Composite nanocapsule-injectable hydrogel double-drug-loading sustained release system and preparation method thereof

A dual drug-loading and nanocapsule technology, applied in the field of biomedicine, can solve the problems of short biological half-life and low image contrast of ultrasound imaging, and achieve the effects of controlling drug release, improving contrast, and prolonging drug action time.

Inactive Publication Date: 2017-12-22
SHANGHAI JIAO TONG UNIV +1
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0007] In view of the above-mentioned defects of the prior art, the purpose of the present invention is to address the deficiencies of the prior art and the demand for sustained release of drugs, to solve the problem of the short biological half-life of existing local anesthetics and nerve repair drugs, and the problems of ultrasound imaging in ultrasound contrast agents. Issues such as low contrast

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  • Composite nanocapsule-injectable hydrogel double-drug-loading sustained release system and preparation method thereof

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preparation example Construction

[0063] The invention provides a preparation method of a composite nanocapsule-injectable hydrogel dual drug-loaded slow-release system, comprising the following steps:

[0064] Step 1, preparing a composite nanocapsule encapsulating the drug;

[0065] Step 2, add an equal volume of crosslinking agent aqueous solution with a weight percentage of 0.2 wt% to 10 wt% to the high molecular polymer aqueous solution with a weight percentage of 4wt% to 20wt%, and stir at 20°C to 50°C After uniformity, let it stand for 4 to 20 hours to obtain an injectable hydrogel;

[0066] Step 3. Mix the composite nanocapsule obtained in step 1 and the injectable hydrogel obtained in step 2 according to the weight-to-volume ratio of 1:3 to 1:5 to obtain a composite nanocapsule-injectable hydrogel dual drug-loaded buffer interpretation system;

[0067] Wherein, in the step 2, the crosslinking agent is 1,4-butanediol diepoxy ether and glutaraldehyde.

[0068] In a preferred embodiment of the present...

Embodiment 1

[0092] Embodiment 1, the preparation of composite nanocapsule

[0093]Mix 1ml lidocaine hydrochloride injection with 5ml polylactic acid-polyethylene glycol polymer (PLA-MPEG) in dichloromethane solution, wherein the molecular weight of PLA-MPEG polymer is 20000, m(MPEG):m(PLA )=1:3, the concentration of lidocaine hydrochloride injection is 20mg / ml, the concentration of polylactic acid-polyethylene glycol is 25mg / ml, the power of 150W is used for ultrasonic emulsification for 30s, and then polyvinyl alcohol with a mass fraction of 4% is added Aqueous solution 10ml, use the power of 90W for the second ultrasonic emulsification for 30s. Then add 20 ml of polyvinyl alcohol aqueous solution with a mass fraction of 0.1%, and stir magnetically at room temperature for 6 hours. After the methylene chloride is completely volatilized, centrifuge the obtained water / oil / water emulsion at a rate of 12,000 rpm for 20 minutes, and repeat washing-ultrasonic dispersion-centrifugation The proc...

Embodiment 2

[0095] Embodiment 2, the preparation of composite nanocapsule

[0096] Mix 1ml of procaine hydrochloride injection with 5ml of poly(lactic-co-glycolic acid)-polyethylene glycol polymer (PLGA-PEG) in dichloromethane, wherein the molecular weight of PLGA-MPEG polymer is 20000, LA:GA =50:50, m(MPEG):m(PLA)=1:3, the concentration of procaine hydrochloride injection is 5mg / ml, the concentration of PLGA-PEG is 50mg / ml, and the power of 150W is used for phacoemulsification for 30s, Then add 20ml of polyvinyl alcohol aqueous solution with a mass fraction of 1%, and use 90W power for the second ultrasonic emulsification for 30s. Then add 20 ml of polyvinyl alcohol aqueous solution with a mass fraction of 0.1%, and stir magnetically at room temperature for 6 hours. After the methylene chloride is completely volatilized, centrifuge the obtained water / oil / water emulsion at a rate of 12,000 rpm for 20 minutes, and repeat washing-ultrasonic dispersion-centrifugation The process was perform...

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Abstract

The invention discloses a composite nanocapsule-injectable hydrogel double-drug-loading sustained release system, comprising a nanocapsule used for encapsulating a drug, and injectable hydrogel, wherein the average particle size of the nanocapsule is 100nm-1000nm, and the weight volume ratio of the composite nanocapsule to the injectable hydrogel is (1 to 1) to (1 to 10); the injectable hydrogel is prepared from a high molecular polymer and a crosslinking agent; the nanocapsule is prepared from a high molecular base material; a local anesthetic, a nerve repair drug or a contrast medium can be encapsulated in the nanocapsule, so that the effect of slowly releasing the drug is achieved; injectable hydrogel matrix in the double-drug-loading sustained release system can be used for locating a nanocapsule carrier in a human body, so that the whole drug sustained release system is fixed at the site of lesion, and the long-term slow release treatment for the site of lesion is facilitated. The composite nanocapsule-injectable hydrogel double-drug-loading sustained release system has good application prospects in the fields such as analgesia, tumor therapy, local anaesthesia and nerve repair which need local long-term drug slow release.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a composite nanocapsule-injectable hydrogel dual drug-loaded slow-release system and its preparation method and application. Background technique [0002] With the development of medical technology, there is an increasing demand for local anesthetics and nerve repairing drugs. Due to the short biological half-life of some local anesthetics or nerve repairing drugs, they need to be administered in small doses frequently in clinical use. Maintain its drug effect, bring bigger misery and inconvenience to the patient. Ultrasound imaging, as a non-toxic, safe and economical medical imaging technology, has been widely used in medical testing, but some ultrasonic contrast agents currently used still have the disadvantage of low contrast in the image of ultrasound imaging. Therefore, research and improvement Immobilization and sustained release of local anesthetics or nerve repair drugs with ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/52A61K9/51A61K9/06A61K47/34A61K47/36A61K47/42A61K47/32A61K45/06A61P23/02A61P25/28A61K49/22A61K49/12A61K49/18A61K49/04
CPCA61K9/0019A61K9/06A61K9/5153A61K9/5161A61K9/5169A61K45/06A61K47/32A61K47/34A61K47/36A61K47/42A61K49/04A61K49/126A61K49/14A61K49/1803A61K49/1857A61K49/221A61K49/225A61K49/226
Inventor 窦红静贵苑郑拥军王华
Owner SHANGHAI JIAO TONG UNIV
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