Composition containing sodium hyaluronate and preparation and application thereof

[0034] The preparation of the sodium hyaluronate of preparation example 1 different molecular weights

[0035] The present invention uses sodium hyaluronate (molecular weight 500kDa-1200kDa) as a raw material (provided by Xi'an Libang Pharmaceutical Co., Ltd.), and adopts gel column chromatography to separate and obtain sodium hyaluronate with different molecular weight distributions. details as follows:

[0036] Take sodium hyaluronate and prepare solution A with a concentration of 2.5 g / L in terms of sodium hyaluronate with 0.2M sodium nitrate solution.

[0037] Boil SephadexG 100 dry powder in boiling water for 3 hours, pack the evenly stirred gel column to 30cm, and then equilibrate with 10 times the volume of 0.2M sodium nitrate solution eluent. Use a pipette to measure 3mL of solution A and add it from the top of the column. Use a constant flow pump to continuously add 0.2M sodium nitrate solution for elution (flow rate 0.5mL / min). Collect the eluate every 3 minutes,

[0040] The synthesis of preparation example 2 caprolactam compounds

[0041] The present invention is based on the compound shown in formula II (R in formula II) recorded in the prior art 1 Same as formula I) as raw materials, and the compound shown in formula I was prepared by referring to the method disclosed in Tetrahedron 54 (1998) 9207-9222, and the specific reaction formula was shown in formula III.

[0042]

[0043] Preparation Example 2.1 Preparation and structure confirmation of 3-(oct-2-yl)azepan-2-one (compound 2)

[0044] Take 0.5mol of diisopropylamine and 250mL of tetrahydrofuran, place in a three-neck round bottom flask, cool to 0°C, add dropwise a 2.5M n-butyllithium / n-hexane solution with 0.5mol of n-butyllithium content under stirring . After stirring at 0°C for 15 minutes, the reaction solution was cooled to -78°C, and then 0.5 mol of azepan-2-one (compound 1) was slowly added thereto, and after stirring at -78°C for 30 minutes, 0.55 mol octan-2-yl iodide. The mixture was stirred at -30°C for 3 hours and then allowed to warm to room temperature. The lower layer reaction containing the target compound was collected by gentle inclination, then water was added, and the resulting amide was extracted with chloroform. The organic phase was dried over magnesium sulfate, concentrated, and distilled at atmospheric pressure, and the fraction at 182-185°C was collected to obtain