Method for the improvement of transplantation techniques and for the preservation of tissue

Claim 2

A process for improvement and enhancement of transplantation comprising: (a) introducing particles not greater than about 1 micron into tissue selected from the group consisting of donor tissue, host tissue and combinations thereof, wherein the particles are selected from the group consisting of ferromagnetic, paramagnetic, and diamagnetic particles; (b) allowing time sufficient to promote intracellular accumulation and compartmentalization of said particles; (c) subjecting the tissue to an alternating electromagnetic field to inductively heat the particles; and (d) allowing time sufficient to inhibit or destroy cells in the tissue wherein said cells mediate the immunological response of rejection.

Claim 3

The process of claim 1 wherein the method of introduction of the particles is selected from the group consisting of intravenous injection, intra-arterial injection, intra-lymphatic injection, local perfusion and any combination thereof.

Claim 4

The process of claim 1 or 2 wherein the tissue is the host tissue prior to receiving the transplant.

Claim 5

The process of claim 1 or 2 wherein the tissue is the donor tissue prior to being transplanted.

Claim 6

The process of claim 1 or 2 wherein the tissue is both the donor tissue and host tissue after transplantation.

Claim 7

The process of claim 1 wherein the particles are introduced after transplantation when an episode of rejection at a local area has occurred.

Claim 8

The process of claim 6 further comprising the step of using a localized magnetic field to help guide the particles to the local area of rejection.

Claim 9

The process of claim 1 wherein the particles are characterized by a magnetic susceptibility greater than about 10 6 cgs.

Claim 10

The process of claim 1 wherein the electromagnetic field is characterized by a field strength range of 300 gauss to 100 kilogauss.

Claim 11

The process of claim 9 wherein the particles are selected from the group consisting of elements, inorganic compounds, organic compounds and combinations thereof.

Claim 12

The process of claim 10 wherein said elements and inorganic compounds are selected from the group consisting of cobalt, zinc, chromium, iron, nickel, platinum, rare earth metals such as dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium and compounds and complexes thereof such as dysprosium sulfate, erbium sulfate, europium oxide, europium sulfate, gadolinium oxide, gadolinium sulfate, homium oxide, ferric oxide, ferric hydroxide, samarium sulfate, terbium sulfate, thulium oxide, ytterbium sulfide, yttrium oxide, yttrium sulfate, yttrium ferrioxide (Y 3 Fe 5 O 12 ), yttrium aluminum oxide (Y 3 Al 5 O 12 ), dysprosium-nickel, dysprosium cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-ytterium, dysprosium-gallium, and actinide series elements and compounds and complexes thereof.

Claim 13

The process of claim 10 wherein said organic compounds are selected from the group consisting of (a) dextran metal complexes wherein said metal is selected from the group consisting of cobalt, zinc, chromium, gallium, manganese, nickel, platinum, dysprosium, erbium, europium, gadolinium, holmium, iron, samarium, terbium, thulium, ytterbium, yttrium, dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron cobalt-samarium, gadolinium-yttrium, and dysprosium-gallium, and iron such as FeOOH-dextran complexes; (b) iron transporting and chelating compounds comprising ferric ammonium citrate, enterochelin, hydroxamates, phenolates, ferrichromes, desferri-ferrichromes, ferritin, ferric mycobactins and iron sulfur proteins such as ferredoxin and rubredoxin, as well as transferrin and transferrin compounds and complexes; (c) porphyrins comprising etioporphyrins, mesoporphyrins, uroporphyrins, coproporphyrins, protoporphyrins, dicarboxylic acid containing porphyrins, substituted porphyrins such as tetraphenylporphyrin sulfonate (TPPS and protoporphyrin containing molecules such as hematoporphyrins, chlorophylls, and cytochromes, as well as mixed-metal or di-metal hybrid porphyrins, and porphyrin-dextran complexes; and (d) metal complexes selected from the group consisting of metalloporphyrin-transferrin, antibody-ferritin-particles, antibody-ferritin-transferrin-particles, antibody-transferrin-particles, metal-porphyrin-metal complexes, metallothionein particles, and lectin particles.

Claim 14

The process of claim 10 wherein the natural occurring metal moiety of said porphyrin is optionally substituted with a metal selected from the group consisting of cobalt, zinc, chromium, gallium, manganese, nickel, platinium, dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium, dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-yttrium, and dysporsium-gallium.

Claim 15

The process of claim 12 wherein said iron transporting, iron chelating and porphyrin compounds are chemically complexed with dextran.

Claim 16

The process of claim 13 wherein said compounds are chemically complexed with dextran.

Claim 17

The process of claim 1 wherein the magnetic qualities of the ferromagnetic, paramagnetic or diamagnetic particles in the tissue are used as a monitor of the state of the rejection process.

Claim 18

The process of claim 1 wherein the magnetic field is used in conjunction with a known tissue preservation technique selected from the group consisting of local cooling, vascular cooling, pharmacologic preservation, pulsatile perfusion and combinations thereof.

Claim 19

A process for improvement and enhancement of transplantation comprising: (a) introducing particles not greater than about 1 micron into tissue selected from the group consisting of donor tissue, host tissue and combinations thereof, wherein the particles are selected from the group consisting of ferromagnetic, paramagnetic, and diamagnetic particles; (b) allowing time sufficient to promote intracellular accumulation and compartmentalization of said particles; (c) subjecting the tissue to a constant electromagnetic field.

Claim 20

A process for improvement and enhancement of transplantation comprising: (a) introducing particles not greater than about 1 micron into tissue selected from the group consisting of donor tissue, host tissue and combinations thereof, wherein the particles are selected from the group consisting of ferromagnetic, paramagnetic, and diamagnetic particles; (b) allowing time sufficient to promote intracellular accumulation and compartmentalization of said particles; (c) subjecting the tissue to a constant electromagnetic field.

Claim 21

The process of claim 18 wherein the method of introduction of the particles is selected from the group consisting of intravenous injection, intra-arterial injection, intra-lymphatic injection, local perfusion and any combination thereof.

Claim 22

The process of claim 18 or 19 wherein the tissue is the host tissue prior to receiving the transplant.

Claim 23

The process of claim 18 or 19 wherein the tissue is the donor tissue prior to being transplanted.

Claim 24

The process of claim 18 or 19 wherein the tissue is both the donor tissue and host tissue after transplantation.

Claim 25

The process of claim 18 wherein the particles are introduced after transplantation when an episode of rejection at a local area has occurred.

Claim 26

The process of claim 23 further comprising the step of using a localized magnetic field to help guide the particles to the local area of rejection.

Claim 27

The process of claim 18 wherein the particles are characterized by a magnetic susceptibility greater than about 10 6 cgs.

Claim 28

The process of claim 18 wherein the electromagnetic field is characterized by a field strength range of 300 gauss to 100 kilogauss.

Claim 29

The process of claim 18 or 26 wherein the particles are selected from the group consisting of elements, inorganic compounds, organic compounds and combinations thereof.

Claim 30

The process of claim 27 wherein said elements and inorganic compounds are selected from the group consisting of cobalt, zinc, chromium, iron, nickel, platinum, rare earth metals such as dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium and compounds and complexes thereof such as dysprosium sulfate, erbium sulfate, europium oxide, europium sulfate, gadolinium oxide, gadolinium sulfate, homium oxide, ferric oxide, ferric hydroxide, samarium sulfate, terbium sulfate, thulium oxide, ytterbium sulfide, yttrium oxide, yttrium sulfate, yttrium ferrioxide (Y 3 Fe 5 O 12 ), yttrium aluminum oxide (Y 3 Al 5 O 12 ), dysprosium-nickel, dysprosium cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-ytterium, dysprosium-gallium, and actinide series elements and compounds and complexes thereof.

Claim 31

The process of claim 27 wherein said organic compounds are selected from the group consisting of (a) dextran metal complexes wherein said metal is selected from the group consisting of cobalt, zinc, chromium, gallium, manganese, nickel, platinum, dysprosium, erbium, europium, gadolinium, holmium, iron, samarium, terbium, thulium, ytterbium, yttrium, dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron cobalt-samarium, gadolinium-yttrium, and dysprosium-gallium, and iron such as FeOOH-dextran complexes; (b) iron transporting and chelating compounds comprising ferric ammonium citrate, enterochelin, hydroxamates, phenolates, ferrichromes, desferri-ferrichromes, ferritin, ferric mycobactins and iron sulfur proteins such as ferredoxin and rubredoxin, as well as transferrin and transferrin compounds and complexes; (c) porphyrins comprising etioporphyrins, mesoporphyrins, uroporphyrins, coproporphyrins, protoporphyrins, dicarboxylic acid containing porphyrins, substituted porphyrins such as tetraphenylporphyrin sulfonate (TPPS and protoporphyrin containing molecules such as hematoporphyrins, chlorophylls, and cytochromes, as well as mixed-metal or di-metal hybrid porphyrins, and porphyrin-dextran complexes; and (d) metal complexes selected from the group consisting of metalloporphyrin-transferrin, antibody-ferritin-particles, antibody-ferritin-transferrin-particles, antibody-transferrin-particles, metal-porphyrin-metal complexes, metallothionein particles, and lectin particles.

Claim 32

The process of claim 29 wherein said iron transporting, iron chelating and porphyrin compounds are chemically complexed with dextran.

Claim 33

The process of claim 27 wherein the natural occurring metal moiety of said porphyrin is optionally substituted with a metal selected from the group consisting of cobalt, zinc, chromium, gallium, manganese, nickel, platinium, dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium, dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-yttrium, and dysporsium-gallium.

Claim 34

The process of claim 31 wherein said compounds are chemically complexed with dextran.