Intermittent reaction production process of hyperbranched polylysine

Abstract

The invention discloses a batch reaction production process of hyperbranched polylysine, which comprises the following steps: by taking a 50% feed-grade L-lysine solution as a raw material, preparing, evaporating, polymerizing and recovering a product, and producing HBPL with the molecular weight of more than 20,000 Da in a special reactor with the volume of 2500-10,000 liters. In the evaporation stage, moisture is removed by adopting a controlled heating rate (not more than 50 DEG C / h before 160 DEG C and not more than 30 DEG C / h before 200 DEG C) and high-torque stirring; the polymerization stage is carried out at 200-210 DEG C for 1-3 hours, and the stirring speed can be adjusted to 120 rpm; in the product recovery stage, condensate water is rapidly added for dilution to 60% solution, and the solution is cooled to 40 DEG C or below. The process is efficient, extensible, stable in product quality and suitable for industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical engineering, and in particular to a batch reaction production process for hyperbranched polylysine. Background Art

[0002] Hyperbranched polylysine (HBPL) has broad application prospects in gene delivery, antimicrobial agents, and biomedical materials due to its highly branched structure. Traditional production methods mostly use solid raw materials such as L-lysine hydrochloride, which is thermally polymerized at 150-180°C under alkaline conditions. This requires dissolving or melting the solid raw materials, which increases the complexity of the process. In addition, when the production is scaled up, it is easy to cause unstable product quality due to uneven mixing. Some processes require catalysts, which introduce impurities and increase purification costs. In the existing technology, there are few reports on intermittent processes starting from liquid L-lysine solutions, which are difficult to meet the efficiency and consistency requirements of large-scale production.

[0003] This invention provides a batch reaction process starting with a 50% feed-grade L-lysine solution. Through precise temperature and agitation control, combined with a specialized reactor design, it enables the efficient production of HBPL with a molecular weight greater than 20,000 Da. This process requires no catalysts, simplifies operation, and is suitable for industrial application, filling a technological gap in the production of HBPL from liquid feedstocks. Summary of the Invention

[0004] The purpose of this section is to summarize some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of this application to avoid obscuring the purpose of this section, the abstract and the title of the invention, and such simplifications or omissions should not be used to limit the scope of the present invention.

[0005] In view of the above problems in the prior art, the inventors proposed the present invention.

[0006] Therefore, the object of the present invention is to overcome the deficiencies in the prior art and provide a batch reaction production process for hyperbranched polylysine.

[0007] To solve the above technical problems, the present invention provides the following technical solution: a batch reaction production process for hyperbranched polylysine, comprising the following steps: 1.

[0008] (a) charging a 50% feed grade L-lysine solution into a stainless steel reactor with a capacity of 2500-10000 liters, with at least 30% extra space reserved in the reactor;

[0009] (b) adding 0.05% by weight of a silicone defoamer to the solution to control bubble generation during the reaction;

[0010] (c) evaporating water from the solution at a controlled heating rate to obtain a concentrated lysine mixture, wherein the heating rate does not exceed 50° C. / h before 160° C. and does not exceed 30° C. / h between 160° C. and 200° C., and the initial stirring speed is 30 rpm, which is increased to 60-100 rpm at 160° C.;

[0011] (d) polymerizing the concentrated lysine mixture at 200-210° C. for 1-3 hours with a stirring speed of 120 rpm and a processing viscosity of up to 2,000 mPa·s to form a hyperbranched polylysine having a molecular weight greater than 20,000 Da;

[0012] (e) rapidly adding condensed water within 5 minutes to dilute the hyperbranched polylysine to a 60% solution, wherein the condensed water is the water collected during the evaporation stage;

[0013] (f) cooling the hyperbranched polylysine solution to below 40° C. and unloading the solution into a 1000-liter IBC container through a discharge pipe having a diameter of not less than 150 mm.

[0014] As a preferred embodiment of the batch reaction production process of hyperbranched polylysine described in the present invention, the reactor is equipped with a thermal oil jacketed heating system with a heating temperature of up to 240° C. Thermal oil is used as the heating medium, avoiding the use of coil heating to prevent material agglomeration.

[0015] As a preferred embodiment of the batch reaction production process for hyperbranched polylysine of the present invention, in the evaporation step, the ammonia and sulfur dioxide generated in the reactor are treated by a reflux column and a Liebig-type condenser connected to the top, and a gas outlet and a condensed water receiver are provided after the condenser.

[0016] As a preferred embodiment of the batch reaction production process for hyperbranched polylysine of the present invention, in the polymerization step, nitrogen or negative pressure is applied to the reactor, with the nitrogen pressure being 0.05-0.1 MPa and the negative pressure being -0.01 to -0.05 MPa, to accelerate the discharge of condensate and reduce side reactions.

[0017] As a preferred solution of the batch reaction production process of hyperbranched polylysine described in the present invention, the reactor is made of stainless steel with corrosion resistance and is equipped with a cooling system to reduce the product temperature to below 40°C through a heat exchanger.

[0018] As a preferred embodiment of the batch reaction production process of hyperbranched polylysine described in the present invention, the stirring device is a high-torque stirrer, which mixes close to the reactor wall and has an adjustable speed within the range of 30-120 rpm, meeting the requirement of processing viscosities up to 2,000 mPa.s.

[0019] As a preferred solution of the batch reaction production process of hyperbranched polylysine of the present invention, the condensed water contains components such as sulfate, nitrate and ammonium, which are recovered through the condenser and then used in the dilution step.

[0020] As a preferred embodiment of the batch reaction production process of hyperbranched polylysine of the present invention, the molecular weight of the hyperbranched polylysine is greater than 20,000 Da as determined by gel permeation chromatography (GPC), the purity is greater than 97.5% as determined by high performance liquid chromatography (HPLC), and the yield is greater than 94%.

[0021] As a preferred solution of the batch reaction production process of hyperbranched polylysine described in the present invention, the process does not require the addition of a catalyst and directly forms hyperbranched polylysine through thermal polymerization, thereby reducing the risk of impurity introduction and simplifying subsequent purification.

[0022] As a preferred solution of the batch reaction production process of hyperbranched polylysine described in the present invention, the reactor is equipped with a temperature and torque control system to monitor the jacket temperature, reactor fluid temperature and agitator torque in real time to ensure precise control of process parameters.

[0023] Beneficial effects of the present invention: Starting with a 50% feed-grade L-lysine solution, the present invention simplifies raw material processing and reduces operational complexity. Precise temperature control (50°C / h before 160°C, 30°C / h before 200°C) and high-torque stirring (up to 120 rpm) optimize the evaporation and polymerization processes, ensuring a HBPL molecular weight greater than 20,000 Da, a purity exceeding 97.5%, and a yield exceeding 94%. A dedicated reactor (2,500-10,000 liters) supports large-scale production, with thermal oil jacket heating to prevent agglomeration and a gas control system to improve emission efficiency, making it suitable for industrial applications.

[0024] Compared to traditional solid raw material processes, this method requires no catalyst, reducing impurities and purification costs. Rapid dilution and cooling steps effectively terminate the reaction, prevent side reactions, and maintain product consistency. The process is simple to operate, low-cost, and produces consistent product quality, providing a reliable solution for the industrial production of HBPL and meeting the needs of the biomedical and antimicrobial fields. DETAILED DESCRIPTION

[0025] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0026] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0027] Secondly, the term "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in various places throughout this specification does not necessarily refer to the same embodiment, nor does it constitute a separate or selective embodiment that is mutually exclusive with other embodiments.

[0028] Example 1

[0029] This embodiment provides a batch reaction production process for hyperbranched polylysine, specifically, production in a 2500-liter reactor.

[0030] Equipment and Materials: A 2500-liter stainless steel reactor (total volume 3250 liters, 30% reserved headroom) equipped with a thermal oil jacketed heating system (maximum 240°C), a high-torque stirrer (maximum 120 rpm), and a Liebig-type condenser was used. 2000 kg of 50% feed-grade L-lysine solution (solids content 1000 kg, viscosity 400 mPa·s) and 1 kg of a 0.05% silicone defoamer were loaded.

[0031] Preparation stage: pump the raw materials into the reactor through the large-diameter inlet (diameter 200 mm), add the defoaming agent through the additional inlet, stir at a speed of 30 rpm, mix evenly, and the initial temperature is 25°C.

[0032] Evaporation Stage: Heat to 160°C at 45°C / h (3 hours), stir at 30 rpm, and mix close to the reactor wall. Viscosity increases to 3200 mPa.s at 160°C, stir to 60 rpm, and torque increases to eight times the initial value. Heat to 200°C at 30°C / h (1.3 hours), allowing complete evaporation of water, for a total of 4.3 hours. The generated gases (ammonia and sulfur dioxide) are processed through a condenser and gas outlet, and the condensed water is collected in a receiver.

[0033] Polymerization stage: Polymerization was carried out at 200°C for 2 hours, with a stirring speed of 120 rpm and nitrogen gas (0.1 MPa). The viscosity dropped to 2000 mPa·s, and lysine was polycondensed to form HBPL. The condensate was discharged through a reflux column and condenser.

[0034] Product recovery: Add 500 kg of condensed water (containing sulfate, nitrate, and ammonium) within 5 minutes to dilute to 60% solution. Cool to 35°C using a heat exchanger and unload into a 1000-liter IBC container through a discharge pipe (150 mm diameter).

[0035] Product characteristics: Molecular weight determined by gel permeation chromatography (GPC) is 25,300 Da; purity determined by high performance liquid chromatography (HPLC) is 98.0%, and yield is 95.0%.

[0036] A controlled heating rate avoids local overheating and protects the active amino and carboxyl groups of lysine. A polymerization temperature of 200°C promotes polycondensation, while a 2-hour reaction time balances molecular weight with the risk of side reactions. Rapid dilution terminates the reaction, ensuring high purity.

[0037] Example 2

[0038] This embodiment provides a batch reaction production process for hyperbranched polylysine, specifically, production in a 5000-liter reactor.

[0039] Equipment and Materials: A 5,000-liter stainless steel reactor (total volume 6,500 liters) equipped with a thermal oil jacket heating system, a high-torque agitator, and a gas control system was used. 4,000 kg of 50% feed-grade L-lysine solution (solids content 2,000 kg) and 2 kg of silicone defoamer were loaded.

[0040] Preparation stage: pump the raw materials in through the inlet, add the defoamer and stir at 30 rpm, initial temperature 25 ° C.

[0041] Evaporation stage: Heat to 160°C at 48°C / h (2.9 hours), stirring at 30 rpm. Viscosity increases to 3200 mPa.s at 160°C, stirring at 80 rpm. Heat to 210°C at 28°C / h (1.8 hours), evaporating water for a total of 4.7 hours. The gas passes through a condenser, and the condensed water is collected.

[0042] Polymerization stage: Polymerization was carried out at 210°C for 1.5 hours, with a stirring speed of 120 rpm and negative pressure (-0.05 MPa). The viscosity was approximately 1800 mPa·s. The condensate was discharged through a condenser.

[0043] Product recovery: Add 1000kg of condensed water within 5 minutes, dilute to 60% solution, cool to 38℃, and unload into a 1000L IBC container

[0044] Product characteristics: molecular weight 28,000Da, purity 97.7%, yield 96.0%.

[0045] 210°C accelerates polycondensation, shortens reaction time, and negative pressure promotes the removal of volatiles and reduces side reactions. 80 rpm stirring speed is suitable for large-volume systems, ensuring uniformity and reducing the risk of gelation.

[0046] Example 3

[0047] This embodiment provides a batch reaction production process for hyperbranched polylysine, specifically, production in a 10,000-liter reactor.

[0048] Equipment and Materials: A 10,000-liter stainless steel reactor (total volume 13,000 liters) equipped with a thermal oil jacketed heating system, a high-torque agitator, and a condensing system was used. 8,000 kg of 50% feed-grade L-lysine solution (solids content 4,000 kg) and 4 kg of a silicone defoamer were loaded.

[0049] Preparation stage: Raw materials and defoaming agent were pumped into the reactor, stirred at 30 rpm, and the initial temperature was 25°C.

[0050] Evaporation stage: Heat at 40°C / h to 160°C (3.5 hours), stirring at 30 rpm. Viscosity increases to 3300 mPa·s at 160°C, stirring at 100 rpm. Heat at 25°C / h to 205°C (1.8 hours), total time 5.3 hours. Gases are collected via a condenser.

[0051] Polymerization stage: polymerization at 205°C for 3 hours, stirring speed 120 rpm, nitrogen gas (0.1 MPa) applied. Viscosity about 1900 mPa·s.

[0052] Product recovery: Add 2000 kg of condensed water within 5 minutes, dilute to 60% solution, cool to 40 ° C, and unload into a 1000 liter IBC container.

[0053] Product characteristics: molecular weight 26,500Da, purity 98.2%, yield 94.8%.

[0054] Technical Analysis: A 3-hour polymerization time promotes molecular chain growth, and a temperature of 205°C balances reaction rate and stability. A stirring speed of 100 rpm ensures uniformity in large-scale systems, and nitrogen protection reduces oxidation risks.

[0055] This process uses a 50% feed-grade L-lysine solution (50% solids, initial viscosity approximately 400 mPa.s) as raw material to produce hyperbranched polylysine with a molecular weight greater than 20,000 Da through a batch reaction. The process consists of four stages: preparation, evaporation, polymerization, and product recovery:

[0056] Preparation: L-lysine solution and 0.05% silicone defoamer are added to a stainless steel reactor with a volume of 2,500-10,000 liters. The defoamer reduces the surface tension of the solution, suppressing bubbles generated by rapid water vaporization during evaporation, thereby preventing reaction system instability and equipment clogging. Silicone defoamer is selected for its chemical inertness and high efficiency, and is added at a minimum of 0.05% to ensure it does not interfere with subsequent polymerization reactions.

[0057] Evaporation Stage: Water is evaporated from the solution using a thermal oil jacketed heating system (maximum 240°C). The heating rate is strictly controlled (no more than 50°C / h before 160°C and no more than 30°C / h before 200°C). The key to this stage is controlling the rate of water removal to prevent rapid heating that could lead to local overheating or a sharp increase in viscosity. A solution with an initial viscosity of 400 mPa.s reaches its maximum viscosity (approximately 3200 mPa.s) at 160°C due to increased intermolecular friction caused by strengthened hydrogen bonds between lysine molecules and reduced water content. Low-speed, high-torque stirring (initial 30 rpm, increasing to 60-100 rpm at 160°C) is used close to the reactor wall to ensure even heat distribution and avoid localized coking. Evaporation takes approximately three hours, producing gases such as ammonia and sulfur dioxide. These gases are processed through a Liebig condenser, and the condensed water is collected for subsequent use.

[0058] Polymerization stage: After the water has completely evaporated, the system is heated to 200-210°C and thermal polymerization is carried out for 1-3 hours. L-lysine forms a hyperbranched structure through the condensation reaction of amino and carboxyl groups, with a molecular weight greater than 20,000 Da. High temperature promotes intermolecular dehydration condensation to produce highly branched polylysine. The stirring speed can be adjusted to 120 rpm, and solutions with viscosities up to 2,000 mPa.s can be processed to ensure the uniformity of the reaction system. Nitrogen or negative pressure (0.05-0.1 MPa or -0.01 to -0.05 MPa) accelerates the discharge of condensate and reduces the risk of side reactions (such as oxidation or cross-linking). Precise control of polymerization temperature and time is key to achieving high molecular weight and consistent branching.

[0059] Product Recovery Stage: After polymerization is complete, condensed water (containing sulfate, nitrate, and ammonium) is rapidly added within 5 minutes to dilute the solution to a 60% solution. This step rapidly terminates the reaction by reducing the system viscosity and temperature, preventing overpolymerization. After cooling to below 40°C, the product is unloaded into a 1000-liter IBC container through a large-diameter discharge pipe (diameter ≥ 150mm). A heat exchanger is used to assist cooling if necessary to ensure product stability and fluidity.

[0060] This process uses a 50% feed-grade L-lysine solution as the raw material. Compared to traditional solid raw materials (such as L-lysine hydrochloride), it does not require a dissolution or melting step, simplifying the operation and reducing energy consumption. Liquid raw materials are easy to pump and load, making them suitable for large-scale continuous feeding.

[0061] The staged heating rate (50°C / h before 160°C, 30°C / h before 200°C) avoids local overheating and protects the lysine molecular structure. The thermal oil jacketed heating system provides uniform heat, superior to coil heating, and prevents material agglomeration.

[0062] The high torque stirrer (speed 30-120 rpm) adapts to viscosity changes (400-3200 mPa.s), ensures the uniformity of the reaction system, and reduces local high viscosity areas.

[0063] Nitrogen or negative pressure accelerates condensate discharge and reduces the risk of ammonia and sulfur dioxide corrosion to the reactor and the environment.

[0064] Furthermore, the reactor is designed to have a volume of 2,500-10,000 liters, with 30% extra space reserved to accommodate volume expansion and efficient mixing.

[0065] Stainless steel is corrosion-resistant and suitable for handling solutions containing sulfates and nitrates.

[0066] Liebig-type condensers and reflux columns effectively treat volatile gases, recover condensed water for dilution, and reduce wastewater discharge.

[0067] Efficient recovery: Rapid dilution (within 5 minutes) to 60% solution, combined with heat exchanger cooling to below 40 ° C, to ensure product fluidity and facilitate unloading and storage.

[0068] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A batch reaction production process for hyperbranched polylysine, characterized in that: The following steps are involved: (a) charging a 50% feed grade L-lysine solution into a stainless steel reactor with a capacity of 2500-10000 liters, with at least 30% extra space reserved in the reactor; (b) adding 0.05% by weight of a silicone defoamer to the solution to control bubble generation during the reaction; (c) evaporating water from the solution at a controlled heating rate to obtain a concentrated lysine mixture, wherein the heating rate does not exceed 50° C. / h before 160° C. and does not exceed 30° C. / h between 160° C. and 200° C., and the initial stirring speed is 30 rpm, which is increased to 60-100 rpm at 160° C.; (d) polymerizing the concentrated lysine mixture at 200-210° C. for 1-3 hours with a stirring speed of 120 rpm and a processing viscosity of up to 2,000 mPa·s to form a hyperbranched polylysine having a molecular weight greater than 20,000 Da; (e) rapidly adding condensed water within 5 minutes to dilute the hyperbranched polylysine to a 60% solution, wherein the condensed water is the water collected during the evaporation stage; (f) cooling the hyperbranched polylysine solution to below 40° C. and unloading the solution into a 1000-liter IBC container through a discharge pipe having a diameter of not less than 150 mm.

2. The batch reaction production process for hyperbranched polylysine according to claim 1, wherein: The reactor is equipped with a thermal oil jacket heating system with a heating temperature of up to 240°C. Thermal oil is used as the heating medium, avoiding the use of coil heating to prevent material agglomeration.

3. The batch reaction production process for hyperbranched polylysine according to claim 2, wherein: In the evaporation step, ammonia and sulfur dioxide generated in the reactor are processed through a reflux column and a Liebig-type condenser connected at the top, and a gas outlet and a condensed water receiver are provided after the condenser.

4. The batch reaction production process for hyperbranched polylysine according to claim 1, wherein: During the polymerization step, nitrogen or negative pressure is applied in the reactor, with the nitrogen pressure being 0.05-0.1 MPa and the negative pressure being -0.01 to -0.05 MPa, to accelerate the discharge of condensate and reduce side reactions.

5. The batch reaction production process for hyperbranched polylysine according to claim 1, wherein: The reactor is made of stainless steel, which is corrosion-resistant, and is equipped with a cooling system to reduce the product temperature to below 40°C through a heat exchanger.

6. The batch reaction production process for hyperbranched polylysine according to claim 1, wherein: The stirring device is a high-torque stirrer, which mixes close to the reactor wall and has an adjustable speed within the range of 30-120 rpm, meeting the needs of processing viscosities up to 2,000 mPa.s.

7. The batch reaction production process for hyperbranched polylysine according to claim 1, wherein: The condensed water contains components such as sulfate, nitrate and ammonium, which are recovered through the condenser and used in the dilution step.

8. The batch reaction production process for hyperbranched polylysine according to claim 1, wherein: The molecular weight of the hyperbranched polylysine is greater than 20,000 Da as determined by gel permeation chromatography (GPC), the purity is greater than 97.5% as determined by high performance liquid chromatography (HPLC), and the yield is greater than 94%.

9. The batch reaction production process for hyperbranched polylysine according to claim 1, wherein: The process does not require the addition of a catalyst and directly forms hyperbranched polylysine through thermal polymerization, thereby reducing the risk of impurity introduction and simplifying subsequent purification.

10. The batch reaction production process for hyperbranched polylysine according to claim 1, wherein: The reactor is equipped with a temperature and torque control system to monitor the jacket temperature, reactor fluid temperature and agitator torque in real time to ensure precise control of process parameters.