Use of PUFAs for treating skin inflammation

1. A topical pharmaceutical composition comprising:

a polyunsaturated fatty acid (PUFA) derivative of formula (I),

or a pharmaceutically acceptable salt thereof, wherein

-Alk- is —CH(OR 2 )-[trans]CH═CH-[cis]CH═CH—CH 2 -[cis]CH═CH—C 3 H 6 —, —(CH 2 ) 3 —CH(OR 2 )-[trans]CH═CH-[cis]CH═CH—CH 2 -[cis]CH═CH—, —(CH 2 ) 3 -[cis]CH═CH—CH 2 -[cis]CH═CH-[trans]CH═CH—CH(OR 2 )— or —(CH 2 ) 3 -[cis]CH═CH—CH 2 -[cis]CH═CH—CH 2 -[cis]CH═CH—;

R 1 is a hydrogen atom;

R 2 is a hydrogen atom; or

R 2 is a group —(C═O)—R 5 , wherein R 5 is a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 6 -C 10 aryl, 5- to 10-membered heteroaryl, C 3 -C 7 carbocyclyl or 5- to 10-membered heterocyclyl group, or R 5 is an aliphatic group having from 3 to 29 carbon atoms; or

R 2 is a group of formula —(CH 2 OCH 2 ) n OH, wherein n is an integer of from 1 to 200;

and wherein

said alkyl, alkenyl, alkynyl and aliphatic groups are the same or different and are each unsubstituted or substituted with 1, 2 or 3 unsubstituted substituents which are the same or different and are selected from halogen atoms and C 1 -C 4 alkoxy, C 2 -C 4 alkenyloxy, C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 1 -C 4 haoalkoxy, C 2 -C 4 haloalkenyloxy, hydroxyl, —SR′, and —NR′R″ groups where R′ and R″ are the same or different and represent hydrogen or unsubstituted C 1 -C 2 alkyl;

said aryl, heteroaryl, carbocyclyl and heterocyclyl groups are the same or different and are each unsubstituted or substituted by 1, 2, 3 or 4 unsubstituted substituents which are the same or different and are selected from halogen atoms, and cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 2 -C 4 alkenyl, C 2 -C 4 alkenyloxy, C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 1 -C 4 haloalkoxy, C 2 -C 4 haloalkenyloxy, hydroxyl, C 1 -C 4 hydroxyalky, —SR′ and —NR′R″ groups wherein each R′ and R″ is the same or different and represents hydrogen or unsubstituted C 1 -C 4 alkyl;

and wherein the PUFA derivative is in the form of a racemate, a stereoisomer or a mixture of stereoisomers;

at least one preservative and at least one pharmaceutical excipient;

and wherein the topical pharmaceutical composition is substantially free of arachidonic acid and glucocorticoids.

2. The topical pharmaceutical composition of claim 1 , wherein R 1 is a hydrogen atom.

3. The topical pharmaceutical composition of claim 1 wherein -Alk- is

—CH(OR 2 )-[trans]CH═CH-[cis]CH═CH—CH 2 -[cis]CH═CH—C 3 H 6 —, —(CH 2 ) 3 —CH(OR 2 )-[trans]CH═CH-[cis]CH═CH—CH 2 -[cis]CH═CH—, or —(CH 2 ) 3 -[cis]CH═CH—CH 2 -[cis]CH═CH-[trans]CH═CH—CH(OR 2 )—.

4. The topical pharmaceutical composition of claim 1 , wherein -Alk- is —(CH 2 ) 3 -[cis]CH═CH—CH 2 -[cis]CH═CH-[trans]CH═CH—CH(OR 2 )—.

5. The topical pharmaceutical composition of claim 1 , wherein R 2 is a hydrogen atom.

6. The topical pharmaceutical composition of claim 1 , wherein the PUFA derivative is present as the R enantiomer.

7. The topical pharmaceutical composition of claim 1 , wherein the PUFA derivative is present as the S enantiomer.

8. The topical pharmaceutical composition of claim 1 , wherein:

(a) R 2 is a group —(C═O)—R 5 , wherein R 5 is a saturated aliphatic group having from 3 to 29 carbon atoms; or

(b) R 2 is a group of formula —(CH 2 OCH 2 ) n OH, wherein n is defined in claim 1 .

9. A method of treating skin inflammation in a mammal comprising administering to skin of said mammal the topical pharmaceutical composition of claim 1 .

10. A topical pharmaceutical composition comprising:

a polyunsaturated fatty acid (PUFA) derivative of formula (II),

or a pharmaceutically acceptable salt thereof, wherein

-Alk- is —(CH 2 ) 3 -[cis]CH═CH—CH 2 -[cis]CH═CH—CH 2 -[cis]CH═CH—; and

R 1 is a hydrogen atom; and

at least one pharmaceutical excipient,

wherein the topical pharmaceutical composition is substantially free of lithium salts, arachidonic acid, and glucocorticoids.

11. A pharmaceutical composition according to claim 10 which contains the polyunsaturated fatty acid (PUFA) derivative of formula (II) as sole active ingredient.

12. The pharmaceutical composition of claim 1 wherein the preservative is selected from methylparaben, propylparaben, benzyl alcohol, ascorbyl palmitate, and ascorbic acid.

13. The method of claim 9 , wherein the mammal is a human.

14. The method of claim 9 , wherein the skin inflammation is caused by atopic eczema, contact dermatitis, psoriasis or uremic pruritis.

15. A topical pharmaceutical composition comprising 15-HETrE, at least one preservative and at least one pharmaceutical excipient.