Pegylated 7-dehydrocholesterol derivative
A technology of PEGylation and dehydrocholesterol, applied in steroids, cosmetics, food science, etc., can solve the stagnation of 7-dehydrocholesterol research, structural denaturation, and no stability involved in the synthesis of 7-dehydrocholesterol sexual issues
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Publication Date
- 2016-11-30
- Estimated Expiration
- Not applicable · inactive patent
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Abstract
Description
technical field
[0001] The present invention relates to PEGylated 7-dehydrocholesterol derivatives (Pegylated 7-dehydrocholesterolderivatives). More particularly, the present invention relates to PEGylated 7-dehydrocholesterol derivatives which have improved stability and solubility and are hydrolyzed in vivo to provide vitamin D, and also relate to wrinkle reduction and anti-aging containing Compositions of said PEGylated 7-dehydrocholesterol derivatives. Background technique
[0002] There are two types of vitamin D, vitamin D 2 (calciferol) and vitamin D 3 (cholecalciferol, compound B), these two substances are metabolized in the liver and kidneys to their active form (calcitriol, compound C). 7-Dehydrocholesterol (7-DHC, Compound A) as Vitamin D 3 The provitamin form, which is converted to vitamin D by sunlight 3 .
[0003]
[0004] Usually, vitamin D 3 Promotes calcium absorption to strengthen bone density, so it is used as a treatment for osteoporosis and as ...
Examples
Embodiment 1
[0152] Example 1: Preparation of mPEG350-S-DHC ester (compound of formula (1A), wherein R is methyl, X is O, n is 7.25 (average value), and m is 1)
Embodiment 1-1
[0153] Example 1-1: Preparation of 7-dehydrocholesterol succinate (compound of formula (5), wherein m is 1)
[0154]Dissolve 7-dehydrocholesterol (DHC) (6.45g, 16.8mmol) (6.45g, 16.8mmol) of chemical formula (4) in 120ml dichloromethane, wherein add triethylamine (3.39g, 33.5mmol) and 4-dimethylaminopyridine (0.82g , 6.7mmol) to obtain a solution. Therein, succinic anhydride (compound of formula (3), wherein m is 1) (3.35 g, 33.5 mmol) was added, followed by stirring at room temperature for 12 hours. The reaction solution was washed successively with 3.5% HCl aqueous solution, saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueous solution. Then, the organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2) to obtain 7.2 g of the target compound.
[0155] 1 H NMR 400MHz (CDCl 3 )δ5.59(dd,1H),5.41(dd,1H),4.75...
Embodiment 1-2
[0156] Example 1-2: Preparation of mPEG350-S-DHC ester (compound of chemical formula (1A), wherein R is methyl, X is O, n is 7.25 (average value), and m is 1)
[0157] Dissolve the 7-dehydrocholesterol succinate of embodiment 1-1 (the compound of chemical formula (5), wherein m is 1) (1.1g, 2.30mmol) and mPEG350-OH (chemical formula (6) in 10ml of dichloromethane A compound wherein R is methyl, n is 7.25 (mean), and X is O) (0.8 g, 2.30 mmol), to which 4-dimethylaminopyridine (0.42 g, 3.44 mmol) was added. To this, N-(3-dimethylaminopropyl)-N'-ethyl-carbodiimide (0.88 g, 4.59 mmol) was slowly added, followed by stirring at room temperature for 12 hours. The reaction solution was washed successively with 1.0N aqueous HCl solution, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution. Then, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and dried under vacuum to obtain 1.77 g o...