 50-60° C. for 5-10 min.

10. A method for rehabilitation of a fever disease caused by an exogenous pathogenic factor, comprising administering to a subject in need thereof the traditional Chinese medicine composition according to claim 1.

11. The method according to claim 10, wherein the fever disease caused by an exogenous pathogenic factor comprises coronavirus disease 2019.

12. The traditional Chinese medicine composition according to claim 6, wherein the traditional Chinese medicine composition is made of the following parts by weight of raw materials: the traditional Chinese medicine composition is made of the following parts by weight of raw materials: 10 parts of Radix Codonopsis, 10 parts of roasted Rhizoma Atractylodis Macrocephalae, 15 parts of Poria cocos, 10 parts of Radix Ophiopogonis, 6 parts of Fructus Schisandrae Chinensis, 15 parts of Herba Agrimoniae, 10 parts of Fructus Perillae, 10 parts of Cortex Mori, 12 parts of stir-fried Folium Eriobotryae, 6 parts of Radix Platycodonis, 6 parts of Semen Armeniacae Amarum and 6 parts of stir-fried Radix Glycyrrhizae.

13. The preparation method according to claim 7, wherein a solvent used in the ultrasonic countercurrent method in step (2) is an aqueous solution of ethanol.

14. The preparation method according to claim 7, wherein the ultrasonic countercurrent method in step (2) is carried out at an extraction temperature of 50-80° C.

15. The preparation method according to claim 7, wherein the ultrasonic countercurrent method in step (2) is carried out at an ultrasonic frequency of 25-35 kHz and an ultrasonic power of 18-22 kW.

16. The preparation method according to claim 7, wherein the pharmaceutically acceptable excipient comprises any one or a combination of at least two of mannitol, sucrose, lactose, cyclodextrin or starch.

Description

DETAILED DESCRIPTION

[0058] Technical solutions of the present application are further described below through specific examples. Those skilled in the art are to understand that the examples described herein are used for a better understanding of the present application and are not to be construed as specific limitations to the present application.

[0059] In the following examples, traditional Chinese medicines can be purchased through conventional paths.

EXAMPLE 1

[0060] This example provides a formulation of and a preparation method for a traditional Chinese medicine composition.

TABLE-US-00001 Function Name Mass/g Name Mass/g Name Mass/g Monarch Radix Codonopsis 10 Minister Roasted Rhizoma 10 Poria cocos 15 Radix 10 Atractylodis Ophiopogonis Macrocephalae Fructus Schisandrae 6 Herba 15 Chinensis Agrimoniae Assistant Fructus Perillae 10 Cortex Mori 10 Stir-fried 12 Folium Eriobotryae Guide Radix Platycodonis 6 Semen 6 Stir-fried Radix 6 Armeniacae Glycyrrhizae Amarum

[0061] The preparation method is described below.

[0062] (1) Components in formulated amounts were separately pulverized to 200 meshes.

[0063] (2) Radix Codonopsis was extracted by an ultrasonic countercurrent method where the solvent used was an aqueous solution of ethanol, the extraction temperature was 60° C., the ultrasonic frequency was 30 kHz, and the ultrasonic power was 20 kW so as to obtain an extract solution and medicine residues, and the extract solution was concentrated to obtain a Radix Codonopsis extractum.

[0064] (3) The medicine residues were mixed with the other traditional Chinese medicines and subjected to decoction, impurity removal and concentration to obtain an aqueous extractum.

[0065] (4) The aqueous extractum was mixed with the Radix Codonopsis extractum, added with starch, formulated into granules, and dispensed to obtain the granules of the traditional Chinese medicine composition.

EXAMPLE 2

[0066] This example provides a formulation of and a preparation method for a traditional Chinese medicine composition.

TABLE-US-00002 Function Name Mass/g Name Mass/g Name Mass/g Monarch Radix Codonopsis 20 Minister Roasted Rhizoma 1 Poria cocos 1 Radix 1 Atractylodis Ophiopogonis Macrocephalae Fructus Schisandrae 10 Herba 30 Chinensis Agrimoniae Assistant Fructus Perillae 1 Cortex Mori 20 Stir-fried 1 Folium Eriobotryae Guide Radix Platycodonis 1 Semen 1 Stir-fried Radix 10 Armeniacae Glycyrrhizae Amarum

[0067] The preparation method is described below.

[0068] (1) Components in formulated amounts were separately pulverized to 300 meshes.

[0069] (2) Radix Codonopsis was extracted by an ultrasonic countercurrent method where the solvent used was an aqueous solution of ethanol, the extraction temperature was 50° C., the ultrasonic frequency was 35 kHz, and the ultrasonic power was 22 kW so as to obtain an extract solution and medicine residues, and the extract solution was concentrated to obtain a Radix Codonopsis extractum.

[0070] (3) The medicine residues were mixed with the other traditional Chinese medicines and subjected to decoction, impurity removal and concentration to obtain an aqueous extractum.

[0071] (4) The aqueous extractum was mixed with the Radix Codonopsis extractum, added with starch, formulated into granules, and dispensed to obtain the traditional Chinese medicine composition.

EXAMPLE 3

[0072] This example provides a formulation of and a preparation method for a traditional Chinese medicine composition.

TABLE-US-00003 Function Name Mass/g Name Mass/g Name Mass/g Monarch Radix Codonopsis 1 Minister Roasted Rhizoma 20 Poria cocos 20 Radix 20 Atractylodis Ophiopogonis Macrocephalae Fructus Schisandrae 1 Herba 1 Chinensis Agrimoniae Assistant Fructus Perillae 20 Cortex Mori 1 Stir-fried 25 Folium Eriobotryae Guide Radix Platycodonis 10 Semen 10 Stir-fried Radix 1 Armeniacae Glycyrrhizae Amarum

[0073] The preparation method is described below.

[0074] (1) Components in formulated amounts were separately pulverized to 250 meshes.

[0075] (2) Radix Codonopsis was extracted by an ultrasonic countercurrent method where the solvent used was an aqueous solution of ethanol, the extraction temperature was 80° C., the ultrasonic frequency was 25 kHz, and the ultrasonic power was 18 kW so as to obtain an extract solution and medicine residues, and the extract solution was concentrated to obtain a Radix Codonopsis extractum.

[0076] (3) The medicine residues were mixed with the other traditional Chinese medicines and subjected to decoction, impurity removal and concentration to obtain an aqueous extractum.

[0077] (4) The aqueous extractum was mixed with the Radix Codonopsis extractum, added with starch, formulated into granules, and dispensed to obtain the traditional Chinese medicine composition.

EXAMPLE 4

[0078] This example provides a formulation of and a preparation method for a traditional Chinese medicine composition.

TABLE-US-00004 Function Name Mass/g Name Mass/g Name Mass/g Monarch Radix Codonopsis 5 Minister Roasted Rhizoma 5 Poria cocos 10 Radix 5 Atractylodis Ophiopogonis Macrocephalae Fructus Schisandrae 5 Herba 10 Chinensis Agrimoniae Assistant Fructus Perillae 5 Cortex Mori 5 Stir-fried 10 Folium Eriobotryae Guide Radix Platycodonis 5 Semen 5 Stir-fried Radix 5 Armeniacae Glycyrrhizae Amarum

[0079] The preparation method is the same as that of Example 1.

EXAMPLE 5

[0080] This example provides a formulation of and a preparation method for a traditional Chinese medicine composition.

TABLE-US-00005 Function Name Mass/g Name Mass/g Name Mass/g Monarch Radix Codonopsis 15 Minister Roasted Rhizoma 15 Poria cocos 20 Radix 15 Atractylodis Ophiopogonis Macrocephalae Fructus Schisandrae 8 Herba 20 Chinensis Agrimoniae Assistant Fructus Perillae 15 Cortex Mori 15 Stir-fried 15 Folium Eriobotryae Guide Radix Platycodonis 8 Semen 8 Stir-fried Radix 8 Armeniacae Glycyrrhizae Amarum

[0081] The preparation method is the same as that of Example 1.

Performance Evaluation 1

[0082] Ten patients (deficient in Qi and Yin and carrying residual pathogens) in a recovery phase of coronavirus pneumonia were treated by using the granules prepared in Example 1, where the patients were 30-50 years old, six male patients and four female patients. Each patient was administered with the granules 10 g each time and twice a day. The results after two weeks are shown below.

[0083] 1. Traditional Chinese Medicine Syndrome Evaluation

[0084] Main traditional Chinese medicine syndromes observed: changes of syndromes of the deficiency of Qi and Yin and residual pathogens: primary symptoms including cough, shortness of breath and fatigue; and, secondary symptoms including no sputum or little sticky sputum, sweating, dry mouth or dry pharynx, poor appetite, glomus and fullness, sloppy stool or constipation.

[0085] The changes of clinical symptoms were observed according to the scores in the “Guidelines for the Clinical Research of Chinese Medicine New Drugs”.

[0086] a. Determination of effects on main symptoms: changes of primary symptoms such as cough, expectoration of phlegm and shortness of breath. The results are shown in Table 1.

[0087] Disappear: The symptoms disappear, which is scored 0.

[0088] Improved: The symptoms are relieved, with a reduced score not being 0.

[0089] Ineffective: The symptoms are not relieved or are aggravated, with the score not reduced.

TABLE-US-00006 TABLE 1 Total Disappear Improved Ineffective Response Item (Case) (Case) (Case) Rate Main indicator/person 5 3 2 80.00%

[0090] As can be seen from the above table, after administration with the granules provided in the present application for two weeks, the primary symptoms of five patients disappeared and the primary symptoms of three patients were improved, with an overall response rate of 80%.

[0091] b. Evaluation of effects on traditional Chinese medicine syndromes (score comparison)

[0092] Clinically controlled: The improvement rate of symptom score after treatment is greater than or equal to 95%.

[0093] Effective: The improvement rate of symptom score after treatment is greater than or equal to 70% and less than 95%.

[0094] Improved: The improvement rate of symptom score after treatment is greater than or equal to 30% and less than 70%.

[0095] Ineffective: The improvement rate of symptom score after treatment is less than 30%. The results are shown in Table 2.

TABLE-US-00007 TABLE 2 Group Pre-treatment Post-treatment P Value Mean score 41.1569 ± 6.0176 11.5093 ± 5.1467 P < 0.05

[0096] As can be seen from the above table, after administration with the granules provided in Example 1, the post-treatment score is lower than the pre-treatment score, and the difference that P<0.05 has statistical significance.

[0097] 2. Quality of Life Evaluation

[0098] The quality of life of patients before and after treatment was evaluated by using an SF-36 scale.

[0099] Each domain (physiological status, social/family status, emotional status, functional status, etc.) in the scale was evaluated at five levels: “none, little, some, much, too much”, where positive items were directly scored 1-5, and negative items were scored inversely.

[0100] Scores of items included in each domain were summed up to obtain a score of this domain, and scores of each domain were summed up to obtain a score of the whole scale. The higher the score, the better the quality of life. The results are shown in Table 3. Statistical analysis was performed by using SPSS 22.0 statistical software, measurement data were represented as (x±s). P<0.05, statistical significant. For self-comparison before and after treatment, paired t-test was used.

TABLE-US-00008 TABLE 3 Comparison of SF-36 Scores Before and After Treatment (x ± s) SF-36 Score Pre-treatment Post-treatment P Value Physiological function(PF) 86.80 ± 15.61 90.80 ± 12.04 P < 0.05 Role physical (RP) 69.33 ± 35.20 88.33 ± 29.17 P < 0.05 Body pain (BP) 63.40 ± 19.53 69.46 ± 19.02 P < 0.05 General health (GH) 61.73 ± 18.40 68.28 ± 16.83 P < 0.05 Social function(SF) 64.20 ± 16.29 78.28 ± 15.41 P < 0.05 Role emotional (RE) 82.81 ± 17.83 88.29 ± 14.60 P < 0.05 Mental health (MH) 88.66 ± 30.99 93.74 ± 20.00 P < 0.05

[0101] As can be seen from the above table, through the comparison of the scores of quality of life, the post-treatment score is obviously higher than the pre-treatment score, indicating that the present application obviously improves the quality of life of patients.

COMPARATIVE EXAMPLE 1

[0102] As a control, ten patients (including five male patients and five female patients and 25-59 years old) deficient in Qi and Yin and carrying residual pathogens in a recovery phase of coronavirus pneumonia were administered with a control formulation in clinics. The formulation included 10 g of Radix Codonopsis, 10 g of Radix Ophiopogonis, 6 g of Fructus Schisandrae Chinensis, 10 g of Poria cocos, 10 g of bamboo leaves, 30 g of raw gypsum (added at the end), 6 g of Rhizoma Pinelliae Preparata, 10 g of Pericarpium Citri Reticulatae, 10 g of Semen Armeniacae Amarum (roasted), 6 g of Radix Platycodonis, 20 g of Herba Agrimoniae, 15 g of Cortex Mori and 3 g of stir-fried Radix Glycyrrhizae. After two weeks of intervention, the results are shown below.

[0103] 1. Traditional Chinese Medicine Syndrome Evaluation

[0104] Main traditional Chinese medicine syndromes observed: changes of syndromes of the deficiency of Qi and Yin and residual pathogens: primary symptoms including cough, shortness of breath and fatigue and secondary symptoms including no sputum or little sticky sputum, sweating, dry mouth or dry pharynx, poor appetite, glomus and fullness, sloppy stool or constipation.

[0105] The changes of clinical symptoms were observed according to the scores in the “Guidelines for the Clinical Research of Chinese Medicine New Drugs”.

[0106] a. Determination of effects on main symptoms: changes of primary symptoms such as cough, expectoration of phlegm and shortness of breath. The results are shown in Table 4. Disappear: The symptoms disappear, which is scored 0.

[0107] Improved: The symptoms are relieved, with a reduced score not being 0.

[0108] Ineffective: The symptoms are not relieved or are aggravated, with the score not reduced.

TABLE-US-00009 TABLE 4 Total Disappear Improved Ineffective Response Item (Case) (Case) (Case) Rate Primary symptoms 3 3 4 60.00%

[0109] As can be seen from the above table, after two weeks of treatment with the control formulation, the primary symptoms of three patients disappeared and the primary symptoms of three patients were improved, with an overall response rate of 60%.

[0110] b. Evaluation of effects on traditional Chinese medicine syndromes (score comparison)

[0111] Clinically controlled: The improvement rate of symptom score after treatment is greater than or equal to 95%.

[0112] Effective: The improvement rate of symptom score after treatment is greater than or equal to 70% and less than 95%.

[0113] Improved: The improvement rate of symptom score after treatment is greater than or equal to 30% and less than 70%.

[0114] Ineffective: The improvement rate of symptom score after treatment is less than 30%. The results are shown in Table 5.

TABLE-US-00010 TABLE 5 Group Pre-treatment Post-treatment P Value Mean score 42.3516 ± 4.3454 22.3862 ± 3.2850 P < 0.05

[0115] As can be seen from the above table, after two weeks of treatment with the control formulation, the post-treatment score is lower than the pre-treatment score, and the difference that P<0.05 has statistical significance.

Performance Test 2

[0116] To further verify the therapeutic effect of the traditional Chinese medicine composition provided in the present application on patients deficient in Qi and Yin in a recovery phase of coronavirus pneumonia, the number of samples was further increased in this example, with 121 patients in hospital as treatment subjects.

[0117] A total of nine patients dropped out during the experiment for the following reasons: three patients were unable to continue the experiment for personal affairs, one patient was lost of follow-up with no reason specified, three patients withdrew for violating the experimental scheme, and three patients withdrew due to adverse reactions and adverse events.

[0118] In this example, test subjects were treated with the granules prepared in Example 1 for two weeks. Each patient was administered with the granules 10 g each time and three times a day and was not administered with other similar medicine. With the score reduction percentage of syndromes as a criterion, the changes of clinical symptoms of the subjects were observed with reference to the “Guidelines for the Clinical Research of Chinese Medicine New Drugs”.

[0119] (1) The main outcomes of clinical effects were analyzed in this example by the method for evaluating effects on traditional Chinese medicine syndromes in Example 1, which is specifically described below.

[0120] Clinically controlled: The improvement rate of symptom score after treatment is greater than or equal to 95%.

[0121] Effective: The improvement rate of symptom score after treatment is greater than or equal to 70% and less than 95%.

[0122] Improved: The improvement rate of symptom score after treatment is greater than or equal to 30% and less than 70%.

[0123] Ineffective: The improvement rate of symptom score after treatment is less than 30%. The obtained score changes (x±s) of traditional Chinese medicine syndromes before and after treatment are shown in Table 6.

TABLE-US-00011 TABLE 6 Group Pre-treatment Post-treatment P Value Mean score 14.56 ± 5.97 5.96 ± 4.26 P < 0.05

[0124] In this example, the administration was performed for two weeks. With the score reduction percentage of syndromes as the criterion, it is obtained that the one-week clinically controlled rate was 0%, the one-week effective rate was 2.68%, the one-week improved rate was 41.07%, and the one-week ineffective rate was 56.25%. To sum up, the one-week overall response rate was 43.75%.

[0125] It is obtained that the two-week clinically controlled rate was 6.25%, the two-week effective rate was 32.14%, the two-week improved rate was 51.79%, and the two-week ineffective rate was 9.82%. To sum up, the two-week overall response rate was 90.18%.

[0126] (2) Safety evaluation: In this example, the changes of the following indicators of the subjects were observed before and after treatment: routine blood, urine and stool tests and liver and renal function tests in the laboratory and rates of adverse reactions.

[0127] I. Routine Blood Test

[0128] In this example, 86 patients underwent the entire routine blood test at the time of enrollment and completion.

[0129] 53 cases were abnormal in the routine blood test at the time of enrollment and 55 cases were abnormal in the routine blood test at the time of completion.

[0130] Comparison of single patients before and after treatment: 14 cases had normal indicators in the routine blood test at the time of enrollment while abnormal indicators in the routine blood test at the time of completion. A statistical analysis was performed on the routine blood test data of 86 patients by a T-test method. The results are shown in Table 7 (where white blood cell 1 represents the level of detected white blood cells on the first day of enrollment, and white blood cell 14 represents the level of white blood cells on the 14th day of enrollment, that is, on the day of completion, so do other indicators).

TABLE-US-00012 TABLE 7 Standard Standard Indicator Mean N Deviation Error of Mean Indicator 1 White blood cell 1 5.8512 86 1.60197 0.17274 White blood cell 14 5.6421 86 1.42146 0.15328 Indicator 2 Neutrophil percentage 1 61.6844 86 7.48568 0.80720 Neutrophil percentage 14 60.0756 86 7.69837 0.83014 Indicator 3 Lymphocyte percentage 1 30.3372 86 8.03658 0.86661 Lymphocyte percentage 14 31.6570 86 7.81688 0.84292 Indicator 4 Absolute neutrophil count 1 3.6606 86 1.30124 0.14032 Absolute neutrophil count 14 3.4273 86 1.13930 0.12285 Indicator 5 Absolute lymphocyte count 1 1.7501 86 0.50572 0.05453 Absolute lymphocyte count 14 1.7951 86 0.59704 0.06438 Indicator 6 Erythrocyte count 1 4.5776 86 0.49736 0.05363 Erythrocyte count 14 4.5481 86 0.49442 0.05331 Indicator 7 Hemoglobin 1 141.2674 86 14.00708 1.51042 Hemoglobin 14 140.7907 86 13.66844 1.47391

[0131] Paired sample examination data are shown in Table 8.

TABLE-US-00013 TABLE 8 Paired Difference 95% Confidence Interval of Standard Difference Standard Error Lower Upper Sig.(Double- Indicator Mean deviation of Mean Limit Limit t df sided) Indicator 1 White 0.20907 0.96282 0.10382 0.00264 0.41550 2.014 85 0.047 blood cell 1-White blood cell 14 Indicator 2 Neutrophil 1.60884 5.42752 0.58526 0.44517 2.77250 2.749 85 0.007 percentage 1-Neutrophil percentage 14 Indicator 3 Lymphocyte −1.31977 6.87092 0.74091 −2.79290 0.15336 −1.781 85 0.078 percentage 1-Lymphocyte percentage 14 Indicator 4 Absolute 0.23326 0.87267 0.09410 0.04616 0.42036 2.479 85 0.015 neutrophil count 1-Absolute neutrophil count 14 Indicator 5 Absolute −0.04500 0.36255 0.03909 −0.12273 0.03273 −1.151 85 0.253 lymphocyte count 1-Absolute lymphocyte count 14 Indicator 6 Erythrocyte 0.02942 0.16662 0.01797 −0.00631 0.06514 1.637 85 0.105 count 1- Erythrocyte count 14 Indicator 7 Hemoglobin 1- 0.47674 5.05436 0.54503 −0.60691 1.56040 0.875 85 0.384 Hemoglobin 14

[0132] As can be seen from the above table, before and after treatment, the changes in white blood cell and neutrophil percentage in the routine blood tests have statistical significance, P<0.05, and after treatment, the means of white blood cell and neutrophil percentage in the routine blood test are lower than those before treatment but are still within normal ranges.

[0133] II. Blood Biochemical Examination and Analysis

[0134] In this example, 92 patients underwent the entire blood biochemical examination at the time of enrollment and completion. 26 cases were abnormal in the blood biochemical examination at the time of enrollment and 21 cases were abnormal in the blood biochemical examination at the time of completion.

[0135] Comparison of single patients before and after treatment: 5 cases had normal indicators in the blood biochemical examination at the time of enrollment while abnormal indicators in the blood biochemical examination at the time of completion. A statistical analysis was performed on the blood biochemical examination data of 92 patients by a T-test method. The results are shown in Table 9.

TABLE-US-00014 TABLE 9 Standard Standard Indicator Mean N Deviation Error of Mean Indicator 1 Alanine transaminase 1 30.8043 92 20.24153 2.11033 Alanine transaminase 14 29.3043 92 19.53905 2.03709 Indicator 2 Aspartate transaminase 1 25.4674 92 8.62459 0.89918 Aspartate transaminase 14 24.8804 92 7.42855 0.77448 Indicator 3 Blood urea nitrogen 1 5.0283 92 1.41517 0.14754 Blood urea nitrogen 14 5.2652 92 1.22765 0.12799 Indicator 4 Creatinine 1 67.1283 92 19.65704 2.04939 Creatinine 14 69.1326 92 15.21276 1.58604

[0136] Paired sample examination data are shown in Table 10.

TABLE-US-00015 TABLE 10 Paired Difference 95% Confidence Interval of Standard Difference Standard Error Lower Upper Sig. (Double- Indicator Mean Deviation of Mean Limit Limit t df sided) Indicator 1 Alanine 1.50000 15.27369 1.59239 −1.66309 4.66309 0.942 91 0.349 transaminase 1-Alanine transaminase 14 Indicator 2 Aspartate 0.58696 5.93953 0.61924 −0.64309 1.81700 0.948 91 0.346 transaminase 1-Aspartate transaminase 14 Indicator 3 Blood urea −0.23696 1.14572 0.11945 −0.47423 .00032 −1.984 91 0.050 nitrogen 1-Blood urea nitrogen 14 Indicator 4 Creatinine 1 −2.00435 11.08917 1.15613 −4.30085 0.29215 −1.734 91 0.086 Creatinine 14

[0137] As can be seen from the above table, before and after treatment, P>0.05 for each indicator in the blood biochemical examination, and the difference has no statistical significance.

[0138] III. Routine Urine Test and Analysis

[0139] In this example, 88 patients underwent the entire routine urine test at the time of enrollment and completion. 39 cases were abnormal in the routine urine test at the time of enrollment and 38 cases were abnormal in the routine urine test at the time of completion.

[0140] Comparison of single patients before and after treatment: 9 cases had normal indicators in the routine urine test at the time of enrollment while abnormal indicators in the routine urine test at the time of completion. A statistical analysis was performed on the routine urine test data of 88 patients by a T-test method. The results are shown in Table 11.

TABLE-US-00016 TABLE 11 Standard Standard Indicator Mean N deviation Error of Mean Indicator 1 White blood cell 1 17.6591 88 77.45713 8.25696 White blood cell 14 12.0000 88 56.80032 6.05493 Indicator 2 Erythrocyte 1 0.2614 88 0.90331 0.09629 Erythrocyte 14 0.2614 88 0.79502 0.08475 Indicator 3 Occult blood 1 11.5341 88 34.50269 3.67800 Occult blood 14 15.3409 88 40.49120 4.31638 Indicator 4 Protein 1 0.0261 88 0.11890 0.01267

[0141] Paired sample examination data are shown in Table 12.

TABLE-US-00017 TABLE 12 Paired Difference 95% Confidence Interval of Standard Difference Standard Error Lower Upper Sig. (Double- Indicator Mean deviation of Mean Limit Limit t df sided) Indicator 1 White 5.65909 90.02131 9.59630 −13.41460 24.73278 0.590 87 0.557 blood cell 1-White blood cell 14 Indicator 2 Erythrocyte 1- 0.00000 0.90972 0.09698 −0.19275 0.19275 0.000 87 1.000 Erythrocyte 14 Indicator 3 Occult −3.80682 43.71403 4.65993 −13.06894 5.45530 −0.817 87 0.416 blood 1- Occult blood 14 Indicator 4 Protein 1- −0.27045 2.66941 0.28456 −0.83605 0.29514 −0.950 87 0.345 Protein 14

[0142] As can be seen from the above table, P≥0.05 for each indicator in the routine urine test, and the difference has no statistical significance.

[0143] IV. Routine Stool Analysis

[0144] 28 patients underwent the entire routine stool test at the time of enrollment and completion. 16 cases were abnormal in the routine stool test at the time of enrollment and 1 case was abnormal in the routine stool test at the time of completion.

[0145] Comparison of single patients before and after treatment: 0 cases had normal indicators in the routine stool test at the time of enrollment while abnormal indicators in the routine stool test at the time of completion.

[0146] According to the above analysis of blood routine, urine routine, stool routine and liver and renal functions, the functions of bodies of the subjects were not obviously affected after the subjects were administered with the granules in the present application, and abnormal test items in the experimental process might be caused by the disease or the body differences of the subjects.

[0147] Therefore, the above safety evaluation experiment proves that the traditional Chinese medicine composition provided in the present application and in which the components follow the formulation principle of “monarch, minister, assistant and guide” causes no obvious adverse reactions and has relatively high safety for patients, especially those deficient in Qi and Yin in the recovery phase of COVID-19.

[0148] (3) According to the shorter version of the World Health Organization Quality of Life Measurement Scale (WHOQOL-Bref scale), secondary outcomes of clinical effects were analyzed, including scores of primary symptoms and body signs (before and after treatment and at follow-up) and quality of life evaluation.

[0149] I. Analysis of changes of scores of body signs: In this example, the effects on main symptoms were determined based on changes of primary symptoms such as cough, expectoration of phlegm and shortness of breath. The evaluation standards in this part are the same as those of Example 1 and specifically include the following:

[0150] Disappear: The symptoms disappear, which is scored 0.

[0151] Improved: The symptoms are relieved, with a reduced score not being 0.

[0152] Ineffective: The symptoms are not relieved or are aggravated, with the score not reduced. The obtained evaluation of effects on clinical symptoms and indicators is shown in Table 13.

TABLE-US-00018 TABLE 13 Total Disappear Improved Ineffective Response Item (Case) (Case) (Case) Rate Main indicator/person 13 91 21 92.85%

[0153] The obtained change (x±s) of scores of primary symptoms and body signs before and after treatment is shown in Table 14.

TABLE-US-00019 TABLE 14 Group Pre-treatment Post-treatment P Value Mean score 10.44 ± 4.26 4.84 ± 3.67 P < 0.05

[0154] As can be seen from the above table, after the use of granules, the score of primary symptoms and body signs of the patients is significantly reduced.

[0155] II. Quality of Life Evaluation

[0156] The quality of life of patients before and after treatment was evaluated by using the WHOQOL-Bref scale.

[0157] Each domain (physiological status, mental status, social score or environmental score) in the scale was evaluated at five levels: “none, little, some, much, too much”, where positive items were directly scored 1-5, and negative items were scored inversely.

[0158] Scores of items included in each domain were summed up to obtain a score of this domain, and scores of each domain were summed up to obtain a score of the whole scale. The higher the score, the better the quality of life. The obtained results are shown in Table 15.

TABLE-US-00020 TABLE 15 Comparison of QOL Scores Before and After Treatment (x ± s) QOL Score Pre-treatment Post-treatment P Value Physiological score (PF) 20.62 ± 3.42 21.70 ± 2.90 P < 0.05 Mental score (RP) 18.26 ± 2.99 18.29 ± 2.80 P > 0.05 Social score (BP)  9.50 ± 2.058  9.60 ± 1.984 P > 0.05 Environmental score (GH) 26.00 ± 7.16  25.43 ± 4.616 P > 0.05

[0159] As can be seen from the above experimental results, the results after two weeks of treatment of 112 patients (deficient in Qi and Yin and carrying residual pathogens) in the recovery phase of COVID-19 with the granules of the traditional Chinese medicine composition of the present application show an overall response rate of 92.85%; through the comparison of scores of traditional Chinese medicine syndromes, the post-treatment score is lower than the pre-treatment score (P<0.05) and the difference has statistical significance; through the comparison of physiological scores in the quality of life scale, the pre-treatment score is lower than the post-treatment score (P<0.05) and the difference has statistical significance, while the differences before and after treatment have no statistical significance (P>0.05) in the aspects of metal, social and environmental scores. Therefore, the traditional Chinese medicine composition of the present application can improve the clinical symptoms and the quality of life of patients (deficient in Qi and Yin and carrying residual pathogens) in the recovery phase of COVID-19.

[0160] In conclusion, the traditional Chinese medicine composition of the present application can improve the clinical symptoms of patients in the recovery phase of a fever disease caused by an exogenous pathogenic factor represented by COVID-19, and the patients in the recovery phase who use the traditional Chinese medicine composition of the present application have excellent performance during traditional Chinese medicine syndrome evaluation or quality of life evaluation. Therefore, the traditional Chinese medicine composition provided in the present application can improve the quality of life of patients and provide medical assistance for the rehabilitation of the patients.

[0161] The applicant states that the above are only the embodiments of the present application and not intended to limit the protection scope of the present application. Those skilled in the art should understand that any changes or substitutions easily conceivable by those skilled in the art within the technical scope disclosed in the present application fall within the protection scope and the disclosed scope of the present application.