CN107648224A - A kind for the treatment of and prevention heart failure drugs and its application in pharmacy - Google Patents
A kind for the treatment of and prevention heart failure drugs and its application in pharmacy Download PDFInfo
- Publication number
- CN107648224A CN107648224A CN201711043421.2A CN201711043421A CN107648224A CN 107648224 A CN107648224 A CN 107648224A CN 201711043421 A CN201711043421 A CN 201711043421A CN 107648224 A CN107648224 A CN 107648224A
- Authority
- CN
- China
- Prior art keywords
- rolipram
- heart failure
- treatment
- pressure
- failure drugs
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
Abstract
The present invention provides a kind for the treatment of, prevention heart failure drugs, its active component is made up of rolipram, also it is aided with pharmaceutically acceptable auxiliary material, any pharmaceutically acceptable formulation is made, the one kind of described formulation in capsule or injection, and disclose its application in treatment, prevention heart failure drugs are prepared.
Description
Technical field
The invention belongs to field of medicaments, is related to application of the rolipram in pharmacy, and in particular to prepared by rolipram
Application in treatment, prevention heart failure drugs.
Background technology
Inotropic agent is widely used in the treatment of congestive heart failure, particularly when the deterioration rank in disease
Section, by inotropic agent come to improve myocardium shrinkage function be a kind of very important treatment method.
At present, conventional inotropic agent mainly has：First, the inotropic agent that cAMP is relied on, including：1. beta-receptor is exciting
Agent：Such medicine includes dopamine, dobutamine and norepinephrine, for improving heart failure patient myocardial function barrier
Hinder the hemodynamic parameter in acute exacerbation stage.Due to the semiotic function obstacle of congestive heart failure early stage or late period occurs
(mediation signal uncoupling under beta receptor), it is relatively poor using the such congestive heart failure curative effect of beta receptor agonist treatment.Also
There is Denopamine, be new oral β1receptor partial agonist.2. the inhibitor of phosphodiesterase (PDE) III：CAMP can be direct
The shrinkage and diastolic of normal myocardium are adjusted, produces the effect of positive inotropic and positivity slackness.Such medicine passes through suppression
The degraded that PDE III reduces cAMP increases cAMP, such as Amrinone (amrinone), milrinone (milrinone), Olprinone
And Vesnarinone (vesnarinone) etc. (olprinone).3. adenyl cyclase activator：Such medicine has Forskolin
(forskolin) and up to general sour colforsin (colforsin daropate, Adehl, NKH477) etc..2nd, cAMP is non-dependent
Inotropic agent, mainly have：1.Na+/K+-ATP enzyme inhibitors：Flowed by suppressing Na+/K+-ATP enzymes so as to increase in Ca2+,
Such as digitalis cardiac glycoside digoxin (digoxin), foxalin (digotoxin) and Lanatoside C (lantoside).2.
Calcium sensitizer：Such as Pimobendan (pimobendam), Sulmazole (sulmazole) and thiazole piperazine ketone (thiadizinone), make
For myocardium excitation-contraction coupling process, cause the transient increases of Ca2+, so as to increase the sensitiveness of myofilament or to the anti-of Ca2+
Ying Xing.Over the past several decades come, progress is achieved in terms of the research of positive inotropic medicament, then medicine with various degree
Side effect, particularly more obvious in arrhythmia cordis etc., therapeutic effect is not fully up to expectations, and room for improvement is still very big.
Rolipram (Rolipram) is phosphodiesteraseⅳ inhibitor (PDE IV), and suppressing phosphodiesterase has raising
Norepinephrine, isoprel, histamine, adenosine etc. largely gather in cerebral cortex area and cerebellum region.It is existing
Show rolipram for pharmaceutical research, to the nervous system disease, such as PD, depression and anxiety disorder have certain treatment
Value, and there is nootropic effect.Report is had no to the positive inotropic activity about rolipram at present.
The structural formula of rolipram is as follows：
The content of the invention
The technical problems to be solved by the invention are treated, in prevention heart failure drugs in offer rolipram in preparation
Application.
To reach above-mentioned purpose, technical scheme is as follows：
One kind treatment, prevention heart failure drugs, it contains rolipram.
The treatment, prevention heart failure drugs, its active component are made up of rolipram.
The treatment, prevention heart failure drugs, are also aided with pharmaceutically acceptable auxiliary material, being made any can pharmaceutically connect
The formulation received.
The treatment, prevention heart failure drugs, the one kind of described formulation in capsule or injection.
Application of the rolipram as active component in treatment, prevention heart failure drugs are prepared.
Application of the rolipram as sole active agent in treatment, prevention heart failure drugs are prepared.
Beneficial effect：Test result indicates that：Rolipram (Rolipram) (3mg/kg) dramatically increases heart rate, end-systole
Pressure, LVEF, cardiac output, left ventricular pressure maximum climbing speed, put out work(and end systolic pressure-volume relations curve
Slope, while rolipram dramatically increases systolic pressure, diastolic pressure, pulse pressure, shortens the aortic valve closing time, shows to cough up Li Pu
Orchid has the function that positive inotropic.
Brief description of the drawings
Fig. 1 is the representative curve that rolipram (3mg/kg) influences on rat in vivo left ventricular pressure-volume ring.
Fig. 2 is that rolipram (3mg/kg) acts on representative curve to rat in vivo ESPVR and EDPVR relation curve.
Fig. 3 is that rolipram (3mg/kg) influences representative curve to rat in vivo angiosthenia.
Embodiment
Form is described in further detail again to the above of the present invention by the following examples, but should not manage this
The scope solved as the above-mentioned theme of the present invention is only limitted to following embodiment, and all technologies for being realized based on the above of the present invention are equal
Belong to the scope of the present invention.
Embodiment 1：Rolipram 30g is taken, adds starch, is pelletized, encapsulating capsule, obtains the capsule of rolipram agent.
Embodiment 2：Rolipram 30g is taken, adds physiological saline to be made, obtains the injection of rolipram.
Embodiment 3：The positive inotropic activity pharmacodynamic study of rolipram
1. instrument：PowerLab polygraphs (Australian AD Instruments, model PowerLab8/
35)；Millar amplifiers (MILLAR companies of the U.S., model：735-2083Rev.F)；Millar intraventricular pressures and P-V
Conduit (model:SPR-901)
2. method：20% urethane 5ml/kg is given in healthy cleaning grade male SD rat, 250-300 grams of weight, abdominal cavity
Row anesthesia.Right carotid and left side vena jugularis externa are separated under narcosis, calibrates pressure-volume catheter pressure.Cough up profit
(Rolipram) (3mg/kg) is first dissolved in 0.2mL DMSO for Pulan, is slowly injected through left side vena jugularis externa, and continuous record coughs up profit
Pulan acts on 30min.Test and carry out volume calibration with 30% (g/100mL) salt solution and self-blood after terminating.Experimental result is used
The AD Instruments software analysis of Labchart 8, index include：Heart rate (heart rate, HR), end-systolic volume
(end-systolic volume, Ves), end-diastolic volume (end-diastolic volume, Ved), end-systolic pressure
(end-systolic pressure, Pes), diastasis pressure (end-diastolic pressure, Ped), output of often fighting
Measure (Stroke volume, SV), LVEF (Ejection fraction, EF), cardiac output (Cardiac output,
CO), maximal ascending rate of internal pressure of left ventricle (Peak rate of rise of left ventricular pressure ,+
dP/dtmax), bulk of left ventricle maximum climbing speed (Peak rate of rise of left volume ,+dP/dtmax) and fight
Go out work((Stroke work, SW), end systolic pressure-volume relations curve (End-systolic pressure-volume
Relationship, ESPVR) and diastasis pressure-PRESSURE-VOLUME RELATION curve (End-diastolic pressure-volume
Relationship, EDPVR), systolic pressure (Systolic blood pressure, SBP), diastolic pressure (Diastolic
Blood pressure, DBP), pulse pressure difference (Pulse Pressure, PP), left ventricular pressure reply 50% time (Left
Ventricular pressure durations at 50%full recovery level, LVPD50), systolic pressure reply
50% time (Systolic blood pressure durations at 50%full recovery level,
) and the aortic valve closing time (Aortic valve closing time, AVCT) SBPD50.
Blank control (Control)：Independent 1mL physiological saline is slowly injected through left side vena jugularis externa.Blank control is tested
Show：Independent 1mL physiological saline is slowly injected through left side vena jugularis externa not to be influenceed the above-mentioned left ventricular pressure-PRESSURE-VOLUME RELATION of rat and moves
Mechanics parameter (n>20).
3. result：Drawn from above-mentioned experiment：Fig. 1 is rolipram (3mg/kg) to rat in vivo left ventricular pressure-volume
The representative curve that ring influences, data are shown in Table 1；Fig. 2 is rolipram (3mg/kg) to rat in vivo ESPVR and EDPVR relation
Curve acts on representative curve, and data are shown in Table 1；Fig. 3 is that rolipram (3mg/kg) influences representativeness to rat in vivo angiosthenia
Curve, data are shown in Table 2.
The rolipram of table 1 influences on normal rat in vivo left ventricle-volume ring
Note：Compared with blank control,*Represent P<0.05**Represent P<0.01
ESPVR:End systolic pressure-volume relations curve；EDPVR:Diastasis pressure-PRESSURE-VOLUME RELATION curve
Influence of the rolipram of table 2 to normal rat in vivo ventricle and arterial pressure and its contraction rate
Note：Compared with blank control,*Represent P<0.05**Represent P<0.01
It can be drawn from the parameter in table 1-2 and Fig. 1-3 and dramatically increase heart rate (HR), end-systole pressure using rolipram
Power (Pes), LVEF (EF), cardiac output (Cardiac output, CO), left ventricular pressure maximum climbing speed (+dP/
Dtmax the slope of work((SW) and end systolic pressure-volume relations curve (ESPVR)), is put out, while rolipram significantly increases
Contractive pressure (SBP) is added, diastolic pressure (DBP), pulse pressure (PP), shortens aortic valve closing time (AVCT), the table from these parameters
Bright rolipram has the function that positive inotropic.
Obviously, the above embodiment of the present invention is only intended to clearly illustrate example of the present invention, and is not pair
The restriction of embodiments of the present invention.For those of ordinary skill in the field, may be used also on the basis of the above description
To make other changes in different forms.There is no necessity and possibility to exhaust all the enbodiments.And these
The obvious changes or variations that the connotation for belonging to of the invention is extended out still falls within protection scope of the present invention.
Claims (6)
1. one kind treatment, prevention heart failure drugs, it is characterised in that it contains rolipram.
2. treat according to claim 1, prevent heart failure drugs, it is characterised in that its active component is by rolipram
Composition.
3. treat according to claim 2, prevent heart failure drugs, it is characterised in that be also aided with pharmaceutically acceptable
Auxiliary material, any pharmaceutically acceptable formulation is made.
4. according to claim 3 treat, prevent heart failure drugs, it is characterised in that described formulation be capsule or
One kind in person's injection.
5. application of the rolipram as active component in treatment, prevention heart failure drugs are prepared.
6. application of the rolipram as sole active agent in treatment, prevention heart failure drugs are prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711043421.2A CN107648224A (en) | 2017-10-31 | 2017-10-31 | A kind for the treatment of and prevention heart failure drugs and its application in pharmacy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711043421.2A CN107648224A (en) | 2017-10-31 | 2017-10-31 | A kind for the treatment of and prevention heart failure drugs and its application in pharmacy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107648224A true CN107648224A (en) | 2018-02-02 |
Family
ID=61095353
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711043421.2A Pending CN107648224A (en) | 2017-10-31 | 2017-10-31 | A kind for the treatment of and prevention heart failure drugs and its application in pharmacy |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107648224A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5059612A (en) * | 1989-12-11 | 1991-10-22 | Schering Aktiengesellschaft | Anti-dementia drug |
| US20030134861A1 (en) * | 1997-10-28 | 2003-07-17 | Doherty Paul C. | Transmucosal phosphodiesterase inhibitors for the treatment of erectile dysfunction |
| CN1791429A (en) * | 2003-05-22 | 2006-06-21 | 奥坦纳医药公司 | Composition comprising a PDE4 inhibitor and a PDE5 inhibitor |
-
2017
- 2017-10-31 CN CN201711043421.2A patent/CN107648224A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5059612A (en) * | 1989-12-11 | 1991-10-22 | Schering Aktiengesellschaft | Anti-dementia drug |
| US20030134861A1 (en) * | 1997-10-28 | 2003-07-17 | Doherty Paul C. | Transmucosal phosphodiesterase inhibitors for the treatment of erectile dysfunction |
| CN1791429A (en) * | 2003-05-22 | 2006-06-21 | 奥坦纳医药公司 | Composition comprising a PDE4 inhibitor and a PDE5 inhibitor |
Non-Patent Citations (1)
| Title |
|---|
| COSKUN USTA等: "comparision of the inotropic effects of levosimendan, rolipram, and dobutamine on human atrial trabeculae", 《J. CARDIOVASC. PHARMACOL.》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wilmshurst et al. | Haemodynamic effects of intravenous amrinone in patients with impaired left ventricular function. | |
| Tabima et al. | Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops | |
| Maturi et al. | Coronary vasoconstriction induced by vasopressin. Production of myocardial ischemia in dogs by constriction of nondiseased small vessels. | |
| CN105073105B (en) | Nitroxyl donors with improved therapeutic index | |
| Awan et al. | Clinical pharmacology and therapeutic application of prazosin in acute and chronic refractory congestive heart failure: balanced systemic venous and arterial dilation improving pulmonary congestion and cardiac output | |
| CN102596010A (en) | UTP for the diagnosis of stenoses and other conditions of restricted blood flow | |
| RU2627842C2 (en) | Means for left ventricle diastolic function improvement | |
| Takaoka et al. | Comparison of the effects on arterial-ventricular coupling between phosphodiesterase inhibitor and dobutamine in the diseased human heart | |
| Betocchi et al. | Effects of diltiazem on left ventricular systolic and diastolic function in hypertrophic cardiomyopathy | |
| CN102223882A (en) | Phosphodiesterase type iii (pde iii) inhibitors or ca2+-sensitizing agents for the treatment of hypertrophic cardiomyopathy | |
| Ward et al. | First clinical experience with ONO-4232: a randomized, double-blind, placebo-controlled healthy volunteer study of a novel lusitropic agent for acutely decompensated heart failure | |
| Kurnik et al. | The dependence of the cardiac effects of nifedipine on the responses of the peripheral vascular system. | |
| CN101262866A (en) | Hemodynamics improving agent | |
| CN106727487A (en) | Application of the Atisine chloride Atractydin in pharmacy | |
| CN102008497A (en) | Application of catalpol in preparing drug for treating cardiac failure disease | |
| Lejemtel et al. | Hemodynamic effects of captopril in patients with severe chronic heart failure | |
| Bhat et al. | Evaluation of the effects of RP5063, a novel, multimodal, serotonin receptor modulator, as single-agent therapy and co-administrated with sildenafil, bosentan, and treprostinil in a monocrotaline-induced pulmonary arterial hypertension rat model | |
| Kawata et al. | Effect on coronary flow velocity reserve in patients with type 2 diabetes mellitus: comparison between angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor antagonist | |
| CN101361740A (en) | Pharmacy use of 2,5- bis (hydroxymethyl)-3,6-dimethyl pyrazine and derivates thereof | |
| Awan et al. | Cardiocirculatory effects of afterload reduction with oral trimazosin in severe chronic congestive heart failure | |
| CN107648224A (en) | A kind for the treatment of and prevention heart failure drugs and its application in pharmacy | |
| CN107550915A (en) | A kind of Ivabradine and rolipram composition and its application in pharmacy | |
| CN107714702A (en) | A kind of Ivabradine and milrinone composition and its application in pharmacy | |
| WO2018152996A1 (en) | Use of nadph in preparation of medicine for treating cardiac hypertrophy and heart failure | |
| EP1743521A1 (en) | Method of constructing animal model suffering from left ventricular diastolic disorder for examining heart failure and method of examining remedy for heart failure caused by left ventricular diastolic failure with the use of the animal model |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180202 |