Vaccine sustained-release implant and application thereof

Abstract

The invention discloses a vaccine sustained-release implant and application thereof, and relates to the technical field of medical supplies, the implant is of a cylindrical structure, and comprises an outer layer and an inner layer; the outer layer is formed by weaving a PGA film or PGA fibers, and a plurality of through holes are formed in the PGA film; the cylindrical inner layer content is filled with one or more of cellulose acetate fibers, absorbable regenerated fibers, polylactic acid fibers or dry agar, agarose and other absorbable materials. The vaccine sustained-release implant provided by the invention is optimized from multiple dimensions, for example, the material and size of each layer, the fixed connection mode of the inner layer and the outer layer and the like are precisely limited, so that the problems that an existing water agent or oil agent inactivated vaccine or some drugs are quickly absorbed locally after being injected, the action time of an organism is very short, and the service life is short are solved. The high-level antibody reaction is difficult to excite, so that the effect consistent with that of live vaccine immunity can be achieved, and meanwhile, a series of safety problems caused by the use of live vaccines can be avoided.

Description

Technical Field

[0001] The present invention relates to the technical field of medical supplies, and particularly to a vaccine sustained-release implant. Background Art

[0002] In the field of public health, vaccination is an important means of preventing infectious diseases. Inactivated vaccines are known for their safety. However, through traditional vaccination methods such as intramuscular injection and subcutaneous injection, although they can stimulate the body's immune response to a certain extent, there are many limitations. These traditional vaccination methods often require multiple injections to achieve the desired immune effect, which not only causes pain to the vaccinated person but also increases the workload of medical staff and the consumption of medical resources. At the same time, it is difficult to achieve continuous and stable release of antigens through traditional injection methods. The antigens are quickly inactivated and absorbed in the tissue, and the interaction time with the body is very short, making it difficult to form a high-level antibody response. Especially for some animal viruses, such as certain coronaviruses and porcine reproductive and respiratory syndrome viruses, the interaction time with the body in the inactivated state is short and is basically insufficient to produce any antibodies, making it difficult to guarantee the effectiveness, persistence, and stability of the immune effect.

[0003] In order to overcome the deficiencies of traditional vaccination methods, scientific researchers have been exploring new vaccine delivery technologies. In existing vaccine sustained-release technologies, some products have defects in structural design. For example, some sustained-release carriers cannot effectively control the release rate of antigens, resulting in premature or uneven release of antigens; some carriers have unstable structures; although oil adjuvants can delay absorption to a certain extent, the effect is still limited, and there are also problems such as high stress, which affect the effectiveness and safety of vaccines.

[0004] Based on the above problems, the vaccine sustained-release implant provided by the present invention has a specific cylindrical structure and can be implanted subcutaneously via a specific syringe. It includes an outer layer made of a PGA membrane and an inner layer filled with absorbable fibers such as cellulose acetate and absorbable regenerated fibers. After the inner layer material is filled, the entire implant can absorb a large amount of vaccine liquid. Different inner fillers can absorb different dosage forms of vaccines. Among them, all these fillers can absorb aqueous inactivated vaccines, and except for fillers of agar and agarose, the others can absorb oil-based inactivated vaccines; moreover, when agar or agarose is used as the content, the cylinder will have a certain deformation. After the implant quickly absorbs a large amount of vaccine liquid, it can be implanted subcutaneously into the animal body as a whole. The outer PGA membrane is provided with evenly distributed small holes, which are conducive to the release of the vaccine and the slow absorption of the implant. This structure is optimized from multiple dimensions, such as precisely defining the materials, dimensions of each layer, and the fixed connection method between the inner layer and the outer layer, aiming to solve the problems of poor structural stability and poor antigen release control existing in existing vaccine sustained-release carriers, enabling the implant to slowly release vaccine antigens in the body for a long time, causing a continuous immune response, and forming a strong immunity. Summary of the Invention

[0005] The object of the present invention is to solve the defects existing in the prior art, and a vaccine sustained-release implant is proposed.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] A vaccine sustained-release implant, the implant is in a cylindrical structure, including an outer layer and an inner layer; the outer layer is made of a PGA film or woven from PGA fibers, and a plurality of through holes are formed in the PGA film; if it is woven from PGA fibers, there is no need to open holes. The inner layer of the cylinder is filled with one or more of cellulose acetate, absorbable regenerated fiber, polylactic acid fiber, or dry agar and agarose; the outer layer and the inner layer filler are closely attached, and the outer layer wraps the inner layer to form a complete cylindrical structure.

[0008] Further, the through holes on the PGA film are evenly distributed, the diameter range of the through holes is 0.1 - 1 mm, and the number of through holes is between 50 - 200; each through hole penetrates the thickness direction of the PGA film to connect the inner layer with the outside.

[0009] Further, the cellulose acetate, absorbable regenerated fiber, agar, agarose, and polylactic acid fiber filled in the inner layer are in the form of granules, fiber filaments, or membrane sheets; when the filling material is in the form of granules, the particle size range is 0.2 - 0.8 mm; when the filling material is in the form of fiber filaments, the diameter range of the fiber filaments is 0.05 - 0.15 mm, and when the filling material is a membrane sheet, it is filled into the cylinder after being rolled up.

[0010] Further, the diameter of the implant is 1 - 5 mm, and the height is 5 - 15 mm; the outer layer is cylindrical, and its side surface and upper and lower bottom surfaces are integrally formed, and the material is a PGA film to form a closed cylindrical surface layer.

[0011] Further, the thickness of the PGA film of the outer layer is 0.05 - 0.2 mm; the PGA film has good flexibility and mechanical strength, is not easily damaged during the implantation process, and can effectively protect the inner layer filling material.

[0012] Further, the surface of the PGA film has a rough texture to avoid sliding in the tissue and at the same time contribute to the adsorption and release of the vaccine.

[0013] Application of the above-mentioned vaccine sustained-release implant in animal vaccines.

[0014] Further, the vaccine sustained-release implant can be used as a vaccine adjuvant or a carrier for vaccine injection.

[0015] Advantageous Effects

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0017] The entire set of implantable materials can be naturally degraded and absorbed in the body without any harmful effects. The PGA membrane is a biodegradable material with good biocompatibility. After being implanted into the human body, it will not cause immune rejection reactions, ensuring the safety of use. It has a certain degree of flexibility and mechanical strength, and can maintain the integrity of its structure during the implantation process, being not easily damaged. It can effectively protect the inner filling material, preventing the premature leakage or damage of the filling material, and providing a reliable external barrier for the stable storage and release of the vaccine.

[0018] The multiple through holes opened on the PGA membrane enable the inner layer to communicate with the outside world. This structural design provides a channel for the release of the vaccine. The uniformly distributed through holes can ensure that the vaccine diffuses more evenly from the inner layer to the outer layer, thereby achieving the stable slow release of the vaccine, continuously releasing antigens for up to several weeks. Compared with the traditional vaccine inoculation method, it can effectively extend the action time of the antigen, maintain a high-intensity immune level, and reduce the number of inoculations.

[0019] The materials filled in the inner layer, such as cellulose acetate, absorbable regenerated fiber, agar, agarose, polylactic acid fiber, etc., all have good adsorption properties and a certain slow-release effect. These materials can fully absorb the vaccine and control the release rate of the vaccine through their own characteristics, further ensuring the stability and persistence of the vaccine slow release. At the same time, these materials also have good biocompatibility and biodegradability, and will gradually degrade in the human body over time without the need for secondary removal, reducing subsequent medical operations and potential risks.

[0020] The cylindrical structure design is simple and practical, with a moderate ratio of surface area to volume. It not only ensures sufficient space to accommodate the inner filling material and the vaccine, but also is conducive to the uniform release of the vaccine through the through holes in the outer layer. The structure of the outer layer tightly wrapping the inner layer ensures the stable connection between the components, enabling the implant to maintain a stable structure after being implanted into the human body, effectively preventing the displacement of the inner filling material, ensuring the normal functioning of the vaccine slow-release function, and thus improving the immune effect and reliability of the vaccine. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The drawings are used to provide a further understanding of the present invention and constitute a part of the specification. They are used together with the embodiments of the present invention to explain the present invention, but do not constitute a limitation to the present invention.

[0022] Figure 1 It is a schematic diagram of the overall structure of the vaccine slow-release implant.

[0023] Figure 2 It is a schematic diagram of the internal structure of the vaccine slow-release implant.

[0024] In the figure: 1. Outer layer; 2. Inner layer. Detailed implementation mode

[0025] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments.

[0026] In the description of the present invention, it should be understood that the orientation or positional relationship indicated by the terms "upper", "lower", "front", "rear", "left", "right", "top", "bottom", "inner", "outer", etc. is based on the orientation or positional relationship shown in the accompanying drawings, and is 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 construed as a limitation of the present invention.

[0027] Refer to Figure 1 - Figure 2 , a vaccine sustained-release implant, the implant is in a cylindrical structure, including an outer layer 1 and an inner layer 2; the outer layer is made of a PGA film, and a plurality of through holes are opened on the PGA film; the inner layer is filled with one or more of cellulose acetate, absorbable regenerated fiber, agar, agarose, and polylactic acid fiber; the outer layer and the inner layer are closely attached, and the outer layer wraps the inner layer to form a complete cylindrical structure.

[0028] The PGA film is a biodegradable material with good biocompatibility. After being implanted into the human body, it will not cause serious immune rejection reactions, ensuring the safety of use. It has certain flexibility and mechanical strength by itself, and can maintain the integrity of the structure during the implantation process, is not easy to break, can effectively protect the inner layer filling material, avoid the premature leakage or damage of the filling material, and provide a reliable external barrier for the stable storage and release of the vaccine.

[0029] The plurality of through holes opened on the PGA film enable the inner layer to communicate with the outside world. This structural design provides a channel for the release of the vaccine. The uniformly distributed through holes can ensure that the vaccine diffuses from the inner layer to the outer layer more evenly, thereby realizing the stable slow release of the vaccine, continuously releasing antigens for about 4 weeks. Compared with the traditional vaccine inoculation method, it can effectively extend the action time of the antigen, maintain a high-intensity immune level, and reduce the number of inoculations.

[0030] The materials filled in the inner layer, such as cellulose acetate, absorbable regenerated fiber, agar, agarose, and polylactic acid fiber, all have good adsorption properties and a certain sustained-release effect. These materials can fully absorb the vaccine and control the release rate of the vaccine through their own characteristics, further ensuring the stability and persistence of the vaccine sustained release. At the same time, these materials also have good biocompatibility and biodegradability, and gradually degrade in the human body over time, eliminating the need for secondary removal, reducing subsequent medical operations and potential risks.

[0031] The cylindrical structure design is simple and practical, with a moderate ratio of surface area to volume. It not only ensures enough space to accommodate the inner layer filling materials and the vaccine, but also facilitates the uniform release of the vaccine through the through-holes in the outer layer. The structure where the outer layer wraps and closely fits the inner layer ensures stable connection between the components, enabling the implant to maintain a stable structure after being implanted into the human body, effectively preventing the displacement of the inner layer filling materials, ensuring the normal functioning of the vaccine sustained-release function, and thus improving the immune effect and reliability of the vaccine.

[0032] In other preferred embodiments, the through-holes on the PGA membrane are evenly distributed, the diameter range of the through-holes is 0.1 - 1 mm, and the number of through-holes is between 50 - 200; each through-hole penetrates through the thickness direction of the PGA membrane, connecting the inner layer to the outside.

[0033] The setting of the through-hole diameter in the range of 0.1 - 1 mm and the cooperation with the number of holes between 50 - 200 form a specific pore area and channel number. The smaller pore diameter and appropriate number of holes limit the outward diffusion rate of the vaccine, enabling the vaccine to be continuously released at a stable rate, achieving a continuous antigen supply for about 4 weeks. By adjusting the diameter and number of the through-holes, the release rate can also be flexibly regulated according to the characteristics and immune requirements of different vaccines to achieve the best immune effect.

[0034] In other preferred embodiments, the cellulose acetate, absorbable regenerated fiber, agar, agarose, and polylactic acid fiber filled in the inner layer are in granular or fibrous filament form; when the filling material is granular, the particle size range is 0.2 - 0.8 mm; when the filling material is fibrous filament, the diameter range of the fiber filament is 0.05 - 0.15 mm.

[0035] The granular or fibrous filament form greatly increases the specific surface area of the filling material. Compared with the block or other forms, it can fully contact the vaccine, significantly enhancing the adsorption capacity of the material for the vaccine. The setting of the particle size between 0.2 - 0.8 mm and the fiber filament diameter between 0.05 - 0.15 mm ensures that while the material has enough internal pore structure to accommodate the vaccine, the adsorption process is efficient, enabling the implant to fully absorb the inactivated vaccine and laying a foundation for the subsequent stable release of the antigen.

[0036] In other preferred embodiments, the diameter of the small animal implant is 2 mm and the height is 5 mm; the outer layer is cylindrical, and its side surface and the upper and lower bottom surfaces are integrally formed. The material is a PGA film, forming a closed cylindrical layer. For the large animal implant, the diameter can directly reach 3.9 mm and the length can reach about 12 mm. When the filling material is a film rolled up and filled into the cylinder, since the inner filling material has extremely strong liquid absorption capacity, the total amount of liquid that can be absorbed is approximately 100 microliters. However, for implants of different animals, the diameter and length are allowed to be adjusted accordingly.

[0037] The size design of the diameter and height of the implant can be set according to the animal body size, which conforms to the physiological structure characteristics of the animal subcutaneous tissue. During the implantation process, there is no need for large-area incisions or complex surgical operations, and it can be easily implanted subcutaneously by injection, greatly reducing the difficulty and risk of the implantation surgery. The smaller size also reduces the damage to animal tissues, has a fast postoperative recovery, reduces the pain and discomfort of the patient, and at the same time reduces the occurrence probability of postoperative complications such as infection.

[0038] In other preferred embodiments, the thickness of the outer PGA film is 0.05 - 0.2 mm; the PGA film has good flexibility and mechanical strength, is not easily damaged during the implantation process, and can effectively protect the inner filling material.

[0039] In other preferred embodiments, the inner filling material is in close contact with the outer PGA film, and the inner wall of the PGA film is provided with a convex structure, and the inner filling material is filled in the groove formed by the convex structure.

[0040] Specifically, the outer PGA film surface has rough textures, which are used to enhance the bonding force with the inner filling material and at the same time contribute to the adsorption and release of the vaccine.

[0041] The present invention also provides the application of the above-mentioned vaccine sustained-release implant in the preparation of vaccines.

[0042] Specifically, the vaccine sustained-release implant is used as a vaccine adjuvant.

[0043] When preparing the implant, a PGA membrane material meeting medical standards is selected and customized into a specific specification according to the designed dimensions. A precision punching device is used to make through-holes on the PGA membrane and make the through-holes evenly distributed. By adjusting the punching parameters, the diameter of the through-holes is controlled to be 0.3 mm, and 100 through-holes are formed on the entire PGA membrane. Subsequently, the PGA membrane is made into a cylindrical structure with a diameter of 2 mm and a height of 10 mm through a hot pressing forming process. Its side surface is integrally formed with the upper and lower bottom surfaces to form a closed cylindrical layer. The thickness of the PGA membrane is controlled at 0.1 mm to ensure its good flexibility and mechanical strength. At the same time, a surface treatment process is used to form rough textures on the surface of the PGA membrane to enhance the bonding force between it and the inner layer filling material and also prevent displacement within the tissue.

[0044] Preparation of the inner layer filling material

[0045] Cellulose acetate is selected as the inner layer filling material, and the cellulose acetate is processed into fiber filaments. According to Claim 3, the fiber diameter is controlled at 0.1 mm.

[0046] Assembly of the implant

[0047] Inside the prepared outer PGA membrane, the prepared cellulose acetate filaments are filled in. Since convex structures are preset on the inner wall of the PGA membrane, during the filling process, the cellulose acetate particles are filled in the grooves formed by the convex structures, making the inner layer filling material in close contact with the outer PGA membrane, and trying to ensure that the outer layer wraps the inner layer to form a complete cylindrical structure.

[0048] The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution and inventive concept of the present invention, makes equivalent replacements or changes, and should be covered by the protection scope of the present invention.

Claims

1. A vaccine sustained-release implant, characterized in that, The implant is in a cylindrical structure and includes an outer layer and an inner layer; the outer layer is made of a PGA film or woven from PGA fibers. Multiple through-holes are formed in the PGA film. If it is woven from PGA fibers, there is no need to form holes. The inner layer of the cylinder is filled with one or more of cellulose acetate, absorbable regenerated fibers, polylactic acid fibers, or dry agar or agarose; the outer layer and the inner layer filler are closely attached, and the outer layer wraps the inner layer to form a complete cylindrical structure.

2. The vaccine sustained-release implant according to claim 1, characterized in that, The through-holes on the PGA film are evenly distributed. The diameter range of the through-holes is 0.1 - 1 mm, and the number of through-holes is between 50 and 200; each through-hole penetrates the thickness direction of the PGA film to connect the inner layer with the outside.

3. The vaccine sustained-release implant according to claim 1, characterized in that, The cellulose acetate, absorbable regenerated fibers, agar, agarose, and polylactic acid fibers filled in the inner layer are in granular, fibrous or sheet form; when the filling material is granular, the particle size range is 0.2 - 0.8 mm; when the filling material is fibrous, the diameter range of the fiber filaments is 0.05 - 0.15 mm. When the filling material is a sheet, it is rolled and filled into the cylinder.

4. The vaccine sustained-release implant according to claim 1, characterized in that, The diameter of the implant is 1 - 5 mm, and the height is 5 - 15 mm; the outer layer is cylindrical, and its side surface and upper and lower bottom surfaces are integrally formed. The material is a PGA film to form a closed cylindrical surface layer.

5. The vaccine sustained-release implant according to claim 1, characterized in that, The thickness of the PGA film of the outer layer is 0.05 - 0.2 mm; the PGA film has good flexibility and mechanical strength, is not easily damaged during the implantation process, and can effectively protect the inner layer filling material.

6. The vaccine sustained-release implant according to any one of claims 5, characterized in that, The surface of the PGA film has rough textures to prevent sliding in the tissue and at the same time helps with the adsorption and release of the vaccine.

7. Application of the vaccine sustained-release implant according to any one of claims 1 - 6 in animal vaccines.

8. The application according to claim 7, wherein The vaccine sustained-release implant can be used as a vaccine adjuvant or a carrier for vaccine injection.

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