CN103142476B - Calcitriol suspension and preparation method thereof - Google Patents
Calcitriol suspension and preparation method thereof Download PDFInfo
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- CN103142476B CN103142476B CN201310092609.1A CN201310092609A CN103142476B CN 103142476 B CN103142476 B CN 103142476B CN 201310092609 A CN201310092609 A CN 201310092609A CN 103142476 B CN103142476 B CN 103142476B
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- 235000020964 calcitriol Nutrition 0.000 title claims abstract description 50
- 239000011612 calcitriol Substances 0.000 title claims abstract description 50
- 229960005084 calcitriol Drugs 0.000 title claims abstract description 50
- 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 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000000725 suspension Substances 0.000 title abstract 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000012153 distilled water Substances 0.000 claims abstract description 15
- 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
- 229960003194 meglumine Drugs 0.000 claims abstract description 10
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims abstract description 10
- 239000000375 suspending agent Substances 0.000 claims abstract description 7
- 239000000080 wetting agent Substances 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims description 21
- 239000004568 cement Substances 0.000 claims description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 9
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 claims description 9
- 238000013019 agitation Methods 0.000 claims description 7
- 239000012467 final product Substances 0.000 claims description 7
- 239000004570 mortar (masonry) Substances 0.000 claims description 7
- 235000011837 pasties Nutrition 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 3
- 229920001503 Glucan Polymers 0.000 claims description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 3
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 3
- 229920002125 Sokalan® Polymers 0.000 claims description 3
- 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 3
- 229960001631 carbomer Drugs 0.000 claims description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 3
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims description 3
- 229960000502 poloxamer Drugs 0.000 claims description 3
- 229920001983 poloxamer Polymers 0.000 claims description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 3
- 229920001027 sodium carboxymethylcellulose Polymers 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
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical class CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- -1 polyoxyethylene Polymers 0.000 claims description 2
- 239000002002 slurry Substances 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
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 2
- 229940080313 sodium starch Drugs 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 5
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a calcitriol suspension and a preparation method thereof. The suspension is prepared from the following ingredients in percentage by weight: 0.0005% of calcitriol, 1.4-1.8% of meglumine, 15-20% of polyethylene glycol 400, 1.5-2.5% of polyethylene glycol 6000, 2.0% of suspending agent, 8.0% of wetting agent and the balance of distilled water. According to the suspension, 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 suspensoid 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 suspensoid 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 suspensoid, 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 suspensoid that a kind of active component content is high, medicine stability good, bioavailability is high.This suspensoid is made up of the component of following percentage by weight:
Its optimizing prescriptions is:
Further, above-mentioned suspending agent is selected from one or more in carbomer, glucosan, hydroxypropyl cellulose, sodium carboxymethyl cellulose, arabic gum, sodium alginate and starch slurry.
Further, above-mentioned wetting agent is selected from one or more in glycerol, polyoxyethylene sorbitan monoleate, poloxamer, sodium lauryl sulphate and polyoxyethylene hydrogenated Oleum Ricini.
The preparation method of this suspensoid is:
1) take the distilled water of recipe quantity 30-40%, 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 DEG C to all dissolving to obtain solution;
2) take the distilled water of recipe quantity 15-25%, add the suspending agent of recipe quantity, rubber cement stirs to obtain;
3) in mortar, add calcitriol and the wetting agent of recipe quantity, grind to form pasty state; Under agitation slowly add above-mentioned rubber cement to grind well; Add again afterwards above-mentioned solution, continue to be ground to evenly;
4) adding distil water, to full dose, shakes up, and to obtain final product.
The preparation method of this suspensoid is more preferably:
1) take the distilled water of recipe quantity 35%, add the PEG400 of recipe quantity, stir; Continue to add meglumine and the polyethylene glycol 6000 of recipe quantity, stir 20min at 50 DEG C to all dissolving to obtain solution;
2) take the distilled water of recipe quantity 20%, add the suspending agent of recipe quantity, rubber cement stirs to obtain;
3) in mortar, add calcitriol and the wetting agent of recipe quantity, grind to form pasty state; Under agitation slowly add above-mentioned rubber cement to grind well; Add again afterwards above-mentioned solution, continue to be ground to evenly;
4) adding distil water, to full dose, shakes up, and to obtain 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 suspensoid
Prescription is:
Preparation method is:
1) take the distilled water of recipe quantity 30%, add the PEG400 of recipe quantity, stir; Continue to add meglumine and the polyethylene glycol 6000 of recipe quantity, stir 15min at 45 DEG C to all dissolving to obtain solution;
2) take the distilled water of recipe quantity 15%, add the sodium carboxymethyl cellulose of recipe quantity, rubber cement stirs to obtain;
3) in mortar, add calcitriol and the glycerol of recipe quantity, grind to form pasty state; Under agitation slowly add above-mentioned rubber cement to grind well; Add again afterwards above-mentioned solution, continue to be ground to evenly;
4) adding distil water, to full dose, shakes up, and to obtain final product.
Embodiment 2 calcitriol suspensoids
Prescription is:
Preparation method is:
1) take the distilled water of recipe quantity 40%, add the PEG400 of recipe quantity, stir; Continue to add meglumine and the polyethylene glycol 6000 of recipe quantity, stir 25min at 55 DEG C to all dissolving to obtain solution;
2) take the distilled water of recipe quantity 25%, add the glucosan of recipe quantity, rubber cement stirs to obtain;
3) in mortar, add calcitriol and the polyoxyethylene sorbitan monoleate of recipe quantity, grind to form pasty state; Under agitation slowly add above-mentioned rubber cement to grind well; Add again afterwards above-mentioned solution, continue to be ground to evenly;
4) adding distil water, to full dose, shakes up, and to obtain final product.
Embodiment 3 calcitriol suspensoids
Prescription is:
Preparation method is:
1) take the distilled water of recipe quantity 35%, add the PEG400 of recipe quantity, stir; Continue to add meglumine and the polyethylene glycol 6000 of recipe quantity, stir 20min at 50 DEG C to all dissolving to obtain solution;
2) take the distilled water of recipe quantity 20%, add the carbomer of recipe quantity, rubber cement stirs to obtain;
3) in mortar, add calcitriol and the poloxamer of recipe quantity, grind to form pasty state; Under agitation slowly add above-mentioned rubber cement to grind well; Add again afterwards above-mentioned solution, continue to be ground to evenly;
4) adding distil water, to full dose, shakes up, and to obtain final product.
Comparing embodiment 1 calcitriol suspensoid
Preparation method is same embodiment 3:
Comparing embodiment 2 calcitriol suspensoids
Preparation method is with embodiment 3.
Comparing embodiment 3 calcitriol suspensoids
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 suspensoid 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 suspensoid of the present invention is obviously better than comparative example.
Table 2 long-term stable experiment assay result (%)
Example 1
Relatively implement
100.1 94.7 87.1 80.0 77.9 73.7
Example 2
Relatively implement
100.2 95.3 87.9 80.2 76.9 74.1
Example 3
The comparative test of embodiment 5 bioavailability
4 beasle dogs (being male) are carried out to oral administration, they are filled with respectively to the calcitriol suspensoid (25 DEG C of temperature, relative humidity are placed 12 months for 60% time) with the embodiment of the present invention 3, comparative example 1, comparative example 2, comparative example 3, 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 suspensoid gained.As seen from table, the maximum haemoconcentration of the calcitriol of calcitriol suspensoid 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 (6)
1. a calcitriol suspensoid, is characterized in that, is made up of the component of following percentage by weight:
2. calcitriol suspensoid according to claim 1, is characterized in that, is made up of the component of following percentage by weight:
3. calcitriol suspensoid according to claim 1 and 2, is characterized in that, described suspending agent is selected from one or more in carbomer, glucosan, hydroxypropyl cellulose, sodium carboxymethyl cellulose, arabic gum, sodium alginate and starch slurry.
4. calcitriol suspensoid according to claim 1 and 2, is characterized in that, described wetting agent is selected from one or more in glycerol, polyoxyethylene sorbitan monoleate, poloxamer, sodium lauryl sulphate and polyoxyethylene hydrogenated Oleum Ricini.
5. the preparation method of the calcitriol suspensoid described in claim 1-4 any one, is characterized in that, the method comprises the steps:
1) take the distilled water of recipe quantity 30-40%, 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 DEG C to all dissolving to obtain solution;
2) take the distilled water of recipe quantity 15-25%, add the suspending agent of recipe quantity, rubber cement stirs to obtain;
3) in mortar, add calcitriol and the wetting agent of recipe quantity, grind to form pasty state; Under agitation slowly add above-mentioned rubber cement to grind well; Add again afterwards above-mentioned solution, continue to be ground to evenly;
4) adding distil water, to full dose, shakes up, and to obtain final product.
6. the preparation method of calcitriol suspensoid claimed in claim 5, is characterized in that, the method comprises the steps:
1) take the distilled water of recipe quantity 35%, add the PEG400 of recipe quantity, stir; Continue to add meglumine and the polyethylene glycol 6000 of recipe quantity, stir 20min at 50 DEG C to all dissolving to obtain solution;
2) take the distilled water of recipe quantity 20%, add the suspending agent of recipe quantity, rubber cement stirs to obtain;
3) in mortar, add calcitriol and the wetting agent of recipe quantity, grind to form pasty state; Under agitation slowly add above-mentioned rubber cement to grind well; Add again afterwards above-mentioned solution, continue to be ground to evenly;
4) adding distil water, to full dose, shakes up, and to obtain final product.
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Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6045517A (en) * | 1983-08-02 | 1985-03-12 | Kureha Chem Ind Co Ltd | Antimyodystrophia agent containing 1alpha-hydroxyvitamin d3 |
| JPS61122214A (en) * | 1984-11-20 | 1986-06-10 | Kureha Chem Ind Co Ltd | Antirheumatic |
| GB0505954D0 (en) * | 2005-03-23 | 2005-04-27 | Bioxell Spa | Novel use |
| CN102038645B (en) * | 2009-10-12 | 2013-11-27 | 杭州赛利药物研究所有限公司 | Desloratadine grain and preparation method thereof |
| CN102258531B (en) * | 2011-04-12 | 2012-09-19 | 宁辉 | Medicinal composition containing adenosine cyclophosphate and meglumine and preparation method thereof |
| CN102743354A (en) * | 2012-07-31 | 2012-10-24 | 南京正科制药有限公司 | Repaglinide tablet and preparation method thereof |
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