CN112641742A - Sacubitril valsartan sodium sustained-release tablet and preparation method thereof - Google Patents
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Abstract
The invention belongs to the field of pharmaceutical preparations, and provides a Sacubitril valsartan sodium sustained-release tablet and a preparation method thereof. The sabotara valsartan sodium sustained-release tablet disclosed by the invention contains sabotara valsartan sodium, a sustained-release material, a filler and other pharmaceutical excipients. In the sabotara valsartan sodium sustained release tablet, the sabotara valsartan sodium accounts for 30-65% of the weight of the tablet core, the sustained release material accounts for 15-40% of the weight of the tablet core, the filling agent accounts for 8-50% of the weight of the tablet core, and the lubricating agent accounts for 0.1-8%. The film coating material accounts for 0-10% of the total weight of the tablet. The invention also discloses a preparation method of the sarubara valsartan sodium sustained-release tablet, and the sarubara valsartan sodium sustained-release tablet prepared by the method has sustained-release characteristics, is beneficial to maintaining long-term and efficient blood concentration in vivo and improves the treatment effect of medicaments.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a Sacubitril valsartan sodium sustained-release tablet and a preparation method thereof.
Background
Heart Failure (HF) is a syndrome of changes in cardiac function caused by myocardial damage, is the terminal manifestation of all cardiovascular diseases, and has a consistently poor therapeutic effect. Epidemiological investigations have shown that chronic HF prevalence in adults in our country is 1.61%, hospitalization mortality accounts for 40% of cardiovascular hospitalization mortality, higher than overall cardiovascular mortality, and about 50% of HF patients die within 5 years after diagnosis, comparable to mortality of malignant tumors. Clinically, the treatment of chronic heart failure should improve the symptoms of patients and improve the quality of life, and should be combined with the mechanism of myocardial remodeling to delay and prevent the development of myocardial remodeling and reduce the clinical mortality.
The valsartan sodium Sacubitril (LCZ696) is developed by Nowa company, is a breakthrough innovative medicine in the field of chronic heart failure treatment in recent years all over the world, is the first angiotensin receptor-enkephalinase inhibitor, and has a dual action mechanism. Valsartan inhibits RAAS, and after entering the body, the sabotarol is metabolized into an active enkephalinase inhibitor LBQ657 under the action of liver enzymes, so that the valsartan has the effect of inhibiting enkephalinase. The medicine is approved in the United states and European Union by marketing in 2015, enters the Chinese market in 2017, and is currently recommended as a first-line treatment medicine for chronic HF by treatment guidelines of various countries.
The chemical name of the sodium valsartan from Sacubitril is as follows: octadecasodium hexa (4- { [ (1S,3R) -1- ([1,1 '-biphenyl) -4-ylmethyl) -4-ethoxy-3-methyl-4-oxobutyl ] amino } -4-oxobutanoic acid) hexa (N-pentanoyl-N- { [ 2' - (1H-tetrazol-5-yl) biphenyl-4-yl ] methyl } -L-valine) -water (1/15), having the following structure:
at present, the preparation of the sarcurbaqu valsartan sodium sold in China is only common tablets (50mg, 100mg and 200mg specifications) of Nowa company, needs to be administrated 2 times a day, is easy to cause blood concentration fluctuation, and has poor patient compliance. The preparation method has the advantages that the sabotara valsartan sodium is prepared into the sustained release tablet which is administrated once a day, the administration frequency can be reduced, the probability of missed administration and wrong administration of a patient is reduced, the compliance of the patient is improved, the blood concentration can be stabilized, the peak valley phenomenon caused by taking a quick release preparation is avoided, and the toxic and side effects of the medicine are reduced.
The invention has the name of Chinese patent No. CN 105748420B: a preparation method of LCZ696 sustained-release matrix tablets for treating heart failure is characterized in that hydroxypropyl methylcellulose is used as a sustained-release matrix material, and the sustained-release tablets are prepared by adopting a powder direct compression mode. The invention has the name of Chinese patent No. CN 105935358B: a Sacubitril valsartan sustained release preparation and a preparation method thereof are characterized in that hydroxypropyl methylcellulose is used as a sustained release framework material, a dry granulation mode is adopted to prepare sustained release tablets, and film coating is carried out.
However, how to provide a preparation method and a prescription suitable for various production and research and development conditions, especially how to prepare the valsartan sodium sustained-release tablet by adopting wet granulation, is a problem to be solved by researchers.
Disclosure of Invention
Aiming at the problems in the prior art, the invention aims to provide the sabotara valsartan sodium sustained release tablet and the preparation method thereof. The sustained-release matrix tablet prepared by the invention can be prepared by adopting a direct powder tabletting, wet granulation or dry granulation process, wherein the wetting agent or the solvent of the adhesive for preparing the sustained-release tablet by wet granulation is absolute ethyl alcohol, and the prepared sustained-release tablet has stable crystal form, good particle fluidity, simple and easily controlled operation, contribution to industrial production and wider popularization and application prospect, and is suitable for various production and research and development conditions.
The sabotara valsartan sodium sustained-release tablet disclosed by the invention contains sabotara valsartan sodium, a sustained-release material, a filler and other pharmaceutical excipients. In the sabotara valsartan sodium sustained release tablet, the sabotara valsartan sodium accounts for 30-65% of the weight of the tablet core, the sustained release material accounts for 15-40% of the weight of the tablet core, the filling agent accounts for 8-50% of the weight of the tablet core, and the lubricating agent accounts for 0.1-8%. The film coating material accounts for 0-10% of the total weight of the tablet.
The slow release material of the Sacubitril valsartan sodium slow release tablet provided by the invention is selected from one or more of hydroxypropyl methylcellulose, sodium alginate, polyoxyethylene, carbomer, hydroxypropyl cellulose and sodium carboxymethylcellulose. The hydroxypropyl methylcellulose is selected from low-viscosity hydroxypropyl methylcellulose with the viscosity of 5-120 centipoises, or high-viscosity hydroxypropyl methylcellulose with the viscosity of 2600 + 100000 centipoises, or a mixture of the two according to the proportion of 1: 5-5: 1.
The filler of the sabotara valsartan sodium sustained release tablet is selected from one or more of anhydrous lactose, mannitol, microcrystalline cellulose, sorbitol and xylitol.
The lubricant of the sabotara valsartan sodium sustained release tablet disclosed by the invention is selected from one or more of magnesium stearate, talcum powder, superfine silica gel powder and sodium stearyl fumarate.
According to the sabotara valsartan sodium sustained release tablet, the film coating material is Opadry.
The preparation method of the sabotara valsartan sodium sustained release tablet comprises wet granulation, direct powder compression and dry granulation.
The invention relates to a Sacubitril valsartan sodium sustained release tablet, wherein a wet granulation process comprises the following steps:
(1) uniformly mixing the sodium valsartan, the filler and the sustained-release material;
(2) adding wetting agent or adhesive to prepare wet granules, drying in an oven, and sieving with a 20-mesh sieve to complete granules;
(3) adding lubricant, mixing, and tabletting to obtain sustained release tablet core;
(4) and performing film coating on the sustained-release tablet core.
The invention relates to a Sacubitril valsartan sodium sustained release tablet, wherein a dry granulation process comprises the following steps:
(1) uniformly mixing the sodium valsartan, the filler, the slow-release material and the lubricant;
(2) preparing granules by using a dry granulating machine;
(3) adding lubricant, mixing, and tabletting to obtain sustained release tablet core;
(4) and performing film coating on the sustained-release tablet core.
The invention relates to a sarkubaqu valsartan sodium sustained release tablet, wherein a direct powder tabletting process comprises the following steps:
(1) uniformly mixing the sodium valsartan, the filler, the slow-release material and the lubricant;
(2) tabletting to obtain sustained-release tablet core;
(3) and performing film coating on the sustained-release tablet core.
According to the invention, the preparation method of the sabotara valsartan sodium sustained release tablet has the advantages that the wet granulation process is adopted, the solvent of the wetting agent or the adhesive is absolute ethyl alcohol, and the prepared sustained release tablet has stable crystal form and good granule fluidity.
The positive progress effects of the invention are as follows:
(1) the sabotara and valsartan sodium sustained-release tablet has a good sustained-release effect, the release of the sabotara and the valsartan is not less than 85% within 8 hours, both active ingredients are released slowly, and the sustained-release characteristic is shown in an in-vitro test.
(2) The invention can be prepared by adopting wet granulation tabletting, direct powder tabletting or dry granulation processes, the main component does not generate crystal transformation, the invention is suitable for various production and research and development conditions, the operation is simple and easy to control, and the invention is beneficial to industrial production.
(3) The tablet prepared by the invention can continuously, slowly and stably release the medicine within a certain time, and can keep effective blood concentration, thereby continuously and effectively treating heart failure and improving the compliance of patients.
Drawings
FIG. 1 is a graph of the in vitro cumulative release percentage versus time for the extended release tablet of valsartan sodium from Sacubitril of example 1;
FIG. 2 is a graph of the in vitro cumulative release percentage versus time for the valsartan sodium sustained release tablet of Sacubitril of example 2;
FIG. 3 is a graph of the in vitro cumulative release percentage versus time for the sustained release tablets of valsartan sodium from Sacubitril according to example 3;
FIG. 4 is a graph of the in vitro cumulative release percentage versus time for the sustained release tablets of valsartan sodium from Sacubitril according to example 4;
FIG. 5 is a graph of the in vitro cumulative release percentage versus time for the valsartan sodium sustained release tablets of example 5;
FIG. 6 is a graph of the in vitro cumulative release percentage versus time for the extended release tablet of valsartan sodium from Sacubitril of example 6;
FIG. 7 is a graph of the in vitro cumulative release percentage versus time for the extended release tablet of valsartan sodium from Sacubitril of example 7;
FIG. 8 is a graph of the in vitro cumulative release percentage versus time for the extended release tablet of valsartan sodium from Sacubitril of example 8;
FIG. 9 is a graph of the in vitro cumulative release percentage versus time for the valsartan sodium sustained release tablet of EXAMPLE 9 Sacubitril;
FIG. 10 is a graph of the in vitro cumulative release percentage versus time for the extended release tablet of valsartan sodium from example 10;
FIG. 11 is a graph of the in vitro cumulative release percentage versus time for the extended release tablet of valsartan sodium from Sacubitril of example 11;
FIG. 12 is a graph of the in vitro cumulative release percentage versus time for the extended release tablet of valsartan sodium from Sacubitril of example 12;
FIG. 13 is a graph of the in vitro cumulative release percentage versus time for the extended release tablet of valsartan sodium from EXAMPLE 13 Sacubitril;
FIG. 14 is a graph of the in vitro cumulative release percentage versus time for the extended release tablet of valsartan sodium from EXAMPLE 14 Sacubitril;
FIG. 15 is a graph of the in vitro cumulative release percentage versus time for the extended release tablet of valsartan sodium from EXAMPLE 15 Sacubitril;
FIG. 16 is a graph of the in vitro cumulative release percentage versus time for the extended release tablet of valsartan sodium from EXAMPLE 16 Sacubitril;
figure 17 is a DSC overlay of the sustained release tablets of example 1 and examples 17-19 of sabotartan sodium and blank excipients and drug substances.
Detailed Description
The invention will be further explained and illustrated by means of examples. It should be understood that: the embodiments of the present invention are given for illustration only and not for limitation, and any simple modification of the present invention based on the technical solution of the present invention falls within the protection scope of the present invention.
Example 1
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Examples 1 and 3-process for preparing the sabotartan sodium sustained release tablet of example 16:
(1) weighing raw and auxiliary materials according to the prescription amount, and uniformly mixing by an equivalent progressive method to obtain premixed powder. Adding appropriate amount of anhydrous ethanol to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 2 hr, and sieving with 20 mesh sieve. Adding the lubricant according to the prescription amount, and uniformly mixing;
(2) tabletting: a special-shaped die with the size of 19.5mm multiplied by 9.6mm is adopted, and the hardness is controlled to be 8-10 kg;
(3) coating with a film coat: the above tablet cores were coated with opadry 00F220009-CN at a weight gain of 2%.
Example 1-method for determining the release rate of the sabotartan sodium sustained release tablet of example 16:
according to a second method of a determination method of the dissolution rate and the release degree of 0931 in the four parts of pharmacopoeia of China 2015 edition, a valsartan sodium sustained-release tablet of Sacuba koji is placed in a dissolution cup, 900mL of degassed phosphate buffer solution with pH6.8 is used as a release medium, the rotating speed is 50rpm, the temperature is (37 +/-0.5) DEG C, the release medium is taken for 1h, 2h, 4h, 6h, 8h, 10h and 12h, meanwhile, an equivalent amount of a same-temperature fresh medium is supplemented, the obtained solution is filtered through a 0.45 mu m microporous membrane, and after the obtained filtrate is diluted, the peak area is determined according to a high performance liquid chromatography, and the detection wavelength is 255 nm; in addition, a proper amount of reference substance is precisely weighed, the cumulative release percentage is calculated by the same method, and the requirement is met.
Example 2
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The preparation process of the sabotary valsartan sodium sustained release tablet of the embodiment 2 comprises the following steps:
(1) weighing raw and auxiliary materials according to the prescription amount, and uniformly mixing by an equivalent progressive method to obtain premixed powder. The premixed powder was then used to prepare granules using a dry granulator. Adding the lubricant according to the prescription amount, and uniformly mixing;
(2) tabletting: a special-shaped die with the size of 19.5mm multiplied by 9.6mm is adopted, and the hardness is controlled to be 8-10 kg;
(3) coating with a film coat: the above tablet cores were coated with opadry 00F220009-CN at a weight gain of 2%.
The release rate of the Sacubitril valsartan sodium sustained release tablet of example 1 is shown in figure 1. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 2 is shown in figure 2. From the release curve it can be seen that: there was almost no difference in the release of valsartan and sabotarol, indicating that the manufacturing process had little effect on the release of the tablets.
Example 3
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 4
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 5
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 6
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 7
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The release rate of the Sacubitril valsartan sodium sustained release tablet of example 3 is shown in figure 3. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 4 is shown in figure 4. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 5 is shown in figure 5. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 6 is shown in figure 6. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 7 is shown in figure 7. From the release curve it can be seen that: hydroxypropyl methylcellulose, sodium alginate, polyoxyethylene, carbomer, hydroxypropyl cellulose and sodium carboxymethylcellulose have slow release effects of different degrees. Wherein the carbomer with the strongest slow release effect is carbomer, and then sodium carboxymethylcellulose, hydroxypropyl cellulose, polyoxyethylene, hydroxypropyl methylcellulose and sodium alginate are sequentially used.
Example 8
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 9
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 10
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The release rate of the Sacubitril valsartan sodium sustained release tablet of example 8 is shown in figure 8. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 9 is shown in figure 9. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 10 is shown in figure 10. From the release curve it can be seen that: the low-viscosity hydroxypropyl methyl cellulose, the high-viscosity hydroxypropyl methyl cellulose or the high-low-viscosity hydroxypropyl methyl cellulose are mixed for use, so that a good in-vitro slow release effect can be achieved.
Example 11
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 12
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The release rate of the Sacubitril valsartan sodium sustained release tablet of example 11 is shown in figure 11. The release rate of the Sacubitril valsartan sodium sustained release tablet of example 12 is shown in figure 12. From the release curve it can be seen that: the weight ratio of the high-viscosity and low-viscosity hydroxypropyl methylcellulose is related to the release speed and the release end point. If the ratio is too small, the early burst release of the medicine cannot be controlled; if the ratio is too large, the drug is not released and the therapeutic effect is not achieved.
Example 13
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 14
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The release rate of the Sacubitril valsartan sodium sustained release tablet of example 13 is shown in figure 13. The release rate of the Sacubitril sodium sustained release tablet of example 14 is shown in figure 14. From the release curve it can be seen that: the more the total dosage of the high-low viscosity hydroxypropyl methylcellulose is, the more obvious the slow release effect is.
Example 15
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
Example 16
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The release rate of the Sacubitril valsartan sodium sustained release tablet of example 15 is shown in figure 15. The release rate of the Sacubitril sodium sustained release tablet of example 16 is shown in figure 16. From the release curve it can be seen that: the kind of the filler has no influence on the release of the drug.
Example 17
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The preparation process of the sabotara valsartan sodium sustained release tablet of example 17 comprises the following steps:
(1) weighing raw and auxiliary materials according to the prescription amount, and uniformly mixing by an equivalent progressive method to obtain premixed powder. Adding appropriate amount of water, making into soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 2 hr, and sieving with 20 mesh sieve. Adding the lubricant according to the prescription amount, and uniformly mixing;
(2) tabletting: a special-shaped die with the size of 19.5mm multiplied by 9.6mm is adopted, and the hardness is controlled to be 8-10 kg;
(3) coating with a film coat: the above tablet cores were coated with opadry 00F220009-CN at a weight gain of 2%.
Example 18
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The preparation process of the sabotara valsartan sodium sustained release tablet of example 18 comprises the following steps:
(1) weighing raw and auxiliary materials according to the prescription amount, and uniformly mixing by an equivalent progressive method to obtain premixed powder. Adding appropriate amount of 50% ethanol to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 2 hr, and sieving with 20 mesh sieve. Adding the lubricant according to the prescription amount, and uniformly mixing;
(2) tabletting: a special-shaped die with the size of 19.5mm multiplied by 9.6mm is adopted, and the hardness is controlled to be 8-10 kg;
(3) coating with a film coat: the above tablet cores were coated with opadry 00F220009-CN at a weight gain of 2%.
Example 19
(1) Core layer (per sheet):
(2) the film coating liquid comprises the following components:
opadry 00F220009-CN 19mg
The preparation process of the sabotara valsartan sodium sustained release tablet of example 19 comprises the following steps:
(1) weighing raw and auxiliary materials according to the prescription amount, and uniformly mixing by an equivalent progressive method to obtain premixed powder. Adding appropriate amount of 75% ethanol to make soft mass, sieving with 20 mesh sieve, granulating, drying at 40 deg.C for 2 hr, and sieving with 20 mesh sieve. Adding the lubricant according to the prescription amount, and uniformly mixing;
(2) tabletting: a special-shaped die with the size of 19.5mm multiplied by 9.6mm is adopted, and the hardness is controlled to be 8-10 kg;
(3) coating with a film coat: the above tablet cores were coated with opadry 00F220009-CN at a weight gain of 2%.
The DSC overlay of example 1 and examples 17-19 and the blank excipients and drug substances is shown in FIG. 17. As can be seen from the figure: the crystal form of the sustained-release tablet prepared by using water, 50% ethanol and 75% ethanol as wetting agents is changed, and the crystal form of the sustained-release tablet prepared by using absolute ethanol as a wetting agent is not changed.
While the preferred embodiments and principles of this invention have been described in detail, it will be apparent to those skilled in the art that variations may be made in the embodiments based on the teachings of the invention and such variations are considered to be within the scope of the invention.
Claims (10)
1. The Sacubitril valsartan sodium sustained-release tablet is characterized by comprising Sacubitril valsartan sodium, sustained-release materials, a filler and other pharmaceutical excipients;
the tablet core of the sustained release tablet comprises the following components in percentage by weight: 30-65% of valsartan sodium from Sacubitril, 15-40% of slow release material, 8-50% of filling agent and 0.1-8% of lubricating agent;
the film coating material accounts for 0-10% of the total weight of the tablet.
2. The Sacubitril sodium valsartan sustained release tablet of claim 1, wherein the sustained release coating material is selected from one or more of hydroxypropyl methylcellulose, sodium alginate, polyoxyethylene, carbomer, hydroxypropyl cellulose, and sodium carboxymethyl cellulose.
3. The sarkobal valsartan sodium sustained-release tablet as claimed in claim 2, wherein the hydroxypropyl methylcellulose is selected from low-viscosity hydroxypropyl methylcellulose with the viscosity of 5-120 centipoises, or high-viscosity hydroxypropyl methylcellulose with the viscosity of 2600 + 100000 centipoises, or a mixture of the two in a ratio of 1: 5 to 5: 1.
4. The Sacubitril sodium valsartan sustained release tablet of claim 1, wherein the filler is selected from one or more of anhydrous lactose, mannitol, microcrystalline cellulose, sorbitol, xylitol; the lubricant is selected from one or more of magnesium stearate, talcum powder, superfine silica gel powder and sodium stearyl fumarate.
5. The slow release tablet of valsartan sodium from claim 1, wherein the film coating material is Opadry.
6. A process for the preparation of the sabotara valsartan sodium sustained release tablets as claimed in any of claims 1 to 5 comprising wet granulation, powder direct compression and dry granulation.
7. A method for preparing the sabotara valsartan sodium sustained release tablet as claimed in claim 6, wherein the process of wet granulation comprises the following steps:
(1) uniformly mixing the sodium valsartan, the filler and the sustained-release material;
(2) adding wetting agent or adhesive to prepare wet granules, drying in an oven, and sieving with a 20-mesh sieve to complete granules;
(3) adding lubricant, mixing, and tabletting to obtain sustained release tablet core;
(4) and performing film coating on the sustained-release tablet core.
8. A method for preparing the sabotara valsartan sodium sustained release tablet as claimed in claim 6, wherein the dry granulation process comprises the following steps:
(1) uniformly mixing the sodium valsartan, the filler, the slow-release material and the lubricant;
(2) preparing granules by using a dry granulating machine;
(3) adding lubricant, mixing, and tabletting to obtain sustained release tablet core;
(4) and performing film coating on the sustained-release tablet core.
9. A method for preparing the sabotara valsartan sodium sustained release tablet as claimed in claim 6, wherein the process of direct compression of the powder comprises the steps of:
(1) uniformly mixing the sodium valsartan, the filler, the slow-release material and the lubricant;
(2) tabletting to obtain sustained-release tablet core;
(3) and performing film coating on the sustained-release tablet core.
10. The sarkubara valsartan sodium sustained-release tablet as claimed in claim 7, wherein the wetting agent or the binder solvent is absolute ethyl alcohol.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113648284A (en) * | 2021-07-16 | 2021-11-16 | 南京海纳医药科技股份有限公司 | Tablet containing Sacubitril valsartan sodium and preparation method thereof |
| CN115444829A (en) * | 2022-10-25 | 2022-12-09 | 南京康川济医药科技有限公司 | Sacubitril valsartan sodium gastric-retention sustained-release tablet and preparation method thereof |
| CN115607544A (en) * | 2021-07-12 | 2023-01-17 | 上海博志研新药物技术有限公司 | Sacubitril valsartan sodium sustained-release composition, preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105935358A (en) * | 2015-12-18 | 2016-09-14 | 重庆两江药物研发中心有限公司 | Sacubitril / valsartan sustained release agent and preparation method thereof |
| 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 |
-
2020
- 2020-12-30 CN CN202011621475.4A patent/CN112641742B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105935358A (en) * | 2015-12-18 | 2016-09-14 | 重庆两江药物研发中心有限公司 | Sacubitril / valsartan sustained release agent and preparation method thereof |
| 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 |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115607544A (en) * | 2021-07-12 | 2023-01-17 | 上海博志研新药物技术有限公司 | Sacubitril valsartan sodium sustained-release composition, preparation method and application thereof |
| WO2023284724A1 (en) * | 2021-07-12 | 2023-01-19 | 上海博志研新药物技术有限公司 | Sacubitril valsartan sodium sustained-release composition, and preparation method therefor and use thereof |
| CN113648284A (en) * | 2021-07-16 | 2021-11-16 | 南京海纳医药科技股份有限公司 | Tablet containing Sacubitril valsartan sodium and preparation method thereof |
| CN115444829A (en) * | 2022-10-25 | 2022-12-09 | 南京康川济医药科技有限公司 | Sacubitril valsartan sodium gastric-retention sustained-release tablet and preparation method thereof |
| CN115444829B (en) * | 2022-10-25 | 2023-08-22 | 南京康川济医药科技有限公司 | Sakuba/valsartan sodium gastric retention sustained release tablet and preparation method thereof |
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| CN112641742B (en) | 2022-12-20 |
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