CN101919855A - Pharmacy application of piperazine ferulate - Google Patents
Pharmacy application of piperazine ferulate Download PDFInfo
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- CN101919855A CN101919855A CN 201010163066 CN201010163066A CN101919855A CN 101919855 A CN101919855 A CN 101919855A CN 201010163066 CN201010163066 CN 201010163066 CN 201010163066 A CN201010163066 A CN 201010163066A CN 101919855 A CN101919855 A CN 101919855A
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Abstract
The invention discloses pharmacy application of piperazine ferulate, and in particular application of piperazine ferulate and/or derivatives thereof to preparing drugs for preventing and/or treating pulmonary hypertension. The invention provides novel application of the piperazine ferulate and/or the derivatives thereof, i.e. application of the piperazine ferulate to preparing drugs for preventing and treating pulmonary hypertension, especially diseases with pulmonary vascular resistance progressive increase as main characteristic.
Description
Technical field
The pharmacy that the present invention relates to piperazine ferulate is used.
Background technology
Pulmonary hypertension is that a class increases with carrying out property of pulmonary vascular resistance is principal character, finally causes seriously limited, the dead disease of right heart failure, function.It is a kind of extreme malignant disease, and patient more than seventy percent is a youngster; It is the non-constant in back more, has the people that its analogy is " cancer in the cardiovascular disease ".Pulmonary hypertension is divided into constitutional (or special property sent out) and Secondary cases two classes.Wherein primary pulmonary hypertension is Pulmonic endothelium tumor, growth and covering with in the pulmonary artery blood tube chamber fast after being equivalent to endotheliocyte and cancerating, all venous blood therefore all by the pulmonary artery retaining in a side.As not having correct treatment, the patient can die from incorrigible right heart failure very soon.
The pulmonary hypertension average age of onset is 36 years old, and 75% patient concentrates on 20～40 years old age bracket, also has 15% patient age below 20 years old, and child how old also can fall ill.Patients with pulmonary hypertension 75% patient dies from after the diagnosis 5 years, and it is 1.9 years that the back mean survival time (MST) appears in symptom; The right heart failure shower is arranged, and the mean survival time was less than 1 year.Along with the progress of treatment means, patient's life span is increasing year by year.Early diagnosis treatment in time can make 20% patient's stable disease, even recovery from illness.
MPAP 〉=30mmHg when pulmonary hypertension (PAH) mean pulmonary arterial pressure when being meant tranquillization (mPAP)＞25mmHg (1mmHg=0.133kPa) or motion, it is by the little vascular proliferation of lung, reinvents the disease that causes, can cause the increase of carrying out property of pulmonary vascular resistance, right heart failure, death finally appear in the patient.The conventional therapy of pulmonary hypertension comprises oxygen uptake, oral anticoagulant medicine, unites and use the diuretic therapy right heart failure at present.In recent years, many new medicines such as prostacyclin and derivant thereof, bosentan, sldenafil etc. begin to be applied to clinical, make patient's exercise tolerance, survival rate, quality of life etc. obviously improve.(1) endogenic prostacyclin all is a kind of strong vasodilation in pulmonary circulation and body circulation, and has powerful antiplatelet aggregative activity; The prostacyclin synthetic significantly reduces in the lung tissue endotheliocyte of patients with pulmonary hypertension.Therefore, using exogenous prostacyclin analogs, as epoprostenol, hilo prostaglandin, bent prostaglandin, beraprost, is a kind of alternative medicine, has played important function in the treatment of modern pulmonary hypertension.(2) bosentan is a kind of non-selective ET receptor antagonist, has antagonism endothelin receptor A and the active oral medicine of endothelin receptor B dual receptor, and its bioavailability of oral back is approximately 50%, and the half-life is about 5h.Bibliographical information, 16 week of treatment back bosentan group 6min walking distance prolongs 36m, and does not have obvious dependency with drug dose, and placebo group shortens 8m; Bosentan can also improve Borg dyspnea index in addition, shortens clinical symptoms and time of worsening occurs, and comprises death, lung transplantation, the number of times of being in hospital, due to illness feelings worsen and withdraw from test or need iloprost therapeutic alliance and interatrial septum fistulation etc.Bosentan mainly by liver metabolism, is removed without kidney substantially.Main adverse reaction is a liver function injury, and relevant with dosage.Other untoward reaction comprises hemogram attenuating, headache, Blushing etc.(3) sldenafil is a kind of high selectivity phosphodiesterase-5 inhibitor, by suppressing the 5-phosphodiesterase, and then increased the concentration of cGMP in the lung blood vessel (cGMP is that nitric oxide is regulated pulmonary vascular second message,second messenger), make endogenic nitric oxide effect more lasting; Sldenafil can reduce pulmonary vascular resistance (PVR), pulmonary artery pressure, and circulation is pressed and then do not made significant difference to body.Although these medicines have been obtained certain curative effect to the treatment of pulmonary hypertension, also alleviate conditions of patients to a certain extent, but still can not satisfy the requirement of clinical treatment, can not control fully as the pulmonary hypertension state of an illness, can increase the weight of gradually; Adverse effect influences therapeutic effect etc.Thereby, seek new pulmonary hypertension medicine safely and effectively, ensure that vast patients with pulmonary hypertension is healthy, be urgent, be necessary.
Piperazine ferulate, chemical name are 3-methoxyl group-4 hydroxyl cinnamic acid piperazine, come by ferulic acid and piperazine chemosynthesis.Modern pharmacological research confirms, piperazine ferulate has following pharmacological action: (1) piperazine ferulate is observed the influence of guinea pig isolated heart coronary flow, increase by 35.55% than average perfusion flow before the administration after the administration, P＜0.001, the difference highly significant, than ligustrazine (27.8%), sodium ferulate (21.7%) coronary flow increases obviously.(2) piperazine ferulate can cause that the tremulous pulse bar shrinks, its inhibitory action average out to 102.43% to antiadrenergic drug, with the suppression ratio (85.43%) of ligustrazine and the suppression ratio (73.97%) of sodium ferulate significant differences (P＜0.001) is arranged more all.(3) piperazine ferulate is assembled for the ADP induced platelet tangible antagonism, the average optical rate of descent is 13.4% in the time of 30 seconds, be 7.1% in the time of 10 minutes, with matched group (being respectively 56.9% and 74.3%) relatively, highly significant difference (P＜o.001) is arranged.Compare with ligustrazine, there were significant differences in the 3-20 timesharing (P＜0.05).Compare with sodium ferulate, there were significant differences (P＜0.05) timesharing in 30 seconds-5.(4) piperazine ferulate obviously prolongs the recalcification time of Canis familiaris L. venous blood, and 15,30,60 minutes and the preceding comparison of administration all have notable difference (P＜0.05) after the administration, then return to normal level after 90 minutes.Prolonging also appears 15,30,60 minutes the time after administration in the prothrombing time, but only there were significant differences in the time of 15 minutes (P＜0.05).(5) experimental result to rabbit ventricular muscle cell action potential on the throne shows, behind intravenous injection piperazine ferulate 7-10 minute, the 297 scholar 54v/ss of myocardial cell action potential zero mutually maximum depolarization speed before the administration drop to 264 scholar 47v/s (P＜0.001), continue 60 minutes, illustrate that this medicine has the effect that delays the conduction of myocardial cell action potential, play the increase myocardial contraction, improve sanguimotor effect.Therefore, piperazine ferulate is mainly used in treatment of diseases such as cerebrovascular, coronary heart disease, renal glomerular disease, diabetic angiopathy change, vasculitis clinically; Therapeutic dose is 100-200mg/ time, three times on the one.(1) be used for the treatment of cerebral infarction 55 examples, produce effects 16 examples, 25 examples that take a turn for the better, total effective rate is 74.54%, compares with low molecular dextran 30 examples, learns by statistics and handles no significant difference.But compare from hemorheology index, do not have before and after the treatment of low molecular dextran group and improve, and be significantly improved after the treatment of piperazine ferulate group (P＜0.05-0.01).(2) be used for the treatment of angina pectoris 51 examples, wherein produce effects 21 examples are improved 20 examples, and total effective rate is 80.2%.ECG curative effect is analyzed, and produce effects 15 examples are improved 16 examples, total effective rate 60.7%.(3) be used for the treatment of thromboangiitis obliterans 8 examples, produce effects 4 examples, 2 examples that take a turn for the better, progressive 2 examples.(4) treatment renal glomerular disease 7 examples, treatment back fibrinogen (Fl) obviously reduces by 6 examples, and urine FDP obviously reduces by 5 examples.
We are through lot of documents retrieval discovery, and piperazine ferulate is not applied to the bibliographical information of pulmonary hypertension aspect in the clinical treatment of diseases such as coronary heart disease, cerebrovascular, renal glomerular disease, diabetic vascular complications, vasculitis that are mainly used in; And piperazine ferulate treatment during these diseases routine dose be 100-200mg/ time, three times on the one.
Summary of the invention
Technical problem to be solved by this invention has provided the new purposes of the derivant of piperazine ferulate and/or piperazine ferulate, specifically is to prevent and/or treat application in the medicine of pulmonary hypertension in preparation.
The present invention addresses the above problem the technical scheme that is adopted: the derivant of piperazine ferulate and/or piperazine ferulate prevents and/or treats application in the medicine of pulmonary hypertension in preparation.
The object of the present invention is to provide the new purposes of piperazine ferulate and derivant thereof, promptly piperazine ferulate is at preparation prevention and treatment pulmonary hypertension, and especially increasing with carrying out property of pulmonary vascular resistance is application in the disease medicament of principal character.
The present invention relates to piperazine ferulate as the application in property pulmonary hypertension before preparing prevention and treating blood capillary such as the medicines such as primary pulmonary hypertension, pulmonary infarction.
The present invention relates to piperazine ferulate as preparation prevention with treat application in high dynamic property pulmonary hypertension such as the medicines such as congenital heart disease, hyperthyroidism.
The present invention relates to piperazine ferulate as the application in property pulmonary hypertension after preparing prevention and treating the hair and blood pipe such as the medicines such as mitral stenosis, left heart failure.
Piperazine ferulate of the present invention, be meant the derivant chemical compound of revising based on any structure of 3-methoxyl group-4 hydroxyl cinnamic acid piperazine similar, comprise and be not limited to piperazine ferulate, sodium ferulate, ferulic acid ligustrazine, ferulic acid ethylester with chemical constitution.
The present invention also further relates to piperazine ferulate as the application in the medicine of prevention and treatment pulmonary hypertension, and its therapeutic dose is for being equal to or greater than 800mg/ day.
The present invention relates to the medicine of piperazine ferulate as prevention and treatment pulmonary hypertension, can be by known method preparation in the pharmaceuticals industry, promptly by piperazine ferulate and derivant and suitable inert solid or the fusion of liquid medicine carrier are got.Can make be suitable for injecting, the pharmaceutical dosage form of oral or rectum, percutaneous drug delivery; Be suitable for the dosage form of ejection preparation, comprise and be not limited to injection with small volume, high-capacity injection, injectable powder; Be suitable for the dosage form of oral drug preparation, comprise and be not limited to tablet, capsule, granule, suspensoid, syrup; The preparation that is suitable for rectally comprises and is not limited to suppository; The preparation that is suitable for percutaneous drug delivery can be a patch.Above-mentioned preparation can contain in the pharmaceuticals industry carrier and/or adjuvant commonly used, for example Icing Sugar, starch, dextrin, solubilizing agent such as tween, lubricant such as ethanol etc.
The present invention has opened up a new application to the purposes of already present piperazine ferulate in the prior art, and result of study shows that piperazine ferulate has following pharmacological action:
(1) diastole pulmonary artery smooth muscle reduces the pulmonary artery blood pressure;
(2) suppress pulmonary artery smooth muscle cell, endothelial cell proliferation;
(3) blood viscosity lowering improves hemodynamics;
(4) improve the right ventricle compensatory hypertrophy;
(5) improve PvO2, SaO2, reduce PvCO2, HCO3-.
In sum, the invention has the beneficial effects as follows: the new purposes that the invention provides the derivant of piperazine ferulate and/or piperazine ferulate, be piperazine ferulate at preparation prevention and treatment pulmonary hypertension, especially increasing with carrying out property of pulmonary vascular resistance is application in the disease medicament of principal character.
The specific embodiment
The present invention will be described in further detail piperazine ferulate as prevention and treatment pulmonary hypertension in conjunction with following result of study, particularly stop the gradual medicine that increases of pulmonary vascular resistance.
Embodiment 1:
Acute toxicity testing
(1) irritates stomach records piperazine ferulate by karber's method LD
50Be 3715 scholar 873mg/ kg body weight/mices, be equivalent to clinical 278 times of drafting adult's dosage.(2) quiet notes are less because of piperazine ferulate dissolubility in water, select its maxima solubility in water to give the once quiet notes of mice per kilogram 391mg, observe 7 days.Do not find dead mouse and abnormal phenomena, this dose is equivalent to clinical 30 times of drafting adult's dosage.The safe dose of this explanation piperazine ferulate is very big, can satisfy the dosage requirement that the present invention treats pulmonary hypertension fully.
Embodiment 2:
Rat teratogenesis mutagenicity test
Carried out rat teratogenic test, Salmonella reversion test, mouse bone marrow cells micronucleus test and chromosomal aberration test with piperazine ferulate, proved that piperazine ferulate does not still have teratogenesis and mutagenesis under heavy dose.
Embodiment 3:
Subacute toxicity test
With piperazine ferulate give every each quiet notes 400mg of Canis familiaris L. next day of (being equivalent to clinical 3 times of drafting adult's dosage) once, totally 30 times, administration time is 2 months, and continues to observe 4 months, has carried out the observation of half a year altogether.Stop solid liquor-saturated, the triglyceride of weight, erythrocyte, leukocyte, platelet, hemoglobin, differential blood count, serum transaminase, alkali phosphatase, blood peroxidase, gallbladder, the total fat of blood, non-protein nitrogen, protein electrophoresis, total protein, albumin, etc. with the matched group comparison, difference that there are no significant, pathological tissue are observed also no abnormality seen pathological changes.
Embodiment 4:
Piperazine ferulate control rat Hypoxic Pulmonary Hypertension in Rats
One, material and method
1. laboratory animal Wister rat is male, 250 ± 10g.
2. experimental technique
2.1 setting up the Hypoxic Pulmonary Hypertension in Rats modelling, animal model adopt the 5000m low-pressure oxygen cabin to build up in 10 days.
2.2 test group technology and handle this experiment and be divided into the Plain matched group, medication therapy groups A, B, C, D and model group in the cabin (PAH group), every group of 20 rats.The Plain matched group is normally raised drinking water every day, simulation 5000m environment high in administration group A, B, C, the D cabin in the cabin, and give and gavage piperazine ferulate 10mg/kg/d, 15mg/kg/d, 20mg/kg/d, 25mg/kg/d, model group is given equal volume 0.9% normal saline, totally 10 days.
2.3 pulmonary artery pressure is measured with the product RM-6200 of Chengdu Instruement Factory type four and is led physiograph mensuration.
2.4 left and right ventricles weight is measured with optical electrobalance.Assay method:
Open breast rapidly and core dirtyly, (mM:NaCl 118, and KCl 14.8, KH with freshly prepared KeobShi solution
2PO
41.0, MgCl
21.2, NaH
2CO
327.2 Glucose 11.1, pH=7.4, logical 95%O
2And 5%CO
2) clean up after, separate left and right ventricles, remove interventricular septum, filter paper blots the back and weighs respectively rapidly on balance.
2.5 the result is with .x ± s for the statistical procedures index, carries out significance test with non-paired t test.
Two, result
1. the influence (seeing Table 1) of blood pressure is compared with the Plain matched group, the model group blood pressure obviously raises (P＜0.05), shows Hypoxic Pulmonary Hypertension in Rats modeling success.Compare with model group, obvious decline all appears in control group A, B, C, D blood pressure, but control group A blood pressure drops amplitude little (P＞0.05), control group B blood pressure drops is (P＜0.05) significantly, and control group C, E be (P＜0.01) significantly.
Blood pressure behind table 1 pulmonary hypertension and the medical treatment (x ± s n=10)
Compare * * p＜0.01 with matched group; Compare #p＜0.05##p＜0.01 with model group
2. the variation of rat right ventricle weight/kg body weight (seeing Table 2) and Plain matched group comparison model group right ventricle obviously increase weight (P＜0.05).Compare with model group, obviously descending all appears in control group A, B, C, the weightening finish of D right ventricle, but control group A right ventricle weightening finish fall little (P＞0.05), the weightening finish of control group B right ventricle descend significantly (P＜0.05), and control group C, E be (P＜0.01) significantly.
Table 2 right ventricle weight/kg body weight is (mg/kg .x ± s n=10) relatively
Compare * * p＜0.01 with matched group; Compare with model group, #p＜0.05##p＜0.01 experimental result shows that the low-pressure oxygen cabin 5000m can cause the model of Hypoxic Pulmonary Hypertension in Rats in 10 days, mainly shows as pulmonary artery pressure and obviously raises, and right ventricle weight/kg body weight obviously increases weight.After piperazine ferulate treatment, when be equal to or greater than 15mg/kg/d when (dosage 800mg/ day is equivalent to be grown up) These parameters be clearly better, its therapeutic effect is dosage correlation, dosage is big more, therapeutic effect is good more; But when dosage is 10mg/kg/d when (dosage 600mg/ day is equivalent to be grown up), its DeGrain is failed to respond to any medical treatment.Experimental result has confirmed that piperazine ferulate can be applied to the control of pulmonary hypertension down in heavy dose of (adult's dosage 800mg/ day).
Embodiment 5:
Piperazine ferulate is to the influence of rabbit pulmonary heart disease model arterial hypertension
1. material and method
1.1 56 of laboratory animal new zealand white rabbits are male, body weight 216～418kg is divided into normal group, model group, scopolamine group, piperazine ferulate A, B, C, D group, 8 every group at random.
1.2 experimental model is according to the method for Shi Xinyou, the liquor ferri trichloridi with 3% begins each 0.5ml by the intravenous injection of rabbit ear edge, 3 times weekly, after increase to gradually 4 times, inject 45～60ml altogether, normally feed during the injection, do not add any processing.
1.3 medication piperazine ferulate A, B, C, D group be lumbar injection piperazine ferulate 10mg/kg/d, 15mg/kg/d, 20mg/kg/d, 25mg/kg/d respectively; The normal saline of model group lumbar injection equal volume.
1.4 index determining is fixed in rabbit on the fixed mount, inserts the swan-ganse conduit from right external jugular vein after the local anaesthesia, measures Drug therapy front and back pulmonary artery pressure respectively, the right ventricle mixed venous blood gas is analyzed.
1.5 statistical analysis adopts the SPSS statistical software, the t check, and data are represented with x ± s.
2. result
2.1 normal group and model group pulmonary artery pressure see Table 3.Compare with normal group, model group animal systolic pressure, diastolic pressure, mean arterial pressure be obviously rising (P＜0.05) all.Show this experiment pulmonary heart disease pulmonary hypertension modeling success.
Table 3 normal group and the comparison of pulmonary heart disease group pulmonary artery pressure (x ± s)
2.2 piperazine ferulate, scopolamine see Table 4 to the influence of experimental lung arterial hypertension.After piperazine ferulate or scopolamine treatment, decline in various degree all appears in animal systolic pressure, diastolic pressure, mean arterial pressure.Systolic pressure, diastolic pressure, mean arterial pressure decline not obvious (P＞0.05) before and after the medication of piperazine ferulate A treated animal; Systolic pressure, diastolic pressure, mean arterial pressure descend comparatively obviously (P＜0.05) before and after the medication of piperazine ferulate B treated animal, and its therapeutic effect is suitable with the scopolamine group.Piperazine ferulate C, D treated animal medication front and back systolic pressure, diastolic pressure, mean arterial pressure decline is (P＜0.01) the most obviously.Show that piperazine ferulate can prevent and treat ferric chloride experimental lung arterial hypertension, when dosage when 15mg/kg/d is above, therapeutic effect is (P＜0.05) significantly.
Table 4 model group injection different pharmaceutical pulmonary artery pressure changes
Compare #P＜0.05 with model group; ##P＜0.01
2.3 piperazine ferulate is analyzed experimental lung arterial hypertension mixed venous blood gas, sees Table 5.Compare with normal group, model group animal PvCO2, HCO3 all enlarge markedly, and PvCO2, SaO2 significantly reduce.After the piperazine ferulate treatment, reversing appears in piperazine ferulate A, B, C treated animal PvCO2, HCO3, PvCO2, SaO2.But piperazine ferulate A organizes therapeutic effect not obvious (P＞0.05), and piperazine ferulate B, C, D group therapeutic effect be (P＜0.05) significantly.
Table 5 normal group and the comparison of pulmonary heart disease group blood gas analysis (x ± s)
| Group | PvCO 2 | PvO 2 | HCO 3 | SaO 2 |
| Normal group | 26.90±3.13 | 91.35±10.73 | 14.38±2.85 | 95.95±11.34 |
| Model group | 45.21±8.91 | 40.99±17.22 | 21.62±3.33 | 63.55±10.87 |
| Piperazine ferulate A group | 43.36±5.83 | 43.05±10.54 | 19.30±3.29 | 65.88±9.49 |
| Piperazine ferulate B group | 39.62±4.80* | 56.95±10.79* | 17.34±3.08* | 78.27±9.84* |
| Piperazine ferulate C group | 35.37±5.18** | 62.33±11.01** | 15.91±3.19* | 84.36±9.05** |
| Piperazine ferulate D group | 30.54±4.97** | 71.48±11.35** | 15.07±2.91** | 90.42±10.22** |
Compare * P＜0.05 with model group; * P＜0.01
This experiment shows that piperazine ferulate can significantly reduce pulmonary arterial systolic pressure, diastolic pressure, mean arterial pressure, and can improve PvO2, SaO2, reduces PvCO2, HCO3-.When piperazine ferulate dosage reaches 15mg/kg/d when (dosage 800mg/d is equivalent to be grown up), the medicine scopolamine effect of its therapeutical effect and known reduction pulmonary artery pressure is suitable; And along with the increase of dosage, its therapeutical effect is more and more stronger.When dosage is 10mg/kg/d when (dosage 600mg/d is equivalent to be grown up), its therapeutical effect is not obvious.
Comprehensive the foregoing description, piperazine ferulate can significantly reduce experimental lung arterial hypertension animal pulmonary arterial systolic pressure, diastolic pressure, mean arterial pressure, and its therapeutic dose scope is for being equal to or greater than 800mg/d; Dosage be 600mg/ during day its therapeutic effect not obvious.And the piperazine ferulate safety is very high, no obvious toxic-side effects, no teratogenesis mutagenic action.The consistent the present invention of showing of experimental result is practicable, has also embodied its huge clinical value.
As mentioned above, just can realize the present invention preferably.
Claims (5)
1. the derivant of piperazine ferulate and/or piperazine ferulate prevents and/or treats application in the medicine of pulmonary hypertension in preparation.
2. purposes according to claim 1 is characterized in that, described pulmonary hypertension comprises property pulmonary hypertension behind property pulmonary hypertension before the blood capillary, the hair and blood pipe, high dynamic property pulmonary hypertension.
3. purposes according to claim 2 is characterized in that, the property pulmonary hypertension comprises primary pulmonary hypertension, pulmonary infarction before the described blood capillary; Property pulmonary hypertension mitral stenosis, left heart failure behind the hair and blood pipe; High dynamic property pulmonary hypertension comprises congenital heart disease, hyperthyroidism.
4. purposes according to claim 1 is characterized in that, the derivant of described piperazine ferulate comprises sodium ferulate, ferulic acid ligustrazine, ferulic acid ethylester.
5. purposes according to claim 1 is characterized in that, described medicine is the pharmaceutical dosage form of injection, oral or rectum, percutaneous drug delivery.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US11667612B2 (en) * | 2017-10-25 | 2023-06-06 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Compositions and methods for delivering pharmaceutical agents |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1830428A (en) * | 2005-03-08 | 2006-09-13 | 诺氏制药（吉林）有限公司 | Sodium ferulate injection and its preparation method |
-
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1830428A (en) * | 2005-03-08 | 2006-09-13 | 诺氏制药（吉林）有限公司 | Sodium ferulate injection and its preparation method |
Non-Patent Citations (7)
| Title |
|---|
| 《中国医药指南》 200906 刘文林等 阿魏酸钠的临床应用 80-81 1-5 第7卷, 第12期 2 * |
| 《中国药房》 2008 王汝涛等 阿魏酸乙酯对急性肺水肿模型大鼠的保护作用研究 1226-1227 1-5 第19卷, 第16期 2 * |
| 《临床内科杂志》 200109 王荣丽等 阿魏酸钠对肺心病急性加重期肺动脉高压、血浆内皮素、D-二聚体的影响 343-344 1-2 第18卷, 第5期 * |
| 《华西药学杂志》 1987 郭玉麟等 阿魏酸哌嗪的合成及其药理与临床研究 52-54 1-5 第2卷, 第1期 * |
| 《华西药学杂志》 1987 郭玉麟等 阿魏酸哌嗪的合成及其药理与临床研究 52-54 1-5 第2卷, 第1期 2 * |
| 《第四军医大学学报》 2009 陈国柱等 阿魏酸钠对低氧性肺动脉高压大鼠肺血管平滑肌细胞Caspase-3，Bcl-2表达的影响 2105-2108 1-2 第30卷, 第20期 * |
| 《第四军医大学学报》 2009 陈国柱等 阿魏酸钠对低氧性肺动脉高压大鼠肺血管平滑肌细胞Caspase-3，Bcl-2表达的影响 2105-2108 1-5 第30卷, 第20期 2 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11667612B2 (en) * | 2017-10-25 | 2023-06-06 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Compositions and methods for delivering pharmaceutical agents |
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