CN103142470B - Calcitriol injection and preparation method thereof - Google Patents
Calcitriol injection and preparation method thereof Download PDFInfo
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- CN103142470B CN103142470B CN201310092701.8A CN201310092701A CN103142470B CN 103142470 B CN103142470 B CN 103142470B CN 201310092701 A CN201310092701 A CN 201310092701A CN 103142470 B CN103142470 B CN 103142470B
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- 238000002360 preparation method Methods 0.000 title abstract description 14
- 229940111194 calcitriol injection Drugs 0.000 title abstract 2
- 235000020964 calcitriol Nutrition 0.000 claims abstract description 38
- 239000011612 calcitriol Substances 0.000 claims abstract description 34
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 5
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 5
- GMRQFYUYWCNGIN-ZVUFCXRFSA-N 1,25-dihydroxy vitamin D3 Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=CC=C1C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-ZVUFCXRFSA-N 0.000 claims description 13
- 229940097712 calcijex Drugs 0.000 claims description 13
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 235000010265 sodium sulphite Nutrition 0.000 claims description 6
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- 235000006708 antioxidants Nutrition 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 3
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 229940046009 vitamin E Drugs 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 229960005084 calcitriol Drugs 0.000 abstract description 21
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 11
- 238000002347 injection Methods 0.000 abstract description 10
- 239000007924 injection Substances 0.000 abstract description 10
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 abstract description 8
- 229960003194 meglumine Drugs 0.000 abstract description 8
- 229940093429 polyethylene glycol 6000 Drugs 0.000 abstract description 8
- 239000008215 water for injection Substances 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 4
- 229940090044 injection Drugs 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 25
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 7
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 7
- 238000003556 assay Methods 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000007689 inspection Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000012982 microporous membrane Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 238000012856 packing Methods 0.000 description 5
- 238000007789 sealing Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 230000001954 sterilising effect Effects 0.000 description 5
- 238000010792 warming Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000013112 stability test Methods 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000010812 external standard method Methods 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 208000007442 rickets Diseases 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 235000005282 vitamin D3 Nutrition 0.000 description 2
- 239000011647 vitamin D3 Substances 0.000 description 2
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 2
- 229940021056 vitamin d3 Drugs 0.000 description 2
- GMRQFYUYWCNGIN-DRQJEBLXSA-N (1r,3s,5e)-5-[(2e)-2-[(1r,3as,7ar)-1-[(2r)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1/C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-DRQJEBLXSA-N 0.000 description 1
- 208000013725 Chronic Kidney Disease-Mineral and Bone disease Diseases 0.000 description 1
- 206010048768 Dermatosis Diseases 0.000 description 1
- 208000029663 Hypophosphatemia Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- 206010047626 Vitamin D Deficiency Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000002990 parathyroid gland Anatomy 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 201000006409 renal osteodystrophy Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108010048734 sclerotin Proteins 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a calcitriol injection and a preparation method thereof. The injection is prepared from the following ingredients in percentage by weight: 0.0005% of calcitriol, 1.2-1.6% of meglumine, 18-24% of polyethylene glycol 400, 1.2-1.7% of polyethylene glycol 6000, 0.1% of antioxidant, an appropriate amount of isotonicity regulator and the balance of water for injection. According to the injection, the content of calcitriol is remarkably increased, so that the drug dosage is reduced; and the stability of calcitriol to light and air is improved, and the bioavailability of calcitriol is also remarkably improved.
Description
Technical field
The present invention relates to pharmaceutical technology field, be specifically related to a kind of Calcijex and preparation method thereof.
Background technology
Calcitriol (Calcitriol) is white crystalline powder, to light and air-sensitive.Be slightly soluble in methanol, ethanol, ethyl acetate.Tm is 111-115 ℃.It is one of most important metabolic activity product of vitamin D3 in human body, has the intestinal absorption of impelling calcium and regulates in sclerotin the effects such as inorganic salt transhipment; Be mainly used in osteoporosis; The renal osteodystrophy of Patients with Chronic Renal Failure, particularly needs the patient of chronic hemodialysis; After operation, spontaneity and false parathyroid gland machine go down; Vitamin D3 dependency rickets and hypophosphatemia vitamin D resistance rickets; The dermatosiss such as psoriasis; And other vitamin D deficiencies.The oral absorption of calcitriol is fast, within 3～6 hours, reaches peak, t1/2 approximately 3～6 hours, and after 7 hours, urinating calcium concentration increases, the sustainable pharmacologically active of single oral dose 3～5 days.
At present, the main dosage form of calcitriol is soft capsule and soft gelatin capsule; Dosage form is more dull, and calcitriol is to light and air-sensitive, and lower for ordinary organic solvents dissolubility, the stability of soft capsule and soft gelatin capsule is bad, and active constituent content is extremely low, and bioavailability is low.Calcijex does not have report in the prior art, and reason is that it can not steady in a long-termly exist, and bioavailability is not high.
Summary of the invention
Research worker is surprisingly found, while preparing Calcijex, the meglumine adding in right amount, PEG400 and polyethylene glycol 6000, can significantly improve content, stability and the bioavailability of calcitriol in preparation, there is unforeseeable technique effect, significant for the clinical use of medicine.
The invention provides the Calcijex that a kind of active component content is high, medicine stability good, bioavailability is high.This injection is made by the component of following percentage by weight:
Its optimizing prescriptions is:
Further, above-mentioned antioxidant is selected from one or more in sodium sulfite, sodium sulfite, sodium pyrosulfite and vitamin E.
Further, above-mentioned isoosmotic adjusting agent is selected from one or more in sodium chloride, glucose, mannitol and glycerol.
The preparation method of this injection is:
1) take the distilled water of recipe quantity 70-80%, add the PEG400 of recipe quantity, stir; Continue to add meglumine and the polyethylene glycol 6000 of recipe quantity, stir 15-25min at 45-55 ℃ to all dissolving;
2) be warming up to 60-70 ℃, under the mixing speed of 500-1000rpm, add the calcitriol of recipe quantity, continue to stir 20-40min to all dissolving;
3) add the antioxidant of recipe quantity and appropriate isoosmotic adjusting agent, stirring and dissolving; Then add 0.1% active carbon of injection gross mass, standing after stirring, remove by filter powdered carbon;
4) after measurement regulator solution pH value, add to the full amount of water for injection; Through 0.45 μ m and 0.22 μ m filtering with microporous membrane, carry out afterwards fill, sealing, sterilizing, lamp inspection and packing.
The preparation method of this injection is more preferably:
1) take the distilled water of recipe quantity 75%, add the PEG400 of recipe quantity, stir; Continue to add meglumine and the polyethylene glycol 6000 of recipe quantity, stir 20min at 50 ℃ to all dissolving;
2) be warming up to 65 ℃, under the mixing speed of 800rpm, add the calcitriol of recipe quantity, continue to stir 30min to all dissolving;
3) add the antioxidant of recipe quantity and appropriate isoosmotic adjusting agent, stirring and dissolving; Then add 0.1% active carbon of injection gross mass, standing after stirring, remove by filter powdered carbon;
4) after measurement regulator solution pH value, add to the full amount of water for injection; Through 0.45 μ m and 0.22 μ m filtering with microporous membrane, carry out afterwards fill, sealing, sterilizing, lamp inspection and packing.
The invention has the beneficial effects as follows:
1. in said preparation, the content of calcitriol significantly increases, and has reduced the dose of medicine;
2. improved the stability of calcitriol to light, air having added of meglumine, PEG400 and polyethylene glycol 6000, its bioavailability is also significantly improved.
The specific embodiment
Below in conjunction with concrete embodiment, technical scheme of the present invention is further described.
Embodiment 1 Calcijex
Prescription is:
Preparation method is:
1) take the distilled water of recipe quantity 70%, add the PEG400 of recipe quantity, stir; Continue to add meglumine and the polyethylene glycol 6000 of recipe quantity, stir 15min at 45 ℃ to all dissolving;
2) be warming up to 60 ℃, under the mixing speed of 500rpm, add the calcitriol of recipe quantity, continue to stir 20min to all dissolving;
3) add the sodium sulfite of recipe quantity and appropriate sodium chloride, stirring and dissolving; Then add 0.1% active carbon of injection gross mass, standing after stirring, remove by filter powdered carbon;
4) after measurement regulator solution pH value, add to the full amount of water for injection; Through 0.45 μ m and 0.22 μ m filtering with microporous membrane, carry out afterwards fill, sealing, sterilizing, lamp inspection and packing.
Embodiment 2 Calcijexes
Prescription is:
Preparation method is:
1) take the distilled water of recipe quantity 80%, add the PEG400 of recipe quantity, stir; Continue to add meglumine and the polyethylene glycol 6000 of recipe quantity, stir 15-25min at 55 ℃ to all dissolving;
2) be warming up to 70 ℃, under the mixing speed of 1000rpm, add the calcitriol of recipe quantity, continue to stir 40min to all dissolving;
3) add the sodium sulfite of recipe quantity and appropriate glucose, stirring and dissolving; Then add 0.1% active carbon of injection gross mass, standing after stirring, remove by filter powdered carbon;
4) after measurement regulator solution pH value, add to the full amount of water for injection; Through 0.45 μ m and 0.22 μ m filtering with microporous membrane, carry out afterwards fill, sealing, sterilizing, lamp inspection and packing.
Embodiment 3 Calcijexes
Prescription is:
Preparation method is:
1) take the distilled water of recipe quantity 75%, add the PEG400 of recipe quantity, stir; Continue to add meglumine and the polyethylene glycol 6000 of recipe quantity, stir 20min at 50 ℃ to all dissolving;
2) be warming up to 65 ℃, under the mixing speed of 800rpm, add the calcitriol of recipe quantity, continue to stir 30min to all dissolving;
3) add the sodium pyrosulfite of recipe quantity and appropriate mannitol, stirring and dissolving; Then add 0.1% active carbon of injection gross mass, standing after stirring, remove by filter powdered carbon;
4) after measurement regulator solution pH value, add to the full amount of water for injection; Through 0.45 μ m and 0.22 μ m filtering with microporous membrane, carry out afterwards fill, sealing, sterilizing, lamp inspection and packing.
Comparing embodiment 1 Calcijex
Preparation method is same embodiment 3:
Comparing embodiment 2 Calcijexes
Preparation method is with embodiment 3.
Comparing embodiment 3 Calcijexes
Preparation method is with embodiment 3.
Stability experiment and result
1. accelerated stability test
Intensity of illumination 4500lx, adopted HPLC method to carry out assay in the 0th, 5 and 10 days after timing sampling.
The condition of HPLC is: chromatographic column: ODS-C18 post, take octadecylsilane chemically bonded silica as filler; Mobile phase: acetonitrile-water (75:25); Detect wavelength: 265nm; Flow velocity: 1.0mL/min; Sample size: 50 μ L.Theoretical cam curve is pressed the calculating of calcitriol peak should be not low by 5000, and calcitriol peak and the peak-to-peak separating degree of trans calcitriol should be greater than 1.0.Adopt external standard method to calculate content.Assay result (percentage ratio of the amount of recording and labelled amount) sees the following form 1.Result shows that the stability of active component calcitriol in Calcijex of the present invention is obviously better than comparative example.
Table 1 accelerated stability test assay result (%)
2. long-term stable experiment
25 ℃ of temperature, relative humidity are placed 36 months for 60% time, respectively at 0,3,6,12,24 and 36 months time sampling adopt HPLC method to carry out assay.The same accelerated stability test of condition of HPLC.Adopt external standard method to calculate content.Assay result (percentage ratio of the amount of recording and labelled amount) sees the following form 2.Result shows that the stability of active component calcitriol in Calcijex of the present invention is obviously better than comparative example.
Table 2 long-term stable experiment assay result (%)
Should be noted that; the foregoing is only preferred embodiment of the present invention; be not limited to scope of the present invention, every any modification of having done within the spirit and principles in the present invention, the replacement being equal to and improvement etc., within all should being included in protection scope of the present invention.
Claims (4)
1. a Calcijex, is characterized in that, by the component of following percentage by weight, is made:
2. Calcijex according to claim 1, is characterized in that, by the component of following percentage by weight, is made:
3. Calcijex according to claim 1 and 2, is characterized in that, described antioxidant is selected from one or more in sodium sulfite, sodium sulfite, sodium pyrosulfite and vitamin E.
4. Calcijex according to claim 1 and 2, is characterized in that, described isoosmotic adjusting agent is selected from one or more in sodium chloride, glucose, mannitol and glycerol.
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| CN201310092701.8A CN103142470B (en) | 2013-03-21 | 2013-03-21 | Calcitriol injection and preparation method thereof |
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| CN201310092701.8A CN103142470B (en) | 2013-03-21 | 2013-03-21 | Calcitriol injection and preparation method thereof |
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| CN103142470B true CN103142470B (en) | 2014-11-12 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2015119183A1 (en) * | 2014-02-05 | 2015-08-13 | 協和発酵キリン株式会社 | Liquid drug containing active vitamin d3 or derivative thereof |
| CN104922620B (en) * | 2014-11-28 | 2018-08-03 | 山西佳能达华禹制药有限公司 | Application and preparation method thereof of the mulberry leaf-ginger common cold injection in preparing atomization and rectally preparation |
| CN104800155A (en) * | 2015-04-22 | 2015-07-29 | 青岛正大海尔制药有限公司 | Alfacalcidol injection and preparation method thereof |
| CN104800156A (en) * | 2015-04-22 | 2015-07-29 | 青岛正大海尔制药有限公司 | Alfacalcidol solution and preparation method thereof |
| CN108030767B (en) * | 2017-12-29 | 2020-07-24 | 河南泰丰生物科技有限公司 | Calcitriol injection and preparation method thereof |
| CN110934821A (en) * | 2019-12-19 | 2020-03-31 | 正大制药（青岛）有限公司 | Blumea ossifying alcohol injection and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4610978A (en) * | 1983-03-22 | 1986-09-09 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Compositions containing 1α-hydroxycholecalciferol for topical treatment of skin disorders and methods employing same |
| CN101141966A (en) * | 2005-03-23 | 2008-03-12 | 拜奥克塞尔有限公司 | Use of vitamin D compounds to treat endometriosis |
| CN101553210A (en) * | 2006-09-20 | 2009-10-07 | 奈克斯特安全有限公司 | Methods and systems of delivering medication via inhalation |
| CN102038645A (en) * | 2009-10-12 | 2011-05-04 | 杭州赛利药物研究所有限公司 | Desloratadine grain and preparation method thereof |
-
2013
- 2013-03-21 CN CN201310092701.8A patent/CN103142470B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4610978A (en) * | 1983-03-22 | 1986-09-09 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Compositions containing 1α-hydroxycholecalciferol for topical treatment of skin disorders and methods employing same |
| CN101141966A (en) * | 2005-03-23 | 2008-03-12 | 拜奥克塞尔有限公司 | Use of vitamin D compounds to treat endometriosis |
| CN101553210A (en) * | 2006-09-20 | 2009-10-07 | 奈克斯特安全有限公司 | Methods and systems of delivering medication via inhalation |
| CN102038645A (en) * | 2009-10-12 | 2011-05-04 | 杭州赛利药物研究所有限公司 | Desloratadine grain and preparation method thereof |
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