Manufacture of partially fused peptide pellet

Claim 1

A method of making a partially-fused pellet capable of sustained release of a peptide when implanted in the body comprising, forming a homogeneous mixture of a bioerodible, nonpolymer carrier having a first melting temperature and a peptide having a second melting temperature, said first melting temperature being lower than said second melting temperature, heating said mixture at least to said first melting temperature to cause said carrier to melt, but not to said second melting temperature such that said peptide does not melt, and causing said partially-melted mixture to cool into a hardened pellet.

Claim 2

A method of making a partially-fused pellet capable of sustained release of a peptide when implanted in the body comprising, forming a homogeneous mixture of a bioerodible, nonpolymer carrier having a first melting temperature and a peptide having a second melting temperature, said first melting temperature being lower than said second melting temperature, heating said mixture at least to said first melting temperature to cause said carrier to melt, but not to said second melting temperature such that said peptide does not melt, and causing said partially-melted mixture to cool into a hardened pellet.

Claim 9

A method for making a partially-fused pellet capable of sustained release of a peptide when implanted in the body as claimed in claims 1 or 5 wherein said homogeneous mixture is formed using a peptide selected from the group consisting of growth hormone and growth hormone-releasing hormone, gonadotropin-releasing hormone, and its agonist and antagonist analogues, somatostatin and its analogues, gonadotropins such as luteinizinq hormone and follicle-stimulating hormone, peptide-T, thyrocalcitonin, parathyroid hormone, glucagon, vasopressin, oxytocin, alpha and beta melanocyte-stimulating hormones, peptide molecules which stimulate erythrocyte, leucocyte and immunocyte growth and function such as colony stimulating factors (CSF 1 and 2), erythropoietin and lymphokines (including interleukin I and II), angiotensin I and II, bradykinin, kallidin, adrenocorticotropic hormone, thyroid stimulating hormone, insulin, glucagon and the numerous analogues and congeners of the foregoing peptides.

Claim 10

A method for making a partially-fused pellet capable of sustained release of a peptide when implanted on the body comprising, forming a homogeneous mixture of a bioerodible, lipophilic nonpolymer carrier and a peptide, said nonpolymer carrier having a lower melting temperature than said peptide, introducing a measured amount of said mixture into a tube having a bore and at least an inner surface of fluorocarbon, plugging one end of the tube with a plug, the plug sized to fit totally and sealingly within a portion of the bore, placing said tubing such that the plugged end abuts a solid surface, introducing a compression pin into the bore at the opposite end of said tubing, compressing said mixture by applying pressure via said compression pin, introducing said tubing into an oven, said oven heated at least to the melting temperature of said carrier, leaving said tubing in said oven a sufficient amount of time to allow a partially-melted suspension to form, substantially all of said carrier being melted and substantially all of said peptide not melted, removing the tubing from the oven, placing said tubing such that said plugged end abuts a solid surface, applying pressure to said partially-melted suspension via said compression pin while said partially-melted suspension cools into a hardened pellet, the carrier forming a crystal matrix capturing the peptide.

Claim 11

A method for making a partially-fused pellet capable of sustained release of a peptide when implanted on the body comprising, forming a homogeneous mixture of a bioerodible, lipophilic nonpolymer carrier and a peptide, said nonpolymer carrier having a lower melting temperature than said peptide, introducing a measured amount of said mixture into a tube having a bore and at least an inner surface of fluorocarbon, plugging one end of the tube with a plug, the plug sized to fit totally and sealingly within a portion of the bore, placing said tubing such that the plugged end abuts a solid surface, introducing a compression pin into the bore at the opposite end of said tubing, compressing said mixture by applying pressure via said compression pin, introducing said tubing into an oven, said oven heated at least to the melting temperature of said carrier, leaving said tubing in said oven a sufficient amount of time to allow a partially-melted suspension to form, substantially all of said carrier being melted and substantially all of said peptide not melted, removing the tubing from the oven, placing said tubing such that said plugged end abuts a solid surface, applying pressure to said partially-melted suspension via said compression pin while said partially-melted suspension cools into a hardened pellet, the carrier forming a crystal matrix capturing the peptide.

Claim 13

A method for making a partially-fused pellet capable of sustained release of a drug when implanted in the body comprising, forming a homogeneous mixture of a bioerodible, nonpolymer carrier and a drug, said nonpolymer carrier having a lower melting temperature than the drug; introducing the mixture into a bored tube; compressing said mixture by applying pressure by way of a compression pin introduced into said bore; heating said mixture to a temperature such that substantially all of the carrier is melted and substantially all of the drug is not melted; cooling said mixture while said compressive force is maintained, the carrier forming a crystal matrix capturing the drug.

Claim 14

A method for making a partially-fused pellet capable of sustained release of a drug when implanted in the body comprising, forming a homogeneous mixture of a bioerodible, nonpolymer carrier and a drug, said nonpolymer carrier having a lower melting temperature than the drug; introducing the mixture into a bored tube; compressing said mixture by applying pressure by way of a compression pin introduced into said bore; heating said mixture to a temperature such that substantially all of the carrier is melted and substantially all of the drug is not melted; cooling said mixture while said compressive force is maintained, the carrier forming a crystal matrix capturing the drug.

Claim 15

A method for making a partially-fused pellet capable of sustained release of a drug when implanted in the body comprising, forming a homogeneous mixture of a bioerodible, nonpolymer carrier and a drug, the nonpolymer carrier having a lower melting temperature than the drug; introducing the mixture into a bored tube having two ends, one end of which abuts a solid surface; providing a compressive force to said mixture only in a single direction by way of a compression pin introduced into a second end of the tube; compressing the mixture against the solid surface in the single direction.

Claim 16

A method for making a partially-fused pellet capable of sustained release of a drug when implanted in the body comprising, forming a homogeneous mixture of a bioerodible, nonpolymer carrier and a drug, the nonpolymer carrier having a lower melting temperature than the drug; introducing the mixture into a bored tube having two ends, one end of which abuts a solid surface; providing a compressive force to said mixture only in a single direction by way of a compression pin introduced into a second end of the tube; compressing the mixture against the solid surface in the single direction.