Polypeptide implant preparation system and method

Abstract

The invention discloses a polypeptide implant preparation system which comprises a laminar flow clean room, an operation area, a liquid preparation mechanism, a freeze-dried powder crushing mechanism and an extrusion mechanism, and the liquid preparation mechanism, the freeze-dried powder crushing mechanism and the extrusion mechanism are all in butt joint with the operation area which is arranged among the liquid preparation mechanism, the freeze-dried powder crushing mechanism and the extrusion mechanism. The liquid preparation mechanism is conveyed into the freeze-drying disc body in the laminar flow cleaning chamber through a liquid conveying pipe, and a feeding and discharging mechanism for feeding and discharging of the freeze-drying powder crushing mechanism and a feeding mechanism for feeding of the extrusion mechanism are arranged in the laminar flow cleaning chamber. The invention also discloses a preparation method of the polypeptide implant, which is carried out by adopting the preparation system of the polypeptide implant. The polypeptide implant preparation system and method have the advantages that irreversible damage to a polypeptide structure is avoided, production can be carried out in a connected mode, and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of food and medicine packaging machinery and equipment, and in particular to a system and method for preparing polypeptide implants. Background Art

[0002] At present, the production method of polypeptide implants (such as lanreotide acetate, which is a prescription drug mainly used to treat diseases such as acromegaly and carcinoid, is a white freeze-dried block, a somatostatin analog, mainly used for the symptomatic treatment of carcinoid and the treatment of acromegaly) is mostly produced by terminal sterilization, generally through irradiation sterilization. Irradiation sterilization will cause irreversible structural damage to the polypeptide structure to a certain extent, and it is difficult to form continuous production. Summary of the invention

[0003] The technical problem to be solved by the present invention is to overcome the deficiencies of the prior art and provide a system and method for preparing polypeptide implants which avoid irreversible damage to the polypeptide structure and enable continuous production.

[0004] In order to solve the above technical problems, the present invention adopts the following technical solutions: A polypeptide implant preparation system comprises a laminar flow clean room, an operation area, and a liquid preparation mechanism, a freeze-drying and pulverizing mechanism and an extruding mechanism which are all connected to the operation area. The operation area is arranged between the liquid preparation mechanism, the freeze-drying and pulverizing mechanism and the extruding mechanism. The liquid preparation mechanism is transported to a freeze-drying tray in the laminar flow clean room through an infusion tube. The laminar flow clean room is provided with an inlet and outlet mechanism for feeding and discharging materials into and out of the freeze-drying and pulverizing mechanism and a feeding mechanism for feeding materials into the extruding mechanism.

[0005] As a further improvement of the above technical solution: The infusion tube is provided with a delivery pump, and the delivery pump is located in the laminar flow clean room.

[0006] The outlet of the liquid dispensing mechanism is connected to the liquid inlet end of the infusion tube.

[0007] The feeding end of the extrusion mechanism is butted against the discharging end of the feeding mechanism.

[0008] The laminar flow clean room is provided with a liquid adding pump for adding water into the feeding mechanism.

[0009] A transfer component is arranged in the laminar flow clean room.

[0010] The transfer component includes a barrel.

[0011] The liquid dispensing mechanism, freeze-drying and pulverizing mechanism and extruding mechanism are respectively located on three sides of the operating area, and the liquid dispensing mechanism and freeze-drying and pulverizing mechanism are respectively located on two opposite sides of the operating area.

[0012] The laminar flow clean room is located between the operating area and the freeze-drying and pulverizing mechanism.

[0013] The laminar flow clean room is provided with a concentration device.

[0014] A method for preparing a polypeptide implant comprises the following steps: S1, the liquid preparation mechanism prepares the polypeptide solution; S2. The prepared polypeptide solution is transported to the laminar flow clean room through an infusion tube, and then enters the freeze-drying and crushing mechanism through the feeding and discharging mechanism; S3, the polypeptide solution is freeze-dried and crushed in a freeze-drying and crushing mechanism to form powder, and then enters the laminar flow clean room through the feeding and discharging mechanism; S4. The powder and water enter the extrusion mechanism through the feeding mechanism and form a colloid in the extrusion mechanism.

[0015] Compared with the prior art, the advantages of the present invention are: The polypeptide implant preparation system of the present invention has the following advantages: on the one hand, the polypeptide solution and powder are transported between the liquid preparation mechanism, the freeze-drying and pulverizing mechanism and the extruding mechanism in a laminar flow clean room, so that the polypeptide solution and powder are prevented from being contaminated by the external environment during the transportation process, and the relative irradiation sterilization is performed to avoid irreversible damage to the polypeptide structure, so that the production can be carried out continuously; on the other hand, the overall structural layout is reasonable, which is convenient for the operation area to assist in the operation of the liquid preparation mechanism, the freeze-drying and pulverizing mechanism and the extruding mechanism.

[0016] In the method for preparing polypeptide implants of the present invention, the transportation process of polypeptide solution and powder between the liquid preparation mechanism, the freeze-drying and pulverizing mechanism and the extrusion mechanism is carried out in a laminar flow clean room, so that the polypeptide solution and powder are prevented from being contaminated by the external environment during the transportation process, and the relative irradiation sterilization is performed to avoid irreversible damage to the polypeptide structure, so that the production can be carried out continuously. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is a schematic diagram of the structure of the polypeptide implant preparation system of the present invention.

[0018] The symbols in the figure represent: 1. Operation area; 2. Liquid preparation mechanism; 3. Freeze drying and crushing mechanism; 4. Extrusion mechanism; 5. Laminar flow clean room; 51. Inlet and outlet mechanism; 52. Feeding mechanism; 53. Liquid adding pump; 54. Transfer component; 6. Infusion tube; 61. Delivery pump. DETAILED DESCRIPTION

[0019] The present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0020] In the description of the present invention, it should be understood that the terms "length", "width", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside" and "outside" etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present invention.

[0021] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0022] In the present invention, unless otherwise clearly specified and limited, the terms "assemble", "connect", "connect", "fix" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0023] Embodiment 1: Figure 1 An embodiment of the polypeptide implant preparation system of the present invention is shown. The polypeptide implant preparation system of this embodiment includes a laminar flow clean room 5, an operation area 1, and a liquid preparation mechanism 2, a freeze-drying and pulverizing mechanism 3, and an extrusion mechanism 4 all connected to the operation area 1. The operation area 1 is arranged between the liquid preparation mechanism 2, the freeze-drying and pulverizing mechanism 3, and the extrusion mechanism 4. The liquid preparation mechanism 2 is transported to the freeze-drying tray body in the laminar flow clean room 5 through an infusion tube 6. The laminar flow clean room 5 is provided with an inlet and outlet mechanism 51 for feeding and discharging materials into and out of the freeze-drying and pulverizing mechanism 3 and a feeding mechanism 52 for feeding materials into the extrusion mechanism 4.

[0024] The production process of the polypeptide implant preparation system is as follows: first, the liquid preparation mechanism 2 prepares the polypeptide solution; second, the prepared polypeptide solution is transported to the laminar clean room 5 through the infusion tube 6, and then enters the freeze-drying and pulverizing mechanism 3 through the inlet and outlet mechanism 51; third, the polypeptide solution is freeze-dried and pulverized in the freeze-drying and pulverizing mechanism 3 to form powder, and then enters the laminar clean room 5 through the inlet and outlet mechanism 51; fourth, the powder and water enter the extrusion mechanism 4 through the feeding mechanism 52, and form a colloid in the extrusion mechanism 4. On the one hand, the transportation process of the polypeptide solution and powder between the liquid preparation mechanism 2, the freeze-drying and pulverizing mechanism 3 and the extrusion mechanism 4 is carried out in the laminar clean room 5, so as to prevent the polypeptide solution and powder from being contaminated by the external environment during the transportation process, and to avoid irreversible damage to the polypeptide structure by relative irradiation sterilization, so that the production can be carried out continuously; on the other hand, the overall structural layout is reasonable, which is convenient for the auxiliary operation of the liquid preparation mechanism 2, the freeze-drying and pulverizing mechanism 3 and the extrusion mechanism 4 by the operation area 1 (such as cleaning and sterilizing the internal parts of the corresponding mechanisms).

[0025] Furthermore, in this embodiment, a delivery pump 61 is provided on the infusion tube 6, and the delivery pump 61 is located in the laminar flow clean room 5. The delivery pump 61 serves as a driving force or a driving force for the delivery of the polypeptide solution in the infusion tube 6. Preferably, the delivery pump 61 is a quantitative pump.

[0026] Furthermore, in this embodiment, the outlet of the liquid dispensing mechanism 2 is connected to the liquid inlet end of the liquid infusion tube 6 .

[0027] Furthermore, in this embodiment, the feeding end of the extrusion mechanism 4 is connected to the discharging end of the feeding mechanism 52. The feeding mechanism 52 is used to convey the powder and water to the extrusion mechanism 4.

[0028] Furthermore, in this embodiment, a liquid adding pump 53 for adding water into the feeding mechanism 52 is provided in the laminar flow clean room 5. The liquid adding pump 53 is used to add water into the feeding mechanism 52.

[0029] Furthermore, in this embodiment, a transfer component 54 is provided in the laminar flow clean room 5 . The transfer component 54 is used to transfer the powder to the feeding mechanism 52 .

[0030] Furthermore, in this embodiment, the liquid dispensing mechanism 2, the freeze-drying and pulverizing mechanism 3 and the extruding mechanism 4 are respectively located on three sides of the operating area 1, and the liquid dispensing mechanism 2 and the freeze-drying and pulverizing mechanism 3 are respectively located on opposite sides of the operating area 1. The structure layout is ingenious, which facilitates manual feeding and unloading of freeze-dried materials in the operating area 1, and the accessories of the liquid dispensing mechanism 2 are offline cleaned and sterilized by a laminar flow cart.

[0031] Furthermore, in this embodiment, the laminar flow clean room 5 is located between the operation area 1 and the freeze-drying and pulverizing mechanism 3. The overall structure is compact.

[0032] Furthermore, the transfer component 54 includes a barrel (aluminum barrel) to collect sterile freeze-dried powder, and the barrel is sealed and stored in the laminar clean room 5 by manually rolling the cover. The sealed barrel increases the shelf life of the drug, and the barrel is transported in the laminar clean room 5 to transfer the powder to the feeding mechanism 52.

[0033] This polypeptide implant preparation system can achieve continuous aseptic production, greatly improving efficiency and stabilizing quality: continuous manufacturing is more stable for product quality. In addition, continuous production can reduce the use of labor, reduce waste and optimize resource utilization, and usually make the equipment smaller and reduce the footprint of the facility.

[0034] Furthermore, the polypeptide implant preparation system is used for preparing lanreotide acetate implants.

[0035] Further, in this embodiment, a concentrator 7 is provided in the laminar clean room 5. The concentrator 7 is used to concentrate the polypeptide solution before it enters the freeze-drying and crushing mechanism 3. The polypeptide solution used in this polypeptide implant preparation system is mainly lanreotide acetate sustained-release injection (prefilled). The preparation process of lanreotide acetate sustained-release injection originally required two concentrations, but the two-concentration process had the problem of secondary concentration uniformity, so the polypeptide implant preparation system can remove the one-time concentration process and change it to the extrusion mechanism 4 (powder feeding twin-screw mixing extruder) extrusion process, which requires sterile powder to be obtained by front-end liquid preparation, sterilization filtration (realized by the concentrator 7), and freeze-drying; the solution after liquid preparation needs to be sterilized and filtered, but the lanreotide acetate sustained-release injection is a special liquid, and it is difficult to sterilize and filter after the concentration is greater than 2.5%, and the sample with a concentration of 2.5% has a low bulk density after freeze-drying (the powder is too light and thin), and it is difficult to feed the feed machine, and the extrusion mechanism 4 cannot eat the material normally. Therefore, a concentrator 7 is added in the laminar clean room 5 to sterilize, filter and concentrate the lanreotide acetate sustained-release injection delivered by the infusion tube 6, and then deliver it to the feeding and discharging mechanism 51, so as to appropriately increase the concentration of the solution before freeze-drying to 5% to 8%, and appropriately increase the bulk density of the sample to facilitate the advancement of the subsequent extrusion mechanism 4.

[0036] Embodiment 2: A method for preparing a polypeptide implant comprises the following steps: S1, liquid preparation mechanism 2 prepares a polypeptide solution; S2, the prepared polypeptide solution is transported to the laminar flow clean room 5 through the infusion tube 6, and then enters the freeze-drying and pulverizing mechanism 3 through the feeding and discharging mechanism 51; S3, the polypeptide solution is freeze-dried and crushed in the freeze-drying and crushing mechanism 3 to form powder, and then enters the laminar flow clean room 5 through the feeding and discharging mechanism 51; S4. The powder and water enter the extrusion mechanism 4 through the feeding mechanism 52 and form a colloid in the extrusion mechanism 4.

[0037] In the method for preparing polypeptide implants, the transportation process of polypeptide solution and powder between the liquid preparation mechanism 2, the freeze-drying and pulverizing mechanism 3 and the extrusion mechanism 4 is carried out in a laminar flow clean room 5, so as to prevent the polypeptide solution and powder from being contaminated by the external environment during the transportation process, and to sterilize by relative irradiation, so as to avoid irreversible damage to the polypeptide structure, so that the production can be carried out continuously.

[0038] Furthermore, the raw material powder is uniformly mixed by the liquid preparation mechanism 2, and the mixed liquid is sterilized and filtered to obtain a sterile polypeptide solution; the sterilized and filtered polypeptide solution liquid from the liquid preparation mechanism 2 is then pumped into the laminar flow clean room 5 through the infusion tube 6 and the delivery pump 61, and then enters the freeze-drying and pulverizing mechanism 3 through the feeding and discharging mechanism 51 for freeze-drying and pulverizing.

[0039] Furthermore, the transfer component 54 is a barrel (aluminum barrel) for collecting sterile freeze-dried powder. The barrel is sealed and stored in the laminar clean room 5 by manually rolling the cap. The sealed barrel increases the shelf life of the drug. The barrel is transported in the laminar clean room 5 to transfer the powder to the feeding mechanism 52.

[0040] The liquid adding pump 53 injects water into the feeding mechanism 52, and the feeding mechanism 52 conveys the powder and water to the extrusion mechanism 4 (screw extruder). The target material, a colloidal material, is obtained through the extrusion mechanism 4, and then cooled and cut to form an implant.

[0041] The entire process after freeze-drying is carried out under a laminar flow system to ensure the compliance of the entire process.

[0042] The freeze-dried trays and barrels are transported through the same laminar flow system, which reduces the laminar flow area and reduces manufacturing costs.

[0043] Furthermore, in S2 , the prepared polypeptide solution is transported to the concentration device 7 of the laminar flow clean room 5 through the infusion tube 6 , and after being concentrated to a concentration of 5% to 8% by the concentration device 7 , it enters the freeze-drying and pulverizing mechanism 3 through the feeding and discharging mechanism 51 .

[0044] Furthermore, the polypeptide implant preparation method is carried out using the polypeptide implant preparation system of Example 1. The polypeptide solution used in the preparation method of the polypeptide implant is mainly lanreotide acetate sustained-release injection (prefilled). The preparation process of lanreotide acetate sustained-release injection originally required two concentrations, but the two-concentration process had the problem of secondary concentration uniformity, so the preparation method of the polypeptide implant removed the one-time concentration process and changed it to the extrusion process of the extrusion mechanism 4 (powder feeding twin-screw mixing extruder), which requires sterile powder, which is obtained by front-end liquid preparation, sterilization filtration (realized by the concentration device 7), and freeze-drying; the solution after liquid preparation needs to be sterilized and filtered, but the lanreotide acetate sustained-release injection is a special liquid, and it is difficult to sterilize and filter after the concentration is greater than 2.5%, and the sample with a concentration of 2.5% has a low bulk density after freeze-drying (the powder is too light and thin), which makes it difficult to feed the feed machine, and the extrusion mechanism 4 cannot eat the feed normally. Therefore, a concentrator 7 is added in the laminar clean room 5 to sterilize, filter and concentrate the lanreotide acetate sustained-release injection delivered by the infusion tube 6, and then deliver it to the feeding and discharging mechanism 51, so as to appropriately increase the concentration of the solution before freeze-drying to 5% to 8%, and appropriately increase the bulk density of the sample to facilitate the advancement of the subsequent extrusion mechanism 4.

[0045] Although the present invention has been disclosed as above with preferred embodiments, it is not intended to limit the present invention. Any technician familiar with the art can make many possible changes and modifications to the technical solution of the present invention by using the technical content disclosed above without departing from the scope of the technical solution of the present invention, or modify it into an equivalent embodiment of equivalent changes. Therefore, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention should fall within the scope of protection of the technical solution of the present invention.

Claims

1. A polypeptide implant preparation system, characterized in that: The invention comprises a laminar flow clean room (5), an operating area (1), and a liquid dispensing mechanism (2), a freeze-drying pulverizing mechanism (3), and an extruding mechanism (4) all connected to the operating area (1); the operating area (1) is arranged between the liquid dispensing mechanism (2), the freeze-drying pulverizing mechanism (3), and the extruding mechanism (4); the liquid dispensing mechanism (2) is transported to a freeze-drying tray body in the laminar flow clean room (5) through a liquid infusion tube (6); and the laminar flow clean room (5) is provided with an inlet and outlet mechanism (51) for feeding and discharging materials into and out of the freeze-drying pulverizing mechanism (3) and a feed mechanism (52) for feeding materials into the extruding mechanism (4).

2. The polypeptide implant preparation system according to claim 1, characterized in that: The infusion tube (6) is provided with a delivery pump (61), and the delivery pump (61) is located in the laminar flow clean room (5).

3. The polypeptide implant preparation system according to claim 2, characterized in that: The outlet of the liquid dispensing mechanism (2) is connected to the liquid inlet end of the liquid infusion tube (6).

4. The polypeptide implant preparation system according to claim 1, characterized in that: The feeding end of the extrusion mechanism (4) is butted against the discharging end of the feeding mechanism (52).

5. The polypeptide implant preparation system according to claim 4, characterized in that: A liquid adding pump (53) for adding water to the feeding mechanism (52) is provided in the laminar flow clean room (5).

6. The polypeptide implant preparation system according to claim 1, characterized in that: A transfer component (54) is provided in the laminar flow clean room (5).

7. The polypeptide implant preparation system according to claim 6, characterized in that: The transfer component (54) comprises a barrel.

8. The polypeptide implant preparation system according to any one of claims 1 to 7, characterized in that: The liquid dispensing mechanism (2), the freeze-drying and pulverizing mechanism (3) and the extrusion mechanism (4) are respectively located on three sides of the operating area (1), and the liquid dispensing mechanism (2) and the freeze-drying and pulverizing mechanism (3) are respectively located on two opposite sides of the operating area (1), and the laminar flow clean room (5) is located between the operating area (1) and the freeze-drying and pulverizing mechanism (3).

9. The polypeptide implant preparation system according to any one of claims 1 to 7, characterized in that: A concentration device (7) is provided in the laminar flow clean room (5).

10. A method for preparing a polypeptide implant, characterized in that: The steps include: S1, liquid preparation mechanism (2) prepares a polypeptide solution; S2, the prepared polypeptide solution is transported to the laminar flow clean room (5) through the infusion tube (6), and then enters the freeze-drying and pulverizing mechanism (3) through the feeding and discharging mechanism (51); S3, the polypeptide solution is freeze-dried and crushed in the freeze-drying and crushing mechanism (3) to form powder, and then enters the laminar flow clean room (5) through the feeding and discharging mechanism (51); S4. The powder and water enter the extrusion mechanism (4) through the feeding mechanism (52) and form a colloid in the extrusion mechanism (4).

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