EP0784474A2 - Parenterale pharmazeutische zusammensetzungen enthaltend gf120918a - Google Patents

Parenterale pharmazeutische zusammensetzungen enthaltend gf120918a

Info

Publication number
EP0784474A2
EP0784474A2 EP95938184A EP95938184A EP0784474A2 EP 0784474 A2 EP0784474 A2 EP 0784474A2 EP 95938184 A EP95938184 A EP 95938184A EP 95938184 A EP95938184 A EP 95938184A EP 0784474 A2 EP0784474 A2 EP 0784474A2
Authority
EP
European Patent Office
Prior art keywords
pharmaceutical composition
composition according
safe
effective amount
group
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.)
Ceased
Application number
EP95938184A
Other languages
English (en)
French (fr)
Inventor
Wei-Qin Tong
Mickey Lee CIMA Labs Inc. WELLS
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Corp
Original Assignee
Glaxo Wellcome Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Glaxo Wellcome Inc filed Critical Glaxo Wellcome Inc
Publication of EP0784474A2 publication Critical patent/EP0784474A2/de
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present Invention relates to novel pharmaceutical compositions that are useful in preventing malignant cells from becoming resistant to a diverse variety of chemotherapeutic agents.
  • the multidrug-resistance inhibitor chemically known as N- ⁇ 4-[2-l,2,3,4- tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl ⁇ -9,10-dihydro-5-methoxy- 9-oxo-4-acridine carboxamide and its physiologically acceptable salts and solvates is described and claimed in World Patent Application WO 92/12132. filed in the name of Laboratires Glaxo S.A. and published July 23, 1992.
  • Multidrug-resistance is a process whereby tumor cells become resistant to structurally diverse chemotherapeutic agents following exposure to treatment with anti-tumor drugs.
  • This acquired drug resistance can be a major obstacle in the clinical treatment and management of malignant disease. It has been shown that this type of resistance can be reversed by GF120918, resensitizing multidrug-resistant tumor cells to various chemotherapeutic agents. It has also been seen that certain rumors are intrinsically multidrug-resistant and the use of multidrug-resistance inhibitors are also beneficial in treating tumors of this type.
  • GF120918A the hydrochloride salt of N- ⁇ 4-[2-l,2,3,4-tetrahydro-6,7- dimethoxy-2-isoquinolinyl)-ethyl]-phenyl ⁇ -9,10-dihydro-5-methoxy-9-oxo-4- acridine carboxamide, to be safely and effectively administered to patients parenterally by either intravenous injection or intravenous infusion must be adequately miscible in the blood. Therefore, any combination of the drug and the various excipients, in a liquid form, must be sufficiently compatible with the physiological composition of the blood to allow sufficient admixing. This mixing with the blood allows the compound to be distributed throughout the body in an unremarkable fashion.
  • GF120918A is a weak base and therefore exhibits a higher solubility at a pH less than about 4. Since the pH of the blood is approximately 7.4, the compound alone in solution precipitates upon injection or infusion into the blood stream.
  • An object of the present Invention is to provide a parenteral formulation that when injected or infused into the blood stream remains miscible and allows the active drug to be distributed throughout the body in an unremarkable fashion.
  • a further object of the present Invention is to provide a parenteral formulation and method of use that will improve or increase the efficacy of a chemotherapeutic agent or restore sensitivity of a tumor to chemotherapeutic agent or rever.se or reduce resistance of a tumor to a chemotherapeutic agent; subsequently abating tumor cell multidrug-resistance and decreasing morbidity.
  • the present Invention relates to pharmaceutical compositions that prevent or minimize precipitation upon injection or infusion; comprising: a) a safe and therapeutically effective amount of N- ⁇ 4-[2-l,2,3,4-tetrahydro- 6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl ⁇ -9,10-dihydro-5-methoxy-9- oxo-4-acridine carboxamide and its physiologically acceptable salts and solvates; b) a safe and effective amount of a surfactant; c) a buffer; and d) a pharmaceutically acceptable carrier or diluent.
  • safety and therapeutically effective amount means a sufficient amount of a drug or pharmaceutical agent to abate or reverse a multidrug-resistance response of a tissue, system or animal that is being sought by the researcher or clinician without harming the tissues of a mammal, including a human to which the drug is administered.
  • compositions of the present Invention employ a safe and therapeutically effective amount of the compound N- ⁇ 4-[2-l,2,3,4-tetrahydro-6,7- dimethoxy-2-isoquinolinyl)-ethyl]-phenyl ⁇ -9,10-dihydro-5-methoxy-9-oxo-4- acridine carboxamide (GF120918) and its physiologically acceptable salts and solvates, a safe and effective amount of a surfactant, a safe and effective amount of a buffer and a carrier or diluent suitable for pharmaceutical use.
  • These compositions are suitable for administration to mammals, including humans through various parenteral routes. These various parenteral routes particularly include both intravenous bolus injection and intravenous infusion.
  • compositions of the present Invention may be administered in conjunction with an antitumor drug.
  • Suitable antitumor drugs for use in conjunction with compositions of the present include, but are not limited to, Vinca alkaloids (e.g. vincristine, vinblastine and vinorelbine, anthracyclines (e.g. daunorubincin, doxorubicin and aclarubin ⁇ n, taxol, and derivatives thereof (e.g. taxotere), podophyllotixins (e.g. etoposide and VP16), mitoxantrone, actinomycin, colchicine, gramidine D, cisplatin, cyclophosphamide, amsacrine or any other chemotherapeutic, antitumor type compounds.
  • Vinca alkaloids e.g. vincristine, vinblastine and vinorelbine
  • anthracyclines e.g. daunorubincin, doxorubicin and aclarubin ⁇ n, taxol, and derivatives thereof (e.g
  • compositions of the present Invention while being given in conjunction with an antitumor drug, could also be given simultaneously with an anti-tumor drug.
  • This type of administration is acceptable as long as the components of the composition of the present Invention and any antitumor compound given simultaneously are both physically and chemically compatible.
  • “simultaneously” means, sequentially with little or no delay or given together from a common single container where the composition of the present Invention and the antitumor drug are physically mixed.
  • compositions of the present Invention may also be administered with various drug formulations to combat side-effects produced by anti-tumor chemotherapy. These other drug formulations may be given either simultaneously or in conjunction with formulations of the present Invention.
  • compositions of the present Invention must be both physically and chemically compatible with compositions of the present Invention. If, however, the formulation given in conjunction with compositions of the present Invention or given together at the same time, but from a different container or is given by another route or given intravenously either prior to or subsequently to compositions of the present Invention physical and chemical reactivity should not be problematic.
  • compositions of the present Invention may also be packaged as articles of manufacture comprising a safe and therapeutically effective amount of GF120918 and its physiologically acceptable salts and solvates; a safe and effective amount of a surfactant; a buffer; and a pharmaceutically acceptable carrier or diluent, packaged as described above.
  • the packaging material may also have labeling and information relating to the pharmaceutical composition printed thereon.
  • an article of manufacture may have a brochure, report, notice, pamphlet, or leaflet containing product information. This form of pharmaceutical product information is sometimes, in the pharmaceutical industry, called the "package insert.”
  • a package in ⁇ rt may be attached to or included with a pharmaceutical article of manufacture.
  • the package insert and any article of manufacture labeling provides information relating to the pharmaceutical composition. This information and labeling provides various forms of information utilized by health care professionals and patients that describes the composition, its dosage and various other parameters required by regulatory agencies, such as the United States Food and Drug Administration.
  • the amount of GF120918 administered to prevent, abate or reverse multidrug resistance in a mammal including a human will vary with the nature of the condition being treated and the age and the condition of the patient and will be ultimately at the discretion of the attendant physician or veterinarian. In general, however, doses employed for adult human treatment will typically be in the range of about 1 mg to about 10 gm per day, particularly from about 10 mg to about 1 gm per day and more particularly from about 25 mg to about 750 mg per day. The desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals, for example as two, three, four or more sub-doses per day.
  • Another of the essential components of by the present Invention is a surface-active agent or a mixture of compatible surface-active agents, sometimes referred to as surfactants. Any compatible surface-active agent is sufficient for use in the present Invention, however, nonionic surface-active agents are particularly suitable.
  • Nonionic surface-active agents are particularly suitable in compositions of the present Invention and can be broadly defined as compounds produced by the condensation of alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound which may be aliphatic or alkylaromatic in nature.
  • suitable nonionic surfactants include, but are not limited to: pluronics, polyethylene oxide condensates of alkyl phenols, products derived from the condensation of ethylene oxide with the reaction product of propylene oxide and ethylene diamine, ethylene oxide condensates of aliphatic alcohol's, long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides and mixtures of such materials.
  • the surface-active agent or mixtures of compatible surface-active agents can be present in the compositions of the present Invention from about 0.05% to about 20.0%, particularly from about 0.1% to about 10.0% and most particularly from about 0.5% to about 5.0% by weight of the total composition.
  • the last essential component of the present Invention is a suitable carrier or diluent that provides an appropriate vehicle for parenteral delivery of the composition without the introduction of untoward side-effects.
  • a suitable carrier or diluent that provides an appropriate vehicle for parenteral delivery of the composition without the introduction of untoward side-effects.
  • suitable carriers and diluents include, but are not limited to: dextrose 5% in water and sterile water for injection.
  • compositions of the present Invention can contain a variety of optional parenteral conventional components known to persons skilled in the art. Any optional components included in compositions of the present Invention must be physically and chemically compatible with the essential components of the present Invention.
  • Optional components include, but are not limited to: cosolvents, including but not limited to, polyethylene glycol (PEG) grades 200 to 600, propylene glycol (1,2- propanediol), ethanol and glycerin, preservatives and agents that adjust isotonicity and osmolality. Further information concerning preservatives and agents to adjust isotonicity and osmolality can be found in Remington's Pharmaceutical Sciences, p. 1278 - 1280, 1455 - 1472, 17th ed. (1985)
  • Optional components may also include other drugs or combinations of drugs that are physically and chemically compatible with compositions of the present Invention.
  • Possible optional additional drugs include, but are not limited to antitumor chemotherapeutic agents, antinausents including, serotonin 5-HT3 receptor antagonists such as ondansetron and granisetron and various other antinausents such as prochlorperazine, chlorpromazine, perphenazine, thiethylperazine, triflupromazine, droperidol, methochlopramide, trimethobenzamide, dronabinol, pherergan, nabilone and methylpredinisone.
  • Other additional optional drugs include: antibiotics, antidepressants, antiulcer compounds, analgesics, anticholornergics, antivirals and a myriad of other drugs suitable to treat conditions that also require the administration of compositions of the present Invention.
  • compositions of the present Invention in their method aspect involves administering to a mammal, including a human a safe and effective amount of the compositions of the present Invention described herein. These safe and effective amounts will vary based on the type and size of mammal being treated and the results wished to be obtained.
  • Glacial acetic acid 2.87 microliters
  • Glacial acetic acid 2.87 microliters
  • Glacial acetic acid 2.87 microliters
  • Glacial acetic acid 17.2 microliters Sodium Hydroxide adjust to pH 3.5 Water for Injection (USP) qs to 1 mL

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)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
EP95938184A 1994-10-05 1995-10-04 Parenterale pharmazeutische zusammensetzungen enthaltend gf120918a Ceased EP0784474A2 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US318308 1981-11-05
US31830894A 1994-10-05 1994-10-05
PCT/US1995/012952 WO1996011007A1 (en) 1994-10-05 1995-10-04 Parenteral pharmaceutical compositions containing gf120918a

Publications (1)

Publication Number Publication Date
EP0784474A2 true EP0784474A2 (de) 1997-07-23

Family

ID=23237614

Family Applications (1)

Application Number Title Priority Date Filing Date
EP95938184A Ceased EP0784474A2 (de) 1994-10-05 1995-10-04 Parenterale pharmazeutische zusammensetzungen enthaltend gf120918a

Country Status (12)

Country Link
EP (1) EP0784474A2 (de)
JP (1) JPH10507177A (de)
KR (1) KR970705997A (de)
AU (1) AU702519B2 (de)
BR (1) BR9509251A (de)
CA (1) CA2201628A1 (de)
CZ (1) CZ104197A3 (de)
HU (1) HUT77883A (de)
NZ (1) NZ295546A (de)
PL (1) PL319511A1 (de)
RU (1) RU2157687C2 (de)
WO (1) WO1996011007A1 (de)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CZ135199A3 (cs) * 1996-10-18 1999-09-15 Xenova Limited Způsob přípravy N-/2-(dimethylamino)ethyl/akridin-4-karboxyamidu
GB9708805D0 (en) 1997-05-01 1997-06-25 Smithkline Beecham Plc Compounds
GB9710612D0 (en) * 1997-05-23 1997-07-16 Glaxo Group Ltd Synthesis of acridine derivatives
GB9810876D0 (en) 1998-05-20 1998-07-22 Smithkline Beecham Plc Compounds
US5922754A (en) * 1998-10-02 1999-07-13 Abbott Laboratories Pharmaceutical compositions containing paclitaxel
WO2000021951A1 (en) 1998-10-08 2000-04-20 Smithkline Beecham Plc Tetrahydrobenzazepine derivatives useful as modulators of dopamine d3 receptors (antipsychotic agents)
AT408186B (de) * 1998-12-15 2001-09-25 Sanochemia Pharmazeutika Ag Wässerige zubereitung von beta-carotin
DE60030283T2 (de) 1999-05-17 2007-09-20 Cancer Research Ventures Ltd. Zusammensetzungen zur erhöhung der bioverfügbarkeit von oral verabreichten pharmazeutischen verbindungen
US6521635B1 (en) 2000-01-20 2003-02-18 The United States Of America As Represented By The Department Of Health And Human Services Inhibition of MXR transport by acridine derivatives
JP2004501955A (ja) * 2000-06-30 2004-01-22 アイネックス　ファーマシューティカルズ　コーポレイション リポソーム抗新生物薬剤およびその使用
US7122201B2 (en) 2001-06-28 2006-10-17 Baxter International Inc. Composition and method for reducing adverse interactions between phenothiazine derivatives and plasma using surfactants and amino acids
RU2205634C1 (ru) * 2002-06-18 2003-06-10 Нестерук Владимир Викторович Лекарственное средство, обладающее противорвотным действием
KR100866728B1 (ko) * 2004-11-12 2008-11-03 주식회사종근당 타크로리무스를 함유하는 주사제
FR2948568B1 (fr) * 2009-07-30 2012-08-24 Sanofi Aventis Formulation pharmaceutique

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4544657A (en) * 1983-05-19 1985-10-01 Hoffmann-La Roche Inc. Substituted isoquinolines
KR100220538B1 (ko) * 1991-01-11 1999-09-15 뮈쉘 쥐르밀 아크리딘 유도체

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9611007A1 *

Also Published As

Publication number Publication date
BR9509251A (pt) 1997-10-21
RU2157687C2 (ru) 2000-10-20
AU702519B2 (en) 1999-02-25
WO1996011007A1 (en) 1996-04-18
HUT77883A (hu) 1998-09-28
NZ295546A (en) 1999-01-28
PL319511A1 (en) 1997-08-18
AU3891395A (en) 1996-05-02
CA2201628A1 (en) 1996-04-18
MX9702473A (es) 1997-07-31
CZ104197A3 (en) 1997-09-17
JPH10507177A (ja) 1998-07-14
KR970705997A (ko) 1997-11-03

Similar Documents

Publication Publication Date Title
US7915317B2 (en) Aqueous 2,6-diisopropylphenol pharmaceutical compositions
US8133918B2 (en) Aqueous pharmaceutical compositions of 2,6-diisopropylphenol (propofol) and their uses
US10688111B2 (en) Liquid formulations of compounds active at sulfonylurea receptors
JP4890732B2 (ja) 癌治療用パクリタキセル・リポソーム組成物およびその製造方法
AU702519B2 (en) Parenteral pharmaceutical compositions containing GF120918A
KR102656841B1 (ko) 레파뮬린의 주사가능한 약제학적 제형
WO2018047074A1 (en) Sterile injectable compositions comprising drug micelles
US10799486B2 (en) Stable nimodipine parenteral formulation
CN111770752A (zh) 瘤内注射制剂
EP1667656A1 (de) Zusammensetzungen und verfahren zur abgabe von biologisch wirksamen mitteln
AU2011273064A1 (en) Pharmaceutical compositions comprising paracetamol and process for preparing the same
JP2011529930A (ja) 注射可能タキサン医薬品組成物
RU2236227C1 (ru) Устойчивая фармацевтическая форма противоракового препарата
MXPA97002473A (en) Parenteral pharmaceutical compositions containing gf1209
US20240156829A1 (en) Stable Antiemetic Emulsions for Parenteral Administration
CN1164189A (zh) 含有gf120918a的非肠道药物组合物
JP2008521834A (ja) 治療学的処方物
WO2024224424A1 (en) Injectable compositions of metolazone
WO2026078715A1 (en) Injectable composition of aprepitant
HK40077694A (en) Stable nimodipine parenteral formulation
JP2025522933A (ja) メルファランを含む安定した液体医薬組成物
WO2018109731A1 (en) Pharmaceutical compositions of taxane and its derivatives
AU2004267882A1 (en) Compositions and methods for delivery of biologically active agents
HK1077515B (en) Aqueous 2,6-diisopropylphenol pharmaceutical compositions

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19970407

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: LT PAYMENT 970407;LV PAYMENT 970407;SI PAYMENT 970407

17Q First examination report despatched

Effective date: 20000410

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED

18R Application refused

Effective date: 20020601