阅读说明：本技术 含有莫西沙星的预填充注射器 (Pre-filled syringe containing moxifloxacin ) 是由 莫业钧 袁旭东 于 2018-04-11 设计创作，主要内容包括：本发明涉及含有莫西沙星且包括柱塞、筒、具有规格的针头的预填充注射器；包括该预填充注射器的试剂盒；以及该注射器用于给药莫西沙星用于白内障手术之后的术后细菌性眼内炎的用途。(The present invention relates to a pre-filled syringe containing moxifloxacin and comprising a plunger, a barrel, a needle with a gauge; a kit comprising the pre-filled syringe; and the use of the syringe for administering moxifloxacin for post-operative bacterial endophthalmitis after cataract surgery.)

1. A pre-filled syringe containing a moxifloxacin liquid formulation and comprising a syringe barrel, wherein the syringe barrel is made of plastic or glass and is silicone-free.

2. The pre-filled syringe of claim 1, wherein moxifloxacin is a fluoroquinolone antibiotic agent.

3. The pre-filled syringe of claim 1, wherein the concentration of moxifloxacin is 0.1 to 500 mg/ml.

4. The pre-filled syringe of claim 1, comprising less than 50 particles having a diameter of 10 μ ι η or greater per ml of liquid formulation.

5. The pre-filled syringe of claim 1, comprising less than 5 particles having a diameter of 25 μ ι η or greater per ml of liquid formulation.

6. The pre-filled syringe of claim 1, having a sliding force of less than or equal to about 10N.

7. The pre-filled syringe according to claim 1, further comprising a piston, preferably a silicone-free piston.

8. Pre-filled syringe according to claim 1, wherein the syringe barrel is made of a polymer such as cyclo olefin or glass.

9. The pre-filled syringe of claim 1, wherein the syringe barrel comprises an inner coating that is a non-silicone coating.

10. The pre-filled syringe of claim 1, comprising a preferably staked needle.

11. A kit comprising the pre-filled syringe of claim 1.

12. Use of a pre-filled syringe as claimed in claim 1 for administering a liquid formulation of moxifloxacin to a patient for the prevention of postoperative endophthalmitis or other related eye diseases and disorders.

13. The use of claim 12, wherein the endophthalmitis is an inflammatory disorder of the ocular lumen.

14. The use according to claim 12, wherein the patient is administered a volume of 1 to 500 μ l of the liquid formulation by anterior chamber injection into the anterior chamber.

15. A method of making the pre-filled syringe of claim 1.

Technical Field

The present invention relates to a pre-filled syringe containing moxifloxacin (levofloxacin) and comprising a plunger, a barrel, a needle of a gauge, a kit comprising the pre-filled syringe, and the use of the syringe for the anterior chamber administration of moxifloxacin for the prevention of post-operative bacterial endophthalmitis after cataract surgery.

Background

Endophthalmitis is an inflammation of the inner layers of the eye, a potentially serious complication of cataract surgery, which occurs in 0.04% to 0.2% of cases. Measures taken to minimize the occurrence of endophthalmitis have been part of cataract surgery. Historically, the majority of options for chemoprevention against bacterial endophthalmitis have been topical and subconjunctival antibiotics on the ocular surface and povidone-iodine formulations and instillations prior to surgery. In the united states, the most common form of chemoprevention is the post-operative administration of topical fluoroquinolones for 1 to 3 days, and continued for one week immediately after the operation. Most european surgeons now prefer an injection of an anterior chamber antibiotic rather than a local antibiotic alone or a subconjunctival antibiotic. There is increasing evidence that the use of anterior chamber injection to prevent bacterial endophthalmitis is more effective than topical administration. However, intracameral injection of antibiotics in the united states is considered off-label (non-adaptive ).

Moxifloxacin by nameIs sold as eye drops of fluoroquinolone antibiotics for treating bacterial infections of the eyes.In the form of a solutionIn a vial, with a concentration of moxifloxacin of 5 mg/ml. In the united states, most surgeons have their patients apply topical applications before and after cataract surgeryCan be used for preventing postoperative endophthalmitis. Also in the United statesOff-label use for endophthalmitis prevention. After cataract surgery, the vial is withdrawn with a syringeFor anterior chamber injection.

The pre-filled syringe of the present invention has many advantages over vials and separately prepared syringes, such as improved safety, affordability, convenience, accuracy and sterility. The use of pre-filled syringes may result in greater dose accuracy, reduce the likelihood of needle damage that may occur when drawing medication from a vial, pre-measured doses reduce the risk of dose errors and contamination due to the need to reconstitute and/or draw medication into the syringe, and less overfilled syringes help to reduce costs by minimizing medication waste. Moxifloxacin as a first-line drug may have advantages over other fluoroquinolone antibiotics because moxifloxacin provides a broader coverage of the disease spectrum and can be used for injection without dilution.

Thus, there is an unmet medical need for a moxifloxacin pre-filled syringe that can safely deliver a drug to the eye and that has the above-mentioned advantages, but in which the drug is stable during storage.

Disclosure of Invention

It has been demonstrated that moxifloxacin solution can maintain potency, sterility and stability during storage when filled into pre-filled syringes (Armstrong et al, 2010). The pre-filled syringe of the present invention does not contain a large amount of particles. The present invention provides a pre-filled syringe containing a moxifloxacin liquid formulation and comprising a syringe barrel, wherein the syringe barrel is preferably made of plastic/glass and is silicone-free.

Moxifloxacin is a fluoroquinolone antibiotic agent and is chemically classified as a quinolone. Moxifloxacin binds and inhibits the bacterial enzymes DNA gyrase and topoisomerase IV, causing inhibition of DNA replication and repair in susceptible bacterial species and resulting cell death.

In a certain embodiment of the invention, the concentration of moxifloxacin is 0.15 to 500 mg/ml. In one aspect of the invention, the pre-filled syringe contains less than 50 particles having a diameter of 10 μm or more per ml of the liquid formulation.

In another aspect of the invention, the pre-filled syringe contains less than 5 particles having a diameter of 25 μm or more per ml of the liquid formulation. In yet another aspect of the present invention, the pre-filled syringe has a glide force of less than or equal to about 10N.

In a preferred embodiment, the pre-filled syringe further comprises a silicone-free piston.

Preferably, the syringe barrel is made of a cyclic olefin polymer or cyclic olefin copolymer. In a preferred embodiment, the syringe barrel includes an inner coating that is a non-silicone coating. Also preferably, the pre-filled syringe comprises a staked needle.

The invention also provides a kit comprising one or more pre-filled syringes according to the invention. Preferably, the kit is a blister pack.

Prefilled syringes may be used to administer moxifloxacin to the anterior chamber of a patient after cataract surgery for post-operative endophthalmitis prevention.

Preferably, the liquid formulation is administered to the patient in a volume of 1 to 500 μ L.

Drawings

Figure 1 shows an example of a pre-filled syringe of the present invention for anterior chamber injection of moxifloxacin. The pre-filled syringe is comprised of a plunger head, plunger, needle cap, needle guard activation clip, needle guard wings, label, syringe barrel, viewing window, dosage indicia.

Detailed Description

The detailed description is merely exemplary in nature and is not intended to limit application and uses. The following examples further illustrate the invention, but do not limit the scope of the invention to those examples. Various changes and modifications may be made by those skilled in the art based on the description of the present invention, and such changes and modifications are also encompassed in the present invention. Unless otherwise indicated, all ingredient concentrations are expressed in% weight/volume (% w/v).

Moxifloxacin is preferably present in the composition of the present invention in the form of a pharmaceutically acceptable salt. Most preferably, the moxifloxacin is present as moxifloxacin hydrochloride. The composition comprises moxifloxacin as a free base in an amount equal to about 0.5%. The amount of moxifloxacin hydrochloride in the composition of the present invention is 0.5-0.6%, and most preferably 0.545%, which corresponds to 0.5% moxifloxacin as base.

The compositions of the invention may comprise boric acid in an amount of between 0.2 and 0.4%, preferably 0.3%.

In one embodiment of the invention, disodium edetate is present in the composition of the invention in an amount of 0.005-0.02%. Most preferably, edetate disodium is present in an amount of 0.01%.

The ionic tonicity modifier is added to the composition of the present invention in a sufficient amount such that the final composition has an osmolality of 270-330 mOsm/Kg. Preferably, the ionic tonicity modifier is sodium chloride and is present in an amount of 0.5 to 0.8%. Most preferably, the composition of the invention comprises 0.65% NaCl.

The compositions of the present invention also comprise an otically and ophthalmically acceptable nonionic surfactant, such as a polysorbate surfactant, a block copolymer surfactant of ethylene oxide and propylene oxide (e.g. a pluronic or tetronic surfactant) or tyloxapol (tyloxapol). Preferably, the composition comprises a nonionic surfactant in an amount of 0.04 to 0.06%. Most preferably, the non-ionic surfactant is tyloxapol and the amount of tyloxapol in the composition of the invention is 0.05%.

The composition may comprise a preservative ingredient or preservative enhancing ingredient selected from the group consisting of benzalkonium chloride and sorbitol. Preferably, the compositions of the invention comprise benzalkonium chloride if they are intended for topical otic administration and sorbitol if they are intended for topical ocular administration. If present, the amount of benzalkonium chloride in the composition is 0.005-0.015%, preferably 0.01%. If present, the amount of sorbitol in the composition of the invention is 0.1-0.3%, preferably 0.2%. In addition, the compositions may be preservative-free and sterile formulations.

The pH of the aqueous solution of the present invention is adjusted with an ophthalmically acceptable pH adjusting agent. Ophthalmically acceptable pH adjusting agents are known and include, but are not limited to, hydrochloric acid (HCl) and sodium hydroxide (NaOH). The composition of the invention preferably comprises NaOH or HCl to obtain the desired pH. The compositions of the present invention are formulated and maintained within a narrow pH range in order to keep the compositions stable over a commercially acceptable shelf life. The compositions of the present invention have a pH of 5.0 to 9.0, and most preferably 7.8 to 8.0.

The compositions of the present invention are preferably packaged in pre-filled syringes or multi-dose plastic containers designed for delivery of droplets to the eye. Preferably, the pre-filled syringe contains a moxifloxacin liquid formulation and comprises a syringe barrel, wherein the syringe barrel is made of plastic/glass and is silicone-free.

Preferably, the pre-filled syringe is disposable and is used for one dose to avoid contamination.