Abstract:
A controlled continuous release composition, articles comprising the continuous release composition, methods of using the composition, and methods of preparing the composition are disclosed. The composition comprises an elastomeric matrix which is a reaction product of a carboxyl-terminated polymer with a polycarbodiimide and at least one active agent which is released from the matrix into the environment substantially continuously over an extended period of time.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     Benefit of Provisional Application Ser. No. 60/455,072 filed Mar. 14, 2003, is claimed. 
    
    
     BACKGROUND OF THE INVENTION 
     This invention relates to the field of controlled release of active agents, controlled release compositions, methods, and articles which comprise such compositions. The need for the controlled and sustained release of an active agent into the environment exists in many fields, for instance, in residential and other consumer fields, in agriculture, and in telecommunications. 
     Matrices that have been used in monolithic controlled release formulations include plasticized polyvinylchloride, rubber (U.S. Pat. No. 3,318,769) and certain polyurethanes (U.S. Pat. Nos. 4,594,380 and 4,189,467). The rubber matrices typically are cured by conventional rubber chemistry, e.g., by sulfur vulcanization or by means of peroxides (U.S. Pat. No. 3,639,583). These curing processes typically comprise a high-temperature step. The high temperature step frequently is a complicating factor when active agents having relatively high vapor pressure, or active agents that are subject to deactivation at the elevated temperature, are to be incorporated into the matrix material. Forming a polyurethane matrix requires polyols to react with isocyanates. Unfortunately, many active ingredients for sustained release contain alcohol functionality which competes with such polyols in the curing reaction. As a result, the polyurethane gel formation is hindered in the presence of alcoholic active ingredients. 
     Because of the importance of controlled release of active agents, a controlled release system that does not have the shortcomings of prior art systems would be of substantial benefit. 
     SUMMARY OF THE INVENTION 
     A first aspect of the present invention is a composition comprising an elastomeric matrix and at least one biologically or non-biologically active agent contained in the matrix which is released from the matrix into the environment substantially continuously over an extended period of time. The matrix can be the reaction product of a hydrophobic or hydrophilic carboxyl-terminated polymer with a polycarbodiimide. 
     In another aspect, the invention comprises a process comprising reacting hydrophobic or hydrophilic carboxyl-terminated polymer with a polycarbodiimide. 
     Another aspect of the invention is an article comprised of the matrix composition. 
     The said hydrophobic carboxyl-terminated polymer comprising a major component selected from the group consisting of carboxyl-terminated polybutadiene, carboxyl-terminated polyisoprene, carboxyl-terminated copolymers of butadiene with acrylonitrile, carboxyl-terminated copolymers of butadiene with styrene, carboxyl-terminated copolymers of isoprene with acrylonitrile, carboxyl-terminated copolymers of isoprene with styrene, and mixtures of the above, the carboxylic acid terminated polymer having an average molecular weight in the range of 1000 to 20000. 
     The hydrophilic carboxyl-terminated polymer preferably comprises a major component selected from the group consisting of carboxyl-terminated polyethylene oxides, carboxyl-terminated polyether polyols which are copolymers of ethylene oxide and of an alkylene oxide having 3-6 carbons atoms, in an amount of not more than 50 mole percent of said copolymer and having molecular weight from 400 to 20,000. 
     The polycarbodiimide is preferably selected from the group consisting of the aromatic, cycloaliphatic, aliphatic and heterocyclic carbodiimides, and mixtures of two of more of the above and the said polycarbodiimide having an average functionality higher or equal to 2. 
     The carbodiimide/carboxylic acid molar ratio, from polycarbodiimide and from carboxyl-terminated polymer, is preferably in the range of 0.7 to 6.0, particularly in the case of a hydrophilic carboxyl-terminated polymer according to b. 
     More preferably this range is from 0.7 to 1.4, particularly when the said article is not a water-based article, which means when the elastomeric matrix is not based on a hydrophilic carboxyl-terminated polymer, but rather on a hydrophobic one, according to a). 
    
    
     DETAILED DESCRIPTION 
     Suitable hydrophobic carboxyl-terminated polymers include carboxyl-terminated polybutadienes, carboxyl-terminated polyisoprenes, carboxyl-terminated copolymers of butadiene with acrylonitrile, carboxyl-terminated copolymers of butadiene with styrene, carboxyl-terminated copolymers of isoprene with acrylonitrile, carboxyl-terminated copolymers of isoprene with styrene, and mixtures thereof. The carboxylic acid-terminated polymers preferably have an average molecular weight in the range of 1000 to 20000. 
     Suitable hydrophilic carboxyl-terminated polymers include, for example, carboxyl-terminated polyethylene oxides, carboxyl-terminated polyether polyols which can be copolymers of ethylene oxide with an alkylene oxide having 3-6 carbon atoms, the alkylene oxide having 3-6 carbon atoms comprising not more than 50 mole percent of said copolymer, wherein the copolymer preferably has a molecular weight from 400 to 20,000. 
     Suitable polycarbodiimides can be, for example, aromatic, cycloaliphatic, aliphatic, or heterocyclic carbodiimides, and mixtures of two of more thereof. The polycarbodiimides preferably have an average functionality higher or equal to 2. 
     The carbodiimide/carboxylic acid molar ratio from polycarbodiimide and from carboxyl-terminated polymer is preferably in the range of 0.7 to 6.0. In embodiments wherein the carboxyl-terminated polymer is hydrophobic, this ratio is preferably 0.7 to 1.4. 
     The article according to the invention comprises an elastomeric matrix and, contained in the matrix material, one or more active agents which are to be released in to the environment substantially continuously over an extended period of time. The elastomer is formed by a process comprising reacting polyacid with carbodiimides. The polyacid or carboxyl-terminated polymer preferably comprises a major component. The major component typically makes up at least 90% by weight of the polyacid and is selected from the group consisting of carboxyl-terminated compounds, such as polybutadiene, polyisoprene, copolymers of butadiene with acrylonitrile, copolymers of butadiene with styrene, copolymers of isoprene with acrylonitrile, copolymers of isoprene with styrene, and mixtures of two or more of the above. The optional minor component is selected from the group consisting of carboxyl-terminated compounds, such as adipic acid, azelaic acid, isophthalic acid and dimer fatty acid. The polyacid preferably has an average molecular weight in the range of 400-20000. The preferred hydrophobic carboxyl-terminated polymer is selected from a carboxyl-terminated polybutadiene having a molecular weight of 1000 to 10000 or a carboxyl-terminated polyisoprene having a molecular weight of 1000 to 10000, and an average carboxylic acid functionality in the range of 1.8 to 8.0. 
     In addition to the hydrophobic polymers with acid functionality, hydrophilic polymers with carboxylic acid functionality can also be employed and are compatible with water soluble or dispersible ingredients so that the resulting system is more environmentally acceptable. The hydrophilic polyacids consist of carboxyl-terminated polymers such as carboxyl-terminated polyethylene oxides and carboxyl-terminated polyether polyols which are a copolymer of ethylene oxide and an alkylene oxide having 3-6 carbons atoms in an amount of not more than 50 mole percent of C 3 -C 6  alkylene oxide, wherein the polymer has molecular weight 400 to 20000. 
     The polycarbodiimide is can be aromatic, cycloaliphatic, aliphatic or heterocyclic carbodiimides, or mixtures of two of more thereof. The polycarbodiimides used are preferably produced by subjecting polyfunctional, preferably bifunctional, aliphatic, araliphatic, or, preferably, aromatic isocyanates to carbodiimide formation. Monofunctional or trifunctional and higher functional isocyanates may be used as chain terminators or branching agents for the polycarbodiimides, although they should be employed in quantities of less than about 20% by weight and preferably in quantities of less than about 10% by weight of the total quantity of isocyanate. 
     Suitable isocyanates include alkyl isocyanates, such as methyl, allyl, butyl, stearyl isocyanate; alkyl diisocyanates such as ethylene diisocyanate, tetramethylene diisocyanate, hexamethylene diisocyanate, isophorone diisocyanate; aromatic monofunctional and bifunctional isocyanates, such as phenyl isocyanate, phenylene diisocyanates, the isomeric toluene diisocyanates, diphenyl methane diisocyanates, dimethyl diphenyl methane diisocyanates, and commercial-grade biphenyl methane diisocyanate mixtures which may optionally contain polynuclear diisocyanates or trifunctional isocyanates as well. 
     Preferred isocyanates are hexamethylene diisocyanate, isophorone diisocyanate, the toluene diisocyanates and diphenyl methane diisocyanates. The isomers of toluene diisocyanate are preferred. 
     The matrix optionally may comprise components that do not participate in the crosslinking reaction between polyacid and carbodiimide. Among such “nonreactive” components are comprised: fillers, plasticizers, stabilizers, pigments, and fungicides. Contained in the matrix is the material to be controllably released into the ambient environment, collectively referred to as the active agent. 
     The active agent can be substantially any biologically or non-biologically active compound that is compatible with the matrix material. Exemplary classes of possible active agent compounds are the aliphatic or aromatic oils, esters, ketones, ethers, halogenated aromatic compounds, alcohols, and organometallics. Fragrances are comprised in these agents. Pheromones may be another class of active agents according to the invention. The active agents according to the present invention are present in an amount of about 10% to 90% by weight based on the total weight of the polymer and the crosslinking agent. In preferred embodiments the active agent is dissolved in the matrix, with the release mechanism comprising diffusion of active agent from the interior of the sample to the release surface. The said agent may also be present dispersed in the said matrix. 
     The matrix and active agent can be formed into a variety of shapes, combined, if desired, with appropriate containment means, to form an article, preferably in the form of gel, which may be comprised in a related device, providing timed-release biological or non-biological action, e.g., insecticidal, fungicidal, deodorant, molluscidcidal, anti-corrosive, pheromone, antistatic action or antiseptic actions. 
     Suitable polycarbodiimides have at least 2 carbodiimide groups, preferably at least 3 carbodiimide groups in one molecule. The term “poly” of the “polycarbodiimide” means multiple number of the carbodiimide groups (multifunctional carbodiimide) and does not mean height of molecular weight. The molecular weight of the polycarbodiimide is not limited, but preferably is within the range of 250 to 10,000. All reference to molecular weights herein is to number average molecular weights. The polycarbodiimide is preferably prepared by polycondensation of an organic polyisocyanate in the presence of a carbodiimide promoting agent. The organic polyisocyanate may be, for example, an aromatic polyisocyanate, such as 2,4- or 2,6-toluene diisocyanate, naphthalene 1,5-diisocyanate and diphenylmethane 4,4′-diisocyanate; and an aliphatic or alicyclic polyisocyanate, such as hexamethylene diisocyanate, hydrogenated diphenylmethane 4,4′-diisocyanate, isophorone diisocyanate, and hydrogenated 2,4- or 2,6-toluene diisocyanate. 
     The carbodiimide promoting agent can be any known to the art, for example as described in Chemical Review, by Andrew Williams, Ibrahim T. Ibrahim, Vo. 81, No. 4, p. 619 (1981). Among them, 1-phenyl-phosphorene-1-oxide, 1-phenyl-3-methyl-phosphorene-1-oxide and 1-ethyl-phosphorene-1-oxide are preferred. 
     In the preparation of the polycarbodiimide, molecular weight can be controlled by terminating the polycondensation with an organic monoisocyanate, for example as disclosed in J. Appl. Polym. Sci. by L. N. Alberine, Vol 21, p. 1999 (1977). Examples of the organic monoisocyanates are phenyl isocyanate, toluene isocyanate, cyclohexyl isocyanate, butyl isocyanate and the like. A blocking technique in which a terminal isocyanate group is blocked with an active-hydrogen containing compound (a blocking agent) can also control the molecular weight of the polycarbodiimide. The blocking agent is described in detail in for example Progress in Organic Coatings, Vol. 3, p.73 (1975). Typical examples of the blocking agents are alcohols, phenols, lactams, N-hydroxyimide, oximes, imidazoles, triazoles, active methylene compounds (e.g. acetyl acetone and diethyl malonate), aromatic secondary amines, acidic sodium sulfite, and the like. 
     The preferred carboxyl-terminated polybutadienes are hydrogenated OH-terminated polybutadienes reacted with a stoichiometric amount of 4-methylhexahydrophthalic anhydride (HHMPA). 
     EXAMPLES 
     The following examples are presented to illustrate a few of the embodiments of the invention but of course many alternative embodiments can be made according to the invention. 
     Preparation of Carboxyl-Terminated Polybutadiene 
     To a 1000-ml resin kettle equipped with an overhead stirrer, heating mantel, inlet and outlet of nitrogen, thermocouple, and condenser is charged the hydroxyl-terminated polybutadiene resin. The resin is heated to 90° C. with stirring under nitrogen and then dried and degassed for 1.5 hrs. at 90° C. in vacuo at &lt;1333 Pa. To the kettle HHMPA is added with stirring at 90° C. The reaction was maintained at 105° C. with stirring under nitrogen for 5 hrs. The viscosity at 30° C. and carboxyl content of four examples of the reaction products are listed in Table 1. 
     
       
         
               
             
               
               
             
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Viscosity and acid content of carboxyl-terminated polybutadienes 
               
             
          
           
               
                   
                 COOH content 
               
             
          
           
               
                 Identification 
                 Viscosity (cp) at 30° C. 
                 (meq/g) 
                 wt % 
               
               
                   
               
               
                 517-120 (NTX6162) 
                 90250 
                 0.783 
                 3.52 
               
               
                 517-121 (NTX6163) 
                 94000 
                 0.583 
                 2.62 
               
               
                 517-123 (NTX6162) 
                 88750 
                 0.798 
                 3.59 
               
               
                 517-129 (NTX6163) 
                 88750 
                 0.563 
                 2.53 
               
               
                   
               
             
          
         
       
     
     Specifications of Starting Materials 
     The equivalent weight, viscosity at 25° C., and Mn of the starting materials used in the following examples are set forth in Table 2. 
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Chemicals specifications 
               
             
          
           
               
                   
                   
                 Viscosity @ 
                   
               
               
                 Reactants 
                 Eq. Wt. 
                 (mPa · s) 
                 Mn 
               
               
                   
               
             
          
           
               
                 Krasol LBH 2000 
                 1100 
                 11050 
                 1989 
               
               
                 Krasol LBH 3000 
                 1600 
                 16430 
                 2931 
               
               
                 Poly bd R45HTLO 
                 1205 
                  7000 
                 2800 
               
               
                 4-Methylhexahydrophthalic 
                 168.19 
                 NA 
                 168.19 
               
               
                 anhydride (HHMPA) from Aldrich 
               
               
                   
               
             
          
         
       
     
     Formulations of Polybutadiene and HJPMA 
     Five formulations of carboxyl-terminated polybutadienes were prepared as set forth in Table 3. 
     
       
         
               
             
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Formulations for preparing carboxyl-terminated polybutadienes 
               
             
          
           
               
                   
                 Lot no. 
               
             
          
           
               
                   
                 507-162 
                 517-120 
                 517-121 
                 517-123 
                 517-129 
               
               
                   
               
             
          
           
               
                 Krasol LBH 2000 
                 — 
                 100 
                 — 
                 100 
                 — 
               
               
                 Krasol LBH 3000 
                 — 
                 — 
                 100 
                 — 
                 100 
               
               
                 Polybd R45HTLO 
                 100 
                 — 
                 — 
                 — 
                 — 
               
               
                 HHMPA 
                 13.96 
                 15.29 
                 10.51 
                 15.29 
                 10.51 
               
               
                   
               
             
          
         
       
     
     Reaction of Carboxyl-Terminated Polybutadienes with Polycarbodiimides in the Presence of Active Reagents 
     The carboxyl-terminated polybutadiene NTX6163 set forth in Table 1 was crosslinked in the presence of a plasticizer, dibutylphthalate (DBP) as shown in Table 5. It was discovered that the addition of OH-containing additives (active ingredients to be released from the controlled release formulation) appeared to have no effect on the curing (Table 4, formulations 2-4). Similarly, the carboxyl-terminated polybutadiene based on Poly bd R45HTLO resin was crosslinked in the presence of fragrance or plasticizer (Table 6). The solvent in commercial Ucarlink was removed and had no significant effect on gelling time (Table 6), but the extra step eliminated the solvent odor for certain applications. 
     
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 Chemicals description 
               
             
          
           
               
                   
                 Description 
                 Eq. wt. 
                 Producer 
               
               
                   
               
               
                 Ucarlink ™ 
                 A multifunctional 
                 400-410 
                 Dow Chemical 
               
               
                 Crosslinker XL- 
                 carbodiimide 
                 (for solid base) 
                 Company 
               
               
                 29SE 
                   
                   
                   
               
               
                 NTX 6163 
                 HHMPA capped 
                 1777 
                 Sartomer 
               
               
                   
                 Krasol LBH-3000 
                 (acid content = 
                   
               
               
                   
                   
                 0.5626 meq/g) 
                   
               
               
                 Arcol ® Polyol 
                   
                   
                 Bayer 
               
               
                 PPG 425 
                   
                   
                   
               
               
                 Pripol 2033 
                   
                   
                 ICI 
               
               
                 Dimerdiol 
                   
                   
                   
               
               
                 2-Ethyl-1,3- 
                   
                   
                 Aldrich 
               
               
                 hexanediol (EHD) 
                   
                   
                   
               
               
                 Dibutyl phthalate 
                   
                   
                 Aldrich 
               
               
                 (DBP) 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Gel formulation derived from NTX 6163 in the presence of active agents 
               
             
          
           
               
                   
                 Wt. of 
                   
                   
                 Gel time 
               
               
                   
                 NTX6163/DBP 
                   
                   
                 (minutes) at 
               
               
                   
                 solution 
                 XL-29SE/DBP solution 
                   
                 room 
               
               
                 No 
                 (1/1 by wt.) 
                 (1/1 by wt.) 
                 Additive 
                 temperature 
               
               
                   
               
               
                 1 
                 7.6 g 
                 3.5 g (XL-29SE/DBP) 
                 — 
                 16.8 
               
               
                 2 
                 7.6 g 
                 3.5 g (XL-29SE/DBP) 
                 0.76 g 
                 23.1 
               
               
                   
                   
                   
                 PPG425 
                   
               
               
                 3 
                 7.6 g 
                 3.5 g (XL-29SE/DBP) 
                 0.76 g 
                 19.7 
               
               
                   
                   
                   
                 Pripol 
                   
               
               
                   
                   
                   
                 2033 
                   
               
               
                   
                   
                   
                 Dimerdiol 
                   
               
               
                 4 
                 7.6 g 
                 3.5 g (XL-29SE/DBP) 
                 0.38 g 
                 18.0 
               
               
                   
                   
                   
                 EHD 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
             
               
               
               
               
               
             
               
               
               
               
               
             
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 Gel formulations based on HHMPA-terminated Poly bd R45HTLO 
               
               
                 resins and polycarbodiimide in the presence of fragrances 
               
             
          
           
               
                   
                 Sample no. 
               
             
          
           
               
                   
                 11-1 
                 11-2 
                 13-1 
                 13-2 
               
               
                   
               
             
          
           
               
                 HHMPA-terminated Polybd 
                 100 
                 100 
                 100 
                 100 
               
               
                 R45HTLO 
                   
                   
                   
                   
               
               
                 Ucarlink XL-29SE (50% solution) 
                 60.4 
                 — 
                 60.4 
                 60.4 
               
               
                 Ucarlink XL-29SE without solvent 
                 — 
                 30.2 
                 — 
                 — 
               
               
                 Fragrances (lemon grass mint) 
                 481 
                 390.6 
                 — 
                 — 
               
               
                 Dibutyl phthalate 
                 — 
                 — 
                 481 
                 481 
               
               
                 Wt. % of fragrances in formula 
                 75 
                 75 
                 75 
                 75 
               
               
                 Wt. % of polymer in formula 
                 20.3 
                 25 
                 25 
                 25 
               
               
                 Gel time (minutes) 
                 Overnight 
                 Overnight 
                 25.1 
                 25.5 
               
               
                 Curing @ ° C. 
                 24 
                 24.6 
                 24.7 
                 24.4 
               
             
          
           
               
                 Appearance of cured gel 
                 Clear, softer 
                 Slight 
               
               
                   
                   
                 yellow, clear 
               
               
                   
               
             
          
         
       
     
     As shown in Table 7, the gelling time was shortened when the gelling was carried out at a slightly elevated temperature instead of room temperature, thus increasing the productivity in commercial operation. 
     
       
         
               
             
               
               
             
               
               
               
             
               
               
               
             
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 Gel formulations based on HHMPA-terminated Poly bd R45HTLO 
               
               
                 resins and polycarbodiimide in the presence of fragrances under  
               
               
                 different gelling temperature 
               
             
          
           
               
                   
                 Sample no. 
               
             
          
           
               
                   
                 1 
                 2 
               
               
                   
               
             
          
           
               
                 HHMPA-terminated Polybd R45HTLO 
                 100 
                 100 
               
               
                 Ucarlink XL-29SE without solvent 
                 36.26 
                 36.26 
               
               
                 Fragrances (lemon grass mint) 
                 408.8 
                 408.8 
               
               
                 Wt. % of fragrances in formula 
                 75 
                 75 
               
               
                 Wt. % of polymer in formula 
                 25 
                 25 
               
               
                 Gel time (minutes) 
                 12.9 
                 36.6 
               
               
                 Curing @ ° C. 
                 38.9 
                 25 
               
             
          
           
               
                 Appearance of cured gel 
                 Yellow, clear gel 
               
               
                   
               
             
          
         
       
     
     As shown in Table 8 the gel system was very robust and could be used with other active ingredients such as “Lavender” fragrance. 
     
       
         
               
             
               
               
             
               
               
               
               
             
               
               
               
               
             
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 Gel formulations based on HHMPA-terminated Poly bd R45HTLO 
               
               
                 resins and polycarbodiimide in the presence of “Lavender” fragrance. 
               
             
          
           
               
                   
                 Sample no. 
               
             
          
           
               
                   
                 1 
                 2 
                 3 
               
               
                   
               
             
          
           
               
                 Acid-terminated Polybd R45HTLO 
                 100 
                 100 
                 100 
               
               
                 Resin (PRO 6340) 
                   
                   
                   
               
               
                 Ucarlink XL-29SE without solvent 
                 36.26 
                 33.24 
                 39.24 
               
               
                 Fragrances (Lavender) 
                 408.8 
                 399.73 
                 417.8 
               
               
                 Wt. % of fragrances in formula 
                 75 
                 75 
                 75 
               
               
                 Wt. % of polymer in formula 
                 25 
                 25 
                 25 
               
               
                 Gel time (minutes) 
                 25.0 
                 33.7 
                 21.5 
               
               
                 Curing @ ° C. 
                 24.0 
                 24.5 
                 25.0 
               
             
          
           
               
                 Appearance of cured gel 
                 Yellow, clear gel 
               
               
                   
               
             
          
         
       
     
     As shown in Table 9, with slightly variation in stoichiometry between acid-terminated polybutadien resin and polycarbodiimide, the hardness of the gel could be altered as desired. The higher equivalent ratios of carbodiimide to acid resulted in harder gels. 
     
       
         
               
             
               
               
             
               
               
               
               
               
             
               
               
               
               
               
             
               
               
             
           
               
                 TABLE 9 
               
             
             
               
                   
               
               
                 Gel formulations based on HHMPA-terminated Poly bd R45HTLO 
               
               
                 Resins and polycarbodiimide in the presence of various fragrances 
               
             
          
           
               
                   
                 Sample no. 
               
             
          
           
               
                   
                 1 
                 2 
                 3 
                 4 
               
               
                   
               
             
          
           
               
                 Acid-terminated Polybd 
                 100 
                 100 
                 100 
                 100 
               
               
                 R45HTLO Resin 
                   
                   
                   
                   
               
               
                 (PRO 6340) 
                   
                   
                   
                   
               
               
                 Ucarlink XL-29SE without 
                 33.24 
                 39.26 
                 36.23 
                 33.23 
               
               
                 solvent 
                   
                   
                   
                   
               
               
                 Fragrances (Lavender) 
                 399.8 
                 417.8 
                 — 
                 — 
               
               
                 Fragrances (Lemon Grass 
                 — 
                 — 
                 408.5 
                 399.7 
               
               
                 Mint) 
                   
                   
                   
                   
               
               
                 Wt. % of fragrances in 
                 75 
                 75 
                 75 
                 75 
               
               
                 formula 
                   
                   
                   
                   
               
               
                 Wt. % of polymer in 
                 25 
                 25 
                 25 
                 25 
               
               
                 formula 
                   
                   
                   
                   
               
               
                 Equivalent ratio of 
                 1.1 
                 1.3 
                 1.2 
                 1.1 
               
               
                 carbodiimide/COOH 
                   
                   
                   
                   
               
               
                 Curing temperature in ° C. 
                 25 
                 25 
                 25 
                 25 
               
               
                 Gel time, minutes (at ° C.) 
                 33.7 
                 21.5 
                 36.6 
                 44.9 
               
               
                   
                 (24.5° C.) 
                 (25° C.) 
                 (25-26° C.) 
                 (39° C.) 
               
               
                 Relative hardness of gel 
                 Softer 
                 Harder 
                 Harder 
                 Softer 
               
             
          
           
               
                 Appearance of cured gel 
                 Yellow, clear gel 
               
               
                   
               
             
          
         
       
     
     Preparation and Curing of Carboxyl-Terminated Poly(Ethylene Glycol) 
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 10 
               
             
             
               
                   
               
               
                 Chemicals specifications 
               
             
          
           
               
                   
                 Lot no. 
                 Mn 
                 Eq. wt 
               
               
                   
               
             
          
           
               
                 Poly(ethylene glycol) from Aldrich 
                 11719LO 
                 1000 
                 500 
               
               
                 Poly(ethylene glycol) from Aldrich 
                 15228EB 
                 579.6 
                 289.8 
               
               
                 Poly(ethylene glycol) from Aldrich 
                 05629KB 
                 2044 
                 1022 
               
               
                 Hexahydro-4-methylphthalic 
                 15903EA 
                 168.19 
                 168.19 
               
               
                 anhydride (HHMPA) from Aldrich 
                   
                   
                   
               
               
                 Succinic anhydride from Aldrich 
                 12121 PA 
                 100.07 
                 100.07 
               
               
                 Polyol TP 200 (a triol from 
                 3168228 
                 — 
                 326.2 
               
               
                 Perstorp company) 
                   
                   
                   
               
               
                 Polyol PP 150 (with 4 OH groups 
                 3368004 
                 — 
                 195.5 
               
               
                 from Perstorp company) 
                   
                   
                   
               
               
                 Glutaric anhydride from Aldrich 
                 04618JB 
                 — 
                 114.1 
               
               
                 1,2-cyclohexanedicarboxylic anhydride 
                 09111BU 
                 — 
                 154.2 
               
               
                 from Aldrich 
                   
                   
                   
               
               
                 Polyethylene glycol 4,000 
                 448936/1 
                 3558 
                 1779 
               
               
                 (Fluka company) 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
             
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 11 
               
             
             
               
                   
               
               
                 Preparation of carboxyl-terminated polymers (1.0 equivalents ratio of polyol/anhydride) 
               
             
          
           
               
                   
                 Chemical and lot no. 550- 
               
             
          
           
               
                   
                 12 
                 13 
                 14 
                 19 
                 23 
                 24 
                 26 
                 31 
                 32 
               
               
                   
               
             
          
           
               
                 Poly(ethylene glycol) (11719LO) 
                 100 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Poly(ethylene glycol) (15228EB) 
                   
                 100 
                   
                 100 
                   
                   
                   
                   
                   
               
               
                 Poly(ethylene glycol) (05629KB) 
                   
                   
                 100 
                   
                   
                   
                   
                   
                   
               
               
                 Polyol TP 200 (3168228) 
                   
                   
                   
                   
                 100 
                   
                 100 
                   
                   
               
               
                 Polyol PP 150 (3368004) 
                   
                   
                   
                   
                   
                   
                   
                 100 
                 100 
               
               
                 Polyethylene glycol 4000  
                   
                   
                   
                   
                   
                 100 
                   
                   
                   
               
               
                 (448936/1) 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 HHMPA (15903EA) 
                 33.64 
                 58.04 
                 16.46 
                   
                 51.56 
                 9.454 
                   
                   
                   
               
               
                 Succinic anhydride (12121PA) 
                   
                   
                   
                 34.53 
                   
                   
                 27.63 
                   
                   
               
               
                 Glutaric anhydride (04618JB) 
                   
                   
                   
                   
                   
                   
                   
                 58.36 
                   
               
               
                 1,2-cyclohexanedicarboxylic 
                   
                   
                   
                   
                   
                   
                   
                   
                 78.87 
               
               
                 anhydride (09111BU) 
               
               
                   
               
             
          
         
       
     
     Preparative Procedures and Product Analysis
     1. PEG or Polyol was dried and degassed in vacuum at &lt;1333 Pa at 95° C. for 2 hrs.   2. Anhydride was charged into resin kettle   3. Reaction was held at 100-105° C. with stirring and N 2  slow purge for 3 hrs.   4. Determination of acid content of products   

     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
               
               
               
             
           
               
                 TABLE 12 
               
             
             
               
                   
               
               
                 Characterization of carboxyl-terminated polyethylene glycols 
               
             
          
           
               
                   
                   
                   
                 Carboxyl 
               
               
                   
                   
                   
                 content 
               
               
                   
                 Lot no. 
                 Eq. Wt. 
                 (meq./g) 
               
               
                   
               
             
          
           
               
                 Carboxyl terminated PEG 
                 550-13 
                 458 
                 2.184 
               
               
                 Carboxyl terminated PEG 
                 550-12 
                 668 
                 1.497 
               
               
                 Carboxyl terminated PEG 
                 550-14 
                 1197 
                 0.835 
               
               
                 Carboxyl terminated PEG 
                 550-19 
                 390.8 
                 2.559 
               
               
                 Carboxyl terminated PEG 
                 550-23 
                 492.1 
                 2.032 
               
               
                 Carboxyl terminated PEG 
                 550-24 
                 1926.8 
                 0.519 
               
               
                 Carboxyl terminated Polyol TP200 
                 550-26 
                 463 
                 2.159 
               
               
                 Carboxyl terminated Polyol PP 150 
                 550-31 
                 304 
                 3.294 
               
               
                 Carboxyl terminated Polyol PP 150 
                 550-32 
                 339 
                 2.953 
               
               
                 De-ionized water 
                   
                   
                   
               
             
          
           
               
                 XL-29SE (50% solution 
                 QI1355T812 
                 Eq. Wt. = 810 
               
               
                 in DOWANOL PMA 
                   
                 (for solution) 
               
               
                   
               
             
          
         
       
     
     Miscibility and Physical Property of Carboxyl-Terminated Poly(Ethylene Glycol) in Water 
     The water miscibility of the acid-capped polyethylene glycol depends on the structure of the capping agent used and the molecular weight of PEG. When the PEG molecular weight is reduced, the capping agent used needs to be more polar to render the resulting carboxyl-terminated PEG (CTPEG) water soluble (Table 13). 
     
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 13 
               
             
             
               
                   
               
               
                 Miscibility of carboxyl-terminated PEG with water 
               
             
          
           
               
                   
                   
                   
                 Carboxyl 
                   
                 Appearance 
                   
               
               
                   
                   
                   
                 content of 
                   
                 of CTPEG 
                 Miscibility 
               
               
                 Lot no. of 
                   
                 Mn of 
                 CTPEG 
                 Eq. wt. of 
                 at room 
                 of CTPEG 
               
               
                 CTPEG 
                 Anhydride used 
                 PEG 
                 (meq/g) 
                 CTPEG 
                 temperature 
                 in water 
               
               
                   
               
             
          
           
               
                 550-19 
                 Succinic 
                  580 
                 2.559 
                 390.8 
                 Clear liquid 
                 Miscible 
               
               
                 550-13 
                 Hexahydro-4-methylphthalic 
                  580 
                 2.184 
                 458 
                 Clear liquid 
                 Not 
               
               
                   
                   
                   
                   
                   
                   
                 miscible 
               
               
                 550-12 
                 Hexahydro-4-methylphthalic 
                 1000 
                 1.497 
                 668 
                 Cloudy 
                 Miscible 
               
               
                   
                   
                   
                   
                   
                 liquid 
                   
               
               
                 550-14 
                 Hexahydro-4-methylphthalic 
                 2044 
                 0.835 
                 1197 
                 Cloudy 
                 Miscible 
               
               
                   
                   
                   
                   
                   
                 solid 
                   
               
               
                 550-23 
                 Hexahydro-4-methylphthalic 
                 NA 
                 2.032 
                 492.1 
                 Clear liquid 
                 Not 
               
               
                   
                   
                   
                   
                   
                   
                 miscible 
               
               
                 550-24 
                 Hexahydro-4-methylphthalic 
                 3558 
                 0.519 
                 1926.8 
                 Cloudy 
                 Miscible 
               
               
                   
                   
                   
                   
                   
                 solid 
                   
               
               
                 550-26 
                 Succinic 
                 — 
                 2.159 
                 463 
                 Clear liquid 
                 Miscible 
               
               
                 550-31 
                 Glutaric 
                 — 
                 3.294 
                 304 
                 Clear liquid 
                 Miscible 
               
               
                 550-32 
                 1,2-cyclohexanedicarboxylic 
                 — 
                 2.953 
                 339 
                 High viscous 
                 Not 
               
               
                   
                   
                   
                   
                   
                 liquid 
                 miscible 
               
               
                   
               
             
          
         
       
     
     Gel Formation of Carboxyl-Terminated Polymers with Ucarlink™ XL-29SE in the Presence of Water 
     The water-containing gels were formed by reaction between carboxyl-capped PEGs and polycarbodiimide (Table 14). 
     
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 14 
               
             
             
               
                   
               
               
                 Aqueous gel formation from carboxyl-terminated 
               
               
                 PEG and polycarbodiimide 
               
             
          
           
               
                   
                   
                   
                 Wt. 
                   
                 Situation 
               
               
                 Checking 
                 Lot no. of 
                 Eqs ratio of XL- 
                 % of 
                 Wt. % of 
                 of 
               
               
                 no. 
                 CTPEG 
                 29SE/CTPEG 
                 H2O 
                 polymers 
                 gelling 
               
               
                   
               
               
                 550-20-5 
                 550-19 
                 3.0 
                 29.86 
                 39.93 
                 Softer gel 
               
               
                 550-20-7 
                 550-19 
                 4.0 
                 24.86 
                 41.62 
                 Gelled 
               
               
                 550-20-11 
                 550-19 
                 5.0 
                 21.29 
                 42.82 
                 Firmer gel 
               
               
                 550-16-7 
                 550-12 
                 2.0 
                 39.25 
                 39.25 
                 Soft gel 
               
               
                 550-16-10 
                 550-12 
                 4.0 
                 53.12 
                 27.44 
                 Soft gel 
               
               
                 550-16-5 
                 550-14 
                 1.0 
                 50.00 
                 39.90 
                 Soft gel 
               
               
                 550-16-11 
                 550-14 
                 3.0 
                 62.40 
                 25.00 
                 Firmer gel 
               
               
                 550-25-3 
                 550-24 
                 1.5 
                 46.55 
                 43.11 
                 Gelled 
               
               
                 550-25-2 
                 550-24 
                 2.0 
                 43.55 
                 43.55 
                 Soft gel 
               
               
                 550-25-6 
                 550-24 
                 4.0 
                 61.38 
                 26.51 
                 Soft gel 
               
               
                 550-28-2 
                 550-26 
                 2.0 
                 37.93 
                 37.93 
                 Gelled 
               
               
                 550-28-6 
                 550-26 
                 5.0 
                 45.85 
                 29.87 
                 Soft gel 
               
               
                 550-36-1 
                 550-31 
                 2.0 
                 36.67 
                 36.67 
                 Gelled 
               
               
                 550-36-3 
                 550-32 
                 4.0 
                 48.53 
                 27.94 
                 Gelled 
               
               
                 550-36-3 
                 550-32 
                 5.0 
                 43.43 
                 30.26 
                 Gelled 
               
               
                   
               
             
          
         
       
     
     While preferred embodiments of the invention have been described and illustrated here, various changes, substitutions and modifications to the described embodiments will become apparent to those of ordinary skill in the art without thereby departing from the scope and spirit of the invention.