Methods of coating substrates to improve lubricity

Abstract

A method of preparing a lubricity coating on a substrate surface comprising providing a substrate having a surface, optionally rinsing, optionally, treating with an alkaline aqueous solution, treating with an oxidising agent, treating with a composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof, incubating, and optionally treating with a further composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof. Also disclosed are substrates comprising such a lubricity coating, and medical devices, such as medical injection devices, comprising such a lubricity coating.

Description

[0001] METHODS OF COATING SUBSTRATES TO IMPROVE LUBRICITY

[0002] FIELD OF THE INVENTION

[0003] The invention relates to methods of coating substrates to improve lubricity. Substrates comprising such a lubricity coating, and medical devices, such as medical injection devices, comprising such a lubricity coating.

[0004] BACKGROUND

[0005] Lubricity is an important consideration for any system where there is friction and / or wear between moving parts of that system. A particular example where lubricity is important are medical injection devices, these are widely used to deliver a drug composition to a patient by injection. Such medical injection devices comprise a sealing stopper in a gliding engagement within a container. Many different types of injection devices have been designed for administering drug compositions. These medical injection devices usually comprise a container, such as a barrel, intended to receive the drug composition and a plunger rod intended to move a stopper within the container so as to expel the drug composition therefrom at the time of injection. Examples of such medical injection devices include cartridges, pen injectors, syringes and the like.

[0006] An important consideration for medical injection devices is to ensure that the plunger can move at a constant speed and with a constant force when pressed into the container. Hence, the medical injection devices ideally have a low gliding force to move the stopper within the container and a lubricity layer may be used for this purpose.

[0007] Another consideration is the break loose force, i.e. the force required to initiate the movement of the plunger. Ideally, this break loose force is low, as a too high break loose force is known to cause problems like overdosing of the drug composition to be administered. This break loose force is particularly pertinent for prefilled medical injection devices, i.e. those filled with a drug composition prior to distribution to the end user.

[0008] Traditionally in glass syringes, silicon oil has been used as a lubricant to allow the plunger to slide in the barrel. However, silicon has been implicated in the precipitation of protein solutions of many medicines. Also, silicon oil is often non-uniform, resulting in failures of syringes. A major constraint is that some drug compositions are sensitive towards their environment and therefore there is a need to find an appropriate container capable of maintaining the integrity of the drugs. This is particularly important for prefilled medical injection devices where the drug compositions may be stored for a long time in injection devices.

[0009] WO 2022 / 144093 and WO2022 / 258713 both disclose coating methods that are suitable for medical devices. Coatings are disclosed that reduce protein aggregation and these coatings comprise a polysaccharide or synthetic derivative thereof.

[0010] US 9,545,360 discloses pharmaceutical packages made from a polymer material, and this polymer material is coated with a barrier coating that comprises SiOxwhere x is from 1.5 to 2.9, and over the barrier coating is a protective coating which contains a saccharide.

[0011] Some carbohydrate coatings, such as pectin-based films, a natural carbohydrate polymer, have been found to have excellent oxidative barrier properties and can decrease oxygen permeability, see Ngo TMP, et al., International Journal of Molecular Sciences, 2020 vol. 21 , page 2224. The ability of such polymeric materials to act as oxidative barriers can be relevant to applications for a range of polymeric materials, such as cyclic olefin polymers.

[0012] Materials such as glass, may provide a UV barrier which is a useful property in a number of applications, see Duarte, I., et al., Photodermatol Photoimmunol Photomed., 2009, vol. 25, pages 181-4.

[0013] There is a need for improved methods of coating substrates to improve lubricity. In addition, there is a need for medical injection devices with lubricity coatings that provide a low gliding force and / or break loose force. There is also a need to provide a lubricity coating that exhibits a good compatibility with sensitive drugs and that maintains the integrity of the drug composition and of the coating.

[0014] It is an aim of the present invention to address these needs.

[0015] SUMMARY

[0016] The present invention provides in a first aspect a method of preparing a lubricity coating on a substrate surface, the method comprising: a) providing a substrate having a surface; b) optionally, rinsing the substrate with one or more solvents; c) optionally, treating at least a portion of the substrate surface with an alkaline aqueous solution; d) treating at least a portion of the substrate surface with an oxidising agent; e) treating at least a portion of the substrate surface with a composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof; f) incubating the treated substrate with the composition for a predetermined time; and g) optionally, treating at least a portion of the substrate surface with a further composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof.

[0017] The present invention accordingly provides in a second aspect a coated substrate obtainable by coating at least one surface of a substrate with a lubricity coating according to a method of the first aspect.

[0018] In a third aspect, there is provided a method of reducing the lubricity of a substrate surface that comprises treating the substrate surface with a method according to the first aspect.

[0019] In a fourth aspect, there is provided a method of reducing the lubricity of a substrate that comprises a) providing a substrate having a surface; b) optionally, rinsing the substrate with one or more solvents; c) optionally, treating at least a portion of the substrate surface with an alkaline aqueous solution; d) treating at least a portion of the substrate surface with an oxidising agent; e) treating at least a portion of the substrate surface with a composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof; f) incubating the treated substrate with the composition for a predetermined time; and g) optionally, treating at least a portion of the substrate surface with a further composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof; wherein the composition, and the optional further composition, form a lubricity coating that reduces the lubricity of the surface.

[0020] In a fifth aspect, there is provided a method of reducing the lubricity of a substrate that comprises a) providing a substrate having a surface; b) rinsing the substrate with one or more solvents; c) optionally, treating at least a portion of the substrate surface with an alkaline aqueous solution; d) optionally, treating at least a portion of the substrate surface with an oxidising agent; e) optionally, treating at least a portion of the substrate surface with a composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof; f) optionally, incubating the treated substrate with the composition for a predetermined time; and g) optionally, treating at least a portion of the substrate surface with a further composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof; wherein the method reduces the lubricity of the surface.

[0021] In a sixth aspect, there is provided a substrate having a lubricity coating on at least one surface, wherein the lubricity coating directly contacts the surface of the substrate and the lubricity coating comprises one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof.

[0022] In a seventh aspect, there is provided a use of a coating layer to reduce the lubricity of a surface, wherein the coating layer directly contacts the surface of the substrate and the lubricity coating comprises one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof.

[0023] The present invention is particularly useful for medical devices. Thus, the present invention accordingly provides in a further aspect a medical device comprising a substrate surface at least partially covered by a lubricity coating according to the second or sixth aspect.

[0024] In a further aspect, the present invention provides a medical injection device comprising a barrel and a stopper in gliding engagement within the barrel, wherein the inner surface of the barrel is a substrate surface at least partially covered by a lubricity coating according to the second aspect.

[0025] Substrate

[0026] Generally, any suitable substrate may be used in the method. Suitably the substrate comprises glass, quartz or one or more polymers.

[0027] Suitably, the substrate is glass. More suitably, the substrate is silica lime glass or borosilicate glass. More suitably, the substrate is borosilicate glass.

[0028] Suitably, the substrate is quartz.

[0029] Suitably, the substrate may comprise one or more polymers (e.g. EVA, polyolefin (for example polyethylene or polypropylene), a polyester (for example polyethylene terephthalate), a polycarbonate, or any combination or copolymer of any of these) may be used in the method, but preferably the substrate may comprise a cyclic olefin polymer or co-polymer. The polymer (for example the cyclic olefin polymer) may comprise, at least partially, recycled polymer.

[0030] Cyclic olefin polymers are useful as high temperature polymers with outstanding optical properties, good chemical and heat resistance, and excellent dimensional stability. The COP may be produced from cyclic olefin monomers such as norbornene, cyclopentadiene (CPD), and / or dicyclopentadiene (DCPD).

[0031] Step b)

[0032] Suitably, in some aspects, the method comprises step b) rinsing the substrate with one or more solvents.

[0033] Suitably, in alternative aspects, the method excludes step b).

[0034] Suitably the one or more solvents are a polar aprotic solvent, a polar protic solvent, or water. Suitably, step b) comprises separately rinsing with each of a polar aprotic solvent, a polar protic solvent, and water. The rinsing of the separate solvents may be carried out in any order.

[0035] More suitably when the substrate is glass, step b) comprises separately rinsing in sequence with a polar aprotic solvent, then a polar protic solvent, and then water. Suitably, the rinsing with water comprises two rinses with water.

[0036] Suitably, the polar aprotic solvent is dichloromethane, tetrahydrofuran, ethyl acetate, acetonitrile, dimethylsulfoxide, acetone, or mixtures thereof. More suitable the polar aprotic solvent is acetone.

[0037] Suitably, the polar protic solvent is methanol, ethanol, isopropyl alcohol, acetic acid, or mixtures thereof. More suitable the polar protic solvent is isopropyl alcohol.

[0038] Suitably, when the substrate comprises one or more polymers, step b) comprises rinsing with water. Suitably, the rinsing with water comprises three rinses with water.

[0039] Suitably, the water is deionized, distilled or ultrapure water. Step c)

[0040] Suitably, in some aspects, the method comprises step c) treating at least a portion of the substrate surface with an alkaline aqueous solution.

[0041] Suitably, when the substrate is glass, the method comprises step c) treating at least a portion of the substrate surface with an alkaline aqueous solution.

[0042] Suitably, the alkaline aqueous solution has a pH 7 to 14, optionally a pH 9 to 14, a pH 10 to14. Suitably, the treatment with an alkaline aqueous solution is carried out at a temperature in the range 40°C to 70 °C. Suitably, the treatment with an alkaline aqueous solution is carried out for from 1 min to 120 min, 1 min to 60 min, 1 min to 30 min, 1 min to 20 min, or 10 min to 20 min.

[0043] More suitably, the alkaline aqueous solution is an aqueous sodium hydroxide solution.

[0044] Suitably, step c) further comprises rinsing with water following the treatment with an alkaline aqueous solution.

[0045] Suitably, in alternative aspects, the method excludes step c).

[0046] Suitably, when the substrate is one or more polymers, the method excludes step c).

[0047] Step d)

[0048] Suitably, step d) comprises one, two, three, four or five treatments of at least a portion of the substrate surface with an oxidising agent. Suitably, step d) comprises three treatments of at least a portion of the substrate surface with an oxidising agent.

[0049] The oxidising agent preferably affects the surface of the substrate but preferably does not adversely affect the bulk of the substrate. The oxidising agent may comprise a peroxide, optionally may comprise hydrogen peroxide, optionally may comprise hydrogen peroxide in at least 30%w / v aqueous solution. Generally, peroxide and / or other oxidising agents may also be suitable, for example O3, hydroxyl radicals, atomic oxygen, ozonated water, ^Chwith and without decomposition catalysts (e.g. Cu ions, Fe ions, manganese oxide), periodate, hypochlorite, and / or permanganate. Suitably, the or each treatment with an oxidising agent is carried out at a temperature in the range from 10 °C to 90 °C, optionally 10 °C to 80 °C, optionally 20 °C to 75 °C, optionally 30 °C to 70 °C, optionally 40 °C to 70 °C.

[0050] Suitably, the or each treatment with an oxidising agent is carried out for from 1 min to 60 min, 1 min to 30 min, 1 min to 20 min, or 5 min to 20 min, or 10 min to 15 min.

[0051] Step e)

[0052] Where the substrate is a polymer, the composition may be applied above one or more other coating layers (except a layer of silica) already deposited on the polymer surface. Preferably, the polymer surface does not comprise a silica coating.

[0053] Preferably, the composition is applied directly to the substrate surface, usually needing no inorganic layers already deposited on the substrate surface. Thus, preferably, the method comprises treating the substrate surface directly.

[0054] In some embodiments, the composition of step e) further comprises an oxidising agent.

[0055] Suitably, the composition of step e) comprises (i) a one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof; and (ii) an oxidising agent.

[0056] Suitably, the composition of step e) comprises (i) one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof; in (ii) an aqueous solution of an oxidising agent.

[0057] Suitably, the composition of step e) may be in aqueous solution. Thus, the composition may comprise water. One or more co-solvent(s) may also be present, if suitable.

[0058] Suitably, the composition of step e) comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is an aqueous solution comprising at least 0.2 mg / mL, at least 0.4 mg / mL, at least 0.6 mg / mL, at least 0.8 mg / mL, at least 1.0 mg / mL, at least 1.2 mg / mL, at least 1.4 mg / mL, at least 1.6 mg / mL, at least 1.8 mg / mL, at least 2.0 mg / mL of the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof. Suitably, this aqueous solution is an aqueous solution of an oxidising agent. One or more cosolvents) may also be present, if suitable. The oxidising agent may be an oxidising agent as described for step d).

[0059] Suitably, the oxidising agent in the composition may comprise a peroxide, optionally may comprise hydrogen peroxide, optionally may comprise hydrogen peroxide in at least 30%w / v aqueous solution.

[0060] Although, it is thought that a number of components may be useful in the method as the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof. In particular, the polysaccharide or synthetic derivative thereof etc. may comprise a hexose derived polysaccharide or synthetic derivative thereof. The polysaccharide or synthetic derivative thereof may be polyhydroxylated. Generally, the polysaccharide or synthetic derivative thereof may provide a relatively hydrophilic surface (e.g. water contact angle below 80°, below 70°, below 60°, below 50°, or lower), preferably once applied to the substrate surface.

[0061] Suitably, in some aspects the polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof, is a synthetic derivative thereof. Suitably, the synthetic derivative thereof of a polysaccharide is a hydroxy Wiylcellulose polymer.

[0062] The preferred one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof of step e) is selected from one or more of dextran, cellulose, hydroxy&thylcellulose polymers, one or more polyols, dextrin, polygalacturonic acid, hyaluronic acid, or salts thereof.

[0063] Preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof of step e) is selected from salts of one or more of dextran, cellulose, hydroxy&thylcellulose polymers, one or more polyols, dextrin, polygalacturonic acid, or hyaluronic acid.

[0064] Preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof of step e) is selected from pharmaceutically acceptable salts of one or more of dextran, cellulose, hydroxy&thylcellulose polymers, one or more polyols, dextrin, polygalacturonic acid, or hyaluronic acid.

[0065] Preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is polygalacturonic acid or a salt thereof. More preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is polygalacturonic acid sodium salt.

[0066] Alternatively, preferably the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is hyaluronic acid or salt thereof. More preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is hyaluronic acid sodium salt

[0067] Surprisingly, use of one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof in the described method protocol significantly improves lubricity.

[0068] The inventors have observed significantly improve lubricity when the method is applied to substrate, both glass and polymer, surfaces.

[0069] Step f)

[0070] Suitably, the predetermined time of step f) is from 0.5 mins to 240 mins. Other optional ranges for the predetermined time is from 1 min to 120 min, from 1 min to 60 min, from 1 min to 30 min, from 1 min to 20 min, from 5 min to 20 min, or from 10 min to 15 min.

[0071] Treating at least a portion of the substrate surface and / or incubation may be at a temperature in the range 10 °C to 90 °C, optionally 10 °C to 85 °C, optionally 20 °C to 85 °C, optionally 30 °C to 80 °C, optionally 40 °C to 80 °C, optionally 50 °C to 80 °C, optionally 60 °C to 80 °C, optionally 65 °C to 75 °C.

[0072] Treating at least a portion of the substrate surface and / or treatment during incubation may comprise mechanical, chemical or electromagnetic acceleration of the process e.g. by sonication, microwave or UV irradiation, and / or ion-catalysis.

[0073] Step e) and f)

[0074] Suitably, treatment step e) and incubation step f) are each carried out one, two, three, four or five times. More suitably, treatment step e) and incubation step f) are each carried out two, three or four times. More suitably, treatment step e) and incubation step f) are each carried out three or four times. More suitably, treatment step e) and incubation step f) are each carried out four times.

[0075] Step g) Suitably, in some aspects, the method comprises step g) treating at least a portion of the substrate surface with a further composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof.

[0076] Suitably, in alternative aspects, the method excludes step g).

[0077] Suitably, step g) comprises an initial rinse with water before treating at least a portion of the substrate surface with a further composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof. Suitably, this initial rinse with water is carried out one, two, three or four times before treating at least a portion of the substrate surface with a further composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof. Suitably, this initial rinse with water is carried out three times before treating at least a portion of the substrate surface with a further composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof.

[0078] Suitably, in some aspects the polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof, is a synthetic derivative thereof. Suitably, the synthetic derivative thereof of a polysaccharide is a hydroxy Wiylcellulose polymer.

[0079] Suitably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof of the further composition of step g) is selected from one or more of dextran, cellulose, hydroxy iylcellulose polymers, one or more polyols, dextrin, polygalacturonic acid, hyaluronic acid, or salts thereof.

[0080] Preferably, this further composition in step g) comprises a different one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, or polyol to that used in the composition of step e). In addition, the further composition may also be a different salt to that used in step e). Thus, for example, the composition of step e) may use polygalacturonic acid, and the further composition of step g) may use hyaluronic acid.

[0081] Although, it is thought that a number of components may be useful in the method as the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof. In particular, the polysaccharide or synthetic derivative thereof etc. may comprise a hexose derived polysaccharide or synthetic derivative thereof. The polysaccharide or synthetic derivative thereof may be polyhydroxylated. Generally, the polysaccharide or synthetic derivative thereof may provide a relatively hydrophilic surface (e.g. water contact angle below 80°, below 70°, below 60°, below 50°, or lower), preferably once applied to the substrate surface.

[0082] Preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof of step g) is selected from salts of one or more of dextran, cellulose, hydroxy&thylcellulose polymers, one or more polyols, dextrin, polygalacturonic acid, or hyaluronic acid. Preferably, this further composition in step g) comprises a different one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, or polyol to that used in the composition of step e). In addition, the further composition may also be a different salt to that used in step e).

[0083] Preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof of step g) is selected from pharmaceutically acceptable salts of one or more of dextran, cellulose, hydroxy&thylcellulose polymers, one or more polyols, dextrin, polygalacturonic acid, or hyaluronic acid. Preferably, this further composition in step g) comprises a different one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, or polyol to that used in the composition of step e). In addition, the further composition may also be a different salt to that used in step e)

[0084] Suitably, the further composition in step g) comprises a different one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, or polyol to that used in step e). In addition, the further composition may also be a different salt to that used in step e).

[0085] Suitably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof in step g) is polygalacturonic acid or a salt thereof. More preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is polygalacturonic acid sodium salt.

[0086] Alternatively, suitably the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof in step g) is hyaluronic acid or a salt thereof. More preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is hyaluronic acid sodium salt Suitably, the one or more polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salt thereof in step e) is polygalacturonic acid or salt thereof; and in step g) is hyaluronic acid or salt thereof.

[0087] Suitably, the further composition of step g) further comprises an oxidising agent.

[0088] Suitably, the further composition of step g) comprises (i) a one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof; and (ii) an oxidising agent.

[0089] Suitably, the further composition of step g) comprises (i) one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof; in (ii) an aqueous solution of an oxidising agent.

[0090] Suitably, the further composition of step g) may be in aqueous solution. Thus, the composition may comprise water. One or more co-solvent(s) may also be present, if suitable.

[0091] Suitably, the further composition of step g) comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is an aqueous solution comprising at least 0.2 mg / mL, at least 0.4 mg / mL, at least 0.6 mg / mL, at least 0.8 mg / mL, at least 1.0 mg / mL, at least 1.2 mg / mL, at least 1.4 mg / mL, at least 1.6 mg / mL, at least 1.8 mg / mL, at least 2.0 mg / mL of the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof. Suitably, this aqueous solution is an aqueous solution of an oxidising agent. One or more cosolvents) may also be present, if suitable.

[0092] The oxidising agent may be an oxidising agent as described for step d).

[0093] Suitably, the oxidising agent in the further composition of step g) may comprise a peroxide, optionally may comprise hydrogen peroxide, optionally may comprise hydrogen peroxide in at least 30%w / v aqueous solution.

[0094] Suitably, step g) is carried out at less than 30 °C, preferably, step g) is carried out at room temperature. Suitably, step g) is carried out from 1 min to 60 min, from 1 min to 30 min, from 1 min to 20 min, from 5 min to 20 min, from 10 min to 15 min.

[0095] Suitably, treatment step g) is repeated one, two, three, four or five times.

[0096] The conditions of treatment step g) are considered insufficient to produce a covalent bond between the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof of the further composition and the surface. Hence, it is considered that the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is non-covalently attached. Hybrid modification in this way may be used to achieve differential functionality through binary (or more) polysaccharide or synthetic derivative thereof combinations. This allows the coating to be tuned.

[0097] The substrates obtained by the present method have significantly improved lubricity.

[0098] Salts

[0099] Suitably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof, is a salt thereof.

[0100] Suitably, the salts thereof, comprises pharmaceutically acceptable salts.

[0101] The one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol may comprise pharmaceutically acceptable salts including nontoxic acid addition salts (including di-acids) and base salts.

[0102] If the compound is cationic or has a functional group which may be cationic (e.g. -NH2may be -NH3+), then an acid addition salt may be formed with a suitable anion. Examples of suitable inorganic anions include, but are not limited to, those derived from the following inorganic acids hydrochloric acid, nitric acid, nitrous acid, phosphoric acid, sulfuric acid, sulphurous acid, hydrobromic acid, hydroiodic acid, hydrofluoric acid, phosphoric acid and phosphorous acids. Examples of suitable organic anions include, but are not limited to, those derived from the following organic acids: 2- acetyoxybenzoic, acetic, ascorbic, aspartic, benzoic, camphorsulfonic, cinnamic, citric, edetic, ethanedisulfonic, ethanesulfonic, fumaric, glucheptonic, gluconic, glutamic, glycolic, hydroxymaleic, hydroxynaphthalene carboxylic, isethionic, lactic, lactobionic, lauric, maleic, malic, methanesulfonic, mucic, oleic, oxalic, palmitic, pamoic, pantothenic, phenylacetic, phenylsulfonic, propionic, pyruvic, salicylic, stearic, succinic, sulfanilic, tartaric, toluenesulfonic, and valeric. Examples of suitable polymeric organic anions include, but are not limited to, those derived from the following polymeric acids: tannic acid, carboxymethyl cellulose. Such salts include acetate, adipate, aspartate, benzoate, besylate, bicarbonate, carbonate, bisulfate, sulfate, borate, camsylate, citrate, cyclamate, edisylate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride / chloride, hydrobromide / bromide, hydroiodide / iodide, isethionate, lactate, malate, maleate, malonate, mesylate, methylsulfonate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate, hydrogen phosphate, dihydrogen phosphate, pyroglutamate, saccharate, stearate, succinate, tannate, tartrate, tosylate, trifluoroacetate and xinofoate salts.

[0103] For example, if the compound is anionic, or has a functional group which may be anionic (e.g. -RCOOH may be -RCOOj, then a base salt may be formed with a suitable cation. Examples of suitable inorganic cations include, but are not limited to, metal cations, such as an alkali or alkaline earth metal cation, ammonium and substituted ammonium cations, as well as amines. Examples of suitable metal cations include sodium (Na+), potassium (K+), magnesium (Mg2+), calcium (Ca2+), zinc (Zn2+), and aluminum (Al3+). Examples of suitable organic cations include, but are not limited to, ammonium ion (i.e. NH4+) and substituted ammonium ions (e.g. NH3R+, NH2R2+, NHRa+, NR4+). Examples of some suitable substituted ammonium ions are those derived from: ethylamine, diethylamine, dicyclohexylamine, triethylamine, butylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine, benzylamine, phenylbenzylamine, choline, meglumine, and tromethamine, as well as amino acids, such as lysine and arginine. An example of a common quaternary ammonium ion is N(CH3)4+. Examples of suitable amines include arginine, N,N'-dibenzylethylene- diamine, chloroprocaine, choline, diethylamine, diethanolamine, dicyclohexylamine, ethylenediamine, glycine, lysine, N-methylglucamine, olamine, 2-amino-2- hydroxymethyl-propane-1 ,3-diol, and procaine. For a discussion of useful acid addition and base salts, see S. M. Berge et al., J. Pharm. Sci. (1977) 66:1-19; see also Stahl and Wermuth, Handbook of Pharmaceutical Salts: Properties, Selection, and Use (2011).

[0104] Preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof, comprise a sodium, potassium, magnesium, calcium, zinc, and aluminum salt. More preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof, comprise a sodium or potassium salt. More preferably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof, comprise a sodium salt.

[0105] Pharmaceutically acceptable salts may be prepared using various methods. For example, one may react a compound of the disclosure with an appropriate acid or base to give the desired salt. One may also react a precursor of the compound of the disclosure with an acid or base to remove an acid- or base-labile protecting group or to open a lactone or lactam group of the precursor. Additionally, one may convert a salt of the compound of the disclosure to another salt through treatment with an appropriate acid or base or through contact with an ion exchange resin. Following reaction, one may then isolate the salt by filtration if it precipitates from solution, or by evaporation to recover the salt. The degree of ionization of the salt may vary from completely ionized to almost non-ionized.

[0106] Portion of a Substrate

[0107] Suitably, the portion of a substrate comprises a portion of the internal surface of a container. Suitably, the portion of a substrate comprises essentially all of the internal surface of a container. Suitably, the portion of a substrate comprises all of the internal surface of a container. Suitably, the portion of a substrate comprises essentially all of the surface of a container. Suitably, the portion of a substrate comprises all of the internal surface of a container.

[0108] Suitably, the container is the barrel of a medical injection device.

[0109] Coated Substrate

[0110] Optionally, the coated substrate does not comprise a silica coating.

[0111] Coated substrates of the present invention have a further great advantage in that they enhance the thermal and intrinsic stability of compositions stored in contact with the coated surface (e.g. when compared with the uncoated surface or other materials).

[0112] Suitably, the lubricity coating is attached directly to the substrate surface, with no inorganic layers between the lubricity coating and the substrate surface.

[0113] Lubricity Coating Suitably, the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is as described above with regard to step e) of the method.

[0114] Suitably, the lubricity coating may further comprise a further one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof. Suitably, the further one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is as described above with regard to step g) of the method. Suitably, this further one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof is non-covalently attached to the substrate.

[0115] Suitably this further polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or mixture thereof is different from the first polysaccharide or synthetic derivative thereof.

[0116] Suitably, this further composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof comprises a different one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, or polyol to that used in the first composition (i.e. the composition used in step e) of the method). In addition, the further composition may also be a different salt to that used in the first composition.

[0117] Suitably the lubricity coating provides at least a 1% reduction in the dynamic glide force (DGF) as compared to the bare uncoated surface. Preferably, the lubricity coating provides at least a 2% reduction, preferably at least a 3% reduction, at least a 4% reduction, at least a 5% reduction, at least a 6% reduction, at least a 7% reduction, at least an 8% reduction, at least a 9% reduction, at least a 10% reduction, at least a 15% reduction, at least a 20% reduction, at least a 25% reduction, at least a 30% reduction, at least a 35% reduction, at least a 40% reduction, at least a 45% reduction, at least a 50% reduction, at least a 55% reduction, at least a 60% reduction, at least a 65% reduction, at least a 70% reduction, at least a 75% reduction, at least a 80% reduction, at least a 85% reduction, in the DGF as compared to the bare uncoated surface.

[0118] Preferably, the substrate comprising a lubricity coating has a DGF of less than 15 N, less than 14 N, less than 13 N, less than 12 N, less than 11 N, less than 10 N, less than 9 N, less than 8 N, less than 7 N, less than 6 N, less than 5 N, less than 4 N, less than 3 N, less than 2 N.

[0119] Medical Device

[0120] Suitably, the medical device is a blood contacting device, dialyser, hose, catheter, urinary catheter, stent or a medical injection device.

[0121] Suitably, the medical device is a blood contacting device, dialyser, hose, catheter, urinary catheter, stent, a medical pump, a dispensing tube, a cartridge injector, a pen injector, a jet injector, or a syringe.

[0122] Preferably, the medical device is a medical injection device.

[0123] Suitably, the medical device is a medical injection device comprises a barrel and a stopper in gliding engagement within the barrel, wherein the inner surface of the barrel is the substrate surface at least partially covered by a lubricity coating as described herein.

[0124] Suitably, the medical injection device is a medical pump, a dispensing tube, a cartridge injector, a pen injector, a jet injector, or a syringe.

[0125] More suitably, the medical injection device is a syringe.

[0126] Such medical injection devices may be pre-filled with the medicament to be injected.

[0127] Syringes for injecting pharmaceutical products, may suitably follow ISO 11040 Part 4 (Glass Barrels), Part 5 (Plungers) and Part 6 (Plastic Barrels) Standards which define suitable dimensions and tolerances.

[0128] In another aspect, the medical injection device comprises a barrel and a stopper in gliding engagement within the barrel, wherein the inner surface of the barrel is a substrate surface at least partially covered by a lubricity coating according to the second aspect.

[0129] Preferably, the lubricity coating on the barrel of the medical injection device provides at least a 1% reduction in the dynamic plunger-stopper break loose force (PDF) as compared to the bare uncoated surface of the barrel. Preferably, the lubricity coating provides at least a 2% reduction, preferably at least a 3% reduction, at least a 4% reduction, at least a 5% reduction, at least a 6% reduction, at least a 7% reduction, at least an 8% reduction, at least a 9% reduction, at least a 10% reduction, at least a 15% reduction, at least a 20% reduction, at least a 25% reduction, at least a 30% reduction, at least a 35% reduction, at least a 40% reduction, at least a 45% reduction, at least a 50% reduction, at least a 55% reduction, at least a 60% reduction, at least a 65% reduction, in the dynamic plunger-stopper break loose force (PDF) as compared to the bare uncoated surface of the barrel.

[0130] For example, if the dynamic plunger-stopper break loose force (PDF) is 20 N for the bare uncoated surface of the barrel of the medical injection device, and the PDF of the lubricity coated barrel of the medical injection device is 12 N, then this represents a reduction of 8 N in the PDF which is a 40% reduction in the PDF.

[0131] Preferably the medical injection device has a glass barrel wherein the inner surface of the barrel is a substrate surface at least partially covered by a lubricity coating.

[0132] Preferably, this medical injection device has a glass barrel and has a PDF of less than 18 N, less than 17 N, less than 16 N, less than 15 N, less than 14 N, less than 13 N, less than 12 N, less than 11 N, less than 10 N, less than 9 N, less than 8 N, less than 7 N, less than 6 N.

[0133] Alternatively, suitably, the medical injection device has a barrel comprising one or more polymers wherein the inner surface of the barrel is a substrate surface at least partially covered by a lubricity coating. Suitably, in such aspects the medical injection device with has a PDF of less than 6 N, less than 5.7 N, less than 5.5 N, less than 5.2 N, less than 5 N, less than 4.8 N, less than 4.7 N, less than 4.5 N, less than 4.2 N, less than 4 N, less than 3.8 N, less than 3.7 N.

[0134] Preferably, the lubricity coating on the barrel of the medical injection device provides at least a 1% reduction in the dynamic glide force (DGF) as compared to the bare uncoated surface of the barrel. Preferably, the lubricity coating provides at least a 2% reduction, preferably at least a 3%reduction, at least a 4% reduction, at least a 5% reduction, at least a 6% reduction, at least a 7% reduction, at least an 8% reduction, at least a 9% reduction, at least a 10% reduction, at least a 15% reduction, at least a 20% reduction, at least a 25% reduction, at least a 30% reduction, at least a 35% reduction, at least a 40% reduction, at least a 45% reduction, at least a 50% reduction, at least a 55% reduction, at least a 60% reduction, at least a 65% reduction, at least a 70% reduction, at least a 75% reduction, at least a 80% reduction, at least a 85% reduction, in the DGF as compared to the bare uncoated surface of the barrel.

[0135] Preferably the medical injection device has a glass barrel wherein the inner surface of the barrel is a substrate surface at least partially covered by a lubricity coating. Preferably, this medical injection device with a lubricity coating has a

[0136] Preferably, this medical injection device has a glass barrel and has a DGF of less than 15 N, less than 14 N, less than 13 N, less than 12 N, less than 11 N, less than 10 N, less than 9 N, less than 8.5 N, less than 8 N, less than 7 N, less than 6 N, less than 5 N, less than 4 N, less than 3 N, less than 2 N.

[0137] Preferably, this medical injection device has a barrel comprising one or more polymers and has a DGF of less than 4.3 N, less than 4.2 N, less than 4.1 N, less than 4.0 N, less than 3.9 N, less than 3.8 N.

[0138] Definitions

[0139] In this specification, the term “at least” means “equal or more” than the integer that follows the term.

[0140] In this specification, and unless the context suggest otherwise, cyclic olefin polymers (COP) as referred to herein include cyclic olefin copolymers (COC).

[0141] As used herein the term “comprising” means “including at least in part of” and is meant to be inclusive or open ended. When interpreting each statement in this specification that includes the term “comprising”, features, elements and / or steps other than that or those prefaced by the term may also be present. Related terms such as “comprise” and “comprises” are to be interpreted in the same manner.

[0142] The term “consisting essentially of’ limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention. When the phrase “consisting essentially of” appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause.

[0143] The term “consisting of” excludes any element, step, or ingredient not specified in the claim; “consisting of” defined as “closing the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase “consists of” appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole. It should be understood that while various embodiments in the specification are presented using “comprising” language, under various circumstances, a related embodiment is also described using “consisting essentially of’ or “consisting of” language.

[0144] As used herein, the “dynamic glide force” (DGF) is the force required to maintain movement once static friction has been overcome. In particular, with regard to a syringe the “dynamic glide force” is the force required to maintain the movement of the plunger in a syringe barrel.

[0145] As used herein, the “dynamic plunger-stopper break loose force” (PBF), or initiating force, is the force required to initiate the movement of the plunger in an injection device such as a syringe.

[0146] Further particular and preferred aspects are set out in the accompanying independent and dependent claims. Features of the dependent claims may be combined with features of the independent claims as appropriate, and in combinations other than those explicitly set out in the claims.

[0147] DETAILED DESCRIPTION

[0148] The substrate may comprise one or more polymers, in particular, cyclic olefin polymers (COP). The general structure of COP materials and examples of polymerisation methods are provided below in Scheme 1.

[0149]

[0150] Scheme 1. General structure of COP materials and examples of polymerisation methods. Structural variations can be achieved via choice of Ri and R2 substituents. The polymerisation methods may be used to prepare Topas (TM) which is obtained via chain polymerization (top route) whereas Zeonor (TM) is obtained via ring opening metathesis (bottom route). [Shin J.Y. et al., Pure and Applied Chemistry, (2005) 77: 801-814; and Nunes et al. Microfluid Nanofluid (2010) 9:145-161],

[0151] The lubricity coatings comprise one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof. The chemical structures of some example a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof are shown below in Scheme 2.

[0152]

[0153] Scheme 2 - Example saccharide structures

[0154] BRIEF DESCRIPTION OF THE DRAWINGS

[0155] Embodiments of the present invention will now be described further, with reference to the accompanying drawings, in which:

[0156] Figure 1 shows a comparison of dynamic glide force (DGF) values obtained for bare glass (Syringes A-C) and COP syringes (Syringes D-E) and after covalent modification using polysaccharides no.1 and no.2 (S1 and S2).

[0157] Figure 2 shows a comparison of dynamic plunger-stopper break loose force (PBF) values obtained for bare glass (Syringes A-C) and COP syringes (Syringes D-E) and after covalent modification using polysaccharides no.1 and no.2 (S1 and S2).

[0158] Figure 3 shows a comparison of dynamic glide force (DGF) values obtained for bare glass syringes (Syringes B and C) and the same syringes after covalent and hybrid modifications. Hybrid modification comprised covalently linked polysaccharide no.1 (S1) and non-covalently attached polysaccharides no.2 (S2).

[0159] Figure 4 shows a comparison of dynamic plunger-stopper break loose force (PBF) values obtained for bare glass syringes (Syringes B and C) and the same syringes after covalent and hybrid modifications. Hybrid modification comprised covalently linked polysaccharide no.1 (S1) and non-covalently attached polysaccharides no.2 (S2). Experimental

[0160] Methods

[0161] Materials:

[0162] Hydrogen peroxide (>30% w / v); sodium hydroxide (99.99%), acetone (HPLC grade), isopropanol (HPLC grade), polygalacturonic acid sodium salt (from citrus fruit >75%), hyaluronic acid sodium salt (1.2-1.5 MDa), water (deionized, distilled or equivalent).

[0163] List of Solutions:

[0164] Sln1. Polysaccharides in peroxide, 1 mg / mL. 10 mg sugar in 10 mL H2O2 30%. Saccharide solution is prepared immediately prior to use.

[0165] Sln2. NaOH 0. 1 M: 0.2 g NaOH in 50 mL water

[0166] Sln3. Polysaccharides in peroxide, 2 mg / mL. 20 mg sugar in 10 mL H2O2 30%. Saccharide solution is prepared immediately prior to use.

[0167] Table 1. List of procotols for syringe modifications:

[0168] The following protocols were used for modifying the syringe barrel surfaces.

[0169] B1 : Bare syringe protocol

[0170] The term “bare” syringe in this document refers to a syringe modified via step #1 .a of the covalent modification protocols P1 or P2 applicable to glass and COP syringes, respectively, that follow.

[0171] P1. covalent modification applied to glass syringes

[0172] 1 . T reat glass syringes according to the following steps: a. WG. rinse syringe sequentially with acetone, isopropanol and water x2 times. b. BP70: syringes are filled with Sln2 and placed for 15 min in a water bath at 50 °C. Rinse with water. Then fill the syringe with H2O2 and place for 15 min in a water bath at 70 °C.

[0173] 2. Syringes prepared as in step #1 are filled with Sin 1 and placed in a water bath at 70 °C for 15 min.

[0174] 3. Repeat step #2 three times by introducing a new volume of Sin 1 after each cycle.

[0175] 4. Rinse syringes from step #3 with water 3 times.

[0176] P2: covalent modification applied to COP syringes

[0177] 1. T reat COP syringes according to the following procedure: a. WC: rinse syringe with water 3 times, changing water after each rinse. b. 3P70 fill syringe with H2O2 and incubate at 70 °C for 10 min; then the process is repeated an additional 2 times, refreshing the H2O2 solution after each cycle.

[0178] 2. Syringes prepared as in step #1 are filled with Sin 1 and placed in a water bath at 70 °C for 15 min.

[0179] 3. Repeat step #2 three times by introducing a new volume of Sin 1 after each cycle.

[0180] 4. Rinse syringes from step #3 with water 3 times.

[0181] P3: hybrid (covalent / non covalent) modification applied to glass syringes

[0182] 1. T reat glass syringes according to the following steps: a. WG. rinse syringe sequentially with acetone, isopropanol and water x2 times. b. BP70: syringes are filled with Sln2 and placed for 15 min in a water bath at 50 °C. Rinse with water. Then fill the syringe with H2O2 and place for 15 min in a water bath at 70 °C.

[0183] 2. Syringes prepared as in step #1 are filled with Sin 1 and placed in a water bath at 70 °C for 15 min.

[0184] 3. Repeat step #2 three times by introducing a new volume of Sin 1 after each cycle.

[0185] 4. Rinse syringes from step #3 with water 3 times.

[0186] 5. Syringes prepared as in step #4 are filled with Sln3 and left at room temperature for 15 min. The syringes are emptied.

[0187] 6. Repeat step #5 3 times, changing Sln3 after each cycle. P4: non covalent modification applied to glass syringes

[0188] 1. A bare syringe is filled with Sln3 and left at room temperature for 15 min. The syringe is emptied.

[0189] 2. Repeat step #1 3 times, changing Sln3 after each cycle.

[0190] Characterization Protocol

[0191] Measurement of glide force parameters on modified and unmodified syringes were obtained using a single column force tester (Mecmesin, MultiTest 2.5 dV) equipped with a syringe holder attachment and with software for automated determination of plunger-stopper break loose force (PBF) and dynamic glide force (DGF). The force testing protocol comprised the following steps:

[0192] 1 Fill Syringes with ultrapure water.

[0193] 2 Place plunger stopper manually, leaving no air between the stopper and the water.

[0194] 3 Place a needle on the syringe, if required.

[0195] 4 Set up the software using the following parameters: i. Name of the samples; ii. Compression test; iii. Pre-Load: 0.5 N; iv. Rate: 200 mm / min; and v. Displacement: between 15 mm and 30 mm, depending on type and dimensions of the syringes being tested.

[0196] 5 Place syringe in syringe holder and fix it in place.

[0197] 6 Start acquisition.

[0198] Samples

[0199] Borosilicate glass syringes from three different suppliers were labelled as Syringes A, B and C respectively. Samples of each of Syringes A, B and C were prepared as described above using each of the following protocols: (i) the bare glass (B1 protocol), (ii) covalent modification with polygalacturonic acid, S1 (P1 protocol, with S1 as the polysaccharide in the Sin 1 solution) and (iii) covalent modification with hyaluronic acid, S2 (P1 protocol, with S2 as the polysaccharide in the Sln1 solution). Similarly, cyclic olefin polymer (COP) syringes from two different suppliers were labelled as Syringes D and E. Samples of each of Syringes D and E were prepared as described above using each of the following protocols: (i) the bare glass (B1 protocol), (ii) covalent modification with polygalacturonic acid, S1 (P2 protocol) and (iii) covalent modification with hyaluronic acid, S2 (P2 protocol).

[0200] The dynamic glide force (DGF) values and the dynamic plunger-stopper break loose force (PBF) values for the samples were measured using the characterization protocol and the numerical results are provided in Tables 2, 3 and 4 below.

[0201] Table 2. Glide force results obtained at bare syringes. N = sample size; PBF = plungerstopper break loose force; DGF = dynamic glide force; s = sample standard deviation; CI95 = width of 95% confidence interval based on tgs score).

[0202] Table 3. Glide force test results obtained at covalently modified syringes using polysaccharide no.1 (S1). N = sample size; PBF = plunger-stopper break loose force; DGF = dynamic glide force; s = sample standard deviation; CI95 = width of 95% confidence interval (based on t95score).

[0203] Table 4. Glide force test results obtained at covalently modified syringes using polysaccharide no.2 (S2). N = sample size; PBF = plunger-stopper break loose force; DGF = dynamic glide force; s = sample standard deviation; CI95 = width of 95% confidence interval (based on tgs score)

[0204] Conclusions - Dynamic Glide Force (DFG) Values

[0205] A comparison of the DGF results is shown in Figure 1 where the error bars represent the standard error on the mean. These results show that modification of either glass syringes (Syringes A-C) or COP syringes (Syringes D-E) via covalent immobilization of polysaccharides results in a reduction of the dynamic glide force. The results are particularly good for the glass syringes (A-C) as can be seen from Figure 1. Therefore, using the covalent modification protocol (P1 or P2) results in improved lubricity.

[0206] Conclusions - Dynamic Plunger-Stopper Break Loose Force (PBF) Values A comparison of the PBF results is shown in Figure 2, where the error bars represent the standard error on the mean. These results show that modification of either glass syringes or COP syringes via covalent immobilization of polysaccharides results in a reduction of the plunger-stopper break loose force. Therefore, using the covalent modification protocol (P1 or P2) results in improved lubricity.

[0207] Hybrid Modification

[0208] Samples of glass syringes (B & C) underwent hybrid modification using the P3 procedure comprising covalently linked polygalacturonic acid, (S1) and non-covalently attaching hyaluronic acid (S2). This is achieved by using S1 as the polysaccharide in the Sin 1 solution used in steps 2 and 3, and then using S2 as the polysaccharide in the Sln3 solution used in steps 5 and 6 of the P3 procedure. The DGF) and the dynamic plunger-stopper break loose force (PBF) for the samples were measured using the characterization protocol and the numerical results are provided in Table 5 below.

[0209] Table 5. Glide force test results obtained at syringes modified with a hybrid coating comprising covalently linked polysaccharide no.1 (S1) and non covalently attached polysaccharides no.2 (S2). N = sample size; PBF = plunger-stopper break loose force; DGF = dynamic glide force; s = sample standard deviation; CI95 = width of 95% confidence interval (based on tgs score)

[0210] The hybrid modified samples were compared with samples of Syringes B and C prepared using each of the following protocols: (i) the bare glass (B1 protocol), (ii) covalent modification with polygalacturonic acid, S1 (P1 protocol, with S1 as the polysaccharide in the Sin 1 solution) and (iii) covalent modification with hyaluronic acid, S2 (P1 protocol, with S2 as the polysaccharide in the Sln1 solution) whose results are provided in Tables 2-3. This comparison of the DGF and the PBF results with those of the hybrid modified samples is shown in Figures 3 and 4 respectively, where the error bars represent the standard error on the mean. Conclusions - Hybrid modification

[0211] Hybrid modification of syringes using a covalently attached polysaccharide followed by a suitable, non-covalently attached polysaccharide results in the best values for a reduction of the dynamic glide force.

[0212] The hybrid modification with covalently attached S1 and non-covalently attached S2 gave better PBF results than using covalently attached S2 alone. However, the hybrid modification was not as effective as covalently attached S1 alone. All of the modified protocols gave improved results as compared to the bare glass syringes.

[0213] Therefore, the hybrid modification protocol results in slight worsening of the PBF but overall improved lubricity as regards the DGF performance.

[0214] Therefore, hybrid modification protocol results in improved lubricity, in particular as regards DGF performance. Hybrid modification can also be tailored to achieve differential functionality through binary (or more) polysaccharide combinations.

[0215] Although illustrative embodiments of the invention have been disclosed in detail herein, with reference to the accompanying drawings, it is understood that the invention is not limited to the precise embodiment and that various changes and modifications can be effected therein by one skilled in the art without departing from the scope of the invention as defined by the appended claims and their equivalents.

Claims

CLAIMS1. A method of preparing a lubricity coating on a substrate surface, the method comprising: a) providing a substrate having a surface; b) optionally, rinsing the substrate with one or more solvents; c) optionally, treating at least a portion of the substrate surface with an alkaline aqueous solution; d) treating at least a portion of the substrate surface with an oxidising agent; e) treating at least a portion of the substrate surface with a composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof; f) incubating the treated substrate with the composition for a predetermined time; and g) optionally, treating at least a portion of the substrate surface with a further composition comprising one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof.

2. The method according to claim 1, wherein the substrate comprises glass, quartz or one or more polymers.

3. The method according to claim 1 or 2, wherein the oxidising agent comprising a peroxide.

4. The method according to any one of the preceding claims, wherein the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof of step e) is selected from pharmaceutically acceptable salts of one or more of dextran, cellulose, hydroxy iylcellulose polymers, one or more polyols, dextrin, polygalacturonic acid, or hyaluronic acid.

5. The method according to any one of the preceding claims, wherein the composition of step e) further comprises an oxidising agent.

6. The method according to any one of the preceding claims, wherein the method comprises step g) which is carried out at a temperature of less than 30 °C.

7. The method according to claim 6, wherein the one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof of the furthercomposition of step g) is selected from one or more of dextran, cellulose, one or more polyols, dextrin, polygalacturonic acid, hyaluronic acid, or salts thereof.

8. The method according to claim 6 or 7, wherein the further composition in step g) comprises a different one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, or polyol to that used in the composition of step e).

9. A coated substrate obtainable by coating at least one surface of a substrate with a lubricity coating according to a method of any one of claims 1-8.

10. A substrate having a lubricity coating on at least one surface, wherein the lubricity coating directly contacts the surface of the substrate and the lubricity coating comprises one or more of a polysaccharide or synthetic derivative thereof, oligosaccharide, polyol or salts thereof.

11. A medical device comprising a substrate surface at least partially covered by a lubricity coating according to any one of claims 9 or 10.

12. A medical injection device comprises a barrel and a stopper in gliding engagement within the barrel, wherein the inner surface of the barrel is a substrate surface at least partially covered by a lubricity coating according to any one of claims 9 or 10.

13. The medical injection device according to claim 12, wherein the medical injection device is a medical pump, a dispensing tube, a cartridge injector, a pen injector, a jet injector, or a syringe.

14. The medical injection device according to claim 12 or 13, wherein the device has a glass barrel and the lubricity coating on the barrel provides at least a 25% reduction in the dynamic plunger-stopper break loose force (PDF) as compared to the bare uncoated surface of the barrel.

15. The medical injection device according to claim 12, 13 or 14, wherein the device has a glass barrel and has a dynamic glide force of less than 9 N.

Images