Claims for Patent: 6,008,198

Summary for Patent: 6,008,198

Title:	Porphyrin metal complex-albumin inclusion compound and oxygen carrier composition comprising the same
Abstract:	A porphyrin metal complex-albumin inclusion compound wherein a substituted porphyrin metal complex comprising, as a central, coordinated metal, a transitional metal belonging to the fourth or fifth period of the periodic law, is included in the albumin, and an oxygen carrier composition comprising said inclusion compound as an active ingredient. The compound functions as an oxygen carrier which is superior in biocompatibility, capable of adsorption and desorption of oxygen under physiological conditions, and is rather easily produced at an industrial scale.
Inventor(s):	Tsuchida; Eishun (Tokyo, JP), Nishide; Hiroyuki (Tokyo, JP), Komatsu; Teruyuki (Tokyo, JP)
Assignee:	Yoshitomi Pharmaceutical Industries, Ltd. (Osaka, JP)
Application Number:	08/639,798
Patent Claims:	1. A porphyrin metal complex-albumin inclusion compound comprising albumin and a substituted porphyrin metal complex wherein said substituted porphyrin metal complex comprising, as a central, coordinated metal, a transitional metal belonging to the fourth or fifth period of the periodic law, is included in the albumin wherein the substituted porphyrin metal complex is a 5,10,15,20-tetra[.alpha.,.alpha.,.alpha.,.alpha.-o-(substituted amide)phenyl]porphyrin metal complex of the following formula (I) ##STR3## wherein R.sup.1 is a hydrogen or a methyl, M is an iron or cobalt ion, n is an integer of from 0 to 17 and m is an integer of from 3 to 17 or ##STR4## wherein the two R.sup.2 groups are the same of different and each is a vinyl or a 1-alkyloxyethyl group of the formula: --(CH.sub.3)CHO(CH.sub.2).sub.h CH.sub.3 wherein h is an integer of from 0 to 17, R.sup.3 is a hydrogen or a methyl, M is an iron or cobalt ion, j is an integer of from 0 to 17 and k is an integer of from 3 to 10. 2. The porphyrin metal complex-albumin inclusion compound of claim 1, wherein the substituted porphyrin metal complex is a 5,10,15,20-tetra[.alpha.,.alpha.,.alpha.,.alpha.-o-(substituted amide)phenyl]porphyrin metal complex of the following formula (I) ##STR5## wherein R.sup.1 is a hydrogen or a methyl, M is an iron or cobalt ion, n is an integer of from 0 to 17 and m is an integer of from 3 to 17. 3. The porphyrin metal complex-albumin inclusion compound of claim 1, wherein the substituted porphyrin metal complex is a porphyrin metal complex of the formula (II) ##STR6## wherein the two R.sup.2 groups are the same or different and each is a vinyl or a 1-alkyloxyethyl group of the formula: --(CH.sub.3)CHO(CH.sub.2).sub.h CH.sub.3 wherein h is an integer of from 0 to 17, R.sup.3 is a hydrogen or a methyl, M is an iron or cobalt ion, j is an integer of from 0 to 17 and k is an integer of from 3 to 10. 4. The inclusion compound of claim 2, wherein the iron or cobalt is divalent. 5. The inclusion compound of claim 3, wherein the iron or cobalt is divalent. 6. The inclusion compound of claim 1, wherein the albumin is a human serum albumin or a recombinant human serum albumin. 7. The inclusion compound of claim 2, wherein the albumin is a human serum albumin or a recombinant human serum albumin. 8. The inclusion compound of claim 1, wherein the substituted porphyrin metal complex is a 2-(8'-(2"-methyl-1"-imidazolyl)octanoyloxymethyl)-5,10,15,20-tetrakis(.alp ha.,.alpha.,.alpha.,.alpha.-o-pivalamidophenyl)porphyrinato iron complex. 9. The inclusion compound of claim 1, wherein the substituted porphyrin metal complex is a 2-(18'-(N-imidazolyl)octadecanoyloxymethyl)-5,10,15,20-tetrakis(.alpha.,.a lpha.,.alpha.,.alpha.-o-(2,2-dimethyloctadecanamidophenyl)porphyrinato iron complex a 2-(8'-(N-imidazolyl)octanoyloxymethyl)-5,10,15,20-tetrakis(.alpha.,.alpha. ,.alpha.,.alpha.-o-pivalamidophenyl)porphyrinato iron complex or a 2-(8'-(N-imidazolyl)octanoyloxymethyl)-5,10,15,20-tetrakis(.alpha.,.alpha. ,.alpha.,.alpha.-o-(2,2-dimethylhexanamido) phenyl)porphyrinato cobalt complex. 10. An oxygen carrier composition comprising, as an active ingredient, a porphyrin metal complex-albumin inclusion compound that comprises albumin and a substituted porphyrin metal complex wherein said substituted porphyrin metal complex comprising, as a central, coordinated metal, a transitional metal belonging to the fourth or fifth period of the periodic law, is included in the albumin wherein the substituted porphyrin metal complex is a 5,10,15,20-tetra[.alpha.,.alpha.,.alpha.,.alpha.-o-(substituted amide)phenyl]porphyrin metal complex of the following formula (I) ##STR7## wherein R.sup.1 is a hydrogen or a methyl, M is an iron or cobalt ion, n is an integer of from 0 to 17 and m is an integer of from 3 to 17 or ##STR8## wherein the two R.sup.2 groups are the same of different and each is a vinyl or a 1-alkyloxyethyl group of the formula: --(CH.sub.3)CHO(CH.sub.2).sub.h CH.sub.3 wherein h is an integer of from 0 to 17, R.sup.3 is a hydrogen or a methyl, M is an iron or cobalt ion, j is an integer of from 0 to 17 and k is an integer of from 3 to 10. 11. The oxygen carrier composition of claim 10, wherein the substituted porphyrin metal complex is a 5,10,15,20-tetra[.alpha.,.alpha.,.alpha.,.alpha.-o-(substituted amide)phenyl]porphyrin metal complex of the following formula (I) ##STR9## wherein R.sup.1 is a hydrogen or a methyl, M is an iron or cobalt ion, n is an integer of from 0 to 17 and m is an integer of from 3 to 17. 12. The oxygen carrier composition of claim 10, wherein the substituted porphyrin metal complex is a porphyrin metal complex of the formula (II) ##STR10## wherein the two R.sup.2 groups are the same or different and each is a vinyl or a 1-alkyloxyethyl group of the formula: --(CH.sub.3)CHO(CH.sub.2).sub.h CH.sub.3 wherein h is an integer of from 0 to 17, R.sup.3 is a hydrogen or a methyl, M is an iron or cobalt ion, j is an integer of from 0 to 17 and k is an integer of from 3 to 10. 13. The oxygen carrier composition of claim 11, wherein the iron or cobalt is divalent. 14. The oxygen carrier composition of claim 12, wherein the iron or cobalt is divalent. 15. The oxygen carrier composition of claim 10, wherein the albumin is a human serum albumin or a recombinant human serum albumin. 16. The oxygen carrier composition of claim 11, wherein the albumin is a human serum albumin or a recombinant human serum albumin. 17. The oxygen carrier composition of claim 10, wherein the substituted porphyrin metal complex is a 2-(8'-(2"-methyl-1"-imidazolyl)octanoyloxymethyl)-5,10,15,20-tetrakis(.alp ha.,.alpha.,.alpha.,.alpha.-o-pivalamidophenyl)porphyrinato iron complex. 18. The oxygen carrier composition of claim 10, wherein the substituted porphyrin metal complex is a 2-(18'-(N-imidazolyl)octadecanoyloxymethyl)-5,10,15,20-tetrakis(.alpha.,.a lpha.,.alpha.,.alpha.-o-(2,2-dimethyloctadecanamidophenyl)porphyrinato iron complex, a 2-(8'-(N-imidazolyl)octanoyloxymethyl)-5,10,15,20-tetrakis(.alpha.,.alpha. ,.alpha.,.alpha.-o-pivalamidophenyl)porphyrinato iron complex or a 2-(8'-(N-imidazolyl)octanoyloxymethyl)-5,10,15,20-tetrakis(.alpha.,.alpha. ,.alpha.,.alpha.-o-(2-,2 -dimethylhexanamido)phenyl)porphyrinato cobalt complex.

Details for Patent 6,008,198

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Grifols Therapeutics Llc	ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5	albumin (human)	For Injection	101138	10/21/1942		2015-04-28
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2015-04-28
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2015-04-28
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	08/15/1978		2015-04-28