CN103450185A - Salts of dehydrocheilanthifoline derivatives - Google Patents
Salts of dehydrocheilanthifoline derivatives Download PDFInfo
- Publication number
- CN103450185A CN103450185A CN2012101717101A CN201210171710A CN103450185A CN 103450185 A CN103450185 A CN 103450185A CN 2012101717101 A CN2012101717101 A CN 2012101717101A CN 201210171710 A CN201210171710 A CN 201210171710A CN 103450185 A CN103450185 A CN 103450185A
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- China
- Prior art keywords
- compound
- pharmaceutically acceptable
- dehydrocheilanthifoline
- derivatives
- formula iii
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- BNXZOIDSAUKXGW-UHFFFAOYSA-O COc(c(O)c1)cc2c1-c1cc3ccc4OCOc4c3c[n+]1CC2 Chemical compound COc(c(O)c1)cc2c1-c1cc3ccc4OCOc4c3c[n+]1CC2 BNXZOIDSAUKXGW-UHFFFAOYSA-O 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to applications of fumarate of dehydrocheilanthifoline and derivatives thereof or pharmacology-acceptable solvate of the fumarate of dehydrocheilanthifoline and derivatives thereof on preparation of drugs for curing hepatitis B virus infection.
Description
Invention field
The present invention relates to the pharmaceutical chemistry field, particularly, the present invention relates to Scoulerine organic acid salt and pharmacy application thereof.
Background technology
For now, although the medicine for the treatment of hepatitis B virus infection is existing a variety of, existing these medicines easily cause many and heavy untoward reaction, some generation resistances, and the result for the treatment of of existing medicine is still not ideal enough.Describe some in the patent that the Chinese invention patent notification number is CN 102078319 B and there is the active compound for the treatment of hepatitis B virus infection.
Summary of the invention
The invention discloses some new compound, the preparation method of these compounds, the pharmacy application of the pharmaceutical composition that contains these compounds and these compounds and composition.
These compounds have shown good water-soluble stability and solid form stability.Some compound of these compounds shows special good stability.These compounds are compared with corresponding free alkali, and it has very high solvability in water.
These compounds are compared with corresponding free alkali and are shown that in surprise its antiviral activity is higher because of synergy between the two.
These compounds are surprising with stability, water-soluble, antiviral activity are effective preparation and a large amount of advantages that provide of using significantly.
Therefore, the invention provides a kind of formula III compound:
｛（Ⅰ）H｝+Ⅱˉ;
Wherein the chemical structure of I is as follows:
Wherein the chemical structure of II is as follows:
And/or pharmaceutically acceptable solvate, wherein:
II-expression counter ion.
Suitable counter ion II-the comprise ion provided by pharmaceutically acceptable organic acid.
The preferred acceptable organic acid of medicine comprises cholic acid, Chenodiol, ursodesoxycholic acid, Deoxycholic Acid, tartrate, toxilic acid, fumaric acid, particularly fumaric acid.
Preferred counter ion are fumarate ions.
The formula III compound is salt.
Suitable pharmaceutically acceptable solvate is hydrate.
In addition, the present invention also provides the preparation method of formula III and/or pharmaceutically acceptable solvate.This method comprises the formula I compound:
React with counter ion defined above II-source, after this if necessary, then prepare its pharmaceutically acceptable solvate.
Suitable counter ion II-source is pharmaceutically acceptable organic acid.
The preferred acceptable organic acid of medicine comprises cholic acid, Chenodiol, ursodesoxycholic acid, Deoxycholic Acid, tartrate, toxilic acid, fumaric acid, particularly fumaric acid.
Preferred source of counter ions is fumaric acid.
Reacting normally between formula I compound and counter ion II-source carried out under conventional salt-forming condition, for example, in solvent, be generally C1---C4 alkanol solvent as ethanol, can provide under the arbitrary temp that generates required suitable speed, usually in the temperature raise for example at the temperature of solvent refluxing, be conveniently molar weight approximately to wait but preferably the formula I compound mixed to then crystallization with counter ion II-source in the situation in the slightly excessive counter ion II-source of use and go out required product (III).
Can prepare by conventional chemical process by the pharmaceutically acceptable solvate of formula III compound.
Prepared by the method that the formula I compound is described in can the patent application that be CN 102078319 B according to the Chinese invention patent notification number.
Suitable source of counter ions is knownly through the business approach, can easily obtain, fumaric acid for example, or can prepare according to known method required source of counter ions.
The stability of the compounds of this invention can be measured with conventional quantitative analysis method; For example the stability of solid chemical compound can be measured with the stability test of accelerating, for example dsc (DSC), thermo-gravimetric analysis (TGA) and the test of the thermoisopleth in intensification.This test comprises the room temperature storage test.(in wherein during known under temperature and humidity control condition storage test compound).The quantitative analysis of test compound is before storage period, in storage period or after storage period.Stability with respect to suitable reference standard determination test compound.
As mentioned above, compound of the present invention is compared with corresponding free alkali, and it has significantly high solvability in water.Measure like this compounds of this invention the ordinary method of the stability in the aqueous solution be included in known temperature condition and known during in mensuration be settled out the degree of parent free alkali in the aqueous solution of test compound, we find that the formula III compound demonstrates good aqueous stability.Particularly wherein the formula III compound of the fumaric acid radical of II-expression is stable especially in the aqueous solution.More surprised is formula III compound abnormal stablizing in the aqueous solution of the fumaric acid radical of wherein II-expression.
Described test compound quantitative analysis test can ordinary method, usually uses chromatography, and for example high pressure lipuid chromatography (HPLC) is carried out.
As mentioned above, compound of the present invention has practical therapeutic activity.
Therefore, the invention provides formula III compound and/or the pharmaceutically acceptable solvate as therapeutic active substance.
Like this, the invention provides formula III compound and/or the pharmaceutically acceptable solvate as treatment and/or inhibition hepatitis B virus infection.
Formula III compound and/or pharmaceutically acceptable solvate can himself form be used, and the form that preferably also can contain the pharmaceutical composition of pharmaceutically acceptable carrier is used.
Therefore, the present invention also provides a kind of pharmaceutical composition that contains formula III compound and/or pharmaceutically acceptable solvate and pharmaceutically acceptable carrier.
Term used herein " pharmaceutically acceptable " comprises compound, composition and the component to people and animal doctor's use, and for example, term " pharmaceutically acceptable salt " comprises the upper acceptable salt of animal doctor.
Suitable pharmaceutical composition is the composition of unit dosage, for example oral liquid, tablet, capsule, injection liquid, sprays.
Optimum pharmaceutical composition is oral liquid, sprays.
According to the convention on conventional medicine, carrier can comprise thinner, weighting agent, disintegrating agent, wetting agent, lubricant, tinting material, seasonings or other conventional additives.
Optimum composition is to be configured to unit dosage.
Usually, activeconstituents can the aforementioned pharmaceutical compositions form be used.
The present invention also provides a kind of contain formula III compound and/or the application of pharmaceutically acceptable solvate on the medicine of production for treating and/or inhibition hepatitis B virus infection.
Below provide embodiments of the invention for further illustrating and describe in more detail the present invention.
Embodiment 1
The Scoulerine fumarate
Compound Scoulerine 3.22 grams (0.01mol) and fumaric acid 1.17 grams (0.01mol) are dissolved in 100 milliliters of the ethanol of boiling.This hot solution is through diatomite filtration, then Slow cooling under mild stirring, standing a few hours in the temperature environment of 0-5 ℃, separate out Scoulerine fumarate crystal, leach Scoulerine fumarate crystal, with washing with alcohol dry under 50 ℃ of vacuum conditions, obtain 4.38 gram products.
Embodiment 2
The Scoulerine fumarate
Compound Scoulerine fumarate 3.22 grams and fumaric acid 1.17 grams are stirred to solid in 100 milliliters of ethanol refluxed all to be dissolved.Add gac, this hot solution, through diatomite filtration, is cooled to room temperature in stirring.Standing a few hours in the temperature environment of 0-5 ℃, separate out the fumarate crystal, leach Scoulerine fumarate crystal, with washing with alcohol dry under 50 ℃ of vacuum conditions, obtain 4.35 gram products.
The present invention can summarize with other the specific form without prejudice to spirit of the present invention or principal character.Therefore, no matter from which point, above-mentioned embodiment of the present invention all can only be thought can not limit the present invention to explanation of the present invention.
Claims (2)
1. Scoulerine (I) fumaric acid (II) salt (III);
2. the application of the compound of claim 1 in preparation is treated hepatitis B virus infection and/or slowed down the hepatitis B virus infection medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101717101A CN103450185A (en) | 2012-05-29 | 2012-05-29 | Salts of dehydrocheilanthifoline derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101717101A CN103450185A (en) | 2012-05-29 | 2012-05-29 | Salts of dehydrocheilanthifoline derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103450185A true CN103450185A (en) | 2013-12-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101717101A Pending CN103450185A (en) | 2012-05-29 | 2012-05-29 | Salts of dehydrocheilanthifoline derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103450185A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110041326A (en) * | 2018-01-15 | 2019-07-23 | 中国医学科学院药物研究所 | Berberine hydrochloride and fumaric acid eutectic object and preparation method and its composition and purposes |
-
2012
- 2012-05-29 CN CN2012101717101A patent/CN103450185A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110041326A (en) * | 2018-01-15 | 2019-07-23 | 中国医学科学院药物研究所 | Berberine hydrochloride and fumaric acid eutectic object and preparation method and its composition and purposes |
| CN110041326B (en) * | 2018-01-15 | 2022-04-15 | 中国医学科学院药物研究所 | Eutectic compound of berberine hydrochloride and fumaric acid, preparation method, composition and application thereof |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20131218 |