Patent Description:
Infusion therapy products have multiple components that require lubrication, including a cannula, catheter, wedge, tipping and blood control actuator. The lubricants are currently applied in a secondary, solvent-based process during the manufacture of the components. The solvents used during the secondary lubrication application process are constantly under scrutiny from regulatory agencies. Manufacturers are constantly seeking to upgrade their manufacturing processes to utilize acceptable solvents to ensure compliance with constantly changing regulatory standards. However, constant conversions and upgrades to manufacturing processes to comply with constantly changing regulatory standards, e.g. a conversion from the use of a HCFC solvents to a VOC-flammable solvent, can be both capital and resource intensive for the manufacturer. Thus, the elimination of the secondary, solvent based lubrication step would lead to substantial savings, not only from the elimination of the solvent but also with respect to the cost of the secondary process itself with regards to capital equipment, time and resources. The elimination of the secondary, solvent based lubrication step would also lead to a substantial environmental benefit and an increase in work-place safety resulting from the elimination of the solvent in the manufacturing process.

Lubricants which are applied as a coating or blended into the plastic itself can leach out into patient's blood stream. While the regulatory bodies currently allow for some controlled amount of silicone based (or other) lubricant into the patient. Thus, the elimination of the potential leaching would result in an increase to patient safety.

Thus, there is a need for a self-lubricating polymer composition which does not require a secondary, solvent based lubrication step while allowing for tailorability without additives or an extra coating. There is also a need for a self-lubricating polymer composition would also result in a consistent coating thickness and amount due to the lubricant being chemically-bounded to the resin, thereby mitigating concerns of variations of lubrication performance due to process variations. There is also a need for a functionalized lubricant which would eliminate migration concerns of the lubricant into the blood stream.

One aspect is directed to a self-lubricating polyurethane composition comprising a areaction product of a diisocyanate and a diol mixture containing a short chain diol, a long chain polyether or polyester diol, and a lubricant. In one or more embodiments, the polyurethane has a lubricant chemically attached within the polyurethane resin. In one embodiment, the lubricant is incorporated into a backbone of the polyurethane resin. In one or more embodiments, the diisocyanate is selected from the group consisting of an aliphatic diisocyanate, alicyclic diisocyanate and an aromatic diisocyanate. In a more specific embodiment, the diisocyanate is selected from the group consisting of <NUM>,<NUM>-diphenyl methane diisocyanate (MDI), toluene diisocyanate (TDI), isophorone diisocyanate (IPDI), and methylene bis (<NUM>-cyclohexyl isocyanate) (HMDI). In one or more embodiments, the short chain diol is selected from the group consisting of ethylene glycol, <NUM>,<NUM>-propylene glycol, <NUM>,<NUM>-butane diol, neopentyl glycol, and alicyclic glycols having up to <NUM> carbon atoms. In one or more embodiments, the polyester diol is a polyalkylene glycol. In one embodiment, the polyalkylene glycol is poly(tetramethylene ether) glycol. The lubricant is polydimethylsiloxane diol. In a specific embodiment, the polydimethylsiloxane is present in an amount ranging from <NUM> to <NUM> weight percent of the polyurethane composition. In one or more embodiments, the self-lubricating polyurethane composition includes an anti-microbial moiety covalently attached to the self-lubricating polyurethane. In one or more embodiments, the self-lubricating polyurethane composition includes an anti-thrombogenic moiety covalently attached to self-lubricating polyurethane. The lubricant is incorporated into a backbone formed by the diisocyanate and the diol mixture.

In one or more embodiments, the reaction further includes a catalyst selected from a group consisting of dibutyltin dilaurate, tertiary amines, and metallic compounds. In a specific embodiment, the tertiary amine is <NUM>,<NUM>-diazabicyclo[<NUM>. <NUM>]octane). In a specific embodiment, the metallic compound is dibutyltin dilaurate or bismuth octanoate.

Another aspect is directed to a polyurethane of Formula I:
<CHM>
wherein the repeating unit of m is in the range from <NUM> to <NUM>; the repeating unit of n is in the range from <NUM> to <NUM> and the overall molecular weight of the polyurethane resins is between <NUM>,<NUM>/mole to <NUM>,<NUM>/mol.

Another aspect is directed to an article molded from the self-lubricated polyurethane composition disclosed herein. In one or more embodiments, the article is a component of a cannula, catheter, wedge, tipping, blood control actuator, or syringe. In a specific embodiment, the article is a stopper.

Before describing several exemplary embodiments of the invention, it is to be understood that the invention is not limited to the details of construction or process steps set forth in the following description. The invention is capable of other embodiments and of being practiced or being carried out in various ways.

The present invention relates to a polyurethane resin having an incorporated lubricant structure which may be used to produce a self-lubricating medical device or component of a medical device. The resin of the present invention eliminates the required secondary lubrication step currently found in the manufacture of many medical device components. Due to the lower surface energy of an incorporated lubricant, the incorporated lubricant has a propensity for migration to the surface both during the catheter fabrication process and as a function of time post-production.

In the present invention, a lubricant is attached chemically to a polyurethane resin. The lubricant is polydimethylsiloxane diol. The lubricants are chemically reacted to attach with or be incorporated into a desired polyurethane resin of interest. The lubricant is incorporated into the backbone structure of the resin. The lubricant may be attached chemically to a desired polyurethane resin using several techniques. One technique to chemically attach the lubricant to the desired polyurethane is the modification of the urethane monomer prior to polymerization of the monomer into a polyurethane polymer. In one embodiment, isocyante monomers are reacted with polyols to create polyurethane. The isocyante monomers can be modified to contain a lubricating moiety and the reaction with polyols will continue to create self-lubricating polyurethane.

Another technique to chemically attach the lubricant to the desired polyurethane is to graft a lubricant onto the resin backbone of an existing resin using controlled chemistry such as ATRP, functional group reactions, or plasma modification of the resin surface followed by grafting of the lubricant onto the surface of the resin.

Another technique to chemically attach the lubricant to the desired polyurethane is to utilize the functional groups on the lubricating chemicals to co-polymerize it with the monomers into a co-polymer thereby adding the lubricating moiety directly into the backbone of the polymer. For example, a lubricant, such as PDMS, can be made with alcohol or "OH" functional groups, which is an essential reactive group to the polyurethane synthesis. The structure of PDMS with the -OH functional group will co-react with the isocyanate to incorporate PDMS chains into polyurethane creating the self-lubricating polymer.

It is intended that the chemical modification process to functionalize the lubricant onto the resin would still enable the resin to be suitable for use in Class II medical devices.

During and after the fabrication process of the medical device component, the lubricant blooms to the surface due to the lower surface energies of the silicone or fluorinated groups. Due to the chemical linkage of the lubricant to the polymer chain of the bulk material, an additional lubrication process step to obtain the lubrication performance required is eliminated.

In another aspect of the present invention, the synthesis technique may also be utilized to incorporate anti-microbial chemicals or anti-thrombogenic chemicals into a polymer resin composition of the present invention including a lubricant structure.

The resin of the present invention may be used in polymer based medical devices which require lubrication such as the injection syringe barrel and/or stopper. The resin of the present invention may also be used in syringes which are prefilled with saline or other solutions which further dissolve the lubricant off the surface of the syringe barrel and carry it into the patient's bloodstream.

A series of polyurethane resins of Formula I as follows were prepared:
<CHM>
wherein the repeating unit of m is in the range from <NUM> to <NUM>. The repeating unit of n is in the range from <NUM> to <NUM>. The overall molecular weight of the polyurethane resins is between <NUM>,<NUM>/mole to <NUM>,<NUM>/mol.

The polyurethane resins of Formula I were prepared from <NUM>/mol to <NUM>,<NUM>/mol of silicone fluid such as Gelest DMS-S31, polyols such as DuPont Tetrathane T-<NUM>, <NUM>,<NUM>-diphenyl methane diisocyanate (MDI), and <NUM>,<NUM> butanediol (BDO). The diols, i.e., DMS-S31, Tetrathane T-<NUM>, and BDO were mixed, heated to <NUM> ± <NUM>. The MDI then was added and the mixture was stirred to prevent phase separation of the liquid mixture. After about <NUM> to <NUM> minutes, the temperature increased to about <NUM>. The liquid mixture then was poured into polytetrafluoroethylene lined trays and heated to <NUM> overnight to complete the polymerization. After cooling to ambient temperature, the resins were chipped and extruded into film for measurement of physical properties. The results are showed in Table <NUM>. As a control, sample #<NUM> "<NUM>% PDMS", was prepared in which the DMS-S31 fluid was omitted and replaced with a like quantity of polyols. The results are also included in Table <NUM>.

As shown in Tables <NUM>-<NUM>,various Polyurethane/Polysiloxane resins were tested for various attributes such as number average molecular weight, weighted average molecular weight, polydispersity, average tensile at break, coefficient of friction and thermal analysis, the results are shown in Tables <NUM>-<NUM>.

As shown from the results in Table <NUM>, the addition of <NUM>% by weight of co-polymer PDMS into the polyurethane synthesis, achieved the same if not lower coefficient of friction as currently lubricated polyurethane material. The current lubrication of polyurethane required an additional coating of <NUM>% by weight addition of PDMS. This method of copolymerizing lubrication functionality into polyurethane is more efficient at achieving lower coefficient of friction than simply coating an additional layer of PDMS.

As shown in Table <NUM>, co-polymerization of PDMS into the resin backbone disrupted the crystallization of the hard segment but did not disturb the tensile properties.

Silicone diols, such as those disclosed in <CIT> are known products which can be prepared by synthetic methods reported in the art may be used as lubricants in the present invention. Non-silicone diols, for example fluorinated diols, such as those marketed as "Krytox" diols commercially available from Dupont may be used as lubricants in the present invention.

From consideration of the synthesis, those skilled in the art will appreciate that the silicone diol may include a mixture of functional R- groups such as a combination of ethylene and butylene groups.

A presently preferred silicone diol for use in the invention is a polydimethylsiloxane diol with molecular weight in range of <NUM>/mole to <NUM>,<NUM>/mol.

As a general rule, the polyurethanes of the present invention are easily prepared by forming a diol mixture containing the short chain diol, a long chain polyether or polyester diol and the silicone diol of formula and adding the diisocyanate to the diol mixture. Catalysts conventionally used in the synthesis of polyurethanes, such as dibutyltin dilaurate, tertiary amines (i.e. <NUM>,<NUM>-diazabicyclo[<NUM>. <NUM>]octane), and metallic compounds (i.e. dibutyltin dilaurate or bismuth octanoate) may be used.

Polyether diols which can be used in the present invention include the polyalkylene glycols. Two polyether diols that are presently preferred for use in the present invention are poly(tetramethylene ether) glycols having molecular weights in the range of <NUM> to about <NUM>. Such polyols are commercially available as Polymeg <NUM> (Quaker Oats Co. , Chemical Division) and Terathane T-<NUM> (DuPont).

The diol included in the polyurethane resins of the invention may include ethylene glycol, <NUM>,<NUM>-propylene glycol, <NUM>,<NUM>-butane diol, neopentyl glycol, etc. Other diols which can be employed are alicyclic glycols having up to <NUM> carbon atoms, e.g., <NUM>,<NUM>-cyclohexane diol, <NUM>,<NUM>-dimethylol cyclohexane, etc..

Representative diisocyanates useful in the present invention include aromatic and alicyclic diisocyanates, such as <NUM>,<NUM>-diphenyl methane diisocyanate (MDI), toluene diisocyanate (TDI), isophorone diisocyanate (IPDI), methylene bis (<NUM>-cyclohexyl isocyanate) (HMDI), etc. Of these, MDI and HMDI are presently preferred.

The diisocyanate and the diols are included in an amount of <NUM> to <NUM> weight percent of the product. In one or more embodiments, the diisocyanate range from <NUM>% to <NUM>% by weight. In one or more embodiments, silicone diol may be added in <NUM> to <NUM> weight %. In general, the ratio of OH to isocyanate functional group is about a <NUM>:<NUM> ratio.

The long chain polyether diol or the long chain polyether diol or a mixture of the two diols constitutes the balance of the polyurethane resin.

The polyurethane resins of the invention can be fabricated into film, tubing and other forms by conventional thermoplastic fabricating techniques including solution casting, extrusion molding, etc. The resin may have incorporated therein, as desired, conventional stabilizers and other additives. The amounts of these materials will vary depending upon the application of the polyurethane, but they are typically present in amounts ranging from about <NUM> to <NUM> weight percent of the polymer.

The polyurethane-polysiloxane resin may include polydimethylsilioxane (PDMS).

In one or more embodiments, it is envisioned that anti-microbial chemicals or anti-thrombogenic chemicals may be covalently bound to the resin.

Claim 1:
A self-lubricating polyurethane composition comprising a reaction product of:
a diisocyanate; and
a diol mixture containing a short chain diol, a long chain polyether or polyester diol, and a lubricant, wherein said lubricant is polydimethylsiloxane diol;
the lubricant being incorporated into a backbone formed by the diisocyanate and the diol mixture;
wherein the lubricant is present in an amount ranging from <NUM> to <NUM> weight percent of the polyurethane composition.