WO2000032219A1 - A pharmaceutical composition comprising cyclosporin in a lipid carrier - Google Patents
A pharmaceutical composition comprising cyclosporin in a lipid carrier Download PDFInfo
- Publication number
- WO2000032219A1 WO2000032219A1 PCT/SE1999/002259 SE9902259W WO0032219A1 WO 2000032219 A1 WO2000032219 A1 WO 2000032219A1 SE 9902259 W SE9902259 W SE 9902259W WO 0032219 A1 WO0032219 A1 WO 0032219A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pharmaceutical composition
- cyclosporin
- lipids
- monoglycerides
- cyclosporine
- Prior art date
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—Liposomes
- A61K9/1274—Non-vesicle bilayer structures, e.g. liquid crystals, tubules, cubic phases, cochleates; Sponge phases
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Definitions
- the present invention refers to a new formulation of a cyclosporin for oral administration giving an improved uptake .
- Cyclosporins are a group of biologically active metabolites produced by different species of fung i imperfecti.
- the major components, cyclosporins A and C are non-polar cyclic oligopeptides with iiranunosuppressive, antifungal and antiphlogistic activity.
- the major use of cyclosporins is to prevent organ rejection after transplantation.
- Cyclosporin A is a cyclic oligopeptide consisting of 11 am no acids.
- the exact mechanism of action of cyclosporine is not known, but it is believed that the effect is due to a specific and reversible inhibition of immunocompetent lymphocytes .
- Cyclosporine is commercially available under the registered trade marks Sandimmun Neoral ® , Neoral ® or Sandi mune ® , as soft gelatin capsules, an oral solution or as a concentrate for injection. Said formulations all contain more than 10 % ethanol .
- Neoral ® , Neoral ® or Sandimmune ® from the gastro-intestinal tract is, however, incomplete and variable and it is recommended that transplant patients taking the soft gelatin capsules or the oral solution over a period of time are monitored .at repeated intervals for cyclosporine blood levels to avoid toxicity due to high levels, and possible organ rejection due to low absorption, respectively.
- Prior art US 4,388,307 refers to a pharmaceutical composition
- a pharmaceutical composition comprising a pharmacologically effective amount of a cyclosporin and a carrier, wherein the carrier comprises a) a transesterification product of a natural vegetable oil, b) a vegetable oil, and c) ethanol.
- Said composition could be formulated as a drink solution or as capsules for oral administration.
- the use of ethanol is, however, not desirable and may also cause difficulties when the composition is presented in soft gelatin encapsulated form.
- a carrier medium for a cyclosporin which comprises b) a fatty acid trigly- ceride, c) a glycerol fatty acid partial ester or propylene glycol or sorbitol complete or partial ester, and d) a tenside having a hydrophilic-lipophilic balance (HLB) of at least 10.
- HLB hydrophilic-lipophilic balance
- compositions obtained are said to provide a reduced variability in cyclosporine blood levels. It is, however, a well known fact that -ethoxylated surfactants might be the cause of allergenic reactions, partly because of oxidation when exposed to air, and thus should be avoided in medical treatment .
- Lipophilic carrier systems have also been described, WO 95/20945 for instance discloses a lipophilic carrier preparation having a continuous lipid phase comprising a polar lipid material in combination with a non-polar lipid.
- the polar lipid material should be a galactolipid material consisting of at least 50 % digalactosyldiacylglycerols and a remainder of other polar lipids .
- a preparation of a lipophilic carrier containing 5 % cyclosporin A, in combination with a galactolipid material and evening primrose oil is disclosed.
- Said galactolipid material had been obtained by an industrially applicable process for preparing glycosylglycerides from plants, preferably cereals, by means of extraction and chro atographic separations.
- WO 92/05771 describes a lipid particle forming matrix of at least two lipid components; one is non-polar and another is amphiphatic and polar.
- This particle forming matrix which can contain bioactive materials, spontaneously forms discrete lipid particles when interacting with aqueous systems.
- the amphiphatic and polar lipid components are said to be bilayer forming and are chosen from phospholipids such as phosphati- dylcholine; the non-polar lipids are mono-, di- or triglycerides .
- a formulation of a cyclosporin in a lipid carrier consisting of a fractionated vegetable oil in combination with monoglycerides and non- polar lipids will give an uptake of the cyclosporin in blood which is bioequivalent to the uptake of cyclosporin from a commercial drug containing in addition to cyclosporin and additives also toxic emulsifiers and ethanol.
- a standard bioequivalence can be defined as a range of 80% to 120% of the product averages for a broad range of drugs (USP 24 NF 19, 2058) .
- the present invention refers to a new pharmaceutical composition
- a cyclosporin as an active substance in a lipid carrier, which carrier comprises membrane lipids in combination with monoglycerides and optionally non-polar lipids, which is characterized in being liquid at room temperature and containing the following in % by weight of the total composition cyclosporin 0.5-25 % membrane lipids 10-45 % monoglycerides 10-55 % non-polar lipids 0-45 %
- the invention especially refers to a pharmaceutical composition wherein the lipid carrier contains 15-20 % membrane lipids, 25-50 % monoglycerides and 5-30 % non-polar lipids.
- the lipid carrier of the pharmaceutical composition contains 15-45 % membrane lipids and 25-50 % monoglycerides.
- Membrane lipids preferably natural membrane lipids for the sake of biocompatibility and safety, which are all polar lipids, can broadly be defined as belonging to any of the categories phospholipids, glycolipids and sphingolipids .
- Phospholipids mainly soy or egg lecithin derived from soybeans and egg respectively, or made by synthetic routes contain different phospholipid classes, which can be zwitter- ionic, such as phospha idylcholine and phosphatidyl- ethanolamine classes, or negatively charged, such as phosphatidylinositol or phosphatidylglycerol classes.
- Glycolipids from plants contain glycolipids which have carbohydrate units, mainly of galactose, linked to glycerol .
- Glycosylglycerides are a type of glycolipids which are well- known constituents of plant cell membranes.
- the most important classes of these contain one to four sugars linked glycosidically to diacylglycerol .
- the two most abundant classes contain one and two galactose units, respectively, and are commonly known as mono- and digalactosyldiacyl- glycerol, MGDG and DGDG representing up to 40 % of the dry weight of the thylakoid membranes.
- Galactolipids primarily DGDG and DGDG-rich materials, have been investigated and found to be a surface active material of interest in industrial application such as food, cosmetics, and pharmaceutical applications .
- Synthetic diglycosyldiacylglycerols based on galactose or any other monosaccharide unit, such as glucose, and natural glycosylglycerides, isolated from any source, based on other carbohydrate units than galactose, such as glucose, can be used in accordance with the invention.
- galactolipids comprising the polar head group in each lipid molecule, which may sterically stabilise the emulsion droplets in an emulsion.
- the galactose groups may also interact strongly with water and other polar substances, such as a water-soluble drug or an excipient, added to the emulsion.
- the membrane lipids of the pharmaceutical composition contain phospholipids and galactolipids.
- the membrane lipids of the pharmaceutical composition contain DGDG in admixture with phosphatidylchcline .
- Galactolipids can be prepared from almost any kind of plant material, for instance according to WO 95/20945 by extraction of the lipids with ethanol and a subsequent purification on a chromatographic column.
- Preferred plant materials are seeds and kernels from grains and cereals, for instance wheat, rye, oats, and barley. Oat groats as well as wheat gluten have a high lipid concentration and are therefore of advantage to use in the preparation process .
- a galactolipid material consisting of 50-70 % digalactosyl- diacylglycerols and 30-50 % other polar lipids is manufactured by Ontario LipidTeknik AB, Sweden, as CPL ® - Galactolipid (registered trade mark owned by Ontario Holdings PLC) .
- the other polar lipids being part of said galactolipid material are a mixture of different glyco- and phospholipids, such as MGDG and phosphatidylcholines .
- WO 97/11141 describes a method for producing a fraction- ated vegetable oil which is characterised in containing 10-90 % by weight of polar lipids, preferably 20-75 %, and a remainder of non-polar lipids .
- Said fractionated vegetable oil contains galactolipids and can also be used for providing the membrane lipids of the invention.
- the fractionated vegetable oil preferably contains more than 5 % by weight, preferably more than 20 %, glycolipids and preferably more than 3 % by weight, preferably more than 15 %, DGDG.
- the fractionated oil is oat oil consisting of 40-60 % polar lipids and a remainder of non-polar lipids.
- the composition depends on the starting material and process used for the manufacture of the galactolipids.
- a fractionated oat oil of this composition consisting of a wide range of polar and amphiphilic lipids in a continuous triglyceride phase is manufactured by Ontario LipidTeknik AB, Sweden, as GalactolecTM, and is also referred to as galactolecithin.
- Sphingolipids can be obtained from milk raw materials by extraction and purification, for instance by chromatography, and contain for example sphingo yelin in combination with phosphatidylcholine, mono- and dihexocylceramides and triglycerides.
- Sphingolipids are a family of lipids based on sphingosine in contrast to the ones previously described which are based on glycerol .
- Examples of sphingolipids are sphingomyelin, mono- and dihexosylceramides, and gangliosides .
- the membrane lipids should contain DGDG in an amount of 0.1 - 90 % by weight based on the membrane lipids, preferably 10 - 70
- Monoglycerides or monoacylglycerols are slightly polar in nature and possess certain surface active properties. They can be obtained by fractionation of vegetable or animal oils. Preferred monoglycerides of the invention are of a medium chain length, that is having a fatty acid chain of 8-12 carbon atoms, especially 8-10 carbon atoms, and can be obtained from coconut and palm kernel oil .
- Non-polar lipids are for example natural or synthetic di- or triacylglycerols, such as, or derived from, vegetable oils, animal oils, synthetic glycerides, fatty acids, fatty alcohols, sterols, such as cholesterol, and their esters with fatty acids.
- the chain length and the degree of saturation of the glycerides should be chosen to give a liquid composition.
- the non-polar lipids of the pharmaceutical composition comprises mainly triacylglycerols .
- the invention especially refers to a pharmaceutical composition of cyclosporine in a lipid carrier comprising a mixture of a fractionated vegetable oil and monoglycerides .
- a preferred composition of the invention comprises, in % by weight of the total composition, 8-12 % cyclosporin, 40-50 % galactolecithin, and 40-50 % MCM, that is C8-C10 monoacyl- glycerols.
- a pharmaceutical composition of the invention preferably comprises cyclosporin A, that is cyclosporine.
- a pharmaceutical composition of the invention can be prepared by mixing, optionally after melting in an open water bath at a temperature range of 40-70°C, non-polar lipids, such as triglycerides, and the monoglycerides with a cyclosporin and the membrane lipids in a vial .
- the mixture is then dispersed with a high shear mixer at approximately 1000 rpm and at a temperature range of 40-70°G for 2-4 min.
- the mixture can optionally contain increasing contents of water or aqueous solution which can lead to the formation of reverse vesicles, reverse micelles or a water-in-oil emulsion. If the lipid mixture is hard to melt or if the content of cyclosporin is high it might be necessary first to dissolve the mixture in ethanol, which is subsequently evaporated.
- the pharmaceutical composition is mainly intended for oral administration, but can also be used for enteral, rectal, vaginal, topical, ocular, nasal or aural administration to animals, especially mammals, including humans.
- the pharmaceutical composition of the invention can also contain conventional additives and excipients, such as antiseptic agents, preservatives, thickening agents, pigments, flavouring and the like, in combinations as needed.
- Oral unit dosage forms such as soft or hard gelatin capsules, can comprise from 5 to 200 mg, preferably from 20 to 100 mg of active substance, that is a cyclosporin, for administration 1-5 times a day.
- the membrane lipid material used in the following examples was a galactolipid material, GalactolecTM (from Ontario LipidTeknik AB, Sweden) , manufactured from oats in accordance with the process described in WO 97/11141 and referred to as galactolecithin.
- Said galactolecithin is composed by about 60 % non-polar lipids and about 40 % polar lipids.
- DGDG constitutes about 20 % by weight of the total mixture .
- cyclosporin A USP XXIII, Medial AG, Switzerland
- a formulation in accordance with WO 95/20945 was prepared by mixing the following ingredients I- g-rfidi-e-n-t -k-b-y weig-ht-
- Cyclosporine 12.50 GL refers to a galactolipid material, CPL ® -Galactolipid (from Ontario LipidTeknik AB, Sweden) , containing about 60 % DGDG, manufactured from oats in accordance with the process described in WO 95/20945.
- EPO stands for evening primrose oil (from Ontario Pharmaceuticals Ltd, UK)
- AP stands for ascorbyl palmitate.
- G-lec galactolecithin, GalactolecTM
- GL galactolipid material
- CPL ® -Galactolipid h-GL hydrogenated galactolipid material
- SL sphingolipid material
- h-PE hydrogenated phosphatidylethanolamine
- MCT medium chain triacylglycerol , from Karlshamns AB
- a MCM Akoline MCM
- CH cholesterol, from Apoteksbolaget AB
- PC phosphatidylcholine, from Lucas Meyer SL, h-GL and h-PE were obtained from Ontario LipidTeknik AB .
- Soy bean oil is a long-chain C16-C20 triglyceride, CPL ® - Soybean oil from Ontario LipidTeknik AB .
- the biological absorption studies were performed in healthy male volunteers.
- the exclusion criteria were known intolerance to cyclosporine, deviations of clinical relevance, blood donor in the last two months, medical treatment which might interfere with the tests, smoking.
- the studies were of an open, cross-over design where the majority of the subjects received two treatments after one reference treatment, that is each subject was its own control.
- Each formulation was tested on three subjects and there were also three subjects who only received the reference composition on all occasions in order to estimate the intraindividual variation.
- the amount of cyclosporine was the same in all treatments .
- the intraindividual variation of Sandimmun eoral ® based on 3 subjects at 3 different observations was 15 %.
- the interindividual variation, that is the variation in uptake of Sandimmun Neoral ® after administration once only to 18 different subjects was 21 %.
- the concentration of the active substance cyclosporine in blood was assessed by a specific method at the Clinical Chemistry laboratory, University Hospital, Lund. Cyclosporine analysis was performed on a Hitachi 917, using an EMIT- (Enzyme Multiple Immunoassay Technique) kit from DADE Behring .
- Example 1 in duplicate
- Example 3 according to the invention were tested, as well as the formulation of Comparative Example 1 and the formulations of Examples 7-14.
- compositions of Examples 1, 4 and 5 can be considered to be bioequivalent to the commercial drug Sandimmun Neoral ® , as having a relative uptake >80 %. It should be noted that said compositions according to the invention do not contain any harmful additives, but only non-toxic lipids.
- Monoglycerides are of importance for the uptake. From Examples 3, 8, 10 and also 9, having a monoglyceride content below 10 %, can be concluded that too low a content of monoglycerides will negatively affect the uptake. This is also true if the content of monoglycerides is too high;
- Example 2 has a monoglyceride content of 60 %, bringing about a high viscosity and a poor uptake.
- Example 12 and Comparative Example 1 both contain too much triglycerides to give an adequate uptake.
- Example 5 The improved variation of the composition of Example 5 compared to the composition of Example 4 is believed to derive from the defined monoglyceride fraction used in Example 5, alternatively on the low content of diglycerides .
- the number of tests is, however, not sufficient for a statistical confirmation thereof.
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000584910A JP2002531412A (en) | 1998-12-03 | 1999-12-03 | Pharmaceutical composition comprising cyclosporin in a lipid carrier |
AU20167/00A AU764413B2 (en) | 1998-12-03 | 1999-12-03 | A pharmaceutical composition comprising cyclosporin in a lipid carrier |
EP99963798A EP1135152A1 (en) | 1998-12-03 | 1999-12-03 | A pharmaceutical composition comprising cyclosporin in a lipid carrier |
PL99348062A PL348062A1 (en) | 1998-12-03 | 1999-12-03 | A pharmaceutical composition comprising cyclosporin in a lipid carrier |
NZ512194A NZ512194A (en) | 1998-12-03 | 1999-12-03 | A pharmaceutical composition comprising cyclosporin in a lipid carrier |
CA002352388A CA2352388A1 (en) | 1998-12-03 | 1999-12-03 | A pharmaceutical composition comprising cyclosporin in a lipid carrier |
NO20012736A NO20012736L (en) | 1998-12-03 | 2001-06-01 | Pharmaceutical composition comprising cyclosporin in a lipid carrier |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9804192-4 | 1998-12-03 | ||
SE9804192A SE9804192D0 (en) | 1998-12-03 | 1998-12-03 | New formulation |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000032219A1 true WO2000032219A1 (en) | 2000-06-08 |
Family
ID=20413540
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE1999/002259 WO2000032219A1 (en) | 1998-12-03 | 1999-12-03 | A pharmaceutical composition comprising cyclosporin in a lipid carrier |
Country Status (10)
Country | Link |
---|---|
EP (1) | EP1135152A1 (en) |
JP (1) | JP2002531412A (en) |
AU (1) | AU764413B2 (en) |
CA (1) | CA2352388A1 (en) |
HU (1) | HUP0105399A3 (en) |
NO (1) | NO20012736L (en) |
NZ (1) | NZ512194A (en) |
PL (1) | PL348062A1 (en) |
SE (1) | SE9804192D0 (en) |
WO (1) | WO2000032219A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005051354A1 (en) * | 2003-11-25 | 2005-06-09 | Ltp Lipid Technologies Provider Ab | Controlled food effect composition |
JP2005520816A (en) * | 2002-02-15 | 2005-07-14 | エルティーピー リピッド テクノロジーズ プロバイダー アクチェボラグ | Composition for oral or rectal administration |
WO2005079860A1 (en) * | 2004-02-24 | 2005-09-01 | Lipopeptide Ab | New complexes |
WO2006115463A1 (en) * | 2005-04-28 | 2006-11-02 | Galenica Technology Ab | Pharmaceutical dosage forms comprising a lipid phase |
WO2012144943A1 (en) * | 2011-04-18 | 2012-10-26 | Lipidor Ab | Liquid carrier for oral delivery of a pharmacologically active agent |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050058671A1 (en) * | 2003-05-09 | 2005-03-17 | Bedding Peter M.J. | Dietary supplement and method for treating digestive system-related disorders |
WO2014103742A1 (en) * | 2012-12-25 | 2014-07-03 | ポーラ化成工業株式会社 | Reverse vesicle composition and method for producing same |
JP6242582B2 (en) * | 2013-04-01 | 2017-12-06 | ポーラ化成工業株式会社 | Method for producing reverse vesicle composition |
JP6334151B2 (en) * | 2012-12-25 | 2018-05-30 | ポーラ化成工業株式会社 | Reverse vesicle composition |
JP6242581B2 (en) * | 2013-04-01 | 2017-12-06 | ポーラ化成工業株式会社 | Method for producing reverse vesicle composition |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2222770A (en) * | 1988-09-16 | 1990-03-21 | Sandoz Ltd | Cyclosporin emulsion compositions |
WO1995020945A1 (en) * | 1994-02-04 | 1995-08-10 | Scotia Lipidteknik Ab | Lipophilic carrier preparations |
WO1996013273A1 (en) * | 1994-10-26 | 1996-05-09 | Novartis Ag | Pharmaceutical compositions |
US5529785A (en) * | 1993-05-12 | 1996-06-25 | Dietl; Hans | Pharmaceutical preparation containing cyclosporin(s) for oral administration and process for producing same |
WO1998036735A1 (en) * | 1997-02-20 | 1998-08-27 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. Spa | Aqueous pharmaceutical composition comprising an active ingredient which is highly insoluble in water |
WO1999000002A2 (en) * | 1997-12-05 | 1999-01-07 | Chong Kun Dang Corp. | Cyclosporin-containing microemulsion preconcentrate composition |
-
1998
- 1998-12-03 SE SE9804192A patent/SE9804192D0/en unknown
-
1999
- 1999-12-03 HU HU0105399A patent/HUP0105399A3/en unknown
- 1999-12-03 WO PCT/SE1999/002259 patent/WO2000032219A1/en not_active Application Discontinuation
- 1999-12-03 AU AU20167/00A patent/AU764413B2/en not_active Ceased
- 1999-12-03 NZ NZ512194A patent/NZ512194A/en unknown
- 1999-12-03 CA CA002352388A patent/CA2352388A1/en not_active Abandoned
- 1999-12-03 PL PL99348062A patent/PL348062A1/en not_active Application Discontinuation
- 1999-12-03 JP JP2000584910A patent/JP2002531412A/en active Pending
- 1999-12-03 EP EP99963798A patent/EP1135152A1/en not_active Withdrawn
-
2001
- 2001-06-01 NO NO20012736A patent/NO20012736L/en not_active Application Discontinuation
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2222770A (en) * | 1988-09-16 | 1990-03-21 | Sandoz Ltd | Cyclosporin emulsion compositions |
US5529785A (en) * | 1993-05-12 | 1996-06-25 | Dietl; Hans | Pharmaceutical preparation containing cyclosporin(s) for oral administration and process for producing same |
WO1995020945A1 (en) * | 1994-02-04 | 1995-08-10 | Scotia Lipidteknik Ab | Lipophilic carrier preparations |
WO1996013273A1 (en) * | 1994-10-26 | 1996-05-09 | Novartis Ag | Pharmaceutical compositions |
WO1998036735A1 (en) * | 1997-02-20 | 1998-08-27 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. Spa | Aqueous pharmaceutical composition comprising an active ingredient which is highly insoluble in water |
WO1999000002A2 (en) * | 1997-12-05 | 1999-01-07 | Chong Kun Dang Corp. | Cyclosporin-containing microemulsion preconcentrate composition |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005520816A (en) * | 2002-02-15 | 2005-07-14 | エルティーピー リピッド テクノロジーズ プロバイダー アクチェボラグ | Composition for oral or rectal administration |
WO2005051354A1 (en) * | 2003-11-25 | 2005-06-09 | Ltp Lipid Technologies Provider Ab | Controlled food effect composition |
WO2005079860A1 (en) * | 2004-02-24 | 2005-09-01 | Lipopeptide Ab | New complexes |
WO2006115463A1 (en) * | 2005-04-28 | 2006-11-02 | Galenica Technology Ab | Pharmaceutical dosage forms comprising a lipid phase |
EA012882B1 (en) * | 2005-04-28 | 2009-12-30 | ДСМ АйПи ЭССЕТС Б.В. | Pharmaceutical dosage forms comprising a lipid phase |
WO2012144943A1 (en) * | 2011-04-18 | 2012-10-26 | Lipidor Ab | Liquid carrier for oral delivery of a pharmacologically active agent |
Also Published As
Publication number | Publication date |
---|---|
EP1135152A1 (en) | 2001-09-26 |
JP2002531412A (en) | 2002-09-24 |
NZ512194A (en) | 2002-09-27 |
NO20012736D0 (en) | 2001-06-01 |
NO20012736L (en) | 2001-06-01 |
CA2352388A1 (en) | 2000-06-08 |
PL348062A1 (en) | 2002-05-06 |
AU764413B2 (en) | 2003-08-21 |
AU2016700A (en) | 2000-06-19 |
HUP0105399A3 (en) | 2005-06-28 |
SE9804192D0 (en) | 1998-12-03 |
HUP0105399A2 (en) | 2002-06-29 |
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