Drug carrier with bone targeting as well as preparation method and application thereof

A bone-targeted and targeted technology, applied in the direction of medical preparations with non-active ingredients, medical preparations containing active ingredients, drug combinations, etc., can solve the problem of drug transport to the whole body or excessive metabolism, systemic blood drug concentration High, slow drug onset and other issues, to achieve the effect of improving hydrophilicity, increasing yield, and ensuring singleness

Inactive Publication Date: 2020-02-07
SOUTHWEST JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The existing small-molecule hydrophobic antibacterial drugs that can treat bone diseases, such as norfloxacin, etc., in the treatment of bone diseases, oral antibacterial drugs, the drug has a slow onset and causes a series of problems such as high blood drug concentration in the whole body, especially Direct medication to the wound during surgery will cause the drug to be transported to the whole body with body fluids or metabolized too quickly. Although this type of drug can have a good therapeutic effect on many bone diseases, such as bone infection, but due to its hydrophobic characteristics, it is difficult to apply it in the treatment of bone diseases, so there is a need for a bone-targeted drug carrier that can improve the solubility of such hydrophobic small molecule drugs and accurately transport them to bone lesions for bone disease treatment

Method used

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  • Drug carrier with bone targeting as well as preparation method and application thereof
  • Drug carrier with bone targeting as well as preparation method and application thereof
  • Drug carrier with bone targeting as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] This embodiment provides a drug carrier with bone targeting, including β-cyclodextrin as the main body of the drug, and aspartic acid hexapeptide as the target with bone targeting; the aspartic acid hexapeptide The peptide is linked to β-cyclodextrin via a flexible chain.

[0046] Wherein, the β-cyclodextrin is only connected with one aspartic acid hexapeptide through a flexible chain; the flexible chain is polyethylene glycol.

[0047] The preparation method of the bone targeting drug carrier comprises the following steps:

[0048] (1) Dissolve 1.5 mM modified β-cyclodextrin (β-CD) containing an amino group in PBS buffer, and protect it with argon for 30 minutes;

[0049] (2) Then add 1 mM polyethylene glycol (NHS-mPEG-MAL) solution with maleimide at one end and succinimide at the other end dropwise, and after stirring at room temperature for 1 hour, add 1 mM modified solution with sulfhydryl group at one end dropwise. Aspartic acid hexapeptide (D6), stirred overnigh...

Embodiment 2

[0053] In this example, a quantitative experiment of HA tablets was carried out on the drug carrier (β-CD-mPEG-D6) prepared in the above examples.

[0054] The specific experimental process is as follows:

[0055] 1. Make the standard curve of CD-D6: prepare a CD-D6 sample with a concentration of 1mg / mL, and after serially diluting it, use a microplate reader to scan the full spectrum of the CD-D6 sample to obtain the maximum absorption of CD-D6 The wavelength is 220nm; set the wavelength of the microplate reader to 220nm, detect the OD value of the CD-D6 sample after gradient dilution, and make a standard curve of CD-D6, such as figure 1 shown.

[0056] 2. Quantitative adsorption experiment of HA: put the HA disc in the orifice plate, take 1mL CD-D6 sample with a concentration of 1mg / mL on the HA disc with a pipette gun, and place it in a refrigerator at 4°C for 24h, take 100 μL of liquid is used for OD value detection at a wavelength of 220 nm. Using the CD-D6 standard cu...

Embodiment 3

[0059] In this example, an in vitro hydroxyapatite adsorption experiment was performed on the drug carrier (β-CD-mPEG-D6) prepared in the above example.

[0060] Experimental principle:

[0061] In order to make β-cyclodextrin have a fluorescent effect, β-cyclodextrin is used to wrap amantadine labeled with the fluorescent marker FICT. Cavities combine and proportion to match the best substances. Then, FITC was used to label ADA, and then a fluorescence microscope could be used to observe whether the drug carrier interacted with HA.

[0062] The specific experimental process is as follows:

[0063] 1. Use FITC to mark ADA:

[0064] 5mgAd-NH 2 , 1.6mg F-NHS, 1m1 anhydrous DMSO, 50μL anhydrous DIPEA were added to a 1.5ml glass bottle, shake overnight at 25°C, 700rpm, in the dark. The product was separated and purified by high-performance liquid chromatography (HPLC) and then dried with a freeze-concentrated centrifugal dryer;

[0065] 2. Load F-Ada into β-CD and CD-D6 resp...

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Abstract

The invention discloses a drug carrier with bone targeting. The drug carrier comprises beta-cyclodextrin serving as an entrapment drug main body and aspartic acid hexapeptide serving as a target and with bone targeting, wherein the aspartic acid hexapeptide is connected with the beta-cyclodextrin through a flexible chain. The preparation method comprises the following steps: 1) dissolving beta-CDin PBS, performing argon deoxygenation protection for 30 min, dropwise adding the flexible chain into a beta-CD solution, stirring the materials at room temperature for 1 h, dropwise adding a D6 solution into the solution, stirring at room temperature overnight, collecting a product, dialyzing the material for 3 days, and freeze-drying to obtain solid powder. The drug carrier can be used for loading hydrophobic antibacterial small molecular drugs which are difficult to encapsulate, has bone targeting performance, and can be prepared into a bone targeting drug, the drug can increase the hydrophilicity of a hydrophobic antibacterial small molecule drug, the antibacterial property of the hydrophobic antibacterial small molecule drug can be completely provided, and bone diseases such as bone infection and the like can be efficiently and accurately treated.

Description

technical field [0001] The invention relates to the technical field of targeted drug carriers, in particular to a bone-targeted drug carrier and its preparation method and application. Background technique [0002] The incidence of bone disease is increasing day by day, and it is highly valued by people. The bone diseases mainly include osteoporosis, osteitis deformans, bone metastases, primary and secondary bone tumors, and osteoarthritis. The main component of bone tissue is hydroxyapatite. Most of the calcium in the human body exists in the bones, accounting for about 99% of the total calcium. Therefore, bone tissue has biological characteristics, such as low blood flow, high density, and poor permeability, which bring great difficulties to clinical application. With the traditional way of administration, it is difficult for the drug to reach the lesion in an ideal state. Low curative effect and large adverse reactions are common shortcomings of bone disease drugs. To ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/60A61K47/62A61K31/496A61K31/546A61K31/635A61K31/505A61K31/407A61P19/10A61P35/00A61P35/04A61P19/02A61P19/08A61P31/04
CPCA61K31/407A61K31/496A61K31/505A61K31/546A61K31/635A61K47/60A61K47/62A61K47/6951A61P19/02A61P19/08A61P19/10A61P31/04A61P35/00A61P35/04
Inventor 陈星羽孙彤翁杰
Owner SOUTHWEST JIAOTONG UNIV
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