[go: up one dir, main page]

WO2025072609A1 - Compositions liposomales d'amphotéricine b et méthodes - Google Patents

Compositions liposomales d'amphotéricine b et méthodes Download PDF

Info

Publication number
WO2025072609A1
WO2025072609A1 PCT/US2024/048780 US2024048780W WO2025072609A1 WO 2025072609 A1 WO2025072609 A1 WO 2025072609A1 US 2024048780 W US2024048780 W US 2024048780W WO 2025072609 A1 WO2025072609 A1 WO 2025072609A1
Authority
WO
WIPO (PCT)
Prior art keywords
amphotericin
ready
use composition
composition
liposomes
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.)
Pending
Application number
PCT/US2024/048780
Other languages
English (en)
Inventor
Sydney Ugwu
Xin He
Jiajin Lin
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.)
Fordoz Pharma Corp
Original Assignee
Fordoz Pharma Corp
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 Fordoz Pharma Corp filed Critical Fordoz Pharma Corp
Publication of WO2025072609A1 publication Critical patent/WO2025072609A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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

Definitions

  • Amphotericin B is designated chemically as: [1R-1R*,3S*,5R*,6R*,9R*,11R*,15S*,16R*,17R*,18S*,19E,21E,23E,25E,27E,29E, 31E,33R*,35S*,36R*,37S*)]-33-[(3-Amino-3,6-dideoxy- ⁇ -D-mannopyranosyl)oxy]- 1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39- dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid (CAS No.
  • Amphotericin B has a molecular formula of C 47 H 73 NO 17 and a molecular weight of 924.09. The structure of amphotericin B is shown below: Currently, amphotericin B is marketed as lyophilized liposomes for injection which must be reconstituted first and further diluted in 5% Dextrose Solution prior to administration to patients. One of the commercially available amphotericin B liposome products that requires reconstitution and dilution is AMBISOME ® available from Astellas Pharm. in 50 mg/vial. Amphotericin B is also commercially available as a lipid complex in a 5 mg/vial suspension product sold by Leadiant Biosciences, Inc.
  • ABELCET ® under the name as ABELCET ® .
  • the ABELCET product requires extracting the appropriate amount of the suspension from the vial into a syringe with an 18-gauge needle, replacing the needle on the syringe with a 5-micron filter needle and passing the contents of the syringe through the 5-micron filter needle and into a 5% dextrose solution.
  • These diluted liposomal amphotericin B formulations lack sufficient storage stability.
  • the diluted liposomal amphotericin B product must be used within 24 to 48 hours after reconstitution or preparation even when stored at refrigerator temperature (2-8°C) and within 6 hours after dilution in 5% dextrose and storage at room temperature.
  • the present invention is a ready-to-use parenteral amphotericin B composition that is stable for at least 1 month, 3 months, 6 months, 9 months, 12 months or longer.
  • the present invention further relates to a method for preparing the ready-to-use parenteral amphotericin B composition and methods of using the ready-to-use parenteral amphotericin B composition.
  • the ready-to-use composition is prepared by: (i) forming amphotericin B liposomes; (ii) mixing the amphotericin B liposomes with an aqueous solution, preferably an aqueous dextrose solution and most preferably a 5% aqueous dextrose solution, to obtain an amphotericin B composition with the desired concentration of amphotericin B for administration to a patient; (iii) filling the liposome solution of step (ii) into a flexible container such as a flexible infusion bag; and (iv) freezing the contents of the filled container of step (iii).
  • the forming of the amphotericin B liposomes may comprise (a) mixing two or more of the liposome components and (b) hydrating the mixed components to form the amphotericin B liposomes.
  • the components used in step (a) comprise amphotericin B, one or more phospholipids and optionally liposome stabilizing agents, antioxidants.
  • the hydration step can employ water, preferably sterile water for injection.
  • the mixing and/or hydration step may further comprise the addition of other excipients such as osmotic adjusting agents, cryoprotectants, pH buffering agents and combinations thereof.
  • the method for preparing the ready-to-use composition may also comprise a sizing step wherein the size of the liposomes are reduced to a size of less than 250 nm, less than 200 nm, less than 150 nm, or less than 100 nm.
  • the sizing may be conducted by any means known in the industry, such as filtration.
  • the sizing step may occur after the formation of the liposomes and before or during filling into the flexible container.
  • the liposomes are sized after formation and prior to the formation of the ready-to-use composition that is added to the flexible container. Once the ready-to-use composition is added to the flexible container and the container sealed, the contents of the container are frozen.
  • the contents may be frozen under normal freezing conditions which include placing the filled and sealed flexible container in a freezer at a temperature of 0°C or less, preferably at least about -5°C, -10°C, -15°C, -20°C, or -25°C and allowing the contents of the filled and sealed container to freeze.
  • the contents are quick frozen wherein the filled and sealed container are exposed to temperatures of -30°C or lower, -35°C or lower, -40°C or lower, -45°C or lower or -50°C or lower for about 5 minutes to about 5 hours, about 10 minutes to about 4 hours, about 20 minutes to about 3 hours, or about 30 minutes to about 2 hours to convert the liquid contents to a solid.
  • the flexible container and frozen contents may be stored in a freezer (about -10°C to about -30°C) for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 months or longer, preferably at least 6-24 months or longer and more preferably at least 12-24 months.
  • the frozen ready-to-use composition may be removed from the freezer and thawed. Once the ready-to-use composition is thawed, can be administered to a patient in need of the amphotericin B treatment.
  • the ready-to-use composition prior to freezing and after thawing should have a pH of about 4 to about 7, preferably a pH of about 4.5 to about 6.5 and more preferably a pH of about 5 to about 6.
  • the ready-to-use composition prior to freezing and after thawing should have an osmolality of about 250-390 mOsmol/L.
  • the ready-to-use composition after storage at about -10°C to about -30°C for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 months should also retain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% of the initial amount of the amphotericin B and the size of the liposomes should not change from the initial size before freezing.
  • the D90 and/or D50 of the liposomes should not change by more than 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% or 10%.
  • terapéuticaally effective amount means an amount effective to deliver a therapeutically effective amount of an active agent needed to delay the onset of, inhibit the progression of, or halt altogether the particular disease, disorder or condition being treated, or to otherwise provide the desired effect on the subject to be treated.
  • a therapeutically effective amount varies with the patient's age, condition, and gender, as well as the nature and extent of the disease, disorder or condition in the patient and the dosage may be adjusted by the individual physician (or veterinarian).
  • treating and “treatment” refer to reversing, alleviating, inhibiting, or slowing the progress of the disease, disorder, or condition to which such terms apply, or one or more symptoms of such disease, disorder, or condition.
  • subject or “patient” used herein refers to a human patient or a mammalian animal, such as cat, dog, cow, horse, monkey, or the like. As disclosed herein, a number of ranges of values are provided. It is understood that each intervening value, to the tenth of the unit of the lower limit, unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention.
  • the upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither, or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.
  • the term “about” generally refers to plus or minus 10% of the indicated number. For example, “about 10%” may indicate a range of 9% to 11%, and “about 20” may mean from 18 to 22. Other meanings of “about” may be apparent from the context, such as rounding off, so, for example “about 1” may also mean from 0.5 to 1.4. Similarly, “about 0.2” may encompass the value 0.22.
  • ready-to-use refers to a composition that may be administered directly to a patient without further diluting or addition of further components.
  • the present invention is a ready-to-use parenteral amphotericin B composition that is stable for at least one month or longer preferably 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 months or longer when stored at about -10°C to about -30°C.
  • the present invention further relates to a method for preparing the ready-to-use parenteral amphotericin B composition and methods of using the ready-to-use parenteral amphotericin B composition.
  • the ready to use composition comprises amphotericin B liposomes in an aqueous composition with one or more pharmaceutically acceptable excipients.
  • the concentration of the amphotericin B in the ready-to-use composition may range from 0.05 mg/ml to 5 mg/mL, preferably 0.075 mg/mL to about 4 mg/mL, and more preferably about 0.1 mg/ml to about 3 mg/mL.
  • the total volume of the ready-to-use compositions may range from 10 mL to about 1,000 ml and any volume between such as 25 mL, 50 mL, 100 mL, 150 mL, 200 mL, 250 mL, 300 mL, 350 mL, 400 mL, 450 mL, 500 mL, 550 mL, 600 mL, 650 mL, 700 mL, 750 mL, 800 mL, 850 mL and 900 mL.
  • the liposomes use in the present invention can be prepared by any methods known in the art such as the methods described in U.S. Patent Nos.
  • the liposomes may also be made the method described in U.S. Patent No. 11,260,028, which is also incorporated herein by reference.
  • the liposomes will comprise amphotericin B and at least one phospholipid.
  • the liposomes may further optionally comprise a lipid stabilizing agent and an antioxidant.
  • the phospholipid may be selected from the group consisting of dioleoylphosphatidylcholine (DOPC), dimyristoylphosphatidylcholine (DMPC), dilauroylphosphatidylcholine (DLPC), soy phosphatidylcholine (SPC), distearoylphophatidylglycerol (DSPG) and salts thereof such as the sodium salt, hydrogenated soy phosphatidylcholine (HSPC) and mixtures of two or more thereof.
  • DOPC dioleoylphosphatidylcholine
  • DMPC dimyristoylphosphatidylcholine
  • DLPC dilauroylphosphatidylcholine
  • SPC soy phosphatidylcholine
  • DSPG distearoylphophatidylglycerol
  • the ratio of phospholipid to amphotericin (wt %:wt %) in the liposome and the ready-to-use composition typically ranges from about 3:1 to about 12:1, about 4:1 to about 10:1, or about 5:1 to about 8:1.
  • the lipid stabilizing agent may be cholesterol, or a derivative or analog thereof.
  • the antioxidant if present, is selected from the group consisting of tocopherol, ascorbic acid, propyl gallate, butylated hydroxyanisole, butylated hydroxytoulene, and tiary butyl hydroquinone, or the like. In certain embodiments the liposomes are free of antioxidant.
  • the ready-to-use composition will further comprise, water, an osmotic agent, and optionally a cryoprotectant, a buffering agent and a pH- adjusting agent.
  • the osmotic agent may be a pharmaceutically acceptable organic compound selected from the group consisting of dextrose, glycerol, sorbitol, xylitol, mannitol, glucose, trehalose, maltose, sucrose, raffinose, lactose, dextran, polyethylene glycol, and propylene glycol.
  • the osmotic agent may be a pharmaceutically acceptable inorganic salt such as sodium chloride, mixtures of sodium chloride and one or more other pharmaceutically acceptable inorganic salts, or the like.
  • the cryoprotectants are molecules, which protect liposomes during freezing, while frozen and the thawing process. These molecules are typically polyhydroxy compounds such as sugars (monosaccharides, disaccharides, or polysaccharides), polyalcohols, and their derivatives. Sucrose and trehalose are naturally occurring cryoprotectants. Sucrose is an example of preferred cryoprotectants for the present invention. In some embodiments the osmotic agent and the cryoprotectants may be the same compound(s).
  • an osmotic agent and a cryoprotectant may be the same compound and provide dual functions.
  • the osmotic agent and cryoprotetant compounds are different compounds.
  • the osmotic agent may be dextrose, sodium chloride or a combination thereof to provide an osmolality of about 250-390 mOsmol/L to the composition and the cryoprotectant is a polyhydroxy sugar or polyalcohol other than dextrose such as sucrose or trehalose.
  • the buffer or buffering agent may be selected from the group consisting of phosphate buffer, citrate buffer, Tris buffer, carbonate buffer, succinate buffer, maleate buffer, borate buffer, histadine, disodium succinate hexahydrate and combinations thereof.
  • the pH adjusting agent may be selected from the group consisting of sodium hydroxide, potassium hydroxide, magnesium hydroxide, sodium carbonate, Tris, sodium linoleate, sodium oleate, potassium carbonate, potassium linoleate, potassium oleate, and mixtures of two or more thereof.
  • the ready-to-use composition has a pH of about 4 to about 7, about 4.5 to about 6.5, or about 5 to about 6 prior to freezing and after storage.
  • the liposomes will have a particle size of less than 250 nm, less than 200 nm, less than 150 nm, or less than 100 nm.
  • the liposomes in the ready-to-use composition before freezing and after storage will exhibit a weighted mean particle size in the range of about 50 nm to about 200 nm, or about 50 to about 250 nm, or about 50 nm to about 300 nm, as determined by dynamic light scattering (DLS).
  • DLS dynamic light scattering
  • the ready-to-use composition is prepared by: (i) forming amphotericin B liposomes; (ii) mixing the amphotericin B liposomes with an aqueous solution, preferably an aqueous dextrose solution and most preferably a 5% aqueous dextrose solution, to obtain an amphotericin B composition with the desired concentration of amphotericin B for administration to a patient; (iii) filling the liposome solution of step (ii) into a flexible container such as a flexible infusion bag; and (iv) freezing the contents of the filled container of step (iii).
  • the ready-to-use amphotericin B parenteral composition is prepared by passive liposome loading process which includes the steps of (1) preparing a dry powder of the liposome forming components, (2) hydrating the dry powder to form a bulk liposome composition, (3) sizing the liposomes created in step (2), e.g. liposome particle size reduction, (4) diluting of sized liposomes with an aqueous solution, preferably a 5% dextrose solution, (5) sterile filtrating the diluted solution and (6) filling and packaging/sealing the sterile solution into flexible infusion bags.
  • passive liposome loading process which includes the steps of (1) preparing a dry powder of the liposome forming components, (2) hydrating the dry powder to form a bulk liposome composition, (3) sizing the liposomes created in step (2), e.g. liposome particle size reduction, (4) diluting of sized liposomes with an aqueous solution, preferably a 5% de
  • the filled and packaged infusion bags are frozen, preferably fast-frozen at temperature ⁇ -45°C for 1-2 hours prior to storage in a freezer at about -10°C to about -30°C for at least 1 month or longer period.
  • the frozen product can be thawed and immediately administered to patients, i.e. within 6 hours or less after thawing, without further preparation.
  • sucrose and 76.8 mg disodium succinate hexahydrate are dissolved in 40 mL of purified water.
  • the pH of the sucrose/disodium succinate hexahydrate buffer was adjusted with 1.0 M HCl or 1.0 M NaOH to 5.5.
  • the sucrose/disodium succinate hexahydrate buffer was filtered through a 0.22 ⁇ m PES membrane filter. Twenty mL of sucrose/disodium succinate hexahydrate buffer was added to the dried Amphotericin B/DSPG Na/HSPC/Cholesterol mixture and mixed at 200 rpm at 40° C for 60 minutes to form a homogenous bulk liposome suspension.
  • the bulk liposome suspension was extruded through double-stacked polycarbonate filters at 65°C using an AvestinTM Homogenizer/Extruder to reduce liposome particle size.
  • the following filters were used: i) 200 nm sized filter ii) 100 nm sized filter iii) 80 nm sized filter
  • the pH of the final sized liposome suspension was measured and if necessary adjusted to between 5-6 with 1.0 M NaOH or 1.0 M HCl.
  • 5 gm dextrose is dissolved in 100 mL purified water (5%dextrose).
  • the intensity-weighted mean particle size diameter measured by dynamic light scattering (DLS) was 95 nm before freezing and remained essentially unchanged after freezing.
  • the pH of the liposomes was 5.7 prior to freezing and unchanged after freeing.
  • Assay, impurities and zeta potential also remained unchanged after freezing.
  • This amphotericin B-containing liposome preparation can be injected to the patients as-is, without further dilution.
  • sucrose/disodium succinate hexahydrate/dextrose buffer is adjusted with 1.0 M HCl or 1.0 M NaOH to 5.5.
  • the sucrose/disodium succinate hexahydrate/dextrose buffer is filtered through a 0.22 ⁇ m PES membrane filter.
  • sucrose/disodium succinate hexahydrate/dextrose buffer is added to the dried Amphotericin B/DSPG Na/HSPC/Cholesterol mixture and mixed at 200 rpm at 40° C for 60 minutes to form a homogenous bulk liposome suspension.
  • the bulk liposome suspension was extruded through double-stacked polycarbonate filters at 65°C using an AvestinTM Homogenizer/Extruder to reduce liposome particle size.
  • the following filters were used: i) 200 nm sized filter ii) 100 nm sized filter iii) 80 nm sized filter
  • the pH of the final sized liposome suspension was measured and if necessary adjusted to between 5-6 with 1.0 M NaOH or 1.0M HCl.
  • the liposome mixture is sterile filtered through a 0.22 ⁇ m PES membrane filter.
  • the filtered liposome suspension is filled and packaged into flexible infusion bag.
  • the packaged liposome is fast-frozen with liquid nitrogen or pre- chilled container to temperature of ⁇ -45 for 10 – 60 min and then stored in the freezer at -10°C to -30°C for longer period.
  • the details of the amphotericin liposome formulation composition are shown in Table 5, and the analytical results are summarized in Tables 6-8.
  • the final liposome suspension was a translucent yellow suspension.
  • the intensity-weighted mean particle size diameter measured by dynamic light scattering (DLS) (Malvern Particle Sizer) was 104 nm and after freezing remained unchanged.
  • the pH of the liposome was 5.7 and after freezing remained unchanged.
  • Assay, impurities and zeta potential also remained unchanged after freezing.
  • This amphotericin B-containing liposome preparation can be injected to the patients as- is, without further dilution.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition parentérale liposomale d'amphotéricine B prête à l'emploi stable et des méthodes de préparation et d'utilisation de la composition. La composition prête à l'emploi est préparée et remplie dans un récipient souple, et stockée congelée pendant au moins un mois ou plus. Après stockage, la composition prête à l'emploi congelée est décongelée et administrée à un patient sans avoir besoin de diluer ou d'ajouter davantage d'ingrédients supplémentaires.
PCT/US2024/048780 2023-09-30 2024-09-27 Compositions liposomales d'amphotéricine b et méthodes Pending WO2025072609A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363587077P 2023-09-30 2023-09-30
US63/587,077 2023-09-30

Publications (1)

Publication Number Publication Date
WO2025072609A1 true WO2025072609A1 (fr) 2025-04-03

Family

ID=95202232

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/048780 Pending WO2025072609A1 (fr) 2023-09-30 2024-09-27 Compositions liposomales d'amphotéricine b et méthodes

Country Status (1)

Country Link
WO (1) WO2025072609A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9655846B2 (en) * 2009-09-23 2017-05-23 Indu JAVERI Methods for the preparation of liposomes comprising drugs
US10039715B2 (en) * 2010-12-23 2018-08-07 Ludwig Institute For Cancer Research Ltd. Liposomal formulation of nonglycosidic ceramides and uses thereof
CN106466299B (zh) * 2015-08-19 2021-09-28 上海本素医药科技有限公司 以人参皂苷为膜材的空白脂质体、其制备方法及应用
US11173178B2 (en) * 2008-05-23 2021-11-16 Liplasome Pharma Aps Liposomes for drug delivery and methods for preparation thereof
CN109833298B (zh) * 2017-11-29 2022-12-13 厦门本素药业有限公司 以人参皂苷衍生物为膜材的新型空白脂质体、其制备方法及应用
US11583544B2 (en) * 2014-08-04 2023-02-21 Celator Pharmaceuticals, Inc. Remote loading of sparingly water-soluble drugs into lipid vesicles

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11173178B2 (en) * 2008-05-23 2021-11-16 Liplasome Pharma Aps Liposomes for drug delivery and methods for preparation thereof
US9655846B2 (en) * 2009-09-23 2017-05-23 Indu JAVERI Methods for the preparation of liposomes comprising drugs
US10039715B2 (en) * 2010-12-23 2018-08-07 Ludwig Institute For Cancer Research Ltd. Liposomal formulation of nonglycosidic ceramides and uses thereof
US11583544B2 (en) * 2014-08-04 2023-02-21 Celator Pharmaceuticals, Inc. Remote loading of sparingly water-soluble drugs into lipid vesicles
CN106466299B (zh) * 2015-08-19 2021-09-28 上海本素医药科技有限公司 以人参皂苷为膜材的空白脂质体、其制备方法及应用
CN109833298B (zh) * 2017-11-29 2022-12-13 厦门本素药业有限公司 以人参皂苷衍生物为膜材的新型空白脂质体、其制备方法及应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ANONYMOUS: "AmBisome (amphotericin B) liposome for injection ", ASTELLAS PHARMA US, INC, 1 July 2018 (2018-07-01), pages 1 - 26, XP093300981, Retrieved from the Internet <URL:https://www.astellas.com/us/system/files/ambisome_1.pdf> *

Similar Documents

Publication Publication Date Title
JP7476161B2 (ja) 凍結乾燥リポソーム
CN103179951B (zh) 磷脂储库
AU2008227852A1 (en) Proliposomal and liposomal compositions
KR102064778B1 (ko) 성상 및 저장안정성이 개선된 암포테리신 b를 함유한 리포좀 제제의 제조방법, 및 이로부터 제조된 리포좀 제제
US11260028B2 (en) Nanosome formulations of aprepitant and methods and applications thereof
JP2006510674A (ja) 脂質：エモジン製剤に関する組成物および方法
CN101472562A (zh) 用于静脉刺激性药物的药物组合物
US8298573B2 (en) Stable sterile filterable liposomal encapsulated taxane and other antineoplastic drugs
WO2025072609A1 (fr) Compositions liposomales d&#39;amphotéricine b et méthodes
TWI500430B (zh) 伊立替康或鹽酸伊立替康脂質體及其製備方法
CN114712309A (zh) 一种人参皂苷多西他赛脂质体、其制备方法和应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24873638

Country of ref document: EP

Kind code of ref document: A1