US 8,802,087 B2Granted

Pharmaceutical compositions of lipase-containing products, in particular of pancreation

AssigneeAbbott Products GmbH

InventorsGeorge Shlieout, Bernd Boedecker, Siegfried Schaefer, Bernd Thumbeck, Peter-Colin Gregory

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Abstract

Orally administrable pharmaceutical compositions of lipase-containing products, particularly pancreatin and pancreatin-containing products, or of enzyme products which contain at least one lipase of non-animal, especially microbial origin, which improve the lipolytic activity and particularly result in stabilization of the lipase in the acidic pH range. These oral pharmaceutical compositions contain a system which includes at least one surfactant and one co-surfactant and optionally a lipophilic phase, and are self-emulsifiable on contact with a hydrophilic and a lipophilic phase. The compositions according to the invention are suitable for treating or inhibiting maldigestion, especially maldigestion due to chronic exocrine pancreatic insufficiency, in mammals and humans.

Claims43

Dependent claims

A pharmaceutical composition for oral administration as a solid dosage form, comprising an active pharmaceutical agent and a surfactant system, which is self-emulsifiable on contact with a hydrophilic phase and a lipophilic phase, said composition comprising:

(i) an active pharmaceutical agent which
(a) is an enzyme or an enzyme mixture with at least lipolytic activity which exerts its action in the gastrointestinal tract, and
(b) is admixed with a surfactant system to form the pharmaceutical composition wherein the pharmaceutical composition does not contain an enteric coating and does not contain any lipophilic active substances to be absorbed into the bloodstream;
and
(ii) wherein the surfactant system comprises
a. a surfactant in an amount of 2% to 90% by weight of the surfactant system selected from either a first group or an ionic surfactant, wherein the first group consists of:
polyethylene glycol fatty acid mono-esters and/or di-esters with aliphatic C6-C22 carboxylic acids;
polyethylene glycol glycerol fatty acid esters with aliphatic C6-C22 carboxylic acids;
polyethylene glycol alkyl mono-ethers and/or di-ethers with aliphatic C12-C18 alcohols, and mixtures of the foregoing;
and wherein the ionic surfactant is selected from the group consisting of:
lecithin, lysolecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylglycerol, lysophosphatidylinositol, lysophosphatidic acid, lysophosphatidylserine, and mixtures of the foregoing;
b. a co-surfactant in an amount of 5% to 60% by weight of the surfactant system, selected from a group consisting of monoacylglycerides with aliphatic C6-C22 carboxylic acids, monoethers of glycerol ethers with aliphatic C12-C18 alcohols, partial esters of propylenglycol with aliphatic C6-C22 carboxylic acids, partial esters of polyglycerol with aliphatic C6-C22 carboxylic acids, and mixtures of the foregoing;
and
c. a lipophilic phase in an amount of 0% to 70% by weight of the surfactant system, represented by diacylglyerides and/or triacylglycerides with aliphatic C6-C22 carboxylic acids;
wherein the surfactant system comprises 10% to 95% by weight of the pharmaceutical composition.

12 more elements

A method of orally administering a pharmaceutical composition as a solid oral dosage form which is self-emulsifying on contact with a hydrophilic phase and a lipophilic phase comprising the step of:

orally administering a pharmaceutical composition comprising:
(i) an active pharmaceutical agent which
(a) is an enzyme or an enzyme mixture with at least lipolytic activity which exerts its action in the gastrointestinal tract, and
(b) is admixed with a surfactant system to form the pharmaceutical composition wherein the pharmaceutical composition does not contain an enteric coating and does not contain any lipophilic active substances to be absorbed into the bloodstream;
and
(ii) wherein the surfactant system comprises
a. a surfactant in an amount of 2% to 90% by weight of the surfactant system selected from either a first group or an ionic surfactant, wherein the first group consists of:
polyethylene glycol fatty acid mono-esters and/or di-esters with aliphatic C6-C22 carboxylic acids;
polyethylene glycol glycerol fatty acid esters with aliphatic C6-C22 carboxylic acids;
polyethylene glycol alkyl mono-ethers and/or di-ethers with aliphatic C12-C18 alcohols, and mixtures of the foregoing;
and wherein the ionic surfactant is selected from the group consisting of:
lecithin, lysolecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylglycerol, lysophosphatidylinositol, lysophosphatidic acid, lysophosphatidylserine, and mixtures of the foregoing;
b. a co-surfactant in an amount of 5% to 60% by weight of the surfactant system, selected from a group consisting of monoacylglycerides with aliphatic C6-C22 carboxylic acids, monoethers of glycerol ethers with aliphatic C12-C18 alcohols, partial esters of propylenglycol with aliphatic C6-C22 carboxylic acids, partial esters of polyglycerol with aliphatic C6-C22 carboxylic acids, and mixtures of the foregoing;
and
c. a lipophilic phase in an amount of 0% to 70% by weight of the surfactant system, represented by diacylglyerides and/or triacylglycerides with aliphatic C6-C22 carboxylic acids;
wherein the surfactant system comprises 10% to 95% by weight of the pharmaceutical composition.

13 more elements

A pharmaceutical composition prepared by a process comprising the step of:

combining
(i) an active pharmaceutical agent which
(a) is an enzyme or an enzyme mixture with at least lipolytic activity which exerts its action in the gastrointestinal tract,
(b) with a surfactant system to form the pharmaceutical composition wherein the pharmaceutical composition does not contain an enteric coating and does not contain any lipophilic active substances to be absorbed into the bloodstream;
and
(ii) wherein the surfactant system comprises
a. a surfactant in an amount of 2% to 90% by weight of the surfactant system selected from either a first group or an ionic surfactant, wherein the first group consists of:
polyethylene glycol fatty acid mono-esters and/or di-esters with aliphatic C6-C22 carboxylic acids;
polyethylene glycol glycerol fatty acid esters with aliphatic C6-C22 carboxylic acids;
polyethylene glycol alkyl mono-ethers and/or di-ethers with aliphatic C12-C18 alcohols, and mixtures of the foregoing;
and wherein the ionic surfactant is selected from the group consisting of:
lecithin, lysolecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylglycerol, lysophosphatidylinositol, lysophosphatidic acid, lysophosphatidylserine, and mixtures of the foregoing;
b. a co-surfactant in an amount of 5% to 60% by weight of the surfactant system, selected from a group consisting of monoacylglycerides with aliphatic C6-C22 carboxylic acids, monoethers of glycerol ethers with aliphatic C12-C18 alcohols, partial esters of propylenglycol with aliphatic C6-C22 carboxylic acids, partial esters of polyglycerol with aliphatic C6-C22 carboxylic acids, and mixtures of the foregoing;
and
c. a lipophilic phase in an amount of 0% to 70% by weight of the surfactant system, represented by diacylglyerides and/or triacylglycerides with aliphatic C6-C22 carboxylic acids;
wherein the surfactant system comprises 10% to 95% by weight of the pharmaceutical composition.

13 more elements

A method of treating pancreatic exocrine insufficiency in a mammal or human comprising the steps of orally administering to a subject in need thereof a pharmaceutical composition in a solid dosage form with is self-emulsifiable on contact with a hydrophilic phase and a lipophilic phase, said composition comprising:

(i) an active pharmaceutical agent which
(a) is an enzyme or an enzyme mixture with at least lipolytic activity which exerts its action in the gastrointestinal tract, and
(b) is admixed with a surfactant system to form the pharmaceutical composition wherein the pharmaceutical composition does not contain an enteric coating and does not contain any lipophilic active substances to be absorbed into the bloodstream;
and
(ii) wherein the surfactant system comprises
a. a surfactant in an amount of 2% to 90% by weight of the surfactant system selected from either a first group or an ionic surfactant, wherein the first group consists of:
polyethylene glycol fatty acid mono-esters and/or di-esters with aliphatic C6-C22 carboxylic acids;
polyethylene glycol glycerol fatty acid esters with aliphatic C6-C22 carboxylic acids;
polyethylene glycol alkyl mono-ethers and/or di-ethers with aliphatic C12-C18 alcohols, and mixtures of the foregoing;
and wherein the ionic surfactant is selected from the group consisting of:
lecithin, lysolecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylglycerol, lysophosphatidylinositol, lysophosphatidic acid, lysophosphatidylserine, and mixtures of the foregoing;
b. a co-surfactant in an amount of 5% to 60% by weight of the surfactant system, selected from a group consisting of monoacylglycerides with aliphatic C6-C22 carboxylic acids, monoethers of glycerol ethers with aliphatic C12-C18 alcohols, partial esters of propylenglycol with aliphatic C6-C22 carboxylic acids, partial esters of polyglycerol with aliphatic C6-C22 carboxylic acids, and mixtures of the foregoing;
and
c. a lipophilic phase in an amount of 0% to 70% by weight of the surfactant system, represented by diacylglyerides and/or triacylglycerides with aliphatic C6-C22 carboxylic acids;
wherein the surfactant system comprises 10% to 95% by weight of the pharmaceutical composition.

12 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/085,073Filed 22 Mar 2005 · us provisional application
Priority: EP 0410116422 Mar 2004
Published: US 2005/0250817 A110 Nov 2005
Granted: 12 Aug 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

A61K 38/54
Enzymes; Proenzymes; Derivatives thereof: mixtures of enzymes or proenzymes covered by more than a single one of groups A61K38/44 - A61K38/46 or…
A61K 9/1075
Emulsions ; Emulsion preconcentrates; Micelles: microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of…
A61K 9/1617
Excipients; Inactive ingredients: organic compounds, e.g. phospholipids, fats
A61K 9/1641
Organic macromolecular compounds: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene…