Crosslinked hyaluronic acid compositions for tissue augmentation

• US 8,124,120 B2
• Filed: 12/22/2003
• Issued: 02/28/2012
• Est. Priority Date: 12/22/2003
• Status: Active Grant

• Current Assignee: Anika Therapeutics Incorporated
• Original Assignee: Anika Therapeutics Incorporated
• Inventors: Sadozai, Khalid K., Gooding, Tamera B., Bui, Kyle, Sherwood, Charles H.
• Primary Examiner(s): Sajjadi, Fereydoun G
• Assistant Examiner(s): BROWN, COURTNEY A
• Application Number:
  US10/743,557
• Publication Number:
  US 20050136122A1
• Time in Patent Office: 2,990 Days
• Field of Search: 424/491, 424/426
• US Class Current: 424/426
• CPC Class Codes: A61K 31/24 having an amino or nitro group
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• 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 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61P 25/02 for peripheral neuropathies

Abstract

Disclosed are hyaluronic acid (HA) compositions including crosslinked, water-insoluble, hydrated HA gel particles. Also disclosed are methods of making the HA compositions, and methods of using the HA composition to augment tissue in a subject.

Claims

1. A method of augmenting tissue in a subject that is in need of tissue augmentation, the method comprising:

a) inserting a needle into a subject at a location in the subject that is in need of tissue augmentation, wherein the needle is coupled to a syringe loaded with a crosslinked hyaluronic acid (HA) composition that includes crosslinked, water-insoluble, hydrated HA gel particles, wherein the HA includes crosslinks with represented by the following structural formula;

HA′

—

U—

R₂—

U—

HA′

wherein;

each HA′

is the same or different crosslinked HA molecule;

each U is independently an O-acyl isourea or N-acyl urea;

and R₂ is alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl aryl, heteroaryl, heterocyclyl, cycloaliphaticalkyl, aralkyl, heteroaralkyl, or heterocyclylalkyl,

wherein the HA gel particles have an average particle diameter distribution selected from the group consisting of a hydrated particle average diameter between about 20 μ

m and about 1000 μ

m, and a dehydrated particle average diameter between about 10 μ

m and about 500 μ

m;

wherein the crosslinked HA composition is a single hydrated particle phase; and

b) applying force to the syringe, whereby at least a portion of the crosslinked HA composition is delivered into the subject;

wherein the crosslinked HA composition is stable in the subject for at least 8 weeks.

2. The method of claim 1, wherein the subject is human.

3. The method of claim 2, wherein the particles include at least one bioactive agent selected from the group consisting of cells, genes, proteins, antibodies, peptides, and pharmaceuticals.

4. The method of claim 3, wherein the bioactive agent includes an anesthetic.

5. The method of claim 4, wherein the anesthetic is lidocaine, mepivacaine, prilocaine, bupivacaine, cocaine, procaine, chlorocaine, or tetracaine, or a salt or solvate thereof.

6. The method of claim 5, wherein the anesthetic is lidocaine.HCl.

7. The method of claim 2, wherein the distribution is a multimodal distribution.

8. The method of claim 7, wherein the HA in the composition consists essentially of the crosslinked, water-insoluble, hydrated HA gel particles.

9. The method of claim 2 wherein the crosslinked HA composition has at least one parameter measured at 37°

C. selected from a storage modulus G′

of at least about 50 Pa when measured at 1 Hz frequency using a 4 cm flat geometry, and a kinematic viscosity of at least about 20,000 cPs when measured at a shear rate of 1 s<sup>−

1</sup>.

10. The method of claim 9, wherein the composition has a storage modulus G′

of at least about 100 Pa.

11. The method of claim 10, wherein the composition has a storage modulus G′

of at least about 400 Pa.