CA2000881A1 - Oral dosage forms of omega-3 polyunsaturated acids - Google Patents
Oral dosage forms of omega-3 polyunsaturated acidsInfo
- Publication number
- CA2000881A1 CA2000881A1 CA 2000881 CA2000881A CA2000881A1 CA 2000881 A1 CA2000881 A1 CA 2000881A1 CA 2000881 CA2000881 CA 2000881 CA 2000881 A CA2000881 A CA 2000881A CA 2000881 A1 CA2000881 A1 CA 2000881A1
- Authority
- CA
- Canada
- Prior art keywords
- acid
- dosage form
- enteric dosage
- omega
- enteric
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4891—Coated capsules; Multilayered drug free capsule shells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
Landscapes
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
ABSTRACT
Omega-3 polyunsaturated acids, especially EPA
and/or DHA, in free acid form or as pharmaceutically acceptable salts are presented in enteric dosage forms to overcome the problems of belching and the risk of oxidation in the stomach associated with the oral administration of said acids. The acids can be used alone or with other active principles, especially linoleic acid, gamma-linolenic acid, and/or dihomo--gamma-linolenic acid. Preferably, the enteric dosage form is an enterically coated capsule such as a soft or, especially, hard gelatine capsule.
Omega-3 polyunsaturated acids, especially EPA
and/or DHA, in free acid form or as pharmaceutically acceptable salts are presented in enteric dosage forms to overcome the problems of belching and the risk of oxidation in the stomach associated with the oral administration of said acids. The acids can be used alone or with other active principles, especially linoleic acid, gamma-linolenic acid, and/or dihomo--gamma-linolenic acid. Preferably, the enteric dosage form is an enterically coated capsule such as a soft or, especially, hard gelatine capsule.
Description
. 2~0(~8~3~
CiRAL DOSA(iE E~ S (JE' C~ME(iA-3 ~'()L~ ;AIIJRATEIJ AS:ILJS
The present invention rela~es to the oral ';
aaministration of omega-3 polyunsaturatea acids especially, but not exclusively, all-cis-5,8,11,14,17--05 eicosapentaenoic acid (i.e. all-cis-fatty acia 20:5 omega-3; EPA) and/or 22:6 omega-3-docosahexaenioc acid (I,HA). In E~articular, it provides enteric ~osa-je forms of omeya-3 polyunsaturatea acids.
It ~las been known for many ~ears that the low 1() occurrence of aetherosclerotic caraiovascular diseases amon~st ~ireenland Eskimos ana th~ low mortalit~ rate of cardiovascular patients in Scandinavia is attributable to the consum~)tion of relativel~ high amounts of fish oil. Thè relevant active ingredients in fish oil have been i~entified as the omega-3 polyunsaturate~ acids ~ ; ;
;
EPA an~ l)HA, which are present in their triglyceride and/or other esteri~ied forms. The use of EiPA in free acid form or as a pharmaceutically acceptable salt, ester or amide is ~isclosed in (~E~-A-16()4554 and G~-A--20 2033745. Further, Ui~-A-4097602 disclosed the inhibition of blooa platelet aggre4ation by aaministra-tion of EPA in its free acid form or as a salt or lower alkyl ester. ~lore recently, tJi~-A-4526~02 disclosed the prophlyaxis of thrombo-embolic conditions by simultan-25 eous aaminis~cration of E;PA ana/or LlhA with one or moreof linoleic, gamma-linolenic or dihomo-gamma-linolenic ~ '~''''';
., ~",...
:; ~,"
CiRAL DOSA(iE E~ S (JE' C~ME(iA-3 ~'()L~ ;AIIJRATEIJ AS:ILJS
The present invention rela~es to the oral ';
aaministration of omega-3 polyunsaturatea acids especially, but not exclusively, all-cis-5,8,11,14,17--05 eicosapentaenoic acid (i.e. all-cis-fatty acia 20:5 omega-3; EPA) and/or 22:6 omega-3-docosahexaenioc acid (I,HA). In E~articular, it provides enteric ~osa-je forms of omeya-3 polyunsaturatea acids.
It ~las been known for many ~ears that the low 1() occurrence of aetherosclerotic caraiovascular diseases amon~st ~ireenland Eskimos ana th~ low mortalit~ rate of cardiovascular patients in Scandinavia is attributable to the consum~)tion of relativel~ high amounts of fish oil. Thè relevant active ingredients in fish oil have been i~entified as the omega-3 polyunsaturate~ acids ~ ; ;
;
EPA an~ l)HA, which are present in their triglyceride and/or other esteri~ied forms. The use of EiPA in free acid form or as a pharmaceutically acceptable salt, ester or amide is ~isclosed in (~E~-A-16()4554 and G~-A--20 2033745. Further, Ui~-A-4097602 disclosed the inhibition of blooa platelet aggre4ation by aaministra-tion of EPA in its free acid form or as a salt or lower alkyl ester. ~lore recently, tJi~-A-4526~02 disclosed the prophlyaxis of thrombo-embolic conditions by simultan-25 eous aaminis~cration of E;PA ana/or LlhA with one or moreof linoleic, gamma-linolenic or dihomo-gamma-linolenic ~ '~''''';
., ~",...
:; ~,"
2~0(:~881 ...
acid. The saia acids can be present as the free acid or as pharmaceutically acceptable salts, or esters or amides thereof.
Eormulations used or propose~ for the 05 administration of EPA and/or D~A incluae oral, rectal, to~ical, vayinal, intrapulmonary and parenteral formulations. ~sually, oral formulations have been emplo~ea, es~ecially soft gelatine capsules. ~owever, a problem associatea with such oral aaministration is belching resulting in an unpleasant fishy smell ana taste following disintegration or aissolution of the oral formulation in the stomach. ~uch a problem previously was well established in the administration of coa liver oil capsules which, because of the vitamin A and D content of the oil, have been use~ for many decades as a aietary supplement.
hhen EPA and/or D~A are administered in the form of a derivative thereof, usually an alkyl ester or ~ ;
triglyceride, it must be convertea into the free fatty ;
acid before bein~ absorbed by the body. ~he conversion of ester is carried out in the stomach by the pancreatic enzyme ~ipase. However, not all ~atients produce sufficient Lipase to properly convert the derivative into free fatty acid form. ~or exam~le, the 25 proauction of Lipase may be reduced, or even -eliminated, as a result of aisease or due to alcohol, smokin~, stress etc. Accordingly, there is good reason ~ ;
to prefer to use EPA and/or ~ in the free acid form.
,': '. ;,,;,' Z~0(;P88~
. .
~owever, because of their polyunsaturation the free fatty acids are prone to rapid oxi~ation, which problem is not encountered with the esters. Although antioxiaants, e.g. gamma-tocopherol, are used to 05 prevent or at least reduce oxidation, the ~resent Inventor suspects that significant oxi~ation of the acia takes place in the stomach thereb~ reaucing the availability of the fatty acids.
The teaching ana practice in the art to aate has been that the free acia is administerea orally in the same manner as the esters.
The present Inventor has appreciatea that the long 8tanding problem of belching with the accompan~ing fishy smell an~ taste associatea with the oral lS administration of EPA and/or DHA and the risk of oxidation in the stomach can simpl~ an~ rea~ily be overcome by use of an enteric dosage form (i.e. a dosage form which, when taken orally, will pass through the stomach substantially without release of the active principle but which will release the active principle in the intestine). Although enteric dosage forms are widely used, there~was, to the best of our knowleage, ~;
no previous ~roposal that omega-3 polyunsaturated free acias should be presentea in enteric dosage form ana it had not been appreciated that thers was any re3son or ':
: ~ ^,."
;~ r : '': ' ' ~i~ 2r~0(~881 aavanta~e arising from the use of that form. lhus, the present invention resiaes in the enteric presentation of omega-3 polyunsaturatea free acids as aistinct from enteric dosage forms in general.
05 lhe present invention provi~es an enteric aosa4e form containing as an active principle an omega-3 polyunsaturated acia in free acid form or as a pharmaceuticall~ acceptable salt thereof. Eurther, the invention provides the use of said enteric aosage forms in the treatment or prophylaxis of thrombo--embolic conditions. It also provides said enteric dosaye forms for the treatment of other conditions for which omega-3 polyunsaturatea acids in their free or precursor form, such as their ~lyceride or alkyl 15 esters, are indicatea. ~uch conaitions incluae ~;
rheumatoid arthritis, diabetes mellitus, mi~raine, psoriasis, cancer, ana hypercholesterolaemia ana as a dietetic.
As indicated ~reviously, it i~ preferred that the ~ ~`
. .
20 omega-3 polyunsaturated acid i5 EPA, DHA or a mixture : ;
thereof. It is present in free acid form or as a pharmaceutically acceptable salt thereof and can be present as the sole active principle or with other active principles, especially linoleic acid, gamma-- ~
25 linolenic aci~ and/or dihomo-gamma-linolenic acid in -;;;~ ;
free acid or salt form. ;~
.,'; '':','',.'''~' .' ,:, ' ;;'. ~
Z~00881 , ~' Omega-3 polyunsaturatea acias are readily oxiaisea and hence an antioxidant usually will be present. The presently preferred antioxidant is gamma-tocopherol but other pharmacologically acceptable antioxidants can be 05 used, tor example butylatea hydroxy anisole, butylatea hydroxy toluene, pro~yl gallate or a quinone. ;
..., ~. .
lhe enteric aosage ~orm may also contain one or 1~;
more pharmaceutically acceptable excipients ~epending upon the precise nature of the dosage form.
i~uitabl~, the enteric dosage form can be an enterically coatea tablets containing the omega-3 polyunsaturated acid in a microencapsulated form or loaded on a suitable absorbent. ~owever, it i6 preferred that the enteric dosage form is an entericall~ coated capsule, especially a soft or, more especially, hard gelatine capsule.
Enteric coatings are wiaely usea in the pharmaceutical industry and are formed of substances ;
which are relativel~ insoluble in the acid medium of 20 the stomach but disintegrate in the medium of the small~ ;
intestine. Suitable enteric coatings inclu~e cellulose acetate phthalate and polymethacrylate. ~i ,, , . , . , - , . :
Usually, the omega-3 polyunsaturatea acia will be a~ministered in a daily dosage of 20 to 50 mg/kg, 25 especially 30-40 mg/kg. The actual dose will vary ~ ;
' ', ,~:: ,,, . . .
' ;, '~.~',.
.. ,,,. ... - ~ . , 2~ 88~
depending inter alia on the identit~ of the omega-3 polyunsaturated acid and the nature and degree of the aisorder being treatea. Usually, each unit aose will contain 250 to 1000 mg, especially 40() to 800 mg.
05 lhe ~ollowing is a ~escription, by wa~ of example onl~, of a presently preferred embo~iment of the invention.
Example lransparent hard gelatine capsules (size 0), consisting of 14% water ana ~6% gelatine were each fillea with 500 my of a fish oil concentrate (~PAC~L
600) supplied by ~essrs. ~A Limitea (~inasor, Ontario, ~anada). The concentrate contains about 32~ by weight free ~P~, about 28~ by weight fr~e D~A ana o.~% by 15 weight gamma-tocopherol. It does not contain any ~;
cholesterol, cetoleic acid or saturatea fatty acias ana , is an oily liquid of brown colour having a ~ ~
.: "" ,.,:
characteristic oaour. It has the following ~
, physico-chemical properties:-acid value 160 iodine value 340 :
peroxide value 3 saponification value 190 -saponifiable matter 1.25 .
relative density 0.935 ~ i~
refractive inaex 1.4 The filled gelatine capsules were placed in a -~
.,: "
' ''',','';,:
,:. :, -,.
z;nQ~ssl coating tower where they were carried in a heatea ~55C) air stream whilst being sprayed with an enteric coating solution. lhe coating solution had the following composition by weight~
05 cellulose acetate phthalate ~PC 40 ethyl phthalate ~PC 12 ~g methylene chlori~e 616 m~ :
ethyl alcohol ~5% I.~. 128 ~g.
Sufficient coating solution was applied to provi~e a theoretical coating of 6 mg/2, which is an excess of that theoretically required in order to allow for losses auring the coating process.
1 5 ' "~
, ,: ,'',,~ ' ;': ' ' ' '','~' ~"''''"'',/'":,''' ''','.", ~
acid. The saia acids can be present as the free acid or as pharmaceutically acceptable salts, or esters or amides thereof.
Eormulations used or propose~ for the 05 administration of EPA and/or D~A incluae oral, rectal, to~ical, vayinal, intrapulmonary and parenteral formulations. ~sually, oral formulations have been emplo~ea, es~ecially soft gelatine capsules. ~owever, a problem associatea with such oral aaministration is belching resulting in an unpleasant fishy smell ana taste following disintegration or aissolution of the oral formulation in the stomach. ~uch a problem previously was well established in the administration of coa liver oil capsules which, because of the vitamin A and D content of the oil, have been use~ for many decades as a aietary supplement.
hhen EPA and/or D~A are administered in the form of a derivative thereof, usually an alkyl ester or ~ ;
triglyceride, it must be convertea into the free fatty ;
acid before bein~ absorbed by the body. ~he conversion of ester is carried out in the stomach by the pancreatic enzyme ~ipase. However, not all ~atients produce sufficient Lipase to properly convert the derivative into free fatty acid form. ~or exam~le, the 25 proauction of Lipase may be reduced, or even -eliminated, as a result of aisease or due to alcohol, smokin~, stress etc. Accordingly, there is good reason ~ ;
to prefer to use EPA and/or ~ in the free acid form.
,': '. ;,,;,' Z~0(;P88~
. .
~owever, because of their polyunsaturation the free fatty acids are prone to rapid oxi~ation, which problem is not encountered with the esters. Although antioxiaants, e.g. gamma-tocopherol, are used to 05 prevent or at least reduce oxidation, the ~resent Inventor suspects that significant oxi~ation of the acia takes place in the stomach thereb~ reaucing the availability of the fatty acids.
The teaching ana practice in the art to aate has been that the free acia is administerea orally in the same manner as the esters.
The present Inventor has appreciatea that the long 8tanding problem of belching with the accompan~ing fishy smell an~ taste associatea with the oral lS administration of EPA and/or DHA and the risk of oxidation in the stomach can simpl~ an~ rea~ily be overcome by use of an enteric dosage form (i.e. a dosage form which, when taken orally, will pass through the stomach substantially without release of the active principle but which will release the active principle in the intestine). Although enteric dosage forms are widely used, there~was, to the best of our knowleage, ~;
no previous ~roposal that omega-3 polyunsaturated free acias should be presentea in enteric dosage form ana it had not been appreciated that thers was any re3son or ':
: ~ ^,."
;~ r : '': ' ' ~i~ 2r~0(~881 aavanta~e arising from the use of that form. lhus, the present invention resiaes in the enteric presentation of omega-3 polyunsaturatea free acids as aistinct from enteric dosage forms in general.
05 lhe present invention provi~es an enteric aosa4e form containing as an active principle an omega-3 polyunsaturated acia in free acid form or as a pharmaceuticall~ acceptable salt thereof. Eurther, the invention provides the use of said enteric aosage forms in the treatment or prophylaxis of thrombo--embolic conditions. It also provides said enteric dosaye forms for the treatment of other conditions for which omega-3 polyunsaturatea acids in their free or precursor form, such as their ~lyceride or alkyl 15 esters, are indicatea. ~uch conaitions incluae ~;
rheumatoid arthritis, diabetes mellitus, mi~raine, psoriasis, cancer, ana hypercholesterolaemia ana as a dietetic.
As indicated ~reviously, it i~ preferred that the ~ ~`
. .
20 omega-3 polyunsaturated acid i5 EPA, DHA or a mixture : ;
thereof. It is present in free acid form or as a pharmaceutically acceptable salt thereof and can be present as the sole active principle or with other active principles, especially linoleic acid, gamma-- ~
25 linolenic aci~ and/or dihomo-gamma-linolenic acid in -;;;~ ;
free acid or salt form. ;~
.,'; '':','',.'''~' .' ,:, ' ;;'. ~
Z~00881 , ~' Omega-3 polyunsaturatea acias are readily oxiaisea and hence an antioxidant usually will be present. The presently preferred antioxidant is gamma-tocopherol but other pharmacologically acceptable antioxidants can be 05 used, tor example butylatea hydroxy anisole, butylatea hydroxy toluene, pro~yl gallate or a quinone. ;
..., ~. .
lhe enteric aosage ~orm may also contain one or 1~;
more pharmaceutically acceptable excipients ~epending upon the precise nature of the dosage form.
i~uitabl~, the enteric dosage form can be an enterically coatea tablets containing the omega-3 polyunsaturated acid in a microencapsulated form or loaded on a suitable absorbent. ~owever, it i6 preferred that the enteric dosage form is an entericall~ coated capsule, especially a soft or, more especially, hard gelatine capsule.
Enteric coatings are wiaely usea in the pharmaceutical industry and are formed of substances ;
which are relativel~ insoluble in the acid medium of 20 the stomach but disintegrate in the medium of the small~ ;
intestine. Suitable enteric coatings inclu~e cellulose acetate phthalate and polymethacrylate. ~i ,, , . , . , - , . :
Usually, the omega-3 polyunsaturatea acia will be a~ministered in a daily dosage of 20 to 50 mg/kg, 25 especially 30-40 mg/kg. The actual dose will vary ~ ;
' ', ,~:: ,,, . . .
' ;, '~.~',.
.. ,,,. ... - ~ . , 2~ 88~
depending inter alia on the identit~ of the omega-3 polyunsaturated acid and the nature and degree of the aisorder being treatea. Usually, each unit aose will contain 250 to 1000 mg, especially 40() to 800 mg.
05 lhe ~ollowing is a ~escription, by wa~ of example onl~, of a presently preferred embo~iment of the invention.
Example lransparent hard gelatine capsules (size 0), consisting of 14% water ana ~6% gelatine were each fillea with 500 my of a fish oil concentrate (~PAC~L
600) supplied by ~essrs. ~A Limitea (~inasor, Ontario, ~anada). The concentrate contains about 32~ by weight free ~P~, about 28~ by weight fr~e D~A ana o.~% by 15 weight gamma-tocopherol. It does not contain any ~;
cholesterol, cetoleic acid or saturatea fatty acias ana , is an oily liquid of brown colour having a ~ ~
.: "" ,.,:
characteristic oaour. It has the following ~
, physico-chemical properties:-acid value 160 iodine value 340 :
peroxide value 3 saponification value 190 -saponifiable matter 1.25 .
relative density 0.935 ~ i~
refractive inaex 1.4 The filled gelatine capsules were placed in a -~
.,: "
' ''',','';,:
,:. :, -,.
z;nQ~ssl coating tower where they were carried in a heatea ~55C) air stream whilst being sprayed with an enteric coating solution. lhe coating solution had the following composition by weight~
05 cellulose acetate phthalate ~PC 40 ethyl phthalate ~PC 12 ~g methylene chlori~e 616 m~ :
ethyl alcohol ~5% I.~. 128 ~g.
Sufficient coating solution was applied to provi~e a theoretical coating of 6 mg/2, which is an excess of that theoretically required in order to allow for losses auring the coating process.
1 5 ' "~
, ,: ,'',,~ ' ;': ' ' ' '','~' ~"''''"'',/'":,''' ''','.", ~
Claims (4)
1. An enteric dosage form containing as an active principle an omega-3 polyunsaturated acid in free acid form or as a pharmaceutically acceptable salt thereof.
2. An enteric dosage form as claimed in Claim 1, wherein said acid is EPA, DHA or a mixture thereof.
3. An enteric dosage form as claimed in Claim 1, wherein said acid is present in free acid form.
4 An enteric dosage form as claimed in claim 1, wherein said acid or salt is present as the sole active principle.
An enteric dosage form as claimed in Claim 1, wherein said acid or salt is present with at least one other active principle selected from linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, in free acid form, and pharmaceutically acceptable salt thereof.
6 An enteric dosage form as claimed in claim 1 containing an antioxidant amount of gamma-tocopherol.
7 An enteric dosage form as claimed claim 1 which is an enterically coated tablet containing the said acid or salt in a microencapsulated form or loaded on an absorbent.
8 An enteric dosage form as claimed in Claim 1 which is an enterically coated capsule.
9 An enteric dosage form as claimed in Claim 8, wherein the capsule is a soft gelatine capsule.
An enteric dosage form as claimed in Claim 8, wherein the capsule is a hard gelatine capsule.
11 An enteric dosage form as claimed in Claim 1, wherein each unit dose contains 250 to 1000 mg of said omega-3 acid or salt.
12 An enteric dosage form as claimed in Claim 11, wherein each unit dose contains 400 to 800 mg of said omega-3 acid or salt.
13 The use of an omega-3 polyunsaturated acid in free acid form or as a pharmaceutically acceptable salt thereof in the manufacture of an enteric dosage form for use in the treatment or prophylaxis of any one of the following conditions, namely:
thrombo-embolic conditions, rheumatoid arthritis, diabetes mellitus, migraine, psoriasis, hypercholesterolaemia; or as a dietetic.
An enteric dosage form as claimed in Claim 1, wherein said acid or salt is present with at least one other active principle selected from linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, in free acid form, and pharmaceutically acceptable salt thereof.
6 An enteric dosage form as claimed in claim 1 containing an antioxidant amount of gamma-tocopherol.
7 An enteric dosage form as claimed claim 1 which is an enterically coated tablet containing the said acid or salt in a microencapsulated form or loaded on an absorbent.
8 An enteric dosage form as claimed in Claim 1 which is an enterically coated capsule.
9 An enteric dosage form as claimed in Claim 8, wherein the capsule is a soft gelatine capsule.
An enteric dosage form as claimed in Claim 8, wherein the capsule is a hard gelatine capsule.
11 An enteric dosage form as claimed in Claim 1, wherein each unit dose contains 250 to 1000 mg of said omega-3 acid or salt.
12 An enteric dosage form as claimed in Claim 11, wherein each unit dose contains 400 to 800 mg of said omega-3 acid or salt.
13 The use of an omega-3 polyunsaturated acid in free acid form or as a pharmaceutically acceptable salt thereof in the manufacture of an enteric dosage form for use in the treatment or prophylaxis of any one of the following conditions, namely:
thrombo-embolic conditions, rheumatoid arthritis, diabetes mellitus, migraine, psoriasis, hypercholesterolaemia; or as a dietetic.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8824709A GB2223943A (en) | 1988-10-21 | 1988-10-21 | Oral disage forms of omega-3 polyunsaturated acids |
| GB8824709.3 | 1988-10-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2000881A1 true CA2000881A1 (en) | 1990-04-21 |
Family
ID=10645593
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2000881 Abandoned CA2000881A1 (en) | 1988-10-21 | 1989-10-17 | Oral dosage forms of omega-3 polyunsaturated acids |
Country Status (4)
| Country | Link |
|---|---|
| AU (1) | AU4485689A (en) |
| CA (1) | CA2000881A1 (en) |
| GB (1) | GB2223943A (en) |
| WO (1) | WO1990004391A1 (en) |
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8906369D0 (en) * | 1989-03-20 | 1989-05-04 | Tisdale Michael J | Eicosapentaenoic acid |
| US5457130A (en) * | 1989-03-20 | 1995-10-10 | Cancer Research Campaign Technology Limited | Eicosapentaenoic acid used to treat cachexia |
| FR2663222A1 (en) * | 1990-06-13 | 1991-12-20 | Medgenix Group Sa | OILY LIQUID MICROCAPSULE. |
| ZA92452B (en) * | 1991-01-24 | 1992-10-28 | Martek Corp | Microbial oil mixtures and uses thereof |
| GB9509764D0 (en) * | 1995-05-15 | 1995-07-05 | Tillotts Pharma Ag | Treatment of inflammatory bowel disease using oral dosage forms of omega-3 polyunsaturated acids |
| GB2300807B (en) * | 1995-05-15 | 1999-08-18 | Tillotts Pharma Ag | Oral dosage forms of omega-3 polynunsaturated acids for the treatment of inflammatory bowel disease |
| EP0855908B1 (en) * | 1995-12-11 | 2002-02-06 | Omni Nutraceuticals, Inc. | Dietary regimen of nutritional supplements for relief of symptoms of arthritis |
| US5840715A (en) * | 1995-12-11 | 1998-11-24 | Inholtra Investment Holdings & Trading, N.V. | Dietary regimen of nutritional supplements for relief of symptoms of arthritis |
| US6797289B2 (en) | 1998-02-13 | 2004-09-28 | Nutramax Laboratories, Inc. | Use of anabolic agents, anti-catabolic agents, antioxidant agents, and analgesics for protection, treatment and repair of connective tissues in humans and animals |
| US20070141181A1 (en) | 1998-02-13 | 2007-06-21 | Nutramax Laboratories, Inc. | Use of anabolic agents, anti-catabolic agents, antioxidant agents, and analgesics for protection, treatment and repair of connective tissues in humans and animals |
| US6451771B1 (en) | 1999-02-12 | 2002-09-17 | Nutramax Laboratories, Inc. | Use of anabolic agents anti-catabolic agents and antioxidant agents for protection treatment and repair of connective tissues in humans and animals |
| GB9901809D0 (en) | 1999-01-27 | 1999-03-17 | Scarista Limited | Highly purified ethgyl epa and other epa derivatives for psychiatric and neurological disorderes |
| DE19930030B4 (en) * | 1999-06-30 | 2004-02-19 | Meduna Arzneimittel Gmbh | Oral dosage form containing CO-3-unsaturated fatty acids |
| EP1407767A4 (en) * | 2001-06-18 | 2007-01-24 | Yamada Sachiko | Pparg agonistic medicinal compositions |
| WO2003043570A2 (en) * | 2001-11-15 | 2003-05-30 | Galileo Laboratories, Inc. | Formulations and methods for treatment or amelioration of inflammatory conditions |
| NZ539624A (en) * | 2002-09-27 | 2008-08-29 | Martek Biosciences Corp | Prophylactic docosahexaenoic acid therapy for patients with subclinical inflammation |
| EP1603551A2 (en) * | 2003-03-05 | 2005-12-14 | Solvay Pharmaceuticals GmbH | Use of omega-3-fatty acids in the treatment of diabetic patients |
| US7759507B2 (en) | 2003-09-05 | 2010-07-20 | Abbott Laboratories | Lipid system and methods of use |
| GB0403247D0 (en) | 2004-02-13 | 2004-03-17 | Tillotts Pharma Ag | A pharmaceutical composition |
| GB0428384D0 (en) * | 2004-12-24 | 2005-02-02 | Sla Pharma Ag | Eicosapentaenoic acid |
| US20090214466A1 (en) * | 2005-05-09 | 2009-08-27 | Levin Bruce H | Methods of Alleviating Disorders and Their Associated Pain |
| MX2008008171A (en) | 2005-12-21 | 2008-11-12 | Brudy Technology S L | Use of dha, epa or dha-derived epa for treating a pathology associated with cellular oxidative damage. |
| ES2277557B1 (en) | 2005-12-21 | 2008-07-01 | Proyecto Empresarial Brudy, S.L. | USE OF DOCOSAHEXAENOIC ACID FOR THE TREATMENT OF OXIDATIVE CELL DAMAGE. |
| EP4137128A1 (en) | 2008-09-02 | 2023-02-22 | Amarin Pharmaceuticals Ireland Limited | Pharmaceutical composition comprising eicosapentaenoic acid and a statin, and methods of using same |
| AU2009334476B2 (en) * | 2008-12-31 | 2013-08-29 | Nitromega Corp. | Nutraceuticals containing nitro fatty acids |
| PT2395991E (en) | 2009-02-10 | 2013-09-03 | Amarin Pharmaceuticals Ie Ltd | Use of eicosapentaenoic acid ethyl ester for treating hypertriglyceridemia |
| EP3791880A1 (en) | 2009-04-29 | 2021-03-17 | Amarin Pharmaceuticals Ireland Limited | Pharmaceutical compositions comprising epa |
| LT3278665T (en) | 2009-04-29 | 2020-12-10 | Amarin Pharmaceuticals Ireland Limited | Stable pharmaceutical composition and methods of using same |
| ES2856959T3 (en) | 2009-06-15 | 2021-09-28 | Amarin Pharmaceuticals Ie Ltd | Compositions and methods for the treatment of stroke in a subject on simultaneous statin therapy |
| RU2012116079A (en) | 2009-09-23 | 2013-10-27 | АМАРИН КОРПОРЕЙШН ПиЭлСи | PHARMACEUTICAL COMPOSITION, INCLUDING OMEGA-3 FATTY ACID AND HYDROXY DERIVATED STATIN AND WAYS OF ITS APPLICATION |
| US20140127289A1 (en) | 2010-11-29 | 2014-05-08 | Armarin Pharmaceuticals Ireland Limited | Low eructation composition and methods for treating and/or preventing cardiovascular disease in a subject with fish allergy/hypersensitivity |
| US11712429B2 (en) | 2010-11-29 | 2023-08-01 | Amarin Pharmaceuticals Ireland Limited | Low eructation composition and methods for treating and/or preventing cardiovascular disease in a subject with fish allergy/hypersensitivity |
| US11291643B2 (en) | 2011-11-07 | 2022-04-05 | Amarin Pharmaceuticals Ireland Limited | Methods of treating hypertriglyceridemia |
| US20130131170A1 (en) | 2011-11-07 | 2013-05-23 | Amarin Pharmaceuticals Ireland Limited | Methods of treating hypertriglyceridemia |
| EP2800469B1 (en) | 2012-01-06 | 2021-08-25 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering levels of high-sensitivity (hs-crp) in a subject |
| US20150004224A1 (en) | 2012-01-06 | 2015-01-01 | Omthera Phrmaceuticals, Inc. | Dpa-enriched compositions of omega-3 polyunsaturated fatty acids in free acid form |
| KR20150028233A (en) | 2012-05-07 | 2015-03-13 | 옴테라 파마슈티칼스, 인크. | Compositions of statins and omega-3 fatty acids |
| DK3363433T3 (en) | 2012-06-29 | 2021-03-08 | Amarin Pharmaceuticals Ie Ltd | PROCEDURES TO REDUCE THE RISK OF A CARDIOVASCULAR EVENT IN AN INDIVIDUAL IN STATIN TREATMENT USING EICOSAPENTA ACID ETHYLESTER |
| US20150265566A1 (en) | 2012-11-06 | 2015-09-24 | Amarin Pharmaceuticals Ireland Limited | Compositions and Methods for Lowering Triglycerides without Raising LDL-C Levels in a Subject on Concomitant Statin Therapy |
| US20140187633A1 (en) | 2012-12-31 | 2014-07-03 | Amarin Pharmaceuticals Ireland Limited | Methods of treating or preventing nonalcoholic steatohepatitis and/or primary biliary cirrhosis |
| US9814733B2 (en) | 2012-12-31 | 2017-11-14 | A,arin Pharmaceuticals Ireland Limited | Compositions comprising EPA and obeticholic acid and methods of use thereof |
| US9452151B2 (en) | 2013-02-06 | 2016-09-27 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing apolipoprotein C-III |
| US9624492B2 (en) | 2013-02-13 | 2017-04-18 | Amarin Pharmaceuticals Ireland Limited | Compositions comprising eicosapentaenoic acid and mipomersen and methods of use thereof |
| US9662307B2 (en) | 2013-02-19 | 2017-05-30 | The Regents Of The University Of Colorado | Compositions comprising eicosapentaenoic acid and a hydroxyl compound and methods of use thereof |
| US9283201B2 (en) | 2013-03-14 | 2016-03-15 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for treating or preventing obesity in a subject in need thereof |
| US20140271841A1 (en) | 2013-03-15 | 2014-09-18 | Amarin Pharmaceuticals Ireland Limited | Pharmaceutical composition comprising eicosapentaenoic acid and derivatives thereof and a statin |
| US10966968B2 (en) | 2013-06-06 | 2021-04-06 | Amarin Pharmaceuticals Ireland Limited | Co-administration of rosiglitazone and eicosapentaenoic acid or a derivative thereof |
| US20150065572A1 (en) | 2013-09-04 | 2015-03-05 | Amarin Pharmaceuticals Ireland Limited | Methods of treating or preventing prostate cancer |
| US9585859B2 (en) | 2013-10-10 | 2017-03-07 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering triglycerides without raising LDL-C levels in a subject on concomitant statin therapy |
| EP3135279A4 (en) * | 2014-04-25 | 2018-01-03 | Yamada Bee Company, Inc. | Unsaturated fatty acid absorption accelerator |
| US10561631B2 (en) | 2014-06-11 | 2020-02-18 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing RLP-C |
| US10172818B2 (en) | 2014-06-16 | 2019-01-08 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing or preventing oxidation of small dense LDL or membrane polyunsaturated fatty acids |
| US10406130B2 (en) | 2016-03-15 | 2019-09-10 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing or preventing oxidation of small dense LDL or membrane polyunsaturated fatty acids |
| US10966951B2 (en) | 2017-05-19 | 2021-04-06 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering triglycerides in a subject having reduced kidney function |
| US11058661B2 (en) | 2018-03-02 | 2021-07-13 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering triglycerides in a subject on concomitant statin therapy and having hsCRP levels of at least about 2 mg/L |
| PT4056176T (en) | 2018-09-24 | 2024-05-27 | Amarin Pharmaceuticals Ie Ltd | Methods of reducing the risk of cardiovascular events in a subject |
| KR20240012390A (en) | 2021-04-21 | 2024-01-29 | 애머린 파마슈티칼스 아일랜드 리미티드 | How to Reduce Your Risk of Heart Failure |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5735512A (en) * | 1980-06-27 | 1982-02-26 | Nippon Oil & Fats Co Ltd | Preventive and remedy for thrombosis |
| SE8604117D0 (en) * | 1986-09-29 | 1986-09-29 | Kabivitrum Ab | COMPOSITION |
-
1988
- 1988-10-21 GB GB8824709A patent/GB2223943A/en not_active Withdrawn
-
1989
- 1989-10-17 CA CA 2000881 patent/CA2000881A1/en not_active Abandoned
- 1989-10-20 WO PCT/GB1989/001251 patent/WO1990004391A1/en unknown
- 1989-10-20 AU AU44856/89A patent/AU4485689A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO1990004391A1 (en) | 1990-05-03 |
| AU4485689A (en) | 1990-05-14 |
| GB2223943A (en) | 1990-04-25 |
| GB8824709D0 (en) | 1988-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2000881A1 (en) | Oral dosage forms of omega-3 polyunsaturated acids | |
| JP5829607B2 (en) | Formulation of ω3 fatty acid | |
| ES2826201T3 (en) | Soft enteric capsules containing polyunsaturated fatty acids | |
| CA2577345C (en) | Jelly composition | |
| CA2432020C (en) | Coenzyme q products exhibiting high dissolution qualities | |
| JP4592681B2 (en) | Hydrophobic nutrient stable beads | |
| CA2742227C (en) | The use of fatty acid compositions as laxatives | |
| MX2013001190A (en) | Pharmaceutical and/or dietary compositions based on short chain fatty acids. | |
| JP2010116414A (en) | Essential fatty acid for prevention of cardiovascular event | |
| JPH04342525A (en) | Method for manufacturing pharmaceutical for suppressing phospholipase a2 | |
| CN102209534A (en) | A polysaccharide capsule enclosing a fatty acid oil-containing emulsion | |
| IE832358L (en) | Compositions comprising a pyrimidopyrimidine derivative | |
| JP2010159276A6 (en) | Hydrophobic nutrient stable beads | |
| EA012371B1 (en) | Pharmaceutical formulation comprising microcapsules of statins suspended in alkyl esters of polyunsaturated fatty acids (pufa) | |
| JP2009541433A (en) | Pharmaceutical compositions for oral administration of omega polyene fatty acids, and one or more incompatible ingredients and the process of their preparation | |
| WO2019008101A1 (en) | Enteric coated solid dosage form comprising omega-3 fatty acid amino acid salts | |
| JPH0761954B2 (en) | Cholesterol lowering or raising inhibitor | |
| US20130224304A1 (en) | Effervescent nutritional and/or dietary supplement composition | |
| CA2335713C (en) | Oral dosage form | |
| MXPA04008151A (en) | Ibuprofen solution for hard shell capsules. | |
| WO2013072767A1 (en) | Compositions and preconcentrates comprising at least one salicylate and omega-3 fatty acid oil mixture | |
| JPS6024767B2 (en) | enteric-coated hard capsules | |
| EP2753305A1 (en) | Coated suppositories | |
| US9314435B2 (en) | Stable formulations of antiplatelet agents, omega-3 fatty acids and amylose in soft gelatin capsules | |
| JP3640005B2 (en) | Soft capsule coating |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |