Drug-loaded emulsion

Abstract

The present invention relates to a drug-loaded emulsion, comprising a modified hydrophobic excipient having the following formula, a hydrophobic drug and a surfactant:where R is a hydrophobic natural compound or a hydrophobic synthetic compound with one to three hydroxyl groups (n=1-3); and R1 is an α-amino protecting group, and R2 is an amino acid side chain, wherein, when m=0, R is reacted with an amino acid derivative with a protecting group by esterification to form a hydrophobic excipient carrying the amino acid derivative with a protecting group; or when m=1, R is firstly introduced with an amino acid linking arm of different chain lengths (l=1, 2, 4, 6) via an ester group, and then introduced with an amino acid derivative with a protecting group.

What is claimed is: 
     
         1 . A drug-loaded emulsion, comprising a modified hydrophobic excipient having the following formula, a hydrophobic drug and a surfactant: 
       
         
           
           
               
               
           
         
         where R is a hydrophobic natural compound or a hydrophobic synthetic compound with one to three hydroxyl groups (n=1-3); and R1 is an α-amino protecting group, and R2 is an amino acid side chain, wherein, when m=0, R is reacted with an amino acid derivative with a protecting group by esterification to form a hydrophobic excipient carrying the amino acid derivative with a protecting group; or when m=1, R is firstly introduced with an amino acid linking arm of different chain lengths (l=1, 2, 4, 6) via an ester group, and then introduced with an amino acid derivative with a protecting group. 
       
     
     
         2 . The drug-loaded emulsion according to  claim 1 , wherein the modified hydrophobic excipient is protected amino acid ester of the hydrophobic excipient or protected amino acid amide of the hydrophobic excipient amino acid ester. 
     
     
         3 . The drug-loaded emulsion according to  claim 1 , wherein the hydrophobic drug is a hydrophobic drug capable of having an intermolecular interaction, including aromatic ring stacking, hydrogen bond or hydrophobic interaction, with the modified hydrophobic excipients, such as paclitaxel and docetaxel. 
     
     
         4 . The drug-loaded emulsion according to  claim 1 , wherein a ratio of the hydrophobic drug to the modified hydrophobic excipient is 0.01% (w/w)-99.9% (w/w) to 99.9% (w/w)-0.01(w/w), preferably 1% (w/w)-50% (w/w) to 99% (w/w)-50(w/w), and more preferably 1:1 to 1:5. 
     
     
         5 . The drug-loaded emulsion according to  claim 1 , wherein the surfactant is a pharmaceutical surfactant excipient having a hydrophilic-lipophilic balance (HLB) value in the range of 0 to 40. 
     
     
         6 . The drug-loaded emulsion according to  claim 1 , wherein the surfactant is a small molecule or large molecule pharmaceutical excipient with a function of solubilizing or emulsifying or wetting or foaming agent or defoaming agent or detergent. 
     
     
         7 . The drug-loaded emulsion according to  claim 1 , wherein the surfactant is a small molecule or large molecule pharmaceutical excipient with a function of stabilizing a nanometer structure. 
     
     
         8 . The drug-loaded emulsion according to  claim 1 , wherein the surfactant is a cationic or anionic or nonionic surfactant. 
     
     
         9 . The drug-loaded emulsion according to  claim 1 , wherein the surfactant is phospholipid or cholesterol, or fatty acid with the chain length of C8-C22, or fatty acid salt with the chain length of C8-C22, sucrose fatty acid ester, sorbitan fatty acid (spans), polysorbate (Tweens) polyoxyethylene fatty acid ester (Myrij), polyoxyethylene fatty alcohol ether, or PEG-cholesterol derivative with different chain lengths, PEG-vitamin E succinate with different chain lengths, or PEG-phospholipid derivative with different chain lengths, or PEG-diglyceride derivative with different chain lengths, or any natural polymer pharmaceutical excipient or synthetic polymer pharmaceutical excipient with surface activity. 
     
     
         10 . The drug-loaded emulsion according to  claim 1 , wherein the surfactant phospholipid is any one selected from a group consisting of phosphatidylcholine (PC), Phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylinositol (PI), eggphosphatidylcholine (EPC), egg phosphatidylglycerol (EPG), phosphatidylethanolamine (EPE), eggphosphatidylserine (EPS), egg phosphatidic acid (EPA), (egg phosphatidylinositol (EPI), soy phosphatidylcholine (SPC), soy phosphatidylglycerol (SPG), soyphosphatidylethanolamine (SPE), soy phosphatidylserine (SPS), (soy phosphatidic acid SPA), soy phosphatidylinositol (SPI), dipalmitoylphosphatidylcholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylglycerol (DPPG), dioleoylphosphatidylglycerol (DOPG), dimyristoylphosphatidylglycerol (DMPG), hexadecylphosphocholine (HEPC), hydrogenated soyphosphatidylcholine (HSPC), distearoylphosphatidylcholine (DSPC), distearoylphosphatidylglycerol (DSPG), dioleoylphosphatidylethanolamine (DSPE), palmitoylstearoylphosphatidylcholine (PSPC), palmitoylstearoylphosphatidylglycerol (PSPG), monooleoylphosphatidylethanolamine (MOPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC), distearoylphosphatidylethanolamine (DSPE), dipalmitoylphosphatidylserine (DPPS), 1,2-dioleoyl-sn-glycero-3-phosphatidylserine (DOPS), dimyristoylphosphatidylserine (DMPS), distearoylphosphatidylserine (DSPS), dipalmitoylphosphatidicacid (DPPA), 1,2-dioleoyl-snglycero-3-phosphatidic acid (DOPA), dimyristoylphosphatidic acid (DMPA), distearoylphosphatidic acid (DSPA), dipalmitoylphosphatidylinositol (DPPI), 1,2-dioleoylsn-glycero-3-phosphatidylinositol (DOPI), dimyristoylphosphatidylinositol (DMPI), distearoylphosphatidylinositol (DSPI), and a mixture thereof. 
     
     
         11 . The drug-loaded emulsion according to  claim 10 , wherein the polyethylene glycol (PEG) with different chain lengths-the lipid derivative with the chain length of C8-C22 is a surfactant formed by connecting PEG with the chain length of 1-1000 repeating units and lipid with the chain length of C8-C22 by an ester bond or an ether bond or an amide bond. 
     
     
         12 . The drug-loaded emulsion according to  claim 11 , wherein the PEG-phospholipid derivative with different chain lengths is a surfactant formed by connecting PEG with a chain length of 1-1000 repeating units and natural or synthetic phospholipid by an ester bond, an amide bond or a carbamoyl bond. 
     
     
         13 . The drug-loaded emulsion according to  claim 11 , wherein, in a surfactant of the PEG-phospholipid derivative with different chain length prepared by connecting PEG with a chain length of 1-1000 repeating units with a natural or synthetic phospholipid by an ester bond or an amide bond or a carbamoyl bond, the natural or synthetic phospholipids is a natural or synthetic phospholipid with a carbon chain length of 12-22. 
     
     
         14 . The drug-loaded emulsion according to  claim 11 , wherein, in a surfactant of the PEG-phospholipid derivative with different chain lengths prepared by connecting PEG with the chain length of 1-1000 repeating units with a natural or synthetic phospholipid by an ester bond or an amide bond or a carbamoyl bond, the natural or synthetic phospholipid is a natural or synthetic phospholipid having a saturated or unsaturated lipid chain with a carbon chain length of 12-22. 
     
     
         15 . The drug-loaded emulsion according to  claim 11 , wherein, in a surfactant of the PEG-phospholipid derivative with different chain lengths prepared by connecting PEG with the chain length of 1-1000 repeating units with a natural or synthetic phospholipid by an ester bond or an amide bond or a carbamoyl bond, the natural or synthetic phospholipid is natural or synthetic cephalin. 
     
     
         16 . The drug-loaded emulsion according to  claim 1 , wherein the natural polymer pharmaceutical excipient or synthetic polymer pharmaceutical excipient surfactant is a polysaccharide or polysaccharide derivative or polyoxyethylene-polyoxypropylene (poloxamer) or protein with surface activity. 
     
     
         17 . The drug-loaded emulsion according to  claim 1 , wherein the pharmaceutical excipient surfactant is a single pharmaceutical excipient or a combination of multiple pharmaceutical excipient surfactants. 
     
     
         18 . The drug-loaded emulsion according to  claim 1 , wherein the surfactant is lecithin or cholesterol or PEG-phospholipid derivative single pharmaceutical excipient or a combination of multiple pharmaceutical excipient surfactants. 
     
     
         19 . The drug-loaded emulsion according to  claim 1 , wherein the surfactant is a combination of lecithin and PEG-cephalin derivative. 
     
     
         20 . The drug-loaded emulsion according to  claim 1 , wherein a ratio of the hydrophobic excipient-the hydrophobic drug to the surfactant is (X+Y):Z, and Z %=100−(X+Y). 
     
     
         21 . The drug-loaded emulsion according to  claim 20 , wherein a ratio of the hydrophobic excipient-the hydrophobic drug to the surfactant is (X+Y):Z=(0-50%):(100-50%).