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Foscarnet sodium eye vitreous intracavity controlled-release medicine

A slow-release drug, foscarnet sodium technology, which is applied in drug combination, drug delivery, and pharmaceutical formulations, can solve the problems of large trauma, easy blockage of needles, and complicated drug delivery process, and achieve high safety, avoid injury, and prolong drug delivery. Effect of Dosing Interval

Active Publication Date: 2015-09-16
QINGDAO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, conventional sustained-release preparations have technical defects in varying degrees. For example, the solid implant invented by the invention patent of CN 101390825B cannot be administered by conventional vitreous injection, especially the 33G needle injection. Surgical implantation is required, the administration process is complicated, and the trauma is large; and because of the large particle size of the microspheres, a large-diameter injection needle is required for intravitreal injection, and it is impossible to use a very fine 33G needle for injection; liposome nanoparticles and other preparations, Due to the small particle size, there is an aggregation effect, it is not easy to disperse, and it is easy to block the needle during injection, and it cannot be injected with a very fine 33G needle; while conventional gels, chitosan and other in-situ gels and other slow-release agents In order to achieve sustained release, high-molecular-weight polymer materials such as chitosan are required, and the solution has a high viscosity and cannot be injected with a very fine 33G needle

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] (1) Take 80 mg of sterile four-arm-polyethylene glycol-maleimide with a molecular weight of 1000 Daltons, dissolve it in 1 ml of pH7.4 phosphate buffer under sterile conditions, and then add 20 mg of sodium foscarnet powder , after dissolving, it is filled into aseptically treated vials and prepared into bottle A solution.

[0021] (2) Weigh 2.98mg of triethylamine, dissolve it in 10ml pH7.4 phosphate buffer, adjust the pH value to 7.4 with sodium hydroxide, prepare a phosphate buffer containing 2mM triethylamine, weigh 64 mg of GPQ peptide was fully dissolved in 1 ml of phosphate buffer containing 2 mM triethylamine, and then filled into aseptically treated vials to prepare bottle B solution.

[0022] (3) When using, use a syringe with a 33G needle to draw out the solution in bottle A (such as 0.1ml) as needed, and then draw an equal volume of solution in bottle B (such as 0.1ml), just shake the syringe twice, or put Invert the syringe twice up and down to mix the sol...

Embodiment 2

[0024] Take 80 mg of sterile four-arm-polyethylene glycol-maleimide with a molecular weight of 2000 Daltons, dissolve it in 1 ml of pH7.4 phosphate buffer under sterile conditions, then add 20 mg of sodium foscarnet powder, after dissolving Fill in aseptically treated vials and prepare bottle A solution.

[0025] Weigh 2.98 mg of triethylamine, dissolve it in 10 ml of pH7.4 phosphate buffer, adjust the pH to 7.4 with sodium hydroxide, prepare a phosphate buffer containing 2 mM of triethylamine, and weigh 64 mg of GPQ peptide , after fully dissolving with 1ml of phosphate buffer solution containing 2mM triethylamine, after dissolving, it is filled in an aseptically treated cillin bottle, and is prepared into bottle B solution.

[0026]When in use, use a syringe with a 33G needle to draw out the solution in bottle A (such as 0.1ml) as needed, and then draw an equal volume of solution in bottle B (such as 0.1ml), just shake the syringe twice, or turn the syringe upside down The ...

Embodiment 3

[0028] Take 80 mg of sterile four-arm-polyethylene glycol-maleimide with a molecular weight of 1000 Daltons, dissolve it with 1 ml of pH7.4 phosphate buffer under sterile conditions, then add 80 mg of sodium foscarnet powder, after dissolving Fill in aseptically treated vials and prepare bottle A solution.

[0029] Weigh 2.98mg of triethylamine, dissolve it in 10ml pH7.4 phosphate buffer, adjust the pH to 7.4 with sodium hydroxide, prepare a phosphate buffer containing 2mM triethylamine, and weigh 64mg of GPQ peptide , after fully dissolving with 1ml of phosphate buffer solution containing 2mM triethylamine, after dissolving, it is filled in an aseptically treated cillin bottle, and is prepared into bottle B solution.

[0030] When in use, use a syringe with a 33G needle to draw out the solution in bottle A (such as 0.1ml) as needed, and then draw an equal volume of solution in bottle B (such as 0.1ml), just shake the syringe twice, or turn the syringe upside down The solutio...

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Abstract

The invention discloses a foscarnet sodium eye vitreous intracavity controlled-release medicine. The controlled-release medicine is characterized in that the controlled-release medicine comprises an ingredient A and an ingredient B; the ingredient A is a uniform an mixed solution formed by foscarnet sodium and a biodegradable medicinal polyethylene glycol auxiliary material, and the ingredient B is a peptide cross-linking agent solution. The ingredient A and the ingredient B can form a gel-like implant rapidly after the ingredient A and the ingredient B are injected into an eye vitreous cavity, rapid release of foscarnet sodium is retarded, therefore the medicine controlled-release effect is achieved and dosage interval time is prolonged. The reaction can be achieved under physiological conditions, namely, the reaction can be carried out in a normal saline or a buffer with a pH value of 7.4, special organic solvents or a strong acidic condition needed by a traditional implant or gelata are not needed, safety is high, and damage to human tissues is avoided effectively. Through control of the concentration of 4arm-PEG-MAL in the solution and the concentration of triethylanmine in the solution, reaction time can be controlled effectively, and the controlled-release medicine can be used for injection of an extremely fine 33G needle.

Description

technical field [0001] The invention relates to a pharmaceutical preparation for injection in the vitreous cavity of the eye, in particular to a sustained-release drug for sodium foscarnet in the vitreous cavity of the eye for injection with a 33G needle. Background technique [0002] Acute retinal necrosis is a severe eye disease caused by herpes virus infection. After the onset, symptoms such as moderate or greater vitreous opacity, extensive retinal necrosis, retinal thinning, multiple holes, and optic atrophy may appear. Herpes viruses associated with the development of acute retinal necrosis include varicella-zoster virus, herpes simplex virus type I, and type II virus, as well as cytomegalovirus and Epstein-Barr virus. The treatment of acute retinal necrosis requires long-term use of one or more antiviral drugs, with many side effects. [0003] Sodium foscarnet is an organic analogue of inorganic pyrophosphate, without affecting the concentration of cellular DNA polym...

Claims

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Application Information

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IPC IPC(8): A61K47/34A61K47/42A61K31/662A61K9/00A61P9/10A61P31/22
Inventor 陈豪王斌吴祥根鲁晓晴华晓敏
Owner QINGDAO UNIV
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