JP6665350B2 - 注射デバイスのための医薬ヒドロコルチゾン溶液 - Google Patents
注射デバイスのための医薬ヒドロコルチゾン溶液 Download PDFInfo
- Publication number
- JP6665350B2 JP6665350B2 JP2019521040A JP2019521040A JP6665350B2 JP 6665350 B2 JP6665350 B2 JP 6665350B2 JP 2019521040 A JP2019521040 A JP 2019521040A JP 2019521040 A JP2019521040 A JP 2019521040A JP 6665350 B2 JP6665350 B2 JP 6665350B2
- Authority
- JP
- Japan
- Prior art keywords
- hydrocortisone
- pharmaceutical solution
- pharmaceutical
- solution according
- sodium
- 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.)
- Active
Links
- 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 title claims description 68
- 239000000243 solution Substances 0.000 title claims description 62
- 229960000890 hydrocortisone Drugs 0.000 title claims description 34
- 239000007924 injection Substances 0.000 title claims description 24
- 238000002347 injection Methods 0.000 title claims description 24
- 239000003186 pharmaceutical solution Substances 0.000 claims description 51
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 18
- 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 description 18
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 11
- 239000000872 buffer Substances 0.000 claims description 10
- 239000011734 sodium Substances 0.000 claims description 10
- 229910052708 sodium Inorganic materials 0.000 claims description 10
- 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 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- BGSOJVFOEQLVMH-UHFFFAOYSA-N Hydrocortisone phosphate Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)(O)C(=O)COP(O)(O)=O)C4C3CCC2=C1 BGSOJVFOEQLVMH-UHFFFAOYSA-N 0.000 claims description 7
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 7
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 7
- 235000019800 disodium phosphate Nutrition 0.000 claims description 7
- 229950000785 hydrocortisone phosphate Drugs 0.000 claims description 7
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 7
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 7
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 7
- 238000007918 intramuscular administration Methods 0.000 claims description 6
- 239000008215 water for injection Substances 0.000 claims description 6
- 208000010981 acute adrenal insufficiency Diseases 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 208000024716 acute asthma Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical group [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 claims description 2
- 229960001067 hydrocortisone acetate Drugs 0.000 claims description 2
- VWQWXZAWFPZJDA-CGVGKPPMSA-N hydrocortisone succinate Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COC(=O)CCC(O)=O)[C@@H]4[C@@H]3CCC2=C1 VWQWXZAWFPZJDA-CGVGKPPMSA-N 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 239000001509 sodium citrate Substances 0.000 claims description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 2
- 235000011083 sodium citrates Nutrition 0.000 claims description 2
- QTQGHKVYLQBJLO-UHFFFAOYSA-N 4-methylbenzenesulfonate;(4-methyl-1-oxo-1-phenylmethoxypentan-2-yl)azanium Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.CC(C)CC(N)C(=O)OCC1=CC=CC=C1 QTQGHKVYLQBJLO-UHFFFAOYSA-N 0.000 claims 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims 1
- 229960001401 hydrocortisone sodium succinate Drugs 0.000 claims 1
- 239000012535 impurity Substances 0.000 description 21
- 239000003963 antioxidant agent Substances 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 13
- RYJIRNNXCHOUTQ-OJJGEMKLSA-L cortisol sodium phosphate Chemical compound [Na+].[Na+].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 RYJIRNNXCHOUTQ-OJJGEMKLSA-L 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 230000003078 antioxidant effect Effects 0.000 description 5
- MFMORLFSDLJUDS-UHFFFAOYSA-L disodium formaldehyde hydrogen sulfite Chemical compound [Na+].S([O-])(O)=O.[Na+].C=O.S([O-])(O)=O MFMORLFSDLJUDS-UHFFFAOYSA-L 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000005352 clarification Methods 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229960004204 hydrocortisone sodium phosphate Drugs 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 238000011146 sterile filtration Methods 0.000 description 3
- DETXZQGDWUJKMO-UHFFFAOYSA-N 2-hydroxymethanesulfonic acid Chemical compound OCS(O)(=O)=O DETXZQGDWUJKMO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 150000001886 cortisols Chemical class 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 206010027654 Allergic conditions Diseases 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- HHZQLQREDATOBM-CODXZCKSSA-M Hydrocortisone Sodium Succinate Chemical compound [Na+].O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COC(=O)CCC([O-])=O)[C@@H]4[C@@H]3CCC2=C1 HHZQLQREDATOBM-CODXZCKSSA-M 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- BMCQMVFGOVHVNG-TUFAYURCSA-N cortisol 17-butyrate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CO)(OC(=O)CCC)[C@@]1(C)C[C@@H]2O BMCQMVFGOVHVNG-TUFAYURCSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 235000021474 generally recognized As safe (food) Nutrition 0.000 description 1
- 235000021472 generally recognized as safe Nutrition 0.000 description 1
- 235000021473 generally recognized as safe (food ingredients) Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960001524 hydrocortisone butyrate Drugs 0.000 description 1
- -1 hydrocortisone sodium phosphate ester Chemical class 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical group [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
Classifications
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
- A61K31/10—Sulfides; Sulfoxides; Sulfones
-
- 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
- A61K31/57—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
-
- 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
-
- 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
- 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
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/30—Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
-
- 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
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Inorganic Chemistry (AREA)
- Vascular Medicine (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
Description
・2つの抗酸化剤:ここで、EDTA二ナトリウムはキレート剤としても機能し、ホルムアルデヒド亜硫酸水素ナトリウムは抗菌剤としても機能する、
・リン酸水素ナトリウム、リン酸二水素ナトリウム、リン酸(10体積%の濃度)、
・注射製剤用水
をさらに含む。
・対象医薬品とみなされるEfcortisol(登録商標)の不純物レベルと、最大でも同等、好ましくはそれより低い不純物レベルを有し、
・特性評価を必要とするあらゆる未知の不純物を相当量で含まない
医薬溶液を開発することに努めた。
・ヒドロコルチゾンまたはその医薬的に許容される塩;
・ロンガリット;
・EDTA二ナトリウム;
・溶媒
を少なくとも含む医薬ヒドロコルチゾン溶液である。
・ヒドロコルチゾンリン酸エステルナトリウム;
・ロンガリット;
・EDTA二ナトリウム;
・少なくとも1つの緩衝剤;
・溶媒、好ましくは注射製剤用水
を含む。
・20 g〜60 g、好ましくは40 g〜45 gのヒドロコルチゾンまたはその医薬的に許容される塩;
・0.2 g〜1.2 g、好ましくは0.3 g〜0.5 gのロンガリット;
・0.1 g〜0.6 g、好ましくは0.15 g〜0.25 gのEDTA二ナトリウム;
・160 g〜200 gの溶媒、好ましくは注射製剤用水
を含み得る。
a) 少なくとも溶媒、ロンガリットおよびEDTA二ナトリウムを含む混合物を撹拌下調製する工程;
b) ヒドロコルチゾンまたはその医薬的に許容される塩を撹拌下加えて、該医薬溶液を得る工程;
を少なくとも含み;
c) 工程b)の完了で得られた医薬溶液に対して少なくとも1つのろ過工程を実施する工程
を含んでもよい方法である。
・注射デバイス;
・上記の本発明による医薬溶液
を含む注射キット、好ましくは筋肉内経路による注射用キットである。
a) 250 rpmにてマグネチックスターラーを用いて撹拌下、リン酸二水素ナトリウムおよびリン酸水素ナトリウムを含む混合物を調製した;
b) 300 rpmにてマグネチックスターラーを用いて撹拌下、水、2つの抗酸化剤(すなわち、本発明による溶液、比較溶液1および比較溶液2について、それぞれEDTA二ナトリウムと、ロンガリット、ホルムアルデヒド亜硫酸水素ナトリウムおよびピロ亜硫酸塩)を加え、9分間撹拌を続けた;
c) 300 rpmにてマグネチックスターラーを用いて撹拌下、ヒドロコルチゾンリン酸エステルナトリウムを加え、この塩の溶解が完了し溶液が得られるまで撹拌を続けた;
d) 工程c)で得られた溶液に対して250 mL/分の速度にて清澄ろ過工程を行い、続いて56 Paの圧力で140 mL/分の速度にて滅菌ろ過工程を行った;
e) 工程d)で得られた溶液を窒素でバブリングした。
・厚さ5μm、寸法(250×4.6 mm)を有する商品名Luna(登録商標)C18(2)でPhenomenex社より市販されているカラム
・1.5 mL/分の流速;
・5μLの注入量;
・190〜400 nmの可変波長を有する紫外線検出器またはフォトダイオード検出器;
・254 mmの波長;
・25℃±2℃のカラム温度;
・周囲温度の試料;
・移動相A:精製水中0.1%(v/v)のトリフルオロ酢酸;
・移動相B:アセトニトリル中0.1%(v/v)のトリフルオロ酢酸。
Claims (18)
- 200 mLの溶液に対してgで:
・20 g〜60 gのヒドロコルチゾンまたはその医薬的に許容される塩、ここで、ヒドロコルチゾンの医薬的に許容される塩は、ヒドロコルチゾンリン酸エステルナトリウム、ヒドロコルチゾンコハク酸エステルナトリウム、コハク酸水素ヒドロコルチゾン、ヒドロコルチゾン酪酸エステルおよびヒドロコルチゾン酢酸エステルより選択される;
・0.2 g〜1.2 gのロンガリット;
・0.1 g〜0.6 gのエチレンジアミン四酢酸二ナトリウム(EDTA二ナトリウム);
・160 g〜200 gの溶媒
を少なくとも含む、医薬ヒドロコルチゾン溶液。 - ヒドロコルチゾンの医薬的に許容される塩が、ヒドロコルチゾンリン酸エステルナトリウムであることを特徴とする請求項1に記載の医薬溶液。
- 少なくとも1つの緩衝剤をさらに含むことを特徴とする請求項1または2に記載の医薬溶液。
- 緩衝剤が、酢酸ナトリウム、クエン酸ナトリウム、リン酸二水素ナトリウムおよびリン酸水素ナトリウムより選択されることを特徴とする請求項3に記載の医薬溶液。
- 医薬溶液のpHが、7〜9であることを特徴とする請求項1〜4のいずれか一項に記載の医薬溶液。
- 医薬溶液のpHが、7.5〜8.5であることを特徴とする請求項1〜5のいずれか一項に記載の医薬溶液。
- 該医薬溶液中のヒドロコルチゾンの濃度が、150 mg/mL〜170 mg/mLであることを特徴とする請求項1〜6のいずれか一項に記載の医薬溶液。
- 200 mLの溶液に対してgで、40 g〜45 gのヒドロコルチゾンまたはその医薬的に許容される塩を含むことを特徴とする請求項1〜7のいずれか一項に記載の医薬溶液。
- 200 mLの溶液に対してgで、0.3 g〜0.5 gのロンガリットを含むことを特徴とする請求項1〜8のいずれか一項に記載の医薬溶液。
- 200 mLの溶液に対してgで、0.15 g〜0.25 gのEDTA二ナトリウムを含むことを特徴とする請求項1〜9のいずれか一項に記載の医薬溶液。
- 溶媒が、注射製剤用水であることを特徴とする請求項1〜10のいずれか一項に記載の医薬溶液。
- 請求項1または2に記載の医薬溶液を製造するための方法であって、下記工程:
a) 少なくとも溶媒、ロンガリットおよびEDTA二ナトリウムを含む混合物を撹拌下調製する工程;
b) ヒドロコルチゾンまたはその医薬的に許容される塩を撹拌下加えて、該医薬溶液を得る工程
を少なくとも含み;
c) 工程b)の完了で得られた医薬溶液に対して少なくとも1つのろ過工程を実施する工程
を含んでもよいことを特徴とする方法。 - 急性副腎不全および喘息の処置における使用のための、請求項1〜11のいずれか一項に記載の医薬溶液。
- 該溶液が、非経腸経路により投与されることを特徴とする請求項13に記載の医薬溶液。
- 非経腸経路が、筋肉内経路であることを特徴とする請求項14に記載の医薬溶液。
- 下記:
・注射デバイス;
・請求項1〜11のいずれか一項に記載の医薬溶液
を含む、注射キット。 - 筋肉内経路による注射のための、請求項16に記載の注射キット。
- 注射デバイスが、火工カートリッジを有するニードルレス注射デバイスであることを特徴とする請求項16または17に記載の注射キット。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR16/60393 | 2016-10-26 | ||
FR1660393A FR3057775B1 (fr) | 2016-10-26 | 2016-10-26 | Solution pharmaceutique d’hydrocortisone pour dispositif d’injection |
PCT/FR2017/052941 WO2018078285A1 (fr) | 2016-10-26 | 2017-10-25 | Solution pharmaceutique d'hydrocortisone pour dispositif d'injection |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2019535668A JP2019535668A (ja) | 2019-12-12 |
JP6665350B2 true JP6665350B2 (ja) | 2020-03-13 |
Family
ID=57906786
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019521040A Active JP6665350B2 (ja) | 2016-10-26 | 2017-10-25 | 注射デバイスのための医薬ヒドロコルチゾン溶液 |
Country Status (10)
Country | Link |
---|---|
US (1) | US10456355B1 (ja) |
EP (1) | EP3532033B1 (ja) |
JP (1) | JP6665350B2 (ja) |
CN (1) | CN109862881A (ja) |
AR (1) | AR110471A1 (ja) |
BR (1) | BR112019008280A2 (ja) |
ES (1) | ES2827551T3 (ja) |
FR (1) | FR3057775B1 (ja) |
MX (1) | MX2019004173A (ja) |
WO (1) | WO2018078285A1 (ja) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR3102057B1 (fr) * | 2019-10-18 | 2021-10-29 | Aguettant Lab | Nouveau lyophilisat d’hémisuccinate d'hydrocortisone |
MX2023003197A (es) * | 2020-09-21 | 2023-08-04 | Antares Pharma Inc | Formulacion farmaceutica acuosa de fosfato sodico de hidrocortisona y monotioglicerol. |
FR3128874A1 (fr) * | 2021-11-09 | 2023-05-12 | Crossject | Solution pharmaceutique d’hydrocortisone pour dispositif d’injection |
US11904046B1 (en) | 2022-11-14 | 2024-02-20 | Eton Pharmaceuticals, Inc. | Hydrocortisone oral liquid formulations |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4191106B2 (ja) * | 1994-09-07 | 2008-12-03 | ジョンソン・エンド・ジョンソン株式会社 | レチノイド組成物 |
FR2807946B1 (fr) * | 2000-04-19 | 2002-06-07 | Poudres & Explosifs Ste Nale | Seringue sans aiguille fonctionnant avec un chargement pyrotechnique bicomposition |
FR2815544B1 (fr) | 2000-10-23 | 2003-02-14 | Poudres & Explosifs Ste Nale | Seringue sans aiguille securisee a architecture compacte |
GB201202433D0 (en) * | 2012-02-13 | 2012-03-28 | Diurnal Ltd | Controlled drug release |
CN102772360B (zh) * | 2012-08-22 | 2014-04-16 | 中国兽医药品监察所 | 一种兽用盐酸多西环素注射液及其制备方法 |
UA119324C2 (uk) * | 2013-04-02 | 2019-06-10 | Теміс Медікер Лімітед | Композиції фармацевтично активних речовин, що містять моноетиловий ефір діетиленгліколю або інші алкільні похідні |
US20170128575A1 (en) * | 2013-12-19 | 2017-05-11 | Dr. Reddy' S Laboratories Ltd | Liquid pharmaceutical formulations of pemetrexed |
CN103816166B (zh) * | 2014-02-21 | 2015-07-15 | 中国兽医药品监察所 | 一种兽用复方盐酸多西环素注射液及其制备方法 |
-
2016
- 2016-10-26 FR FR1660393A patent/FR3057775B1/fr not_active Expired - Fee Related
-
2017
- 2017-10-25 WO PCT/FR2017/052941 patent/WO2018078285A1/fr unknown
- 2017-10-25 AR ARP170102962A patent/AR110471A1/es unknown
- 2017-10-25 US US16/343,163 patent/US10456355B1/en active Active
- 2017-10-25 EP EP17804606.6A patent/EP3532033B1/fr active Active
- 2017-10-25 CN CN201780063128.4A patent/CN109862881A/zh active Pending
- 2017-10-25 BR BR112019008280A patent/BR112019008280A2/pt not_active IP Right Cessation
- 2017-10-25 JP JP2019521040A patent/JP6665350B2/ja active Active
- 2017-10-25 ES ES17804606T patent/ES2827551T3/es active Active
- 2017-10-25 MX MX2019004173A patent/MX2019004173A/es unknown
Also Published As
Publication number | Publication date |
---|---|
FR3057775A1 (fr) | 2018-04-27 |
FR3057775B1 (fr) | 2018-11-02 |
US20190314273A1 (en) | 2019-10-17 |
JP2019535668A (ja) | 2019-12-12 |
CN109862881A (zh) | 2019-06-07 |
BR112019008280A2 (pt) | 2019-07-09 |
EP3532033B1 (fr) | 2020-08-05 |
WO2018078285A1 (fr) | 2018-05-03 |
ES2827551T3 (es) | 2021-05-21 |
EP3532033A1 (fr) | 2019-09-04 |
US10456355B1 (en) | 2019-10-29 |
AR110471A1 (es) | 2019-04-03 |
MX2019004173A (es) | 2019-08-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6665350B2 (ja) | 注射デバイスのための医薬ヒドロコルチゾン溶液 | |
AU2015222150B2 (en) | Process for producing a stable low concentration, injectable solution of noradrenaline | |
JP6516831B2 (ja) | シクロホスファミド液状濃縮物の製剤 | |
KR20070110256A (ko) | 유산나트륨 희석제 내에 피페라실린, 타조박탐 및아미노카르복실산을 함유하는 조성물 | |
WO2016059588A1 (en) | Stable injectable composition of bivalirudin and process for its preparation | |
CA2867295A1 (en) | Formulations of bendamustine | |
JP2017513925A (ja) | 徐放性ブプレノルフィン溶液 | |
JP2007528384A (ja) | 安定な注射可能なジクロフェナク組成物 | |
JP2020511440A (ja) | 液体医薬組成物 | |
JP2020511443A (ja) | 液体医薬組成物 | |
EP3206666A2 (en) | Liquid pharmaceutical composition comprising pemetrexed | |
JP2016530316A (ja) | Cgrp受容体アンタゴニストのための製剤 | |
OA13348A (fr) | Composition pharmaceutique de vinflunine destinée à une administration parentérale, procédé de préparation et utilisation. | |
EP2804597A1 (en) | Aqueous paracetamol composition for injection | |
WO2018102145A1 (en) | Levothyroxine liquid formulations | |
JP6765475B2 (ja) | 医薬組成物 | |
US10772895B2 (en) | Pharmaceutical composition | |
JP2012501331A (ja) | カンフォスファミド製剤及びその製造方法 | |
JP7178512B2 (ja) | 注入器用アドレナリン薬液 | |
JP5628395B1 (ja) | 免疫グロブリン液状組成物 | |
KR20220092404A (ko) | 봉독 추출물로부터 bvPLA2를 50~99% 함량으로 포함하는 봉독 주사제 조성물 및 이의 제조방법 | |
JP2009102381A (ja) | 安定な液状製剤 | |
BG107565A (bg) | Комбинирана '...-на л...кар''в...на "орма ' ан'и'"'ивно д...й''ви... и м...'од за н...йно'о пол"-аван... |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190521 |
|
A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20190521 |
|
A975 | Report on accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A971005 Effective date: 20190912 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20191001 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191226 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200121 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200219 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6665350 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |