CN103923049A - Baicalein-caffeine amorphous compound - Google Patents
Baicalein-caffeine amorphous compound Download PDFInfo
- Publication number
- CN103923049A CN103923049A CN201410185203.2A CN201410185203A CN103923049A CN 103923049 A CN103923049 A CN 103923049A CN 201410185203 A CN201410185203 A CN 201410185203A CN 103923049 A CN103923049 A CN 103923049A
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- CN
- China
- Prior art keywords
- caffeine
- scutellarin
- baicalein
- altogether
- amorphous article
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/12—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1, 3, and 7, e.g. caffeine
Abstract
The invention relates to a baicalein-caffeine amorphous compound formed by combining baicalein and caffeine. By using Cu-Ka radiation, an X-ray powder diffraction spectrum expressed by 2theta does not have a sharp diffraction peak, so the baicalein-caffeine amorphous compound is a novel solid material which is totally different from a baicalein crystal and has significantly improved dissolution compared with baicalein.
Description
Technical field
The invention belongs to medical technical field, be specifically related to scutellarin and caffeine and in conjunction with the scutellarin caffeine forming, be total to amorphous article and preparation method thereof in 1: 1 in molar ratio.
Background technology
Scutellarin (baicalein), is a kind of natural phant flavonoid compound, is trihydroxyflavone aglycon, is mainly present in the dry root of the labiate root of large-flowered skullcap.Scutellarin is yellow needle-like crystal, is dissolved in methyl alcohol, ethanol, acetone, vinyl acetic monomer and hot Glacial acetic acid, is slightly soluble in chloroform, is dissolved in dilute sodium hydroxide and is green brown, but unstable, oxidizable one-tenth is green.Its chemistry 5，6，7-trihydroxyflavone by name, molecular formula and molecular weight are respectively C
15h
10o
5with 270.24, fusing point is 264 ℃-265 ℃, and its structure is as follows:
Scutellarin is as flavonoid compound, have antibacterial, antiviral, protect the liver, cholagogic, diuresis, the multiple pharmacological effect such as anticancer, be mainly used in clinically at present antisepsis and anti-inflammation and anti-infective.Wherein anti-microbial effect is the most obvious, and increasing evidence shows that the root of large-flowered skullcap have stronger anti-microbial effect in recent years, may be the main component of root of large-flowered skullcap anti-microbial effect.Research shows, scutellarin all has certain restraining effect to the infection of intestinal bacteria, Fusarium oxysporum, Candida albicans, set micrococci, staphylococcus epidermidis, human-like staphylococcus, drying rod bacillus, candida albicans and chlamydozoan, helicobacter pylori etc.There is synergy with other antimicrobial agents.In addition; scutellarin also has the effect of removing oxyradical, anti-oxidant, antipyretic-antalgic, antitumor, protection liver, cardiovascular and cerebrovascular and nerve and treatment or prevent diabetes and complication thereof; in addition it is to normal cell nontoxicitys such as blood cell and liver cells, therefore have good clinical value and prospect.
But because scutellarin is water-soluble very poor, oral absorption is poor, has greatly limited its clinical application.The scutellarin preparation also not gone on the market abroad at present.Recent study persons have taked the method for various raising poorly water soluble drugs solubleness, and for example salify, cyclodextrin encapsulated, solid dispersion or self-emulsifying microemulsion system.The problems such as these methods exist uses a large amount of substrate materials as carrier, and drug loading is low.
We find by large quantity research, scutellarin can be prepared into a kind of scutellarin caffeine amorphous article altogether, make its solubleness obtain improving extremely significantly.
Summary of the invention
The object of this invention is to provide a kind of scutellarin caffeine amorphous article altogether.
Scutellarin caffeine 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 scutellarin caffeine altogether powder x-ray diffraction spectrogram of amorphous article does not have sharp-pointed diffraction peak.
Another object of the present invention is to provide prepares the scutellarin caffeine method of amorphous article altogether.
Described scutellarin caffeine is a preparation method for amorphous article altogether, and it comprises dissolves waiting the caffeine of mole number and scutellarin to put in organic solvent, obtains clarified liq, the rotary evaporation solvent that reduces pressure at 25-55 ℃, and vacuum-drying, obtains.
Described organic solvent can be single solvent or the mixed solvent that methyl alcohol, acetone maybe can make scutellarin, caffeine dissolve, particular methanol and acetone or its mixture.
In the present invention, amorphous article is all different from the powder x-ray diffraction of scutellarin, scutellarin caffeine crystallophy mixture (mol ratio 1: 1) altogether for open scutellarin caffeine, be a kind of solid form that is different from scutellarin and caffeine completely, there is the solubleness significantly improving.
Accompanying drawing explanation
Fig. 1 is the x-ray diffractogram of powder of scutellarin.
Fig. 2 is the x-ray diffractogram of powder of scutellarin caffeine physical mixture (mol ratio 1: 1).
Fig. 3 is the scutellarin caffeine x-ray diffractogram of powder of amorphous article altogether.
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 scutellarin caffeine altogether spectrogram of amorphous article does not have sharp-pointed diffraction peak.
2, solubility test
Measure scutellarin crystal and the scutellarin caffeine solubleness of amorphous article in water and various pH damping fluid altogether.Measure respectively the medium (water, pH2.5,3.6,4.5,5.0 and 6.8 phosphate buffered saline buffer) of 5ml in cillin bottle, cillin bottle sealing is placed in to 25 ℃ of constant temperature oscillators after adding overdose of medicine thing.Jolting reaches after balance, gets solution and crosses 0.22 μ m filter membrane, gets subsequent filtrate sample introduction after appropriate dilution and measures solubleness in HPLC.The HPLC chromatographic condition adopting is: adopt Kromasil ODSC18 chromatographic column (4.6mm * 150mm, 5 μ m), 30 ℃ of column temperatures; Methyl alcohol-0.05% phosphoric acid (70: 30) of take is moving phase, and flow velocity is 1.0ml/min; Detection wavelength is 275nm.
Solubility test the results are shown in Table 1.
Table 1 scutellarin crystal and scutellarin caffeine be the solubleness of amorphous article in various media altogether
As can be seen here, the scutellarin caffeine altogether solubleness of amorphous article in various media is all significantly higher than scutellarin crystal, and at main absorption site, the solubleness that is total to amorphous article is 3-8 times of scutellarin crystal.
Embodiment 1: scutellarin caffeine is the preparation of amorphous article altogether
Scutellarin crystal 600mg, caffeine 432mg are put in round-bottomed flask, add the about 50ml of methyl alcohol, stirring at room obtains settled solution, rotary evaporation solvent that this settled solution is reduced pressure at 50 ℃, and 25 ℃ of vacuum-drying 24h, obtain white powder 990mg.Embodiment 2: scutellarin caffeine is the preparation of amorphous article altogether
Scutellarin crystal 600mg, caffeine 432mg are put in round-bottomed flask, add the about 25ml of methyl alcohol and the about 25ml of acetone, stirring at room obtains settled solution, rotary evaporation solvent that this settled solution is reduced pressure at 45 ℃, and 25 ℃ of vacuum-drying 24h, obtain white powder 980mg.
Embodiment 3: scutellarin caffeine is the preparation of amorphous article altogether
Scutellarin 600mg, caffeine 432mg are put in round-bottomed flask, add the about 30ml of acetone, stirring at room obtains settled solution, rotary evaporation solvent that this settled solution is reduced pressure at 35 ℃, and 25 ℃ of vacuum-drying 24h, obtain white powder 950mg.
Claims (2)
1. a scutellarin caffeine amorphous article altogether, is characterized in that, scutellarin and caffeine, within 1: 1 in molar ratio, consists of, and use Cu-K α radiation, does not have sharp-pointed diffraction peak to spend the X-ray powder diffraction spectrum that 2 θ represent.
2. scutellarin caffeine as claimed in claim 1 amorphous article altogether, its preparation method is that the caffeine of equimolar ratio and scutellarin are put in methyl alcohol or acetone and dissolved, then through rotary evaporation except desolventizing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410185203.2A CN103923049A (en) | 2014-05-05 | 2014-05-05 | Baicalein-caffeine amorphous compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410185203.2A CN103923049A (en) | 2014-05-05 | 2014-05-05 | Baicalein-caffeine amorphous compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103923049A true CN103923049A (en) | 2014-07-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410185203.2A Pending CN103923049A (en) | 2014-05-05 | 2014-05-05 | Baicalein-caffeine amorphous compound |
Country Status (1)
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105218500A (en) * | 2015-11-02 | 2016-01-06 | 诸城市浩天药业有限公司 | Scutellarin caffeine eutectic, its preparation method, pharmaceutical composition and application thereof |
| CN105646353A (en) * | 2016-03-02 | 2016-06-08 | 中国药科大学 | Celecoxib and irbesartan coamorphous substance |
| CN109589323A (en) * | 2018-12-11 | 2019-04-09 | 福州乾正药业有限公司 | Nervonic acid and the solid dispersion composition of EGCG and its preparation method and application |
| CN113995764A (en) * | 2021-10-19 | 2022-02-01 | 宁夏医科大学 | Baicalein-baicalin co-amorphous substance, preparation method thereof, tablet containing baicalin-baicalin co-amorphous substance and preparation method of tablet |
Citations (4)
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| WO2009052246A1 (en) * | 2007-10-17 | 2009-04-23 | Ovokaitys, Todd, F. | Process for the modification of the solid state of a compound and co-amorphous compositions produced with same |
| CN102698283A (en) * | 2012-06-07 | 2012-10-03 | 上海中医药大学 | Baicalein clathrate and preparation method thereof |
| CN103819440A (en) * | 2014-03-11 | 2014-05-28 | 上海中医药大学 | Myricetin pharmaceutical eutectic crystal and preparation method thereof |
| CN103848803A (en) * | 2014-01-17 | 2014-06-11 | 中国药科大学 | Baicalein-nicotinamide eutectic crystal |
-
2014
- 2014-05-05 CN CN201410185203.2A patent/CN103923049A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2009052246A1 (en) * | 2007-10-17 | 2009-04-23 | Ovokaitys, Todd, F. | Process for the modification of the solid state of a compound and co-amorphous compositions produced with same |
| CN102698283A (en) * | 2012-06-07 | 2012-10-03 | 上海中医药大学 | Baicalein clathrate and preparation method thereof |
| CN103848803A (en) * | 2014-01-17 | 2014-06-11 | 中国药科大学 | Baicalein-nicotinamide eutectic crystal |
| CN103819440A (en) * | 2014-03-11 | 2014-05-28 | 上海中医药大学 | Myricetin pharmaceutical eutectic crystal and preparation method thereof |
Non-Patent Citations (4)
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| KORBINIAN LOBMANN ET AL: "Coamorphous Drug Systems: Enhanced Physical Stability and Dissolution Rate of Indomethacin and Naproxen", 《MOLECULAR PHARMACEUTICS》 * |
| 姚静等: "共无定型药物系统的研究进展", 《药学学报》 * |
| 郭慧慧等: "共无定形药物——新型单相无定形二元体系", 《化学进展》 * |
| 高缘等: "药物共晶研究进展", 《化学进展》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105218500A (en) * | 2015-11-02 | 2016-01-06 | 诸城市浩天药业有限公司 | Scutellarin caffeine eutectic, its preparation method, pharmaceutical composition and application thereof |
| CN105218500B (en) * | 2015-11-02 | 2018-06-15 | 诸城市浩天药业有限公司 | Baicalein caffeine eutectic, preparation method, pharmaceutical composition and its application |
| CN105646353A (en) * | 2016-03-02 | 2016-06-08 | 中国药科大学 | Celecoxib and irbesartan coamorphous substance |
| CN109589323A (en) * | 2018-12-11 | 2019-04-09 | 福州乾正药业有限公司 | Nervonic acid and the solid dispersion composition of EGCG and its preparation method and application |
| CN113995764A (en) * | 2021-10-19 | 2022-02-01 | 宁夏医科大学 | Baicalein-baicalin co-amorphous substance, preparation method thereof, tablet containing baicalin-baicalin co-amorphous substance and preparation method of tablet |
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Application publication date: 20140716 |