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Bone level targeting-ultrasonic triggering type drug delivery system, preparation method and application

A delivery system and trigger-based technology, which is applied in the fields of pharmaceutical formulations, drug combinations, bone diseases, etc., can solve the problems of reducing the bioavailability of drugs at the injury site, lack of targeting, and low concentration of drug distribution in bone tissue, so as to improve drug delivery. Effects of enrichment concentration and drug bioavailability, improvement of drug stability, and reduction of normal tissue toxicity

Active Publication Date: 2022-01-25
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these artificial delivery systems lack targeting, and there are problems of liver accumulation and reticular endothelial system (Reticular endothelial system, RES) clearance, resulting in low concentration of drug distribution in bone tissue, through the liposome surface PEG, bone tissue and OB targeting molecular modification, bone targeting molecules include bisphosphonates, tetracycline, repetitive polypeptide sequences Asp8 and (DSS)6, single-chain small Nucleic acid aptamer CH6 can effectively improve the effective enrichment of drugs in bone tissue and OB
However, fractures and bone defect-related bone diseases caused by OP occur in fractures and bone defects. Existing drugs that target bone tissue or OB molecules distribute drugs throughout the body's bones and OBs, greatly reducing the bioactivity of drugs at the damaged site. Utilization, reducing the therapeutic effect, making the drug used in high doses, there is also potential systemic toxicity

Method used

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  • Bone level targeting-ultrasonic triggering type drug delivery system, preparation method and application
  • Bone level targeting-ultrasonic triggering type drug delivery system, preparation method and application
  • Bone level targeting-ultrasonic triggering type drug delivery system, preparation method and application

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Embodiment 1

[0040] Such as figure 1 As shown, the bone level targeting-ultrasound-triggered drug delivery system provided by the embodiment of the present invention includes an external level bone tissue targeting-ultrasound-triggered liposome and an internal level two osteoblast-targeted drug-loaded liposome , the external primary bone tissue targeting-ultrasound-triggered liposomes and the internal secondary osteoblast targeting drug-loaded liposomes are both amphiphilic phospholipid molecules with a hydrophilic shell and core and hydrophobic A liposome with a double-layer structure, the inner secondary osteoblast-targeted drug-loaded liposome is encapsulated in the hydrophilic inner core of the outer primary bone tissue-targeted-ultrasound-triggered liposome;

[0041] The outer first-level bone tissue targeting-ultrasound-triggered liposome and the inner second-level osteoblast-targeting drug-loaded liposome are respectively connected with a first-level bone tissue-targeting molecule a...

Embodiment 2

[0051] The bone-level targeted-ultrasound-triggered drug delivery system and its preparation method provided in the embodiment of the present invention are the same as those in the embodiment 1, the only difference is that step S1 is different, and the specific operation process of step S1 in the embodiment of the present invention is as follows:

[0052] S1. Combine 244.4mg of Chol-PEG-Mal with 92.85mg of (DSS) 6 Dissolve in 10ml of N,N-dimethylformamide (DMF), pass through argon, stir at room temperature for 24h, use high performance liquid phase to monitor the reaction process, and wait for (DSS) 6 After the reaction is complete, use a dialysis bag (the molecular weight of the dialysis bag is 3000Da) to remove the unreacted cholesterol-PEG-Mal by dialysis, use a freeze dryer to dry the obtained reaction end product, and perform nuclear magnetic resonance and infrared spectrum detection on it to further determine The synthesized product is the target product, and the sample ...

Embodiment 3

[0054] The bone-level targeted-ultrasound-triggered drug delivery system and its preparation method provided in the embodiment of the present invention are the same as those in the embodiment 1, the only difference is that step S1 is different, and the specific operation process of step S1 in the embodiment of the present invention is as follows:

[0055] Combine 366.6mg of Chol-PEG-Mal with 92.85mg of (DSS) 6Dissolve in 10ml of N,N-dimethylformamide (DMF), pass through argon, stir at room temperature for 24h, use high performance liquid phase to monitor the reaction process, and wait for (DSS) 6 After the reaction is complete, use a dialysis bag (the molecular weight of the dialysis bag is 3000Da) to remove the unreacted cholesterol-PEG-Mal by dialysis, use a freeze dryer to dry the obtained reaction end product, and perform nuclear magnetic resonance and infrared spectrum detection on it to further determine The synthesized product is the target product, and the sample is st...

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Abstract

The invention discloses a bone level targeting-ultrasonic triggering type drug delivery system which comprises an external first-level bone tissue targeting-ultrasonic triggering type liposome and an internal second-level osteoblast targeting drug-loading liposome, the internal second-level osteoblast targeting drug-loading liposome is entrapped in the hydrophilic core of the external first-level bone tissue targeting-ultrasonic triggering type liposome. The drug delivery system disclosed by the invention is obtained by respectively preparing a bone tissue targeting-ultrasonic triggering liposome and an osteoblast targeting drug-loading liposome and then fusing the two liposome. The drug delivery system disclosed by the invention can be used for accurately and controllably releasing entrapped drugs to fracture and bone defect parts under the condition of osteoporosis (OP), so that the drug enrichment concentration and the drug bioavailability of the bone defect parts are improved, the toxicity of normal tissues is reduced, and the healing of the fracture and the bone defect under the condition of OP is effectively promoted.

Description

technical field [0001] The invention belongs to the technical field of drug delivery systems, and in particular relates to a bone-level targeting-ultrasound-triggered drug delivery system, a preparation method and an application. Background technique [0002] Osteoporosis (OP) is a systemic bone disease with abnormal bone metabolism. Abnormal metabolism leads to decreased osteogenic ability of osteoblasts (Osteoblast, OB), bone loss, decreased bone mass, damage to bone microarchitecture, and bone loss. Trabecular reduction and bone thinning lead to increased bone fragility and fractures are the most likely to occur. After fractures in OP patients, due to the reduced OB osteogenesis ability at the fracture site, the formation of new bone is delayed, and healing is delayed, or even nonunion, which is easy to be accompanied by bone defect. [0003] At present, clinical treatment methods are mainly surgical treatment and drug treatment. Surgical treatment mainly includes surgic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K9/127A61K47/28A61K47/24A61P19/08
CPCA61K45/06A61K9/1271A61K47/28A61K47/24A61P19/08A61K41/0028A61K47/6911A61K9/0009A61K9/19
Inventor 孔亮高晔蔡卜磊刘富伟李云鹏戴太强张凯王乐辛河侯燕靳丹吕前欣
Owner FOURTH MILITARY MEDICAL UNIVERSITY