Reverse thermal gellation polymer of chain-extended optional polyester-terminated PEO-PPO-PEO
The present invention relates to novel polymeric compositions based upon A n (BCB)A n polyester/polyether multi-blocks. Compositions according to the present invention exhibit unexpectedly exceptional reverse thermal gellation properties and in certain cases, relatively low viscosities at approximately room temperature and extremely high viscosities at temperatures above room temperature (preferably at approximately physiological or body temperature, i.e., within a temperature range of about 32-40° C.). Compositions according to the present invention may be used advantageously in applications which make use of their reverse thermal gellation properties. Preferred applications for use of the present compositions include, for example, medical applications which make advantageous use of the inherent composition characteristic of being of relatively low viscosity at room temperature and much higher viscosity at elevated temperatures, especially body temperature.
1. A method of reducing adhesions in tissue subsequent to a medical procedure in a patient comprising administering to said patient after said procedure a polymeric composition exhibiting reverse thermal geflation properties according to the structure:
{[A n (BCB)A n ]E} m
where A is a polyester unit, B is a poly(ethylene oxide) unit, C is a poly(propylene oxide) unit, E is a chain extender unit, n ranges from 1 to 20 and m is greater than 2, said polymeric composition having a EO/PO ratio ranging from about 0.2:1 to about 40:1, said composition having a final viscosity at a final temperature which is more than twice the initial viscosity of the composition at an initial temperature, said final temperature being at least 10° C. higher than said initial temperature.
2. The method according to claim 1 wherein said polyester unit is derived from the polymerization of monomers selected from the group consisting of lactic acid, lactide. glycolic acid, glycolide, β-propiolactone, ε-caprolactone, δ-glutarolactone, δ-valerolactone, β-butyrolactone, pivalolactone, α,α-diethylpropiolactone, ethylene carbonate, trimethylene carbonate, γ-butyrolactone, p-dioxanone, 1,4-dioxepan-2-one, 3-methyl-1,4-dioxane-2,5-dione, 3,3,-dimethyl-1-4-dioxane-2,5-dione, cyclic esters of α-hydroxybutyric acid, αhydroxyvaleric acid, α-hydroxyisovaleric acid, α-hydroxycaproic acid, α-hydroxy-α-ethylbutyric acid, α-hydroxyisocaproic acid, α-hydroxy-α-methyl valeric acid, α-hydroxyheptanoic acid, α-hydroxystearic acid, α-hydroxylignoceric acid, salicylic acid and mixtures, thereof.
3. The method according to claim 1 wherein said polyester unit is biodegradable or bioerodible.
4. The method according to claim 1 wherein said polyester comprises poly(aliphatic hydroxy carboxylic acid).
5. The method according to claim 1 wherein said polyester comprises poly(aliphatic α-hydroxy carboxylic acid).
6. The method according to claim 1 wherein said polyester is obtained from polymerization of a lactone selected from the group consisting of lactide, glycolide, caprolactone and mixtures, thereof.
7. The method according to claim 1 wherein said EO/PO ratio ranges from about 7.5:1 to about 1:1 and said BCB block has a molecular weight ranging from about 1,000 to about 25,000 dalton units, said composition having a final viscosity at approximately physiological temperature which is more than 10 times the initial viscosity of the composition at ambient temperature.
8. The method according to claim 1 wherein n is 1.
9. The method according to claim 1 wherein said medical procedure is a surgery.
10. The method according to claim 9 wherein said surgery is laparascopic surgery.