Olopatadine hydrochloride eye drops

Abstract

The invention relates to olopatadine hydrochloride eye drops. Every 1000 ml of the olopatadine hydrochloride eye drops contain 2 g of olopatadine hydrochloride, polysorbate 80 and sodium tartrate, furthermore, 2.2 g of polysorbate 80, 3.5 g of sodium tartrate, 6.5 g of sodium chloride and 8.0 g of povidone K30, the olopatadine hydrochloride eye drops prepared according to the prescription process have extremely high quality stability, the medication safety is improved, and the olopatadine hydrochloride eye drops are suitable for clinical application. The method is obviously superior to the prior art.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to olopatadine hydrochloride eye drops. Background Art

[0002] Olopatadine hydrochloride, English name Olopatadine HCl, molecular formula: C 21 H 23 NO3·HCl. It has a wide range of drug effects, such as histamine H1 receptor antagonist effect, chemical mediator inhibition, tachykinin release inhibition and eosinophil infiltration inhibition. It is suitable for allergic rhinitis, allergic conjunctivitis, urticaria and itching caused by skin diseases. Eye drops are a commonly used dosage form in clinical practice, used to treat the signs and symptoms of allergic conjunctivitis. It can be used to treat external eye infections such as bacterial conjunctivitis, keratitis, dacryocystitis, and postoperative infections. Allergic conjunctivitis, also known as allergic conjunctivitis, is a hypersensitivity reaction of the conjunctiva to external allergens. It mainly includes type I allergic reaction and type IV allergic reaction, among which allergic conjunctivitis caused by type I allergic reaction is the most common. Allergic conjunctivitis caused by type I allergic reaction is rapid-onset, mainly including seasonal allergic conjunctivitis, perennial allergic conjunctivitis, giant papillary conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis, etc. Allergic conjunctivitis caused by type IV allergic reaction is delayed-onset, mainly including vesicular conjunctivitis. Olopatadine hydrochloride eye drops are widely used in clinical practice, but the stability of olopatadine hydrochloride eye drops is poor, especially the light stability. Therefore, it is of great clinical significance to prepare a highly stable olopatadine hydrochloride eye drops.

[0003] The inventors have obtained olopatadine hydrochloride eye drops and a preparation method thereof after long-term and extensive research on olopatadine hydrochloride eye drops. The olopatadine hydrochloride eye drops prepared by the method have extremely high quality stability, increase the safety of medication, and are significantly superior to the prior art. Summary of the invention

[0004] The object of the present invention is to provide an olopatadine hydrochloride eye drop having good stability.

[0005] The technical solution provided by the present invention is: an olopatadine hydrochloride eye drop filled in a plastic ampoule, wherein each 1000 ml of the eye drop contains, in addition to 2 g of olopatadine hydrochloride, polysorbate 80 and sodium tartrate.

[0006] Furthermore, each 1000 ml contains 2.2 g of polysorbate 80 and 3.5 g of sodium tartrate.

[0007] Furthermore, the specification of Olopatadine Hydrochloride Eye Drops is 0.4ml:0.8mg (0.2%).

[0008] Furthermore, each 1000 ml of eye drops may also contain 6.5 g of sodium chloride.

[0009] Furthermore, each 1000 ml of eye drops may also contain 8.0 g of povidone K30.

[0010] Furthermore, the preparation method of the above eye drops comprises the following steps:

[0011] (1) Dissolve the prescribed amount of polysorbate 80 and sodium tartrate in 600 ml of water for injection at 45-50°C.

[0012] (2) Maintaining the temperature at 45-50°C, add the prescribed amount of olopatadine hydrochloride and stir to dissolve, adjust the pH value to 7.0 with hydrochloric acid or sodium hydroxide, and add water for injection to 1000 ml;

[0013] (3) Cool the solution to 24°C to 26°C, determine the pH value and content of the solution, filter and sterilize with a 0.22 µm filter cartridge, and fill the solution into an eye drop bottle according to the specifications to obtain olopatadine hydrochloride eye drops.

[0014] The present invention also provides a method for preparing olopatadine hydrochloride eye drops, comprising the following steps:

[0015] (1) Dissolve the prescribed amount of polysorbate 80, sodium tartrate, sodium chloride, and povidone K30 in 600 ml of water for injection at 45-50°C in sequence;

[0016] (2) Maintaining the temperature at 45-50°C, add the prescribed amount of olopatadine hydrochloride and stir to dissolve, adjust the pH value to 7.0 with hydrochloric acid or sodium hydroxide, and add water for injection to 1000 ml;

[0017] (3) Cool the solution to 24°C to 26°C, determine the pH value and content of the solution, filter and sterilize with a 0.22 µm filter cartridge, and fill the solution into an eye drop bottle according to the specifications to obtain olopatadine hydrochloride eye drops.

[0018] Furthermore, the prescription amount is:

[0019] Each 1000ml of the eye drops contains:

[0020] Olopatadine hydrochloride: 2g

[0021] Polysorbate 80: 2.2 g

[0022] Sodium tartrate: 3.5g

[0023] Sodium chloride: 6.5g

[0024] Povidone K30: 8.0g

[0025] The present invention adopts polysorbate 80 and sodium tartrate as excipients of olopatadine hydrochloride eye drops. The combined use of the two excipients is beneficial to increasing the stability of olopatadine hydrochloride eye drops and has an unexpected effect. In particular, the specific ratio of adding 2.2g of polysorbate 80 and 3.5g of sodium tartrate per 1000ml has the best effect.

[0026] The following experiment illustrates the effect of the combined use of polysorbate 80 and sodium tartrate on olopatadine hydrochloride eye drops, making the technical effect of the combined use of polysorbate 80 and sodium tartrate easier to understand.

[0027] Table 1 Polysorbate 80 and sodium tartrate eye drops in different prescription amounts

[0028]

[0029] The above prescriptions of Olopatadine Hydrochloride Eye Drops are prepared according to the following steps: (Specification 0.4ml: 0.8mg.)

[0030] (1) Dissolve the prescribed amount of polysorbate 80 and sodium tartrate in 600 ml of water for injection at 45-50°C.

[0031] (2) Maintaining the temperature at 45-50°C, add the prescribed amount of olopatadine hydrochloride and stir to dissolve, adjust the pH value to 7.0 with hydrochloric acid or sodium hydroxide, and add water for injection to 1000 ml;

[0032] (3) Cool the solution to 24°C to 26°C, determine the pH value and content of the solution, filter and sterilize with a 0.22 µm filter cartridge, and fill the solution into an eye drop bottle according to the specifications to obtain olopatadine hydrochloride eye drops.

[0033] The above 8 prescription samples were subjected to the influencing factor test, and were placed at 60℃ and strong light (4500lx±500lx) for 10 days. Samples were taken for testing on the 10th day, and the results were compared with those on the 0th day to investigate the stability of the samples. The results are shown in Table 2-Table 3:

[0034] Table 2 60℃ stability test results

[0035]

[0036] Table 3 Strong light (4500LX) stability test results

[0037]

[0038] It can be seen from the test results in Tables 2 and 3 that the combined use of polysorbate 80 and sodium tartrate is beneficial to increasing the stability of olopatadine hydrochloride eye drops, especially the specific ratio of adding 2.2g of polysorbate 80 and 3.5g of sodium tartrate per 1000ml has the best effect. Even if the usage changes slightly, it will produce significantly different technical effects. DETAILED DESCRIPTION

[0039] Example 1 Preparation of Olopatadine Hydrochloride Eye Drops (0.4 ml: 0.8 mg)

[0040] prescription:

[0041] Olopatadine hydrochloride: 2g

[0042] Polysorbate 80: 2.2 g

[0043] Sodium tartrate: 3.5g

[0044] Add water for injection to 1000ml

[0045] Made into 2500 pieces

[0046] Preparation method:

[0047] (1) Dissolve the prescribed amount of polysorbate 80 and sodium tartrate in 600 ml of water for injection at 45°C;

[0048] (2) Maintaining the temperature at 45°C, add the prescribed amount of olopatadine hydrochloride and stir to dissolve, adjust the pH value to 7.0 with hydrochloric acid or sodium hydroxide, and add water for injection to 1000 ml;

[0049] (3) Cool the solution to 24°C, determine the pH value and content of the solution, filter and sterilize with a 0.22 µm filter cartridge, and fill the solution into an eye drop bottle according to the specifications to obtain olopatadine hydrochloride eye drops.

[0050] Example 2 Preparation of Olopatadine Hydrochloride Eye Drops (0.4 ml: 0.8 mg)

[0051] prescription:

[0052] Olopatadine hydrochloride: 2g

[0053] Polysorbate 80: 2.2 g

[0054] Sodium tartrate: 3.5g

[0055] Add water for injection to 1000ml

[0056] Made into 2500 pieces

[0057] Preparation method:

[0058] (1) Dissolve the prescribed amount of polysorbate 80 and sodium tartrate in 600 ml of water for injection at 50°C;

[0059] (2) Maintaining the temperature at 50°C, add the prescribed amount of olopatadine hydrochloride and stir to dissolve, adjust the pH value to 7.0 with hydrochloric acid or sodium hydroxide, and add water for injection to 1000 ml;

[0060] (3) Cool the solution to 26°C, determine the pH value and content of the solution, filter and sterilize with a 0.22 µm filter cartridge, and fill the solution into an eye drop bottle according to the specifications to obtain olopatadine hydrochloride eye drops.

[0061] Example 3 Preparation of Olopatadine Hydrochloride Eye Drops (0.4 ml: 0.8 mg)

[0062] prescription:

[0063] Olopatadine hydrochloride: 2g

[0064] Polysorbate 80: 2.2 g

[0065] Sodium tartrate: 3.5g

[0066] Add water for injection to 1000ml

[0067] Made into 2500 pieces

[0068] Preparation method:

[0069] (1) Dissolve the prescribed amount of polysorbate 80 and sodium tartrate in 600 ml of water for injection at 47°C;

[0070] (2) Maintaining the temperature at 47°C, add the prescribed amount of olopatadine hydrochloride and stir to dissolve, adjust the pH value to 7.0 with hydrochloric acid or sodium hydroxide, and add water for injection to 1000 ml;

[0071] (3) Cool the solution to 25°C, determine the pH value and content of the solution, filter and sterilize with a 0.22 µm filter cartridge, and fill the solution into an eye drop bottle according to the specifications to obtain olopatadine hydrochloride eye drops.

[0072] Example 4 Preparation of Olopatadine Hydrochloride Eye Drops (0.4 ml: 0.8 mg)

[0073] prescription:

[0074] Olopatadine hydrochloride: 2g

[0075] Polysorbate 80: 2.2 g

[0076] Sodium tartrate: 3.5g

[0077] Sodium chloride: 6.5g

[0078] Povidone K30: 8.0g

[0079] Add water for injection to 1000ml

[0080] Made into 2500 pieces

[0081] Preparation method:

[0082] (1) Dissolve the prescribed amount of polysorbate 80, sodium tartrate, sodium chloride, and povidone K30 in 600 ml of water for injection at 45°C in sequence;

[0083] (2) Maintaining the temperature at 45°C, add the prescribed amount of olopatadine hydrochloride and stir to dissolve, adjust the pH value to 7.0 with hydrochloric acid or sodium hydroxide, and add water for injection to 1000 ml;

[0084] (3) Cool the solution to 24°C, determine the pH value and content of the solution, filter and sterilize with a 0.22 µm filter cartridge, and fill the solution into an eye drop bottle according to the specifications to obtain olopatadine hydrochloride eye drops.

[0085] Example 5 Preparation of Olopatadine Hydrochloride Eye Drops (0.4 ml: 0.8 mg)

[0086] prescription:

[0087] Olopatadine hydrochloride: 2g

[0088] Polysorbate 80: 2.2 g

[0089] Sodium tartrate: 3.5g

[0090] Sodium chloride: 6.5g

[0091] Povidone K30: 8.0g

[0092] Add water for injection to 1000ml

[0093] Made into 2500 pieces

[0094] Preparation method:

[0095] (1) Dissolve the prescribed amount of polysorbate 80, sodium tartrate, sodium chloride, and povidone K30 in 600 ml of water for injection at 50°C in sequence;

[0096] (2) Maintaining the temperature at 50°C, add the prescribed amount of olopatadine hydrochloride and stir to dissolve, adjust the pH value to 7.0 with hydrochloric acid or sodium hydroxide, and add water for injection to 1000 ml;

[0097] (3) Cool the solution to 26°C, determine the pH value and content of the solution, filter and sterilize with a 0.22 µm filter cartridge, and fill the solution into an eye drop bottle according to the specifications to obtain olopatadine hydrochloride eye drops.

[0098] Example 6 Preparation of Olopatadine Hydrochloride Eye Drops (0.4 ml: 0.8 mg)

[0099] prescription:

[0100] Olopatadine hydrochloride: 2g

[0101] Polysorbate 80: 2.2 g

[0102] Sodium tartrate: 3.5g

[0103] Sodium chloride: 6.5g

[0104] Povidone K30: 8.0g

[0105] Add water for injection to 1000ml

[0106] Made into 2500 pieces

[0107] Preparation method:

[0108] (1) Dissolve the prescribed amount of polysorbate 80, sodium tartrate, sodium chloride, and povidone K30 in 600 ml of water for injection at 47°C in sequence;

[0109] (2) Maintaining the temperature at 47°C, add the prescribed amount of olopatadine hydrochloride and stir to dissolve, adjust the pH value to 7.0 with hydrochloric acid or sodium hydroxide, and add water for injection to 1000 ml;

[0110] (3) Cool the solution to 25°C, determine the pH value and content of the solution, filter and sterilize with a 0.22 µm filter cartridge, and fill the solution into an eye drop bottle according to the specifications to obtain olopatadine hydrochloride eye drops.

[0111] The present invention provides the following test and comparison results:

[0112] 1. Sample 1: Olopatadine hydrochloride eye drops prepared in Example 1 of the present invention

[0113] 2. Sample 2: Olopatadine hydrochloride eye drops prepared in Example 4 of the present invention

[0114] 3. Sample 3: Olopatadine hydrochloride eye drops prepared according to Example 1 of Chinese application No. 202010657007.6

[0115] 4. Sample 4: Olopatadine hydrochloride eye drops prepared according to Example 2 of Chinese application No. 201910386956.2

[0116] 5. Sample 5: Commercially available olopatadine hydrochloride eye drops

[0117] Samples 1, 2 and 5 were subjected to accelerated stability tests (40°C ± 2°C, RH 75% ± 5%) for 6 months. The results are shown in Table 4:

[0118] Table 4 Accelerated test stability results

[0119]

[0120] Samples 1 to 5 were tested for influencing factors, and were placed at 60°C and strong light (4500lx±500lx) for 10 days. Samples were taken for testing on the 10th day, and the results were compared with those on the 0th day to investigate the stability of the samples. The results are shown in Table 5:

[0121] Table 5 Stability results of influencing factors test

[0122]

[0123] It can be seen from the results in Tables 4 and 5 that the olopatadine hydrochloride eye drops prepared by the prescription and process of the present invention maintain extremely high stability and have significant advantages over marketed products and prior art. The olopatadine hydrochloride eye drops prepared by other embodiments of the present invention were also subjected to the same test and obtained similar results.

[0124] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. Olopatadine hydrochloride eye drops, characterized in that: In addition to 2g of olopatadine hydrochloride, each 1000ml of eye drops also contains polysorbate 80 and sodium tartrate.

2. The olopatadine hydrochloride eye drops according to claim 1, characterized in that: The dosage of polysorbate 80 in each 1000 ml of eye drops is 2.2 g, and the dosage of sodium tartrate is 3.5 g.

3. The olopatadine hydrochloride eye drops according to claim 1, characterized in that: The specifications of Olopatadine Hydrochloride Eye Drops are 0.2%, 0.4ml: 0.8mg.

4. The olopatadine hydrochloride eye drops according to any one of claims 1 to 3, characterized in that: Prepared by the following method: (1) Dissolve the prescribed amount of polysorbate 80, sodium tartrate, sodium chloride, and povidone K30 in 600 ml of water for injection at 45-50°C in sequence; (2) Maintaining the temperature at 45-50°C, add the prescribed amount of olopatadine hydrochloride and stir to dissolve, adjust the pH value to 7.0 with hydrochloric acid or sodium hydroxide, and add water for injection to 1000 ml; (3) Cool the solution to 24°C to 26°C, determine the pH value and content of the solution, filter and sterilize with a 0.22 µm filter cartridge, and fill the solution into an eye drop bottle according to the specifications to obtain olopatadine hydrochloride eye drops.

5. A method for preparing olopatadine hydrochloride eye drops, characterized in that: The following steps are involved: (1) Dissolve the prescribed amount of polysorbate 80 and sodium tartrate in 600 ml of water for injection at 35-40°C. (2) Maintaining the temperature at 35-40°C, add the prescribed amount of olopatadine hydrochloride and stir to dissolve, then add water for injection to make up to 1000 ml; (3) Determine the pH value and content of the solution, filter it with a 0.22 µm filter membrane, fill it into a plastic ampoule according to the specifications, and then sterilize it at 121°C for 15 minutes to obtain olopatadine hydrochloride eye drops; The prescription amount is: Each 1000ml of the eye drops contains: Olopatadine hydrochloride: 2g Polysorbate 80: 2.2 g Sodium tartrate: 3.5g Sodium chloride: 6.5 g Povidone K30: 8.0 g.