阅读说明：本技术 一种复方洛索洛芬滴眼剂及其制备方法 (Compound loxoprofen eye drops and preparation method thereof ) 是由 谭上彬 陈宇明 崔明 黄俊杰 王延东 于 2019-12-03 设计创作，主要内容包括：一种复方洛索洛芬滴眼剂及其制备方法,按其重量份包括以下组分：洛索洛芬钠1份；玻璃酸钠0.05～1份；依地酸二钠0.02～0.2份；氯化钠4.5份,黄芩苷1-2份；本发明的有益效果在于：具有良好的眼内穿透性,眼内生物利用度较高,渗透力强、靶向作用强、毒副作用小优点；适用于治疗及预防非感染性炎症引起的外眼及眼前节疾病以及术后炎症；原料易得,成本低,可以实现工业化大规模生产,具有显著的经济效益。(The compound loxoprofen eye drop comprises the following components in parts by weight: 1 part of loxoprofen sodium; 0.05-1 part of sodium hyaluronate; 0.02-0.2 parts of edetate disodium; 4.5 parts of sodium chloride and 1-2 parts of baicalin; the invention has the beneficial effects that: has the advantages of good intraocular penetrability, high intraocular bioavailability, strong penetrability, strong targeting effect and small toxic and side effect; is suitable for treating and preventing external eye and anterior segment diseases and postoperative inflammation caused by non-infectious inflammation; the raw materials are easy to obtain, the cost is low, the industrial large-scale production can be realized, and the economic benefit is remarkable.)

1. The compound loxoprofen eye drop comprises the following components in parts by weight:

1 part of loxoprofen sodium;

0.05-1 part of sodium hyaluronate;

0.02-0.2 parts of edetate disodium;

4.5 parts of sodium chloride;

it is characterized in that 1-2 parts of baicalin is also added.

2. The compound loxoprofen eye drop as claimed in claim 1, wherein:

the eye drops further comprise an osmotic pressure regulator and a pH regulator, and also comprise a bacteriostatic agent, wherein the mass fraction ratio of the bacteriostatic agent to the loxoprofen sodium is that the loxoprofen sodium: bacteriostatic agent = 1: 0.004, the eye drops further comprise a thickening agent, and the mass fraction ratio of the thickening agent to the loxoprofen sodium is loxoprofen sodium: thickener = 1: 1.

3. The compound loxoprofen eye drop as claimed in claim 2, wherein:

the bacteriostatic agent is one or more of thimerosal, quaternary ammonium salt, domiphen bromide, Xibitai, chlorobutanol, nipagin, and sorbic acid.

4. The compound loxoprofen eye drop as claimed in claim 2, wherein:

the thickening agent is one or more of methyl cellulose, sodium hyaluronate, polyvinyl alcohol and polyvinylpyrrolidone.

5. The method for preparing the compound loxoprofen eye drop as claimed in any one of claims 1 to 4, which comprises the following steps:

step 1), dissolving loxoprofen sodium by using sodium hyaluronate, edetate disodium and sodium chloride for later use;

step 2), dispersing the thickening agent with water for injection, cooling, adding a bacteriostatic agent, stirring uniformly, filtering, and adding the mixture into the loxoprofen sodium solution obtained in the step 1);

step 3), dissolving a pH regulator by using water for injection, slowly adding the pH regulator into the loxoprofen sodium solution obtained in the step 2), and stopping when the pH value is regulated to 6;

step 4), dissolving an osmotic pressure regulator in water for injection, slowly adding the osmotic pressure regulator into the solution obtained in the step 3), and stopping adding the osmotic pressure regulator when the osmotic pressure molar concentration is regulated to 300 mOsmol/kg;

step 5), adding water for injection to a constant volume, so that the concentration of loxoprofen sodium in the eye drops is 0.5-5 mg/ml, filtering, and subpackaging to obtain single loxoprofen eye drops;

step 6), adding baicalin to obtain the compound loxoprofen eye drop.

Technical Field

The invention relates to an ophthalmic medicinal preparation for treating non-infectious inflammation, in particular to a compound loxoprofen eye drop and a preparation method thereof.

Background

Inflammation is a manifestation of host tissue's vascular and cellular responses to injury. Physical or chemical causes may cause tissue damage, such as pathogen invasion, ischemia, allergy, or immune mechanisms that function improperly (autoimmunity). At this time, arachidonic acid is released from cell membrane phospholipid, forms endoperoxides (PGG 2 and PGH 2) under the catalysis of cyclooxygenase, and is converted into prostaglandins (PGE 2, PGF2 and PGD 2) through the action of isomerase, and the prostaglandins are the most powerful ocular inflammatory substances in the natural substances known at present, and can cause the damage of blood-aqueous humor barrier in eyes, so that proteins, various cells, toxins, immune complexes and other components permeate into the aqueous humor to cause inflammatory reaction, hyperemia, edema, pruritus and pain of ocular tissues. The non-steroidal anti-inflammatory drug (NSAIDS) has the effects of resisting inflammation, relieving fever and relieving pain, and the defect that the sugar-free corticoid drugs easily cause more serious adverse reactions, so the non-steroidal anti-inflammatory drug is an important anti-inflammatory drug in ophthalmic clinic at present. The eye drops are used for diminishing inflammation after eye trauma, laser surgery and cataract surgery and inhibiting miosis during surgery, and have good effect.

Disclosure of Invention

In summary, the invention needs to provide a compound loxoprofen eye drop, which comprises the following components in parts by weight:

1 part of loxoprofen sodium;

1 part of sodium hyaluronate;

0.02-0.2 parts of edetate disodium;

0.45 part of sodium chloride;

1-2 parts of baicalin

The loxoprofen sodium accounts for 0.5-5 mg/ml of the concentration of the eye drops.

Preferably: the eye drops further comprise an osmotic pressure regulator and a pH regulator, and also comprise a bacteriostatic agent, wherein the mass fraction ratio of the bacteriostatic agent to the loxoprofen sodium is that the loxoprofen sodium: bacteriostatic agent = 1: 0.004, the eye drops further comprise a thickening agent, and the mass fraction ratio of the thickening agent to the loxoprofen sodium is loxoprofen sodium: thickener = 1: 1.

In the scheme, the method comprises the following steps: the bacteriostatic agent is one or more of thimerosal, quaternary ammonium salt, domiphen bromide, Xibitai, chlorobutanol, nipagin, and sorbic acid.

In the scheme, the method comprises the following steps: the thickening agent is one or more of methyl cellulose, sodium hyaluronate, polyvinyl alcohol and polyvinylpyrrolidone.

A preparation method of the compound loxoprofen eye drop comprises the following steps:

step 1), dissolving loxoprofen sodium by using sodium hyaluronate, edetate disodium and sodium chloride for later use;

step 2), dispersing the thickening agent with water for injection, cooling, adding a bacteriostatic agent, stirring uniformly, filtering, and adding the mixture into the loxoprofen sodium solution obtained in the step 1);

step 3), dissolving a pH regulator by using water for injection, slowly adding the pH regulator into the loxoprofen sodium solution obtained in the step 2), and stopping when the pH value is regulated to 6;

step 4), dissolving an osmotic pressure regulator in water for injection, slowly adding the osmotic pressure regulator into the solution obtained in the step 3), and stopping adding the osmotic pressure regulator when the osmotic pressure molar concentration is regulated to 300 mOsmol/kg;

step 5), adding water for injection to a constant volume, so that the concentration of loxoprofen sodium in the eye drops is 0.5-5 mg/ml, filtering and subpackaging;

and 6) adding baicalin to obtain the medicine.

The invention has the beneficial effects that: currently, NSAIDS commonly used for ophthalmology include 0.1% pranoprofen eye drops, 0.1% diclofenac sodium eye drops, 0.5% and 0.4% ketorolac tromethamine eye drops, 0.03% flurbiprofen sodium eye drops, 1.0% suprofen sodium eye drops, nepafenac, bromfenac sodium, indomethacin and other eye drops. The unilateral loxoprofen eye drops are propionic acid precursor non-steroidal anti-inflammatory drugs (NSAIDs), are metabolized into trans-OH type drugs in vivo after being taken orally, and are combined with cyclooxygenase to cover the active center of the cyclooxygenase, so that the metabolic process of converting arachidonic acid catalyzed by the cyclooxygenase into prostaglandin is blocked, and the analgesic and anti-inflammatory effects are achieved.

Compared with the single loxoprofen eye drops, the compound loxoprofen eye drops have higher loxoprofen sodium concentration in each main tissue in eyes, particularly the highest concentration in conjunctiva, cornea and iris, which shows that the compound loxoprofen eye drops have good intraocular penetrability and high concentration, and can completely reach effective treatment concentration when used for treating non-infectious diseases in the eyes.

The compound loxoprofen eye drops have obviously better curative effect than single loxoprofen eye drops and long action time. The external seepage amount of EB treated by the medicines in each group is lower than that of eyes treated by normal saline, the inhibition rate of the compound loxoprofen eye drops is 60.52% + -16.40%, and is remarkably higher than that of 37.82% + -18.35% and P =0.028 of a single loxoprofen eye drop group. Therefore, the compound loxoprofen eye drops have good anti-inflammatory effect.

Detailed Description

The invention relates to a compound loxoprofen eye drop and a preparation method thereof, which are disclosed in the following embodiments. The specific examples are intended to illustrate the present invention in further detail, and are not intended to limit the scope of the present invention.

The features used in the present invention are all commercially available.

Pranoprofen eye drops used in comparative examples: the quasi-character number of the medicine is as follows: h20030026

Firstly, preparing materials according to the formula shown in table 1;

step 1), dissolving loxoprofen sodium by using sodium hyaluronate, edetate disodium and sodium chloride for later use;

step 2), dispersing the thickening agent with water for injection, cooling, adding a bacteriostatic agent, stirring uniformly, filtering, and adding the mixture into the loxoprofen sodium solution obtained in the step 1);

step 3), dissolving a pH regulator by using water for injection, slowly adding the pH regulator into the loxoprofen sodium solution obtained in the step 2), and stopping when the pH value is regulated to 6;

step 4), dissolving an osmotic pressure regulator in water for injection, slowly adding the osmotic pressure regulator into the solution obtained in the step 3), and stopping adding the osmotic pressure regulator when the osmotic pressure molar concentration is regulated to 300 mOsmol/kg;

step 5), adding water for injection to 100ml, filtering and subpackaging to obtain the single loxoprofen eye drops;

the method comprises the following specific steps:

TABLE 1 raw materials and compounding ratio of eye drops