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Drug sustained release type composite eye drops and preparation method and application thereof

An eye drop, slow-release technology, applied in the field of biomedical materials, can solve the problems of inability to effectively prevent the rapid migration of small molecule drugs, the inability to realize drugs, weak van der Waals force, etc., to improve drug delivery efficiency and prolong residence time The effect of simple time and preparation method

Inactive Publication Date: 2017-03-15
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, simply relying on increasing the viscosity of the drug solution cannot achieve long-term slow release of the drug, because tears will continue to dilute the eye drops, and the interaction between small molecule drugs and hyaluronic acid is a weak van der Waals force, which cannot effectively prevent the release of small molecules. Rapid migration of drugs outward
Therefore, the hyaluronic acid eye drops currently available on the market cannot achieve sustained and slow release of the drug in the eyeball.

Method used

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  • Drug sustained release type composite eye drops and preparation method and application thereof
  • Drug sustained release type composite eye drops and preparation method and application thereof
  • Drug sustained release type composite eye drops and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] (1) Preparation of liquid A

[0061] Dissolve 0.3g of collagen in 30mL of 0.1mol / L dilute hydrochloric acid to prepare a collagen solution with a concentration of 0.01g / mL and a pH of 4.0 as liquid A;

[0062] (2) Preparation of liquid B

[0063] ① Weigh 0.1mol β-CD and put it in 1000mL water, add 40mL of 0.33g / mL NaOH dropwise under ice cooling to make the solution clear, then add 0.1mol p-toluenesulfonyl chloride (p -TsCl) in acetonitrile solution, stirred for 5h. Filtrate under reduced pressure to remove unreacted p-TsCl, neutralize the filtrate with 1mol / L hydrochloric acid to neutrality, and then let it stand at 4°C for 24 hours. Acylated β-CD.

[0064] figure 2 (a) for sulfonylated β-CD 1 H NMR spectrum, such as figure 2 As shown in the spectrum line in (a), the proton peaks of sulfonylated β-CD are assigned as follows: 2.42ppm (H-9'), 3.24~3.67ppm (H-2'~H-6'), 4.77ppm ( H-1′), 5.73ppm (OH-2′~3′), 7.76ppm (H-7′), 7.44ppm (H-8′); the results showed that th...

Embodiment 2

[0080] (1) Preparation of liquid A

[0081] Dissolve 1.5g of collagen in 30mL of 0.1mol / L dilute hydrochloric acid to prepare a collagen solution with a concentration of 0.05g / mL and a pH of 5.0 as liquid A;

[0082] (2) Preparation of liquid B

[0083] ① Weigh 0.1mol β-CD and put it in 1000mL water, add 40mL of 0.33g / mL NaOH dropwise under ice bath cooling to make the solution clear, then add 0.05mol p-toluenesulfonyl chloride (p -TsCl) in acetonitrile solution, stirred for 5h. Filtrate under reduced pressure to remove unreacted p-TsCl, neutralize the filtrate with 1mol / L hydrochloric acid to neutrality, and then let it stand at 4°C for 24 hours. Acylated β-CD.

[0084] ②Take 10g of the sulfonylated β-CD prepared in step ① and 20g of hexamethylenediamine, mix and dissolve in 60mL of dimethylformamide, stir and react at 75°C for 4h, add 500mL of cold acetone after cooling, a white precipitate is precipitated, reduce Suction pressure filtration, and then successively dissol...

Embodiment 3

[0094] (1) Preparation of liquid A

[0095] Dissolve 3g of collagen in 30mL of 0.1mol / L dilute hydrochloric acid to prepare a collagen solution with a concentration of 0.1g / mL and a pH of 4.0 as liquid A;

[0096] (2) Preparation of liquid B

[0097] ① Weigh 0.1mol β-CD and place it in 1000mL water, add 40mL of 0.33g / mL NaOH dropwise under ice cooling to make the solution clear, and then add 0.02mol p-toluenesulfonyl chloride (p -TsCl) in acetonitrile solution, stirred for 5h. Filtrate under reduced pressure to remove unreacted p-TsCl, neutralize the filtrate with 1mol / L hydrochloric acid to neutrality, and then let it stand at 4°C for 24 hours. Acylated β-CD.

[0098] ②Take 10g of the sulfonylated β-CD prepared in step ① and 20g of hexamethylenediamine, mix and dissolve in 60mL of dimethylformamide, stir and react at 80°C for 2h, add 500mL of cold acetone after cooling, a white precipitate is precipitated, reduce Suction pressure filtration, and then successively dissolve...

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Abstract

The invention discloses drug sustained release type composite eye drops and a preparation method and application thereof, and belongs to the field of biomedical materials. The composite eye drops comprise a liquid A and a liquid B, wherein the liquid A is a positively charged collagen solution; and the liquid B is a beta-CD-HA solution loaded with a target drug and is negatively charged. The liquid A and the liquid B are electrostatically assembled on the surface of cornea so as to form a composite eye drops coating. The preparation method of the invention is simple and has good repeatability and strong operationality. The prepared drug sustained release type composite eye drops is nontoxic, has functions of drug loading and drug slow-release. By the electrostatic assembly principle, the multilayer composite eye drops coating is formed on the surface of cornea; and drug loading capacity and drug slow-release rate of the composite eye drops coating are regulated. Therefore, retention time of the composite eye drops on the cornea can be prolonged, and administration efficiency is enhanced. The drug sustained release type composite eye drops is a good long-acting administration system for eye disease treatment, is used for eye disease treatment, and has important scientific research significance and good application prospect.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a drug slow-release compound eye drop and its preparation method and application. Background technique [0002] Eye diseases such as cataract and glaucoma seriously affect human health, and the annual treatment cost is as high as hundreds of billions of dollars. For the treatment of ophthalmic diseases, the most convenient and direct method at present is eye drops, but after eye drops are excreted, tears or conjunctival absorption will cause drug loss, resulting in short drug residence time and low drug delivery efficiency. In order to obtain long-term drug However, it is usually necessary to frequently drop high-concentration drugs to maintain a long-term drug concentration for a short period of time, which not only wastes money, but may also cause toxic and side effects to the human body. Therefore, how to improve the administration efficiency of eye drops and d...

Claims

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Application Information

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IPC IPC(8): A61K9/08A61K47/42A61K47/40A61P27/02
CPCA61K47/40A61K47/42A61K9/0048A61K9/08
Inventor 赵剑豪张晓婷张秋语刘婳婳容建华屠美曾戎
Owner JINAN UNIVERSITY
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