Lipid construct for delivery of insulin to a mammal
A construct and insulin technology, applied in drug delivery, liposome delivery, drug combination, etc., can solve unmet problems
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[0154] In one embodiment, the amphiphilic lipid molecules include 1,2-distearoyl-sn-glyceryl-3-phosphocholine, cholesterol, cetyl phosphate, 1,2-dipalmitoyl-sn- Glyceryl-3-phosphoethanolamine-N-(Cap biotinyl); 1,2-Distearoyl-sn-glyceroyl-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glyceryl-3 -Phosphoethanolamine-N-(succinyl), 1,2-dipalmitoyl-sn-glyceryl-3-[phospho-rac-(1-glycerol)] (sodium salt), triethylammonium 2,3-di Acetoxypropyl 2-(5-((3aS,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)ethyl phosphate and any A mixture of the aforementioned lipids.
[0155] Extended amphiphilic lipid molecules, also known as receptor binding molecules, comprise a proximal portion, a middle portion and a distal portion. The proximal portion links the extended lipid molecule to the construct, and the distal portion targets the construct to receptors displayed by hepatocytes. The proximal and distal sections are connected by an intermediate section. The composition of variou...
experiment Embodiment 1
Experimental Example 1: Pharmaceutical Composition 1
[0298] Lipid constructs include lipids 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, cetyl phosphate, 1,2-distearoyl-sn-glyceryl-3 -Phosphoethanolamine, 1,2-dipalmitoyl-sn-glyceryl-3-phosphoethanolamine-N-(succinyl), 1,2-dipalmitoyl-sn-glyceroyl-3-[phospho-rac-( 1-glycerol)] (sodium salt), a mixture of the receptor binding molecule 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(Cap biotinyl), and insulin.
experiment Embodiment 2
Experimental Example 2: Pharmaceutical Composition 2
[0299]Lipid constructs include lipids 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, cetyl phosphate, 1,2-distearoyl-sn-glyceryl-3 -Phosphoethanolamine, 1,2-dipalmitoyl-sn-glyceryl-3-phosphoethanolamine-N-(succinyl), 1,2-dipalmitoyl-sn-glyceroyl-3-[phospho-rac-( 1-glycerol)] (sodium salt), insulin, receptor binding molecule 1,2-dipalmitoyl-sn-glyceryl-3-phosphoethanolamine-N-(Cap biotinyl), and / or polychromium-poly (two)-[N-(2,6-(diisopropylphenyl)carbamoylmethyl)imino]diacetic acid] mixture. Lipid-anchored hepatocyte receptor-binding molecules 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(Cap biotinyl) and polychromium-poly(di)-[N-(2 , 6-(diisopropylphenyl)carbamoylmethyl)iminodiacetic acid] was added to the lipid construct at levels of 1.68%±0.5% by weight and 1.2%±0.5% by weight, respectively.
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