Vitamin B12 eye drops

Abstract

The invention relates to vitamin B12 eye drops. Specifically, the invention provides the vitamin B12 eye drops, and the vitamin B12 eye drops comprise vitamin B12, propylene glycol, glycerol, polyvinyl alcohol, glycine, disodium hydrogen phosphate, sodium chloride and water. The vitamin B12 eye drops have excellent illumination and high-temperature stability, so that the vitamin B12 eye drops have excellent stability in the transportation and storage process, the transportation and storage cost is reduced, and the quality safety of the vitamin B12 eye drops is improved.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical preparations, in particular to vitamin B12 eye drops. Background Art

[0002] Vitamin B12 (CAS registration number: 68-19-9) participates in methyl conversion and folic acid metabolism in the body, promotes the conversion of methylmalonic acid into succinic acid, and thus participates in the tricarboxylic acid cycle. It plays an important role in the synthesis of myelin lipids and maintaining the integrity of sheathed nerve fiber function. Vitamin B12 is often used to treat eye discomfort symptoms such as eye fatigue.

[0003] Vitamin B12 eye drops are commonly used eye preparations for the treatment of eye discomfort symptoms such as eye fatigue in clinical practice. Compared with other vitamin B12 preparations, vitamin B12 eye drops are widely used in clinical practice for the treatment of eye discomfort symptoms such as eye fatigue by eye drop administration, which has the advantages of convenient administration and rapid efficacy on eye diseases. However, existing vitamin B12 eye drops have the problem of poor light and heat stability, which not only increases the transportation and storage costs of vitamin B12 eye drops, but also easily leads to quality and safety problems of vitamin B12 eye drops during transportation and storage, thereby easily leading to the emergence of drug safety problems of vitamin B12 eye drops. Therefore, how to improve the stability of vitamin B12 eye drops is of great significance for reducing transportation and storage costs and improving drug safety.

[0004] Therefore, there is a need in the art to develop a vitamin B12 eye drop with excellent stability. Summary of the Invention

[0005] The object of the present invention is to provide a vitamin B12 eye drop with excellent stability.

[0006] In a first aspect, the present invention provides a vitamin B12 eye drop, which comprises vitamin B12, propylene glycol, glycerol, polyvinyl alcohol, glycine, disodium hydrogen phosphate, sodium chloride and water.

[0007] Preferably, the vitamin B12 is 0.01-0.05 parts by weight, more preferably 0.01-0.04 parts by weight, more preferably 0.01-0.03 parts by weight, and most preferably 0.02 parts by weight.

[0008] Preferably, the content of vitamin B12 is 0.01-0.05g / 100ml, more preferably 0.01-0.04g / 100ml, more preferably 0.01-0.03g / 100ml, and most preferably 0.02g / 100ml.

[0009] Preferably, the propylene glycol is 0.4-1.2 parts by weight, more preferably 0.6-1.0 parts by weight, more preferably 0.7-0.9 parts by weight, and most preferably 0.8 parts by weight.

[0010] Preferably, the content of propylene glycol is 0.4-1.2 g / 100 ml, more preferably 0.6-1.0 g / 100 ml, more preferably 0.7-0.9 g / 100 ml, and most preferably 0.8 g / 100 ml.

[0011] Preferably, the glycerol is 0.2-0.8 parts by weight, more preferably 0.3-0.7 parts by weight, more preferably 0.4-0.6 parts by weight, and most preferably 0.5 parts by weight.

[0012] Preferably, the content of glycerol is 0.2-0.8 g / 100 ml, more preferably 0.3-0.7 g / 100 ml, more preferably 0.4-0.6 g / 100 ml, and most preferably 0.5 g / 100 ml.

[0013] Preferably, the polyvinyl alcohol is 0.5-2.0 parts by weight, more preferably 0.8-1.6 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 polyvinyl alcohol is 0.5-2.0 g / 100 ml, more preferably 0.8-1.6 g / 100 ml, more preferably 1.0-1.4 g / 100 ml, and most preferably 1.2 g / 100 ml.

[0015] Preferably, the glycine is 0.1-0.7 parts by weight, more preferably 0.2-0.6 parts by weight, more preferably 0.3-0.5 parts by weight, and most preferably 0.4 parts by weight.

[0016] Preferably, the content of glycine is 0.1-0.7 g / 100 ml, more preferably 0.2-0.6 g / 100 ml, more preferably 0.3-0.5 g / 100 ml, and most preferably 0.4 g / 100 ml.

[0017] Preferably, the content of disodium hydrogen phosphate is 0.02-0.2 parts by weight, more preferably 0.05-0.15 parts by weight, more preferably 0.08-0.12 parts by weight, and most preferably 0.1 parts by weight.

[0018] Preferably, the content of disodium hydrogen phosphate is 0.02-0.2 g / 100 ml, more preferably 0.05-0.15 g / 100 ml, more preferably 0.08-0.12 g / 100 ml, and most preferably 0.1 g / 100 ml.

[0019] Preferably, the sodium chloride is 0.1-0.6 parts by weight, more preferably 0.1-0.5 parts by weight, more preferably 0.2-0.4 parts by weight, and most preferably 0.3 parts by weight.

[0020] Preferably, the content of sodium chloride is 0.1-0.6 g / 100 ml, more preferably 0.1-0.5 g / 100 ml, more preferably 0.2-0.4 g / 100 ml, and most preferably 0.3 g / 100 ml.

[0021] Preferably, the water is 80-120 parts by weight, more preferably 90-110 parts by weight, more preferably 95-105 parts by weight, and most preferably 100 parts by weight.

[0022] Preferably, the water comprises water for injection.

[0023] Preferably, the vitamin B12 eye drops include:

[0024]

[0025] Preferably, the vitamin B12 eye drops include:

[0026]

[0027] Preferably, the vitamin B12 eye drops include:

[0028]

[0029] Preferably, the vitamin B12 eye drops include:

[0030]

[0031]

[0032] Preferably, the vitamin B12 eye drops include:

[0033]

[0034] The second aspect of the present invention provides a method for preparing the vitamin B12 eye drops according to the first aspect of the present invention, the method comprising the steps of:

[0035] The vitamin B12 eye drops are obtained by mixing vitamin B12, propylene glycol, glycerol, polyvinyl alcohol, glycine, disodium hydrogen phosphate, sodium chloride and water.

[0036] Preferably, the method comprises the steps of:

[0037] Add 80% of the prescribed amount of water into a dispensing tank, add propylene glycol and glycerin, stir and dissolve, add polyvinyl alcohol, stir and dissolve, add vitamin B12, stir and dissolve, add glycine, disodium hydrogen phosphate and sodium chloride, stir and dissolve, add the remaining prescribed amount of water to the dispensing volume, filter, and obtain the vitamin B12 eye drops.

[0038] Preferably, the stirring and mixing temperature is 35-45°C, such as 40°C.

[0039] Preferably, the filtration comprises filtering through 0.45 μm and 0.22 μm microporous membranes in sequence.

[0040] In a third aspect, the present invention provides a medicine kit, comprising the vitamin B12 eye drops as described in the first aspect of the present invention.

[0041] Preferably, the vitamin B12 eye drops are packaged in plastic bottles (such as low-density polyethylene bottles).

[0042] In a fourth aspect, the present invention provides a use of the vitamin B12 eye drops according to the first aspect of the present invention for preparing a medicament for preventing and / or treating eye fatigue.

[0043] 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

[0044] The present invention provides vitamin B12 eye drops, comprising vitamin B12, propylene glycol, glycerol, polyvinyl alcohol, glycine, disodium hydrogen phosphate, sodium chloride, and water. The vitamin B12 eye drops of the present invention have excellent light and high temperature stability, are non-irritating to the eye, are highly safe, and have strong compliance to ocular administration.

[0045] the term

[0046] 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.

[0047] As used herein, the terms "comprise," "include," and "contain" are used interchangeably to include not only closed definitions but also semi-closed and open definitions. In other words, the terms include "consisting of," "consisting essentially of."

[0048] As used herein, "propylene glycol" refers to 1,2-propylene glycol.

[0049] As used herein, the term "parts by weight" can 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 can be a composition consisting of 1 gram of component a + 9 grams of component b, or a composition consisting of 10 grams of component a + 90 grams of component b, etc. In the vitamin B12 eye drops, the percentage content of a component = (parts by weight of the component / the 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%.

[0050] Vitamin B12 eye drops

[0051] The present invention provides a vitamin B12 eye drop, which may include (but is not limited to) vitamin B12, propylene glycol, glycerol, polyvinyl alcohol, glycine, disodium hydrogen phosphate, sodium chloride and water.

[0052] In a preferred embodiment of the present invention, the vitamin B12 eye drops include:

[0053]

[0054] Typically, the vitamin B12 eye drops of the present invention include:

[0055]

[0056] Specifically, the vitamin B12 eye drops of the present invention are as described above in the first aspect of the present invention.

[0057] The vitamin B12 eye drops of the present invention can be prepared by a mixing method, for example, by mixing vitamin B12, propylene glycol, glycerol, polyvinyl alcohol, glycine, disodium hydrogen phosphate, sodium chloride and water to obtain the vitamin B12 eye drops.

[0058] use

[0059] The present invention also provides a use of the vitamin B12 eye drops of the present invention in preparing a medicament for preventing and / or treating eye fatigue.

[0060] The main excellent technical effects of the present invention include:

[0061] The present invention develops a vitamin B12 eye drop. The vitamin B12 eye drop has excellent light and high temperature stability, thereby having excellent stability during transportation and storage, reducing transportation and storage costs, and improving the quality and safety of the vitamin B12 eye drop. The vitamin B12 eye drop is non-irritating and highly safe when administered to the eye, and can significantly improve the compliance of ocular administration, thereby improving the application value of the vitamin B12 eye drop.

[0062] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended only 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 generally based on conventional conditions.

[0063] Example 1 Vitamin B12 Eye Drops

[0064] In this Example 1, a vitamin B12 eye drop solution was prepared. The prescription composition of the vitamin B12 eye drop solution is shown in Table 1:

[0065] Table 1 Prescription composition of vitamin B12 eye drops

[0066] Components Dosage Vitamin B12 0.02g Propylene glycol 0.8g glycerin 0.5g polyvinyl alcohol 1.2g Glycine 0.4g Disodium hydrogen phosphate 0.1g Sodium chloride 0.3g Add water for injection to 100ml

[0067] The preparation method of the vitamin B12 eye drops of this embodiment 1 is as follows:

[0068] Add 80% of the prescribed amount of water for injection into the dispensing tank, add the prescribed amount of propylene glycol and the prescribed amount of glycerol, stir and dissolve at 40°C, add the prescribed amount of polyvinyl alcohol, stir and dissolve, add the prescribed amount of vitamin B12, stir and dissolve, add the prescribed amount of glycine, the prescribed amount of disodium hydrogen phosphate and the prescribed amount of sodium chloride, stir and dissolve, add the remaining prescribed amount of water for injection to the dispensing volume, and filter through 0.45μm and 0.22μm microporous filter membranes in sequence to obtain vitamin B12 eye drops.

[0069] Example 2 Vitamin B12 Eye Drops

[0070] In this Example 2, a vitamin B12 eye drop solution was prepared. The prescription composition of the vitamin B12 eye drop solution is shown in Table 2:

[0071] Table 2 Prescription composition of vitamin B12 eye drops

[0072] Components Dosage Vitamin B12 0.02g Propylene glycol 0.4g glycerin 0.5g polyvinyl alcohol 0.8g Glycine 0.4g Disodium hydrogen phosphate 0.1g Sodium chloride 0.3g Add water for injection to 100ml

[0073] The preparation method of the vitamin B12 eye drops of this embodiment 2 is as follows:

[0074] Add 80% of the prescribed amount of water for injection into the dispensing tank, add the prescribed amount of propylene glycol and the prescribed amount of glycerol, stir and dissolve at 40°C, add the prescribed amount of polyvinyl alcohol, stir and dissolve, add the prescribed amount of vitamin B12, stir and dissolve, add the prescribed amount of glycine, the prescribed amount of disodium hydrogen phosphate and the prescribed amount of sodium chloride, stir and dissolve, add the remaining prescribed amount of water for injection to the dispensing volume, and filter through 0.45μm and 0.22μm microporous filter membranes in sequence to obtain vitamin B12 eye drops.

[0075] Example 3 Vitamin B12 Eye Drops

[0076] In this Example 3, a vitamin B12 eye drop solution was prepared. The prescription composition of the vitamin B12 eye drop solution is shown in Table 3:

[0077] Table 3 Prescription composition of vitamin B12 eye drops

[0078] Components Dosage Vitamin B12 0.02g Propylene glycol 0.5g glycerin 0.2g polyvinyl alcohol 1.2g Glycine 0.4g Disodium hydrogen phosphate 0.1g Sodium chloride 0.3g Add water for injection to 100ml

[0079] The preparation method of the vitamin B12 eye drops of this embodiment 3 is as follows:

[0080] Add 80% of the prescribed amount of water for injection into the dispensing tank, add the prescribed amount of propylene glycol and the prescribed amount of glycerol, stir and dissolve at 40°C, add the prescribed amount of polyvinyl alcohol, stir and dissolve, add the prescribed amount of vitamin B12, stir and dissolve, add the prescribed amount of glycine, the prescribed amount of disodium hydrogen phosphate and the prescribed amount of sodium chloride, stir and dissolve, add the remaining prescribed amount of water for injection to the dispensing volume, and filter through 0.45μm and 0.22μm microporous filter membranes in sequence to obtain vitamin B12 eye drops.

[0081] Example 4 Vitamin B12 Eye Drops

[0082] In this Example 4, a vitamin B12 eye drop solution was prepared. The prescription composition of the vitamin B12 eye drop solution is shown in Table 4:

[0083] Table 4 Prescription composition of vitamin B12 eye drops

[0084] Components Dosage Vitamin B12 0.02g glycerin 0.5g polyvinyl alcohol 0.8g Glycine 0.4g Disodium hydrogen phosphate 0.1g Sodium chloride 0.3g Add water for injection to 100ml

[0085] The preparation method of the vitamin B12 eye drops of this embodiment 4 is as follows:

[0086] Add 80% of the prescribed amount of water for injection into the dispensing tank, add the prescribed amount of glycerol, stir and dissolve at 40°C, add the prescribed amount of polyvinyl alcohol, stir and dissolve, add the prescribed amount of vitamin B12, stir and dissolve, add the prescribed amount of glycine, the prescribed amount of disodium hydrogen phosphate and the prescribed amount of sodium chloride, stir and dissolve, add the remaining prescribed amount of water for injection to the dispensing volume, and filter through 0.45μm and 0.22μm microporous filter membranes in sequence to obtain vitamin B12 eye drops.

[0087] Study on the stability and eye irritation of vitamin B12 eye drops

[0088] 1. Stability investigation

[0089] 1.1 Light stability study

[0090] The vitamin B12 eye drops prepared in Examples 1-4, packaged in low-density polyethylene medicinal eye drop bottles, were placed under light conditions (4500 lx, 25°C) for 0 days, 5 days, and 10 days. The appearance, content, and total impurities of the vitamin B12 eye drops at different time points were examined in accordance with the Chinese Pharmacopoeia Preparation Stability Test Guidelines. The results are shown in Table 5 below.

[0091] Table 5 Stability of the vitamin B12 eye drops prepared in Examples 1-4 under illumination conditions (4500 lx, 25°C)

[0092]

[0093] As can be seen from Table 5, the vitamin B12 eye drops prepared in Example 1 have excellent light stability and can maintain excellent stability during transportation and storage, thereby reducing transportation and storage costs and improving the quality and safety of the vitamin B12 eye drops.

[0094] 1.2 Accelerated stability investigation

[0095] The vitamin B12 eye drops prepared in Example 1, packaged in low-density polyethylene medicinal eye drop bottles, were placed at a temperature of 40±2°C and a relative humidity of RH 75±5% for 0 days, 1, 3, and 6 months. The appearance, content, and total impurities of the vitamin B12 eye drops at different time points were examined in accordance with the Chinese Pharmacopoeia Preparation Stability Test Guidelines. The results are shown in Table 6 below.

[0096] Table 6 Stability test results of the vitamin B12 eye drops prepared in Example 1 under accelerated conditions (40±2°C, RH 75±5%)

[0097]

[0098]

[0099] As can be seen from Table 6, the vitamin B12 eye drops prepared in Example 1 have excellent accelerated stability and can maintain excellent stability during transportation and storage, thereby reducing transportation and storage costs and improving the quality and safety of the vitamin B12 eye drops.

[0100] 2. Eye irritation test

[0101] Ten healthy rabbits were taken, and one drop of the vitamin B12 eye drops prepared in Example 1 was instilled into the left eye of each rabbit, while one drop of normal saline was instilled into the right eye of the rabbit as a control. The drops were instilled once a day for 10 consecutive days. The eye irritation of the vitamin B12 eye drops prepared in Example 1 was investigated 1 hour after the first eye drop and 1 hour after the eye drop on the 10th day by sodium fluorescein staining and slit lamp examination.

[0102] The evaluation items and scores for eye irritation degree are as follows:

[0103] Cornea: 0 points - no opacity; 1 point - scattered or diffuse opacity, the iris is clearly visible; 2 points - translucent areas are easy to distinguish, the iris is blurred; 3 points - grayish-white translucent areas appear, the iris details are unclear, and the pupil size can be barely seen; 4 points - the cornea is opaque and the iris cannot be identified.

[0104] Iris: 0 points - normal; 1 point - obvious deepening of wrinkles, congestion, swelling, mild congestion around the cornea, and pupil still responds to light; 2 points - hemorrhage / visible necrosis / no response to light (or more than one of the above).

[0105] Conjunctival congestion (referring to the palpebral conjunctiva and bulbar conjunctiva): 0 points - normal blood vessels; 1 point - bright red blood vessels due to congestion; 2 points - dark red blood vessels that are difficult to distinguish; 3 points - diffuse purplish red blood vessels.

[0106] Edema: 0 points - no edema; 1 point - mild edema (including eyelids); 2 points - obvious edema with partial ectropion of the eyelids; 3 points - edema to the eyelids to half-close; 4 points - edema to the eyelids more than half-closed;

[0107] Discharge: 0 points - no discharge; 1 point - a small amount of discharge; 2 points - discharge makes the eyelids and eyelashes moist or sticky; 3 points - discharge makes the entire eye area moist or sticky.

[0108] The total score of eye irritation evaluation and its corresponding evaluation criteria are as follows:

[0109] Non-irritation: 0-3 (including 0 and excluding 3);

[0110] Mild irritation: 3-8 (including 3 and excluding 8) points;

[0111] Moderate irritation: 8-12 (including 8 and excluding 12) points;

[0112] Severe irritation: 12-16 (inclusive) points.

[0113] The higher the total score of the eye irritation evaluation, the stronger the eye irritation.

[0114] The eye irritation evaluation results of the vitamin B12 eye drops prepared in Example 1 are shown in Table 7 below.

[0115] Table 7 Eye irritation evaluation results of vitamin B12 eye drops prepared in Example 1

[0116]

[0117] As can be seen from Table 7, the vitamin B12 eye drops prepared in Example 1 have no eye irritation. Therefore, the vitamin B12 eye drops prepared in Example 1 have excellent medication safety and strong medication compliance of patients.

[0118] 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 principles of the present invention, and these improvements should also be regarded as the scope of protection of the present invention.

Claims

1. A vitamin B12 eye drop, characterized in that: The vitamin B12 eye drops include vitamin B12, propylene glycol, glycerol, polyvinyl alcohol, glycine, disodium hydrogen phosphate, sodium chloride and water.

2. The vitamin B12 eye drops according to claim 1, wherein The vitamin B12 is 0.01-0.05 parts by weight, preferably 0.01-0.04 parts by weight, more preferably 0.01-0.03 parts by weight, and most preferably 0.02 parts by weight; The propylene glycol is 0.4-1.2 parts by weight, preferably 0.6-1.0 parts by weight, more preferably 0.7-0.9 parts by weight, and most preferably 0.8 parts by weight; The glycerol is 0.2-0.8 parts by weight, preferably 0.3-0.7 parts by weight, more preferably 0.4-0.6 parts by weight, and most preferably 0.5 parts by weight; The polyvinyl alcohol is 0.5-2.0 parts by weight, preferably 0.8-1.6 parts by weight, more preferably 1.0-1.4 parts by weight, and most preferably 1.2 parts by weight; The glycine is 0.1-0.7 parts by weight, preferably 0.2-0.6 parts by weight, more preferably 0.3-0.5 parts by weight, and most preferably 0.4 parts by weight; The content of disodium hydrogen phosphate is 0.02-0.2 parts by weight, preferably 0.05-0.15 parts by weight, more preferably 0.08-0.12 parts by weight, and most preferably 0.1 parts by weight; The sodium chloride is 0.1-0.6 parts by weight, preferably 0.1-0.5 parts by weight, more preferably 0.2-0.4 parts by weight, and most preferably 0.3 parts by weight; and The water is 80-120 parts by weight, preferably 90-110 parts by weight, more preferably 95-105 parts by weight, and most preferably 100 parts by weight.

3. The vitamin B12 eye drops according to claim 1, wherein The vitamin B12 eye drops include:

4. The vitamin B12 eye drops according to claim 1, wherein The vitamin B12 eye drops include:

5. The vitamin B12 eye drops according to claim 1, wherein The vitamin B12 eye drops include:

6. The vitamin B12 eye drops according to claim 1, wherein The vitamin B12 eye drops include:

7. The vitamin B12 eye drops according to claim 1, wherein The vitamin B12 eye drops include:

8. A method for preparing the vitamin B12 eye drops according to claim 1, characterized in that: The method comprises the steps of: The vitamin B12 eye drops are obtained by mixing vitamin B12, propylene glycol, glycerol, polyvinyl alcohol, glycine, disodium hydrogen phosphate, sodium chloride and water.

9. A use of the vitamin B12 eye drops according to claim 1, characterized in that: Used for preparing medicines, which are used for preventing and / or treating eye fatigue.

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