HYPERBRANCHED POLYLYSINE POWDER WITH LOW POLYDISPERSITY INDEX AND PRODUCTION METHOD THEREOF

Abstract

The present application belongs to the technical field of polymer materials, and hyperbranched polylysine powder with a low polydispersity index and a production method thereof provided. The present application adopts a thermal initiation polymerization method, Compared with the traditional method, the production method of hyperbranched polylysine has the advantages of no additional steps of introducing and removing amino protecting groups, no need of activating carboxyl groups, easy purification of products, short production period, controllable molecular weight of products and low polydispersity index (1.01-1.2), and is suitable for industrial production of hyperbranched polylysine materials, especially medical-grade hyperbranched polylysine materials.

Claims

1. A production method of hyperbranched polylysine powder with a low polydispersity index, by a thermal initiation polymerization method, comprising: adding 10-90 parts by weight of an amino acid monomer, 1-10 parts by weight of alkali, and 0.01-5 parts by weight of a catalyst into a kettle reactor, heating to 120-180 C., reacting for 12-24 hours under the condition of stirring and nitrogen protection, then cooling to stop the reaction to obtain a crude product, and performing a purifying and drying treatment on the crude product to obtain the hyperbranched polylysine powder, wherein the polydispersity index PDI of the hyperbranched polylysine powder is 1.01-1.2, wherein the amino acid monomer is at least one of L-lysine, L-lysine monohydrate, L-lysine dihydrate, L-lysine acetate, L-lysine monohydrochloride, L-lysine dihydrochloride and L-lysine sulfate, wherein the alkali is at least one of ammonia hydroxide, lithium hydroxide, sodium hydroxide and potassium hydroxide, wherein the catalyst is at least one of zirconium n-butanol, titanium n-butanol, dibutyltin dilaurate, tripyridine boric acid and antimony ethoxide.

2. The production method of hyperbranched polylysine powder with a low polydispersity index according to claim 1, wherein a number average molecular weight of the hyperbranched polylysine powder is 3000-7000 Da.

3. The production method of hyperbranched polylysine powder with a low polydispersity index according to claim 1, wherein the stirring is mechanical stirring, and has a stirring speed of 300-500 rpm.

4. The production method of hyperbranched polylysine powder with a low polydispersity index according to claim 1, wherein the purifying and drying treatment comprises that: dissolving 50-100 parts by weight of the crude product in 50-200 parts by weight of alcohol, centrifuging a suspension to separate supernatant, and drying the supernatant by aerosol to obtain the hyperbranched polylysine powder.

5. The production method of hyperbranched polylysine powder with a low polydispersity index according to claim 4, wherein the alcohol is at least one of methanol and ethanol.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0017] FIG. 1 is an exhibition diagram of hyperbranched polylysine powder prepared by the present application;

[0018] FIG. 2 is a FTIR spectrum of hyperbranched polylysine prepared by the present application;

[0019] FIG. 3 is a GPC chart of hyperbranched polylysine with a number average component of 3438 Da and a dispersion of 1.19;

[0020] FIG. 4 is a GPC chart of hyperbranched polylysine with a number average component of 4899 Da and a dispersion of 1.07;

[0021] FIG. 5 is a GPC chart of hyperbranched polylysine with a number average component of 5299 Da and a dispersion of 1.11;

[0022] FIG. 6 shows the hyperbranched polylysine prepared in Comparative Example 4.

DESCRIPTION OF EMBODIMENTS

[0023] The present application will be further explained with the attached drawings and specific examples.

EXAMPLE 1

[0024] 2000 g of L-lysine sulfate, 655.7 g of solid sodium hydroxide and 2 g of dibutyltin dilaurate were added into a 5 L reactor equipped with a stirrer, an internal thermometer, an air inlet pipe, a condenser with a collector. The mixture was gradually heated to the internal temperature of 140 C., the stirring speed was 400 rpm, and the nitrogen flow rate was 50 cm.sup.3/min. After 12 hours, the heating was stopped, and a hyperbranched polylysine crude product was discharged from outlet at the bottom while it was hot. The crude product was added into 3000 mL of ethanol and fully mixed to obtain a suspension containing hyperbranched polylysine. An ethanol solution of hyperbranched polylysine was obtained after centrifugal separation of the suspension at 3000 rpm, and the solution was injected into an aerosol drying tower for drying to obtain pure hyperbranched polylysine powder.

[0025] The hyperbranched polylysine prepared in this example was yellow powder, as shown in FIG. 1.

[0026] The FTIR spectrum of hyperbranched polylysine prepared in this example is shown in FIG. 2.

[0027] The number average molecular weight of the hyperbranched polylysine prepared in this example is 3438 Da, the PDI is 1.19, and its GPC spectrum is shown in FIG. 3.

TABLE-US-00001 GPC results MW MW Distribution Mn Mw Mz Mz + 1 marker 1 marker 2 name (Dalton) (Dalton) MP (Dalton) (Dalton) Polydispersity (Dalton) (Dalton) 1 3438 4079 3513 4853 5708 1.186405

[0028] EXAMPLE 2

[0029] 2000 g of L-lysine sulfate, 600 g of solid lithium hydroxide and 2 g of zirconium n-butoxide were added into a 5 L reactor equipped with a stirrer, an internal thermometer, an air inlet pipe, a condenser and a collector. The mixture was gradually heated to the internal temperature of 140 C., the stirring speed was 400 rpm, and the nitrogen flow rate was 50 cm.sup.3/min. After 16 hours, the heating was stopped, and a hyperbranched polylysine crude product was discharged from the bottom collector while it was hot. The crude product was added into 2000 mL of ethanol and fully mixed to obtain a suspension containing hyperbranched polylysine. An ethanol solution of hyperbranched polylysine was obtained after centrifugal separation of the suspension at 3000 rpm, and the solution was injected into an aerosol drying tower for drying to obtain pure hyperbranched polylysine powder.

[0030] The number average molecular weight of the hyperbranched polylysine prepared in this example is 4899 Da, the PDI is 1.07, and its GPC spectrum is shown in FIG. 4.

TABLE-US-00002 GPC results MW MW Distribution Mn Mw Mz Mz + 1 marker 1 marker 2 name (Dalton) (Dalton) MP (Dalton) (Dalton) Polydispersity (Dalton) (Dalton) 1 4899 5250 4634 5672 6166 1.071614

[0031] EXAMPLE 3

[0032] 2000 g of L-lysine sulfate, 700 g of solid potassium hydroxide and 2 g of tripyridine boric acid were added into a 5 L reactor equipped with a stirrer, an internal thermometer, an air inlet pipe, a condenser and a collector. The mixture was gradually heated to the internal temperature of 140 C. under stirring and nitrogen protection. After 20 hours, the heating was stopped, and a hyperbranched polylysine crude product was discharged from the bottom collector while it was hot. The crude product was added into 1500 mL of ethanol and fully mixed to obtain a suspension containing hyperbranched polylysine. An ethanol solution of hyperbranched polylysine was obtained after centrifugal separation of the suspension at 3000 rpm, and the solution was injected into an aerosol drying tower for drying to obtain pure hyperbranched polylysine powder. The number average molecular weight of hyperbranched polylysine prepared in this example is 5299 Da, the PDI is 1.11, and its GPC spectrum is shown in FIG. 5.

TABLE-US-00003 GPC results MW MW Distribution Mn Mw Mz Mz + 1 marker 1 marker 2 name (Dalton) (Dalton) MP (Dalton) (Dalton) Polydispersity (Dalton) (Dalton) 1 5299 5907 5274 6625 7425 1.114665

[0033] COMPARATIVE EXAMPLE 4

[0034] Hyperbranched polylysine was prepared according to the method in the previous reported work (for example, CN111035803B, a titanium implant material with anti-infection and bone bonding promoting functions and a preparation method thereof, specification, page 2, [0014]).

[0035] A KOH solution (8.4 g dissolved in 30 mL water) was slowly dropped into a lysine hydrochloride solution (27.45 g dissolved in 50 mL water), with a molar ratio of lysine hydrochloride to KOH being 1:1, and the reaction was carried out for 4-5 h at 40 C., and then the temperature was raised to 150 C., during which the water in the reaction system was maintained timely, and the stirring was continued for 2-3-5 d. After stopping stirring, methanol was added to dissolve the melt, and then the solvent was converted into water and dialyzed for 3-5 d, followed by freezing and drying.

[0036] The total synthesis time was 3-4 days, the reaction rate was low, the post-treatment time was 3-5 days, and the period was long; during the reaction process, it was required to to add water at different reaction times according to the experience of operators, which cannot be used in automatic industrial production process; the product must be dialyzed to remove the low molecular weight polymer without antibacterial function; before dialysis, the number average molecular weight of the polymer as determined by GPC was 3860, and the PDI was 2.14; after dialysis, the number average molecular weight of the polymer as determined by GPC was 6100, and the PDI was 1.34; the obtained product (as shown in FIG. 6) was a hard block material, which could only be weighed for use after grinding.

[0037] The above-mentioned embodiment is the preferred embodiment of the present application, but the embodiment of the present application is not limited by the above-mentioned embodiment, and any other changes, modifications, substitutions, combinations and simplifications made without departing from the spirit and principle of the present application shall be equivalent substitutions, which are all included in the protection scope of the present application.