WO2024089705A1

WO2024089705A1 - Hydrophilic coating compositions and formulations thereof

Info

Publication number: WO2024089705A1
Application number: PCT/IN2023/050974
Authority: WO
Inventors: Milind CHOUDHARI; Prasad Bhagat; Sandeep Sonawane
Original assignee: Weinnovate Biosolutions Pvt. Ltd
Priority date: 2022-10-23
Filing date: 2023-10-21
Publication date: 2024-05-02

Abstract

The present invention discloses a hydrophilic coating composition and formulation thereof to develop advanced medical devices having self-lubricating (hydrophilic) surfaces upon contact with water for frictionless application in patients. The hydrophilic composition for coating of the present invention comprises of a supporting polymer, hydrophilic polymer, a humectant or wetting agent, a cross linker and solvents. The hydrophilic coating composition of the present invention creates uniform, durable and self-lubricating film on the surface of the medical devices and ensures there is no injury during insertion, improved patient compliance, improved quality of life, no additional hospital stays and no extra financial burden on patients.

Description

TITLE OF THE INVENTION

HYDROPHILIC COATING COMPOSITIONS AND FORMULATIONS THEREOF

FIELD OF INVENTION

The present invention relates to hydrophilic coating compositions and formulations thereof. More particularly the invention relates to a hydrophilic coating compositions and formulations thereof that can be used to coat different materials such as silicone, silicon resins, polyvinyl chloride, polyvinyl chloride resins, polypropylene, polypropylene resins, polyethylene, polyethylene resins, latex rubber, glass, glass resins, stainless steel, ceramic, certain polyurethane etc. Even particularly the present invention relates to hydrophilic coating to coat various surfaces, such as medical devices, including urinary catheters, vascular catheters, oxygen tubing, endotracheal and nasogastric tubes, hemodialysis tubing, stents, non-invasive ventilation masks etc. to make them hydrophilic.

BACKGROUND OF INVENTION

Medical devices are being used widely in the critical sector of hospital settings and therefore considered as a lifesaving invention in the medical field. However, the use of these commonly used conventional medical devices such as urinary catheters, vascular catheters, oxygen tubing, endotracheal and nasogastric tubes, hemodialysis tubing, stents, non-invasive ventilation masks etc. is associated with device-related pressure ulcers (DRPU) and frictional injuries. These hospital-acquired injuries in turn lead to medical devices associated infections which makes them life-threatening instead of life saving in most of the critically ill patients. Apart from infections, frictional injuries can result in unnecessary pain, patient incompliance, reduced quality of life, increased length of hospital stay, extra financial burden etc. Therefore, considering this serious problem of frictional injuries, there is an urgent need to develop a hydrophilic coating for coating medical devices to make their surfaces self-lubricating (hydrophilic) upon contact with water for frictionless application in patients.

Many prior studies have explored the development of hydrophilic coatings using different materials such as prepolymers, polymers, chain extenders, and various cross-linkers, including photo-initiators. Some of these coatings rely on a UV light curing process, while others use thermal curing to create a covalent bond within the polymer network. In some prior research, hydrophilic coatings were developed using polyurethaneurea, which is synthesized using NCO-terminated polyurethane prepolymers and bifunctional amines as chain extenders or cross-linkers. These coatings often included various hydrophilic polymers like polyalkylene glycols, alkoxy polyalkylene glycols, poly(vinylpyrrolidone), methyl cellulose, carboxy methyl cellulose, and polyethylene oxide. However, these previous studies mainly focused on short-term hydrophilic performance and frequently lacked uniformity, durability, stability, and long-term functionality in their coatings. Additionally, using polyurethaneurea or polyurethane with a chemical reagent as a cross-linker resulted in covalently bonded coatings that could lose their hydrophilic (lubricious) properties over time. This combination of polyurethane polymer and cross-linkers also had a short pot life and often led to significant composition wastage due to the polymer initiating irreversible curing in the coating solution itself. Conversely, using polyurethane dispersions without crosslinkers could result in less durable and easily removable hydrophilic coatings upon contact with water.

Considering these challenges with polyurethane as a supporting polymer in hydrophilic coating development, there is a need to find a suitable cross-linker that forms an optimized polyurethane network through ion-pairing (ionic bond) rather than covalent bonding. Additionally, optimizing the concentrations of the coating composition ingredients is essential to produce uniform, durable, and long-term functional hydrophilic coatings on various substrate surfaces, including latex, silicone, polyvinyl chloride, and polyurethane.

OBJECTIVES OF THE INVENTION

The primary object of the present invention is to provide a hydrophilic coating composition for prevention of device-associated frictional injuries and infections.

Another object of the present invention is to provide a hydrophilic coating composition for uniform, durable and self-lubricating (hydrophilic) films or coatings.

Yet another object of the present invention is to provide a hydrophilic coating composition having polyurethane as a supporting polymer, ethylenediamine as a cross linker, polyvinyl pyrrolidone (K90) as a hydrophilic polymer and glycerol as a humectant or wetting agent. Still another object of the present invention is to provide a hydrophilic coating composition suitable for various coating methods such as dip coating, spray coating, roll coating, spin coating, brushing, flow coating etc.

Still another object of the present invention is to provide a hydrophilic coating composition with an extended pot-life or shelf life at room temperature.

SUMMARY OF THE INVENTION

Accordingly, the present invention provides a hydrophilic coating formulation having the appropriate combination and quantities of the added components which are synergistically important for achieving the desired properties of hydrophilic coating formed on the surfaces of various medical devices. While there have been reports of using NCO-terminated polyurethane prepolymers as supporting polymers and amino functional reagents as cross-linkers or chain extenders to create hydrophilic coatings on medical devices, the combination of a water-based polyurethane with no -NCO terminal as a supporting polymer and ethylenediamine as a crosslinker to form an optimized polyurethane network through ion-pairing (ionic bond) instead of a covalent bond for creating desired hydrophilic coatings is being reported for the first time in this invention. The present invention, the composition of polyurethane as a supporting polymer, ethylenediamine as a cross linker, polyvinyl pyrrolidone (K90) as a hydrophilic polymer and glycerol as a humectant or wetting agent are combined in appropriate quantities which results into synergistic effect by formulating uniform, durable and self-lubricating (hydrophilic) films on the surfaces of medical devices.

When the substrates are coated with the formulation of the present invention a long-lasting, functional and uniform film formation on substrate surface was observed. Stable bonding of crosslinked polyurethane network with substrate surface holding hydrophilic polymer was observed. Lubricating substrate surface was observed after dipping in to water for up to 30 days. DETAILED DESCRIPTION OF THE INVENTION

The hydrophilic composition for coating of the present invention comprises of a supporting polymer, hydrophilic polymer, a humectant or wetting agent, a cross linker and solvents

In the present invention, hydrophilic coating composition comprises polyurethane as a supporting polymer. The selection of a suitable polyurethane polymer having appropriate functional groups available for cross linking is crucial for achieving desired hydrophilic coatings on the various substrate surfaces. Also, an appropriate or optimized concentration of polyurethane in the composition is important to hold hydrophilic polymer without affecting its long-lasting functionality. Higher concentration of it in the composition could result into loss of hydrophilic (lubricating) property and stripping of the film formed on the substrate. Whereas, lower concentration of it in the composition could lead to weak networking and bonding with the substrate surface holding hydrophilic polymer, this could further result into quick removal of a film formed upon contact with water. In the present invention, the polyurethane employed is water based aromatic hybrid N-Methyl-2-Pyrrolidone (NMP) free polyurethane dispersion having pendant carboxylic acid functional groups available for ion-pairing (ionic cross linking). The carboxylate (COO ) ions from the pendant carboxylic acid functional groups present in the structure of polyurethane polymer form stable and desired polymer network through ion-pairing with the ammonium (NH3⁺) ions of cross linker used. This network securely anchors the hydrophilic polymer to the substrate surface for an extended duration.

In the present invention, hydrophilic coating composition comprises polyvinylpyrrolidone (K90) as a hydrophilic polymer. Considering the need of non-ionic hydrophilic polymer in the formulation of hydrophilic coating composition, polyvinylpyrrolidone (K90) was selected as a hydrophilic polymer. Apart from the charges present on the polymer molecules, an optimized concentration of polyvinylpyrrolidone (K90) in the composition is important to achieve long- lasting hydrophilic coatings. Higher concentration of it in the composition could mask the functional groups of supporting polymer and cross linker to form a weak cross-linked networking of supporting polymer, this could in turn result into removal of a hydrophilic film formed upon contact with water. Whereas, lower concentration of it in the composition could lead to loss of an instant hydrophilic (lubricating) property of a hydrophilic film formed upon contact with water. In the present invention, a non-ionic nature and an appropriate concentration of the selected hydrophilic polymer in the hydrophilic coating composition resulted into formation of highly functional long-lasting hydrophilic film on various substrate surfaces.

In the present invention, hydrophilic coating composition comprises glycerol as a humectant or wetting agent. The curing step of hydrophilic coating films on substrate surface involves the heating in the range of 60 °C to 80 °C for 30 min. An over drying of the hydrophilic films on substrate surface during curing process could lead to breaking and stripping of the films formed. Therefore, to avoid this over drying by retaining moisture in the hydrophilic films formed, glycerol was used as a humectant or wetting agent. An optimized concentration of glycerol in the composition is important to achieve the non-sticky and intact hydrophilic coatings. Higher concentration of it in the composition could result into formation of sticky hydrophilic films, whereas lower concentration of it in the composition could lead to breaking and stripping of the films formed during their handling. In the present invention, use of an appropriate concentration of the selected humectant or wetting agent in the hydrophilic coating composition resulted into formation of the non-sticky and intact hydrophilic coatings.

The selection of a cross linker having appropriate functional groups available for ionic cross linking (ion-pairing) with carboxylic acid functional groups of polyurethane (supporting polymer) is an important step for achieving desired hydrophilic coatings. In the present invention, hydrophilic coating composition comprises ethylenediamine as a cross linker. The chain length of the selected bifunctional amine, base strength, solubility in water and alcohol, boiling point and its affinity towards carboxylic acid functional groups of polyurethane are equally important in achieving the optimized cross-linking network of polyurethane for effectively holding the hydrophilic polymer on the substrate surface. An appropriate concentration of ethylenediamine was used in the composition based on the mole equivalent ratio of carboxylic acid and amine functional groups available for cross-linking. In the present invention, use of an appropriate concentration of the selected cross-linker in the hydrophilic coating composition resulted into formation of highly functional long-lasting hydrophilic films on various substrate surfaces.

The developed hydrophilic coating composition involves the use of alcohol to make the alcoholdistilled water mixture as a solvent. Though all the composition ingredients are freely soluble in water, the use of completely water-based composition was avoided to get the desired hydrophilic films on substrate surface. The completely water-based hydrophilic composition produces non- uniform films on the substrate surfaces after drying due to high boiling point and slow evaporation rate of water at curing temperature (70 °C). The examples of the alcohols used for making alcohol- water solvent system includes ethanol, isopropyl alcohol, methanol etc. An appropriate concentration of alcohol used in the hydrophilic composition of the present invention produced uniform hydrophilic (lubricating) films/coatings on various substrate surfaces by accelerating the evaporation rate of the solvent system used at 70 °C.

The developed hydrophilic coating composition involves the use of distilled water for making alcohol-water mixture as a solvent. As polyurethane, a supporting polymer is soluble in plain water or alcohol-water mixture, the use of completely alcohol-based composition was not preferred to avoid the precipitation of polyurethane in alcohol and to get the desired hydrophilic films on substrate surface. An appropriate concentration of water used in the hydrophilic composition of the present invention produced uniform hydrophilic (lubricating) films/coatings on various substrate surfaces by keeping polyurethane uniformly dispersed in the formulated composition.

Example 1

Table 1. Optimization of a hydrophilic coating composition using various composition ingredients.

Optimization of hydrophilic coating compositions

Composition Compo Compo Compo Compo Compo Compo Compo Compo Compo Compo ingredients 1 2 3 4 5 6 7 8 9 10

(14 ml) (14 ml) (14 ml) (14 ml) (14 ml) (14 ml) (180 ml) (I L) (14 ml) (I L)

Amount (% v/v)

Polyurethane 7.142 10.714 7.142 7.142 7.142 7.142 7.777 7.8 5.6 5.6

Distilled water 35/714 I 7.S57 21 28 21428 21428 10.71 1 1222 12.2 15.6 152

Mixture of 10 % 28.571 21.428 21.428 21.428 21.428 w/v of PVP K90 and 2.4 % w/v of glycerol in distilled water l lliyleiiedianiine 28.571 T()5T : 10714 -- 10714 1126 112 84 84 Jeffamine D230 10.714

4,4 - - - - 10.714 methylenediamine solution

Methanol - 39.285 39.285 39.285 39.285 42.857 43.33 43.4

Mixture of 11 % - - - - - 28.571 25 25 w/v of PVP K90 and 2.4 % w/v of glycerol in distilled water

Mixture of 11 % — — — — — — — — 22.8 22.8 w/v of PVP K90 and 8 % w/v of glycerol in distilled water

Ethanol 48 48

The various compositions were tested during the optimization process of a hydrophilic coating solution, as shown in Table 1. In Compo 1, not using methanol resulted in the formation of uneven coating films on the substrate surfaces. Compo 2, which included methanol and distilled water to speed up drying, produced uniform coatings but they were a bit hard with cracks in the films after twisting the substrates. However, Compo 3, 4, and 5, which had a lower concentration of polyurethane compared to Compo 2, combined with PVP K90, glycerol, and methanol, produced uniform coatings without cracks and displayed a slippery (hydrophilic) surface when in contact with water. Among these, only Compo 3 created well-adhered coatings due to a stable crosslinking between polyurethane and ethylenediamine. Compo 4 and 5 failed to produce strongly adhered coating films because of weak or no cross-linking between polyurethane and jeffamine D230 in Compo 4 and polyurethane and 4,4 methylenediamine in Compo 5. Although all three screened cross-linkers were bifunctional amines, only ethylenediamine could form the optimized cross-linking network of polyurethane to effectively hold a hydrophilic polymer on the substrate surface. This highlights the importance of selecting a suitable cross-linker, considering factors like its base strength, solubility in water and alcohol, chain length, boiling point, and affinity towards carboxylate (COO ) ions of polyurethane. This choice not only determines the durability of the coating films containing hydrophilic polymer but also allows water to penetrate the porous films and swell the hydrophilic polymer, resulting in the long-term maintenance of their slippery properties on the surface. Compo 6 successfully produced uniform, durable, and long-term functional (hydrophilic) coating films on the substrate surfaces using the optimum concentrations of hydrophilic polymer (PVP K90) and an alcohol-water solvent system. Therefore, Compo 6 was considered the optimized coating composition and scaled up to 180 ml (Compo 7) and 1 L (Compo 8). Similarly, Compo 9 also created uniform, durable, and long-term functional coating films on the substrate surfaces using the optimum concentrations of the composition ingredients. However, Compo 9 used ethanol as a solvent instead of methanol. Therefore, it was also considered an optimized coating composition and scaled up to 1 L (Compo 10) for use on various substrates such as latex rubber, silicone, polyvinyl chloride, and polyurethane.

In an embodiment of an optimized hydrophilic coating composition of the present invention can be used to coat the uncoated latex Foley balloon catheters.

In an embodiment of an optimized hydrophilic coating composition of the present invention can be used to coat the uncoated silicone Foley balloon catheters.

In an embodiment of an optimized hydrophilic coating composition of the present invention can be used to coat the uncoated endotracheal tubing made up of polyvinyl chloride.

In an embodiment of an optimized hydrophilic coating composition of the present invention can be used to coat the uncoated hemodialysis tubing and central venous catheter made up of polyurethane.

Example 2

Coating and curing process

The present invention also discloses a coating and curing method utilizing an optimized hydrophilic coating composition of the present invention. The coating and curing process comprises the following steps: Cleaning the substrate surfaces (latex rubber, silicone, polyvinyl chloride and polyurethane) using isopropyl alcohol and drying in a hot air oven at 60-80 °C for 5 min.

• Dipping the cleaned substrates into primer solution for 1 to 2 min at room temperature.

• After 1 to 2 min of dipping, removing all the substrates from the primer solution tank and immediately transferring into the hot air oven maintained at 60-80 °C for 30 min.

• After 30 min of drying of a primer layer, dipping all the substrates into hydrophilic coating solution for 10 min at room temperature.

• After 10 min of dipping, removing all the substrates from the hydrophilic solution tank and immediately transferring into the hot air oven maintained at 60-80 °C for 30 min.

• After 30 min of drying, dipping all the substrates into distilled water for 30 sec and transferring into the hot air oven maintained at 60-80 °C for 3 to 10 min.

• After complete drying, removing all the substrates from the hot air oven and testing separately to measure their hydrophilic properties, which including contact angle and coefficient of friction.

Example 3

Coating of various medical devices

We coated various uncoated medical devices, including latex Foley balloon catheters, silicone Foley balloon catheters, endotracheal tubing, hemodialysis tubing, and central venous catheters, using an optimized hydrophilic coating compositions and the method described in Example 2. The optimized hydrophilic coating composition had a density of 0.886 gm/ml and a viscosity of 30-40 cps. The latex Foley balloon catheters had an outer diameter of 5.33 mm (16 Fr), an inner diameter of 2.3 mm, and a length of 40 cm. The silicone Foley balloon catheters had the same specifications. The endotracheal tubing had an outer diameter of 9.3 mm and an inner diameter of 7 mm. The hemodialysis tubing was 13.5 cm long and had a 2-lumen indwelling catheter measuring 11.5 Fr x 5-2/5". The central venous catheter was 16 cm long and had an indwelling catheter measuring 7 Fr x 6-2/5". After coating these devices, the coated latex Foley balloon catheter and coated silicone Foley balloon catheters were further utilized for the in-depth evaluation of coatings.

Example 4

Hydrophilic coating film/layer morphology

The morphology analysis was performed to determine the structural uniformity of the coated hydrophilic film on the silicone and the latex Foley catheter surfaces. We used scanning electron microscopy to analyze the structure of the hydrophilic coating films on the surfaces of silicone and latex Foley catheters. In Fig. 1, SEM images of the coated silicone Foley catheter show a continuous, uniform, and porous hydrophilic coating without any uncovered areas. The pore sizes in this film ranged from 0.2 to 1.1 pm (Fig. lb). The images also clearly reveal the boundary between the coated and uncoated sections of the silicone Foley catheter (Fig. 1c). In Fig. 2, SEM images of the coated latex Foley catheter similarly show a continuous and uniform hydrophilic coating layer with no uncovered areas. However, the coating on the latex surface was found to be non-porous compared to the silicone catheter (Fig. 2b). SEM analysis also clearly distinguishes between the coated and uncoated sections of the latex Foley catheter (Fig. 2c).

Example 5

Hydrophilic coating film thickness

A hydrophilic coating film thickness analysis was performed to measure the thickness and uniformity of the hydrophilic coating films on both silicone and latex Foley catheter surfaces using the scanning electron microscopy. SEM images in Fig. 3 and Fig. 4 confirmed that there are continuous and uniform hydrophilic coating films along the periphery of both silicone (Fig. 3a) and latex (Fig. 4a) Foley catheters. We also examined the uniformity of the coating towards the upper and lower portions of the catheters. For silicone Foley catheters, the thickness of the coating film was consistent, measuring around 4 pm (Fig. 3b and 3c). Similarly, for latex Foley catheters, the coating film had a consistent thickness in the range of 5-6 pm (Fig. 4b and 4c).

In summary, these results confirm that the hydrophilic coating films, produced using our optimized composition, are uniform and have consistent thicknesses on both silicone and latex surfaces. Example 6

Distribution of hydrophilic polymer in the cured coating films

Table 2. Water contact angle values measured on the upper, middle and lower portions of both the coated silicone and latex Foley catheters using ImageJ software.

Samples tested Water contact angle values obtained (degree)

Upper side Middle side Lower side portion portion portion

Coated silicone catheter 59.4 55.5 56.4

Coated latex catheter 65.9 61 58.7

The water contact angle values were measured on the upper, middle and lower portions of the coated silicone and latex Foley catheters to check how evenly the hydrophilic coating films were distributed. To perform this, we gently placed 10 pl drops of distilled water onto the upper, middle, and lower portions of the coated silicone and latex Foley catheters using a micropipette. After 20 sec, we captured photographs of the water droplets on the surface of each portion. These images were later analyzed with ImageJ software to determine the water contact angle on the catheter's surface. After 20 sec of applying water drops on the coated silicone catheter, we found contact angle values of 59.4° on the upper portion, 55.5° on the middle portion, and 56.4° on the lower portion (Fig. 5a, 5b, 5c, and Table 2). These similar water contact angle values across all three portions indicate that the hydrophilic polymer (PVP K90) was evenly distributed throughout the length of the silicone catheter due to the uniform coating film formation. Similarly, after 20 sec of applying water drops on the coated latex catheter, we observed contact angle values of 65.9° on the upper portion, 61° on the middle portion, and 58.7° on the lower portion (Fig. 5d, 5e, 5f, and Table 2). Once again, the similar water contact angle values across all three portions suggest the uniform distribution of the hydrophilic polymer (PVP K90) throughout the length of the latex catheter, likely due to uniform coating film formation. The cured hydrophilic coatings exhibit a stable bonding between the cross-linked polyurethane network and the substrate surfaces, securely holding the hydrophilic polymer with consistent concentration across the entire length. This results in similar water contact angles on all tested portions, confirming the uniformity of the hydrophilic coating films on the surfaces of silicone and latex Foley catheters.

Therefore, the results discussed in examples 4, 5, and 6 collectively validate the uniformity of hydrophilic coating films produced using an optimized hydrophilic coating formula on silicone and latex surfaces.

Example 7

Durability of hydrophilic coatings

The durability of the coatings was determined by making slight modifications to the previously reported percent weight loss method (Zhang et al., 2023). To investigate how effectively the hydrophilic coating films held up in an aqueous environment, we cut the coated silicone and latex Foley catheter samples into 4 cm lengths and weighed them individually to determine their initial mass using an analytical weighing balance. After weighing, we immersed both sets of samples in 30 ml of artificial urine and placed them in an incubator at 100 rpm for up to 20 days at 37 °C. At specific time intervals, we removed the samples from the artificial urine, dried them at 60 °C, and weighed them to check for any weight loss compared to their initial masses.

Additionally, to assess their durability under shear stress, we cut the samples into 2 cm lengths and weighed them individually to determine their initial mass using an analytical weighing balance. After weighing, we placed all the samples separately in 2 ml eppendorf tubes containing 1.5 ml of artificial urine. Each set of samples was then spun at 1500, 3000, and 6000 rpm for 2 min, and we monitored any weight loss.

The percentage of weight lost by the hydrophilic coating films after being incubated in artificial urine at 100 rpm for 20 days

The percentage of weight lost by the hydrophilic coating films after being spun in artificial urine for 2 min at 1500, 3000, and 6000 rpm.

The purpose of the durability testing was to evaluate how effectively the hydrophilic coating films adhered to the surfaces of silicone and latex Foley catheters when exposed to an aqueous system. To do this, an artificial urine was utilized as a representative aqueous system, considering the commercial application of these catheters in assisting urination. After 20 days of incubation in artificial urine, the coated films on both silicone and latex Foley catheters exhibited weight losses of 1.4 % and 1.8 %, respectively. Additionally, we performed durability tests to evaluate the ability of coating films to maintain adherence under shear stress. The coating films on silicone and latex Foley catheters showed no weight loss (0 %) and minimal weight loss of 0.2 % at 1500 rpm and the highest weight losses of 0.2 % and 1.6 % at 6000 rpm, respectively. These negligible weight losses in the coating films after 20 days in artificial urine and exposure to shear stress confirm the robust and stable bonding between the cross-linked polyurethane network and the substrate surfaces, which holds hydrophilic polymer (PVP K90) in place for long-term hydrophilic effectiveness. In summary, these findings further highlight the durability of the hydrophilic coating films on silicone and latex Foley catheters.

Example 8

Adhesion test of coating films

An adhesion test was performed on the hydrophilic coating films applied to silicone and latex Foley catheters. This test involved slight modifications to an X-cut method described in standard guideline (ASTM D3359-09). An adhesive tape as per USP was utilized to measure the force required to peel off the coating films. Briefly, one end of the said adhesive tape was fixed firmly to the intersection of the X-shaped cut on the coating films and the other end of the tape was attached to a universal testing machine. Subsequently within 90 sec of applying the tape, the said tape was rapidly removed by pulling the machine up at an angle of 180° and the X-cut area on the coating films was inspected to check if any of the coatings has been removed from the catheter surfaces.

The purpose of adhesion test was to determine how effectively the hydrophilic coating films adhered to the surfaces of the silicone and latex Foley catheters when subjected to the applied peel- off force. The results revealed that there was no removal or peel-off of the coating films from the surfaces of the silicone and latex Foley catheters, even when subjected to forces of 80 and 70 gm/cm, respectively.

In addition to the standard adhesion test, we used a non-standard qualitative method to assess how effectively the coatings adhered to the surfaces of silicone and latex Foley catheters. In this approach, we turned and twisted the coated samples, then observed them under an optical microscope to look for any signs of microcracking or the removal of coating films. As shown in Fig.6, the optical microscope images confirmed that there were no microcracks or removed coating films on the surfaces of the silicone (Fig. 6a) and latex (Fig. 6b) Foley catheters.

These findings suggest that the coatings are durable because they demonstrate strong adhesion between the cross-linked polyurethane network and the substrate surfaces, which holds hydrophilic polymer in place for long-term hydrophilic effectiveness.

Therefore, the results discussed in examples 7 and 8 collectively validate the durability of hydrophilic coating films produced using an optimized hydrophilic coating formula on silicone and latex surfaces.

Example 9

Mechanism of bonding of coating films with the substrate surfaces

There have been a few reports on the use of NCO-terminated polyurethane prepolymer along with amino functional cross linkers forming a covalently bonded network to create durable coatings on medical devices. However, this invention introduces a novel approach, utilizing water-based polyurethane without -NCO terminals as the supporting polymer and ethylenediamine as the crosslinker. This method results in an optimized polyurethane network formed through ion-pairing (ionic bonding) instead of covalent bonding to produce the desired hydrophilic coatings. In this process, the carboxylate (COO ) ions from the pendant carboxylic acid functional groups within the polyurethane polymer form a stable and desired polymer network through ion-pairing with the ammonium (NH3⁺) ions from the cross-linker.

The ionic bonding between the carboxylate (COO ) ions and the ammonium (NH3⁺) ions was confirmed using FT-IR spectroscopic analysis of the ingredients in the optimized hydrophilic coating composition. The FT-IR spectrum of the plain polyurethane dispersion displayed a carbonyl stretching peak from the pendant carboxylic group at 1725 cm'¹ (Fig. 7a). In contrast, the FT-IR spectrum of plain ethylenediamine exhibited absorption peaks at 3352 and 3276 cm ¹, corresponding to the asymmetric and symmetric stretching of NH2 groups, respectively (Fig. 7b). The FT-IR spectrum of the physical mixture of polyurethane dispersion, ethylenediamine, PVP K90, and glycerol showed combined peaks at 1725 cm'¹ (carbonyl stretching of the pendant carboxylic group from polyurethane dispersion) and 3356 cm'¹ (asymmetric stretching of NH2 groups) and 3293 cm'¹ (symmetric stretching of NH2 groups) from ethylenediamine (Fig. 7c). Nevertheless, in the FT-IR spectrum of the cured hydrophilic coating film (Fig. 7d), a notable absorption peak at 1725 cm'¹ was observed, while there were no absorption peaks at 3356 and 3293 cm ¹. This suggests that the NH2 groups of ethylenediamine formed ionic bonds with the pendant carboxylic groups of polyurethane, resulting in the creation of carboxylate (COO ) ions and ammonium (NH3⁺) ions through ion-pairing. Therefore, the characteristic absorption peak observed at 1725 cm'¹ in the FT-IR spectrum of the cured hydrophilic coating film corresponds to the carbonyl stretching of the carboxylate (COO ) ions in the ion pair formed (Fig. 7d).

The actual ionic cross-linking process occurs during the curing step of a hydrophilic coating method. In this step, a coating composition applied to substrate surfaces is heated to approximately 60 to 80 °C for 30 min. The polyurethane dispersion within the coating composition is a base salt of triethylamine, formed through the interaction between the carboxylic acid group of polyurethane and the amine group of monofunctional triethylamine. This results in having one monofunctional and one bifunctional amine (ethylenediamine) available in the coating composition during the curing process. When the coating composition is heated during curing, triethylamine dissociates from the carboxylic groups and evaporates due to its lower boiling point (89.28 °C) compared to ethylenediamine (116 °C). Meanwhile, the higher boiling point of ethylenediamine causes minimal loss through evaporation, allowing it to remain available for ion pairing with the dissociated carboxylic groups. This forms an optimized cross-linked polyurethane network. A similar ionpairing reaction between the carboxylic group of polyurethane and hexamethoxymethyl melamine has been reported previously to demonstrate the effect of the neutralizing amines on the curing of polyurethane dispersions (Mequanint et al., 2003).

The bonding of the coating films occurs in a series of steps on the substrate surfaces. First, a preliminary primer layer is applied, which attaches to the substrate surfaces and leaves the outer side epoxy functional group accessible on the surface after the curing step. Second, the secondary hydrophilic coating layer is applied, creating an optimized cross-linked network through a combination of both covalent and ionic bonding. This happens by covalently linking one end of ethylenediamine's terminal amine group to the epoxy functional group provided by the primer and simultaneously ion pairing the other terminal amine group of ethylenediamine with the pendant carboxylic groups of polyurethane. Lastly, the pendant carboxylic groups of polyurethane can further create an additional polyurethane network by ion pairing with both terminal amine groups of ethylenediamine.

This unique combination of covalent and ionic bonding led to stable coatings on the substrate surfaces. These coatings securely hold hydrophilic polymer in position, enabling its swelling upon contact with water for long-term hydrophilic effectiveness. Furthermore, when combining polyurethane dispersion having no -NCO terminal and bifunctional amines as a cross linker, it resulted in a hydrophilic coating composition with a long pot life. This is because there are no covalently reactive functional groups in the composition that would cause it to cure at room temperature and thus avoids significant loss.

Example 10

Coefficient of friction of hydrophilic coatings

Many medical devices often feature hydrophobic polymer surfaces, which can pose challenges during insertion into the human body, as they require significant force and can lead to friction- related injuries. Therefore, it's crucial to assess the coefficient of friction of the hydrophilic-coated medical devices developed to address these friction-related issues. We determined the coefficient of friction for uncoated, hydrophilic-coated, and commercially available (positive control) coated surfaces of silicone and latex Foley catheters, with slight modifications to a previously reported method (Ramesh et al., 2001). We used uncoated silicone and latex Foley catheters as a negative control and commercially available coated silicone and latex Foley catheters as a positive control. To measure the static coefficient of friction against a glass surface in an aqueous medium, we designed an in-house setup attached to a universal testing machine, which utilized a glass plate. Each catheter sample was cut into two 12 cm long portions and affixed parallel to each other on a moving acrylic plate (12 cm x 5 cm, weighing 30 gm) using glue. This acrylic plate, with the catheter samples, was positioned above a glass plate (20 cm x 10 cm) and connected to a universal testing machine via a lightweight nylon filament over a pulley. We applied a 200 gm total weight to the acrylic plate, pulled it at a rate of 50 mm/min against a glass surface evenly sprayed with water, and recorded the force. The static coefficient of friction was then calculated using the force values obtained from the load versus displacement graph. Before testing each new sample, we thoroughly cleaned the glass surface with water and allowed it to air dry.

The purpose of measuring the coefficient of friction was to assess how effectively the hydrophilic coating on silicone and latex Foley catheters reduced friction compared to uncoated catheters when a force (load) was applied. For the silicone Foley catheters, the static coefficient of friction values were 0.5 for uncoated, 0.5 for commercially available positive control coated, and 0.2 for hydrophilic coated samples when a 200 gm load was applied (Fig. 8). Similarly, for the latex Foley catheters, the static coefficient of friction values were 0.45 for uncoated, 0.25 for commercially available positive control coated, and 0.2 for hydrophilic coated samples under the same 200 gm load (Fig.8). These results clearly show that the hydrophilic coated surfaces of silicone and latex Foley catheters have significantly less friction compared to the uncoated and commercially available positive control coated surfaces. The 2.5-fold reduction in the coefficient of friction for silicone Foley catheters and a 2.25-fold reduction for latex Foley catheters, when comparing the hydrophilic coated samples to the uncoated ones, confirms the successful transformation of hydrophobic surfaces into hydrophilic ones. Furthermore, the decrease in the coefficient of friction of the hydrophilic coated samples, compared to the commercially available positive control coated samples of silicone and latex Foley catheters, demonstrates the superiority of our hydrophilic coating composition over commercially available hydrophilic coatings.

Therefore, this innovation has the potential to improve patient compliance and benefit the medical field by facilitating the friction-free insertion of hydrophilic coated medical devices into the human body.

Example 11

Measurement of water contact angle on hydrophilic coatings

The purpose of measuring contact angles was to determine surface hydrophobicity or hydrophilicity. We performed water contact angle measurements on the surfaces of uncoated, commercially available positive control coated, and hydrophilic coated silicone and latex Foley catheter samples to assess their surface properties. For this, we gently applied 10 pl drops of distilled water onto the surfaces using a micropipette. After 20 sec of water drop application, we captured photographs of the water droplets on the surface of each sample. These images were later analyzed with ImageJ software to determine the water contact angle on the catheter's surface.

Table 3. Water contact angle values measured on the surfaces of uncoated, commercially available positive control coated, and hydrophilic coated silicone and latex Foley catheter samples using ImageJ software.

Samples tested Water contact angle values obtained (degree)

Uncoated (Plain) Positive control Hydrophilic coated

Silicone Foley 108.4 83.4 55.5 catheter

Latex Foley catheter 104.9 59.2 61

After 20 sec of applying water drops on the surfaces of uncoated, commercially available positive control coated, and hydrophilic coated silicone Foley catheters, we obtained water contact angle values of 108.4°, 83.4°, and 55.5°, respectively (Fig. 9a, 9b, 9c, and Table 3). Similarly, after 20 sec of applying water drops on the surfaces of uncoated, commercially available positive control coated, and hydrophilic coated latex Foley catheters, we obtained water contact angle values of 104.9°, 59.2°, and 61° (Fig. 9d, 9e, 9f, and Table 3). Substrate surfaces with water contact angles less than 90° are considered hydrophilic, while angles greater than 90° indicate hydrophobic surfaces (Latthe et al., 2014). Contact angles greater than 90° confirmed that the uncoated surfaces of the silicone and latex Foley catheters were hydrophobic. Conversely, contact angles less than 90° confirmed that the hydrophobic surfaces of the silicone and latex Foley catheters, when coated with the optimized hydrophilic coating composition developed in this invention, were successfully transformed into hydrophilic surfaces. The hydrophilic property of the hydrophilic coated latex Foley catheter was found to be equivalent to that of the commercially available positive control coated latex Foley catheter. Meanwhile, the hydrophilic property of the hydrophilic coated silicone Foley catheter was found to be superior to that of the commercially available positive control coated silicone Foley catheter. These outcomes confirm the successful transformation of hydrophobic catheter surfaces into hydrophilic catheter surfaces using the optimized hydrophilic coating composition developed in this invention.

Example 12

Water absorption within the hydrophilic coatings

We measured water absorption in the hydrophilic coatings by observing changes in water contact angles over different time intervals on the hydrophilic coated surfaces of silicone and latex Foley catheters. To do this, we gently placed 10 pl drops of distilled water onto the hydrophilic coated surfaces of silicone and latex Foley catheters using a micropipette. After intervals of 0, 5, 10, 15, 20, 25, and 30 sec following water drop application, we captured photographs of the water droplets on the surface of each sample. These images were later analyzed with ImageJ software to determine the water contact angle on the catheter's surface.

We conducted water absorption analysis on the hydrophilic coatings to assess their capacity to absorb and maintain water, thus providing a long-lasting hydrophilic property when exposed to water. As depicted in Fig. 10a, the hydrophilic coated surface of the silicone Foley catheter showed a decrease in water contact angle values from 106.2° to 47.8° and an increase in absorbed water droplet volume over the 30 sec period. Similarly, the hydrophilic coated surface of the latex Foley catheter exhibited a decrease in water contact angle values from 86.5° to 42.9° and an increase in absorbed water droplet volume during the same time frame (Fig. 10b). These findings align with previous research indicating that as the measured contact angle decreases, the absorbed water droplet volume increases (Krainer et al., 2021). The increased absorbed water droplet volume, coupled with decreased contact angle values over the tested time points, confirms the ability of hydrophilic coatings to absorb and retain water, ensuring a long-term hydrophilic property upon contact with water.

Example 13

Long-term hydrophilic property

Given the potential for long-term use of silicone and latex Foley catheters in assisting urination, and considering the issues related to catheter-associated frictional injuries and infections, it is essential to assess the long-term hydrophilic performance of the coatings on these catheters. To do this, we immersed the hydrophilic-coated silicone and latex Foley catheters in artificial urine and incubated them at 100 rpm for 20 days at 37 °C. After the 20 days of incubation period, we removed the samples from the artificial urine and dried them at 60 °C for 1 h. Once the samples were dry, we measured the contact angles on the hydrophilic-coated surfaces of both the unprocessed samples (those not incubated in artificial urine) and the processed samples (incubated for 20 days in artificial urine). This was done by gently placing 10 pl drops of distilled water on the hydrophilic-coated surfaces of the processed and unprocessed samples of catheters using a micropipette. After waiting for 20 sec, we captured photographs of the water droplets on the surface of each sample. These images were later analyzed with ImageJ software to determine the water contact angle on the catheter's surface. By comparing the contact angle values obtained for the processed samples with those of the unprocessed samples, we assessed whether the surface properties had changed due to prolonged contact with artificial urine.

Table 4. Water contact angle values measured on the hydrophilic coated surfaces of silicone and latex Foley catheters after 0 days and 20 days of incubation in artificial urine using ImageJ software.

Hydrophilic coated Water contact angle values obtained (degree) samples .

After 0 day of incubation After 20 days of incubation in artificial urine in artificial urine

Silicone Foley catheter 55.5 68.3

Latex Foley catheter 61 65.4

We assessed the long-term hydrophilic capability of the hydrophilic coated surfaces on silicone and latex Foley catheters to see how effectively they maintain their hydrophilic properties after extended exposure to artificial urine, aiming to prevent catheter-related frictional injuries and infections. In Fig. 11, after 20 sec of applying water drops to both the unprocessed (0-day incubation in artificial urine) and processed (20-day incubation in artificial urine) hydrophilic surfaces of silicone Foley catheters, we obtained water contact angle values of 55.5° and 68.3°, respectively (Fig. I la, 11b and Table 4). Similarly, after 20 sec of applying water drops to the unprocessed and processed hydrophilic surfaces of latex Foley catheters, we obtained water contact angle values of 61° and 65.4°, respectively (Fig. 11c, l id and Table 4). Substrate surfaces with water contact angles less than 90° are considered hydrophilic, while angles greater than 90° indicate hydrophobic surfaces (Latthe et al., 2014). The contact angle values for both the processed and unprocessed samples of silicone and latex Foley catheters were less than 90°. These results confirm that the hydrophilic coated surfaces of these catheters maintained their hydrophilic properties even after prolonged exposure to artificial urine. This long-lasting hydrophilic property can be attributed to the effective bonding between the cross-linked polyurethane network and the catheter surfaces, securely holding the hydrophilic polymer (PVP K90) in place and enabling its swelling upon contact with water for long-term hydrophilic effectiveness.

Therefore, the results discussed in examples 11, 12, 13 and 14 collectively validate the successful transformation of the hydrophobic surfaces of silicone and latex Foley catheters into long-lasting hydrophilic surfaces using an optimized hydrophilic coating formula developed in this invention.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig 1 shows Scanning electron microscopic (SEM) images of surfaces of silicone Foley catheter.

Fig 2 shows Scanning electron microscopic (SEM) images of surfaces of latex Foley catheter.

Fig 3 shows Scanning electron microscopic (SEM) images showing thickness of coating layer of various portions of Silicone Catheter.

Fig 4 shows Scanning electron microscopic (SEM) images showing thickness of coating layer of various portions of Latex Catheter.

Fig 5 shows Images displaying contact angles (CA) of water droplet on the coated surface of different portions.

Fig 6 shows Optical microscopic images of the hydrophilic coatings on the surfaces of silicone (a) and latex (b) Foley catheters after turning and twisting.

Fig 7 shows FT-IR spectra of plain polyurethane dispersion (a), plain ethylenediamine (Yang et al., 2017) (b), physical mixture (c) and cured hydrophilic coating film (d).

Fig 8 shows static coefficient of friction values for the uncoated, hydrophilic coated and commercially available positive control coated surfaces of silicone and latex Foley catheters.

Fig 9 are images showing water droplet contact angles (CA) on various sample surfaces.

Fig 10 shows the graphs displaying the reduction in contact angle (CA).

Fig 11 shows the images of water contact angles (CA) on the surfaces of catheters after dipping in artificial urine.

DETAILED DESCRIPTION OF DRAWINGS

Figure 1 further explains SEM images of the uncoated (Fig. la), coated silicone Foley catheter (Fig. lb) that shows a continuous, uniform, and porous hydrophilic coating without any uncovered areas. The pore sizes in this film ranges from 0.2 to 1.1 pm (Fig. lb). The images also clearly reveal the boundary between the coated and uncoated sections of the silicone Foley catheter (Fig. 1c). Figure 2 further describes SEM images of the uncoated (Fig. 2a), coated latex Foley catheter (Fig. 2b) that shows a continuous and uniform hydrophilic coating layer with no uncovered areas. However, the coating on the latex surface was found to be non-porous compared to the silicone catheter (Fig. 2b). SEM analysis also clearly distinguishes between the coated and uncoated sections of the latex Foley catheter (Fig. 2c).

Figure 3 and Figure 4 describes SEM images in Fig. 3 and Fig. 4 confirmed that there are continuous and uniform hydrophilic coating films along the periphery of both silicone (Fig. 3a) and latex (Fig. 4a) Foley catheters. We also examined the uniformity of the coating towards the upper and lower portions of the catheters. For silicone Foley catheters, the thickness of the coating film was consistent, measuring around 4 pm (Fig. 3b and 3c). Similarly, for latex Foley catheters, the coating film had a consistent thickness in the range of 5-6 pm (Fig. 4b and 4c).

Figure 5 further explains the contact angle values of 59.4° on the upper portion, 55.5° on the middle portion, and 56.4° on the lower portion (Fig. 5a, 5b, 5c). These similar water contact angle values across all three portions indicate that the hydrophilic polymer (PVP K90) was evenly distributed throughout the length of the silicone catheter due to the uniform coating film formation. Similarly, after 20 sec of applying water drops on the coated latex catheter, we observed contact angle values of 65.9° on the upper portion, 61° on the middle portion, and 58.7° on the lower portion (Fig. 5d, 5e, 5f)

Figure 6 explains the Foley catheters were turned and twisted and then observed under an optical microscope to look for any signs of microcracking or the removal of coating films. The optical microscope images confirms that there were no microcracks or removal of coated film on the surfaces of the silicone (Fig. 6a) and latex (Fig. 6b) Foley catheters.

Figure 7 explains the FT-IR spectrum of the plain polyurethane dispersion displayed a carbonyl stretching peak from the pendant carboxylic group at 1725 cm'¹ (Fig. 7a). In contrast, the FT-IR spectrum of plain ethylenediamine exhibited absorption peaks at 3352 and 3276 cm ¹, corresponding to the asymmetric and symmetric stretching of NH2 groups, respectively (Fig. 7b). The FT-IR spectrum of the physical mixture of polyurethane dispersion, ethylenediamine, PVP K90, and glycerol showed combined peaks at 1725 cm'¹ (carbonyl stretching of the pendant carboxylic group from polyurethane dispersion) and 3356 cm'¹ (asymmetric stretching of NH2 groups) and 3293 cm'¹ (symmetric stretching of NH2 groups) from ethylenediamine (Fig. 7c). Nevertheless, in the FT-IR spectrum of the cured hydrophilic coating film (Fig. 7d), a notable absorption peak at 1725 cm'¹ was observed, while there were no absorption peaks at 3356 and 3293 cm ¹. This suggests that the NH2 groups of ethylenediamine formed ionic bonds with the pendant carboxylic groups of polyurethane, resulting in the creation of carboxylate (COO ) ions and ammonium (NH3⁺) ions through ion-pairing.

Figure 8 explains the static coefficient of friction values of the silicone Foley catheters were 0.5 for uncoated, 0.5 for commercially available positive control coated, and 0.2 for hydrophilic coated samples when a 200 gm load was applied (Fig. 8). Similarly, for the latex Foley catheters, the static coefficient of friction values were 0.45 for uncoated, 0.25 for commercially available positive control coated, and 0.2 for hydrophilic coated samples under the same 200 gm load (Fig.8).

Figure 9 explains the water contact angle values of uncoated, commercially available positive control coated, and hydrophilic coated silicone Foley catheters After 20 sec of applying water drops on the surfaces, the water contact angle values observed were 108.4°, 83.4°, and 55.5°, respectively (Fig. 9a, 9b, 9c). Similarly, after 20 sec of applying water drops on the surfaces of uncoated, commercially available positive control coated, and hydrophilic coated latex Foley catheters, water contact angle values observed were of 104.9°, 59.2°, and 61° respectively (Fig. 9d, 9e, 9f)

Figure 10 explains the hydrophilic coated surface of the silicone Foley catheter showed a decrease in water contact angle values from 106.2° to 47.8° and an increase in absorbed water droplet volume over the 30 sec period (Fig.10a) Similarly, the hydrophilic coated surface of the latex Foley catheter exhibited a decrease in water contact angle values from 86.5° to 42.9° and an increase in absorbed water droplet volume over 30 sec time frame (Fig. 10b).

Figure 11 explains after 20 sec of applying water drops to both the unprocessed (0-day incubation in artificial urine) and processed (20-day incubation in artificial urine) hydrophilic surfaces of silicone Foley catheters, we obtained water contact angle values of 55.5° and 68.3°, respectively (Fig. 1 la, 1 lb). Similarly, after 20 sec of applying water drops to the unprocessed and processed hydrophilic surfaces of latex Foley catheters, we obtained water contact angle values of 61° and 65.4°, respectively (Fig. 11c, l id) ADVANTAGES OF THE PRESENT INVENTION The developed composition makes the self-lubricating (hydrophilic) surfaces of medical devices for prevention of device-associated frictional injuries and infections. This further results in to no pain due to injuries, improved patient compliance, improved quality of life, no additional hospital stays and no extra financial burden on patients. Apart from this, the appropriate combination and quantities of the selected components in the hydrophilic coating composition provides the uniform, long-lasting and highly functional lubricious coatings on various medical devices. The hydrophilic coating composition of the present invention is suitable for any type of coating method and does not involve any harsh conditions in the curing process. The hydrophilic coating composition of the present invention has long pot life and therefore can be utilized up to 1 month for effective hydrophilic coating on medical devices.

Claims

We Claim,

1. Hydrophilic coating compositions and formulations thereof wherein the compositions comprise: a. Polyurethane as a supporting polymer, b. Ethylenediamine as a cross linker, c. An alcohol-water mixture as a solvent wherein alcohol is selected from ethanol, methanol; and d. A mixture of a hydrophilic polymer, a humectant or wetting agent and distilled water wherein, said hydrophilic polymer is polyvinylpyrrolidone (K90) and said humectant or wetting agent is glycerol.

2. Hydrophilic coating compositions and formulations thereof as claimed in claim 1, wherein, said polyurethane with no -NCO terminal and said ethylenediamine as a cross-linker forms an optimized polyurethane network through ion-pairing to create hydrophilic coatings.

3. Hydrophilic coating compositions and formulations thereof as claimed in claim 1, wherein, the hydrophilic coating formulation of said composition comprises polyurethane concentration in the range of 5.6 % v/v to 12.32% v/v, specifically at 5.6 % v/v.

4. Hydrophilic coating compositions and formulations thereof as claimed in claim 1 , wherein, the hydrophilic coating formulation of said composition comprises ethylenediamine concentration in the range of 8.4 % v/v to 32.85 % v/v, specifically at 8.4 % v/v.

5. Hydrophilic coating compositions and formulations thereof as claimed in claim 1, wherein, the hydrophilic coating formulation of said composition comprises an alcohol-water mixture concentration in the range of 58.714 % v/v to 83.714 % v/v, specifically at 63.6 % v/v.

6. Hydrophilic coating compositions and formulations thereof as claimed in claim 1 , wherein, the hydrophilic coating formulation of said composition comprises of a said mixture of Polyvinylpyrrolidone (K90), glycerol and distilled water concentration in the range of 20.52 % v/v to 25.08 % v/v, specifically at 22.8 % v/v.

7. Hydrophilic coating compositions and formulations thereof as claimed in claim 1 , wherein the thickness of the coating achieved with the said formulation is in the range 3pm to 7 pm.