NZ204223A - Veterinary compositions containing 24,24-difluoro-1 alpha,25-dihydroxycholecalciferol - Google Patents
Veterinary compositions containing 24,24-difluoro-1 alpha,25-dihydroxycholecalciferolInfo
- Publication number
- NZ204223A NZ204223A NZ204223A NZ20422383A NZ204223A NZ 204223 A NZ204223 A NZ 204223A NZ 204223 A NZ204223 A NZ 204223A NZ 20422383 A NZ20422383 A NZ 20422383A NZ 204223 A NZ204223 A NZ 204223A
- Authority
- NZ
- New Zealand
- Prior art keywords
- dihydroxycholecalciferol
- difluoro
- compound
- fluorinated compound
- alpha
- Prior art date
Links
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)
Description
New Zealand Paient Spedficaiion for Paient Number £04223
204223
Priority Date(s): . 7
Complete Specification Filed:
Class:
Publication Date: M f~. .NQ.V J98S • •.
P.O. Journal, No: . mr
HO DRAH2IH6S
NEW ZEALAND
PATENTS ACT, 1953
No.: Date:
COMPLETE SPECIFICATION
USE OF CHOLECALCIFEROL DERIVATIVE
t?We, F. HOFFMANN-LA ROCHE s CO. AKTIENGESELLSCHAFT, 124 - 184 Grenzacherstrasse, Basle, Switzerland, a Swiss Company,
hereby declare the invention for which K/ we pray that a patent may be granted to ***/„*, and the method by which u to be to be particularly described in and by the following statement: -
(followed by la)
- la -
204223
The invention is based on the finding of novel physiological properties of 24,24-difluoro-la, 25-dihydroxycholecalciferol, hereinafter demonimated the fluorinated compound. Specifically it has been found that the fluorinated compound is active in preventing milk fever, and can thus be utili2ed in the prevention of milk fever by administering to a preparturient female ruminant an effective amount of the fluorinated compound.
Accordingly the invention relates to a method for the prevention of milk fever in ruminant animals comprising the administration of the fluorinated compound prior to parturation.
The foregoing activities of the fluorinated compound can be demonstrated in the following tests :
a) Anti-rachitogenic activity in chicks
White Leghorn chicks are placed on a vitamin D-deficient diet containing 1% calcium and 0.7% phosphorous, and are housed under ultraviolet-free lighting. The test compound is dissolved 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
20422
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 5 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/day)
Mean tibia ash weight (mq)
0
1 3
30
120.7+5.9 111.7+5.8 151.5+4.7 227.1+8.2 244.8+7.4
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 30 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) 35 and consequently possesses utility in the prevention of milk fever in preparturient female ruminants.
204223
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
Compound B 100 ng
11
1539
+
99
Vehicle 0.2 ml
72
647
+
69
Compound A 200 ng
11
710
+
62
Compound B 100 ng
11
1164
+
90
Vehicle 0.2 ml
96
586
+
70
Compound B 100 ng
998
+
61
c) Prevention of
EHDP-induced mineralization block in rats
Charles River male rats are treated for
consecutive
days with the disodium salt of ethane-1-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 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 30 and the tibias are processed by silver impregnation of the bone salts. The epiphyseal plate widths are measured with 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) 35 and negative (vehicles alone) control groups of ten rats each are included in each experiment. The results given in Table III show that the fluorinated compound calcified the tibial epiphyseal plate in EHDP-blocked rats.
♦
20422
Table III
Dose Mean tibial epiphyseal plate width ( nq/rat/day) (micron)
0
1 3
30
Vehicle controls (no EHDP)
1182 + 51
839 + 18
674 + 18
540 + 16
412 + 9
440 + 2
The fluorinated compound can be administered- in
,7
dosages in the range of substantially 30-500 microgramss*j6aj^r day for the prevention of milk fever in pregnant ruminant animals, especially in pregnant female bovines, preferably one to four days prior to parturation. 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 practice by dissolving or suspending the fluorinated compound in a vehicle, such as a 5-10% 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 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 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 antioxidants can be incorporated into the foregoing formulations as required.
204223
Example
A capsule for the treatment of osteoporosis 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 10 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.
c
204223
Claims (4)
1 . A method for the prevention of milk fever in ruminant animals which comprises administering to such an animal an effective amount of 24,24-difluoro-la, 25--dihydroxycholecalciferol prior to parturation.
2 . The method according to claim 1 wherein said ruminant animals are female bovine animals.
3. The method according to claim 1 or claim 2 wherein said effective amount of 24,24-difluoro-la,25--dihydroxycholecalciferol is administered one to four days prior to parturation.
4 . The method according to any one of claims 1 to 3 wherein said effective amount of 24,24-difluoro-la, 25-dihydroxycholecalciferol is an amount in the range of substantially 30 to 500 micrograms per day. DAIT:D Tr!:s P'VC"%19?^ A . J . r /-•. , . 3 C U r E.' l J' ^ ^ uCA AGENTS FC- t THk. APPLICANTS ' tV. » — 15SEP3SSI :
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 (1)
| Publication Number | Publication Date |
|---|---|
| NZ204223A true NZ204223A (en) | 1986-11-12 |
Family
ID=27008599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ204223A NZ204223A (en) | 1982-05-17 | 1983-05-13 | Veterinary compositions containing 24,24-difluoro-1 alpha,25-dihydroxycholecalciferol |
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 (3)
| 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 |
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 NZ NZ204223A patent/NZ204223A/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 IL IL68695A patent/IL68695A/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 |
| IT1171672B (en) | 1987-06-10 |
| CA1221031A (en) | 1987-04-28 |
| IL68695A0 (en) | 1983-09-30 |
| EP0094644B1 (en) | 1986-07-30 |
| IT8321128A0 (en) | 1983-05-17 |
| AU563733B2 (en) | 1987-07-23 |
| EP0094644A1 (en) | 1983-11-23 |
| IE55230B1 (en) | 1990-07-04 |
| AU1456283A (en) | 1983-11-24 |
| IE831131L (en) | 1983-11-17 |
| DE3317562A1 (en) | 1983-11-17 |
| DE3364904D1 (en) | 1986-09-04 |
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