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A nano drug delivery system loaded with 5-aminolevulinic acid and its preparation method and application

A technology of aminolevulinic acid and delivery system, which is applied in the field of nano drug delivery system loaded with 5-aminolevulinic acid and its preparation, which can solve the problems such as difficult to pass through the biofilm barrier, achieve convenient preparation and use, and reduce drug side effects Small, well-dispersed effect

Active Publication Date: 2021-03-30
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Based on this, the purpose of the present invention is to provide a nano-drug delivery system for the treatment of melanoma with synergistic 5-ALA, which overcomes the problem that the existing photosensitizer 5-ALA is difficult to penetrate the biofilm barrier, so as to induce tumor cells Production of PpIX reaches doses effective in killing tumor cells

Method used

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  • A nano drug delivery system loaded with 5-aminolevulinic acid and its preparation method and application
  • A nano drug delivery system loaded with 5-aminolevulinic acid and its preparation method and application
  • A nano drug delivery system loaded with 5-aminolevulinic acid and its preparation method and application

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preparation example Construction

[0022] The preparation method of the above-mentioned nano drug delivery system is as follows:

[0023] Dissolve CDG2 in water, slowly add the aqueous solution of 5-ALA, the molar ratio of CDG2 to 5-ALA is 1:(2~3), stir for 22~28h, and ultrafilter to obtain CDG2 / 5-ALA complex ; Slowly add the aqueous solution of hyaluronic acid to the aqueous solution of the CDG2 / 5-ALA complex, stir for 11 to 13 hours, and ultrafilter to obtain the product. Specifically, its preparation method includes: weighing 110-130 mg of CDG2, dissolving in water, slowly adding 150-170 mg of 5-ALA aqueous solution, stirring for 22-28 hours, ultrafiltration, and freeze-drying to obtain the CDG2 / 5-ALA complex ; Slowly add 110-120 mg of hyaluronic acid aqueous solution to the CDG2 / 5-ALA complex aqueous solution, stir for 11-13 hours, ultra-filter and freeze-dry to obtain. In some embodiments, the ultrafiltration is: ultrafiltration at 10000-14000 rpm for 18-22 minutes. Preferably, the ultrafiltration condit...

Embodiment 1

[0039] The preparation process of the nano drug delivery system CAH of the synergistic 5-ALA treatment of melanoma in this example is as follows figure 1 As shown, the nano-drug delivery system CAH-NH 2 with -COOH(M -NH2 / M -COOH ) molar ratio is 3:1, and its preparation method comprises the following steps:

[0040] (1) Preparation method of CDG2 / 5-ALA complex

[0041] Weigh 120 mg of a lyophilized sample of CDG2 purified by dialysis and dissolve it in 5 mL of ultrapure water. After it was completely dissolved, slowly add 160 mg of 5-ALA aqueous solution, wherein the molar ratio of 5-ALA carboxyl group to CDG2 amino group was 2:1, and stirred on a magnetic stirrer for 24 hours at room temperature and protected from light. The resulting reaction solution was ultrafiltered and centrifuged for 20 min at 12000 rpm, and freeze-dried to obtain the CDG2 / 5-ALA complex. The content of free 5-ALA not bound to CDG2 / 5-ALA in the supernatant was detected by ultraviolet light.

[0042...

Embodiment 2

[0045] A nano drug delivery system (CAH) for the treatment of melanoma with synergistic 5-ALA in this embodiment, the molar ratio of CAH (M-NH2 / M-COOH) is 2:1, and its preparation method includes the following steps:

[0046] (1) Preparation method of CDG2 / 5-ALA complex

[0047] Weigh 120 mg of a lyophilized sample of CDG2 purified by dialysis and dissolve it in 5 mL of ultrapure water. After it was completely dissolved, slowly add 160 mg of 5-ALA aqueous solution, wherein the molar ratio of 5-ALA carboxyl group to CDG2 amino group was 2:1, and stirred on a magnetic stirrer for 24 hours at room temperature and protected from light. The resulting reaction solution was ultrafiltered and centrifuged for 20 min at 12000 rpm, and freeze-dried to obtain the CDG2 / 5-ALA complex. The content of free 5-ALA not bound to CDG2 / 5-ALA in the supernatant was detected by ultraviolet light.

[0048] (2) Preparation of CAH

[0049] Dissolve the CDG2 / 5-ALA complex prepared above in 5mL ultrapur...

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Abstract

The invention provides a nanometer drug delivery system. The nanometer drug delivery system is characterized by being compounded from CDG2, 5-ALA and hyaluronic acid through electrostatic interaction,wherein the CDG2 is obtained through grafting PAMAM-G2 on the outside of alpha-cyclodextrin. The nanometer drug delivery system is easier to be subjected to pyrolysis to obtain separate 5-ALA in cells, besides, PpIX having photosensitization can be efficiently produced in a melanoma cell system, and apoptosis of tumor cells can be effectively induced; and the nanometer drug delivery system is convenient to prepare and use, has synergistic effect on treatment of melanoma through the 5-ALA, and is small in drug side effects.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a nano drug delivery system loaded with 5-aminolevulinic acid, its preparation method and application. Background technique [0002] Melanoma is a malignant tumor derived from skin melanocytes, which has the characteristics of easy metastasis, high invasion, poor prognosis and difficult treatment. In recent years, its new morbidity and mortality continue to rise, and once systemic metastasis occurs, the survival rate of patients within 10 years is only 10-15%. Melanoma is clinically divided into four stages. Stage I and II melanomas are in situ in the skin and can be treated by surgical resection. However, stage III and IV melanomas with lymphatic sinus and distant organ metastasis are advanced melanomas, which cannot be removed by surgery and require drug treatment. Melanoma drugs currently approved for treatment include the chemotherapy drug dacarbazine, small molecule tar...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/51A61K47/36A61K47/40A61K41/00A61P35/00
CPCA61K9/5161A61K41/0061A61P35/00
Inventor 冯敏利智王翠峰邓慧慧
Owner SUN YAT SEN UNIV
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