CN104230808A - Amorphous ivabradine hydrochloride, and preparation method and application thereof - Google Patents
Amorphous ivabradine hydrochloride, and preparation method and application thereof Download PDFInfo
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- CN104230808A CN104230808A CN201410418013.0A CN201410418013A CN104230808A CN 104230808 A CN104230808 A CN 104230808A CN 201410418013 A CN201410418013 A CN 201410418013A CN 104230808 A CN104230808 A CN 104230808A
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- 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
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
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- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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Abstract
The invention belongs to the field of pharmaceutical chemistry, and particularly relates to an amorphous ivabradine hydrochloride, and a preparation method and application thereof. The preparation method comprises the following steps: dissolving ivabradine hydrochloride in water to prepare an ivabradine hydrochloride water solution, filtering, taking the filtrate, and carrying out freeze-drying treatment under vacuum conditions to obtain the amorphous ivabradine hydrochloride. The preparation method has the advantages of favorable repetitiveness and stable technique, and is suitable for industrial production. The prepared amorphous ivabradine hydrochloride is controllable and single in crystal form.
Description
Technical field
The invention belongs to medicinal chemistry art, be specifically related to a kind of amorphous ivabradine hydrochloride and preparation method thereof and application.
Background technology
Hydrochloric acid Ivabradine (Ivabradine hydrochloride), chemical name: 3-[3-[[(8S)-3,4-dimethoxy-8-dicyclo [4.2.0] pungent-1,3,5-triolefin] methyl-methylamino-] propyl group]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepine-4-keto hydrochloride, chemical structural formula is as follows:
Hydrochloric acid Ivabradine is first selectivity and specificity If channel blocker developed by French Shi Weiya company, there is simple reduction heart rate function, be used for the treatment of with normal sinus rhythm, to beta-blockers taboo or the symptomatic treatment of not tolerant chronic stable angina pectoris.
About hydrochloric acid Ivabradine, develop the product reporting all polymorphic structures at present, usually, the same medicine of different crystal forms has difference in outward appearance, solubleness, fusing point, dissolution rate and biological effectiveness etc., even significant difference be may have, the stability of medicine, bioavailability and curative effect etc. thus can be affected.The patent CN1683341A that Shi Weiya applies in China, CN1827600A, CN100404512A, CN1948292A, CN1948293A, CN100402502A, CN100432057A report the product of several crystal formation of α, β, β d, δ, δ d, γ and γ d respectively.And the document such as CN101597261A, CN101463008A, CN102050784A, WO2008146308A2 also reports the product of amorphous crystal formation respectively in prior art, and disclose the method for the unformed hydrochloric acid Ivabradine product of preparation conventional in prior art.The method of above-mentioned record is all generally be raw material with hydrochloric acid Ivabradine, after utilizing dissolution with solvents, then adopts the method such as concentrating under reduced pressure method, mixed solvent crystallization method to carry out crystallization treatment.But aforesaid method all existing poor repeatability, the problem of technique instability when preparing unformed hydrochloric acid Ivabradine product, being not only difficult to control the product for single crystal form, not also being suitable for the demand of suitability for industrialized production simultaneously.
Summary of the invention
For this reason, the present invention will solve preparation method's poor repeatability of existing amorphous ivabradine hydrochloride, the technical problem of technique instability, thus proposes a kind of preparation method of new amorphous ivabradine hydrochloride.
For solving the problems of the technologies described above, the present invention is achieved through the following technical solutions:
A kind of preparation method of amorphous ivabradine hydrochloride, described method comprises: prepare the hydrochloric acid Ivabradine aqueous solution by soluble in water for hydrochloric acid Ivabradine, after filtration, get filtrate and carry out lyophilize process under vacuum, obtain required amorphous ivabradine hydrochloride.
Further, the step of described lyophilize process specifically comprises:
(1) control described temperature and be cooled to-70 DEG C ~-40 DEG C in 0.2-1 hour, and be incubated 0.5-2 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature-40 DEG C ~-20 DEG C, and be incubated 1-3 hour;
(4) control described temperature in 0.5-1.5 hour, be warmed up to-5 DEG C ~ 0 DEG C, and be incubated 4-6 hour;
(5) control described temperature in 0.5-1.5 hour, be warmed up to 10 DEG C ~ 20 DEG C, and be incubated 0.5-2 hour;
(6) control described temperature and be warmed up to 35-45 DEG C in 1-3 hour, and be incubated 15-25 hour.
Preferably, the step of described lyophilize process specifically comprises:
(1) control described temperature and be cooled to-70 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-30 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to-5 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 15 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
Or
(1) control described temperature and be cooled to-50 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-30 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to 0 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 10 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
Or
(1) control described temperature and be cooled to-60 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-40 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to 0 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 10 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
Or
(1) control described temperature and be cooled to-40 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-20 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to 0 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 20 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
Or
(1) control described temperature and be cooled to-40 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-20 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to-5 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 20 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours.
The described step preparing the hydrochloric acid Ivabradine aqueous solution is dissolved in 50-250 parts by volume water by 4-6 weight part hydrochloric acid Ivabradine to be prepared from; Described weight part and parts by volume are the relation of g/mL.
And preferred further, 5 weight part hydrochloric acid Ivabradines are dissolved in 200 parts by volume water and are prepared from; Or
5 weight part hydrochloric acid Ivabradines are dissolved in 50 parts by volume water and are prepared from; Or
5 weight part hydrochloric acid Ivabradines are dissolved in 100 parts by volume water and are prepared from; Or
5 weight part hydrochloric acid Ivabradines are dissolved in 150 parts by volume water and are prepared from; Or
5 weight part hydrochloric acid Ivabradines are dissolved in 250 parts by volume water and are prepared from.
Preparation Method of the present invention, also comprises further by the amorphous ivabradine hydrochloride obtained further dry, the step pulverizing and sieve.
Present invention also offers a kind of amorphous ivabradine hydrochloride prepared by described method, use CuK α radiation, its X-ray Powder Diffraction pattern is the amorphous characteristic spectrum without any diffraction peak, and concrete collection of illustrative plates is shown in shown in Fig. 1-5.
Present invention also offers a kind of pharmaceutical composition comprising above-mentioned amorphous ivabradine hydrochloride.
Present invention also offers and a kind of add customary adjuvant by aforementioned pharmaceutical compositions, conveniently the clinical acceptable pharmaceutical preparation made of technique, described preparation preferred oral preparation, includes but not limited to tablet, capsule or granule.
The amount containing amorphous ivabradine hydrochloride in described unit formulation is calculate for 5-40mg/ days according to taking amount of formulation day.
Present invention also offers a kind of medicinal tablet containing amorphous ivabradine hydrochloride, be made up of following raw material: amorphous substance 8.09g, the W-Gum 20g of hydrochloric acid Ivabradine, anhydride silica 0.2g, mannitol 63.91g, PVP10g and Magnesium Stearate 0.5g; Conveniently technique makes 1000.
Compared with prior art, the preparation method of amorphous ivabradine hydrochloride of the present invention reproducible and experiment display, the X-ray Powder Diffraction pattern of the amorphous ivabradine hydrochloride obtained is basically identical, process stabilizing, be suitable for suitability for industrialized production, and be easy to control the amorphous ivabradine hydrochloride for single.
Accompanying drawing explanation
In order to make content of the present invention be more likely to be clearly understood, below according to a particular embodiment of the invention and by reference to the accompanying drawings, the present invention is further detailed explanation, wherein
Fig. 1-5 is respectively the X-ray Powder Diffraction pattern of the amorphous ivabradine hydrochloride prepared in embodiment 1-5.
Embodiment
Embodiment 1
Described in the present embodiment, amorphous ivabradine hydrochloride is prepared as follows: after being dissolved completely by the deionized water of the crystal type hydrochloric acid Ivabradine 200mL of 5.0g, after 0.45 μm of membrane filtration, filtrate slowly pours lyophilized plate into, opens Freeze Drying Equipment, freeze-drying program is set as follows:
(1) control described temperature and be cooled to-70 DEG C by room temperature in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-30 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to-5 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 15 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
After vacuum breaker outlet, pulverize, sieve, to obtain final product.
Embodiment 2
Described in the present embodiment, amorphous ivabradine hydrochloride is prepared as follows: after being dissolved completely by the deionized water of the crystal type hydrochloric acid Ivabradine 50mL of 5.0g, after 0.45 μm of membrane filtration, filtrate slowly pours lyophilized plate into, opens Freeze Drying Equipment, freeze-drying program is set as follows:
(1) control described temperature and be cooled to-50 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-30 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to 0 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 10 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
After vacuum breaker outlet, pulverize, sieve, to obtain final product.
Embodiment 3
Described in the present embodiment, amorphous ivabradine hydrochloride is prepared as follows: after being dissolved completely by the deionized water of the crystal type hydrochloric acid Ivabradine 100mL of 5.0g, after 0.45 μm of membrane filtration, filtrate slowly pours lyophilized plate into, opens Freeze Drying Equipment, freeze-drying program is set as follows:
(1) control described temperature and be cooled to-60 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-40 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to 0 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 10 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
After vacuum breaker outlet, pulverize, sieve, to obtain final product.
Embodiment 4
Described in the present embodiment, amorphous ivabradine hydrochloride is prepared as follows: after being dissolved completely by the deionized water of the crystal type hydrochloric acid Ivabradine 150mL of 5.0g, after 0.45 μm of membrane filtration, filtrate slowly pours lyophilized plate into, opens Freeze Drying Equipment, freeze-drying program is set as follows:
(1) control described temperature and be cooled to-40 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-20 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to 0 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 20 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
After vacuum breaker outlet, pulverize, sieve, to obtain final product.
Embodiment 5
Described in the present embodiment, amorphous ivabradine hydrochloride is prepared as follows: after being dissolved completely by the deionized water of the crystal type hydrochloric acid Ivabradine 250mL of 5.0g, after 0.45 μm of membrane filtration, filtrate slowly pours lyophilized plate into, opens Freeze Drying Equipment, freeze-drying program is set as follows:
(1) control described temperature and be cooled to-40 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-20 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to-5 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 20 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
After vacuum breaker outlet, pulverize, sieve, to obtain final product.
As can be seen from accompanying drawing 1-5, under the method for the invention instructs, the X-ray Powder Diffraction pattern of the amorphous ivabradine hydrochloride that different embodiment prepares is basically identical, visible described method process stabilizing, is suitable for suitability for industrialized production; And Fig. 1-5 is visible, X-ray Powder Diffraction pattern is the characteristic spectrum of amorphous ivabradine hydrochloride, illustrates that the inventive method is easy to control the amorphous ivabradine hydrochloride for single.
Embodiment 6 is containing the tablet of amorphous ivabradine hydrochloride
[formula]
By above-mentioned raw materials, conveniently technique makes 1000, every sheet is containing the tablet of 7.5mg amorphous ivabradine hydrochloride.
Obviously, above-described embodiment is only for clearly example being described, and the restriction not to embodiment.For those of ordinary skill in the field, can also make other changes in different forms on the basis of the above description.Here exhaustive without the need to also giving all embodiments.And thus the apparent change of extending out or variation be still among the protection domain of the invention.
Claims (10)
1. the preparation method of an amorphous ivabradine hydrochloride, it is characterized in that, described method comprises: prepare the hydrochloric acid Ivabradine aqueous solution by soluble in water for hydrochloric acid Ivabradine, after filtration, get filtrate and carry out lyophilize process under vacuum, obtain required amorphous ivabradine hydrochloride.
2. the preparation method of amorphous ivabradine hydrochloride according to claim 1, is characterized in that, the step of described lyophilize process specifically comprises:
(1) control described temperature and be cooled to-70 DEG C ~-40 DEG C in 0.2-1 hour, and be incubated 0.5-2 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature-40 DEG C ~-20 DEG C, and be incubated 1-3 hour;
(4) control described temperature in 0.5-1.5 hour, be warmed up to-5 DEG C ~ 0 DEG C, and be incubated 4-6 hour;
(5) control described temperature in 0.5-1.5 hour, be warmed up to 10 DEG C ~ 20 DEG C, and be incubated 0.5-2 hour;
(6) control described temperature and be warmed up to 35-45 DEG C in 1-3 hour, and be incubated 15-25 hour.
3. the preparation method of amorphous ivabradine hydrochloride according to claim 1 and 2, is characterized in that, the step of described lyophilize process specifically comprises:
(1) control described temperature and be cooled to-70 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-30 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to-5 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 15 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
Or
(1) control described temperature and be cooled to-50 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-30 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to 0 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 10 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
Or
(1) control described temperature and be cooled to-60 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-40 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to 0 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 10 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
Or
(1) control described temperature and be cooled to-40 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-20 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to 0 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 20 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours;
Or
(1) control described temperature and be cooled to-40 DEG C in 0.5 hour, and be incubated 1 hour;
(2) vacuum pump evacuation is opened;
(3) control described temperature to-20 DEG C, and be incubated 2 hours;
(4) control described temperature and be warmed up to-5 DEG C in 1 hour, and be incubated 5 hours;
(5) control described temperature and be warmed up to 20 DEG C in 1 hour, and be incubated 1 hour;
(6) control described temperature and be warmed up to 40 DEG C in 2 hours, and be incubated 20 hours.
4. according to the preparation method of the arbitrary described amorphous ivabradine hydrochloride of claim 1-3, it is characterized in that, the described step preparing the hydrochloric acid Ivabradine aqueous solution is dissolved in 50-250 parts by volume water by 4-6 weight part hydrochloric acid Ivabradine to be prepared from; Described weight part and parts by volume are the relation of g/mL.
5. according to the preparation method of the arbitrary described amorphous ivabradine hydrochloride of claim 1-4, it is characterized in that, also comprise the amorphous ivabradine hydrochloride obtained dry, the step pulverizing and sieve further.
6. according to the amorphous ivabradine hydrochloride that the arbitrary described method of claim 1-5 prepares, it is characterized in that, use CuK α radiation, its X-ray Powder Diffraction pattern is the amorphous characteristic spectrum without any diffraction peak.
7. comprise the pharmaceutical composition of amorphous ivabradine hydrochloride according to claim 6.
8. add customary adjuvant by pharmaceutical composition described in claim 7, conveniently the clinical acceptable pharmaceutical preparation made of technique.
9. pharmaceutical preparation according to claim 8, is characterized in that, the amount containing amorphous ivabradine hydrochloride in described unit formulation is calculate for 5-40mg/ days according to taking amount of formulation day.
10. the medicinal tablet containing amorphous ivabradine hydrochloride, it is characterized in that, be made up of following raw material: amorphous substance 8.09g, the W-Gum 20g of hydrochloric acid Ivabradine, anhydride silica 0.2g, mannitol 63.91g, PVP10g and Magnesium Stearate 0.5g; Conveniently technique makes 1000.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410418013.0A CN104230808B (en) | 2014-08-22 | 2014-08-22 | Amorphous ivabradine hydrochloride and preparation method thereof and application |
| PCT/CN2014/085997 WO2016026172A1 (en) | 2014-08-22 | 2014-09-05 | Amorphous ivabradine hydrochloride, and preparation method therefor and uses thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410418013.0A CN104230808B (en) | 2014-08-22 | 2014-08-22 | Amorphous ivabradine hydrochloride and preparation method thereof and application |
Publications (2)
| Publication Number | Publication Date |
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| CN104230808A true CN104230808A (en) | 2014-12-24 |
| CN104230808B CN104230808B (en) | 2016-05-18 |
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| CN201410418013.0A Active CN104230808B (en) | 2014-08-22 | 2014-08-22 | Amorphous ivabradine hydrochloride and preparation method thereof and application |
Country Status (2)
| Country | Link |
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| CN (1) | CN104230808B (en) |
| WO (1) | WO2016026172A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107963991A (en) * | 2017-12-29 | 2018-04-27 | 成都百裕制药股份有限公司 | A kind of production method of amorphous tolvaptan |
| WO2020088481A1 (en) * | 2018-10-30 | 2020-05-07 | 中国科学院化学研究所 | Method for preparing drug or drug intermediate single crystal or amorphous substance |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008146308A2 (en) * | 2007-05-30 | 2008-12-04 | Ind-Swift Laboratories Limited | Process for the preparation of ivabradine hydrochloride and polymorph thereof |
| CN101463008A (en) * | 2009-01-11 | 2009-06-24 | 山东鲁抗辰欣药业有限公司 | Ivabradine amorphous article and preparation thereof |
| CN101597261A (en) * | 2008-06-06 | 2009-12-09 | 北京深蓝海生物医药科技有限公司 | Amorphous ivabradine hydrochloride |
| CN102050784A (en) * | 2009-11-04 | 2011-05-11 | 扬子江药业集团北京海燕药业有限公司 | Novel method for preparing amorphous Ivabradine hydrochloride |
| WO2013150544A2 (en) * | 2012-04-02 | 2013-10-10 | Hetero Research Foundation | Ivabradine hydrochloride solid dispersion |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8158152B2 (en) * | 2005-11-18 | 2012-04-17 | Scidose Llc | Lyophilization process and products obtained thereby |
| WO2014102827A1 (en) * | 2012-12-28 | 2014-07-03 | Glenmark Pharmaceuticals Limited; Glenmark Generics Limited | Process for preparation of ivabradine |
-
2014
- 2014-08-22 CN CN201410418013.0A patent/CN104230808B/en active Active
- 2014-09-05 WO PCT/CN2014/085997 patent/WO2016026172A1/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008146308A2 (en) * | 2007-05-30 | 2008-12-04 | Ind-Swift Laboratories Limited | Process for the preparation of ivabradine hydrochloride and polymorph thereof |
| CN101597261A (en) * | 2008-06-06 | 2009-12-09 | 北京深蓝海生物医药科技有限公司 | Amorphous ivabradine hydrochloride |
| CN101463008A (en) * | 2009-01-11 | 2009-06-24 | 山东鲁抗辰欣药业有限公司 | Ivabradine amorphous article and preparation thereof |
| CN102050784A (en) * | 2009-11-04 | 2011-05-11 | 扬子江药业集团北京海燕药业有限公司 | Novel method for preparing amorphous Ivabradine hydrochloride |
| WO2013150544A2 (en) * | 2012-04-02 | 2013-10-10 | Hetero Research Foundation | Ivabradine hydrochloride solid dispersion |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107963991A (en) * | 2017-12-29 | 2018-04-27 | 成都百裕制药股份有限公司 | A kind of production method of amorphous tolvaptan |
| WO2020088481A1 (en) * | 2018-10-30 | 2020-05-07 | 中国科学院化学研究所 | Method for preparing drug or drug intermediate single crystal or amorphous substance |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016026172A1 (en) | 2016-02-25 |
| CN104230808B (en) | 2016-05-18 |
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