Method of Treating Disorders using a Pharmaceutical Composition of Oligopeptides

Patent metadata

Field	Value
Publication number	US-2016228551-A1
Application number	US-201214122956-A
Country	US
Kind code	A1
Filing date	May 16, 2012
Priority date	Jun 9, 2011
Publication date	Aug 11, 2016
Grant date	—

Abstract

The present invention relates to a pharmaceutical composition of oligopeptides, preferably cyclic oligopeptides, said composition further comprising one or more lipophilic and/or amphiphilic compounds, in the presence or absence of water as the main ingredients, the use of the lipophilic and/or amphiphilic compounds for making pharmaceutical compositions of said oligopeptides, and methods of making said pharmaceutical composition.

First claim

1 .- 41 . (canceled)

42 . A method for treating disorders, said method comprising administering to a subject a composition, wherein said composition comprises:
a) 7 to 80% or 12 to 90% of at least one oligopeptide, said oligopeptide having a solubility in water at 20° C. between 1 mg/ml and 20 mg/ml, b) 0.01 to 60% of one or more lipophilic and/or amphiphilic compounds having a molar weight in the range of 200 g/mol to 2000 g/mol, and optionally c) 0 to 89% of water, with the proviso that the sum of a), b) and c) sums up to 40 or more % of the total composition.

43 . A method according to claim 42 , wherein said composition is a pharmaceutical composition.

44 . A method according to claim 42 , wherein said subject is from the group consisting of a mammalian and a human.

45 . The method as claimed in claim 42 , wherein in said composition at least one of the lipophilic and/or amphiphilic compounds according to b) comprises
α) a glycerol moiety, β) one or more fatty acid moieties, and/or γ) one or more fatty alcohol moieties.

46 . The method as claimed in claim 42 , wherein in said composition at least one of the amphiphilic compounds according to b) comprises a hydrophilic moiety.

47 . A method according to claim 46 , wherein in said composition the hydrophilic moiety comprises an ethanolamine moiety, a choline moiety, a phosphatidyl moiety and/or a sulfatidyl moiety, and/or a salt thereof.

48 . The method as claimed in claim 46 , wherein in said composition the hydrophilic moiety comprises an phosphoethanolamine moiety, a phosphatidylcholine moiety, a phosphatidylglycerol moiety and/or a sulfatidylglycerol moiety, and/or a salt thereof.

49 . The method as claimed in claim 47 , wherein in said composition the hydrophilic moiety comprises an phosphoethanolamine moiety, a phosphatidylcholine moiety, a phosphatidylglycerol moiety and/or a sulfatidylglycerol moiety, and/or a salt thereof.

50 . The method according to claim 42 , wherein in said composition the at least one lipophilic compounds according to b) comprise one or more compounds selected from natural oils and synthetic oils, and mixtures thereof, and/or wherein the at least one amphiphilic compounds according to b) comprise one or more compounds selected from amphiphilic lipids having phosphatidyl-polyol or sulfatidyl-polyol groups as the hydrophilic part, and derivatives, salts and/or alcoholates thereof.

51 . The method according to claim 42 , wherein said composition comprises
a) 7 to 79.99% of at least one oligopeptide, b) 0.01 to 20% of one or more amphiphilic compounds, c) 20 to 92.9% of water, with the proviso that the sum of a), b) and c) sums up to 90 or more % of the total composition.

52 . A method for treating disorders, said method comprising administering to a subject a pharmaceutical composition, said composition comprising:
a) 12 to 79.99% of at least one oligopeptide, b) 0.01 to 60% of one or more amphiphilic compounds, selected from b1) fatty acid mono-, di- or polyesters of phosphatidyl- or sulfatidyl-polyoles, and derivatives, salts and/or alcoholates thereof, and b2) fatty alcohol mono-, di- or polyethers of phosphatidyl- or sulfatidyl-polyoles, and derivatives, salts and/or alcoholates thereof, c) 20 to 89.9% of water, with the proviso that the sum of a), b) and c) sums up to 40 or more % of the total weight of the composition.

53 . The method according to claim 50 , wherein in said composition the phosphatidyl- or sulfatidyl-polyoles are selected from
a) polyphosphatidylglycerol, triphosphatidylglycerol, diphosphatidylglycerol, monophosphatidylglycerol, and/or b) polysulfatidylglycerol, trisulfatidylglycerol, disulfatidylglycerol, and monosulfatidylglycerol.

54 . The method according to claim 52 , wherein in said composition the phosphatidyl- or sulfatidyl-polyoles are selected from:
a) polyphosphatidylglycerol, triphosphatidylglycerol, diphosphatidylglycerol, monophosphatidylglycerol, and/or b) polysulfatidylglycerol, trisulfatidylglycerol, disulfatidylglycerol, and monosulfatidylglycerol.

55 . The method according to claim 42 , wherein in said composition:
i) the fatty acids are independently selected from the group consisting of oleic acid, myristic acid, palmitic acid, stearic acid, margaric acid, arachic acid, behenic acid, erucic acid, linolic acid and linolenic acid, and ii) the fatty alcohols are independently selected from the group consisting of oleic alcohol, myristic alcohol, palmitic alcohol, stearic alcohol, margaric alcohol, arachic alcohol, behenic alcohol, erucic alcohol, linolic alcohol and linolenic alcohol, iii) the fatty acid moieties are independently selected from the acyl residues of the fatty acids according to i), and/or iv) the fatty alcohol moieties are independently selected from the alkyl residues of the fatty alkohols according to ii).

56 . The method according to claim 42 , wherein, in said composition the amphiphilic compounds and/or the fatty acid di- or polyesters of polyphosphatidyl-polyoles are selected from the group consisting of dioleoylphosphatidylglycerol, dimyristoylphosphatidylglycerol, dimyristoylphosphatidylcholine, distearoylphosphatidylglycerol, dioleoylglycerophosphocholine, dipalmitoylglycerophosphoglycerol, distearoylglycerophosphoethanolamine, egg phosphatidylcholine and soy phosphatidylcholine, and the pharmaceutically acceptable derivatives, salts and/or alcoholates thereof.

57 . The method according to claim 42 , wherein, in said composition the amphiphilic compounds and/or the fatty acid di- or polyesters of polyphosphatidyl-polyoles are selected from the group consisting of dioleoylphosphatidylglycerol and dimyristoylphosphatidylglycerol, and the pharmaceutically acceptable derivatives, salts and/or alcoholates thereof.

58 . The method according to claim 42 , wherein, said composition additionally comprises:
d) 0 to 50% of one or more compounds other than a), b) and c), selected from: d1) pharmaceutically active ingredients, d2) pharmaceutically acceptable excipients.

59 . The method according to claim 42 , wherein, said composition further comprises, 0 to 10% of one or more compounds other than a), b) and c), selected from pharmaceutically excipients.

60 . The method according to claim 42 , wherein, in said composition at least 10% of the contained oligopeptide according to a) is present in the composition in a suspended or suspendable solid form at a temperature of 20° C.

61 . The method according to claim 42 , wherein, in said composition the oligopeptide is a cyclic oligopeptide and/or an oligopeptide that comprises the Arg-Gly-Asp-subsequence.

62 . The method according to claim 42 , wherein, the oligopeptide or cyclic oligopeptide in said composition is selected from the group consisting of cyclo-(Arg-Gly-Asp-DPhe-NMeVal), cyclo-(Arg-Gly-Asp-DPhe-Val),
and the pharmaceutically acceptable derivatives, solvates and/or salts thereof.

63 . The method according to claim 42 , wherein, in said composition the oligopeptide or cyclic oligopeptide is selected from the group consisting of cyclo-(Arg-Gly-Asp-DPhe-NMeVal) and the pharmaceutically acceptable derivatives, solvates and/or salts thereof having a solubility in water at 20° C. between 1 mg/ml and 15 mg/ml.

64 . The method according to claim 42 , wherein the oligopeptide or cyclic oligopeptide contained in said composition comprises solid cyclo-(Arg-Gly-Asp-DPhe-NMeVal) in a polymor

Assignees

• Goodman Simon
• Amendt Christiane
• Eber Marcus
• Merck Patent Gmbh

Inventors

• Goodman Simon
• Amendt Christiane
• Eber Marcus

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61K9/14

  Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K38/12

  Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K9/1611

  Inorganic compounds · CPC title