CN101120939A - Medicinal composition containing nitrate esters for treating ventricular hypertrophy or myocardial fibrosis - Google Patents
Medicinal composition containing nitrate esters for treating ventricular hypertrophy or myocardial fibrosis Download PDFInfo
- Publication number
- CN101120939A CN101120939A CNA200610104332XA CN200610104332A CN101120939A CN 101120939 A CN101120939 A CN 101120939A CN A200610104332X A CNA200610104332X A CN A200610104332XA CN 200610104332 A CN200610104332 A CN 200610104332A CN 101120939 A CN101120939 A CN 101120939A
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- Prior art keywords
- myocardial
- heart
- hypertrophy
- group
- nitroglycerin
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Landscapes
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Abstract
Myocardial hypertrophy is a pathological change of a plurality of kinds of angiocardiopathy. The main mode is the heart remodeling comprising cardiac muscle cell hypertrophy and change of the interstitial tissue component mainly. In the present invention, the nitrate medicine is used in treatment for myocardial hypertrophy caused by various reasons and excellent therapy effect is obtained. Currently the nitrate medicine is extensively applied in treatment for the coronary heart disease, the heart colicky pain and heart failure. Preload of the heart and myocardial consumption of oxygen are reduced by extension of the venous system. The drugs used in clinical field currently comprise Nitroglycerin, Amyl Nitrite, dicho nitric acid sorbite, sorbide dinitrate, 5-isosorbide dinitrate, Nitroglycerin, pentanitrol ters and itramine tosylate.
Description
Affiliated technical field
The invention belongs to the Western medicine new technique, be characterized in increasing the treatment of new clinical symptoms.
Background technology
Myocardial hypertrophy, or be called ventricular hypertrophy, left ventricular hypertrophy is an independent hazard factor of cardiovascular system diseases.Since the eighties, people recognize that progressively myocardial hypertrophy is myocardial cell and the myocardium Interstitial cell adaptation response to multiple stimulation (pressure load, stretching, the neuro humor factor, vasoactive peptide, cytokine, somatomedin etc.), are the results that series of genes unconventionality expression and cell phenotype change in the cell.Myocardial hypertrophy and myocardial fibrosis can be described as two aspects of a disease, and the myocardial hypertrophy due to the factors such as hypertension is all with myocardial fibrosis.
Myocardial hypertrophy is the common a kind of pathological change of hyperpietic, and the statistics of China show, the hyperpietic myocardial hypertrophy probability is taken place is 6 times of normal person.It is main forms that this disease is changed into main heart reconstruction with a myocardial cell hypertrophy and a matter composition.Behind the myocardial hypertrophy, the not corresponding increase of the blood supply of myocardial cell, on the contrary, and myocardial hypertrophy, the tension force of ventricle wall increases, and oxygen consumption increases, and remerges cardiac dilatation and then forms hypertensive heart disease.
Blood in human body in voltage rise height, heart need stronger contraction blood could be extruded.In the course of time, cardiac muscle will become plump.Under the effect of Angiotensin II, unusual reconstruct has taken place in cardiac muscle, and plump cardiac muscle is mainly the disorderly myocardial cell of arranging, and fibrosis occurs, so its contractility descends.And Fibrotic myocardial wall hardening, flexibility decrease has also influenced the ability that heart contraction is penetrated blood.Long-term hypertension can cause heart damage, makes heart be the centration myocardial hypertrophy, and the chambers of the heart diminishes, each oligemia that penetrates that shrinks.Though the overweight initial stage myocardial hypertrophy of heart long-term load is a kind of useful compensation response, the persistence myocardial hypertrophy finally can cause DCM (dilated cardiomyopathy), heart failure or sudden death.
Cause the reason of hyperpietic's myocardial hypertrophy to have following several: patients with hypertension blood plasma catechlolamine concentration raises, and norepinephrine induces myocardium protein synthetic, causes myocardial hypertrophy.Interventricular septum is high to the sensitivity of norepinephrine than right ventricle and LVPW, may thicken one of reason early than LVPW for interventricular septum.Blood pressure raises has for a long time increased the burden of left ventricle, and left ventricle is shunk load excessively, also is the reason of myocardial hypertrophy.Different antihypertensive drug is very not identical to the influence of myocardial hypertrophy.Data shows, angiotensin converting enzyme inhibitor (captopril, enalapril) can effectively prevent and reverse left ventricular hypertrophy, beta-blocker, fragrance propylhomoserin decarboxylase inhibitor (alpha-methyldopa) and calcium antagonist also have similar curative effect, and the function of diuretic reverse myocardial hypertrophy a little less than.
Nitrate esters can particularly increase the venous blood capacity by the expansion peripheral blood vessel, reduces capacity of returns, reduces heart front and back load, and reduces myocardial oxygen consumption.Be mainly used in the long-term treatment of coronary heart disease; Anginal prevention; Continue anginal treatment behind the myocardial infarction; With Folium Digitalis Purpureae or diuretic use in conjunction, the treatment chronic heart failure.The main pharmacological of organic nitrates is lax vascular smooth muscle, discharge nitric oxide (NO), nitric oxide is identical with the relaxing factor that endothelium discharges, activate guanylate cyclase, cyclic guanylic acid (cGMP) is increased, myosin light chain dephosphorylation, thereby lax vascular smooth muscle, coronary artery dilator, coronary blood flow increasing; The expansion peripheral arterial reduces peripheral vascular resistance, brings high blood pressure down; Stronger to the venous dilating effect.
This class medicine is distributed to whole body rapidly through intravenously administrable, and content is higher in heart, cerebral tissue and pancreas, and fatty tissue, skin, colon, adrenal gland and liver content are lower, and plasma protein binding rate is low.Almost completely by metabolism, phenomenon does not appear accumulating to nitrate esters in the hepatopath at liver.In the experimental study process, find that nitrate esters medicine has the obvious suppression effect to myocardial hypertrophy.
Summary of the invention
We are in to the further research process of the pharmacological action of nitrate esters medicine, and beyond thought discovery nitrate esters medicine is to myocardial hypertrophy or myocardial fibrosis better curative effect.Therefore, we are in conjunction with the clinical practice case characteristics of nitrate esters medicine, constructively propose nitrate esters medicine is used for the myocardial hypertrophy due to a variety of causes or the treatment of myocardial fibrosis.
Except that known coronary artery dilator, allevating angina pectoris are to load, improve the main effect of cardiac function before and after nitrate, medicament for expanding vascellum reduce heart, find by more deep pharmacological research that also nitrate esters medicine also can be used as the medicinal application of prevention and treatment myocardial hypertrophy or myocardial fibrosis in clinical.
We find in experiment, nitrate esters medicine has the obvious suppression effect to ventricular hypertrophy or the myocardial fibrosis due to the multiple reason, as the left room index of the left room index of the left room index of salt Hypertensive Rats, Levothyroxinnatrium myocardial hypertrophy rat model and myocardial collagen content, chronic stress Hypertensive Rats and myocardial collagen content or the like are all had significant treatment effect.Our zoopery result is indicating, nitrate esters medicine can be used in the future a kind of treatment of new indication clinically, and present this indication does not still have ideal medicine clinically, though a lot of antihypertensive drug can effectively reduce patient's blood pressure, but the ventricular hypertrophy to the hyperpietic does not have tangible curative effect, only several antihypertensive drug, though for example angiotensin-convertion enzyme inhibitor, angiotensin receptor antagonist etc. can reverse patient's ventricular hypertrophy, effect is not very good yet.We also find in experiment, nitrate esters medicine and process clinical verification now, there is the antihypertensive drug that reverses the ventricular hypertrophy effect to unite use, on every index to myocardial hypertrophy and myocardial fibrosis, for example left room index and ventricular muscles collagen content have been obtained ideal concertedness effect.Myocardial hypertrophy or to be called left ventricular hypertrophy, ventricular hypertrophy be one of the most significant complication of hyperpietic, it is one of the strongest prediction index of hyperpietic's prognosis, also be the therapeutic goal that needs most concern in the hypertension therapeutic process, this for the prophylaxis of hypertension patient various cardiovascular disease takes place later on crucial meaning.Right ventricular hypertrophy is a pulmonary hypertension severe complications the most, also is the most important cause of death of patients with pulmonary hypertension later stage.
Myocardial hypertrophy extensively sees multiple diseases such as hypertensive heart disease, pulmonary heart disease and heart failure.When the clinical epidemiology data shows the hypertensive patients myocardial hypertrophy, the incidence rate of cardiovascular accident obviously increases, as sudden death, myocardial infarction, arrhythmia, myocardial ischemia, heart failure etc., therefore, prevention and reverse myocardial hypertrophy are the problems of attracting attention in the current treatment cardiovascular disease.
Administering mode that the present invention adopts is an oral administration, and simple, the easy row of this kind route of administration is workable, is easy to accept into patient.
The specific embodiment
According to the scope of getting involved of myocardial hypertrophy, can be divided into left heart plumpness, the plump plumpness whole-heartedly that reaches of the right heart.Wherein the caused by hypertension myocardial hypertrophy is mainly seen in hypertensive pulmonary vascular disease.Serious myocardial hypertrophy can merge hypertensive pulmonary vascular disease, thereby may involve whole heart.
Embodiment 1
Isosorbide mononitrate is to the inhibitory action of DOCA-salt type rat hypertension myocardial hypertrophy
DOCA-salt type rat hypertension myocardial hypertrophy model belongs to endocrine type hypertension hypertrophy model, for the low renin type, adds saline to deoxycorticosterone, forms capacity overload hypertension myocardial hypertrophy model.
1. experiment material
1.1 medicine isosorbide mononitrate (southern Shandong pharmacy joint-stock company) sodium chloride (the safe chemical actual company limited lot number 20040318 specification 500g analytical pure in Shen, Tianjin) normal saline (Accessories during Binzhou pharmaceutical factory lot number 04111304 specification 500ml) nifedipine (Surabaja Xi Erkang pharmaceutical Co. Ltd lot number 200410224 specification 10mg100 sheets)
1.2 instrument Sartorius analytical balance (Beijing Sai Duolisi instrument system company limited) electronic scale (Shanghai big magnificent electronic scale factory)
1.3 animal SD rat cleaning level body weight 150～200g male and female dual-purpose, Shandong Xinshidai Pharmaceutical Industry Co., Ltd.'s animal center provides, the animal quality certification number: SYXK (Shandong) 0057
2. experimental technique
2.1 the foundation of model and 60 of grouping SD rats, body weight 100～150g, male and female half and half.Laboratory rearing is divided into model group, sham operated rats, positive drug (nifedipine) matched group, the basic, normal, high dosage group of isosorbide mononitrate at random by body weight after two weeks, amounts to 6 groups.All the other each treated animal lumbar injection 3% pentobarbital sodium 50mg/kg anesthesia except that sham operated rats, the animal lateral position is placed, the wild cropping of art, skin degerming removes left kidney (not extracing the adrenal gland) in abdomen median line incision scissors, does not touch right kidney, sews up.Every Mus right hind intramuscular injection penicillin 20,000 unit prevention infection.Sham operated rats is only done to cut to handle and is not made the kidney excising operation, and all the other are operated with other treated animals.All rat postoperative one peritheliums down injection give deoxycorticosterone (DOCA is dissolved in normal saline) dosage 50mg/kg, and 5 times weekly, totally 5 weeks.The conventional raising, and freely drink for 1% sodium chloride.In 5 weeks of postoperative, each administration group rat oral gavage gives relative medicine; Model group is irritated stomach and is given pure water; Sham operated rats freely gives fresh water.
2.2 experimental index is measured 9 weeks of postoperative, puts to death rat, weighs.Take out heart, remove the cardiovascular injuries undesirable root, wash residual to the greatest extent blood, claim left ventricle weight in wet base (LV+VS) behind the filter paper suck dry moisture, calculate LV+VS/ body weight value (g/g).
2.3 all data of statistical analysis with
Expression, t check and variance analysis are adopted in each index contrast between group, relatively calculate the p value in twos.
3. experimental result
Table 1. isosorbide mononitrate is to the inhibitory action of DOCA-salt type rat hypertension myocardial hypertrophy
| Group | Dosage (mg/kg) | LV+VS/ body weight (g/g) |
| Dosage list nitre high dose in the single nitre low dosage of the model group sham operated rats positive controls list nitre | - - 7 1.5 4.5 13.5 | 4.53±0.52 2.17±0.33 △△ 4.26±0.38 △ 4.21±0.31 △ 3.77±0.52 △△▲ 4.63±0.79 |
Annotate: compare with model group
△P＜0.05
△ △Compare with positive controls p＜0.01
▲P＜0.05.
4 discuss
This institute drug dose get for converting according to people and laboratory animal dosage, thereby the result has certain significance for reference to clinical application.
This paper adopts the method give DOCA and high salt drinking-water to set up rat left chamber's hypertrophy model due to the capacity overload, and its LV/ body weight all obviously increases than sham operated rats.When preventative and therapeutic give single nitre after, These parameters significantly descends, and shows that single nitre can prevent and reverse the left ventricular hypertrophy of rat due to the capacity overload.And this experiment finds that single nitre low dosage does not reduce rat left chamber's plumpness significantly, and middle dosage suppresses the plump effect of rat heart muscle obviously, points out that the left ventricular hypertrophy of rat has the doses dependency due to single nitre prevention and the overload of the capacity of reverse.
Embodiment 2
Nitroglycerin is to the inhibitory action of myocardial hypertrophy due to the Levothyroxinnatrium
Thereby heavy dose of Levothyroxinnatrium can promote human body myocardial cell mRNA and protein synthesis to make myocardial hypertrophy.ATP exhausts that oxygen consumption increases, and heart muscle capillary density reduces, thereby the distance of oxygen from the blood capillary disperse to the myocardial cell center increased, so myocardial hypertrophy has the ischemia tendency, exists to be dispersed in the ischemia infringement.
1. experiment material
1.1 ( 200506075mg/ ) ( F20050302500g ) L- ( 360060150μg/ ) MDA、SOD ( 05030606 ) ( 20041020500g ) ( 20050324500g ) ( 20050620500ml ) ( 2006011725g ) T ( 20051121500g ) ( 20040125500ml )
1.2 instrument Sartorius analytical balance (Beijing Sai Duolisi instrument system company limited) electronic scale (Shanghai big magnificent electronic scale factory) 721UV spectrophotometer
1.3 animal SD rat cleaning level body weight 150～200g male and female dual-purpose, Shandong Xinshidai Pharmaceutical Industry Co., Ltd.'s animal center provides, the animal quality certification number: SYXK (Shandong) 0057
2. experimental technique
2.1 the foundation of model and 60 of grouping SD rats, male and female are regardless of, body weight 250-300g.Be divided into blank group, model group, positive control (captopril) group, the basic, normal, high dosage group of nitroglycerin at random by body weight, amount to 6 groups, 10 every group.Except that the normal control group, all the other each treated animals are irritated stomach and are given Levothyroxinnatrium (0.5% sodium carboxymethyl cellulose is mixed with suspension) 1mg/ (kgd), successive administration 10 days, and each administration group gives relative medicine, continuous 14 days in irritating stomach on the 8th day for Levothyroxinnatrium.
2.2 experimental index is put to death animal after measuring last administration 24h, take out heart, calculate cardiac index and ventricle index according to cardiac weight, ventricular weight and body weight, with cardiac muscular tissue's homogenate, measure its MDA (thiobarbituricacid method) and collagen protein (hydroxyproline content algoscopy) content then.
2.3 all data of statistical analysis with
Expression, t check and variance analysis are adopted in each index contrast between group, relatively calculate the p value in twos.
3. experimental result
Table 2. nitroglycerin is to the inhibitory action of myocardial hypertrophy due to the Levothyroxinnatrium
| Group | Dosage (mg/kg) | The ventricle index |
| Dosage nitroglycerin high dose in the blank group model group positive controls nitroglycerin low dosage nitroglycerin | - - 25 1.5 4.5 13.5 | 2.54±0.17 2.99±0.19 2.81±0.17 ▲ 2.84±0.26 2.55±0.20 ▲▲△△ 2.63±0.16 ▲▲△△ |
Annotate: compare with model group
▲ ▲P＜0.01,
▲P＜0.05 is compared with positive controls
△ △P＜0.01
Table 3. nitroglycerin is to the influence of rat hypertrophic cardiomyopathy MDA
| Group | Dosage | The OD value |
| Dosage nitroglycerin high dose in the blank group model group positive controls nitroglycerin low dosage nitroglycerin | - - 25 1.5 4.5 13.5 | 0.65±0.17 ▲▲ 0.96±0.21 1.00±0.40 0.91±0.35 0.75±0.28 ▲△△ 0.69±0.30 ▲▲△△ |
Annotate: compare with model group
▲ ▲P＜0.01,
▲P＜0.05,
Compare with positive controls
△P＜0.05,
△ △P＜0.01.
Table 4. nitroglycerin is to the influence of rat hypertrophic cardiomyopathy collagen content
| Group | Dosage | The OD value |
| Dosage nitroglycerin high dose in the blank group model group positive controls nitroglycerin low dosage nitroglycerin | - - 25 1.5 4.5 13.5 | 0.25±0.06 ▲▲ 0.44±0.09 0.36±0.04 ▲▲ 0.21±0.05 ▲▲△△ 0.15±0.03 ▲▲△△ 0.13±0.04 ▲▲△△ |
Annotate: compare with model group
▲ ▲P＜0.01 is compared with positive controls
△ △P＜0.01.
4. discuss
Compare with matched group, model group cardiac index, ventricle index be obviously rising (P＜0.01) all, the middle and high dosage of nitroglycerin (P＜0.01) group can suppress the exponential rising of rat heart that Levothyroxinnatrium causes effectively, the formation (table 1) of antagonism rat heart muscle plumpness.Compare with matched group, nitroglycerin can significantly improve SOD activity (table 2) in the rat heart muscle, and reduces the generation (table 3) of MDA, is good (P＜0.05, P＜0.01) with middle and high dosage especially, and presents dose-dependence.Compare with matched group, nitroglycerin can obviously alleviate myocardial hypertrophy rat heart muscle fibrosis (table 4).Explanation thus, nitroglycerin has obvious therapeutic action to the myocardial hypertrophy model that Levothyroxinnatrium causes.
We find that by test isosorbide mononitrate is inhibited equally to myocardial hypertrophy due to the Levothyroxinnatrium, and have obtained the effect same with nitroglycerin.
Embodiment 3
Isosorbidi dinitras is to the inhibitory action of irritability rat hypertension model
Adopt cold water stimulating to prepare the irritability hypertensive rat model in conjunction with the method that noise stress stimulates.Irritability is hypertensive to be the result of multiple factor interaction in the body.As in stress process, renin-angiotensin system (RAS) hyperfunctioning, sympatheticotonia increase, adrenal medulla discharge epinephrine and norepinephrine or the like, and some have material synthetic of antagonism or discharge with above-mentioned functions and occur unusually simultaneously.
1. experiment material
1.1 medicine isosorbidi dinitras slow releasing capsule (self-control) dehydrated alcohol (beach, Qingdao chemical reagent factory lot number 200511019 specification 500ml analytical pure)
1.2 instrument Sartorius analytical balance (Beijing Sai Duolisi instrument system company limited) electronic scale (Shanghai big magnificent electronic scale factory) 721UV spectrophotometer speaker electric bell
1.3 animal SD rat cleaning level body weight 150～200g male and female dual-purpose, Shandong Xinshidai Pharmaceutical Industry Co., Ltd.'s animal center provides, the animal quality certification number: SYXK (Shandong) 0057
2. experimental technique
2.1 the foundation of model is adopted 50 of SD rat, male and female half and half with grouping.Be divided into normal group, model group, the basic, normal, high dosage group of isosorbidi dinitras at random by body weight, amount to 5 groups, 10 every group.Except that the normal control group, all the other each treated animals are put into soundproof room and are raised in cages, and noise stimulation can be sent by electric bell or speaker, and noise jamming is day and night more than; Daytime every animal is placed 6 ℃ of cold water simultaneously, continue 5min; Crowd evening and spend the night; Continuous March.Each administration treated animal is irritated stomach and give relative medicine, same continuous 3 months every day during this time.
2.2 experimental index is measured the last crowded back of spending the night and is put to death animal, take out heart left ventricle and interventricular septum (LV+VS), calculate the ventricle index according to (LV+VS) weight and body weight, then with cardiac muscular tissue's homogenate, measure its MDA and collagen content, method is with embodiment 2.
2.3 all data of statistical analysis with
Expression, t check and variance analysis are adopted in each index contrast between group, relatively calculate the p value in twos.
3. experimental result
Table 5. isosorbidi dinitras is to the influence of rat heart muscle plumpness
| Group | Dosage | The LV+VS/ body weight |
| Dosage isosorbidi dinitras high dose in the blank group model group isosorbidi dinitras low dosage isosorbidi dinitras | - - 1.56 4.67 14.0 | 1.79±0.14 2.85±0.29 2.56±0.25 ▲ 2.16±0.28 ▲▲ 2.07±0.27 ▲▲ |
Annotate: compare with model group
▲P＜0.05,
▲ ▲P＜0.01.
Table 6. isosorbidi dinitras is to the influence of rat hypertrophic cardiomyopathy MDA
| Group | Dosage | The OD value |
| Dosage isosorbidi dinitras high dose in the blank group model group isosorbidi dinitras low dosage isosorbidi dinitras | - - 1.56 4.67 14.0 | 0.14±0.02 0.76±0.02 △△ 0.63±0.05 0.46±0.02 ▲ 0.29±0.03 ▲▲ |
Annotate: compare with model group
▲ ▲P＜0.01,
▲P＜0.05.
Table 7. isosorbidi dinitras is to the influence of rat hypertrophic cardiomyopathy collagen content
| Group | Dosage | The OD value |
| Dosage isosorbidi dinitras high dose in the blank group model group isosorbidi dinitras low dosage isosorbidi dinitras | - - 1.56 4.67 14.0 | 0.23±0.06 0.41±0.10 0.38±0.04 0.35±0.05 0.28±0.03 ▲ |
Annotate: compare with model group
▲P＜0.05
4. discuss
The hypertension model that this experiment is adopted is a stress in rats hypertension myocardial hypertrophy model.Rat is in noise or key over a long time and stings the When sound and stimulate listening under the sexual tension situation of source of causing, but inducing neural originality hypertension, and it and people's hypertension is similar, is applicable to the screening of antihypertensive drugs.Compare this experimental model modeling success with the blank group.With model group relatively, each dosage group of isosorbidi dinitras all shows the inhibitory action to myocardial hypertrophy due to this model.Isosorbidi dinitras has reduced the ventricular hypertrophy index of stress rats, is highly resistant to the myocardial cell lipid peroxidation, alleviates stress rats myocardial fibrosis degree.
Embodiment 4
Isosorbide mononitrate sustained release tablets
1. write out a prescription
Per 1000 contain following material
Isosorbide mononitrate 2.6g (10% alcoholic solution 29.5ml)
Stearic acid 60.g
Hexadecanol 66.g
Polyvidone (PVP) 31.g
Microcrystalline Cellulose 58.8g
Micropowder silica gel 5.4g
Lactose 49.8g
Pulvis Talci 24.9g
Magnesium stearate 1.5g
2. technological process
PVP is dissolved in the isosorbide mononitrate alcoholic solution, adds the micropowder silica gel mixing, add stearic acid and hexadecanol, heating in water bath to 60 ℃ makes molten.Microcrystalline Cellulose, lactose, talcous homogeneous mixture are added in the system of above-mentioned fusing, stirred 1 hour; Above-mentioned heavy-gravity mixture is spread out in dish, and room temperature was placed 20 minutes, when treating into agglomerate, granulated with 16 mesh sieves.30 ℃ of dryings, granulate adds magnesium stearate, tabletting, promptly.
Embodiment 5
The isosorbidi dinitras slow releasing capsule
1. write out a prescription
Isosorbidi dinitras 300g
Microcrystalline Cellulose 40g
5% hypromellose solution is an amount of
Eudragit E udragitRS100 (coating solution) is an amount of
Sodium lauryl sulphate 0.8g
Pulvis Talci 108.8g
Make 1000 isosorbidi dinitras slow releasing capsule.
2. technological process
2.1 the preparation of ball core: isosorbidi dinitras is pulverized, crossed 120 mesh sieves, standby.Take by weighing recipe quantity 40 orders～60 order microcrystalline Cellulose kinds nuclear, place in the coating pan, open coating pan, spray adhesive (5% hypromellose solution) moistening kind nuclear surface, add a spot of isosorbidi dinitras, so repeatedly, kind of nuclear is increased.After treating that isosorbidi dinitras adds, be rotated further machine, polishing 6min takes the dish out of the pot, 60 ℃ of oven dry, and sieve is got 18 orders～24 order medicated core.
2.2 coating: take by weighing 1000g18 order～24 order medicated core and place in the coating pan, other gets coating solution aqueous dispersion 372g, Pulvis Talci 108.8g, sodium lauryl sulphate 0.8g, water 320ml starts coating pan, treats to take the dish out of the pot after coating solution has sprayed, 40 ℃ of oven dry 24h: the capsule of packing into No. 1, take a sample, check, pack, promptly get the isosorbidi dinitras slow releasing capsule.
Claims (3)
1. a pharmaceutical composition that contains nitrate esters medicine is characterized in that it is to be used to prepare a kind of medicine for the treatment of myocardial hypertrophy or myocardial fibrosis.
2. nitrate esters medicine as claimed in claim 1, it is isosorbide mononitrate, sorbide nitrate, nitroglycerin or pentaerithrityl tetranitrate.
3. a kind of pharmaceutical composition that contains nitrate esters medicine as claimed in claim 1 is characterized in that it is used to prepare myocardial hypertrophy that a kind of treatment causes by hypertension or the medicine of the myocardial fibrosis that caused by hypertension.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101597231B (en) * | 2009-07-10 | 2012-07-04 | 中国人民解放军第四军医大学 | NO donor medicine and synthesis method thereof |
| CN112121025A (en) * | 2019-06-24 | 2020-12-25 | 翰宇药业（武汉）有限公司 | Isosorbide mononitrate sustained-release tablet and preparation method thereof |
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2006
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101597231B (en) * | 2009-07-10 | 2012-07-04 | 中国人民解放军第四军医大学 | NO donor medicine and synthesis method thereof |
| CN112121025A (en) * | 2019-06-24 | 2020-12-25 | 翰宇药业（武汉）有限公司 | Isosorbide mononitrate sustained-release tablet and preparation method thereof |
| WO2020258472A1 (en) * | 2019-06-24 | 2020-12-30 | 深圳翰宇药业股份有限公司 | Isosorbide mononitrate sustained release tablet and preparation method therefor |
| CN112121025B (en) * | 2019-06-24 | 2022-05-31 | 翰宇药业（武汉）有限公司 | Isosorbide mononitrate sustained-release tablet and preparation method thereof |
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