Levocetirizine hydrochloride eye drop composition, preparation method and application

Abstract

The invention discloses a levocetirizine hydrochloride eye drop composition as well as a preparation method and application thereof, and belongs to the field of pharmaceutical preparations. The composition is prepared from levocetirizine hydrochloride, polyvinyl alcohol, povidone K30, sodium chloride, sodium benzoate, sodium hydroxide, hydrochloric acid and water, discomfort such as eye dryness caused by allergic conjunctivitis is remarkably relieved, and irritation caused by preservative sodium benzoate in multi-dose eye drops is reduced. The preparation method of the composition comprises the following steps: dissolving polyvinyl alcohol with a first part of water to obtain a product 1; dissolving povidone K30, sodium chloride and sodium benzoate with a second part of water, adjusting the pH value with sodium hydroxide and / or hydrochloric acid, and adding levocetirizine hydrochloride to obtain a product 2; and finally, adding the product 1 into the product 2, and supplementing water to the total amount. The composition is mainly used for treating eye itching related to allergic conjunctivitis. The levocetirizine hydrochloride eye drops provided by the invention do not contain antioxidants and buffering agents, and are non-irritant and good in stability.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations and relates to a composition containing levocetirizine hydrochloride eye drops, a preparation method and uses thereof. Background Art

[0002] Allergic conjunctivitis, also known as allergic conjunctivitis, is a hypersensitivity reaction of the conjunctiva to external allergens. The most common symptom of allergic conjunctivitis is itchy eyes, which can occur in almost all patients with allergic conjunctivitis, among which spring keratoconjunctivitis is usually the most obvious.

[0003] However, in addition to causing itchy eyes, allergic conjunctivitis is usually accompanied by irritation and dryness symptoms such as dry eyes, foreign body sensation, and eye fatigue.

[0004] Levocetirizine hydrochloride belongs to the third generation of antihistamine drugs. It is the R configuration isomer obtained from cetirizine hydrochloride by chiral separation. Its CAS number is 130018-87-0. Its chemical name is R-(-)2-[2-[4-[4-(chlorophenyl)benzyl]-1-piperazinyl]ethoxy]acetic acid dihydrochloride. Its molecular formula is C 21 H 27 Cl3N2O3, chemical structure is shown below.

[0005]

[0006] The affinity of levocetirizine hydrochloride to histamine H1 receptor is about 2 times higher than that of cetirizine, and about 30 times higher than that of dextrocetirizine hydrochloride. Compared with cetirizine hydrochloride, levocetirizine hydrochloride requires less dosage, has a faster onset of action, and has fewer adverse reactions.

[0007] Levocetirizine hydrochloride is used to relieve allergic symptoms of allergic diseases. It is clinically used to treat allergic rhinitis, urticaria, angioedema and other skin and mucous membrane allergic diseases. It is also used to relieve allergic symptoms during colds.

[0008] Currently, no levocetirizine hydrochloride eye drops have been registered or marketed.

[0009] Cetirizine hydrochloride eye drops were developed by Eyevance Pharmaceuticals Llc in the United States. The specification is 0.24% and the trade name is It was approved for marketing in the United States by the FDA on May 30, 2017, with the indication being "for the treatment of ocular itching associated with allergic conjunctivitis." Although using 0.01% benzalkonium chloride as a preservative can ensure the stability of the product while preventing the growth of bacteria and fungi, patients with allergic conjunctivitis need long-term and continuous medication. However, long-term and frequent use of eye drops containing preservatives may cause irritation symptoms such as eye discomfort, dryness, and burning sensation, and may increase the risk of infection. Moreover, cetirizine hydrochloride contains right cetirizine hydrochloride, which is the main component that causes adverse reactions.

[0010] Polyvinyl alcohol eye drops were developed by Allergan in a 1.4% strength and sold under the trade name It was first launched in the UK in the 1970s with the indication of "being used as a lubricant to prevent or treat irritation symptoms such as dry eyes, foreign body sensation, eye fatigue, or to improve symptoms of dry eyes."

[0011] Patent CN113876702A discloses a levocetirizine hydrochloride eye drop and a preparation method thereof. The dosage of levocetirizine hydrochloride is 0.01% to 0.5%, and the eye drop also contains a buffer and a metal chelating agent.

[0012] At present, there is still a need to develop levocetirizine hydrochloride eye drops with more reasonable dosage and more comfortable use. Summary of the invention

[0013] In order to solve the persistent imbalance between supply and demand, the inventors have conducted in-depth research and experiments, and have provided an eye drop composition containing levocetirizine hydrochloride and a preparation method thereof, aiming at the problems of high drug concentration, slow onset of effect and many adverse reactions of the currently marketed cetirizine hydrochloride eye drops.

[0014] The levocetirizine hydrochloride eye drop composition provided by the invention is based on levocetirizine hydrochloride and uses polyvinyl alcohol eye drops as an excipient, thereby providing a pH close to that of tears and a salt concentration isotonic with that of tears.

[0015] The polyvinyl alcohol eye drops of the present invention contain 1.4% polyvinyl alcohol as an active ingredient, 0.6% povidone K30 as a lubricant, 0.78% sodium chloride as an osmotic pressure regulator, sodium hydroxide and / or hydrochloric acid as a pH regulator, and water as a solvent.

[0016] Polyvinyl alcohol is a high molecular polymer with hydrophilicity and film-forming properties. At an appropriate concentration, it can play a role similar to artificial tears. Therefore, polyvinyl alcohol eye drops can significantly relieve allergic conjunctivitis accompanied by dry eyes, foreign body sensation, eye fatigue and other irritation and dryness symptoms.

[0017] Moreover, for multi-dose products containing preservatives, the composition provided by the present invention uses polyvinyl alcohol eye drops as an excipient, which significantly alleviates eye discomfort, dryness, burning sensation and other irritation symptoms that may be caused by long-term and frequent use of preservatives, and reduces the risk of increased infection.

[0018] The preservative described in the present invention refers to sodium benzoate. Sodium benzoate has low toxicity and good solubility, and is widely used as a preservative in drug production and storage.

[0019] The inventors unexpectedly discovered that adding an appropriate amount of sodium benzoate, a preservative, to levocetirizine hydrochloride eye drops can not only ensure the sterility of the product but also improve the stability of the product, thereby eliminating the need to add additional antioxidants and buffers.

[0020] Implementation of the present invention:

[0021] In the first aspect, the present invention provides a levocetirizine hydrochloride eye drop composition free of antioxidants and buffers, wherein the composition uses polyvinyl alcohol eye drops as an excipient, specifically comprising levocetirizine hydrochloride, polyvinyl alcohol, povidone K30, sodium chloride, sodium benzoate, sodium hydroxide and / or hydrochloric acid, and water. Among them, polyvinyl alcohol is used as a thickener, povidone K30 is used as a lubricant, sodium chloride is used as an osmotic pressure regulator, sodium benzoate is used as a preservative, sodium hydroxide and / or hydrochloric acid are used as pH regulators, and water is used as a solvent.

[0022] In certain embodiments, the eye drop composition is composed of 0.12% levocetirizine hydrochloride, 1.4% polyvinyl alcohol, 0.6% povidone K30, 0.78% sodium chloride, 0.1% to 0.4% sodium benzoate, appropriate amount of sodium hydroxide and / or hydrochloric acid, and the balance water.

[0023] In certain embodiments, the amount of sodium benzoate in the eye drop composition is 0.1%, 0.2%, 0.3% or 0.4%.

[0024] In certain embodiments, the eye drop composition is composed of 0.12% levocetirizine hydrochloride, 1.4% polyvinyl alcohol, 0.6% povidone K30, 0.78% sodium chloride, 0.1% sodium benzoate, appropriate amount of sodium hydroxide and / or hydrochloric acid, and the balance water.

[0025] In certain embodiments, the eye drop composition is composed of 0.12% levocetirizine hydrochloride, 1.4% polyvinyl alcohol, 0.6% povidone K30, 0.78% sodium chloride, 0.2% sodium benzoate, appropriate amount of sodium hydroxide and / or hydrochloric acid, and the balance water.

[0026] In certain embodiments, the eye drop composition is composed of 0.12% levocetirizine hydrochloride, 1.4% polyvinyl alcohol, 0.6% povidone K30, 0.78% sodium chloride, 0.3% sodium benzoate, appropriate amount of sodium hydroxide and / or hydrochloric acid, and the balance water.

[0027] In certain embodiments, the eye drop composition is composed of 0.12% levocetirizine hydrochloride, 1.4% polyvinyl alcohol, 0.6% povidone K30, 0.78% sodium chloride, 0.4% sodium benzoate, appropriate amount of sodium hydroxide and / or hydrochloric acid, and the balance water.

[0028] In certain embodiments, the preservative further comprises benzalkonium chloride, potassium sorbate, methylparaben or chlorobutanol.

[0029] In certain embodiments, the antioxidant further comprises disodium edetate, sodium thiosulfate, sodium bisulfite or ascorbic acid.

[0030] In certain embodiments, the buffer further comprises sodium dihydrogen phosphate monohydrate, sodium dihydrogen phosphate dodecahydrate, or sodium phosphate dodecahydrate.

[0031] In a second aspect, the present invention also provides a method for preparing levocetirizine hydrochloride eye drops, comprising the following steps:

[0032] (1) adding polyvinyl alcohol to the first part of water and stirring to dissolve;

[0033] (2) Add povidone K30, sodium chloride and sodium benzoate to the second portion of water and stir to dissolve;

[0034] (3) adjusting the pH value of the product obtained in (2) to 6.3 to 6.5 with sodium hydroxide and / or hydrochloric acid, and stirring to make it uniform;

[0035] (4) adding levocetirizine hydrochloride to the product obtained in (3) and stirring to make it uniform;

[0036] (5) adding the product obtained in (1) to the product obtained in (4) and stirring until uniform;

[0037] (6) Replenish water to full volume.

[0038] In a third aspect, the levocetirizine hydrochloride eye drops provided by the present invention are used to treat eye itching associated with allergic conjunctivitis. The composition is used for eye drops, 1 drop at a time, twice a day.

[0039] In the present invention, unless otherwise specified, the term "%" refers to w / v%, i.e. weight / volume percentage. For example, 0.12% levocetirizine hydrochloride means that the content of levocetirizine hydrochloride in the composition is 0.12 g / 100 ml, or 1.2 mg / ml, or 1.2 g / L.

[0040] Beneficial effects achieved by the present invention:

[0041] (1) It solves the problems of high drug concentration, slow onset of effect and many adverse reactions of the cetirizine hydrochloride eye drops that are already on the market;

[0042] (2) It solves the irritation and dryness symptoms of allergic conjunctivitis, such as dry eyes, foreign body sensation, and eye fatigue;

[0043] (3) Solved the irritation problem of preservatives in multi-dose eye drops;

[0044] (4) It does not contain antioxidants and buffers and can be stored stably for 24 months. DETAILED DESCRIPTION

[0045] The embodiments of the present invention will be described in detail below with reference to examples. Those skilled in the art will understand that the following examples are only used to illustrate the present invention and are not to be regarded as limiting the scope of the present invention. However, the following examples all fall within the scope of the present invention.

[0046] Although many materials and operating methods used in the following examples are well known in the art, the present invention is still described in as much detail as possible. It is clear to those skilled in the art that the materials and operating methods used in the following examples are well known in the art unless otherwise specified.

[0047] In the embodiments or comparative examples of the present invention, when describing the dosage, "%" refers to w / v%, i.e., weight / volume percentage. For example, 0.12% levocetirizine hydrochloride means that the content of levocetirizine hydrochloride in the composition is 0.12 g / 100 ml, or 1.2 mg / ml, or 1.2 g / L.

[0048] 1. Implementation Method

[0049] Example 1: Polyvinyl alcohol eye drops are used as excipients only, without adding preservatives, antioxidants, and buffers

[0050] Ingredients Example 1 Levocetirizine hydrochloride 0.12％ Polyvinyl alcohol 1.4％ Povidone K30 0.6％ Sodium chloride 0.78％ Sodium hydroxide and / or hydrochloric acid Adjust pH to 6.3-6.5 water to 100%

[0051] The preparation method of embodiment 1:

[0052] (1) adding polyvinyl alcohol to the first part of water and stirring to dissolve;

[0053] (2) Add povidone K30 and sodium chloride to the second portion of water and stir to dissolve;

[0054] (3) adjusting the pH value of the product obtained in (2) to 6.3 to 6.5 with sodium hydroxide and / or hydrochloric acid, and stirring to make it uniform;

[0055] (4) adding levocetirizine hydrochloride to the product obtained in (3) and stirring to make it uniform;

[0056] (5) adding the product obtained in (1) to the product obtained in (4) and stirring until uniform;

[0057] (6) Replenish water to full volume.

[0058] Example 2 to Example 8: Adding an appropriate amount of sodium benzoate as a preservative

[0059]

[0060] The preparation methods of Examples 2 to 8:

[0061] (1) adding polyvinyl alcohol to the first part of water and stirring to dissolve;

[0062] (2) Add povidone K30, sodium chloride and sodium benzoate to the second portion of water and stir to dissolve;

[0063] (3) adjusting the pH value of the product obtained in (2) to 6.3 to 6.5 with sodium hydroxide and / or hydrochloric acid, and stirring to make it uniform;

[0064] (4) adding levocetirizine hydrochloride to the product obtained in (3) and stirring to make it uniform;

[0065] (5) adding the product obtained in (1) to the product obtained in (4) and stirring until uniform;

[0066] (6) Replenish water to full volume.

[0067] Comparative Examples 1 to 4: Adding benzalkonium chloride, potassium sorbate, methyl paraben or chlorobutanol as preservatives

[0068]

[0069] Comparative Examples 5 to 8: Adding disodium edetate, sodium thiosulfate, sodium bisulfite or ascorbic acid as an antioxidant

[0070]

[0071] Comparative Examples 9 to 11: Adding sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate dodecahydrate or sodium phosphate dodecahydrate as a buffer

[0072] Ingredients Comparative Example 9 Comparative Example 10 Comparative Example 11 Levocetirizine hydrochloride 0.12％ 0.12％ 0.12％ Polyvinyl alcohol 1.4％ 1.4％ 1.4％ Povidone K30 0.6％ 0.6％ 0.6％ Sodium chloride 0.78％ 0.78％ 0.78％ Sodium dihydrogen phosphate monohydrate 0.25％ / / Disodium hydrogen phosphate dodecahydrate / 0.25％ / Sodium phosphate dodecahydrate / / 0.25％ Sodium hydroxide and / or hydrochloric acid Adjust pH to 6.3-6.5 Adjust pH to 6.3-6.5 Adjust pH to 6.3-6.5 water to 100% to 100% to 100%

[0073] Comparative Examples 12 to 14: No polyvinyl alcohol was added or polyvinyl alcohol eye drops were not used as an excipient

[0074] Ingredients Comparative Example 12 Comparative Example 13 Comparative Example 14 Levocetirizine hydrochloride 0.12％ 0.12％ 0.12％ Polyvinyl alcohol / / / Povidone K30 0.6％ / / Sodium chloride 0.78％ 0.78％ / Sodium Benzoate 0.1％ 0.1％ 0.1％ Sodium hydroxide and / or hydrochloric acid Adjust pH to 6.3-6.5 Adjust pH to 6.3-6.5 Adjust pH to 6.3-6.5 water to 100% to 100% to 100%

[0075] Preparation methods of Comparative Examples 1 to 14:

[0076] (1) Add polyvinyl alcohol (if any) to the first part of water and stir to dissolve;

[0077] (2) adding povidone K30, sodium chloride, preservative (if any), antioxidant (if any), and buffer (if any) to the second portion of water and stirring to dissolve;

[0078] (3) adjusting the pH value of the product obtained in (2) to 6.3 to 6.5 with sodium hydroxide and / or hydrochloric acid, and stirring to make it uniform;

[0079] (4) adding levocetirizine hydrochloride to the product obtained in (3) and stirring to make it uniform;

[0080] (5) adding the product obtained in (1) to the product obtained in (4) and stirring until uniform;

[0081] (6) Replenish water to full volume.

[0082] 2. Quality Research

[0083] (I) Investigation of antibacterial efficacy

[0084] According to the antibacterial efficacy test method in 1121 of the fourth general rule of the 2020 edition of the "Chinese Pharmacopoeia", Examples 2 to 8 were taken for antibacterial efficacy determination. The results showed that the antibacterial efficacy of Examples 2 and 3 met the B standard requirements, and the antibacterial efficacy of Examples 4 to 8 all met the A standard requirements.

[0085] The results of the antibacterial efficacy test show that Examples 2 to 8 using 0.01% to 0.5% sodium benzoate as a preservative can ensure that the products are sterile.

[0086] (II) Comparative study on quality characteristics

[0087] Take Example 1, Example 2 to Example 8, and compare the properties, pH value, osmotic pressure molar concentration, related substances, and content. Among them, the pH value determination method is the general rule 0631 of the fourth volume of the 2020 edition of the Chinese Pharmacopoeia, the osmotic pressure molar concentration determination method is the general rule 0632 of the fourth volume of the 2020 edition of the Chinese Pharmacopoeia, and the related substances and content determination method is the related substance determination method of levocetirizine hydrochloride in the European Pharmacopoeia 11.0. The test results are shown in the table below.

[0088] Table 1 Quality characteristics comparison inspection results

[0089]

[0090] The results of the quality characteristics comparison show that:

[0091] (1) The properties, related substances and contents of each example meet the limit requirements;

[0092] (2) In Example 1, in which no sodium benzoate was added, the pH value after volume fixing was unstable, and the decrease was larger than the pH value of 6.4 before volume fixing; in Examples 2 to 8, in which 0.01% to 0.5% sodium benzoate was added, the decreasing trend of the pH value after volume fixing became smaller as the amount of sodium benzoate increased;

[0093] (3) As the amount of sodium benzoate increases, the osmotic pressure molar concentration of the solution gradually increases. The osmotic pressure molar concentrations of Examples 1 to 3 and 8 do not meet the limit requirements, and the osmotic pressure molar concentrations of Examples 4 to 7 are close to that of tears.

[0094] (4) That is, in Examples 4 to 7, which use 0.1% to 0.4% sodium benzoate as a preservative, the stability of the pH value of the product can be effectively ensured on the basis of ensuring the sterility of the product, and will not affect the osmotic pressure molar concentration.

[0095] (III) Stability investigation

[0096] 1. Test of influencing factors

[0097] Take Example 1, Example 2 to Example 8, Comparative Example 1 to Comparative Example 11, and carry out influencing factor tests (high temperature 60°C, light 4500lx) according to the general principles of 9001 raw material drug and preparation stability test of the 2020 edition of the Chinese Pharmacopoeia, and compare the pH value and related substances (the content of the oxidized impurity cetirizine N-oxide). The test results are shown in the table below.

[0098] Table 2 pH value test results

[0099]

[0100] The results of pH stability test showed that:

[0101] (1) In Example 1, in which no sodium benzoate and buffer were added, the pH value of the product was unstable, showing a significant downward trend, and did not meet the limit requirements;

[0102] (2) Examples 2 to 8 in which 0.01% to 0.5% sodium benzoate is added as a preservative not only ensure the sterility of the product but also improve the pH stability of the product;

[0103] (3) As the amount of sodium benzoate increases, the downward trend of the pH value becomes significantly smaller; when the amount of sodium benzoate is ≥0.1%, the pH value stability is better, which is not inferior to that of adding sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate dodecahydrate (if any) and sodium phosphate dodecahydrate as a buffer in Comparative Examples 9 to Comparative Examples 11;

[0104] (4) That is, Examples 4 to 7 in which 0.1% to 0.4% sodium benzoate is added as a preservative not only ensure the sterility of the product, but also improve the pH stability of the product without adding an additional buffer.

[0105] Table 3 Test results of related substances (content of oxidized impurity cetirizine N-oxide)

[0106]

[0107] The results of the investigation on the stability of relevant substances show that:

[0108] (1) Example 1 without adding sodium benzoate and antioxidant, and Comparative Examples 1 to 4 with adding benzalkonium chloride, potassium sorbate, methyl paraben (if any) and chlorobutanol as preservatives but without adding antioxidant, all have poor stability and the content of cetirizine N-oxide increases rapidly;

[0109] (2) Examples 2 to 8 in which 0.01% to 0.5% sodium benzoate was added as a preservative not only ensured the sterility of the product, but also improved the stability of the product. When placed under high temperature of 60° C. and light of 4500 lx for 30 days, the content of cetirizine N-oxide did not exceed the limit requirement;

[0110] (2) As the amount of sodium benzoate increases, the content of cetirizine N-oxide shows a significant downward trend; when the amount of sodium benzoate is ≥0.1%, the stability is better, which is not inferior to Comparative Examples 5 to 8 in which disodium edetate, sodium thiosulfate, sodium bisulfite (if any) and ascorbic acid are added as antioxidants;

[0111] (4) That is, Examples 4 to 7, in which 0.1% to 0.4% sodium benzoate is added as a preservative, not only ensure the sterility of the product, but also improve the stability of the product without adding additional antioxidants.

[0112] 2. Accelerated testing

[0113] Take Example 4 to Example 7, according to the "Chinese Pharmacopoeia 2020 Edition General Rules 9001 Raw Material Drug and Preparation Stability Test Guidance Principles", accelerated tests (temperature 40 ° C ± 2 ° C, relative humidity 25% ± 5%), long-term tests (temperature 25 ° C ± 2 ° C, relative humidity 40% ± 5%) were carried out, and the results are shown in the table below.

[0114] Table 4 Accelerated test results (Example 4, Example 5)

[0115]

[0116] Table 5 Accelerated test results (Example 6, Example 7)

[0117]

[0118] The results of accelerated tests show that:

[0119] (1) All the results of Examples 4 to 7 meet the limit requirements;

[0120] (2) The content change does not exceed 5%;

[0121] (3) That is, adding 0.1% to 0.4% sodium benzoate can effectively ensure that the product can be stored stably for 6 months under accelerated test conditions.

[0122] 3. Long-term test

[0123] Take samples such as Example 4 to Example 7, and carry out long-term tests (temperature 25°C ± 2°C, relative humidity 40% ± 5%) in accordance with the guidelines for stability testing of raw materials and preparations in Part IV of the 2020 edition of the Chinese Pharmacopoeia (Chinese Pharmacopoeia). The results are shown in the table below.

[0124] Table 6 Long-term test results (Example 4, Example 5)

[0125]

[0126] Table 7 Long-term test results (Example 6, Example 7)

[0127]

[0128] Long-term test results show that:

[0129] (1) All the results of Examples 4 to 7 meet the limit requirements;

[0130] (2) The content change does not exceed 5%;

[0131] (3) That is, the addition of 0.1% to 0.4% sodium benzoate can effectively ensure the stable storage of the product for 24 months under long-term test conditions.

[0132] 3. Stimulus Investigation

[0133] Take Example 1, Example 4 to Example 7, and Comparative Example 12 to Comparative Example 14 to observe whether levocetirizine hydrochloride eye drops are irritating to rabbits after being instilled into the eyes, so as to provide a basis for the evaluation of medication comfort and safety.

[0134] Evaluation method: Three male Japanese white rabbits were selected, and levocetirizine hydrochloride eye drops were instilled into the left eyes of the three animals in the drug administration group, 6 times a day, with an interval of at least 1 hour, for 7 consecutive days. The eyes were examined before the first administration of the day and 1h, 2h, 4h, 24h, 48h, and 72h after the last administration.

[0135] Table 8 Eye irritation response scoring table

[0136]

[0137] Table 9 Eye irritation evaluation standard

[0138]

[0139]

[0140] Table 10 Statistics of irritation test scores

[0141]

[0142] The results of the irritation test showed that:

[0143] (1) Example 1 using polyvinyl alcohol eye drops as an excipient and without adding preservatives was non-irritating;

[0144] (2) Examples 4 to 7 using polyvinyl alcohol eye drops as an excipient and adding 0.1% to 0.4% sodium benzoate as a preservative were all non-irritating;

[0145] (3) Comparative Examples 12 to 14, which did not use polyvinyl alcohol eye drops as an excipient and added 0.1% sodium benzoate as a preservative, all had mild irritation.

[0146] (4) That is, using polyvinyl alcohol eye drops as an excipient can significantly reduce the irritation caused by preservatives in multi-dose eye drops.

[0147] Although the specific embodiments of the present invention have been described in detail, it will be understood by those skilled in the art that various modifications and substitutions may be made to those details based on all the teachings disclosed, and these changes are within the scope of protection of the present invention. The full scope of the present invention is given by the attached claims and any equivalents thereof.

Claims

1. A levocetirizine hydrochloride eye drop composition, consisting of levocetirizine hydrochloride, polyvinyl alcohol, povidone K30, sodium chloride, sodium benzoate, sodium hydroxide and / or hydrochloric acid, and water.

2. The composition according to claim 1, characterized in that The composition is composed of 0.12% levocetirizine hydrochloride, 1.4% polyvinyl alcohol, 0.6% povidone K30, 0.78% sodium chloride, 0.1-0.4% sodium benzoate, appropriate amount of sodium hydroxide and / or hydrochloric acid, and the balance of water, and the amount is calculated by weight / volume percentage.

3. The composition according to claim 2, characterized in that The dosage of sodium benzoate is 0.1%, 0.2%, 0.3% or 0.4%.

4. The composition according to claim 3, characterized in that The composition is composed of 0.12% levocetirizine hydrochloride, 1.4% polyvinyl alcohol, 0.6% povidone K30, 0.78% sodium chloride, 0.1% sodium benzoate, appropriate amount of sodium hydroxide and / or hydrochloric acid, and the balance of water; or It is composed of 0.12% levocetirizine hydrochloride, 1.4% polyvinyl alcohol, 0.6% povidone K30, 0.78% sodium chloride, 0.2% sodium benzoate, appropriate amount of sodium hydroxide and / or hydrochloric acid, and the balance of water; or It is composed of 0.12% levocetirizine hydrochloride, 1.4% polyvinyl alcohol, 0.6% povidone K30, 0.78% sodium chloride, 0.3% sodium benzoate, appropriate amount of sodium hydroxide and / or hydrochloric acid, and the balance water; or The invention is composed of 0.12% levocetirizine hydrochloride, 1.4% polyvinyl alcohol, 0.6% povidone K30, 0.78% sodium chloride, 0.4% sodium benzoate, appropriate amount of sodium hydroxide and / or hydrochloric acid, and the balance of water.

5. The composition according to claims 1 to 4, characterized in that The preparation method of the composition comprises the following steps: (1) adding polyvinyl alcohol to the first part of water and stirring to dissolve; (2) Add povidone K30, sodium chloride and sodium benzoate to the second portion of water and stir to dissolve; (3) adjusting the pH value of the product obtained in (2) to 6.3 to 6.5 with sodium hydroxide and / or hydrochloric acid, and stirring to make it uniform; (4) adding levocetirizine hydrochloride to the product obtained in (3) and stirring to make it uniform; (5) adding the product obtained in (1) to the product obtained in (4) and stirring until uniform; (6) Replenish water to full volume.

6. The composition according to claims 1 to 5, characterized in that The composition is primarily used to treat ocular itching associated with allergic conjunctivitis.

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