Chinese patent medicine preparation for tonifying qi and nourishing blood and preparation method therefor

Abstract

A Chinese patent medicine preparation for tonifying qi and nourishing blood and a preparation method therefor. The Chinese patent medicine preparation is prepared by the following traditional Chinese medicine raw materials in parts by weight: 139 parts of Polygonum multiflorum, 113.5 parts of Radix Rehmanniae Praeparata, 172 parts of Chinese Wolfberry Root Bark, 103.5 parts of Radix Rehmanniae, 172 parts of Poria cocos, 103.5 parts of Radix Asparagi, 103.5 parts of Radix Ophiopogonis, and 103 parts of Ginseng. The preparation method comprises steps of adding a specific type and amount of grinding aid and liquid nitrogen freezing in the process of treating the traditional Chinese medicine raw materials.

Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims the benefit of Chinese Application No. 2022102001906, filed Mar. 02, 2022. The application No. 20221020019067 is hereby incorporated by reference in its entirety. TECHNICAL FIELD

[0001] The invention belongs to the field of a Chinese patent medicine preparation, and specifically, relates to Chinese patent medicine preparation for tonifying qi and nourishing blood and preparation method therefor. DESCRIPTION OF RELATED ART

[0002] Kangshou Pill is composed of Polygonum multiflorum, Radix rehmanniae praeparata, Chinese wolfberry root bark, Radix rehmanniae, Poria cocos, Radix asparagi, Radix ophiopogonis, and ginseng. The prescription is derived from "Pill for Prolonging Life and antiaging (Yannianyishou Bulao Dan)" in "Shen's Prescription for Prolonging Life (Shenshi Zunsheng Fang)" on page 1252 of "Grand Dictionary of Chinese Medicine". It has been proposed by Professor Luo yuankai of Guangzhou University of Chinese Medicine, and developed into pilule by Guangzhou Baiyunshan Jingxiutang Pharmaceutical Company Limited under the name of "Kangshou Pill". The preparation of Kangshou Pill (Traditional Chinese Medicine Prescription Preparation of Drug Standard of Ministry of Public Health of the Peoples Republic of China, Volume 11, WS3-B-2231-96) is as follows: A half of the prescription amount of Polygonum multiflorum is taken, mixed with black bean juice, and moistened sufficiently; after dried, it was then mixed with licorice juice to homogeneity and dried; Chinese wolfberry root bark and Poria cocos were washed by white spirit and dried; Radix rehmanniae praeparata and Radix rehmanniae was soaked in white spirit overnight; Radix asparagi and Radix ophiopogonis were soaked in white spirit for 3 h, and each dried; The above seven materials were pulverized together with ginseng, and the rest of Polygonum multiflorum into fine powder, which was sieved, mixed to homogeneity, pelleted with water, dried, coated with licorice carbon powder, and polished. Kangshou Pill has the functions of tonifying qi and nourishing blood, moistening lung and nourishing kidney, and can be used for treating deficiency of both qi and blood, and the shortage of essence and blood may lead to poor health, mental and body fatigue, dizziness, amnesia, hyperhidrosis, dry cough with little phlegm, palpitation, short breath, and soreness of waist and knees. The usage and dosage of Kangshou Pill is oral administration with light salt brine or honey water, 5 g each time, and 2-3 times a day.

[0003] Conventional processing and pulverization methods can not effectively destroy the cell structure of the medicinal materials, affecting the dissolution, release and absorption of active ingredients in the Chinese patent medicines. At present, Kangshou Pill has the problem of relatively low bioavailability, which leads to a large dosage required for single administration, thus reducing the compliance of patients due to the difficulty in administration.

[0004] Ultrafine grinding technology has the characteristics of improving the physicochemical properties, strengthening the efficacy, and expanding the application scope of materials. At present, ultrafine grinding technologies include airflow ultrafine grinding, rotary ball milling ultrafine grinding, mechanical shearing ultrafine grinding, high-frequency vibration ultrafine grinding and the like. However, the above ultrafine grinding technologies have poor grinding effect on Chinese medicinal materials with high sugar content and toughness, resulting in large particle size and adhesion of the finished products, and the heat generated in the grinding process is easy to cause the loss and decomposition of the medicinal ingredients. In the prescription of 2023226989   06 Aug 2026 Kangshou Pill, medicinal materials, such as Polygonum multiflorum, Radix rehmanniae praeparata, Chinese wolfberry root bark, Radix rehmanniae and the like, have high sugar content and multiple tenacious fibers, so that the purpose of the invention can not be achieved simply by adopting the superfine grinding technology. 5 SUMMARY

[0005] Aiming at the defects of the prior art, the invention aims to provide a Chinese patent medicine preparation for tonifying qi and nourishing blood and preparation method therefor based on Kangshou Pill. The Chinese patent medicine preparation prepared by the present preparation 10 method for tonifying qi and nourishing blood improves the bioavailability and efficacy of the medicine, and reduces the dosage required for single administration, thereby improving the compliance of the patient.

[0006] Specifically, the present invention provides the following aspects:

[0007] In the first aspect, the invention provides a Chinese patent medicine preparation for 15 tonifying qi and nourishing blood, wherein the Chinese patent medicine preparation comprises the following traditional Chinese medicine raw materials in parts by weight: 69.5-278 parts of Polygonum multiflorum, 56.8-227 parts of Radix rehmanniae praeparata, 86-344 parts of Chinese wolfberry root bark, 51.8-207 parts of Radix rehmanniae, 86-344 parts of Poria cocos, 51.8-207 parts of Radix asparagi, 51.8-207 parts of Radix ophiopogonis, 51.5-206 parts of ginseng. 20

[0008] Preferably, the Chinese patent medicine preparation is prepared from the following traditional Chinese medicine raw materials in parts by weight: 69.5-278 parts of Polygonum multiflorum, 56.8-227 parts of Radix rehmanniae praeparata, 86-344 parts of Chinese wolfberry root bark, 51.8-207 parts of Radix rehmanniae, 86-344 parts of Poria cocos, 51.8-207 parts of Radix asparagi, 51.8-207 parts of Radix ophiopogonis, 51.5-206 parts of ginseng.

[0009] Alternatively, in the above Chinese patent medicine preparation, the Chinese patent medicine preparation comprises the following traditional Chinese medicine raw materials in parts by weight: 139 parts of Polygonum multiflorum, 113.5 parts of Radix rehmanniae praeparata, 172 parts of Chinese wolfberry root bark, 103.5 parts of Radix rehmanniae, 172 parts of Poria cocos, 103.5 parts of Radix asparagi, 103.5 parts of Radix ophiopogonis, and 103 parts of ginseng.

[0010] Preferably, the Chinese patent medicine preparation is prepared from the following traditional Chinese medicine raw materials in parts by weight: 139 parts of Polygonum multiflorum, 113.5 parts of Radix rehmanniae praeparata, 172 parts of Chinese wolfberry root bark, 103.5 parts of Radix rehmanniae, 172 parts of Poria cocos, 103.5 parts of Radix asparagi, 103.5 parts of Radix ophiopogonis, and 103 parts of ginseng.

[0011] In the second aspect, the invention provides a method for preparing the Chinese patent medicine preparation according to the first aspect, which is characterized by comprising the following steps: (1) weighing out Polygonum multiflorum in the amount equivalent to 1 / 2-1 of said parts by weight of Polygonum multiflorum, adding black bean juice in the amount equivalent to 1 / 3-1 / 5 of the parts by weight of Polygonum multiflorum weighed out, mixing to homogeneity, moistening sufficiently, drying, and then adding liquorice juice in the amount equivalent to 1 / 9-1 / 11 of the parts by weight of Polygonum multiflorum weighed out, mixing to homogeneity, and drying for later use; (2) washing the Chinese wolfberry root bark and Poria cocos with white spirit and drying for later use; (3) soaking the Radix rehmanniae praeparata and Radix rehmanniae in white spirit for 2-24 h, and drying each for later use; (4) soaking Radix asparagi and Radix ophiopogonis in white spirit for 2-6 h, and drying each for later use; (5) mixing the above seven medicine ingredients with ginseng and the remaining parts by weight of Polygonum multiflorum required, pulverizing with a pulverizer, and sieving with a 2450 mesh pharmacopoeia sieve to obtain crude medicine powder; (6) adding a grinding aid to the resultant crude medicine powder from step (5) and mixing, wherein the grinding aid accounts for 0%-2.0% of the weight of the crude medicine powder; (7) placing the resultant mixed powder from step (6) in liquid nitrogen for freezing treatment for 0.5 to 4 h; (8) placing the resultant mixed powder from step (7) at a low temperature of -10 to 0 oC for superfine grinding to obtain superfine ground mixed powder; (9) the Chinese patent medicine preparation for tonifying qi and nourishing blood is any one of the common dosage forms prepared from the resultant mixed powder from step (8) using the conventional traditional Chinese medicine preparation method.

[0012] Alternatively, in the above preparation method, the materials is dried to the water content less than 0.5% by weight in step (1), step (2), step (3) and step (4).

[0013] Alternatively, in the above preparation method, in step (6), the grinding aid is one or two of the pharmaceutical excipients, including silicon dioxide or magnesium stearate, recorded in the Chinese Pharmacopoeia.

[0014] Preferably, the grinding aid is silicon dioxide in the amount of 0.2% to 1.0% of the weight of the crude medicine powder, or magnesium stearate in the amount of 0.4% to 2.0% of the weight of the crude medicine powder, or the mixture of 50% of silicon dioxide and 50% of magnesium stearate in the amount of 0.2% to 1.5% of the weight of the crude medicine powder.

[0015] More preferably, the grinding aid is silicon dioxide in the amount of 0.8% of the weight of the crude medicine powder, or magnesium stearate in the amount of 1.5% of the weight of the crude medicine powder, or the mixture of 50% of silicon dioxide and 50% of magnesium stearate in the amount of 1.0% of the weight of the crude medicine powder.

[0016] Alternatively, in the above preparation method, in step (7), the resultant mixed powder from step (6) is preliminarily pulverized and then placed in liquid nitrogen for freezing treatment for 2 h.

[0017] Alternatively, in the above preparation method, in step (8), the average particle size of the mixed powder is less than 35 pm, and preferably in the range from 25 to 30 pm.

[0018] Alternatively, in the above preparation method, in step (9), the dosage form is selected from the group consisting of tablet, pulvis, capsule, pill, electuary, oral liquid, granule, dropping pill, pilule, intramuscular injection, dropping injection, and ointment.

[0019] Preferably, in step (9), the dosage form is selected from tablet, pill, granule, or capsule.

[0020] Preferably, in step (9), the tablet is a sugar-coated tablet, a film-coated tablet, or an enteric coated tablet, the capsule is a soft capsule, and the ointment is an ointment or a plaster.

[0021] In the Chinese patent medicine preparation of the present invention for tonifying qi and nourishing blood, it contains both "Radix rehmanniae praeparata" and "Radix rehmanniae", wherein "Radix rehmanniae praeparata" is sweet in taste and slightly warm in nature, and can nourish blood, kidney and yin; "Radix rehmanniae" (also known as "raw Radix rehmanniae") is sweet in taste and cool in nature, and has the functions of reducing fever, nourishing yin, strengthening heart and diuresis. The synergistic mixture of Radix rehmanniae praeparata and Radix rehmanniae has the functions of nourishing blood, nourishing yin, replenishing kidney water, strengthening heart, diuresis, anti-allergy, and the like.

[0022] As compared with the prior art, the invention has the following beneficial effects:

[0023] The preparation method of the invention has solved the problem that the bioavailability of the Chinese patent medicine Kangshou Pill is relatively low in clinical use by adding a specific type and amount of grinding aid and adopting liquid nitrogen freezing as the freezing treatment method in the treatment process of the traditional Chinese medicine raw materials. The Chinese patent medicine preparation prepared by the preparation method of the invention for tonifying qi and nourishing blood has improved the bioavailability of the medicine, increased the 6 drug efficacy, and reduced the dosage required for a single administration, thereby improving the compliance of the patients. BRIEF DESCRIPTION OF DRAWINGS

[0024] Fig. 1: a graph showing the relationship between the liquid nitrogen freezing time and the particle size of the ultrafine powder.

[0025] Fig. 2: a graph showing the relationship between the amount of the grinding aid added and the particle size of the ultrafine powder.

[0026] Fig. 3: a graph showing the cumulative dissolution of Kangshou Pill and the Chinese patent medicine preparation for tonifying qi and nourishing blood. DETAILED DESCRIPTION

[0027] The invention is further described below with reference to specific examples. It should be understood that the specific examples described herein are merely illustrative of the invention, and are not intended to limit the scope of the invention.

[0028] If no specific technology or conditions are specified in the examples, the technology or conditions described in the literatures in this field or in the product specification shall be followed. If no manufacturer is indicated for the reagent or instrument used, it is a conventional product that can be purchased through regular channels.

[0029] The experimental methods in the following examples are all conventional methods, unless otherwise specified. The test materials used in the following examples are commercially available, unless otherwise specified. Example 1:

[0030] A. 139 g of Polygonum multiflorum, 113.5 g of Radix rehmanniae praeparata, 172 g of Chinese wolfberry root bark, 103.5 g of Radix rehmanniae, 172 g of Poria cocos, 103.5 g of Radix asparagi, 103.5 g of Radix ophiopogonis and 103 g of ginseng were weighed out for later use.

[0031] B. 69.5 g of Polygonum multiflorum as mentioned above was uniformly mixed with 17.4 g of black bean juice, sufficiently moistened, and dried, and then it was uniformly mixed with 7.0 g of liquorice juice, and dried; The Chinese wolfberry root bark and Poria cocos were washed with white spirit and dried; Radix rehmanniae praeparata and Radix rehmanniae were soaked in white spirit for 24 h; Radix asparagi and Radix ophiopogonis were soaked in white spirit for 6 h, and each dried; The above seven processed medicine ingredients were mixed with ginseng and the rest of Polygonum multiflorum, pulverized with a pulverizer, and sieved with a 24 mesh pharmacopoeia sieve to obtain crude medicine powder; Silicon dioxide was then added in the amount of 0.8% of the weight of the crude medicine powder into the powder and mixed; The above mixed powder was frozen in liquid nitrogen for 2 h; The above crude medicine powder was placed in a low temperature environment at 0-10 oC for superfine grinding, to give superfine mixed powder with the average particle size less than 28 pm.

[0032] C. Oral formulation:

[0033] An appropriate amount of water was added to the above ultrafine mixed powder, wet-pelleted and dried;

[0034] The pellets were coated with licorice carbon powder, and polished to give the final product. Example 2:

[0035] A. 139 g of Polygonum multiflorum, 113.5 g of Radix rehmanniae praeparata, 172 g of Chinese wolfberry root bark, 103.5 g of Radix rehmanniae, 172 g of Poria cocos, 103.5 g of Radix asparagi, 103.5 g of Radix ophiopogonis and 103 g of ginseng were weighed out for later use.

[0036] B. 69.5 g of Polygonum multiflorum as mentioned above was uniformly mixed with 17.4 g of black bean juice, sufficiently moistened, and dried, and then it was uniformly mixed with 7.0 g of liquorice juice, and dried; The Chinese wolfberry root bark and Poria cocos were washed with white spirit and dried; Radix rehmanniae praeparata and Radix rehmanniae were soaked in white spirit for 24 h; Radix asparagi and Radix ophiopogonis were soaked in white spirit for 6 h, and each dried; The above seven processed medicine ingredients were mixed with ginseng and the rest of Polygonum multiflorum, pulverized with a pulverizer, and sieved with a 50 mesh pharmacopoeia sieve to obtain crude medicine powder; Magnesium stearate was then added in the amount of 1.5% of the weight of the crude medicine powder into the powder and mixed; The above mixed powder was frozen in liquid nitrogen for 2 h; The above crude medicine powder was placed in a low temperature environment at 0-10 oC for superfine grinding, to give superfine mixed powder with the average particle size less than 28 pm.

[0037] C. Oral formulation:

[0038] An appropriate amount of water was added to the above ultrafine mixed powder, wet-pelleted and dried;

[0039] The pellets were sieved and encapsulated to give the final product. Example 3: Test of liquid nitrogen freezing time 1. Test materials

[0040] 139 g of Polygonum multiflorum, 113.5 g of Radix rehmanniae praeparata, 172 g of Chinese wolfberry root bark, 103.5 g of Radix rehmanniae, 172 g of Poria cocos, 103.5 g of Radix asparagi, 103.5 g of Radix ophiopogonis and 103 g of ginseng were weighed out for later use.

[0041] 69.5 g of Polygonum multiflorum as mentioned above was uniformly mixed with 17.4 g of black bean juice, sufficiently moistened, and dried, and then it was uniformly mixed with 7.0 g of liquorice juice, and dried; The Chinese wolfberry root bark and Poria cocos were washed with white spirit and dried; Radix rehmanniae praeparata and Radix rehmanniae were soaked in white spirit for 24 h; Radix asparagi and Radix ophiopogonis were soaked in white spirit for 6 h, and each dried; The above seven processed medicine ingredients were mixed with ginseng and the rest of Polygonum multiflorum, pulverized with a pulverizer, and sieved with a 24 mesh pharmacopoeia sieve. Silicon dioxide was added in the amount of 1.0% of the weight of the crude medicine powder into the powder and mixed to give the test sample. 2. Test method

[0042] The samples were frozen in liquid nitrogen for 0, 0.5, 1, 2 and 4 h, respectively, at the same rotation speed of the pulverizer and the same water content of the powder, and then subjected to ultrafine grinding at a low temperature of 0-10 oC. Subsequently, the particle size of the powder sample was measured and analyzed. 3. Conclusion

[0043] The effect of freezing time on the particle size of the ultrafine powder is shown in Fig. 1. As shown in Fig. 1, under the same other conditions, the particle size (D90) of the ultrafine powder decreases significantly with the increased freezing time in liquid nitrogen, and the particle size (D90) changes more after freezing for 0.5 h than that after freezing for 0 h. After liquid nitrogen freezing, the interaction force between the molecules in the crude powder is reduced, and the material is brittle and easy to crush. When the freezing time reaches 2 h to 4 h, the particle size (D90) changes slightly, indicating that the intermolecular force has reached the optimal level after freezing for 2 h, and further increased freezing time has little effect. Therefore, 2 h can be used as the best freezing time in actual production practice. Example 4: Test of the addition amount of the grinding aid 1. Test materials

[0044] 139 g of Polygonum multiflorum, 113.5 g of Radix rehmanniae praeparata, 172 g of Chinese wolfberry root bark, 103.5 g of Radix rehmanniae, 172 g of Poria cocos, 103.5 g of Radix asparagi, 103.5 g of Radix ophiopogonis and 103 g of ginseng were weighed out for later use.

[0045] 69.5 g of Polygonum multiflorum as mentioned above was uniformly mixed with 17.4 g of black bean juice, sufficiently moistened, and dried, and then it was uniformly mixed with 7.0 g of liquorice juice, and dried; The Chinese wolfberry root bark and Poria cocos were washed with white spirit and dried; Radix rehmanniae praeparata and Radix rehmanniae were soaked in white spirit for 24 h; Radix asparagi and Radix ophiopogonis were soaked in white spirit for 6 h, and each dried;

[0046] The above seven processed medicine ingredients were mixed with ginseng and the rest of Polygonum multiflorum, pulverized with a pulverizer, and sieved with a 24 mesh pharmacopoeia sieve to obtain crude medicine powder as the test sample. 2. Test method

[0047] Under the same rotation speed of the pulverizer and the same water content of the powder, the test samples were each mixed with silicon dioxide, magnesium stearate, or the mixture of 50% silicon dioxide and 50% magnesium stearate in the amount of 0, 0.2, 0.4, 0.6, 0.8, 1.0, 1.5, and 2.0% of the weight of the test sample, and the resultant mixed powder was frozen in liquid nitrogen for 4 h; subsequently, the mixture was placed in a low temperature environment at 0-10 oC for ultrafine grinding, and then the particle size of the powder sample was measured and analyzed. 3. Conclusion

[0048] The effect of the addition amount of the grinding aid on the particle size of the ultrafine powder is shown in Fig. 2. As shown in Fig. 2, under the same other conditions, the particle size (D90) of the ultrafine powder is significantly reduced with the increased amount of the grinding aid added. The grinding aid can reduce the adhesion and aggregation of the ultrafine powder on the inner wall of the equipment, reduce the inter-adhesion between the powder of the polysaccharide, reduce the moisture absorption rate of the powder, reduce the saturated moisture absorption of the powder, and make the ultrafine powder easier to disperse and crush. The particle size of the ultrafine powder is reduced obviously after adding the grinding aid; the particle size of the ultrafine powder reaches the optimal level when the addition amount of silicon dioxide reaches 0.8%, the addition amount of magnesium stearate reaches 1.5%, and the addition amount of the mixture of 50% silicon dioxide and 50% magnesium stearate reaches 1.0%, and the particle size is not obviously affected by further increased amount of the grinding aid added.

[0049] Preferably, the grinding aid is silicon dioxide in the amount of 0.2% to 1.0% of the weight of the crude medicine powder, or magnesium stearate in the amount of 0.4% to 2.0% of the weight of the crude medicine powder, or the mixture of 50% of silicon dioxide and 50% of magnesium stearate in the amount of 0.2% to 1.5% of the weight of the crude medicine powder. Preferably, the grinding aid added is silicon dioxide in the amount of 0.8% of the weight of the crude medicine powder, or magnesium stearate in the amount of 1.5% of the weight of the crude medicine powder, or the mixture of 50% of silicon dioxide and 50% of magnesium stearate in the amount of 1.0% of the weight of the crude medicine powder. Example 5: Dissolution test 1. Instruments and Reagents

[0050] Electronic analytical balance (0.0001g, Mettler Toledo); Agilent 1260 high performance liquid chromatograph (equipped with a quaternary pump, an autosampler, a column oven and a DAD detector); OpenLab CDS chromatographic workstation. 2,3,5,4'-tetrahydroxystilbene-2-O-P-D-glucoside was purchased from China National Institute for Food and Drug Control. Acetonitrile is of chromatographic grade, water is ultrapure water, and all other reagents are of analytical grade. The sample of Kangshou Pill was provided by Guangzhou Baiyunshan Jingxiutang Pharmaceutical Company Limited (Lot number: B11013); the Chinese patent medicine preparation for tonifying qi and nourishing blood was prepared according to the method of Example 1. 2. Methods and results 2.1. Preparation of artificial gastric juice

[0051] 800 mL of water and 10 g of pepsin were added into 16.4 mL of diluted hydrochloric acid, and shaken to homogeneity, which was then diluted to 1000 mL. The pH value of the solution is 1.8. 2.2. Preparation of the test solution

[0052] Kangshou Pill or the Chinese patent medicine preparation for tonifying qi and nourishing blood containing about 3 g of the raw Polygonum multiflorum was each weighed out. The dissolution was detected based on the second method (paddle method) for dissolution and release determination , General Rule 0931, Volume 4, Chinese Pharmacopoeia (Edition 2020). The test was conducted using the artificial gastric juice in "2.1" as the dissolution medium, at a rotation speed of 75 r / min and temperature of (37.0±0.5) oC. 1 mL samples were taken at 5, 10, 15, 20, 30, 40, 50 and 60 min respectively, and the dissolution medium at the same temperature was supplemented with the same volume in time. After filtration through a 0.45 pm microporous filter, the filtrate obtained was the test solution. 2.3. Preparation of reference solution

[0053] About 6 mg of 2,3,5,4'-tetrahydroxystilbene-2-O-P-D-glucoside was precisely weighed out as the reference. It was placed into a 100 mL volumetric flask, into which 5 mL of methanol was added to dissolve it. After dissolution, it was diluted to the scale by the dissolution medium, shaken up, and used as the reference solution. 2.4. Chromatographic conditions

[0054] Column: Thermo ODS-2 HYPERSIL (250 mm* 4.6 mm, 5 ^m, Thermo Fisher, USA); mobile phase: acetonitrile-water (volume ratio of 20:80); detection wavelength: 320 nm; flow rate: 1.0 m L / min; column temperature: 40 oC; injection volume: 10 ^L. 2.5. Determination of dissolution

[0055] The test solution and the reference solution were each injected into the HPLC according to the chromatographic conditions in "2.4". The chromatogram was recorded, and the cumulative dissolution was calculated based on the peak area according to the external standard method, and the dissolution curve was plotted. The results are shown in Fig. 3. 3. Conclusions

[0056] As compared with the Kangshou Pill prepared by the prior art, the content of the 2,3,5,4'-tetrahydroxystilbene-2-O—P—D-glucoside has been improved by about 30%, indicating that the cell wall is damaged during pulverization, and the effective components can be released without penetrating the cell wall, so that the release rate and amount are improved, and the original efficacy of the medicinal materials can be maintained. Example 6: Pharmacodynamic Experiment 1. Test materials

[0057] SPF Kunming mice, purchased from Guangdong Medical Laboratory Animal Center, animal production license No. SCXF (Yue) 2018-0002. The sample of Kangshou Pill was provided by Guangzhou Baiyunshan Jingxiutang Pharmaceutical Company Limited (Lot number: B11013); the Chinese patent medicine preparation for tonifying qi and nourishing blood was prepared according to the method of Example 1; normal saline. 2. Statistical analysis

[0058] All data were input into EXCEL2010 for statistical analysis. In different groups, the mean ± standard deviation ( v ^) was calculated, analysis of variance was performed, and t-test was used for comparison between groups. 3. Hypoxia tolerance test under normal pressure in mice

[0059] Fifty-four mice weighing 18-22 g, both male and female, were randomly divided into three groups: Kangshou Pill group, Chinese patent medicine preparation for tonifying qi and nourishing blood group and normal saline control group, with 18 mice in each group. The mice in the administration groups were treated with Kangshou Pill or Chinese patent medicine 5 preparation for tonifying qi and nourishing blood at a dose of 5 g / kg by gastric gavage, while the mice in the control group were treated with the same volume of normal saline at a dose of 0.5 mL / mouse. One hour after gastric gavage, the mice were placed in 250 mL ground bottles with 5 g of soda lime placed in advance. Each bottle contained one mouse and was sealed with vaseline. The survival time was recorded using death as the index. The results are shown in Table 1. 10                    Table 1. Hypoxia tolerance test under normal pressure in mice Group Number of the animals Survival time .v    S) (min, P Normal saline 18 52.2±14.1 <0.05 Kangshou Pill 18 65.3±15.1 (Compared to the normal saline group) Chinese         patent <0.01 medicine preparation 18 78.8±14.6 (Compared to the for tonifying qi and Kangshou Pill group) nourishing blood

[0060] As shown in Table 1, the survival time of the mice in the Chinese patent medicine preparation for tonifying qi and nourishing blood group was significantly longer than that in the Kangshou Pill group (P < 0.01), indicating that the medicine has the effect of improving the hypoxia tolerance ability of the mice under normal pressure. 15   4. Memory test on old mice

[0061] Sixty-six 15-month-old mice were used in the experiment, with an average body weight of 37.5 g per mouse. The mice were randomly divided into three groups: Kangshou Pill group, Chinese patent medicine preparation for tonifying qi and nourishing blood group and normal saline control group. There were 22 mice in each group, both male and female. For the 5 administration groups, Kangshou Pill or Chinese patent medicine preparation for tonifying qi and nourishing blood (2.7 g / kg) was given at a dose of 2.7 g / kg by gastric gavage once daily for 8 consecutive days. The mice in the control group were given the same volume of saline at a dose of 0.5 mL / mouse. Memory was measured by the maze method. Before the memory test, the mice were fasted for half a day, and the mice were allowed to go through the maze twice to understand 10 the way to the terminal of the maze, and then the memory was measured for each mouse . The time required for the mice to walk from the entrance to the termini of the maze was used as an indicator of memory, i.e., the shorter the time was used, the better the memory was. The experimental results are shown in Table 2. Table 2. Memory test on old mice Group Number of the animals The time required to arrive at the terminal of the maze (second, i ■-) P Normal saline 22 619.5±335.4 <0.01 Kangshou Pill 22 410.1±213.3 (Compared to the normal saline group) Chinese         patent medicine preparation for tonifying qi and nourishing blood 22 247.6±206.5 <0.05 (Compared to the Kangshou Pill group)

[0062] As shown in Table 2, the time required for the mice in the Chinese patent medicine preparation for tonifying qi and nourishing blood group to arrive at the terminal of the maze was shorter than that in the Kangshou Pill group (P < 0.05), indicating that the Chinese patent medicine preparation for tonifying qi and nourishing blood can improve the maze memory of the old mice. 5. Swimming endurance test

[0063] Thirty-three male mice weighing 17-19 g were randomly divided into three groups: Kangshou Pill group, Chinese patent medicine preparation for tonifying qi and nourishing blood group and normal saline control group, with 11 mice in each group. The mice in the administration groups were treated with Kangshou Pill or Chinese patent medicine preparation for tonifying qi and nourishing blood at a dose of 5 g / kg by gastric gavage once daily for 8 consecutive days, while the mice in the control group were treated with the same volume of normal saline at a dose of 0.5 mL / mouse. Endurance test was carried out by load swimming until complete fatigue, that is, a copper wire ring equivalent to 5% of its own weight was tied to the tail root of the mouse, and then the mouse was forced to swim in a glass pool with the water temperature of 27°C. The time was recorded from entering the water to sinking to the bottom for more than 10 seconds, as the load swimming time. The effects in each group on the swimming time of the mouse were observed. The results are shown in Table 3. Table 3. Swimming endurance test Number of the Load swimming time Group P animals          (min, + S) Normal saline 11               15.21±1.45 <0.05 Kangshou Pill 11              17.62±1.38               (Compared to the normal saline group) Chinese patent <0.01 medicine preparation 11              21.53±1.73               (Compared to the for tonifying qi and Kangshou Pill group) nourishing blood

[0064] The load swimming time can truly reflect the endurance of animals. As shown in Table 3, the swimming time of mice in the Chinese patent medicine preparation for tonifying qi and nourishing blood group was significantly different from that in the Kangshou Pill group (P < 0.01). It is believed that the Chinese patent medicine preparation for tonifying qi and nourishing 5 blood has the effect of enhancing the swimming endurance of mice. 6. Androgen activity test

[0065] The test was performed by measuring the increased weight of prostate and spermary. thirty-nine young male mice weighing 12-14 g were randomly divided into 3 groups: Kangshou Pill group, Chinese patent medicine preparation for tonifying qi and nourishing blood group and 10 normal saline control group, with 13 mice in each group. For the administration group, the mice were given Kangshou Pill or Chinese patent medicine preparation for tonifying qi and nourishing blood at a dose of 6 g / kg by gastric gavage, while the mice in the control group were given the same volume of saline at a dose of 0.4 mL / mouse once a day for 9 days. On day 10, the mice were sacrificed and the total weight of prostate and spermary was measured. The average 15 weights of prostate and spermary per 10 g body weight were compared. The results are shown in Table 4. Table 4. Androgen Activity Test Total weight of prostate Number of the Group                                 and spermary (mg / 10 g P animals body weight, z t ) Normal saline           13               8.0±3.7 <0.01 Kangshou Pill           13              23.0±10.1                (Compared to the normal saline group) Chinese patent <0.01 medicine preparation 13              36.5±16.7                (Compared to the for tonifying qi and Kangshou Pill group) nourishing blood

[0066] As shown in Table 4, the weight of prostate and spermary per 10 g body weight of the male mice in the Chinese patent medicine preparation for tonifying qi and nourishing blood group was significantly different from that in the Kangshou Pill group (P < 0.01). According to the fact that the growth and development of accessory sex organs, such as spermary and 5 prostate, depend on androgen, it is considered that the Chinese patent medicine preparation for tonifying qi and nourishing blood has the effect of enhancing the activity of androgen. 7. Estrogen activity test

[0067] The test was performed by measuring the increased weight of uterus. thirty-three young female mice weighing 12-14 g were randomly divided into 3 groups: Kangshou Pill group, 10 Chinese patent medicine preparation for tonifying qi and nourishing blood group and normal saline control group, with 11 mice in each group. For the administration group, the mice were given Kangshou Pill or Chinese patent medicine preparation for tonifying qi and nourishing blood at a dose of 6 g / kg by gastric gavage, while the mice in the control group were given the same volume of saline at a dose of 0.4 mL / mouse once a day for 9 days. On day 10, the mice 15 were sacrificed and the weight of uterus was measured. The average weights of uterus per 10 g body weight were compared. The results are shown in Table 5. Table 5. Estrogen activity test Group                 Number of the Weight of uterus (mg / 10g P animals body weight, 1 ) Normal saline 11 9.4±5.0 <0.01 Kangshou Pill 11 15.0±2.4 (Compared to the normal saline group) Chinese         patent medicine preparation for tonifying qi and nourishing blood 11 19.6±3.9 <0.05 (Compared to the Kangshou Pill group)

[0068] As shown in Table 5, the uterus weight per 10 g of body weight of the mice in the Kangshou Pill group was significantly different from that in the normal saline control group (P < 0.05). According to the fact that the growth and development of the uterus depend on estrogen, it is considered that the Chinese patent medicine preparation for tonifying qi and nourishing blood 5 has the effect of enhancing the activity of estrogen. 8. Life span test on old mice

[0069] Forty-eight 15-month-old Kunming mice, both male and female, were randomly divided into three groups with 16 mice in each group, including Kangshou Pill group, Chinese patent medicine preparation for tonifying qi and nourishing blood group and normal saline control 10 group. The total weights of the mice in three groups were basically the same. The administration was divided into two stages. At the first stage (gastric gavage), the mice in the administration groups were given Kangshou Pill or Chinese patent medicine preparation for tonifying qi and nourishing blood at a dose of 3.3 g / kg by gastric gavage once a day for 13 days, while the mice in the control group were given the same volume of saline at a dose of 0.5 mL per mouse. At the 15 second stage, each mouse in the administration groups was fed with 2.5 g of biscuit soaked in 100 mg / mL Kangshou Pill solution at a dose of 6 g / kg once a day for 47 days. The total administration duration was 60 days by combining the first stage (13 days) and the second stage 20 (47 days). In the control group, all of the test conditions were the same as those in the administration group, except that the mice were given the same volume of normal saline instead of drugs. The life span of each mouse was recorded by registering the number of dead animals on a daily basis. The data were processed by statistical analysis for the animals in the two groups. 5 The results are shown in Table 6. Table 6. Life span test on old mice Group Numbe r of the animal s Shortest Longest life span (day / mouse ) Average life span (day / mouse, A ■ S) Prolonged life (day / ) span ouse days         P (day / mouse) Normal saline Kangshou 16 464 591 525.4±46.8 31.1          <0.05 Pill Chinese patent medicine preparation 16 468 606 556.5±31.7 (Compared to the normal saline group) 25.9          <0.05 for tonifying qi     and nourishing blood 16 472 695 592.4±30.7 (Compared to the Kangshou Pill group)

[0070] As shown in Table 6, the average life span of the mice in the Chinese patent medicine preparation for tonifying qi and nourishing blood group is 25.9 days longer than that of the mice in the Kangshou Pill group, with significant difference (P < 0.05) through statistical analysis. The mice in the Chinese patent medicine preparation for tonifying qi and nourishing blood group not only can prolong the shortest life span, but also can increase the longest life span, indicating that the Chinese patent medicine preparation for tonifying qi and nourishing blood has the effect of prolonging the life span of the old mice. 9. Conclusion

[0071] The above results show that Kangshou Pill and the Chinese patent medicine preparation for tonifying qi and nourishing blood have the effects of enhancing the hypoxia tolerance of mice under normal pressure, improving the maze memory of old mice, enhancing the swimming endurance of mice, enhancing the activity of androgen and estrogen of mice and prolonging the life span of old mice. Therefore, it is believed that Kangshou Pill and Chinese patent medicine preparation for tonifying qi and nourishing blood have the effects of tonifying qi and nourishing blood, moistening lung and nourishing kidney, strengthening body and prolonging life. In the above experiments, the effect of Chinese patent medicine preparation for tonifying qi and nourishing blood is more obvious than that of Kangshou Pill. Example 7: Safety Test 1. Test materials

[0072] SPF Kunming mice, purchased from Guangdong Medical Laboratory Animal Center, animal production license No.: SCXF (Yue) 2018-0002. 2. Statistical analysis

[0073] All data were input into EXCEL2010 for statistical analysis. In different groups, the mean ± standard deviation ( v ' s) was calculated, analysis of variance was performed, and t-test was used for comparison between groups. 3. Preparation of the test sample

[0074] 139 g of Polygonum multiflorum, 113.5 g of Radix rehmanniae praeparata, 172 g of Chinese wolfberry root bark, 103.5 g of Radix rehmanniae, 172 g of Poria cocos, 103.5 g of Radix asparagi, 103.5 g of Radix ophiopogonis and 103 g of ginseng were weighed out for later use.

[0075] 69.5 g of Polygonum multiflorum as mentioned above was uniformly mixed with 17.4 g of black bean juice, sufficiently moistened, and dried, and then it was uniformly mixed with 7.0 g of liquorice juice, and dried; The Chinese wolfberry root bark and Poria cocos were washed with white spirit and dried; Radix rehmanniae praeparata and Radix rehmanniae were soaked in white spirit for 24 h; Radix asparagi and Radix ophiopogonis were soaked in white spirit for 6 h, and each dried;

[0076] The above seven processed medicine ingredients were mixed with ginseng and the rest of Polygonum multiflorum, pulverized with a pulverizer, and sieved with a 24 mesh pharmacopoeia sieve to obtain crude medicine powder. Under the same rotation speed of the pulverizer and the same water content of the powder, silicon dioxide or magnesium stearate was each mixed with the weight of 2.0% of the weight of the above crude medicine powder into the powder. The above mixed powder was frozen in liquid nitrogen for 4 h, and placed in a low temperature environment of 0-10 oC for superfine grinding to give a silicon dioxide test preparation sample and a magnesium stearate test preparation sample, respectively. 4. Test method

[0077] Forty-eight old Kunming mice, both male and female, were randomly divided into three groups: silicon dioxide preparation group, magnesium stearate preparation group and normal saline control group. For the administration groups, the mice were given silicon dioxide test preparation sample or magnesium stearate test preparation sample at a dose of 7 g / kg for 10 consecutive days by gastric gavage, while the mice in the control group was given the corresponding volume of deionized water for 10 consecutive days at fixed time twice daily. The mice were observed for 14 consecutive days. Body mass, behavior, diet and excretion of the mice in each group were recorded. On day 14, the eyeball blood, liver and kidney of the mice were collected, and subjected to biochemical index determination and the pathological staining. 5. Conclusions 2023226989   06 Aug 2026

[0078] There were no significant changes in body mass, diet, behavior, and excretion, and the detected values of serum glucose, total protein, creatinine and triglyceride before and after gavage (P > 0.05), and there were no significant differences between the two administration groups and 5 the control group. In addition, there were no toxicological changes in liver and kidney pathological staining. The above results suggest that no acute toxicity has been observed for the preparations with silicon dioxide or magnesium stearate added into the Chinese patent medicine for tonifying qi and nourishing blood under the experiment conditions.

[0079] It will be apparent to those skilled in the art that various modifications and variations can 10 be made in the present invention without departing from the spirit and scope of the invention. Thus, the present invention is intended to include such modifications and variations provided they come within the scope of the appended claims and their equivalents.

[0080] Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be 15 understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0081] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or 20 known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

Claims

2023226989   06 Aug 20261.     A Chinese patent medicine preparation for tonifying qi and nourishing blood, wherein theChinese patent medicine preparation comprises the following traditional Chinese medicine raw materials in parts by weight: 139 parts of Polygonum multiflorum, 113.5 parts of Radix rehmanniae 5 praeparata, 172 parts of Chinese wolfberry root bark, 103.5 parts of Radix rehmanniae, 172 partsof Poria cocos, 103.5 parts of Radix asparagi, 103.5 parts of Radix ophiopogonis, and 103 parts of ginseng, wherein the preparation method of the Chinese patent medicine preparation comprises the following steps:(1) weighing out Polygonum multiflorum in the amount equivalent to 1 / 2-1 of said parts by 10 weight of Polygonum multiflorum, adding black bean juice in the amount equivalent to 1 / 3-1 / 5 of the parts by weight of Polygonum multiflorum weighed out, mixing to homogeneity, moistening sufficiently, drying, and then adding liquorice juice in the amount equivalent to 1 / 9-1 / 11 of the parts by weight of Polygonum multiflorum weighed out, mixing to homogeneity, and drying for later use;15        (2) washing the Chinese wolfberry root bark and Poria cocos with white spirit and drying forlater use;(3) soaking the Radix rehmanniae praeparata and Radix rehmanniae in white spirit for 2-24 h, and drying each for later use;(4) soaking Radix asparagi and Radix ophiopogonis in white spirit for 2-6 h, and drying each 20 for later use;(5) mixing the above seven medicine ingredients with ginseng and the remaining parts by weight of Polygonum multiflorum required, pulverizing with a pulverizer, and sieving with a 2450 mesh pharmacopoeia sieve to obtain crude medicine powder;(6) adding a grinding aid to the resultant crude medicine powder from step (5) and mixing, 25 wherein the grinding aid is one or two of the pharmaceutical excipients, including silicon dioxide or magnesium stearate, recorded in the Chinese Pharmacopoeia, wherein the grinding aid is silicon2023226989   06 Aug 2026dioxide in the amount of 0.2% to 1.0% of the weight of the crude medicine powder, or magnesium stearate in the amount of 0.4% to 2.0% of the weight of the crude medicine powder, or a mixture of 50% of silicon dioxide and 50% of magnesium stearate in the amount of 0.2% to 1.5% of the weight of the crude medicine powder;5        (7) placing the resultant mixed powder from step (6) in liquid nitrogen for freezing treatmentfor 2 h;(8) placing the resultant mixed powder from step (7) at a low temperature of -10 to 0 oC for superfine grinding to obtain superfine ground mixed powder; and(9) formulating the resultant mixed powder from step (8) as any one of the dosage forms10 selected from the group consisting of tablet, pulvis, capsule, pill, electuary, oral liquid, granule, dropping pill, pilule, intramuscular injection, dropping injection, and ointment.

2. A method of preparing the Chinese patent medicine preparation according to claim 1,wherein the method comprises the following steps:15        (1) weighing out Polygonum multiflorum in the amount equivalent to 1 / 2-1 of said parts byweight of Polygonum multiflorum, adding black bean juice in the amount equivalent to 1 / 3-1 / 5 of the parts by weight of Polygonum multiflorum weighed out, mixing to homogeneity, moistening sufficiently, drying, and then adding liquorice juice in the amount equivalent to 1 / 9-1 / 11 of the parts by weight of Polygonum multiflorum weighed out, mixing to homogeneity, and drying for20 later use;(2) washing the Chinese wolfberry root bark and Poria cocos with white spirit and drying for later use;(3) soaking the Radix rehmanniae praeparata and Radix rehmanniae in white spirit for 2-24 h, and drying each for later use;25        (4) soaking Radix asparagi and Radix ophiopogonis in white spirit for 2-6 h, and drying eachfor later use;2023226989   06 Aug 2026(5) mixing the above seven medicine ingredients with ginseng and the remaining parts by weight of Polygonum multiflorum required, pulverizing with a pulverizer, and sieving with a 2450 mesh pharmacopoeia sieve to obtain crude medicine powder;(6) adding a grinding aid to the resultant crude medicine powder from step (5) and mixing,5 wherein the grinding aid is one or two of the pharmaceutical excipients, including silicon dioxide or magnesium stearate, recorded in the Chinese Pharmacopoeia, wherein the grinding aid is silicon dioxide in the amount of 0.2% to 1.0% of the weight of the crude medicine powder, or magnesium stearate in the amount of 0.4% to 2.0% of the weight of the crude medicine powder, or a mixture of 50% of silicon dioxide and 50% of magnesium stearate in the amount of 0.2% to 1.5% of the10 weight of the crude medicine powder;(7) placing the resultant mixed powder from step (6) in liquid nitrogen for freezing treatment for 2 h;(8) placing the resultant mixed powder from step (7) at a low temperature of -10 to 0 oC for superfine grinding to obtain superfine ground mixed powder;15        (9) formulating the resultant mixed powder from step (8) as any one of the dosage formsselected from the group consisting of tablet, pulvis, capsule, pill, electuary, oral liquid, granule, dropping pill, pilule, intramuscular injection, dropping injection, and ointment.

3. The method according to claim 2, wherein the materials are dried to the water content less20 than 0.5% by weight in step (1), step (2), step (3) and step (4).

4. The method according claim 3, wherein in step (8), the average particle size of the mixedpowder is in the range from 25 to 30 gm.25   5.     The method according to claim 4, wherein in step (9), the dosage form is selected fromtablet, pill, granule, or capsule.2023226989   06 Aug 2026106.     The method according to claim 4, wherein in step (9), the tablet is a sugar-coated tablet, afilm-coated tablet, or an enteric coated tablet.

7. The method according to claim 4, wherein in step (9), the capsule is a soft capsule.

8. The method according to claim 4, wherein in step (9), the ointment is an ointment or aplaster.

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