CN105902506A - Sacubitril/valsartan preparation and application thereof - Google Patents
Sacubitril/valsartan preparation and application thereof Download PDFInfo
- Publication number
- CN105902506A CN105902506A CN201610405917.9A CN201610405917A CN105902506A CN 105902506 A CN105902506 A CN 105902506A CN 201610405917 A CN201610405917 A CN 201610405917A CN 105902506 A CN105902506 A CN 105902506A
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- CN
- China
- Prior art keywords
- valsartan
- kabu
- sha
- song
- purposes
- 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.)
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
Abstract
The invention discloses a sacubitril/valsartan preparation and application thereof. The sacubitril/valsartan preparation is prepared from sacubitril/valsartan, lactose, microcrystalline cellulose and a pharmaceutically acceptable carrier. The sacubitril/valsartan preparation with the good flowability, stability and dissolubility can be obtained, and therefore the sacubitril/valsartan preparation is suitable for mass industrial production. The sacubitril/valsartan preparation treats a chronic cardiac failure, is a hypertensive pharmaceutical composition, is reasonable in ratio, can rapidly release medicine and can have the good curative effect on diseases.
Description
Technical field
The present invention relates to Sha Kabu song valsartan for preparing the purposes of medicine, be suitable to be administered orally in particular for preparation
Tablet and capsule.
Sha Kabu song valsartan (sacubitril/valsartan), molecular formula: (C24H29N5O3). (C24H29NO5)
.2.5 (H2O) .3Na, molecular weight: 961.03
It is for chronic heart failure；Three kind new medicines of hypertension, currently carry out preclinical study.
Background technology
Sha Kabu song valsartan is a kind of economic benefits and social benefits angiotensin receptor enkephalinase inhibitor, Novartis research and develop, have
Unique binding mode, is believed to reduce the strain of failure heart.LCZ696(Sha Kabu song valsartan) combine Novartis
Hypertension drug valsartan and experimental drug enkephalinase inhibitor AHU-377(Sacubitril, Sha Kabu bent).
AHU377 can block the mechanism of action of 2 peptide species that threat is responsible for reducing blood pressure, and valsartan then can improve vasodilation, stimulates body
Body excretion sodium and water.In November, 2014, LCZ-696(Sha Kabu song valsartan) the up-to-date III phase studies PARADI ARADI
GM-HF studies announcement.8000 many cases HFrEF patients, wherein 353 Chinese patients are included in this research in, compared for LCZ-696 and
Two therapeutic schemes of ACEI enalapril.With wide clinical application, the angiotensin-convertion enzyme inhibitor of improvement existence
(ACEI) enalapril is compared, and LCZ696 can substantially reduce sudden death rate, emergency treatment rate, admission rate, deterioration symptom and to intensive treatment
Demand, concrete data are as follows: sudden death rate: reduce by 20% in HFrEF patient, 45% cardiovascular death and 36% complete
Cause death is sudden death property；Emergency treatment rate: make symptom drastically deteriorate caused emergency treatment rate and reduce by 30%；Admission rate: make first with follow-up
HFrEF admission rate reduces by 21% and 23% respectively；Because admission rate caused by cardiovascular reason or any reason all reduces by 16%；Strengthening
Treatment need: be in and strengthen the probability reduction by 16% for the treatment of；Under Hospitalization situation, LCZ696 group patient accepts in intensive care unit
Strengthen the time fewer than enalapril group 18% for the treatment of, need to use intravenous pharmacy to help the probability of cardiac pumping to compare enalapril
Group few 31%.After patient medication, the assessment report of Disease severity is all shown by impression and doctor, and LCZ696 is significantly better than and depends on
That Puli can make the cardiac biomarkers level relevant to cardiac load and heart and injury the most relatively low.In November, 2014
26, Europe drug administration (EMA) people authorized LCZ696 Accelerated evaluation qualification with medical product committee (CHMP), becomes
The most first cardiovascular drugs harvesting Accelerated evaluation qualification of European Union's Drug Administration.Before this, the Accelerated evaluation money of European Union
Lattice never authorize cardiovascular field.On July 9th, 2015, FDA ratified Entresto(LCZ-696) it is used for the heart that ejection fraction reduces
Force failure patient, reduces cardiovascular death and heart failure and is in hospital risk.
Summary of the invention
The present invention relates to the pharmaceutical composition containing Sha Kabu song valsartan and this based composition for safely and effectively treatment
Chronic heart failure；The application of hypertension.
The invention still further relates to the drug regimen containing Sha Kabu song valsartan Yu the oral administration of other drug active substance
Thing.Said composition is to be obtained by the surface making the granule of pharmaceutically active substance adhere to carrier matrix.Make pharmaceutical actives
The calm method on carrier matrix of matter is minimum in order to make the gathering of active substance/carrier substrate particles be reduced to.
The present invention relates to the pharmaceutical composition containing about 10mg--300 mg Sha Kabu song valsartan, said composition is given every day
Medicine is used for chronic heart failure three times；The Sha Kabu that the preferred pharmaceutical composition of hypertension contains about 50mg--250 mg is bent
Valsartan, most preferred pharmaceutical composition contains the Sha Kabu song valsartan of about 50mg--200 mg.Further, this kind of preferably and
Most preferably pharmaceutical composition is given daily 2 times for chronic heart failure；It is given daily 1 hypertension.
Above-mentioned Sha Kabu song valsatan medicinal composition for being given daily also can be the most regular to some patient
It is administered.This maintaining treatment scheme include every day not enough once take Sha Kabu song valsatan medicinal composition.Such as, every three
Or within four days, be administered once with regard to it is enough.
The Sha Kabu song valsatan medicinal composition of the present invention can be configured to the form through any suitable administration, such as
Preferably oral administration combination can be tablet, capsule, granule or powder type.According to method well known in the art, Sha Kabu
Bent valsatan medicinal composition can be to be configured to the form that parenteral, rectum or via intranasal application are administered.This kind of preparation can include can
Pharmaceutical excipient, described excipient includes in this based composition conventional filler, fluidizer, lubricant, disintegrating agent, binding agent
Deng.Present invention additionally comprises slow releasing preparation.
Tablet and capsule preparations containing about 50mg 200mg Sha Kabu song valsartan can be made by the following method
Standby, to guarantee the efficient of product and good uniformity.First by the surface of Sha Kabu song valsartan calmness to carrier matrix
On prepare compositions.This step is completed by following operation: form Sha Kabu song valsartan and the solution of adhesive material, so
After carrier substrate particles keep motion while by spraying in the way of apply this solution.Control condition is so that the gathering of granule is dropped
To minimum.
Any other composition that will comprise in granule and compositions after drying, such as disintegrating agent/fluidizer/lubricant mix
Close.Then the powder obtained it is pressed into sheet or is filled into capsule.
Preferred solvent in said method is the ethanol of water or variable concentrations.
Adhesive material preferably has the polymer of high-consistency.The material being suitable for includes polyvidone, methylcellulose, hydroxyl
Methylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, polyvidone, hydroxymethyl cellulose are preferred
's.In whole compositions, the content of adhesive material is preferably the about 1%--about 10%(weight of compositions gross weight).
The disintegrant content that whole compositions includes is preferably the about 1%--7% of compositions gross weight.The disintegrating agent being suitable for includes
Polyvinylpolypyrrolidone, cross-linked carboxymethyl cellulose, low-substituted hydroxypropyl methylcellulose, Explotab, pregelatinized Starch and Semen Maydis
Starch, polyvinylpolypyrrolidone is preferred.
The lubricant content that whole compositions includes is preferably the about 1%--5% of compositions gross weight.The lubricant being suitable for includes
Micropowder silica gel, magnesium stearate, stearic acid, stearyl fumarate and sodium lauryl sulfate, micropowder silica gel, magnesium stearate are preferred
's.
Detailed description of the invention
The Sha Kabu song valsartan composition of the following example explanation present invention
Embodiment 1
Said method is used to prepare 50 milligrams of Sha Kabu song valsartan capsules
| Composition | Amount %(w/w) | Amount/grain |
| Sha Kabu song valsartan | 20.00 | 50mg |
| Microcrystalline Cellulose | 37.60 | 94 mg |
| Lactose | 28.00 | 70 mg |
| Polyvidone | 4.00 | 10 mg |
| Low-substituted hydroxypropyl methylcellulose | 8.00 | 20.0mg |
| Magnesium stearate | 0.80 | 2.0mg |
| Silicon dioxide | 1.6 | 4.0 mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 250.00 mg |
Embodiment 2
Said method is used to prepare 100 milligrams of Sha Kabu song valsartan capsules
| Composition | Amount %(w/w) | Amount/grain |
| Sha Kabu song valsartan | 27.60 | 100 mg |
| Microcrystalline Cellulose | 27.60 | 100 mg |
| Lactose | 41.44 | 150 mg |
| Polyvidone | 8.29 | 30mg |
| Polyvinylpolypyrrolidone | 8.29 | 30mg |
| Silicon dioxide | 0.55 | 2.00mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 362.00 mg |
Embodiment 3
Said method is used to prepare 150 milligrams of Sha Kabu song valsartan capsules
| Composition | Amount %(w/w) | Amount/piece |
| Sha Kabu song valsartan | 25.50 | 150 mg |
| Microcrystalline Cellulose | 25.50 | 50 mg |
| Lactose | 38.30 | 150 mg |
| Polyvidone | 2.50 | 10 mg |
| Polyvinylpolypyrrolidone | 5.00 | 20 mg |
| Low-substituted hydroxypropyl methylcellulose | 2.50 | 10 mg |
| Magnesium stearate | 0.4 | 1.5 mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 391.50 mg |
Embodiment 4
Said method is used to prepare 100 milligrams of Sha Kabu song valsartan sheets
| Composition | Amount %(w/w) | Amount/piece |
| Sha Kabu song valsartan | 25.00 | 100 mg |
| Microcrystalline Cellulose | 25.00 | 100 mg |
| Lactose | 37.50 | 150 mg |
| Polyvidone | 2.50 | 10 mg |
| Low-substituted hydroxypropyl methylcellulose | 5.00 | 20 mg |
| Magnesium stearate | 2.5 | 10 mg |
| Silicon dioxide | 2.5 | 10 mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 401.50 mg |
Embodiment 5
Said method is used to prepare 150 milligrams of Sha Kabu song valsartan sheets
| Composition | Amount %(w/w) | Amount/piece |
| Sha Kabu song valsartan | 25.50 | 150 mg |
| Microcrystalline Cellulose | 25.50 | 50 mg |
| Lactose | 38.30 | 150 mg |
| Polyvidone | 2.50 | 10 mg |
| Polyvinylpolypyrrolidone | 5.00 | 20 mg |
| Low-substituted hydroxypropyl methylcellulose | 2.50 | 10 mg |
| Magnesium stearate | 0.4 | 1.5 mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 391.50 mg |
Embodiment 6
Said method is used to prepare 200 milligrams of Sha Kabu song valsartan sheets
| Composition | Amount %(w/w) | Amount/grain |
| Sha Kabu song valsartan | 51.02 | 200 mg |
| Microcrystalline Cellulose | 12.76 | 50 mg |
| Lactose | 38.27 | 150 mg |
| Polyvidone | 5.10 | 20mg |
| Polyvinylpolypyrrolidone | 5.10 | 20mg |
| Magnesium stearate | 0.5 | 2.00mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 392.00 mg |
Embodiment 7
Said method is used to prepare 50 milligrams of Sha Kabu song valsartan sheets
| Composition | Amount %(w/w) | Amount/grain |
| Sha Kabu song valsartan | 20.00 | 50mg |
| Microcrystalline Cellulose | 37.60 | 94 mg |
| Lactose | 28.00 | 70 mg |
| Polyvidone | 4.00 | 10 mg |
| Low-substituted hydroxypropyl methylcellulose | 8.00 | 20.0mg |
| Magnesium stearate | 0.80 | 2.0mg |
| Silicon dioxide | 1.6 | 4.0 mg |
| Purified water | In right amount | In right amount |
| Amount to | 100.00 | 250.00 mg |
Claims (9)
1. Sha Kabu song valsartan is used for preparing oral administration every day 2 times for chronic heart failure；Every day is used for controlling for 1 time
Treating hypertension, the purposes of pharmaceutical composition in the form of tablets or capsules, wherein said pharmaceutical composition contains 10mg 300mg
Sha Kabu song valsartan.
2. the purposes of claim 1, the content of wherein said Sha Kabu song valsartan is 20mg 250mg.
3. the purposes of claim 1, the content of wherein said Sha Kabu song valsartan is 50mg 200mg.
4. the purposes of claim 3, the content of wherein said Sha Kabu song valsartan is 50mg.
5. the purposes of claim 3, the content of wherein said Sha Kabu song valsartan is 100mg.
6. the purposes of claim 3, the content of wherein said Sha Kabu song valsartan is 150mg.
7. the purposes of claim 3, the content of wherein said Sha Kabu song valsartan is 200mg.
8. the purposes of claim 1, described compositions therein contains one or more other drug active substances.
9. the purposes of claims 1, wherein said filler is selected from lactose, xylitol, microcrystalline Cellulose, dextrin, manna
Alcohol, sorbitol, sucrose, starch, pregelatinized Starch, glucose, calcium phosphate, calcium hydrogen phosphate, calcium carbonate, and mixture, and
Described Sha Kabu song valsartan be by have enough stickiness polymerization emplastic stick together on described filler.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610405917.9A CN105902506A (en) | 2016-06-12 | 2016-06-12 | Sacubitril/valsartan preparation and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610405917.9A CN105902506A (en) | 2016-06-12 | 2016-06-12 | Sacubitril/valsartan preparation and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105902506A true CN105902506A (en) | 2016-08-31 |
Family
ID=56750895
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610405917.9A Pending CN105902506A (en) | 2016-06-12 | 2016-06-12 | Sacubitril/valsartan preparation and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105902506A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106074421A (en) * | 2015-07-11 | 2016-11-09 | 凌莉 | A kind of pharmaceutical composition improving stability |
| CN106176725A (en) * | 2015-07-11 | 2016-12-07 | 凌莉 | A kind of pharmaceutical composition improving stability and its production and use |
| CN111358783A (en) * | 2018-12-25 | 2020-07-03 | 北京福元医药股份有限公司 | Sacubitril valsartan sodium pharmaceutical preparation |
| CN112315926A (en) * | 2020-11-23 | 2021-02-05 | 常州制药厂有限公司 | Valsartan oral solid preparation |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101848700A (en) * | 2007-11-06 | 2010-09-29 | 诺瓦提斯公司 | Dual-acting pharmaceutical compositions based on superstructures of angiotensin receptor antagonist/blocker (arb) and neutral endopeptidase (nep) inhibitor |
| CN104473938A (en) * | 2014-12-30 | 2015-04-01 | 北京瑞都医药科技有限公司 | Medicine for treating chronic heart failure and preparation method thereof |
| CN105461647A (en) * | 2014-09-28 | 2016-04-06 | 四川海思科制药有限公司 | Solid forms of Valsartan-Sacubitril trisodium compound, and preparation method and use thereof |
-
2016
- 2016-06-12 CN CN201610405917.9A patent/CN105902506A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101848700A (en) * | 2007-11-06 | 2010-09-29 | 诺瓦提斯公司 | Dual-acting pharmaceutical compositions based on superstructures of angiotensin receptor antagonist/blocker (arb) and neutral endopeptidase (nep) inhibitor |
| CN105461647A (en) * | 2014-09-28 | 2016-04-06 | 四川海思科制药有限公司 | Solid forms of Valsartan-Sacubitril trisodium compound, and preparation method and use thereof |
| CN104473938A (en) * | 2014-12-30 | 2015-04-01 | 北京瑞都医药科技有限公司 | Medicine for treating chronic heart failure and preparation method thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106074421A (en) * | 2015-07-11 | 2016-11-09 | 凌莉 | A kind of pharmaceutical composition improving stability |
| CN106176725A (en) * | 2015-07-11 | 2016-12-07 | 凌莉 | A kind of pharmaceutical composition improving stability and its production and use |
| CN111358783A (en) * | 2018-12-25 | 2020-07-03 | 北京福元医药股份有限公司 | Sacubitril valsartan sodium pharmaceutical preparation |
| CN112315926A (en) * | 2020-11-23 | 2021-02-05 | 常州制药厂有限公司 | Valsartan oral solid preparation |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
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| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160831 |