WO2004064716A2 - Eicosapentaenoic acid and docosapentaenoic acid for treating inflammatory disorders - Google Patents
Eicosapentaenoic acid and docosapentaenoic acid for treating inflammatory disorders Download PDFInfo
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- WO2004064716A2 WO2004064716A2 PCT/GB2004/000242 GB2004000242W WO2004064716A2 WO 2004064716 A2 WO2004064716 A2 WO 2004064716A2 GB 2004000242 W GB2004000242 W GB 2004000242W WO 2004064716 A2 WO2004064716 A2 WO 2004064716A2
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- 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
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- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
- A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
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- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- 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
- A61K31/66—Phosphorus compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- 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]
Definitions
- Psoriasis is a common inflammatory disease of the skin, which affects between 1% and 2% of the population in Western countries. It occurs in all races. Psoriasis consists of raised plagues of red and scaly inflammatory tissue which can occur anywhere on the body but which are particularly common on the limbs and trunk. Biochemically, the inflamed tissue is characterised by increased release of arachidonic acid and by the formation of large amounts of arachidonic acid metabolites (K Ikai, Journal of Dermatological Science 1999; 21: 135-146) . Two fatty acids found in fish oils, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can antagonise the actions of arachidonic acid under certain circumstances .
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- psoriasis Some patients with psoriasis also have a rheumatoid- like arthritis which, however, is negative for rheumatoid factor and is considered part of the psoriatic syndrome. Thus the mention in this specification to the treatment and prevention of "psoriasis” includes the treatment and prevention of psoriatic arthritis.
- Fish oils and the fatty acids found in fish oils are well known to produce anti-inflammatory effects in a wide variety of conditions including joint diseases (including osteoarthritis and rheumatoid arthritis) , bowel diseases (including Crohn's disease, ulcerative colitis and irritable bowel syndrome) , respiratory diseases (such as asthma and chronic obstructive pulmonary disease) , autoimmune "collagen” diseases (such as systemic lupus erythematosus , systemic sclerosis and polymyalgia rheumatica) , kidney diseases (such as glomerulonephritis and IgA nephropathy) and reproductive tract diseases (such as endometriosis, dysmenorrhoea and prostatitis) .
- joint diseases including osteoarthritis and rheumatoid arthritis
- bowel diseases including Crohn's disease, ulcerative colitis and irritable bowel syndrome
- respiratory diseases such as asthma and chronic obstructive pulmonary disease
- Bittner et al (Lancet 1988; Feb 20: 378-380) gave 1.8g/day EPA and 1.2g/day DHA and found an approximately 30% improvement as compared to placebo.
- Gupta et al (British Journal of Dermatology 1989; 120: 801-7) gave 3.6g/day of EPA and 2.4g/day of DHA and found about a 50% improvement as compared to placebo.
- Maurice et al (British Journal of Dermatology 1987; 117:599-606) gave 12g/day of EPA and 8g/day of DHA but showed only a modest improvement in some patients and no improvement in others .
- Danno et al (Journal of Dermatology 1998; 25: 703-5) gave what they describe as 1.8g of "highly purified" ethyl-EPA (without giving any precise specification) to 20 patients who were also taking etretinate (an anti- psoriasis drug) and compared them with patients given etretinate alone. It is therefore impossible to know what effect ethyl-EPA alone might have had. 9/20 patients on etretinate + EPA had an excellent improvement as compared to 3/20 on etretinate alone.
- the main fatty acids in fish oil which are thought to exert anti-inflammatory actions are three omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (20:5n-3, EPA), docosapentaenoic acid (22:5n-3, DPA) and docosahexaenoic acid (22:6n-3, DHA) .
- EPA is readily converted to DPA, which shares many of the biological effects of EPA.
- DPA can be converted to DHA, in practice very little of this conversion seems to occur in humans, so that administration of EPA raises levels of EPA and DPA in blood and tissues, but not those of DHA.
- Fish oils contain many other fatty acids as well.
- the present invention provides a new method for the treatment and prevention of psoriasis involving the use of a formulation comprising more than 95% EPA, or an appropriate derivative, and less than 2% DHA.
- the formulation comprises less than 0.2% DHA and, very preferably, no significant amount of DHA.
- the formulation comprises 97% EPA, and very preferably 99% or more EPA.
- the present invention also provides use of such formulations in the manufacture of a medicament for the treatment of psoriasis.
- the effect is dose-related with 2g/day having some effect but 4g/d and 6g/d having much greater therapeutic effects. It is therefore likely that the optimum therapeutic dose will be in the range from about 2g/day to about 6g/day, although there will be some therapeutic effects at doses of lg/day upwards and higher doses than 6g/day will also be effective.
- the dose of EPA may be from 0.2g to 30g per day, preferably from lg to lOg per day, and very preferably from 2g to 6g/day.
- the EPA derivative may be any assimilable derivative suitable for delivery of the EPA; the EPA maybe administered in any appropriate form.
- EPA is used to refer to the acid or any derivative. It may be administered as the free acid, an ester of EPA, salts of EPA such as those of sodium or potassium, mono-, di-, or triglycerides, cholesterol esters, phospholipids, amides or propane-diol derivatives.
- a particularly preferred derivative is ethyl-EPA, which acts as a prodrug for EPA.
- the EPA or derivative must make up more than 95% of the total fatty acid component of the product and DHA must be less than 2%, preferably less than 0.2% and very preferably absent.
- the EPA maybe administered in any appropriate dosage form known to those skilled in the art.
- oral administration as examples, hard or soft gelatin or agar or other non-protein capsules, or any type of microcapsules are all appropriate, as are flavoured liquids and emulsions .
- the absence of smell with the highly purified ethyl-EPA means that, unlike the situation with fish oils or less pure products, there is little risk of gastrointestinal upsets, or regurgitation of gas, or foul-smelling breath.
- topical administration the EPA maybe incorporated into any appropriate cream, ointment or emulsion.
- the highly purified ethyl-EPA has no odour, which is a major advantage over fish oil and less purified products with regard to topical administration.
- the pure EPA for example in the form of the ethyl ester, maybe prepared in sterile vials and then mixed with any commercial intravenous lipid formulation for administration to the patient.
- the pure EPA maybe injected directly by slow intravenous injection or an intravenous sterile emulsion may be made for administration to the patient .
- the present invention therefore provides the treatment and prevention of psoriasis using the above formulations, but where the EPA is replaced by DPA.
- the present invention provides DPA formulations which comprise more than 95% DPA and less than 2%, preferably less than 0.2%, and very preferably no, DHA.
- the present invention further provides methods of treatment and prevention of other disorders including, any other inflammatory skin disorder, including eczema or allergic dermatitis; any inflammatory joint disease, including rheumatoid arthritis, osteoarthritis or ankylosing spondylitis; any inflammatory bowel disease, including Crohn's disease, ulcerative colitis or irritable bowel syndrome; any inflammatory respiratory disease, including asthma, chronic obstructive pulmonary disease or cystic fibrosis; any inflammatory autoimmune or "collagen" disease, including systemic sclerosis, systemic lupus erythematosus, polymyalgia rheumatica or temporal arteritis; any inflammatory kidney disease, including glomerulonephritis, nephrotic syndrome or IgA nephropathy; and any inflammatory disorder of the reproductive tract
- any other inflammatory skin disorder including eczema or allergic dermatitis
- any inflammatory joint disease including rheumatoid arthritis, osteo
- the invention provides the use of the formulations disclosed in the manufacture of medicaments for the treatment of the disorders discussed, as well as the disclosed formulations when used in the particular treatments discussed.
- ethyl ester of EPA ethyl- EPA
- EPA ethyl- EPA
- the ethyl group is removed by digestive processes in the lumen and the wall of the small intestine and no ethyl ester enters the blood or the lymph.
- the EPA released from the ethyl ester enters the circulation either as free EPA or as a triglyceride, a phospholipid or a cholesterol ester. It is transported in these forms to the tissues.
- the ethyl-EPA used in these studies contained 97% of its fatty acids as EPA, less than 0.2% as DHA, and less than 1% of any other individual fatty acid. Two patients were given 2g/day, two patients were given
Abstract
Use of eicosapentaenoic acid or derivative in the treatment or prevention of psoriasis or other inflammatory disorder.
Description
PSORIASIS AND EICOSAPENTAENOIC ACID
Psoriasis is a common inflammatory disease of the skin, which affects between 1% and 2% of the population in Western countries. It occurs in all races. Psoriasis consists of raised plagues of red and scaly inflammatory tissue which can occur anywhere on the body but which are particularly common on the limbs and trunk. Biochemically, the inflamed tissue is characterised by increased release of arachidonic acid and by the formation of large amounts of arachidonic acid metabolites (K Ikai, Journal of Dermatological Science 1999; 21: 135-146) . Two fatty acids found in fish oils, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can antagonise the actions of arachidonic acid under certain circumstances .
Some patients with psoriasis also have a rheumatoid- like arthritis which, however, is negative for rheumatoid factor and is considered part of the psoriatic syndrome. Thus the mention in this specification to the treatment and prevention of "psoriasis" includes the treatment and prevention of psoriatic arthritis.
There are many different treatments for psoriasis, including anti-inflammatory steroids, extracts of coal tar, light activated psoralens, which are given in conjunction with ultraviolet light therapy, vitamin D derivatives, vitamin A derivatives and various monoclonal antibodies against the cytokines which can be produced by the psoriatic lesions . All have good therapeutic effects, but none produces reliable and
consistent clearing of the whole skin in the great majority of patients.
Fish oils and the fatty acids found in fish oils are well known to produce anti-inflammatory effects in a wide variety of conditions including joint diseases (including osteoarthritis and rheumatoid arthritis) , bowel diseases (including Crohn's disease, ulcerative colitis and irritable bowel syndrome) , respiratory diseases (such as asthma and chronic obstructive pulmonary disease) , autoimmune "collagen" diseases (such as systemic lupus erythematosus , systemic sclerosis and polymyalgia rheumatica) , kidney diseases (such as glomerulonephritis and IgA nephropathy) and reproductive tract diseases (such as endometriosis, dysmenorrhoea and prostatitis) . There are hundreds of references to the uses of fish oil in these inflammatory conditions .
Because of the known effects of fish oils on other inflammatory disorders they have also been tested in inflammatory skin diseases such as psoriasis, eczema and allergic dermatitis. On the whole the results have been beneficial but modest in psoriasis. The following examples include only placebo-controlled studies of oral administration of fish oil and give the doses of EPA delivered per day. Bjorneboe et al (British Journal of Dermatology 1988; 118: 77-83) gave 1.8g/day of EPA and 1.2g/day of DHA as fish oil but found no beneficial effect as compared to placebo. Gupta et al (International Journal of Dermatology 1990; 29: 591- 595) gave 5.4g/day of EPA and 3.6g/day of DHA but found no beneficial effect as compared to placebo. Soyland
et al (New England Journal of Medicine 1993; 328: 1812- 6) gave 3. lg/day of EPA and 1.9g/day of DHA and also found no beneficial effect as compared to placebo.
On the other hand, Bittner et al (Lancet 1988; Feb 20: 378-380) gave 1.8g/day EPA and 1.2g/day DHA and found an approximately 30% improvement as compared to placebo. Gupta et al (British Journal of Dermatology 1989; 120: 801-7) gave 3.6g/day of EPA and 2.4g/day of DHA and found about a 50% improvement as compared to placebo. In an open label study, notable for its high dosage, Maurice et al (British Journal of Dermatology 1987; 117:599-606) gave 12g/day of EPA and 8g/day of DHA but showed only a modest improvement in some patients and no improvement in others .
Terano et al (Advances in Prostaglandin, Thromboxane and Leukotriene Research 1989; 19: 610-3) gave 3.6g/day of a preparation containing 90% of EPA and so provided about 3.2g/day of EPA. In the first two months of an open label study they showed only about 10% improvement, but this then developed and after 6 months of treatment the improvement was about 50%.
Danno et al (Journal of Dermatology 1998; 25: 703-5) gave what they describe as 1.8g of "highly purified" ethyl-EPA (without giving any precise specification) to 20 patients who were also taking etretinate (an anti- psoriasis drug) and compared them with patients given etretinate alone. It is therefore impossible to know what effect ethyl-EPA alone might have had. 9/20 patients on etretinate + EPA had an excellent improvement as compared to 3/20 on etretinate alone.
However 8/20 on etretinate alone had a moderate improvement as compared to 4/20 on etretinate + EPA so that 13/20 patients on etretinate + EPA and 11/20 patients on etretinate alone had a moderate to excellent improvement .
Fish oils have also been given intravenously for treating psoriasis and have shown consistent but modest beneficial effects (P Mayser et al, Journal of the American Academy of Dermatology 1998; 38: 539-47. P
Mayser et al, Journal of Dermatological Treatment 1996; 7:211-214) . Fish oils have also shown modest beneficial effects when given topically although the bad smell proved a problem for some patients (SO Escobar et al, Clinical and Experimental Dermatology 1992; 17: 159-162. H-H Henneicke-von Zepelin et al British Journal of Dermatology 1993; 129: 713-7) .
The main fatty acids in fish oil which are thought to exert anti-inflammatory actions are three omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (20:5n-3, EPA), docosapentaenoic acid (22:5n-3, DPA) and docosahexaenoic acid (22:6n-3, DHA) . In humans EPA is readily converted to DPA, which shares many of the biological effects of EPA. However, although theoretically DPA can be converted to DHA, in practice very little of this conversion seems to occur in humans, so that administration of EPA raises levels of EPA and DPA in blood and tissues, but not those of DHA. Fish oils contain many other fatty acids as well.
Usually between 15% and 40% of natural oils consists of EPA, DPA and DHA, with the rest being made up of a complex mixture of other fatty acids . In studies on
fish oils and psoriasis, little attempt has been made to distinguish between the various fatty acid components of the oils or to determine which might be responsible for the anti-psoriasis effect. This is because it is generally believed that EPA, DPA and DHA have similar anti-inflammatory actions.
The present invention provides a new method for the treatment and prevention of psoriasis involving the use of a formulation comprising more than 95% EPA, or an appropriate derivative, and less than 2% DHA.
Preferably the formulation comprises less than 0.2% DHA and, very preferably, no significant amount of DHA.
Preferably the formulation comprises 97% EPA, and very preferably 99% or more EPA.
The present invention also provides use of such formulations in the manufacture of a medicament for the treatment of psoriasis.
These pure EPA compositions are unexpectedly much more effective than the same or larger amounts of EPA in the form of fish oils in treating psoriasis.
The effect is dose-related with 2g/day having some effect but 4g/d and 6g/d having much greater therapeutic effects. It is therefore likely that the optimum therapeutic dose will be in the range from about 2g/day to about 6g/day, although there will be some therapeutic effects at doses of lg/day upwards and higher doses than 6g/day will also be effective.
Overall, therefore, the dose of EPA may be from 0.2g to 30g per day, preferably from lg to lOg per day, and very preferably from 2g to 6g/day.
The EPA derivative may be any assimilable derivative suitable for delivery of the EPA; the EPA maybe administered in any appropriate form. In this specification the abbreviation "EPA" is used to refer to the acid or any derivative. It may be administered as the free acid, an ester of EPA, salts of EPA such as those of sodium or potassium, mono-, di-, or triglycerides, cholesterol esters, phospholipids, amides or propane-diol derivatives. A particularly preferred derivative is ethyl-EPA, which acts as a prodrug for EPA. In each case, the EPA or derivative must make up more than 95% of the total fatty acid component of the product and DHA must be less than 2%, preferably less than 0.2% and very preferably absent.
The EPA maybe administered in any appropriate dosage form known to those skilled in the art. For oral administration, as examples, hard or soft gelatin or agar or other non-protein capsules, or any type of microcapsules are all appropriate, as are flavoured liquids and emulsions . The absence of smell with the highly purified ethyl-EPA means that, unlike the situation with fish oils or less pure products, there is little risk of gastrointestinal upsets, or regurgitation of gas, or foul-smelling breath. For topical administration the EPA maybe incorporated into any appropriate cream, ointment or emulsion. The highly purified ethyl-EPA has no odour, which is a major advantage over fish oil and less purified
products with regard to topical administration. For intravenous administration, the pure EPA, for example in the form of the ethyl ester, maybe prepared in sterile vials and then mixed with any commercial intravenous lipid formulation for administration to the patient. Alternatively the pure EPA maybe injected directly by slow intravenous injection or an intravenous sterile emulsion may be made for administration to the patient .
Because substantial amounts of EPA are always converted to DPA when administered to humans, it is likely that DPA will have effects similar to EPA. The present invention therefore provides the treatment and prevention of psoriasis using the above formulations, but where the EPA is replaced by DPA.
In addition, the present invention provides DPA formulations which comprise more than 95% DPA and less than 2%, preferably less than 0.2%, and very preferably no, DHA.
It is well known that anti-inflammatory agents which have actions in one inflammatory condition often have actions in other conditions where inflammation is important. As with psoriasis, it is already known that fish oils containing EPA and DHA have effects, although modest, in other inflammatory conditions. Because the effects of highly purified EPA substantially free of DHA and other fatty acids are so much better than EPA in the form of fish oil in psoriasis, the present invention further provides methods of treatment and prevention of other disorders including,
any other inflammatory skin disorder, including eczema or allergic dermatitis; any inflammatory joint disease, including rheumatoid arthritis, osteoarthritis or ankylosing spondylitis; any inflammatory bowel disease, including Crohn's disease, ulcerative colitis or irritable bowel syndrome; any inflammatory respiratory disease, including asthma, chronic obstructive pulmonary disease or cystic fibrosis; any inflammatory autoimmune or "collagen" disease, including systemic sclerosis, systemic lupus erythematosus, polymyalgia rheumatica or temporal arteritis; any inflammatory kidney disease, including glomerulonephritis, nephrotic syndrome or IgA nephropathy; and any inflammatory disorder of the reproductive tract, including endometriosis, dysmenorrhoea, prostatitis or urethritis .
As well as the therapeutic applications of the present invention, the invention provides the use of the formulations disclosed in the manufacture of medicaments for the treatment of the disorders discussed, as well as the disclosed formulations when used in the particular treatments discussed.
Examples
Six patients with psoriasis were given highly purified ethyl eicosapentaenoate, the ethyl ester of EPA (ethyl- EPA) . This acts as a prodrug for EPA. The ethyl group is removed by digestive processes in the lumen and the wall of the small intestine and no ethyl ester enters the blood or the lymph. The EPA released from the ethyl ester enters the circulation either as free EPA or as a triglyceride, a phospholipid or a cholesterol ester. It is transported in these forms to the tissues.
The ethyl-EPA used in these studies contained 97% of its fatty acids as EPA, less than 0.2% as DHA, and less than 1% of any other individual fatty acid. Two patients were given 2g/day, two patients were given
4g/day and two patients were given 6g/day. All of the patients had previously tried various types of fish oil with only modest improvements in their condition.
Surprisingly, all four of the patients who were given 4g/day or 6g/day ethyl-EPA had a complete or near complete (more than 90%) clearing of all their psoriatic lesions. The two patients given 2g/day ethyl-EPA had a partial clearing (about 40-50%) of their lesions, which was still considerably greater than anything they had experienced previously while taking fish oils. The clearing took place rapidly, beginning after about 2 weeks, becoming maximal between 4 and 8 weeks, and then persisting.
One of the patients who was given 4g/day also had psoriatic arthritis, which resolved at the same time as the skin lesions .
Two of the studies discussed in the introduction of this application used partially purified EPA in studies on psoriasis, but neither achieved the striking results reported above. The Terano et al experiments using 90% EPA clearly showed a much slower effect, which was much less complete than in the six patients described above. There would have been 10% of other fatty acids present in these known formulations. The results of the Danno et al tests are clearly worse than the ones reported in this specification and suggest that either the dose of EPA was too low or etretinate in some way interfered with the action of EPA.
Claims
Use of a formulation comprising more than 95% eicosapentaenoic acid (EPA) , or an appropriate derivative, and less than 2% docosahexaenoic acid (DHA) in the manufacture of a medicament for the treatment or prevention of psoriasis .
10
Use according to claim 1 in which the formulation comprises less than 0.
2% DHA.
3. Use according to claim 1 in which the 15 formulation comprises no significant amount of
DHA.
4. Use according to any of claims 1 - 3 in which the EPA derivative is ethyl-EPA.
20
5. Use according to any of claims 1 - 3 in which the EPA derivative is selected from the free acid, other esters of EPA, salts of EPA such as those of sodium or potassium, mono-, di-, or
25 triglycerides, cholesterol esters, phospholipids, amides or propane-diol derivatives .
6. Use according to any preceding claim in which '30 the medicament is for oral administration.
7. Use according to any of claims 1 - 5 in which the medicament is for topical administration.
8. Use according to any of claims 1 - 5 in which the medicament is for intravenous administration.
9. Use according to any preceding claim but where the medicament is for the treatment of a inflammatory skin disorder other than psoriasis, including eczema or allergic dermatitis.
10. Use according to any of claims 1 - 8, but where the medicament is for treatment of an inflammatory joint disease, rheumatoid arthritis, osteoarthritis or ankylosing spondylitis .
11. Use according to any of claims 1 - 8, but where the medicament is for treatment of any inflammatory bowel disease, Crohn's disease, ulcerative colitis or irritable bowel syndrome.
12. Use according to any of claims 1 - 8, but where the medicament is for treatment of any inflammatory respiratory disease, asthma, chronic obstructive pulmonary disease or cystic fibrosis .
13. Use according to any of claims 1 - 8 , but where the medicament is for treatment of any inflammatory autoimmune or "collagen" disease, systemic sclerosis, systemic lupus erythematosus, polymyalgia rheumatica or temporal arteritis .
14. Use according to any of claims 1 - 8, but where the medicament is for treatment of any inflammatory kidney disease, glomerulonephritis, nephrotic syndrome or IgA nephropathy .
15. Use according to any of claims 1 - 8, but where the medicament is for treatment of any inflammatory disorder of the reproductive tract, endometriosis, dysmenorrhoea, prostatitis or urethritis.
16. Use according to any preceding claim but where the EPA is replaced by its immediate metabolite, DPA(22 :5n-3) .
17. A method for the treatment or prevention of psoriasis comprising administering to a subject a formulation comprising more than 95% EPA, or an appropriate derivative, and less than 2% DHA.
18. A method according to claim 17 in which the formulation comprises less than 0.2% DHA.
19. A method according to claim 17 in which the formulation comprises no significant amount of DHA.
20. A method according to any of claims 17 - 19 in which the EPA derivative is ethyl-EPA.
21. A method according to any of claims 17 - 19 in which the EPA derivative is selected from the free acid, other esters of EPA, salts of EPA such as those of sodium or potassium, mono-, di-, or triglycerides, cholesterol esters, phospholipids, amides or propane-diol derivatives .
22. A method according to any of claims 17 - 21 in which the formulation is administered orally.
23. A method according to any of claims 17 - 21 in which the formulation is administered topically.
24. A method according to any of claims 17 - 21 in which the medicament is administered intravenously.
25. A method according to any of claims 17 - 24 but for the treatment of a inflammatory skin disorder other than psoriasis, including eczema or allergic dermatitis.
26. A method according to any of claims 17 - 24, but for treatment of an inflammatory joint disease, rheumatoid arthritis, osteoarthritis or ankylosing spondylitis.
27. A method according to any of claims 17 - 24, but for treatment of any inflammatory bowel disease, Crohn's disease, ulcerative colitis or irritable bowel syndrome .
28. A method according to any of claims 17 - 24, but for treatment of any inflammatory respiratory disease, asthma, chronic obstructive pulmonary disease or cystic fibrosis.
29. A method according to any of claims 17 - 24, but for treatment of any inflammatory autoimmune or "collagen" disease, systemic sclerosis, systemic lupus erythematosus, polymyalgia rheumatica or temporal arteritis.
30. A method according to any of claims 17 - 24, but for treatment of any inflammatory kidney disease, glomerulonephritis, nephrotic syndrome or IgA nephropathy.
31. A method according to any of claims 17 - 24, but for treatment of any inflammatory disorder of the reproductive tract, endometriosis, dysmenorrhoea, prostatitis or urethritis.
32. A method according to any of claims 17 - 32 but where the EPA is replaced by its immediate metabolite, DPA(22 :5n-3) .
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0301701.9 | 2003-01-24 | ||
GBGB0301701.9A GB0301701D0 (en) | 2003-01-24 | 2003-01-24 | Psoriasis and Eicosapentaenoic acid |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2004064716A2 true WO2004064716A2 (en) | 2004-08-05 |
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PCT/GB2004/000242 WO2004064716A2 (en) | 2003-01-24 | 2004-01-22 | Eicosapentaenoic acid and docosapentaenoic acid for treating inflammatory disorders |
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GB0301701D0 (en) | 2003-02-26 |
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