Process and device for preparing bioactive peptide medicine

Abstract

The invention relates to the technical field of peptide preparation, in particular to a preparation process and device of a bioactive peptide medicine, and the preparation process comprises the following steps: gradually synthesizing a pre-selected amino acid sequence on a solid-phase carrier to obtain a peptide fragment; purifying the synthesized peptide fragment to remove impurities; carrying out post-treatment on the peptide fragment by using an enzyme digestion system to form a target peptide with biological activity; and collecting and storing the target peptide. The invention further provides a preparation device of the bioactive peptide medicine, the preparation device comprises a solid-phase synthesis module, a purification module, an enzyme digestion reactor and a storage unit, and the solid-phase synthesis module is used for synthesizing an amino acid sequence; the purification module is used for separating and purifying the synthetic peptide fragment; the enzyme digestion reactor is used for post-treatment of the target peptide; and the storage unit is used for collecting and storing the target peptide, so that impurities in the medicine can be better removed, and the product quality is improved.

Description

Technical Field

[0001] The invention relates to the technical field of peptide preparation, and in particular to a preparation process and device for a bioactive peptide drug. Background Art

[0002] Bioactive peptide drugs are a class of short-chain molecules composed of amino acid units connected by peptide bonds. They have a variety of important physiological functions in the body and show unique therapeutic potential as drugs. These peptides are usually smaller than proteins, but more complex than simple amino acids. Their structure and sequence determine their biological activity. Bioactive peptide drugs can mimic the functions of natural peptides, such as hormones, neurotransmitters or cell signaling molecules, and are used to regulate biochemical processes in the body.

[0003] Existing bioactive peptide drugs produce a lot of impurities during the production process, which reduces the quality of the product. Summary of the invention

[0004] The purpose of the present invention is to provide a preparation process and device for a bioactive peptide drug, so as to better remove impurities in the drug and improve product quality.

[0005] To achieve the above-mentioned object, in a first aspect, the present invention provides a process for preparing a bioactive peptide drug, comprising synthesizing a preselected amino acid sequence stepwise on a solid phase carrier to obtain a peptide segment;

[0006] The synthesized peptides are purified to remove impurities;

[0007] The peptides are post-processed using an enzyme cleavage system to form target peptides with biological activity;

[0008] Collect and store the target peptide.

[0009] The solid phase carrier is a resin matrix, which allows efficient and highly selective amino acid connection.

[0010] The purification process is carried out by high performance liquid chromatography to ensure that the product purity is higher than 95%.

[0011] In a second aspect, the present invention also provides a device for preparing a bioactive peptide drug, comprising a solid phase synthesis module, a purification module, an enzyme cleavage reactor and a storage unit;

[0012] The solid phase synthesis module is used for the synthesis of amino acid sequences; the purification module is used for separating and purifying synthetic peptide segments; the enzyme cleavage reactor is used for post-processing of target peptides; the storage unit is used for collecting and storing target peptides. The solid phase synthesis module includes a base, a support frame, a synthesis component and a detection component. The support frame is fixedly connected to the base and is located on the top of the base. The synthesis component includes a reaction shell, a cover plate, a lifter, a filter screen, an agitator and a discharger. The reaction shell is fixed to the support frame, the lifter is arranged on one side of the reaction shell, the cover plate is arranged on the lifter, the agitator is arranged below the cover plate, the filter screen is arranged below the cover plate, the discharger is arranged at the bottom of the reaction shell, and the detection component is arranged on the discharger for detecting the DMF solution of the alkali solution.

[0013] Wherein, the lifter includes a lifting cylinder, a lifting rod and a buffer spring, the lifting cylinder is fixed to the reaction shell, the lifting rod is connected to the output end of the lifting cylinder and fixed to the cover plate, and the buffer spring is arranged on the lifting cylinder and the lifting rod.

[0014] Wherein, the filter includes a support rod, a filter body, a baffle and a first spring, the baffle is slidably arranged on a slip ring at the bottom of the cover plate, the first spring is arranged between the baffle and the slip ring, a slot is arranged on the slip ring, the support rod is clamped in the slot, the filter body is fixedly connected to the support rod and is located at the bottom of the support rod.

[0015] Wherein, the stirrer includes a stirring motor, a stirring rod and a stirring blade, the stirring rod is rotatably connected to the cover plate and is located below the cover plate, and the stirring blade is fixedly connected to the stirring rod and is located on one side of the stirring rod.

[0016] Wherein, the discharger includes a discharge pipe, a rotating joint, a telescopic tube, a second spring, a driver and a discharge pump, the rotating joint is rotatably arranged at the bottom of the reaction shell, the telescopic tube is slidably arranged above the rotating joint, the second spring is arranged between the rotating joint and the telescopic tube, the driver is used to drive the rotating joint to rotate, the discharge pump is arranged below the rotating joint, the discharge pipe is connected to the rotating joint, and is located in a groove opened at the bottom of the reaction shell.

[0017] The present invention provides a process and device for preparing a bioactive peptide drug, including selecting an amino acid sequence based on the structural requirements of the target bioactive peptide. This sequence is determined through extensive research and experiments to achieve the best bioactive effect. Then, using solid phase synthesis technology, single amino acid molecules are gradually added to an inert, separable solid phase carrier to construct the desired peptide chain.

[0018] After the synthesis is completed, the obtained peptide may contain some by-products or incompletely reacted raw materials. In order to ensure the purity of the final product, the peptide needs to be purified. Commonly used purification methods include high performance liquid chromatography (HPLC), reverse phase high performance liquid chromatography (RP-HPLC) and ion exchange chromatography.

[0019] The purified peptide may not be the final target bioactive peptide. It may contain additional amino acid residues or require further modification to exhibit its biological activity. At this time, the peptide can be processed by the enzymatic cleavage system, that is, the enzyme that selectively cuts certain connection sites in the peptide chain. This enzymatic cleavage treatment can transform the peptide into the final form with the desired biological activity.

[0020] The bioactive peptides formed after the above steps are finally collected. Since such substances are often very sensitive to environmental conditions, they are usually stored under strictly controlled conditions, such as low temperature and light-proof environment, to maintain their stability and activity. At the same time, for large-scale production, it is also necessary to consider how to effectively collect and package finished products on a large scale to ensure that product quality is maintained throughout the transportation and storage process. This can improve the production quality of drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0022] Figure 1 The present invention is a flow chart of a process for preparing a bioactive peptide drug.

[0023] Figure 2 It is a structural diagram of a preparation device for a bioactive peptide drug of the present invention.

[0024] Figure 3 is a structural diagram of the synthesis component of the present invention.

[0025] Figure 4 It is the right structural diagram of the synthesis component of the present invention.

[0026] Figure 5 It is the left structural diagram of the synthesis component of the present invention.

[0027] Figure 6 It is a cross-sectional structural diagram of the synthesis component of the present invention.

[0028] Figure 7 yes Figure 6 A partial enlargement of detail A.

[0029] Figure 8 yes Figure 6 A partial enlargement of detail B.

[0030] Solid phase synthesis module 101, purification module 102, enzyme cleavage reactor 103, storage unit 104, base 105, support frame 106, synthesis component 107, detection component 108, reaction shell 109, cover plate 110, lifter 111, filter 112, stirrer 113, discharger 114, lifting cylinder 115, lifting rod 116, buffer spring 117, support rod 118, filter body 119, retaining frame 120, first spring 121, stirring motor 122, stirring rod 123, stirring blade 124, discharge pipe 125, rotating joint 126, telescopic tube 127, second spring 128, driver 129, discharge pump 130, positioning block 131, third spring 132, magnetic unit 133, sensing unit 134. DETAILED DESCRIPTION

[0031] Embodiments of the present invention are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present invention, and should not be construed as limiting the present invention.

[0032] First embodiment

[0033] See also Figure 1 The present invention provides a process for preparing a bioactive peptide drug, comprising:

[0034] S101 synthesizes the preselected amino acid sequence step by step on a solid support to obtain a peptide segment;

[0035] A pre-designed amino acid sequence is selected and built step by step on a solid phase support. The solid phase support is a resin matrix that is particularly suitable for efficient connection between amino acids and can achieve highly selective chemical reactions, thus ensuring that each step of the synthesis process can be carried out accurately. The peptides synthesized in this way will serve as the basis for subsequent processing.

[0036] S102 purifies the synthesized peptides to remove impurities;

[0037] Once the peptide is synthesized, the next step is to purify it. This step is crucial because it aims to remove any impurities that may affect the quality or potency of the final product. To achieve this goal, high performance liquid chromatography (HPLC) technology is used. HPLC is a powerful separation and analysis tool that can separate the components in a mixture based on different properties such as molecular size, shape and charge. In this case, HPLC is used to ensure that the collected peptides are at least 95% pure, providing pure raw materials for subsequent processing.

[0038] S103 uses an enzyme cleavage system to post-process peptides to form biologically active target peptides;

[0039] After obtaining high-purity peptides, the next step is to use an enzyme cleavage system to post-process these peptides. The application of the enzyme cleavage system is to simulate the protein hydrolysis process that occurs in the natural environment, and release the target peptide with biological activity by cutting sites on the peptide chain. This step requires precise control, because different cutting modes may lead to different products, which in turn affect the activity and effect of the target peptide.

[0040] S104 collects and stores the target peptides.

[0041] The final step is to collect and properly store the bioactive peptides formed after the above treatment. Considering the sensitivity of biomolecules, appropriate storage conditions must be adopted to maintain their stability and activity until they are further processed into pharmaceutical preparations or directly used in clinical treatment.

[0042] Second embodiment

[0043] See also Figure 2 to Figure 8The present invention also provides a preparation device for a bioactive peptide drug, comprising a solid phase synthesis module 101, a purification module 102, an enzyme cleavage reactor 103 and a storage unit 104; the solid phase synthesis module 101 is used for the synthesis of amino acid sequences; the purification module 102 is used for separating and purifying synthetic peptide segments; the enzyme cleavage reactor 103 is used for post-processing of target peptides; the storage unit 104 is used for collecting and storing target peptides, the solid phase synthesis module 101 comprises a base 105, a support frame 106, a synthesis component 107 and a detection component 108, the support frame 106 is fixedly connected to the base 105 and is located on the base 10 5, the synthesis component 107 includes a reaction shell 109, a cover plate 110, a lifter 111, a filter 112, an agitator 113 and a discharger 114, the reaction shell 109 is fixed to the support frame 106, the lifter 111 is arranged on one side of the reaction shell 109, the cover plate 110 is arranged on the lifter 111, the agitator 113 is arranged below the cover plate 110, the filter 112 is arranged below the cover plate 110, the discharger 114 is arranged at the bottom of the reaction shell 109, and the detection component 108 is arranged on the discharger 114 for detecting the DMF solution of the alkali solution.

[0044] In this embodiment, the base 105 serves as the basic structure of the entire synthesis module, which provides stable support and carries all other components. The support frame 106 is fixedly connected to the top of the base 105, and the support frame 106 provides necessary support and positioning for the synthesis component 107.

[0045] Reaction shell 109 of synthesis component 107: This is the main container for amino acid sequence synthesis, and its internal environment is strictly controlled to ensure the best chemical reaction conditions. Cover plate 110 is located on lifter 111, which can open or close reaction shell 109 to facilitate adding raw materials or removing products. Lifter 111 is set on one side of reaction shell 109, allowing cover plate 110 to move up and down, so as to achieve the sealed or open state of reaction shell 109. Agitator 113 is installed under cover plate 110 to evenly mix the reactants to ensure that each amino acid unit can fully participate in the reaction. Filter screen 112 is also located under cover plate 110 to filter and prevent the generated amino acid sequence from leaking. Discharger 114 is located at the bottom of reaction shell 109 and is responsible for discharging the wastewater generated by the reaction. Detection component 108 is placed on discharger 114, mainly used to monitor the state of alkaline N, N-dimethylformamide (DMF) solution in wastewater, ensure that the reaction progress is as expected, and help determine when to stop the reaction and when to start the next step.

[0046] By adopting the above method, after the reaction substances are fully contacted, the filter screen 112 can be lifted up so that the peptides generated by the reaction can move upward, and the waste liquid is left at the bottom for detection, thereby making the reaction more complete.

[0047] The purification module 102 uses advanced separation technology, such as high performance liquid chromatography (HPLC), to deeply purify the crude peptide fragments obtained from the solid phase synthesis module 101 and remove possible by-products and impurities to ensure the high purity of the final product.

[0048] The purified peptides are treated by the enzyme digestion system in the enzyme digestion reactor 103. These enzymes can recognize and cut sites on the peptide chain, thereby releasing the target peptide with biological activity. This process requires precise control of parameters such as temperature and pH value to ensure the effectiveness and selectivity of the enzyme digestion reaction.

[0049] Once the target peptides are generated and verified to be qualified, they are collected in the storage unit 104, where appropriate preservation measures are taken, such as low-temperature freezing or dry storage, to maintain their stability and activity until use.

[0050] In summary, this preparation device not only integrates multiple key steps, but also realizes a one-stop solution from amino acid sequence synthesis to final product storage through carefully designed components, greatly improving the efficiency and quality of bioactive peptide drug production.

[0051] The lifter 111 includes a lifting cylinder 115, a lifting rod 116 and a buffer spring 117. The lifting cylinder 115 is fixed to the reaction shell 109. The lifting rod 116 is connected to the output end of the lifting cylinder 115 and fixed to the cover plate. The buffer spring 117 is arranged on the lifting cylinder 115 and the lifting rod 116.

[0052] The lifting cylinder 115 is used as a power source and is firmly fixed to one side of the reaction shell 109. It is the core part of the entire lifting system and is responsible for providing the required thrust and pull to drive the movement of the cover. In order to ensure the stability and accuracy of operation, the lifting cylinder 115 is made of high-performance materials and is equipped with a sophisticated control system.

[0053] One end of the lifting rod 116 is connected to the output end of the lifting cylinder 115, and the other end is fixed to the cover plate. Through this direct mechanical connection, when the lifting cylinder 115 is working, it can drive the cover plate to achieve precise rising or lowering action. The design of the lifting rod 116 takes into account strength and durability, and can maintain good performance during frequent operations.

[0054] The buffer spring 117 arranged between the lifting cylinder 115 and the lifting rod 116 plays a vital role. It can not only absorb the impact force caused by rapid movement and reduce the wear between mechanical parts, but also provide a certain elastic support to make the closing process of the cover plate softer and avoid unnecessary pressure on the internal structure of the reaction shell 109.

[0055] The filter 112 includes a support rod 118, a filter body 119, a retaining frame 120 and a first spring 121. The retaining frame 120 is slidably set on the sliding ring at the bottom of the cover plate. The first spring 121 is set between the retaining frame 120 and the sliding ring. A slot is set on the sliding ring. The support rod 118 is clamped in the slot. The filter body 119 is fixedly connected to the support rod 118 and is located at the bottom of the support rod 118.

[0056] The support rod 118 serves as a mounting base for the filter body 119. The support rod 118 is clamped in a clamping groove on the slip ring to ensure that the position of the filter body 119 is fixed. This design not only increases the stability of the filter 112, but also facilitates disassembly, cleaning or replacement.

[0057] The filter body 119 is located at the bottom of the support rod 118, and the filter body 119 directly participates in the filtering work. The material selection of the filter body 119 needs to take into account strength, chemical corrosion resistance and appropriate pore size to ensure that it can effectively block large molecular impurities while not hindering the flow of target peptides.

[0058] The retaining frame 120 is a frame structure surrounding the filter body 119, which is slidably arranged on the sliding ring at the bottom of the cover plate. The existence of the retaining frame 120 allows the filter 112 to move freely within a certain range to adapt to different operating requirements. In addition, the retaining frame 120 also provides additional support to protect the filter 112 from external force damage.

[0059] The first spring 121 is arranged between the retaining frame 120 and the slip ring, and the function of the first spring 121 is to maintain the retaining frame 120 in a proper working position to prevent the support rod 118 from sliding. When the reactant needs to be taken out, the retaining frame 120 is pushed upward so that the support rod 118 can rotate relative to the slip ring, so that the support rod 118 and the filter body 119 can be removed, making it more convenient to use.

[0060] The agitator 113 includes a stirring motor 122 , a stirring rod 123 and a stirring blade 124 . The stirring rod 123 is rotatably connected to the cover plate and is located below the cover plate. The stirring blade 124 is fixedly connected to the stirring rod 123 and is located on one side of the stirring rod 123 .

[0061] The stirring motor 122 is the power source of the entire stirring system, providing the necessary rotational force to drive the movement of the stirring rod 123 and the stirring blade 124. The motor is designed with high efficiency and low noise, which can reduce interference during operation while ensuring sufficient power output.

[0062] The stirring rod 123 is rotatably connected to the cover plate through a precise bearing structure, ensuring that it can rotate freely under the cover plate without affecting the sealing performance of the cover plate. The bearing is selected taking into account corrosion resistance and long-term reliability to cope with the harsh conditions in the chemical reaction environment.

[0063] The stirring blade 124 is firmly fixed to one side of the stirring rod 123, usually by welding, threaded connection or embedded design, to ensure that it will not loosen or fall off during high-speed rotation. The design of the blade must take into account both strength and flexibility, and can withstand certain physical stress and flexibly respond to changes in the fluid.

[0064] The shape and arrangement of the stirring blades 124 have a direct impact on the mixing effect. Common designs include straight, spiral, and paddle types, and the specific selection depends on the desired degree of mixing and the nature of the reactants. For example, spiral blades can produce better axial flow, while paddle blades are more suitable for promoting radial diffusion.

[0065] The discharger 114 includes a discharge pipe 125, a rotating joint 126, a telescopic tube 127, a second spring 128, a driver 129 and a discharge pump 130. The rotating joint 126 is rotatably arranged at the bottom of the reaction shell 109, the telescopic tube 127 is slidably arranged above the rotating joint 126, the second spring 128 is arranged between the rotating joint 126 and the telescopic tube 127, the driver 129 is used to drive the rotating joint 126 to rotate, the discharge pump 130 is arranged below the rotating joint 126, the discharge pipe 125 is connected to the rotating joint 126, and is located in a groove opened at the bottom of the reaction shell 109.

[0066] In order to more fully discharge the wastewater remaining in the reaction shell 109, the present application is provided with the discharge pipe 125. When the discharge pipe 125 is working, the second spring 128 pops out from the groove at the bottom of the reaction shell 109, and then the discharge pump 130 generates negative pressure to suck the wastewater from the multiple liquid inlets on the discharge pipe 125 and then discharge it. Then, the driver 129 is started to drive the rotating joint 126 to rotate, so that the discharge pipe 125 can rotate along the bottom of the reaction shell 109 to absorb the corresponding wastewater, so that the wastewater can be discharged more fully.

[0067] The discharger 114 also includes a positioning block 131, a third spring 132, a magnetic unit 133 and a sensing unit 134. The positioning block 131 is slidably arranged on one side of the rotating joint 126, the third spring 132 supports the positioning block 131, the magnetic unit 133 is arranged on the positioning block 131, and the sensing unit 134 is connected to the magnetic unit 133.

[0068] When resetting, the discharge pipe 125 needs to be aligned with the groove at the bottom of the reaction shell 109. At this time, the groove can be detected by the positioning block 131. Specifically, when the positioning block 131 moves to the position of the groove, the positioning block 131 can pop up under the support of the third spring 132. At this time, the magnetic unit 133 pops up following the positioning block 131, so that the magnetic change can be detected by the sensing unit 134, so that the rotation can be stopped, and then the filter body 119 is moved downward, and the discharge pipe 125 can be pressed down into the groove of the reaction shell 109, so that it can be reset.

[0069] What is disclosed above is only a preferred embodiment of the present invention, and it certainly cannot be used to limit the scope of rights of the present invention. Ordinary technicians in this field can understand that all or part of the processes of the above embodiment and equivalent changes made according to the claims of the present invention still fall within the scope of the invention.

Claims

1. A process for preparing a bioactive peptide drug, characterized in that: include: The preselected amino acid sequence is synthesized step by step on a solid support to obtain a peptide segment; The synthesized peptides are purified to remove impurities; The peptides are post-processed using an enzyme cleavage system to form target peptides with biological activity; Collect and store the target peptide.

2. The process for preparing a bioactive peptide drug according to claim 1, characterized in that: The solid support is a resin matrix that allows efficient and highly selective amino acid attachment.

3. The process for preparing a bioactive peptide drug according to claim 2, characterized in that: The purification process is achieved by high performance liquid chromatography, ensuring that the product purity is higher than 95%.

4. A preparation device for a bioactive peptide drug, applied to the preparation process of a bioactive peptide drug according to claim 1, comprising a solid phase synthesis module, a purification module, an enzyme cleavage reactor and a storage unit; the solid phase synthesis module is used for the synthesis of amino acid sequences; the purification module is used for separating and purifying synthetic peptide segments; the enzyme cleavage reactor is used for post-processing of target peptides; the storage unit is used for collecting and storing target peptides, characterized in that: The solid phase synthesis module includes a base, a support frame, a synthesis component and a detection component. The support frame is fixedly connected to the base and is located on the top of the base. The synthesis component includes a reaction shell, a cover plate, a lifter, a filter screen, an agitator and a discharger. The reaction shell is fixed to the support frame, the lifter is arranged on one side of the reaction shell, the cover plate is arranged on the lifter, the agitator is arranged below the cover plate, the filter screen is arranged below the cover plate, the discharger is arranged at the bottom of the reaction shell, and the detection component is arranged on the discharger for detecting the DMF solution of the alkali solution.

5. The device for preparing a bioactive peptide drug according to claim 4, characterized in that: The lifter comprises a lift cylinder, a lift rod and a buffer spring. The lift cylinder is fixed to the reaction shell. The lift rod is connected to the output end of the lift cylinder and fixed to the cover plate. The buffer spring is arranged on the lift cylinder and the lift rod.

6. The device for preparing a bioactive peptide drug according to claim 5, characterized in that: The filter includes a support rod, a filter body, a baffle and a first spring. The baffle is slidably arranged on a slip ring at the bottom of the cover plate. The first spring is arranged between the baffle and the slip ring. A slot is arranged on the slip ring. The support rod is clamped in the slot. The filter body is fixedly connected to the support rod and is located at the bottom of the support rod.

7. The device for preparing a bioactive peptide drug according to claim 6, characterized in that: The stirrer comprises a stirring motor, a stirring rod and a stirring blade. The stirring rod is rotatably connected to the cover plate and is located below the cover plate. The stirring blade is fixedly connected to the stirring rod and is located on one side of the stirring rod.

8. The device for preparing a bioactive peptide drug according to claim 7, characterized in that: The discharger includes a discharge pipe, a rotating joint, a telescopic tube, a second spring, a driver and a discharge pump. The rotating joint is rotatably arranged at the bottom of the reaction shell, the telescopic tube is slidably arranged above the rotating joint, the second spring is arranged between the rotating joint and the telescopic tube, the driver is used to drive the rotating joint to rotate, the discharge pump is arranged below the rotating joint, and the discharge pipe is connected to the rotating joint and is located in a groove opened at the bottom of the reaction shell.

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