Negative pressure concentration system and method for rhinotrichine

By using a negative pressure concentration system and method, and combining a vacuum pump and a stirring paddle, rapid concentration of glandersin was achieved, solving the problems of low concentration efficiency and poor activity, protecting the biological activity of glandersin, and shortening the production cycle.

CN121360385APending Publication Date: 2026-01-20DALIAN UNIV
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Patent Information

Application Number
CN202511444307.5
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-10-10
Publication Date
2026-01-20

AI Technical Summary

Technical Problem

Existing technologies for melilotinib have low concentration efficiency, poor activity after concentration, long production cycles, and high-temperature environments lead to a decline in product quality.

Method used

A negative pressure concentration system is adopted, which uses a vacuum pump to create a negative pressure environment inside the tank. Combined with a stirring paddle, the culture medium is heated evenly and kept in a boiling state. Rapid evaporation is achieved by lowering the boiling point of the liquid, and the temperature of the culture medium is controlled at 65-70℃, with the help of jacketed steam heating.

Benefits of technology

The concentration time was shortened, the biological activity of glandersin was protected, the concentration efficiency was improved, the high temperature exposure time was reduced, and the effectiveness of glandersin was guaranteed.

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Abstract

The invention relates to the technical field of biological diagnosis product production equipment, in particular to a negative pressure concentration system and method for rhinotrichine. Comprising a reaction tank, the upper part of the reaction tank is provided with a stirrer, a feed port and a vacuumizing port, and the vacuumizing port is connected with a vacuum pump through a second pipeline; the bottom of the reaction tank is provided with a discharge port; the output end of the stirrer is connected with a stirring paddle in the tank; and the outer wall of the reaction tank is provided with a steam inlet and a steam outlet which are communicated with the interlayer. The system constructs a negative pressure environment in the tank through the vacuum pump, and cooperates with the stirring paddle to uniformly heat a culture solution and maintain boiling, so that water evaporation is accelerated; the boiling point is reduced by utilizing negative pressure, only the temperature of the culture solution needs to be controlled at 65-70 DEG C, single-batch concentration only needs 12-15 hours, the period is shortened by 60%-75%, the high-temperature exposure time of the rhinotrichine is greatly shortened, the biological activity of the rhinotrichine is protected, and the problem of quality reduction caused by high temperature in a traditional process is avoided.
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Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological diagnostic product production equipment, in particular to a negative pressure concentration system and method for lepromin. BACKGROUND

[0002] Lepromin is a core biological product for diagnosing equine leprosy, which is made based on the principle of allergen and divided into two types of crude lepromin and purified lepromin. The activity directly determines the accuracy of the diagnostic results, so the concentration efficiency and activity retention need to be considered during production.

[0003] Currently, the industry generally uses a natural evaporation concentration method of a sandwiched open reaction kettle. The lepromin culture solution is injected into an open reaction kettle with a heating sandwich, the high-temperature steam is introduced into the sandwich to maintain the temperature of the culture solution in the kettle at about 98℃, and the water is removed by natural evaporation under high-temperature environment to finally achieve a 10-fold concentration target.

[0004] However, in the open system of the open reaction kettle, the water evaporation rate is slow, and a single batch of concentration needs to be continued for 48-60 hours. The long production cycle not only reduces the equipment utilization rate and production capacity, but also prolongs the exposure time of lepromin in a high-temperature environment, and the concentration efficiency is low. At the same time, the high temperature of 98℃ will reduce the activity of lepromin. SUMMARY

[0005] In order to solve the technical problems of low concentration efficiency and poor activity after concentration of lepromin in the prior art, the present application provides a negative pressure concentration system and method for lepromin, Therefore, the present application provides the following technical solutions: A negative pressure concentration system for lepromin, comprising a reaction kettle, a stirrer arranged on the upper part of the reaction kettle, a feed inlet and a vacuum outlet communicated with the internal cavity of the reaction kettle, the vacuum outlet being connected with a vacuum pump through a second pipeline; a discharge outlet communicated with the internal cavity of the reaction kettle is arranged at the bottom of the reaction kettle; the output end of the stirrer is connected with a stirring paddle located in the reaction kettle; a sandwich is arranged in the wall of the reaction kettle, and a steam inlet and a steam outlet communicated with the sandwich are arranged on the outer wall of the reaction kettle.

[0006] Further, a compressed air inlet communicated with the internal cavity of the reaction kettle is arranged on the upper part of the reaction kettle, and the compressed air inlet is connected with an air compressor through a first pipeline.

[0007] Further, a thermometer and a pressure gauge are installed on the wall of the reaction kettle, and the detection ends of the thermometer and the pressure gauge are located in the cavity of the reaction kettle.

[0008] Further, independent valves are respectively arranged on the pipelines connected with the feed inlet, the discharge outlet, the steam inlet, the steam outlet, the compressed air inlet and the vacuum outlet.

[0009] Further, the vacuum pump is a water ring vacuum pump.

[0010] A method for negative pressure concentration of lepromin based on the negative pressure concentration system for lepromin, comprising the following steps: The lepromin culture solution to be concentrated is injected into the reaction tank through the feed inlet on the upper part of the reaction tank; Steam is introduced into the interlayer of the reaction tank; The stirrer is started to make the stirring paddle stir the lepromin culture solution; The vacuum pump is started to perform vacuumization on the reaction tank to generate negative pressure in the reaction tank and perform concentration operation; When the lepromin culture solution concentration is completed, the vacuum pump is closed, compressed air is introduced into the reaction tank through the compressed air inlet, and the concentrated lepromin culture solution is discharged through the discharge port.

[0011] Further, the step of introducing steam into the interlayer of the reaction tank ensures that the pressure in the interlayer is 0.08-0.1 MPa, and at the same time, the temperature of the lepromin culture solution in the reaction tank is uniformly reached 65-80 DEG C.

[0012] Advantages and positive effects of the present application: The negative pressure concentration system of the present application constructs a negative pressure environment in the tank by means of the vacuum pump, cooperates with the stirring paddle to make the culture solution uniformly heated and maintained in a boiling state, accelerates water evaporation, and only needs 12-15 hours for single batch concentration, and the production cycle is shortened by 60%-75%.

[0013] The negative pressure concentration system of the present application utilizes the principle of reducing liquid boiling point in negative pressure environment, only needs to control the culture solution temperature at 65-70 DEG C, and can realize rapid evaporation by maintaining boiling. The lower heating temperature combined with the shortened concentration time greatly reduces the exposure time of lepromin in high temperature environment, protects the biological activity of lepromin, effectively avoids the problem of product quality decline caused by high temperature in the traditional process, and guarantees the use effect of lepromin. BRIEF DESCRIPTION OF DRAWINGS

[0014] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced. Obviously, the drawings in the following description are some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor.

[0015] Figure 1 The structural principle diagram of the negative pressure system provided by the present application.

[0016] In the diagram: 1. Vacuum port; 2. Feed inlet; 3. Agitator; 4. Second pipeline; 5. Steam outlet; 6. Water ring vacuum pump; 7. Discharge port; 8. Jacket; 9. Reactor; 10. Steam inlet; 11. Compressed air inlet; 12. Pressure gauge; 13. First pipeline; 14. Agitator. Detailed Implementation

[0017] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0018] This invention provides a negative pressure concentration system for melilotinib, such as... Figure 1 As shown, the system includes a reaction vessel 9. The upper part of the reaction vessel 9 is equipped with a stirrer 14, a feed inlet 2, a vacuum port 1, and a compressed air inlet 11, all communicating with the internal cavity of the reaction vessel 9. The output end of the stirrer 14 is connected to a stirring paddle 3, which is located inside the reaction vessel 9. The vacuum port 1 is connected to a vacuum pump 6 via a second pipeline 4; the vacuum pump 6 is a water ring vacuum pump. The compressed air inlet 11 is connected to an air compressor via a first pipeline 13. The water ring vacuum pump uses water as a medium, which can absorb water vapor and trace impurities generated during the concentration process, reducing pump blockage or corrosion, extending equipment life, and providing moderate vacuum strength, effectively preventing excessive or insufficient pressure within the reaction vessel 9 cavity, which could affect the negative pressure concentration operation.

[0019] The bottom of the reaction vessel 9 is provided with a discharge port 7 that communicates with the internal cavity of the reaction vessel 9. The inner wall of the reaction vessel 9 is provided with a jacket 8, and the outer wall of the reaction vessel 9 is provided with a steam inlet 10 and a steam outlet 5 that communicate with the jacket.

[0020] A thermometer and a pressure gauge 12 are installed on the wall of the reaction vessel 9, and the detection ends of the thermometer and pressure gauge 12 are located inside the cavity of the reaction vessel 9.

[0021] Valves are installed at the feed inlet 2, discharge outlet 7, steam inlet 10, steam outlet 5, compressed air inlet 11, and vacuum port 1.

[0022] A method for negative pressure concentration of melilotinib based on the aforementioned negative pressure concentration system for melilotinib includes the following steps: The nose leptin culture liquid to be concentrated is injected into the reaction tank through the feed inlet at the upper part of the reaction tank, and the valve at the feed inlet is closed after the injection is completed. At this time, the reaction tank forms a relatively closed cavity, which provides a basis for subsequent negative pressure concentration and temperature control, and at the same time ensures that the culture liquid will not leak due to pressure changes in subsequent operations.

[0023] The valve at the steam inlet is opened, steam is introduced into the interlayer in the wall of the reaction tank, and the steam circulation rate is adjusted through the steam outlet to stabilize the pressure in the interlayer at 0.08-0.1 MPa. The steam exchanges heat with the cavity of the reaction tank through the interlayer, and transfers heat to the nose leptin culture liquid in the tank; at the same time, the thermometer and pressure gauge on the wall of the reaction tank monitor the temperature and pressure in the tank in real time, to ensure that the temperature of the culture liquid is uniformly raised to 65-70℃, which avoids the destruction of the activity of nose leptin by high temperature and provides a suitable basic temperature for subsequent negative pressure evaporation. The steam pressure in the interlayer is generally 0.08-0.1 MPa, which is to ensure that the temperature of the nose leptin stock solution in the tank is maintained at 65-70℃. The temperature in the tank is adjusted appropriately according to the temperature in the tank. The interlayer steam provides heat to the tank, and due to heat loss from the outer wall, plus the heat absorption required for evaporation of the nose leptin stock solution in the tank, the temperature and pressure in the tank are maintained within the normal operating range.

[0024] The stirrer at the upper part of the reaction tank is started, and the stirrer drives the stirring paddle in the tank to rotate at a uniform speed, so that the culture liquid flows uniformly in the tank, avoiding temperature differences caused by uneven heating, and ensuring that all the culture liquid can be stably maintained at 65-70℃, laying a foundation for subsequent uniform evaporation.

[0025] The valve at the vacuum suction port is opened, and the vacuum pump is started; the vacuum pump reduces the air pressure in the cavity of the reaction tank through the air suction effect, forming a stable negative pressure environment. Under the condition of negative pressure, the boiling point of the nose leptin culture liquid is significantly reduced, and the culture liquid which originally needs 98℃ to boil can reach the boiling state at 65-70℃, and the water in the culture liquid is quickly evaporated into water vapor; the water vapor is discharged out of the tank through the vacuum suction port and the second pipeline during the air suction process of the vacuum pump, thereby realizing the removal of water in the culture liquid and the increase of the concentration.

[0026] Because there are nutrients in the culture liquid, the boiling points of the culture liquid and water are not completely consistent. According to tests, the concentration effect is best when the temperature is 65-70℃, and the test data are shown in the following table: Concentration test data table

[0027] When the concentration of the culture solution of the glanders bacillus is confirmed to reach the designed concentration, the valve at the vacuum pump and the vacuum port is closed, the negative pressure state is terminated, and the concentration is generally stopped when the concentration of the concentrated solution is ten times of the original solution. When the concentration of the concentrated solution is too high, dilution operation can be performed. After harvesting, potency test is performed, and then the semi-finished product is accurately prepared according to the potency. After the semi-finished product is qualified, it is packaged, and then product test is performed. The specific test method is as follows: the sensitized antigen is prepared from the glanders bacillus, and the guinea pigs are injected intraperitoneally with the sensitized antigen. After 14-20 days of immunization, the potency test is performed. When testing, 0.1 ml of the tested glanders bacillus is injected intradermally, and the skin swelling area is detected. When performing the potency test, the standard glanders bacillus is used as a control, and the tested product is diluted at different multiples and compared with the standard product. If the swelling area of the tested product is lower than that of the standard product, it is unqualified. If the swelling area of the tested product is basically the same as that of the standard product, the dilution multiple is the dilution multiple when the semi-finished product is prepared.

[0028] After the negative pressure state is terminated, the valve at the compressed air inlet is opened, and the compressed air generated by the air compressor is introduced into the cavity of the reaction tank through the first pipeline. The compressed air forms a positive pressure in the tank, which generates a pushing force on the concentrated glanders bacillus culture solution, and drives the culture solution to flow to the bottom of the reaction tank. Finally, the valve at the discharge port is opened, and the concentrated solution is discharged from the tank through the discharge port under the action of air pressure, and the entire concentration process is completed.

[0029] Finally, it should be noted that: the above embodiments are only used to illustrate the technical solutions of the present application, and are not limited thereto; although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or make equivalent replacement for part or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A negative pressure concentration system for melilotinib, characterized in that, The reaction vessel (9) includes a stirrer (14) on the upper part of the reaction vessel (9), and a feed port (2) and a vacuum port (1) communicating with the internal cavity of the reaction vessel (9). The vacuum port (1) is connected to a vacuum pump (6) through a second pipeline (4). The bottom of the reaction vessel (9) is provided with a discharge port (7) communicating with the internal cavity of the reaction vessel (9). The output end of the stirrer (14) is connected to a stirring paddle (3), which is located inside the reaction vessel (9). The reaction vessel (9) has a jacket (8) inside its wall, and a steam inlet (10) and a steam outlet (5) communicating with the jacket are provided on the outer wall of the reaction vessel (9).

2. The negative pressure concentration system for melilotinib according to claim 1, characterized in that, The upper part of the reaction vessel (9) is provided with a compressed air inlet (11) that communicates with the internal cavity of the reaction vessel (9). The compressed air inlet (11) is connected to an air compressor through a first pipeline (13).

3. The negative pressure concentration system for melilotinib according to claim 1, characterized in that, A thermometer and a pressure gauge (12) are installed on the wall of the reaction vessel (9), and the detection end of the thermometer and pressure gauge (12) is located inside the cavity of the reaction vessel (9).

4. A negative pressure concentration system for melilotinib according to claim 2, characterized in that, Each of the feed inlet (2), discharge outlet (7), steam inlet (10), steam outlet (5), compressed air inlet (11), and vacuum port (1) is connected to an independent valve on its respective pipeline.

5. A negative pressure concentration system for melilotinib according to claim 1, characterized in that, The vacuum pump (6) is a water ring vacuum pump.

6. A method for negative pressure concentration of melilotinib based on the negative pressure concentration system for melilotinib according to any one of claims 1-5, characterized in that, Includes the following steps: The concentrated melilotinic culture solution is injected into the reaction vessel through the feed inlet at the top of the reaction vessel; Steam is introduced into the jacket of the reaction vessel; Start the stirrer to agitate the glandersin culture medium. A vacuum pump is used to create a vacuum inside the reaction vessel, thereby generating negative pressure for concentration. Once the glandersin culture medium has been concentrated, turn off the vacuum pump and introduce compressed air into the reaction vessel through the compressed air inlet, then discharge the concentrated glandersin culture medium through the discharge port.

7. A method for negative pressure concentration of melilotinib according to claim 6, characterized in that, The step involves introducing steam into the jacket of the reaction vessel to ensure that the pressure inside the jacket is 0.08-0.1 MPa, while simultaneously ensuring that the temperature of the glandersin culture medium inside the reaction vessel reaches a uniform 65-80℃.