IE55230B1 - Use of a cholecalciferol derivative - Google Patents
Use of a cholecalciferol derivativeInfo
- Publication number
- IE55230B1 IE55230B1 IE1131/83A IE113183A IE55230B1 IE 55230 B1 IE55230 B1 IE 55230B1 IE 1131/83 A IE1131/83 A IE 1131/83A IE 113183 A IE113183 A IE 113183A IE 55230 B1 IE55230 B1 IE 55230B1
- Authority
- IE
- Ireland
- Prior art keywords
- difluoro
- dihydroxycholecalciferol
- treatment
- compound
- fluorinated compound
- Prior art date
Links
- 150000003704 vitamin D3 derivatives Chemical class 0.000 title 1
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 206010037660 Pyrexia Diseases 0.000 claims description 9
- 235000013336 milk Nutrition 0.000 claims description 9
- 239000008267 milk Substances 0.000 claims description 9
- 210000004080 milk Anatomy 0.000 claims description 9
- 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 claims description 8
- 230000002265 prevention Effects 0.000 claims description 5
- 241000282849 Ruminantia Species 0.000 claims description 4
- 230000003449 preventive effect Effects 0.000 claims description 4
- 230000032696 parturition Effects 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 241000283690 Bos taurus Species 0.000 claims description 2
- 239000012876 carrier material Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 2
- 241001465754 Metazoa Species 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000011612 calcitriol Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 27
- 239000003981 vehicle Substances 0.000 description 14
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000011575 calcium Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 229940126062 Compound A Drugs 0.000 description 4
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 210000004349 growth plate Anatomy 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 210000002303 tibia Anatomy 0.000 description 4
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 2
- 229940093471 ethyl oleate Drugs 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- 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 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 230000033558 biomineral tissue development Effects 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- -1 carrier Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 238000005470 impregnation Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- QMYDVDBERNLWKB-UHFFFAOYSA-N propane-1,2-diol;hydrate Chemical compound O.CC(O)CO QMYDVDBERNLWKB-UHFFFAOYSA-N 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 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
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
1. The use 24,24-difluoro-1 alpha, 25-dihydroxycholecalciferol in the manufacture of a medicament for the treatment of osteoporosis.
[EP0094644A1]
Description
3 3 55230 The invention is based on the finding of novel physiological properties of 24,24-difluoro-la,25-dihydroxy-cholecaIci-ferol, hereinafter denominated the fluorinated compound. Specifically it has been found that the fluorinated compound 5 is active against osteoporosis and in preventing milk fever, and can thus be utilized in the treatment of osteoporosis by administering to a patient suffering from osteoporosis an effective amount of the fluorinated compound, or can be utilized in the prevention of milk fever by administering to a pre-10 parturient female ruminant an effective amount of the fluorinated compound.
From US-A-4 201 881 and FR-A-2 453 151 it is known that 24, 24-difluoro-ΐα,25^dihydrorycholecalciferol (designated hereinafter as 24,24-(F)2-la,25-(OH)2~d3) can be used as a medicament on the 15 basis of its vitamin D activity (stimulation of intestinal calcium transport, mobilization of bone calcium).
Accordingly, the invention provides the use of the fluorinated compound in the manufacture of a medicament for the treatment of osteoporosis or the preventive treatment of milk fever.
The invention also provides preparations containing about 30 to 500 micrograms of difluoro-lo,25-dihydroxycholecalciferol in combination with a pharmaceutically acceptable inert carrier material for the preventive treatment of milk fever.
The foregoing activities of the fluorinated compound can 25 be demonstrated in the following tests: a) Anti-rachitogenlc activity in chicks White Leghorn chicks are placed in a vitamin O-deficient diet containing 1% calcium and 0.7% phosphorus, and arfe housed under ultraviolet-free lighting. The test compound is dissolved 30 in propylene glycol and administered orally for 21 consecutive days to the chicks which are one to two days of age at the start of treatment. Controls are treated 35S230 with vehicle alone. The chicks are autopsied on the day after the last treatment day and the tibia ash weights are determined. Nine to ten chicks are used for each treatment group and for the control group. The mean tibia ash weights expressed in mg are given in Table I. The results show that the fluorinated compound possess potent anti-rachito-genic activity.
Table I Dose (nq/chick^dav) Mean tibia ash weight (mg) 120.7+5.9 111.7+5.8 151.5+4.7 227.1+8.2 244.8+7.4 0 1 3 10 30 b) Intestinal calcium absorption in chicks White Leghorn chicks are placed on a vitamin D-defi- cient diet and are housed under ultraviolet-free lighting for 21 days. A single oral dose of test compound dissolved in propylene glycol is administered. At various times 45 after dosing, 2 uCi of Ca (chloride) are given orally and serum radioactivity is measured 45 minutes after administration of the isotope. Vehicle-treated controls are included at each time period. Ten or eleven chicks are used in each treatment and control group. The results given in Table II for la,25-dihydroxycholecalciferol (compound A) and for the fluorinated compound (B), show that the latter has potent intestinal calcium absorption activity of long duration (96 hours after a single oral 100 nanogram dose) and consequently possesses utility in the prevention of milk fever in preparturient female ruminants. 4 Table II Treatment Time (hours) Number of 45 Serum Ca chicks (cpm/0.2 ml) Vehicle 0.2 ml 24 11 992 + 81 Compound A 100 ng 11 1800 + 181 Compound B 100 ng 11 2064 + 170 Vehicle 0.2 ml 48 11 769 + 90 Compound A 100 ng 11 1006 + 133 m Compound B 100 ng 11 1539 + 99 Vehicle 0.2 ml 72 10 647 + 69 Compound A 200 ng 11 710 + 62 Compound B 100 ng 11 1164 + 90 Vehicle 0.2 ml 96 10 586 + 70 Compound B 100 ng 10' 998 + 61 15 c) Prevention of EHDP-induced mineralization block in rats 55230 Charles River male rats are treated for 10 consecutive days with the disodium salt of ethane-l-hydroxy-1,1-diphos-phonate (EHDP). This compound is given subcutaneously on each treatment day at a dose of 2 mg/0.2 ml/rat in distilled 20 water. The fluorinated compound is administered orally dissolved in propylene glycol on each treatment day. The rats are autopsied on the day after the last treatment day * and the tibias are processed by silver impregnation of the bone salts. The epiphyseal plate widths are measured with 25 a microscope. Activity is based upon dose-dependent narrowing of the widened epiphyseal plate induced by EHDP. Ten rats are used in each treatment group. Positive (EHDP alone) and negative (vehicles alone) control groups of ten rats each are included in each experiment. The results given in 30 Table III show that the fluorinated compound calcified the tibial epiphyseal plate in EHDP-blocked rats. 55230 Table III Dose Mean tibial epiphyseal plate width (no/rat/dav) _(micron)_' 1182 + 51 839 + 18 674 + 18 540 + 16 412 + 9 440 + 2 0 3 10 30 Vehicle controls (no EHDP) The fluorinated compound can be administered in dosages that are in the range of about 50-200, preferably 100 nanograms per day for the treatment of osteoporosis.
It can be administered orally, subcutaneously, intramuscularly, intravenously or intraperitoneally, for instance as tablets, capsules or elixirs for oral administration, or in sterile solutions or suspensions for parenteral administration. About 50-200 nanograms of the fluorinated compound is compounded with a pharmaceutically acceptable vehicle, carrier, excipient, binder, preservative, stabilizer and/or flavor in a unit dosage form. Illustrative of the adjuvants which may be incorporated into capsules are a binder, such as corn starch or gelatin; an excipient, such as dicalcium phosphate; a disintegrating, such as corn or potato starch or algenic acid; a lubricant, such as magnesium stearate; a sweetening agent, such as sucrose; a flavoring agent, such as peppermint, other materials may be present as coatings or to otherwise modify the physical form of the dosage unit. For instance, tablets may be coated with shellac, sugar or both. A syrup or elixir may contain the active compound, sucrose as a sweetening agent, methyl and propyl parabens as preservatives, a dye and a flavoring, such as orange flavor. Sterile compositions for injection can be formulated according to conventional pharmaceutical practice by dissolving or suspending the 6 6 5S230 fluorinated compound in a vehicle, such as water for injection, a naturally-occurring vegetable oil, such as sesame oil, or a synthetic fatty vehicle, such as ‘ethyl oleate. Buffers, preservatives and antioxidants can also be incor-5 porated.
The fluorinated compound can be administered in dosages in the range of about 30-500 micrograms per day for the prevention of milk fever in pregnant ruminant animals, especially in pregnant female bovines, preferably 10 about one to four days prior to parturition. The fluorinated compound can be formulated for oral administration by incorporation of 30-500 micrograms into fatty acid pellets. Sterile compositions for injection and/or topical administration can be formulated according to conventional 15 practice by dissolving or suspending the fluorinated compound in a vehicle, such as a 5-10¾ ethanol-water mixture; a naturally-occurring vegetable oil, such as sesame oil; or a synthetic fatty vehicle, such as ethyl oleate. For example, a suitable formulation for intravenous injection 20 would be 2-3 ml of a 5-10% ethanol-water solution containing 30-500, preferably 30-400 micrograms of the fluorinated compound. Exemplary of a suitable formulation for topical administration would be a vegetable oil solution or suspension containing 30-500, preferably 250-500 micrograms of 25 the fluorinated compound. The fluorinated compound may also be formulated for intramuscular injection by suspension of 50-500 micrograms of the fluorinated compound in a vehicle such as a 5-10% ethanol-water mixture or a 5-10% propylene glycol-water mixture. Buffers, preservatives and/or anti-30 oxidants can be incorporated into the foregoing formulations as required. 7 755230 Example A capsule containing pro capsule: 1. 24,24-difluoro-la,25-dihydroxycholecalciferol 50 ng 100 ng 200 ng 2. polyethylene glycol 400 200 mg 200 mg 200 mg 3. butylated hydroxyanisole 0.1 mg 0.1 mg 0.1 mg 4. ascorbyl palmitate 1.0 mg 1.0 mg 1.0 mg may be ' obtained by dissolving items 1, 3 and 4 in item 2 under an atmophere of nitrogen and encapsulating.
Claims (7)
1. Use of 24,24-difluoro-la,25-dihydroxycholecalciferol in the manufacture of a medicament for the treatment of osteoporosis.
2. use of 24,24-difluoro-la,25-dihydroxycholecaliferol in the manufacture of a medicament for the preventive treatment of milk fever.
3. A preparation containing about 30 to 500 micrograms of 24, 24-difluoro-la,25-dihydroxycholecalciferol in combination with a pharmaceutically acceptable inert carrier material for the preventive treatment of milk fever,
4. A method for the prevention of milk fever in ruminant animals, particularly in female bovine, which comprises administering to such an animal about 30 to 500 micrograms of 24,24-difluoro-lct,25-dihydroxycholecalciferol per day prior to parturition.
5. A method according to Claim 4, wherein said 24,24-difluoro-la,25-dihydroxycholecalciferol is administered about one to four days prior to parturition.
6. Use according to Claim 1 or 2 of 24,24-difluro-la,25-dihydro-xycholecalciferol, substantially has hereinbefore described.
7. A preparation according to Claim 3, substantially as hereinbefore described with particular reference to the accompanying Example. F. R. KELLY & CO., AGENTS FOR THE APPLICANTS.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/379,385 US4599330A (en) | 1982-05-17 | 1982-05-17 | Method of treating milk fever |
| US06/379,384 US4397847A (en) | 1982-05-17 | 1982-05-17 | Method of treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE831131L IE831131L (en) | 1983-11-17 |
| IE55230B1 true IE55230B1 (en) | 1990-07-04 |
Family
ID=27008599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE1131/83A IE55230B1 (en) | 1982-05-17 | 1983-05-16 | Use of a cholecalciferol derivative |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0094644B1 (en) |
| AU (1) | AU563733B2 (en) |
| CA (1) | CA1221031A (en) |
| DE (2) | DE3317562A1 (en) |
| IE (1) | IE55230B1 (en) |
| IL (1) | IL68695A (en) |
| IT (1) | IT1171672B (en) |
| NZ (1) | NZ204223A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4428946A (en) * | 1982-07-26 | 1984-01-31 | Wisconsin Alumni Research Foundation | Method of preventing milk fever in dairy cattle |
| CA1272953A (en) | 1984-10-08 | 1990-08-21 | Yuji Makino | Pharmaceutical composition for external use containing active-type vitamin d.sub.3 |
| JP2856444B2 (en) * | 1989-07-28 | 1999-02-10 | 呉羽化学工業株式会社 | Vitamin D lower 3 metabolite preparation |
| GB202016614D0 (en) | 2020-10-20 | 2020-12-02 | King S College London | Compounds |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3646203A (en) * | 1969-04-30 | 1972-02-29 | Wisconsin Alumni Res Found | Method of treating milk fever in dairy cattle with 25-hydroxycholecalciferol |
| US3879548A (en) * | 1974-01-21 | 1975-04-22 | Wisconsin Alumni Res Found | Method of treating milk fever in dairy cattle with 1-alpha-hydroxycholecalciferol |
| US4110446A (en) * | 1977-07-14 | 1978-08-29 | Wisconsin Alumni Research Foundation | Method of treating milk fever in dairy cattle with 1,25-dihydroxycholecalciferol |
| US4284577A (en) * | 1979-02-16 | 1981-08-18 | Sachiko Yamada | Novel vitamin D3 derivative and process for preparing the same |
| US4201881A (en) * | 1979-03-28 | 1980-05-06 | Wisconsin Alumni Research Foundation | 24,24-Difluoro-1α,25-dihydroxycholecalciferol |
-
1983
- 1983-05-13 DE DE19833317562 patent/DE3317562A1/en not_active Withdrawn
- 1983-05-13 CA CA000428169A patent/CA1221031A/en not_active Expired
- 1983-05-13 IL IL68695A patent/IL68695A/en unknown
- 1983-05-13 DE DE8383104746T patent/DE3364904D1/en not_active Expired
- 1983-05-13 EP EP83104746A patent/EP0094644B1/en not_active Expired
- 1983-05-13 NZ NZ204223A patent/NZ204223A/en unknown
- 1983-05-16 IE IE1131/83A patent/IE55230B1/en unknown
- 1983-05-16 AU AU14562/83A patent/AU563733B2/en not_active Ceased
- 1983-05-17 IT IT21128/83A patent/IT1171672B/en active
Also Published As
| Publication number | Publication date |
|---|---|
| IL68695A (en) | 1986-01-31 |
| EP0094644B1 (en) | 1986-07-30 |
| IL68695A0 (en) | 1983-09-30 |
| AU1456283A (en) | 1983-11-24 |
| IT8321128A0 (en) | 1983-05-17 |
| DE3364904D1 (en) | 1986-09-04 |
| DE3317562A1 (en) | 1983-11-17 |
| NZ204223A (en) | 1986-11-12 |
| CA1221031A (en) | 1987-04-28 |
| EP0094644A1 (en) | 1983-11-23 |
| IE831131L (en) | 1983-11-17 |
| AU563733B2 (en) | 1987-07-23 |
| IT1171672B (en) | 1987-06-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1045695B1 (en) | Use of 9-deoxy-2', 9-alpha-methano-3- oxa-4,5,6- trinor-3, 7-(1',3'-interphenylene) -13,14-dihydro- prostaglandin f 1? to treat peripheral vascular disease | |
| AU719773B2 (en) | Use of vitamin D2 or vitamin D4-derivatives for the manufacture of a medicament for the treatment of secondary hyperparathyroidism | |
| US5348979A (en) | Method of promoting nitrogen retention in humans | |
| Edelstein et al. | Gastrointestinal absorption of lead in chicks: involvement of the cholecalciferol endocrine system | |
| US4438138A (en) | Reduction of cholesterol with meta-chloro α-t-butylaminopropiophenone | |
| GB2098066A (en) | Vitamin d3 derivatives for preventing parturient paresis in dairy cattle | |
| WO1995013062A1 (en) | Butyric ester cyto-differentiating agents | |
| IE55230B1 (en) | Use of a cholecalciferol derivative | |
| US3852453A (en) | Method of enhancing vincamine compositions | |
| KR100304312B1 (en) | Zinc Supplemented Prostate Extract | |
| Fullmer et al. | Effect of cadmium administration on intestinal calcium absorption and vitamin D-dependent calcium-binding protein | |
| CA1206882A (en) | Use of cholecalciferol derivatives | |
| US3317381A (en) | Method for treating peptic ulcer | |
| JPS63107929A (en) | Drug containing novel vitamin d3 derivative as active ingredient | |
| EP0385446A2 (en) | Osteogenesis promotion with use of vitamin D derivatives | |
| HK1005015B (en) | Osteogenesis promotion with use of vitamin d derivatives | |
| JPS58208231A (en) | Medicine containing cholecalsiferol derivative | |
| JPH0563452B2 (en) | ||
| GB2050164A (en) | Ionising radiation protective compositions | |
| US3360434A (en) | Method for reducing blood pressure with phenylalanine derivatives | |
| Boris et al. | In vivo studies in chicks and rats of bone calcium mobilization by 1α, 25-dihydroxycholecalciferol (calcitriol) and its congeners | |
| JPH07233062A (en) | Composition for treating skin pruritus of patient requiring artificial dialysis and composition for treating hyperparathyroidism | |
| US3786157A (en) | Method of treating hyperglycemia | |
| JPH0377173B2 (en) | ||
| Ershoff et al. | Comparative effects of a purified diet and a natural food stock ration on the occurrence of periodontal lesions in thyrotoxic rats |