Metastable polymer compositions for ophthalmic implant injection devices

Abstract

The invention relates to metastable polymer compositions, use thereof for manufacturing medical devices or medical device components having a slippery surface as well as the devices with slippery surfaces resulting from these metastable polymer compositions, in particular in the field of ophthalmic injectors.

Claims

1. A metastable polymer composition consisting of a mixture of one constituent polymer and one functional copolymer, in which said constituent polymer is a thermoplastic polymer having a glass transition temperature (Tg) or a melting temperature (Tm) above or equal to 80 C., and is present in the mixture in a mass proportion comprised between 85% and 99.9%, and said functional copolymer has a glass transition temperature (Tg) or a melting temperature (Tm) above or equal to 40 C., comprises at least 60% by mass of monomer units with a hydrophilic character, and hydrophobic sequences or blocks, wherein said hydrophobic sequences or blocks are miscible with the constituent polymer and has a molecular weight greater that 5000 g/mole, wherein the molecular weight is expressed in average number.

2. The composition of claim 1, wherein the constituent polymer provides the material prepared from said mixture with mechanical properties and the functional copolymer provides said material with a character of slipperiness.

3. The composition of claim 1, wherein the constituent polymer is chosen from the polyolefins.

4. The composition of claim 1, wherein the functional copolymer has a glass transition temperature (Tg) below the Tg value of the constituent polymer or a melting temperature (Tm) below the Tm value of the constituent polymer.

5. The composition of claim 1, wherein the functional copolymer comprises between 60 and 99% by mass of hydrophilic monomer units.

6. The composition of claim 1, wherein the functional copolymer is chosen from random copolymers, block copolymers, comb copolymers and star copolymers.

7. The composition of claim 1, wherein the functional copolymer is chosen from the polyethers, polyesters and polyurethanes, wherein each of the polyethers, polyesters and polyurethanes have both hydrophilic and hydrophobic sequences or blocks, and copolymers based on (meth)acrylic acid, ethylene oxide, acrylamide, vinyl alcohol, vinyl pyrrolidone or hydroxyethyl(meth)acrylate combined with hydrophobic units partially miscible or compatible with the constituent polymer.

8. The composition of claim 1, wherein the functional copolymer moreover comprises reactive groups capable of reacting in the presence of free radicals in order to generate covalent bonds between the chains of the functional copolymer and the chains of the constituent polymer.

9. The composition of claim 1, wherein the composition is in a non-changing morphological state, at temperatures below the Tg/Tm of the different polymer components of the mixture and in that the composition is capable of changing towards a different multiphase morphological state at temperatures above the Tg/Tm of the polymer constituents.

10. A material prepared from a metastable composition according to claim 1.

11. A medical device part comprising a metastable composition according to claim 1, which forms all or part of an ophthalmic implant injection device.

12. An ophthalmic implant injection device comprising at least one part prepared from a metastable composition according to claim 1.

13. Method for manufacturing a material, a medical device part or a medical device, comprising: introducing a mixture of at least one constituent polymer and at least one partially miscible or compatible functional copolymer as defined in claim 1 in an extruder; recovering a metastable polymer composition as defined in claim 1; processing the metastable polymer composition by injection molding; and recovering a medical device part or a medical device formed from the metastable polymer composition.

14. The method of claim 13, wherein said medical device is an ophthalmic implant injection device.

Description

EXAMPLE 1

(1) Preparation of a Polyurethane Urea Based on Poly(Ethylene Oxide-b-Propylene Oxide-b-Ethylene Oxide) (PEO-PPO-PEO) Tribiock Copolymers Terminated by Acid Units

(2) The synthesis is carried out in two steps. In a first step, 3.8.Math.10.sup.3 mole of F127 Pluronic polymer, not dried, containing 0.3% by mass of water is dissolved in 150 ml of 2-butanone. Then 1.5.Math.10.sup.2 mole of 4,4-methylene biscyclohexyl di-isocyanate is added dropwise over 10 minutes under a continuous flow of nitrogen. When approximately 81% of the isocyanate functions have been consumed (monitored by Fourier transform infrared spectroscopy), 2.9.Math.10.sup.3 mole of 2,2-bis(hydroxymethyl) butyric acid is added. Polycondensation continues for 2 hours at 70 C. until the isocyanate functions have completely disappeared. The copolymer is collected by precipitation from diethyl ether and dried under vacuum at ambient temperature.

(3) The copolymer has a melting temperature of 52 C. Analysis by steric exclusion chromatography (SEC) indicates the presence of chains of copolymers with molar masses greater than 10,000 g/mol (polystyrene calibration).

EXAMPLE 2

(4) Preparation of a Polyurethane Urea Based on Copolymer PEO-PPO-PEO Terminated at its Ends by PEO Chains

(5) 7.69.Math.10.sup.3 mole of Pluronic F127 is dried under vacuum at 80 C. over 2 hours then solubilized in 300 ml of 2-butanone containing 0.2 g of water. 15.84.Math.10.sup.3 mole of 4,4 methylene biscyclohexyl di-isocyanate is then added dropwise over 10 minutes under a continuous flow of nitrogen. 500 ppm of a tin-based catalyst are introduced after 30 minutes following the addition of isocyanate. 13.98.Math.10.sup.3 mole of a monohydroxylated poly(ethylene oxide) with a molar mass equal to 600 g/mol is introduced when 58% of the isocyanate functions have disappeared (monitored by Fourier transform infrared spectroscopy). The reaction is continued until the isocyanate functions have completely disappeared and can take up to 12 hours. The copolymer is then precipitated from a non-solvent (petroleum ether) then dried under vacuum at 40 C.

(6) The copolymer has a melting temperature of 52 C. SEC analysis (polystyrene calibration) indicates the presence of chains of copolymers with molar masses greater than 10,000 g/mol.

EXAMPLE 3

(7) Preparation of a Copolyurethane Based on Poly(Ethylene Oxide) and Poly(-Caprolactone)

(8) 400 g of a dihydroxytelechelic PEO with a molar mass of 6000 g/mol (6.67.Math.10.sup.2 mole) and 100 g of a dihydroxytelechelic poly(-caprolactone) (PCL) (8.Math.10.sup.2 mole) with a molar mass of 1,250 g/mol, are dried under vacuum for 2 hours at 100 C. then solubilized in 1.45 liters of 2-butanone previously dried over CaCl.sub.2. The solution is cooled down to 85 C. during the introduction of 38.43 g (14.67.Math.10.sup.2 mole) of Desmodur W di-isocyanate marketed by Bayer. 0.5 g of a bismuth-based catalyst is added 5 minutes after completion of the introduction of the isocyanate.

(9) The reaction is terminated after 19 hours by the addition of 1 ml of ethanol. The solution is then cooled down to ambient temperature then diluted in 1.5 liters of acetone then precipitated from 8 liters of heptane.

(10) The molar mass by number of the polymer obtained (PS equivalent) 25000 g/mol. The multiblock-type copolymer has a block melting temperature ranging from 40 to 53 C.

EXAMPLE 4

(11) Preparation of a Poly(Methylmethacrylate-Co-Polyethyleneoxide Methacrylate) Random Copolymer

(12) 200 g of polyethylene glycol methacrylate (MAPEG with a molar mass of 1100 g/mol) are solubilized in 800 ml of 2-butanone at ambient temperature over 1 hour 30 minutes. 1.6 g of 2,2-azobis 2-methylbutane nitrile (radical initiator) is added to the medium which is then heated to 100 C. just before the addition of 20 g of methyl methacrylate (MMA). The reaction medium is left at 100 C. for 4 hours, then precipitated from heptane and dried under vacuum at 40 C. The molar mass by number (PS equivalent) of the polymer obtained is 31000 g/mol. It exhibits in particular a Tm of approximately 50 C. of the ethylene polyoxide blocks.

EXAMPLE 5

(13) Preparation of a Poly(Vinylpyrrolidone-Co-2-Hydroxyethylmethacrylate-Co-Polyester Methacrylate) Random Copolymer

(14) a) Synthesis of Polyester Methacrylate (FTL11228)

(15) 200 g of -caprolactone, 67.66 g of 2-hydroxyethyl methacrylate and 0.759 g of a tin-based catalyst are solubilized in 216 ml of distilled anhydrous toluene. The system is heated at 90 C. for 18 hours. The recovered macromonomer, characterized by proton NMR, has a molar mass of 562 g/mol.

(16) b) Synthesis of the Poly(Vinylpyrrolidone-Co-2-Hydroxyethylmethacrylate-Co-Polyester Methacrylate) Random Copolymer 166.53 g of 2-hydroxyethyl methacrylate, 7.24 g of FTL 11228 polyester methacrylate and 1.18 liters of technical-grade ethanol are introduced into a reactor equipped with a condenser with a bubbler under a light flow of nitrogen. This first mixture is called a starter. 2A second mixture is prepared alongside, constituted by 59.69 g of 1-vinyl 2-pyrrolidone, 28.96 g of FTL 11228 polyester methacrylate, 216 g of 2-hydroxyethyl methacrylate, 19.29 g of dodecanethiol, 5.79 g of AIBN and 415 ml of technical grade ethanol. This mixture No. 2 is left under stirring until solubilized. 3Mixture No, 2 is poured dropwise over 60 minutes onto the starter taken to reflux. 4The mixture is left under reflux under a light flow of nitrogen for 3 hours 30 minutes as from the end of pouring. 5The final medium is left to cool down, reconcentrated, precipitated from water and lyophilized.
The copolymer obtained has a Tg of 63 C.
The molar masses determined by Size Exclusion Chromatography (solvent DMF/LiBr-Column DMFext-PS calibration) of the copolymer are Mw=22,000 g/mol; Mp=21,420 g/mol; Mn=13,900 g/mol; and the polydispersity index is 1.6.

EXAMPLE 6

(17) Preparation of a Polyurethane Copolymer Based on PEO and PCL Terminated by Acrylate Units at Both its' Ends

(18) 400 g of a dihydrotelechelic PEO with a molar mass=6000 g/mol (6.67.Math.10.sup.2 mole) and 100 g of a dihydroxytelechelic poly(-caprolactone) (PCL) (8.Math.10.sup.2 mole) with a molar mass of 1250 g/mol are dried under vacuum for 2 hours at 100 C. then solubilized in 1.45 l of dried 2-butanone. 34 g of Desmodur W (di-isocyanate) and 0.5 g of a bismuth-based catalyst are added to the reaction medium which is heated to 85 C.

(19) After complete consumption of the isocyanates, the reaction medium is cooled down and 2 g of acryloyl chloride is added to the reaction medium. The reaction is stopped 2 hours after the addition of the acryloyl chloride. The polymer is then precipitated from ether. Analysis by Fourier transform infrared spectroscopy (FTIR) shows the presence of unsaturations on the polymer chains. The multiblock-type copolymer has a block melting temperature ranging from 40 to 53 C.

EXAMPLE 7

(20) Preparation of a Polyvinylpyrrolidone-Co-2-Hydroxyethylmethacrylate-Co-Polyester Methacrylate) Random Copolymer Bearing Pendant Acrylate Groups

(21) 100 g of copolymer of Example 6 is solubilized in 500 ml of dry THF, 2 g of acryloyl chloride is added to the solution at ambient temperature. After 4 hours, the reaction is stopped and the copolymer precipitated from heptane. FTIR analysis shows the presence of acrylic-type unsaturations on the copolymer chains.

EXAMPLE 8

(22) A reference polypropylene PPR 10222 marketed by TOTAL is mixed (or compounded) with the copolymer described in Example 2 under the following conditions: Twin-screw extruder 26 mm L=50 D Flow rate: 10 kg/h Screw speed: 300 rpm Temperature profile: (base) 210-210-200-190-180-170-170-160-160-160 (die): programmed in this way because of the very great fluidity of the compound obtained. The temperature is lowered in the die to approximately the melting temperature of the PP. Each temperature block is 5 D in length.

(23) The 2 polymer components are mixed and introduced via a gravimetric doser into the base of the extruder. The copolymer of Example 2 is mixed with the polypropylene PPR 10222 in percentages of 1, 2, 5 and 10%. The different metastable compositions obtained (compounds) are recovered at the extruder exit in the form of granules and stored at ambient temperature.

(24) The different metastable compositions obtained are then processed by injection/moulding in order to manufacture cartridges/tips of ophthalmic implant injectors with an outlet diameter of 2 mm.

(25) The slipperiness properties were evaluated on the injectors corresponding to regular intervals over 2 months after their date of manufacture. The tests were carried out with 27 D diopter hydrophilic implants made from hydroxyethylmethacrylate (HEMA) (water content 28%) after the addition of an aqueous solution of hyaluronate (0.1 to 0.2 ml, HA at 2.1%). Comparative tests were carried out under the same conditions on cartridges/tips made of polypropylene (PPR10222) compounded with glycerol monostearate (GMS).

(26) The slippery character was determined from the compression force needed for injecting the implant through the 2 mm exit diameter. These measurements were carried out with an Intron 3367-type dynamometer equipped with a 0.5 kN sensor, at a compression speed of 8.5 mm/s. The results are classified as a function of force in three categories: low, moderate, high. The results are shown in Table 1 below.

(27) TABLE-US-00001 TABLE 1 Test carried out Test carried out Test carried out Test carried out Test carried out Nature of the 1 day after the 7 days after the 15 days after the 1 month after the 2 months after the No. cartridge/tip processing step* processing step* processing step* processing step* processing step* 1.1 PP + GMS Low slipperiness Moderate High slipperiness. High slipperiness. High slipperiness. slipperiness Presence of white Presence of white A lot of white traces. traces. traces. 1.2 PP + 1% of the Moderate Moderate Moderate Moderate Moderate copolymer of slipperiness slipperiness slipperiness slipperiness slipperiness Example 2 1.3 PP + 2% of the High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 2 1.4 PP + 5% of the High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 2 1.5 PP + 10% of High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness the copolymer of Example 2 *Each test is carried out 3 times in order to validate the result obtained Low slipperiness: possibly leading to significant degradation of the implants (Applied force > 10N) Moderate slipperiness: requiring a high force for the injection with the risk of alteration of the implants (5N < Applied force < 10N) High slipperiness: allowing easy injection without risk of alteration of the implants (1N < Applied force < 5N)

(28) The results show that the tips manufactured from the metastable composition (polypropylene (PP)+copolymer of Example 2) exhibit properties of slipperiness which are constant over time, which is not the case with the tips containing GMS. This slipperiness is high for metastable compositions containing more than 1% of the copolymer of Example 2. The Ups containing 5 and 10% functional copolymer are more opaque than their homologues containing 1 and 2% of the copolymer of Example 2.

(29) For all the cartridges/tips prepared from metastable compositions (PP+polymer of Example 2), no traces are observed on the implant after injection.

EXAMPLE 9

(30) The same cartridges/tips are used for injection tests with a 25 D diopter flexible hydrophobic implant.

(31) The results are shown in Table 2 below.

(32) TABLE-US-00002 TABLE 2 Test carried out Test carried out Test carried out Test carried out Test carried out Nature of the 1 day after the 7 days after the 15 days after the 1 month after the 2 months after the No. cartridge/tip processing step * processing step * processing step * processing step * processing step * 2.1 PP + GMS Low slipperiness Low to moderate Moderate to high High slipperiness High slipperiness slipperiness slipperiness Presence of traces A lot of traces Presence of traces 2.2 PP + 1% of the High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 2 2.3 PP + 2% of the High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 2 2.4 PP + 5% of the High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 2 2.5 PP + 10% of the High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 2 * Each test is carried out 3 times in order to validate the result obtained. Low slipperiness: possibly leading to significant degradation of the implants (Applied force > 10N) Moderate slipperiness: requiring a high force for the injection with the risk of alteration of the implants (5N < Applied force < 10N) High slipperiness: allowing easy injection without risk of alteration of the implants (1N < Applied force < 5N)
The results show that the tips/cartridges prepared in the presence of the copolymer of Example 2 exhibit the same properties of slipperiness with the hydrophilic implants as with the hydrophobic implants.

EXAMPLE 10

(33) A commercial reference polypropylene, PPR 10222, from Total is mixed (compounded) with the copolymer of Example 3 introduced in percentages of 1, 2 and 5% under the following conditions: Twin-screw extruder 026 mm L=50 D Flow rate: 10 kg/h Screw speed: 300 rpm Temperature profile: (base) 210-210-200-190-180-170-170-160-160-160 (die): programmed in this way because of the very great fluidity of the compound obtained. The temperature is reduced in the die to approximately the melting temperature of the PP. Each temperature block is 5 D in length.

(34) The 2 polymer components are mixed and introduced via a gravimetric dower into the base of the extruder. The different metastable compositions obtained (compounds) are recovered at the extruder exit in the form of granules and stored at ambient temperature.

(35) The different metastable compositions obtained are then processed by injection moulding in order to manufacture cartridges/tips of ophthalmic implant injectors with an outlet diameter of 2 mm. No problem with removal from the mould is noted during the processing step.

(36) The slipperiness measurements were evaluated on the injectors at regular intervals over 2 months after their date of manufacture. All the injection tests were carried out with 28 D diopter HEMA hydrophilic implants (28% water content) after the addition of a viscous agent, hyaluronic acid. Two reference cartridges/tips made from PP were used as a comparison. The first contains 025% GMS, the second, following plasma treatment, is coated with a hydrophilic polymer.

(37) The results are shown in Table 3 below. The cartridges/tips manufactured in one step from metastable compositions of PP+copolymer of Example 3 exhibit properties of slipperiness comparable to those of the cartridges/tips treated with plasma then coated with a hydrophilic polymer

(38) TABLE-US-00003 TABLE 3 Test carried out Test carried out Test carried out Test carried out Test carried out Nature of the 1 day after the 7 days after the 15 days after the 1 month after the 2 months after the No. cartridge/tips processing step * processing step * processing step * processing step * processing step * 3.1 PP + GMS Low slipperiness Low to moderate Moderate to high High slipperiness High slipperiness slipperiness slipperiness Presence of A lot of traces traces 3.2 PP + hydrophilic High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness coating 3.3 PP + 1% of the High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 3 3.4 PP + 2% of the High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 3 3.5 PP + 5% of the High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 3 * Each test is carried out 3 times in order to validate the result obtained. Low slipperiness: possibly leading to significant degradation of the implants (Applied force > 10N) Moderate slipperiness: requiring a high force for the injection with the risk of alteration of the implants (5N < Applied force < 10N) High slipperiness: allowing easy injection without risk of alteration of the implants (1N < Applied force < 5N)

(39) As regards the tips/cartridges prepared from the metastable compositions of PP+copolymer of Example 3, lubrication comparable to the coating route as well as the absence of any traces on the injected implants can be noted. The main advantage of this approach compared with the coating route is the great simplicity of making use of it.

EXAMPLE 11

(40) A PEBAX 7033-type polyimide from Arkema is mixed (compounded) with the copolymer of Example 3.

(41) The preparation of the metastable compositions is carried out according to the protocol of Example 8 using an injection temperature of 260 C.

(42) Similarly, the cartridges/tips produced from these metastable compositions are prepared according to the protocol of Example 8 using a mould temperature of 4550 C. The prepared tips also have an outlet diameter of 2 mm.

(43) As regards the properties of slipperiness, the implant injection tests were carried out with 27 D diopter hydrophilic implants made from HEMA (28% water content) after the addition of a viscous agent, hyaluronic acid.

(44) Two reference cartridges/tips, the first manufactured from the same PEBAX loaded with 0.25% by mass of GMS, the second constituted by a PEBAX cartridge/tip coated with a hydrophilic polymer were used in order to allow comparison with the existing systems.

(45) The results are shown in Table 4 below.

(46) TABLE-US-00004 TABLE 4 Test carried out Test carried out Test carried out Test carried out Test carried out Nature of the 1 day after the 7 days after the 15 days after the 1 month after the 2 months after the No. cartridge/tip processing step * processing step * processing step * processing step * processing step * 4.1 PA** + GMS Low slipperiness Low slipperiness Moderate High slipperiness High slipperiness slipperiness Presence of traces Presence of traces 4.2 PA + hydrophilic High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness coating 4.3 PA + 1% High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 3 4.4 PA + 2% High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 3 4.5 PA + 5% High slipperiness High slipperiness High slipperiness High slipperiness High slipperiness copolymer of Example 3 * Each test is carried out 3 times in order to validate the result obtained, **PA = polyamide Low slipperiness: possibly leading to significant degradation of the implants (Applied force > 10N) Moderate slipperiness: requiring a high force for the injection with the risk of alteration of the implants (5N < Applied force < 10N) High slipperiness: allowing easy injection without risk of alteration of the implants (1N < Applied force < 5N)
The results show that the injected implants using cartridges/tips manufactured from the metastable composition PP+copolymer of Example 3 slip perfectly and can easily be introduced through a 2 mm incision. The slipperiness which characterizes these cartridges/tips is in every way comparable to, or even better than that of the cartridges/tips coated with a hydrophilic polymer.

EXAMPLE 12

(47) The cartridges/tips described in Example 11 served to inject 26 D diopter hydrophobic flexible implants; the protocol used is similar to that described for the hydrophilic implants.

(48) The slipperiness is high for all the cartridges/tips manufactured from the metastable composition PA+copolymer of Example 3. The results are identical to those obtained with the hydrophilic implants.

EXAMPLE 13

(49) The polyurethane copolymer of Example 6 with a molar mass of 25500 g/mol having two acrylate ends was compounded with the polypropylene PPR 10222 in an extruder at 240 C. in order to prepare the corresponding metastable compositions according to the protocol of Example 8. The compositions are stored at ambient temperature.

(50) The utilization of the cartridge/tip is then carried out by injection/moulding of the corresponding metastable compositions in the presence of dicumyl peroxide (a radical initiator) at 220 C. The objective of the presence of the initiator is to allow the radical grafting of part of the functional copolymer chains by their acrylate ends to the polypropylene in order to create covalent bonds in the metastable composition. This makes it possible to have a hydrophilic surface which swells in the presence of water but does not solubilize. This characteristic makes it a device particularly suited to the systems using pre-loaded implants in a physiological liquid.

(51) In order to validate the chemical grafting, the cartridges/tips are rinsed 5 times with water and ethanol, the chains not covalently bonded thus being removed. Raman microscopy analysis of the surface of the cartridge/tip shows the presence of the copolymer after the different washes.

(52) The protocol adopted in order to characterize the properties of slipperiness is as follows: the polyhydroxyethylmethacrylate (PHEMA)-based hydrophilic implant is placed in the cartridge/tip then the physiological liquid is added and the pre-loaded device is stored at ambient temperature. Implant injection tests are then carried out at regular intervals, namely after one day, 7 days, 15 days, 30 days and 60 days of immersion. The results are summarized in Table 5 where they can be compared to those obtained with a commercially available cartridge/tip coated with a hydrophilic polymer.

(53) The implant injection tests are carried out with 27 D diopter implants and the outlet diameter of the cartridges/tips is 2 mm.

(54) The results are summarized in Table 5 below.

(55) TABLE-US-00005 TABLE 5 Test carried out Test carried out Test carried out Test carried out Test carried out Nature of the after 1 day of after 7 days of after 15 days of after 30 days of after 60 days of No. cartridge/tip immersion immersion immersion immersion immersion 6.1 PP + hydrophilic Low slipperiness No slipperiness No slipperiness No slipperiness No slipperiness coating 6.2 PP + 1% Moderate Moderate Moderate Moderate Moderate copolymer acrylate slipperiness slipperiness slipperiness slipperiness slipperiness of Example 6 6.3 PP + 2% Moderate High slipperiness High slipperiness High slipperiness High slipperiness copolymer acrylate slipperiness of Example 6 6.4 PP + 5% Moderate High slipperiness High slipperiness High slipperiness High slipperiness copolymer acrylate slipperiness of Example 6 *Each test is carried out 3 times in order to validate the result obtained. Low slipperiness: possibly leading to significant degradation of the implants (Applied force > 10N) Moderate slipperiness: requiring a high force for the injection with the risk of alteration of the implants (5N < Applied force < 10N) High slipperiness: allowing easy injection without risk of alteration of the implants (1N < Applied force < 5N)
The results show that the slipperiness is high for cartridges/tips prepared from a metastable composition containing at least 2% of the copolymer comprising acrylate groups of Example 6. Unlike the PP-based reference system coated with a hydrophilic polymer the devices obtained from the metastable compositions exhibit identical behaviour after 2 months still with high slipperiness properties indicating that the functional copolymer is not leached out, nor solubilized by the physiological liquid.