CN111632582B - Silica gel reverse phase chromatographic packing and preparation method and application thereof - Google Patents
Silica gel reverse phase chromatographic packing and preparation method and application thereof Download PDFInfo
- Publication number
- CN111632582B CN111632582B CN201910155766.XA CN201910155766A CN111632582B CN 111632582 B CN111632582 B CN 111632582B CN 201910155766 A CN201910155766 A CN 201910155766A CN 111632582 B CN111632582 B CN 111632582B
- Authority
- CN
- China
- Prior art keywords
- silica gel
- reverse phase
- acetonitrile
- acid
- octadecylsilane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
- B01J20/10—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate
- B01J20/103—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate comprising silica
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/223—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material containing metals, e.g. organo-metallic compounds, coordination complexes
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0003—General processes for their isolation or fractionation, e.g. purification or extraction from biomass
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/40—Aspects relating to the composition of sorbent or filter aid materials
- B01J2220/48—Sorbents characterised by the starting material used for their preparation
- B01J2220/4806—Sorbents characterised by the starting material used for their preparation the starting material being of inorganic character
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/40—Aspects relating to the composition of sorbent or filter aid materials
- B01J2220/48—Sorbents characterised by the starting material used for their preparation
- B01J2220/4812—Sorbents characterised by the starting material used for their preparation the starting material being of organic character
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
- B01J2220/52—Sorbents specially adapted for preparative chromatography
Landscapes
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Polymers & Plastics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Inorganic Chemistry (AREA)
- Sustainable Development (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention provides a silica gel reverse phase chromatographic packing and a preparation method and application thereof. The silica gel reversed phase chromatographic packing has simple preparation method, and can be used for purifying sugammadex sodium, so that the purity of the sugammadex sodium in a sample eluent is more than 99.2 percent, the industrial production requirement is met, and the quality standard of raw material medicines is completely met.
Description
Technical Field
The invention relates to a medical synthesis technology, in particular to a silica gel reversed phase chromatographic packing and a preparation method and application thereof.
Background
Sugammadex sodium is a derivative of gamma-cyclodextrin, the molecule of which consists of a lipophilic core and a hydrophilic outer end, and is a selective muscle relaxant antagonist with the chemical name: 6-Perdeoxy-6-per (2-carboxyethyl) thio-gamma-cyclodextrin sodium salt (octasodium salt) having the following structural formula:
the sugammadex sodium is used for reversing the effect of a conventionally used neuromuscular blocking drug rocuronium bromide or vecuronium bromide, can immediately reverse the effect of rocuronium bromide used by adults and conventionally reverse the effect of rocuronium bromide used by children and adolescents (2-17 years old). In recent years, with the development of preparation or purification technology, various sugammadex sodium purification processes have been reported, but sugammadex sodium has a complex structure and contains a plurality of chiral centers, and particularly, many gamma-cyclodextrin structural analogs exist, and the methods reported in the existing documents cannot provide high-purity sugammadex sodium and meet the requirements of industrial mass production.
Therefore, it is desirable to provide a new method for purifying sugammadex sodium to solve the above problems.
It is noted that the information disclosed in the foregoing background section is only for enhancement of background understanding of the invention and therefore it may contain information that does not constitute prior art that is already known to a person of ordinary skill in the art.
Disclosure of Invention
The invention aims to overcome at least one defect of the prior art and provides a silica gel reversed phase chromatographic packing and a preparation method thereof, wherein the silica gel reversed phase chromatographic packing can be used for purifying sugammadex sodium, so that the purity of the sugammadex sodium in a sample eluent is more than 99 percent, the industrial production requirement is met, and the quality standard of a bulk drug is completely met.
In order to achieve the purpose, the invention adopts the following technical scheme:
one aspect of the invention provides a silica gel reverse phase chromatography packing comprising: silica gel and organosilane bonded on the surface of the silica gel, wherein the organosilane comprises octadecylsilane and other silane, and the chemical structural general formula of the octadecylsilane is as follows:
wherein R is 1 、R 2 Each independently selected from hydrogen or C 1-4 Alkyl of (A), X 1 As reactive groups, preference is given to chlorine, methoxy or ethoxy.
According to one embodiment of the invention, the chemical structure of the other silanes is of the general formula:
wherein R is 3 、R 4 Is C 1-4 Alkyl of (a), X 2 Is a reactive group, preferably chlorine, methoxy or ethoxy; m and n are selected from integers of 1-3, and m + n is less than or equal to 4.
According to one embodiment of the invention, the other silane is selected from one or more of methyltrimethoxysilane, trimethylchlorosilane, monomethyltrichlorosilane and dimethyldichlorosilane.
According to one embodiment of the invention, wherein the octadecylsilane is selected from the group consisting of octadecyldimethylchlorosilane, octadecylmonomethylchlorosilane, octadecyldimethylmethoxysilane, octadecyldimethylethoxysilane, octadecylmethylmethylmethoxysilane and octadecylmonomethylethoxysilane.
Another aspect of the present invention provides a method for preparing the silica gel reverse phase chromatography packing, comprising the steps of:
activating and pretreating silica gel to obtain activated silica gel with silicon hydroxyl on the surface;
mixing octadecylsilane and other silanes as a premix;
and mixing the premix and the activated silica gel in an organic solvent, and carrying out reflux reaction to obtain the silica gel reverse phase chromatographic packing.
According to one embodiment of the present invention, the mass ratio of the octadecylsilane and the other silane is 1 (0.2-1.3); the mass ratio of the silica gel to the premix is 1 (0.2-1.3).
According to one embodiment of the present invention, wherein the reflux reaction is performed under an inert atmosphere, the time of the reflux reaction is 12 to 48 hours.
In another aspect of the present invention, a method for purifying sugammadex sodium is provided, wherein the method for purifying sugammadex sodium by using the silica gel reverse phase chromatography packing comprises the following steps:
loading the crude sugammadex sodium product on a chromatographic column of a silica gel reversed phase chromatographic packing, and collecting a sample eluent after elution, wherein the purity of the sugammadex sodium in the sample eluent is more than 99%.
According to an embodiment of the present invention, wherein the purity of the crude sugammadex sodium is 80%, the single impurity content in the sample eluate is less than 0.05%.
According to one embodiment of the invention, wherein the chromatography column is eluted with acetonitrile/water solution, the acetonitrile content is 5-40%, preferably 10-30%, more preferably 19% by volume percentage; the acetonitrile/water solution also contains acid, and the acid is selected from one or more of formic acid, perchloric acid, acetic acid, trifluoroacetic acid and phosphoric acid; the concentration of the acid is 0.05wt% to 1.0wt%, preferably 0.2wt%.
According to the technical scheme, the invention has the beneficial effects that:
the invention provides a novel silica gel reversed phase chromatographic packing and a preparation method thereof, and the preparation method of the silica gel chromatographic packing has the advantages of simplicity, good stability, good reproducibility, easiness in large-scale production and the like. The silica gel reverse phase chromatographic packing is adopted for purifying the sugammadex sodium, the purity of the sugammadex sodium in a sample eluent can reach 99.2 percent, the single impurity content is less than 0.05 percent, the yield is high, and the production standard of raw material medicines is met.
Drawings
FIG. 1 is a liquid chromatogram of purified sugammadex sodium of example 1.
Detailed Description
The following presents various embodiments or examples in order to enable those skilled in the art to practice the invention with reference to the description herein. These are, of course, merely examples and are not intended to be limiting. The endpoints of the ranges and any values disclosed in the present application are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to yield one or more new ranges of values, which ranges of values should be considered as specifically disclosed herein.
One aspect of the invention provides a silica gel reverse phase chromatography packing comprising: silica gel and organosilane bonded on the surface of the silica gel, wherein the organosilane comprises octadecylsilane and other silanes, and the general chemical structure of the octadecylsilane is as follows:
wherein R is 1 、R 2 Independently selected from hydrogen or C 1-4 Alkyl of (A), X 1 As reactive groups, preference is given to chlorine, methoxy or ethoxy.
The "other silane" refers to other kinds of organosilanes other than octadecylsilane. According to the invention, octadecylsilane and other silanes are selected as bonding reaction reagents, octadecylsilane is taken as a main functional group, so that a good nonpolar acting force is obtained, intermolecular action can be carried out on the octadecylsilane and a target substance, and a substance is properly retained, and the action of other silanes provides multiple selectivity and retention mechanisms, so that the target substance and other unnecessary substances can be well separated, the stability of the bonding phase in a mobile phase is increased, the service life of the filler is prolonged to a great extent, and the production cost is reduced.
In some embodiments, the other silane coupling agent has the general chemical formula:
wherein R is 3 、R 4 Is C 1-4 Alkyl of (A), X 2 Is a reactive group, preferably chloro, methoxy or ethoxy; m and n are selected from integers of 1-3, and m + n is less than or equal to 4.
Further, the other silanes include, but are not limited to, one or more of methyltrimethoxysilane, trimethylchlorosilane, monomethyltrichlorosilane, or dimethyldichlorosilane.
In some embodiments, wherein the octadecylsilane is selected from the group consisting of octadecyldimethylchlorosilane, octadecylmonomethylchlorosilane, octadecyldimethylmethoxysilane, octadecyldimethylethoxysilane, octadecylmethylmethylmethoxysilane, and octadecylmonomethylethoxysilane.
Another aspect of the present invention provides a method for preparing the silica gel reverse phase chromatography packing, comprising the steps of:
the silica gel is activated and pretreated to obtain activated silica gel with silicon hydroxyl on the surface, specifically, for example, the silica gel, pyridine and imidazole are placed in an organic solvent to be mixed and stirred for reaction, heated and stirred for refluxing for a certain time, and preferably, water evaporated after the reaction is separated by a water separator to obtain a solution containing the activated silica gel. Mixing octadecylsilane and other silanes to obtain a premix, adding the premix into a solution containing activated silica gel to perform reflux reaction, and treating to obtain the bonded silica gel reversed-phase chromatographic packing.
Preferably, the silica gel reverse phase chromatography packing of the present invention has a particle size of preferably 5 to 60 μm and a specific surface area of preferably 100 to 300m 2 /g。
In some embodiments, the organic solvent is preferably a non-polar solvent, such as toluene, xylene, n-hexane, or n-heptane. Toluene is preferred. Silica gel is catalyzed to become active and further to be bonded with chemical functional groups by reacting the silica gel with pyridine and imidazole at 50-120 ℃ for a certain time, preferably 12-24 hours.
In some embodiments, the mass ratio of octadecylsilane to other silanes is 1 (0.2-1.3), preferably 1 (0.5-1.1); the mass ratio of the silica gel to the premix is 1 (0.2-1.3), preferably 1 (0.5-1.1).
In some embodiments, the reflux reaction is performed under an inert atmosphere, such as nitrogen (N) 2 ) (ii) a The time for the reflux reaction is 12 to 24 hours, preferably 18 hours.
In another aspect of the present invention, a method for purifying sugammadex sodium is provided, wherein the method for purifying silica gel reverse phase chromatography packing prepared by the method comprises the following steps:
loading the crude sugammadex sodium product on a chromatographic column of silica gel reversed phase chromatographic packing, and collecting a sample eluent after elution, wherein the purity of the sugammadex sodium in the sample eluent is more than 99.2%.
In some embodiments, the crude sugammadex sodium has a purity of 80%, and the single impurity content of the resulting sample eluate after elution with the silica gel chromatography packing of the present invention may be less than 0.05%.
In some embodiments, the chromatography column is eluted with acetonitrile/water solution, the acetonitrile content being 5 to 40%, preferably 10 to 30%, more preferably 19% by volume; i.e. the acetonitrile content refers to the volume percentage of acetonitrile in the solution. Specifically, water and acetonitrile may be pumped separately through a A, B conduit to a silica gel reverse phase chromatography column for elution.
In order to reduce the adsorption of sugammadex on the silica gel reverse phase and ensure the purification effect and yield, in some embodiments, the acetonitrile/water solution also contains an acid, and the acid is selected from one or more of formic acid, perchloric acid, acetic acid, trifluoroacetic acid and phosphoric acid; the concentration of the acid is 0.05wt% to 1.0wt%, preferably 0.2wt%.
In some embodiments, the flow rate of the eluent in the purification process is 1-2L/min, and can be adjusted according to the actual inner diameter of the column.
The invention is further described below by means of specific examples, without restricting the scope of the invention in any way.
It should be noted that the "purity" or "content" of the samples described in the following examples was obtained by HPLC assay; the detection conditions are as follows: the column was a Boltimate C18 (2.7um, 4.6 x 150mm); the mobile phase is phosphoric acid water and acetonitrile, the speed is 0.8ml/min, and the detection wavelength is 210nm.
Preparation example 1
10.0g of silica gel, 3.0g (0.044 mol) of pyridine imidazole and 90mL of toluene are accurately weighed and placed in a 100mL three-neck flask, stirring and refluxing are carried out at 120 ℃ for 2h, and the water evaporated out is separated out by a water separator. Then cooled to room temperature under N 2 Adding 8.0g of premixed octadecyldimethylchlorosilane and methyltrimethoxysilane under protection, wherein the mass ratio of the octadecyldimethylchlorosilane to the methyltrimethoxysilane is 4:1, reacting for 18h under the reflux condition, and then carrying out treatment reaction to obtain a bonded stationary phase, namely the silica gel reversed phase chromatographic packing.
Example 1
Filling a preparation column: after 11kg of the silica gel reverse phase chromatography packing (10 μm particle size, 300mm DAC column) obtained in preparation example 1 was wetted with 28L of isopropanol, the homogenate was carried out using a homogenizing apparatus, and the homogenate was loaded into a DAC column tube, dynamic axial compression was employed so that the packing pressure reached 80 to 100Bar, and the preparation column was washed with 5 to 10 times CV (column volume) of methanol as a mobile phase for backup.
300g of crude sugammadex sodium (purity 82%) was dissolved in 1000ml of 0.1% formic acid water and filtered through a 0.45 μm filter.
The solution was loaded onto a preparative column and 0.2% formic acid in water and acetonitrile were pumped to the DAC column using A, B tubing, respectively, for elution, keeping the acetonitrile content at 19%. The main peak eluted is divided into different fractions, qualified fractions are combined and concentrated to obtain 255g of sugammadex sodium, the yield is 85%, the purity is 99.87%, and the single impurity content is less than 0.05%. Fig. 1 shows a liquid chromatogram of purified sugammadex sodium of example 1.
Example 2:
the preparative column packed according to example 1 was ready for use.
300g of crude sugammadex sodium (purity 83.1%) are dissolved in 1000ml of 0.15% formic acid water and filtered through a 0.45 μm filter.
The solution was loaded onto a preparative column and 0.15% formic acid in water and acetonitrile were pumped to the DAC column using A, B tubing, respectively, for elution, keeping the acetonitrile content at 19%. The main peak eluted is divided into different fractions, qualified fractions are combined and concentrated to obtain 255g of sugammadex sodium, the yield is 85%, the purity is 99.96%, and the single impurity content is less than 0.05%.
Example 3:
preparative columns packed according to example 1 were ready for use
300g of crude sugammadex sodium (purity 85.5%) was dissolved in 1000ml of 0.1% formic acid water and filtered through a 0.45 μm filter.
The solution was loaded onto a preparative column and 0.2% formic acid in water and acetonitrile were pumped to the DAC column using A, B tubing, respectively, for elution, keeping the acetonitrile content at 19%. The main peak eluted is divided into different fractions, qualified fractions are combined and concentrated to obtain 249g of sugammadex sodium, the yield is 83%, the purity is 99.83%, and the single impurity content is less than 0.05%.
Example 4:
the preparative column packed according to example 1 was ready for use.
300g of crude sugammadex sodium (purity 90.3%) are dissolved in 1000ml of 0.1% formic acid water and filtered through a 0.45 μm filter.
The solution was loaded onto a preparative column and 0.2% formic acid in water and acetonitrile were pumped to the DAC column using A, B tubing, respectively, for elution, keeping the acetonitrile content at 19%. The main peak eluted is divided into different fractions, qualified fractions are combined and concentrated to obtain 260g of sugammadex sodium, the yield is 87%, the purity is 99.83%, and the single impurity content is less than 0.05%.
Therefore, the silica gel reversed phase chromatographic packing has good purification effect on the sugammadex sodium, the purity can basically reach more than 99.2%, and the single impurities are less than 0.05%, so that the quality standard of the sugammadex sodium as a raw material medicine is completely met.
It should be noted by those skilled in the art that the described embodiments of the present invention are merely exemplary and that various other substitutions, alterations, and modifications may be made within the scope of the present invention. Accordingly, the present invention is not limited to the above-described embodiments, but is only limited by the claims.
Claims (17)
1. A silica gel reverse phase chromatography packing comprising: silica gel and organosilanes bonded to the surface of the silica gel, the organosilanes including octadecylsilane and other silanes, wherein:
the general chemical structure formula of the octadecylsilane is as follows:
wherein R is 1 Is C 2-4 Alkyl of R 2 Is C 2-4 Alkyl of (a), X 1 Is a reactive group, and the preparation method comprises the following steps: the method comprises the following steps:
activating and pretreating silica gel to obtain activated silica gel with silicon hydroxyl on the surface;
mixing octadecylsilane and other silanes into a premix;
mixing the premix and the activated silica gel in an organic solvent and carrying out reflux reaction to obtain the silica gel reverse phase chromatographic packing;
the preactivation is as follows: silica gel, pyridine and imidazole are placed in an organic solvent to be mixed, stirred and reacted, heated, stirred and refluxed;
the silica gel reverse phase chromatography packing is used for purifying sugammadex sodium.
2. The silica gel reverse phase chromatography packing of claim 1, wherein X is 1 Is chlorine, methoxy or ethoxy.
3. The silica gel reverse phase chromatography packing of claim 1, wherein the other silane has the general chemical structure of:
wherein R is 3 、R 4 Is selected from C 1-4 Alkyl of (a), X 2 Is a reactive group, m and n are selected from integers of 1 to 3, and m + n is less than or equal to 4.
4. The silica gel reverse phase chromatography packing of claim 1, wherein the other silane has the general chemical structure of:
wherein R is 3 、R 4 Is selected from C 1-4 Alkyl of (A), X 2 Is chlorine, methoxy or ethoxy; m and n are selected from integers of 1-3, and m + n is less than or equal to 4.
5. The silica gel reverse phase chromatography packing material of claim 3 or 4, wherein the other silane is selected from one or more of methyltrimethoxysilane, trimethylchlorosilane, monomethyltrichlorosilane, and dimethyldichlorosilane.
6. A silica gel reverse phase chromatography packing material according to any one of claims 1 to 5, wherein the octadecylsilane is selected from one or more of octadecyldimethylchlorosilane, octadecylmonomethylchlorosilane, octadecyldimethylmethoxysilane, octadecyldimethylethoxysilane, octadecylmethylmethylmethoxysilane, and octadecylmonomethylethoxysilane.
7. A process for preparing the silica gel reverse phase chromatography packing of any one of claims 1-4 comprising the steps of:
activating and pretreating silica gel to obtain activated silica gel with silicon hydroxyl on the surface;
mixing octadecylsilane and other silanes into a premix;
and mixing the premix and the activated silica gel in an organic solvent and carrying out reflux reaction to obtain the silica gel reversed phase chromatographic packing.
8. The method of claim 7, wherein the mass ratio of octadecylsilane and the other silane is 1 (0.2-1.3); the mass ratio of the silica gel to the premix is 1 (0.2-1.3), and the premix is a mixture of octadecylsilane and other silanes.
9. The method of claim 7, wherein the reflux reaction is carried out under an inert atmosphere for a time period of 12 to 48 hours.
10. A purification method of sugammadex sodium, which uses the silica gel reverse phase chromatography packing material of any one of claims 1-6 for purification, comprising the following steps:
and loading the crude sugammadex sodium on a chromatographic column of the silica gel reverse phase chromatographic packing, and collecting a sample eluent after elution, wherein the purity of the sugammadex sodium in the sample eluent is more than 99.2%.
11. A purification process according to claim 10, wherein the purity of the crude sugammadex sodium is 80% and the single impurity content in the sample eluate is less than 0.05%.
12. The purification process according to claim 10, wherein the chromatography column is eluted with acetonitrile/water solution, the acetonitrile content being 5-40% by volume; the acetonitrile/water solution also contains acid, and the acid is selected from one or more of formic acid, perchloric acid, acetic acid, trifluoroacetic acid and phosphoric acid; the concentration of the acid is 0.05wt% -1.0 wt%.
13. The purification process according to claim 12, wherein the column is eluted with acetonitrile/water solution, the acetonitrile content being comprised between 10 and 30% by volume.
14. The purification process according to claim 13, wherein the chromatography column is eluted with acetonitrile/water solution, the acetonitrile content being 19% by volume.
15. The purification process according to claim 12, wherein the chromatography column is eluted with acetonitrile/water solution, the acid concentration being 0.2wt% in volume percentage.
16. The purification process according to claim 13, wherein the chromatography column is eluted with acetonitrile/water solution, the acid concentration being 0.2wt% in volume percentage.
17. The purification process according to claim 14, wherein the chromatography column is eluted with acetonitrile/water solution, the acid concentration being 0.2wt% in volume percentage.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910155766.XA CN111632582B (en) | 2019-03-01 | 2019-03-01 | Silica gel reverse phase chromatographic packing and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910155766.XA CN111632582B (en) | 2019-03-01 | 2019-03-01 | Silica gel reverse phase chromatographic packing and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111632582A CN111632582A (en) | 2020-09-08 |
| CN111632582B true CN111632582B (en) | 2023-02-28 |
Family
ID=72322747
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910155766.XA Active CN111632582B (en) | 2019-03-01 | 2019-03-01 | Silica gel reverse phase chromatographic packing and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111632582B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101234337A (en) * | 2007-11-14 | 2008-08-06 | 天津大学 | Silica matrix chromatogram packing |
| CN103357390A (en) * | 2012-11-12 | 2013-10-23 | 北京迪马欧泰科技发展中心 | Multi-layer structure bonded silica gel liquid chromatography packing and synthesis method thereof |
| CN108176387A (en) * | 2018-03-08 | 2018-06-19 | 浙江月旭材料科技有限公司 | A kind of silica gel chromatographic column filling material, preparation method and applications |
| CN108456264A (en) * | 2017-02-22 | 2018-08-28 | 江苏恒瑞医药股份有限公司 | A kind of purification process for the more glucose sodium that relaxes |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5993653C1 (en) * | 1997-08-11 | 2001-11-06 | Phenomenex | Composition and column used in hplc |
-
2019
- 2019-03-01 CN CN201910155766.XA patent/CN111632582B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101234337A (en) * | 2007-11-14 | 2008-08-06 | 天津大学 | Silica matrix chromatogram packing |
| CN103357390A (en) * | 2012-11-12 | 2013-10-23 | 北京迪马欧泰科技发展中心 | Multi-layer structure bonded silica gel liquid chromatography packing and synthesis method thereof |
| CN108456264A (en) * | 2017-02-22 | 2018-08-28 | 江苏恒瑞医药股份有限公司 | A kind of purification process for the more glucose sodium that relaxes |
| CN108176387A (en) * | 2018-03-08 | 2018-06-19 | 浙江月旭材料科技有限公司 | A kind of silica gel chromatographic column filling material, preparation method and applications |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111632582A (en) | 2020-09-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| O'Gara et al. | Simple preparation of a C8 HPLC stationary phase with an internal polar functional group | |
| EP0128886B1 (en) | Separation material, methods of producing a separation material and use of orosomucoid, functional analogs thereto or derivatives or fragments thereof for separation purposes | |
| US5202433A (en) | Polysaccharide derivatives as separating agents | |
| WO1995000463A1 (en) | Optical isomer separating agent and process for producing the same | |
| EP2028487B1 (en) | Filler for optical isomer separation | |
| CN111632582B (en) | Silica gel reverse phase chromatographic packing and preparation method and application thereof | |
| CN108892601B (en) | Preparation method of polycyclic aromatic hydrocarbon with benzofluorene structure | |
| WO2004046714A1 (en) | Separating agent for optical isomer | |
| WO1995031420A1 (en) | Separating agent for optical isomers | |
| JP2012509479A (en) | Novel chromatographic media based on phenoxyalkyl, alkoxyphenylalkyl or phenoxyphenylalkyl ligands | |
| Sutthivaiyakit et al. | Immobilization of 5-methylene-2-(2′-thiazolylazo)-anisole on silica and its application in preconcentration of palladium | |
| CN116262837A (en) | Anion exchange gel filler based on activation of alkenyl-terminated halohydrocarbon and preparation method thereof | |
| JPS61267537A (en) | Optical resolution of oxycyclopentenone and derivative thereof | |
| WO1998009913A1 (en) | Reversible covalent attachment of fullerenes to insoluble supports | |
| CN111153909B (en) | A double-template molecular imprinting purification method for alpha-and beta-carotene in Stephania tetrandra | |
| JPH06211902A (en) | Substituted aromatic carbamate derivative of polysaccharide, and separating agent | |
| JPH07260762A (en) | Filler for high-speed liquid chromatography and manufacture thereof | |
| CN110845310A (en) | Method for iodinating ortho-position of benzaldehyde compound | |
| CN117138762A (en) | Low-loss mixed separation mode liquid chromatographic packing and preparation method and application thereof | |
| JP3634929B2 (en) | Method for producing packing material for high performance liquid chromatography | |
| JPH02289601A (en) | New polysaccharide and separating agent | |
| JP3029302B2 (en) | Packing material for chromatography and method for producing the same | |
| CN1472003A (en) | Aromatic hydrocarbon linked silica gel solid phase and its preparation and use | |
| CN1034851C (en) | Preparation of bonded stationary phase of cyclodextrin used in chromatograph | |
| JPH05148163A (en) | Separating agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20210126 Address after: 203201 1001b, area a, building 1, 3000 Longdong Avenue, Pudong New Area pilot Free Trade Zone, Shanghai Applicant after: WELCH MATERIALS (SHANGHAI) Inc. Applicant after: Shanghai wellrich Testing Technology Co.,Ltd. Address before: 203201 1001b, area a, building 1, 3000 Longdong Avenue, Pudong New Area pilot Free Trade Zone, Shanghai Applicant before: WELCH MATERIALS (SHANGHAI) Inc. |
|
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 201613 Room 102, 2 / F and 3 / F, 1 / F, building 10, 85 Mingnan Road, Songjiang District, Shanghai Applicant after: WELCH MATERIALS (SHANGHAI) Inc. Applicant after: Shanghai wellrich Testing Technology Co.,Ltd. Address before: 203201 1001b, area a, building 1, 3000 Longdong Avenue, Pudong New Area pilot Free Trade Zone, Shanghai Applicant before: WELCH MATERIALS (SHANGHAI) Inc. Applicant before: Shanghai wellrich Testing Technology Co.,Ltd. |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |