LU501932B1

LU501932B1 - Traditional chinese medicine composition for treating hypertension and preparation method thereof

Info

Publication number: LU501932B1
Application number: LU501932A
Authority: LU
Inventors: Yunlun Li
Original assignee: Univ Shandong Traditional Chinese Medicine
Priority date: 2021-12-22
Filing date: 2022-04-26
Publication date: 2023-06-22
Also published as: CN114010699B; CN114010699A

Abstract

The present invention provides a traditional Chinese medicine composition for treating hypertension and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine. The traditional Chinese medicine composition is composed of the following traditional Chinese medicine raw materials based on parts by weight: 10-15 parts of uncaria, 5-10 parts of radix scrophulariae and 5-10 parts of stir-baked semen raphani. The traditional Chinese medicine composition of the present invention, which is simple in recipe and powerful in function, has the functions of calming the liver, suppressing yang and nourishing the kidney yin, and has a significant therapeutic effect on hypertension.

Description

TRADITIONAL CHINESE MEDICINE COMPOSITION FOR TREATING LUS01932

HYPERTENSION AND PREPARATION METHOD THEREOF

TECHNICAL FIELD

[01] The present application relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for treating hypertension and a preparation method thereof.

BACKGROUND ART

[02] Essential hypertension is a cardiovascular syndrome with uncertain causes and mainly manifested by steady elevation of systemic arterial blood pressure. According to investigations, there are trends that a prevalence rate is increasing and an age of onset is getting younger year by year among Chinese residents. Hypertension can not only cause dizziness, headache and other clinical symptoms, but also is the most important risk factor for cardiovascular and cerebrovascular events, as well as an important cause of disability and death. Western medicine alone has certain limitations in the treatment of hypertension, including fluctuation in blood pressure and obvious side effects; while traditional Chinese medicines not only have a good effect on reducing blood pressure, but also can significantly improve clinical symptoms of patients. Since traditional

Chinese medicines can realize comprehensive regulation of multiple levels, multiple links and multiple targets for a body and have the advantages of no toxic and side effects, they have become the main means for treating hypertension.

[03] There are numerous existing traditional Chinese medicine compositions for treating hypertension, but they all contain several pharmaceutical raw materials. During preparation, a medicine can be prepared only by gathering multiple raw materials by a cumbersome and complicated preparation procedure, and moreover medicines aiming at different symptoms and causes of disease can achieve different drug effects. As a result, only a few traditional Chinese medicine compositions are applied in clinic. Therefore, there is a clinical need for a new traditional Chinese medicine composition that can effectively treat hypertension with simple compatibility and has a protective effect on organs.

SUMMARY

[04] The present invention is intended to provide a traditional Chinese medicine composition for treating hypertension. The traditional Chinese medicine composition provided by the present invention has the functions of calming the liver, suppressing yang and nourishing the kidney yin, and has a significant therapeutic effect on hypertension.

[05] In order to realize the above-mentioned purpose, the present invention adopts the following technical solutions:

[06] The present invention provides a traditional Chinese medicine composition for treating hypertension, which is composed of the following traditional Chinese medicine raw materials based on parts by weight: 10-15 parts of uncaria, 5-10 parts of radix scrophulariae and 5-10 parts of stir-baked semen raphani. 1

[07] Preferably, the traditional Chinese medicine composition for treating LU501932 hypertension is composed of the following traditional Chinese medicine raw materials based on parts by weight: 12 parts of uncaria, 9 parts of radix scrophulariae and 9 parts of stir-baked semen raphani.

[08] The present invention further provides a method for preparing the traditional

Chinese medicine composition, including the following steps:

[09] (1) taking the uncaria, the radix scrophulariae and the stir-baked semen raphani, firstly adding water to soak such materials, then performing heating and reflux extraction one to three times, 1-2 h each time, combining extracting solutions, and filtering the extracting solutions through a screen to obtain a filtrate; and

[10] (2) concentrating the filtrate into a clear paste with a relative density of 1.10-1.20, and drying and sieving the clear paste to obtain a traditional Chinese medicine composition.

[11] Preferably, a part by weight of the water is 6-12 folds the total weight of the traditional Chinese medicine raw materials in the traditional Chinese medicine composition.

[12] Preferably, the concentration is performed at a temperature of 60-75°C and a pressure of -0.06 to -0.08 Mpa.

[13] Preferably, the drying is one of ambient-pressure drying, reduced-pressure drying, and spray drying.

[14] The present invention further provides a drug for treating hypertension, including the traditional Chinese medicine composition and a pharmaceutically acceptable excipient.

[15] Preferably, the drug includes powder, pills, tablets, mixtures, granules or capsules.

[16] The present invention further provides a method for preparing traditional

Chinese medicine composition granules, including the following steps: taking uncaria, radix scrophulariae and stir-baked semen raphani, firstly adding water to soak such materials, then performing heating and reflux extraction one to three times, 1-2 h each time, combining extracting solutions, and filtering the extracting solutions through a screen to obtain a filtrate, concentrating the filtrate into a clear paste with a relative density of 1.10-1.20, and adding dextrin according to a weight ratio of a solid content of the clear paste to the dextrin being (1-1.3):(1-1.3), and performing fluidized spray granulation using the dextrin as a substrate to obtain traditional Chinese medicine composition granules.

[17] Preferably, an inlet air temperature for the fluidized spray granulation is 100-140°C, and a spray rate is 100-300 r/min.

[18] Compared with the prior art, the present invention has the following advantages:

[19] The traditional Chinese medicine composition has the functions of calming the liver, suppressing yang and nourishing the kidney yin, and has a significant therapeutic effect on hypertension without any toxic or side effect, laying a good foundation for further researches on traditional Chinese medicine preparations. The traditional Chinese medicine composition of the present invention only using three medicinal materials is 2 concise in constitution and convenient in application, and thus has a broad clinical LU501932 application prospect.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[20] The present invention provides a traditional Chinese medicine composition for treating hypertension, which is preferably composed of the following traditional

Chinese medicine raw materials based on parts by weight: 10-15 parts of uncaria, 5-10 parts of radix scrophulariae and 5-10 parts of stir-baked semen raphani, and more preferably composed of the following traditional Chinese medicine raw materials based on parts by weight: 12 parts of uncaria, 9 parts of radix scrophulariae and 9 parts of stir-baked semen raphani. In the present invention, the uncaria, which is used as medicine with hooked stems and branches, has the effects of clearing heat and calming the liver, relieving wind and calming convulsions; the radix scrophulariae, which is used as medicine with dry roots, has slightly cold nature, and has the effects of cooling blood, nourishing yin, purging fire and detoxifying, and it is used for the symptoms including fever-induced impairment of yin, dark tongue, polydipsia, speckles caused by warm toxins, constipation caused by impaired body fluid, cough induced by hectic fever, red eyes, sore throat, scrofula, diphtheria, carbuncle and sore; the stir-baked semen raphani has the functions of helping digestion, eliminating flatulence, lowering qi and resolving phlegm, and it is used for the symptoms of stagnation of diet, abdominal distention and pain, constipation, accumulation of stagnation and diarrhea, phlegm and cough. A combination of the three medicinal materials of the present invention, including uncaria, radix scrophulariae and stir-baked semen raphani, has the functions of calming the liver, suppressing yang and nourishing the kidney yin, and has a significant therapeutic effect on hypertension without any toxic or side effect.

[21] The present invention further provides a method for preparing the traditional

Chinese medicine composition, including the following steps:

[22] (1) taking the uncaria, the radix scrophulariae and the stir-baked semen raphani, firstly adding water to soak such materials, then performing heating and reflux extraction one to three times, 1-2 h each time, combining extracting solutions, and filtering the extracting solutions through a screen to obtain a filtrate; and

[23] (2) concentrating the filtrate into a clear paste with a relative density of 1.10-1.20, and drying and sieving the clear paste to obtain a traditional Chinese medicine composition.

[24] In the present invention, the extraction is preferably performed two times, and preferably 1.5 h for each extraction; a part by weight of the water is preferably 6-12 folds the total weight of the traditional Chinese medicine raw materials in the traditional

Chinese medicine composition, and more preferably 6-8 folds. As an embodiment of the present invention, for the first extraction, an 8-fold amount of water is added and the extraction lasts 1.5 h; and for the second extraction, a 6-fold amount of water is added and the extraction lasts 1.5 h. In the present invention, a relative density of the clear paste corresponds to a temperature of 60°C. In the present invention, the water is preferably distilled water.

[25] In the present invention, a transfer rate of harpagoside component gradually 3 decreases along with a rising temperature of concentration. Therefore, in the present LU501932 invention, the concentration is preferably performed at a temperature of 60-75°C and a pressure of -0.06 to -0.08 Mpa; and more preferably, the concentration is performed at a temperature of 65-70°C.

[26] In the present invention, the drying is preferably one of ambient-pressure drying, reduced-pressure drying and spray drying, and more preferably the spray drying. In the present invention, for the spray drying, an inlet air temperature is preferably 120-140°C, and an outlet air temperature is preferably 45-90°C. In the present invention, the traditional Chinese medicine composition obtained by the spray drying is soluble and clear without scorch residue; a drying efficiency is high; and there is a high content of harpagoside in the traditional Chinese medicine composition.

[27] The present invention provides a drug for treating hypertension, which is composed of the traditional Chinese medicine composition and a pharmaceutically acceptable excipient.

[28] In the present invention, the drug includes powder, pills, tablets, mixtures, granules or capsules. The present invention further provides a method for preparing traditional Chinese medicine composition granules, including the following steps: taking the clear paste, and adding dextrin according to a weight ratio of a solid content of the clear paste to the dextrin being (1-1.3):(1-1.3), and performing fluidized spray granulation using the dextrin as a substrate to obtain traditional Chinese medicine composition granules. In the present invention, when the weight ratio of the solid content of the clear paste to the dextrin is 1.3:1, the uneven granules in different sizes are formed, and some granules are adhered; when the weight ratio of the solid content of the clear paste to the dextrin is 1:1 or 1:1.3, the granules are uniform, but some granules are adhered when the ratio is 1:1.

[29] In the present invention, a relative density of the clear paste is preferably 1.10-1.20, and more preferable 1.10-1.15. In the present invention, the relative density of the clear paste corresponds to a temperature of 60°C. In the present invention, a moderate relative density of the clear paste makes the granulation smooth, and the prepared granules are uniform and loose with good formation.

[30] In the present invention, an inlet air temperature for the fluidized spray granulation is preferably 100-140°C, and a spray rate is preferably 100-300 r/min. In the present invention, a proper air inlet temperature makes it smooth to prepare uniform and well-formed granules; a lower inlet air temperature will result in unsmooth granulation, a higher inlet air temperature will result in a darker color of the prepared granules with a scorched smell. In the present invention, a proper spray rate makes it smooth to prepare uniform and well-formed granules.

[31] Unless otherwise noted, the components of all the raw materials in the present invention are commercially available products familiar to those skilled in the art.

[32] The technical solutions of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. It is obvious that the described embodiments are only parts of, rather than all of, the embodiments of the present invention. On the basis of the embodiments of the present invention, all the other embodiments obtained by those skilled in the art without 4 creative efforts will fall within the protection scope of the present invention. LU501932

[33] Example 1

[34] (1) 12 parts of uncaria, 9 parts of radix scrophulariae and 9 parts of stir-baked semen raphani were taken, 240 parts of distilled water were added to soak such materials, and then heating and reflux extraction were performed for 1.5 h to obtain an extracting solution; then 180 parts of distilled water were added, and heating and reflux extraction were performed for 1.5 h to obtain an extracting solution; the two extracting solutions were combined and filtered through a screen to obtain a filtrate.

[35] (2) The filtrate was concentrated at a reduced pressure under the conditions of a temperature of 65-70°C and a pressure of -0.06 to -0.08 Mpa to obtain a clear paste with a relative density of 1.10 (60°C); and spray drying was performed for the clear paste under the conditions of an inlet air temperature of 120°C and an outlet air temperature of 75°C, and then the dried clear paste was filtered through a screen to obtain a traditional Chinese medicine composition.

[36] Example 2

[37] (1) 10 parts of uncaria, 5 parts of radix scrophulariae and 5 parts of stir-baked semen raphani were taken, 240 parts of distilled water were added to soak such materials, and then heating and reflux extraction were performed for 2 h to obtain an extracting solution; then 240 parts of distilled water were added, and heating and reflux extraction were performed for 2 h to obtain an extracting solution; the two extracting solutions were combined and filtered through a screen to obtain a filtrate.

[38] (2) The filtrate was concentrated at a reduced pressure under the conditions of a temperature of 65-70°C and a pressure of -0.06 to -0.08 Mpa to obtain a clear paste with a relative density of 1.15 (60°C); and spray drying was performed for the clear paste under the conditions of an inlet air temperature of 125°C and an outlet air temperature of 85°C, and then the dried clear paste was sieved to obtain a traditional Chinese medicine composition.

[39] Example 3

[40] (1) 15 parts of uncaria, 10 parts of radix scrophulariae and 10 parts of stir-baked semen raphani were taken, 280 parts of distilled water were added to soak such materials, and then heating and reflux extraction were performed for 1.5 h to obtain an extracting solution; then 210 parts of distilled water were added for soaking, and heating and reflux extraction were performed for 2 h to obtain an extracting solution; the two extracting solutions were combined and filtered through a sieve to obtain a filtrate.

[41] (2) The filtrate was concentrated at a reduced pressure under the conditions of a temperature of 65-70°C and a pressure of -0.06 to -0.08 Mpa to obtain a clear paste with a relative density of 1.10 (60°C); and spray drying was performed for the clear paste under the conditions of an inlet air temperature of 120°C and an outlet air temperature of 90°C, and then the dried clear paste was sieved to obtain a traditional Chinese medicine composition.

[42] Example 4: research on the extraction process for the traditional Chinese medicine composition of the present invention

[43] 1. Inspection of water absorption amount

[44] 400 g of uncaria, 300 g of radix scrophulariae and 300 g of stir-baked semen LU501932 raphani were taken as a portion, and there were a total of three portions; an 8-fold amount (8,000 mL) of water was added to each portion, and then heating and reflux extraction were performed for 1 h; after filtration, a volume of the filtrate was measured, and a liquid absorption amount was calculated. The results are as shown in Table 1. The results show that the liquid absorption amount of the traditional Chinese medicine composition of the present invention 1s 2 folds the amount of the medicinal materials.

[45] Table 1 Determination Results of Liquid Absorption Amount of Medicinal

Materials

No. Amount of = Water Amount Filtrate Liquid

Medicinal (mL) Amount (mL) Absorption

Material (g) Amount (folds) 1 1,000 8,000 5,970 2.03 2 1,000 8,000 6,120 1.88 3 1,000 8,000 5,840 2.16

[46] 2. Optimization of process conditions for water extraction

[47] A content of harpagoside in the extracting solution was taken as an evaluation indicator, and an L9 (34) orthogonal test was used for optimizing the process conditions for water extraction of the traditional Chinese medicine composition of the present invention.

[48] 2.1 Setting of a factor level table

[49] The number of extraction times, extraction time and water amount (folds) were taken as factors, with 3 levels for each factor. The factor level table is as shown in Table 2.

[50] Table 2 Factor Level Table

Level A Number of B Extraction time (h) ~~ C Water Amount

Extraction Times (folds) (times) 1 1 1.0 6 2 2 1.5 8 3 3 2.0 10 [S1] 2.2 Orthogonal test

[52] 200 g of uncaria, 150 g of radix scrophulariae and 150 g of stir-baked semen raphani were taken as a portion, and there were a total of nine portions, with 500 g of medicinal materials in each portion; a test was performed in accordance with an L9 (34) orthogonal test table. Each extracting solution was concentrated at a reduced pressure (60-65°C, -0.06 to -0.08Mpa) to 500 mL, and a content of harpagoside was determined and calculated. The results are as shown in Table 3 and Table 4. [S3] Table 3 Results of Extraction Orthogonal Test

Factor Harpagoside

Test No. A B C Content (ug/ml) 1 1 1 1 9.3095 2 1 2 2 10.9080 3 1 3 3 11.1585 6

4 2 1 2 15.8240 LUS01932 2 2 3 17.8665 6 2 3 1 16.4669 7 3 1 3 16.1892 8 3 2 1 16.5293 9 3 3 2 17.2172

K1 31.3760 41.3230 42.3057 -

K2 50.1574 45.3038 43.9492 -

K3 49.9360 44.8426 452145 -

R 18.7814 3.9808 2.9088 -

[54] Table 4 Analysis of Variance Results

Factor Sum of Mean Value Degree of Significance

Squares of Freedom

Deviations

A 714737 387369 2 Ex

B 3.1608 1.5804 2 *

C 0.1629 0.0815 2 - [S5] From the above data analysis, it can be seen that an effect sequence of the three factors A, B and C on the extraction of harpagoside in a descending order is: A>B>C, that is, the number of extraction times > extraction time > water amount; an optimal process by direct analysis is A2B2C3, that is, water is add and the mixture is decocted two times, wherein a 10-fold amount of water is added and the mixture is decocted for 1.5 h for the first time, and a 10-fold amount of water is added and the mixture is decocted for 1.5 h for the second time. It can be known from the analysis of variance results that factors A and B are significant factors (A>B), and C is an insignificant factor; in order to save energy and save a cost, for convenience of subsequent concentration, the extraction process is planned as adding water and decocting the mixture two times, wherein a 8-fold amount of water is added and the mixture is decocted for 1.5 h for the first time, and a 6-fold amount of water is added and the mixture is decocted for 1.5 h for the second time. [S6] 2.3 Proof test of the extraction process [S7] In order to compare whether there is a significant difference between the optimal process and the planned process for the extraction of harpagoside, the two processes were verified. 900 g of uncaria, 675 g of radix scrophulariae and 675 g of stir-baked semen raphani were taken as a portion, and there were a total of two portions; extraction was performed according to the conditions of the optimal process and the planned process, an extracting solution was concentrated at a reduced pressure (60-65°C, -0.06 to -0.08 Mpa) to 2,250 mL, and a content of harpagoside was determined and calculated. The determination results are shown in Table 5. [S8] Table 5 Results of Process Comparison and Proof Test (n=3)

Amount of Content of Harpagoside

Process Extracting

Solution (L) (ug/ml)

Optimal Process (A2B2C3) 44.9 18.05

Planned Process (A2B2C1) 27.2 17.83 [S9] The results show that the contents of harpagoside are equivalent between the 7 optimal process and the planned process; however, a fold amount of solvent is reduced LU501932 in the planned process, which saves a production cost and improves the production efficiency; therefore, the extraction process of the traditional Chinese medicine composition of the present invention is determined as follows: water is added and the mixture is decocted two times, wherein a 8-fold amount of water is added and the mixture is decocted for 1.5 h for the first time, and a 6-fold amount of water is added and the mixture is decocted for 1.5 h for the second time.

[60] 2.4. Research on concentration process

[61] An appropriate amount of extracting solution of the traditional Chinese medicine composition was taken, a transfer rate of harpagoside (taking the content of harpagoside in the water extract as 100%) was used as an indicator, different concentration conditions at a reduced pressure were studied, the extracting solution was concentrated to about 1.5 g of crude drug/mL, which was equivalent to a relative density of about 1.10 at 60°C. The determination results are as shown in Table 6.

[62] Table 6 Effects of Different Concentration Conditions at a Reduced Pressure on the Transfer Rate of Harpagoside

Concentration Condition Relative Transfer Rate of

Density Harpagoside/% 60-65°C, -0.06 to -0.08 MPa 1.084 95.15 65-70°C, -0.06 to -0.08 MPa 1.103 93.45 70-75°C, -0.06 to -0.08 MPa 1.094 87.26

[63] The results show that different concentration conditions at a reduced pressure have certain effects on the transfer rate of harpagoside; as a temperature becomes higher, the transfer rate of harpagoside is gradually reduced. In combination with actual production, the condition of reduced pressure is selected as 65-70°C and -0.06 to -0.08

MPa for concentration.

[64] Example 5

[65] The clear paste with a relative density of 1.10 (60°C) prepared in example 1 was taken, dextrin was added according to a weight ratio of a solid content of the clear paste to the dextrin of 1:1.3, and the dextrin was used as substrate powder; an inlet air temperature was set as 120+5°C, a spray rate was set as 200 r/min (or an outlet air temperature was controlled at 70+5°C), and fluidized spray granulation was performed to obtain traditional Chinese medicine composition granules.

[66] Example 6

[67] Compared with example 5, a difference was that a weight ratio of a solid content of the clear paste to the dextrin was 1.1, and the rest of operations were all the same as those in example 5.

[68] Example 7

[69] Compared with example 5, a difference was that a weight ratio of a solid content of the clear paste to the dextrin was 1.3:1, and the rest of operations were all the same as those in example 5.

[70] Example 8

[71] Compared with example 5, a difference was that a relative density was 1.15, and the rest of operations were all the same as those in example 5.

[72] Example 9 8

[73] Compared with example 5, a difference was that a relative density was 1.20, and LU501932 the rest of operations were all the same as those in example 5.

[74] Example 10

[75] Compared with example 5, a difference was that a spray rate was 100 r/min (with an outlet air temperature of about 90°C), and the rest of operations were all the same as those in example 5.

[76] Example 11

[77] Compared with example 5, a difference was that a spray rate was 300 r/min (with an outlet air temperature of about 45°C), and the rest of operations were all the same as those in example 5.

[78] Example 12

[79] Compared with example 5, a difference was that an inlet air temperature was (100+ 5)°C, and the rest of operations were all the same as those in example 5.

[80] Example 13

[81] Compared with example 5, a difference was that an inlet air temperature was (140+ 5)°C, and the rest of operations were all the same as those in example 5.

[82] The research results of the preparation processes for the traditional Chinese medicine composition of examples 5-13 are as shown in Table 7.

[83] Table 7 Research Results of the Preparation Processes for the Traditional

Chinese Medicine Composition of the Present Invention

Group Granulation State of Granules

Process

The granules were uniform

Example 5 Smooth without adhesion

The granules were uniform

Example 6 Smooth with partial adhesion

The granules were uneven

Example 7 Smooth in size, and most of them were adhered

Example 8 Smooth The granules were uniform and well-formed

The spray was

Example 9 not smooth

Example 10 Smooth The granules were uniform and well-formed

Example 11 The granulation Adhesion occurred proceeded.

The granulation

Example 12 was failed ;

The granules were in a dark

Example 13 Smooth color with starched smell.

[84] Example 14

[85] (1) 2,700 g of uncaria, 2,025 g of radix scrophulariae and 2,025 g of stir-baked semen raphani were taken, 54 kg of distilled water was added to soak such materials, then heating and reflux extraction were performed for 1.5 h to obtain an extracting solution; then 40.5 kg of distilled water was added, and heating and reflux extraction were performed for 2 h to obtain an extracting solution; the two extracting solutions 9 were combined and filtered through a sieve to obtain a filtrate. LU501932

[86] (2) The filtrate was concentrated at a reduced pressure under the conditions of a temperature of 65-70°C and a pressure of -0.06 to -0.08 MPa to obtain a clear paste with a relative density of 1.15 (60°C); and spray drying was performed on the clear paste under the conditions of an inlet air temperature of 120°C and an outlet air temperature of 90°C, and then the dried clear paste was sieved to obtain a traditional Chinese medicine composition.

[87] Example 15

[88] Compared with example 14, a difference was that ambient-pressure drying was performed under the condition of a temperature of 105°C, and the rest of operations were all the same as those in example 14.

[89] Example 16

[90] Compared with example 14, a difference was that reduced-pressure drying was performed under the conditions of a temperature of 70°C and a pressure of -0.1 MPa, and the rest of operations were all the same as those in example 14.

[91] The research results of the drying processes in the granulation processes for the traditional Chinese medicine composition granules of examples 14-16 are as shown in

Table 8.

[92] Table 8 Research Results of the Drying Processes in the Granulation Processes for the Traditional Chinese Medicine Composition Granules of the Present Invention . . Extraction

Group Solubility pris ime Rate of Paste Harpacoside on el

Clear paste

Example 14 without 0.5 377.4 0.0621 peacoke

Example 15 Paste with 30 4153 0.0514 peacoke

Example 16 fe encore 20 4243 0.0567

[93] Example 17 Clinical test

[94] 1. Case enrollment

[95] Referring to the diagnostic criteria in the Chinese Guidelines for the Prevention and Treatment of Hypertension (2018 Edition) and the syndrome differentiation criteria for hypertensive yin deficiency and yang hyperactivity in the Guiding Principles of

Clinical Research on New Chinese Medicines, 200 patients with grade 1 hypertension were selected, and those with various secondary hypertension were excluded.

[96] 2. Treatment methods

[97] The patients in the treatment group were treated with the granules prepared in example 5 of the present invention, and each dose contained the contents of 12 g of uncaria, 9 g of radix scrophulariae and 9 g of stir-baked semen raphani. One dose was taken every day by two times in the morning and evening, respectively. A period of 4 weeks was a course of treatment. If serious hypertension occurred after administration, treatment for acute symptoms should be given immediately; during the administration, spicy food, liquor, strong tea and coffee were forbidden.

[98] 3. Observation indicators LU501932

[99] a. Safety indicators: including pulse, respiration, heart rate, blood pressure, body weight, etc, which were examined once a week; blood and urine routine examinations, and the liver and kidney functions, which were tested once a month; adverse reactions.

[100] b. Observation indicators for therapeutic effects:

[101] (1) Changes in blood pressure: an average value of three blood pressure values obtained on different days before treatment was used as the blood pressure for observation; and an average value of three blood pressure values obtained on different days at the last week of treatment was used as the blood pressure for evaluation on the therapeutic effects. During the observation, the blood pressure was measured twice a week for the patients.

[102] (2) TCM symptom measurement score: the common symptoms of the hypertensive yin deficiency and yang hyperactivity syndrome were observed, the symptoms were inquired and recorded one by one before treatment and after treatment, respectively, the symptoms were judged and scored according to symptom scoring standards, and a sum of a case’s symptoms was taken as an integral score of the symptoms of the case.

[103] 4. Evaluation criteria for therapeutic effects

[104] a: evaluation criteria for the therapeutic effect on blood pressure: refer to the

Guiding Principles for Clinical Trials of New Chinese Medicines in Treating

Hypertension for the evaluation criteria for the therapeutic effect on reducing blood pressure.

[105] (1) Significantly effective: the diastolic blood pressure has dropped by more than 10 mmHg and has reached a normal range; the diastolic blood pressure has not dropped to the normal range, but has dropped by 20 mmHg or more; the systolic blood pressure has dropped by more than 30 mmHg as compared with that before treatment, and has reached a normal range, whichever is met.

[106] (2) Effective: the diastolic blood pressure has dropped by less than 10 mmHg, but has reached the normal range; the diastolic blood pressure has dropped by 10-19 mmHg, but has not reached the normal range; the systolic blood pressure has dropped by more than 30 mmHg as compared with that before treatment, but has not reached the normal range, whichever is met.

[107] (3) Invalid: none of the above criteria is met.

[108] b: evaluation criteria for the therapeutic effect on clinical symptom: refer to the specifications in the Guiding Principles of Clinical Research on New Chinese Medicines for evaluation:

[109] Reduction in syndrome score=[(score before treatment - score after treatment) + score before treatment] x 100%

[110] (1) Significantly effective: the clinical symptoms and signs are obviously improved, and the syndrome score is reduced by >70%.

[111] (2) Effective: the clinical symptoms and signs turn better, and the syndrome score is reduced by >30%.

[112] (3) Invalid: the clinical symptoms and signs are not obviously improved, or 11 even aggravated, and the syndrome score is reduced by < 30%. LU501932

[113] 5. Statistical methods

[114] The 7 test was employed for the measurement data, the chi-square test was employed for the enumeration data, and the Ridit test was employed for the clinical grade data. The data were expressed as mean + standard deviation, P< 0.05 represents a significant difference, and P< 0.01 represents a very significant difference.

[115] 6. Treatment results

[116] (1) Therapeutic effect on hypertension: in the test group, it is significantly effective in 84 cases (42%), effective in 88 cases (44%) and invalid in 28 cases (14%), with a total effective rate of 86%.

[117] (2) Therapeutic effect on clinical symptom: in the test group, it is significantly effective in 82 cases (41%), effective in 92 cases (46%) and invalid in 26 cases (13%), with a total effective rate of 87%.

[118] (3) Evaluation on safety: the 200 patients with grade 1 hypertension were examined for the liver and kidney functions before and after treatment, and the result show that there is no obvious change in the blood and urine routine examinations and the liver and kidney functions of the patients.

[119] Example 18

[120] 1. Case enrollment

[121] The syndrome differentiation criteria are the same as those in example 17. A total of 129 patients with grade 1 hypertension after strict lifestyle intervention were selected, and meanwhile those with various secondary hypertension were excluded. The 129 patients were divided into 2 groups by a random number table method, and the two groups were comparable without significant differences in age, course of disease and blood pressure level (P>0.05).

[122] 2. Treatment methods

[123] The patients in the treatment group were treated with the traditional Chinese medicine granules prepared in example 5 of the present invention, and each dose contained the contents of 12 g of uncaria, 9 g of radix scrophulariae and 9 g of stir-baked semen raphani. One dose was taken every day by two times in the morning and evening, respectively.

[124] Control group: a placebo of uncaria and radix scrophulariae granules was selected. One dose was orally taken every day by two times in the morning and evening, respectively.

[125] Other requirements and standards were the same as those in example 17.

[126] 3. Observation indicators

[127] The same as those in example 17.

[128] 4. Evaluation criteria for therapeutic effects

[129] The same as those in example 17.

[130] 5. Statistical methods

[131] The same as those in example 17.

[132] 6. Treatment results

[133] (1) Therapeutic effect on hypertension: in the test group, it is significantly effective in 22 cases, effective in 33 cases and invalid in 9 cases, with a total effective 12 rate of 85.9%. In the control group, it is significantly effective in 6 cases, effective in 25 LU501932 cases and invalid in 34 cases, with a total effective rate of 47.7%. By inspection, there are significant differences between the two groups (P<0.05).

[134] (2) Therapeutic effect on clinical symptom: in the test group, it is significantly effective in 15 cases, effective in 33 cases and invalid in 16 cases, with a total effective rate of 75%. In the control group, it is significantly effective in 2 cases, effective in 22 cases and invalid in 41 cases, with a total effective rate of 36.9%. By inspection, there are significant differences between the two groups (P<0.05). Wherein the therapeutic effects on dizziness, headache, chest tightness, fatigue, dry mouth and unfavorable defecation in the test group are obviously better than those in the control group (P< 0.05).

[135] (3) Evaluation on safety: before treatment, the 129 patients with hypertension were examined for the liver and kidney functions and the blood, urine and excrement examinations, and the result show that there is no obvious change; after treatment, all the patients were reexamined, and there is no obvious change in the blood and urine routine examinations and the liver and kidney functions of the patients (P>0.05).

[136] The placebo of uncaria and radix scrophulariae granules in the present invention does not contain any active ingredient, but the patients with grade 1 hypertension are easily affected by their mental states and lifestyles. Therefore, after the intervention to the 129 hypertensive patients during the clinical test, the total effective rates of the therapeutic effect on hypertension and the therapeutic effect on clinical symptoms after taking the placebo of uncaria and radix scrophulariae granules are 47.7% and 36.9%.

[137] Typical clinical cases

[138] Case 1:

[139] Mr. Zhang, gender: male, age: 45 years old. Time of first visit: January 17, 2019, diagnosis: suffering from hypertension for 9 years, with blood pressure up to 151/94 mmHg, accompanied by occasional dizziness and headache but without feeling fullness in the head, dry eyes, occasional tinnitus, dry mouth, without palpitation or chest tightness, feeling upset and irritable, feeling heavy in the head and light in the feet, soreness of waist, fatigue, proper appetite, poor sleeping quality with dreamful sleep, yellowish urine, dry stool, red tongue with thin white fur, and stringy pulse. Impression: dizziness, yin deficiency and yang hyperactivity. The patient found an elevation in blood pressure 9 years ago; but the patient did not accept any standard treatment, and took medicines discontinuously. The patient now came to the hospital for further treatment. The patient took the drug of the present invention for one week. Time of second visit: January 24, 2019. By physical examination, blood pressure was 138/88 mmHg; current symptoms: occasional dizziness, alleviated headache, dry eyes, occasional tinnitus, dry mouth, alleviation in feeling heavy in the head and light in the feet, alleviated soreness of waist and fatigue, feeling upset and irritable, proper appetite, normal sleep, regular urination, a little dry stool, red tongue with thin white fur, and stringy pulse. Then the patient took the drug of the present invention for two week.

Time of third visit: February 8, 2019. Blood pressure dropped to 136/80 mmHg; the symptoms of dizziness, headache, and feeling fullness in the head disappeared; other symptoms: occasional fatigue without other obvious discomfort; proper appetite and 13 sleep, regular urination and defecation, red tongue with thin white fur, and stringy pulse. LU501932

A follow-up shows that no recurrence has been observed up to now.

[140] Case 2:

[141] Ms. Wang, gender: female, age: 53 years old. Time of first visit: May 9, 2019; self-reported symptoms: headache accompanied by chest tightness for seven days, with aggravated symptoms for one day. diagnosis: hypertension, with blood pressure up to 153/88 mmHg. The patient suffered from paroxysmal dull headache without obvious inducing factors, accompanied by chest tightness but without chest pain; the symptoms were alleviated after taking Danshen Dropping Pills by herself, but the above symptoms were aggravated after tiredness one day ago. The patient now came to the hospital for further treatment. Current symptoms: paroxysmal headache, occasional dizziness, chest tightness, without palpitation or chest pain, without dry eyes, without deafness or tinnitus, dry mouth and bitter taste in the mouth, without gaseous distention or acid reflux, proper appetite, poor sleep quality and easy to wake up, and regular urination and defecation; red tongue with white fur, and thready pulse. The patient was healthy previously. Impression: headache yin deficiency and yang hyperactivity. The patient took the drug of the present invention for one week. Time of second visit: May 16, 2019.

Blood pressure dropped to 142/76 mmHg; current symptoms: paroxysmal headache, occasional dizziness, alleviated chest tightness, without palpitation; dry eyes, dry mouth and bitter taste in the mouth, without other obvious discomfort; proper appetite, general sleep quality, and regular urination and defecation; red tongue with white fur, and thready pulse. Then the patient took the drug of the present invention for two weeks.

Time of third visit: May 30, 2019. Blood pressure dropped to 136/78 mmHg; the symptoms of headache and dizziness disappeared; other symptoms: occasional chest tightness, without palpitation; alleviated dry mouth and bitter taste in the mouth, without other obvious discomfort; proper appetite and sleep, regular urination and defecation; red tongue with white fur, and thready pulse. A follow-up shows that no recurrence has been observed up to now.

[142] Case 3:

[143] Mr. Xu, gender: male, age: 54 years old. Self-reported symptom: dizziness for ten days. Time of first visit: January 4, 2019; diagnosis: hypertension. By physical examination, blood pressure was 157/93 mmHg; the patient suffered from dizziness and fatigue without obvious inducing factors, and the symptoms were aggravated after movement, the blood pressure was elevated by visual observation, and the symptoms were slightly alleviated after a rest; the patient did not pay attention to it. The patient now came to the hospital for further treatment. Current symptoms: occasional dizziness and headache, dry mouth, tinnitus, dry eyes, feeling upset and irritable, feeling heavy in the head and light in the feet, hot face, soreness of waist, fatigue, proper appetite, poor sleeping quality with dreamful sleep, dry stool, yellow urine, red tongue with white fur, and thready pulse. The patient was healthy previously. Impression: dizziness, yin deficiency and yang hyperactivity. The patient took the drug of the present invention for one week. Time of second visit: January 11, 2019. The blood pressure dropped to 137/86 mmHg; current symptoms: alleviated dizziness and headache as compared with those before, dry mouth, occasional tinnitus, without chest tightness or palpitation, 14 without gaseous distention or acid reflux, easy to get worried and angry, alleviated LU501932 soreness of waist and fatigue as compared with those before, proper appetite, normal sleep quality, regular defecation, yellow urine, red tongue with white fur, and thready pulse. Then the patient took the drug of the present invention for two weeks. Time of third visit: January 25, 2019. Blood pressure dropped to 135/79 mmHg; symptoms: alleviated dizziness and headache, occasional tinnitus, dry mouth without bitter taste in the mouth, occasional soreness of waist, without other obvious discomfort; proper appetite and sleep, regular urination and defecation, red tongue with white fur, and thready pulse. A follow-up shows that no recurrence has been observed up to now.

[144] Case 4:

[145] Mr. Zhou, gender: male, age: 40 years old. Time of first visit: July 4, 2017; self-reported symptoms: headache accompanied by tinnitus for six days, with aggravated symptoms for two days. The patient suffered from paroxysmal headache without obvious inducing factors 6 days ago, accompanied by obvious tinnitus; the patient did not pay attention to it; the above symptoms were aggravated after staying up late in the recent two days. The patient now came to the hospital for further treatment.

Diagnosis: hypertension, with blood pressure up to 146/92 mmHg; current symptoms: headache, dizziness, without nausea or vomiting; accompanied by obvious tinnitus without deafness; dry mouth and bitter taste in the mouth, bad appetite, feeling upset, insomnia, and regular urination and defecation; light red tongue with thin white fur, and stringy pulse. The patient was healthy previously. Impression: dizziness, yin deficiency and yang hyperactivity. The patient took the drug of the present invention for one week.

After taking the drug, the symptoms of the patient were obvious ameliorated, and the blood pressure dropped to 142/88 mmHg; current symptoms: alleviated headache and occasional tinnitus; time of second visit: July 11, 2017; symptoms: proper appetite, normal sleep quality, regular urination and defecation; light red tongue with thin white fur, and stringy pulse. Then the patient took the drug of the present invention for two weeks. Time of third visit: July 27, 2017. Blood pressure dropped to 130/80 mmHg within a normal range; the symptoms were obviously ameliorated, without other obvious discomfort; other symptoms: proper appetite and sleep, regular urination and defecation; light red tongue with thin white fur, and stringy pulse. After drug withdrawal, a follow-up shows that no recurrence has been observed.

[146] Case S:

[147] Mr. Sun, gender: male, age: 66 years old. Time of first visit: May 25, 2017; self-reported symptoms: dizziness accompanied by discomfort in regions pectoris anterior for ten days, with aggravated symptoms for one day. Diagnosis: hypertension, with blood pressure up to 152/90 mmHg. Impression: dizziness, yin deficiency and yang hyperactivity. The patient suffered from dizziness without obvious inducing factors more than ten days ago, accompanied by discomfort in regions pectoris anterior; no systematic treatment was received, the symptoms were alleviated after taking

Danshen Dropping Pills by himself, but the symptoms were aggravated after tiredness yesterday. Current symptoms: dizziness, discomfort in regions pectoris anterior, palpitation, fatigue, without palpitation or deafness; proper appetite, poor sleep quality and easy to wake up, and regular urination and defecation; red tongue with thin white fur, and thready pulse. The patient took the drug of the present invention for one week. LU501932

Time of second visit: June 1, 2017. After taking the drug, the symptoms were alleviated, and the blood pressure dropped to 145/83 mmHg; at present, the patient still felt dizzy after tiredness, without chest tightness or chest pain; other symptoms included proper appetite and sleep, regular urination and defecation; red tongue with white fur, and stringy pulse. Then the patient took the drug of the present invention for two weeks.

Time of third visit: June 16, 2017. Blood pressure dropped to 130/81 mmHg; the symptoms were obviously ameliorated as compared with those before, without other obvious discomfort. Other symptoms included proper appetite and sleep, regular urination and defecation; red tongue with thin white fur, and stringy pulse. After drug withdrawal, a follow-up shows that no recurrence has been observed.

[148] Case 6:

[149] Ms. Hua, gender: female, age: 64 years old. Time of first visit: March 27, 2014; self-reported symptoms: feeling fullness in the head accompanied by fatigue for one week. Diagnosis: hypertension, with blood pressure up to 152/94 mmHg. The patient had a history of hypertension for more than two years. She usually took nifedipine controlled-release tablets regularly, with unstable control of blood pressure. The patient suffered from feeling fullness in the head without obvious inducing factors one week ago, accompanied by a sense of fatigue. Current symptoms: fullness in the head, especially in the forehead; accompanied by a sense of fatigue, especially fatigue in the limbs. She felt a decline in movement ability and an obvious sense of fatigue after movement, accompanied by soreness of waist, without obvious chest tightness or dizziness; other symptoms included proper appetite, poor sleep quality, dry stool and regular urine; red tongue with thin white fur, and thready pulse. The patient took the drug of the present invention for one week. Time of second visit: April 4, 2014. The blood pressure dropped to 141/90 mmHg, the symptoms turned better as compared with those before, and the fatigue in the limbs were ameliorated; paroxysmal fullness in the head occurs occasionally, the soreness of waist still existed but turned better; other symptoms included proper appetite and sleep, regular urination and defecation; light red tongue with white fur, and thready pulse. Then the patient took the drug of the present invention continuously. Time of third visit: April 22, 2014. The blood pressure dropped to 138/88 mmHg; the symptoms turned better as compared with those before, headache and fatigue were ameliorated as compared with those before; other symptoms included proper appetite and sleep, regular urination and defecation; light red tongue with thin white fur, and thready pulse.

[150] The foregoing descriptions are merely some of the embodiments of the present invention. It should be noted that for those of ordinary skill in the art, a number of improvements and modifications may be made without departing from the principle of the present invention. These improvements and modifications should also fall within the protection scope of the present invention. 16

Claims

WHAT IS CLAIMED IS: LUS01932

1. A traditional Chinese medicine composition for treating hypertension, wherein the composition is composed of the following traditional Chinese medicine raw materials based on parts by weight: 10-15 parts of uncaria, 5-10 parts of radix scrophulariae and 5-10 parts of stir-baked semen raphani.

2. The traditional Chinese medicine composition for treating hypertension of claim 1, wherein the composition is composed of the following traditional Chinese medicine raw materials based on parts by weight: 12 parts of uncaria, 9 parts of radix scrophulariae and 9 parts of stir-baked semen raphani.

3. A method for preparing the traditional Chinese medicine composition of claim 1, comprising the following steps: (1) taking the uncaria, the radix scrophulariae and the stir-baked semen raphani, firstly adding water to soak such materials, then performing heating and reflux extraction one to three times, 1-2 h each time, combining extracting solutions, and filtering the extracting solutions through a screen to obtain a filtrate; and (2) concentrating the filtrate into a clear paste with a relative density of 1.10-1.20, and drying and sieving the clear paste to obtain a traditional Chinese medicine composition.

4. The preparation method of claim 3, wherein a part by weight of the water is 6-12 folds the total weight of the traditional Chinese medicine raw materials in the traditional Chinese medicine composition.

5. The preparation method of claim 3, wherein the concentration is performed at a temperature of 60-75°C and a pressure of -0.06 to -0.08 MPa.

6. The preparation method of claim 3, wherein the drying is one of ambient-pressure drying, reduced-pressure drying, and spray drying.

7. A drug for treating hypertension, comprising the traditional Chinese medicine composition of any of claims 1-2 and a pharmaceutically acceptable excipient.

8. The drug of claim 7, wherein the drug comprises powder, pills, tablets, mixtures, granules or capsules.

9. The drug of claim 8, wherein a method for preparing the granules comprises the following steps: taking traditional Chinese medicine raw materials at the above proportions, firstly adding water to soak such materials, then performing heating and reflux extraction one to three times, 1-2 h each time, combining extracting solutions, and filtering the extracting solutions through a screen to obtain a filtrate; and concentrating the filtrate into a clear paste with a relative density of 1.10-1.20, and adding dextrin according to a weight ratio of a solid content of the clear paste to the dextrin being (1-1.3):(1-1.3), and performing fluidized spray granulation using the dextrin as a substrate to obtain traditional Chinese medicine composition granules.

10. The drug of claim 9, wherein an inlet air temperature for for the fluidized spray granulation is 100-140°C, and a spray rate is 100-300 r/min. 1