Preparation and application of vitamin E polyethylene glycol succinate_Industrial additives

Background and overview^[1]

Vitamin E polyethylene glycol succinate (TPGS for short) is a water-soluble derivative of vitamin E. It is formed by the reaction between the carboxyl group of vitamin E succinate and the hydroxyl group of polyethylene glycol. Because it contains both the lipophilic group of vitamin E and the long hydrophilic chain of polyethylene glycol, it has good surfactant properties and water solubility, which can significantly increase the absorption of poorly soluble drugs in the gastrointestinal tract and improve bioavailability.

Abroad, vitamin E polyethylene glycol succinate has been widely used in the research of preparations as a solubilizer, absorption enhancer, emulsifier, plasticizer, and insoluble water-soluble or fat-soluble drug delivery system. Carriers, such as solid dispersions, carriers for ocular administration, carriers for intranasal administration, etc.

In recent years, many studies have found that in addition to being used as pharmaceutical excipients, TPGS also has many unique properties, such as being an absorption enhancer and a multidrug resistance reversal agent. TPGS can also be used in prodrugs, glues, etc. Bundles, liposomes, and TPGS-copolymer carriers are used to improve the solubility, permeability, and stability of the preparation, thereby achieving slow, controlled release, and targeting effects and promoting drug absorption.

Purification method^[1]

Take 150g of commercially available vitamin E polyethylene glycol succinate (containing 81.5% of monoesterified polyethylene glycol and double esterified polyethylene glycol, 15% of polyethylene glycol, and 3.5% of vitamin E succinate) , add to 600g of ethyl acetate, heat to dissolve, add 600g of 20wt% salt water (sodium chloride solution), keep stirring at 40°C, let stand and separate into layers, wash the organic layer twice according to the law, add dioxide to the organic layer 50g of silicon, keep stirring at 40°C for 3 hours, filter, and evaporate the solvent under reduced pressure to obtain high-purity vitamin E polyethylene glycol succinate. Among them, .5g of monoesterified polyethylene glycol and diesterified polyethylene glycol 118 waterproofing agent, the total ester yield is 96.9%, the purity is greater than 99%, the polyethylene glycol content is 0.18%, and vitamin E succinate is 0.05%.

Preparation^[2]

Weigh 5.6 grams of natural vitamin E succinate with a purity of 90%, 20 grams of polyethylene glycol 600 with a molecular weight of 600, and 0.8 grams of concentrated sulfuric acid with a mass concentration of 98%, and put them into a three-neck bottle , react with constant stirring at 100°C for 2 hours, and cool to room temperature after the reaction is completed. Transfer the reaction product to a round-bottomed flask, then add 150 ml of ethyl acetate to the round-bottomed flask to obtain a mixture. Transfer the mixture to a separatory funnel, extract three times with saturated brine, and collect the organic phase. The solvent was evaporated from the organic phase to obtain 8.3 grams of TPGS. The purity of the obtained product was 90.1% as measured by HPLC. The conversion rate of vitamin E succinate was 89.2%, and the yield of TPGS was 79.2%.

Apply^[3-4]

Application 1,

CN201811027763.X reports an orlistat soft capsule and its preparation method. The orlistat soft capsule provided by the invention is composed of content and rubber. The content is mainly composed of orlistat, polysorbate 80 and vitamin E polyethylene glycol succinate; the film is composed of fish gelatin , glycerin and purified water. The orlistat soft capsule provided by the invention has the advantages of high dissolution, low content of related substances, high stability and low side effects, and can effectively improve the efficacy of orlistat. At the same time, the orlistat soft capsule has The production process will not cause problems such as adhesion, bonding and re-aggregation, and is easy to control, which is conducive to large-scale production.

Application 2,

CN201911403699.5 discloses a traditional Chinese medicine composition with antibacterial, anti-inflammatory, hemostatic and analgesic effects and a preparation method thereof. The method uses monkey earring extract and Duyiwei extract as raw materials, and polylactic acid-glycolic acid copolymer PLGA, vitamin E polyethylene glycol succinate TPGS, and poloxamer are used as drug-carrying matrices. By mixing the original medicinal materials with the drug-carrying matrix to form an oil phase and an oil-in-water phase, the nanosuspension is obtained through ultrasonic emulsification with a probe. liquid, and then add carbomer, collagen tripeptide, oat beta-glucan, and propylene glycol as gel matrix to prepare a nanogel of traditional Chinese medicine composition. The nanogel particle size of the traditional Chinese medicine composition prepared by the invention is 120nm to 260nm, has good drug loading capacity, and at the same time significantly improves the solubility and bioavailability of hydrophobic drugs, has antibacterial, anti-inflammatory, hemostatic and analgesic effects, and has definite curative effect. .

References

[1][Chinese invention] CN201711417254.3 A method for purifying vitamin E polyethylene glycol succinate

[2][China invention, China invention authorization] CN201010121073.8 Solvent-free synthesis method of water-soluble vitamin E polyethylene glycol succinate

DuPont titanium dioxide [3] CN201811027763.X orlistat soft capsule and preparation method thereof

[4]CN201911403699.5 A traditional Chinese medicine composition with antibacterial, anti-inflammatory, hemostatic and analgesic effects and its preparation method