CN101455634A - Composite aspartate, vitamin B6 and dipotassium glycyrrhetate eye drops without bacteria inhibitor and preparation method thereof - Google Patents

Abstract

The invention discloses a compound aspartic and vegan eye drop without bacteriostatic agents and a preparation method thereof, which comprises aspartic acid, vitamin B ₆ , dipotassium glycyrrhizinate, naphazoline hydrochloride, neomethazine Stigmine, chlorpheniramine maleate, pH regulator, isotonic agent, stabilizer, thickener and cooling agent etc., its preparation method adopts aseptic operation filling process, and eye drops of the present invention adopts The single-dose single-dose individual packaging ensures the aseptic performance of the product and makes the product safer, more reliable, more convenient and hygienic.

Description

Compound Aspart Vigan eye drops without bacteriostatic agent and preparation method thereof

technical field

The invention belongs to the field of pharmacy, and particularly relates to compound aspartic and vigan eye drops without bacteriostatic agents and a preparation method thereof.

Background technique

Compound Aspart Vigan Eye Drops is used for the treatment of eye fatigue, chronic conjunctivitis, eye membrane hyperemia, and allergic conjunctivitis. The compound aspart Vigan eye drops that have been on the market all contain antibacterial agents and are packaged in multiple doses for repeated use. Once the preparation is opened, it is easy to be contaminated by tears and microbes in the air during use and storage, thereby causing safety hazards. In order to prevent ophthalmic preparations from being contaminated by microorganisms during repeated use after opening, bacteriostatic agents (preservatives) are added to ophthalmic preparations, which are used in almost all eye drop prescriptions in the "Chinese Hospital Preparation Specifications" antibacterial agent. Bacteriostatic agents, also known as preservatives or preservatives, refer to chemicals that inhibit the growth and reproduction of pathogenic microorganisms. Their primary application in pharmaceutical practice is to prevent microbial contamination of drugs.

Although bacteriostatic agents have certain positive significance in preventing microbial contamination, the adverse reactions of bacteriostatic agents have gradually been recognized by people. It is reported that the presence of antibacterial agents can stimulate the surface cells of the eye (see literature: Liu Aiming, Li Wei, Wang Benmin, "Ocular Surface Damage of Antibacterial Agents in Ophthalmic Preparations", Chinese Journal of Hospital Pharmacy, 2002, 22( 6), 371-373). The antibacterial components in eye drops can directly affect the composition of tears, change the microenvironment of the eyeball surface, and damage the structure of the epithelial cells that were originally tightly connected. Corneal dissolution, perforation, blindness. The problems caused by the abuse of bacteriostatic agents are getting more and more attention (see literature: Ning Lili, "Rational use and quality control of bacteriostatic agents should be paid attention to during the development of ophthalmic preparations", Chinese Journal of Hospital Pharmacy, 2007, 42(23 ), 1836-1838). Especially for eye drops that need to be used frequently, its potential danger is even greater.

Contents of the invention

The technical problem to be solved in the present invention is to provide a kind of compound asparagine and Vigan eye drops without bacteriostatic agent and its preparation method, which can avoid the secondary pollution of microorganisms in the process of using the eye drops, and can also avoid Toxic side effects and potential risks caused by bacteriostatic agents to eyes in the prior art.

In order to solve the problems in the prior art, the present invention adopts the following technical solutions to achieve:

The present invention does not contain the compound asparagine Vigan eye drops of antibacterial agent, and it comprises following component:

Aspartic acid 7.02～8.58g

Vitamin _B6 0.45～0.55g

Dipotassium glycyrrhizinate 0.9～1.1g

Naphazoline hydrochloride 0.027～0.033g

Neostigmine Methosulfate 0.45～0.55g

Chlorpheniramine maleate 0.85～0.115g

pH adjuster 0.1～50g

Isotonic agent 0.1～50g

Add water for injection to make up to 1000mL

The pH regulator is sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, boric acid, borax, acetic acid, sodium acetate, citric acid, sodium citrate, tartaric acid, sodium tartrate, sodium carbonate, One or more compounds of potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, hydrochloric acid, phosphoric acid.

The function of the pH regulator is to make the pH of the eye drops equal or close to that of the tears, so as to reduce the irritation of the eye drops, stabilize the medicine and improve the drug efficacy. The pH range of the bacteriostatic-free compound asparagine eye drops is 5.0-6.0.

The isotonic agent is one or more of sodium chloride, potassium chloride, boric acid, borax, sodium sulfate, potassium sulfate, sodium nitrate, potassium nitrate, sodium acetate, mannitol, glycerin, propylene glycol, and glucose. .

The function of the isotonic agent is to make the osmotic pressure of the eye drops equal to or close to that of the tears, so as to reduce the irritation of the eye drops and improve the drug efficacy.

The compound aspart Vigan eye drops without bacteriostatic agent also includes one or more combinations of stabilizer, thickener and cooling agent:

The stabilizer is: 0.01～5g

The thickener is: 0.01～10g

The cooling agent is: 0.001～1.0g

Described stabilizing agent is sodium sulfite, sodium bisulfite, sodium pyrosulfite, sodium nitrite, sodium thiosulfate, ascorbic acid (vitamin C), thiourea, ascorbyl stearate, dibutylcresol, cysteine, tocopherol Acetate, Dichloroisocyanate, Disodium EDTA (EDTA-2Na, Disodium Edetate), Calcium Sodium EDTA, Dimercaptopropanol, Glycerin, Mannitol, Butylated Hydroxy One or more compounds of anisole.

The role of the stabilizer is to increase the stability of the eye drops and improve the efficacy.

The thickener is sodium hyaluronate, chondroitin sulfate, methylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, povidone, polyvinylpyrrolidone, polyethylene Alcohol, chitosan, β-cyclodextrin, carbomer, glucosamine polymer, glycerin, propylene glycol, polyethylene glycol, polyvinyl alcohol or one or more compounds.

Thickeners can prolong the residence time of the drug in the eye, reduce eye irritation and improve drug efficacy.

The cooling agent (or called: aromatic agent) is one or more compounds of peppermint, eucalyptus oil, camphor, borneol, and ethanol.

The preparation method of the described compound asparagine eye drops not containing bacteriostatic agent, it may further comprise the steps:

a. Precisely weigh 7.02-8.58g of aspartic acid, 0.45-0.55g of vitamin _B6 , 0.9-1.1g of dipotassium glycyrrhizinate, 0.027-0.033g of naphazoline hydrochloride, and 0.45-0.55g of neostigmine methosulfate. g, chlorpheniramine maleate 0.85-0.115g, pH regulator 0.1-50g, isotonic agent 0.1-50g, stabilizer 0.01-5g, cooling agent 0.001-1.0g, add 1/5 of the total amount of water for injection Dissolve ~1/4, adjust the pH range: 5.0-6.0, stir and mix, and dilute to 1000mL with water for injection to obtain a medicinal solution.

b. Under a Class 100 environment, filter the medicinal solution obtained in step a for 1 to 5 times with a 0.22-0.45 μm microporous membrane.

c. After the liquid medicine is tested to pass the test, fill the liquid medicine into a single-dose packaging container under a class 100 environment and seal it to obtain the finished product. The above method is called aseptic filling process.

In the process of the above step b, the 0.45 μm microporous membrane can also be used for filtration first, and then the 0.22 μm microporous membrane can be used for filtration after the clarity is qualified, and the number of filtration can also be appropriately increased according to the actual production situation. The bacteriostatic-free compound asparagine eye drops of the present invention should meet the requirements of "Chinese Pharmacopoeia" for eye drops.

Preferably, the compound aspart-Vigan eye drops without bacteriostatic agent is packaged in a single-dose independent package (or called: small-dose independent package), and the volume of the container in the single-dose independent package is in the range of 0.1 to 5.0 ml /branch.

Finished eye drops are usually packaged in disposable single-dose plastic individual packaging.

Preferably, the compound Aspart-Vigant eye drop without bacteriostatic agent is packaged in a single dose with a volume ranging from 0.01 to 5.0 milliliters per bottle.

The finished eye drops should meet the requirements for eye drops in the Chinese Pharmacopoeia.

Each single-dose individual sachet should not be reused after each use. It can be made into one or more groups of single-dose eye drops finished products during production.

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

1. The eye drops of the present invention do not contain bacteriostatic agents, which avoids the potential danger caused by bacteriostatic agents and the side effects on the eyes, and it is safer and more reliable to use the product of the present invention.

2. The present invention adopts aseptic filling process or sterilization process to ensure the aseptic requirement of the product.

3. The present invention adopts single-dose independent packaging, which is discarded after one-time use, so that the medicinal liquid cannot be polluted twice, and the integrity of other single-dose independent packaging is not affected.

Four, the product of the present invention does not contain bacteriostatic agent, has saved the cost of auxiliary materials such as bacteriostatic agent must be added in multi-dose packaging.

Detailed ways

The present invention will be further described below by specific examples.

Embodiment one

prescription:

Its preparation method:

a. Accurately weigh 7.8g aspartic acid, 0.5g vitamin _B6 , 1.0g dipotassium glycyrrhizinate, 0.03g naphazoline hydrochloride, 0.05g neostigmine methosulfate, 0.1g chlorpheniramine maleate Mint, 1.0g polysorbate 80, 6.5g sodium chloride, 0.1g mint, add 200mL water for injection to dissolve, stir evenly, adjust the pH value to 5.0-6.0 with 5% sodium hydroxide solution, and dilute to 5.0-6.0 with water for injection. 1000mL, to obtain liquid medicine.

b. Filter the above medicinal solution once with a 0.45 μm microporous membrane, and then filter twice with a 0.22 μm microporous membrane under a Class 100 environment.

c. After the medicinal liquid is tested and passed, fill 0.4mL of the above medicinal liquid into a 1mL single-dose packaging plastic container in a class 100 environment, and seal it to obtain the finished product.

Embodiment two

prescription:

Its preparation method:

a. Accurately weigh 0.5g of sodium hyaluronate, add 300mL of water for injection to dissolve it, fully swell, and cool to obtain solution 1 for later use; accurately weigh 7.8g of aspartic acid, 0.5g of vitamin _B6 , and 1.0g of glycyrrhizinic acid Potassium, 0.03g naphazoline hydrochloride, 0.05g neostigmine methosulfate, 0.1g chlorpheniramine maleate, 18.0g sodium citrate, after adding 200mL water for injection to dissolve, it was stirred and mixed to obtain a solution 2 for later use; mix solution 1 and solution 2, stir evenly, and dilute to 1000 mL with water for injection to obtain a medicinal solution.

b. Filter the above medicinal solution once with a 0.45 μm microporous membrane, and then filter twice with a 0.22 μm microporous membrane under a Class 100 environment.

c. After the medicinal liquid is tested and passed, fill 0.6mL of the above medicinal liquid into a 1mL single-dose packaging plastic container under a class 100 environment, and seal it to obtain the finished product.

Embodiment Three

prescription:

Its preparation method:

a. Accurately weigh 7.8g aspartic acid, 0.5g vitamin _B6 , 1.0g dipotassium glycyrrhizinate, 0.03g naphazoline hydrochloride, 0.05g neostigmine methosulfate, 0.1g chlorpheniramine maleate Min, 7.2g sodium dihydrogen phosphate, 0.9g disodium hydrogen phosphate, 12.0g glycerol, add 200mL water for injection to dissolve, stir well, and dilute to 1000mL with water for injection to obtain a medicinal solution.

b. Filter the above medicinal solution once with a 0.45 μm microporous membrane, and then filter twice with a 0.22 μm microporous membrane under a Class 100 environment.

c. After the medicinal liquid is tested and passed, fill 0.6mL of the above medicinal liquid into a 1mL single-dose packaging plastic container under a class 100 environment, and seal it to obtain the finished product.

Embodiment Four

prescription:

Its preparation method:

a. Accurately weigh 7.8g aspartic acid, 0.5g vitamin _B6 , 1.0g dipotassium glycyrrhizinate, 0.03g naphazoline hydrochloride, 0.05g neostigmine methosulfate, 0.1g chlorpheniramine maleate Mint, 1.0g polysorbate 80, 18g glycerin, add 200mL water for injection to dissolve; dissolve 0.01g mint in 5mL95% ethanol, add to the above solution and stir to mix, adjust the pH value to 5.0-6.0 with 5% sodium hydroxide solution, Dilute to 1000mL with water for injection to obtain a medicinal solution.

b. Filter the above medicinal solution once with a 0.45 μm microporous membrane, and then filter twice with a 0.22 μm microporous membrane under a Class 100 environment.

c. After the medicinal solution is qualified, fill 1.0mL of the above medicinal solution into a 2mL single-dose packaging plastic container in a class 100 environment, and seal it to obtain the finished product.

Embodiment five

prescription:

Its preparation method:

a. Accurately weigh 7.8g aspartic acid, 0.5g vitamin _B6 , 1.0g dipotassium glycyrrhizinate, 0.03g naphazoline hydrochloride, 0.05g neostigmine methosulfate, 0.1g chlorpheniramine maleate Min, 7.2g sodium dihydrogen phosphate, 0.9g disodium hydrogen phosphate, 10.0g glycerin, 1.0g sodium bisulfite, 0.1g ethylenediaminetetraethylene disodium, add 200mL water for injection to dissolve, stir well, and use water for injection Dilute to 1000mL to obtain liquid medicine.

b. Filter the above medicinal solution once with a 0.45 μm microporous membrane, and then filter twice with a 0.22 μm microporous membrane under a Class 100 environment.

c. After the medicinal liquid is tested and passed, fill 0.6mL of the above medicinal liquid into a 1mL single-dose packaging plastic container under a class 100 environment, and seal it to obtain the finished product.

Embodiment six

prescription:

Its preparation method:

a. Accurately weigh 7.8g aspartic acid, 0.5g vitamin _B6 , 1.0g dipotassium glycyrrhizinate, 0.03g naphazoline hydrochloride, 0.05g neostigmine methosulfate, 0.1g chlorpheniramine maleate Mint, 1g polyoxyethylene hydrogenated castor oil 60, add 200mL water for injection to dissolve, adjust the pH value to 5.0-6.0 with 5% sodium hydroxide solution; accurately weigh 0.15g L-mint, 0.07g eucalyptus oil, 0.07g d- Borneol, 0.05g of disodium edetate, dissolved in 1mL of 95% ethanol, added to the above solution, stirred evenly, then dilute to 1000mL with water for injection to obtain a medicinal solution.

b. Filter the above medicinal solution once with a 0.45 μm microporous membrane, and then filter through a 0.22 μm microporous membrane for 3 times under a class 100 environment.

c. After the medicinal liquid is tested and passed, fill 0.6mL of the above medicinal liquid into a 1mL single-dose packaging plastic container under a class 100 environment, and seal it to obtain the finished product.

The prescriptions in the embodiments of the present invention are all taken as an example of 1000mL, and the preparation amount can be increased correspondingly with reference to the prescription ratio in actual industrial production.

Claims (5)

1, the aspartic vitamin eye drops of bacteriostatic agent not is characterized in that it comprises following component:

Aspartic Acid 7.02～8.58g

Vitamin B ₆0.45～0.55g

Glycyrrhizic acid dipotassium 0.9～1.1g

Naphcon 0.027～0.033g

Methyl-sulfuric acid neostigmine 0.45～0.55g

Chlorphenamine maleate 0.85～0.115g

PH regulator agent 0.1～50g

Isotonic agent 0.1～50g

Add the injection water and be settled to 1000mL

Described pH regulator agent is that in sodium dihydrogen phosphate, sodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, boric acid, Borax, acetic acid, sodium acetate, citric acid, sodium citrate, tartaric acid, sodium tartrate, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, hydrochloric acid, the phosphoric acid one or more are composite;

Described isotonic agent is that in sodium chloride, potassium chloride, boric acid, Borax, sodium sulfate, potassium sulfate, Chile saltpeter, potassium nitrate, sodium acetate, mannitol, glycerol, propylene glycol, the glucose one or more are composite.

2, the aspartic vitamin eye drops of not bacteriostatic agent as claimed in claim 1 is characterized in that it also comprises one or more assembly in stabilizing agent, thickening agent, the freshener:

Described stabilizing agent is: 0.01～5g

Described thickening agent is: 0.01～10g

Described freshener is: 0.001～1.0g

Described stabilizing agent is that in sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium nitrite, sodium thiosulfate, ascorbic acid (vitamin C), thiourea, ascorbyl stearate, dibutyl hydroxy toluene, cysteine, tocopherol acetas, dichloro isocyanide, disodiumedetate (EDTA-2Na, disodium edetate), calcio-disodium edetate, dimercaptopropanol, BAL, glycerol, mannitol, the butylated hydroxyanisol one or more are composite;

Described thickening agent is that in hyaluronate sodium, chondroitin sulfate, methylcellulose, hydroxy methocel, hydroxypropyl methylcellulose, cellulose, polyvidone, polyvinylpyrrolidone, polyvinyl alcohol, chitosan, beta cyclodextrin, carbomer, glucosamine polymer, glycerol, propylene glycol, Polyethylene Glycol, the polyvinyl alcohol one or more are composite.

Described freshener (or claims: aromatic) be that in Herba Menthae, Oleum Eucalypti, Camphora, Borneolum Syntheticum, the ethanol one or more are composite.

3, as the preparation method of the aspartic vitamin eye drops of claim 1 or the described not bacteriostatic agent of claim 2, it is characterized in that it may further comprise the steps:

A. precision takes by weighing Aspartic Acid 7.02～8.58g, vitamin B ₆0.45～0.55g, glycyrrhizic acid dipotassium 0.9～1.1g, naphcon 0.027～0.033g, methyl-sulfuric acid neostigmine 0.45～0.55g, chlorphenamine maleate 0.85～0.115g, pH regulator agent 0.1～50g, isotonic agent 0.1～50g, stabilizing agent 0.01～5g, freshener 0.001～1.0g, 1/5～1/4 dissolving that adds the water for injection total amount, transfer the pH scope to be: 5.0～6.0, mix, be settled to 1000mL with water for injection, get medicinal liquid;

B. under hundred grades of environment, with step a gained medicinal liquid with 0.22～0.45 μ m filtering with microporous membrane 1 to 5 time;

C. testing sequence b gained medicinal liquid, qualified after, under hundred grades of environment, liquid drug is sealed to the unit dose package container, gets product.

4, the aspartic vitamin eye drops of not bacteriostatic agent as claimed in claim 1 or 2, it is characterized in that: the aspartic vitamin eye drops of described not bacteriostatic agent adopts the single dose independent packaging, and the volume scope of the container of described single dose independent packaging is 0.1～5.0 milliliter/.

5, the aspartic vitamin eye drops of not bacteriostatic agent as claimed in claim 4 is characterized in that: the medicine liquid volume scope of described single dose independent packaging is 0.01～5.0 milliliter/.