CN102100665B - Eye drops containing vitamin E derivatives and preparation method thereof - Google Patents

Abstract

The invention discloses an eye drop containing vitamin E derivatives and a preparation method thereof. The main components of the invention are water-soluble vitamin E derivatives, thickening agents, pH regulators, isotonic agents and water for injection. The eye drops are mainly used for treating xerophthalmia, and can be added with active pharmacological components as required to be used for assisting in treating various ophthalmic diseases such as cataract, retinopathy, macular degeneration, keratitis, conjunctivitis and the like. The invention has good moisturizing and lubricating effects, simultaneously has an antioxidation effect, can inhibit the reaction of lipid peroxide in eyes, has the effects of expanding peripheral blood vessels, improving blood circulation, protecting and promoting wound healing, and has good curative effects on various ophthalmic diseases.

Description

Eye drops containing vitamin E derivatives and preparation method thereof

technical field

The invention belongs to the technical field of medicines. The invention relates to an eye drop and a preparation method thereof, in particular to an eye drop containing a vitamin E derivative and a preparation method thereof. The eye drops of the present invention are mainly used for the treatment of dry eye, and can also be used as an auxiliary treatment for various ophthalmic diseases such as cataract, retinopathy, macular degeneration, keratitis and conjunctivitis.

Background technique

Eye diseases mainly include dry eye, cataract, glaucoma, ocular infectious inflammation, macular degeneration, retinopathy and other diseases. Among them, dry eye syndrome refers to a class of diseases that cause symptoms such as eye discomfort due to tear film instability and ocular surface damage caused by abnormal tear quality or quantity, or abnormal tear dynamics. Environmental pollution, wearing contact lenses, unhygienic eye use, taking certain medications, and advancing age can all cause dry eye. The clinical manifestations of dry eye are symptoms such as eye dryness, foreign body sensation, photophobia, blurred vision or vision fluctuation. According to epidemiological research surveys in recent years, 10% to 20% of people suffer from different degrees of dry eye.

Biological cell membranes are rich in polyvalent unsaturated fatty acids, so they are easily attacked by free radicals and lipid peroxidation occurs. Lipid peroxidation is a chain reaction process mediated by free radicals. The generation of lipid free radicals can lead to the continuous oxidation and consumption of lipids on the cell membrane, and generate a large amount of lipid peroxides, which will eventually cause serious damage to the cell membrane and lead to various ophthalmic diseases.

At present, the dosage forms of ophthalmic medicines for the treatment of ophthalmic diseases mainly include eye drops, ointments, tablets and granules. Among them, the eye drop dosage form is the most commonly used ophthalmic drug administration method, accounting for more than 85% of the dosage forms. It is easy to prepare, low in price, easy to use, and has good patient compliance. Early eye drops were mainly to dissolve antibiotics, antivirals, etc. directly in distilled water, and prepare them to a certain concentration before use. This type of eye drops is often quickly drained on the eye surface, and at the same time is blocked by the tear film, cornea, and conjunctival epithelial barriers, resulting in short drug absorption time, low local concentration, low bioavailability, and short duration of effect. the therapeutic effect. Adding thickeners to eye drops can increase the time of action of the drug on the ocular surface and improve the bioavailability of the drug. Commonly used thickeners are sodium hyaluronate, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, chitosan, polyvinyl alcohol, polyvinylpyrrolidone, etc. Among them, sodium hyaluronate is a high-molecular mucopolysaccharide extracted from animal tissues or obtained through a fermentation process. It has high viscoelasticity, non-Newtonian fluid properties, and good pharmacological and pharmacodynamic properties.

Vitamin E has been highly valued by the medical community for a long time. Its unique antioxidant effect enables it to play a variety of physiological functions in clinical practice. It can be used as an antioxidant to protect polyvalent unsaturated fatty acids from oxidative damage and maintain the normality of biofilms. It has a good auxiliary effect on the treatment of dry eye, cataract, diabetic retinopathy, macular degeneration, optic atrophy, ophthalmoplegia, corneal degeneration, keratitis and other ophthalmic diseases.

Contents of the invention

The object of the present invention is to provide an eye drop containing vitamin E derivatives and a preparation method thereof. It is used to treat ophthalmic diseases such as dry eye syndrome.

The eye drop of the invention contains a water-soluble vitamin E derivative-polyethylene glycol 1000 vitamin E succinate, which has unique antioxidant properties and physiological functions. In addition, the substance is also a good emulsifier and solubilizer. There are active groups in its molecule, which can release active hydrogen and capture free radicals, thereby blocking the chain reaction of free radicals. During the reaction process, with the intervention of polyethylene glycol 1000 vitamin E succinate, the free radicals are eliminated midway, which can interrupt the progress of the reaction, so that the cells, tissues and organs of the organism will not be attacked by free radicals, and the maintenance of biological Normal structure of the membrane. Therefore, eye drops added with polyethylene glycol 1000 vitamin E succinate not only maintain the moisturizing and lubricating effects of the eye drops, but also increase the action time of the active ingredients of the drug and the ocular surface, and have a unique antioxidant effect. It has a good effect on the treatment of dry eye, cataract, diabetic retinopathy, macular degeneration, optic atrophy, ophthalmoplegia, corneal degeneration, keratitis and other ophthalmic diseases.

The object of the invention is achieved by the following methods:

An eye drop containing a vitamin E derivative, the formula of which is:

Based on 1000ml of eye drops, it contains 0.01-2 grams of water-soluble vitamin E derivatives, 0.1-10 grams of thickeners, 0.1-20 grams of pH regulators, 0.1-50 grams of isotonic agents, and the rest is water for injection.

The water-soluble vitamin E derivative of the present invention is polyethylene glycol 1000 vitamin E succinate; the thickener is sodium hyaluronate, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, shell One or more of polysaccharides, polyvinyl alcohol, or polyvinylpyrrolidone; the pH regulator is carbonic acid-carbonate buffer pair reagent, phosphoric acid-phosphate buffer pair reagent or boric acid-borate buffer pair reagent; etc. The osmotic agent is one or more of sodium chloride, potassium chloride, mannitol, sorbitol, glucose, dextran or glycerin.

The eye drops containing vitamin E derivatives of the present invention can also be formulated with antibiotic drugs, antiviral drugs, antibacterial drugs, non-steroidal anti-inflammatory drugs or anti-allergic drugs as required.

The antibiotic drug of the present invention is gentamicin sulfate, lincomycin or chloramphenicol; the antiviral drug is acyclovir or ribavirin; the antibacterial drug is levofloxacin; The non-steroidal anti-inflammatory drug is diclofenac sodium; the antiallergic drug is cromolyn sodium.

The preparation method of the eye drops containing vitamin E derivatives of the present invention comprises the following steps:

(1) Weigh vitamin E derivatives and dissolve them in water for injection at 50-90°C, and cool to room temperature for later use;

(2) According to the formula of eye drops described in claim 1, take thickener, pH regulator and isotonic agent, add in the vitamin E derivative solution that step (1) makes, add injection after mixing uniformly Use water to adjust pH to 6.5-7.4, osmotic pressure to 280-340mOsM, filter and sterilize with 0.2 μm microporous membrane or high-pressure steam, and obtain the eye drops of the present invention after subpackaging.

The application of the eye drops containing vitamin E derivatives in the present invention in the treatment of dry eye syndrome.

The application of the eye drops containing vitamin E derivatives of the present invention in the auxiliary treatment of cataract, retinopathy, macular degeneration, keratitis or conjunctivitis.

Compared with the prior art, the present invention has the following beneficial effects:

1. Adding thickeners such as sodium hyaluronate can slow down the flow rate of the liquid medicine, increase the action time of the active ingredients of the medicine and the ocular surface, and improve the therapeutic effect;

2. Vitamin E derivatives are added, which has a unique antioxidant effect;

3. Other active pharmacological ingredients can be added for auxiliary treatment of cataract, retinopathy, macular degeneration, keratitis, conjunctivitis and other ophthalmic diseases.

Detailed ways

The following examples are further descriptions of the present invention, not limitations of the present invention.

Example 1

Weigh 0.01g of polyethylene glycol 1000 vitamin E succinate and dissolve it in 50ml of water for injection at 90°C, cool to room temperature for later use; weigh 0.1g of sodium hyaluronate and dissolve it in 100ml of water for injection at 80°C, cool to room temperature for later use Weigh 0.1 g of phosphoric acid-phosphate buffer reagent and 5.8 g of sodium chloride and dissolve it in 700 ml of water for injection, add cooled polyethylene glycol 1000 vitamin E succinate solution and sodium hyaluronate solution, add water for injection Set the volume to 1000ml, adjust the pH to 6.5-7.4, and sterilize with high-pressure steam to obtain the eye drops of the present invention.

Example 2

Weigh 0.1g of polyethylene glycol 1000 vitamin E succinate and dissolve it in 50ml of water for injection at 80°C, cool to room temperature for later use; weigh 0.2g of sodium hyaluronate and dissolve it in 100ml of water for injection at 80°C, cool to room temperature for later use Take by weighing 5 grams of phosphoric acid-phosphate buffer reagent and 6.5 grams of potassium chloride and dissolve in 700ml water for injection, add cooled polyethylene glycol 1000 vitamin E succinate solution and sodium hyaluronate solution, add water for injection Set the volume to 1000ml, adjust the pH to 6.5-7.4, and sterilize with high-pressure steam to obtain the eye drops of the present invention.

Example 3

Weigh 0.2g of polyethylene glycol 1000 vitamin E succinate and dissolve it in 100ml of water for injection at 85°C, cool to room temperature for later use; weigh 0.5g of hydroxypropyl methylcellulose and dissolve it in 100ml of water for injection at 4°C; weigh Phosphate-phosphate buffered reagent 6 g and sodium chloride 5.8 g were dissolved in 700 ml of water for injection, added cooled polyethylene glycol 1000 vitamin E succinate solution and hydroxypropyl methylcellulose solution, added water for injection Make up to 1000ml, adjust the pH to 6.5-7.4, filter and sterilize with a 0.2 μm filter membrane to obtain the eye drops of the present invention.

Example 4

Weigh 0.2 g of polyethylene glycol 1000 vitamin E succinate and dissolve it in 100 ml of water for injection at 80°C, cool to room temperature for later use; weigh 1 g of hydroxypropyl cellulose and dissolve it in 100 ml of water for injection at 4°C; weigh phosphoric acid - Dissolve 5 g of phosphate buffered reagent and 6.5 g of mannitol in 700 ml of water for injection, add cooled polyethylene glycol 1000 vitamin E succinate solution and hydroxypropyl cellulose solution, add water for injection to make up to 1000 ml , adjust the pH to 6.5-7.4, filter and sterilize with a 0.2 μm membrane to obtain the eye drops of the present invention.

Example 5

Weigh 0.5g of polyethylene glycol 1000 vitamin E succinate and dissolve it in 50ml of water for injection at 85°C, cool to room temperature for later use; weigh 1g of sodium hyaluronate and dissolve it in 100ml of water for injection at 80°C, cool to room temperature for later use Take by weighing 6 grams of phosphoric acid-phosphate buffer reagent, 0.1 gram of sorbitol, 2.5 grams of chloramphenicol and dissolve in 700ml water for injection, add cooling polyethylene glycol 1000 vitamin E succinate solution and sodium hyaluronate solution , adding water for injection to make the volume to 1000ml, adjusting the pH to 6.5-7.4, and sterilizing with a 0.2 μm filter membrane to obtain the eye drops of the present invention.

Example 6

Weigh 1 gram of polyethylene glycol 1000 vitamin E succinate, dissolve it in 50ml of water for injection at 70°C, cool to room temperature for later use; weigh 2 grams of sodium hyaluronate, dissolve it in 100ml of water for injection at 80°C, and cool to room temperature for later use Take by weighing 6 grams of phosphoric acid-phosphate buffer reagent, 10 grams of glucose, and 3 grams of levofloxacin and dissolve them in 700 ml of water for injection, add cooling polyethylene glycol 1000 vitamin E succinate solution and sodium hyaluronate solution, add The volume of water for injection is adjusted to 1000ml, the pH is adjusted to 6.5-7.4, and the eye drops of the present invention are obtained by filtering and sterilizing through a 0.2 μm filter membrane.

Example 7

Weigh 1.5 grams of polyethylene glycol 1000 vitamin E succinate and dissolve it in 50ml of water for injection at 60°C, cool to room temperature for later use; weigh 5 grams of sodium hyaluronate and dissolve it in 100ml of water for injection at 80°C, and cool to room temperature for later use ; Take by weighing 2 grams of carbonic acid-carbonate buffer reagents, 16 grams of sodium chloride, and 1 gram of diclofenac sodium and dissolve them in 700 ml of water for injection, add cooled polyethylene glycol 1000 vitamin E succinate solution and sodium hyaluronate solution, add water for injection and make the volume to 1000ml, adjust the pH to 6.5-7.4, filter and sterilize with a 0.2 μm membrane to obtain the eye drops of the present invention.

Example 8

Weigh 2 grams of polyethylene glycol 1000 vitamin E succinate and dissolve it in 50ml of water for injection at 50°C, cool to room temperature for later use; weigh 8 grams of chitosan and dissolve it in 100ml of water for injection at 4°C, and cool to room temperature for later use; Weigh 10 grams of boric acid-borate buffer reagent, 30 grams of dextran, and 1 gram of diclofenac sodium, dissolve them in 700 ml of water for injection, add cooled polyethylene glycol 1000 vitamin E succinate solution and chitosan solution, and add The volume of water for injection is adjusted to 1000ml, the pH is adjusted to 6.5-7.4, and the eye drops of the present invention are obtained by autoclaving.

Example 9

Weigh 2 grams of polyethylene glycol 1000 vitamin E succinate and dissolve it in 50ml of water for injection at 50°C, cool to room temperature for later use; weigh 10 grams of methylcellulose and dissolve it in 100ml of water for injection at 80°C, and cool to room temperature for later use Take by weighing 20 grams of phosphoric acid-phosphate buffer reagent, 6 grams of glycerin, 1 gram of diclofenac sodium and dissolve in 700ml water for injection, add cooling polyethylene glycol 1000 vitamin E succinate solution and methyl cellulose solution, replenish Add water for injection to make the volume to 1000ml, adjust the pH to 6.5-7.4, and sterilize with high-pressure steam to obtain the eye drops of the present invention.

The eye drops of the present invention contain vitamin E derivatives-polyethylene glycol 1000 vitamin E succinate, which has active groups in its molecule, which can release active hydrogen and capture free radicals, thereby blocking the chain reaction and making Biological cells, tissues, and organs will not be attacked by free radicals and maintain the normal structure of the biofilm. Therefore, adding polyethylene glycol 1000 vitamin E succinate eye drops to the treatment of dry eye, cataract, diabetic retinopathy, macular degeneration, optic atrophy, ophthalmoplegia, corneal degeneration, keratitis and other ophthalmic diseases is effective. good effect.

Claims (8)

1. an eye drop that contains vitamin e derivative is characterized in that, the prescription of eye drop is:

In the 1000ml eye drop, contain watermiscible vitamin E derivant 0.01～2 gram, thickening agent 0.1～10 gram, pH regulator agent 0.1～20 gram, isotonic agent 0.1～50 gram, all the other are water for injection;

Said watermiscible vitamin E derivant is a polyethylene glycol 1000 vitamin E succinic acid ester.

2. according to the said eye drop that contains vitamin e derivative of claim 1, it is characterized in that said watermiscible vitamin E derivant is a polyethylene glycol 1000 vitamin E succinic acid ester; Thickening agent is one or more in hyaluronate sodium, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, chitosan, polyvinyl alcohol or the polyvinylpyrrolidone; The pH regulator agent is that carbonic acid-carbonate buffering cushions reagent reagent or boric acid-borate reagent, phosphoric acid-phosphate-buffered; Isotonic agent is one or more in sodium chloride, potassium chloride, mannitol, sorbitol, glucose, dextran or the glycerol.

3. according to the said eye drop that contains vitamin e derivative of claim 1, it is characterized in that, also can add antiviral class medicine, anti-microbial type medicine, non-steroid antiinflammatory drug or antiallergic class medicine in the prescription as required.

4. according to the said eye drop that contains vitamin e derivative of claim 3, it is characterized in that said anti-microbial type medicine is an antibiotics.

5. according to the said eye drop that contains vitamin e derivative of claim 4, it is characterized in that said antibiotics is levofloxacin, gentamycin sulfate, lincomycin or chloromycetin; Said antiviral class medicine is acyclovir or ribavirin; Said non-steroid antiinflammatory drug is a diclofenac sodium; Said antiallergic class medicine is a sodium cromoglicate.

6. the said method for preparing that contains the eye drop of vitamin e derivative of claim 1 is characterized in that may further comprise the steps:

(1) take by weighing vitamin e derivative and be dissolved in 50～90 ℃ of waters for injection, it is subsequent use to be cooled to room temperature;

(2) by the prescription of the said eye drop of claim 1; Take by weighing thickening agent, pH regulator agent and isotonic agent, in the vitamin e derivative solution that adding step (1) makes, add water for injection behind the mix homogeneously; Regulating pH is 6.5～7.4; Osmotic pressure is 280～340mOsM, with filtering with microporous membrane degerming or the high pressure steam sterilization of 0.2 μ m, gets eye drop of the present invention after the packing.

7. according to the said eye drop that contains vitamin e derivative of claim 1, it is characterized in that the application in dry eye treatment.

8. according to claim 3 or the 5 said eye drops that contain vitamin e derivative, it is characterized in that the application in cataract, retinopathy, degeneration of macula, keratitis or conjunctivitis auxiliary treatment.