CN104211961B - Poly-aspartate derivant, it prepares, nanostructured, Plumbum removing activity and application - Google Patents
Poly-aspartate derivant, it prepares, nanostructured, Plumbum removing activity and application Download PDFInfo
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Abstract
Poly-aspartate derivant, it prepares, nanostructured, Plumbum removing activity and application.The invention discloses the poly-aspartate derivant that Formulas I a b represents, in formula, AA is L Met, L Cys residue, disclose their preparation method, disclose their nanostructured, disclose the stepwise stability constant of they and Pb (II) complexation, disclose they lead-eliminating effects on mice lead acetate poisoning model, further disclose them in Mice Body and free of toxic effects.Thus the present invention illustrates the poly-aspartate derivant Ia b potential applicability in clinical practice as lead displacement agent..
Description
Invention field
The present invention relates to the poly-aspartate derivant that Ia-b represents, in formula, AA is L-Met, L-Cys residue, relates to them
Preparation method, relate to their nanostructured, relate to the stepwise stability constant of they and Pb (II) complexation, relate to them little
Lead-eliminating effect on Mus lead acetate poisoning model, further to them in Mice Body and free of toxic effects.Thus this
Bright illustrate the poly-aspartate derivant Ia-b potential applicability in clinical practice as lead displacement agent.The invention belongs to biological medicine neck
Territory.
Background technology
One of heavy metal that lead uses the earliest as the mankind, while bringing cheaply to our life, also brings to us
The problem of heavy metal pollution.Lead enters our blood circulation through respiratory system, digestive system and skin, thus to ours
Histoorgan produces toxic and side effects.The most commonly used drives lead medicine (penicillamine etc.) or due to complexing of metal ion
Poor selectivity, or owing to organ toxic and side effects, Essential metal elements of human maybe can be discharged, it is impossible in order to prevent lead poisoning.Seek
Looking for safety, orally available, toxic and side effects is little, and lead sequestering power is strong, and the lead poisoning antidote not affecting Essential metal elements of human has
Clear and definite application prospect.
Poly-aspartate derivant and hydroxy compounds have the effect of potential drive row heavy metal, it is not easy to savings.Poly-
Aspartic acid is the macromolecule that a class has excellent biological degradability, biodegradation can become endogenous material Radix Asparagi ammonia in human body
Acid, does not produce toxic and side effects.Poly-aspartate and L-Met, L-Cys are formed conjugate by the early stage of inventor, find that it is to respectively
Individual organ all has certain Plumbum removing ability, but does not has drive row effect to blood lead.Inventor's early stage is recognized, with 2-amino-1,
Mice with lead poisoning is treated by ammediol, and it shows definite drive row effect to blood lead.Recognize according to these, inventor
2-amino-1,3-propanediol is puted together with poly-aspartate with L-Met and L-Cys for linking arm, the row's of making organ lead and blood lead
Activity is more excellent.Inventor is it is also to be recognized that with L-Met and L-Cys for linking arm by 2-amino-1,3-propanediol and poly-Radix Asparagi ammonia
The trace element not interfering with needed by human is puted together in acid.Inventor is it is further recognized that incite somebody to action with L-Met and L-Cys for linking arm
2-amino-1,3-propanediol and poly-aspartate are puted together can form nanostructured, the most internal conveying.Recognize according to these
Know, inventors herein propose the present invention.
The prominent creativeness of the present invention is, 1) with L-Met and L-Cys for linking arm by 2-amino-1,3-propanediol with
Poly-aspartate is puted together, and the activity of the row's of making organ lead and blood lead is more excellent；2) with L-Met and L-Cys for linking arm by 2-ammonia
Base-1,3-PD and poly-aspartate put together the trace element not interfering with needed by human；3) with L-Met and L-Cys for even
Connect arm 2-amino-1,3-propanediol and poly-aspartate to be puted together and can form nanostructured, the most internal conveying.
Summary of the invention
First content of the present invention is to provide the novel lead expelling agent that Ia-b represents.
Second content of the present invention is to provide the preparation method of the novel lead expelling agent that Ia-b represents, and comprises the following steps:
1) ice bath oxolane is made under solvent, prepares L-methionyl-2-amino-1 through sodium borohydride reduction, 3-the third two
Alcohol, L-cysteinyl-2-amino-1,3-propanediol；
2) in distilled water, L-methionyl-2-amino-1,3-propanediol, L-cysteinyl-2-ammonia are regulated with triethylamine
The pH of base-1,3-PD is 8, at 40 DEG C, carries out reaction with polysuccinimide and generates poly-Radix Asparagi acyl methionyl-2-ammonia
Base-1,3-PD (Ia), poly-Radix Asparagi acyl cysteinyl-2-amino-1,3-propanediol (Ib).
3rd content of the present invention is the nanostructured measuring the novel lead expelling agent that Ia-b represents.
4th content of the present invention is the complexing measuring Ia-b with lead.
5th content of the present invention is the Plumbum removing activity measuring the novel lead expelling agent that Ia-b represents.
6th content of the present invention is the novel lead expelling agent the measuring Ia-b representative impact on internal trace element.
7th content of the present invention is the toxicity measuring the novel lead expelling agent that Ia-b represents.
Accompanying drawing explanation
Fig. 1 poly-Radix Asparagi acyl methionyl-2-amino-1,3-propanediol (Ia), poly-Radix Asparagi acyl cysteinyl-2-amino-1,
The synthetic route chart of ammediol (Ib).
Fig. 2 poly-Radix Asparagi acyl methionyl-2-amino-1,3-propanediol (Ia) concentration is 10-9The transmission electron microscope photo of M.
Fig. 3 poly-Radix Asparagi acyl cysteinyl-2-amino-1,3-propanediol (Ib) concentration is 10-9The transmission electron microscope photo of M.
Embodiment
In order to be further elucidated with the present invention, a series of embodiment is given below.It must be noted that these embodiments are complete
It is illustrative.The purpose providing these embodiments is to fully express meaning of the present invention and content, never to the present invention
Cause any type of restriction.
Embodiment 1 heats decompression method and prepares the polysuccinimide of chain a length of 59
Finely ground for 5g (37.6mmol) L-Aspartic acid, 2mL (85%) phosphoric acid and 2mL distilled water thoroughly mix.Reaction is mixed
Compound Depressor response under 180 DEG C of air baths adds 20mL DMF after 2.5 hours while hot, drips to 100mL and steam after solution is clarified
In distilled water.Collect precipitation, be washed till neutrality with distilled water, be dried, obtain 2.9g (84%) title compound, for colorless solid.Element
Analyze (C4H3NO2)n: C:48.70%, H:3.64%, N:14.22%.
Embodiment 2 prepares tertiary fourth oxygen acyl-L-methionyl serine methylester
Under ice bath, 996mg (4mmol) tertiary fourth oxygen acyl-METHIONINE dissolves with anhydrous THF, adds 540mg
(4mmol) I-hydroxybenzotriazole (HOBt), adds 988mg (4.8mmol) DCC and activates 0.5h.By 684mg (4.4mmol) silk
Propylhomoserin methyl ester hydrochloride is dissolved in anhydrous tetrahydro furan, adjusts pH7-8 with N-methylmorpholine (NMM), mixed liquor is added reaction bulb
In, then adjust pH7-8 with NMM, remove ice bath, room temperature reaction.TLC monitoring raw material speckle disappears, and by reacting liquid filtering, reduces pressure dense
Contracting, with acetic acid ethyl dissolution, filters, and ester layer saturated sodium bicarbonate solution is washed 3 times, saturated nacl aqueous solution 3 times, 5% sulphuric acid
Hydrogen potassium is washed 3 times, saturated sodium-chloride 3 times, and 5% sodium bicarbonate washes 3 times, and saturated sodium-chloride washes 3 times, and ester layer anhydrous sodium sulfate is done
Dry, filter, filtrate reduced in volume is to dry.Obtain 980mg (70%) title compound, for water white transparency oily thing.
Embodiment 3 prepares tertiary fourth oxygen acyl-L-methionyl-2-amino-1,3-propanediol
Under ice bath, the tertiary fourth oxygen acyl-L-methionyl serine methylester THF of 700mg (2mmol) is dissolved, slowly drip
It is added to the NaBH of 83.2mg (2.2mmol)4THF in suspension, reactant mixture stirs at room temperature, TLC detect.Reaction completes
After, hydrochloric acid (1M) adjust pH to 7, filter, be evaporated to do, wear away with methanol, filter, be concentrated under reduced pressure to give colorless oil
Thing, product separates (CH through column chromatography silica gel2Cl2: MeOH, 10: 1) obtain 386mg (60%) title compound, for colorless oil
Thing.ES I-MS(m/e)323[M+H]+；1H-NMR (300MHz, DMSO-d6): δ/ppm=7.38 (d, J=8.1Hz, 1H),
6.93 (d, J=7.8Hz, 1H), 4.60-4.63 (t, J=6.0Hz, 2H), 3.99 (m, 1H), 3.66-3.72 (m, 1H), 3.39-
3.42 (m, 4H), 2.43 (t, J=15.0Hz, 2H), 2.03 (s, 3H), 1.71-1.91 (m, 2H), 1.38 (s, 9H).
Embodiment 4 prepares tertiary fourth oxygen acyl-l-half Guang (benzyl sulfide) aminoacyl-2-amino-1,3-propanediol
According to the method for embodiment 3, from tertiary fourth oxygen acyl-L-half Guang (benzyl sulfide) the aminoacyl silk ammonia of 300mg (0.73mmol)
Acid methyl ester obtains 151.4mg (54%) title compound, for colorless solid.ESI-MS(m/e)385[M+H]+；1H-NMR (300MHz,
DMSO-d6): δ/ppm=7.38 (d, J=8.1Hz, 1H), 7.14 (m, 5H), 4.82 (m, 1H), 3.70-3.85 (m, 7H),
2.82-3.02 (dd, 2H), 1.38 (s, 9H).
Embodiment 5 prepares L-methionyl-2-amino-1,3-propanediol
Under ice bath, by 300mg (0.9mmol) tertiary fourth oxygen acyl-L-methionyl-2-amino-1,3-propanediol and 2mL chlorine
Changing hydrogen to mix ethyl acetate solution (4M), connect drying tube, be stirred at room temperature 2 hours, TLC display raw material point disappears, stopped reaction.
Ethyl acetate is removed in water pump decompression.Residue with Ethyl acetate dissolves and reduces pressure removal ethyl acetate.This operation is in triplicate.Residual
Stay thing ether dissolution the removal ether that reduces pressure.This operation is in triplicate.Methanol-diethyl ether recrystallization, obtains 200mg (97%) title
Compound, for colorless solid powder.ESI-MS(m/e)223[M+H]+；1H-NMR (300MHz, DMSO-d6): δ/ppm=8.41
(d, J=7.5Hz, 2H), 4.76 (s, 1H), 3.84 (t, J=12.3Hz, 1H), 3.74 (q, J=16.2Hz, 1H), 3.38-
3.45 (m, 4H), 2.47-2.51 (m, 2H), 2.05 (s, 3H), 1.95-2.02 (m, 2H).
Embodiment 6 prepares L-cysteinyl-2-amino-1,3-propanediol
Under ice bath, by 100mg (0.26mmol) tertiary fourth oxygen acyl-L-half Guang (benzyl sulfide) aminoacyl-2-amino-1,3-the third two
Alcohol mixes with 1m L trifluoromethanesulfonic acid, connects drying tube, and reaction 2 hour is stirred at room temperature, and TLC display raw material point disappears, stopped reaction.
Ether on the rocks makes product separate out, and repeatedly wears away with ether 3 times, filters to obtain 39.3mg (78%) title compound, for yellow oil
Shape thing.ESI-MS(m/e)195[M+H]+。
Embodiment 7 prepares poly-Radix Asparagi acyl methionyl-2-amino-1,3-propanediol (Ia)
100mg (0.45mmol) L-methionyl-2-amino-1,3-propanediol suitable quantity of water is dissolved, adjusts with triethylamine
Joint pH8, decompression pumps remaining triethylamine, it is slowly added drop-wise to the polysuccinimide containing 45mg (0.45mmol) (by fourth
Imidodicarbonic diamide molecular weight calculates) in distilled water suspension.Reacting at 40 DEG C, after reacting about 7d, reactant liquor is clarified substantially, from
The heart, supernatant, through Sephadex G10 purification, is monitored without starting material left by TLC.Lyophilizing obtains 58.0mg (40%) title thing,
For colourless powder, water solublity is good, has hygroscopicity.Mp:206-208 DEG C；[α]D 25=-19.3 (c=0.60, water)；IR
(KBr): 3385,3259,3078,2943,2644,1718,1654,1560,1400,1249,1062,997cm-1。
Embodiment 8 prepares poly-Radix Asparagi acyl cysteinyl-2-amino-1,3-propanediol (Ib)
According to the method for embodiment 5, obtain from the L-cysteinyl-2-amino-1,3-propanediol of 30mg (0.15mmol)
15.3mg (34%) title compound, for dark yellow solid, water solublity is good, has hygroscopicity.Mp:198-204 DEG C；[α]D 25
=-61.5 (c=0.40, water)；IR (KBr): 3475,2951,2366,1718,1654,1608,1527,1406,1261,
1174,1037,644,516cm-1。
Embodiment 9 is to Ia, b amino acid composition analysis
Instrument uses full-automatic amino-acid analyzer (Sykam S433D).Use anaerobism pipe nitrogen-filled seal Hydrolyze method, weigh
Sample 5mg Ia, b, in 20mL anaerobic hydrolysis pipe, add 10mL HCl (6M, the phenol containing 0.1%), by whole for sample submergences,
Put into freezing 10min in frozen water, fill high pure nitrogen 1min-2min, build cork, screwing hermetic lid after removing nitrogen immediately, incite somebody to action
Hydrolysis pipe is placed in 110 DEG C of constant temperature ovens hydrolysis 20h, cools down after having hydrolyzed, and mixing takes 0.5mL hydrolyzed solution, with 45 DEG C of concentrations
To dry, adding 2mL sample diluting liquid, concussion mixes, after filtering by 0.22 μm syringe filter, and sample introduction.Finally record Ia-b's
Access rate is respectively 13.4% and 14.9%.
Experimental example 1 evaluates the Plumbum removing activity of Ia, b
Taking the healthy ICR male mice that body weight is 18-20g, lumbar injection (0.1mL/10g) is made into acetic acid with deionized water
Lead water solution, dosage is 8.2mg Pb (CH3CO2)2·3H2O/kg, continuously injection 7 days, stop contamination, and laboratory animal is random
It is divided into 4 groups, often group 12.All animals start gavage after 48h, positive controls penicillamine (D-PA) gavage, dosage
For 0.4mmol/kg.Treatment group Ia-b gavage, dosage is 10nmol/kg, blank group matched group normal saline gavage, dosage
For 2ml/kg.
After being given daily 2h, start to collect mice 24h urine and feces；Continue 7 days, every day 1 group of mice urine, excrement divides
Not as a sample.After last administration 24h, after excision eyeball of mouse takes whole blood, de-neck is put to death, and observes internal organs change
Change, separate and take out brain, heart, liver, kidney, spleen and left femur, with whole blood in the lump as sample.
All biological specimens all use HNO3∶H2O2(2: 1) nitrification in MARS-xpress microwave nitre solution instrument is molten to becoming to clarify
Liquid, is transferred in 10mL volumetric flask, uses tri-distilled water constant volume, by Varian ICP-700ES inductively coupled plasma spectrophotometer
Lead and the content of other trace element in sample.
By Varian ICP-700ES inductively coupled plasma atomic emission institute test sample in this concentration of metal ions carry out
Data process, and calculate lead content in every gram of sample (urine is lead content in every milliliter of sample), carry out statistical test.In each tissue
The content (μ g/g) of lead list table 1 in and table 1 continues, in excrement and urine, the content (μ g/g excrement or urine μ g/mL) of lead lists table 2 in.Result
Showing, Ia, b have significant expulsion action to blood lead, and the drive row rate on heart lead, brain lead, liver lead is obvious.
The accumulation of lead in the mice with lead poisoning organ of table 1 Ia, b treatment
Lead accumulation is usedμ g/g organ represents, n=12.a) with normal saline group than p ＜ 0.05；B) with physiology salt
Water group is than p ＜ 0.01.
Table 1 continues the accumulation of lead in the mice with lead poisoning organ that Ia, b treat
Lead accumulation is usedμ g/g organ represents, n=12.
The content of lead in the mice with lead poisoning excrement of table 2 Ia-b treatment and urine
Lead content is usedμ g/mL urine orμ g/g excrement represents, n=6.a) p ＜ 0.05 compared with normal saline；
B) p ＜ 0.01. compared with normal saline
Experimental example 2Ia, b dose-effect relationship
Ia, b have also been done the investigation of dose-effect relationship by the present invention, and the dosage of 10nmol/kg/d is reduced by 10 times and 100 respectively
Times.The content (μ g/g) of the lead in each tissue lists table 3 in and table 3 continues, content (μ g/g excrement or the μ g/mL urine) row of lead in excrement and urine
Enter table 4.
The accumulation of lead in organ after Ia, the b treatment mice with lead poisoning of table 3 various dose
Lead accumulation is usedμ g/g organ represents, n=12.a) compared with Pb+NS, p ＜ 0.05；B) with Pb+NS phase
Ratio, p ＜ 0.01；C) representing the various dose of Ia respectively, unit is nmol/kg/d, the most all with；D) difference of Ib is represented respectively
Dosage, unit is nmol/kg/d, the most all with
Table 3 continues after the Ia of various dose, b treatment mice with lead poisoning the accumulation of lead in organ
Lead accumulation is usedμ g/g organ represents, n=12.a) compared with Pb+NS, p ＜ 0.05；B) with Pb+NS phase
Ratio, p ＜ 0.01；
The mice with lead poisoning excrement lead of table 4 various dose Ia-b treatment and the content of lead in urine
Lead content is usedμ g/mL urine orμ g/g excrement represents, n=6.a) p ＜ 0.05 compared with normal saline；
B) p ＜ 0.01. compared with normal saline
Experimental example 3 evaluates Ia, the b impact on indispensable element
The present invention also been evaluated Ia, the b treatment impact on essential trace element.By Varian ICP-700ES inductive
Plasma-speetrometer institute test sample in this concentration of various metallic elements carry out data process, carry out variance analysis, the results are shown in Table 5 to
Table 8.Result shows, trace element is had no significant effect by Ia, b treatment.
The content of trace element in table 5 Ia, b treatment mice with lead poisoning liver
Lead accumulation is usedμ g/g liver represents, n=12.a) p ＜ 0.01. compared with normal saline
The content of trace element in table 6 Ia, b treatment mice with lead poisoning brain
Lead accumulation is usedμ g/g brain represents, n=12.
The content of trace element in table 7 Ia, b treatment mice with lead poisoning bone
Lead accumulation is usedμ g/g bone represents, n=12.*. unit is mg/g tissue
The content of trace element in table 8 Ia, b treatment mice with lead poisoning blood
Lead accumulation is usedμ g/g blood represents, n=12.
Experimental example 4Ia acute toxicity test
As a example by Ia, ICR male mice is randomly divided into 4 groups, often group 10, respectively NS group, Ia100, Ia400,
Ia1600 (representing dosage respectively is 100nmol/kg, 400nmol/kg, 1600nmol/kg).Use disposable gavage to
Medicine, normally feeds 14 days, observes existence and the active situation of mice.Result shows, in after accepting gavage 6 hours of mice,
Do not observe tremble, jump, the toxicity performance such as tic, have no in fur exception or behavior later in the observation of 14 days is different
Often, after 14 days, all mices the most normally survive, and body weight is in normal range, do not have significant difference compared with normal saline.
Taking blood in the 15th day eyeball, put to death and dissect mice, having no the exception of each internal organs, each internal organs are also without significant difference.
Blood is done biochemical indicator test, result such as table 9.Illustrate that Ia does not has liver, nephrotoxicity.
Table 9 Ia treats mouse blood biochemical indicator table
GPT and GOT usesU/L represents, serum creatinine is usedμM represent, n=10
The diameter characterization of experimental example 5Ia, b
Ia in the present invention, b can form nanoparticle in aqueous.Present invention nano particle size instrument determines its simulation blood
Particle diameter under liquid physiological environment.Test temperature is 37 DEG C, and pH is to set up complexation group and non-complexing group, complexation group in the case of 7.4
It is initially added into Pb (NO3)2, make Pb in solution2+Concentration is 2g/mL (suitable with blood lead concentration), uses MaLvern company of Britain
Zeta Sizer (Nano-ZS90) type laser nano particle size analyzer, surveys 5 days continuously, the results are shown in Table 10.Result shows, the particle diameter of Ia
It is down to the 60-350nm after complexation by the 220-420nm before complexation, and the amplitude that the less particle diameter of concentration reduces is larger；Ib
Particle diameter be down to the 100-400nm after complexation by the 220-460nm before complexation.
The particle diameter before and after Ia under physiological environment, b network lead simulated by table 10
Experimental example 6 measures the transmission electron microscope photo of Ia, b
It is 10 by the concentration that is configured to soluble in water to Ia, b-9M solution, drops on special copper mesh, and room temperature is volatilized dry naturally, thoroughly
Penetrate ultramicroscope (TEM, JEM-200CX；JEOL, Tokyo, Japan) under observe its form and particle diameter and use photo record.Knot
Fruit shows, when concentration is 10-9Ia during M, d exist with the form of nanosphere in water.As representative photo, Fig. 2 and Fig. 3 is
The transmission electron microscope photo of Ia, b.A diameter of 25-205nm of their nanosphere.
Experimental example 7 measures the stepwise stability constant of Ia, b and bivalence lead complex
Use 211A, HANNA type pH meter, with the standard buffer solution of pH6.86 and pH4.01 calibration instrument respectively.Preparation
0.0459M KOH standard solution, 0.0912M HCl standard solution, 0.10946M plumbi nitras titer, 0.5MKCl solution.
As a example by measuring the Ia stepwise stability constant with bivalence lead complex, first precision weighing Ia48.15mg, with moving liquid
Pipe pipettes 1.5mL HCl, 6.0mL KCl, 7.5mL H respectively2O, in 50mL beaker, adds stirrer, on magnetic stirrer
Stir, pH value determination.Use 20mL base buret, load KOH standard solution, titrate.Every 0.2mLKOH, surveys one
Secondary solution ph.
Next weighs Ia48.15mg, pipettes 1.5mL HCl, 6.0mL KCl, 3.75mL H respectively with pipet2O,
3.75mLPb(NO3)2In 50mL beaker, titrate with KOH standard solution by above same method.
Protonation constants by Origin7.5 computed in software IaWithFurther according toPH Origin7.5
Software obtains stepwise stability constant K by nonlinear fitting1, K2Logarithm value.Ib and the stepwise stability constant of bivalence lead complex
The same Ia of assay method, data such as table 11.
Table 11 Ia, b and the stepwise stability constant logarithm value of bivalence lead complex
Claims (4)
1. Formulas I a, poly-Radix Asparagi acyl methionyl-2-amino-1,3-propanediol (Ia) that b represents, poly-Radix Asparagi acyl cysteinyl-2-
Amino-1,3-propanediol (Ib),
In formula, AA is L-Met, L-Cys residue.
2. the method for poly-Radix Asparagi acyl methionyl-2-amino-1,3-propanediol (Ia) of preparation claim 1, the method includes
Following steps:
1) tertiary fourth oxygen acyl-METHIONINE is converted into tertiary fourth oxygen acyl-L-methionyl serine methylester；
2) by tertiary fourth oxygen acyl-L-methionyl serine methylester NaBH4Be reduced to tertiary fourth oxygen acyl-L-methionyl-2-amino-
1,3-propylene glycol；
3) ethyl acetate solution of tertiary fourth oxygen acyl-L-methionyl-2-amino-1,3-propylene glycol hydrogen chloride is taken off tertiary fourth oxygen acyl
Base obtains L-methionyl-2-amino-1,3-propylene glycol；
4) in distilled water, pH with triethylamine regulation L-methionyl-2-amino-1,3-propanediol is 8, at 40 DEG C, with poly-
Succimide carries out reaction and generates poly-Radix Asparagi acyl methionyl-2-amino-1,3-propylene glycol (Ia).
3. the preparation method of poly-Radix Asparagi acyl cysteinyl-2-amino-1,3-propanediol (Ib) of preparation claim 1, the method
Comprise the following steps:
1) NaBH is used4Tertiary fourth oxygen acyl-L-half Guang (benzyl sulfide) aminoacyl serine methylester is reduced to tertiary fourth oxygen acyl-L-half Guang (benzyl sulfur
Ether) aminoacyl-2-amino-1,3-propylene glycol；
2) by trifluoromethanesulfonic acid, tertiary fourth oxygen acyl-L-half Guang (benzyl sulfide) aminoacyl-2-amino-1,3-propylene glycol is taken off tertiary fourth oxygen acyl group
Obtain L-cysteinyl-2-amino-1,3-propylene glycol；
3) in distilled water, pH with triethylamine regulation L-cysteinyl-2-amino-1,3-propanediol is 8, at 40 DEG C, with poly-
Succimide carries out reaction and generates poly-Radix Asparagi acyl cysteinyl-2-amino-1,3-propylene glycol (Ib).
4. claim 1 Formulas I a, poly-Radix Asparagi acyl methionyl-2-amino-1,3-propanediol (Ia) that b represents, poly-Radix Asparagi acyl half
The cystyl-2-amino-1,3-propylene glycol (Ib) effect in preparation Plumbum removing medicine.
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