DRUG DELIVERY FROM RAPID GELLING POLYMER COMPOSITION

• US 20090192214A1
• Filed: 10/28/2008
• Published: 07/30/2009
• Est. Priority Date: 12/30/2002
• Status: Abandoned Application

• Current Assignee: Angiotech Pharmaceuticals Incorporated
• Original Assignee: Angiotech Pharmaceuticals Incorporated
• Inventors: Embree, Leanne, Takacs-Cox, Aniko, Toleikis, Philip M., Gravett, David M., Maiti, Arpita
• Application Number:
  US12/259,916
• Publication Number:
  US 20090192214A1
• Time in Patent Office: Days
• US Class Current: 514/449
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/54 having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/6903 the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
• CPC Class Codes: A61K 51/1213 Semi-solid forms, gels, hydrogels, ointments, fats and waxes that are solid at room temperature
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 2300/434 of enzymes
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin

Abstract

Compositions are disclosed that afford drug delivery from two-part polymer compositions that rapidly form covalent linkages when mixed together. Such compositions are particularly well suited for use in a variety of tissue related applications when rapid adhesion to the tissue and gel formation is desired along with drug delivery. For example, the compositions are useful as tissue sealants, in promoting hemostasis, in effecting tissue adhesion, in providing tissue augmentation, and in the prevention of surgical adhesions.

Claims

1-126. -126. (canceled)

127. A drug-delivery system comprising:

a first component comprising a sulfhydryl group-containing compound of formula;

Compound₁ —

(SH)_m wherein m≧

2; and

a second component comprising a sulfhydryl reactive group-containing compound of formula;

Compound₂ —

Y_n, wherein Y is a sulfhydryl reactive group and wherein n≧

2; and

a hydrophobic drug,

wherein, when the first component contacts the second component in a liquid medium, Compound₁ —

(SH)_m and Compound₂ —

Y_n, form covalent bonds between the sulfhydryl groups and Y to form a biocompatible gel in less than one minute, and wherein the hydrophobic drug is admixed in the biocompatible gel.

128. The drug-delivery system of claim 127, wherein m and n are each 4 or 12.

129. The drug-delivery system of claim 127, wherein Compound₁ and Compound₂ are each a polyalkylene oxide.

130. The drug-delivery system of claim 129, wherein the polyalkylene oxide is polyethylene glycol.

131. The drug-delivery system of claim 127, wherein Y is succinimidyl ester or maleimidyl.

132. The drug-delivery system of claim 127 wherein the first component is in a first container and the second component is in a second container.

133. The drug-delivery system of claim 132 wherein the first component is in a in a liquid medium having an alkaline pH and the second component is in either a liquid medium having a neutral or acidic pH or in powder form.

134. The drug-delivery system of claim 127 wherein the first component and the second component are a mixture of powders in a first container, and the drug-delivery system further comprises an acidic buffer solution in a second container.

135. The drug-delivery system of claim 134 further comprises an alkaline buffer solution.

136. The drug-delivery system of claim 127 wherein the hydrophobic drug is a cell cycle inhibitor or an analogue or derivative thereof.

137. The drug-delivery system of claim 136 wherein the cell cycle inhibitor is a microtubule stabilizing agent.

138. The drug-delivery system of claim 137, wherein the microtubule stabilizing agent is paclitaxel, docetaxel, or Peloruside A.

139. The drug-delivery system of claim 138, wherein the cell cycle inhibitor is a taxane.

140. The drug-delivery system of claim 139, wherein the taxane is paclitaxel or an analogue or derivative thereof.

141. A method for forming a drug-loaded biocompatible gel in situ, comprising:

providing a first component comprising a sulfhydryl group-containing compound

of formula;

Compound₁ —

(SH)_m in a liquid medium having an alkaline pH, wherein m≧

2;

providing a second component comprising a sulfhydryl reactive group-containing compound of formula;

Compound₂ —

Y_n in either a liquid medium having a neutral or acidic pH or in powder form, wherein Y is a sulfhydryl reactive group and wherein n≧

2;

combining a hydrophobic drug with either the first component or the second component; and

combining the first component and the second component to form a gel incorporating the hydrophobic drug, wherein the sulfhydryl groups and the sulfhydryl reactive groups react with one another to form covalent bonds therebetween.

142. The method of claim 141, wherein m and n are each 4 or 12.

143. The method of claim 141, wherein Compound₁ and Compound₂ are each a polyalkylene oxide.

144. The method of claim 141, wherein Y is succinimidyl ester or maleimidyl.

145. The method of claim 141 wherein the hydrophobic drug is a cell cycle inhibitor or an analogue or derivative thereof.

146. A method for forming a drug-loaded biocompatible gel in situ, comprising:

providing a powdered mixture of a sulfhydryl group-containing compound of formula;

Compound₁ —

(SH)_m, wherein m≧

2, a sulfhydryl reactive group-containing compound of formula;

Compound₂ —

Y_n, wherein Y is a sulfhydryl reactive group and wherein n≧

2, and a hydrophobic drug;

providing a first buffer having an acidic pH;

providing a second buffer having an alkaline pH;

combining the powdered mixture with the first buffer to obtain a solution;

combining the solution of the powdered mixture with the second buffer form a gel incorporating the hydrophobic drug, wherein the sulfhydryl groups and the sulfhydryl reactive groups react with one another to form covalent bonds therebetween.

147. The method of claim 146, wherein m and n are each 4 or 12.

148. The method of claim 146, wherein Compound₁ and Compound₂ are each a polyalkylene oxide.

149. The method of claim 146, wherein Y is succinimidyl ester or maleimidyl.

150. The method of claim 146 wherein the hydrophobic drug is a cell cycle inhibitor or an analogue or derivative thereof.