CN107266674A - A kind of end diaminourea Phosphorylcholine modified poly (ethylene glycol) compound and preparation method thereof - Google Patents
A kind of end diaminourea Phosphorylcholine modified poly (ethylene glycol) compound and preparation method thereof Download PDFInfo
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- CN107266674A CN107266674A CN201710488729.1A CN201710488729A CN107266674A CN 107266674 A CN107266674 A CN 107266674A CN 201710488729 A CN201710488729 A CN 201710488729A CN 107266674 A CN107266674 A CN 107266674A
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/333—Polymers modified by chemical after-treatment with organic compounds containing nitrogen
- C08G65/33396—Polymers modified by chemical after-treatment with organic compounds containing nitrogen having oxygen in addition to nitrogen
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/321—Polymers modified by chemical after-treatment with inorganic compounds
- C08G65/322—Polymers modified by chemical after-treatment with inorganic compounds containing hydrogen
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/335—Polymers modified by chemical after-treatment with organic compounds containing phosphorus
- C08G65/3356—Polymers modified by chemical after-treatment with organic compounds containing phosphorus having nitrogen in addition to phosphorus
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2650/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G2650/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule characterized by the type of post-polymerisation functionalisation
- C08G2650/04—End-capping
Abstract
The invention discloses a kind of end diaminourea Phosphorylcholine modified poly (ethylene glycol) and preparation method thereof, double amino are introduced in the basic upper end of Phosphorylcholine modified poly (ethylene glycol), obtained end diaminourea Phosphorylcholine modified poly (ethylene glycol) has higher biocompatibility, catabolite is nontoxic can be by organism Absorption And Metabolism, expand the application space of Phosphorylcholine modified poly (ethylene glycol), contrast end diaminourea Phosphorylcholine compound, the present invention in flexible chain make Phosphorylcholine group material surface be more easy to carry out self assembly and preparation method is simple and quick, be easy to purification, cost it is low.
Description
Technical field
The invention belongs to technical field of biological materials, more particularly to biological medical polymer material biocompatibility is modified neck
A kind of domain, and in particular to end diaminourea Phosphorylcholine modified poly (ethylene glycol) compound and preparation method thereof.
Background technology
With developing rapidly for biotechnology, bio-medical material has become a big focus of current scientific research field.So
And, existing bio-medical material and device are in clinical practice, different degrees of presence infection, blood coagulation and postoperative hyperblastosis
The problems such as, these biocompatibility issues have become key factor of the restriction bio-medical material in clinical practice.At present, it is right
It is to improve the very effective mode of its biocompatibility that material, which carries out surface to be modified,.In general, improving the bio-compatible of material
Property can form hydrated sheath by coating hydroaropic substance in substrate surface, utilize the blood components such as hydrated sheath and protein molecule
Between repulsive interaction improve the stable against biological contamination ability of material.
Phosphorylcholine (PC) has-PO- 4(CH2)2N+(CH3)3The compound of group, is composition membrane structure unit
The terminal hydrophyllic group of soft phosphatide, is the outer layer functional group in extracellular tunic, simultaneous with positive and negative xenogenesis electric charge, with stronger
With reference to the ability and hydrophilicity of water, surface and the physiological environment interaction of this structure and composition not only will not be adsorbed and sunk
Product protein, will not also trigger platelet activation, cause the adverse reactions such as blood coagulation, with good biocompatibility.In certain bar
The polymer comprising Phosphorylcholine group can form the bilayer of similar biomembrane under part, rich in the effective group of Phosphorylcholine
High polymer material disguise oneself as in vivo the natural component of surrounding, improve the biocompatibility of material, its surface is difficult
Adsorbed proteins, blood platelet etc., so as to eliminate many problems that surface smut is brought.So as to significantly decrease the shape of thrombus
Into, the reaction such as inflammation, cytotoxic.The polymer of the group containing Phosphorylcholine carries out hydrophilic modifying to material surface, can be effective
Ground improves the biocompatibility of material.
Polyethylene glycol (PEG) strand has very high hydrophily and compliance, on the one hand can be with water formation hydration PEG
Chain, is formed based on stable space, platelet etc. is adsorbed in material surface；On the other hand, hydration PEG chains have in water
Relatively low surface energy, the water miniflow of formation can hinder the adhesion and deformation of protein.Therefore PEG molecules and its derivative are utilized
The effect for improving biocompatibility can be reached to material surface modifying.
Therefore, biomaterial is changed with the polymer of hydrophilic PEG molecules and its derivative or Phosphorylcholine PC groups
Property, the blood compatibility of material can be improved.It is particularly long but PEG and PC compounds are used alone and are implanted into material in vivo
In terms of phase implantation material, the problem of biocompatibility can not fully meet clinical requirement is still suffered from.Research in recent years shows,
Being built using Phosphorylcholine group and its polymer in material surface has anti-cell outer-layer membrane structure, can reduce fibrinogen
Absorption, and by reduce it is hematoblastic stick and activate increase the biocompatibility of matrix material.Therefore, change to improve
The various functions such as biocompatibility, water-retaining property, the water imbibition of kind material, people just energetically exploitation imported can be with various base materials
Compound reactive group, as dressing agent containing the similar group of Phosphorylcholine that surface is reacted.For example, patent
Document CN102070780B discloses a kind of polyethylene glycol Phosphorylcholine compound, though imported various functions group, with base
When material surface conditioning agent is chemically bonded, the functional group being complementary to is not present in substrate surface, and its reactivity can be very low, because
This need for a long time and the reaction condition of high temperature and cause to destroy base material, or grafting processing can not be carried out.Patent document
CN106565772A discloses a kind of double amino Phosphorylcholine compounds in end, but it lacks flexible chain, material surface be difficult into
Row self assembly, causes Phosphorylcholine group utilization rate relatively low, thus the biocompatibility of matrix material is unsatisfactory.
Thus, though the polyethylene glycol that PC groups and PEG molecules are combined into preparation end connection PC groups meets and is chronically implanted
The requirement of biomaterial (particularly contacting blood in terms of) clinically biological environment compatibility, but this kind of compound at this stage
End-capping group activity it is not enough, limit application of such compound in technical field of biological material, still suffer to polymer biological material
Material carries out the problems such as backbone modification, surface grafting are difficult etc..
The content of the invention
In order to overcome above-mentioned deficiency, the end diaminourea of blood compatibility can be improved it is an object of the present invention to provide a kind of
Phosphorylcholine modified poly (ethylene glycol) compound, the material introduces two with greater activity in the end of PC modified PE G compounds
Amino, overcomes simple polyethylene glycol or the compound modified deficiency of Phosphorylcholine and end mono amino Phosphorylcholine compound is being answered
The deficiency used, makes it prepare novel biomaterial as surface conditioning agent, chain extender or crosslinking agent etc., has widened and has made up
The application space in the fields such as product, organizational project, medicine controlled releasing, gene therapy.
Second object of the present invention is to provide a kind of preparation of end diaminourea Phosphorylcholine modified poly (ethylene glycol) compound
Method.
3rd purpose of the invention is to provide a kind of surface of the diaminourea Phosphorylcholine modified poly (ethylene glycol) compound containing end
Inorganic agent.
4th purpose of the invention is to provide a kind of chain extension of the diaminourea Phosphorylcholine modified poly (ethylene glycol) compound containing end
Agent or crosslinking agent.
5th purpose of the invention is to provide a kind of end diaminourea Phosphorylcholine modified poly (ethylene glycol) compound, surface treatment
The application of agent, chain extender or crosslinking agent in cosmetics, organizational project, medicine controlled releasing, gene therapy is prepared.
To achieve these goals, the present invention is adopted the following technical scheme that：
A kind of end diaminourea Phosphorylcholine modified poly (ethylene glycol), its structural formula is as follows：
Wherein n=4~200；It is preferred that n=4~50.
On the one hand, compound is with double amino structures, and end is connected to the high-molecular compound of Phosphorylcholine, by double ammonia
Base and PC groups have been incorporated into PEG strands, and not only PEG molecules are combined with the high-biocompatibility and hydrophily of PC groups
Together, modified function, and the superiority of double amino structures due to the other end have greatly been played, even more compensate for
Such macromolecule modified compound can only be not enough as the application of graft materials, expands in the sky for being modified and preparing on new material
Between.On the other hand, the present invention combines the Phosphorylcholine group of hydrophilic flexible peg molecule chain and high-biocompatibility,
The biocompatibility of compound can be not only improved, and compound group has flexibility so that in material surface modifying, have
Beneficial to progress surface self-organization.Relative to the double amino Phosphorylcholine compounds in existing end, end diaminourea phosphinylidyne courage of the invention
In alkali modification polyethylene glycol, PC groups are located at the end of flexible polyethylene glycol, are more easy to carry out self assembly in material surface, disguise oneself as
Around natural component, reduce the absorption of fibrinogen, and by reduce it is hematoblastic stick and activate increase matrix material
The biocompatibility of material.The third aspect, utilizes characteristic (such as nucleophilic substitution, addition of double amino in high-molecular compound
Reaction etc.) matrix material can be introduced directly into as chain extender and crosslinking agent.
Present invention also offers a kind of preparation method of the Phosphorylcholine compound of new pair of amino, comprise the following steps：
(1) using 1B as raw material, on lysine two amino carry out protect amido protecting 1B
Compound (I)；
(2) the polyethylene glycol chemical combination of Phosphorylcholine group is connected to the 1B compound (I) of amido protecting and end
Thing (II), under conditions of catalyst presence, carries out esterification and obtains compound (III)；
(3) compound (III) is hydrogenated under palladium carbon catalyst existence condition, takes off amido protecting group, produce end two
Amino Phosphorylcholine modified poly (ethylene glycol) compound (IV).
The present invention is direct by the 1B compound of the common Phosphorylcholine modified poly (ethylene glycol) being easy to get and amido protecting
Generation esterification, on the one hand makes Phosphorylcholine modified poly (ethylene glycol) two ends introduce the double amino in the higher end of terminal reactive, and end is double
The Phosphorylcholine modified poly (ethylene glycol) compound of amino can be introduced directly into matrix material or progress as chain extender and crosslinking agent
Grafting is handled；On the other hand, due to the presence of polyethylene glycol functional group, the introducing and connection of Phosphorylcholine group and 1B
It directly can be achieved by 1B and polyethylene glycol reaction, overcome 1B when introducing Phosphorylcholine group
Need additionally with 2- oxos -1,3,2- dioxaphospholane (COP) react at low temperature and trimethylamine ring-opening reaction, reduce
The purifying of technique and impurity removal process, method are simple, are easily purified；The conjunction of the third aspect, here the Phosphorylcholine compound of double amino
Into from the 1B in gal4 amino acid as initiation material, 1B contains many ammonia compared to D-Lys with other
The amino acid of base, its raw material is easy to get, and cost is lower, and 1B contains the amino acid of double amino, such as day relative to other in addition
Winter acid amides, glutamine, citrulling etc., more preferably, structure is simpler, and other many ammonia for its water-soluble and organic matter dissolubility
In base amino acid, second group containing amino is mostly amide groups, and amide groups activity is smaller than amino more, changes it is difficult to pass through
Amide groups is changed into amino by method, therefore they are not the optimal choosing for synthesizing this kind of pair of amino Phosphorylcholine compound
Select.
It is preferred that, the end is connected to repeat unit n=4~200 in the polyethylene glycol compound of Phosphorylcholine group；It is excellent
Select n=4~50.
It is preferred that, the amido protecting group is benzyloxycarbonyl group.
It is preferred that, two amino on lysine are protected from benzyl chloroformate (Cbz-Cl).
It is preferred that, the catalyst is thionyl chloride.
It is preferred that, the catalyst is p-methyl benzenesulfonic acid.
It is preferred that, specific synthetic route is as follows：
1. (mol ratio is 1 for polyethylene glycol and aldehyde-base Phosphorylcholine that a certain proportion of mono amino is blocked:1~1:
1.5) be dissolved in Isosorbide-5-Nitrae-dioxane or DMF, reaction temperature be maintained at 30 DEG C -70 DEG C reaction 12h -
48h, cools the temperature to 0 DEG C of -15 DEG C of addition NaBH4Reducing agent (being twice of aldehyde-base Phosphorylcholine molal quantity), keeping temperature
Continue to react 12h-48h, ether sedimentation, purification obtains the polyethylene glycol compound (compound II) that end connects Phosphorylcholine.
The 1B that (2. a) is protected using benzyloxycarbonyl group is initiation material, from tetrahydrofuran or dichloromethane as molten
Agent, triethylamine does acid binding agent, and -10 DEG C--20 DEG C of keeping temperature (is controlled under thionyl chloride effect with the mol ratio of lysine
2:1—3:1) N, N '-bis- benzyloxycarbonyl groups -1B (compound I) are reacted to obtain；
3. a certain proportion of thionyl chloride is dissolved in acetone by (a), reaction temperature is adjusted to -10 DEG C, and control thionyl chloride is molten
The rate of addition of liquid is added dropwise in the N of the gained of reaction 2, N '-bis- benzyloxycarbonyl groups -1B (compound I), 2h completion of dropping,
Continue to react 2h, be warmed to room temperature and be further continued for that the polyethylene glycol (chemical combination that the end containing 0.08mol is connected to Phosphorylcholine group is added dropwise
Thing II) tetrahydrofuran solution, N, N '-bis- benzyloxycarbonyl group -1Bs (compound I) are connected with the end of gained in reaction 1
The polyethylene glycol (compound II) of Phosphorylcholine carries out esterification and (controlled with the mol ratio of lysine 1.1:1—1.5:1),
Compound (III) is obtained after purification；
(b) end or by a certain proportion of reaction 1 obtained is connected to the polyethylene glycol (compound of Phosphorylcholine group
II) be added in the obtained N of reaction 1, N '-bis- benzyloxycarbonyl groups -1B (compound I) (its acid alcohol mol ratio is 1.0~
2.0) a certain proportion of catalyst p-methyl benzenesulfonic acid (its quality is the 2%~10% of alcohol quality), is added and a certain proportion of
Azeotropic agent toluene (its quality is the 110%~200% of alcohol quality), in dry N2Protection is lower to carry out esterification, reaction temperature
Spend for 80 DEG C~140 DEG C, reactant mixture is detected with infrared during reaction, until-OH (3400cm in infrared spectrum-1)
Vibration peak disappear, you can stop reaction, purification obtain compound (III).
4. taking off Cbz protections group using the method for palladium carbon (Pd/C) catalytic hydrogenation, final product end diaminourea phosphorus is obtained
Phatidylcholine modified poly (ethylene glycol) compound (compound IV).
Present invention also offers end diaminourea Phosphorylcholine modified poly (ethylene glycol) compound prepared by any above-mentioned method.
Present invention also offers a kind of surface conditioning agent, including：Any above-mentioned end diaminourea Phosphorylcholine is modified poly- second
Diol compound.
Present invention also offers a kind of chain extender or crosslinking agent, including：Any above-mentioned end diaminourea Phosphorylcholine is modified
Polyethylene glycol compound.
Present invention also offers it is any it is above-mentioned containing end diaminourea Phosphorylcholine modified poly (ethylene glycol), surface conditioning agent,
Chain extension connects or application of the crosslinking agent in cosmetics, organizational project, medicine controlled releasing, gene therapy is prepared.
The present invention compared with prior art, has the following advantages that：
(1) new compound of the invention is with double amino structures, and end is connected to the macromolecule chemical combination of Phosphorylcholine
Thing, double amino and PC groups have been incorporated into PEG strands, not only the high-biocompatibility of PEG molecules and PC groups and
Hydrophily is combined together, has greatly played modified function, and the superiority of double amino structures due to the other end,
Even more compensate for such macromolecule modified compound can only be not enough as the application of graft materials, expands new in modified and preparation
Space on material.
(2) using the characteristics of double amino in the Novel polymer of the present invention, (such as nucleophilic substitution, addition is anti-
Should wait) matrix material can be introduced directly into as chain extender and crosslinking agent.
(3) present invention combines the Phosphorylcholine group of hydrophilic flexible peg molecule chain and high-biocompatibility,
The biocompatibility of compound can be not only improved, and compound group has flexibility so that in material surface modifying, have
Beneficial to progress surface self-organization.
(4) the raw material lysine and polyethylene glycol that the present invention is used, it is ensured that it is applied to the nonhazardous of medical material
Property, occurring to degrade in human body will not also damage to human body.
(5) present invention can prepare the different end diaminourea Phosphorylcholine modified poly (ethylene glycol) of molecular weight.
(6) raw material used in the present invention is easy to get, and cost is low, and method is simple, is easily purified, quantitative to carry out, and yield is higher.
Embodiment
It is noted that described further below is all exemplary, it is intended to provide further instruction to the application.Unless another
Indicate, all technologies used herein and scientific terminology are with usual with the application person of an ordinary skill in the technical field
The identical meanings of understanding.
With reference to embodiment, the present invention is further described, in order to the understanding of technical staff of the same trade：
Embodiment 1：
Step 1：The polyethylene glycol that 1mol mono aminos are blocked, n=10 is dissolved in DMF, is added
1.2mol aldehyde radical Phosphorylcholine compounds, react 12h at 50 DEG C, cool to after 8 DEG C, and addition concentration is 0.02g/
ML NaBH4Methanol solution (wherein NaBH4Material amount be 2.4mol), adjustment reaction temperature to 20 DEG C, react 12h,
Ether, which is settled, must arrive the polyethylene glycol that end is connected to Phosphorylcholine group.
Step 2：By 0.055mol N, N '-bis- benzyloxycarbonyl groups -1B is added in dry reaction bulb, is being added
After 0.11mol triethylamines and 200mL tetrahydrofurans are well mixed, 0.145mol thionyl chloride is dissolved in 50mL acetone, reacted
Temperature adjustment controls the rate of addition of thionyl chloride solution to -10 DEG C, and 2h completion of dropping continues to react 2h, is warmed to room temperature, then
Continue the tetrahydrofuran solution that end of the dropwise addition containing 0.08mol is connected to the polyethylene glycol of Phosphorylcholine group, react 6 hours,
Mixture progress suction filtration is obtained into thick product, ether is washed 3 times, solvent evaporated, yield 60.3%.
Step 3：Take the product obtained by 0.05mol steps 2 to be dissolved in 250mL absolute methanols, 15min is stirred under hydrogen shield
Afterwards, excess 15%Pd/C is added, is reacted at room temperature after terminating, is filtered away solid, obtain filtrate, rotary evaporation is gone out solvent,
Thick product is obtained, final product compound end diaminourea Phosphorylcholine modified poly (ethylene glycol) is obtained.1H NMR (DMSO,
TMS, 400MHz) δ：5.11 (4H, NH2-)；4.31-4.42 (br, 4nH ,-COO (CH2CH2O)n-)；3.25 (t, H ,-CH
(NH2)-)；2.90 (s, 9H ,-N+(CH3)3)；2.65 (q, 2H, NH2CH 2-)；1.47-1.7 (br, 6H ,-CH2CH2CH2-)；8.0
(t, H ,-NHCO-)；4.90 (s, 2H ,-COCH2PC)。
Embodiment 2：
Step 1：The polyethylene glycol that 1mol mono aminos are blocked, n=50 is dissolved in DMF, is added
1.2mol reacts 12h with aldehyde radical Phosphorylcholine compound at 50 DEG C, cools to after 8 DEG C, and addition concentration is 0.02g/
ML NaBH4Methanol solution (wherein NaBH4The amount of material is 2.4mol), adjustment reaction temperature reacts 12h, second to 20 DEG C
Ether, which is settled, must arrive the polyethylene glycol that end is connected to Phosphorylcholine.
Step 2：By a certain proportion of N, N '-bis- benzyloxycarbonyl group -1Bs and end are connected to the poly- of Phosphorylcholine group
Ethylene glycol (acid alcohol mol ratio is 1.5) is added in dry reaction bulb, adds a certain proportion of catalyst p-methyl benzenesulfonic acid
(its quality is the 5% of alcohol quality) and a certain proportion of toluene (its quality is the 140% of alcohol quality), in dry N2Under protection
Esterification is carried out, reaction temperature is 120 DEG C, and reactant mixture is detected with infrared during reaction, until infrared spectrum
In-OH (3400cm-1) vibration peak not occur, you can stop reaction.Solid sodium carbonate is slowly added to aqueous solution pH=7,
The aqueous solution is extracted with dichloromethane and saturated aqueous common salt, obtained organic layer is subjected to vacuum distillation, obtains powdered
Product.
Step 3：Take the product obtained by 0.05mol steps 2 to be dissolved in 250mL absolute methanols, 15min is stirred under hydrogen shield
Afterwards, excess 15%Pd/C is added, is reacted at room temperature after terminating, is filtered away solid, obtain filtrate, rotary evaporation is gone out solvent,
Powdered product is obtained, final product compound end diaminourea Phosphorylcholine modified poly (ethylene glycol) is obtained.1H NMR (DMSO,
TMS, 400MHz) δ：5.11 (4H, NH2-)；4.31-4.42 (br, 4nH ,-COO (CH2CH2O)n-)；3.25 (t, H ,-CH
(NH2)-)；2.90 (s, 9H ,-N+(CH3)3)；2.65 (q, 2H, NH2CH 2-)；1.47-1.7 (br, 6H ,-CH2CH2CH2-)；8.0
(t, H ,-NHCO-)；4.90 (s, 2H ,-COCH2PC)。
The preferred embodiment of the application is the foregoing is only, the application is not limited to, for the skill of this area
For art personnel, the application can have various modifications and variations.It is all within spirit herein and principle, made any repair
Change, equivalent substitution, improvement etc., should be included within the protection domain of the application.
Claims (10)
1. a kind of end diaminourea Phosphorylcholine modified poly (ethylene glycol), it is characterised in that structural formula is as follows：
,
Wherein n=4~200；It is preferred that n=4~50.
2. a kind of end is connected with the preparation method of the end diaminourea polyethylene glycol polymer compound of Phosphorylcholine group, it is special
Levy and be, comprise the following steps：
(1) using 1B as raw material, on lysine two amino carry out protect amido protecting 1B chemical combination
Thing (I)；
(2) polyethylene glycol compound of Phosphorylcholine group is connected to the 1B compound (I) of amido protecting and end
(II), under conditions of catalyst presence, carry out esterification and obtain compound (III)；
(3) compound (III) is hydrogenated under palladium carbon catalyst existence condition, takes off amido protecting group, produce end diaminourea
Phosphorylcholine modified poly (ethylene glycol) compound.
3. method as claimed in claim 2, it is characterised in that the end is connected to the polyethylene glycol chemical combination of Phosphorylcholine group
Repeat unit n=4~200 in thing；It is preferred that n=4~50.
4. method as claimed in claim 2, it is characterised in that the amido protecting group is benzyloxycarbonyl group.
5. method as claimed in claim 4, it is characterised in that from benzyl chloroformate (Cbz-Cl) to two on lysine
Amino is protected.
6. method as claimed in claim 2, it is characterised in that the preferred thionyl chloride of catalyst, p-methyl benzenesulfonic acid.
7. end diaminourea Phosphorylcholine modified poly (ethylene glycol) compound prepared by the method described in claim any one of 2-6.
8. a kind of surface conditioning agent, it is characterised in that including：The double amino Phosphorylcholines of novel end described in claim 7 are modified
Polyethylene glycol compound.
9. a kind of chain extender or crosslinking agent, it is characterised in that change including the double amino Phosphorylcholines of novel end described in claim 7
Property polyethylene glycol compound.
10. contain the double amino Phosphorylcholine modified poly (ethylene glycol) compounds of novel end, claim 8 institute described in claim 7
Chain extension described in the surface conditioning agent stated, claim 9 connects or crosslinking agent is preparing cosmetics, organizational project, medicine controlled releasing, base
Because of the application in treatment.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113150270A (en) * | 2021-03-19 | 2021-07-23 | 广东丁沃生医疗器械有限公司 | Phospholipid polymer and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102070780A (en) * | 2010-12-21 | 2011-05-25 | 天津大学 | Polyethyleneglycol connected with phosphorylcholine group at tail end and preparation method thereof |
| CN106565772A (en) * | 2016-11-10 | 2017-04-19 | 山东师范大学 | Novel bis-amidogen phosphoryl choline compound Lys-EG-PC and preparation method thereof |
-
2017
- 2017-06-23 CN CN201710488729.1A patent/CN107266674A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102070780A (en) * | 2010-12-21 | 2011-05-25 | 天津大学 | Polyethyleneglycol connected with phosphorylcholine group at tail end and preparation method thereof |
| CN106565772A (en) * | 2016-11-10 | 2017-04-19 | 山东师范大学 | Novel bis-amidogen phosphoryl choline compound Lys-EG-PC and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113150270A (en) * | 2021-03-19 | 2021-07-23 | 广东丁沃生医疗器械有限公司 | Phospholipid polymer and preparation method and application thereof |
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