Targeted nano-preparation modified by mannose

A nano-formulation, mannose technology, applied in the field of medicine, can solve the problems of large particle size of liposomes, difficult to control conditions, and inability to guarantee the exposure of mannose, and achieve precise targeted therapy and good tumor targeting. Effect

Pending Publication Date: 2019-12-03
CHENGDU RIBOCURE PHARMATECH CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Synthesized by Liu Ran et al. (Liu R, Li H, Gao X, et al.mannose-conjugated platinum complexes reveals effective tumor targeting mediated by glucose transporter[J].Biochem Biophys Res Commun,2017,487(1):34-40.) discovered a mannose-modified platinum complex, and found that it has a stronger inhibitory effect on human colon cancer cells (HT29), and can prolong the lifespan of leukemia mice, but the complex has obvious toxicity when administered in a large amount. And the complex is at a relative disadvantage in its internal circulation due to the absence of a long linker (such as a PEG chain) connection
Zeng Junfen et al. (Zeng Junfen, Huang Ling, Lu Jianwu, et al. Preparation of lung-targeted hydroxycamptothecin liposome and its tissue distribution in mice [J]. Journal of National Hospital Pharmacy, 2016, 36(16 ): 1374-1379.) D-mannose and octadecylamine were added during the preparation of liposomes to obtain lung-targeted hydroxycamptothecin liposomes, although the results showed that the residence time in the lungs was longer than that of ordinary injections Significantly prolonged, its relative uptake rate is 60.72, lung targeting efficiency is 17.57, and it has a certain lung targeting effect, but this method cannot guarantee that mannose must be exposed to the receptors to achieve the targeting effect, and its liposome preparation The process is cumbersome, the conditions are not easy to control, the particle size of the prepared liposome is too large, and the properties of the f

Method used

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  • Targeted nano-preparation modified by mannose

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Experimental program
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Effect test

Embodiment 1

[0083] The synthesis of embodiment 1 carrier material

[0084] Mannose-PEG n -Chol: Taking the synthesis of mannose-PEG100-Chol as an example, other PEGs of different lengths are also synthesized according to this synthesis route. Take diethylene glycol, p-toluenesulfonyl chloride and triethylamine, dissolve in DCM, react at room temperature for 24 hours, and separate the product TosOC by silica gel column chromatography 2 h 4 OC 2 h 4 OH (Formula I). Take the compound of formula I with pentaacetylated mannose and boron trifluoride ether (BF 3 ·Et 2 O), be dissolved in DCM, room temperature reaction 24h, silica gel column chromatography separates and obtains product Aco-Mannose-OC 2 h 4 OC 2 h 4 OTos (Formula II). Take the compound of formula II and sodium azide, dissolve in DMF, react at 60°C for 24 hours, and separate by silica gel column chromatography to obtain the solid product Aco-Mannose-OC 2 h 4 OC 2 h 4 N 3 (Formula III). Dissolve the compound of form...

Embodiment 2

[0089] The preparation of embodiment 2 liposomes

[0090] prescription composition

[0091]

[0092]

[0093] Note: The main drug of prescription 1 to prescription 5 is GFP-mRNA.

[0094] Preparation method 1: Take phospholipids in different weight ratios according to the above prescription (when the main drug is PTX, add them together with phospholipids), add them to a round bottom flask, add chloroform / ethanol=1:1 (v / v) to dissolve, The organic solvent was removed by rotary evaporation under reduced pressure, and a thin film was formed on the inner wall of the bottle. PBS7.4 buffer solution was added for hydration, and 100W ultrasonic wave was used for 3 minutes to obtain liposomes. When encapsulating pGFP, it can be obtained by incubating blank liposomes with pGFP at room temperature, and the nanoparticles obtained from mannose-PEG1000-Chol can be recorded as MP1000-LPX. The liposome obtained is characterized, and the result shows that the particle size of liposome ...

Embodiment 3

[0097] The preparation of embodiment 3 solid fat nanoparticles

[0098] Solid lipid nanoparticles are nanostructured carriers prepared from lipids as the skeleton material, and have the characteristics of physiological compatibility, cell affinity, and targeting. In this example, adding mannose-modified lipids improves the targeting of solid lipid nanoparticles.

[0099] prescription composition

[0100]

[0101]

[0102] Preparation method: Precisely weigh the prescribed amount of medicines and lipid materials, dissolve them in ethanol, stir in a constant temperature water bath to form an oil phase; weigh the prescribed amount of surfactants, dissolve them in pure water, and heat them in a constant temperature water bath to form a water phase; , inject the oil phase into the water phase, stir and emulsify and concentrate at a constant temperature. After the emulsion is concentrated to a certain volume, pour it into cold water at a constant temperature of 4°C, stir and ...

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Abstract

The invention relates to the technical field of medicine, in particular to a targeted nano-preparation modified by mannose and mannose derivatives. In order to solve technical problems, the mannose and the mannose derivatives are adopted to conduct nano-preparation modification to prepare the nano-preparation; and the prepared nano-preparation has improved targeting capability and can be applied to vaccine delivery, tumor-targeted therapies, arteriosclerosis therapies, and therapies of various inflammatory diseases and the like.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a targeted nano preparation modified with mannose. Background technique [0002] In recent years, drug receptor-mediated targeted drug delivery systems have been extensively studied. Targeted drug delivery systems can improve their specific targeting and overcome the problems of wide distribution of drugs in vivo and serious side effects. Among them, lectin receptors are a kind of glycoproteins, glycolipids or carbohydrate complexes distributed on the surface of cell membranes, which can specifically recognize and bind to some sugar groups. Mannose receptor is the most important high-efficiency endocytic lectin receptor. Its functions include clearing endogenous molecules, promoting antigen presentation, and regulating cell activation and trafficking. It is also closely related to immune escape and metastasis of tumors. It is mainly expressed in Macrophages, dendritic cells and tumor cel...

Claims

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Application Information

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IPC IPC(8): A61K47/26A61K47/10A61K47/54A61K47/60A61K39/00A61K48/00A61K31/704A61K31/352A61K31/337A61P35/00A61P9/10A61P29/00
CPCA61K47/26A61K47/10A61K47/549A61K47/60A61K39/00A61K48/005A61K31/704A61K31/352A61K31/337A61P35/00A61P9/10A61P29/00A61K9/127A61K47/6911A61K47/6917A61K47/6907A61K47/6929B82Y5/00A61K31/4745A61K31/475A61K31/7048A61K31/519A61K31/513A61K31/5377A61K31/17C12N15/88A61K48/0041A61K9/1271A61K47/34B82Y40/00
Inventor 宋相容魏于全
Owner CHENGDU RIBOCURE PHARMATECH CO LTD
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