CN101653430A - Combined capsule filled with solid preparation of angiotensin II receptor antagonist and solid preparation of hydrochlorothiazide - Google Patents
Combined capsule filled with solid preparation of angiotensin II receptor antagonist and solid preparation of hydrochlorothiazide Download PDFInfo
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- CN101653430A CN101653430A CN200910307827A CN200910307827A CN101653430A CN 101653430 A CN101653430 A CN 101653430A CN 200910307827 A CN200910307827 A CN 200910307827A CN 200910307827 A CN200910307827 A CN 200910307827A CN 101653430 A CN101653430 A CN 101653430A
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Abstract
The invention relates to a combined capsule filled with a solid preparation of an angiotensin II receptor antagonist and a solid preparation of hydrochlorothiazide. The combined capsule comprises a first capsule and solid preparations filled in the first capsule, wherein the first capsule comprises an upper capsule body and a lower capsule body; and the first capsule is at least filled with a solid preparation containing an active component of hydrochlorothiazide and a solid preparation containing an active component of angiotensin II receptor antagonist. Compared with the prior art, the invention has the following advantages that components do not generate chemical variance and side products so as to improve the product stability. The product is extremely suitable for industrialized production and has favorable patient compliance.
Description
Technical field
The present invention relates to a kind of oral hard capsule, be filled with the complex capsule of hydrochlorothiazide solid preparation and angiotensin-ii receptor blockers solid preparation in particularly a kind of capsule.
Background technology
For many hyperpietics, only use folk prescription to be difficult to control hypertension, this drops to expected effect to blood pressure with regard to needing the different antihypertensive drug of the mechanism of action to unite use, increase the side effect that drug dose brings in the time of so not only can reducing owing to folk prescription, and antihypertensive effect can be stronger than any folk prescription wherein.The compound candesartan cilexetil capsule is the compound preparation that is formed by angiotensin-ii receptor blockers candesartan Cilexetil and diuretic hydrochlorothiazide compatibility, uses the out of contior hyperpietic of single medicine in order to treatment.
Husky smooth class antihypertensive drug is the new antihypertensive drug that occurs the nineties, is angiotensin ii receptor antagonist.Compare safety and curative effect makes candesartan Cilexetil more be better than calcium antagonist, thiazide diuretic and ACE inhibitor certainly with other antihypertensive drug.But candesartan Cilexetil is increased to its drug effect of doses not to be strengthened thereupon, the treatment of most of patients need with other depressor use in conjunction to reach effective blood pressure lowering purpose.The compound candesartan cilexetil sheet has solved this problem preferably.Studies show that angiotensin-ii receptor blockers plays a role by suppressing Angiotensin II, Angiotensin II is the polypeptide with vasoconstrictive effect, and it can cause hypertension.The diuretic hydrochlorothiazide reduces blood pressure by strengthening kidney ability of row's sodium and row's body fluid in the body.Hydrochlorothiazide and candesartan Cilexetil can produce synergism, its possible mechanism of action is that diuretic can activate renin-angiotensin system, make blood pressure more depend on renin-angiotensin system, thereby strengthen the hypotensive effect of candesartan Cilexetil, remedied single this shortcoming simultaneously with hydrochlorothiazide.In addition, single also may cause hypokalemia with hydrochlorothiazide, can reduce hypokalemic generation when it and candesartan Cilexetil use in conjunction, reason is that candesartan Cilexetil both can reduce the consumption of diuretic and alleviate the change of electrolyte that causes because of diuretic.From the compliance of treatment, these product make patient more be ready to cooperate doctor's treatment.Therefore, the husky smooth hypotensor thing of hypertension therapeutic expert advice should use simultaneously with diuretic in the pertinent literature.
The compound preparation of candesartan Cilexetil and hydrochlorothiazide is developed by U.S. AstraZeneca company, in May, 2000 in Sweden's Initial Public Offering.Also having multiple this type of compound preparation at present, is respectively valsartan+hydrochlorothiazide, losartan+hydrochlorothiazide, irbesartan+hydrochlorothiazide, telmisartan+hydrochlorothiazide, amlodipine+benazepril, enalapril+hydrochlorothiazide, quinapril+hydrochlorothiazide, moexipril+hydrochlorothiazide.Amlodipine+valsartan+hydrochlorothiazide tablet the compound preparation that also has the Novartis Co.,Ltd of U.S.'s approval.
The nervous plain II receptor blocking agent of above-mentioned dosage form medium vessels and two kinds of active component of hydrochlorothiazide, and there be contact possible in angiotensin-ii receptor blockers and three kinds of active component of hydrochlorothiazide and amlodipine.And the various active composition is all in same minimum preparation unit.
If active component contacts with each other, have following shortcoming: 1, because multicomponent mixing homogeneity degree influences, each composition is difficult to accurately quantitatively; When 2, product detects,, influence the qualitative and quantitative analysis result because the phase mutual interference is difficult for measuring each component content; 3, during long preservation, change because chemical compatibility may take place between each composition, be easy to generate by-product, reduce effect or increase side effect, product stability is not ideal enough.Because above-mentioned defective exists, there are many advantages although contain the existing compound recipe dosage form of hydrochlorothiazide, but still may cause harmful effect product quality and human body health.
Though can come the quality of strict control medicine in the pharmaceuticals industry by the GMP standard, find simple production technology to guarantee that the quality of medicine remains one of direction of drug research and development, also meets the aim of medicine GMP.
Summary of the invention
The invention provides a kind of complex capsule that angiotensin-ii receptor blockers solid preparation and hydrochlorothiazide solid preparation are housed, do not contact mutually between the various active component in the capsule, thereby obtain stability complex capsule better, easy to process.
Complex capsule of the present invention, form by the solid preparation in first capsule and first capsule, first capsule comprises utricule and following utricule, wherein in first capsule at least active component of filling be the solid preparation of angiotensin-ii receptor blockers and active component of filling solid preparation that is hydrochlorothiazide at least.
Angiotensin-ii receptor blockers of the present invention comprises candesartan Cilexetil, valsartan, losartan, irbesartan, telmisartan etc.Wherein optimum is candesartan Cilexetil.
Complex capsule of the present invention also is filled with the solid preparation that at least one amlodipine is an active component in first capsule.
The preferred scheme of complex capsule of the present invention is active component of filling is a benazepril in first capsule solid preparation and a solid preparation and the solid preparation that hydrochlorothiazide is an active component that hydrochlorothiazide is an active component.
Complex capsule of the present invention, solid preparation wherein are the tablet or second capsule.
Complex capsule of the present invention, wherein tablet is a coating.
Above-mentioned amlodipine also can be other calcium ion antagonists.
Complex capsule of the present invention, wherein first capsule is No. 0 or No. 1 capsule, thus for the first capsular compliance that increases the patient attractive in appearance, the first capsular utricule of going up is colourless with following utricule.
In order to be fit to that mechanization is produced and to be convenient to be identified, but various tablets or the identical color difference of the second capsular shape in first capsule.
Particularly in order to adapt to the capsule filling machine that goes on the market and use, the shape of described various tablets is made into column type.Automatic capsule filling machine (KF-S50) such as Korea S INNOTECH SYSTEMS LTD. company.
Also in order to adapt to the slice, thin piece of different content active component, also can select the capsule of other models simultaneously.
The utilization of technique scheme, the present invention compared with prior art have following advantage:
1. because the active component in first capsule is not contacted each other, so chemistry 5 can not take place between each composition becomes and produce by-product, the stability of product is improved.
2. owing to adopted the design of column type slice, thin piece and different colours, and the application of transparent softgel shell, make product of the present invention be fit to very much suitability for industrialized production, strengthened patient's compliance.
3. because the present invention adopts is active component film-making respectively, on the check of medicine and quality control, be more prone to.
Description of drawings
Accompanying drawing 1 is the axonometric chart of the complex capsule of embodiments of the invention 1.Wherein, 1, capsule body down; 2, go up capsule body; 3, candesartan cilexetil; 4, hydrochlorothiazide tablet; 5, amlodipine sheet.
Accompanying drawing 2 is the exploded perspective view of the complex capsule of embodiment 1.1, following capsule body; 2, go up capsule body; 3, candesartan Cilexetil; 4, hydrochlorothiazide tablet; 5, amlodipine sheet.
Accompanying drawing 3 is the A A cutaway view of the complex capsule of embodiment 1.Wherein, 1, capsule body down; 2, go up capsule body; 3, candesartan cilexetil; 4, hydrochlorothiazide tablet; 5, amlodipine sheet.
Accompanying drawing 4 is the cutaway view of embodiments of the invention 2.Wherein, 1, capsule body down; 2, go up capsule body; 3, candesartan cilexetil; 4, hydrochlorothiazide tablet.
The specific embodiment
Below in conjunction with drawings and Examples the present invention is further described: candesartan cilexetil/hydrochlorothiazide: 16mg/12.5mg; 32mg/12.5mg; 32mg/25mg
Embodiment 1: shown in accompanying drawing 1-3, and the complex capsule of valsartan sheet of filling, a hydrochlorothiazide tablet and an amlodipine in the seed capsules.The first capsule specification is No. 0.First capsule housing is by capsule body 1 and last capsule body 2 suits constitute down, the slice of cylinder of above-mentioned 3 different colours coatings is housed, is respectively benazepril sheet (containing valsartan 160mg), hydrochlorothiazide (containing hydrochlorothiazide 12.5mg) and amlodipine sheet (containing amlodipine 5mg).
Benazepril is that yellow stomach dissolution type film-coat, hydrochlorothiazide tablet are that red film-coat, amlodipine is black stomach dissolution type film-coat or all adopts identical color.
Embodiment 2: shown in accompanying drawing 4, and the complex capsule of a candesartan cilexetil of filling and a hydrochlorothiazide tablet in the seed capsules.The first capsule specification is No. 0.First capsule housing is made of with last capsule body 2 suits following capsule body 1, and the slice of cylinder of above-mentioned 2 different colours coatings is housed, and is respectively candesartan cilexetil (containing candesartan Cilexetil 16mg), hydrochlorothiazide tablet (hydrochlorothiazide 12.5mg).Hydrochlorothiazide tablet is that yellow stomach dissolution type film-coat, benazepril sheet are red film-coat.
Embodiment 3-5: the kind of institute's load is embodiment 2 roughly the same, and different is the active component content of each slice, thin piece:
| Candesartan Cilexetil mg | Color | Hydrochlorothiazide mg | Color | |
| |
??32 | Red tab | ??12.5 | |
| Embodiment | ||||
| 4 | ??32 | White tablets | ??25 | Black patch |
The steadiness of complex capsule of the present invention is described below in conjunction with the test example
Test example 1 is carried out hot test (60 ℃), high wet test (RH75%), exposure experiments to light (3000LX) respectively with embodiment 1,2 prepared complex capsules and is carried out test in 10 days, the results are shown in Table 1-3:
Table 1, hot test
| |
|
||
| 0 day content | Valsartan (%) | ?99.46 | |
| Hydrochlorothiazide (%) | ?99.29 | ?100.7 | |
| Amlodipine (%) | ?99.11 | ||
| Candesartan Cilexetil (%) | ?99.57 | ||
| 5 days content | Valsartan (%) | ?99.57 | |
| Hydrochlorothiazide (%) | ?99.45 | ?100.3 | |
| Amlodipine (%) | ?99.83 | ||
| Candesartan Cilexetil (%) | ?99.95 | ||
| 10 days content | Valsartan (%) | ?99.55 | |
| Hydrochlorothiazide (%) | ?99.47 | ?100.2 | |
| Amlodipine (%) | ?100.1 | ||
| Candesartan Cilexetil (%) | ?100.0 |
Annotate: content is sign content in the table
Table 2, high wet test
| |
|
||
| 0 day content | Valsartan (%) | ?99.46 | |
| Hydrochlorothiazide (%) | ?99.29 | ?100.7 | |
| Amlodipine (%) | ?99.11 | ||
| Candesartan Cilexetil (%) | ?99.57 | ||
| 5 days content | Valsartan (%) | ?99.47 | ?99.69 |
| Hydrochlorothiazide (%) | ?99.46 | ?99.33 | |
| Amlodipine (%) | ?99.98 | ||
| Candesartan Cilexetil (%) | |||
| 10 days content | Valsartan (%) | ?99.36 | |
| Hydrochlorothiazide (%) | ?99.72 | ?99.43 | |
| Amlodipine (%) | ?99.36 | ||
| Candesartan Cilexetil (%) | ?99.39 |
Annotate: content is sign content in the table
Table 3, exposure experiments to light
| |
|
||
| 0 day content | Valsartan (%) | ?99.46 | |
| Hydrochlorothiazide (%) | ?99.29 | ?100.7 | |
| Amlodipine (%) | ?99.11 | ||
| Candesartan Cilexetil (%) | ?99.57 | ||
| 5 days content | Valsartan (%) | ?99.57 | |
| Hydrochlorothiazide (%) | ?99.73 | ?99.76 | |
| Amlodipine (%) | ?99.68 | ||
| Candesartan Cilexetil (%) | |||
| 10 days content | Valsartan (%) | ?99.19 | |
| Hydrochlorothiazide (%) | ?99.32 | ?99.43 | |
| Amlodipine (%) | ?100.2 | ||
| Candesartan Cilexetil (%) | ?99.37 |
Annotate: content is sign content in the table
Stability test is the result show, embodiments of the invention obtain product content does not have significant change.Owing to be to measure respectively, detection method is easy, needn't consider compound medicine between the phase mutual interference.
Claims (7)
1. complex capsule, form by the solid preparation in first capsule and first capsule, first capsule comprises utricule and following utricule, it is characterized in that, in described first capsule at least active component of filling be the solid preparation of angiotensin-ii receptor blockers and active component of filling solid preparation that is hydrochlorothiazide at least.
2. complex capsule as claimed in claim 1 is characterized in that, also is filled with the solid preparation that at least one amlodipine is an active component in described first capsule.
3. complex capsule as claimed in claim 2, it is characterized in that, active component of filling is an angiotensin-ii receptor blockers in described first capsule solid preparation and a solid preparation and the solid preparation that amlodipine is an active component that hydrochlorothiazide is an active component.
4. as the described complex capsule of claim 1-3, it is characterized in that described solid preparation is the tablet or second capsule.
5. complex capsule as claimed in claim 4 is characterized in that described tablet is a coating.
6. complex capsule as claimed in claim 4 is characterized in that, the coating of described tablet is a different colours, and described tablet is the identical cylinder of shape.
7. complex capsule as claimed in claim 1 is characterized in that, described first capsule is No. 0 or No. 1 capsule, and the first capsular utricule of going up is colourless with following utricule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910307827A CN101653430A (en) | 2009-09-27 | 2009-09-27 | Combined capsule filled with solid preparation of angiotensin II receptor antagonist and solid preparation of hydrochlorothiazide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910307827A CN101653430A (en) | 2009-09-27 | 2009-09-27 | Combined capsule filled with solid preparation of angiotensin II receptor antagonist and solid preparation of hydrochlorothiazide |
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| Publication Number | Publication Date |
|---|---|
| CN101653430A true CN101653430A (en) | 2010-02-24 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910307827A Pending CN101653430A (en) | 2009-09-27 | 2009-09-27 | Combined capsule filled with solid preparation of angiotensin II receptor antagonist and solid preparation of hydrochlorothiazide |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102614189A (en) * | 2012-04-17 | 2012-08-01 | 北京哈三联科技股份有限公司 | Pellet medicine combination containing valsartan, amlodipine and hydrochlorothiazide |
-
2009
- 2009-09-27 CN CN200910307827A patent/CN101653430A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102614189A (en) * | 2012-04-17 | 2012-08-01 | 北京哈三联科技股份有限公司 | Pellet medicine combination containing valsartan, amlodipine and hydrochlorothiazide |
| CN102614189B (en) * | 2012-04-17 | 2014-10-22 | 北京哈三联科技股份有限公司 | Pellet medicine combination containing valsartan, amlodipine and hydrochlorothiazide |
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| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| ASS | Succession or assignment of patent right |
Owner name: HEILONGJIANG FUHE HUAXING PHARMACY GROUP CO., LTD. Free format text: FORMER OWNER: WU GUANGYAN Effective date: 20110518 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20110518 Address after: 151100 Heilongjiang Zhaodong Taiping Road 34, Heilongjiang Dilong pharmaceutical Limited by Share Ltd Applicant after: Heilongjiang Fuhe Huaxing Pharmaceutical Group Co., Ltd. Address before: 151100 Heilongjiang Zhaodong Taiping Road 34, Heilongjiang Dilong pharmaceutical Limited by Share Ltd Applicant before: Wu Guangyan |
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20100224 |