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mof materials, nano drug-loaded materials, pharmaceutical compositions and their applications

A nano-drug-carrying and composition technology is applied in the fields of nano-drug-carrying materials, MOF materials, ionizing radiation damage protection, and pharmaceutical compositions. effect of drug administration

Active Publication Date: 2021-09-17
INST OF RADIATION MEDICINE CHINESE ACADEMY OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Amifostine is the only chemical drug with radiation protection effect approved by the FDA, but its effective time is short, it cannot be taken orally and can only be used by injection
Poor effect when taken orally (N.P.Praetorius, T.K.Mandal, J.Pharm.Pharmacol.60(2008) 809-815)

Method used

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  • mof materials, nano drug-loaded materials, pharmaceutical compositions and their applications
  • mof materials, nano drug-loaded materials, pharmaceutical compositions and their applications
  • mof materials, nano drug-loaded materials, pharmaceutical compositions and their applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 MOF material

[0047] Such as figure 1 As shown, the MOF material provided in this example includes a metal organic framework and a modified ligand, wherein the organic framework is Fe 3 Cl(H 2 O) 2 O[(O 2 C)-C 6 h 4 -(CO 2 )] 3 It is abbreviated as MIL-101. The modified ligand contains an alkynyl group and a benzoic acid group, and the benzoic acid group of the modified ligand coordinates with the iron in the metal organic framework.

[0048] The preparation method of the MOF material includes adding iron trichloride, terephthalic acid, and a modified ligand into dimethylformamide for dissolution. The modifying ligand in this embodiment may be benzoic acid containing an alkynyl group, and the molar ratio of ferric chloride: terephthalic acid: modifying ligand is 1:1:0.5-10. The molar ratio of iron trichloride: terephthalic acid: modifying ligand in the specific examples is shown in Table 1 below.

[0049] Iron trichloride in each example of table 1:...

Embodiment 2

[0054] Embodiment 2 Nano drug-loaded material

[0055] The nano drug-loaded material in this example is MIL-101-PEG, which is obtained by modifying the MIL-101-L prepared in Example A of Example 1 with PEG. The schematic diagram of the structure of MIL-101-PEG is shown in figure 2 shown. In this example, the molecule containing PEG is N 3 - PEG-OH, other molecules containing PEG groups and azide groups can also be selected. The molecular weight of the PEG group is 500Da-20000Da. Preferably, the molecular weight of PEG is 500Da~10000Da, for example, the molecular weight of PEG group is 500Da, 800Da, 1000Da, 1500Da, 2000Da, 2500Da, 3000Da, 3500Da, 4000Da, 4500Da, 5000Da, 6000Da, 7000Da, 8000Da, 9000Da or 10000Da etc. . In this embodiment, PEG2000 and PEG10000 are taken as examples for illustration, and their synthesis processes can be found in Figure 4 The second step in the synthesis process.

[0056] Case 1: Preparation of MIL-101-PEG2000

[0057] MIL-101-L (0.20 g) ...

Embodiment 3

[0060] Example 3 MOF loading drug

[0061] The MIL-101-PEG prepared in Example 2 above can be combined with various biologically active molecules to form MOF-loaded drugs for radiation protection. In the following, only amifostine (Am) and its metabolite WR-1065 are used as examples for illustration.

[0062] The synthetic process of pharmaceutical compounds can be found in Figure 4 The third step of the synthetic process is shown. Wherein, R represents the small molecule radioprotectant amifostine or its metabolite WR-1065.

[0063] MOF loaded drug 1: Synthesis of WR1065@MIL-101-PEG2000

[0064] MIL-101-PEG2000 (200 mg) prepared in Case 1 of Example 2, WR-1065 (1.0 g), and methanol (20 ml) were added to a round bottom flask, and stirred at room temperature for 24 hours under nitrogen protection. The supernatant was discarded by centrifugation at 800 rpm for 30 minutes, and the obtained solid was vacuum-dried. The obtained brown solid (312 mg) is WR1065@MIL-101-PEG2000, ...

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Abstract

The invention provides a kind of MOF material, is characterized in that, comprises metal-organic framework and modification ligand, and described metal-organic framework is Fe 3 Cl(H 2 O) 2 O[(O 2 C)‑C 6 h 4 -(CO 2 )] 3 , the modified ligand contains an alkynyl group and a benzoic acid group, and the carboxyl group of the modified ligand coordinates with the iron in the metal organic framework. The MOF material provided by the present invention has at least one of the following advantages: the MOF material provided by the present invention can be used to prepare nano drug-loaded materials, which can stabilize drug molecules and realize oral administration through the encapsulation of metal organic framework structures.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the protection of ionizing radiation damage, and in particular to MOF materials, nanometer drug-loaded materials, pharmaceutical compositions and applications thereof. Background technique [0002] Radiation damage is tissue damage caused by ionizing radiation (IR), which usually occurs in nuclear leak accidents, radioactive source loss accidents, and radiotherapy for tumor patients. Instantaneous exposure to high-dose rays or prolonged exposure to low-dose rays can cause tissue damage. Ionizing radiation can generate reactive oxygen species (ROS) free radicals in tissues and cells, interfere with DNA, protein and other macromolecules, induce cell damage and abnormal cell function, and eventually lead to functional disorders and pathological changes in various organs of the body Even cause the body to die. Many biological and chemical drugs can prevent radiation damage, but few drugs...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08G83/00C08G81/00A61K31/661A61K31/145A61P17/16A61P7/00A61K47/24
CPCA61K31/145A61K31/661A61K47/24A61P7/00A61P17/16C08G81/00C08G83/008
Inventor 曹健李雪娇田红旗
Owner INST OF RADIATION MEDICINE CHINESE ACADEMY OF MEDICAL SCI
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