Antibacterial compositions comprising metal phthalocyanine analogues

1. Pharmaceutical compositions comprising at least a metal phthalocyanine analogue of formula (I)

wherein

n is 0, 1 or 2;

M is chosen in the group consisting of Zn, Si(OR 3 ) 2 and AlOR 3 wherein R 3 is chosen in the group consisting of H and C 1-15 alkyl;

R is chosen from H and W, wherein W is represented by the group (X) p R 4 , wherein:

X is chosen in the group consisting of O, S, —NR 7 and —CH 2 —;

and R 4 is

where:

Y is chosen in the group consisting of C 1-10 alkyl and phenyl, or it forms with the Z group, to which it is bound, a saturated or unsaturated heterocycle selected from the group consisting of: morpholine, piperidine, pyridine, pyrimidine, piperazine, pyrrolidine, pyrroline, imidazole, julolidine (2,3,6,7-tetrahydro-1H,5H-pirido[3,2,1-Ij] quinoline;

Z is chosen in the group consisting of —N, —CH 2 N and —CONHCH 2 CH 2 N;

R 5 and R 6 , equal or different from one another, are chosen in the group consisting of C 1-15 alkyl and phenyl, or form with the Z group, to which they are bound, a saturated or unsaturated heterocycle selected from the group consisting of: morpholine, piperidine, pyridine, pyrimidine, piperazine, pyrrolidine, pyrroline, imidazole, julolidine (2,3,6,7-tetrahydro-1H,5H-pirido[3,2,1-Ij] quinoline;

R 7 and R 8 , equal or different from one another, are chosen in the group consisting of H and C 1-15 alkyl;

m, n, p, s, t and u, independently from one another, are 0 or 1; and

v is an integer comprised between 1 and 3;

R 1 and R 2 , same or different from each other, are chosen from H, W and K, wherein W is as defined above, and K is selected from the group consisting of —COOH, —SH, —OH, —NH 2 , —COCH 2 Br, SO 2 Cl, maleimide, hydrazide, phenol, imidate, and biotine, bound to the phthalocyanine nucleus, either directly or through an aliphatic moiety which acts as a spacer;

with the proviso that:

when n=0:

a) R 1 ═R 2 ═W in the position 1, 4 or 2,3; or

b) R 1 ═H and R 2 ═W in the position 1 or 2; or

c) R 1 ═H and R 2 ═K in the position 1 or 2;

when n=1:

d) R 1 ═H, and R═R 2 ═W; or

e) R 1 ═H, R═W and R 2 ═K;

in both cases d) and e) R is in the positions 8(11), 15(18), 22(25), or 9(10), 16(17), 23(24); and R 2 is in the position 1(4) or 2(3);

when n=2:

f) R═R 1 ═R 2 ═W; or

g) R 1 ═H, R═W and R 2 ═K;

in both cases f) and g) R is in the positions 8,11,15,18,22,25, or 9,10,16,17,23,24; and in the case f) R 1 and R 2 are in the positions 1, 4 or 2,3; whereas in the case g) R 2 is in the position 1(4) or 2(3);

in combination with at least a metal chelating agent.

2. The pharmaceutical compositions according to claim 1 , wherein M is Zn or Si(OR 3 ) 2 , where R 3 is defined as above in claim 1 .

3. The pharmaceutical compositions according to claim 1 , wherein the group (X) p R 4 is chosen in the group consisting of:

4. The pharmaceutical composition according to claim 1 , wherein the said metal phthalocyanine analogue is defined by the following formulas:

{2,3,9,10,16,17,23,24-octa[3-(N,N,N-trimethylammonium)phenoxy]zinc(II) phthalocyanine}octaiodide (compound 1);

{2(3),9(10),16(17),23(24)-tetra[1,3-bis-(trimethylammonium)propyl-2-oxy]zinc(II) phthalocyanine}octaiodide (compound 2);

2(3),9(10),16(17),23(24)-tetra[1,3-bis-(dimethylamino)propyl-2-oxy]zinc(II) phthalocyanine (compound 3);

{2(3),9(10),16(17),23(24)-tetra[3-(N,N,N-trimethylammonium)phenoxy]zinc(II) phthalocyanine}tetraiodide (compound 4);

{2(3),9(10),16(17),23(24)-tetra[3-(N,N,N-diethylmethylammonium)phenoxy]zinc(II) phthalocyanine}tetraiodide (compound 5);

{1(4),8(11),15(18),22(25)-tetra[3-(N,N,N-trimethylammonium)phenoxy]zinc(II) phthalocyanine}tetraiodide (compound 6);

{1(4),8(11),15(18),22(25)-tetra[3-(N,N,N-diethylmethylammonium)phenoxy]zinc(II) phthalocyanine}tetraiodide (compound 7);

{2,3,9,10,16,17,23,24-octa[3-(N,N,N-diethylmethylammonium)phenoxy]zinc(II) phthalocyanine}octaiodide (compound 8);

2(3),9(10),16(17),23(24)-tetra[4-(1-methylpiperidinil)oxy]zinc(II) phthalocyanine (compound 9);

1(4),8(11),15(18),22(25)-tetra[4-(1-methylpiperidinil)oxy]zinc(II) phthalocyanine (compound 10);

2(3),9(10),16(17),23(24)-tetra[2-(piperidin-1-yl)ethoxy]zinc(II) phthalocyanine (compound 11);

2(3),9(10),16(17),23(24)-tetra[2-(morpholin-4-yl)ethoxy]zinc(II) phthalocyanine (compound 12);

1(4),8(11),15(18),22(25)-tetra[2-(piperidin-1-yl)ethoxy]zinc(II) phthalocyanine (compound 13);

1,4,8,11,15,18,22,25-octa[2-(morpholin-4-yl)ethoxy]zinc(II) phthalocyanine (compound 14);

1,4,8,11,15,18,22,25-octa[3-(piperidin-1-yl)propoxy]zinc(II) phthalocyanine (compound 15);

1(4),8(11),15(18),22(25)-tetra[2-(morpholin-4-yl)ethoxy]zinc(II) phthalocyanine (compound 16);

{2(3),9(10),16(17),23(24)-tetra[N-(2-aminoethyl)benzamidoyl-4-oxy]zinc(II) phthalocyanine}tetra(trifluoroacetate) (compound 18);

{2(3),9(10),16(17),23(24)-tetra[2-(4-methylmorpholin-4-ium)ethoxy]zinc(II) phthalocyanine}tetraiodide (compound 19);

{2(3),9(10),16(17),23(24)-tetra[2-(1-methylpiperidin-1-ium)ethoxy]zinc(II) phthalocyanine}tetraiodide (compound 20);

{1(4),8(11),15(18),22(25)-tetra[2-(1-methylpiperidin-1-ium)ethoxy]zinc(II) phthalocyanine}tetraiodide (compound 21);

{1(4),8(11),15(18),22(25)-tetra[2-(4-methylmorpholin-4-ium)ethoxy]zinc(II) phthalocyanine}tetraiodide (compound 22);

{2(3),9(10),16(17),23(24)-tetra[4-(1-dimethylpiperidin-1-ium)oxy]zinc(II) phthalocyanine}tetraiodide (compound 23);

{2(3),9(10),16(17),23(24)-tetra[3-(N,N,N-triethylmethylammonium)phenoxy]zinc(II) phthalocyanine}tetraiodide (compound 24);

{2(3),9(10),16(17),23(24)-tetra[N-methyl-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolinium-8-yl)oxy)]phthalocyanine}zinc(II) iodide (compound 25);

2,3,9,10,16,17,23,24-tetra[(N,N′-dimethyl)piperazo]zinc(II) phthalocyanine (compound 26);

2,3,9,10,16,17,23,24-octa[2-(N,N-diethylamino)ethylthio]zinc(II) phthalocyanine (compound 27);

{2,3,9,10,16,17,23,24-octa[3-(N,N,N-trimethylammonium)phenoxy]-dihydroxy Si(IV) phthalocyanine}octaiodide (compound 28);

{2,3,9,10,16,17,23,24-tetra[(N,N,N′,N′-tetramethyl)piperazinediium]zinc(II) phthalocyanine}octaiodide (compound 29);

{2,3,9,10,16,17,23,24-octa[3-(N,N,N-trimethylammonium)phenylthio]zinc(II) phthalocyanine}octaiodide (compound 30);

{2,3,9,10,16,17,23,24-octa[3-(1-methylpiridin-ium)oxy]zinc(II) phthalocyanine}octaiodide (compound 31);

2,3,9,10,16,17,23,24-octa[2-(N,N-dimethylamino)ethylthio]zinc(II) phthalocyanine (compound 32);

{2,3,9,10,16,17,23,24-octa[2-(N,N,N-trimethylammonium)ethylthio]zinc(II) phthalocyanine}octaiodide (compound 33).

5. The pharmaceutical compositions according to claim 1 , wherein the said metal chelating agent is selected from the metal chelating agents having specificity for Ca 2+ and Mg 2+ ions.

6. The pharmaceutical compositions according to claim 5 , wherein the said metal chelating agent is selected from 1,2-diaminocyclohexane-N,N,N′,N′-tetraacetic acid (CDTA), diethylenetriamine-pentaacetic acid (DTPA) and ethylenediamine-N,N,N′,N′-tetraacetic acid (EDTA).

7. The pharmaceutical compositions according to claim 6 , wherein the said metal chelating agent is EDTA.

8. The pharmaceutical compositions according to claim 1 , in a formulation selected from solutions, liposome or microvesicle preparations, dispersions, ointments, and other suitable topical dermatological preparations or preparations suitable for in vivo/ex vivo applications.

9. A process for preparing a pharmaceutical composition for photodynamic therapy, said process comprising combining at least a metal phthalocyanine analogue of formula (I) according to claim 1 with at least a metal chelating agent.

10. A method of treating infectious diseases by photodynamic therapy, said method comprising administering to a patient in need of such a treatment a pharmaceutical composition comprising at least a metal phthalocyanine analogue of formula (I) in combination with at least a metal chelating agent according to claim 1 .

11. The method according to claim 10 , wherein said pharmaceutical composition is administered by topical or parenteral way.

12. The method according to claim 10 , wherein said infectious diseases are bacterial, fungal or viral infections.

13. The method according to claim 10 , wherein said infectious diseases are skin or mucosal diseases caused by Gram negative bacteria.

14. A method of sterilizing blood or blood derivatives, said method comprising adding to blood or blood derivatives in need of such a treatment a pharmaceutical composition comprising at least a metal phthalocyanine analogue of formula (I) in combination with at least a metal chelating agent according to claim 1 , and thereafter irradiating.

15. The pharmaceutical composition according to claim 1 , wherein the said metal phthalocyanine analogue is defined by the following formulas:

{2,3,9,10,16,17,23,24-octa[3-(N,N,N-trimethylammonium)phenoxy]zinc(II) phthalocyanine}octaiodide (compound 1);

{2(3),9(10),16(17),23(24)-tetra[1,3-bis-(trimethylammonium)propyl-2-oxy]zinc(II) phthalocyanine}octaiodide (compound 2);

{2(3),9(10),16(17),23(24)-tetra[3-(N,N,N-trimethylammonium)phenoxy]zinc(II) phthalocyanine}tetraiodide (compound 4); and

{1(4),8(11),15(18),22(25)-tetra[3-(N,N,N-trimethylammonium)phenoxy]zinc(II) phthalocyanine}tetraiodide (compound 6).