IL301352A - Aqueous pharmaceutical formulation of hydrocortisone sodium phosphate and monothioglycerol - Google Patents
Aqueous pharmaceutical formulation of hydrocortisone sodium phosphate and monothioglycerolInfo
- Publication number
- IL301352A IL301352A IL301352A IL30135223A IL301352A IL 301352 A IL301352 A IL 301352A IL 301352 A IL301352 A IL 301352A IL 30135223 A IL30135223 A IL 30135223A IL 301352 A IL301352 A IL 301352A
- Authority
- IL
- Israel
- Prior art keywords
- sodium phosphate
- impurities
- hydrocortisone sodium
- monothioglycerol
- pharmaceutical formulation
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 348
- BGSOJVFOEQLVMH-VWUMJDOOSA-N cortisol phosphate Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 BGSOJVFOEQLVMH-VWUMJDOOSA-N 0.000 title claims description 288
- 229960004204 hydrocortisone sodium phosphate Drugs 0.000 title claims description 287
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 title claims description 200
- 239000012535 impurity Substances 0.000 claims description 269
- 239000000203 mixture Substances 0.000 claims description 216
- 238000009472 formulation Methods 0.000 claims description 182
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 166
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 106
- 238000003860 storage Methods 0.000 claims description 78
- 238000000034 method Methods 0.000 claims description 68
- 201000010099 disease Diseases 0.000 claims description 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 53
- 208000035475 disorder Diseases 0.000 claims description 47
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 32
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 32
- 229940045641 monobasic sodium phosphate Drugs 0.000 claims description 31
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 31
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 31
- 229940061607 dibasic sodium phosphate Drugs 0.000 claims description 24
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 17
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 17
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- 229950000785 hydrocortisone phosphate Drugs 0.000 claims description 3
- 102100033051 40S ribosomal protein S19 Human genes 0.000 claims description 2
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- 208000006820 Arthralgia Diseases 0.000 claims 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims 1
- 229960000890 hydrocortisone Drugs 0.000 description 87
- -1 hydrocortisone ester Chemical class 0.000 description 51
- 239000008186 active pharmaceutical agent Substances 0.000 description 42
- 239000000651 prodrug Substances 0.000 description 37
- 229940002612 prodrug Drugs 0.000 description 37
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 35
- 235000002639 sodium chloride Nutrition 0.000 description 32
- 150000003839 salts Chemical class 0.000 description 31
- 150000001875 compounds Chemical class 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 238000002347 injection Methods 0.000 description 27
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- 230000000694 effects Effects 0.000 description 18
- 125000000753 cycloalkyl group Chemical group 0.000 description 17
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- 125000003118 aryl group Chemical group 0.000 description 16
- 125000004432 carbon atom Chemical group C* 0.000 description 16
- 125000003342 alkenyl group Chemical group 0.000 description 15
- 125000001072 heteroaryl group Chemical group 0.000 description 15
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 14
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 13
- UBANCVOKRLKBGJ-KGWLDMEJSA-N [2-[(8s,9s,10r,11s,13s,14s,17r)-11,17-dihydroxy-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl] 4-(nitrooxymethyl)benzoate Chemical compound O=C([C@@]1(O)CC[C@H]2[C@H]3[C@@H]([C@]4(CCC(=O)C=C4CC3)C)[C@@H](O)C[C@@]21C)COC(=O)C1=CC=C(CO[N+]([O-])=O)C=C1 UBANCVOKRLKBGJ-KGWLDMEJSA-N 0.000 description 12
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 9
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
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Classifications
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- 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
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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- 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
- A61K47/02—Inorganic compounds
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- 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
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- 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
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063081164P | 2020-09-21 | 2020-09-21 | |
| PCT/US2021/051349 WO2022061303A1 (en) | 2020-09-21 | 2021-09-21 | Aqueous pharmaceutical formulation of hydrocortisone sodium phosphate and monothioglycerol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL301352A true IL301352A (en) | 2023-05-01 |
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| IL301352A IL301352A (en) | 2020-09-21 | 2021-09-21 | Aqueous pharmaceutical formulation of hydrocortisone sodium phosphate and monothioglycerol |
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| FR3128874B1 (fr) * | 2021-11-09 | 2025-04-18 | Crossject | Solution pharmaceutique d’hydrocortisone pour dispositif d’injection |
| EP4496575A4 (en) | 2022-03-21 | 2026-04-01 | Antares Pharma Inc | AQUEOUS PHARMACEUTICAL FORMULATION OF SODIUM PHOSPHATE, HYDROCORTISONE AND MONOTHIOGLYCEROL |
| US11904046B1 (en) | 2022-11-14 | 2024-02-20 | Eton Pharmaceuticals, Inc. | Hydrocortisone oral liquid formulations |
| WO2024214110A1 (en) * | 2023-04-08 | 2024-10-17 | Cipla Limited | A safe pharmaceutical composition of hydrocortisone |
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| CA911885A (en) * | 1972-10-10 | Gruppo Lepetit S.P.A. | Stable aqueous steroid phosphate solutions | |
| US2970944A (en) | 1958-04-04 | 1961-02-07 | Merck & Co Inc | Parenteral solutions of steroid phosphates stabilized with creatinines |
| IL34366A (en) * | 1969-05-07 | 1973-06-29 | Lepetit Spa | Stable aqueous 21-hydroxy steroid phosphate solutions |
| US5173488A (en) | 1989-08-21 | 1992-12-22 | American Cyanamid Company | Stable injectable pharmaceutical formulation for folic acid and leucovorin salts and method |
| US5733572A (en) * | 1989-12-22 | 1998-03-31 | Imarx Pharmaceutical Corp. | Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles |
| AU702871B2 (en) * | 1993-08-23 | 1999-03-11 | Nexell Therapeutics Inc. | (In vitro) growth of neutrophil and megakaryocyte precursors in serum-free media |
| US6090800A (en) * | 1997-05-06 | 2000-07-18 | Imarx Pharmaceutical Corp. | Lipid soluble steroid prodrugs |
| US20020039594A1 (en) * | 1997-05-13 | 2002-04-04 | Evan C. Unger | Solid porous matrices and methods of making and using the same |
| WO2006079064A1 (en) | 2005-01-24 | 2006-07-27 | Antares Pharma, Inc. | Prefilled needle assisted jet injector |
| US8067433B2 (en) * | 2005-11-09 | 2011-11-29 | Zalicus Inc. | Methods, compositions, and kits for the treatment of ophthalmic disorders |
| ES2548447T3 (es) | 2008-03-10 | 2015-10-16 | Antares Pharma, Inc. | Dispositivo de seguridad para inyector |
| US8579865B2 (en) | 2009-03-20 | 2013-11-12 | Antares Pharma, Inc. | Hazardous agent injection system |
| WO2014165142A1 (en) | 2013-03-13 | 2014-10-09 | Benjamin Newton | Multiple dosage injector with rotating screw dosage system |
| UA119324C2 (uk) * | 2013-04-02 | 2019-06-10 | Теміс Медікер Лімітед | Композиції фармацевтично активних речовин, що містять моноетиловий ефір діетиленгліколю або інші алкільні похідні |
| EP3189855B1 (en) * | 2016-01-11 | 2018-03-21 | Lamda Laboratories S.A. | Oral pharmaceutical solutions containing hydrocortisone sodium phosphate |
| FR3047904B1 (fr) | 2016-02-18 | 2018-03-23 | Crossject | Dispositif d’injection sans aiguille a membrane coulissante |
| FR3057775B1 (fr) * | 2016-10-26 | 2018-11-02 | Crossject | Solution pharmaceutique d’hydrocortisone pour dispositif d’injection |
| EP3787671A4 (en) * | 2018-05-04 | 2022-06-15 | Ohio State Innovation Foundation | NON-PEPTIDE CELL-PENETRATING MOTIFS |
| US11034710B2 (en) * | 2018-12-04 | 2021-06-15 | Sumitomo Dainippon Pharma Oncology, Inc. | CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer |
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| EP4213827A4 (en) | 2024-10-23 |
| US20220096496A1 (en) | 2022-03-31 |
| MX2023003197A (es) | 2023-08-04 |
| US11857555B2 (en) | 2024-01-02 |
| AU2021345429A9 (en) | 2024-08-08 |
| KR20230104131A (ko) | 2023-07-07 |
| EP4213827A1 (en) | 2023-07-26 |
| JP2023542345A (ja) | 2023-10-06 |
| US20230099165A1 (en) | 2023-03-30 |
| WO2022061303A1 (en) | 2022-03-24 |
| US20240131035A1 (en) | 2024-04-25 |
| AU2021345429A1 (en) | 2023-05-04 |
| CA3192530A1 (en) | 2022-03-24 |
| CN116367835A (zh) | 2023-06-30 |
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