Pranoprofen eye drops

Abstract

The invention relates to pranoprofen eye drops. Specifically, the invention provides the pranoprofen eye drops, and the pranoprofen eye drops comprise pranoprofen, propylene glycol, glycerol, polysorbate-80, glycine, boric acid and water. The pranoprofen eye drops have excellent illumination and high-temperature stability, the stability of the pranoprofen eye drops in the storage and transportation process is improved, the storage and transportation cost is reduced, and therefore the safety of the pranoprofen eye drops is improved.

Description

Technical Field

[0001] The invention relates to the field of pharmaceutical preparations, in particular to pranoprofen eye drops. Background Art

[0002] Pranoprofen (CAS No.: 52549-17-4) is a propionic acid derivative and a non-steroidal anti-inflammatory drug with significant anti-inflammatory effects.

[0003] Pranoprofen eye drops are widely used clinically, and can be quickly and effectively applied to the symptomatic treatment (blepharitis, conjunctivitis, keratitis, scleritis, superficial scleritis, iridocyclitis, postoperative inflammation) of external eye and frontal inflammation by simple eye drop administration mode, therefore, patient's administration compliance is high.But, there is the problem of poor stability in existing pranoprofen eye drops, makes pranoprofen eye drops in storage and transportation process, is difficult to effectively ensure pranoprofen eye drops stability, thus easily occurs quality problem, and then causes the appearance of medication safety problem.How to improve the stability of pranoprofen eye drops to improve storage and transportation stability and reduce storage and transportation cost, is of great significance for ensuring the medication safety of pranoprofen eye drops.

[0004] Therefore, there is a need in the art to develop a pranoprofen eye drop with excellent stability. Summary of the invention

[0005] The object of the present invention is to provide a pranoprofen eye drops with excellent stability.

[0006] A first aspect of the present invention provides pranoprofen eye drops, which include pranoprofen, propylene glycol, glycerol, polysorbate 80, glycine, boric acid and water.

[0007] Preferably, the pranoprofen is 0.2-3.0 parts by weight, more preferably 0.5-1.5 parts by weight, more preferably 0.8-1.2 parts by weight, and most preferably 1.0 parts by weight.

[0008] Preferably, the content of pranoprofen is 0.2-3.0 mg / ml, more preferably 0.5-1.5 mg / ml, more preferably 0.8-1.2 mg / ml, and most preferably 1.0 mg / ml.

[0009] Preferably, the propylene glycol is 0.1-1.0 parts by weight, more preferably 0.2-0.8 parts by weight, more preferably 0.4-0.6 parts by weight, and most preferably 0.5 parts by weight.

[0010] Preferably, the content of propylene glycol is 0.1-1.0 mg / ml, more preferably 0.2-0.8 mg / ml, more preferably 0.4-0.6 mg / ml, and most preferably 0.5 mg / ml.

[0011] Preferably, the glycerol is 0.2-3.0 parts by weight, more preferably 0.5-1.5 parts by weight, more preferably 0.8-1.2 parts by weight, and most preferably 1.0 parts by weight.

[0012] Preferably, the content of glycerol is 0.2-3.0 mg / ml, more preferably 0.5-1.5 mg / ml, more preferably 0.8-1.2 mg / ml, and most preferably 1.0 mg / ml.

[0013] Preferably, the polysorbate 80 is 0.2-3.0 parts by weight, more preferably 0.4-2.0 parts by weight, more preferably 1.0-1.4 parts by weight, and most preferably 1.2 parts by weight.

[0014] Preferably, the content of polysorbate 80 is 0.2-3.0 mg / ml, more preferably 0.4-2.0 mg / ml, more preferably 1.0-1.4 mg / ml, and most preferably 1.2 mg / ml.

[0015] Preferably, the glycine is 0.2-4.0 parts by weight, more preferably 1.5-2.5 parts by weight, more preferably 1.8-2.2 parts by weight, and most preferably 2.0 parts by weight.

[0016] Preferably, the content of glycine is 0.2-4.0 mg / ml, more preferably 1.5-2.5 mg / ml, more preferably 1.8-2.2 mg / ml, and most preferably 2.0 mg / ml.

[0017] Preferably, the boric acid is 2-6 parts by weight, more preferably 3.5-4.5 parts by weight, more preferably 3.8-4.2 parts by weight, and most preferably 4.0 parts by weight.

[0018] Preferably, the content of boric acid is 2-6 mg / ml, more preferably 3.5-4.5 mg / ml, more preferably 3.8-4.2 mg / ml, and most preferably 4.0 mg / ml.

[0019] Preferably, the water is 900-1100 parts by weight, more preferably 950-1050 parts by weight, more preferably 990-1010 parts by weight, and most preferably 1000 parts by weight.

[0020] Preferably, the water comprises water for injection.

[0021] Preferably, the pH of the pranoprofen eye drops is 6.0-8.0, more preferably 7.0-8.0, more preferably 7.4-7.8, and most preferably 7.6.

[0022] Preferably, the pH of the pranoprofen eye drops is adjusted with sodium hydroxide.

[0023] Preferably, the pH of the pranoprofen eye drops is adjusted to 6.0-8.0 with sodium hydroxide, preferably 7.0-8.0, more preferably 7.4-7.8, and most preferably 7.6.

[0024] Preferably, the pranoprofen eye drops include:

[0025]

[0026] Adjust the pH of pranoprofen eye drops to 6.0-8.0 with sodium hydroxide.

[0027] Preferably, the pranoprofen eye drops include:

[0028]

[0029] Adjust the pH of pranoprofen eye drops to 7.0-8.0 with sodium hydroxide.

[0030] Preferably, the pranoprofen eye drops include:

[0031]

[0032] Adjust the pH of pranoprofen eye drops to 7.4-7.8 with sodium hydroxide.

[0033] Preferably, the pranoprofen eye drops include:

[0034]

[0035]

[0036] The pH of pranoprofen eye drops was adjusted to 7.6 with sodium hydroxide.

[0037] Preferably, the pranoprofen eye drops include:

[0038]

[0039] The pH of pranoprofen eye drops was adjusted to 7.6 with sodium hydroxide.

[0040] The second aspect of the present invention provides a method for preparing the pranoprofen eye drops according to the first aspect of the present invention, wherein the method comprises the steps of:

[0041] The pranoprofen eye drops are obtained by mixing pranoprofen, propylene glycol, glycerin, polysorbate-80, glycine, boric acid and water.

[0042] Preferably, the pH of the pranoprofen eye drops is adjusted to 6.0-8.0 with sodium hydroxide, preferably 7.0-8.0, more preferably 7.4-7.8, and most preferably 7.6.

[0043] Preferably, the method comprises the steps of:

[0044] Add 83-87% of the prescribed amount of water into a dispensing tank, add propylene glycol and glycerin, stir and mix, add pranoprofen, polysorbate-80 and glycine, stir and mix, add boric acid, stir and mix, adjust the pH to 7.6 with sodium hydroxide water, add water to the dispensing volume, filter, and obtain pranoprofen eye drops.

[0045] Preferably, the mixing temperature is 40-50°C, more preferably 45°C.

[0046] Preferably, the filtration comprises microporous membrane filtration.

[0047] Preferably, the filtration comprises filtering through 0.45 μm and 0.22 μm microporous membranes in sequence.

[0048] The third aspect of the present invention provides a medicine kit, wherein the medicine kit comprises the pranoprofen eye drops as described in the first aspect of the present invention.

[0049] Preferably, the medicine box further comprises a transparent container.

[0050] Preferably, the transparent container comprises a transparent PET bottle.

[0051] Preferably, the pranoprofen eye drops are packaged in the transparent container.

[0052] The fourth aspect of the present invention provides a use of the pranoprofen eye drops according to the first aspect of the present invention in the preparation of a medicament for treating ocular inflammation.

[0053] Preferably, the inflammation is selected from the group consisting of blepharitis, conjunctivitis, keratitis, scleritis, superficial scleritis, iridocyclitis, postoperative inflammation, or a combination thereof.

[0054] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described below (such as embodiments) can be combined with each other to form new or preferred technical solutions. DETAILED DESCRIPTION

[0055] The invention provides pranoprofen eye drops, which include pranoprofen, propylene glycol, glycerol, polysorbate 80, glycine, boric acid and water. The pranoprofen eye drops composed of the specific components of the invention have excellent light and high temperature stability, improve the storage and transportation stability of the pranoprofen eye drops and reduce the storage and transportation costs, thereby improving the safety of the pranoprofen eye drops.

[0056] the term

[0057] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0058] As used herein, the terms "comprise", "include", and "contain" are used interchangeably and include not only closed definitions, but also semi-closed and open definitions. In other words, the terms include "consisting of", "consisting essentially of".

[0059] As used herein, polysorbate 80 is also known as Tween 80.

[0060] As used herein, the term "PET" refers to polyethylene terephthalate, also known as Poly (ethylene Terephthalate)

[0061] As used herein, the term "parts by weight" may be any fixed weight expressed in milligrams, grams or kilograms (such as 1 mg, 1 g or 1 kg, etc.). For example, a composition consisting of 1 part by weight of component a and 9 parts by weight of component b may be a composition consisting of 1 gram of component a + 9 grams of component b, or 10 grams of component a + 90 grams of component b, etc. In the pranoprofen eye drops, the percentage content of a component = (parts by weight of the component / sum of the parts by weight of all components) × 100%. For example, in a composition consisting of 1 part by weight of component a and 9 parts by weight of component b, the content of component a is 10%, and the content of component b is 90%.

[0062] Pranoprofen eye drops

[0063] The invention provides a pranoprofen eye drop with excellent light and heat stability, thereby improving the safety of the pranoprofen eye drop.

[0064] The pranoprofen eye drops of the present invention may include (but not limited to) pranoprofen, propylene glycol, glycerol, polysorbate-80, glycine, boric acid and water.

[0065] In a preferred embodiment of the present invention, the pranoprofen eye drops include:

[0066]

[0067] Adjust the pH of pranoprofen eye drops to 6.0-8.0 with sodium hydroxide.

[0068] Preferably, the pranoprofen eye drops include:

[0069]

[0070] The pH of pranoprofen eye drops was adjusted to 7.6 with sodium hydroxide.

[0071] Typically, the pranoprofen eye drops include:

[0072]

[0073] The pH of pranoprofen eye drops was adjusted to 7.6 with sodium hydroxide.

[0074] Specifically, the pranoprofen eye drops are as described above in the first aspect of the present invention.

[0075] The pranoprofen eye drops of the present invention can be prepared by a mixing method, for example, by mixing pranoprofen, propylene glycol, glycerol, polysorbate 80, glycine, boric acid and water to obtain the pranoprofen eye drops.

[0076] In a preferred embodiment of the present invention, the pranoprofen eye drops of the present invention are prepared by the following method:

[0077] Add 83-87% of the prescribed amount of water into a dispensing tank, add propylene glycol and glycerin, stir and mix, add pranoprofen, polysorbate-80 and glycine, stir and mix, add boric acid, stir and mix, adjust the pH to 7.6 with sodium hydroxide water, add water to the dispensing volume, filter, and obtain pranoprofen eye drops.

[0078] The main excellent technical effects of the present invention include:

[0079] The invention develops pranoprofen eye drops, which have excellent light and high temperature stability, improve the stability of the pranoprofen eye drops during storage and transportation, reduce storage and transportation costs, and thus improve the safety of the pranoprofen eye drops.

[0080] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples where specific conditions are not specified are usually based on conventional conditions.

[0081] Example 1 Pranoprofen eye drops

[0082] This embodiment 1 prepares a kind of pranoprofen eye drops, and the composition of pranoprofen eye drops is shown in Table 1:

[0083] Table 1 Prescription composition of pranoprofen eye drops

[0084] Components Dosage Pranoprofen 1.0g Propylene glycol 0.5g glycerin 1.0g Polysorbate-80 1.2g Glycine 2.0g Boric acid 4.0g Sodium hydroxide Moderate Add water for injection to 1000ml

[0085] Preparation method

[0086] Add 85% of the prescribed amount of water for injection after boiling and cooling to a dispensing tank, add the prescribed amount of propylene glycol and the prescribed amount of glycerol, stir and mix at 45°C, add the prescribed amount of pranoprofen, the prescribed amount of polysorbate-80 and the prescribed amount of glycine, stir and mix, add the prescribed amount of boric acid, stir and mix, adjust the pH to 7.6 with a 1.0 mol / L sodium hydroxide aqueous solution, add the boiled and cooled water for injection to the dispensing volume, filter through 0.45 μm and 0.22 μm microporous filter membranes in sequence to obtain pranoprofen eye drops.

[0087] Example 2

[0088] This embodiment 2 prepares a kind of pranoprofen eye drops, and the composition of pranoprofen eye drops is shown in Table 2:

[0089] Table 2 Prescription composition of pranoprofen eye drops

[0090] Components Dosage Pranoprofen 1.0g Propylene glycol 0.3g glycerin 0.5g Polysorbate-80 1.2g Glycine 2.0g Boric acid 4.0g Sodium hydroxide Moderate Add water for injection to 1000ml

[0091] Preparation method

[0092] Add 85% of the prescribed amount of water for injection after boiling and cooling to a dispensing tank, add the prescribed amount of propylene glycol and the prescribed amount of glycerol, stir and mix at 45°C, add the prescribed amount of pranoprofen, the prescribed amount of polysorbate-80 and the prescribed amount of glycine, stir and mix, add the prescribed amount of boric acid, stir and mix, adjust the pH to 7.6 with a 1.0 mol / L sodium hydroxide aqueous solution, add the boiled and cooled water for injection to the dispensing volume, filter through 0.45 μm and 0.22 μm microporous filter membranes in sequence to obtain pranoprofen eye drops.

[0093] Example 3 Pranoprofen eye drops

[0094] This embodiment 3 prepares a kind of pranoprofen eye drops, and the composition of pranoprofen eye drops is shown in Table 3:

[0095] Table 3 Prescription composition of pranoprofen eye drops

[0096] Components Dosage Pranoprofen 1.0g Polyethylene glycol 400 0.5g glycerin 1.0g Polysorbate-80 1.2g Glycine 1.5g Boric acid 4.0g Sodium hydroxide Moderate Add water for injection to 1000ml

[0097] Preparation method

[0098] Add 85% of the prescribed amount of water for injection after boiling and cooling into a dispensing tank, add the prescribed amount of polyethylene glycol 400 and the prescribed amount of glycerol, stir and mix at 45°C, add the prescribed amount of pranoprofen, the prescribed amount of polysorbate 80 and the prescribed amount of glycine, stir and mix, add the prescribed amount of boric acid, stir and mix, adjust the pH to 7.6 with a 1.0 mol / L sodium hydroxide aqueous solution, add the boiled and cooled water for injection to the dispensing volume, filter through 0.45 μm and 0.22 μm microporous filter membranes in sequence, and obtain pranoprofen eye drops.

[0099] Example 4 Pranoprofen eye drops

[0100] This embodiment 4 prepares a kind of pranoprofen eye drops, and the composition of pranoprofen eye drops is shown in Table 4:

[0101] Table 4 Prescription composition of pranoprofen eye drops

[0102]

[0103]

[0104] Preparation method

[0105] Add 85% of the prescribed amount of water for injection after boiling and cooling into a dispensing tank, add the prescribed amount of glycerol, stir and mix at 45°C, add the prescribed amount of pranoprofen, the prescribed amount of polysorbate-80 and the prescribed amount of glycine, stir and mix, add the prescribed amount of boric acid, stir and mix, adjust the pH to 7.6 with a 1.0 mol / L sodium hydroxide aqueous solution, add the boiled and cooled water for injection to the dispensing volume, filter through 0.45 μm and 0.22 μm microporous filter membranes in sequence, and obtain pranoprofen eye drops.

[0106] Study on the stability of eye drops

[0107] 1. Light stability test

[0108] According to the guidelines for the stability test of preparations in the Chinese Pharmacopoeia, the pranoprofen eye drops prepared in Examples 1-4 and packaged in transparent PET bottles were examined under illumination conditions (4500 lx, 25° C.) for 0, 510 and 30 days, and the appearance of the pranoprofen eye drops at different time points was examined. The pranoprofen content (limit 90%-110%) and total impurity content (limit less than 1.0%) of the pranoprofen eye drops were determined by high performance liquid chromatography. The results of the light stability test of the pranoprofen eye drops prepared in Examples 1-4 are shown in Table 5.

[0109] Table 5 Stability study results of pranoprofen eye drops prepared in Examples 1-4 under illumination conditions (4500 lx, 25 ° C)

[0110]

[0111] As can be seen from Table 5, under light conditions, the pranoprofen eye drops prepared in Example 1 have the most excellent stability, which improves the storage and transportation stability of the pranoprofen eye drops and reduces the storage and transportation costs, thereby improving the safety of the pranoprofen eye drops.

[0112] 2. Accelerated stability test

[0113] According to the guidelines for the stability test of preparations in the Chinese Pharmacopoeia, the pranoprofen eye drops prepared in Example 1 and packaged in a transparent PET bottle were examined at a temperature of 40 ± 2 ° C. and a relative humidity of RH 75 ± 5% for 0 days, 1, 3 and 6 months, and the appearance properties of the pranoprofen eye drops at different time points were examined. The pranoprofen content (limit 90%-110%) and the total impurity content (limit less than 1.0%) of the pranoprofen eye drops were determined by high performance liquid chromatography. The results of the accelerated stability study of the pranoprofen eye drops prepared in Example 1 are shown in Table 6.

[0114] Table 6 Stability test results of pranoprofen eye drops prepared in Example 1 under accelerated conditions (40±2°C, RH 75±5%)

[0115]

[0116] As can be seen from Table 6, the pranoprofen eye drops prepared in Example 1 have excellent stability under accelerated conditions of high temperature and high humidity, which improves the storage and transportation stability of the pranoprofen eye drops and reduces the storage and transportation costs, thereby improving the safety of the pranoprofen eye drops.

[0117] The above is an implementation scheme of the present invention designed for a case. It should be pointed out that for ordinary technicians in this technical field, several improvements can be made without departing from the principle of the present invention, and these improvements should also be regarded as the scope of protection of the present invention.

Claims

1. A pranoprofen eye drop, characterized in that, The pranoprofen eye drops include pranoprofen, propylene glycol, glycerin, polysorbate-80, glycine, boric acid and water.

2. The pranoprofen eye drops according to claim 1, characterized in that The pranoprofen is 0.2-3.0 parts by weight, preferably 0.5-1.5 parts by weight, more preferably 0.8-1.2 parts by weight, and most preferably 1.0 parts by weight; The propylene glycol is 0.1-1.0 parts by weight, preferably 0.2-0.8 parts by weight, more preferably 0.4-0.6 parts by weight, and most preferably 0.5 parts by weight; The glycerol is 0.2-3.0 parts by weight, preferably 0.5-1.5 parts by weight, more preferably 0.8-1.2 parts by weight, and most preferably 1.0 parts by weight; The polysorbate 80 is 0.2-3.0 parts by weight, preferably 0.4-2.0 parts by weight, more preferably 1.0-1.4 parts by weight, and most preferably 1.2 parts by weight; The glycine is 0.2-4.0 parts by weight, preferably 1.5-2.5 parts by weight, more preferably 1.8-2.2 parts by weight, and most preferably 2.0 parts by weight; The boric acid is 2-6 parts by weight, preferably 3.5-4.5 parts by weight, more preferably 3.8-4.2 parts by weight, and most preferably 4.0 parts by weight; The water is 900-1100 parts by weight, preferably 950-1050 parts by weight, more preferably 990-1010 parts by weight, and most preferably 1000 parts by weight; and The pH of the pranoprofen eye drops is adjusted to 6.0-8.0 with sodium hydroxide, preferably 7.0-8.0, more preferably 7.4-7.8, and most preferably 7.

6.

3. The pranoprofen eye drops according to claim 1, characterized in that The content of pranoprofen is 0.2-3.0 mg / ml, preferably 0.5-1.5 mg / ml, more preferably 0.8-1.2 mg / ml, and most preferably 1.0 mg / ml; The content of propylene glycol is 0.1-1.0 mg / ml, preferably 0.2-0.8 mg / ml, more preferably 0.4-0.6 mg / ml, and most preferably 0.5 mg / ml; The content of glycerol is 0.2-3.0 mg / ml, preferably 0.5-1.5 mg / ml, more preferably 0.8-1.2 mg / ml, and most preferably 1.0 mg / ml; The content of polysorbate 80 is 0.2-3.0 mg / ml, preferably 0.4-2.0 mg / ml, more preferably 1.0-1.4 mg / ml, and most preferably 1.2 mg / ml; The content of glycine is 0.2-4.0 mg / ml, preferably 1.5-2.5 mg / ml, more preferably 1.8-2.2 mg / ml, and most preferably 2.0 mg / ml; The content of boric acid is 2-6 mg / ml, preferably 3.5-4.5 mg / ml, more preferably 3.8-4.2 mg / ml, and most preferably 4.0 mg / ml; and The pH of the pranoprofen eye drops is adjusted to 6.0-8.0 with sodium hydroxide, preferably 7.0-8.0, more preferably 7.4-7.8, and most preferably 7.

6.

4. The pranoprofen eye drops according to claim 1, characterized in that The pranoprofen eye drops include: Adjust the pH of pranoprofen eye drops to 6.0-8.0 with sodium hydroxide.

5. The pranoprofen eye drops according to claim 1, characterized in that The pranoprofen eye drops include: Adjust the pH of pranoprofen eye drops to 7.4-7.8 with sodium hydroxide.

6. The pranoprofen eye drops according to claim 1, characterized in that The pranoprofen eye drops include: The pH of pranoprofen eye drops was adjusted to 7.6 with sodium hydroxide.

7. The pranoprofen eye drops according to claim 1, characterized in that The pranoprofen eye drops include: The pH of pranoprofen eye drops was adjusted to 7.6 with sodium hydroxide.

8. A method for preparing the pranoprofen eye drops as claimed in claim 1, characterized in that: The method comprises the steps of: The pranoprofen eye drops are obtained by mixing pranoprofen, propylene glycol, glycerin, polysorbate-80, glycine, boric acid and water.

9. A medicine box comprising the pranoprofen eye drops according to claim 1.

10. Use of the pranoprofen eye drops according to claim 1 in preparing a medicament for treating ocular inflammation.

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