CN103467363A - Carvedilol-asccharin amorphous compound - Google Patents
Carvedilol-asccharin amorphous compound Download PDFInfo
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- CN103467363A CN103467363A CN2013104460442A CN201310446044A CN103467363A CN 103467363 A CN103467363 A CN 103467363A CN 2013104460442 A CN2013104460442 A CN 2013104460442A CN 201310446044 A CN201310446044 A CN 201310446044A CN 103467363 A CN103467363 A CN 103467363A
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- carvedilol
- asccharin
- amorphous article
- amorphous compound
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Abstract
The invention relates to a carvedilol-asccharin amorphous compound. The carvedilol-asccharin amorphous compound is obtained by combination of carvedilol and asccharin. Based on Cu-K alpha radiation, an X-ray powder diffraction spectrum represented by a degree of 2 theta does not comprise a sharp diffraction peak. The powder X-ray diffraction spectrum of the carvedilol-asccharin amorphous compound is different from those of carvedilol crystals and a physical mixture of carvedilol crystals and asccharin crystals and thus the carvedilol-asccharin amorphous compound is a novel amorphous compound completely different from carvedilol crystals and the physical mixture of carvedilol crystals and asccharin crystals. The carvedilol-asccharin amorphous compound can obviously improve solubility of carvedilol in various mediums.
Description
Technical field
The invention belongs to medical technical field, be specifically related to carvedilol and asccharin and be total to amorphous article and preparation method thereof in conjunction with the carvedilol asccharin formed in 1: 1 in molar ratio.
Background technology
Carvedilol (carvedilol), chemical name is 1-carbazole-4-oxygen base-3-[2-(2-methoxyphenoxy) ethylamino]-the 2-propyl alcohol, be novel medicament for expanding vascellum.Clinically, can be used for treating essential hypertension, cardiac insufficiency.
Carvedilol, in the therapeutic dose scope, has α 1 and non-selective beta receptor retardation concurrently, without intrinsic sympathomimetic acitivity.This product retardance postsynaptic membrane α acceptor, thereby expansion blood. pipe, reduction peripheral vascular resistance; The retardance beta receptor, suppress the renal secretion feritin, and the blocking-up renin-angiotensin-aldosterone system, produce hypotensive effect.The carvedilol step-down is rapid, can maintain for a long time hypotensive effect.
Carvedilol is biopharmacy categorizing system II class medicine, and it is insoluble in water, first pass effect is obvious, makes its absolute bioavailability only have 25%-35%.The present invention is prepared into a kind of carvedilol asccharin amorphous article altogether, its solubleness is improved, to reaching the purpose of improving bioavailability.
Summary of the invention
The purpose of this invention is to provide a kind of carvedilol asccharin amorphous article altogether.
Carvedilol asccharin of the present invention is amorphous article altogether, has following feature:
1, powder x-ray diffraction
Instrument: XTRA/3KW X-ray diffractometer (Switzerland Arl Inc.)
Target: Cu-K α radiation
Wavelength: 1.5406A
Pipe is pressed: 40KV
Pipe stream: 40mA
Step-length: 0.02 °
Sweep velocity: 8 °/min
Result shows: the carvedilol asccharin spectrogram of amorphous article does not altogether have sharp-pointed diffraction peak.
Another object of the present invention is to provide and prepares the carvedilol asccharin method of amorphous article altogether.
A kind of described carvedilol asccharin is the preparation method of amorphous article altogether, and it comprises asccharin and carvedilol are added in organic solvent, stirring and dissolving, obtain clarified liq, decompression rotary evaporation solvent under 40-60 ℃, vacuum-drying, obtain carvedilol asccharin amorphous article altogether.
Described organic solvent can be single solvent or the mixed solvent that ethanol maybe can make carvedilol, asccharin dissolve, preferred alcohol.
The consumption of carvedilol is 0.8-1.2 times of molar equivalent of asccharin, 1 times of molar equivalent that preferably consumption of carvedilol is the asccharin consumption.
The temperature of decompression rotary evaporation solvent is chosen as 40-60 ℃, and preferably temperature is 55 ℃.
A kind of described carvedilol asccharin is the preparation method of amorphous article altogether, and it comprises asccharin and carvedilol are added in organic solvent, and stirring and dissolving, obtain clarified liq, and slow evaporation solvent under normal temperature obtains carvedilol asccharin amorphous article altogether.
Described organic solvent can be single solvent or the mixed solvent that ethanol maybe can make carvedilol, asccharin dissolve, preferred alcohol.
The consumption of carvedilol is 0.8-1.2 times of molar equivalent of asccharin, 1 times of molar equivalent that preferably consumption of carvedilol is the asccharin consumption.
In the present invention, the powder x-ray diffraction of carvedilol, the carvedilol asccharin crystallophy mixture of amorphous article and existing patent report is all different altogether in open carvedilol asccharin Lip river, so described solid form is a kind of form that is different from carvedilol and the asccharin of prior art fully.
The accompanying drawing explanation
Fig. 1 is the x-ray diffractogram of powder of carvedilol.
Fig. 2 is the x-ray diffractogram of powder of carvedilol asccharin crystallophy mixture.
Fig. 3 is the carvedilol asccharin x-ray diffractogram of powder of amorphous article altogether.
Embodiment
Embodiment
1, powder x-ray diffraction
Instrument: XTRA/3KW X-ray diffractometer (Switzerland Arl Inc.)
Target: Cu-K α radiation
Wavelength: 1.5406A
Pipe is pressed: 40KV
Pipe stream: 40mA
Step-length: 0.02 °
Sweep velocity: 8 °/min
Result shows: the carvedilol asccharin spectrogram of amorphous article does not altogether have sharp-pointed diffraction peak.
Embodiment 1: the carvedilol asccharin is the preparation of amorphous article altogether
By carvedilol 1.11g, asccharin 0.5g, add ethanol 15ml, room temperature (20 ± 5 ℃) stirs to obtain settled solution, rotary evaporation solvent that this settled solution is reduced pressure under 55 ℃, 25 ℃ of vacuum-drying 24h, obtain white powder 1.20g.
Embodiment 2: the carvedilol asccharin is the preparation of amorphous article altogether
By carvedilol 222mg, asccharin 100mg, add ethanol 10ml, room temperature (20 ± 5 ℃) stirs to obtain settled solution, slowly volatilizes solvent under room temperature, and 25 ℃ of vacuum-drying 24h, obtain white powder 200mg.
Solubility test
Measure respectively carvedilol, carvedilol asccharin crystallophy mixture, the carvedilol asccharin solubleness of amorphous article carvedilol in water and various pH damping fluid altogether.Measure respectively the medium (pH3.5,4.5,5.5,6.8 phosphate buffered saline buffer, water) of 5ml in cillin bottle, the cillin bottle sealing is placed in to 25 ℃ of constant temperature oscillators after adding the overdose of medicine thing.After jolting 12h reaches balance, get solution and cross the 0.22um filter membrane, get subsequent filtrate sample introduction HPLC after appropriate dilution and record solubleness.The results are shown in Table 1.
The dissolubility data of the various samples of table 1
As can be seen here, the solubleness of the common amorphous article carvedilol in various media of carvedilol asccharin all is significantly higher than carvedilol crystal and carvedilol asccharin crystallophy mixture.
Claims (5)
1. carvedilol asccharin amorphous article altogether, is characterized in that, be by carvedilol and asccharin 1: 1 in molar ratio in conjunction with forming, use Cu-K α radiation, do not have sharp-pointed diffraction peak to spend the X-ray powder diffraction spectrum that 2 θ mean.
2. carvedilol asccharin according to claim 1 is total to the preparation method of amorphous article, it is characterized in that, its preparation method is that carvedilol and asccharin are added in ethanol, stirring and dissolving, decompression rotary evaporation solvent under 40-60 ℃, vacuum-drying, obtain carvedilol asccharin amorphous article altogether.
3. carvedilol asccharin according to claim 1 is total to the preparation method of amorphous article, it is characterized in that, its preparation method is that carvedilol and asccharin are added in ethanol, stirring and dissolving, under normal temperature, (25 ℃) slowly volatilize solvent, vacuum-drying, obtain carvedilol asccharin amorphous article altogether.
4. carvedilol asccharin as claimed in claim 2 is total to the preparation method of amorphous article, it is characterized in that, the consumption of carvedilol is 1 times of molar equivalent of asccharin consumption.
5. carvedilol asccharin as claimed in claim 3 is total to the preparation method of amorphous article, it is characterized in that, the consumption of carvedilol is 1 times of molar equivalent of asccharin consumption.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2013104460442A CN103467363A (en) | 2013-09-27 | 2013-09-27 | Carvedilol-asccharin amorphous compound |
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| CN2013104460442A CN103467363A (en) | 2013-09-27 | 2013-09-27 | Carvedilol-asccharin amorphous compound |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108976234A (en) * | 2018-08-29 | 2018-12-11 | 浙江工业大学 | It is a kind of to replace Buddhist nun and the total amorphous article of saccharin and preparation method thereof according to Shandong |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008084494A1 (en) * | 2007-01-08 | 2008-07-17 | Matrix Laboratories Limited | Novel polymorphic forms of carvedilol dihydrogen phosphate and process for preparing the same |
| WO2009024997A1 (en) * | 2007-08-21 | 2009-02-26 | Lupin Limited | Stable amorphous form of carvedilol dihydrogen phosphate with stabilizer |
| CN101891671A (en) * | 2010-07-26 | 2010-11-24 | 天津大学 | Crystals of carvidilol dihydric phosphate and preparation method thereof |
| CN102336701A (en) * | 2010-07-26 | 2012-02-01 | 江苏恒瑞医药股份有限公司 | Carvedilol sulphate crystals, preparation method and application thereof in medicine |
-
2013
- 2013-09-27 CN CN2013104460442A patent/CN103467363A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008084494A1 (en) * | 2007-01-08 | 2008-07-17 | Matrix Laboratories Limited | Novel polymorphic forms of carvedilol dihydrogen phosphate and process for preparing the same |
| WO2009024997A1 (en) * | 2007-08-21 | 2009-02-26 | Lupin Limited | Stable amorphous form of carvedilol dihydrogen phosphate with stabilizer |
| CN101891671A (en) * | 2010-07-26 | 2010-11-24 | 天津大学 | Crystals of carvidilol dihydric phosphate and preparation method thereof |
| CN102336701A (en) * | 2010-07-26 | 2012-02-01 | 江苏恒瑞医药股份有限公司 | Carvedilol sulphate crystals, preparation method and application thereof in medicine |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108976234A (en) * | 2018-08-29 | 2018-12-11 | 浙江工业大学 | It is a kind of to replace Buddhist nun and the total amorphous article of saccharin and preparation method thereof according to Shandong |
| CN108976234B (en) * | 2018-08-29 | 2020-03-17 | 浙江工业大学 | Co-amorphous substance of ibrutinib and saccharin and preparation method thereof |
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Application publication date: 20131225 |