In-vivo gelling pharmaceutical pre-formulation

• US 10,189,773 B2
• Filed: 05/06/2011
• Issued: 01/29/2019
• Est. Priority Date: 05/07/2010
• Status: Active Grant

• Current Assignee: Theragenics Corporation (Juniper Investment Co. LLC)
• Original Assignee: Medicus Biosciences, LLC
• Inventors: Askari, Syed H., Horng, George
• Primary Examiner(s): Ricci, Craig D
• Application Number:
  US13/696,032
• Publication Number:
  US 20130116341A1
• Time in Patent Office: 2,825 Days
• Field of Search: None
• 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 49/04 X-ray contrast preparations
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07C 229/24 having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid
• CPC Class Codes: C08G 65/34 from hydroxy compounds or their metallic derivatives C08G65/26 takes precedence

Abstract

Provided herein are in vivo gelling pharmaceutical pre-formulations forming biocompatible hydrogel polymers that are polymerized in vivo and kits comprising at least one nucleophilic compound or monomer unit, at least one electrophilic compound or monomer unit, and optionally at least one therapeutic agent. The biocompatible hydrogel polymer is bioabsorbable and releases the therapeutic agent at a target site, avoiding systemic exposure.

Claims

1. An in vivo gelling pharmaceutical pre-formulation, comprising:

(a) at least one multifunctional nucleophilic monomer comprising a polyol core, wherein the polyol core is selected from the group consisting of;

2. The in vivo gelling pharmaceutical pre-formulation of claim 1, wherein the molecular weight of each of the second compound is independently between about 500 and 40000.

3. The in vivo gelling pharmaceutical pre-formulation of claim 1, wherein the second compound is selected from the group consisting of ethoxylated pentaerythritol succinimidyl succinate, ethoxylated pentaerythritol succinimidyl glutarate, and ethoxylated pentaerythritol succinimidyl glutaramide.

4. The in vivo gelling pharmaceutical pre-formulation of claim 1, further comprising a therapeutic agent selected from the group consisting of an anticancer agent, an antiviral agent, an antibacterial agent, antifungal agent, an immunosuppressant agent, an hemostasis agent, and an anti-inflammatory agent.

5. The in vivo gelling pharmaceutical pre-formulation of claim 1, wherein the pH of the aqueous buffer is from about 6.9 to about 7.9.

6. The in vivo gelling pharmaceutical pre-formulation of claim 1, wherein the biocompatible hydrogel polymer is bioabsorbed within about 1 to 70 days.

7. The in vivo gelling pharmaceutical pre-formulation of claim 1, wherein the biocompatible hydrogel polymer is substantially non-bioabsorbable.

8. The biocompatible hydrogel polymer of claim 1.

9. The in vivo gelling pharmaceutical pre-formulation of claim 1, further comprising a second multifunctional nucleophilic monomer comprising more than one nucleophilic group, wherein the second multifunctional nucleophilic monomer is a polyol substituted with R′

, wherein R′

is;

10. The in vivo gelling pharmaceutical pre-formulation of claim 1, wherein the polyol core of the multifunctional nucleophilic monomer is:

11. The in vivo gelling pharmaceutical pre-formulation of claim 1, wherein the polyol core of the multifunctional nucleophilic monomer is:

12. The in vivo gelling pharmaceutical pre-formulation of claim 1, wherein the in vivo gelling pharmaceutical pre-formulation does not contain biological materials.

13. The in vivo gelling pharmaceutical pre-formulation of claim 1, wherein the molecular weight of the multifunctional nucleophilic monomer is between about 5,000 to about 20,000.

14. The in vivo gelling pharmaceutical pre-formulation of claim 1, wherein the mixture comprising at least one multifunctional nucleophilic monomer and the at least one water soluble second compound comprising more than one electrophilic group comprising 4ARM-20k-AA and 4ARM-20k-SGA.