CN103127015A - Alfacalcidol dropping pill and preparation method thereof - Google Patents
Alfacalcidol dropping pill and preparation method thereof Download PDFInfo
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- CN103127015A CN103127015A CN2013100534593A CN201310053459A CN103127015A CN 103127015 A CN103127015 A CN 103127015A CN 2013100534593 A CN2013100534593 A CN 2013100534593A CN 201310053459 A CN201310053459 A CN 201310053459A CN 103127015 A CN103127015 A CN 103127015A
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- alfacalcidol
- drop pill
- cyclodextrin
- clathrate
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Abstract
The invention discloses an alfacalcidol dropping pill and a preparation method thereof. The alfacalcidol dropping pill comprises an alfacalcidol clathrate compound, a matrix and a stabilizing agent. The alfacalcidol clathrate compound comprises active ingredients and clathration material. The clathration material is alpha-cyclodextrin, beta-cyclodextrin or hydroxy beta-cyclodextrin, and the matrix is a mixer formed by more than two of polyethylene glycol 6000, polyethylene glycol 4000, polyoxyethylene monostearate, sodium stearate, glycerin gelatin, poloxamer, stearic acid and the like. The weight ratio of the active ingredients to the clathration material is 4:2-2:3. The alfacalcidol dropping pill is good in rounding degree, high in medicine dissolving-out speed and high in biological availability.
Description
Technical field
The present invention relates to a kind of drop pill, relate in particular to a kind of drop pill that comprises the alfacalcidol clathrate and preparation method thereof, belong to the alfacalcidol formulation art.
Background technology
Drop pill has the following characteristics: 1, equipment simple, easy to operate, be beneficial to labor protection, process cycle is short, productivity ratio is high; 2, process conditions are easy to control, steady quality, and dosage is accurate, and heated time is short, after easily oxidation and the volatile medicine of tool are dissolved in substrate, can increase its stability; 3, to hold the liquid drug amount large for substrate, therefore liquid drug is solidified; 4, the drop pill with the solid dispersion technology preparation has the characteristics rapid, that bioavailability is high that absorb.Clathrate has the following advantages: cover bad stink, reduce zest; Increase drug dissolution and bioavailability; Improve medicine stability.
Alfacalcidol works the balanced action of regulating calcium, phosphorus in vivo, and can increase calcium and phosphorus in the absorption of intestinal, reduce in blood plasma the parathyroid hormone level and improve postmenopausal women and use hormone medicine to cause osteoporosis, be applicable to Prevention and Treatment of Osteoporosis, kidney originality osteopathia (rachitis renalis, the rickets of the rickets that hyperparathyroidism (with the bone patient), hypoparathyroidism, nutrition and malabsorption cause and osteomalacia, false calcium deficiency (D-dependent form I) and osteomalacia etc.
The water solublity of alfacalcidol is relatively poor, and the lower defective of existing alfacalcidol oral formulations ubiquity bioavailability affects its therapeutic effect clinically, haves much room for improvement.
Summary of the invention
The low shortcoming of poor stability, bioavailability that the present invention exists in order to solve existing alfacalcidol oral formulations has been invented alfacalcidol clathrate drop pill.
The application first is prepared into clathrate with alfacalcidol, and then is prepared into drop pill, and enclose and drop pill technology are united two into one, and brings into play the advantage of two aspects.
The alfacalcidol clathrate comprises active component and enclose material, and the enclose material is alpha-cyclodextrin, beta-schardinger dextrin-, hydroxyl beta-schardinger dextrin-, one or more of hydroxypropylβ-cyclodextrin.The part by weight of active component and enclose material is 4:2-2:3.
The preparation method of alfacalcidol clathrate comprises:
(1) in water or aquiferous ethanol medium, by a certain percentage, with alfacalcidol and alpha-cyclodextrin, beta-schardinger dextrin-, hydroxyl beta-schardinger dextrin-, one or more reactions of hydroxypropylβ-cyclodextrin, gained solution through extremely clarification of filtering with microporous membrane, is isolated clathrate from mixture; Or
(2) with solid form, with alfacalcidol and alpha-cyclodextrin, beta-schardinger dextrin-, hydroxyl beta-schardinger dextrin-, one or more reactions of hydroxypropylβ-cyclodextrin; Or
(3) alfacalcidol and alpha-cyclodextrin, beta-schardinger dextrin-, the hydroxyl beta-schardinger dextrin-, high energy milling is carried out in one or more reactions of hydroxypropylβ-cyclodextrin.
The above-mentioned alfacalcidol clathrate for preparing is crossed the 100-200 mesh sieve, be mixed into solid dispersion system with substrate and stabilizing agent, splash into the condensed fluid of 0-20 ℃ under 70 ± 5 ℃, adsorption condensing liquid, the drop pill drying, and get final product.
The substrate of indication of the present invention is selected from the two or more mixture such as polyethylene glycol 6000, Macrogol 4000, polyoxyethylene monostearate, sodium stearate, glycerin gelatine, poloxamer, stearic acid.
The applicant is surprised to find that, selects the compositions of Macrogol 4000 and poloxamer when substrate, and part by weight both is when being 70:30, and the drop pill that makes becomes the roundness of ball best.
The stabilizing agent of indication of the present invention comprises that phosphatic pH buffering is right, as sodium hydrogen phosphate and sodium dihydrogen phosphate; Dipotassium hydrogen phosphate and potassium dihydrogen phosphate.
The condensed fluid of indication of the present invention comprises condensed fluid dimethicone, liquid paraffin, Oleum Camelliae, vegetable oil etc.
Metering of the present invention is weight.
Embodiment 1
The prescription of drop pill is (by weight):
Preparation method:
1. prepare by the following method the alfacalcidol clathrate:
(1) in water or aquiferous ethanol medium, in proportion, with alfacalcidol and hydroxypropylβ-cyclodextrin reaction, gained solution through extremely clarification of filtering with microporous membrane, is isolated clathrate from mixture; Or
(2) with solid form, with alfacalcidol and hydroxypropylβ-cyclodextrin reaction; Or
(3) high energy milling is carried out in the reaction of alfacalcidol and hydroxypropylβ-cyclodextrin.
2. the alfacalcidol clathrate was pulverized the 100-200 mesh sieve; Macrogol 4000, poloxamer, dipotassium hydrogen phosphate and potassium dihydrogen phosphate ground and mixed is even, heating and melting on water-soluble, and mixing; The alfacalcidol clathrate is added in the fused mass of Macrogol 4000, poloxamer, dipotassium hydrogen phosphate and potassium dihydrogen phosphate, mixing, in the impouring material fluid bath, kept 65-75 ℃ of temperature 10 minutes, above-mentioned medicinal liquid is splashed in the liquid paraffin of 0-20 ℃ and form drop pill, absorb condensed fluid, dry drop pill, packing.
Embodiment 2
The prescription of drop pill is (by weight):
Preparation method is with embodiment 1.
Embodiment 3
The prescription of drop pill is (by weight):
Preparation method is with embodiment 1.
Embodiment 4
The prescription of drop pill is (by weight):
Preparation method is with embodiment 1.
Embodiment 5
The prescription of drop pill is (by weight):
Preparation method is with embodiment 1.
Embodiment 6
The prescription of drop pill is (by weight):
Preparation method is with embodiment 1.
Matched group 1
The prescription of drop pill is (by weight):
Alfacalcidol clathrate (alfacalcidol: hydroxypropylβ-cyclodextrin is 2:3) 4g
Polyethylene glycol 6000 10g
Dipotassium hydrogen phosphate and potassium dihydrogen phosphate 0.2g
Condensed fluid is liquid paraffin.
Preparation method is with embodiment 1.
Matched group 2
The prescription of drop pill is (by weight):
Alfacalcidol clathrate (alfacalcidol: hydroxypropylβ-cyclodextrin is 2:3) 4g
Macrogol 4000 10g
Dipotassium hydrogen phosphate and potassium dihydrogen phosphate 0.2g
Condensed fluid is liquid paraffin.
Preparation method is with embodiment 1.
Matched group 3
The prescription of drop pill is (by weight):
Alfacalcidol clathrate (alfacalcidol: hydroxypropylβ-cyclodextrin is 2:3) 4g
Stearic acid 10g
Dipotassium hydrogen phosphate and potassium dihydrogen phosphate 0.2g
Condensed fluid is liquid paraffin.
Preparation method is with embodiment 1.
Matched group 4
The prescription of drop pill is (by weight):
Alfacalcidol clathrate (alfacalcidol: hydroxypropylβ-cyclodextrin is 2:3) 4g
PLURONICS F87 10g
Dipotassium hydrogen phosphate and potassium dihydrogen phosphate 0.2g
Condensed fluid is liquid paraffin.
Preparation method is with embodiment 1.
The smooth rounding rate of test example 1 alfacalcidol drop pill and dissolve scattered time limit test
The method of pressing Chinese Pharmacopoeia (2000 editions) detects smooth rounding rate and the dissolve scattered time limit of drop pill, and testing result sees Table 1.
Table 1
| Group | Smooth rounding rate (%) | Dissolve scattered time limit (min) |
| Embodiment 1 | 99.12 | 2.0 |
| Embodiment 2 | 90.41 | 2.9 |
| Embodiment 3 | 91.32 | 2.8 |
| Embodiment 4 | 85.46 | 3.0 |
| Embodiment 5 | 83.94 | 2.7 |
| Embodiment 6 | 86.15 | 2.5 |
| Matched group 1 | 80.28 | 5.8 |
| Matched group 2 | 77.86 | 6.2 |
| Matched group 3 | 74.24 | 5.9 |
| Matched group 4 | 76.93 | 5.5 |
Result shows, alfacalcidol clathrate drop pill provided by the invention meets Chinese Pharmacopoeia (2000 editions) about the regulation of drop pill.And according to Macrogol 4000: the poloxamer part by weight is that the clathrate drop pill of 70:30 preparation has more excellent effect with respect to drop pill and the non-clathrate drop pill of non-this special ratios.
Claims (6)
1. drop pill, wherein active component is alfacalcidol.
2. drop pill as claimed in claim 1, wherein alfacalcidol is clathrate, the enclose material is alpha-cyclodextrin, beta-schardinger dextrin-, the hydroxyl beta-schardinger dextrin-, one or more of hydroxypropylβ-cyclodextrin, the part by weight of alfacalcidol and enclose material is 4:2-2:3.
3. drop pill as claimed in claim 2, wherein drop pill comprises the alfacalcidol clathrate, substrate and stabilizing agent.
4. drop pill as claimed in claim 3, its mesostroma is selected from polyethylene glycol 6000, Macrogol 4000, polyoxyethylene monostearate, sodium stearate, glycerin gelatine, poloxamer, the two or more mixture of stearic acid; Described stabilizing agent comprises that phosphatic pH buffering is right, as sodium hydrogen phosphate and sodium dihydrogen phosphate; Dipotassium hydrogen phosphate and potassium dihydrogen phosphate.
5. drop pill as claimed in claim 4, wherein Basic compose is the compositions of Macrogol 4000 and poloxamer, and the part by weight of Macrogol 4000 and poloxamer is 70:30.
6. drop pill as claimed in claim 4, wherein the prescription of drop pill is (by weight):
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201310053459.3A CN103127015B (en) | 2013-02-19 | 2013-02-19 | Alfacalcidol dropping pill and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201310053459.3A CN103127015B (en) | 2013-02-19 | 2013-02-19 | Alfacalcidol dropping pill and preparation method thereof |
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| CN103127015A true CN103127015A (en) | 2013-06-05 |
| CN103127015B CN103127015B (en) | 2014-05-21 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110898016A (en) * | 2019-12-11 | 2020-03-24 | 正大制药（青岛）有限公司 | Preparation method of aldocalcitol drops for preventing and treating rickets in children |
| CN111000810A (en) * | 2019-12-26 | 2020-04-14 | 北京华氏开元医药科技有限公司 | Dolichocalcitol solid preparation and preparation method thereof |
| CN115350149A (en) * | 2022-08-30 | 2022-11-18 | 南通华山药业有限公司 | Stable alfacalcidol water-based solution preparation and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101254196A (en) * | 2008-04-03 | 2008-09-03 | 沈阳药科大学 | Composite preparations containing double phosphinic acid compounds and vitamin D clathrate and method of preparing the same |
| CN101554372B (en) * | 2009-05-20 | 2011-07-20 | 青岛正大海尔制药有限公司 | Calcitriol dripping pill and preparation method thereof |
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2013
- 2013-02-19 CN CN201310053459.3A patent/CN103127015B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101254196A (en) * | 2008-04-03 | 2008-09-03 | 沈阳药科大学 | Composite preparations containing double phosphinic acid compounds and vitamin D clathrate and method of preparing the same |
| CN101554372B (en) * | 2009-05-20 | 2011-07-20 | 青岛正大海尔制药有限公司 | Calcitriol dripping pill and preparation method thereof |
Non-Patent Citations (1)
| Title |
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| 王顺义: "阿法骨化醇治疗老年性骨质疏松症的疗效和预防分析", 《实用预防医学》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110898016A (en) * | 2019-12-11 | 2020-03-24 | 正大制药（青岛）有限公司 | Preparation method of aldocalcitol drops for preventing and treating rickets in children |
| CN111000810A (en) * | 2019-12-26 | 2020-04-14 | 北京华氏开元医药科技有限公司 | Dolichocalcitol solid preparation and preparation method thereof |
| CN111000810B (en) * | 2019-12-26 | 2022-07-26 | 北京华氏开元医药科技有限公司 | Adelacitol solid preparation and preparation method thereof |
| CN115350149A (en) * | 2022-08-30 | 2022-11-18 | 南通华山药业有限公司 | Stable alfacalcidol water-based solution preparation and preparation method thereof |
| CN115350149B (en) * | 2022-08-30 | 2023-12-15 | 南通华山药业有限公司 | Stable alfacalcidol water-based solution preparation and preparation method thereof |
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| CN103127015B (en) | 2014-05-21 |
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Address after: 266103 Qingdao economic and Technological Development Zone, unity Road, No. 3601, Shandong Applicant after: Qingdao Zhengda Haier Pharmaceutical Co., Ltd. Address before: 266103 Haier Road, Shandong, Qingdao, No. 1 Applicant before: Qingdao Zhengda Haier Pharmaceutical Co., Ltd. |
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Address after: 266103 3601 Tuen Jie Road, Qingdao economic and Technological Development Zone, Shandong Patentee after: Zhengda Pharmaceutical (Qingdao) Co., Ltd. Address before: 266103 3601 Tuen Jie Road, Qingdao economic and Technological Development Zone, Shandong Patentee before: Qingdao Zhengda Haier Pharmaceutical Co., Ltd. |
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