EP0000667A1 — Intravascularly-administrable, magnetically-local…

Claim 1

Independent Claim 180 words

An intravascularly-administrable, magnetically- localizable biodegradable carrier, comprising microspheres formed from an amino acid polymer matrix with magnetic particles embedded therein, said microspheres having an average size of less than 1.5 microns and said magnetic particles having an average size of not over 1,000 Angstroms, said microspheres containing from 5 to 350 parts by weight of said magnetic particles per 100 parts of said amino acid polymer, at least 90% of said microspheres being immobilizable by a magnetic.induction of 8,000 gauss when an aqueous suspension'of said microspheres is pumped at a rate of 0.05 centimeters per second through a conduit of 0.168 centimeter internal diameter but not over 10% of said microspheres being immobilizable by said magnetic induction when pumped through said conduit at a flow rate of 10 centimeters per second, said magnetic induction being applied by a bipolar magnet with its poles equidistant from the centerline of said tube, said 8,000'gauss being referenced to a plane intersecting said tube at right angles to the direction of flow and extending for at least 10 centimeters in the direction of flow.

Claim 2

Dependent Claim 180 words

An intravascularly-administrable, magnetically- localizable biodegradable carrier, comprising microspheres formed from an amino acid polymer matrix with magnetic particles embedded therein, said microspheres having an average size of less than 1.5 microns and said magnetic particles having an average size of not over 1,000 Angstroms, said microspheres containing from 5 to 350 parts by weight of said magnetic particles per 100 parts of said amino acid polymer, at least 90% of said microspheres being immobilizable by a magnetic.induction of 8,000 gauss when an aqueous suspension'of said microspheres is pumped at a rate of 0.05 centimeters per second through a conduit of 0.168 centimeter internal diameter but not over 10% of said microspheres being immobilizable by said magnetic induction when pumped through said conduit at a flow rate of 10 centimeters per second, said magnetic induction being applied by a bipolar magnet with its poles equidistant from the centerline of said tube, said 8,000'gauss being referenced to a plane intersecting said tube at right angles to the direction of flow and extending for at least 10 centimeters in the direction of flow.

Claim 3

Dependent Claim 19 words

. The carrier of claim 1 in which said magnetic particles'are concentrated in the peripheral portions of said microspheres.

Claim 4

Dependent Claim 29 words

The carrier of claim 1 in which said microspheres contain from 10 to 150 parts by weight of said magnetic material per 100 parts of said amino acid polymer.

Claim 5

Dependent Claim 22 words

The carrier of claim 3 in which said magnetic material is Fe 3 0 4 and said amino acid polymer is albumin.

Claim 6

Dependent Claim 74 words

The carrier of claim 1 in which said microspheres have an average size of less than 1.2 microns, said magnetic particles have an average size of not over 300 Angstroms, said microspheres containing from 10 to 150 parts by weight of said magnetic particles per 100 parts of said amino acid polymer, and at least 95% of said microspheres are immobilized by the magnetic induction of 8,000 gauss as further indicated by claim 1.

Claim 7

Dependent Claim 19 words

The carrier of claim 5 in which said magnetic particles are concentrated in the peripheral portions of said microspheres.

Claim 8

Dependent Claim 22 words

The carrier of claim 5 in which said magnetic material is Fe 3 0 4 and said amino acid polymer is albumin.

Claim 9

Dependent Claim 124 words

The process of incorporating a water-soluble therapeutic agent in albumin microspheres, comprising the process in which all steps thereof are carried out at a temperature within the range from 1 to 45°C, including the steps of preparing an aqueous albumin solution of the said therapeutic agent, said solution containing from 5 to 50 parts by weight of albumin per 100 parts of water and from 1 to'20 parts by weight of said therapeutic agent per 100 parts of albumin, emulsifying said solution with a vegetable oil to form a water-in-oil emulsion containing dispersed droplets of the albumin solution, removing the oil by washing the dispersed droplets with an oil-soluble water-immiscible organic solvent, and recovering the resulting microspheres in a portion of said organic solvent.

Claim 10

Dependent Claim 124 words

The process of incorporating a water-soluble therapeutic agent in albumin microspheres, comprising the process in which all steps thereof are carried out at a temperature within the range from 1 to 45°C, including the steps of preparing an aqueous albumin solution of the said therapeutic agent, said solution containing from 5 to 50 parts by weight of albumin per 100 parts of water and from 1 to'20 parts by weight of said therapeutic agent per 100 parts of albumin, emulsifying said solution with a vegetable oil to form a water-in-oil emulsion containing dispersed droplets of the albumin solution, removing the oil by washing the dispersed droplets with an oil-soluble water-immiscible organic solvent, and recovering the resulting microspheres in a portion of said organic solvent.

Claim 11

Dependent Claim 26 words

; 9. The process of claim 8 in which said solution contains from 20 to 30 parts by weight of albumin per 100 parts of water.

Claim 12

Dependent Claim 33 words

The process of claim 8 in which said microspheres in said organic solvent are further treated by adding a hardening agent selected from aldehydes and glyoxals to said solvent which is soluble therein.

Claim 13

Dependent Claim 26 words

The process of claim 10 in which said hardening agent is formaldehyde, which is added to said organic solvent by transference from an aqueous solution thereof.'

Claim 14

Dependent Claim 174 words

The process of incorporating a water-soluble heat-sensitive therapeutic agent in intravascularly-adinin- istrable magnetically responsive microspheres, comprising the process in which all steps are carried out at a temperature in the range of 1 to 45°C, including the steps of preparing an aqueous albumin solution of said therapeutic agent, said solution containing from 5 to 50 parts by weight of albumin per 100 parts of water and from 1 to 20 parts by weight of said therapeutic agent per 100 parts of albumin, said solution also containing from 5 to 350 parts by weight of magnetic particles per 100 parts of said albumin, said magnetic particles having an average size of not over 1,000 Angstroms, emulsifying said solution with a vegetable oil to form a water-in-oil emulsion containing dispersed droplets of the albumin solution, reducing the size of the dispersed droplets to an average size of less than 1.5 microns, removing the oil by washing dispersed droplets with an oil-soluble water-immiscible organic solvent, and recovering the resulting microspheres in a portion of said organic solvent.

Claim 15

Dependent Claim 174 words

The process of incorporating a water-soluble heat-sensitive therapeutic agent in intravascularly-adinin- istrable magnetically responsive microspheres, comprising the process in which all steps are carried out at a temperature in the range of 1 to 45°C, including the steps of preparing an aqueous albumin solution of said therapeutic agent, said solution containing from 5 to 50 parts by weight of albumin per 100 parts of water and from 1 to 20 parts by weight of said therapeutic agent per 100 parts of albumin, said solution also containing from 5 to 350 parts by weight of magnetic particles per 100 parts of said albumin, said magnetic particles having an average size of not over 1,000 Angstroms, emulsifying said solution with a vegetable oil to form a water-in-oil emulsion containing dispersed droplets of the albumin solution, reducing the size of the dispersed droplets to an average size of less than 1.5 microns, removing the oil by washing dispersed droplets with an oil-soluble water-immiscible organic solvent, and recovering the resulting microspheres in a portion of said organic solvent.

Claim 16

Dependent Claim 24 words

The process of claim 12 in which said solution contains from 20 to 30 parts by weight of albumin per 100 parts of water.

Claim 17

Dependent Claim 37 words

1 4 . The process of claim 12 in which said micro- spheres in said organic solvent are further treated by adding a hardening agent selected from aldehydes and glyoxals to said solvent which is soluble therein.

Claim 18

Dependent Claim 26 words

The process of claim 14 in which said hardening agent is formaldehyde., which is added to said organic solvent by transference from an aqueous solution thereof.

Claim 19

Dependent Claim 156 words

The process of incorporating a water-soluble heat-sensitive therapeutic agent in albumin microspheres, comprising the process in which all steps thereof are carried out at a temperature of from about 20 to 30°C, including the steps of preparing an aqueous solution of human serum albumin containing from 5 to 50 parts by weight of albumin per 100 parts of water, said solution also containing from 1 to 20 parts by weight of said therapeutic agent per 100 parts of albumin, emulsifying said solution with a vegetable oil to form a water-in-oil emulsion containing dispersed droplets of the albumin solution, reducing the size of the dispersed droplets of said solution to an average size of less than 3 microns, introducing said emulsion into a body of vegetable oil to further disperse said droplets, removing the oil by washing-the dispersed droplets with an oil-soluble water-immiscible organic solvent, and recovering the resulting microspheres in a portion of said organic solvent.

Claim 20

Dependent Claim 156 words

The process of incorporating a water-soluble heat-sensitive therapeutic agent in albumin microspheres, comprising the process in which all steps thereof are carried out at a temperature of from about 20 to 30°C, including the steps of preparing an aqueous solution of human serum albumin containing from 5 to 50 parts by weight of albumin per 100 parts of water, said solution also containing from 1 to 20 parts by weight of said therapeutic agent per 100 parts of albumin, emulsifying said solution with a vegetable oil to form a water-in-oil emulsion containing dispersed droplets of the albumin solution, reducing the size of the dispersed droplets of said solution to an average size of less than 3 microns, introducing said emulsion into a body of vegetable oil to further disperse said droplets, removing the oil by washing-the dispersed droplets with an oil-soluble water-immiscible organic solvent, and recovering the resulting microspheres in a portion of said organic solvent.

Claim 21

Dependent Claim 27 words

The process of claim 16 in which said solution contains from 20 to 30 parts by weight of said human serum albumin per 100 parts of water.

Claim 22

Dependent Claim 33 words

The process of claim 16, in which said microspheres in said organic solvent are further treated by adding a bardening agent selected from aldehydes and glyoxals to said solvent which is soluble therein.

Claim 23

Dependent Claim 26 words

The process of claim 18 in which said hardening agent is formaldehyde, which is added to said organic solvent by transference from an aqueous solution thereof.

Intravascularly-administrable, magnetically-localizable biodegradable carrier and process for its preparation

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