WO1996007416A1 - Estrogens and parathyroid hormone for treating osteoporosis - Google Patents
Estrogens and parathyroid hormone for treating osteoporosis Download PDFInfo
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- WO1996007416A1 WO1996007416A1 PCT/US1995/011386 US9511386W WO9607416A1 WO 1996007416 A1 WO1996007416 A1 WO 1996007416A1 US 9511386 W US9511386 W US 9511386W WO 9607416 A1 WO9607416 A1 WO 9607416A1
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- Prior art keywords
- osteoporosis
- bone
- parathyroid hormone
- estrogen
- methods
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Classifications
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- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/29—Parathyroid hormone (parathormone); Parathyroid hormone-related peptides
-
- 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
Definitions
- This invention relates to methods of increasing bone mass in humans and other animals, i.e., for the treatment of osteoporosis and related bone metabolic disorders.
- this invention relates to such methods of treatment by the administration of an estrogen compound and parathyroid hormone.
- Osteoporosis can be generally defined as the reduction in the quantity of bone, or the atrophy of skeletal tissue. In general, there are two types of osteoporosis: primary and secondary "Secondary osteoporosis" is the result of an identifiable disease process or agent. However, approximately 90% of all osteoporosis cases is "primary osteoporosis”. Such primary osteoporosis includes postmenopausal osteoporosis, age-associated osteoporosis (affecting a majority of individuals over the age of 70 to 80), and idiopathic osteoporosis affecting middle-aged and younger men and women.
- Bone fractures often occur, for example, in the hip and spine of women suffering from postmenopausal osteoporosis. Kyphosis (abnormally increased curvature of the thoracic spine) may also result.
- Bone remodeling occurs throughout life, renewing the skeleton and maintaining the strength of bone.
- This remodeling involves the erosion and filling of discrete sites on the surface of bones, by an organized group of cells called “basic multicellular units” or “BMUs".
- BMUs primarily consist of "osteoclasts", “osteoblasts”, and their cellular precursors.
- osteoclasts primarily consist of "osteoclasts", “osteoblasts”, and their cellular precursors.
- osteoclasts primarily consist of "osteoclasts”, "osteoblasts”, and their cellular precursors.
- This cavity is then filled with bone by osteoblasts.
- osteoporosis Although its etiology is not fully understood, there are many risk factors thought to be associated with osteoporosis. These include low body weight, low calcium intake, physical inactivity, and estrogen deficiency.
- compositions and methods are described in the medical literature for the "treatment” of osteoporosis. Many of these compositions and methods attempt to either slow the loss of bone or to produce a net gain in bone mass. See, for example, R. C. Haynes, Jr. et al., "Agents affecting Calcification", The Pharmacological Basis of Therapeutics. 7th Edition (A. G. Gilman, . S. Goodman et al., Editors, 1985); G. D. Whedon et al., "An Analysis of Current Concepts and Research Interest in Osteoporosis", Current Advances in Skeletogenesis (A. Ornoy et al., Editors, 1985); and W. A. Peck, et al., Physician's Resource Manual on Osteoporosis (1987), published by the National Osteoporosis Foundation.
- Patent 4,812,304 Anderson et al., issued March 14, 1989; U.S. Patent 4,812,311, Uchtman, issued March 14, 1989; and U.S. Patent 4,822,609, Flora, issued April 18, 1989.
- the use of such phosphonates for the treatment of osteoporosis, and other disorders involving abnormal calcium and phosphate metabolism, is also described in U.S. Patent 3,683,080, Francis, issued August 8, 1972; U.S. Patent 4,330,537, Francis, issued October 28, 1980; U.S.
- estrogen is also used as a means to prevent osteoporosis in postmenopausal women. This therapy typically involves daily administration of from about 0.625 milligrams to about 1.25 milligrams of conjugated estrogens, or equivalent amounts of other estrogen hormones. Estrogen may also be used to treat osteoporosis (i.e., actual building of bone in osteoporotics), although this has not been fully established.
- Parathyroid hormone has also been suggested as a therapy for osteoporosis. Treatments using parathyroid hormone are disclosed in the following references: Hefti, et al., "Increase of Whole-Body Calcium and Skeletal Mass in Normal and Osteoporotic Adult Rats Treated with Parathyroid Hormone", 62 Clin. Sci. 389-396 (1982); Hock, et al., "Resorption Is Not Essential for the Stimulation of Bone Growth by hPT ⁇ -(l-34) in Rats In Vivo", 4(3) Jnl. of Bone and Mineral Res. 449-458 (1989); German Patent Publication DE 3935 738, Forssman, published May 8, 1991; U.S.
- the methods of this invention provide effective methods of preventing and treating osteoporosis, with improved efficacy and reduced side effects compared to methods among those known in the art.
- the present invention provides methods of treating a human or other animal subject having a bone metabolism disorder, consisting essentially of the steps of:
- the methods of the present invention comprise the administration of an estrogen compound and parathyroid hormone compound to a human or other animal subject.
- Specific compounds and compositions to be used in these processes must, accordingly, be pharmaceutically-acceptable.
- a "pharmaceutically-acceptable" component is one that is suitable for use with humans and/or animals without undue adverse side effects (such as toxicity, irritation, and allergic response) commensurate with a reasonable benefit/risk ratio.
- an "estrogen compound” refers to naturally occurring hormones, synthetic steroidal compounds, and non-steroidal compounds, and conjugates, metabolites and derivatives thereof, which having estrogenic activity.
- Naturally-occurring estrogen compounds are steroids which contain a cyclopentanoperhydrophenathrene ring system.
- Such naturally-occurring estrogen compounds are obtained from pregnant mares' urine or prepared synthetically, using methods well-known in the art. See: “Estrogens", Drug Information 1765 (1990); and Rudy, "Hormone Replacement Therapy - How to Select the Best Preparation and Regimen," 88 Postgraduate Medicine 157 (1990); and C. Christiansen et al., “Estrogens, Bone Loss and Prevention," 1 Osteoporosis Int. 7 (1990); all of which are incorporated by reference herein.
- Estrogen compounds useful in the methods of this invention include, for example, estradiol, estrone, estriol, equilin, equilenin, estradiol cypionate, estradiol valerate, ethinyl estradiol, polyestradiol phosphate, estropipate, diethylstilbestrol, dienestrol, chlorotrianisene, and mixtures thereof.
- a preferred estrogen hormone useful herein is "conjugated estrogen", which is a mixture of sodium salts of the water-soluble sulfate esters of estrone and equilin. Such conjugated estrogens may also contain other estrogenic substances found in pregnant mares' urine, such as 17-a-dihydroequiline, 17-a-estradiol, equilenin, and 17-a-dihydroequilenin.
- an "antiestrogen compound” is a compound which has the estrogen agonist activity of inhibition of bone resorption, but which has estrogen antagonist activity on other tissues, notably breast and uterus.
- Antiestrogens may be steroids or non-steroids.
- Steroidal antiestrogens are exemplified by tamoxifen and related compounds. Many compounds that have been discovered for reasons of other activities, such as anti-progesterones or anti- androgens, are also antiestrogens useful in the methods of this invention.
- Non- steroidal antiestrogens also include, for example, raloxifene, and related compounds disclosed in U.S. Patent 4,418,068, issued November 29, 1983 (incorporated by reference herein).
- Parathyroid Hormone The methods of this invention also comprise administration of a parathyroid hormone.
- parathyroid hormone refers to the naturally occurring human parathyroid hormone, synthetic analogs thereof, parathyroid hormone and parathyroid hormone fragments manufactured by recombinant DNA technology, and parathyroid hormone fragments and parathyroid hormone fragment analogs.
- Parathyroid hormone useful in the methods of this invention includes, for example hPTH (1-38), hPTH (1-34), hPTH (1-37), hPTH (2-34), and hPTH (2-38).
- Patent 4,105,602 Colescott, et al., issued August 8, 1978; U.S. Patent 4,698,328, Neer, et al., issued October 6, 1987; U.S. Patent 4,833,125, Neer, et al., issued May 23, 1987; DE 32 43 358, Hesch, publication date May 24, 1984; and DE 3935 738, Forssmann, et al., publication date May 8, 1991.
- This invention provides methods for treating a human or other animal subject having a bone metabolism disorder, consisting essentially of the steps of: (a) administering to said subject a safe and effective amount of an antireso ⁇ tive compound, during a period of from about 2 weeks to about 6 months;
- step (a) said antireso ⁇ tive compound is administered for greater than about 8 months.
- step (b) said parathyroid hormone is administered for from about 4 months to about 8 months, more preferably for about 6 months.
- steps (a) and (b) are repeated from 1 to 5 times (i.e, so the entire method comprises performance of each step, in sequence, 2 to 6 times).
- the estrogen compound and parathyroid hormone are administered in a "safe and effective amount", which, as referred to herein, is the quantity of a material which is sufficient to yield a desired therapeutic response without undue adverse side effects (such as toxicity, irritation, or allergic response) commensurate with a reasonable benefit/risk ratio when used in the manner of this invention.
- a safe and effective amount is the quantity of a material which is sufficient to yield a desired therapeutic response without undue adverse side effects (such as toxicity, irritation, or allergic response) commensurate with a reasonable benefit/risk ratio when used in the manner of this invention.
- the specific "safe and effective amount” will, obviously, vary with such factors as the particular condition being treated, the physical condition of the patient, the duration of the treatment, the nature of concurrent therapy (if any), and the specific formulations employed.
- the specific amount and dosage regimen of a particular estrogen compound administered during the methods of this invention is a function of the potency of the compound, as well as other factors.
- the antireso ⁇ tive compound is administered in amounts and in regimens recognized in the art of useful for treating osteoporosis in accordance with sound medical practice.
- Potency of an estrogen compound can be expressed in terms of its "LED” or "least effective dose", which is the minimum dose of compound that is effective, by itself, to cause a significant inhibition of bone reso ⁇ tion.
- the antireso ⁇ tive compound is administered at a level of at least about 0.8 LED of the compound, more preferably from about .8 LED to about 5 LED, more preferably from about .8 to about 3 LED.
- the specific LEDs of a given estrogen compound will vary depending upon its chemical composition, and method of administration (i.e., oral or parenteral). The lower the LED, the more potent the compound. Generally, it is desirable to administer higher potency estrogen compounds in lower doses and on a fewer number of days in the period of treatment. Likewise, the higher the LED, the less potent the compound. Accordingly, then, in general, it is desirable to administer a lower potency estrogen compound in higher doses and on a greater number of days in the period of treatment.
- the LED of the estrogen hormone is that level of the hormone which, by itself, is effective to prevent bone loss in subjects having osteoporosis. That level is generally recognized to be about 0.625 g per day of conjugated estrogen or an equivalent dose of other estrogen hormones (for example, 25 mg per day of ethinyl estradiol; or 2 mg per day of 17-b-estradiol). Conjugated estrogen is preferably administered at a level of from about 0.3 mg to about 1.25 mg per day, preferably about 0.63 mg per day.
- Parathyroid hormone is routinely dosed in International Units (IU).
- parathyroid hormone is preferably administered at levels of from about 100 to about 700 IU per day, more preferably from about 200 to about 600 IU per day, more preferably from about 400 to about 500 IU per day.
- the estrogen compound can be administered daily, or in a cyclical fashion.
- the parathyroid hormone must be given at least one day every seven days of every thirty(30)-days.
- the parathyroid hormone is administered at least about 50% of the days during the period of step (b).
- the methods of this invention comprise treatment of osteoporosis at all stages of the disorder. Since osteoporosis is an ongoing process of bone loss, rather than a disorder having a discrete beginning- or end-point, "treatment", as referred to herein, consists of any method which stops, slows, or reverses the process of bone loss which occurs in osteoporosis.
- Preferred methods of this invention comprise treatment of osteoporosis in subjects who have already lost skeletal mass (herein referred to as "established osteoporosis").
- Such methods of this invention for the treatment of established osteoporosis preferably comprise administering the actives for a period of time sufficient to achieve an increase in the net skeletal mass of said subject.
- the increase in mass may be in cortical bone, trabecular bone, or both.
- the net skeletal mass is increased by at least about 5% per year, preferably by at least about 10% per year.
- the specific period of time sufficient to achieve an increase in the net skeletal mass of the subject may depend on a variety of factors.
- Such factors include, for example, the specific actives employed, the amount of actives administered, the age and sex of the subject, the specific disorder to be treated, concomitant therapies employed (if any), the general physical health of the subject (including the presence of other disorders), the extent of bone loss in the individual, and the nutritional habits of the individual.
- the therapeutic regimen utilizing the methods of this invention are preferably continued for at least about twelve months.
- a therapeutic regimen may be continued indefinitely, according to sound medical practice.
- the subject is treated until a net skeletal mass is obtained commensurate with reduced fracture risk as assessed by the patient's physician.
- the subject is administered nutritional and other therapeutic agents to aid in the increase of bone mass.
- nutritional and other therapeutic agents include, for example, Vitamin D and calcium.
- administering refers to any method which, in sound medical practice, delivers the actives used in this invention to the subject to be treated in such a manner so as to be effective in the building of bone.
- the actives may be administered by any of a variety of known methods of administration, e.g., orally, dermatomucosally (for example, dermally, sublingually, intranasally, and rectally), parenterally (for example, by subcutaneous injection, intramuscular injection, intra-articular injection, intravenous injection), and by inhalation.
- specific modes of administration include, but are not limited to, for example, oral, transdermal, mucosal, sublingual, intramuscular, intravenous, intraperitoneal, subcutaneous administration, and topical application.
- a preferred method for the treatment of osteoporosis includes an initial diagnostic step, to determine the presence of the disorder.
- a preferred method of this invention comprises the steps of performing a diagnostic on a human subject for the detection of osteoporosis and, upon obtaining a positive result from said diagnostic, administering the actives according to the methods of this invention.
- said initial diagnostic step comprises performing a diagnostic for determining menopause.
- Such methods are well known in the art, and include, for example, determination of the bone mass and rate of bone remodeling. The rate of bone remodeling can be determined by measurement of biochemical markers. See, Hui, et al., "The Contribution of Bone Loss to Postmenopausal Osteoporosis," 1 Osteoporosis Int. 30 (1990), inco ⁇ orated by reference herein.
- Suitable diagnostics for the detection of established osteoporosis are also well known in the art. Such methods include the measurement of the radiodensity of skeletal radiographs, quantitative computerized tomography, single energy photon abso ⁇ tiometry, dual-energy photon abso ⁇ tiometry, dual energy X-ray abso ⁇ tiometry, and quantitative digital radiography. Diagnostic techniques among those useful herein are described in W. A. Peck et al., Physician's Resource Manual on Osteoporosis (1987), published by the National Osteoporosis Foundation (inco ⁇ orated by reference herein).
- the estrogen compound and parathyroid hormone may be administered in any of a variety of pharmaceutically-acceptable compositions.
- Such compositions may comprise an active and a pharmaceutically-acceptable carrier.
- Pharmaceutically-acceptable carriers include solid or liquid filler diluents or encapsulating substances, and mixtures thereof, that are suitable for administration to a human or lower animal.
- the term "compatible", as used herein, means that the components of the pharmaceutical composition are capable of being commingled with the actives, and with each other, in a manner such that there is no interaction which would substantially reduce the pharmaceutical efficacy of the pharmaceutical composition under ordinary use situations.
- Pharmaceutically-acceptable carriers must, of course, be of sufficiently high purity and sufficiently low toxicity to render them suitable for administration to the human or lower animal being treated.
- substances which can serve as pharmaceutical carriers are: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, cellulose acetate; powdered tragacanth; malt; gelatin; talc; stearic acid; magnesium stearate; vegetable oils, such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil and oil of theobroma; polyols such as propylene glycol, glycerin, sorbitol, mannitol, and polyethylene glycol; agar; alginic acid; pyrogen-free water; isotonic saline; phosphate buffer solutions; wetting agents and lubricants such as sodium lauryl sulfate; coloring agents; flavoring agents; and preservatives.
- sugars such as lactose, glucose and sucrose
- starches such as corn starch and
- compositions of the present invention may be included in the pharmaceutically-acceptable carrier for use in the compositions of the present invention.
- a pharmaceutically-acceptable carrier to be used in conjunction with the active is determined by the way the active is to be administered. If the active is to be injected, the preferred pharmaceutical carrier is sterile water, physiological saline, or mixtures thereof. The pH of such parenteral composition is preferably adjusted to about 7.4.
- Suitable pharmaceutically- acceptable carriers for topical application include those known in the art for use in creams, gels, tapes, patches, and similar topical delivery means.
- the pharmaceutically-acceptable carrier employed in conjunction with the actives is used at a concentration sufficient to provide a practical size to dosage relationship.
- the pharmaceutically-acceptable carriers in total, may comprise from about 0.1% to about 99.9% by weight of the pharmaceutical compositions of the present invention, preferably from about 5% to about 80%, and most preferably from about 10% to about 50%.
- a preferred method of administering bisphosphonates is orally, in a unit- dosage form (i.e., a dosage form containing an amount of active suitable for administration in one single dose, according to sound medical practice).
- Preferred unit dosage forms for bisphosphonate include tablets, capsules, suspensions, and solutions, comprising a safe and effective amount of active.
- Pharmaceutically- acceptable carriers suitable for the preparation of unit dosage forms for oral administration are well known in the art. Their selection will depend on secondary considerations like taste, cost, shelf stability, which are not critical for the pu ⁇ oses of the present invention, and can be made without difficulty by a person skilled in the art.
- oral unit dosage forms of the bone-active phosphonate comprise from about 0.0005 mgP/kg oral per day to about 1.0 gP kg oral per day of the phosphonate.
- a preferred method of administering parathyroid hormone is via subcutaneous injection in a unit dosage form.
- Preferred unit dosage forms for injection include sterile solutions of water, physiological saline, or mixtures thereof. The pH of said solutions should be adjusted to about 7.4.
- unit dosage forms of parathyroid hormone comprise from about 4 IU to about 15 IU per kg per day.
- kits for example, nasal, trandsermal, rectal, sublingual, and oral.
- Preferred oral forms include, for example, liposomes, lipid emulsions, and proteinaceous cages. Kits:
- kits for conveniently and effectively implementing the methods of this invention comprise one or more unit doses of estrogen compound, one or more unit doses of parathyroid hormone, and a means for facilitating compliance with methods of this invention.
- kits provide a convenient and effective means for assuring that the subject to be treated takes the appropriate active in the correct dosage in the correct manner.
- the compliance means of such kits includes any means which facilitates administering the actives according to a method of this invention.
- Such compliance means includes instructions, packaging, and dispensing means, and combinations thereof. Examples of packaging and dispensing means are well known in the art, including those described in U.S. Patents 4,761,406, Flora et al., issued August 2, 1988; and U.S. Patent 4,812,311, Uchtman, issued March 14, 1989 and U.S. 4,833,125, Neer et al., issued May 23, 1989, all inco ⁇ orated by reference herein.
- An Asian female human patient weighing approximately 62 kg and diagnosed with postmenopausal osteoporosis is treated by a method of this invention. Specifically, for a period of eight months, the patient is administered the bisphosphonate, 2-(3-pyridyl)-l-hydroxyethane-l,l-bisphosphonic acid. The patient is orally administered one tablet per day, with each tablet containing 0.002 mgP/kg per day of the bisphosphonate. The estrogen treatment is discontinued. Then, for the next six months, the patient is administered parathyroid hormone (human synthetic fragment 1-34, or h PTH 1-34). The hormone is subcutaneously administered at a dose of 13 IU/kg via insulin syringe to the anterior thigh for five days out of every week during the six-month period.
- parathyroid hormone human synthetic fragment 1-34, or h PTH 1-34
- a biopsy of iliac crest bone is taken and reveals an increase in mean wall thickness of the remodeling units (BMU) compared to her baseline biopsy.
- BMU remodeling units
- the activation frequency and depth of reso ⁇ tion cavities on cancellous, cortical and endocortical surfaces are not significantly increased above the values observed at baseline. Bone mineral density is measured, indicating an increase of 11%.
- EXAMPLE 2 A human Caucasian female patient weighing approximately 60 kg and diagnosed with postmenopausal osteoporosis is treated by a method of this invention. Specifically, the patient is administered conjugated estrogen for a period of one year. The estrogen is administered via a transdermal patch, delivering estrogen at a level of 0.625 mg per day. After the one year month period, the estrogen administration is discontinued. However, the patient is then also administered parathyroid hormone (human synthetic fragment 1-34, or h PTH 1- 34) for six months, as a daily nasal spray delivering 5 IU/kg.
- parathyroid hormone human synthetic fragment 1-34, or h PTH 1- 34
- a blood sample is then obtained and analyzed for the bone specific marker, osteocalcin, and bone-derived and total alkaline phosphatase. Osteocalcin values are increased by 57% and both bone and total alkaline phosphatase are slightly elevated compared to pretreatment values. Base mineral density is measured, indicating an increase of 10%.
Abstract
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
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JP50968396A JP2001503728A (en) | 1994-09-09 | 1995-09-06 | Estrogens and parathyroid hormone for the treatment of osteoporosis |
AU36748/95A AU3674895A (en) | 1994-09-09 | 1995-09-06 | Estrogens and parathyroid hormone for treating osteoporosis |
EP95934405A EP0804202A4 (en) | 1994-09-09 | 1995-09-06 | Estrogens and parathyroid hormone for treating osteoporosis |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US08/303,926 | 1994-09-08 | ||
US30392694A | 1994-09-09 | 1994-09-09 |
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WO1996007416A1 true WO1996007416A1 (en) | 1996-03-14 |
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PCT/US1995/011386 WO1996007416A1 (en) | 1994-09-09 | 1995-09-06 | Estrogens and parathyroid hormone for treating osteoporosis |
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EP (1) | EP0804202A4 (en) |
JP (1) | JP2001503728A (en) |
KR (1) | KR970705397A (en) |
CN (1) | CN1158569A (en) |
AU (1) | AU3674895A (en) |
CA (1) | CA2199250A1 (en) |
IL (1) | IL115225A0 (en) |
WO (1) | WO1996007416A1 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0744176A2 (en) * | 1995-05-23 | 1996-11-27 | Eli Lilly And Company | Methods for inhibiting bone loss |
US6284730B1 (en) | 1997-06-19 | 2001-09-04 | Nps Allelix Corp. | Methods useful in the treatment of bone resorption diseases |
WO2001068074A2 (en) * | 2000-03-10 | 2001-09-20 | Endeavor Pharmaceuticals | Pharmaceutical compositions of conjugated estrogens and methods of analyzing mixtures containing estrogenic compounds |
US7994129B2 (en) | 2005-11-10 | 2011-08-09 | Michigan Technological University | Methods of using black bear parathyroid hormone |
US8987201B2 (en) | 2009-12-07 | 2015-03-24 | Michigan Technological University | Black bear parathyroid hormone and methods of using black bear parathyroid hormone |
WO2015057836A2 (en) * | 2013-10-15 | 2015-04-23 | The Trustees Of Columbia University In The City Of New York | Bone anabolic parathyroid hormone and parathyroid hormone related-protein analogs |
Citations (1)
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US5118667A (en) * | 1991-05-03 | 1992-06-02 | Celtrix Pharmaceuticals, Inc. | Bone growth factors and inhibitors of bone resorption for promoting bone formation |
Family Cites Families (1)
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TW303299B (en) * | 1993-07-22 | 1997-04-21 | Lilly Co Eli |
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1995
- 1995-09-06 WO PCT/US1995/011386 patent/WO1996007416A1/en active IP Right Grant
- 1995-09-06 EP EP95934405A patent/EP0804202A4/en not_active Withdrawn
- 1995-09-06 CA CA002199250A patent/CA2199250A1/en not_active Abandoned
- 1995-09-06 CN CN95195016A patent/CN1158569A/en active Pending
- 1995-09-06 JP JP50968396A patent/JP2001503728A/en active Pending
- 1995-09-06 KR KR1019970701533A patent/KR970705397A/en active IP Right Grant
- 1995-09-06 AU AU36748/95A patent/AU3674895A/en not_active Abandoned
- 1995-09-08 IL IL11522595A patent/IL115225A0/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5118667A (en) * | 1991-05-03 | 1992-06-02 | Celtrix Pharmaceuticals, Inc. | Bone growth factors and inhibitors of bone resorption for promoting bone formation |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0744176A2 (en) * | 1995-05-23 | 1996-11-27 | Eli Lilly And Company | Methods for inhibiting bone loss |
EP0744176A3 (en) * | 1995-05-23 | 2002-05-15 | Eli Lilly And Company | Methods for inhibiting bone loss |
US7749543B2 (en) | 1997-06-19 | 2010-07-06 | Nps Pharmaceuticals, Inc. | Methods useful in the treatment of bone resorption diseases |
US6284730B1 (en) | 1997-06-19 | 2001-09-04 | Nps Allelix Corp. | Methods useful in the treatment of bone resorption diseases |
US8765674B2 (en) | 1997-06-19 | 2014-07-01 | Nps Pharmaceuticals, Inc. | Methods useful in the treatment of bone resorption diseases |
US8153588B2 (en) | 1997-06-19 | 2012-04-10 | Nps Pharmaceuticals, Inc. | Methods useful in the treatment of bone resorption diseases |
US7018982B2 (en) | 1997-06-19 | 2006-03-28 | Nps Allelix Corp. | Methods useful in the treatment of bone resorption diseases |
US7507715B2 (en) | 1997-06-19 | 2009-03-24 | Nps Allelix Corp. | Methods useful in the treatment of bone resorption diseases |
WO2001068074A3 (en) * | 2000-03-10 | 2002-03-21 | Endeavor Pharmaceuticals | Pharmaceutical compositions of conjugated estrogens and methods of analyzing mixtures containing estrogenic compounds |
US6855703B1 (en) | 2000-03-10 | 2005-02-15 | Endeavor Pharmaceuticals | Pharmaceutical compositions of conjugated estrogens and methods of analyzing mixtures containing estrogenic compounds |
WO2001068074A2 (en) * | 2000-03-10 | 2001-09-20 | Endeavor Pharmaceuticals | Pharmaceutical compositions of conjugated estrogens and methods of analyzing mixtures containing estrogenic compounds |
US7994129B2 (en) | 2005-11-10 | 2011-08-09 | Michigan Technological University | Methods of using black bear parathyroid hormone |
US8987201B2 (en) | 2009-12-07 | 2015-03-24 | Michigan Technological University | Black bear parathyroid hormone and methods of using black bear parathyroid hormone |
WO2015057836A2 (en) * | 2013-10-15 | 2015-04-23 | The Trustees Of Columbia University In The City Of New York | Bone anabolic parathyroid hormone and parathyroid hormone related-protein analogs |
WO2015057836A3 (en) * | 2013-10-15 | 2015-06-18 | The Trustees Of Columbia University In The City Of New York | Bone anabolic parathyroid hormone and parathyroid hormone related-protein analogs |
Also Published As
Publication number | Publication date |
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JP2001503728A (en) | 2001-03-21 |
CA2199250A1 (en) | 1996-03-14 |
CN1158569A (en) | 1997-09-03 |
EP0804202A4 (en) | 1999-01-13 |
AU3674895A (en) | 1996-03-27 |
KR970705397A (en) | 1997-10-09 |
EP0804202A1 (en) | 1997-11-05 |
IL115225A0 (en) | 1995-12-31 |
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