US20040242478A1 - 5-cnac as oral delivery agent for parathyroid hormone fragments - Google Patents
5-cnac as oral delivery agent for parathyroid hormone fragments Download PDFInfo
- Publication number
- US20040242478A1 US20040242478A1 US10/484,331 US48433104A US2004242478A1 US 20040242478 A1 US20040242478 A1 US 20040242478A1 US 48433104 A US48433104 A US 48433104A US 2004242478 A1 US2004242478 A1 US 2004242478A1
- Authority
- US
- United States
- Prior art keywords
- pth
- cnac
- pharmaceutical composition
- fragment
- chlorosalicyloyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- XRTHAPZDZPADIL-UHFFFAOYSA-N [H]N(CCCCCCCC(=O)O)C(=O)C1=C(O)C=CC(Cl)=C1 Chemical compound [H]N(CCCCCCCC(=O)O)C(=O)C1=C(O)C=CC(Cl)=C1 XRTHAPZDZPADIL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
-
- 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
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
Definitions
- the present invention relates to the oral delivery of parathyroid hormone (PTH).
- the mammalian parathyroid hormones e.g. human (hPTH), bovine (bPTH) and porcine (pPTH) are single polypeptide chains of 84 amino acid residues having molecular weights of approximately 9500.
- the present invention relates to PTH fragments incorporating at least the first 28 N-terminal amino acid residues (PTH (1-28)) up to and including the first 41 N-terminal amino acid residues (PTH (1-41)).
- the invention is directed to pharmaceutical compositions for the oral delivery of PTH, said compositions comprising PTH (1-28) to (1-41) and N-(5-chlorosalicyloyl)-8-aminocaprylic acid (5-CNAC).
- U.S. Pat. No. 5,773,647 (the '647 patent) describes 193 carrier compounds useful for the delivery of active agents, including PTH.
- One of the carrier compounds expressly described therein is N-(5-chlorosalicyloyl)-8-aminocaprylic acid (5-CNAC) having the formula
- Example 2 in Column 6 of the '647 patent describes the preparation of 11 different dosing compositions some intracolonic (IC) and some oral gavage (PO) each containing parathyroid hormone and a carrier, the carrier being different for each composition.
- An IC dosing composition was prepared using 5-CNAC as the carrier.
- Example 3 therein describes in vivo tests carried out dosing male Sprague-Dawley rats with the dosing solutions prepared in Example 2. Blood samples were collected and the serum PTH concentration was quantified for each rat.
- the present invention is directed to pharmaceutical compositions suitable for oral delivery of PTH fragments and to methods of administering such compositions.
- the invention is directed to a method for orally administering an effective dose of PTH comprising orally administering to a patient in need of PTH a pharmaceutical composition comprising a therapeutically effective amount of a PTH fragment and 5-CNAC, said PTH fragment selected from PTH (1-28) to PTH (1-41).
- the invention is also directed to a method of stimulating new bone formation comprising orally administering to a patient in need of new bone formation a pharmaceutical composition comprising a therapeutically effective amount of a PTH fragment and 5-CNAC, said PTH fragment selected from PTH (1-28) to PTH (1-41).
- the invention is directed to a method of treatment or prevention of osteoporosis comprising orally administering to a patient in need of said treatment or prevention a pharmaceutical composition comprising a therapeutically effective amount of a PTH fragment and 5-CNAC, said PTH fragment selected from PTH (1-28) to PTH (1-41).
- the PTH fragments can be of any parathyroid hormone, particularly mammalian parathyroid hormone, e.g. human (hPTH), bovine (bPTH), and porcine (pPTH) and particularly hPTH and will incorporate at least the first 28 N-terminal residues (PTH (1-28)) up to and including the first 41 N-terminal residues (PTH (1-41)) and include without limitation PTH (1-28), PTH (1-31), PTH (1-34), PTH (1-37), PTH (1-38) and PTH (1-41). Human parathyroid hormone (1-34) is particularly preferred. These parathyroid hormone fragments are commercially available or can be obtained recombinantly or by peptide synthesis.
- the disodium salt may be prepared from the ethanol solvate by evaporating or drying the ethanol solvate by methods known in the art to form the anhydrous disodium salt. Drying is generally carried out at a temperature of from about 80 to about 120° C., preferably from about 85 to about 90° C., and most preferably at about 85° C. The drying step is generally performed at a pressure of 26′′ Hg or greater.
- the anhydrous disodium salt generally contains less than about 5% by weight of ethanol and preferably less than about 2% by weight of ethanol, based on 100% total weight of anhydrous disodium salt.
- the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid can also be prepared by making a slurry of N-(5-chlorosalicyloyl)-8-aminocaprylic acid in water and adding two molar equivalents of aqueous sodium hydroxide, sodium alkoxide or the like.
- Suitable sodium alkoxides include, but are not limited to, sodium methoxide, sodium ethoxide, and combinations thereof.
- a still further method of preparing the disodium salt is by reacting N-(5-chlorosalicyloyl)-8-aminocaprylic acid with one molar equivalent of sodium hydroxide to form a monosodium salt and then adding an additional one molar equivalent of sodium hydroxide to yield the disodium salt.
- the disodium salt can be isolated as a solid by concentrating the solution containing the disodium salt to a thick paste by vacuum distillation. This paste may be dried in a vacuum oven to obtain the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid as a solid.
- the solid can also be isolated by spray drying an aqueous solution of the disodium salt.
- N-(5-chlorosalicyloyl)-8-aminocaprylic acid/ethanol solution is then reacted with a molar excess of a sodium containing salt, such as a monosodium containing salt, relative to N-(5-chlorosalicyloyl)-8-aminocaprylic acid, i.e. for every mole of N-(5-chlorosalicyloyl)-8-aminocaprylic acid there is more than one mole of sodium cations, yielding the ethanol solvate.
- a sodium containing salt such as a monosodium containing salt
- Suitable monosodium salts include, but are not limited to, sodium hydroxide; sodium alkoxides, such as sodium methoxide and sodium ethoxide; and any combination of the foregoing.
- at least about two molar equivalents of the monosodium containing salt are added to the ethanol solution, i.e. for every mole of N-(5-chlorosalicyloyl)-8-aminocaprylic acid there is at least about two moles of sodium cations.
- the reaction is performed at or below the reflux temperature of the mixture, such as at ambient temperature.
- the ethanol solvate is then recovered by methods known is the art, such as, concentration of the resulting slurry at atmospheric distillation, cooling the concentrated slurry and filtering the solid.
- the recovered solid can then be vacuum dried to obtain the ethanol solvate.
- the hydrates of the disodium salts of the N-(5-chlorosalicyloyl)-8-aminocaprylic acid may be prepared by drying the ethanol solvate to form an anhydrous disodium salt, as described above, and hydrating the anhydrous disodium salt.
- the monohydrate of the disodium salt is formed.
- the hydrate forms upon exposure to atmospheric moisture.
- the hydrating step is performed at from about ambient temperature to about 50° C., preferably ambient temperature to about 30° C. and in an environment having at least 50% relative humidity.
- the anhydrous disodium salt may be hydrated with steam.
- the amount of PTH fragment to be administered is generally an amount effective to stimulate new bone formation i.e. a therapeutically effective amount. This amount will necessarily vary with the age, size, sex and condition of the subject to be treated, the nature and severity of the disorder to be treated and the like. However, the amount can be less than that amount when a plurality of the compositions are to be administered, i.e., the total effective amount can be administered in cumulative dosage units. The amount of PTH can also be more than the effective amount when the composition provides sustained release of the pharmacologically active agent The total amount of PTH to be used can be determined by methods known to those skilled in the art. However, in general, satisfactory results will be obtained systemically at daily dosages of from about 0.001 ⁇ g/kg to about 10 mg/kg animal body weight, preferably 1 ⁇ g/kg to about 6 ⁇ g/kg body weight.
- Oral administration of the pharmaceutical compositions according to the invention can be accomplished regularly, e.g. once or more on a daily or weekly basis; intermittently, e.g. irregularly during a day or week; or cyclically, e.g. regularly for a period of days or weeks followed by a period without administration.
- the dosage form of the pharmaceutical compositions of the instant invention can be any known form, e.g. liquid or solid dosage forms.
- the liquid dosage forms include solution emulsions, suspensions, syrups and elixirs.
- the liquid formulations may also include inert excipients commonly used in the art such as, solubilizing agents e.g. ethanol; oils such as cottonseed, castor and sesame oils; wetting agents; emulsifying agents; suspending agents; sweeteners; flavorings; and solvents such as water.
- composition may also include one or more enzyme Inhibitors, such as actinonin or epiactinonin and derivatives thereof; aprotinin, Trasylol and Bowman-Birk inhibitor.
- enzyme Inhibitors such as actinonin or epiactinonin and derivatives thereof; aprotinin, Trasylol and Bowman-Birk inhibitor.
- Parathyroid hormones are indicated for preventing or treating all bone conditions which are associated with increased calcium depletion or resorption or in which stimulation of bone formation and calcium fixation in the bone is desirable, e.g. osteoporosis of various genesis (e.g. juvenile, menopausal, post-menopausal, post-traumatic, caused by old age or by corticoid-steroid therapy or inactivity), fractures, osteopathy, including acute and chronic states associated with skeletal demineralization, osteo-malacia, periodontal bone loss or bone loss due to arthritis or osteoarthritis or cancer (e.g. bone metastis) or for treating hypoparathyroidism.
- osteoporosis of various genesis e.g. juvenile, menopausal, post-menopausal, post-traumatic, caused by old age or by corticoid-steroid therapy or inactivity
- fractures e.g. juvenile, menopausal, post-menopausal, post-traumatic, caused by old age
- dosages for the co-administered inhibitor will of course vary depending on the type of inhibitor drug employed, e.g. whether it is a steroid or a calcitonin, on the condition to be treated, whether it is a curative or preventive therapy, on the regimen and so forth.
- the oral administration of the present invention may be to any animal in need thereof, including, but not limited to, mammals, such as rodents, cows, pigs, dogs, cats, and primates, particularly humans.
- Example 1 The capsules prepared in Example 1 are administered to Rhesus monkeys as follows: four monkeys in a group are each dosed with one capsule prepared as in Example 1 as follows:
- Plasma hPTH levels are determined by radioimmunoassay.
- the primate plasma PTH results from each group of monkeys are averaged and the maximum mean plasma calculated.
- the results for the PTH only group are reported in Table 1 and the results for the hPTH/5-CNAC group are reported in Table 2.
- TABLE 1 hPTH ONLY hPTH PLASMA CONCENTRATIONS (pg/mL) AFTER ORAL ADMINISTRATION TO THE RHESUS MONKEY Dose: 1 Capsule 1 D Animal Time [hours] no.
- the 5-CNAC significantly facilitates the oral delivery of the hPTH fragment.
- the data in Table 2 indicate a sharp C max in the PTH plasma profile allowing for a bone formation effect.
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/484,331 US20040242478A1 (en) | 2001-08-17 | 2002-08-16 | 5-cnac as oral delivery agent for parathyroid hormone fragments |
US11/443,528 US20060217313A1 (en) | 2001-08-17 | 2006-05-30 | 5-CNAC as oral delivery agent for parathyroid hormone fragments |
US12/495,966 US20090264367A1 (en) | 2001-08-17 | 2009-07-01 | 5-cnac as oral delivery agent for parathyroid hormone fragments |
US13/327,114 US9272040B2 (en) | 2001-08-17 | 2011-12-15 | 5-CNAC as oral delivery agent for parathyroid hormone fragments |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US31304801P | 2001-08-17 | 2001-08-17 | |
US60313048 | 2001-08-17 | ||
PCT/EP2002/009181 WO2003015822A1 (en) | 2001-08-17 | 2002-08-16 | 5-cnac as oral delivery agent for parathyroid hormone fragments |
US10/484,331 US20040242478A1 (en) | 2001-08-17 | 2002-08-16 | 5-cnac as oral delivery agent for parathyroid hormone fragments |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/443,528 Continuation US20060217313A1 (en) | 2001-08-17 | 2006-05-30 | 5-CNAC as oral delivery agent for parathyroid hormone fragments |
Publications (1)
Publication Number | Publication Date |
---|---|
US20040242478A1 true US20040242478A1 (en) | 2004-12-02 |
Family
ID=23214149
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/484,331 Abandoned US20040242478A1 (en) | 2001-08-17 | 2002-08-16 | 5-cnac as oral delivery agent for parathyroid hormone fragments |
US11/443,528 Abandoned US20060217313A1 (en) | 2001-08-17 | 2006-05-30 | 5-CNAC as oral delivery agent for parathyroid hormone fragments |
US12/495,966 Abandoned US20090264367A1 (en) | 2001-08-17 | 2009-07-01 | 5-cnac as oral delivery agent for parathyroid hormone fragments |
US13/327,114 Expired - Fee Related US9272040B2 (en) | 2001-08-17 | 2011-12-15 | 5-CNAC as oral delivery agent for parathyroid hormone fragments |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/443,528 Abandoned US20060217313A1 (en) | 2001-08-17 | 2006-05-30 | 5-CNAC as oral delivery agent for parathyroid hormone fragments |
US12/495,966 Abandoned US20090264367A1 (en) | 2001-08-17 | 2009-07-01 | 5-cnac as oral delivery agent for parathyroid hormone fragments |
US13/327,114 Expired - Fee Related US9272040B2 (en) | 2001-08-17 | 2011-12-15 | 5-CNAC as oral delivery agent for parathyroid hormone fragments |
Country Status (26)
Country | Link |
---|---|
US (4) | US20040242478A1 (ko) |
EP (1) | EP1420827B8 (ko) |
JP (2) | JP4959917B2 (ko) |
KR (1) | KR20040030120A (ko) |
CN (1) | CN1279981C (ko) |
AT (1) | ATE443527T1 (ko) |
AU (1) | AU2002333443C1 (ko) |
BR (1) | BRPI0211932B1 (ko) |
CA (1) | CA2453646C (ko) |
CO (1) | CO5560586A2 (ko) |
CY (1) | CY1109661T1 (ko) |
DE (1) | DE60233803D1 (ko) |
DK (1) | DK1420827T3 (ko) |
EC (1) | ECSP044961A (ko) |
ES (1) | ES2333587T3 (ko) |
HU (1) | HUP0401441A3 (ko) |
IL (2) | IL159714A0 (ko) |
MX (1) | MXPA04001418A (ko) |
NO (1) | NO328069B1 (ko) |
NZ (1) | NZ531018A (ko) |
PL (1) | PL210258B1 (ko) |
PT (1) | PT1420827E (ko) |
RU (1) | RU2322256C2 (ko) |
SI (1) | SI1420827T1 (ko) |
WO (1) | WO2003015822A1 (ko) |
ZA (1) | ZA200400242B (ko) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006063819A2 (en) * | 2004-12-16 | 2006-06-22 | Novartis Ag | Manufacture process of n-substituted salicylamides |
US20070219132A1 (en) * | 2005-11-10 | 2007-09-20 | Board Of Control Of Michigan Technological University | Black bear parathyroid hormone and 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 |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101837120A (zh) * | 2001-06-01 | 2010-09-22 | 诺瓦提斯公司 | 口服施用甲状旁腺激素和降钙素 |
NZ531018A (en) * | 2001-08-17 | 2006-03-31 | Novartis Ag | 5-CNAC as oral delivery agent for parathyroid hormone fragments |
DE60318192T2 (de) * | 2002-04-10 | 2008-04-30 | The University Of Virginia Patent Foundation | Verwendung von a2a adenosin rezeptor agonisten und anti-pathogene mittel enthaltenden kombinationen zur behandlung von entzündungskrankheiten |
US20050054557A1 (en) * | 2002-05-09 | 2005-03-10 | Goldberg Michael M. | Compositions for delivering parathyroid hormone and calcitonin |
PT2316473E (pt) | 2003-07-23 | 2013-09-20 | Novartis Ag | Utilização de calcitonina na osteoartrite |
US8110547B2 (en) * | 2005-01-12 | 2012-02-07 | Emisphere Technologies, Inc. | Compositions for buccal delivery of parathyroid hormone |
EP1896134A2 (en) * | 2005-06-13 | 2008-03-12 | Rigel Pharmaceuticals, Inc. | Methods and compositions for treating degenerative bone disorders |
EP1937627A4 (en) | 2005-09-19 | 2010-09-01 | Emisphere Tech Inc | CRYSTALLINE FORMS OF N-(5-CHLOROSALICYLOYL) -8-AMINOCAPRYL ACETATE |
GB0522566D0 (en) * | 2005-11-04 | 2005-12-14 | Novartis Ag | Organic compounds |
JP5042312B2 (ja) * | 2006-08-31 | 2012-10-03 | ノバルティス アーゲー | Hghを含む経口送達用医薬組成物 |
PL2131810T3 (pl) * | 2007-03-02 | 2011-09-30 | Novartis Ag | Podawanie doustne kalcytoniny |
NZ585080A (en) | 2007-11-02 | 2012-05-25 | Emisphere Tech Inc | Composition comprising Vitamin B12 and N-[8-(2-hydroxybenzoyl) amino ]caprylic acid and salts thereof for treating Vitamin B12 deficiency |
WO2012130193A1 (en) | 2011-03-31 | 2012-10-04 | Zentiva, K.S. | Non-covalent soluble complexes of teriparatide with polysaccharides and a dosage form of teriparatide for oral administration |
IL253802B (en) * | 2015-02-09 | 2022-06-01 | Entera Bio Ltd | A preparation for the treatment of osteoporosis |
KR101796604B1 (ko) * | 2016-08-30 | 2017-11-10 | 목포대학교 산학협력단 | 위장관 흡수증진제를 함유하는 부갑상선 호르몬의 경구 투여 제형 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
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US4692433A (en) * | 1983-10-12 | 1987-09-08 | The Regents Of The University Of California | Method and composition for regulating serum calcium levels of mammals |
US5773647A (en) * | 1997-02-07 | 1998-06-30 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6080721A (en) * | 1992-09-29 | 2000-06-27 | Inhale Therapeutic Systems | Pulmonary delivery of active fragments of parathyroid hormone |
US6537965B1 (en) * | 1998-11-25 | 2003-03-25 | The General Hospital Corporation | Amino-terminal modified parathyroid hormone (PTH) analogs |
US20040106825A1 (en) * | 1999-04-05 | 2004-06-03 | Emisphere Technologies, Inc. | Disodium salts, monohydrates, and ethanol solvates for delivering active agents |
US6900344B2 (en) * | 2000-03-21 | 2005-05-31 | Emisphere Technologies, Inc. | Method of preparing alkylated salicylamides via a dicarboxylate intermediate |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
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EP0618805A1 (en) * | 1991-12-17 | 1994-10-12 | PROCTER & GAMBLE PHARMACEUTICALS, INC. | Methods for the treatment of osteoporosis using bisphosphonates and parathyroid hormone |
DK0993831T3 (da) * | 1997-02-07 | 2008-03-25 | Emisphere Tech Inc | Forbindelser og præparater til tilförsel af aktive stoffer |
CN101837120A (zh) | 2001-06-01 | 2010-09-22 | 诺瓦提斯公司 | 口服施用甲状旁腺激素和降钙素 |
NZ531018A (en) * | 2001-08-17 | 2006-03-31 | Novartis Ag | 5-CNAC as oral delivery agent for parathyroid hormone fragments |
EP1651248B1 (en) * | 2003-07-11 | 2009-09-09 | Novartis AG | Orally dosed pharmaceutical compositions comprising a delivery agent in micronized form |
-
2002
- 2002-08-16 NZ NZ531018A patent/NZ531018A/xx not_active IP Right Cessation
- 2002-08-16 SI SI200230866T patent/SI1420827T1/sl unknown
- 2002-08-16 DE DE60233803T patent/DE60233803D1/de not_active Expired - Lifetime
- 2002-08-16 PT PT02794796T patent/PT1420827E/pt unknown
- 2002-08-16 PL PL365388A patent/PL210258B1/pl unknown
- 2002-08-16 JP JP2003520780A patent/JP4959917B2/ja not_active Expired - Fee Related
- 2002-08-16 DK DK02794796T patent/DK1420827T3/da active
- 2002-08-16 CN CNB028160843A patent/CN1279981C/zh not_active Expired - Fee Related
- 2002-08-16 AU AU2002333443A patent/AU2002333443C1/en not_active Ceased
- 2002-08-16 AT AT02794796T patent/ATE443527T1/de active
- 2002-08-16 WO PCT/EP2002/009181 patent/WO2003015822A1/en active Application Filing
- 2002-08-16 MX MXPA04001418A patent/MXPA04001418A/es active IP Right Grant
- 2002-08-16 IL IL15971402A patent/IL159714A0/xx unknown
- 2002-08-16 BR BRPI0211932A patent/BRPI0211932B1/pt not_active IP Right Cessation
- 2002-08-16 KR KR10-2004-7002277A patent/KR20040030120A/ko active Search and Examination
- 2002-08-16 EP EP02794796A patent/EP1420827B8/en not_active Expired - Lifetime
- 2002-08-16 ES ES02794796T patent/ES2333587T3/es not_active Expired - Lifetime
- 2002-08-16 US US10/484,331 patent/US20040242478A1/en not_active Abandoned
- 2002-08-16 RU RU2004107899/15A patent/RU2322256C2/ru not_active IP Right Cessation
- 2002-08-16 HU HU0401441A patent/HUP0401441A3/hu unknown
- 2002-08-16 CA CA002453646A patent/CA2453646C/en not_active Expired - Lifetime
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2004
- 2004-01-05 IL IL159714A patent/IL159714A/en not_active IP Right Cessation
- 2004-01-13 ZA ZA200400242A patent/ZA200400242B/en unknown
- 2004-01-29 EC EC2004004961A patent/ECSP044961A/es unknown
- 2004-02-10 NO NO20040598A patent/NO328069B1/no not_active IP Right Cessation
- 2004-02-17 CO CO04013136A patent/CO5560586A2/es not_active Application Discontinuation
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2006
- 2006-05-30 US US11/443,528 patent/US20060217313A1/en not_active Abandoned
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2009
- 2009-06-09 JP JP2009138067A patent/JP2009242410A/ja not_active Withdrawn
- 2009-07-01 US US12/495,966 patent/US20090264367A1/en not_active Abandoned
- 2009-11-25 CY CY20091101231T patent/CY1109661T1/el unknown
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2011
- 2011-12-15 US US13/327,114 patent/US9272040B2/en not_active Expired - Fee Related
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Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2006063819A2 (en) * | 2004-12-16 | 2006-06-22 | Novartis Ag | Manufacture process of n-substituted salicylamides |
WO2006063819A3 (en) * | 2004-12-16 | 2006-09-14 | Novartis Ag | Manufacture process of n-substituted salicylamides |
US20090234010A1 (en) * | 2004-12-16 | 2009-09-17 | Bernhard Riss | Manufacture process of organic compounds |
US8013184B2 (en) | 2004-12-16 | 2011-09-06 | Novartis Ag | Manufacture process of organic compounds |
NO338831B1 (no) * | 2004-12-16 | 2016-10-24 | Novartis Ag | Fremgangsmåte for fremstilling av N-substituerte salisylamider |
US20070219132A1 (en) * | 2005-11-10 | 2007-09-20 | Board Of Control Of Michigan Technological University | Black bear parathyroid hormone and methods of using black bear parathyroid hormone |
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 |
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