Ophtalmic pharmaceutical compositions for the treatment of conjunctivitis

Abstract

The present invention relates to a single dose plastic container comprising between 0.2 and 3.0 ml of an aqueous pharmaceutical composition comprising from 0.50 to 1.20 % by weight of povidone-iodine and to its use in the treatment of conjunctivitis.

Description

[0001] OPHTALMIC PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF CONJUNCTIVITIS

[0002] The present invention relates to a single dose plastic container comprising between 0.2 and 3.0 ml of an aqueous pharmaceutical composition comprising from 0.50 to 1.20 % by weight of povidone-iodine and to its use in the treatment of conjunctivitis.

[0003] BACKGROUND

[0004] Conjunctivitis, also known as pink eye, is mainly caused by infection or allergies. Infectious conjunctivitis can be caused by bacteria or virus. Approximately 80% of cases of conjunctivitis in adults and less than 20% in children are due to viruses, with 65% to 90% of these cases being attributed to adenoviruses. Bacteria are responsible for approximately 70% of conjunctivitis in children and less than 20% of cases in adults. Common bacteria responsible for bacterial conjunctivitis are Staphylococcus including S. aureus. Infection with Escherichia coli may also cause conjunctivitis, particularly in the neonatal subtype ophthalmia neonatorum. Both bacterial and viral infections are contagious, passing from person to person or spread through contaminated objects or water. Contact with contaminated fingers is a common cause of conjunctivitis.

[0005] Povidone-iodine (PVP-I) is a complex obtained by combining the polymer polyvinylpyrrolidone (PVP) and iodine. PVP-I has a widely known bactericidal action, due to the free molecular iodine I2.

[0006] PVP-I has been used as antimicrobial agent for eye treatment because it has several advantages: (i) in the appropriate concentration, it is not toxic to the eye as are other iodine bearing compounds, (ii) it has a very broad antimicrobial spectrum, including bacteria, viruses, and fungi, given enough contact time in vitro, (iii) resistance by bacteria is rare, (iv) it is widely available and (v) it is not expensive.

[0007] 5% solutions of PVP-I are commonly used as antiseptic before eye surgery or ocular injections. These solutions are applied in 2 or 3 drops to the eye and to the skin around the eye, and the eyes are rinsed after 2 minutes. Because of the high concentration of PVP-I in these solutions, they cause burning and irritation in the eye and are thus used after local anesthesia.

[0008] WO2017175075 discloses ophthalmic compositions of PVP-I in lower concentrations (0.2 to 1.0 % w / w). However, these compositions are packed in glass bottles for stability.W02013027065 also discloses ophthalmic PVP-I compositions useful for treating eye infections, but these compositions comprise much higher concentrations of PVP-I, i.e. from 4.0 to 6.5 % w / w.

[0009] EP0526695 also discloses PVP-I ophthalmic compositions with antimicrobial effect and with low PVP-I amounts (0.3 to 0.6 % w / w) but packed in glass containers for stability.

[0010] However, despite all the disclosures on PVP-I use for eye disease treatment, no PVP-I pharmaceutical product has been approved for the treatment of conjunctivitis.

[0011] There is still the need for ophthalmic compositions with low amounts of PVP-I that are tolerable for the eye and that have germicidal activity, which can be packed in plastic single dose containers and be stable over time so to be approved as pharmaceutical products.

[0012] SUMMARY OF THE INVENTION

[0013] The present invention provides new aqueous ophthalmic pharmaceutical compositions with low PVP-I concentrations (from 0.50 to 1.20 % w / w) conveniently packaged in single dose plastic containers of up to 3.0 ml volume, which are stable over time and have proven to be effective over both bacterial and viral eye infections.

[0014] In a first aspect, the present invention relates to a single dose plastic container comprising between 0.2 and 3.0 ml of an aqueous pharmaceutical composition comprising from 0.50 to 1.20 % by weight of povidone-iodine, from 0.50 to 1.20 % by weight of a stabilizer comprising iodide and from 0.20 to 0.90 % by weight of a tonicity agent.

[0015] In a second aspect, the present invention relates to the single dose plastic containers of the first aspect, for use in the treatment of bacterial or viral conjunctivitis.

[0016] In a third aspect, the present invention relates to a single dose plastic container having a volume between 0.2 and 3.0 ml and comprising between 0.2 and 3.0 ml of an aqueous pharmaceutical composition comprising from 0.50 to 1.20 % by weight of povidone-iodine, for use in the treatment of bacterial or viral conjunctivitis.

[0017] DETAILED DESCRIPTION OF THE INVENTION

[0018] The percent of the ingredients in the aqueous pharmaceutical compositions is by weight. Percent by weight is always with respect to the total weight of the pharmaceutical composition, not including the weight of the container.

[0019] In the present invention, the PVP-I contains on average 9-12 % by weight of available iodine, understood as the available iodine titratable with sodium thiosulphate and is not more than 6% by weight of iodide ion (tested in accordance with the method in European Pharmacopoeia edition 11, monograph 1142).

[0020] In a preferred embodiment of the first aspect, the aqueous ophthalmic pharmaceutical composition has a PVP-I concentration between 0.50 and 1.00 % by weight or between 0.60 and 1.00 % by weight. In preferred embodiment, the aqueous ophthalmic pharmaceutical composition has a PVP-I concentration of about 0.60 % by weight or about 1.00 % by weight. Thus, preferred PVP-I concentrations are 0.50, 0.55, 0.60 ,0.65, 0.70, 0.75, 0.80, 0.85, 0.90, 0.95, 1.00, 1.05, and 1.10 % by weight.

[0021] In a preferred embodiment of the first aspect, the plastic container has a volume of between 0.2 and 3.0 ml. Preferably, it has a volume between 0.3 and 2.8 ml, or from 0.3 to 2.6 ml or from 0.3 to 2.4 ml, or from 0.3 to 2.2 ml, or from 0.3 to 2.0 ml. More preferably, the plastic container has a volume of between 0.4 and 1.8 ml, even more preferably between 0.6 and 1.6 ml. Preferred embodiments are those where the container’s volume is 0.4 ml, 0.5 ml, 0.6 ml, 0.7 ml, 0.8 ml, 0.9 ml, 1.0ml, 1.1 ml, 1.2 ml, 1.3 ml, 1.4 ml or 1.5 ml. More preferred embodiments are those where the container’s volume is 0.9 ml or 1.6 ml.

[0022] In a preferred embodiment of the first aspect, the plastic container has a volume of between 0.3 and 2.5 ml and comprises between 0.3 and 2.5 ml of the aqueous pharmaceutical composition. In a preferred embodiment of the first aspect, the plastic container has a volume of between 0.4 and 2.2 ml and comprises between 0.4 and 2.2 ml of the aqueous pharmaceutical composition. In a preferred embodiment of the first aspect, the plastic container has a volume of between 0.5 and 2.0 ml and comprises between 0.5 and 2.0 ml of the aqueous pharmaceutical composition. Preferably, the plastic container comprises between 0.6 and 1.6 ml of the aqueous pharmaceutical composition.

[0023] In a preferred embodiment of the first aspect, the plastic container is made of polyethylene (PE), polypropylene (PP) or polyethylene terephthalate (PET). In a preferred embodiment, the plastic container is made of PE. The PE may be HDPE (high density PE) or LDPE (low density PE). In a more preferred embodiment, the container is made of LDPE. In another embodiment, the container is made of PP, such as soft PP.

[0024] As used herein, a single dose plastic container is meant to be used once, i.e. for a single administration. An example of single dose plastic container is a plastic minims. The single dose plastic containers may also be packed in sachets, such as aluminium sachets.In a preferred embodiment of the first aspect, the stabilizer comprising iodide is selected between an iodide and an iodate, preferably the stabilizer is potassium iodide. Preferably, the aqueous pharmaceutical composition in the container of the first aspect comprises from 0.5 to 1.2 % of potassium iodide.

[0025] In a preferred embodiment of the first aspect, the tonicity agent is sodium chloride. In a preferred embodiment, the aqueous pharmaceutical composition comprises a sufficient amount of tonicity agent (NaCl) to have an osmolality between 260 and 320 mOsmol / kg. In a preferred embodiment, the aqueous pharmaceutical composition comprises between 0.02 and 0.90 % by weight, or between 0.20 and 0.60 % by weight, or between 0.20 and 0.40 % by weight, or between 0.20 and 0.30 % by weight, or between 0.30 and 0.60 % by weight, or between 0.37 and 0.54 % by weight or is about 0.37 % by weight or is about 0.54 % by weight or is about 0.70% by weight of sodium chloride.

[0026] In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition further comprises a buffer or buffers. Preferably, the buffer or buffers are citric acid and / or sodium citrate. More preferably, the amount of buffer or buffers in the aqueous pharmaceutical composition is between 0.30 and 0.80 % by weight. In a particularly preferred embodiment, the aqueous pharmaceutical composition in the container of the first aspect comprises about 0.56 % by weight of citric / citrate buffer. Preferably, the buffered aqueous pharmaceutical composition comprises 0.07 % of citric acid dihydrate and 0.49 % by weight of sodium citrate dihydrate.

[0027] In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition has a pH between 4.0 and 6.0. In a more preferred embodiment, the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The desired pH of the aqueous pharmaceutical composition is adjusted with sodium hydroxide or hydrochloric acid. Preferably, the aqueous pharmaceutical composition comprises sodium hydroxide to adjust to the desired pH.

[0028] The problem of iodine leaching through a plastic packaging has been known for a long time and different ways of stabilizing the aqueous pharmaceutical composition have been described (with stabilisers, such as iodide donating species, as iodate salts or iodide salts, with viscosity increasing agents, etc). However, the inventors have found that not all stabilisers work for the specific case of single dose plastic containers of up to 3.0 ml volume.In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition further comprises at least one of sodium hyaluronate, sodium carboxymethylcellulose, poloxamer, glycerol and any combination thereof.

[0029] In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition comprises from 0.05 to 0.40 % by weight of sodium hyaluronate, preferably 0.05, 0.1, 0.15 or 0.20 % by weight.

[0030] In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition comprises from 0.20 - 0.50 % by weight of sodium carboxymethylcellulose, preferably 0.2, 0.3 or 0.5 % by weight, more preferably 0.3 % by weight.

[0031] In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition comprises from 0.10 - 0.20 % by weight of poloxamer, preferably 0.2 % by weight.

[0032] In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition comprises from 0.20 - 0.40 % by weight of glycerol, preferably 0.4 % by weight.

[0033] In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition comprises from 1.00 - 2.00 % by weight of ectoine, preferably 2.00 % by weight.

[0034] The following are preferred embodiments of the first aspect of the invention:

[0035] The single dose plastic container of the first aspect wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0036] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentrationof about 0.56 % by weight, further comprising poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0037] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0038] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0039] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0040] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0041] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0042] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0043] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0044] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0045] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerol in a concentration of 0.40 % by weight, andpoloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0046] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0047] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0048] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0049] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentrationof about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0050] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0051] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, and sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0052] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0053] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentrationof about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0054] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0055] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0056] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.03 % by weight, the buffer is citric acid and sodium citrate in a total concentrationof about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerol in a concentration of 0.40 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0057] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0058] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0059] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in aconcentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0060] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0061] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0062] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, and sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0063] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0064] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0065] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0066] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0067] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0068] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentrationof about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0069] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0070] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, glycerol in a concentration of 0.40 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0071] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, and sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0072] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, andectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0073] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0074] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0075] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerolin a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0076] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerol in a concentration of 0.40 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0077] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0078] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0079] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0080] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0081] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, and sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0082] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentrationof about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0083] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0084] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0085] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.60 % by weight, the stabilizer is potassium iodide in a concentrationof about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0086] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0087] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0088] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0089] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0090] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0091] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising glycerol in a concentration of 0.40 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0092] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0093] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentrationof about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0094] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0095] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0096] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0097] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerol in a concentration of 0.40 % by weight, andpoloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0098] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0099] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0100] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0101] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentrationof about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0102] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0103] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, and sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0104] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0105] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentrationof about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0106] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0107] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.05 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0108] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentrationof about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0109] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0110] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0111] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0112] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, and sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0113] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0114] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0115] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.10 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0116] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentrationof about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0117] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0118] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0119] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0120] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15% by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0121] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, and sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0122] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0123] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0124] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight,poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0125] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.15 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0126] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0127] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0128] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.40 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0129] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.4 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0130] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentrationof about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, and sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0131] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0132] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0133] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.02 and 0.04 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, poloxamer in a concentration of 0.20 % by weight, and ectoine in a concentration of 2.00 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0. The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, and glycerol in a concentration of 0.40 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0134] The single dose plastic container of the first aspect, wherein the povidone-iodine concentration is about 0.80 % by weight, the stabilizer is potassium iodide in a concentration of about 0.80 % by weight, the tonicity agent is sodium chloride in a concentration between 0.20 and 0.30 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight, further comprising sodium hyaluronate in a concentration of 0.20 % by weight, sodium carboxymethylcellulose in a concentration of 0.30 % by weight, glycerol in a concentration of 0.40 % by weight, and poloxamer in a concentration of 0.20 % by weight, and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0135] In a preferred embodiment of the first aspect, the povidone-iodine concentration in the aqueous pharmaceutical composition is about 0.60 % by weight, the stabilizer is potassium iodide in a concentration of about 0.60 % by weight, the tonicity agent is sodium chloride in a concentration of about 0.51 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0136] In another preferred embodiment of the first aspect, the povidone-iodine concentration in the aqueous pharmaceutical composition is about 1.00 % by weight, the stabilizer is potassium iodide in a concentration of about 0.50 % by weight or of about 1.00 % by weight, the tonicity agent is sodium chloride in a concentration of between 0.30 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

[0137] In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition consists of about 0.60 % by weight of povidone-iodine, about 0.60 % by weight of potassium iodide, about 0.51 % by weight of sodium chloride, about 0.56 % by weight of citric acid and sodium citrate and sodium hydroxide necessary to bring the pH between 5.0 and 6.0, in purified water.

[0138] In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition consists of about 1.00 % by weight of povidone-iodine, about 0.50 % by weight of potassiumiodide, about 0.54 % by weight of sodium chloride, about 0.56 % by weight of citric acid and sodium citrate and sodium hydroxide necessary to bring the pH between 5.0 and 6.0, in purified water.

[0139] All these pharmaceutical compositions have an osmolality between 260 and 320 mOsmol / kg. In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition consists of about 1.00 % by weight of povidone-iodine, about 1.00 % by weight of potassium iodide, about 0.37 % by weight of sodium chloride, about 0.56 % by weight of citric acid and sodium citrate and sodium hydroxide necessary to bring the pH between 5.0 and 6.0, in purified water.

[0140] In a preferred embodiment of the first aspect, the povidone-iodine concentration is from 0.50 to 0.70 % by weight, from 0.55 to 1.25 % by weight, from 0.55 to 0.65 % by weight, from 0.90 to 1.10 % by weight, from 0.95 to 1.05 % by weight or from 0.60 or 1.00 % by weight. In a preferred embodiment of the first aspect, the aqueous pharmaceutical composition comprises a buffer or buffers in a concentration from 0.35 to 0.70 % by weight, from 0.35 to 0.60 % by weight, from 0.40 to 0.60 % by weight, or from 0.42 to 0.56 % by weight, preferably from 0.42 % or 0.56 % by weight.

[0141] In a preferred embodiment of the first aspect, the stabilizer concentration in the aqueous pharmaceutical composition is from 0.50 to 1.00 % by weight.

[0142] In the present invention, the pH adjusting agent in the aqueous pharmaceutical composition is in a quantity sufficient to adjust the pH to the indicated value.

[0143] In a preferred embodiment of the second aspect, the conjunctivitis is bacterial. In a preferred embodiment, it is caused by Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Pseudomonas aeruginosa, Moraxella lucunata or E. coli. In a preferred embodiment, it is caused by S. aureus.

[0144] In a preferred embodiment of the second aspect, the conjunctivitis is caused by yeast infection. In a preferred embodiment, it is caused by C. albicans.

[0145] In a preferred embodiment of the second aspect, the conjunctivitis is viral. In a preferred embodiment, it is caused by Adenovirus type 19. In a preferred embodiment, it is caused by Adenovirus type 37. In a preferred embodiment, it is caused by Adenovirus type 8.

[0146] The preferred volumes of the container and for the aqueous pharmaceutical composition defined above for the first aspect, apply also for the third aspect of the present invention. As used herein, the term “about” means plus / minus 10% of the indicated values.In the present invention, when the term “comprising” is used, it also can mean “consisting of’ or “consisting essentially of’.

[0147] All the embodiments apply to any of the aspects of the invention.

[0148] EXAMPLES

[0149] The following examples illustrate various aspects of the present invention. The percentage of ingredients for each aqueous pharmaceutical composition are expressed as % w / w.

[0150] Example 1: aqueous ophthalmic pharmaceutical composition preparation

[0151] The following aqueous pharmaceutical compositions were prepared:

[0152] All ingredients are indicated in % by weight with respect to the total weight of the aqueous pharmaceutical composition (not including the container).

[0153]

[0154]

[0155]

[0156]

[0157] The compositions were prepared as follows:

[0158] The container was filled with purified water, then PVP-I was added while continuously mixing. Dissolution continued for at least 30 minutes. Then the buffer and the tonicity agent (sufficient amount to have an osmolality between 260 and 320 mOsmol / kg) were added and dissolved while continuously mixing. Dissolution continued for at least 10 minutes. In the separate vessel viscosity agent was added into purified water and dissolved while continuously mixing for at least 1 hour. The polymer solution was combined with the buffered povidone-iodine solution and mixed for at least 10 minutes. If necessary, the pH was adjusted by adding 10 % sodium hydroxide solution. Then, the final adjustment of the volume of the solution was performed with purified water.

[0159] For sterilizing the compositions, they were filtered through 0.2 pm hydrophilic modified polyvinylidene fluoride (PVDF) membrane directly to the sterile empty container.

[0160] The viscosity agents tested were sodium hyaluronate at 0.40 % by weight and polyvinyl alcohol (PVA) 40-88 at 0.90 % by weight.

[0161] Further compositions were prepared in a similar way following the standard procedures for preparation of aqueous ophthalmic pharmaceutical compositions:

[0162]

[0163]

[0164]

[0165]

[0166]

[0167] *CMC: carboxymethylcellulose

[0168] Example 2: stability tests.

[0169] Stability tests were carried out at 2-8 °C in single dose polyethylene (LDPE) or polypropylene (soft PP) minims of 0.9 ml and 1.6 ml volume, respectively, and in glass vials as reference. The stability was analysed by performing an assay of available iodine. The % available iodine for each example was determined by the method described in the British Pharmacopeia Monograph 2024 “Povidone-Iodine Eye Drops”, modified changing the titrant concentration from 0.0 IM sodium thiosulfate to 0.005 M sodium thiosulfate to adapt the method to the low available iodine concentration in the compositions of the invention.

[0170] The stabilities of the following aqueous pharmaceutical compositions were not acceptable:Composition 9 (with sodium hyaluronate as viscosity agent):

[0171]

[0172] Composition 9 (with PVA as viscosity agent):

[0173]

[0174] Composition s:

[0175]

[0176] Composition 14:

[0177]

[0178] Composition 15:

[0179]

[0180]

[0181] Composition 25 (with sodium hyaluronate as viscosity agent):

[0182]

[0183] Composition 25 (with PVA as viscosity agent):

[0184]

[0185] Composition 21 :

[0186]

[0187] Composition 30

[0188]

[0189] Surprisingly, the following aqueous pharmaceutical compositions were found to be stable:Composition 16:

[0190]

[0191] Composition 31 :

[0192]

[0193] Composition 32:

[0194]

[0195] Therefore, the inventors concluded that in single dose plastic containers of up to 3.0 ml, aqueous pharmaceutical compositions with 0.50 to 1.20 % povidone-iodine and 0.50 to 1.20 % of a stabilizer comprising iodide, comprising a tonicity agent, were stable. However, viscosity agents such as sodium hyaluronate or PVA did not improve the stability. Neither did stabilizer concentrations below 0.50 %. Also, pH between 4 and 5 did not improve the stability versus pH between 5 and 6.Example 3: Antimicrobial activity

[0196] The antimicrobial activity of the different aqueous pharmaceutical compositions was tested using a time-kill procedure. Bacteria Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were tested. Also yeast Candida albicans was tested. Adenovirus type 19 was also tested.

[0197]

[0198] > > > > > >

[0199]

[0200] The antimicrobial efficacy was tested according to the following methods:

[0201] For bacteria E. coli, S. aureus, P aeruginosa and yeast C. albicans, we followed the method for determination of bactericidal, fungicidal or yeasticidal activity of antiseptic medicinal products in the European Pharmacopeia 5.1.11. A product is assessed as effective against bacteria when log reduction > 5. A product is assessed as effective against yeast when log reduction > 4. It was found that compositions having at least 0.6 % of PVP-I are effective against bacteria and yeast. The contact times of the product with the microorganism were the following:

[0202] Staphylococcus aureus ATCC 6538, contact time 5 min.

[0203] Escherichia coli NCTC 10538, contact time 5 min.

[0204] Pseudomonas aeruginosa ATCC 15442, contact time 5 min.

[0205] Candida albicans ATCC 10231, contact time 15 min.

[0206] For adenovirus 19, the following method was used: Polish standard, published 31 December 2020, PN-EN 14476+A2:2019-08+Apl:2020-05 Chemical disinfectants and antiseptics -Quantitative suspension method for determining virucidal activity in the medical area - Testmethod and requirements (Phase 2 / Stage 1). The eye drop sample was added to a suspension of the test Adenovirus type 19 in the loading substance solution. The mixture was kept at 20°C for a contact time of 30 s, 120 s. After contacting the mixture with the virus suspension, subsequent decimal dilutions were made directly in the neutralizer, which is also the culture medium. Plaque testing or testing for the presence or absence of a cytopathic effect incubation, infectious titers were calculated according to the Spearman-Karber method (testing for the presence or absence of cytopathic effect) or by plaque counting and assessed. The reduction in virus infectivity was calculated from the difference between logarithmic virus titers before (virus control) and after treatment with the product.

[0207] According to the Polish standard PN-EN 14476+A2:2019-08+Ap 1:2020-05, a product is assessed as effective against viruses when log reduction > 4. It was found that compositions having at least 0.6 % of PVP-I are effective against viruses.

[0208] Example 4: EpiOcular™ Eye Irritation Test (ref: OCL-200-EIT) - Human Construct (MatTek Corporation). The model consists of layered human keratinocytes in a three-dimensional structure. The toxicity of the test product (and therefore the potential for eye irritation) is assessed based on the relative viability of treated tissues compared to the treated control tissues. Viability is determined using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and measures the continuous redox cycle of the cell population within each tissue construct. Tissue viability is determined by the amount of dye reduced over a given time under conditions where the dye is not limited and the cells receive glucose to maintain metabolic activity. The result is presented as relative survival (relative MTT conversion).

[0209] Example 5: preclinical study in rabbits of bacterial conjunctivitis

[0210] General design: Repeated-dose In vivo study in bacterial ocular infection model with adaptive design in New Zealand Albino rabbits, double-blind. Aim of the study: to verify efficacy and find an optimal concentration of PVP-I eyedrops solution in animal ocular infection model relevant for bacterial conjunctivitis.

Claims

CLAIMS1. A single dose plastic container comprising between 0.2 and 3.0 ml of an aqueous pharmaceutical composition comprising from 0.50 to 1.20 % by weight of povidone- iodine, from 0.50 to 1.20 % by weight of a stabilizer comprising iodide and from 0.02 to 0.90 % by weight of a tonicity agent.

2. The single dose plastic container according to claim 1, wherein the plastic container has a volume of between 0.2 and 3.0 ml.

3. The single dose plastic container according to any one of claims 1 or 2, wherein the plastic container has a volume of between 0.5 and 2.0 ml and comprises between 0.5 and 2.0 ml of the aqueous pharmaceutical composition.

4. The single dose plastic container according to any one of claims 1 to 3, wherein the stabilizer is selected between an iodide and an iodate, preferably the stabilizer is potassium iodide.

5. The single dose plastic container according to any one of claims 1 to 4, wherein the tonicity agent is sodium chloride.

6. The single dose plastic container according to any one of claims 1 to 5, wherein the plastic container is made of polyethylene, polypropylene or polyethylene terephthalate, preferably is made of PE, more preferably it is made of LDPE.

7. The single dose plastic container according to any one of claims 1 to 6, wherein the aqueous pharmaceutical composition further comprises a buffer or buffers.

8. The single dose plastic container according to claim 7, wherein the buffer or buffers are citric acid and sodium citrate.

9. The single dose plastic container according to any one of claims 7 or 8, wherein the amount of buffer or buffers is between 0.30 and 0.80 % by weight.

10. The single dose plastic container according to any one of claims 1 to 9, wherein the aqueous pharmaceutical composition has a pH between 4.0 and 6.0.

11. The single dose plastic container according to any one of claims 1 to 10, wherein the aqueous pharmaceutical composition further comprises at least one of sodium hyaluronate, sodium carboxymethylcellulose, poloxamer, glycerol and any combination thereof.

12. The single dose plastic container according to any one of claims 1 to 11, wherein the aqueous pharmaceutical composition comprises from 0.05 to 0.40 % by weight of sodium hyaluronate, preferably 0.05, 0.1, 0.15 or 0.20 % by weight.

13. The single dose plastic container according to any one of claims 1 to 12, wherein the aqueous pharmaceutical composition comprises from 0.20 - 0.50 % by weight of sodium carboxymethylcellulose, preferably 0.2, 0.3 or 0.5 % by weight, more preferably 0.3 % by weight.

14. The single dose plastic container according to any one of claims 1 to 13, wherein the aqueous pharmaceutical composition comprises from 0.10 - 0.20 % by weight of poloxamer, preferably 0.2 % by weight.

15. The single dose plastic container according to any one of claims 1 to 14, wherein the aqueous pharmaceutical composition comprises from 0.20 - 0.40 % by weight of glycerol, preferably 0.4 % by weight.

16. The single dose plastic container according to any one of claims 1 to 15, wherein the aqueous pharmaceutical composition comprises from 1.00 - 2.00 % by weight of ectoine, preferably 2.00 % by weight.

17. The single dose plastic container according to any one of claims 1 to 16, wherein the povidone-iodine concentration is about 0.6 % by weight, the stabilizer is potassiumiodide in a concentration of about 0.6 % by weight, the tonicity agent is sodium chloride in a concentration of about 0.51 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

18. The single dose plastic container according to any one of claims 1 to 17, wherein the povidone-iodine concentration is about 1.0 % by weight, the stabilizer is potassium iodide in a concentration of about 0.5 % by weight or of about 1.0 % by weight, the tonicity agent is sodium chloride in a concentration between 0.30 and 0.60 % by weight, the buffer is citric acid and sodium citrate in a total concentration of about 0.56 % by weight and the aqueous pharmaceutical composition has a pH between 5.0 and 6.0.

19. The single dose plastic container according to any one of claims 1 to 18 for use in the treatment of bacterial or viral conjunctivitis.

20. A single dose plastic container having a volume between 0.2 and 3.0 ml and comprising between 0.2 and 3.0 ml of an aqueous pharmaceutical composition comprising from 0.50 to 1.20 % by weight of povidone-iodine, for use in the treatment of bacterial or viral conjunctivitis.

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