Sustained release composition using biobased biodegradable hyperbranched polyesters

Abstract

The present invention provides a sustained release composition having hyperbranched polymers that are polyesters that are biobased and biodegradable, and that have at least one active ingredient, which composition delivers the active ingredient over time. These active ingredients can be a wide variety of compounds so long as they can covalently bind to the polymer or be encapsulated in the polymer in a manner that is released at the point of delivery, usually by acid hydrolysis or enzymatic bond scission.

What is claimed is: 
     
         1 . A composition comprising a synthetic or natural biobased, biodegradable hyperbranched polyester that has at least one active ingredient either covalently bonded to or encapsulated in the hyperbranched polyester. 
     
     
         2 . The composition of  claim 1 , wherein the polyester linkage degrades into its starting monomers or other environmentally benign degradation products and the active ingredient is released and is effective. 
     
     
         3 . The composition of  claim 1 , wherein the active ingredient has a carboxylate, hydroxy, amino, ketone, aldehyde, double- or triple-bond, or triazole groups to covalently bond to the hyperbranched polyester. 
     
     
         4 . The composition of  claim 1 , wherein the polyester is synthetic and formed from glycerol and adipic acid and/or succinic acid and is prepared using bimolecular non-linear polymerization (BMNLP) methodology. 
     
     
         5 . The composition of  claim 1 , wherein the hyperbranched polyester is formed from a multifunctional biobased alcohol and a multifunctional biobased carboxylic acid using bimolecular non-linear polymerization (BMNLP) methodology. 
     
     
         6 . The composition of  claim 5 , wherein the multifunctional biobased alcohol glycerol, pentaerythritol, sugars, sugar alcohols, or multifunctional biobased acids. 
     
     
         7 . The composition of  claim 1 , wherein a ketal is formed by the hyperbranched polyester and the active ingredient. 
     
     
         8 . The composition of  claim 7 , wherein the ketal is a dioxane, dioxolane, inter- or intra-molecular ketal or mixtures thereof. 
     
     
         9 . The composition of  claim 2 , wherein the active ingredient is released from the hyperbranched polyester either by hydrolysis or enzymatic bond scission. 
     
     
         10 . The composition of  claim 9 , wherein the hydrolysis is catalyzed by a biobased acid having a pKa of from about −8 to about 2.2. 
     
     
         11 . The composition of  claim 10 , wherein the biobased acid is HCl, p-toluenesulfonic acid, or phytic acid. 
     
     
         12 . The composition of  claim 9 , wherein the rate of release is adjusted by one or more of the following: 1) the level of acid catalyst present in the formulation or in situ; 2) the pKa of the acid catalyst; 3) the MW of the BBB-HB-PE; 4) the composition of the BBB-HB-PE; 5) the amount of water in the formulation; or 6) the temperature of the formulation. 
     
     
         13 . The composition of  claim 9 , wherein the enzyme used for enzymatic bond scission is an esterase, lipase or ketalase. 
     
     
         14 . The composition of  claim 1 , wherein the active ingredient is encapsulated and held by secondary forces within the hyperbranched polyester. 
     
     
         15 . The composition of  claim 14 , wherein the active ingredient is released by diffusion. 
     
     
         16 . The composition of  claim 1 , wherein the active ingredient is released from the hyperbranched polyester over time from about 1 day to several months. 
     
     
         17 . The composition of  claim 1 , wherein the hyperbranched polyester has been formed into a network. 
     
     
         18 . The composition of  claim 17 , wherein the network is formed into films, sheets or coatings. 
     
     
         19 . The composition of  claim 1 , wherein the active ingredient is an agent for wound healing. 
     
     
         20 . The composition of  claim 1 , wherein the active ingredient is a transdermal drug. 
     
     
         21 . The composition of  claim 1 , wherein the active ingredient is a topical drug. 
     
     
         22 . The composition of  claim 21 , wherein the topical drug is for dermatological disorders, venereal disease, an analgesic, or an anti-inflammatory. 
     
     
         23 . The composition of  claim 22 , wherein the topical drug for an analgesic is capsaicin, salicylic acid, ketoprofen, or ferulic acid. 
     
     
         24 . The composition of  claim 22 , wherein the topical drug for an anti-inflammatory is a hydrocortisone derivative. 
     
     
         25 . The composition of  claim 1 , wherein the active ingredient is an antibiotic. 
     
     
         26 . The composition of  claim 1 , wherein the active ingredient is an antitumor agent. 
     
     
         27 . The composition of  claim 26 , wherein the antitumor agent is organo-platinum. 
     
     
         28 . The composition of  claim 1 , wherein the active ingredient is an herbicide. 
     
     
         29 . The composition of  claim 28 , wherein the herbicide is atrazine, 2,4-D esters, or glyphosate. 
     
     
         30 . The composition of  claim 1 , wherein the active ingredient is a miticide 
     
     
         31 . The composition of  claim 30 , wherein the miticide is oxalic acid. 
     
     
         32 . The composition of  claim 1 , wherein the active ingredient is a veterinary drug. 
     
     
         33 . The composition of  claim 1 , wherein the active ingredient is a plant growth regulator. 
     
     
         34 . The composition of  claim 33 , wherein the plant growth regulator is auxin, cytokinin, gibberellic acid, or naphthalene acetic acid. 
     
     
         35 . The composition of  claim 1 , wherein the active ingredient is disinfectant or sanitizer. 
     
     
         36 . The composition of  claim 35 , wherein the disinfectant or sanitizer is triclosan, benzalkonium chloride, cetylpyridinium chloride, or chlorhexidine gluconate. 
     
     
         37 . The composition of  claim 36 , wherein the disinfectant or sanitizer is triclosan. 
     
     
         38 . The composition of  claim 1 , wherein the active ingredient is an insect repellant. 
     
     
         39 . The composition of  claim 38 , wherein the insect repellant is 2-undecanone. 
     
     
         40 . A BMNLP process for preparing the compound as defined in  claim 1 , which comprises the reaction of:
 a monomer of the form A x , where A is either an OH or O(O)CR group for the polyfunctional acids, or is C(O)OH, C(O)OR, or C(O)Cl group for the polyfunctional alcohols;   with another monomer of the form B y , where B is either a C(O)OH, C(O)OR or C(O)Cl group for the polyfunctional acids, or OH or O(O)CR group for the polyfunctional alcohols;   under conditions at which neither A nor B groups can react with themselves but only with each other; and   where x and y are integers where one integer is equal to or larger than 2 and the other is equal or larger than 3; and   the molar ratio of the reacting A groups and B groups (r=A/B) and the extent of the reaction must be selected to avoid gelation; and   an active ingredient having carboxylate, hydroxyl, carbonyl or amine groups is covalently bonded to the alcohol or acid end groups of the polyester.   
     
     
         41 . The process of  claim 40 , wherein the polyester forms networks. 
     
     
         42 . The process of  claim 40 , wherein the process is in the bulk system wherein the extent of the reaction of the minor component (either p A  or p B ) is about unity, and the value of r is outside of the “gelation window” defined by the following equation: 1[(x−1)(y−1)]≦r≦(x−1)(y−1). 
     
     
         43 . A dioxane, dioxolane, inter- or intra-molecular ketal or mixtures thereof formed by reacting a hydroxyl terminated HBPE with a
   H 3 C—C(O)—R
   wherein: R is a C 4  to C 20  straight- or branched-chain alkyl.   
     
     
         44 . The ketal of  claim 43  wherein R is C 7  to C 13 . 
     
     
         45 . The ketal of  claim 44  wherein R is R is C 9  (UD; 2-undecanone) or C 13  (2-tridecanone).