Downstream plasma treated silicided plastic syringe barrels and related syringes and methods

Abstract

The presently disclosed subject matter provides a plasma treated plastic syringe barrel having a plasma treated lubricant coating and an inner surface having a reduced number of particles compared to an inner surface of a plastic syringe barrel having an untreated lubricant coating; a plasma treated plastic syringe barrel having a plasma treated lubricant coating and an inner surface having a very low particle surface density; an associated syringe; the content of particles in the solution is extremely low; methods of treating the eye; a method for producing a plastic syringe barrel having a stable lubricating layer; related methods of producing syringes; an associated syringe; and related methods of treating an eye.

Description

[0001] Divisional application This application is a divisional application of the invention application filed on July 27, 2021, with application number 202180066165.7 and titled "Downstream plasma-treated siliconized plastic syringe barrel and related syringes and methods". Cross-references to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 057,284, filed July 27, 2020, the contents of which are incorporated herein by reference in their entirety.

[0003] Statement regarding federally funded research or development This invention was developed with government funding granted by the National Eye Institute, a division of the National Institutes of Health, under license number R44EY024461. The United States holds certain rights to this invention. Technical Field

[0004] This invention relates to plastic syringes for delivering drugs. Background Technology

[0005] As the biopharmaceutical market continues to grow, the demand for injectable drug dosage forms is also increasing. Pre-filled syringes and drug products supplied in glass vials for administration using universal syringes are the most common packaging configurations. Syringes are typically made of glass or plastic.

[0006] Current trends regarding pre-filled syringes favor glass pre-filled syringes utilizing baked silica gel (e.g., Gerrescheimer Gx® Baked-on RTF® glass syringes), plastic pre-filled syringes utilizing chemically cross-linked silica gel (Schott TopPac®), and silicone-free plastic syringe systems (e.g., Terumo PLAJEX). TM , West Daikyo CZ® and BD Sterifill TM However, these unassembled, nested pre-filled syringes and associated manufacturing equipment—even without considering the cost of the biopharmaceutical itself—can be costly.

[0007] Compared to pre-filled syringes, user-fillable plastic syringes and assembled generic plastic syringes offer significant cost reductions (sometimes up to 95%) for compound drug products. However, generic plastic syringes are associated with sub-visible particles derived from lubrication to allow the plunger stop to slide within the syringe barrel, and protein aggregation induced by sub-visible silicone oil particles after drug filling. Silicone-modified plastic pre-filled syringes are also associated with silicone oil sub-visible particles; therefore, glass pre-filled syringes continue to account for a large portion (approximately 70%) of the pre-filled syringe market, and product development for plastic pre-filled syringes focuses on silicone-free plastic syringes.

[0008] There is still a need for a simple and safe solution that can take advantage of the stability and safety provided by lyophilization of biopharmaceuticals in vials, the extremely low cost of universal plastic syringes for bedside drug delivery or compound drug administration, while providing a more stable silicone oil layer with minimal subvisible particle content.

[0009] Plastic syringes are also used for intravitreal injections into the eye to treat macular degeneration and diabetic retinopathy. These expensive biological drugs are supplied in vials that need to be filled into universal syringes before administration. The silicone oil used in these universal syringes can introduce particulate contaminants into the drug solution injected into the patient's eye. Several complications, ranging from increased intraocular pressure to visual floaters, have been reported due to these silicone oil particles. The FDA requires ophthalmic solutions to comply with its USP 789 particulate contamination guidance. USP 789 requires... ≥ No more than 50 particles / ml of 10 micrometers and ≥ No more than 5 particles / ml of 25 micrometers. While the biological solutions in the vials must comply with USP 789, the syringes used to administer these medications are unregulated and can introduce particulate contaminants that can cause patient complications. Low-particle plastic syringes are still required for injecting ophthalmic solutions provided in vials. Summary of the Invention

[0010] The currently disclosed subject matter describes a plastic syringe barrel comprising a plasma-treated plastic syringe barrel coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma treatment consists substantially of an excited gaseous substance without charge; and wherein, compared to the inner surface of the plasma-treated plastic syringe barrel with the polysiloxane lubricant coating, the number of particles with a diameter greater than 8 micrometers in the inner surface of the plasma-treated plastic syringe barrel with the plasma-treated polysiloxane lubricant coating is reduced by at least 75%, 80%, 85%, 90%, or 95%. The currently disclosed subject matter describes a plastic syringe barrel comprising a plasma-treated plastic syringe barrel coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma treatment includes a downstream plasma generated at atmospheric pressure; and wherein, compared to the inner surface of the plasma-treated plastic syringe barrel with the polysiloxane lubricant coating, the number of particles with a diameter greater than 8 micrometers in the inner surface of the plasma-treated plastic syringe barrel with the plasma-treated polysiloxane lubricant coating is reduced by at least 75%, 80%, 85%, 90%, or 95%.

[0011] The currently disclosed subject describes a plastic syringe barrel comprising a plastic syringe barrel that has been plasma-treated and coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma treatment consists substantially of an uncharged excited gaseous substance; and wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated polysiloxane lubricant coating is ≤ 600 particles / 12 cm³. 2 ≤ 500 particles / 12 cm 2 Or ≤ 400 particles / 12 cm 2 The particle diameter is greater than 8 micrometers. This currently disclosed subject describes a plastic syringe barrel comprising a plasma-treated plastic syringe barrel coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma is a downstream plasma generated at atmospheric pressure; and wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated polysiloxane lubricant coating is ≤ 600 particles / 12 cm⁻¹. 2 ≤ 500 particles / 12 cm 2 Or ≤ 400 particles / 12cm 2 The particle diameter is greater than 8 micrometers.

[0012] The presently disclosed subject describes a plastic syringe barrel comprising a plasma-treated plastic syringe barrel coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma treatment consists substantially of an uncharged excited gaseous substance; and wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated polysiloxane lubricant coating is ≤ 100 particles / cm³. 2 ≤ 90 particles / cm 2 ≤ 50 particles / cm 2 ≤ 40 particles / cm 2 ≤ 35 particles / cm 2 or ≤ 30 particles / cm 2 The particle diameter is greater than 8 micrometers. This currently disclosed subject matter describes a plastic syringe barrel comprising a plasma-treated plastic syringe barrel coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma treatment includes a downstream plasma generated at atmospheric pressure; and wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated polysiloxane lubricant coating is ≤ 100 particles / cm³. 2 ≤ 90 particles / cm 2 ≤ 50 particles / cm 2 ≤ 40 particles / cm 2 ≤ 35 particles / cm 2 or ≤ 30 particles / cm 2 The particle diameter is greater than 8 micrometers.

[0013] The currently disclosed subject matter describes a syringe comprising a plastic syringe barrel, a plunger rod, a plunger stopper, and a needle as described herein. In some embodiments, the polysiloxane lubricant coating is a silicone oil coating. In some embodiments, the plastic syringe barrel comprises approximately 0.005 mg / cm³ of lubricant. 2 To approximately 0.5 mg / cm 2 Silicone oil. In some embodiments, the polysiloxane lubricant coating is a polydimethylsiloxane coating.

[0014] The currently disclosed subject matter describes a syringe comprising a plastic syringe barrel containing a solution as described herein. In some embodiments, for any particle with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particle with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml. In some embodiments, the syringe comprises a plastic syringe barrel containing a solution comprising an anticoagulant, a vaccine, or a recombinant protein. In some embodiments, the syringe comprises a plastic syringe barrel containing an anti-VEGF protein solution. In some embodiments, the syringe comprises a plastic syringe barrel containing a solution comprising pilghatinib, ranibizumab, aflibercept, or bevacizumab. In some embodiments, the syringe comprises a plastic syringe barrel containing an ophthalmic solution. In some embodiments, for any particle with a diameter ≥ 10 μm, the particle content in the ophthalmic solution is ≤ 50 particles / ml, or for any particle with a diameter ≥ 25 μm, the particle content in the ophthalmic solution is ≤ 5 particles / ml. In some implementations, the maximum filling volume of the plastic syringe cartridge is 1.0 ml, 0.5 ml, 0.3 ml, 0.25 ml, 0.10 ml, or 0.05 ml.

[0015] The currently disclosed subject describes a method for treating the eye, including administering a solution or ophthalmic solution intravitreally into the eye using the syringe described herein.

[0016] The currently disclosed subject describes a method for producing a plastic syringe barrel with a stable silicone oil layer, comprising providing the plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a plasma consisting substantially of an uncharged excited gaseous substance for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of... 2 Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; and the uniform silicone oil coating is exposed to a plasma consisting essentially of uncharged excited gaseous material for 0.1 to 10 seconds; wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel with the plasma-treated silicone oil coating is ≤ 600 particles / 12 cm³. 2 ≤500 particles / 12 cm 2 Or ≤ 400 particles / 12 cm 2 The particles have a diameter greater than 8 micrometers. The currently disclosed subject describes a method for producing a plastic syringe barrel with a stable silicone oil layer, comprising providing a plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a downstream plasma generated at atmospheric pressure for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of [unclear - possibly a specific concentration or concentration]. 2Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; the uniform silicone oil coating is then exposed to downstream plasma generated at atmospheric pressure for 0.1 to 10 seconds; wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel with the plasma-treated silicone oil coating is ≤600 particles / 12 cm⁻¹. 2 ≤ 500 particles / 12 cm 2 Or ≤ 400 particles / 12 cm 2 The particles have a diameter greater than 8 micrometers. In some embodiments, the method further includes waiting for at least 10 minutes, 20 minutes, 30 minutes, 40 minutes, 1 hour, 2 hours, or 3 hours before exposing the uniform silicone oil coating to plasma.

[0017] The currently disclosed subject describes a method for producing a plastic syringe barrel with a stable silicone oil layer, comprising providing the plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a plasma consisting substantially of an uncharged excited gaseous substance for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of... 2 Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; and the uniform silicone oil coating is exposed to a plasma consisting essentially of uncharged excited gaseous material for 0.1 to 10 seconds; wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel with the plasma-treated silicone oil coating is ≤ 100 particles / cm³. 2 ≤ 90 particles / cm 2 ≤ 50 particles / cm 2 ≤ 40 particles / cm 2 ≤ 35 particles / cm 2 or ≤ 30 particles / cm 2 The particles have a diameter greater than 8 micrometers. The currently disclosed subject describes a method for producing a plastic syringe with a stable silicone oil layer, comprising providing a plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a downstream plasma generated at atmospheric pressure for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of [unclear - possibly a specific concentration or concentration]. 2 Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; the uniform silicone oil coating is then exposed to downstream plasma generated at atmospheric pressure for 0.1 to 10 seconds; wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel with the plasma-treated silicone oil coating is ≤ 100 particles / cm³. 2 ≤ 90 particles / cm 2 ≤ 50 particles / cm 2≤ 40 particles / cm 2 ≤ 35 particles / cm 2 or ≤ 30 particles / cm 2 The particles have a diameter greater than 8 micrometers. In some embodiments, the method further includes waiting for at least 10 minutes, 20 minutes, 30 minutes, 40 minutes, 1 hour, 2 hours, or 3 hours before exposing the uniform silicone oil coating to plasma.

[0018] The currently disclosed subject describes a method for producing a plastic syringe barrel with a stable silicone oil layer, comprising providing the plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a plasma consisting substantially of an uncharged excited gaseous substance for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of... 2 Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; and the uniform silicone oil coating is exposed to a plasma consisting essentially of uncharged excited gaseous material for 0.1 to 10 seconds; wherein, compared to the inner surface of a plastic syringe barrel with a silicone oil coating, the number of particles larger than 8 micrometers in diameter in the inner surface of the plasma-treated plastic syringe barrel with the plasma-treated silicone oil coating is reduced by at least 75%, 80%, 85%, 90%, or 95%, respectively. The currently disclosed subject matter describes a method for producing a plastic syringe barrel with a stable silicone oil layer, comprising providing a plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a downstream plasma generated at atmospheric pressure for 0.1 to 10 seconds; and exposing the inner surface of the plastic syringe barrel to a plasma consisting of 0.005 to 0.5 mg / cm³ of activated gaseous material. 2 Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; and the uniform silicone oil coating is exposed to downstream plasma generated at atmospheric pressure for 0.1 to 10 seconds; wherein, compared to the inner surface of a plastic syringe barrel with a silicone oil coating, the number of particles with a diameter greater than 8 micrometers in the plasma-treated inner surface of the plasma-treated plastic syringe barrel with the plasma-treated silicone oil coating is reduced by at least 75%, 80%, 85%, 90%, or 95%, respectively. In some embodiments, the method further includes waiting for at least 10 minutes, 20 minutes, 30 minutes, 40 minutes, 1 hour, 2 hours, or 3 hours before exposing the uniform silicone oil coating to the plasma.

[0019] In some embodiments, the uncharged excited gaseous substance includes excited argon atoms. In some specific embodiments, the plastic is a cyclic olefin polymer (COP), a cyclic olefin copolymer (COC), polyethylene (PE), polycarbonate (PC), polypropylene (PP), or polyethylene terephthalate (PET). In some embodiments, the maximum filling volume of the plastic syringe is 1.0 ml, 0.5 ml, 0.3 ml, 0.25 ml, 0.10 ml, or 0.05 ml.

[0020] The currently disclosed subject matter describes a method for producing a syringe with a plastic syringe barrel having a stable polysiloxane lubricant coating. The method includes a method for generating the plastic syringe barrel described herein, and assembling the plastic syringe barrel with a plunger rod, a plunger stopper, and a needle. In some embodiments, the plastic syringe barrel contains a solution, and wherein for any particles with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particles with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml.

[0021] The currently disclosed subject describes a plastic syringe comprising a plastic barrel, a plunger rod, and a plunger stopper, wherein the plastic barrel has a stable silicone oil coating and is manufactured by the following steps: providing the plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a plasma consisting substantially of an uncharged excited gaseous substance for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of... 2 Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; and the uniform silicone oil coating is exposed to a plasma consisting essentially of uncharged excited gaseous matter; wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated silicone oil coating is ≤ 600 particles / 12 cm⁻¹. 2 ≤ 500 particles / 12 cm 2 Or ≤ 400 particles / 12 cm 2 The particle diameter is greater than 8 micrometers. The currently disclosed subject describes a plastic syringe comprising a plastic barrel, a plunger rod, and a plunger stopper, wherein the plastic barrel has a stable silicone oil coating and is manufactured by the following steps: providing the plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a downstream plasma generated at atmospheric pressure for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of [something unclear - possibly a specific concentration or concentration]. 2Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; and the uniform silicone oil coating is exposed to downstream plasma generated at atmospheric pressure; wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated silicone oil coating is ≤600 particles / 12 cm⁻¹. 2 ≤ 500 particles / 12 cm 2 Or ≤ 400 particles / 12 cm 2 The particles have a diameter greater than 8 micrometers.

[0022] The currently disclosed subject describes a plastic syringe comprising a plastic barrel, a plunger rod, and a plunger stopper, wherein the plastic barrel has a stable silicone oil coating and is manufactured by the following steps: providing the plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a plasma consisting substantially of an uncharged excited gaseous substance for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of... 2 Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; and the uniform silicone oil coating is exposed to a plasma consisting essentially of uncharged excited gaseous matter; wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated silicone oil coating is ≤ 100 particles / cm³. 2 ≤ 90 particles / cm 2 ≤ 50 particles / cm 2 ≤ 40 particles / cm 2 ≤ 35 particles / cm 2 or ≤ 30 particles / cm 2 The particle diameter is greater than 8 micrometers. The currently disclosed subject describes a plastic syringe comprising a plastic barrel, a plunger rod, and a plunger stopper, wherein the plastic barrel has a stable silicone oil coating and is manufactured by the following steps: providing the plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a downstream plasma generated at atmospheric pressure for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of [something unclear - possibly a specific concentration or concentration]. 2 Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; and the uniform silicone oil coating is exposed to downstream plasma generated at atmospheric pressure; wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated silicone oil coating is ≤ 100 particles / cm³. 2 ≤ 90 particles / cm 2 ≤ 50 particles / cm 2 ≤ 40 particles / cm 2 ≤ 35 particles / cm2 or ≤ 30 particles / cm 2 The particles have a diameter greater than 8 micrometers.

[0023] The currently disclosed subject describes a plastic syringe comprising a plastic barrel, a plunger rod, and a plunger stopper, wherein the plastic barrel has a stable silicone oil coating and is manufactured by the following steps: providing the plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a plasma consisting substantially of an uncharged excited gaseous substance for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of... 2 Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; and the uniform silicone oil coating is exposed to a plasma consisting essentially of uncharged excited gaseous matter; wherein, compared to the inner surface of a plastic syringe barrel with a silicone oil coating, the number of particles larger than 8 micrometers in diameter in the inner surface of the plasma-treated plastic syringe barrel with the plasma-treated silicone oil coating is reduced by at least 75%, 80%, 85%, 90%, or 95%, respectively. The currently disclosed subject matter describes a plastic syringe comprising a plastic barrel, a plunger rod, and a plunger stopper, wherein the plastic barrel has a stable silicone oil coating and is manufactured by the following steps: providing a plastic syringe barrel; exposing the inner surface of the plastic syringe barrel to a downstream plasma generated at atmospheric pressure for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of silicone oil to the inner surface of the syringe barrel. 2 Silicone oil is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform silicone oil coating; and the uniform silicone oil coating is exposed to downstream plasma generated at atmospheric pressure; wherein, compared with the inner surface of a plastic syringe barrel with a silicone oil coating, the number of particles with a diameter greater than 8 micrometers in the inner surface of the plasma-treated plastic syringe barrel with the plasma-treated silicone oil coating is reduced by at least 75%, 80%, 85%, 90%, or 95%, respectively.

[0024] In some embodiments, the plastic syringe includes a plastic syringe barrel containing a solution. In some embodiments, for any particles ≥ 10 μm in diameter, the particle content in the solution is ≤ 50 particles / ml, or for any particles ≥ 25 μm in diameter, the particle content in the solution is ≤ 5 particles / ml. In some embodiments, the plastic syringe includes a plastic syringe barrel containing a biological agent. In some embodiments, the plastic syringe includes a plastic syringe barrel containing a solution including an anticoagulant, vaccine, or recombinant protein. In some embodiments, the plastic syringe includes a plastic syringe barrel containing an anti-VEGF protein solution. In some embodiments, the plastic syringe includes a plastic syringe barrel containing a solution including pilgatanib, ranibizumab, aflibercept, or bevacizumab. In some embodiments, the plastic syringe includes a plastic syringe barrel containing an ophthalmic solution. In some embodiments, for any particles ≥ 10 μm in diameter, the particle content in the ophthalmic solution is ≤ 50 particles / ml, or for any particles ≥ 25 μm in diameter, the particle content in the ophthalmic solution is ≤ 5 particles / ml.

[0025] The currently disclosed subject describes a method for treating the eye, comprising administering a solution or ophthalmic solution intravitreally into the eye using a syringe produced by the method described herein.

[0026] Current syringes comprise a plasma-treated plastic syringe barrel coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma treatment consists essentially of an uncharged, excited gaseous substance, a plunger rod, a plunger stopper, and a needle; wherein the plastic syringe barrel contains a solution, and for any particles ≥10 μm in diameter, the particle content in the solution is ≤50 particles / ml, or for any particles ≥25 μm in diameter, the particle content in the solution is ≤5 particles / ml. The currently disclosed subject matter describes a method for treating an eye, comprising administering a solution intravitreally into the eye using a syringe. The syringe comprises a plasma-treated plastic syringe barrel coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma treatment is a downstream plasma generated at atmospheric pressure, comprising a plunger rod, a plunger stopper, and a needle; wherein the plastic syringe barrel contains a solution, and for any particles ≥10 μm in diameter, the particle content in the solution is ≤50 particles / ml, or for any particles ≥25 μm in diameter, the particle content in the solution is ≤5 particles / ml. The currently disclosed subject matter describes a method for treating an eye, comprising administering a solution intravitreally into the eye using a syringe. In some embodiments, the solution is an anti-VEGF protein solution. In some embodiments, the solution comprises an anticoagulant, a vaccine, or a recombinant protein. In some embodiments, the solution is an ophthalmic solution. In some embodiments, the solution comprises pilghatinib, ranibizumab, aflibercept, or bevacizumab. The currently disclosed subject matter describes a syringe comprising a plasma-treated plastic syringe barrel coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma treatment consists substantially of an uncharged excited gaseous substance, a Luer lock or sliding head, a plunger rod, and a plunger stopper; wherein the plastic syringe barrel contains a solution, and for any particles ≥10 μm in diameter, the particle content in the solution is ≤50 particles / ml, or for any particles ≥25 μm in diameter, the particle content in the solution is ≤5 particles / ml. The currently disclosed subject describes an syringe comprising a plasma-treated plastic syringe barrel coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma treatment is a downstream plasma generated at atmospheric pressure, comprising a Luer lock or sliding head, a plunger rod, and a plunger stopper; wherein the plastic syringe barrel contains a solution, and for any particles with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particles with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml.

[0027] The currently disclosed subject describes a plastic syringe barrel comprising a plasma-treated plastic syringe barrel coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma treatment consists substantially of an uncharged excited gaseous substance or each plasma treatment is a downstream plasma; and wherein the number of particles with a diameter greater than 8 micrometers in the inner surface of the plasma-treated plastic syringe barrel with the plasma-treated polysiloxane lubricant coating is reduced by at least 75%, 80%, or 95%, respectively, compared to the inner surface of the plastic syringe barrel with the plasma-treated polysiloxane lubricant coating.

[0028] The currently disclosed subject describes a plastic syringe barrel comprising a plasma-treated syringe barrel coated with a plasma-treated perfluoropolyether lubricant coating, wherein each plasma treatment consists substantially of an uncharged excited gaseous substance or each plasma treatment includes a downstream plasma; and wherein the surface density of the inner surface of the plasma-treated syringe barrel having the plasma-treated perfluoropolyether lubricant coating is ≤ 600 particles / 12 cm⁻¹. 2 ≤ 500 particles / 12 cm 2 Or ≤ 400 particles / 12 cm 2 The particles have a diameter greater than 8 micrometers.

[0029] The currently disclosed subject describes a plastic syringe barrel comprising a plasma-treated plastic syringe barrel coated with a plasma-treated perfluoropolyether lubricant coating, wherein each plasma treatment consists substantially of an uncharged excited gaseous substance or each plasma treatment includes a downstream plasma; and wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated perfluoropolyether lubricant coating is ≤ 100 particles / cm³. 2 ≤ 90 particles / cm 2 ≤ 50 particles / cm 2 ≤ 40 particles / cm 2 ≤ 35 particles / cm 2 or ≤ 30 particles / cm 2 The particles have a diameter greater than 8 micrometers.

[0030] The currently disclosed subject matter describes a syringe comprising a plastic syringe barrel, plunger rod, plunger stopper, and needle as described herein. In some embodiments, the plastic syringe contains a solution. In some embodiments, for any particles ≥ 10 μm in diameter, the particle content in the solution is ≤ 50 particles / ml, or for any particles ≥ 25 μm in diameter, the particle content in the solution is ≤ 5 particles / ml. In some embodiments, the plastic syringe barrel contains a solution comprising an anticoagulant, vaccine, or recombinant protein. In some embodiments, the plastic syringe barrel contains an antiVEGF protein solution comprising pilgartanib, ranibizumab, aflibercept, or bevacizumab. In some embodiments, the plastic syringe contains an ophthalmic solution. In some embodiments, the particle content in the ophthalmic solution is ≤ 50 particles / ml for any particles with a diameter ≥ 10 μm, or ≤ 5 particles / ml for any particles with a diameter ≥ 25 μm. The currently disclosed subject matter describes a method for treating an eye, comprising administering a solution or ophthalmic solution intravitreally into the eye using the syringe described herein.

[0031] The currently disclosed subject describes a method for producing a plastic syringe barrel with a stable lubricating layer, comprising providing the plastic syringe barrel, exposing the inner surface of the plastic syringe barrel to a plasma consisting substantially of an uncharged excited gaseous substance for 0.1 to 10 seconds; and applying 0.005 to 0.5 mg / cm³ of a plasma. 2 A perfluoropolyether is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform perfluoropolyether coating; and the uniform perfluoropolyether coating is exposed to a plasma consisting essentially of uncharged excited gaseous material for 0.1 to 10 seconds; wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated perfluoropolyether coating is ≤ 600 particles / 12cm³. 2 ≤ 500 particles / 12cm 2 ≤ 400 particles / 12cm 2 ≤ 100 particles / cm 2 ≤ 90 particles / cm 2 ≤ 50 particles / cm 2 ≤ 40 particles / cm 2 ≤ 35 particles / cm 2 or ≤ 30 particles / cm 2 The particles have a diameter greater than 8 micrometers.

[0032] The currently disclosed subject matter describes an injector comprising a plasma-treated plastic syringe barrel coated with a plasma-treated perfluoropolyether lubricant coating, wherein each plasma treatment consists essentially of an uncharged, excited gaseous substance, a plunger rod, a plunger stopper, and a needle; wherein the plastic syringe barrel contains a solution, and for any particles ≥10 μm in diameter, the particle content in the solution is ≤50 particles / ml, or for any particles ≥25 μm in diameter, the particle content in the solution is ≤5 particles / ml. The currently disclosed subject matter describes a method for treating an eye, comprising administering a solution intravitreally into the eye using the injector described herein. In some embodiments, the solution comprises an anticoagulant, a vaccine, or a recombinant protein, wherein the solution is an ophthalmic solution, and wherein the solution is an antiVEGF protein solution containing pegattatanib, ranibizumab, aflibercept, or bevacizumab.

[0033] The currently disclosed subject describes an syringe comprising a plasma-treated plastic syringe barrel coated with a plasma-treated perfluoropolyether lubricant coating, wherein each plasma treatment consists essentially of an uncharged excited gaseous substance, a Luer lock or sliding head, a plunger rod, and a plunger stopper; wherein the plastic syringe barrel contains a solution, and for any particles with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particles with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml. Attached Figure Description

[0034] The accompanying drawings, which are incorporated herein and constitute a part of this specification, illustrate various embodiments of the invention and, together with the specification, further serve to explain the principles of the invention and enable those skilled in the art to make and use the invention. In the drawings, the same reference numerals denote the same or functionally similar elements.

[0035] Figure 1A is an exploded perspective view (left) of the syringe, along with an illustration of the Luer slider (top) and Luer lock (bottom).

[0036] Figure 1B The image shows a cross-sectional view of the plastic syringe barrel and syringe head (left), and a cross-sectional view showing various surfaces (right).

[0037] Figure 1C-1 This is a bright-field image of the inner surface of an empty / unfilled COP syringe barrel without any coating.

[0038] Figure 1C-2 The images show corresponding dark-field images (left) of the inner surface of an empty / unfilled COP syringe barrel without any coating, and magnified views (right) of a portion of these dark-field images.

[0039] Figure 1D-1 This is a bright-field image of the inner surface of an empty / unfilled COP syringe barrel after spraying with 1000 cSt silicone oil.

[0040] Figure 1D-2 The images show corresponding dark-field images (left) of the inner surface of an empty / unfilled COP syringe barrel coated with silicone oil, and magnified views (right) of a portion of these dark-field images.

[0041] Figure 1E-1 This is a bright-field image of the inner surface of an empty / unfilled plasma-treated COP syringe barrel with plasma-treated silicone oil according to an embodiment of the present invention. The plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatment consisting essentially of uncharged excited gaseous substances.

[0042] Figure 1E-2 These are corresponding dark-field images (left) of the inner surface of an empty / unfilled plasma-treated COP syringe barrel with plasma-treated silicone oil according to an embodiment of the present invention, and a magnified view (right) of a portion of these dark-field images. The plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatments consisting essentially of uncharged, excited gaseous substances.

[0043] Figure 1F-1 These are magnified bright-field images of the inner surface of an empty / unfilled COP syringe barrel without any coating (left), the inner surface of an empty / unfilled COP syringe barrel with sprayed silicone oil (middle), and the inner surface of an empty / unfilled COP syringe barrel with plasma-treated silicone oil, according to embodiments of the present invention. The plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatment consisting essentially of uncharged excited gaseous substances (right).

[0044] Figure 1F-2 These are magnified dark-field images of the inner surface of an empty / unfilled COP syringe barrel without any coating (left), the inner surface of an empty / unfilled COP syringe barrel with sprayed silicone oil (middle), and the inner surface of an empty / unfilled COP syringe barrel with plasma-treated silicone oil, according to embodiments of the present invention. The plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatment consisting essentially of uncharged excited gaseous material (right).

[0045] Figure G-1 is a bright-field image of the inner surface of an empty / unfilled COP injector barrel with sprayed silicone oil after downstream plasma treatment.

[0046] Figure G-2 is a dark field image (left) of the inner surface of an empty / unfilled COP injector barrel coated with silicone oil after downstream plasma treatment, and a magnified view (right) of a portion of these dark field images.

[0047] Figure 1H-1 It is a bright-field image of the inner surface of an empty / unfilled COP syringe barrel with downstream plasma-treated silicone oil.

[0048] Figure 1H-2 The images show corresponding dark-field images (left) of the empty / unfilled inner surface of a COP injector barrel with downstream plasma-treated silicone oil, and magnified views (right) of a portion of these dark-field images.

[0049] Figure 1I These are dark field images of the inner surface of an empty / unfilled COP syringe barrel without any coating (left), the inner surface of an empty / unfilled COP syringe barrel with sprayed silicone oil after downstream plasma treatment (middle), and the inner surface of an empty / unfilled COP syringe barrel with plasma-treated silicone oil, according to an embodiment of the present invention. The plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatment consisting essentially of uncharged excited gaseous material (right).

[0050] Figure 1J These are dark field images of the inner surface of an empty / unfilled COP syringe barrel without any coating (left), the inner surface of an empty / unfilled COP syringe barrel with downstream plasma-treated silicone oil (middle), and the inner surface of an empty / unfilled plasma-treated COP syringe with plasma-treated silicone oil, according to an embodiment of the present invention, wherein the plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatment consisting essentially of uncharged excited gaseous material (right).

[0051] Figure 1K The images show dark field (left) and bright field (right) images of the inner surface of an empty / unfilled COP syringe barrel without any coating. Figure 1L These are dark field images (left) and bright field images (right) of the inner surface of an empty / unfilled COP syringe barrel after spraying with 1000 cSt silicone oil.

[0052] Figure 1MThese are bright-field images (left) and dark-field images (middle) of the inner surface of an empty / unfilled plasma-treated COP syringe barrel with plasma-treated silicone oil according to an embodiment of the present invention, and a magnified view (right) of a portion of these dark-field images. The plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatment consisting essentially of uncharged excited gaseous substances.

[0053] Figure 2 This is a bar graph comparing particle concentrations (particle count / mL) of ≥5 μm particles among the following biological solution sources: Avastin® directly from vials, BD U100 insulin syringes filled with Avastin®, Exel U100 insulin syringes filled with Avastin®, and general 0.25 ml syringes processed and filled with Avastin® according to the methods described herein.

[0054] Figure 3A This is a bar graph comparing particle concentrations (particle count / mL) of ≥ 10 μm particles among the following biological solution sources: Avastin® directly from vials, BD U100 insulin syringes filled with Avastin®, Exel U100 insulin syringes filled with Avastin®, and general 0.25 ml syringes processed and filled with Avastin® according to the methods described herein. Figure 3B yes Figure 3A A magnified view of the medium bar chart.

[0055] Figure 4A This is a bar graph comparing particle concentrations (particles / mL) of ≥ 25 μm particles among the following biological solution sources: Avastin® directly from vials, BD U100 insulin syringes filled with Avastin®, Exel U100 insulin syringes filled with Avastin®, and general 0.25 ml syringes processed and filled with Avastin® according to the methods described herein. Figure 4B yes Figure 4A A magnified view of the medium bar chart.

[0056] Figure 5 This is a bar graph comparing particle concentrations (particle count / mL) of ≥ 5 μm particles among the following biological solution sources: Avastin® directly from vials, filtered Avastin® directly from vials, a universal 0.25 ml syringe processed and filled with Avastin® according to the methods described herein, and a universal 0.25 ml syringe processed and filled with filtered Avastin® according to the methods described herein.

[0057] Figure 6This is a bar graph comparing particle concentrations (particle count / mL) of ≥ 10 μm particles among the following biological solution sources: Avastin® directly from vials, filtered Avastin® directly from vials, a universal 0.25 ml syringe processed and filled with Avastin® according to the methods described herein, and a universal 0.25 ml syringe processed and filled with filtered Avastin® according to the methods described herein.

[0058] Figure 7 This is a bar graph comparing particle concentrations (particles / mL) of ≥25 μm particles among the following biological solution sources: Avastin® directly from vials, filtered Avastin® directly from vials, a universal 0.25 ml syringe processed and filled with Avastin® according to the methods described herein, and a universal 0.25 ml syringe processed and filled with filtered Avastin® according to the methods described herein. Detailed Implementation

[0059] While the invention may be embodied in many different forms, it should be understood that this disclosure is intended to provide for embodiments that embody the principles of the invention, and such embodiments are not intended to limit the invention to the preferred embodiments described herein and / or those illustrated herein. The claimed subject matter may also be embodied in other ways, incorporating other existing or future techniques, including different steps or elements similar to those described in this document. Furthermore, although the term “step” may be used herein to imply different aspects of the method employed, it should not be construed as implying any particular order of the various steps disclosed herein, unless the order of the steps is explicitly described.

[0060] Embodiments of the invention will now be described more fully below with reference to the accompanying drawings, which illustrate some, but not all, of the embodiments of the invention. In fact, the invention may be embodied in many different forms and should not be construed as limited to the embodiments described herein; rather, these embodiments are provided so that this disclosure satisfies applicable legal requirements. The same numerals refer to elements throughout. Further details of the embodiments of the invention will be apparent to those skilled in the art. Although the invention has been described based on these preferred embodiments, it will be apparent to those skilled in the art that certain modifications, variations, and alternative constructions will be readily apparent while still remaining within the spirit and scope of the invention.

[0061] Now, let's describe the currently published topic in more detail.

[0062] Figure 1A-1Figure 1A is an exploded perspective view (left) of an exemplary syringe 20, and an illustration of a Luer sliding head (top) and a Luer lock head (bottom). Figure 1A shows a plastic syringe barrel 1, a syringe head 2, a plunger rod 3 inserted into the plastic syringe barrel and movable forward or backward along the length of the plastic syringe barrel, a plunger stop or seal 4 connected to the front of the plunger rod 3 and in airtight contact with a portion of the inner surface of the plastic syringe barrel as the plunger rod moves forward or backward, a needle 6 and a needle hub 5 connected to the syringe head 2, and a needle safety cap 7. In other embodiments, the syringe 20 does not include the needle 6, the needle hub 5 connected to the syringe head 2, and the needle safety cap 7. The illustration in Figure 1A shows two configurations of the syringe head 2: a Luer lock head 8 and a sliding head 9. The Luer lock head 8 provides a threaded male threaded fitting such that a female needle interface is screwed onto the Luer lock head. The sliding head 9 provides a male threaded fitting configured to allow the female needle interface to slide on and be mounted onto the sliding head. In one embodiment, the syringe includes a plastic syringe barrel, a plunger rod, a plunger stop, and a needle. In one embodiment, the needle is a fixed needle or pre-attached to the syringe barrel. In one embodiment, the needle is bonded to the syringe barrel. In one embodiment, the syringe includes a plastic syringe barrel, a Luer lock or sliding head, a plunger rod, and a plunger stop.

[0063] Figure 1A-2 Images (left) show an exemplary syringe including a plastic syringe barrel 1, syringe head 2, plunger rod 3, plunger stopper 4, and fixed (or pre-connected) needle 6a, needle safety cap 7, and plunger rear cover 15; and an exemplary syringe assembled with or covered with the needle safety cap 7 and plunger rear cover 15.

[0064] Figure 1B This is a cross-sectional view (left) of a plastic syringe barrel 1 and syringe head 15. The plastic syringe barrel 1 includes a proximal end 10, a distal end 11, and a cylindrical wall 12 extending between the proximal and distal ends. The cylindrical wall 12 of the syringe barrel has an inner surface 13 and defines a chamber 14 for receiving a substance (e.g., a solution). According to an embodiment of the invention, the inner surface 13 is the inner surface of a plasma-treated plastic syringe barrel having a plasma-treated silicone oil coating, or the inner surface of a plastic syringe barrel that is plasma-treated and coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma treatment consists substantially of an uncharged, excited gaseous substance. See, for example, Figures 1G and 1H. Figure 1BThe cross-sectional view on the right shows various surfaces: the inner surface of the plastic syringe barrel 17 to be plasma-treated and the internal space of the plastic syringe barrel 18; the plasma-treated plastic syringe barrel 19; the uniform polysiloxane lubricant coating 20 to be plasma-treated (e.g., a uniform silicone oil coating); the inner surface 21 of the plasma-treated plastic syringe barrel with a plasma-treated polysiloxane lubricant coating (e.g., a plasma-treated plastic syringe barrel with a plasma-treated silicone oil coating) from which surface density particle images and measurements are obtained; and the plasma-treated polysiloxane lubricant coating 22. The syringe barrel chamber 14 can be pre-filled with a drug, ophthalmic solution, biologic, or any other substance including water or diluent for reconstitution of the drug, in dry or liquid form. The distal end 11 of the syringe barrel is connected to a syringe head 15 having a channel 16 that extends through the distal end 11 of the syringe barrel and communicates with the syringe barrel chamber 14. The plunger rod 3 (as shown in Figure 1A) can extend into the proximal end 10 of the plastic syringe barrel 1, wherein the plunger stopper 4 slides within the cylindrical wall 12 of the chamber 14 in a fluid-tight engagement manner.

[0065] This document describes an exemplary embodiment of a method for generating a plastic syringe barrel with a stable polysiloxane lubricating layer, the method comprising the steps of: providing a plastic syringe barrel; exposing the inner surface of the plastic syringe barrel to a plasma consisting substantially of an excited gaseous substance without charge; applying a polysiloxane lubricant coating to the plasma-treated inner surface of the plastic syringe barrel to form a uniform polysiloxane lubricant coating; and exposing the uniform polysiloxane lubricant coating to the plasma consisting substantially of an excited gaseous substance without charge. This method surprisingly produces an extremely low surface density particle number on the inner surface of a plasma-treated plastic syringe barrel with a plasma-treated polysiloxane lubricant coating, wherein the plastic syringe barrel is unfilled or empty. In one embodiment, the number of particles larger than 8 micrometers in diameter is reduced by at least 95% on the inner surface of a plasma-treated plastic syringe barrel with a plasma-treated polysiloxane lubricant coating compared to the inner surface of a plastic syringe barrel with a polysiloxane lubricant coating. In one embodiment, the surface density of the inner surface of the plasma-treated plastic syringe barrel having a plasma-treated polysiloxane lubricant coating is ≤ 600 particles / 12cm³. 2 Among them, the particle diameter is greater than 8 micrometers. (e.g., "12 cm" as used in this article) 2 "12 cm²" is the approximate total surface area of ​​the inner surface of a 1 ml plastic syringe barrel, and the term "12 cm²" is used in this context. 2(This typically covers the total surface area of ​​the inner surface of a 1 ml plastic syringe barrel in various configurations). In one embodiment, the surface density of the inner surface of the plasma-treated plastic syringe barrel having a plasma-treated polysiloxane lubricant coating is ≤ 30 particles / cm³. 2 The particles have a diameter greater than 8 micrometers.

[0066] While it is well known that plasma treatment of plastics can enhance the wettability of fluids with reactive functional groups or polarity, plasma treatment of plastic surfaces is not common in industrial practice because the additional treatment step is inconvenient without any known significant advantages or superior lubricant stability. Importantly, those skilled in the art would not expect plasma treatment of plastics with commonly used silicone oil lubricants to enhance wettability; silicone oil lubricants are nonpolar and lack any reactive functional groups. Plastic materials such as polypropylene and other cyclic olefin polymers, commonly used in syringe manufacturing, are difficult to bond because they are hydrophobic, have poor surface wettability (low surface energy), lack any surface reactive functional groups, and are nonpolar. This non-reactive or inert nature of these plastics is crucial for maintaining the stability of pharmaceuticals in direct contact with the plastic material. Downstream plasma treatment of plastics slightly increases the surface energy of the plastic by generating functional groups on the surface, thereby improving wettability. However Because silicone oil is nonpolar and lacks any functional groups, those skilled in the art expect that minute changes in the wettability of the plastic will only provide an incremental improvement in the wettability of the silicone oil, without further improving the chemical bond between the plastic and the silicone oil. Due to the lack of adhesion between the silicone oil and the plastic surface, the lubricant can easily migrate under mechanical or chemical stress. Mechanical stress refers to the movement of the plunger rod within the syringe barrel, while chemical stress is the contact with polar fluids such as aqueous pharmaceutical products. Due to the significant surface energy difference between aqueous solutions and nonpolar and inert silicone oils, the lubricant tends to recede into droplets on the plastic surface to reduce the surface area for contact between the silicone oil and the drug fluid. Because there are no permanent chemical bonds between the silicone oil and the plastic, the silicone oil can easily migrate on or from the plastic surface into the drug solution. Consistent with these expectations, product development for plastic syringes no longer utilizes silicone oil or plasma treatment. This is evident in industry product development that typically focuses on silicone-free plastic syringes (e.g., West Daikyo Crystal Zenith (CZ®)) and plastic syringes using chemically crosslinked silicone oils (e.g., Schott TopPac®).

[0067] This publication confirms an unexpected result: the combination of plasma treatments for plastics described herein first increases the wettability of the silicone oil, causing the silicone layer to flatten into a thin film rather than remaining as discrete droplets or islands on the surface. Subsequent plasma treatment of the lubricating layer, as described herein, results in permanent cross-linking of the lubricating film to produce a permanent coating rather than cross-linked particles. The plasma-induced cross-linking of the lubricant prevents further flow of the silicone oil, which remains a uniform coating even under the aforementioned mechanical or chemical stresses. This, in turn, provides the unexpected result of silicone oil-lubricated plastic syringe barrels with extremely low particle numbers on the inner surface, and filled silicone oil-lubricated plastic syringe barrels with extremely low particle numbers in solution.

[0068] As used herein, "plasma composed substantially of uncharged excited gaseous matter" refers to plasmas limited to the listed uncharged excited gaseous matter and plasmas composed of potentially charged excited gaseous matter, without substantially affecting the fundamental and novel characteristics of plasmas composed substantially of uncharged excited gaseous matter. These fundamental and novel features are the ability to produce at least one of the following, as applicable or described in the corresponding claims: a polysiloxane-lubricated plastic syringe barrel having an inner surface with at least 95% fewer particles larger than 8 micrometers in diameter compared to the inner surface of a plastic syringe barrel having a polysiloxane lubricant coating; having a surface density ≤ 600 particles / 12cm². 2 A plastic syringe barrel with a polysiloxane-lubricated inner surface (for particles larger than 8 micrometers in diameter); having a surface density ≤ 50 particles / cm³. 2 A plastic syringe barrel with a polysiloxane-lubricated inner surface, wherein the particle diameter is greater than 8 micrometers; or a plastic syringe barrel with a polysiloxane-lubricated inner surface, which may contain a solution with a particle content of ≤ 50 particles / ml (for any particles with a diameter ≥ 10 µm) or ≤ 5 particles / ml (for any particles with a diameter ≤ 25 µm).

[0069] In one embodiment, the uncharged excited gaseous material comprises excited argon atoms. In one embodiment, the reactive gas is oxygen. In another embodiment, the reactive gas is air. In yet another embodiment, a mixture of the reactive gas and argon is used. In one embodiment, the method comprises exposing the inner surface of a plastic syringe barrel to a plasma consisting substantially of uncharged excited gaseous material for 0.1 to 10 seconds; and applying 0.005 mg / cm³ of oxygen. 2 Up to 0.5 mg / cm 2 Silicone oil is applied to the plasma-treated inner surface of the plastic syringe barrel to form a uniform silicone oil coating.

[0070] In one embodiment, the plastic syringe cartridge is composed of cyclic olefin polymer (COP), cyclic olefin copolymer (COC), polyethylene (PE), polycarbonate (PC), polypropylene (PP), or polyethylene terephthalate (PET). In one embodiment, the maximum filling volume of the plastic syringe cartridge is 10 ml, 3 ml, 1 ml, 0.5 ml, 0.3 ml, 0.25 ml, 0.10 ml, or 0.05 ml.

[0071] A method of manufacturing a plastic syringe barrel with a stable silicone oil layer includes exposing the inner surface of the plastic syringe barrel to a plasma consisting substantially of an uncharged, excited gaseous substance. In one embodiment, the plasma consisting substantially of an uncharged, excited gaseous substance is, for example, a downstream plasma generated by a configuration for plasma processing described in U.S. Patent No. 9,133,412. The downstream plasma configuration described in U.S. Patent No. 9,133,412 generates a gas flow having a mixture of uncharged, excited gaseous substance and charged substance at one location, and then allows a filtered or separated gaseous plasma rich in uncharged, excited gaseous substance to flow "downstream" to a second location where the article is plasma-treated. U.S. Patent No. 9,133,412 describes treating lubricants with downstream plasma and further describes how thermal and electronic energy can be locally released, almost instantaneously or through a continuous reaction process, by the excited gaseous substance creating reaction sites between lubricant molecules, potentially producing the desired material properties. Downstream plasma, which is essentially composed of uncharged excited gaseous matter, differs from the atmospheric plasma process described in U.S. Patent No. 7,553,529 and the vacuum plasma process described in U.S. Patent Application No. 14 / 347,677 and U.S. Patent Application No. 4,767,414; all of these describe a direct ionization plasma radiation process that may result in the retention of embedded charges at or near the treated surface and alter the material properties of the treated surface in different ways.

[0072] In one embodiment, the uncharged excited gaseous substance includes a high-energy neutral substance, a free radical, a neutral atom, or a molecule formed by the combination of electrons and ions, or excited inert gas atoms. In one embodiment, the free radical is a reactive gas atom or a polymerizable gas atom.

[0073] In one embodiment, the downstream plasma, or plasma consisting primarily of uncharged excited gaseous material, is partially generated by an initial gas flow containing an inert gas. In one embodiment, the inert gas is helium, neon, argon, or krypton. In one embodiment, the downstream plasma, or plasma consisting primarily of uncharged excited gaseous material, is partially generated by an initial gas flow containing an oxidizing gas. In one embodiment, the oxidizing gas is air, oxygen, carbon dioxide, carbon monoxide, water vapor, or a mixture thereof. In one embodiment, the downstream plasma, or plasma consisting primarily of uncharged excited gaseous material, is partially generated by an initial gas flow containing a non-oxidizing gas. In one embodiment, the non-oxidizing gas is nitrogen or hydrogen. In one embodiment, the downstream plasma, or plasma consisting primarily of uncharged excited gaseous material, is partially generated by an initial gas flow containing a gas mixture.

[0074] In one embodiment, the downstream plasma, or plasma consisting primarily of uncharged excited gaseous matter, is generated in part from a gas plasma and a mixture of charged and uncharged excited gaseous matter produced by microwave energy, high-voltage direct current (DC), radio frequency (RF) power, or thermal activation processes such as passing gas through a catalytic surface or heating wire. Examples of devices for generating excited gaseous matter include capacitively coupled plasma generators with two counter electrodes, inductively coupled plasma generators with coils surrounding the gas flow, microwave generators electrically coupled to a power source to generate electromagnetic radiation that excites the gas flow, and catalysts comprising wires or other resistive materials coupled to the power source.

[0075] In one embodiment, the downstream plasma, or plasma consisting primarily of uncharged excited gaseous matter, is partially separated or filtered from ions, electrons, and other charged matter by means of one or more electrostatic or electromagnetic fields via electrical grounding (e.g., by one or more wires, gates, grids, or any other conductive and electrically groundable structure known in the art), or by means of neutralizing charged matter in the gas stream via recombination in a transfer region.

[0076] In one embodiment, the downstream plasma, or plasma consisting essentially of uncharged excited gaseous material, is generated in a vacuum (typically less than about 200 Torr) or at about atmospheric pressure (typically about 760 Torr).

[0077] The method for producing plastic syringe barrels using a stable polysiloxane lubricant further includes applying the polysiloxane lubricant to a plasma-treated inner surface of the plastic syringe barrel to form a uniform polysiloxane lubricant coating. In one embodiment, the method includes applying 0.005 mg / cm³ of the lubricant. 2 Up to 0.05 mg / cm2 The polysiloxane lubricant is applied to the plasma-treated inner surface of a plastic syringe barrel. In one embodiment, the polysiloxane compound is a silicone oil of dimethylpolysiloxane having the following general chemical structure:

[0078] The number of repeating siloxane units (n) in the polymer chain determines the molecular weight and viscosity of the silicone oil. As the number of siloxane units increases, the polymer becomes longer, and both the molecular weight and viscosity increase. Typically, silicone oils have a usable viscosity range of about 5 to 100,000 centiliters at ambient temperature. Preferably, the polysiloxane lubricant has a viscosity of about 1,000 to 12,500 centiliters at ambient temperature. Preferably, the polysiloxane lubricant is polydimethylsiloxane (PDMS), which has a viscosity of 1,000 centiliters at ambient temperature. In another embodiment, the method includes the use of other non-silicone inert lubricants. These include inert fluorinated chemical lubricants, such as perfluoropolyethers (PFPEs). A representative example of commercially available PFPEs includes Fomblin M from Solvay Solexis. ® Fomblin Z ® Fomblin Y ® Series of lubricants; Krytox from DuPont (EIdu Pont de Nemours and Company) ® A range of lubricants; and Demnum from Daikin Industries, Ltd. ® A uniform coating can be achieved by heating the lubricant before application, adding solvent, or mechanically wiping the lubricant after spraying.

[0079] Lubricants can be used in diluted or undiluted form, or in combinations of diluted or undiluted lubricants. In embodiments, silicone oil lubricants are applied as aqueous dispersions or emulsions. Any suitable solvent can be used as a diluent compatible with the lubricant or lubricant combination used. Lubricants can be diluted to facilitate the application of a thin film of lubricant to the surface of an object. The amount or weight percentage of lubricant diluted in the lubricant-solvent solution is not essential for the performance of the invention. When using a solvent, the weight percentage of lubricant in the solvent can be greater than or equal to about 0.1%, for example, 1%, 10%, 20%, 30%, 40%, and 50%. The weight percentage of lubricant in the solvent can also be less than or equal to about 95%, for example, 90%, 80%, 70%, and 60%. The diluent solvent evaporates before exposure to downstream plasma or plasma consisting substantially of uncharged excited gaseous material.

[0080] A method for producing a plastic syringe barrel with a stable polysiloxane lubricant further includes exposing a uniform silicone oil coating to a downstream plasma or a downstream plasma consisting substantially of uncharged excited gaseous material. The term "plasma consisting substantially of uncharged excited gaseous material" is as described above. In one embodiment, the surface density of the inner surface of the plasma-treated plastic syringe barrel with the plasma-treated polysiloxane lubricant coating is ≤ 600 particles / 12cm³. 2 (For any particles larger than 8 micrometers in diameter). In one embodiment, the surface density of the inner surface of the plasma-treated plastic syringe barrel having a plasma-treated polysiloxane lubricant is ≤ 40 particles / cm³. 2 (For any particles with a diameter greater than 8 micrometers). In one embodiment, the resulting inner surface of a plasma-treated plastic syringe barrel with a plasma-treated polysiloxane lubricant coating has at least a 95% reduction in the number of particles compared to the inner surface of a plastic syringe barrel with silicone oil.

[0081] In another embodiment, the method of generating a plastic syringe barrel with a stable polysiloxane-based lubricating layer further includes assembling the plastic syringe barrel with the stable polysiloxane-based lubricating layer with a plunger rod, a plunger stopper, and a needle. Due to the surprisingly low particle count on the inner surface of the syringe and in the solution, the plastic syringe according to embodiments of the invention is particularly advantageous for user-fillable syringes (which require more plunger rod movement to aspirate and deliver medication) and pre-filled ophthalmic syringes (which are adjusted to ensure extremely low subvisible particle content).

[0082] In one embodiment, the syringe contains a solution comprising a biological agent. In one embodiment, the syringe contains an ophthalmic solution. In one embodiment, the syringe contains an ophthalmic solution or a solution comprising a biological agent, and for any particles ≥ 10 μm in diameter, the particle content in the solution is ≤ 50 particles / ml, or for any particles ≥ 25 μm in diameter, the particle content in the solution is ≤ 5 particles / ml.

[0083] This document describes an exemplary embodiment of a plastic syringe comprising a plastic barrel, a plunger rod, a plunger stopper, and a needle, wherein the plastic barrel has a stable polysiloxane lubricating layer and is manufactured by the following steps: exposing the inner surface of the plastic syringe barrel to a plasma consisting substantially of an uncharged excited gaseous substance for 0.1 to 10 seconds; and introducing 0.005 mg / cm³ of plasma into the syringe barrel. 2 Up to 0.5 mg / cm 2A polysiloxane lubricant coating is applied to the plasma-treated inner surface of a plastic syringe barrel to form a uniform polysiloxane lubricant coating; and the uniform polysiloxane lubricant coating is exposed to a plasma consisting essentially of uncharged excited gaseous material. Advantageously, the surface density of particles with a diameter greater than 8 micrometers on the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated polysiloxane lubricant coating is ≤ 600 particles / 12 cm. 2 Advantageously, the surface density of particles larger than 8 micrometers in diameter on the inner surface of the plasma-treated plastic syringe barrel containing a plasma-treated polysiloxane lubricant is ≤ 40 particles / cm³. 2 Advantageously, the inner surface of a plasma-treated plastic syringe barrel with plasma-treated silicone oil has at least 95% fewer particles compared to the inner surface of a plastic syringe barrel with silicone oil.

[0084] This document describes an exemplary embodiment of a plastic syringe barrel comprising plasma-treated and coated with a plasma-treated polysiloxane lubricant coating, wherein each plasma is a downstream plasma generated at atmospheric pressure; and wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated polysiloxane lubricant coating is ≤ 600 particles / 12 cm⁻¹. 2 ≤ 500 particles / 12 cm 2 Or ≤ 400 particles / 12 cm 2 The particles have a diameter greater than 8 micrometers.

[0085] This document further describes an exemplary embodiment of a syringe comprising a plastic syringe barrel containing a plasma-treated and plasma-coated polysiloxane lubricant coating, wherein each plasma treatment consists substantially of an uncharged, excited gaseous substance; and wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated polysiloxane lubricant coating is ≤ 100 particles / cm³. 2 ≤90 particles / cm 2 ≤ 50 particles / cm 2 ≤ 40 particles / cm 2 ≤ 35 particles / cm 2 or ≤ 30 particles / cm 2 The particles have a diameter greater than 8 micrometers; the syringe further includes a plunger rod, a plunger stopper, and a needle.

[0086] This document further describes an exemplary embodiment of a syringe comprising a plastic syringe barrel containing a plasma-treated and plasma-coated polysiloxane lubricant coating, wherein each plasma treatment consists substantially of an uncharged, excited gaseous substance; and wherein the surface density of the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated polysiloxane lubricant coating is ≤ 100 particles / cm³. 2 ≤90 particles / cm 2 ≤ 50 particles / cm 2 ≤ 40 particles / cm 2 ≤ 35 particles / cm 2 or ≤ 30 particles / cm 2 The syringe further includes a Luer lock head, a sliding head, a plunger rod, and a plunger stopper. In one embodiment, the 0.25 ml plastic syringe cartridge contains about 50 micrograms to about 500 micrograms of silicone oil. In one embodiment, the plastic cartridge contains a solution, and for any particles ≥ 10 μm in diameter, the particle content in the solution is ≤ 50 particles / ml, or for any particles ≥ 25 μm in diameter, the particle content in the solution is ≤ 5 particles / ml. In one embodiment, the plastic cartridge contains a solution comprising a biological agent. In one embodiment, the biological agent is an anticoagulant, a vaccine, or a recombinant protein. In one embodiment, the biological agent is pilghatinib, ranibizumab, aflibercept, or bevacizumab. In one embodiment, the plastic cartridge contains an ophthalmic solution, and for any particles ≥ 10 μm in diameter, the particle content in the ophthalmic solution is ≤ 50 particles / ml, or for any particles ≥ 25 μm in diameter, the particle content in the ophthalmic solution is ≤ 5 particles / ml. In one embodiment, the maximum filling volume of the plastic syringe cartridge is 1 ml, 0.5 ml, 0.3 ml, 0.25 ml, 0.10 ml, or 0.05 ml. Further described herein is a method of treating an eye, comprising administering an ophthalmic solution intravitreally into the eye using a plastic syringe according to the embodiment described herein.

[0087] Example 1: Extremely low particle count on the inner surface of a plastic syringe barrel Materials / Methods: Prepare COP syringe barrels, COP syringe barrels with sprayed silicone oil and downstream plasma treated COP syringe barrels with downstream plasma treated silicone oil.

[0088] Step 1: Plasma treatment of the COP syringe barrel: Treat a 1 ml COP syringe with downstream plasma.

[0089] a. Syringe form - 1 ml Luer lock.

[0090] b. Use a gas - argon.

[0091] c. Gas flow rate - 3 standard liters per minute, continuously flowing through the syringe barrel. The pressure inside the syringe barrel is approximately atmospheric pressure because no head cap is installed on the syringe during downstream plasma treatment. The gas flow direction starts from the flange end and the gas exits from the Luer end. The syringe is allowed to be purged with argon for 2 seconds.

[0092] d. Downstream plasma starts 1.5 seconds.

[0093] Step 2: Apply silicone oil to two plasma-treated COP syringe barrels: Using an IVEK Sonicair spray instrument, apply 1000 cSt of Dow Corning DC360 medical fluid to the inner surface of the COP syringe barrel. Heat the nozzle to 150°F (approximately 66°C). Spray a total of 0.4 μL of DC360 oil into a 1 ml COP syringe at a rate of 0.4 μL / s. The total spray duration is 1 second. During the spraying step, the syringe barrel is simultaneously moved vertically so that the nozzle enters the syringe barrel, thereby creating a uniform spray pattern along the inner surface of the syringe barrel. Adjust the start and stop positions of the syringe barrel during the spraying process to achieve uniform spray coverage.

[0094] Step 3: Plasma treatment of COP syringe barrels containing silicone oil: a. Use a gas - argon.

[0095] b. Gas flow rate - 3 standard liters per minute, continuously flowing through the syringe barrel. The pressure inside the syringe barrel is approximately atmospheric pressure because no head cap is installed on the syringe during downstream plasma treatment. The gas flow direction starts from the flange end and the gas exits from the Luer end. The syringe is allowed to be purged with argon for 2 seconds.

[0096] c. Downstream plasma is initiated 0.5 seconds later.

[0097] Zebrasci Flex-S imaging: The inner surface of each sample COP syringe barrel was imaged using a camera-based inspection tool, the ZebraSci Flex S benchtop combined spray system, methods, and algorithms. The imaging system imaged each syringe barrel, capturing multiple high-resolution images of the syringe (note that for plasma-treated COP syringe barrels coated with silicone oil, images were captured after silicone oil application). The imaging system utilized a backlight paired with a photomask and camera; the mask generated a light pattern with alternating dark and bright areas to detect changes in refractive index. Bright-field images were generated, where light was reflected into the camera, and dark-field images were generated, where light was reflected away from the camera. The imaging system identified the edge definitions of silicone oil droplets or particles on the surface by stitching together multiple images to reveal the entire mapped surface of the syringe. See Figures 1C-H and... Figure 1J In each of these images, multiple vertical rows represent images of the same syringe barrel. Each row is a stitched or compiled image of multiple images (approximately 18 images) taken at different rotations of the syringe barrel (6 vertical, 6 horizontal, and 6 z-directions).

[0098] Example 1a Samples: Empty / unfilled uncoated COP injector barrels (no steps), empty / unfilled COP injector barrels with sprayed silicone oil (COP injector barrels treated with step 2), and empty / unfilled downstream plasma-treated COP injector barrels with downstream plasma-treated silicone oil (COP injector barrels treated with steps 1 to 3). For COP injector barrels with sprayed silicone oil, Zebrasci images were taken 0–10 minutes after spraying. For COP injector barrels with downstream plasma-treated silicone oil, the time shift was 30 minutes to 1 hour between steps 2 and 3. The inner surface of the injector barrels was imaged using the ZebraSci Flex S benchtop combined spray system, methods, and algorithms.

[0099] Example 1b: Samples: Empty / unfilled COP injector barrels with sprayed silicone oil (COP injector barrels treated with steps 1 and 2); empty / unfilled COP injector barrels with downstream plasma-treated silicone oil (COP injector barrels treated with steps 2 and 3); empty / unfilled downstream plasma-treated COP injector barrels with downstream plasma-treated silicone oil (COP injector barrels treated with steps 1 to 3). Time shift of 0–10 minutes between steps 2 and 3 was applied to the downstream plasma-treated COP injector barrels with downstream plasma-treated silicone oil. The inner surface of the injector barrels was imaged using the ZebraSci Flex S benchtop combined spray system, method, and algorithm.

[0100] Predictive Example 1c:Sample: Multiple downstream plasma-treated COP syringe barrels (COP syringe barrels treated in steps 1 to 3) containing downstream plasma-treated silicone oil. Test processing times, including the following:

[0101] The inner surface of the syringe barrel was imaged using the ZebraSci Flex S benchtop combined spray system, methods, and algorithms.

[0102] Particle count in solution measurement: Syringe filled with water for injection (WFI). Particles in solution were measured using photoresist method with an Accusizer 780 device and microfluidic imaging with an MFI 5200 device. Measurements were performed according to the standard USP particle measurement protocol or the instrument manufacturer's recommended settings. Particle testing involved filling the syringe to 0.05 ml through the syringe needle, dispensing the solution into a clean tube at time 0, diluting the contents to 5 ml with WFI, allowing the tube to stand for approximately 1 hour to reduce air bubbles, and vortexing the tube before measurement. Particle analysis by MFI included analyzing the images to identify particle types. Silicone oil droplets had an aspect ratio ≥ 0.85; other particles had an aspect ratio < 85. The unique processing time further improved and reduced particle count in solution because the short time shift between steps 1 and 2 allowed the generated surface functional groups to be utilized, while the longer time shift between steps 2 and 3 allowed the silicone oil to flatten on the surface before final plasma treatment.

[0103] Example 1d: Calculation of surface density particle count: Samples: Uncoated COP syringe barrel (no steps), COP syringe barrel with sprayed silicone oil (COP syringe barrel treated with step 2), and COP syringe barrel with downstream plasma treated silicone oil (COP syringe barrel treated with steps 1 to 3).

[0104] Images of the inner surface of these syringe barrel samples were obtained using the Flex S benchtop combined spray system, methods, and algorithms. These images were then further characterized using the system to count the number of particles and provide particles / cm². 2 The surface density measurement value. The system resolution for particle counting is 7.33 micrometers / pixel; therefore, the smallest particle size measured is 7.33 micrometers.

[0105] Example 1a result: Images of the inner surface of an empty / unfilled, uncoated COP syringe barrel, the inner surface of an empty / unfilled COP syringe barrel coated with silicone oil, and the inner surface of an empty / unfilled, downstream plasma-treated COP syringe barrel with downstream plasma-treated silicone oil are shown below. Features caused by silicone oil droplets (white) are more easily visualized in dark-field images. These droplets present on the surface are referred to as surface particles.

[0106] Figure 1C-1 This is a bright-field image of the inner surface of an empty / unfilled COP syringe barrel without any coating.

[0107] Figure 1C-2 The images show corresponding dark-field images (left) of the inner surface of an empty / unfilled COP syringe barrel without any coating, and magnified views (right) of a portion of these dark-field images.

[0108] Figure 1D-1 This is a bright-field image of the inner surface of an empty / unfilled COP syringe barrel after spraying with 1000 cSt silicone oil.

[0109] Figure 1D-2 These are corresponding dark-field images (left) of the inner surface of an empty / unfilled COP syringe barrel coated with silicone oil, and a magnified view (right) of a portion of these dark-field images. Numerous microdroplets of silicone oil are shown, which are considered droplet features on the inner surface of the syringe.

[0110] Figure 1E-1 This is a bright-field image of the inner surface of an empty / unfilled plasma-treated COP syringe barrel with plasma-treated silicone oil according to an embodiment of the present invention. The plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatments consisting essentially of uncharged, excited gaseous substances.

[0111] Figure 1E-2 These are corresponding dark-field images (left) of the inner surface of an empty / unfilled plasma-treated COP syringe barrel with plasma-treated silicone oil according to an embodiment of the present invention, and a magnified view (right) of a portion of these dark-field images. The plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatments consisting essentially of uncharged excited gaseous substances.

[0112] Figure 1F-1These are magnified bright-field images of the inner surface of an empty / unfilled COP syringe barrel without any coating (left), the inner surface of an empty / unfilled COP syringe barrel with sprayed silicone oil (middle), and the inner surface of an empty / unfilled COP syringe barrel with plasma-treated silicone oil, according to an embodiment of the present invention. The plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatment consisting essentially of uncharged excited gaseous substances (right).

[0113] Figure 1F-2 These are magnified dark-field images of the inner surface of an empty / unfilled COP syringe barrel without any coating (left), the inner surface of an empty / unfilled COP syringe barrel with sprayed silicone oil (middle), and the inner surface of an empty / unfilled COP syringe barrel with plasma-treated silicone oil, according to embodiments of the present invention. The plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatments consisting essentially of uncharged, excited gaseous substances (right). As shown, the inner surface of the empty / unfilled plasma-treated COP syringe barrel with plasma-treated silicone oil is surprisingly comparable to the inner surface of the empty / unfilled plasma-treated COP syringe barrel without any coating (which has no silicone oil droplets). As shown, the particle count in the inner surface of the empty / unfilled plasma-treated COP syringe barrel with plasma-treated silicone oil is surprisingly reduced by at least 95% compared to the inner surface of the empty / unfilled COP syringe barrel with sprayed silicone oil.

[0114] Results of Example 1b: Images of the inner surfaces of empty / unfilled COP injector barrels (processed with steps 1 and 2) with sprayed silicone oil, empty / unfilled COP injector barrels (processed with steps 2 and 3) with sprayed silicone oil, and empty / unfilled COP injector barrels (processed with steps 1 to 3) with sprayed silicone oil are shown in the figures below. Features caused by silicone oil droplets (white) are more easily visualized in dark-field images. These droplets present on the surface are referred to as surface particles.

[0115] Figure G-1 is a bright-field image of the inner surface of an empty / unfilled COP injector barrel with sprayed silicone oil after downstream plasma treatment.

[0116] Figure G-2 is a dark field image (left) of the inner surface of an empty / unfilled COP injector barrel coated with silicone oil after downstream plasma treatment, and a magnified view (right) of a portion of these dark field images.

[0117] Figure 1H-1 It is a bright-field image of the inner surface of an empty / unfilled COP syringe barrel with downstream plasma-treated silicone oil. Figure 1H-2 The images show corresponding dark-field images (left) of the inner surface of an empty / unfilled COP syringe barrel with downstream plasma-treated silicone oil, and a magnified view (right) of a portion of these dark-field images. Figure 1I These are dark field images of the inner surface of an empty / unfilled COP syringe barrel without any coating (left), the inner surface of an empty / unfilled COP syringe barrel with sprayed silicone oil after downstream plasma treatment (middle), and the inner surface of an empty / unfilled COP syringe with plasma-treated silicone oil, according to an embodiment of the present invention, wherein the plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatments consisting essentially of uncharged, electrically charged substances (right).

[0118] Figure 1J These are dark field images of the inner surface of an empty / unfilled COP syringe barrel without any coating (left), the inner surface of an empty / unfilled COP syringe barrel with downstream plasma-treated silicone oil (middle), and the inner surface of an empty / unfilled plasma-treated COP syringe barrel with plasma-treated silicone oil, according to an embodiment of the present invention, wherein the plasma treatment of the COP syringe barrel and the plasma treatment of the silicone oil are each plasma treatment consisting essentially of uncharged excited gaseous material (right).

[0119] Results of Example 1d: The following surface density particle counts were obtained: inner surface of empty / unfilled uncoated COP syringe barrels (without steps), inner surface of empty / unfilled COP syringe barrels with sprayed silicone oil (COP syringe barrels treated in step 2), and inner surface of empty / unfilled downstream plasma-treated COP syringe barrels with downstream plasma-treated silicone oil (COP syringe barrels treated in steps 1 to 3). Figure 1K The images show dark-field (left) and bright-field (right) images of the inner surface of an empty, uncoated COP syringe barrel. The corresponding surface density particle count on the inner surface of the empty, uncoated COP syringe barrel is 3 particles / cm². 2 .

[0120] Figure 1L These are dark-field (left) and bright-field (right) images of the inner surface of an empty COP syringe barrel after spraying with 1000 cSt silicone oil. The corresponding surface density particle count on the inner surface of the empty COP syringe barrel with silicone oil spraying is 31,419 particles / cm². 2 .

[0121] Figure 1M These are bright-field images (left) and dark-field images (right) of the inner surface of an empty plasma-treated COP injector barrel with plasma-treated silicone oil according to an embodiment of the present invention, and a magnified view (right) of a portion of these dark-field images. The plasma treatment of the COP injector barrel and the plasma treatment of the silicone oil are each plasma treatments consisting essentially of uncharged, excited gaseous substances. On the inner surface of the empty downstream plasma-treated COP injector barrel with downstream plasma-treated silicone oil, the corresponding surface density particle count is 30 particles / cm². 2 .

[0122] Example 2 - Particle counting using WFI The test was conducted on a 0.25 mL polypropylene syringe with a 31G needle attached. The syringe type tested was: - Becton Dickenson U100 insulin injector, and - A general-purpose 0.25 ml StaClear syringe is used as an embodiment of the present invention and is processed as described below.

[0123] Process a 0.25 ml polypropylene syringe according to the following steps: - A plastic cartridge (containing no silicone oil lubricant) is used for downstream plasma treatment, consisting primarily of an excited gaseous substance that is essentially uncharged. Argon gas is purged into the syringe cartridge at a rate of 3 standard liters per minute. After a purging time of at least 1 second, the downstream plasma is excited for a treatment time of 1.5 seconds.

[0124] - Using an IVEK Sonicair spraying system, apply 1000 cSt Dow Corning DC360 silicone oil to the downstream plasma-treated inner surface of the plastic syringe barrel. Heat the nozzle to 150°F (approximately 66°C) and spray 0.15 µL of total lubricant evenly onto the inside of the syringe barrel at a rate of 0.15 µL / s. Simultaneously move the syringe and spray trigger vertically so that the nozzle is inserted into the syringe barrel to evenly cover the spray.

[0125] The lubricated inner surface of the plastic syringe is then treated with downstream plasma, which consists primarily of an uncharged, excited gaseous substance. Argon gas is purged into the syringe barrel at a rate of 3 standard liters per minute. After a purging time of at least 1 second, the downstream plasma is excited for a treatment time of 0.5 seconds.

[0126] Ten syringes of each syringe were filled with water for injection (WFI). Particles in the solution were measured using light obscuration with an Accusizer 780 device and microfluidic imaging with an MFI 5200 device. Measurements were performed according to the standard USP particle measurement protocol or the instrument manufacturer's recommended settings. Particle testing involved filling the syringe to 0.05 ml through the syringe needle, dispensing the solution into a clean tube [at time 0], diluting the contents to 5 ml with WFI, allowing the tube to stand for approximately 1 hour to reduce air bubbles, and vortexing the tube before measurement. Particle analysis with MFI included analyzing the images to identify particle types. Silicone oil droplets had an aspect ratio ≥ 0.85; other particles had an aspect ratio < 85.

[0127] Table 1 below reports the light obscuration method measurement of the cumulative particle concentration (particles / mL) of ≥ 2 μm particles, ≥ 5 μm particles, ≥ 10 μm particles, ≥ 25 μm particles, and ≥ 50 μm particles between the following solution sources: WFI stock solution in a clean container, a BD U100 insulin syringe filled with WFI, and a StaClear 0.25 ml syringe processed and filled with WFI according to the above method.

[0128] Table 1: Optical Obscuration Method

[0129] Table 2 below reports the MFI method measurement of cumulative particle concentration (particles / mL) for ≥ 2 μm, ≥ 5 μm, ≥ 10 μm, ≥ 25 μm, and ≥ 50 μm particles between the following solution sources: WFI stock solution in a clean container, a BD U100 insulin syringe filled with WFI, and a StaClear universal 0.25 ml syringe processed and filled with WFI according to the above method.

[0130] Table 2: Microfluidic Imaging

[0131] Example 3 - Particle counting using Avastin The test was performed on a 0.25 mL polypropylene syringe with a 31G needle attached. Avastin (bevacizumab) is supplied in 4 mL glass vials. The syringe type used for the test was: -Becton Dickenson U100 insulin injector -Exel U100 insulin injector, and - (TL) Universal 0.25 ml Syringe Process a general-purpose 0.25 ml syringe according to the teachings outlined in Example 1: Each syringe contains 32 syringes filled with 25 mg / ml bevacizumab (Avastin®). Particles in the solution are measured using microfluidic imaging with the MFI 5200 device. The MFI 5200 device is capable of measuring particles in the range of 1 μm to 70 μm in size and distinguishes sub-visible particles by subgroups (protein aggregates, silica droplets, or bubbles).

[0132] a. First, perform a particle test on the Avastin solution in the vial to obtain a baseline measurement of particles before filling the syringe. Transfer 0.1 ml of Avastin from the vial to another clean container. Allow the container to stand for 1 hour to eliminate any air bubbles. Then, using a vortex mixer, vortex the solution in the clean container to the minimum setting to suspend any particles back into the solution. This solution is then introduced into the MFI instrument for particle measurement. The result gives the baseline particle content in the Avastin stock solution.

[0133] b. Syringe test - Fill the syringe with Avastin to the 0.1 ml mark through the syringe needle.

[0134] c. Within one minute, Avastin from the filled syringe is expelled into a clean, particle-free container.

[0135] d. After draining the Avastin solution into the container, let it stand for 1 hour to eliminate any air bubbles.

[0136] e. Mix the fluid using a vortex mixer at its lowest setting before measurement to suspend any generated particles back into the solution. f. The solution is then introduced into the MFI instrument for particle measurement.

[0137] Particle analysis involves analyzing images to identify particle types. Silicone oil droplets have an aspect ratio ≥ 0.85; other particles have an aspect ratio < 85. The MFI instrument can apply an aspect ratio filter to identify spherical particles, which are typically lubricating oil particles or other shapes associated with protein aggregates. This aspect ratio filter is used to distinguish lubricating oil particles labeled as silicon in the image from other protein aggregates (…). Figure 2-7 ).

[0138] Figure 2This is a bar graph comparing the particle concentration (particle count / mL) of ≥5 μm particles among the following biological solution sources: Avastin® vials, BD U100 insulin syringes filled with Avastin®, Exel U100 insulin syringes filled with Avastin®, and universal 0.25 ml syringes (TL) treated and filled with Avastin® according to the teachings of this example. Figure 2 As shown, for any particle with a diameter ≥ 5 μm, the TL universal 0.25 ml syringe surprisingly has a total of 1330 particles (silicone particles and other particles) / mL.

[0139] Figure 3A This is a bar graph comparing the particle concentration (particle count / mL) of ≥10 μm particles among the following biological solution sources: Avastin® vials, BD U100 insulin syringes filled with Avastin®, Exel U100 insulin syringes filled with Avastin®, and TL universal 0.25 ml syringes (TL) processed and filled with Avastin® according to the method described in this example. Figure 3A and Figure 3B (yes Figure 3A As shown in the enlarged view of the medium bar graph, the TL universal 0.25 ml syringe surprisingly has a total of 50 particles (silicone particles and other particles) / mL for any particle with a diameter ≥ 10 μm.

[0140] Figure 4A This is a bar graph comparing the particle concentration (particle count / mL) of ≥ 25 μm particles among the following biological solution sources: Avastin® stock solution from vials, BD U100 insulin syringes filled with Avastin®, Exel U100 insulin syringes filled with Avastin®, and universal 0.25 ml syringes (TL) treated and filled with Avastin® according to the teachings of this example. Figure 4A and Figure 4B (yes Figure 4A As shown in the enlarged view of the medium bar graph, the TL universal 0.25 ml syringe surprisingly has a total of <7 particles (silicone particles and other particles) / mL for any particles with a diameter ≥ 25 μm. This is because the Avastin stock solution itself does not meet the USP 789 guideline regarding particle size. ≥ The number of particles with a diameter of 10 micrometers is less than 50 / ml, and the particle size is... ≥ The number of 25-micron particles is less than 5 per ml, therefore the Avastin solution needs to be filtered.

[0141] Example 4 - Particle counting using filtered Avastin® like Figure 4AAs shown, the Avastin® solution in the vial has a certain particle count. In this embodiment, the Avastin® solution from the vial is filtered through a 5 μm filter needle before filling the syringe.

[0142] In this embodiment, 0.25 ml universal syringes (TL) were processed according to the coating conditions described in Example 1. A total of 64 syringes were divided into two groups. One group was filled with unfiltered Avastin solution in vials, and the second group was filled with filtered Avastin solution.

[0143] Measure the baseline particle content in the Avastin solutions before and after filtration. For unfiltered Avastin, remove 0.1 ml from the vial and transfer it to a clean, particle-free container. For filtered Avastin, withdraw 0.1 ml of solution from the vial through a BD 5-micron filter needle and transfer it to a clean, particle-free container. Let both containers stand for 1 hour to eliminate air bubbles. Vortex them using minimal settings before introducing them into the MFI for measurement to resuspend any particles back into the solution. This constitutes the baseline particle content for unfiltered and filtered Avastin.

[0144] Thirty-two 0.25 ml syringes prepared according to the teaching protocol were filled with 25 mg / ml bevacizumab (Avastin®) to the 0.1 ml mark, and another 32 0.25 ml syringes prepared according to the teaching protocol were filled with 25 mg / ml bevacizumab (Avastin®) filtered through a 5 μm filter needle to the 0.1 ml mark. MFI measurements were performed on both sets of syringes following the steps outlined in Example 2.

[0145] Figure 5 This is a bar graph comparing the particle concentration (particle count / mL) of ≥5 μm particles among the following biological solution sources: Avastin® stock solution from vials, filtered Avastin® solution, a universal 0.25 ml syringe (TL) treated and filled with Avastin® according to the teachings of Example 1, and a universal 0.25 ml syringe (TL-F) treated and filled with filtered Avastin® according to the teachings of Example 1. Figure 5 As shown, filtered Avastin® has a reduced total particle count compared to unfiltered Avastin®. Furthermore, for any particles ≥ 5 μm in diameter, a universal 0.25 ml syringe filled with filtered Avastin® processed according to the above method surprisingly yielded a total of 812 particles (silicone particles and other particles) / mL.

[0146] Figure 6This is a bar graph comparing the particle concentration (particle count / mL) of ≥10 μm particles among the following biological solution sources: Avastin® stock solution from vials, filtered Avastin® from vials, a universal 0.25 ml syringe treated according to the teachings of Example 1 and filled with Avastin®, and a universal 0.25 ml syringe treated according to the teachings of Example 1 and filled with filtered Avastin®. Figure 6 As shown, filtered Avastin® has a reduced total particle count compared to unfiltered Avastin®. Furthermore, for any particles with a diameter ≥ 10 μm, a universal 0.25 ml syringe filled with filtered Avastin® after treatment according to the teachings of Example 1 surprisingly had a total of <30 particles (silicone particles and other particles) / mL.

[0147] Figure 7 This is a bar graph comparing the particle concentration (particle count / mL) of ≥ 25 μm particles among the following biological solution sources: Avastin® stock solution from vials, filtered Avastin® from vials, a universal 0.25 ml syringe (TL) treated and filled with Avastin® according to the teachings of Example 1, and a universal 0.25 ml syringe (TL-F) treated and filled with filtered Avastin® according to the teachings of Example 1. Figure 7 As shown, filtered Avastin® has a reduced total particle count compared to unfiltered Avastin®. Furthermore, for any particles with a diameter ≥ 25 μm, a universal 0.25 ml syringe filled with filtered Avastin® after treatment according to the teachings of Example 1 surprisingly showed a total of < 3 particles (silicone particles and other particles) / mL.

Claims

1. A plastic syringe barrel, comprising: A plastic syringe barrel, wherein the plastic syringe barrel is downstream plasma treated and coated with a downstream plasma treated polysiloxane alkyl lubricant coating; and The number of particles with a diameter greater than 8 micrometers in the inner surface of the downstream plasma-treated plastic syringe barrel having the downstream plasma-treated polysiloxane lubricant coating is reduced by at least 75% compared to the inner surface of the plastic syringe barrel having the downstream plasma-treated polysiloxane lubricant coating, and wherein the plastic syringe barrel is empty when the particles are counted.

2. The plastic syringe barrel of claim 1, wherein the number of particles with a diameter greater than 8 micrometers in the inner surface of the downstream plasma-treated plastic syringe barrel having the downstream plasma-treated polysiloxane lubricant coating is reduced by at least 80% compared to the inner surface of the plastic syringe barrel having the downstream plasma-treated polysiloxane lubricant coating, and wherein the plastic syringe barrel is empty when the particles are counted.

3. The plastic syringe barrel of claim 1, wherein the number of particles with a diameter greater than 8 micrometers in the inner surface of the downstream plasma-treated plastic syringe barrel having the downstream plasma-treated polysiloxane lubricant coating is reduced by at least 95% compared to the inner surface of the plastic syringe barrel having the downstream plasma-treated polysiloxane lubricant coating, and wherein the plastic syringe barrel is empty when the particles are counted.

4. A plastic syringe barrel, comprising: A plastic syringe barrel, wherein the plastic syringe barrel is downstream plasma treated and coated with a downstream plasma treated polysiloxane alkyl lubricant coating; and The surface density of the inner surface of the downstream plasma-treated plastic syringe barrel having the downstream plasma-treated polysiloxane lubricant coating is ≤ 600 particles / 12 cm³. 2 The particle diameter is greater than 8 micrometers, and the plastic syringe barrel is empty when the particles are counted.

5. The plastic syringe cartridge according to any one of claims 1 to 4, wherein the plastic syringe cartridge comprises about 0.005 mg / cm³. 2 To approximately 0.5 mg / cm 2 Silicone oil.

6. The plastic syringe barrel according to any one of claims 1 to 4, wherein the polysiloxane lubricant coating is a silicone oil coating.

7. The plastic syringe barrel according to any one of claims 1 to 4, wherein the polysiloxane lubricant coating is polydimethylsiloxane.

8. The plastic syringe barrel according to any one of claims 1 to 4, wherein the maximum filling volume of the plastic syringe barrel is 1.0 ml, 0.5 ml, 0.3 ml, 0.25 ml, 0.10 ml or 0.05 ml.

9. A syringe, comprising: The plastic syringe barrel according to any one of claims 1-4, plunger rod, Piston stopper, and Needle.

10. The syringe of claim 9, wherein the plastic syringe barrel contains a solution.

11. The syringe of claim 9, wherein the plastic syringe barrel contains a solution comprising an anticoagulant, a vaccine, or a recombinant protein.

12. The syringe of claim 9, wherein the plastic syringe barrel contains an anti-VEGF protein solution comprising pilgatanib, ranibizumab, aflibercept, or bevacizumab.

13. The syringe of claim 9, wherein the plastic syringe barrel contains an ophthalmic solution.

14. The syringe of claim 13, wherein for any particles with a diameter ≥ 10 μm, the particle content in the ophthalmic solution is ≤ 50 particles / ml, or for any particles with a diameter ≥ 25 μm, the particle content in the ophthalmic solution is ≤ 5 particles / ml.

15. The syringe of claim 10, wherein for any particle with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particle with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml.

16. A syringe, comprising: The plastic syringe barrel according to any one of claims 1 to 4, Luer lock head or sliding head, Piston rod, and Plunger stopper.

17. The syringe of claim 16, wherein the plastic syringe barrel contains a solution.

18. The syringe of claim 16, wherein the plastic syringe barrel contains a solution comprising an anticoagulant, a vaccine, or a recombinant protein.

19. The syringe of claim 16, wherein the plastic syringe barrel contains an anti-VEGF protein solution comprising pilgatanib, ranibizumab, aflibercept, or bevacizumab.

20. The syringe of claim 16, wherein the plastic syringe barrel contains an ophthalmic solution.

21. The syringe of claim 20, wherein for any particle with a diameter ≥ 10 μm, the particle content in the ophthalmic solution is ≤ 50 particles / ml, or for any particle with a diameter ≥ 25 μm, the particle content in the ophthalmic solution is ≤ 5 particles / ml.

22. The syringe of claim 17, wherein for any particle with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particle with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml.

23. Use of the syringe according to any one of claims 9-22 in the preparation of a solution for treating the eye or an ophthalmic solution.

24. A method for producing a plastic syringe barrel having a stable silicone oil layer, comprising: Plastic syringe cartridges are provided. The inner surface of the plastic syringe barrel is exposed to downstream plasma for 0.1 to 10 seconds; 0.005 to 0.5 mg / cm 2 Silicone oil is applied to the downstream plasma-treated inner surface of the plastic syringe barrel to form a uniform silicone oil coating. as well as The uniform silicone oil coating was exposed to downstream plasma for 0.1 to 10 seconds; The surface density of the inner surface of the downstream plasma-treated plastic syringe barrel, which has a silicone oil coating treated with downstream plasma, is ≤ 600 particles / 12 cm³. 2 The particle diameter is greater than 8 micrometers, and the plastic syringe barrel is empty when the particles are counted.

25. A method for producing a plastic syringe barrel having a stable silicone oil layer, comprising: Plastic syringe cartridges are provided. The inner surface of the plastic syringe barrel is exposed to downstream plasma for 0.1 to 10 seconds; 0.005 to 0.5 mg / cm 2 Silicone oil is applied to the downstream plasma-treated inner surface of the plastic syringe barrel to form a uniform silicone oil coating. as well as The uniform silicone oil coating was exposed to downstream plasma for 0.1 to 10 seconds; The number of particles with a diameter greater than 8 micrometers in the inner surface of the downstream plasma-treated plastic syringe barrel is reduced by at least 75% compared to the inner surface of the plastic syringe barrel with a polysiloxane lubricant coating, and the plastic syringe barrel is empty when the particles are counted.

26. The method of claim 25, wherein, compared to the inner surface of a plastic syringe barrel having a polysiloxane lubricant coating, the number of particles with a diameter greater than 8 micrometers in the inner surface of the downstream plasma-treated plastic syringe barrel having a downstream plasma-treated silicone oil coating is reduced by at least 80%, and wherein the plastic syringe barrel is empty when the particles are counted.

27. The method of claim 25, wherein the number of particles with a diameter greater than 8 micrometers in the inner surface of the downstream plasma-treated plastic syringe barrel having a downstream plasma-treated silicone oil coating is reduced by at least 95% compared to the inner surface of the plastic syringe barrel having a polysiloxane lubricant coating, and wherein the plastic syringe barrel is empty when the particles are counted.

28. The method according to any one of claims 24 to 27, wherein the downstream plasma comprises excited argon atoms.

29. The method according to any one of claims 24 to 27, wherein the plastic is a cyclic olefin polymer (COP), a cyclic olefin copolymer (COC), polyethylene (PE), polycarbonate (PC), polypropylene (PP), or polyethylene terephthalate (PET).

30. The method according to any one of claims 24 to 27, wherein the maximum filling volume of the plastic syringe barrel is 1.0 ml, 0.5 ml, 0.3 ml, 0.25 ml, 0.10 ml or 0.05 ml.

31. The method according to any one of claims 24 to 27, wherein the plastic is a cyclic olefin polymer (COP).

32. The method of claim 24 or 25, wherein the method further comprises waiting for at least 10 minutes, 20 minutes, 30 minutes, 40 minutes, 1 hour, 2 hours or 3 hours before exposing the uniform silicone oil coating to the downstream plasma.

33. A method for producing a syringe with a plastic syringe barrel having a stable polysiloxane lubricant coating, comprising: The method according to any one of claims 24 to 32, and Assemble the plastic syringe barrel using a plunger rod, a plunger stopper, and a needle.

34. The method of claim 33, wherein the plastic syringe contains a solution, and wherein for any particles with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particles with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml.

35. A plastic syringe comprising a plastic syringe barrel, a plunger rod, and a plunger stopper, wherein the plastic syringe barrel has a stable silicone oil coating and is manufactured by the following steps: Plastic syringe cartridges are provided. The inner surface of the plastic syringe barrel is exposed to downstream plasma for 0.1 to 10 seconds; 0.005 to 0.5 mg / cm 2 Silicone oil is applied to the downstream plasma-treated inner surface of the plastic syringe barrel to form a uniform silicone oil coating. as well as The uniform silicone oil coating is then exposed to downstream plasma. The surface density of the inner surface of the downstream plasma-treated plastic syringe barrel, which has a silicone oil coating treated with downstream plasma, is ≤ 600 particles / 12 cm³. 2 The particle diameter is greater than 8 micrometers, and the plastic syringe barrel is empty when the particles are counted.

36. A plastic syringe comprising a plastic syringe barrel, a plunger rod, and a plunger stopper, wherein the plastic syringe barrel has a stable silicone oil coating and is manufactured by the following steps: Plastic syringe cartridges are provided. The inner surface of the plastic syringe barrel is exposed to downstream plasma for 0.1 to 10 seconds; 0.005 to 0.5 mg / cm 2 Silicone oil is applied to the downstream plasma-treated inner surface of the plastic syringe barrel to form a uniform silicone oil coating; and The uniform silicone oil coating is then exposed to downstream plasma. The number of particles with a diameter greater than 8 micrometers in the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated silicone oil coating is reduced by at least 75% compared to the inner surface of the plastic syringe barrel having a polysiloxane lubricant coating, and the plastic syringe barrel is empty when the particles are counted.

37. The plastic syringe of claim 36, wherein the number of particles with a diameter greater than 8 micrometers in the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated silicone oil coating is reduced by at least 80% compared to the inner surface of the plastic syringe barrel having a polysiloxane lubricant coating, and wherein the plastic syringe barrel is empty when the particles are counted.

38. The plastic syringe of claim 36, wherein the number of particles with a diameter greater than 8 micrometers in the inner surface of the plasma-treated plastic syringe barrel having the plasma-treated silicone oil coating is reduced by at least 95% compared to the inner surface of the plastic syringe barrel having a polysiloxane lubricant coating, and wherein the plastic syringe barrel is empty when the particles are counted.

39. The plastic syringe according to claim 35 or 36, wherein the plastic syringe barrel contains a solution.

40. The plastic syringe of claim 35 or 36, wherein the plastic syringe barrel contains a solution comprising an anticoagulant, a vaccine, or a recombinant protein.

41. The plastic syringe of claim 35 or 36, wherein the plastic syringe barrel contains an anti-VEGF protein solution comprising pilgatanib, ranibizumab, aflibercept, or bevacizumab.

42. The plastic syringe according to claim 35 or 36, wherein the plastic syringe barrel contains an ophthalmic solution.

43. The plastic syringe of claim 42, wherein for any particles with a diameter ≥ 10 μm, the particle content in the ophthalmic solution is ≤ 50 particles / ml, or for any particles with a diameter ≥ 25 μm, the particle content in the ophthalmic solution is ≤ 5 particles / ml.

44. The plastic syringe of claim 39, wherein for any particle with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particle with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml.

45. Use of the plastic syringe according to any one of claims 35 to 44 in the preparation of a solution for treating the eye or an ophthalmic solution.

46. ​​A syringe, comprising: A plastic syringe barrel, wherein the plastic syringe barrel is downstream plasma treated and coated with a downstream plasma treated polysiloxane alkyl lubricant coating; plunger rod, Piston stopper, and needle; The plastic syringe contains a solution, and for any particles with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particles with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml.

47. Use of the syringe of claim 46 in the preparation of a solution for treating the eye or an ophthalmic solution.

48. The application according to claim 47, wherein the solution comprises an anticoagulant, a vaccine, or a recombinant protein.

49. The application according to claim 47, wherein the solution is an ophthalmic solution.

50. The application according to claim 47, wherein the solution comprises pilgatanib, ranibizumab, aflibercept, or bevacizumab.

51. A syringe, comprising: A plastic syringe barrel, wherein the plastic syringe barrel is downstream plasma treated and coated with a downstream plasma treated polysiloxane alkyl lubricant coating; Luer lock head or sliding head, Piston rod, and Piston stopper; The plastic syringe contains a solution, and for any particles with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particles with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml.

52. A plastic syringe barrel, comprising: A plastic syringe barrel, wherein the plastic syringe barrel is downstream plasma treated and coated with a downstream plasma treated perfluoropolyether lubricant coating; and Compared to the inner surface of a plastic syringe barrel with a perfluoropolyether lubricant coating, the number of particles with a diameter greater than 8 micrometers in the inner surface of the downstream plasma-treated plastic syringe barrel with the downstream plasma-treated perfluoropolyether lubricant coating is reduced by at least 75%, 80%, or 95%, respectively, and wherein the plastic syringe barrel is empty when the particles are counted.

53. A plastic syringe barrel, comprising: A plastic syringe barrel, wherein the plastic syringe barrel is downstream plasma treated and coated with a downstream plasma treated perfluoropolyether lubricant coating; and The surface density of the inner surface of the downstream plasma-treated plastic syringe barrel having the downstream plasma-treated perfluoropolyether lubricant coating is ≤ 600 particles / 12 cm³. 2 ≤ 500 particles / 12cm 2 Or ≤ 400 particles / 12 cm 2 The particle diameter is greater than 8 micrometers, and the plastic syringe barrel is empty when the particles are counted.

54. A plastic syringe barrel, comprising: A plastic syringe barrel, wherein the plastic syringe barrel is downstream plasma treated and coated with a downstream plasma treated perfluoropolyether lubricant coating; and The surface density of the inner surface of the downstream plasma-treated plastic syringe barrel having the downstream plasma-treated perfluoropolyether lubricant coating is ≤ 100 particles / cm³. 2 ≤ 90 particles / cm 2 ≤50 particles / cm 2 ≤ 40 particles / cm 2 ≤ 35 particles / cm 2 or ≤ 30 particles / cm 2 The particle diameter is greater than 8 micrometers, and the plastic syringe barrel is empty when the particles are counted.

55. A syringe, comprising: The plastic syringe barrel according to any one of claims 52 to 54, plunger rod, Piston stopper, and Needle.

56. A syringe, comprising: The plastic syringe barrel according to any one of claims 52 to 54, Luer lock head or sliding head, Piston rod, and Plunger stopper.

57. The syringe according to any one of claims 55 to 56, wherein the plastic syringe barrel contains a solution.

58. The syringe according to any one of claims 55 to 56, wherein the plastic syringe barrel contains a solution comprising an anticoagulant, a vaccine, or a recombinant protein.

59. The syringe according to any one of claims 55 to 56, wherein the plastic syringe barrel contains an anti-VEGF protein solution comprising pilgatanib, ranibizumab, aflibercept, or bevacizumab.

60. The syringe according to any one of claims 55 to 56, wherein the plastic syringe barrel contains an ophthalmic solution.

61. The syringe of claim 60, wherein for any particle with a diameter ≥ 10 μm, the particle content in the ophthalmic solution is ≤ 50 particles / ml, or for any particle with a diameter ≥ 25 μm, the particle content in the ophthalmic solution is ≤ 5 particles / ml.

62. Use of the syringe according to any one of claims 55-61 in the preparation of a solution or ophthalmic solution for treating the eye.

63. A method for producing a plastic syringe barrel having a stable lubricant layer, comprising: Plastic syringe cartridges are provided. The inner surface of the plastic syringe barrel is exposed to downstream plasma for 0.1 to 10 seconds; 0.005 to 0.5 mg / cm 2 The perfluoropolyether is applied to the downstream plasma-treated inner surface of the plastic syringe barrel to form a uniform perfluoropolyether coating. as well as The uniform perfluoropolyether coating was exposed to downstream plasma for 0.1 to 10 seconds; The surface density of the inner surface of the downstream plasma-treated plastic syringe barrel having a downstream plasma-treated perfluoropolyether coating is ≤ 600 particles / 12 cm³. 2 ≤ 500 particles / 12 cm 2 ≤400 particles / 12 cm 2 ≤ 100 particles / cm 2 ≤ 90 particles / cm 2 ≤ 50 particles / cm 2 ≤ 40 particles / cm 2 ≤ 35 particles / cm 2 or ≤ 30 particles / cm 2 , The particle diameter is greater than 8 micrometers, and the plastic syringe barrel is empty when the particles are counted.

64. A syringe, comprising: A plastic syringe barrel, wherein the plastic syringe barrel is downstream plasma treated and coated with a downstream plasma treated perfluoropolyether lubricant coating; plunger rod, Piston stopper, and needle; The plastic syringe contains a solution, and for any particles with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particles with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml.

65. Use of the syringe of claim 64 in the preparation of a solution for treating the eye or an ophthalmic solution.

66. The application of claim 65, wherein the solution comprises an anticoagulant, a vaccine, or a recombinant protein, wherein the solution is an ophthalmic solution, and wherein the solution is an anti-VEGF protein solution comprising pilgatanib, ranibizumab, aflibercept, or bevacizumab.

67. A syringe comprising a plastic syringe barrel, the plastic syringe barrel being downstream plasma treated and coated with a downstream plasma treated perfluoropolyether lubricant coating. Luer lock head or sliding head, Piston rod, and Piston stopper; The plastic syringe contains a solution, and for any particles with a diameter ≥ 10 μm, the particle content in the solution is ≤ 50 particles / ml, or for any particles with a diameter ≥ 25 μm, the particle content in the solution is ≤ 5 particles / ml.

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