WO2003017947A2 - Spontaneous emulsions containing cyclosporine - Google Patents
Spontaneous emulsions containing cyclosporine Download PDFInfo
- Publication number
- WO2003017947A2 WO2003017947A2 PCT/US2002/027531 US0227531W WO03017947A2 WO 2003017947 A2 WO2003017947 A2 WO 2003017947A2 US 0227531 W US0227531 W US 0227531W WO 03017947 A2 WO03017947 A2 WO 03017947A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cyclosporine
- pharmaceutical composition
- present
- ethanol
- polyoxyethylene glycerol
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
- A61K38/13—Cyclosporins
-
- 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
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- A61K47/14—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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the invention relates to pharmaceutical compositions containing cyclosporine as the active ingredient. More specifically, the invention relates to orally administered pharmaceutical compositions in the form of a spontaneous emulsion comprising cyclosporine.
- Cyclosporines are a group of nonpolar cyclic oligopep tides, which have a broad spectrum of useful pharmacological activities, particularly immuno-suppressive activity and anti- inflammatory activity.
- the major cyclosporine metabolite is cyclosporine A.
- Cyclosporine A is a neutral, lipophilic, cyclic endecapeptide with a low aqueous solubility and a molecular weight of 1200 daltons.
- Cyclosporine inhibits T cell activation and causes suppression of cell-mediated immune response. Cyclosporine has been used for suppression of immunological responses caused by tissue and organ transplantation, for example, transplantation of the heart, lung, liver, kidney, pancreas, bone marrow, skin and cornea, and especially the transplantation of foreign tissues and organs. In addition, cyclosporine is useful for the suppression of hematological disorders such as anemia, various autoimmune diseases such as systemic lupus erythematosus and idiopathic malabsorption syndrome, and inflammatory diseases such as arthritis and rheumatoid disorders. Cyclosporine is also useful in treatment of protozoal diseases such as malaria and schistosomiasis, and has recently been used in chemotherapy.
- tissue and organ transplantation for example, transplantation of the heart, lung, liver, kidney, pancreas, bone marrow, skin and cornea, and especially the transplantation of foreign tissues and organs.
- cyclosporine is useful for the suppression of hemat
- Cyclosporine is highly lipophilic and hydrophobic. Therefore, cyclosporine is sparingly soluble in water, and well dissolved in an organic solvent such as methanol, ethanol, acetone, ether, chloroform and the like. Due to the low water-solubility of cyclosporine having the above-mentioned properties, when cyclosporine is administered orally, its bioavailability is extremely low and may be greatly influenced by the conditions of each individual patient. Accordingly, it is very difficult to retain an effective therapeutic concentration. Moreover, cyclosporine may show considerable side effects such as nephrotoxicity. Thus, cyclosporine is very difficult to formulate into a preparation for oral administration due to its low water solubility.
- the 'Neoral' formulation is a microemulsion pre-concentrate which contains cyclosporine in an anhydrous oily vehicle, medium chain triglycerides, surfactants, glycerol and alcohol.
- 'SangCya' is a formulation of cyclosporine, the surfactant Tween 80, ethanol, and glycols. Upon dilution, 'SangCya' forms droplet sizes between 200 to 300 nm, which may represent a micellar solution. Recently, however, studies indicate that 'SangCya' has a lower bioavailability upon dilution than other commercially available cyclosporine formulations. Table 1 : Comparison of Various Cyclosporine Formulations
- the present invention provides an orally administered pharmaceutical composition and a method of preparing such composition.
- the prevention invention further provides an orally administered pharmaceutical composition comprising cyclosporine, ethanol, polyoxyethylene glycerol trioleate, and an oil component.
- the present invention also provides a method of preparing an orally administered pharmaceutical composition. The method involves first dissolving cyclosporine in ethanol.
- the present invention provides a stable cyclosporine composition in the form of a spontaneous emulsion or self-emulsifying drug delivery system (SEDDS).
- SEDDS self-emulsifying drug delivery system
- Emulsions are dispersions of one immiscible phase in another, usually in the form of droplets. Generally, emulsions are created by vigorous mechanical dispersion. SEDDS, as opposed to emulsions or microemulsions, spontaneously form emulsions when added to an excess of water without any external mechanical dispersion or agitation.
- SEDDS provides an effective delivery system for oral and parenteral delivery of hydrophobic active ingredients. SEDDS may provide improvements in the bioavailability of hydrophobic active ingredients.
- emulsion droplet size determines the rate and extent of drug release and absorption, it is considered to be a critical feature for self-emulsification or spontaneous emulsion.
- Table 1 which compares various cyclosporine formulations, demonstrates the variability in droplet size of different delivery systems.
- the formulation of the present invention provides a spontaneous emulsion or self-emulsifying delivery system in which the droplets are 50 to 185 nm, preferably from 50 to 150 nm.
- the present invention provides an orally administered pharmaceutical composition comprising cyclosporine, ethanol, polyoxyethylene glycerol trioleate, and an oil component.
- the present invention more specifically provides an orally administered pharmaceutical composition comprising cyclosporine, ethanol, polyoxyethylene. glycerol trioleate, and ethyl oleate.
- the present invention discloses methods for preparing an orally administered pharmaceutical composition.
- Cyclosporines are known in the art to exhibit immunosuppressive activity and anti-inflammatory activity. There are a number of cyclosporines available for use in accordance with the present invention. These cyclosporines include Cyclosporine A, Cyclosporine B, Cyclosporine C, Cyclosporine D and Cyclosporine F.
- the major cyclosporine metabolite, cyclosporine A is particularly suited for the formulations of the present invention.
- cyclosporine A is present at a concentration of from 5 to 20% by weight, preferably from 8 to 12% by weight, and most preferably about 10% by weight.
- the formulations of the present invention also comprise an oil component.
- the chain length, degree of saturation, molecular weight and concentration of the oil influence the final droplet size and polarity in the final emulsion.
- the oil component may be present in formulations of the present invention at about 40 to about 65 v/v%, more preferably from 55 to 65 v/v%, and most preferably 60 v/v% .
- the oil component comprises ethyl oleate.
- the solvent used in accordance with the present invention must be non-toxic and be well tolerated physiologically. In addition, the solvent should allow for the incorporation of the pharmaceutically active constituent into solution.
- the preferred solvent for use in formulations of the present invention is ethanol. Ethanol may be in the form of pure or substantially pure ethanol or a highly concentrated aqueous ethanol solution, such as alcohol USP (95% w/w ethanol), or any other form of ethanol suitable for this use. As used herein, the term "ethanol” shall mean any such form. Ethanol may be present in formulations of the present invention at about 15 to about 40 v/v%, more preferably from 15 to 25 v/v% , and most preferably 20 v/v% .
- a surfactant which is polyoxyethylene glycerol trioleate.
- the surfactant should also be non-toxic and be well tolerated physiologically.
- the surfactant should be capable of lowering the surface tension of water and stabilizing the oil/ water interface after the emulsion is formed.
- Non- ionic surfactants are more appropriate as they generally have low irritation potential and high chemical stability.
- the most efficient non- ionic surfactants for the formation of spontaneous emulsions are those with unsaturated acyl chains. These include oleates with HLB values of approximately 11.
- Polyoxyethylene glycerol trioleate is commercially available under the tradename Tagat TO.
- Polyoxyethylene glycerol trioleate is present in formulations of the present invention at about 20 to about 50 v/v% .
- the preferred formulation of the composition of the present invention comprises cyclosporine, ethanol, polyoxyethylene glycerol trioleate and ethyl oleate in a weight ratio of cyclosporine, pure ethanol, polyoxyethylene glycerol trioleate and ethyl oleate between 5: 18:25.9:50.1 to 15: 16:23.1 :44.9, preferably about 10: 17.1:24.5:47.5.
- the compositions of the present invention upon dilution with an aqueous media at a ratio of 1 part composition to 100 parts aqueous media form a spontaneous emulsion.
- the spontaneous emulsion is formed as the ethanol is rapidly passed into the aqueous phase, which causes violent perturbation of the oil/water interface and leaves the oil system stranded in the aqueous phase.
- the oil/water interface develops hexagonal liquid crystals because of the penetration of water molecules into the surfactant and oil/water/interface. Negative interfacial tension forms and disappears rapidly, thereby increasing the violent perturbation along the interface. This results in the formation of smaller oil droplets with hexagonal hydrophilic structures at the interface.
- the spontaneous emulsion comprises particles having a diameter of 50 to 150 nm.
- compositions of the present invention can be prepared by first dissolving the cyclosporine in ethanol. Polyoxyethylene glycerol trioleate and an oil component are then combined to the cyclosporine/ethanol solution to form a mixture. The mixture is diluted in an aqueous media to allow for the formation of a spontaneous emulsion. In the preferred embodiment, the mixture is diluted 1 part with 100 parts aqueous media. In another preferred embodiment, the diluted mixture is gently mixed to allow dispersion of the droplets formed from the spontaneous emulsion throughout the mixture.
- a composition in accordance with the present invention and using the constituents in the amounts shown in Table 2 below can be prepared as follows: Cyclosporine, 10 g, is dissolved in 18 g (potable) alcohol USP (95% w/w ethanol) to form a solution. The solution is added with stirring to a mixture of 24.5 g polyoxyethylene glycerol trioleate ('Tagat TO,' Goldschmidt) and 47.5 g ethyl oleate (Croda) to form 100 g of a self- emulsifying mixture. This is generally administered orally as a 1:100 dilution in water or fruit juice. Table 2
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002458448A CA2458448A1 (en) | 2001-08-31 | 2002-08-29 | Spontaneous emulsions containing cyclosporine |
AU2002356137A AU2002356137B2 (en) | 2001-08-31 | 2002-08-29 | Spontaneous emulsions containing cyclosporine |
GB0405785A GB2395902A (en) | 2001-08-31 | 2002-08-29 | Spontaneous emulsions containing cyclosporine |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/943,687 US6960563B2 (en) | 2001-08-31 | 2001-08-31 | Spontaneous emulsions containing cyclosporine |
US09/943,687 | 2001-08-31 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2003017947A2 true WO2003017947A2 (en) | 2003-03-06 |
WO2003017947A3 WO2003017947A3 (en) | 2004-01-29 |
Family
ID=25480095
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2002/027531 WO2003017947A2 (en) | 2001-08-31 | 2002-08-29 | Spontaneous emulsions containing cyclosporine |
Country Status (5)
Country | Link |
---|---|
US (1) | US6960563B2 (en) |
AU (1) | AU2002356137B2 (en) |
CA (1) | CA2458448A1 (en) |
GB (1) | GB2395902A (en) |
WO (1) | WO2003017947A2 (en) |
Families Citing this family (65)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HUP0303313A2 (en) * | 2003-10-09 | 2005-07-28 | Richter Gedeon Vegyészeti Gyár Rt. | Transdermal pharmaceutical compositions |
CN101547687A (en) * | 2005-11-17 | 2009-09-30 | 生物药效率有限公司 | Biocompatible latent emulsifiers |
US8022054B2 (en) | 2005-11-28 | 2011-09-20 | Marinus Pharmaceuticals | Liquid ganaxolone formulations and methods for the making and use thereof |
EP2056818B1 (en) | 2006-08-11 | 2011-05-25 | The Johns Hopkins University | Compositions and methods for neuroprotection |
HUE028086T2 (en) | 2006-09-22 | 2016-11-28 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
EP2101735A2 (en) | 2006-11-28 | 2009-09-23 | Marinus Pharmaceuticals, Inc. | Nanoparticulate formulations and methods for the making and use thereof |
US8263641B2 (en) | 2007-09-10 | 2012-09-11 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
EP2193798A1 (en) * | 2007-09-10 | 2010-06-09 | Maruho Co., Ltd. | Liquid crystal emulsion-type pharmaceutical composition containing cyclosporine, and method of treating cutaneous disease therewith |
US20090130198A1 (en) | 2007-11-21 | 2009-05-21 | Innopharmax Inc. | Pharmaceutical composition with enhanced bioavailability |
WO2010027875A2 (en) | 2008-08-27 | 2010-03-11 | Calcimedica Inc. | Compounds that modulate intracellular calcium |
WO2010071866A2 (en) | 2008-12-19 | 2010-06-24 | Nuon Therapeutics, Inc. | Combination therapy for arthritis with tranilast |
US7718662B1 (en) | 2009-10-12 | 2010-05-18 | Pharmacyclics, Inc. | Pyrazolo-pyrimidine inhibitors of bruton's tyrosine kinase |
EP2558866B1 (en) | 2010-04-15 | 2016-08-17 | Tracon Pharmaceuticals, Inc. | Potentiation of anti-cancer activity through combination therapy with ber pathway inhibitors |
JP2013525448A (en) | 2010-04-27 | 2013-06-20 | カルシメディカ,インク. | Compounds that regulate intracellular calcium |
WO2011139489A2 (en) | 2010-04-27 | 2011-11-10 | Calcimedica Inc. | Compounds that modulate intracellular calcium |
US20130259875A1 (en) | 2010-05-11 | 2013-10-03 | Questcor Pharmaceuticals, Inc. | Acth for treatment of amyotrophic lateral sclerosis |
CA2800913C (en) | 2010-06-03 | 2019-07-23 | Pharmacyclics, Inc. | The use of inhibitors of bruton's tyrosine kinase (btk) |
AU2011293201B2 (en) | 2010-08-27 | 2015-11-05 | Calcimedica Inc. | Compounds that modulate intracellular calcium |
US8796416B1 (en) | 2010-10-25 | 2014-08-05 | Questcor Pharmaceuticals, Inc | ACTH prophylactic treatment of renal disorders |
US8377946B1 (en) | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
AR091857A1 (en) | 2012-07-25 | 2015-03-04 | Sova Pharmaceuticals Inc | CISTATIONIN-g-LIASA INHIBITORS (CSE) |
AR091858A1 (en) | 2012-07-25 | 2015-03-04 | Sova Pharmaceuticals Inc | CISTATIONIN-g-LIASA INHIBITORS (CSE) |
WO2014059333A1 (en) | 2012-10-12 | 2014-04-17 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
US10232018B2 (en) | 2013-03-14 | 2019-03-19 | Mallinckrodt Ard Ip Limited | ACTH for treatment of acute respiratory distress syndrome |
WO2015054283A1 (en) | 2013-10-08 | 2015-04-16 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
AU2014360446A1 (en) | 2013-12-05 | 2016-06-09 | Pharmacyclics, Llc | Inhibitors of Bruton's tyrosine kinase |
US9839644B2 (en) | 2014-09-09 | 2017-12-12 | ARKAY Therapeutics, LLC | Formulations and methods for treatment of metabolic syndrome |
US9359316B1 (en) | 2014-11-25 | 2016-06-07 | Concentric Analgesics, Inc. | Prodrugs of phenolic TRPV1 agonists |
US10227333B2 (en) | 2015-02-11 | 2019-03-12 | Curtana Pharmaceuticals, Inc. | Inhibition of OLIG2 activity |
CA2977521C (en) | 2015-02-27 | 2024-03-19 | Curtana Pharmaceuticals, Inc. | 1-(aryl)-3-(heteroaryl) urea compounds and their use as olig2 inhibitors |
US20170209462A1 (en) | 2015-08-31 | 2017-07-27 | Pharmacyclics Llc | Btk inhibitor combinations for treating multiple myeloma |
WO2017074957A1 (en) | 2015-10-26 | 2017-05-04 | MAX BioPharma, Inc. | Oxysterols and hedgehog signaling |
US9637514B1 (en) | 2015-10-26 | 2017-05-02 | MAX BioPharma, Inc. | Oxysterols and hedgehog signaling |
US10851123B2 (en) | 2016-02-23 | 2020-12-01 | Concentric Analgesics, Inc. | Prodrugs of phenolic TRPV1 agonists |
CN116509869A (en) | 2016-04-04 | 2023-08-01 | 希诺皮亚生物科学公司 | Treatment of extrapyramidal syndrome with trapidil |
CA3024556A1 (en) | 2016-05-12 | 2017-11-16 | The Regents Of The University Of Michigan | Ash1l inhibitors and methods of treatment therewith |
JP2019516773A (en) | 2016-05-25 | 2019-06-20 | コンセントリック アナルジジックス,インク. | Prodrugs of phenol TRPV1 agonists in combination with local anesthetics and vasoconstrictors for improved local anesthesia |
WO2017205766A1 (en) | 2016-05-27 | 2017-11-30 | Pharmacyclics Llc | Inhibitors of interleukin-1 receptor-associated kinase |
WO2017205769A1 (en) | 2016-05-27 | 2017-11-30 | Pharmacyclics Llc | Inhibitors of interleukin-1 receptor-associated kinase |
WO2017205762A1 (en) | 2016-05-27 | 2017-11-30 | Pharmacyclics Llc | Inhibitors of interleukin-1 receptor-associated kinase |
JP7028860B2 (en) | 2016-08-26 | 2022-03-02 | カーテナ ファーマシューティカルズ,インク. | Inhibition of OLIG2 activity |
CN112739345A (en) | 2017-11-06 | 2021-04-30 | 斯奈普生物公司 | PIM kinase inhibitor compositions, methods and uses thereof |
US10632209B2 (en) | 2017-11-10 | 2020-04-28 | The Regents Of The University Of Michigan | ASH1L inhibitors and methods of treatment therewith |
WO2019113469A1 (en) | 2017-12-07 | 2019-06-13 | The Regents Of The University Of Michigan | Nsd family inhibitors and methods of treatment therewith |
US11685722B2 (en) | 2018-02-28 | 2023-06-27 | Curtana Pharmaceuticals, Inc. | Inhibition of Olig2 activity |
SI3774897T1 (en) | 2018-04-30 | 2024-01-31 | Cedars-Sinai Medical Center | Methods and systems for selection and treatment of patients with inflammatory diseases |
EP4155293A1 (en) | 2018-06-07 | 2023-03-29 | The Regents of The University of Michigan | Prc1 inhibitors and methods of treatment therewith |
EP3830078A4 (en) | 2018-07-27 | 2022-03-30 | Concentric Analgesics, Inc. | Pegylated prodrugs of phenolic trpv1 agonists |
US20200069742A1 (en) | 2018-08-29 | 2020-03-05 | Myos Rens Technology Inc. | Methods for alleviating, inhibiting or reversing muscle disuse atrophy in mammals |
US20200108102A1 (en) | 2018-10-03 | 2020-04-09 | Myos Rens Technology Inc. | Spray dried follistatin product |
WO2020096660A1 (en) | 2018-11-06 | 2020-05-14 | Myos Rens Technology, Inc. | Methods and compositions for improving skeletal muscle protein fractional synthetic rate |
SG11202106304RA (en) | 2018-12-31 | 2021-07-29 | Biomea Fusion Llc | Irreversible inhibitors of menin-mll interaction |
US11833186B2 (en) | 2019-02-01 | 2023-12-05 | Myos Corp. | Methods and compositions for improving quality of life and increasing activity in aging and chronically ill mammals |
US20220265630A1 (en) | 2019-03-15 | 2022-08-25 | Unicycive Therapeutics Inc. | Nicorandil derivatives |
JP2022533956A (en) | 2019-05-14 | 2022-07-27 | プロメテウス バイオサイエンシーズ,インク. | Methods, Systems, and Devices for Selecting TL1A Patients |
WO2020257710A1 (en) | 2019-06-21 | 2020-12-24 | Entelexo Biotherapeutics Inc. | Platforms, compositions, and methods for therapeutics delivery |
JP2023533982A (en) | 2020-07-10 | 2023-08-07 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | GAS41 inhibitor and method of use thereof |
WO2022133064A1 (en) | 2020-12-16 | 2022-06-23 | Biomea Fusion, Inc. | Fused pyrimidine compounds as inhibitors of menin-mll interaction |
CA3228627A1 (en) | 2021-08-11 | 2023-02-16 | Thomas Butler | Covalent inhibitors of menin-mll interaction for diabetes mellitus |
WO2023027966A1 (en) | 2021-08-24 | 2023-03-02 | Biomea Fusion, Inc. | Pyrazine compounds as irreversible inhibitors of flt3 |
WO2023039240A1 (en) | 2021-09-13 | 2023-03-16 | Biomea Fusion, Inc. | IRREVERSIBLE INHIBITORS OF KRas |
WO2023086341A1 (en) | 2021-11-09 | 2023-05-19 | Biomea Fusion, Inc. | Inhibitors of kras |
WO2023119230A1 (en) | 2021-12-22 | 2023-06-29 | L'oreal | Coagulation pathway and nicotinamide-adenine dinucleotide pathway modulating compositions and methods of their use |
TW202340177A (en) | 2021-12-30 | 2023-10-16 | 美商拜歐米富士恩股份有限公司 | Pyrazine compounds as inhibitors of flt3 |
WO2023235618A1 (en) | 2022-06-03 | 2023-12-07 | Biomea Fusion, Inc. | Fused pyrimidine compounds as inhibitors of menin |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5583105A (en) * | 1994-11-21 | 1996-12-10 | Biogal Gyogyszerguar Rt | Oral pharmaceutical preparation |
US5958876A (en) * | 1996-06-19 | 1999-09-28 | Novartis Ag | Cyclosporin-containing pharmaceutical compositions |
US5962019A (en) * | 1995-08-25 | 1999-10-05 | Sangstat Medical Corporation | Oral cyclosporin formulations |
US5965160A (en) * | 1995-04-24 | 1999-10-12 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Self-emulsifiable formulation producing an oil-in-water emulsion |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3406497A1 (en) | 1984-02-23 | 1985-09-05 | Mueller Bernhard Willi Werner | HIGHLY DISPERSAL PHARMACEUTICAL MULTI-COMPONENT SYSTEMS AND METHOD FOR THEIR PRODUCTION |
US5639724A (en) | 1984-07-24 | 1997-06-17 | Sandoz Ltd. | Cyclosporin galenic forms |
NL8601767A (en) | 1986-07-07 | 1988-02-01 | Schreuder Chem Adviesbureau | SKIN TANNING AGENT. |
US4943560A (en) | 1988-04-06 | 1990-07-24 | Regents Of The University Of Minnesota | Solvent system for chronic vascular infusion of hydrophobic drugs |
KR0148748B1 (en) | 1988-09-16 | 1998-08-17 | 장 크라메르, 한스 루돌프 하우스 | A multiphase cyclosporin composition |
US5294604A (en) | 1989-12-20 | 1994-03-15 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating ocular diseases by periocular administration of cyclosporine A or G |
IL102236A0 (en) | 1991-06-27 | 1993-01-14 | Ltt Inst Co Ltd | Topical preparations containing cyclosporin |
SK278290B6 (en) | 1992-09-07 | 1996-08-07 | Milan Stuchlik | Medicaments with n-methylated cyclic undecapeptides |
US5639474A (en) | 1993-07-01 | 1997-06-17 | Hanmi Pharm. Ind., Ltd. | Cyclosporin soft capsule composition |
NZ280689A (en) | 1995-12-15 | 1997-08-22 | Bernard Charles Sherma Sherman | Pharmaceutical composition comprising a cyclosporipharmaceutical composition comprising a cyclosporin; a tocol, tocopherol or tocotrienol; and propylen; a tocol, tocopherol or tocotrienol; and propylene carbonate or polyethylene glycol ne carbonate or polyethylene glycol |
JP4718653B2 (en) | 1997-03-12 | 2011-07-06 | アボツト・ラボラトリーズ | Hydrophilic two-component system for administration of cyclosporine |
US6063762A (en) | 1997-12-05 | 2000-05-16 | Chong Kun Dang Corp. | Cyclosporin-containing microemulsion preconcentrate composition |
ID25908A (en) | 1998-03-06 | 2000-11-09 | Novartis Ag | EMULSION PRACTONCENTRATES CONTAINING CYCLOSPORINE OR MACROLIDES |
-
2001
- 2001-08-31 US US09/943,687 patent/US6960563B2/en not_active Expired - Fee Related
-
2002
- 2002-08-29 AU AU2002356137A patent/AU2002356137B2/en not_active Expired - Fee Related
- 2002-08-29 WO PCT/US2002/027531 patent/WO2003017947A2/en not_active Application Discontinuation
- 2002-08-29 GB GB0405785A patent/GB2395902A/en not_active Withdrawn
- 2002-08-29 CA CA002458448A patent/CA2458448A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5583105A (en) * | 1994-11-21 | 1996-12-10 | Biogal Gyogyszerguar Rt | Oral pharmaceutical preparation |
US5965160A (en) * | 1995-04-24 | 1999-10-12 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Self-emulsifiable formulation producing an oil-in-water emulsion |
US5962019A (en) * | 1995-08-25 | 1999-10-05 | Sangstat Medical Corporation | Oral cyclosporin formulations |
US5958876A (en) * | 1996-06-19 | 1999-09-28 | Novartis Ag | Cyclosporin-containing pharmaceutical compositions |
Non-Patent Citations (1)
Title |
---|
LI ET AL.: 'The influence of oleic acid on the formation of a spontaneous emulsion' S.T.P. PHARMA SCIENCES vol. 10, no. 4, 2000, pages 341 - 344, XP002964569 * |
Also Published As
Publication number | Publication date |
---|---|
AU2002356137B2 (en) | 2007-02-15 |
US6960563B2 (en) | 2005-11-01 |
WO2003017947A3 (en) | 2004-01-29 |
GB0405785D0 (en) | 2004-04-21 |
CA2458448A1 (en) | 2003-03-06 |
GB2395902A (en) | 2004-06-09 |
US20030049280A1 (en) | 2003-03-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2002356137B2 (en) | Spontaneous emulsions containing cyclosporine | |
AU2002356137A1 (en) | Spontaneous emulsions containing cyclosporine | |
US5660858A (en) | Cyclosporin emulsions | |
JP3391961B2 (en) | Cyclosporin-containing soft capsule composition | |
NL194781C (en) | Pharmaceutical preparation for oral administration containing a cyclosporine. | |
US6432445B1 (en) | Pharmaceutical capsules comprising a cyclosporin | |
RU2279895C2 (en) | Pharmaceutical compositions for oral and topical using | |
US9278065B2 (en) | Delivery systems for solubilising water-insoluble pharmaceutical active ingredients | |
JP2002534370A (en) | Dispersible concentrate for delivering cyclosporin | |
CZ83498A3 (en) | Preparation containing cyclosporin and process for preparing thereof | |
WO2006123354A2 (en) | Oral pharmaceutical composition | |
WO2001054675A2 (en) | Pharmaceutical compositions comprising terbinafine | |
JP2002533401A (en) | Cyclosporine solution | |
KR100525234B1 (en) | Soft capsule containing cyclosporin and it's manufacturing process | |
KR100524700B1 (en) | Pharmaceutical compositions for Hyperlipidemia treatment using of Self Emulsifying drug delivery system | |
SK123299A3 (en) | Pharmaceutical compositions containing cyclosporin | |
KR19990047897A (en) | Cyclosporine-containing pharmaceutical composition |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG UZ VC VN YU ZA ZM ZW Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BY BZ CA CH CN CO CR CU CZ DE DM DZ EC EE ES FI GB GD GE GH HR HU ID IL IN IS JP KE KG KP KR LC LK LR LS LT LU LV MA MD MG MN MW MX MZ NO NZ OM PH PL PT RU SD SE SG SI SK SL TJ TM TN TR TZ UA UG UZ VC VN YU ZA ZM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG Kind code of ref document: A2 Designated state(s): GH GM KE LS MW MZ SD SL SZ UG ZM ZW AM AZ BY KG KZ RU TJ TM AT BE BG CH CY CZ DK EE ES FI FR GB GR IE IT LU MC PT SE SK TR BF BJ CF CG CI GA GN GQ GW ML MR NE SN TD TG |
|
ENP | Entry into the national phase |
Ref document number: 0405785 Country of ref document: GB Kind code of ref document: A Free format text: PCT FILING DATE = 20020829 |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2458448 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2002356137 Country of ref document: AU |
|
122 | Ep: pct application non-entry in european phase | ||
NENP | Non-entry into the national phase |
Ref country code: JP |
|
WWW | Wipo information: withdrawn in national office |
Country of ref document: JP |