Gastric retention apparatus

Abstract

The present invention relates to the field of gastric retention systems. Disclosed is a gastric retention apparatus, comprising an elastic central part, a plurality of expanding arms, and a plurality of elastic end caps. The plurality of expanding arms are fixed circumferentially around the elastic central part. The expanding arms extend in a radial direction of the elastic central part. The elastic end caps are arranged at free ends of the expanding arms. The elastic end caps are configured to generate at least 20% of elastic deformation in a pressure direction when bearing a pressure of 2 N. The configuration of the elastic end caps effectively avoids scratches on inner wall tissues of the gastrointestinal tract.

Description

A gastric retention device Technical Field

[0001] The present invention relates to the field of gastric retention systems, in particular to a gastric retention device. Background Art

[0002] Gastric retention devices are designed to be administered into a patient's stomach, typically in capsule form, swallowed or introduced into the stomach via other administration methods (e.g., a feeding tube or a gastric tube). After the capsule dissolves in the stomach, the gastric retention device expands or deploys to a certain size, which is retained in the stomach and resists passage through the pyloric sphincter during the desired residence period (e.g., three days, seven days, two weeks, etc.). This requires maintaining mechanical stability during the desired residence period while releasing one or more active drugs, and the gastric retention device should be expelled from the stomach at the end of the desired residence time and easily expelled from the patient's body. Currently, gastric retention devices are typically configured such that connecting components undergo a strength weakening process such as degradation, dissolution, dissociation, or mechanical weakening in the gastric environment, so that some of the deployment arms are separated from the elastic core component or the deployment arms can be folded relative to the elastic core component in the gastrointestinal tract, ultimately allowing the elastic core component and deployment arms to be expelled from the body.

[0003] To ensure that the gastric retention device can remain in the gastric cavity for a sufficient period of time, the deployment arms need to be configured with sufficient mechanical strength to avoid structural damage due to gastric peristaltic pressure. The deployment arms are generally configured to have a hardness of at least 50D. Therefore, during gastrointestinal transit of the gastric retention device, especially when the gastric retention device is squeezed and deformed by the inner wall of the stomach and enters the smaller small intestine, the ends of the rigid deployment arms are prone to scratching / crushing the inner wall of the small intestine, causing damage to the inner wall of the small intestine and inflammation, thereby affecting the medical application of the gastric retention device. Summary of the Invention

[0004] Therefore, it is necessary to provide a gastric retention device to solve the problem that after the gastric retention device is squeezed into the small intestine, the end of the unfolded arm is likely to scratch the inner wall mucosa of the small intestine, thereby limiting the medical application of the gastric retention device.

[0005] To achieve the above objectives, the present invention provides a gastric retention device comprising:

[0006] elastic centerpiece;

[0007] a plurality of deployment arms, each having a fixed end and a free end, the fixed end of each deployment arm being connected to the elastic central component, the plurality of deployment arms being fixed circumferentially around the elastic central component, and at least one of the deployment arms being loaded with an active substance;

[0008] The free end of the deployment arm is provided with an elastic end cap, and the elastic end cap is configured to undergo elastic deformation of at least 20% in the direction of pressure when subjected to a pressure of 2N.

[0009] The gastric retention device comprises a folded configuration and an expanded configuration, and the elastic central component is used to provide elastic force to enable the gastric retention device to be transformed from the folded configuration to the expanded configuration.

[0010] Furthermore, the Shore hardness of the elastic end cover is 20A-80A.

[0011] For elastic end caps of the same structure, the lower the hardness, the lower the elastic coefficient of the elastic end cap. When subjected to gastrointestinal peristalsis pressure, the elastic deformation of the elastic end cap is greater, thereby effectively avoiding hard collision with the inner wall of the gastrointestinal tract and reducing damage to the inner wall.

[0012] Furthermore, the Shore hardness of the elastic end cap is 20-60A. Through experiments, it is preferred that the Shore hardness of the elastic end cap does not exceed 60A, which can minimize the damage to the gastrointestinal tract caused by the gastric retention device. At the same time, the elastic end cap is greater than 20A to ensure a firm connection between the elastic end cap and the deployment arm.

[0013] Furthermore, the deployment arm includes a first section and a second section along the axial direction, wherein the hardness of the first section, the second section, and the elastic end cap decreases in sequence. The second section of the deployment arm, which has a lower hardness, can also bend relative to the intestinal wall when subjected to gastrointestinal peristalsis, thereby further preventing scratches on the intestinal wall.

[0014] Furthermore, the elastic end cap has a hollow structure. The hollow structure enables the elastic end cap to have a lower elastic coefficient. For elastic end caps made of the same material, the hollow structure further enhances the deformation capacity of the elastic end cap.

[0015] Furthermore, the deployment arm is at least 5 mm long, and the ratio of the elastic end cap to the deployment arm length is 0.08-0.5. The axial length of the elastic end cap cannot be too short, as it will not function as an elastic buffer. If it is too long, the gastric retention device will not achieve a good gastric retention effect and the elastic end cap will be more likely to detach from the deployment arm.

[0016] Furthermore, the elastic end cover includes a first end surface and a second end surface, the first end surface is bonded to the free end of the deployment arm, and a curved surface transition or an inclined surface transition is formed between the second end surface and the side surface.

[0017] Furthermore, the sides of the deployable arms and the sides of the elastic end caps are all curved transitions. The curved or inclined transitions can further prevent overly sharp ends / edges from scratching the stomach lining tissue.

[0018] Furthermore, the deployment arm and the elastic end cap are hot-melt bonded, and the hot-melt bonding is one of the following methods:

[0019] (1) The free end of the elastic end cap and / or the deployment arm is provided with a molten adhesive, and the molten adhesive is heated and melted to bond the deployment arm and the elastic end cap;

[0020] (2) The elastic end cap and the free end of the deployment arm are directly heated and hot-melt bonded.

[0021] Furthermore, a positioning structure is provided between the elastic end cap and the free end of the deployment arm. After the elastic end cap and the free end of the deployment arm are fixed by the positioning structure, the elastic end cap and the free end of the deployment arm are bonded together.

[0022] Furthermore, the positioning structure is one of the following structures:

[0023] (1) The positioning structure includes a protrusion and a groove respectively provided on the free end of the deployment arm and the elastic end cover, wherein the protrusion and the groove engage with each other, and vice versa;

[0024] (2) The positioning structure includes an axial through hole provided on the elastic end cover and a molten material that enters and is cooled and formed in the axial through hole during hot melt bonding.

[0025] The positioning structure allows the deployment arm and the elastic end cover to be fixed and then heated and hot-melt bonded, which can effectively improve the fixing effect of the elastic end cover and the deployment arm.

[0026] In method (2), when the elastic end cover and the expansion arm are hot-melt bonded, the melt enters the axial through hole and cools to form the positioning structure. After the melt enters the axial through hole and cools, the bonding and fixing effect can be enhanced, and the part of the axial through hole that is not filled with the melt is a hollow structure.

[0027] Another aspect of the present invention provides a gastric retention device comprising:

[0028] elastic centerpiece;

[0029] a plurality of deployment arms, each deployment arm comprising a first rigid arm, a flexible segment, and a second rigid arm connected in sequence;

[0030] The first rigid arm is connected to the elastic central component, and a plurality of expansion arms are fixed circumferentially to the elastic central component, at least one of the expansion arms is loaded with an active substance,

[0031] The flexible segment has a bending modulus smaller than that of the first rigid arm and the second rigid arm;

[0032] The gastric retention device comprises a folded configuration and an expanded configuration, and the elastic central component provides elastic force to enable the gastric retention device to be transformed from the folded configuration to the expanded configuration.

[0033] Furthermore, the flexural modulus of the flexible segment is less than 26.9 MPa.

[0034] Furthermore, the elastic central member and the first rigid arm have an expanded diameter of at least 2 cm.

[0035] The above technical solution has the following beneficial effects:

[0036] (1) The present invention provides a gastric retention device with an elastic end cap. In the gastrointestinal environment, especially when the gastric retention device is squeezed from the stomach cavity into the smaller small intestine, since the free end of the deployed arm is sealed by the elastic end cap, under the action of gastrointestinal peristalsis, the elastic end cap will undergo elastic deformation of at least 20%, thereby avoiding sharp collision with the inner wall of the gastrointestinal tract, and can effectively prevent damage to the arm and inflammation in the gastrointestinal tract.

[0037] (2) Another aspect of the present invention discloses a gastric retention device having an unfolded arm with a flexible section. The flexible section is configured so that the two rigid arms connected thereto can bend relative to each other when subjected to pressure. When subjected to pressure from the inner wall of the gastrointestinal tract, the flexible section can play a certain buffering role, thereby preventing the end of the second rigid arm from scratching the inner wall of the gastrointestinal tract. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] FIG1 is a schematic diagram of a gastric retention device in an expanded configuration according to a specific embodiment of the present invention within the gastric cavity.

[0039] FIG2 is a schematic diagram of a state in which the gastric retention device according to a specific embodiment is about to be discharged from the gastric cavity.

[0040] FIG3 is a schematic diagram of the state of the gastric retention device in the duodenum according to a specific embodiment.

[0041] 4 is a block diagram of a gastric retention device in a deployed configuration according to a specific embodiment.

[0042] 5 is a structural diagram of a gastric retention device in a folded configuration according to a specific embodiment.

[0043] FIG. 6 is a structural diagram of the interior of the elastic core component according to a specific embodiment.

[0044] FIG7 is an axial cross-sectional structural diagram of a gastric retention device according to a specific embodiment.

[0045] FIG8 is a schematic diagram of a method for testing elastic deformation of an elastic end cap according to a specific embodiment.

[0046] FIG9 is a schematic cross-sectional view of the elastic end cover with a hollow structure according to a specific embodiment.

[0047] FIG10 is a cross-sectional structural diagram of an embodiment of the positioning structure described in the specific embodiment.

[0048] FIG11 is a cross-sectional structural diagram of another embodiment of the positioning structure described in the specific embodiment.

[0049] FIG. 12 is a structural diagram of a gastric retention device according to another embodiment.

[0050] FIG. 13 is a structural diagram of a gastric retention device according to another embodiment.

[0051] FIG14 is a schematic diagram of a second rigid arm bending test according to a specific embodiment.

[0052] FIG15 is a schematic diagram of the bending angle of the second rigid arm according to a specific embodiment.

[0053] FIG. 16 is a picture of duodenum sampling of a dog after the gastric retention device of Example 1 was used in an animal test.

[0054] FIG17 is a picture of duodenum sampling of a dog after the gastric retention device of Comparative Example 2 was used in an animal test.

[0055] Explanation of the accompanying drawings: 1. Elastic central component; 11. Elastic alloy component; 12. Polymer outer layer; 121. Central area; 122. Distal area; 2. Deployment arm; 21. First section; 22. Second section; 23. Second rigid arm; 24. First rigid arm; 25. Flexible section; 3. Connecting component; 4. Elastic end cap; 41. Curved surface transition; 42. Axial through hole; 5. Positioning structure; 51. Groove; 52. Protrusion; 53. Melt; 10. Gastric retention device; 20. Gastric cavity; 30. Small intestine; 40. Workbench; 50. Press head; 60. Sliding table; 70. Bending side stop. DETAILED DESCRIPTION

[0056] FIG1 shows the expanded configuration of the gastric retention device 10 in the gastric cavity 20. At this time, because the expanded diameter of the gastric retention device 10 is larger than the pylorus of the stomach and the gastric retention device 10 has sufficient resistance to withstand the peristaltic pressure of the stomach, it can remain in the gastric cavity 20 for a sufficient time to release the active substance.

[0057] When the retention period is reached, the ideal state is that the deployment arms are separated from the elastic central component at the same time, thereby being discharged from the gastric cavity 20 and entering the small intestine 30. However, due to the complexity of the environment in the gastric cavity 20, some deployment arms are detached prematurely. After losing some deployment arms, the gastric retention device 10 may be compressed into the small intestine 30 under the action of gastric peristalsis pressure. Figure 2 shows a schematic diagram of the gastric retention device 10 being squeezed through the pylorus and entering the duodenum of the small intestine 30 after some deployment arms are broken.

[0058] As shown in FIG3 , after the gastric retention device 10 enters the small intestine 30, the deployment arms are still partially connected to the elastic central component, and the elastic central component still provides a certain degree of compression resistance for the deployment arms. However, due to the small cavity of the small intestine 30, when the peristaltic pressure of the small intestine 30 compresses and delivers the gastric retention device 10, the relatively hard ends of the deployment arms are prone to scratching the interior of the small intestine 30.

[0059] Referring to Figures 4-7, one aspect of the present invention provides a gastric retention device, comprising an elastic central component 1, a plurality of deployment arms 2, a plurality of connecting components 3, and a plurality of elastic end caps 4. The two ends of the deployment arms 2 correspond one-to-one with the connecting components 3 and the elastic end caps 4, respectively. The deployment arms 2 are connected to the elastic central component 1 via the connecting components 3.

[0060] FIG4 shows the gastric retention device in an expanded configuration, and FIG5 shows the gastric retention device in a folded configuration. In the folded configuration, the deployment arms 2 of the gastric retention device are folded and tightly attached to each other, so that the folded configuration can be filled into the capsule shell. After the capsule is swallowed, the capsule shell dissolves in the stomach, and the elastic center provides a rebound force to cause the deployment arms 2 of the gastric retention device to expand and transform into the expanded configuration.

[0061] 6-7 , the internal structure of the elastic central component 1 of the gastric retention device is shown. In the gastric cavity, the elastic central component 1 provides the gastric retention device with sufficient resistance to resist the peristaltic pressure of the stomach and prevent the expanded configuration from being refolded. In this embodiment, the elastic central component 1 includes an elastic alloy member 11, which is fixed in a polymer outer layer 12. The elastic alloy member 11 provides the main resistance.

[0062] The elastic alloy part 11 can be an elastic alloy or a memory alloy, for example, nickel-titanium alloy, which has sufficient biosafety. In this embodiment, the elastic alloy includes a central metal ring of an integral structure and six circumferentially extending metal ribs, and the metal ribs are respectively connected to one end of the deployment arm 2 through a connecting component 3.

[0063] The polymer outer layer 12 is selected from one or more of polypropylene, polystyrene, polyvinyl chloride, synthetic rubber, phenolic resin, neoprene, nylon, polyacrylonitrile, PVB, silicone, acrylonitrile-butadiene-styrene, high-density polyethylene, polycarbonate, nylon, acrylic, polyethylene terephthalate, polybutylene terephthalate, acetal, polyimide, polyurethane and epoxy resin.

[0064] As shown in FIG. 4-7 , the polymer outer layer 12 includes a central region 121 with lower hardness and a distal region 122 with higher hardness. Metal ribs are inserted into the distal region 122 , and the distal region 122 is connected to the connecting component 3 .

[0065] In another embodiment, the elastic core part 1 is made entirely of elastic polymer material.

[0066] In another embodiment, the elastic alloy component is composed of an elastic alloy piece 11 .

[0067] In order to facilitate control of the retention time of the gastric retention device, a connecting component 3 is provided between the elastic central component 1 and the deployment arms 2. The connecting component 3 is constructed so that the deployment arms 2 are separated from the elastic central component 1 after being weakened; the strength weakening process may include degradation, dissolution, dissociation or mechanical weakening, thereby causing the gastric retention device to lose the shape of the deployed configuration.

[0068] In one embodiment, the connecting component 3 can be mixed with a water-soluble material by a matrix to achieve dissolution of the connecting component 3 .

[0069] A plurality of deployment arms 2 are fixed circumferentially around the elastic central component 1 , and at least one deployment arm 2 is loaded with an active substance; the active substance may be a therapeutic agent or a diagnostic agent.

[0070] The gastric retention device comprises at least three deployment arms 2 . In this embodiment, the gastric retention device has six deployment arms 2 .

[0071] The deployment arm 2 is made of at least one material selected from the group consisting of polypropylene, polystyrene, polyvinyl chloride, synthetic rubber, phenolic resin, chloroprene rubber, nylon, polyacrylonitrile, PVB, silicone, acrylonitrile-butadiene-styrene, high-density polyethylene, polycarbonate, acrylic acid, polyethylene terephthalate, polybutylene terephthalate, acetal, polyimide, polyurethane and epoxy resin.

[0072] The two ends of the deployment arm 2 are a fixed end and a free end respectively. The fixed end of the deployment arm 2 is connected to the distal region 122 of the elastic central component 1 through the connecting component 3. Multiple deployment arms 2 are circumferentially fixed on the elastic central component 1.

[0073] An elastic end cap 4 is provided on the free end of the deployment arm 2. To avoid scratching the inner wall of the gastrointestinal tract, the elastic end cap 4 is configured to undergo at least 20% elastic deformation in the pressure direction when subjected to a pressure of 2N.

[0074] In some embodiments, when the elastic end cap 4 is subjected to a pressure of 2N, its elastic deformation is 20%-25%, 25-30%, 30-35%, 35-40%, 40-50% or 20-50%.

[0075] In order for the gastric retention device to remain in the gastric cavity, the deployed diameter of the gastric retention device in the deployed configuration needs to be at least 2 cm.

[0076] The "expanded diameter" is defined as the diameter of the circumscribed circle of a polygon formed by connecting the ends of the elastic end caps 4 when the gastric retention device is in the expanded configuration.

[0077] In some embodiments, the diameter of the elastic central component 1 is 10 mm, the length of a single deployment arm 2 is 5-20 mm, and the length of the elastic end cap 4 is 1.6 mm-5 mm.

[0078] In some embodiments, the ratio of the length of the elastic end cap 4 to the length of the deployment arm 2 is 0.08-0.5. The axial thickness, i.e., the length, of the elastic end cap 4 cannot be too short, as it will not function as an elastic buffer. However, if it is too long, the gastric retention device will not achieve a good gastric retention effect and the elastic end cap 4 will be more likely to detach from the deployment arm 2.

[0079] As shown in Figure 8, a test method for the deformation of the elastic end cover 4 is shown. A tensile testing machine is used for testing. The elastic end cover 4 is fixed on the workbench 40 of the tensile testing machine. In the initial stage, the bottom surface of the pressure head 50 of the tensile testing machine abuts against the top of the elastic end cover 4. At this time, no pressure is applied to the elastic end cover 4. After setting the program, the pressure head 50 is controlled to press down. When the force sensor on the pressure head 50 reaches the specified force value -2N, the distance traveled by the motor is the deformation of the elastic end cover 4.

[0080] The elastic end cap 4 can achieve deformation performance parameters within a corresponding range in a variety of ways. In the present invention, the elastic end cap 4 is made to meet the elastic deformation performance requirements through material selection and / or hollow structure setting of the elastic end cap 4.

[0081] In terms of material selection, the elastic end cap 4 is made of a material with a Shore hardness of no more than 80A and no less than 20A. For elastic end caps 4 of the same structure, the lower the hardness, the lower the elastic modulus of the elastic end cap 4. When subjected to gastrointestinal peristalsis pressure, the elastic deformation is greater, i.e., the relative elastic deformation is higher, thereby providing a good buffering effect, effectively avoiding hard collisions with the inner wall of the gastrointestinal tract and reducing damage to the inner wall.

[0082] In some embodiments, the Shore hardness of the deployment arm 2 is at least 50D, and the Shore hardness of the elastic end cap 4 is between 20A and 60A. The Shore hardness of the deployment arm 2 is at least 50D to prevent bending under pressure, while the Shore hardness of the elastic end cap 4 is selected, through experiments, to be no more than 60A, thereby minimizing damage to the gastrointestinal tract caused by the gastric retention device. Furthermore, the Shore hardness of the elastic end cap 4 is greater than 20A, ensuring a secure connection between the elastic end cap 4 and the deployment arm 2.

[0083] In some specific embodiments, the elastic end cap 4 is made of a material with a Shore hardness of 20A, 30A, 40A, 50A, 60A, 70A and 80A.

[0084] As shown in Figure 9, in terms of structural arrangement, a hollow structure is provided on the elastic end cap 4. The elastic end cap 4 is made of the same material, and the hollow structure can further enhance the deformation capability of the elastic end cap 4.

[0085] As shown in FIG. 9 , the hollow structure is an axial through hole 42 .

[0086] In some embodiments, the elastic end cap 4 may also be provided with a hollow chamber inside to achieve a hollow structure.

[0087] In some embodiments, the elastic end cap 4 is made of one or more polymers selected from the group consisting of polyurethane, polyether-polyamide copolymer, thermoplastic elastomer, thermoplastic polyurethane, polycaprolactone polylactic acid copolymer, polytrimethylene carbonate, polyglyceryl sebacate natural rubber and silicone.

[0088] The elastic end cover 4 includes a first end face and a second end face opposite to each other along its axial direction. The first end face is bonded to the free end of the deployment arm 2, and a curved surface transition 41 or an inclined surface transition is formed between the second end face and the side surface of the elastic end cover 4; and / or the side surfaces of the deployment arm 2 and the side surfaces of the elastic end cover 4 are both curved surface transitions 41.

[0089] The curved or beveled transition can further prevent the sharp end from scratching the stomach lining tissue.

[0090] The curved surface transition 41 mentioned in the present invention can be implemented in the following ways:

[0091] In the first method, the curved surface transition 41 is an arc surface transition.

[0092] In the second method, the curved surface transition 41 is a streamlined transition.

[0093] Mode three: the curved surface transition 41 is an elliptical surface transition.

[0094] Method 4: the curved surface at the curved surface transition 41 is not limited to a single curved surface, that is, the curved surface has different curvatures and can be a combination of multiple curved surfaces (the curved surface can also be regarded as an arc surface here).

[0095] In this embodiment, the curved surface transition 41 takes an arc surface transition as an example.

[0096] In some embodiments, the cross-sectional shapes of the deployment arm 2 and the elastic end cap 4 are both triangular, and the connection between the side surfaces of the deployment arm 2 and the connection between the side surfaces of the elastic end cap 4 are both curved transitions 41 .

[0097] The edges of the deployment arm 2 and the elastic end cap 4 also have a curved transition 41 to prevent overly sharp edges from scratching the stomach wall tissue.

[0098] The deployment arm 2 and the elastic end cap 4 can be bonded by adhesive or hot melt bonding, and the hot melt bonding method is one of the following methods:

[0099] (1) A molten adhesive is provided on the first end surface of the elastic end cap 4 and / or the free end of the deployment arm 2, and the molten adhesive is heated and melted so that the deployment arm 2 and the elastic end cap 4 are bonded;

[0100] (2) Directly heat and melt the first end surface of the elastic end cap 4 and the free end of the deployment arm 2; when the material of the deployment arm 2 and / or the elastic end cap 4 itself is a hot-melt material, light heating and melting bonding can be directly added at the connection point.

[0101] There is a positioning structure 5 between the first end surface of the elastic end cover 4 and the free end of the deployment arm 2. After the first end surface of the elastic end cover 4 and the free end of the deployment arm 2 are fixed by the positioning structure 5, the first end surface of the elastic end cover 4 and the free end of the deployment arm 2 are hot-melt bonded, and the positioning mechanism strengthens the connection relationship between the elastic end cover 4 and the deployment arm 2.

[0102] As shown in Figure 10, the positioning structure 5 includes a protrusion 52 and a groove 51 arranged on the free end of the deployment arm 2 and the elastic end cover 4. The protrusion 52 and the groove 51 are engaged with each other, and vice versa. The elastic end cover 4 and the deployment arm 2 are first positioned and fixed by an engaging nesting structure, and then laser heating is performed for hot melt bonding, which effectively enhances the fixing effect between the elastic end cover 4 and the deployment arm 2.

[0103] As shown in Figure 11, the positioning structure 5 includes an axial through hole 42 set on the elastic end cover 4 and a molten material 53 that enters and is cooled and formed in the axial through hole 42 during hot melt bonding. When the elastic end cover 4 and the expansion arm 2 are hot melt bonded, the molten material 53 enters the axial through hole 42 and is cooled and formed to form the positioning structure 5.

[0104] In the embodiment of FIG11 , the heated molten melt 53 flows into the axial through hole 42 and is able to bond the elastic end cover 4 and the deployment arm 2 after cooling. At the same time, after the melt 53 cools in the axial through hole 42 , the unfilled portion of the axial through hole 42 becomes a hollow structure, providing deformation space for the elastic end cover 4 .

[0105] As shown in Figure 12, to enable relative bending of the deployment arm 2, thereby further preventing scratches on the stomach lining, the deployment arm 2 comprises a first section 21 and a second section 22 along the axial direction. The hardness of the first section 21, the second section 22, and the elastic end cap 4 decreases in sequence. The second section 22 of the deployment arm 2, which has a lower hardness, can also bend relative to each other when subjected to gastrointestinal peristalsis, thereby further preventing scratches on the intestinal lining.

[0106] In some embodiments, the TPU of the first section 21 is Lubrizol TT-2075D-B40, and the TPU of the second section 22 is Covestro 1350D.

[0107] In the present invention, the elastic end cap 4 can be configured to be non-drug-loaded, and the diffusion rate of the active substance on the elastic end cap 4 can be lower than the diffusion rate on the deployment arm 2 by selecting the material.

[0108] When the elastic end cap 4 is squeezed by the inner wall of the stomach, since the elastic end cap 4 does not contain active drugs, it does not affect the drug release curve of the gastric retention device in the gastric environment. The elastic end cap 4 closes the free end surface of the deployment arm 2, so that the active substance can only be released from the side, extending the release time of the active drug in the deployment arm 2, and at the same time eliminating the pressure release factor of the free end surface, which can more effectively control the release curve of the active drug.

[0109] Referring to FIG. 13 , another aspect of the present invention provides a gastric retention device comprising an elastic central component 1, a connecting component 3, and a plurality of deployment arms 2. The gastric retention device comprises a folded configuration and an deployed configuration. The elastic central component 1 provides an elastic force to enable the gastric retention device to transition from the folded configuration to the deployed configuration.

[0110] The deployment arm 2 includes a first rigid arm 24, a flexible segment 25 and a second rigid arm 23 connected in sequence. The flexible segment 25 is less rigid than the first rigid arm 24. The first rigid arm 24 is connected to the elastic central component 1. Multiple deployment arms 2 are fixed circumferentially around the elastic central component 1. At least one deployment arm 2 is loaded with an active substance. The flexible segment 25 has a bending modulus smaller than that of the first rigid arm 24 and the second rigid arm 23, so that the first rigid arm 24 and the second rigid arm 23 can bend relative to each other. When in the gastrointestinal tract, gastrointestinal peristalsis exerts peristaltic force on the gastric retention device.

[0111] In some embodiments, the bending modulus of the flexible section 25 does not exceed 26.9 MPa, thereby enabling the first rigid arm 24 and the second rigid arm 23 to bend relative to each other at a certain angle.

[0112] In some embodiments, the material of the flexible segment 25 can be selected from materials with a hardness of TPU-50A, TPU-60A, TPU-70A, and TPU-85A, wherein the bending modulus of TPU-85A is 26.9 MPa and the bending modulus of TPU-70A is 14.5 MPa.

[0113] The bending test results of the deployment arm 2 are shown in Figures 14-15. The deployment arm 2 includes a sliding platform 60 and a bending side stop 70. The first rigid arm 24 of the deployment arm 2 of the gastric retention device is fixed on the sliding platform 60. The bending side stop 70 has a pressure sensor. The deployment arm 2 is driven to slide by the sliding platform 60. The bending side stop 70 blocks the end of the second rigid arm 23, thereby causing the second rigid arm 23 to bend relative to the first rigid arm 24. As shown in Figure 15, the angle α is the bending angle of the second rigid arm 23.

[0114] In some embodiments, the flexible section 25 allows the second rigid arm 23 to bend at least 5° relative to the second rigid arm 23 when a pressure of 2N is applied to the end of the second rigid arm 23 .

[0115] To prevent premature expulsion of the gastric retention device from the stomach, the elastic central member 1 and the first rigid arms 24 have an expanded diameter of at least 2 cm.

[0116] The length ratio of the first rigid arm 24 to the second rigid arm 23 is 2:1-8:2. In a specific embodiment, the length ratio of the first rigid arm 24 to the second rigid arm 23 may be 2:1, 3:1, or 4:1.

[0117] In order to explain the technical content, structural features, achieved objectives and effects of the technical solution in detail, the following is a detailed description in conjunction with specific embodiments and accompanying drawings.

[0118] Examples 1-5

[0119] Preparation of the gastric retention device shown in FIG4 includes the following steps:

[0120] 1. Nickel-titanium alloy is used as the elastic alloy part 11, and thermoplastic polyurethane elastomer is externally injection-molded as the polymer outer layer 12, with the central region 121 being Lubrizol TPU: PC-3575A and the distal region 122 being Covestro TPU: 1350D, thereby forming an elastic central component 1;

[0121] 2. Polycaprolactone (PCL) and hydroxymethyl cellulose (HPMC-AS-HG) are mixed and extruded using an extruder, and then cut into 3 mm segments to form connecting parts 3;

[0122] 3. Polycaprolactone (PCL) powder (50D), polyolefin powder, active ingredients, and excipients such as silica are mixed, then extruded through an extruder and cut into 10 mm segments to form deployment arms 2;

[0123] 4. Silicone-20A, TPU-40A, TPU-60A, TPU-70A, and TPU-80A materials are respectively extruded and formed by an extruder, and then cut to form elastic end caps 4;

[0124] 5. The elastic center component 1, the connecting component 3, the deployment arm 2, and the elastic end cover 4 are sequentially bonded by laser heating and hot-melt bonding.

[0125] Example 6

[0126] TPU-60A material is extruded and cut through an extruder to form an elastic end cap, which is then axially punched to form an axial through hole, which is then hot-melt bonded to the deployment arm to prepare a gastric retention device.

[0127] Comparative Example 1

[0128] Silicone-10A material is selected to prepare the elastic end cap, which is bonded to the free end of the deployment arm. Since the elastic end cap made of Silicone-10A material is too soft, the elastic end cap is easily separated from the deployment arm.

[0129] Comparative Example 2

[0130] TPU-90A material was used to prepare the elastic end cap, which was hot-melt bonded to the deployment arm to prepare the gastric retention device.

[0131] Example 7

[0132] The elastic end caps prepared in Examples 1-6 and Comparative Example 2 were tested for elastic deformation under a pressure of 2N. The results are shown in Table 1 below:

[0133] Table 1. Elastic deformation test results of elastic end caps

[0134] Example 8, Different Animal Experiments

[0135] The gastric retention devices were filled into the corresponding capsule shells and fed to the test dogs. The dogs' activities were observed. X-ray observation showed that the gastric retention devices remained in the digestive tracts of the test dogs for approximately 7-14 days. The dogs were fed once every 7 days for three consecutive feedings, and their conditions were observed. The test results are shown in Table 2 below.

[0136] Table 2. Animal trials of gastric retention devices

[0137] The test dogs of Example 6 and Comparative Example 2 were dissected, and samples were taken from the duodenal portion of the small intestine, as shown in Figures 16 and 17. No changes or signs of trauma were found in the sample in Figure 16, indicating that the treatment was safe. In the sample in Figure 17, a large amount of congestion occurred on the inner wall of the duodenum (the inner wall was purple in color) and there was partial tissue depression, which should be scratches / compression injuries caused by the end of the deployment arm.

[0138] Example 9

[0139] Preparation of the gastric retention device shown in FIG13 includes the following steps:

[0140] 1. Nickel-titanium alloy is used as the elastic alloy part, and thermoplastic polyurethane elastomer is injection-molded as the polymer outer layer. The central area is Lubrizol TPU: PC-3575A, and the distal area is Covestro TPU: 1350D, thereby forming an elastic central component 1;

[0141] 2. Polycaprolactone (PCL) and hydroxymethyl cellulose (HPMC-AS-HG) are mixed and extruded using an extruder, and then cut into 3 mm segments to form connecting parts 3;

[0142] 3. Polycaprolactone (PCL) powder, polyolefin powder, active ingredients, and excipients such as silicon dioxide are mixed, extruded through an extruder, and cut into 8 mm and 4 mm segments to form the first rigid arm 24 and the second rigid arm 23;

[0143] 4. Extruding a material with a hardness of TPU-70A (flexural modulus 14.5 MPa) through an injection extruder and cutting the material to form a flexible segment 25;

[0144] 5. The first rigid arm 24, the flexible section 25, and the second rigid arm 23 are sequentially bonded by laser heating and hot-melt bonding to form a deployment arm;

[0145] 5. The elastic center component 1, the connecting component 3, and the deployment arm 2 are sequentially bonded by laser hot melt bonding.

[0146] In the present invention, an elastic end cap that can undergo at least 20% elastic deformation is provided at the free end of the deployment arm and / or the deployment arm is configured as two rigid arms that can be folded relative to each other. As a result, when the gastric retention device enters the small intestine, the peristalsis of the small intestine applies pressure to the deployment arm, causing the elastic end cap to undergo elastic deformation or the second rigid arm to bend, thereby providing a certain buffering effect, increasing the contact area, avoiding sharp collisions, and reducing the possibility of damage to the small intestinal mucosa.

[0147] It should be noted that, in this document, relational terms such as first and second, etc., are used solely to distinguish one entity or operation from another, and do not necessarily require or imply any actual relationship or order between these entities or operations. Furthermore, the terms "include," "comprise," or any other variations thereof are intended to encompass non-exclusive inclusion, such that a process, method, article, or terminal device comprising a series of elements includes not only those elements, but also other elements not explicitly listed, or elements inherent to such process, method, article, or terminal device. Without further limitation, elements defined by the phrase "include..." or "comprising..." do not exclude the presence of additional elements in the process, method, article, or terminal device comprising the elements. Furthermore, in this document, "greater than," "less than," "exceeding," etc., are understood to exclude the number itself; "above," "below," "within," etc., are understood to include the number itself.

[0148] Although the above embodiments have been described, those skilled in the art may make additional changes and modifications to these embodiments once they know the basic creative concepts. Therefore, the above descriptions are merely embodiments of the present invention and do not limit the scope of patent protection of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention's description and drawings, or directly or indirectly applied in other related technical fields, are also included in the scope of patent protection of the present invention.

Claims

1. A gastric retention device, characterized in that, include: a flexible center member; A plurality of deployment arms, wherein two ends of the deployment arm are respectively a fixed end and a free end, the fixed end of the deployment arm is connected to the elastic central component, the plurality of deployment arms are fixed around the elastic central component, and at least one of the deployment arms is loaded with an active substance; The free end of the deployment arm is provided with an elastic end cap, and the elastic end cap is configured to undergo at least 20% elastic deformation in the pressure direction when subjected to a pressure of 2N; The gastric retention device comprises a folded configuration and an expanded configuration, and the elastic central component is used to provide elastic force to transform the gastric retention device from the folded configuration to the expanded configuration.

2. The gastric retention device according to claim 1, characterized in that, The Shore hardness of the elastic end cover is 20-80A.

3. The gastric retention device according to claim 2, wherein The Shore hardness of the elastic end cover is 20-60A.

4. The gastric retention device according to claim 2, characterized in that, The deployment arm comprises a first section and a second section respectively along the axial direction, and the hardness of the first section, the second section and the elastic end cover decreases in sequence.

5. The gastric retention device according to any one of claims 1-4, characterized in that, The elastic end cover has a hollow structure.

6. The gastric retention device according to claim 1, wherein, The length of the expansion arm is at least 5 mm, and the ratio of the length of the elastic end cap to the length of the expansion arm is 0.08-0.

5.

7. The gastric retention device according to claim 1, wherein The elastic end cover comprises a first end face and a second end face, the first end face is bonded to the free end of the deployment arm, and a curved surface transition or an inclined surface transition is formed between the second end face and the side face.

8. The gastric retention device according to claim 7, characterized in that, There are curved transitions between the side surfaces of the unfolding arms and between the side surfaces of the elastic end covers.

9. The gastric retention device according to claim 1, wherein The deployment arm and the elastic end cap are hot-melt bonded, and the hot-melt bond is one of the following methods: (1) The free end of the elastic end cap and / or the deployment arm is provided with a molten adhesive, and the molten adhesive is heated and melted to bond the deployment arm and the elastic end cap; (2) The elastic end cover and the free end of the deployment arm are directly heated and hot-melt bonded.

10. The gastric retention device according to claim 9, characterized in that, A positioning structure is provided between the elastic end cap and the free end of the deployment arm. After the elastic end cap and the free end of the deployment arm are fixed by the positioning structure, the elastic end cap and the free end of the deployment arm are bonded to each other.

11. The gastric retention device according to claim 10, wherein The positioning structure is one of the following structures: (1) The positioning structure comprises a protrusion and a groove respectively arranged on the free end of the deployment arm and the elastic end cover, wherein the protrusion and the groove engage with each other, and vice versa; (2) The positioning structure includes an axial through hole provided on the elastic end cover and a molten material that enters and is cooled and formed in the axial through hole during hot melt bonding.

12. A gastric retention device, characterized in that, include a flexible center member; A plurality of deployment arms, each deployment arm comprising a first rigid arm, a flexible segment, and a second rigid arm connected in sequence; The first rigid arm is connected to the elastic central component, a plurality of expansion arms are fixed around the elastic central component, and at least one of the expansion arms is loaded with active material; the flexible segment has a bending modulus smaller than that of the first rigid arm and the second rigid arm; The gastric retention device comprises a folded configuration and an expanded configuration, and the elastic central component provides elastic force to enable the gastric retention device to transform from the folded configuration to the expanded configuration.

13. The gastric retention device according to claim 12, wherein The bending modulus of the flexible section does not exceed 26.9 MPa.

14. The gastric retention device according to claim 12, wherein The resilient central member and the first rigid arm have an expanded diameter of at least 2 cm.

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