CN101574525A - Hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments, and preparation method thereof - Google Patents
Hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments, and preparation method thereof Download PDFInfo
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- CN101574525A CN101574525A CNA2008101061810A CN200810106181A CN101574525A CN 101574525 A CN101574525 A CN 101574525A CN A2008101061810 A CNA2008101061810 A CN A2008101061810A CN 200810106181 A CN200810106181 A CN 200810106181A CN 101574525 A CN101574525 A CN 101574525A
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- cyclodextrin inclusion
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Abstract
The invention discloses a hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments, and a preparation method thereof. The preparation method can be performed in ethanol, avoids adopting other common organic solvents such as acetone, chloroform, methanol, tert-butanol together with homologues thereof, isopropyl alcohol, cosolvent, pH modifier and the like, avoids organic solvent residue, can be performed at a low temperature, saves energy, and is beneficial to operation. Inclusion compound solution is easy to dry and beneficial to the preparation of heat-sensitive medicinal inclusion compounds, and also has the function of masking the taste of the medicaments with medicinal taste not easy to accept.
Description
Technical field
The present invention relates to hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments and preparation method thereof.
Background technology
Cyclodextrin (CD) be a kind of by D (+)-glucose unit by 1, the ring-type oligosaccharide that the 4-glycosidic bond couples together.Usually contain 6,7,8 sugar units, be referred to as respectively α-, β-, gamma-cyclodextrin, under the shielding of its cavity inboard by the oxygen atom place c h bond of two circle hydrogen atoms and a circle sugar circle glycuronide, have hydrophobicity; And outside frame is hydrophilic because hydroxyl is assembled.
Beta-cyclodextrin derivative is of a great variety, mainly be divided into and methylate or several big classes such as alkyl derivative, hydroxyalkylation derivant, branch cladodification derivant, sulfoalkyl etherification derivative, wherein 2 important derivants are respectively HP-(hydroxypropyl-β-cyclodextrin, HP-β-CD) and sulfobutyl ether-beta-cyclodextrin (sulfobutylether-β-cyclodextrin, SBE-β-CD).HP-β-CD is that first of drugs approved by FDA can intravenous β-CDYan Shengwu.The itraconazole intravenous injection of the 40%HP of Johnson Co. β-CD solubilising goes on the market, and China also digoxin oral liquid of approved 2%HP-β-CD solubilising carries out clinical trial.
The existing at home long applicating history of beta-schardinger dextrin-is mainly used in the fat-soluble medicine of inclusion, improves dissolubility, the liquid medicine solidification, improves effects such as medicine stability.But beta-schardinger dextrin-poorly water-soluble and nephrotoxicity, hemolytic etc. are arranged can not be used for the dosage form of injection administration, is restricted in the application of field of medicaments.HP-is that beta-schardinger dextrin-and 1,2 epoxy prapane condensation form, and nephrotoxicity is low, and hemolytic activity is low, and zest is low, can be used for non-oral administration, can be used for improving fat-soluble medicine dissolubility and stability.
The hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments preparation method of having reported is more, and methods such as coprecipitation, polishing, supercritical ultrasonics technology, lyophilization, spray drying are arranged.Dissolving fat-soluble medicines such as many in the preparation employing organic solvents of these methods such as ethyl acetate, acetone, isopropyl alcohol, chloroform are made solution, join in the HP-aqueous solution, adopt the whole bag of tricks to obtain inclusion complex as required.These class methods are often introduced organic solvent, easily cause dissolvent residual, and owing to there is relatively large water to exist, organic solvent is difficult for removing, and there have relatively large water to be difficult in the inclusion complex solution to be dry, needs the long period, also can expend a large amount of energy.
Summary of the invention
The object of the invention is to provide hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments.
Another purpose of the present invention is to provide hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments and preparation method thereof.
The present invention is implemented by the following technical programs.
Hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments of the present invention contains HP-and lipophilic drugs in the clathrate, this clathrate carries out the enclose operation in ethanol.That lipophilic drugs is meant is molten in the water part omitted, slightly soluble, soluble,very slightly, insoluble or insoluble medicine almost.
The stoichiometric amount ratio of HP-and lipophilic drugs is more than about 1: 1 scope, and scope was meant about 0.5-1.5 in wherein about 1: 1: 1.
The present invention also comprises the hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments of amount of calculation non-chemically.
Normal 95% ethanol that adopts of ethanol of the present invention, also can select the ethanol of dehydrated alcohol or low concentration for use, can add in the ethanol and dissolve in alcoholic acid hydroxypropyl methylcellulose, polyvinyl alcohol, carbomer, poloxamer, polyvinylpyrrolidone, ethyl cellulose, middle carbon chain fatty acid glyceride, acrylic resin and other dissolves in alcoholic acid cellulose derivative.
The preparation method of hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments of the present invention can for: get lipophilic drugs and hydroxypropyl-beta-cyclodextrin inclusion, add ethanol, can adopt ultrasonic, stirring, homogenizing method to carry out enclose.Wherein the ethanol consumption may be selected to be and can make the HP-dissolving.
The present invention can add in the ethanol and dissolves in alcoholic acid hydroxypropyl methylcellulose, polyvinyl alcohol, carbomer, poloxamer, polyvinylpyrrolidone, ethyl cellulose, middle carbon chain fatty acid glyceride, acrylic resin and other dissolves in alcoholic acid cellulose derivative in preparation.
Clathrate preparation method of the present invention can be: get lipophilic drugs and hydroxypropyl-beta-cyclodextrin inclusion, add ethanol, can adopt ultrasonic, stirring, homogenizing method to carry out enclose.
Clathrate preparation method of the present invention, the gained inclusion complex in solution can adopt spray drying, drying under reduced pressure, obtains inclusion complex.
The hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments of the present invention's preparation can be made tablet, granule, capsule, injection, injectable powder, powder, pill, drop pill, gel, oral liquid, Emulsion, ointment, ophthalmic preparation, nasal formulations, tincture, liniment and other clinical acceptable forms.
The present invention carries out inclusion with lipophilic drugs and hydroxypropyl-beta-cyclodextrin inclusion in ethanol, also can add other pharmaceutic adjuvant as required.The present invention adopts ethanol as solvent, inclusion is easy to carry out, but short time even a few minutes both enclose, and can under situation about not heating, carry out, can not expend the energy, can keep it stable to heat sensitive medicine, ethanol more easily volatilizes under low temperature simultaneously, even but also lower temperature of inclusion complex drying, use the less time, can reduce the medicine heated time, also improve efficient simultaneously, simultaneously the not acceptant medicine of flavour of a drug also be had the taste masking effect.
The specific embodiment
The present invention is described further by embodiment, but is not limited to the present invention.
Embodiment 1
Get the ginsenoside Rg
310g, HP-30g, 10g polyvinylpyrrolidone k-30 adds ethanol 200ml, and ultrasonic 10 minutes, 50 ℃ of drying under reduced pressure of solution promptly got inclusion complex.
Embodiment 2
Get the ginsenoside Rg
37g, the HP-of respective amount (with medicine mol ratio 0.5: 1) adds dehydrated alcohol 300ml, and ultrasonic 15 minutes, 45 ℃ of drying under reduced pressure of solution promptly got inclusion complex.
Embodiment 3
Get rosiglitazone 8g, the HP-of respective amount (with medicine mol ratio 1: 1) adds 50% ethanol 380ml, stirs 30 minutes, and 55 ℃ of drying under reduced pressure of solution promptly get inclusion complex.
Embodiment 4
Get coenzyme Q10 12g, the HP-of respective amount (with medicine mol ratio 1: 1.3) adds ethanol 500ml, and 600rpm stirred 20 minutes, and 35 ℃ of drying under reduced pressure of solution promptly get inclusion complex.
Embodiment 5
Get coenzyme Q10 20g, the HP-of respective amount (with medicine mol ratio 1: 1.5) adds 50% ethanol 1500ml, and 800rpm stirred 30 minutes, and the solution spray drying promptly gets inclusion complex.
Embodiment 6
Get cantharidin 10g, HP-100g adds ethanol 220ml, and ultrasonic 30 minutes, the solution spray drying promptly got inclusion complex.
Embodiment 7
Get indomethacin 10g, HP-54g adds ethanol 180ml, and ultrasonic 20 minutes, the solution spray drying promptly got inclusion complex.
Embodiment 8
Get ambroxol hydrochloride 10g, HP-47g adds ethanol 166ml, and 1200rpm stirred 30 minutes, and the solution spray drying promptly gets inclusion complex.
Embodiment 9
Get berberine hydrochloride 10g, HP-61g adds ethanol 190ml, and 1500rpm stirred 20 minutes, and the solution spray drying promptly gets inclusion complex.
Embodiment 10
Get rabdosia rubescens diterpene 8g, HP-47g adds ethanol 250ml, stirs 15 minutes, and 44 ℃ of drying under reduced pressure of solution promptly get inclusion complex.
Embodiment 11
Get berberine hydrochloride 5g, HP-52g adds 30% ethanol 200ml, stirs 20 minutes, and the solution spray drying promptly gets inclusion complex.
Claims (10)
1, hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments is characterized in that: contain HP-and lipophilic drugs in the clathrate, this clathrate carries out the enclose operation in ethanol.
2, hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments according to claim 1 is characterized in that: the stoichiometric amount ratio of HP-and lipophilic drugs is more than about 1: 1 scope.
3, hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments according to claim 2 is characterized in that: about 1: 1 scope of the stoichiometric amount ratio of HP-and lipophilic drugs is 0.5-1.5: 1.
4, hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments according to claim 1 is characterized in that: also comprise the hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments of amount of calculation non-chemically.
5, hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments according to claim 1 is characterized in that: ethanol is used 95% ethanol always, also can select the ethanol of dehydrated alcohol or low concentration for use.
6, hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments according to claim 1 is characterized in that: can add in the ethanol and dissolve in alcoholic acid hydroxypropyl methylcellulose, polyvinyl alcohol, carbomer, poloxamer, polyvinylpyrrolidone, ethyl cellulose, middle carbon chain fatty acid glyceride, acrylic resin and other dissolves in alcoholic acid cellulose derivative.
7, the preparation method of hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments according to claim 1, it is characterized in that: get lipophilic drugs and hydroxypropyl-beta-cyclodextrin inclusion, add ethanol, can adopt ultrasonic, stirring, homogenizing method to carry out enclose, amount of alcohol is wanted to make the hydroxypropyl-beta-cyclodextrin inclusion dissolving at least.
8, the preparation method of hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments according to claim 7 is characterized in that: the gained inclusion complex in solution can adopt spray drying, drying under reduced pressure, obtains inclusion complex.
9, the preparation method of hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments according to claim 7 is characterized in that: the hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments of preparation can be made tablet, granule, capsule, injection, injectable powder, powder, pill, drop pill, gel, oral liquid, Emulsion, ointment, ophthalmic preparation, nasal formulations, tincture, liniment and other clinical acceptable forms.
10, hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments according to claim 1, hydroxypropyl-beta-cyclodextrin inclusion also has the taste masking effect.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008101061810A CN101574525A (en) | 2008-05-09 | 2008-05-09 | Hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments, and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2008101061810A CN101574525A (en) | 2008-05-09 | 2008-05-09 | Hydroxypropyl-beta-cyclodextrin inclusion compound for lipophilic medicaments, and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101836966A (en) * | 2010-05-27 | 2010-09-22 | 北京万全阳光医药科技有限公司 | Agomelatine-containing orally disintegrating tablet |
| CN110170058A (en) * | 2019-06-24 | 2019-08-27 | 李建恒 | A kind of abiraterone inclusion compound and preparation method thereof |
| EP3737396A4 (en) * | 2018-01-13 | 2021-10-20 | Pure Green Pharmaceuticals, Inc. | Transformation of cannabinol and terpene oils into water soluble dry powders for solid form sublingual delivery |
| CN115381732A (en) * | 2022-08-01 | 2022-11-25 | 广州市博之越精细化工有限公司 | Preparation method of hydroxypropyl cyclodextrin inclusion retinol |
-
2008
- 2008-05-09 CN CNA2008101061810A patent/CN101574525A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101836966A (en) * | 2010-05-27 | 2010-09-22 | 北京万全阳光医药科技有限公司 | Agomelatine-containing orally disintegrating tablet |
| EP3737396A4 (en) * | 2018-01-13 | 2021-10-20 | Pure Green Pharmaceuticals, Inc. | Transformation of cannabinol and terpene oils into water soluble dry powders for solid form sublingual delivery |
| CN110170058A (en) * | 2019-06-24 | 2019-08-27 | 李建恒 | A kind of abiraterone inclusion compound and preparation method thereof |
| CN110170058B (en) * | 2019-06-24 | 2022-02-11 | 李建恒 | Abiraterone clathrate compound and preparation method thereof |
| CN115381732A (en) * | 2022-08-01 | 2022-11-25 | 广州市博之越精细化工有限公司 | Preparation method of hydroxypropyl cyclodextrin inclusion retinol |
| CN115381732B (en) * | 2022-08-01 | 2023-05-12 | 广州市博之越精细化工有限公司 | Preparation method of hydroxypropyl cyclodextrin inclusion retinol |
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