Gastric retention device

Abstract

The invention relates to the field of gastric retention systems, and discloses a gastric retention device which comprises an elastic center part, a plurality of unfolding arms and a plurality of elastic end covers, the unfolding arms are fixed around the elastic center part in the circumferential direction and extend in the radial direction of the elastic center part, and the elastic end covers are arranged at the free ends of the unfolding arms. The elastic end cover is arranged to generate at least 20% of elastic deformation in the pressure direction when bearing 2N pressure, and the arrangement of the elastic end cover effectively avoids scratching of gastrointestinal tract inner wall tissues.

Description

Technical Field

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

[0002] The gastric retention device is designed to be administered into the patient's stomach, usually in the form of a capsule that is swallowed or introduced into the stomach through other methods of administration (e.g., a feeding tube or a gastric tube). After the capsule in the stomach dissolves, the gastric retention device expands or unfolds to a certain size, which is retained in the stomach and resists passing through the pyloric sphincter during the required residence period (e.g., three days, seven days, two weeks, etc.). This requires maintaining mechanical stability during the required residence period while releasing one or more active drugs, and the gastric retention device should be discharged from the stomach at the end of the required residence time and easily discharged from the patient's body. At present, the gastric retention device is usually provided with a connecting component that undergoes a strength weakening process such as degradation, dissolution, dissociation or mechanical weakening in the gastric environment, so that part of the expansion arm is separated from the elastic central component or the expansion arm can be folded relative to the elastic central component in the gastrointestinal tract, and finally the elastic central component and the expansion arm can be discharged from the body.

[0003] In order to ensure that the gastric retention device can be retained in the gastric cavity for a sufficient period of time, the deployment arm needs to be configured to have sufficient mechanical strength to avoid structural damage due to gastric peristaltic pressure. The deployment arm is generally configured to have a hardness of at least 50D. Therefore, during the gastrointestinal transport of the gastric retention device, especially when the gastric retention device enters the smaller small intestine stage after being squeezed and deformed by the inner wall of the stomach, the end of the rigid deployment arm is prone to scratch / crush the inner wall of the small intestine, thereby 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 object, the present invention provides a gastric retention device, comprising:

[0006] a flexible center member;

[0007] 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;

[0008] 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.

[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 transform the gastric retention device 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 peristaltic 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] 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 of the gastric retention device to the gastrointestinal tract. 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, and the hardness of the first section, the second section and the elastic end cap decreases in sequence. When the second section of the deployment arm with lower hardness is subjected to gastrointestinal peristalsis, it can also bend relative to the inner wall of the intestine, thereby further avoiding scratches on the inner wall of the intestine.

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

[0015] Furthermore, the length of the deployment arm is at least 5 mm, and the ratio of the length of the elastic end cap to the deployment arm is 0.08-0.5. The axial length of the elastic end cap cannot be too short, otherwise it cannot play the role of elastic buffering, and if it is too long, the gastric retention device cannot play a good gastric retention effect, and the elastic end cap is more likely to detach from the deployment arm.

[0016] Furthermore, 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.

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

[0018] Furthermore, the deployment arm and the elastic end cover are hot-melt bonded, and the hot-melt bond 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 cover 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 to each other.

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

[0023] (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;

[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-melted, 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 deployment 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] a flexible center member;

[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 circumferentially fixed 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 transform from the folded configuration to the expanded configuration.

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

[0034] Further, 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, the free end of the deployed arm is sealed by the elastic end cap. Under the action of the peristaltic force of the gastrointestinal tract, 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 inner arm of the gastrointestinal tract and inflammation.

[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] Figure 1 It is a schematic diagram of the state of the gastric retention device in the expanded configuration according to the specific embodiment in the gastric cavity.

[0039] Figure 2 It is a schematic diagram of a state in which the gastric retention device described in a specific embodiment is about to be discharged from the gastric cavity.

[0040] Figure 3 It is a schematic diagram of the state of the gastric retention device in the duodenum according to a specific implementation method.

[0041] Figure 4 FIG. 1 is a structural diagram of a gastric retention device in an expanded configuration according to a specific embodiment.

[0042] Figure 5 FIG. 4 is a structural diagram of a gastric retention device in a folded configuration according to a specific embodiment.

[0043] Figure 6 It is a structural diagram of the interior of the elastic central component described in a specific implementation method.

[0044] Figure 7 It is an axial cross-sectional structural diagram of the gastric retention device described in a specific embodiment.

[0045] Figure 8 It is a schematic diagram of a method for testing elastic deformation of an elastic end cap according to a specific implementation manner.

[0046] Fig. 9It is a cross-sectional schematic diagram of the elastic end cover with a hollow structure described in a specific implementation manner.

[0047] Fig.10 It is a cross-sectional structural diagram of an implementation manner of the positioning structure described in the specific implementation manner.

[0048] Fig.11 It is a cross-sectional structural diagram of another implementation of the positioning structure described in the specific implementation.

[0049] Fig.12 FIG. 4 is a structural diagram of a gastric retention device according to another embodiment.

[0050] Fig.13 FIG. 4 is a structural diagram of a gastric retention device according to another embodiment.

[0051] Fig.14 Schematic diagram of the second rigid arm bending test described in the specific implementation manner.

[0052] Fig.15 It is a schematic diagram of the bending angle of the second rigid arm described in the specific implementation manner.

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

[0054] Fig.17 This 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] Description of reference numerals:

[0056] 1. elastic central component; 11. elastic alloy component; 12. polymer outer layer; 121. central region; 122. distal region;

[0057] 2. Deployment arm; 21. First section; 22. Second section; 23. Second rigid arm; 24. First rigid arm; 25. Flexible section;

[0058] 3. Connecting parts;

[0059] 4. Elastic end cover; 41. Curved surface transition; 42. Axial through hole;

[0060] 5. Positioning structure; 51. Groove; 52. Protrusion; 53. Melt;

[0061] 10. Gastric retention device; 20. Gastric cavity; 30. Small intestine; 40. Workbench; 50. Press head; 60. Sliding table; 70. Bending side stop. DETAILED DESCRIPTION

[0062] Figure 1, the expanded configuration of the gastric retention device 10 in the gastric cavity 20 is shown. At this time, since 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 be retained in the gastric cavity 20 for a sufficient time to release the active substance.

[0063] 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, so as to be discharged from the gastric cavity 20 and enter the small intestine 30. However, due to the complexity of the environment in the gastric cavity 20, some deployment arms are separated in advance. 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 Schematic diagram of the gastric retention device 10 being extruded through the pylorus and into the duodenum of the small intestine 30 after the partial deployment arm is broken off is shown in FIG.

[0064] like Figure 3 As shown, after the gastric retention device 10 enters the small intestine 30, part of the expansion arm is still connected to the elastic central component, and the elastic central component still provides a certain compression resistance for the expansion arm. Since the cavity of the small intestine 30 is relatively small, when the peristaltic pressure of the small intestine 30 compresses and transports the gastric retention device 10, the end of the expansion arm with a relatively strong hardness is easy to scratch the inside of the small intestine 30.

[0065] See also Figure 4-7 On the one hand, the present invention provides a gastric retention device, including an elastic central component 1, a plurality of expansion arms 2, a plurality of connecting components 3, and a plurality of elastic end caps 4, wherein the two ends of the expansion arms 2 correspond one-to-one to the connecting components 3 and the elastic end caps 4, respectively, and the expansion arms 2 are connected to the elastic central component 1 through the connecting components 3.

[0066] Figure 4 A gastric retention device is shown in an expanded configuration, Figure 5 The gastric retention device is shown in a folded configuration. In the folded configuration, the deployment arms 2 of the gastric retention device are closed and tightly attached to each other, so that its folded configuration can be filled into a capsule shell. After the capsule is swallowed into the body, the capsule shell dissolves in the stomach, and the elastic center provides a rebound force to enable the deployment arms 2 of the gastric retention device to unfold and transform into the deployed configuration.

[0067] like Figure 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 sufficient resistance for the gastric retention device to resist the peristaltic pressure of the stomach and prevent the unfolded 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.

[0068] The elastic alloy part 11 can be an elastic alloy or a memory alloy, for example, nickel-titanium alloy. Nickel-titanium alloy 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.

[0069] The polymer outer layer 12 is selected from one or more of polypropylene, polystyrene, polyvinyl chloride, synthetic rubber, phenolic resin, chloroprene rubber, nylon, polyacrylonitrile, PVB, silicone, acrylonitrile-butadiene-styrene, high-density polyethylene, polycarbonate, nylon, acrylic, polyethylene terephthalate, polybutylene terephthalate, acetal, polyimide, polyurethane and epoxy resin.

[0070] like Figure 4-7 As shown, the polymer outer layer 12 includes a central region 121 with lower hardness and a distal region 122 with higher hardness, a metal rib is inserted into the distal region 122 , and the distal region 122 is connected to the connecting component 3 .

[0071] In another embodiment, the elastic core part 1 is made entirely of an elastic polymer material.

[0072] In another embodiment, the elastic alloy component is composed of an elastic alloy piece 11 .

[0073] In order to facilitate the 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 arm 2. The connecting component 3 is constructed so that the deployment arm 2 is separated from the elastic central component 1 after strength weakening; 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.

[0074] In one embodiment, the connecting component 3 can be dissolved by mixing a water-soluble material with a matrix.

[0075] 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.

[0076] The gastric retention device comprises at least three deployment arms 2 . In this embodiment, the gastric retention device has six deployment arms 2 .

[0077] 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.

[0078] 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. A plurality of deployment arms 2 are circumferentially fixed on the elastic central component 1.

[0079] An elastic end cap 4 is provided on the free end of the unfolding 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.

[0080] In some embodiments, when the elastic end cap 4 is subjected to a pressure of 2N, its elastic deformation amount is 20%-25%, 25-30%, 30-35%, 35-40%, 40-50% or 20-50%.

[0081] In order for the gastric retention device to be retained in the gastric cavity, the deployed diameter of the gastric retention device in the deployed configuration needs to be at least 2 cm.

[0082] 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.

[0083] 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.

[0084] 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, otherwise it cannot play the role of elastic buffering, and if it is too long, the gastric retention device cannot play a good gastric retention effect, and the elastic end cap 4 is also more likely to detach from the deployment arm 2.

[0085] like Figure 8 In the figure, 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.

[0086] 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 meets the elastic deformation performance requirements through material selection and / or hollow structure setting of the elastic end cap 4.

[0087] In terms of material selection, the elastic end cap 4 is made of a material with a Shore hardness of not more than 80A and not less than 20A. For elastic end caps 4 of the same structure, the lower the hardness, the lower the elastic coefficient of the elastic end cap 4, and the greater the elastic deformation when subjected to gastrointestinal peristalsis pressure, that is, the higher the relative elastic deformation, thereby playing a good buffering role, effectively avoiding hard collision with the inner wall of the gastrointestinal tract, and reducing damage to the inner wall.

[0088] 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 20A-60A. The deployment arm 2 is at least 50D to avoid bending under pressure. Through experiments, the Shore hardness of the elastic end cap 4 is selected to be no more than 60A, which can minimize the damage of the gastric retention device to the gastrointestinal tract. At the same time, the elastic end cap 4 is greater than 20A, ensuring a firm connection between the elastic end cap 4 and the deployment arm 2.

[0089] 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.

[0090] like Fig. 9 As shown, in terms of structural setting, a hollow structure is provided on the elastic end cap 4. The elastic end cap 4 made of the same material, the hollow structure can further enhance the deformation capacity of the elastic end cap 4.

[0091] like Fig. 9 In the embodiment, the hollow structure is an axial through hole 42 .

[0092] In some embodiments, the elastic end cap 4 may also be provided with a hollow chamber inside to achieve a hollow structure.

[0093] In some embodiments, the elastic end cap 4 is made of one or more polymers selected from: polyurethane, polyether-polyamide copolymer, thermoplastic elastomer, thermoplastic polyurethane, polycaprolactone polylactic acid copolymer, polytrimethylene carbonate, polysebacic acid glycerol natural rubber and silicone.

[0094] 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 there is a curved surface transition 41 or an inclined surface transition between the second end face and the side surface of the elastic end cover 4; and / or there are curved surface transitions 41 between the side surfaces of the deployment arm 2 and the side surfaces of the elastic end cover 4.

[0095] The curved or inclined surface transition can further prevent the overly sharp end from scratching the stomach lining tissue. The curved surface transition 41 mentioned in the present invention can be implemented in the following ways:

[0096] Mode 1: the curved surface transition 41 is an arc surface transition.

[0097] Mode 2: the curved surface transition 41 is a streamline transition.

[0098] Mode three: the curved surface transition 41 is an elliptical surface transition.

[0099] Method 4: the curved surface at the curved surface transition 41 is not limited to a single curved surface, that is, the curved surfaces have different curvatures and can be a combination of multiple curved surfaces (the curved surfaces can also be regarded as arc surfaces here).

[0100] In this embodiment, the curved surface transition 41 takes an arc surface transition as an example.

[0101] 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 .

[0102] The edges of the unfolding arm 2 and the elastic end cover 4 also have a curved transition 41 to prevent overly sharp edges from scratching the stomach lining tissue.

[0103] 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:

[0104] (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 together;

[0105] (2) Directly heat and hot-melt the first end surface of the elastic end cover 4 and the free end of the deployment arm 2; when the material of the deployment arm 2 and / or the elastic end cover 4 is a hot-melt material, light heating and melting bonding can be directly performed at the connection point.

[0106] A positioning structure 5 is provided between the first end surface of the elastic end cover 4 and the free end of the unfolding arm 2. After the first end surface of the elastic end cover 4 and the free end of the unfolding 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 unfolding arm 2 are hot-melt bonded, and the positioning mechanism strengthens the connection relationship between the elastic end cover 4 and the unfolding arm 2.

[0107] like Fig.10 In the figure, 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.

[0108] like Fig.11In the figure, the positioning structure 5 includes an axial through hole 42 arranged 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 unfolding 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.

[0109] exist Fig.11 In the embodiment, the heated molten melt 53 flows into the axial through hole 42 and can 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 part of the axial through hole 42 is a hollow structure, providing deformation space for the elastic end cover 4.

[0110] like Fig.12 As shown, in order to enable the deployment arm 2 to be relatively bent, thereby further avoiding scratches on the inner wall of the stomach, the deployment arm 2 includes a first section 21 and a second section 22 along the axial direction, and the hardness of the first section 21, the second section 22 and the elastic end cap 4 decreases in sequence. When the second section 22 of the deployment arm 2 with a lower hardness is subjected to gastrointestinal peristalsis, it can also be relatively bent, thereby further avoiding scratches on the inner wall of the intestine.

[0111] In some embodiments, the first section 21 TPU is Lubrizol TT-2075D-B40, and the second section 22 is: TPU: Covestro 1350D.

[0112] In the present invention, the elastic end cap 4 can be configured to be non-drug-carrying, 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.

[0113] 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.

[0114] See also Fig.13 On the other hand, the present invention provides a gastric retention device, including an elastic central component 1, a connecting component 3 and a plurality of unfolding arms 2, wherein the gastric retention device includes a folded configuration and an unfolded configuration, and the elastic central component 1 provides an elastic force to transform the gastric retention device from the folded configuration to the unfolded configuration.

[0115] 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, 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 active substances; 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, and when in the gastrointestinal tract, the gastrointestinal peristalsis exerts peristaltic force on the gastric retention device.

[0116] In some embodiments, the bending modulus of the flexible section 25 does not exceed 26.9 MPa, so that the first rigid arm 24 and the second rigid arm 23 can be bent at a certain angle relative to each other.

[0117] In some embodiments, the material of the flexible segment 25 can be selected from materials with hardness such as 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.

[0118] The bending test results of the unfolding arm 2 are as follows Figure 14-15 As shown, the first rigid arm 24 of the deployment arm 2 of the gastric retention device is fixed on the sliding platform 60, and the bending side block 70 has a pressure sensor. The deployment arm 2 is driven by the sliding platform 60 to slide, and the bending side block 70 blocks and contacts the end of the second rigid arm 23 so that the second rigid arm 23 is bent relative to the first rigid arm 24. Fig.15 , the angle α is the bending angle of the second rigid arm 23 .

[0119] 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 .

[0120] To prevent the gastric retention device from being prematurely expelled from the stomach, the elastic central member 1 and the first rigid arms 24 have an expanded diameter of at least 2 cm.

[0121] 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.

[0122] 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.

[0123] Examples 1-5

[0124] Preparation Figure 4 The gastric retention device shown includes the following process:

[0125] 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, the central area 121: Lubrizol TPU: PC-3575A, the distal area 122: Covestro TPU: 1350D, thereby forming an elastic central part 1;

[0126] 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 a connecting part 3;

[0127] 3. Polycaprolactone (PCL) powder (50D), polyolefin powder, active ingredients and auxiliary materials such as silicon dioxide are mixed, then extruded through an extruder, and cut into 10 mm segments to form a deployment arm 2;

[0128] 4. Silicone-20A, TPU-40A, TPU-60A, TPU-70A and TPU-80A materials are respectively extruded and cut by an extruder to form elastic end caps 4;

[0129] 5. The elastic central component 1, the connecting component 3, the unfolding arm 2, and the elastic end cover 4 are sequentially hot-melt-bonded by laser heating.

[0130] Example 6

[0131] The 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.

[0132] Comparative Example 1

[0133] The elastic end cap is made of silicone-10A material and bonded to the free end of the deployment arm. Since the elastic end cap of silicone-10A material is too soft, the elastic end cap is easily separated from the deployment arm.

[0134] Comparative Example 2

[0135] 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.

[0136] Example 7

[0137] 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:

[0138] Table 1. Elastic deformation test results of elastic end caps

[0139]

[0140] Example 8, Different Animal Experiments

[0141] The gastric retention devices were filled into the corresponding capsule shells and fed to the test dogs respectively. The activities of the test dogs were observed. X-ray observation showed that the gastric retention devices were retained in the digestive tract of the test dogs for about 7-14 days. The dogs were fed once every 7 days for 3 consecutive times, and the status of the test dogs was observed. The test results are shown in Table 2 below.

[0142] Table 2. Animal testing of gastric retention devices

[0143]

[0144] The test dogs of Example 6 and Comparative Example 2 were dissected and samples were taken from the duodenal part of the small intestine. Fig.16 and Fig.17 As shown, Fig.16 No changes or signs of trauma were found in the samples, suggesting the treatment was safe. Fig.17 In the sample, the inner wall of the duodenum had a large amount of congestion (the inner wall was purple in color) and some tissue depressions, which should be scratches / compression injuries caused by the end of the deployment arm.

[0145] Example 9

[0146] Preparation Fig.13 The gastric retention device shown includes the following process:

[0147] 1. Nickel-titanium alloy is used as the elastic alloy part, and thermoplastic polyurethane elastomer is externally injection-molded as the polymer outer layer, the central area: Lubrizol TPU: PC-3575A, the distal area: Covestro TPU: 1350D, thereby forming an elastic central part 1;

[0148] 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 a connecting part 3;

[0149] 3. Polycaprolactone (PCL) powder, polyolefin powder, active ingredients and auxiliary materials such as silicon dioxide are mixed, then extruded through an extruder, and cut into 8 mm and 4 mm segments to form a first rigid arm 24 and a second rigid arm 23;

[0150] 4. Extruding and cutting a material with a hardness of TPU-70A (bending modulus 14.5 MPa) through an injection extruder to form a flexible segment 25;

[0151] 5. The first rigid arm 24, the flexible segment 25, and the second rigid arm 23 are sequentially heat-melted and bonded by laser to form a deployment arm;

[0152] 5. The elastic center component 1, the connecting component 3, and the unfolding arm 2 are sequentially bonded by laser hot-melt bonding.

[0153] 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 provided as two rigid arms that can be folded relative to each other. Thus, 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.

[0154] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that the process, method, article or terminal device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or terminal device. In the absence of further restrictions, the elements defined by the sentence "include..." or "comprise..." do not exclude the existence of other elements in the process, method, article or terminal device including the elements. In addition, in this article, "greater than", "less than", "exceed" and the like are understood to exclude the number itself; "above", "below", "within" and the like are understood to include the number itself.

[0155] Although the above embodiments have been described, once those skilled in the art know the basic creative concepts, they can make additional changes and modifications to these embodiments. Therefore, the above description is only an embodiment of the present invention and does not limit the patent protection scope of the present invention. Any equivalent structure or equivalent process transformation made by using the contents of the specification and drawings of the present invention, or directly or indirectly used in other related technical fields, are also included in the patent protection scope 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, characterized in that The Shore hardness of the elastic end cover is 20-60A.

4. The gastric retention device according to claim 2, wherein: 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 to 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 cap and the free end of the deployment arm are directly heated and hot-melt bonded.

10. The gastric retention device according to claim 9, wherein: 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, characterized in that: The bending modulus of the flexible section does not exceed 26.9 MPa.

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

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