CN103800307A - Medicinal composition for reducing blood pressure and preparation method thereof - Google Patents
Medicinal composition for reducing blood pressure and preparation method thereof Download PDFInfo
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- CN103800307A CN103800307A CN201310714374.5A CN201310714374A CN103800307A CN 103800307 A CN103800307 A CN 103800307A CN 201310714374 A CN201310714374 A CN 201310714374A CN 103800307 A CN103800307 A CN 103800307A
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Abstract
The invention relates to a medicinal composition for reducing blood pressure and a preparation method thereof. The composition comprises menthol and a pharmaceutically acceptable carrier, wherein the menthol accounts for 30-50wt% of the medicinal composition. The medicinal composition is prepared from pure natural plate extract menthol, can be used for effectively and smoothly reducing the blood pressure of a patient in prehypertension (120-139/80-89mmHg) and with mild hypertension to improve the vasodilatation function of the patient, and does not have remarkable adverse response. The medicinal composition is particularly suitable for a patient in prehypertension, as well as a patient with confirmed primary hypertension.
Description
Technical field
The present invention relates to a kind of blood pressure lowering pharmaceutical composition and preparation method, in particular, relate to a kind of blood pressure lowering pharmaceutical composition and be made up of menthol and pharmaceutically acceptable carrier, its medicine is for hypertension treatment and diagnosis and the hypertensive auxiliary treatment in early stage.
Background technology
Hypertension is global great controllability chronic disease, become the main cause of apoplexy, coronary heart disease and cardiorenal function exhaustion etc., also be the topmost risk factor of cardiovascular and cerebrovascular disease, the major complications such as its apoplexy, myocardial infarction, heart failure and chronic kidney disease, not only disable, fatality rate is high, and seriously consume medical treatment and social resources, cause heavy burden to family and country.At present, China's blood pressure normal population (<120/80mmHg) proportion is less than 1/2, and hyperpietic approximately has 200,000,000, in every 10 adults, just has 2 to suffer from hypertension, accounts for 1/5 of global hypertension total number of persons.In China's Hypertensive Population, the overwhelming majority is light, moderate hypertension (accounting for 90%), and mild hypertension accounts for more than 60%.Both domestic and external facts have proved, hypertension is the disease that can prevent and control, reduces hyperpietic's blood pressure level, can obviously reduce the generation of apoplexy and cardiovascular event, significantly improve patient's life quality, effectively reduce society and financial burden that hypertension is brought.
Hypertensive generation development is the process of a chronic concealment, blood pressure develops into hypertension from desirable level (<120/80mmHg) a crucial transition period, this stage blood pressure level is 120-139/80-89mmHg, and Hypertension Guideline is defined as " In Prehypertensive " or " hypertension early stage " (Prehypertension) both at home and abroad.There are some researches show; in the time of hypertension early stage, inflammatory factor, vascular endothelial function, cardiorenal function etc. have started to occur abnormal; develop to hypertension from normal high value if can effectively check blood pressure in hypertension intervention in time in early stage; the target organs such as protection heart and brain kidney and blood vessel; significantly reduce the generation of cardiocerebrovasculaevents events; once and blood pressure enters hypertension state, even if take the measures such as medicine blood pressure lowering, curative effect is also limited.China's epidemiological study shows, the prevalence of the pre-hypertension of China has reached 44%-60%, and take the young and the middle aged as main; Wherein approximately 45% will after 10 years, develop into hypertension, be " reserves " that China's Hypertension number increases severely.China's the past mainly concentrates on treatment and the Intervention Strategy of hypertensive Treatment of Hypertension and target organ damage to hypertensive treatment and research, also obtained obvious curative effect, but the toxic and side effects of most medicine for lowering high blood pressure is larger, and there is no at present for the hypertension curative drug in early stage.
Antihypertensive therapy comprises non-drug therapy and two kinds of methods of Drug therapy.Non-drug therapy mainly refers to life style intervention, and major measure comprises: reduce sodium salt and take in, increase potassium salt absorption; Control body weight; Non-smoking; Not excessive consumption of alcohol; Sports; Alleviate stress, maintain one's mental balance.But in daily life, will accomplish that these are usually difficult to adhere to, the compliance of Most patients is poor.Conventional antihypertensive drugs comprises clinically: calcium channel blocker, angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), diuretic and beta-blocker five classes.In addition, the antihypertensive drugs of alpha-blocking agent or other kinds also can be applicable to some Hypertensive Population sometimes.These antihypertensive drugs all have obvious untoward reaction and toxic and side effects.As: the curative effect of ACEI depressor is limited, and overall effectiveness is only 60%, and compared with other antihypertensive drugs, its target organ protection function there is no clear superiority, is not improved hyperpietic's prognosis curative effect; ARB is one of the most frequently used clinically antihypertensive drugs, can effectively reduce blood pressure, but also exists efficacy of antihypertensive treatment limited, not enough to waiting a little less than the protective effect of target organ.Headache, flushing, atrioventricular block, cardiac function suppress, blood potassium blood sodium is abnormal, cough, angioedema, postural hypotension, bronchial asthma etc. are all main adverse reaction of clinical conventional Altace Ramipril; Also there is the shortcoming and defect that adverse reaction rate is high in most antihypertensive drugs, toleration is poor, has therefore reduced patient's the compliance of taking medicine.(Chinese hypertension prevention and control guide Drafting Committee. Chinese hypertension prevention and control guide. hypertension magazine, 2011:19 (8): 701-743).In addition,, after Definite Hypertension, Most patients need be adhered to Long-term taking medicine, even lifelong medication.
Above-mentioned antihypertensive antihypertensive drugs is all for hyperpietic, and still there is no bibliographical information for hypertension patient's in early stage therapeutic antihypertensive drugs at present.
Therefore, active and effective treatment hypertension is the hypertensive key links of prevention and control in earlier stage, we need find the new curative drug for pre-hypertension, actively control China's pre-hypertension, and reducing China hypertensive " reserves " has important meaning.
Summary of the invention
For above-mentioned deficiency, the invention provides a kind of hypertension antihypertensive medical composite and preparation method in earlier stage, said composition is for the treatment in hypertension early stage and diagnosis and hyperpietic's auxiliary treatment, this medicine can reduce hypertension early stage and mild hypertension patient's blood pressure effectively, reposefully, importantly this medicine can significantly improve hypertension early stage and mild hypertension patient's arterial dilation, and showing without obvious untoward reaction and toxic and side effects through clinical practice, is a kind of safe Treatment of Hypertension medicine.This pharmaceutical composition is specially adapted to hypertension patient in early stage, also can be used for the hyperpietic's who has made a definite diagnosis auxiliary treatment.
Technical scheme of the present invention is as follows:
The pharmaceutical composition that blood pressure lowering is used, comprises menthol and pharmaceutically acceptable carrier, described menthol C
10h
20o, its structural formula is:
The percentage by weight that described menthol accounts for this pharmaceutical composition is 30～50%.
On described medicine, acceptable carrier comprises PVP K30, micropowder silica gel or magnesium stearate.
On described medicine, acceptable carrier comprises filler.
Described filler comprises one or more in microcrystalline Cellulose, starch, lactose, dextrin, carboxymethylstach sodium.
The weight portion of aforementioned pharmaceutical compositions is:
The preparation method of the medicinal composition tablets that blood pressure lowering is used, has following steps:
1) get menthol and pharmaceutically acceptable carrier by above-mentioned dosage, after acceptable carrier sieves respectively, mixes on medicine, add menthol, equivalent incremental method mix homogeneously;
2) add PVP K30 soft material processed, 20 mesh sieves are granulated, 24 mesh sieve granulate, and 40-45 ℃ is dry;
3) dry granule adds magnesium stearate, mixes, and tabletting, obtains blood pressure lowering pharmaceutical composition.
The preparation method of blood pressure lowering pharmaceutical composition capsule, has following steps:
1) getting menthol by above-mentioned dosage mixes for subsequent use;
2) by being that the dosage stated is got lactose, microcrystalline Cellulose, starch, carboxymethylstach sodium in 100 ℃ of left and right dry 2 hours respectively, cross 100 mesh sieves;
3) above-mentioned adjuvant is mixed homogeneously by equivalent incremental method with mixed crude drug, pelletizing machine granulate, pellet moisture >5%, 30 mesh sieve granulate, capsule fill, obtains blood pressure lowering pharmaceutical composition.
The application of blood pressure lowering pharmaceutical composition in preparation treatment hypertension drug.
The molecular structural formula of menthol of the present invention is:
In pharmaceutical composition of the present invention, contain pharmaceutics acceptable carrier, can be made into common oral preparation, comprise conventional tablet, conventional capsule, granule etc.Described in while making tablet pharmaceutically acceptable carrier comprise contribute to by reactive compound be mixed with the excipient of pharmaceutical formulation and accessory drugs as carboxymethyl starch sodium, starch, microcrystalline Cellulose, inorganic salts, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, citric acid etc. the compositions etc. of one or more materials.
Drug composition oral of the present invention is pressed menthol 1.125-3.75mg/kg/d administration, is divided into three every day and takes.
Herba Menthae has another name called thin severe, wild mint of luxuriant lotus dish, Ba Jian, Wu Ba Jian, southern Herba Menthae, cat etc., is labiate Herba Menthae.Main effect of Herba Menthae is dispelling wind, heat radiation, removing toxic substances.Be usually used in treating affection due to external wind and heat, headache, conjunctival congestion, laryngopharynx swelling and pain, dyspepsia flatulence, aphtha, toothache etc.Fresh mentha leave is containing volatile oil 0.8～1%, and scapus leaf is containing 1.3～2%.Main constituent in Oleum menthae is menthol, and secondly content approximately 77～78% be menthone, and content is 8～12%, also containing menthyl acetate, camphene, limonene, isomenthone, pinene, piperitenone, resin and a small amount of tannin, rosmarinic acid.
The present invention has following beneficial effect:
Described pharmaceutical composition can effectively reduce hypertension patient's in early stage systolic pressure and diastolic pressure, and hypotensive effect gentleness, occurs without obvious adverse reaction; Can improve hypertension patient's in early stage arterial dilation, alleviate the important organ inadequate blood perfusion causing due to long-term hypertension, the infringement of protection heart and brain kidney target organ simultaneously.Also can be used for the hyperpietic's who has made a definite diagnosis adjuvant therapy medicaments.
The effective ingredient of institute's pharmaceutical composition---the native compound that menthol is plant origin, unartificial synthetic, without obvious toxic-side effects, safe and effective.This pharmaceutical composition is specially adapted to patient in hypertension early stage, also can be used for 1 grade of patient of hypertension of having made a definite diagnosis, also can be used as hyperpietic's adjuvant therapy medicaments.
Pharmaceutical composition of the present invention is for preventing, treat and delay the related cardiovascular disease of hypertension early stage and caused by hypertension.Through experimental verification; pharmaceutical composition of the present invention is used for the treatment of hypertension in earlier stage; safety, effective; can reduce reposefully hypertension early stage (120-139/80-89mmHg) and mild hypertension patient's blood pressure; improve its arterial dilation; the target organs such as protection heart and brain kidney and blood vessel, and without significantly untoward reaction.
Below in conjunction with the specific embodiment, the present invention will be further described, not limitation of the invention, and the equal replacement of all any this areas of carrying out according to content of the present invention, all belongs to protection scope of the present invention.
Accompanying drawing explanation
Fig. 1 is the result schematic diagram that menthol pharmaceutical composition is intervened animal blood pressure; Wherein, Figure 1A is that menthol is intervened wild-type mice (C57BL/6J) blood pressure systolic pressure (SBP) schematic diagram; Figure 1B is TRPM8 knock-out mice blood pressure systolic pressure (SBP) schematic diagram that menthol is intervened C57BL/6J background; Fig. 1 C is that menthol is intervened wild-type mice (C57BL/6J) blood pressure diastolic pressure (DBP) schematic diagram; Fig. 1 D is TRPM8 knock-out mice blood pressure diastolic pressure (DBP) schematic diagram of menthol intervention C57BL/6J background; Fig. 1 E is TRPM8 knock-out mice blood pressure systolic pressure (SBP) schematic diagram that menthol is intervened C57BL/6J background; Fig. 1 F is TRPM8 knock-out mice blood pressure diastolic pressure (DBP) schematic diagram that menthol is intervened C57BL/6J background;
Fig. 2 is that menthol pharmaceutical composition is used for the treatment of hypertensive clinical test results schematic diagram; Wherein, Fig. 2 A is the result of taking hypertension patient's systolic pressure in early stage (SBP) of menthol capsule after 8 weeks; Fig. 2 B is the result of taking hypertension patient's diastolic pressure in early stage (DBP) of menthol capsule after 8 weeks; Fig. 2 C is the result of taking hypertension patient in early stage 24 hours systolic pressures (SBP) and 24 hours diastolic pressures (DBP) of menthol capsule after 8 weeks and treating front baseline comparison; Fig. 2 D is the hypertension patient vessel's diastolic function in early stage (FMD) and the front baseline comparative result for the treatment of of taking menthol capsule after 8 weeks.
The specific embodiment
1. instrument and reagent
(1) animal:
Wild type (WT) mice (C57BL/BJ) is purchased from Jackson Lab of the U.S.; TRPM8
-/-mice is purchased from doctor's Patapoutian laboratory; Spontaneous hypertensive rat (SHR) is purchased from Charles River's laboratory.
2. reagent
Menthol is selected commercially available pharmaceutical quality standard, the product of content >=99.99% of meeting;
Magnesium stearate, 5% PVP K-30, microcrystalline Cellulose, starch, carboxymethylstach sodium are all selected commercially available pharmaceutical grade product;
Embodiment 1: 1000 of blood pressure lowering pharmaceutical composition of the present invention (tablet), gross weight 117.59325g.
The menthol of getting formula ratio mixes for subsequent use;
(1) adjuvant cross respectively after 100 mesh sieves 75 ℃ dry 2 hours;
(2) mix homogeneously with mixed crude drug menthol equivalent incremental method again after mixing by the starch of formula ratio, microcrystalline Cellulose, sodium carboxymethylstarch;
(3) add 5% PVP K-30 2.3g soft material processed, 24 mesh sieves are granulated, 20 mesh sieve granulate, and 40-45 ℃ dry;
(4) dry granule adds magnesium stearate 0.29325g to mix, tabletting after assay.
Embodiment 2: 1000 of blood pressure lowering pharmaceutical composition of the present invention (tablet), gross weight 141g.
Preparation technology:
(1) menthol of getting formula ratio mixes for subsequent use;
(2) dressing cross respectively after 100 mesh sieves 75 ℃ dry 2 hours;
(3) mix homogeneously with mixed crude drug equivalent incremental method again after mixing by the starch of formula ratio, microcrystalline Cellulose, sodium carboxymethylstarch;
(4) add 5% PVP K-30 6.75g soft material processed, 24 mesh sieves are granulated, 20 mesh sieve granulate, and 40-45 ℃ dry;
(5) dried particles adds magnesium stearate 1.4175g to mix, tabletting after assay.
Embodiment 3: 1000 of blood pressure lowering pharmaceutical composition of the present invention (capsule), gross weight 90g.
Preparation technology:
(1) menthol of getting formula ratio mixes for subsequent use;
(2) lactose, microcrystalline Cellulose, starch, carboxymethylstach sodium of getting formula ratio dry 2 hours respectively in 100 ℃ of left and right, crosses 100 mesh sieves;
(3) above-mentioned adjuvant is mixed homogeneously by equivalent incremental method with mixed crude drug, be placed in pelletizing machine granulate, pellet moisture >5%, 30 mesh sieve granulate, capsule fill.
Embodiment 4: 1000 of blood pressure lowering pharmaceutical composition of the present invention (capsule), gross weight 110g.
Preparation technology:
The menthol of getting formula ratio mixes for subsequent use;
Lactose, microcrystalline Cellulose, starch, the carboxymethylstach sodium of getting formula ratio are dried 2 hours respectively in 100 ℃ of left and right, cross 100 mesh sieves;
Above-mentioned adjuvant is mixed homogeneously by equivalent incremental method with mixed crude drug, be placed in pelletizing machine granulate, pellet moisture >5%, 30 mesh sieve granulate, capsule fill.
Wild type (WT) mice (C57BL/BJ) is purchased from Jackson Lab of the U.S., TRPM8
-/-mice is purchased from doctor's Patapoutian laboratory.Spontaneous hypertensive rat (SHR) is purchased from Charles River's laboratory.Large mice is divided into respectively general food group and Herba Menthae group at random, and (menthol content is 0.5%, w/w), intervene continuously after 28 weeks, rat anesthesia pneumoretroperitoneum is implanted into blood pressure implanted device Monitoring of blood pressure situation of change, recovers 10 days after rat operation, then starts to measure 24 h ABP, every 30 minutes acquisition and recording blood pressure datas in 10 second, monitoring 3 days, gets its mean blood pressure value per hour continuously, does statistical procedures.
Mus arteria caudalis blood pressure measuring method: adopt rat tail blood pressure determination instrument (Powerlab, Australia) to measure according to the requirement of instrument.Before measurement, first allow rat at the warm 5min of incubator of 35 ℃, in measuring process, rat keeps waking state, and activity is restricted.Every animal is surveyed 3 times, gets its meansigma methods.In surveying Mus tail blood pressure, variation that can monitor heart rate.
The mensuration of Blood pressure of carotid artery: before rat is put to death, urethane intraperitoneal injection of anesthesia, carotid artery intubate, after tranquillization 30min, adopts eight road physiograph recording blood pressure and hearts rate.The mensuration of biochemical indicator blood insulin: adopt radio immunoassay, specifically carry out according to test kit explanation.The mensuration of blood glucose: fasting 12 hours, blood is got in second day docking in early morning, by micro-blood glucose meter measuring blood.The mensuration of blood fat: TC, TG, HDL and LDL measure and adopt automatic clinical chemistry analyzer to measure, and carry out according to test kit explanation.The mensuration of free fatty is strictly undertaken by test kit explanation.The results are shown in Figure 1.
Wild-type mice (C57BL/6J) is divided into matched group and the menthol group (composition tablet described in embodiment 1-2 at random, lower same), intervene continuously after 28 weeks, anesthesia pneumoretroperitoneum is implanted into blood pressure implanted device, and post-operative recovery 10 days, then measures 24 h ABP, at interval of 30 minutes acquisition and recording blood pressure datas in 10 second, monitoring 3 days, gets its mean blood pressure value per hour continuously, does statistical procedures.24h ambulatory blood pressure result shows that the systolic pressure (SBP) of menthol group mice is starkly lower than matched group, and result has statistical significance, referring to Figure 1A.
The TRPM8 knock-out mice of C57BL/6J background is divided into matched group and menthol group at random, intervene continuously after 28 weeks, anesthesia pneumoretroperitoneum is implanted into blood pressure implanted device, post-operative recovery 10 days, then measure 24 h ABP, at interval of 30 minutes acquisition and recording blood pressure datas in 10 second, monitor continuously 3 days, get its mean blood pressure value per hour, do statistical procedures.24h ambulatory blood pressure result shows that menthol group mice systolic pressure (SBP) does not have statistical significance compared with matched group blood pressure.Result is referring to Figure 1B.
Wild-type mice (C57BL/6J) is divided into matched group and menthol group at random, intervene continuously after 28 weeks, anesthesia pneumoretroperitoneum is implanted into blood pressure implanted device, post-operative recovery 10 days, then measure 24 h ABP, at interval of 30 minutes acquisition and recording blood pressure datas in 10 second, monitor continuously 3 days, get its mean blood pressure value per hour, do statistical procedures.24h ambulatory blood pressure result shows that the diastolic pressure (DBP) of menthol group mice is starkly lower than matched group, and result has statistical significance, referring to Fig. 1 C.
The TRPM8 knock-out mice of C57BL/6J background is divided into matched group and menthol group at random, intervene continuously after 28 weeks, anesthesia pneumoretroperitoneum is implanted into blood pressure implanted device, post-operative recovery 10 days, then measure 24 h ABP, at interval of 30 minutes acquisition and recording blood pressure datas in 10 second, monitor continuously 3 days, get its mean blood pressure value per hour, do statistical procedures.24h ambulatory blood pressure result shows that menthol group mice diastolic pressure (DBP) does not have statistical significance compared with matched group blood pressure.Result is referring to Fig. 1 D.
SHR rat (spontaneous hypertensive rat) is divided into matched group and menthol group at random, intervene continuously after 28 weeks, anesthesia pneumoretroperitoneum is implanted into blood pressure implanted device, post-operative recovery 10 days, then measure 24 h ABP, at interval of 30 minutes acquisition and recording blood pressure datas in 10 second, monitor continuously 3 days, get its mean blood pressure value per hour, do statistical procedures.24h ambulatory blood pressure result shows that the systolic pressure (SBP) of menthol group SHR rat is starkly lower than matched group, and result has statistical significance, sees Fig. 1 E.
SHR rat (spontaneous hypertensive rat) is divided into matched group and menthol group at random, intervene continuously after 28 weeks, anesthesia pneumoretroperitoneum is implanted into blood pressure implanted device, post-operative recovery 10 days, then measure 24 h ABP, at interval of 30 minutes acquisition and recording blood pressure datas in 10 second, monitor continuously 3 days, get its mean blood pressure value per hour, do statistical procedures.24h ambulatory blood pressure result shows that the diastolic pressure (DBP) of menthol group SHR rat is starkly lower than matched group, and result has statistical significance, sees Fig. 1 F.
In sum, as shown in Figure 1A-1D, meals menthol (mentho1) has reduced systolic pressure (SBP) and the diastolic pressure (DBP) of wild-type mice by activating the cold passage of TRPM8, and to TRPM8 knock-out mice (TRPM8
-/-) without this effect.Compared with matched group, also there is significance decline (1E, 1F in SHR on the feed 28 weeks after-contraction pressures of menthol and diastolic pressure; P < 0.01).Results of animal shows that menthol intervention can significantly reduce the blood pressure of wild-type mice and spontaneous hypertensive rat, and to the cold passage knock-out mice of TRPM8 without effect.Therefore, the hypotensive effect of menthol is relevant with the cold passage of activation TRPM8.
Embodiment 6 clinical trials
Recruit hypertension volunteer in early stage, its baseline characteristic is as shown in table 1 after testing:
Table 1 hypertension volunteer's in early stage baseline characteristic
Hypertension diagnostic criteria is in earlier stage (systolic pressure 120-139mmHg is or/and diastolic pressure 80-89mmHg), hypertension early stage, patient was divided into 2 groups by random, double blinding: placebo group and the menthol group (composition capsule described in embodiment 3-4, lower same) (table 1), the medicine outer package of two groups is identical, it is the menthol capsule for hypertension previous tretament that experimenter is all apprised of intervened medicine, within 2 weeks, follows up a case by regular visits to the various indexs of one-time detection.Cebo-Caps is except not containing effective ingredient menthol, and the outer package of all the other capsule compositions and medicine and matched group menthol capsule (144mg/ days, point three oral meals) are identical.Before on-test and the detection of measuring respectively clinic blood pressure, 24 h ABP, arterial dilation (FMD) and metabolic index after 8 weeks.Measuring method with standard clinic blood pressure: patient gets seat rest 15min, then adopt standard mercury sphygmomanometer, cuff is tied up in right upper arm, speed with decline 2mmHg per second after inflation is slowly exitted and is measured systolic pressure and diastolic pressure, diastolic pressure disappears as main take Ke Shi the 5th sound, continuous measurement 3 times, every minor tick 2min, averages.
Measure height, body weight, waistline (Waist circumference with standard method, WC), hip circumference, waist-to-hipratio (Waist-hip Ratio, WHR): experimenter takes off one's shoes without a hat on, measure respectively height, body weight, calculate Body Mass Index (BMI) by body weight (kg)/height (m2); Waistline (midtread of two side-draw arcus costarum lower edges and crista iliaca, point among the about umbilicus of veutro and xiphoid-process), hip circumference (measurement ring is around the Zhou Jing of the pelvis most salient point of buttocks) are measured in vertical position, calculate waist-to-hipratio (WHR).The measuring method of 24 h ABP: gathered a blood pressure data every 15 minutes during 08:00-20:00, gathered a blood pressure data during 20:00-08:00 every 30 minutes.The results are shown in Figure 2.
Hypertension early stage, patient was divided into 2 groups by random, double blinding: menthol group and placebo group.The medicine outer package of two groups is the same, and Cebo-Caps is not except containing effective ingredient menthol, and the outer package of all the other capsule compositions and medicine is identical with menthol capsule, and menthol group gives menthol capsule 144mg/ days, point three oral meals.Before on-test and when the 8th week finishes, measure respectively clinic blood pressure.Hypertension patient's systolic pressure in early stage (SBP) of taking menthol capsule after the 8th week finishes obviously reduces before treatment, and result has statistical significance, sees Fig. 2 A.
Hypertension early stage, patient was divided into 2 groups by random, double blinding: menthol group and placebo group.The medicine outer package of two groups is just the same, and Cebo-Caps is not except containing effective ingredient menthol, and the outer package of all the other capsule compositions and medicine is identical with menthol capsule, and menthol group gives menthol capsule 144mg/ days, point three oral meals.Before on-test and when the 8th week finishes, measure respectively clinic blood pressure.Hypertension patient's diastolic pressure in early stage (DBP) of taking menthol capsule after the 8th week obviously reduces before treatment, and result has statistical significance, Fig. 2 B.
Hypertension early stage, patient was divided into 2 groups by random, double blinding: menthol group and placebo group.The medicine outer package of two groups is just the same, and Cebo-Caps is not except containing effective ingredient menthol, and the outer package of all the other capsule compositions and medicine is identical with menthol capsule, and menthol group gives menthol capsule 144mg/ days, point three oral meals.Before on-test and when the 8th week finishes, measure respectively 24 h ABP.24 hours systolic pressures (SBP) of patient in hypertension early stage and the obvious reduction compared with the front baseline for the treatment of of 24 hours diastolic pressures (DBP) of after 8 weeks, taking menthol capsule, result has statistical significance, sees Fig. 2 C.
Hypertension early stage, patient was divided into 2 groups by random, double blinding: menthol group and placebo group.The medicine outer package of two groups is just the same, and Cebo-Caps is not except containing effective ingredient menthol, and the outer package of all the other capsule compositions and medicine is just the same, and menthol group gives menthol capsule 144mg/ days, point three oral meals.Difference measuring tube diastolic function (FMD) before on-test and when the 8th week finishes.Hypertension patient vessel's diastolic function in early stage (FMD) obvious increase compared with baseline before treatment of taking menthol capsule after 8 weeks, result has statistical significance, sees Fig. 2 D.
Metabolic index detects: all patients all adopt venous blood and measure fasting glucose (FPG), the rear 2h blood glucose (2hPG) of load, fasting insulin (FIN), glycolated hemoglobin (HbAlC) and plasma lipid profile (T-CHOL (TCh), triglyceride (TG), HDL-C (HDL-c), low-density lipoprotein cholesterol (LDL-c)) after 8 hours in empty stomach; And calculate HOMA index (HOMA-IR=(FPG × FIN)/22.5).Statistical procedures method: data typing and data management are carried out in Epidata3.02, statistical analysis adopts SPSS For Windows10.0.Between continuous variable group, relatively adopt t check or one factor analysis of variance (ANOVA); There is significant take P < 0.05 as difference.The results are shown in Figure 2.
In sum, hypertension early stage volunteer take menthol capsule after 8 weeks compared with placebo group, clinic systolic pressure and diastolic pressure all obviously decline (2A, 2B); After taking medicine with take medicine before compare menthol group and 24 h ABP descent amplitudes be significantly greater than placebo group (2C), and after menthol treatment, arterial dilation improves obviously (2D).Human trial result shows that menthol can effectively reduce hypertension patient's in early stage blood pressure, and effectively improves hypertension patient's in early stage arterial dilation.
The foregoing is only preferred embodiment of the present invention, not in order to limit substantive technology contents scope of the present invention, substantive technology contents of the present invention is in the claim scope that is defined in application of broad sense, technology entity or method that other people complete, if defined identical with the claim scope of application, also or a kind of change of equivalence, be all covered by among this claim scope being regarded as.
Claims (9)
1. a blood pressure lowering pharmaceutical composition, is characterized in that, comprises menthol and pharmaceutically acceptable carrier, and the structural formula of described menthol is as follows:
2. compositions according to claim 1, is characterized in that: the percentage by weight that described menthol accounts for said composition is 30～50%.
3. compositions according to claim 1, is characterized in that: on described medicine, acceptable carrier comprises PVP K30, micropowder silica gel or magnesium stearate.
4. compositions according to claim 1, is characterized in that: on described medicine, acceptable carrier comprises filler.
5. compositions according to claim 4, is characterized in that: described filler comprises one or more in microcrystalline Cellulose, starch, lactose, dextrin, carboxymethylstach sodium.
6. compositions according to claim 1, is characterized in that, the weight portion of described pharmaceutical composition is:
7. the preparation method of blood pressure lowering pharmaceutical composition, is characterized in that, has following steps:
1) get menthol and pharmaceutically acceptable carrier by dosage claimed in claim 6, after acceptable carrier sieves respectively, mixes on medicine, add menthol, equivalent incremental method mix homogeneously;
2) add PVP K30 soft material processed, 20 mesh sieves are granulated, 24 mesh sieve granulate, and 40-45 ℃ is dry;
3) dry granule adds magnesium stearate, mixes, and tabletting, obtains blood pressure lowering pharmaceutical composition.
8. the preparation method of blood pressure lowering pharmaceutical composition, is characterized in that, has following steps:
1) getting menthol by dosage claimed in claim 6 mixes for subsequent use;
2) get lactose, microcrystalline Cellulose, starch, carboxymethylstach sodium by dosage claimed in claim 6 and be dried 2 hours respectively in 100 ℃ of left and right, cross 100 mesh sieves;
3) above-mentioned adjuvant is mixed homogeneously by equivalent incremental method with mixed crude drug, pelletizing machine granulate, pellet moisture >5%, 30 mesh sieve granulate, capsule fill, obtains blood pressure lowering pharmaceutical composition.
9. the application of blood pressure lowering pharmaceutical composition claimed in claim 1 in preparation treatment hypertension drug.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106491628A (en) * | 2016-12-17 | 2017-03-15 | 郑州郑先医药科技有限公司 | A kind of Western medicine compound for treating hypertension |
| CN106822234A (en) * | 2016-12-17 | 2017-06-13 | 郑州郑先医药科技有限公司 | It is a kind of to treat Chinese and western medicinal composition of hypertension and preparation method thereof |
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| CN103442727A (en) * | 2011-02-11 | 2013-12-11 | Zx制药有限责任公司 | Multiparticulate l-enthol formulations and related methods |
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| CN106491628A (en) * | 2016-12-17 | 2017-03-15 | 郑州郑先医药科技有限公司 | A kind of Western medicine compound for treating hypertension |
| CN106822234A (en) * | 2016-12-17 | 2017-06-13 | 郑州郑先医药科技有限公司 | It is a kind of to treat Chinese and western medicinal composition of hypertension and preparation method thereof |
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