The Capsule Patent 8445003 is OB'd, this is a new IP wall.
We claim:
1. A method of lowering triglycerides without increasing LDL-C in a subject having fasting baseline triglycerides of 500 mg/dl to about 1500 mg/dl comprising, administering to the subject a pharmaceutical composition comprising at least about 95%, by weight of all fatty acids present, ethyl eicosapentaenoate in one or more capsules comprising a capsule wall composed of a film-forming material that is free of succinated gelatin, wherein the composition is administered in an amount and for a period effective to reduce triglycerides by at least 25% without increasing LDL-C in the subject compared to a second subject having fasting baseline triglycerides of 500 mg/dl to about 1500 mg/dl who has not received the pharmaceutical composition.
2. The method of claim 1 wherein the film-forming material comprises gelatin, carrageenan, alkylated or hydroxyalkylated cellulose ethers, starch, alpha-starch, hydroxyalkyl starch, sodium alginate, sodium salt of a gelatin copolymer and acrylic acid, hydroxypropyl methyl cellulose, hydroxyethyl cellulose or polyvinyl alcohol.
3. The method of claim 1 wherein the film-forming material comprises at least one plasticizer.
4. The method of claim 1 wherein the at least one plasticizer comprises a hygroscopic plasticizer.
5. The method of claim 4 wherein the hygroscopic plasticizer comprises glycerol.
6. The method of claim 1 wherein the film-foaming material comprises gelatin.
7. The method of claim 1 comprising administering the composition to the subject for a period effective to reduce triglycerides by at least 30% without increasing LDL-C compared to the second subject.
8. The method of claim 7 comprising administering the composition to the subject for a period effective to reduce triglycerides by at least about 35% without increasing LDL-C compared to the second subject.
9. The method of claim 1 wherein said period is at least about 12 weeks.
10. The method of claim 1 comprising administering the composition to the subject to effect a reduction in apolipoprotein B compared to the second subject.
11. The method of claim 1 comprising administering the composition to the subject to effect at least a 5% reduction in apolipoprotein B compared to the second subject.
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Description
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BACKGROUND
Mixed omega-3 fatty acid esters are typically encapsulated in type 2a gelatin capsules containing gelatin (.about.43.4%), glycerol (.about.20%) and water (.about.36.6%) and do not experience stability problems throughout their shelf life. While chemically modified gelatins such as succinated/succinylated gelatin have been used to encapsulate reactive fill ingredients, such gelatin is not approved for use in the U.S. and other markets.
SUMMARY
We have unexpectedly found that high purity eicosapentaenoic acid (EPA) is more susceptible to oxidative degradation than mixed omega-3-acid ethyl esters. In various embodiments, the invention provides pharmaceutical compositions comprising a fatty acid or a derivative thereof in a capsule shell that resists, hinders, attenuates, or prevents oxidation of the fatty acid or fatty acid derivative, for example to a greater extent than is provided by a standard type IIa capsule shell. In a related embodiment, the fatty acid comprises eicosapentaenoic acid (EPA) or a derivative of EPA, for example ethyl eicosapentaenoate (ethyl-EPA or E-EPA). In another embodiment, the fatty acid comprises ultra-pure EPA.
In one embodiment, the invention provides a pharmaceutical composition comprising ultra-pure EPA encapsulated in a capsule shell, where the ultra-pure EPA has a baseline peroxide value not greater than about 5 meq/mg and upon storage of the composition at 23.degree. C. and 50% RH for a period of time, that ultra-pure EPA has a second peroxide value not greater than about 20 meq/mg.
In other embodiments, the invention provides a pharmaceutical composition comprising EPA (e.g. E-EPA or ultra pure E-EPA) encapsulated in a capsule shell comprising a film forming material and a hygroscopic plasticizer, wherein the weight ratio of film-forming material to hygroscopic plasticizer is not less than about 2.5:1. Further, the capsule shell can optionally comprise a non-hygroscopic plasticizer. In one embodiment, the capsule contains no chemically modified gelatin, for example succinated or succinylated gelatin.
In still other embodiments, the present invention provides methods of treating or preventing a cardiovascular-related disease using compositions as described herein.
These and other embodiments of the present invention will be disclosed in further detail herein below.
