HRP20201300T1 - Lyophilized preparation of cytotoxic dipeptides - Google Patents

Lyophilized preparation of cytotoxic dipeptides Download PDF

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Publication number
HRP20201300T1
HRP20201300T1 HRP20201300TT HRP20201300T HRP20201300T1 HR P20201300 T1 HRP20201300 T1 HR P20201300T1 HR P20201300T T HRP20201300T T HR P20201300TT HR P20201300 T HRP20201300 T HR P20201300T HR P20201300 T1 HRP20201300 T1 HR P20201300T1
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HR
Croatia
Prior art keywords
cyclodextrin
pharmaceutical preparation
lyophilized pharmaceutical
melphalan flufenamide
solution
Prior art date
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HRP20201300TT
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Croatian (hr)
Inventor
Jack Spira
Fredrik Lehmann
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Oncopeptides Ab
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Publication date
Priority claimed from EP17173249.8A external-priority patent/EP3228319B1/en
Application filed by Oncopeptides Ab filed Critical Oncopeptides Ab
Publication of HRP20201300T1 publication Critical patent/HRP20201300T1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic 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
    • A61K31/198Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/222Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05Dipeptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10Peptides having 12 to 20 amino acids
    • A61K38/105Bombesin; Related peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12Carboxylic acids; Salts or anhydrides thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40Cyclodextrins; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F26DRYING
    • F26BDRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
    • F26B5/00Drying solid materials or objects by processes not involving the application of heat
    • F26B5/04Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum
    • F26B5/06Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum the process involving freezing

Claims (17)

1. Liofilizirani farmaceutski pripravak, naznačen time, da sadržava i. melfalan flufenamid ili njegovu farmaceutski prihvatljivu sol; i ii. barem jedan ekscipijens izabran iz skupine koju tvore β-ciklodekstrin; α-ciklodekstrin; hidroksipropil-β-ciklodekstrin; i sulfobutileter- β -ciklodekstrin.1. Lyophilized pharmaceutical preparation, characterized in that it contains i. melphalan flufenamide or its pharmaceutically acceptable salt; and ii. at least one excipient selected from the group consisting of β-cyclodextrin; α-cyclodextrin; hydroxypropyl-β-cyclodextrin; and sulfobutyl ether-β-cyclodextrin. 2. Liofilizirani farmaceutski pripravak u skladu s patentnim zahtjevom 1, naznačen time, da je količina pomoćne tvari oko 10 do 100 % težinskog udjela navedenog melfalan flufenamida.2. Lyophilized pharmaceutical preparation in accordance with patent claim 1, characterized in that the amount of auxiliary substance is about 10 to 100% of the weight share of said melphalan flufenamide. 3. Liofilizirani farmaceutski pripravak u skladu s patentnim zahtjevom 2, naznačen time, da je količina pomoćne tvari 10 do 50 % težinskog udjela navedenog melfalan flufenamida.3. Lyophilized pharmaceutical preparation in accordance with patent claim 2, characterized in that the amount of auxiliary substance is 10 to 50% of the weight share of said melphalan flufenamide. 4. Liofilizirani farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time, da je navedeni melfalan flufenamid melfalan flufenamid hidroklorid (J1).4. A lyophilized pharmaceutical preparation according to any of claims 1 to 3, characterized in that said melphalan flufenamide is melphalan flufenamide hydrochloride (J1). 5. Liofilizirani farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time, da dodatno sadržava fiziološki prihvatljivu otopinu.5. Lyophilized pharmaceutical preparation according to any one of patent claims 1 to 4, characterized in that it additionally contains a physiologically acceptable solution. 6. Liofilizirani farmaceutski pripravak u skladu s patentnim zahtjevom 5, naznačen time, da je navedena fiziološki prihvatljiva otopina otopina glukoze.6. Lyophilized pharmaceutical preparation according to claim 5, characterized in that the specified physiologically acceptable solution is a glucose solution. 7. Liofilizirani farmaceutski pripravak u skladu s patentnim zahtjevom 6, naznačen time, da je količina glukoze 4,5 do 5,5 % težinskog udjela liofiliziranog pripravka.7. Lyophilized pharmaceutical preparation according to claim 6, characterized in that the amount of glucose is 4.5 to 5.5% by weight of the lyophilized preparation. 8. Liofilizirani farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time, da je slobodan ili u osnovi bez organskih otapala.8. A lyophilized pharmaceutical preparation according to any one of claims 1 to 7, characterized in that it is free or essentially free of organic solvents. 9. Komplet kombinacije dijelova, naznačen time, da sadržava i. liofilizirani farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 1 do 4; i ii. fiziološki prihvatljivu otopinu.9. A set of combination of parts, indicated that it contains i. a lyophilized pharmaceutical preparation according to any of claims 1 to 4; and ii. physiologically acceptable solution. 10. Liofilizirani farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time, da se upotrebljava kao lijek.10. Lyophilized pharmaceutical preparation according to any one of claims 1 to 4, characterized in that it is used as a medicine. 11. Liofilizirani farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time, da je namijenjen upotrebi u liječenju i / ili prevenciji karcinoma.11. Lyophilized pharmaceutical preparation according to any one of patent claims 1 to 4, characterized in that it is intended for use in the treatment and/or prevention of cancer. 12. Liofilizirani farmaceutski pripravak za uporabu u skladu s patentnim zahtjevom 11, naznačen time, da je navedeni karcinom bilo koji od sljedećih bolesti: karcinom jajnika, rak pluća, rak mokraćnog mjehura, mezoteliom, multipli mijelom, karcinom dojke ili hematološki rak.12. A lyophilized pharmaceutical preparation for use according to claim 11, characterized in that said cancer is any of the following diseases: ovarian cancer, lung cancer, bladder cancer, mesothelioma, multiple myeloma, breast cancer or hematological cancer. 13. Komplet kombinacija dijelova u skladu s patentnim zahtjevom 9, naznačen time, da se upotrebljava za liječenje raka.13. A set of combinations of parts according to claim 9, characterized in that it is used for the treatment of cancer. 14. Postupak za pripremu liofiliziranog farmaceutskog pripravka u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time, da: a. melfalan flufenamid ili njegova farmaceutski prihvatljiva sol otopi se u organskom otapalu da se dobije otopina melfalan flufenamida; b. u otopinu melfalan flufenamida dodaje se voda kako bi se dobila vodena otopina melfalan flufenamida, u koncentraciji od oko 0,2 do 3,0 mg/ml; c. barem jedan ekscipijens izabran iz skupine koja sadržava β-ciklodekstrin; α-ciklodekstrin; hidroksipropil-β-ciklodekstrin; i sulfobutileter- β-ciklodekstrin dodan je otopini melfalan flufenamida; i d. vodena otopina melafana flufenamida koja sadržava ekscipijens podvrgnuta je liofilizaciji.14. Process for the preparation of a lyophilized pharmaceutical preparation in accordance with any of patent claims 1 to 3, characterized in that: a. melphalan flufenamide or its pharmaceutically acceptable salt is dissolved in an organic solvent to obtain a solution of melphalan flufenamide; b. water is added to the melphalan flufenamide solution to obtain an aqueous solution of melphalan flufenamide, in a concentration of about 0.2 to 3.0 mg/ml; c. at least one excipient selected from the group consisting of β-cyclodextrin; α-cyclodextrin; hydroxypropyl-β-cyclodextrin; and sulfobutyl ether-β-cyclodextrin was added to the melphalan flufenamide solution; and d. the aqueous solution of melafan flufenamide containing the excipient was subjected to lyophilization. 15. Postupak u skladu s patentnim zahtjevom 14, naznačen time, da: a. melfalan flufenamid, ili njegova farmaceutski prihvatljiva sol, otopljen je u organskom otapalu; b. u otopinu dobivenu u koraku a) dodaje se voda kako bi se dobila otopina spomenutog melfalan flufenamida ili njegove farmaceutski prihvatljive soli u koncentraciji od oko 0,2 do 3,0 mg / ml; c. barem jedan ekscipijens izabran iz skupine koja sadržava β-ciklodekstrin; α-ciklodekstrin; hidroksipropil-β-ciklodekstrin; i otopini dobivenoj u koraku b) doda se sulfobutileter- β -ciklodekstrin; i d. otopina dobivena u koraku c) podvrgnuta je liofilizaciji.15. The procedure according to patent claim 14, characterized in that: a. melphalan flufenamide, or its pharmaceutically acceptable salt, is dissolved in an organic solvent; b. water is added to the solution obtained in step a) to obtain a solution of the mentioned melphalan flufenamide or its pharmaceutically acceptable salt in a concentration of about 0.2 to 3.0 mg/ml; c. at least one excipient selected from the group consisting of β-cyclodextrin; α-cyclodextrin; hydroxypropyl-β-cyclodextrin; and sulfobutyl ether-β-cyclodextrin is added to the solution obtained in step b); and d. the solution obtained in step c) is subjected to lyophilization. 16. Postupak u skladu sa zahtjevom 14 ili 15, naznačen time, da je organsko otapalo odabrano između jednog od sljedećeg: etanola, etanola koji sadržava kiselinu, glicerina, propilen glikola, benzil alkohola dimetilacetamida (DMA), N-metil-2-pirolidona izopropanola n-butanola, terc-butanola, metil terc-butil etera, propilen glikola, dimetilsulfoksida, tetrahidrofurana, 2-metil tetrahidrofurana, acetona, dimetilformamida, acetonitrila, dioksana, octene kiseline, mliječne kiseline, propionske kiseline, n-butanola, izopropanola, n-propanola, terc-butanola, sec-butanola, metanol i mješavine etanola i vode.16. The method according to claim 14 or 15, characterized in that the organic solvent is selected from one of the following: ethanol, ethanol containing acid, glycerin, propylene glycol, benzyl alcohol dimethylacetamide (DMA), N-methyl-2-pyrrolidone isopropanol n-butanol, tert-butanol, methyl tert-butyl ether, propylene glycol, dimethyl sulfoxide, tetrahydrofuran, 2-methyl tetrahydrofuran, acetone, dimethylformamide, acetonitrile, dioxane, acetic acid, lactic acid, propionic acid, n-butanol, isopropanol, n-propanol, tert-butanol, sec-butanol, methanol and mixtures of ethanol and water. 17. Postupak u skladu s bilo kojim od patentnih zahtjeva 14 do 16, naznačen time, da je navedeni melafanal flufenamid melfalan flufenamid hidroklorid (J1).17. The method according to any one of claims 14 to 16, characterized in that said melaphanal flufenamide is melphalan flufenamide hydrochloride (J1).
HRP20201300TT 2011-04-28 2020-08-20 Lyophilized preparation of cytotoxic dipeptides HRP20201300T1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
SE1150371 2011-04-28
US201161535126P 2011-09-15 2011-09-15
EP17173249.8A EP3228319B1 (en) 2011-04-28 2012-04-25 Lyophilized preparation of cytotoxic dipeptides

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HRP20201300T1 true HRP20201300T1 (en) 2020-11-27

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HRP20201300TT HRP20201300T1 (en) 2011-04-28 2020-08-20 Lyophilized preparation of cytotoxic dipeptides

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KR (2) KR102194376B1 (en)
ES (1) ES2813979T3 (en)
HK (1) HK1250492A1 (en)
HR (1) HRP20201300T1 (en)
HU (1) HUE051690T4 (en)
IL (1) IL280812B2 (en)
LT (1) LT3228319T (en)
PT (1) PT3228319T (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2023539154A (en) * 2020-08-19 2023-09-13 セラクト ファーマ ジーエムビーエイチ Etoposide tonilibate formulation
WO2022231347A1 (en) * 2021-04-28 2022-11-03 인천대학교 산학협력단 Freeze-dry protective agent for extracellular vesicles
EP4233837A1 (en) * 2022-02-24 2023-08-30 CellAct Pharma GmbH Solid and oral etoposide toniribate compositions

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DE60141398D1 (en) * 2000-06-13 2010-04-08 Oncopeptides Ab MELPHALAN DERIVATIVES AND THEIR USE AS CHEMOTHERAPEUTICS AGAINST CANCER
SE0002202D0 (en) * 2000-06-13 2000-06-13 Karolinska Innovations Ab New peptides
US6780324B2 (en) * 2002-03-18 2004-08-24 Labopharm, Inc. Preparation of sterile stabilized nanodispersions
US20040034099A1 (en) * 2002-06-27 2004-02-19 Ramsey Beverly J. Pharmaceutical composition

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HK1250492A1 (en) 2018-12-21
ES2813979T3 (en) 2021-03-25
HUE051690T4 (en) 2023-09-28
HUE051690T2 (en) 2021-03-29
KR102122429B1 (en) 2020-06-12
IL280812B2 (en) 2023-04-01
KR20200014947A (en) 2020-02-11
LT3228319T (en) 2020-09-25
IL280812A (en) 2021-04-29
KR20200084890A (en) 2020-07-13
IL280812B (en) 2022-12-01
PT3228319T (en) 2020-08-27
KR102194376B1 (en) 2020-12-23

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