Solid polyglycol-based biocompatible pre-formulation

• US 8,987,339 B2
• Filed: 03/14/2014
• Issued: 03/24/2015
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Theragenics Corporation (Juniper Investment Co. LLC)
• Original Assignee: Medicus Biosciences, LLC
• Inventors: Askari, Syed H., Choi, Yeon S.
• Primary Examiner(s): Singh, Anoop
• Assistant Examiner(s): FALKOWITZ, ANNA R
• Application Number:
  US14/212,457
• Publication Number:
  US 20140271528A1
• Time in Patent Office: 375 Days
• Field of Search: 514/772.3, 524/879
• US Class Current: 514/772.3
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/635 having a heterocyclic ring, e.g. sulfadiazine
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 31/795 Polymers containing sulfur
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/00 Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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 49/0404 containing barium sulfate
• CPC Class Codes: A61K 49/0409 Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is not a halogenated organic compound
• CPC Class Codes: A61K 49/0457 Semi-solid forms, ointments, gels, hydrogels
• 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: A61L 2300/206 : Biguanides, e.g. chlorohexidine
• CPC Class Codes: A61L 2300/404 : Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/41 : Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2400/06 : Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/24 : for joint reconstruction
• CPC Class Codes: A61L 2430/34 : for soft tissue reconstruction
• CPC Class Codes: A61L 26/0019 : obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 26/0066 : Medicaments; Biocides
• CPC Class Codes: A61L 26/008 : Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/18 : obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/3604 : characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3695 : characterised by the function or physical properties of the final product, where no specific conditions are defined to achieve this A61L27/3687, A61L27/3691 take precedence
• CPC Class Codes: A61L 27/52 : Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides

Abstract

Provided herein are pre-formulations forming a biocompatible hydrogel polymer comprising at least one nucleophilic compound or monomer unit, at least one electrophilic compound or monomer unit, and optionally a therapeutic agent and/or viscosity enhancer. In some embodiments, the biocompatible hydrogel polymer covers a wound in a mammal and adheres to the surrounding skin tissue. In other embodiments, the hydrogel polymer is delivered into a joint space to treat joint disease or navicular disease.

Claims

1. A solid polyglycol-based, fully synthetic, pre-formulation, comprising:

(a) at least one solid first compound comprising more than two nucleophilic groups;

(b) at least one solid second compound comprising more than two electrophilic groups;

(c) optionally, a solid buffer component;

(d) optionally, a solid therapeutic agent; and

(e) optionally, a solid viscosity enhancer

wherein the solid polyglycol-based, fully synthetic, pre-formulation polymerizes and/or gels to form a polyglycol-based, fully synthetic, biocompatible hydrogel polymer after addition of a liquid component, wherein the liquid component does not contain any first compound or second compound, and provided that the solid polyglycol-based, fully synthetic, pre-formulation does not contain any aqueous component.

2. The solid polyglycol-based, fully synthetic, pre-formulation of claim 1, wherein the liquid component comprises water, saline, a buffer, a therapeutic agent or a combination thereof.

3. The solid polyglycol-based, fully synthetic, pre-formulation of claim 1, wherein the nucleophilic group comprises a thiol or amino group.

4. The solid polyglycol-based, fully synthetic, pre-formulation of claim 1, wherein the solid first compound is a MULTIARM (5k-50k) polyol derivative comprising polyglycol subunits and more than two nucleophilic groups.

5. The solid polyglycol-based, fully synthetic, pre-formulation of claim 1, wherein the electrophilic group comprises an epoxide, N-succinimidyl succinate, N-succinimidyl glutarate, N-succinimidyl succinamide or N-succinimidyl glutaramide.

6. The solid polyglyol-based, fully synthetic, pre-formulation of claim 1, wherein the solid second compound is a MULTIARM (5k-50k) polyol derivative comprising polyglycol subunits and more than two electrophilic groups.

7. The solid polyglycol-based, fully synthetic pre-formulation of claim 1, wherein the solid first compound is a MULTIARM-(5-50k)-SH, a MULTIARM-(5-50k)-NH2, a MULTIARM-(5-50k)-AA, or a combination thereof, and the second compound is a MULTIARM-(5-50k)-SG, a MULTIARM-(5-50k)-SGA, a MULTIARM-(5-50k)-SS, or a combination thereof.

8. The solid polyglycol-based, fully synthetic pre-formulation of claim 7, wherein the solid first compound is 4ARM-5k-SH, 4ARM-2k-NH2, 4ARM-5k-NH2, 8ARM-20k-NH2, 4ARM-20k-AA, 8ARM-20k-AA, or a combination thereof, and the second compound is 4ARM-10k-SG, 8ARM-15k-SG, 4ARM-20k-SGA, 4ARM-10k-SS, or a combination thereof.

9. The solid polyglycol-based pre-formulation of claim 8, wherein the solid first compound is 8ARM-20k-NH2 and/or 8ARM-20k-AA, and the second compound is 4ARM-20k-SGA.

10. The solid polyglycol-based, fully synthetic, pre-formulation of claim 2, wherein the therapeutic agent is selected from an antibacterial agent, an antifungal agent, an immunosuppressant agent, an anti-inflammatory agent, a bisphosphonate, gallium nitrate, stem cells, an antiseptic agent, and a lubricity agent.

11. The solid polyglycol-based, fully synthetic, pre-formulation of claim 10 wherein the therapeutic agent is a lubricity agent.

12. The solid polyglycol-based, fully synthetic, pre-formulation of claim 11, wherein the lubricity agent is hyaluronic acid.

13. The polyglycol-based, fully synthetic, biocompatible hydrogel polymer of claim 1.

14. The solid polyglycol-based, fully synthetic, pre-formulation of claim 1, wherein the solid therapeutic agent is selected from an antibacterial agent, an antifungal agent, an immunosuppressant agent, an anti-inflammatory agent, a bisphosphonate, gallium nitrate, stem cells, an antiseptic agent, and a lubricity agent.

15. The solid polyglycol-based, fully synthetic, pre-formulation of claim 14, wherein the solid therapeutic agent is a lubricity agent.

16. The solid polyglycol-based, fully synthetic, pre-formulation of claim 15, wherein the lubricity agent is hyaluronic acid.