CN102266407A - Traditional Chinese medicinal composition for treating hypertension and preparation method thereof - Google Patents
Traditional Chinese medicinal composition for treating hypertension and preparation method thereof Download PDFInfo
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- CN102266407A CN102266407A CN 201110223918 CN201110223918A CN102266407A CN 102266407 A CN102266407 A CN 102266407A CN 201110223918 CN201110223918 CN 201110223918 CN 201110223918 A CN201110223918 A CN 201110223918A CN 102266407 A CN102266407 A CN 102266407A
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- ramulus uncariae
- uncariae cum
- cum uncis
- semen raphani
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Abstract
The invention discloses a traditional Chinese medicinal composition for treating hypertension, and the traditional Chinese preparation comprises the following effective components in parts by weight: uncaria alcohol extract 5-20 parts and radish seed water extract 3-12 parts. The invention also discloses a preparation method of the composition, and the preparation method is simple and easy for operation. The traditional Chinese medicinal composition disclosed by the invention has good antihypertensive effect and can be used for treating hypertension due to hyperactivity of the liver-yang. Also, the composition can improve vertigo, headache, tinnitus, dryness and uncomfortable feeling of eyes, giddiness, ache and weakness at waist and knees, asthenia, constipation and other symptoms.
Description
Technical field
The present invention relates to hypertensive medicine of a kind of treatment and preparation method thereof, be specifically related to a kind of pharmaceutical composition form and preparation method thereof that extracts by Chinese medicine ingredients with the effect of treatment hypertension.
Background technology
Hypertension (EH) is modal cardiovascular diseases, and sickness rate has become worldwide commonly encountered diseases, frequently-occurring disease, serious threat human life quality and life and health up to 10～20% at present.Have the chemicals product of the antihypertensive drug of clear and definite pharmacological effect and evidence-based medicine EBM evidence at present, and have certain side effect more based on transnational medical group.The market share of the resisting hypertension Chinese medicine of having researched and developed at present (as Bezoar pill for lowering blood pressure, Zhenju Jiangya Tablet, compound recipe Ramulus Uncariae Cum Uncis sheet and QINGXUAN JIANGYA PIAN) is lower, and at curative effect, technology, mouthfeel, single oral dose, carry aspect such as convenient degree and also have obvious deficiency.
Utilization Chinese medicine prevention hypertension is the characteristic and the advantage of China's hypertension prevention and control work.Tradition thinks that excessive rising of liver-YANG is the main pathogenesis of hypertension; nourishing YIN for suppressing the hyperactive YANG is its main method of treatment; TIANMA GOUTENG YIN, Zhengan Xifeng Tang etc. are square medicine commonly used; and develop blood pressure lowering Chinese patent medicine Bezoar pill for lowering blood pressure, Zhenju Jiangya Tablet, compound recipe Ramulus Uncariae Cum Uncis sheet etc. in view of the above, obtain application to a certain degree clinically.In recent years, along with deepening continuously to the research of senile hypertension etiology and pathogenesis, it is the important pathogenesis of senile hypertension that the proposition kidney qi is lost void, invigorating kidney qi is the important method of treatment of senile hypertension, JISHENG SHENQI WAN, eight flavor blood pressure lowering soup are square medicine commonly used, and develop the Chinese patent medicine Kang Heng blood pressure lowering granule and the celestial Mulberry blood pressure lowering granule for the treatment of senile hypertension in view of the above, its curative effect and safety are still needed and are wanted further clinical verification, do not obtain the approval in market as yet.So the pure Chinese medicinal preparation that present efficacy of antihypertensive treatment is definite, side effect is little, market prospect is clear and definite is still few; Can improve the metabolism disorder of patient's substance in vivo, pay attention to target-organ protection, to reverse the bad Chinese patent medicine preparation of reinventing of blood vessel more rarely seen; And under the traditional Chinese medical science rule of treatment method of treatment guide of theory screening of medicaments, extract its antihypertensive activity component, adopt the resisting hypertension Chinese medicine preparation of " design of hypotensive effect mechanism, active component synergistic combination, make up target spot comprehensively intervene " still to belong to blank.
Summary of the invention
The present invention provides a kind of treatment hypertensive Chinese medicine composition in order to overcome the deficiency of existing resisting hypertension Chinese medicine preparation, and this Chinese medicine composition efficacy of antihypertensive treatment is definite, few side effects.
The present invention also provides the preparation method of this Chinese medicine composition, and the present invention optimizes the extraction process of each effective ingredient, fully extracts effective ingredient, and the gained effect of drugs is good.
The present invention is under the guidance of Chinese medical theory, filter out antihypertensive Ramulus Uncariae Cum Uncis and Semen Raphani Chinese medicine compound, optimize extraction process, extract its antihypertensive active component (being respectively Ramulus Uncariae Cum Uncis total alkaloids, Semen Raphani water-soluble alkaloid), principle according to " design of hypotensive effect mechanism, active component synergistic combination, combination target spot are comprehensively intervened ", the dosage ratio of preferred blood pressure lowering component, be prepared into the compositions of Ramulus Uncariae Cum Uncis Semen Raphani resisting hypertension active component, lay the foundation for further developing modern Chinese medicine.
Realize that technical scheme of the present invention is as follows:
The hypertensive Chinese medicine composition of a kind of treatment is characterized in that effective ingredient comprises: Ramulus Uncariae Cum Uncis ethanol extract 5～20 mass parts, Semen Raphani water extract 3～12 mass parts.
Preferred effective ingredient comprises: Ramulus Uncariae Cum Uncis ethanol extract 10～20 mass parts, Semen Raphani water extract 6～12 mass parts.
Most preferred, effective ingredient comprises that mass ratio is Ramulus Uncariae Cum Uncis ethanol extract and the Semen Raphani water extract of 5:6.
Main effective ingredient is the Ramulus Uncariae Cum Uncis total alkaloids in the above-mentioned Ramulus Uncariae Cum Uncis ethanol extract, and the Ramulus Uncariae Cum Uncis total alkaloid content is more than 50%, and main effective ingredient is the Semen Raphani water-soluble alkaloid in the Semen Raphani water extract, and Semen Raphani water-soluble biological alkali content is more than 50%.
The present invention treats the preparation method of hypertensive Chinese medicine composition, it is characterized in that may further comprise the steps:
A. adopt ethanol refluxing process to extract the Ramulus Uncariae Cum Uncis ethanol extract
(1) with ethanol extraction repeatedly with Ramulus Uncariae Cum Uncis, merge extractive liquid,, concentrating under reduced pressure ethanol gets concentrated solution;
(2) concentrated solution pH is reconciled to 9～10, extremely colourless with chloroform extraction then, the chloroform extraction liquid of merging gained boils off chloroform and gets dry extract;
(3) dried cream dilute hydrochloric acid ultrasonic dissolution, sucking filtration is got filtrate then, and filtrate is used the chloroform defat, the water intaking phase;
(4) water is reconciled pH to 9～10, and then with chloroform extraction repeatedly, combining extraction liquid is washed to neutrality with extract, removes then and anhydrates, boils off chloroform, gets the Ramulus Uncariae Cum Uncis ethanol extract;
B. adopt the decocting cooking method to extract the Semen Raphani water extract
(1) the Semen Raphani water is decocted repeatedly merge extractive liquid;
(2) extracting solution is concentrated, adding ethanol to pure content is 80 volume %, and standing over night is filtered, and supernatant evaporate to dryness ethanol is got dry extract;
(3) with dried cream water dissolution, last AB-8 absorption with macroporous adsorbent resin carries out gradient elution with distilled water eluting, reuse ethanol then, collects the ethanol part eluent of 10～30vol%;
(4), get the Semen Raphani water extract with eluent evaporate to dryness ethanol;
C. Ramulus Uncariae Cum Uncis alcohol extract and the Semen Raphani water extract that makes mixed by proportioning, add the adjuvant of survival dose, make.
In the said method, when extracting the Ramulus Uncariae Cum Uncis ethanol extract, alcoholic acid volumetric concentration is 70～80%, consumption be Ramulus Uncariae Cum Uncis 8～12 quality doubly, extract 2h at every turn; The quality of concentrated solution is 1～2 times of drug quality.
In the said method, the concentration of dilute hydrochloric acid is 1～5wt%.
In the said method, when extracting the Semen Raphani water extract, the consumption of water be Semen Raphani 8～12 quality doubly, extract 1.5h at every turn; Extracting solution is concentrated into 1-2 times of drug quality.
The mensuration of Ramulus Uncariae Cum Uncis total alkaloid content adopts the Ramulus Uncariae Cum Uncis total alkaloids through water dissolution, it is 10 that ammonia is transferred pH, chloroform extraction, chloroform solution washing back evaporate to dryness, residue adds the chloroform dissolving, precision adds 0.0100mol/l sulphuric acid liquid 20m1, methylate is red-the methylene blue indicator, with the molten titration of 0.0175mol/l caustic lye of soda to solution by the shallow orange red yellow green that changes into, adopt Ramulus Uncariae Cum Uncis total alkaloids that the inventive method extracts more than 50wt%, reach as high as more than the 99wt%, but along with the raising of alkaloid, cost also improves, and therefore the Ramulus Uncariae Cum Uncis total alkaloids about general use 50wt% can reach good effect in actual production.
Semen Raphani water-soluble alkaloid assay, adopt ammonium tetrathiocyanodiaminochromate method precipitation, washing of precipitate is dried to precision weighing behind the constant, the same with the Ramulus Uncariae Cum Uncis total alkaloids, the Semen Raphani alkaloid also can reach more than the 99wt%, just cost can increase, the therefore general Semen Raphani water-soluble alkaloid that uses about 50wt%.
Now, there are some researches prove, Ramulus Uncariae Cum Uncis and Semen Raphani extract all have the effect that brings high blood pressure down, but find through retrieval, listing now or document, patent in Ramulus Uncariae Cum Uncis extract of no use and Semen Raphani extract carry out composite pharmacy, most of Chinese medicine medicines all are that to adopt multiple medicine material to carry out composite to reach the hypertensive purpose of treatment.These medicine material kinds are many, and need assemble plurality of raw materials when producing simultaneously could patent medicine, relatively very complicated.And the present invention is a raw material with Semen Raphani and Ramulus Uncariae Cum Uncis, be simple and easy to, therapeutic effect is good, is beneficial to more and applies.
Chinese medicine composition dosage form of the present invention can be tablet, granule, capsule, mixture or pill.It is identical with the method for Semen Raphani effective ingredient to extract Ramulus Uncariae Cum Uncis in the preparation, and just the later stage is made corresponding dosage forms according to different dosage forms according to the adjuvant that prior art adds dosage forms, and the therapeutic effect of the medicine of gained different dosage form is close.The used adjuvant of preparation tablet is starch, microcrystalline Cellulose, pregelatinized Starch, lactose, carboxymethylstach sodium, hypromellose, Pulvis Talci, magnesium stearate etc., the adjuvant of granule is a multitudinous Icing Sugar etc., and the adjuvant of capsule is starch, pregelatinized Starch, carboxymethylstach sodium, hypromellose, magnesium stearate etc.; Mixture with water as solvent; The adjuvant of pill is starch, microcrystalline Cellulose, carboxymethylstach sodium, hypromellose etc.The consumption of adjuvant adds according to existing pharmaceutic adjuvant consumption or adjusts slightly.
The inventor is through for many years experience, drawn that Ramulus Uncariae Cum Uncis total alkaloids and Semen Raphani water-soluble alkaloid are composite treats hypertensive inventive concept, in order better to improve the invention technical scheme and to verify the reasonable feasibility of this compound medicine, carried out a large amount of research experiments, to draw the magnitude relation of using of these two kinds of compositions, further prioritization scheme is to determine best drug ratio relation.Experimental technique is as follows:
1. experiment grouping
Effective ingredient with Ramulus Uncariae Cum Uncis and Semen Raphani---Ramulus Uncariae Cum Uncis total alkaloids and Semen Raphani water-soluble alkaloid experimentize, these two kinds of effective ingredients are got basic, normal, high three dosage respectively during experiment, combination obtains 9 groups of medicine groups, and these 9 groups are respectively: Ramulus Uncariae Cum Uncis total alkaloids (greatly)
+Semen Raphani water-soluble alkaloid (greatly), Ramulus Uncariae Cum Uncis total alkaloids (greatly)
+The Semen Raphani water-soluble alkaloid (in), Ramulus Uncariae Cum Uncis total alkaloids (greatly)
+Semen Raphani water-soluble alkaloid (low), Ramulus Uncariae Cum Uncis total alkaloids (in)
+Semen Raphani water-soluble alkaloid (greatly), Ramulus Uncariae Cum Uncis total alkaloids (in)
+The Semen Raphani water-soluble alkaloid (in), the Ramulus Uncariae Cum Uncis total alkaloids (in)
+Semen Raphani water-soluble alkaloid (low), Ramulus Uncariae Cum Uncis total alkaloids (low)
+Semen Raphani water-soluble alkaloid (greatly), Ramulus Uncariae Cum Uncis total alkaloids (low)
+The Semen Raphani water-soluble alkaloid (in), Ramulus Uncariae Cum Uncis total alkaloids (low)
+Semen Raphani water-soluble alkaloid (low).
Select 8 ages in week, male spontaneously hypertensive rat model (SHR), purchase laboratory animal company limited in Beijing dimension tonneau China.According to the dosage modular design, this research is divided into following 10 groups with animal, and every group of 5 SHR are respectively SHR model group (model control group) and above-mentioned 9 groups of medicine groups.In addition, get 5 healthy rats as Wistar group (normal control group).
2. experimental technique
All laboratory animals are all adopted raise in cages, light and shade each 12 hours.Experimental session carries out gastric infusion to each rat, and the administration volume is each 2ml200g
-1, administration 7d, afternoon regularly administration every day weekly, continuous 2 weeks are by the corresponding dosage of body weight situation adjustment.It is as follows specifically respectively to organize dosage:
Normal group: 0.9%NaCl irritates stomach
,2ml200g
-1Model group: 0.9%NaCl irritates stomach
,2ml200g
-1Ramulus Uncariae Cum Uncis total alkaloids (greatly)
+Semen Raphani water-soluble alkaloid (greatly) group: Ramulus Uncariae Cum Uncis total alkaloids (20mg200g
-1)
+Semen Raphani water-soluble alkaloid (12mg200g
-1); Ramulus Uncariae Cum Uncis total alkaloids (greatly)
+The Semen Raphani water-soluble alkaloid (in) group: Ramulus Uncariae Cum Uncis total alkaloids (20mg200g
-1)
+Semen Raphani water-soluble alkaloid (6mg200g
-1); Ramulus Uncariae Cum Uncis total alkaloids (greatly)
+Semen Raphani water-soluble alkaloid (low) group: Ramulus Uncariae Cum Uncis total alkaloids (20mg200g
-1)
+Semen Raphani water-soluble alkaloid (3mg200g
-1); The Ramulus Uncariae Cum Uncis total alkaloids (in)
+Semen Raphani water-soluble alkaloid (greatly) group: Ramulus Uncariae Cum Uncis total alkaloids (10mg200g
-1)
+Semen Raphani water-soluble alkaloid (12mg200g
-1); The Ramulus Uncariae Cum Uncis total alkaloids (in)
+The Semen Raphani water-soluble alkaloid (in) group: Ramulus Uncariae Cum Uncis total alkaloids (10mg200g
-1)
+Semen Raphani water-soluble alkaloid (6mg200g
-1); The Ramulus Uncariae Cum Uncis total alkaloids (in)
+Semen Raphani water-soluble alkaloid (low) group: Ramulus Uncariae Cum Uncis total alkaloids (10mg200g
-1)
+Semen Raphani water-soluble alkaloid (3mg200g
-1); Ramulus Uncariae Cum Uncis total alkaloids (low)
+Semen Raphani water-soluble alkaloid (greatly) group: Ramulus Uncariae Cum Uncis total alkaloids (5mg200g
-1)
+Semen Raphani water-soluble alkaloid (12mg200g
-1); Ramulus Uncariae Cum Uncis total alkaloids (low)
+The Semen Raphani water-soluble alkaloid (in) group: Ramulus Uncariae Cum Uncis total alkaloids (5mg200g
-1)
+Semen Raphani water-soluble alkaloid (6mg200g
-1); Ramulus Uncariae Cum Uncis total alkaloids (low)
+Semen Raphani water-soluble alkaloid (low) group: Ramulus Uncariae Cum Uncis total alkaloids (5mg200g
-1)
+Semen Raphani water-soluble alkaloid (3mg200g
-1).
, experimental result
Each treated animal tail venous systolic pressure under 4 hours, one week of administration, administration two all waking states before measuring administration respectively, after the first administration.It is as follows that each organizes the blood pressure result:
4, conclusion
Meansigma methods with administration 2 all blood pressures is a foundation, adopts the variance analysis method of orthogonal design to carry out statistical procedures, with
P＜0.05 for having significant difference.Statistical result showed, Ramulus Uncariae Cum Uncis and Semen Raphani resisting hypertension active component---Ramulus Uncariae Cum Uncis total alkaloids and Semen Raphani water-soluble alkaloid compatible combination are at Ramulus Uncariae Cum Uncis total alkaloids (5mg200g
-1～20mg200g
-1) dosage range and Semen Raphani water-soluble alkaloid (3mg200g
-1～12mg200g
-1) compatibility all has the experimental effect that reduces the SHR blood pressure in the dosage range, wherein with Ramulus Uncariae Cum Uncis total alkaloids (10mg200g
-1) compatibility Semen Raphani water-soluble alkaloid (12mg200g
-1) the pressure reduction effect optimum.
From top zoopery as can be seen, the compositions that makes in drug ratio scope provided by the invention all has treats hypertensive effect preferably, and laboratory animal does not have the sudden death phenomenon during medication, and toxic and side effects is little.In order better to prove the human body adaptability of this medicine, further carried out following clinical experiment, verify the clinical efficacy of this medicine to the hypertension syndrome of upper hyperactivity of liver yang.
Clinical trial
One, carries out the clinical comparison experiment with QINGXUAN JIANGYA PIAN and medicine of the present invention
1, case source
With reference to the diagnostic criteria of " 1999WHO/ISH hypertension therapeutic guide " and the dialectical standard of " new Chinese medicine treatment hypertension clinical research guideline " syndrome of upper hyperactivity of liver yang, select 1 grade and 2 grades of essential hypertension syndrome of upper hyperactivity of liver yang patient 72 examples, get rid of 3 grades of essential hypertensions, secondary hypertensions simultaneously and do not meet the dialectical standard person of traditional Chinese medical science syndrome of upper hyperactivity of liver yang.Adopt the table of random number method to be divided into 2 groups 36 routine patients, treatment group age reckling 28 years old, the oldest person 72 years old, 54 ± 12.34 years old mean age; Matched group age reckling 31 years old, the oldest person 68 years old, 52.8 ± 11.74 years old mean age.The shortest person of the treatment group course of disease 0.5 year, the elder of the course of disease 40 years, average 9.37 ± 10.17 years; The shortest person of the matched group course of disease 0.5 year, the most normal elder of the course of disease 36 years.Average 8.86 ± 9.73 years.Treatment group blood pressure level belongs to 1 grade of person's 14 example, 2 grades of person's 22 examples; The matched group blood pressure level belongs to 1 grade of person's 17 example, 2 grades of person's 19 examples.Two groups at equal zero differences in aspect (p＜0.05) such as age, the course of disease and blood pressure level, has comparability.
2, Therapeutic Method:
The treatment group gives medicine of the present invention and treats, and its medicine is a tablet, and every contains Ramulus Uncariae Cum Uncis total alkaloids 75mg and Semen Raphani water-soluble alkaloid 90mg, and each 2, every day 3 times, warm water takes.
Matched group: select QINGXUAN JIANGYA PIAN for use, oral, one time 3,2～3 times on the 1st.Two groups all with 4 Zhou Weiyi courses of treatment.Take medicine to rise in preceding 1 week and withdraw other antihypertensive drug or to keep the dosage of original antihypertensive drugs and kind stable, back as serious hypertension occurs should give emergency case at once and handle, and period in a medicine is avoided spicy food and spirits, strong tea, coffee etc.
3, observation index
The a safety indexes: comprise pulse, breathing, heart rate, blood pressure, body weight etc., weekly; Blood, urine, just routine and hepatic and renal function inspection, every month once.
B parameters for observation on effect: mainly refer to blood pressure and tcm syndrome integration, with the meansigma methods of non-3 blood pressures on the same day before treating as observing blood pressure, with the course of treatment last the week non-3 blood pressures on the same day meansigma methods as the efficacy evaluation blood pressure, viewing duration outpatient pressure measurement 2 times weekly, inpatient's pressure measurement 3～5 times weekly.Observe the common sympton of hypertension syndrome of upper hyperactivity of liver yang simultaneously, respectively at before the treatment, treatment is inquired after finishing item by item and note down, and is judged by symptom score standard and keep the score that every routine case symptom sum is this case disease total mark value.
4, statistical method
Measurement data adopts the t check, and enumeration data adopts X 2 test, and clinical ranked data adopt the Ridit check, and data represent that with mean ± standard deviation p＜0.05 is a significant difference, and p＜0.01 is a significant differences.
5, efficacy assessment standard
A. the blood pressure efficacy evaluation is with reference to " new Chinese medicine treatment hypertension clinical guidance principle ".
⑴ produce effects: more than the diastolic pressure decline 10mmHg (1.3KPa), and reach normal range; Though diastolic pressure is not reduced to normally, descended 20mmHg (2.67KPa) or more than; Systolic pressure is treated more than the preceding decline 30mmHg, and reaches normal range.Possesses wherein one.
⑵ effective: diastolic pressure descends not as good as 10mmHg (1.67KPa), but reaches normal range; Diastolic pressure decline 10～19mmHg, but do not reach normal range; Systolic pressure is treated more than the preceding decline 30mmHg, but does not reach normal range.Possesses wherein one.
⑶ invalid: do not reach above standard.
B. the efficacy evaluation of clinical symptoms is evaluated with reference to the regulation of " new Chinese medicine clinical research guideline ".
⑴ produce effects: all transference cures of treatment back, or total mark reduces 〉=66.7%;
⑵ effective: treatment back total mark reduces more than 33.3%, and does not reach 66.7%;
⑶ invalid: treatment back total mark reduces less than 33.3%.
Therapeutic index n=［ integration before (integration before the treatment-treatment back integration) ÷ treatment ］ * 100%.
6, result
A, hypertension curative effect: test group produce effects 10 examples, effective 19 examples, invalid 7 examples, total effective rate 80.6%; Matched group produce effects 6 examples, effective 16 examples, invalid 14 examples, total effective rate 61.1%.Two groups significant difference (P＜0.05) is arranged through young and check.
B, clinical symptoms curative effect: test group produce effects 11 examples, effective 20 examples, invalid 5 examples, total effective rate 86.1%; Matched group produce effects 6 examples, effective 17 examples, invalid 13 examples, total effective rate 63.9%.Through checking two groups of obvious effective rates and total effective rate that significant difference (P＜0.05) is all arranged.Wherein to dizzy, headache, dizzy expand, the curative effect of vexed irritability, xerostomia hardship, constipation with dry stool, flushing scorching hot, uncomfortable in chest pain, yellow fur all is better than matched group (P＜0.05) significantly.
C, safety evaluatio: before the treatment 72 routine patients have been carried out hepatic and renal function, the inspection of hematuria stool routine examination, the result shows all no abnormal, finishes the back course of treatment all patients are all checked, and (P＞0.05) also has no significant change.36 routine patients are organized in treatment, and slight stomachache, diarrhoea appear in 2 examples, continue 1～2 day respectively, and without drug withdrawal, symptom is died away; Matched group 36 routine patients also have 2 examples to occur feeling sick or diarrhoea, continue 1～2 day, and without drug withdrawal, symptom is died away.
Two, carry out the clinical comparison experiment with Bezoar pill for lowering blood pressure and medicine of the present invention
1, case source
With reference to the diagnostic criteria of " 1999WHO/ISH hypertension therapeutic guide " and the dialectical standard of " new Chinese medicine treatment hypertension clinical research guideline " syndrome of upper hyperactivity of liver yang, select 1 grade and 2 grades of essential hypertension syndrome of upper hyperactivity of liver yang patient 92 examples, get rid of 3 grades of essential hypertensions, secondary hypertensions simultaneously and do not meet the dialectical standard person of traditional Chinese medical science syndrome of upper hyperactivity of liver yang.Adopt the table of random number method to be divided into 2 groups 92 routine patients, treatment group age reckling
25Year, the oldest person
68Year, the mean age
52 ± 10.96Year; Matched group age reckling
27Year, the oldest person
67Year, the mean age
53 ± 12.12Year.The shortest person of the treatment group course of disease 1 year, the elder of the course of disease
35Year, average
10.02 ± 12.33Year; The shortest person of the matched group course of disease 0.5 year, the most normal elder of the course of disease
37Year, average
11.02 ± 9.99Year.Treatment group blood pressure level belongs to 1 grade of person's 6 example, 2 grades of person's 40 examples; The matched group blood pressure level belongs to 1 grade of person's 10 example, 2 grades of person's 38 examples.Two groups at equal zero differences in aspect (p＜0.05) such as age, the course of disease and blood pressure level, has comparability.
2, method
The treatment group gives medicine of the present invention and treats, and its medicine is a tablet, and every contains Ramulus Uncariae Cum Uncis total alkaloids 75mg and Semen Raphani water-soluble alkaloid 90mg, and each 2, every day 3 times, warm water takes.
Matched group gives Bezoar pill for lowering blood pressure and treats, and is oral, one time 1～2 ball, 2～3 times on the 1st.
Two groups all with 4 Zhou Weiyi courses of treatment.Take medicine to rise in preceding 1 week and withdraw other antihypertensive drug, back as serious hypertension occurs should give emergency case at once and handle, and period in a medicine is avoided spicy food and spirits, strong tea, coffee etc.
3, result
Adopt and with top identical observation index, statistical method, efficacy assessment standard curative effect of medication is estimated, the result is as follows:
A. hypertension curative effect: test group produce effects 14 examples (30.4%), effective 24 examples (52.2%), invalid 8 examples (17.4%), total effective rate 82.6%; Matched group produce effects 4 examples (15.4%), effective 13 examples (50%), invalid 9 examples (34.4%), total effective rate 65.39%.Through checking two groups of obvious effective rates and total effective rate that significant difference (P＜0.05) is all arranged.
B. clinical symptoms curative effect: test group produce effects 18 examples (39.1%), effective 22 examples (54.35%), invalid 6 examples (6.52%), total effective rate 93.48%; Matched group produce effects 5 examples (19.2%), effective 13 examples (50%), invalid 8 examples (30.3%), total effective rate 69.23%.Through checking two groups of obvious effective rates and total effective rate that significant difference (P＜0.05) is all arranged.Wherein to dizzy, headache, dizzy expand, the curative effect of vexed irritability, xerostomia hardship, constipation with dry stool, flushing scorching hot, uncomfortable in chest pain, yellow fur all is better than matched group (P＜0.05) significantly.
C. safety evaluatio: before the treatment 92 routine patients have been carried out hepatic and renal function, the inspection of hematuria stool routine examination, the result shows all no abnormal, finishes the course of treatment then all patients all to be checked, and (P＞0.05) also has no significant change.46 routine patients are organized in treatment, and slight stomachache, diarrhoea appear in 2 examples, continue 1～2 day respectively, and without drug withdrawal, symptom is died away; Matched group 46 routine patients also have 2 examples to occur feeling sick or diarrhoea, continue 1～2 day, and without drug withdrawal, symptom is died away.
Can draw from above-mentioned clinical data; the sick syndrome of upper hyperactivity of liver yang of being made up of Ramulus Uncariae Cum Uncis total alkaloids and Semen Raphani water-soluble alkaloid of hypertension therapy has good pressure reduction effect expression; effect all is better than QINGXUAN JIANGYA PIAN and Bezoar pill for lowering blood pressure; and can improve that dizzy, headache, tinnitus, fever sensation of the face are lit a fire, the puckery dim eyesight of order, soreness of the waist and knees, fatigue and weakness, symptom such as be hard and dry; and do not have obvious toxic-side effects, thereby regulate and the treatment effect from too many levels, multi-level, many target spots performance function.
It is that Ramulus Uncariae Cum Uncis total alkaloids and Semen Raphani water-soluble alkaloid are carried out the composite medicine of making that the present invention mainly fills a prescription, be raw material with Ramulus Uncariae Cum Uncis and Semen Raphani in the preparation, adopt special means fully to extract their effective ingredient, be used for the treatment of hypertension, from the data of above-mentioned zoopery and clinical trial as can be seen, this two kinds of effective ingredient composite played good therapeutical effect.Except Ramulus Uncariae Cum Uncis total alkaloids and Semen Raphani water-soluble alkaloid, can also be in the present invention's prescription according to the compatibility relationship of mutual reinforcement between, the mutual-assistance, add some medicines identical or close with the Semen Raphani drug effect to increase curative effect with Ramulus Uncariae Cum Uncis, for example can also add Chinese medicine ingredients such as Radix Scrophulariae, Spica Prunellae, Flos Chrysanthemi, Radix Salviae Miltiorrhizae, play synergism, increase curative effect.
The specific embodiment
The present invention will be further elaborated below by specific embodiment, should be understood that, following explanation only is in order to explain the present invention, its content not to be limited.
Embodiment 1
With Semen Raphani and Ramulus Uncariae Cum Uncis is raw material, prepares medicine of the present invention, and method is as follows:
(1) with Ramulus Uncariae Cum Uncis with the ethanol extraction of 75vol% 3 times, each 2h, alcoholic acid amount is 10 times of Ramulus Uncariae Cum Uncis quality, merges the Ramulus Uncariae Cum Uncis extracting solution, concentrating under reduced pressure ethanol gets concentrated solution, concentrated solution be drug quality 1-2 doubly; It is 10 that concentrated solution adds strong aqua ammonia accent pH, extremely colourless with chloroform extraction then, and combining extraction liquid reclaims chloroform to doing, and gets dry extract; Dried cream dissolves with the hydrochloric ultrasonic wave of 1wt%, sucking filtration, and filtrate is used the chloroform defat, the water intaking phase, transfer pH to 9-10 with ammonia, use chloroform extraction then, combining extraction liquid is washed to neutrality, use anhydrous sodium sulfate dehydration, extract reclaims chloroform to doing, and gets the Ramulus Uncariae Cum Uncis total alkaloids, and content is more than 50%.
(2) Semen Raphani is boiled 3 times with 10 quality decocting doubly, each 1.5h, merge extractive liquid,, the 1-2 that is concentrated into the extracting solution quality and is drug quality is doubly, concentrated solution adds ethanol and is 80vol% to containing the alcohol amount, and standing over night is filtered, reclaim ethanol, water bath method, drying obtains dried cream; Dried cream is dissolved in water, last AB-8 macroporous adsorbent resin, earlier with distilled water flush away impurity, carry out gradient elution with ethanol then, collect 10～30vol% ethanol part eluent, resin column can continue to carry out gradient elution with the ethanol of 30-70vol%, deviates from totally until material, and macroporous resin is recycled.With 10～30vol% ethanol part eluent water bath method of gained, the dry Semen Raphani water-soluble alkaloid that gets, content is more than 50%.
(3) Ramulus Uncariae Cum Uncis extract and the Semen Raphani extract mass ratio (being the mass ratio of 10:12) according to 5:6 is mixed, the adjuvant that adds survival dose, make tablet, capsule, granule, mixture or pill, Ramulus Uncariae Cum Uncis extract 75mg in the tablet, Semen Raphani extract 90mg.
Embodiment 2
With Semen Raphani and Ramulus Uncariae Cum Uncis is raw material, prepares medicine of the present invention, and method is as follows:
(1) with Ramulus Uncariae Cum Uncis with the ethanol extraction of 70wt% 3 times, each 2h, alcoholic acid amount is 12 times of Ramulus Uncariae Cum Uncis quality, merges the Ramulus Uncariae Cum Uncis extracting solution, concentrating under reduced pressure ethanol gets concentrated solution, concentrated solution be drug quality 1-2 doubly; It is 9-10 that concentrated solution adds strong aqua ammonia accent pH, extremely colourless with chloroform extraction then, and combining extraction liquid reclaims chloroform to doing, and gets dry extract; Dried cream dissolves with the hydrochloric ultrasonic wave of 5wt%, sucking filtration, and filtrate is used the chloroform defat, the water intaking phase, transfer pH to 9-10 with ammonia, use chloroform extraction then, combining extraction liquid is washed to neutrality, use anhydrous sodium sulfate dehydration, extract reclaims chloroform to doing, and gets the Ramulus Uncariae Cum Uncis total alkaloids, and content is more than 50%.
(2) Semen Raphani is boiled 3 times with 12 quality decocting doubly, each 1.5h, merge extractive liquid,, the 1-2 that is concentrated into the extracting solution quality and is drug quality is doubly, it is 80% to containing the alcohol amount that concentrated solution adds ethanol, and standing over night is filtered, reclaim ethanol, water bath method, drying obtains dried cream; Dried cream is dissolved in water, and last AB-8 macroporous adsorbent resin is earlier with distilled water flush away impurity, carry out gradient elution with ethanol then, collect 10～30vol% ethanol part eluent, reclaim ethanol, water bath method, the dry Semen Raphani water-soluble alkaloid that gets, content is more than 50%.
(3) Ramulus Uncariae Cum Uncis extract and the Semen Raphani extract mass ratio (being the mass ratio of 10:6) according to 5:3 is mixed, the adjuvant that adds survival dose, make tablet, capsule, granule, mixture or pill, Ramulus Uncariae Cum Uncis extract 103mg in the tablet, Semen Raphani extract 62mg.
Embodiment 3
With Semen Raphani and Ramulus Uncariae Cum Uncis is raw material, prepares medicine of the present invention, and method is as follows:
(1) with Ramulus Uncariae Cum Uncis with the ethanol extraction of 80wt% 3 times, each 2h, alcoholic acid amount is 12 times of Ramulus Uncariae Cum Uncis quality, merges the Ramulus Uncariae Cum Uncis extracting solution, concentrating under reduced pressure ethanol gets concentrated solution, concentrated solution be drug quality 1-2 doubly; It is 9-10 that concentrated solution adds strong aqua ammonia accent pH, extremely colourless with chloroform extraction then, and combining extraction liquid reclaims chloroform to doing, and gets dry extract; Dried cream dissolves with the hydrochloric ultrasonic wave of 1wt%, sucking filtration, and filtrate is used the chloroform defat, the water intaking phase, transfer pH to 9-10 with ammonia, use chloroform extraction then, combining extraction liquid is washed to neutrality, use anhydrous sodium sulfate dehydration, extract reclaims chloroform to doing, and gets the Ramulus Uncariae Cum Uncis total alkaloids, and content is more than 50%.
(2) Semen Raphani is boiled 3 times with 8 quality decocting doubly, each 1.5h, merge extractive liquid,, the 1-2 that is concentrated into the extracting solution quality and is drug quality is doubly, it is 80% to containing the alcohol amount that concentrated solution adds ethanol, and standing over night is filtered, reclaim ethanol, water bath method, drying obtains dried cream; Dried cream is dissolved in water, and last AB-8 macroporous adsorbent resin is earlier with distilled water flush away impurity, carry out gradient elution with ethanol then, collect 10～30vol% ethanol part eluent, reclaim ethanol, water bath method, the dry Semen Raphani water-soluble alkaloid that gets, content is more than 50%.
(3) Ramulus Uncariae Cum Uncis extract and the Semen Raphani extract mass ratio (being the mass ratio of 10:10) according to 1:1 is mixed, the adjuvant that adds survival dose, make tablet, capsule, granule, mixture or pill, Ramulus Uncariae Cum Uncis extract 82.5mg in the tablet, Semen Raphani extract 82.5mg.
Embodiment 4
Adopt the method for embodiment 1 that this medicine is made tablet, different is that the mass ratio of Ramulus Uncariae Cum Uncis extract and Semen Raphani extract is that 10:3(is the mass ratio of 20:6), every middle Ramulus Uncariae Cum Uncis extract 127mg, Semen Raphani extract 38mg.
Embodiment 5
Adopt the method for embodiment 1 that this medicine is made tablet, different is that the mass ratio of Ramulus Uncariae Cum Uncis extract and Semen Raphani extract is that 2:1(is the mass ratio of 20:10), every middle Ramulus Uncariae Cum Uncis extract 110mg, Semen Raphani extract 55mg.
Embodiment 6
Adopt the method for embodiment 1 that this medicine is made tablet, different is that the mass ratio of Ramulus Uncariae Cum Uncis extract and Semen Raphani extract is that 3:2(is the mass ratio of 15:10), every middle Ramulus Uncariae Cum Uncis extract 99mg, Semen Raphani extract 66mg.
Embodiment 7
Adopt the method for embodiment 1 that this medicine is made tablet, different is that the mass ratio of Ramulus Uncariae Cum Uncis extract and Semen Raphani extract is 5:3, every middle Ramulus Uncariae Cum Uncis extract 103mg, Semen Raphani extract 62mg.
Embodiment 8
Adopt the method for embodiment 1 that this medicine is made tablet, different is that the mass ratio of Ramulus Uncariae Cum Uncis extract and Semen Raphani extract is 5:12, every middle Ramulus Uncariae Cum Uncis extract 68.3mg, Semen Raphani extract 96.7mg.
Embodiment 9
Adopt the method for embodiment 1 that this medicine is made tablet, different is that the mass ratio of Ramulus Uncariae Cum Uncis extract and Semen Raphani extract is 20:3, every middle Ramulus Uncariae Cum Uncis extract 143.2mg, Semen Raphani extract 21.8mg.
With the tablet is example, and the medicine of the foregoing description is carried out clinical experiment, and its curative effect is as follows:
1, choose patient's 250 examples of suffering from 1 grade and 2 grades essential hypertension syndrome of upper hyperactivity of liver yang at this city, patient age between 30～68 years old, the course of disease between 1～20 year, 1 grade of person's 60 example of blood pressure level, 2 grades of person's 190 examples; The patient is equally divided into 5 groups, and each group has comparability at equal zero differences in aspect (p＜0.05) such as age, the course of disease and blood pressure level.
2, the patient with grouping adopts medicine of the present invention to treat respectively, and each 2, every day 3 times, warm water takes, course of treatment of logotype, according to top clinical experiment according to observation index and efficacy assessment standard evaluate curative effect, its result is as follows.
The curative effect of other embodiment is close with embodiment 2,4,8,9, and the proportioning of embodiment 1 is best to hypertensive therapeutic effect as can be known by data.
Claims (9)
1. the hypertensive Chinese medicine composition of treatment is characterized in that effective ingredient comprises: Ramulus Uncariae Cum Uncis ethanol extract 5～20 mass parts, Semen Raphani water extract 3～12 mass parts.
2. Chinese medicine composition according to claim 1 is characterized in that effective ingredient comprises: Ramulus Uncariae Cum Uncis ethanol extract 10～20 mass parts, Semen Raphani water extract 6～12 mass parts.
3. Chinese medicine composition according to claim 1 is characterized in that: effective ingredient comprises that mass ratio is Ramulus Uncariae Cum Uncis ethanol extract and the Semen Raphani water extract of 5:6.
4. according to each described Chinese medicine composition among the claim 1-3, it is characterized in that: main effective ingredient is the Ramulus Uncariae Cum Uncis total alkaloids in the Ramulus Uncariae Cum Uncis ethanol extract, the Ramulus Uncariae Cum Uncis total alkaloid content is more than 50%, main effective ingredient is the Semen Raphani water-soluble alkaloid in the Semen Raphani water extract, and Semen Raphani water-soluble biological alkali content is more than 50%.
5. Chinese medicine composition according to claim 1 is characterized in that: dosage form is tablet, granule, capsule, mixture or pill.
6. the preparation method of the hypertensive Chinese medicine composition of the described treatment of claim 1 is characterized in that may further comprise the steps:
A. adopt ethanol refluxing process to extract the Ramulus Uncariae Cum Uncis ethanol extract
(1) with ethanol extraction repeatedly with Ramulus Uncariae Cum Uncis, merge extractive liquid,, concentrating under reduced pressure ethanol gets concentrated solution;
(2) concentrated solution pH is reconciled to 9～10, extremely colourless with chloroform extraction then, the chloroform extraction liquid of merging gained boils off chloroform and gets dry extract;
(3) dried cream dilute hydrochloric acid ultrasonic dissolution, sucking filtration is got filtrate then, and filtrate is used the chloroform defat, the water intaking phase;
(4) water is reconciled pH to 9～10, and then with chloroform extraction repeatedly, combining extraction liquid is washed to neutrality with extract, removes then and anhydrates, boils off chloroform, gets the Ramulus Uncariae Cum Uncis ethanol extract;
B. adopt the decocting cooking method to extract the Semen Raphani water extract
(1) the Semen Raphani water is decocted repeatedly merge extractive liquid;
(2) extracting solution is concentrated, adding ethanol to pure content is 80vol%, and standing over night is filtered, and supernatant evaporate to dryness ethanol is got dry extract;
(3) with dried cream water dissolution, last AB-8 absorption with macroporous adsorbent resin carries out gradient elution with distilled water eluting, reuse ethanol then, collects the ethanol part eluent of 10～30vol%;
(4), get the Semen Raphani water extract with eluent evaporate to dryness ethanol;
C. Ramulus Uncariae Cum Uncis alcohol extract and the Semen Raphani water extract that makes mixed by proportioning, add the adjuvant of survival dose, make.
7. preparation method according to claim 6 is characterized in that: when extracting the Ramulus Uncariae Cum Uncis ethanol extract, alcoholic acid volumetric concentration is 70～80%, consumption be Ramulus Uncariae Cum Uncis 8～12 quality doubly, extract 2h at every turn; The quality of concentrated solution is 1～2 times of drug quality.
8. preparation method according to claim 6 is characterized in that: the concentration of dilute hydrochloric acid is 1～5wt%.
9. preparation method according to claim 6 is characterized in that: when extracting the Semen Raphani water extract, the consumption of water be Semen Raphani 8～12 quality doubly, extract 1.5h at every turn; Extracting solution is concentrated into 1～2 times of drug quality.
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| CN103948909A (en) * | 2014-05-29 | 2014-07-30 | 张军 | Traditional Chinese medicine preparation for lowering blood pressure |
| CN104256576A (en) * | 2014-07-04 | 2015-01-07 | 凯泽（武汉）健康管理有限公司 | Functional food capable of regulating blood pressure |
| CN105535924A (en) * | 2016-01-13 | 2016-05-04 | 安徽生物肽产业研究院有限公司 | Compound lumbricus small peptide composition for treating cardiovascular diseases |
| CN106138514A (en) * | 2016-08-02 | 2016-11-23 | 山东中医药大学附属医院 | A kind of Chinese medicine composition treating intermingled phlegm and blood stasis type hypertension and preparation method thereof |
| CN112741832A (en) * | 2021-03-04 | 2021-05-04 | 山东中医药大学 | Antihypertensive pharmaceutical composition and preparation method and application thereof |
| CN114010699A (en) * | 2021-12-22 | 2022-02-08 | 山东中医药大学 | Traditional Chinese medicine composition for treating hypertension and preparation method thereof |
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| CN1302635A (en) * | 2000-01-01 | 2001-07-11 | 邵章祥 | Medical capsule for dredging channels and lowering blood pressure and its preparing process |
| CN101757569A (en) * | 2010-01-19 | 2010-06-30 | 泰一和浦（北京）中医药研究院有限公司 | Traditional Chinese medicine composition for treating cerebral thrombosis and cerebral infarction and preparation method thereof |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103948909A (en) * | 2014-05-29 | 2014-07-30 | 张军 | Traditional Chinese medicine preparation for lowering blood pressure |
| CN104256576A (en) * | 2014-07-04 | 2015-01-07 | 凯泽（武汉）健康管理有限公司 | Functional food capable of regulating blood pressure |
| CN104256576B (en) * | 2014-07-04 | 2017-03-22 | 武汉哈福科技有限公司 | Functional food capable of regulating blood pressure |
| CN105535924A (en) * | 2016-01-13 | 2016-05-04 | 安徽生物肽产业研究院有限公司 | Compound lumbricus small peptide composition for treating cardiovascular diseases |
| CN106138514A (en) * | 2016-08-02 | 2016-11-23 | 山东中医药大学附属医院 | A kind of Chinese medicine composition treating intermingled phlegm and blood stasis type hypertension and preparation method thereof |
| CN112741832A (en) * | 2021-03-04 | 2021-05-04 | 山东中医药大学 | Antihypertensive pharmaceutical composition and preparation method and application thereof |
| CN114010699A (en) * | 2021-12-22 | 2022-02-08 | 山东中医药大学 | Traditional Chinese medicine composition for treating hypertension and preparation method thereof |
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