CN103724162A - Preparation method of medicine calcipotriol solvate for treating psoriasis - Google Patents
Preparation method of medicine calcipotriol solvate for treating psoriasis Download PDFInfo
- Publication number
- CN103724162A CN103724162A CN201410006182.3A CN201410006182A CN103724162A CN 103724162 A CN103724162 A CN 103724162A CN 201410006182 A CN201410006182 A CN 201410006182A CN 103724162 A CN103724162 A CN 103724162A
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- Prior art keywords
- calcipotriol
- solvate
- preparation
- alcohol
- low mass
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C401/00—Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/24—All rings being cycloaliphatic the ring system containing nine carbon atoms, e.g. perhydroindane
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method of a medicine calcipotriol solvate for treating psoriasis. The preparation method comprises the following steps: dissolving calcipotriol into an organic solvent and adding a lower molecular weight alcohol to react for 1-3 hours; cooling to be lower than -10 DEG C; and filtering to obtain the calcipotriol solvate. The method disclosed by the invention is simple in process and high in yield; the compound stability of the obtained calcipotriol solvate is obviously improved; the calcipotriol solvate is not easy to degrade and degenerate and has a good storage period.
Description
Technical field
The present invention relates to a kind of preparation method of solvation medicine, particularly a kind of preparation method of calcipotriol solvate.
Background technology
Calcipotriol is that Denmark Leo drugmaker succeeds in developing for 1987, commodity are called Daivonex, and worldwide licensing to the first spirit (trade(brand)name Psorcutan) of Shi Guibao, Japanese Teng Ze (trade(brand)name Dovonex), Germany, calendar year 2001, commodity were called Daivonex in Discussion on Chinese Listed.Calcipotriol is as the representative of vitamin D 3 analogs, and can suppress IL-1, IL-8 and tumour necrosis factor stimulates epidermal cell proliferation, and promotes cytodifferentiation, has local anti-inflammatory and immunoregulation effect, in the light moderate psoriatic for the treatment of, has remarkable curative effect.
The preparation method of calcipotriol is described in patent US4866048, the calcipotriol anhydride obtaining by the method.The preparation method of calcipotriol hydrate is described in patent US5763426.Now studies have found that, calcipotriol anhydride is to light, thermo-responsive, degrades depositing in process, and content reduces.
Summary of the invention
The object of the invention is to overcome calcipotriol in prior art and, to light, thermo-responsive, be not easy to the deficiency of storage, a kind of preparation method of calcipotriol solvate is provided.
In order to realize foregoing invention object, the invention provides following technical scheme:
A preparation method for curing psoriasis medicine calcipotriol solvate, is dissolved in calcipotriol in organic solvent, adds low mass molecule alcohol, reacts 1 ~ 3 hour, is cooled to below-10 ℃, filters the solvate that obtains calcipotriol.
The method technique is simple, yield is high, is applicable to suitability for industrialized production.
Further, described organic solvent is selected from: methyl acetate, ethyl acetate, butylacetate or methylene dichloride.
Further, described low mass molecule alcohol is methyl alcohol or ethanol.
Further, specifically, the method of preparing calcipotriol solvate is: calcipotriol is dropped in organic solvent, be heated to 25 ~ 35 ℃, dissolve completely, drip the low mass molecule alcohol of 0.8 ~ 1.2 times of molar weight, insulation reaction 1 ~ 2 hour, cooling, as for-10 ℃, is filtered, and obtains the solvate that calcipotriol and ethanol form.
Compared with prior art, beneficial effect of the present invention: the inventive method technique is simple, yield is high, the calcipotriol solvated compounds stability obtaining significantly improves, and is difficult for occurring degraded sex change, has the good preservation cycle.
Embodiment
Below in conjunction with test example and embodiment, the present invention is described in further detail.But this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following embodiment, all technology realizing based on content of the present invention all belong to scope of the present invention.Per-cent not specified in the present invention is all weight percentage.
The method of describing according to patent US4866048 prepares calcipotriol anhydride: (5Z, 7E, 22E, 24S)-24-cyclopropyl-9,10-open loop courage steroid-5,7,10 (19), 22-tetraene-1 α, 3 β, 24-triol.
The method of describing according to patent US5763426 prepares calcipotriol monohydrate: (5Z, 7E, 22E, 24S)-24-cyclopropyl-9,10-open loop courage steroid-5,7,10 (19), 22-tetraene-1 α, 3 β, 24-triol monohydrate.
Embodiment 1
Calcipotriol anhydride 20g is dissolved in ethyl acetate 300ml, keeps 30 ℃ of temperature to drip anhydrous methanol 10g, drip and finish, insulation reaction 1 hour.Then lower the temperature as for-10 ℃, filter, obtain the solvate (ratio of calcipotriol and methyl alcohol is 1:1) of calcipotriol and the formation of methanol.
Embodiment 2
Calcipotriol anhydride 20g is dissolved in ethyl acetate 300ml, keeps 30 ℃ of temperature to drip dehydrated alcohol 10g, drip and finish, insulation reaction 1 hour.Then lower the temperature as for-10 ℃, filter, obtain the solvate (ratio of calcipotriol and ethanol is 1:1) that calcipotriol and ethanol form.
Claims (5)
1. a preparation method for curing psoriasis medicine calcipotriol solvate, is characterized in that, calcipotriol is dissolved in organic solvent, adds low mass molecule alcohol, reacts 1 ~ 3 hour, is cooled to below-10 ℃, filters the solvate that obtains calcipotriol.
2. the preparation method of curing psoriasis medicine calcipotriol solvate as claimed in claim 1, is characterized in that, described organic solvent is selected from: methyl acetate, ethyl acetate, butylacetate or methylene dichloride.
3. the preparation method of curing psoriasis medicine calcipotriol solvate as claimed in claim 2, is characterized in that, described low mass molecule alcohol is methyl alcohol or ethanol.
4. the preparation method of curing psoriasis medicine calcipotriol solvate as claimed in claim 1, it is characterized in that, calcipotriol is dropped in organic solvent, be heated to 25 ~ 35 ℃, dissolve completely, drip the low mass molecule alcohol of 0.8 ~ 1.2 times of molar weight, insulation reaction 1 ~ 2 hour, cooling, as for-10 ℃, is filtered, and obtains the solvate that calcipotriol and low mass molecule alcohol form.
5. the preparation method of curing psoriasis medicine calcipotriol solvate as described in claim 3 or 4, is characterized in that, the solvate of formation comprises calcipotriol/methanol solvate compound, calcipotriol/alcohol solvent compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410006182.3A CN103724162A (en) | 2014-01-07 | 2014-01-07 | Preparation method of medicine calcipotriol solvate for treating psoriasis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410006182.3A CN103724162A (en) | 2014-01-07 | 2014-01-07 | Preparation method of medicine calcipotriol solvate for treating psoriasis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103724162A true CN103724162A (en) | 2014-04-16 |
Family
ID=50448499
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410006182.3A Pending CN103724162A (en) | 2014-01-07 | 2014-01-07 | Preparation method of medicine calcipotriol solvate for treating psoriasis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103724162A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5763426A (en) * | 1993-01-15 | 1998-06-09 | Leo Pharmaceutical Products Ltd. | Crystalline form of a vitamin D analogue |
-
2014
- 2014-01-07 CN CN201410006182.3A patent/CN103724162A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5763426A (en) * | 1993-01-15 | 1998-06-09 | Leo Pharmaceutical Products Ltd. | Crystalline form of a vitamin D analogue |
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| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
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| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20140416 |