WO1994018985A1 - USE OF 26,26,26,27,27,27-HEXAFLUORO-1α,25-DIHYDROXYCHOLECALCIFEROL FOR THE TREATMENT OF CALCIUM METABOLISM DISORDERS - Google Patents
USE OF 26,26,26,27,27,27-HEXAFLUORO-1α,25-DIHYDROXYCHOLECALCIFEROL FOR THE TREATMENT OF CALCIUM METABOLISM DISORDERS Download PDFInfo
- Publication number
- WO1994018985A1 WO1994018985A1 PCT/US1994/001895 US9401895W WO9418985A1 WO 1994018985 A1 WO1994018985 A1 WO 1994018985A1 US 9401895 W US9401895 W US 9401895W WO 9418985 A1 WO9418985 A1 WO 9418985A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- administered
- osteoporosis
- vitamin
- hexafluoro
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a novel method of treating diseases resulting from calcium metabolism disorders. More specifically, this invention relates to a method comprising the use of 26,26,26,27,27,27-hexafluoro-1 ⁇ , 25-dihydroxy- cholecalciferol, a derivative of vitamin D 3 .
- Vitamin D 3 is a well-known agent for the control of calcium and phosphorous homeostasis. It is also now well known that to be effective, vitamin D 3 must be converted to its hydroxylated forms. For example, the vitamin is first hydroxylated in the liver to form 25-hydroxyvitamin D 3 and is further hydroxylated in the kidney to produce 1 ⁇ , 25-dihydroxy vitamin D 3 or 24,25- dihydroxy vitamin D 3 .
- the l ⁇ -hydroxylated form of the vitamin is generally considered to be the physiologically active or hormonal form of the vitamin and to be responsible for what are termed the vitamin D-like activities, such as increasing intestinal absorption of calcium phosphate, mobilizing bone mineral, and reabsorbing calcium in the kidneys.
- vitamin D-like compounds have been synthesized. See, for example, U.S. Pat. Nos. 3,741,996 directed to 1 ⁇ -hydroxycholecalciferol; 3,907,843 directed to 1 ⁇ - hydroxyergocalciferol; 3,786,062 directed to 22-dehydro-25- hydroxycholecalciferol; 3,906,014 directed to 3-deoxy-1 ⁇ - hydroxycholecalciferol; and 4,069,321 directed to the preparation of various side chain-fluorinated vitamin D3
- a fluoro derivative of the accepted hormonal form of vitamin D 3 , 1,25-dihydroxycholecalciferol (1,25-(OH) 2 D 3 ), of particular interest is 24,24-difluoro-1,25-(OH) 2 D3 because it is characterized by at least as great if not greater activity than1,25- ⁇ OH) 2 D 3 (see U.S. Pat. No. 4,201,881).
- D compounds were no more effective in a patient than were the less active vitamin D compounds. It is well known that females at the time of menopause suffer a marked loss of bone mass giving rise ultimately to osteopenia, which in turn gives rise to spontaneous crush fractures of the vertebrae and fractures of the long bones. This disease is generally known as postmenopausal osteoporosis and presents a major medical problem, both in the United States and most other countries where the life-span of females reaches ages of at least 60 and 70 years. Generally, the disease which is often accompanied by bone pain and decreased physical activity, is diagnosed by one or two vertebral crush fractures with evidence of diminished bone mass. It is known that this disease is accompanied by diminished ability to absorb calcium, decreased levels of sex hormones, especially estrogen and androgen, and a negative calcium balance.
- osteoporosis the latter being a recognized result of long term glucocorticoid (cortico-steroid) therapy for certain disease states.
- a conventional treatment is to administer a calcium supplement to the patient.
- calcium supplementation by itself has not been successful in preventing or curing the disease.
- Another conventional treatment is the injection of sex hormones, especially estrogen, which has been reported to be effective in preventing the rapid loss of bone mass experienced in
- osteoporosis who received calcitriol, i.e. 1 ⁇ ,25-dihydroxyvitamin D3, at dosages of 0.5 ⁇ g per day for three years had a significant reduction in the rate of new vertebral fractures over women who were treated over the same period of time with supplemental calcium in the form of 1 gram of elemental calcium daily.
- Calcitriol treatment of the women in the Tilyard et al study was not accompanied by hypercalcemia of any severity, and thus it was concluded that calcitriol given orally in a dose of 0.25 ⁇ g twice a day to postmenopausal women with an average dietary calcium intake of 800 mg has limited potential to induce hypercalcemia. However, it was also concluded in the Tilyard et al study that serum calcium concentrations should be monitored in patients receiving calcitriol therapy due to the possibility of hypercalcemia as a side effect of such treatment.
- calcitriol may be a viable therapeutic option in the treatment of women with postmenopausal osteoporosis.
- 25-hydroxyvitamin D3 and 1 ⁇ -hydroxyvitamin D 3 for treatment of osteoporosis in a general expression of utility for those compounds. It is well known that both of those compounds express traditional vitamin D-like activity, including the danger of hypercalcemia.
- the 24-epi compound may be administered alone or in combination with a bone mobilization- inducing compound such as a hormone or a vitamin D compound such as 1 ⁇ -hydroxyvitamin D 3 or -D 2 , or 1 ⁇ ,25-dihydroxyvitamin D 3 or -D 2 .
- a method of treating diseases resulting from calcium disorders comprises the administration of an effective amount of 26,26,26,27,27,27-hexafluoro- 1 ⁇ ,25- dihydroxyvitamin D 3 .
- the above compound may be administered alone or in combination with other pharmaceutically acceptable agents. Dosages of from not less than about 0.05 ⁇ g/day to not more than about 2.0 ⁇ g/day of the individual compound per se, or in combinations, are generally effective.
- This method has the distinct advantage that it will treat the disease, and at the same time this compound advantageously will not cause hypercalcemia even if the compound is administered continuously on a daily basis, as long as the appropriate compound dosages are used, it being understood that the dosage levels will be adjusted dependent on the response of the subject as monitored by methods known to those skilled in the art. It has been
- the above method involving the administration of the indicated dosages of 26,26,26,27,27,27-hexafluoro- 1 ⁇ ,25- dihydroxyvitamin D 3 provides a novel method for the treatment or prevention of a variety of human diseases resulting from calcium metabolism disorders such as renal osteodystrophy, hypoparathyroidism, pseudohypoparathyroidism, hypocalcemia, osteomalacia, vitamin D-deficient rickets and various forms of osteoporosis such as postmenopausal osteoporosis, estrogen-lack osteoporosis, senile osteoporosis and steroid-induced
- osteoporosis It will be evident that the method will find ready application for the prevention or treatment of disease states other than those named, in which the loss of bone mass is an indication.
- Figs. 1-4 are graphs of blood serum concentration of Ca, P and Mg over time after administration of 0.25 ⁇ g, 0.5 ⁇ g, 1 ⁇ g and 2 ⁇ g/man of ST-630, respectively;
- Figs. 5-8 are graphs of urinary excretions of Ca, P and Mg over time after administration of 0.25 ⁇ g, 0.5 ⁇ g, 1 ⁇ g and 2 ⁇ g/man of ST-630, respectively;
- Figs. 9-12 are graphs of urinary excretions of Ca/Cr, P/Cr and Mg/Cr ratios over time after administration of 0.25 ⁇ g, 0.5 ⁇ g, 1 ⁇ g and 2 ⁇ g/man of ST-630, respectively;
- Fig. 13 is a graph illustrating the dietary effect on the absorption of ST-630 at a dose of 2.0 ⁇ g over time
- Fig. 14 is a graph of blood serum concentration of Ca, P and Mg over time after daily administration of ST-630 at a daily dose of 1.0 ⁇ g for 7 days;
- Fig. 15 is a graph of blood serum concentration of ALP over time after daily administration of ST-630 at a daily dose of 1.0 ⁇ g for 7 days;
- Figs. 16-17 are graphs of urinary excretions of Ca and Ca/Cr ratio, respectively, over time after daily administration of ST-630 at a daily dose of 1 ⁇ g for 7 days;
- Figs. 18-19 are graphs of urinary excretions of P and P/Cr ratio, respectively, over time after daily administration of ST- 630 at a daily dose of 1 ⁇ g for 7 days;
- Figs. 20-21 are graphs of urinary excretions of Mg and Mg/Cr ratio, respectively, over time after daily administration of ST-630 at a daily dose of 1 ⁇ g for 7 days;
- Fig. 24 is a graph of the relationship between serum calcium and breaking load of the femur in ovariectomized rats treated with ST-630 and 1 ⁇ -hydroxyvitamin D 3 at various doses.
- 26,26, 26,27,27,27-F 6 -1 ⁇ ,25(OH) 2 D 3 in an amount from about 0.05 ⁇ g to about 2.0 ⁇ g per day for an extended period, i.e. a minimum of at least 7 days.
- the preferred dosage range is dependent upon the disease being treated and the response of the patient to treatment, as is well known by those skilled in the art. For example, preferred ranges for the treatment of osteoporosis might be 0.1 ⁇ g/day to 0.5 ⁇ g/day while for the treatment of renal osteodystrophy it might be 0.1 ⁇ g/day to 0.3 ⁇ g/day.
- the 26,26,26,27, 27,27-F 6 -1 ⁇ ,25-(OH) 2 D 3 compound used in the method of this invention may be readily synthesized in accordance with known procedures.
- ST-630 was administered postprandially at a daily dose of 1.0 ⁇ g for 7 days.
- the serum Ca concentration tended to be elevated slightly but the change was within the normal range.
- the urinary Ca/Cr ratio increased with the number of dosings but recovered to the control value immediately after completion of administration.
- Step 5 headache was found in one case in Step 5 (0.25 ⁇ g) and an increase in erythrocyte sedimentation rate was observed in one case each in Step 1 (0.0125 ⁇ g) and Step 8 (2.0 ⁇ g) in the single- dose study. No symptom was found in the study of dietary effect or in the repeated-dose study.
- ST-630 promoted calcium absorption but caused no hypercalcemia, indicating no remarkable problem on safety.
- the “window” or tolerance between effectiveness and toxicity of ST-630 in humans is thus relatively large.
- 26,26,26,27,27,27-F 6 -1 ⁇ ,25-(OH) 2 D 3 may be administered to patients having a variety of human diseases resulting from
- diseases such as renal osteodystrophy,
- hypoparathyroidism hypoparathyroidism, pseudohypoparathyroidism, hypocalcemia, osteomalacia, vitamin D-deficient rickets and various forms of osteoporosis such as postmenopausal osteoporosis, estrogen-lack osteoporosis, senile osteoporosis and steroid-induced
- osteoporosis may be treated with ST-630.
- the foregoing data shows that 26,26,26,27,27,27-F 6 -1 ⁇ ,25-(OH) 2 D 3 may be administered in the manner and dosages described below.
- the 26,26,26,27,27,27-F 6 -1,25-(OH) 2 D 3 used in the method of this invention may be readily administered in sterile parenteral solutions by injection or intravenously or by
- 1 ⁇ -hydroxylated vitamin D compounds are effective in obtaining physiological responses which are characteristic of vitamin D- like activity, with maintenance doses of about 0.1 ⁇ g to 1.0 ⁇ g being suitable for at least the above-described time period without inducing patient toxicity.
- the proportions of the hexafluoro compound, or of each of the compounds in the combination are dependent upon the particular disease state being addressed and the degree of response desired. Amounts in excess of about 2.0 micrograms per day of the hexafluoro compound or the combination of that compound with other 1 ⁇ -hydroxylated vitamin D compounds, are generally unnecessary to achieve the desired results, may result in hypercalcemia, and may not be an economically sound practice. In practice the higher doses are used where
- Dosage forms of the compound can be prepared by combining them with a non-toxic pharmaceutically acceptable carrier to make either immediate or slow release formulations as is well known in the art.
- a non-toxic pharmaceutically acceptable carrier may be either solid or liquid such as, for example, corn starch, lactose, sucrose, peanut oil, olive oil, sesame oil, propylene glycol and water.
- a solid carrier is used the dosage forms of the compounds of the invention may be tablets, capsules, powders, troches or lozenges.
- a liquid carrier is used, soft gelatin capsules, or syrup or liquid suspensions, emulsions or solutions may be the dosage form.
- the dosage forms may also contain adjuvants, such as preserving, stabilizing, wetting or emulsifying agents, solution promoters, etc. They may also contain other therapeutically valuable substances.
- the rats were given 15IU of vitamin D 3 orally once a week throughout this experiment. Four weeks after the surgery, the rats were orally adminstered three times a week for 23 weeks with ST-630 (30, 100 or 300 pmole/kg) or 1 ⁇ -hydroxyvitamin D 3 (100 or 300 pmole/kg).
- LD50 data represent the dose administered resulting in the death of 50% of the test group.
- the LD 50 at 14 days for ST-630 was 0.043 mg/kg and for 1 ⁇ - hydroxyvitamin D 3 was 0.2 mg/kg. It thus appears that ST-630 is about five times more toxic than 1 ⁇ -hydroxyvitamin D 3 in rats.
- 1 ⁇ g/day is the safe dose used for human
- ST-630 can be administered in much higher doses to humans without toxicity problems as shown by the data in Fig. 2 (0.5 ⁇ g), Fig. 3 (1 ⁇ g) and Fig. 4 (2 ⁇ g).
- ST-630 will be more effective against osteoporosis.
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Nutrition Science (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP94909755A EP0684827A1 (en) | 1993-02-19 | 1994-02-18 | USE OF 26,26,26,27,27,27-HEXAFLUORO-1$g(a),25-DIHYDROXYCHOLECALCIFEROL FOR THE TREATMENT OF CALCIUM METABOLISM DISORDERS |
BR9405735A BR9405735A (en) | 1993-02-19 | 1994-02-18 | Use of 26,26,26,27,27,27-hexafluoro-1-alpha 25-dihydroxy cholecalciferol for the treatment of disorders of calcium metabolism |
JP6519231A JPH08507073A (en) | 1993-02-19 | 1994-02-18 | Use of 26,26,26,27,27,27-hexafluoro-1alpha, 25-dihydroxycholecalciferol for the treatment of calcium metabolism disorders |
AU62471/94A AU6247194A (en) | 1993-02-19 | 1994-02-18 | Use of 26,26,26,27,27,27-hexafluoro-1alpha,25-dihydroxycholecalcife rol for the treatment of calcium metabolism disorders |
KR1019950703446A KR960700729A (en) | 1993-02-19 | 1995-08-17 | Use of 26,26,26,27,27,27-hexafluoro-1 alpha, 25-dihydroxycholecalciferol for the treatment of calcium metabolic disorders (Use of 26,26,26,27,27,27- Hexafluoro-1alpha, 25-Dihydroxycholecalciferol for the treatment of Calcium Metabolism Disorders) |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US2021893A | 1993-02-19 | 1993-02-19 | |
US020,218 | 1993-02-19 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1994018985A1 true WO1994018985A1 (en) | 1994-09-01 |
Family
ID=21797387
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1994/001895 WO1994018985A1 (en) | 1993-02-19 | 1994-02-18 | USE OF 26,26,26,27,27,27-HEXAFLUORO-1α,25-DIHYDROXYCHOLECALCIFEROL FOR THE TREATMENT OF CALCIUM METABOLISM DISORDERS |
Country Status (7)
Country | Link |
---|---|
US (2) | US5571802A (en) |
EP (1) | EP0684827A1 (en) |
JP (1) | JPH08507073A (en) |
KR (1) | KR960700729A (en) |
AU (2) | AU6247194A (en) |
BR (1) | BR9405735A (en) |
WO (1) | WO1994018985A1 (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006515623A (en) * | 2003-01-13 | 2006-06-01 | セダーズ−シナイ メディカル センター | Paricalcitol as a chemotherapeutic agent |
AU2014316766B2 (en) | 2013-09-05 | 2019-10-10 | Waitaki Biosciences | High osteocalcin microcrystalline hydroxyapatite for calcium supplement |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1983000335A1 (en) * | 1981-07-27 | 1983-02-03 | Wisconsin Alumni Res Found | 26,26,26,27,27,27-HEXAFLUORO-1'alpha',25-DIHYDROXYCHOLECALCIFEROL AND PROCESS FOR PREPARING SAME |
GB2139627A (en) * | 1983-05-09 | 1984-11-14 | Wisconsin Alumni Res Found | 1 alpha ,25-Dihydroxylated vitamin D2 compounds and intermediates in the preparation thereof |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4248791A (en) * | 1980-02-04 | 1981-02-03 | Wisconsin Alumni Research Foundation | 25-Hydroxy-26,26,26,27,27,27-hexafluorocholecalciferol |
US4411833A (en) * | 1982-05-26 | 1983-10-25 | Wisconsin Alumni Research Foundation | Method for preparing 26,26,26,27,27,27-hexafluoro-1α,25-dihydroxycholesterol |
CA1314872C (en) * | 1986-04-25 | 1993-03-23 | Toshio Nishizawa | Fluorine derivatives of vitamin d _and process for producing the same |
-
1994
- 1994-02-18 BR BR9405735A patent/BR9405735A/en not_active Application Discontinuation
- 1994-02-18 AU AU62471/94A patent/AU6247194A/en not_active Abandoned
- 1994-02-18 JP JP6519231A patent/JPH08507073A/en active Pending
- 1994-02-18 WO PCT/US1994/001895 patent/WO1994018985A1/en not_active Application Discontinuation
- 1994-02-18 EP EP94909755A patent/EP0684827A1/en not_active Withdrawn
- 1994-02-18 US US08/199,991 patent/US5571802A/en not_active Expired - Fee Related
-
1995
- 1995-08-17 KR KR1019950703446A patent/KR960700729A/en not_active Application Discontinuation
-
1998
- 1998-04-06 AU AU60764/98A patent/AU6076498A/en not_active Abandoned
- 1998-08-10 US US09/131,471 patent/US5942502A/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1983000335A1 (en) * | 1981-07-27 | 1983-02-03 | Wisconsin Alumni Res Found | 26,26,26,27,27,27-HEXAFLUORO-1'alpha',25-DIHYDROXYCHOLECALCIFEROL AND PROCESS FOR PREPARING SAME |
GB2139627A (en) * | 1983-05-09 | 1984-11-14 | Wisconsin Alumni Res Found | 1 alpha ,25-Dihydroxylated vitamin D2 compounds and intermediates in the preparation thereof |
Non-Patent Citations (4)
Title |
---|
DELUCA, H.F. ET AL: "VITAMIN D RESEARCH-FIRST INTERNATIONAL CONGRESS ON VITAMINS AND BIOFACTORS IN LIFE SCIENCES", BIOFACTORS, vol. 3, no. 4, April 1992 (1992-04-01), pages 271 * |
NAKATSUKA, K. ET AL: "BIOLOGICAL POTENCY OF A FLUORINATED VITAMIN D ANALOGUE IN HYPOPARATHYROIDISM", BONE AND MINERAL, vol. 16, no. 1, January 1992 (1992-01-01), pages 73 - 81 * |
OKUMURA, H. ET AL: "26,27-HEXAFLUORO-1,25-DIHYDROXYVITAMIN D3 (F6-1,25(OH)2D3) PREVENTS OSTEOPOROSIS INDUCED BY IMMOBILIZATION COMBINED WITH OVARIECTOMY IN THE RAT", BONE AND MINERAL, vol. 9, no. 2, May 1990 (1990-05-01), pages 101 - 109 * |
TANAKA, Y. ET AL: "26,26,26,27,27,27-HEXAFLUORO-1,25-DIHYDROXYVITAMIN D3: A HIGHLY POTENT, LONG-LASTING ANALOG OF 1,25-DIHYDROXYVITAMIN D3", ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, vol. 229, no. 1, 1984, pages 348 - 354 * |
Also Published As
Publication number | Publication date |
---|---|
US5942502A (en) | 1999-08-24 |
AU6247194A (en) | 1994-09-14 |
JPH08507073A (en) | 1996-07-30 |
BR9405735A (en) | 1995-12-05 |
KR960700729A (en) | 1996-02-24 |
EP0684827A1 (en) | 1995-12-06 |
AU6076498A (en) | 1998-06-11 |
US5571802A (en) | 1996-11-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5707980A (en) | Method for treating and preventing secondary hyperparathyroidism | |
US5104864A (en) | Method for treating and preventing loss of bone mass | |
US5869473A (en) | Method for treating and preventing hyperparathyroidism | |
DE69737066T2 (en) | Use of active vitamin D analogous to the treatment of prostate diseases | |
US20090137536A1 (en) | Method for treating and preventing hyperparathyroidism | |
US4897388A (en) | Method of treating Alzheimer's disease | |
US20040043971A1 (en) | Method of treating and preventing hyperparathyroidism with active vitamin D analogs | |
US6376479B1 (en) | Method for treating and preventing hyperparathyroidism | |
US5395830A (en) | Method of treating osteoporosis with 1α,24(R)-dihydroxy-22(E)-dehydro-vitamin D3 | |
EP1722856B1 (en) | Use of 2-methylene-19-nor-20(s)-1alpha,25-dihydroxyvitamin d3 for the prophylaxis of bone diseases | |
US5393749A (en) | Method of treating osteoporosis with 1 α25-dihydroxy-22(E)-dehydro-vitamin D3 | |
US5571802A (en) | Method of treating post menopausal osteoporosis with hexafluro-vitamin D | |
JPH0780773B2 (en) | New Vitamin D (3) A drug containing a derivative as an active ingredient | |
EP0634173B1 (en) | 24-epi-1-alpha-hydroxyvitamin D2 for treating osteoporosis | |
US10105375B2 (en) | Combination of low dose 2-methylene-19-nor-(20S)1α, 25-dihydroxyvitamin D3 and calcimimetics to treat secondary hyperparathyroidism | |
WO1997016193A1 (en) | Pharmaceutical composition for treating osteoporosis | |
US20050192256A1 (en) | Methods of using vitamin D compounds in the treatment of patients undergoing hemodialysis | |
Nishii et al. | CHARACTERISTIC OF TWO NOVEL VITAMIN D. ANALOGUES; 22-OXA-1 a, 25-DIHYDROXYVITAMIN D3 [OCT] AND 2p-(3-HYDROXYPROPOXY)-1a, 25-DIHYDROXYVITAMIN D3 [ED-71]. | |
Juan | Vitamin D metabolism: update for the clinician |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AT AU BB BG BR BY CA CH CN CZ DE DK ES FI GB HU JP KP KR KZ LK LU LV MG MN MW NL NO NZ PL PT RO RU SD SE SK UA UZ VN |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 1994909755 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1994909755 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
NENP | Non-entry into the national phase |
Ref country code: CA |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1994909755 Country of ref document: EP |