CN103142547B - Calcitriol enteric capsule and preparation method thereof - Google Patents
Calcitriol enteric capsule and preparation method thereof Download PDFInfo
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- CN103142547B CN103142547B CN201310092574.1A CN201310092574A CN103142547B CN 103142547 B CN103142547 B CN 103142547B CN 201310092574 A CN201310092574 A CN 201310092574A CN 103142547 B CN103142547 B CN 103142547B
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- 235000020964 calcitriol Nutrition 0.000 title claims abstract description 51
- 239000011612 calcitriol Substances 0.000 title claims abstract description 51
- 229960005084 calcitriol Drugs 0.000 title claims abstract description 51
- 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 title claims abstract description 51
- 239000002775 capsule Substances 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000011230 binding agent Substances 0.000 claims abstract description 21
- 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 claims abstract description 10
- 239000000463 material Substances 0.000 claims abstract description 10
- 229960003194 meglumine Drugs 0.000 claims abstract description 10
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims abstract description 10
- 239000000945 filler Substances 0.000 claims abstract description 8
- 239000011248 coating agent Substances 0.000 claims description 21
- 238000000576 coating method Methods 0.000 claims description 21
- 238000007873 sieving Methods 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 12
- 229920002472 Starch Polymers 0.000 claims description 11
- -1 acetate benzenetricarboxylic acid ester Chemical class 0.000 claims description 11
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 9
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 9
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 9
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 claims description 9
- 239000008107 starch Substances 0.000 claims description 9
- 235000019698 starch Nutrition 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 8
- 239000012153 distilled water Substances 0.000 claims description 7
- 239000012467 final product Substances 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 7
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 239000007779 soft material Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 229920002301 cellulose acetate Polymers 0.000 claims description 4
- 229920001353 Dextrin Polymers 0.000 claims description 3
- 239000004375 Dextrin Substances 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 3
- 229920000881 Modified starch Polymers 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 235000019425 dextrin Nutrition 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 3
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 235000019890 Amylum Nutrition 0.000 claims description 2
- 229920008347 Cellulose acetate propionate Polymers 0.000 claims description 2
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 229950005770 hyprolose Drugs 0.000 claims description 2
- 229960003943 hypromellose Drugs 0.000 claims description 2
- 229940117841 methacrylic acid copolymer Drugs 0.000 claims description 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims description 2
- 229940083542 sodium Drugs 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 5
- 239000002702 enteric coating Substances 0.000 abstract 2
- 238000009505 enteric coating Methods 0.000 abstract 2
- 239000010410 layer Substances 0.000 abstract 2
- 239000007884 disintegrant Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 10
- 238000003556 assay Methods 0.000 description 6
- 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
- 238000013112 stability test Methods 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 206010018873 Haemoconcentration Diseases 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
- 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
- 229960001375 lactose Drugs 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
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 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
- 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
- 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
- 239000000047 product 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
- 238000012360 testing method Methods 0.000 description 1
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- 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
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a calcitriol enteric capsule and a preparation method thereof. The enteric capsule consists of a core and an enteric coating layer, wherein the enteric coating layer contains an enteric material accounting for 10-20% by weight, and the core is prepared from the following ingredients in percentage by weight: 0.0005% of calcitriol, 2.0-4.0% of meglumine, 1.2-1.8% of polyethylene glycol 400, 15-25% of polyethylene glycol 6000, 50.0-70.0% of filler, 5.0-10.0% of disintegrant and an appropriate amount of binder. According to the enteric capsule, 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 calcitriol enteric coated capsule 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 DEG C.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.Calcitriol enteric coated capsule do not 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 calcitriol enteric coated capsule, the meglumine, PEG400 and the polyethylene glycol 6000 that add in right amount, 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 calcitriol enteric coated capsule that a kind of active component content is high, medicine stability good, bioavailability is high.This enteric coated capsule is made up of core core and enteric coat layer, and wherein enteric coat layer comprises the enteric material that percentage by weight is 10-20%, and core core is made up of the component of following percentage by weight:
In its optimizing prescriptions, to comprise percentage by weight be 15% enteric material to enteric coat layer, and core core is made up of the component of following percentage by weight:
Further, above-mentioned filler is selected from one or more in starch, lactose, dextrin, amylum pregelatinisatum and Icing Sugar.
Further, above-mentioned disintegrating agent is selected from one or more in carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose and sodium alginate.
Further, above-mentioned binding agent is selected from one or more in starch, pregelatinized Starch, hyprolose, hypromellose and polyvidone.
Further, above-mentioned enteric material is selected from one or more in CAP, methacrylic acid copolymer, cellulose acetate benzenetricarboxylic acid ester and hydroxypropyl cellulose phthalate ester.
The preparation method of this enteric coated capsule is:
1) take the supplementary material of recipe quantity, cross respectively 80-120 mesh sieve for subsequent use;
2) binding agent and the enteric material got after sieving add respectively distilled water, make binder solution and coating solution;
3) by the calcitriol after sieving, meglumine, PEG400, polyethylene glycol 6000, filler and disintegrating agent by equivalent incremental method mix homogeneously, add above-mentioned binder solution to make soft material;
4) after granulating with 40 mesh sieves, dry 30-60min, crosses 20 mesh sieve granulate at 50-70 DEG C; Remove fine powder after No. 4 sieve sieves, make core core;
5) with above-mentioned coating solution, the core core making is carried out to fluidized bed coating, dry, pack in capsulae vacuus and get final product.
The preparation method of this enteric coated capsule is more preferably:
1) take the supplementary material of recipe quantity, cross respectively 100 mesh sieves for subsequent use;
2) binding agent and the enteric material got after sieving add respectively distilled water, make binder solution and coating solution;
3) by the calcitriol after sieving, meglumine, PEG400, polyethylene glycol 6000, filler and disintegrating agent by equivalent incremental method mix homogeneously, add above-mentioned binder solution to make soft material;
4) after granulating with 40 mesh sieves, dry 45min, crosses 20 mesh sieve granulate at 60 DEG C; Remove fine powder after No. 4 sieve sieves, make core core;
5) with above-mentioned coating solution, the core core making is carried out to fluidized bed coating, dry, pack in capsulae vacuus and get final product.
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.
Detailed description of the invention
Below in conjunction with concrete embodiment, technical scheme of the present invention is further described.
Embodiment 1 calcitriol enteric coated capsule
Prescription is:
Core core is made up of the component of following percentage by weight:
It is 10% CAP that enteric coat layer comprises percentage by weight.
Preparation method is:
1) take the supplementary material of recipe quantity, cross respectively 80 mesh sieves for subsequent use;
2) starch and the CAP got after sieving add respectively distilled water, make binder solution and coating solution;
3) by the calcitriol after sieving, meglumine, PEG400, polyethylene glycol 6000, starch and carboxymethyl starch sodium by equivalent incremental method mix homogeneously, add above-mentioned binder solution to make soft material;
4) after granulating with 40 mesh sieves, dry 30min, crosses 20 mesh sieve granulate at 50 DEG C; Remove fine powder after No. 4 sieve sieves, make core core;
5) with above-mentioned coating solution, the core core making is carried out to fluidized bed coating, dry, pack in capsulae vacuus and get final product.
Embodiment 2 calcitriol enteric coated capsulees
Prescription is:
Core core is made up of the component of following percentage by weight:
It is 20% cellulose acetate benzenetricarboxylic acid ester that enteric coat layer comprises percentage by weight.
Preparation method is:
1) take the supplementary material of recipe quantity, cross respectively 120 mesh sieves for subsequent use;
2) pregelatinized Starch and the cellulose acetate benzenetricarboxylic acid ester got after sieving add respectively distilled water, make binder solution and coating solution;
3) by the calcitriol after sieving, meglumine, PEG400, polyethylene glycol 6000, lactose and low-substituted hydroxypropyl cellulose by equivalent incremental method mix homogeneously, add above-mentioned binder solution to make soft material;
4) after granulating with 40 mesh sieves, dry 60min, crosses 20 mesh sieve granulate at 70 DEG C; Remove fine powder after No. 4 sieve sieves, make core core;
5) with above-mentioned coating solution, the core core making is carried out to fluidized bed coating, dry, pack in capsulae vacuus and get final product.
Embodiment 3 calcitriol enteric coated capsulees
Prescription is:
Core core is made up of the component of following percentage by weight:
It is 15% hydroxypropyl cellulose phthalate ester that enteric coat layer comprises percentage by weight.
Preparation method is:
1) take the supplementary material of recipe quantity, cross respectively 100 mesh sieves for subsequent use;
2) polyvidone and the hydroxypropyl cellulose phthalate ester got after sieving add respectively distilled water, make binder solution and coating solution;
3) by the calcitriol after sieving, meglumine, PEG400, polyethylene glycol 6000, dextrin and microcrystalline Cellulose by equivalent incremental method mix homogeneously, add above-mentioned binder solution to make soft material;
4) after granulating with 40 mesh sieves, dry 45min, crosses 20 mesh sieve granulate at 60 DEG C; Remove fine powder after No. 4 sieve sieves, make core core;
5) with above-mentioned coating solution, the core core making is carried out to fluidized bed coating, pack in capsulae vacuus and get final product.
Comparing embodiment 1 calcitriol enteric coated capsule
Core core is made up of the component of following percentage by weight:
It is 15% hydroxypropyl cellulose phthalate ester that enteric coat layer comprises percentage by weight.
Preparation method is same embodiment 3:
Comparing embodiment 2 calcitriol enteric coated capsulees
Core core is made up of the component of following percentage by weight:
It is 15% hydroxypropyl cellulose phthalate ester that enteric coat layer comprises percentage by weight.
Preparation method is with embodiment 3.
Comparing embodiment 3 calcitriol enteric coated capsulees
Core core is made up of the component of following percentage by weight:
It is 15% hydroxypropyl cellulose phthalate ester that enteric coat layer comprises percentage by weight.
Preparation method is with embodiment 3.
Embodiment 4 stability experiments 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, taking 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 calcitriol enteric coated capsule of the present invention is obviously better than comparative example.
Table 1 accelerated stability test assay result (%)
2. long-term stable experiment
25 DEG C 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 calcitriol enteric coated capsule of the present invention is obviously better than comparative example.
Table 2 long-term stable experiment assay result (%)
The comparative test of embodiment 5 bioavailability
4 beasle dogs (being male) are carried out to oral administration, feed respectively the calcitriol enteric coated capsule with the embodiment of the present invention 3, comparative example 1, comparative example 2, comparative example 3 (25 DEG C of temperature, relative humidity are placed 12 months for 60% time) to them, dosage is only (in calcitriol) of 10.0 μ g/, and be 7 days the interval time of each administration.Give after medicine, blood sample collection under different time, and carry out the maximum haemoconcentration (C of calcitriol
max) and bioavailability (AUC
0 → 48) calculating.Acquisition time is 0h, 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h, 24h, 32h, 48h.
Following table 3 provides the average result that 4 beasle dogs is given to the embodiment of the present invention 3, comparative example 1, comparative example 2, comparative example's 3 calcitriol enteric coated capsule gained.As seen from table, the maximum haemoconcentration of the calcitriol of calcitriol enteric coated capsule of the present invention (embodiment 3) and bioavailability are apparently higher than comparative example.
The comparison (10.0 μ g, n=3) of table 3 bioavailability
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 amendment of having done within the spirit and principles in the present invention, replacement and the improvement etc. being equal to, within all should being included in protection scope of the present invention.
Claims (7)
1. a calcitriol enteric coated capsule, is characterized in that, this enteric coated capsule is made up of core core and enteric coat layer, and it is 15% enteric material that described enteric coat layer comprises percentage by weight, and described core core is made up of the component of following percentage by weight:
2. calcitriol enteric coated capsule according to claim 1, is characterized in that, described filler is selected from one or more in starch, lactose, dextrin, amylum pregelatinisatum and Icing Sugar.
3. calcitriol enteric coated capsule according to claim 1 and 2, is characterized in that, described disintegrating agent is selected from one or more in carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose and sodium alginate.
4. calcitriol enteric coated capsule according to claim 1 and 2, is characterized in that, described binding agent is selected from one or more in starch, pregelatinized Starch, hyprolose, hypromellose and polyvidone.
5. calcitriol enteric coated capsule according to claim 1 and 2, is characterized in that, described enteric material is selected from one or more in CAP, methacrylic acid copolymer, cellulose acetate benzenetricarboxylic acid ester and hydroxypropyl cellulose phthalate ester.
6. the preparation method of the calcitriol enteric coated capsule described in one of claim 1-5, is characterized in that, the method comprises the steps:
1) take the supplementary material of recipe quantity, cross respectively 80-120 mesh sieve for subsequent use;
2) binding agent and the enteric material got after sieving add respectively distilled water, make binder solution and coating solution;
3) by the calcitriol after sieving, meglumine, PEG400, polyethylene glycol 6000, filler and disintegrating agent by equivalent incremental method mix homogeneously, add above-mentioned binder solution to make soft material;
4) after granulating with 40 mesh sieves, dry 30-60min, crosses 20 mesh sieve granulate at 50-70 DEG C; Remove fine powder after No. 4 sieve sieves, make core core;
5) with above-mentioned coating solution, the core core making is carried out to fluidized bed coating, dry, pack in capsulae vacuus and get final product.
7. the preparation method of calcitriol enteric coated capsule claimed in claim 6, is characterized in that, the method comprises the steps:
1) take the supplementary material of recipe quantity, cross respectively 100 mesh sieves for subsequent use;
2) binding agent and the enteric material got after sieving add respectively distilled water, make binder solution and coating solution;
3) by the calcitriol after sieving, meglumine, PEG400, polyethylene glycol 6000, filler and disintegrating agent by equivalent incremental method mix homogeneously, add above-mentioned binder solution to make soft material;
4) after granulating with 40 mesh sieves, dry 45min, crosses 20 mesh sieve granulate at 60 DEG C; Remove fine powder after No. 4 sieve sieves, make core core;
5) with above-mentioned coating solution, the core core making is carried out to fluidized bed coating, pack in capsulae vacuus and get final product.
Priority Applications (1)
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| 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 |
| 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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| 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 |
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