Oral gastric retention device and dosage form thereof

Abstract

The invention relates to a gastric retention system, and discloses an oral gastric retention device and a dosage form thereof, where the oral gastric retention device comprises an elastic central member, a plurality of elongated arms, a connecting member and a flexible connecting piece, the oral gastric retention device comprises a folded configuration and an unfolded configuration, the elongated arms are connected with the elastic central member through the connecting member, and the elongated arms are connected with the flexible connecting piece through the flexible connecting piece. Each extension arm is connected with the elastic center part or the other extension arms through the flexible connecting piece, in the oral gastric retention device, through the arrangement of the flexible connecting pieces, the extension arms have the same retention time in the stomach under the condition that the configuration transformation of the oral gastric retention device is not affected, so that the extension arms are prevented from being emptied in advance, and the utilization rate of medicine is guaranteed.

Description

Technical Field

[0001] The present invention relates to a gastric retention system, in particular to an oral gastric retention device and a dosage form thereof. Background Art

[0002] Patients on long-term medication regimens have very poor medication compliance, and current methods to improve compliance rates, such as educational interventions and counseling, have only achieved modest improvements. One method of reducing the frequency of dosing of oral dosage forms over an extended duration is to add a self-expansion mechanism to the dosage form that physically prevents the dosage form from leaving the gastric cavity. Current gastric retention devices generally include an elastic center, an extension arm, and a connecting component that can be weakened and broken. The gastric retention device is in an expanded configuration in the stomach. At this time, the gastric retention device has a sufficiently large projected area, generally greater than 2 cm (the diameter of the human stomach pylorus is about 2 cm), making it difficult for the gastric retention device to pass through the pylorus, thereby being retained in the stomach for continued drug administration. For example, patent CN108697649A discloses a gastric retention device, in which an elastomer is directly or indirectly connected to each slender member through an anchor between components. Patent CN106573999A discloses a retention structure and related methods. The retention structure is designed to controllably retain and release therapeutic agents and diagnostic agents in the stomach. In the prior art, after the gastric retention device enters the human stomach, the drug-loaded polymer begins to release active drugs. At this time, the connecting component begins to undergo strength weakening processes such as degradation, dissolution, dissociation or mechanical weakening in the gastric environment. In order to ensure that the drugs on the extended arms are fully released in the stomach, the connecting component needs to be constructed so that only when the active substances on the extended arms are completely released, the weakening degree of the connecting component can make the extended arms separate from the elastic central component in the gastric environment, so that the elastic central component and the extended arms can be discharged from the body.

[0003] However, in the actual production of gastric retention devices, it is difficult to ensure that the connecting parts are completely consistent. Moreover, when the gastric retention device enters the human body, since the gastric retention device needs to remain in the stomach for a long time and the gastric environment and movement are complex, some connecting parts may break prematurely, causing the corresponding extension arm to detach from the gastric retention device prematurely before the drug is completely released. The detached extension arm is difficult to continue to stay in the stomach and will immediately enter the small intestine stage and be discharged after detachment. The prematurely discharged extension arm will reduce the utilization rate of the drug on the gastric retention device and affect the therapeutic effect of the gastric retention drug. Summary of the invention

[0004] Therefore, it is necessary to provide an oral gastric retention device and a dosage form thereof to solve the problem that some drug-carrying arms of the existing oral gastric retention device are detached prematurely in the stomach, resulting in reduced drug utilization of the retention device.

[0005] To achieve the above object, the present invention provides an oral gastric retention device, comprising:

[0006] a flexible center member;

[0007] A plurality of extension arms, wherein the plurality of extension arms are arranged circumferentially around the elastic central component, and at least one of the extension arms is loaded with an active substance;

[0008] A connecting component, one end of the extension arm is connected to the elastic central component through the connecting component, and the connecting component is constructed to separate the extension arm from the elastic central component after being weakened;

[0009] A flexible connector, each of the extension arms is connected to the extension arm of the elastic central component through the flexible connector so that the plurality of extension arms have the same residence time;

[0010] The oral gastroretention device comprises a folded configuration and an unfolded configuration, and the oral gastroretention device completes the transformation from the folded configuration to the unfolded configuration by providing elastic force through an elastic central component.

[0011] Furthermore, the flexible connector is in the form of a line, a wire bundle, a belt or a mesh structure.

[0012] The linear structure connection can use conventional filaments, the belt structure can strengthen the fixed connection area between the flexible connector and the extension arm, and improve the fixing effect of the flexible connector and the extension arm. The wire harness and mesh structure can increase the connection points between the flexible connector and the extension arm, and have a better fixing effect on the separated extension arm. The wire harness structure can bundle the middle part of the filament to avoid multiple linear filaments from being entangled with each other, which affects the deployment of the deployment configuration of the oral gastric retention device.

[0013] Furthermore, the flexible connector corresponds to the extension arm one by one, and the flexible connector connects the extension arm and the elastic central component.

[0014] The extension arm is connected to the elastic central component. When individual connecting components are weakened and broken prematurely in the stomach, the corresponding extension arm is separated from the elastic central component. At this time, the flexible connector prevents it from being completely separated from the oral gastric retention device as a whole, and the extension arm that is separated in advance does not affect the continued retention of the entire device in the stomach. Therefore, the extension arm connected and separated by the flexible connector continues to remain in the stomach. At the same time, the extension arms are not connected to each other. The separation of a single extension arm will not affect the force applied to the remaining extension arms, thereby ensuring that the remaining extension arms are separated from the elastic central component within the normal separation time.

[0015] When the medicine on the extension arm is completely released, the strength of the connecting component is weakened, causing the extension arm and the elastic central component to completely break, so that the oral gastric retention device can no longer stay in the stomach and is then discharged through the stomach. At this time, the extension arm connected to the flexible connector is also discharged.

[0016] Furthermore, when the oral gastric retention device is in an expanded configuration, the length of the flexible connector has a redundant amount.

[0017] In the expanded configuration, the length of the flexible connector can be set redundantly or tensioned, preferably with a redundant length setting. The redundant setting makes the flexible connector easier to install and connect. At the same time, when part of the extension arm is separated from the elastic center component in advance, the redundant length line reduces the impact of the separated extension arm on the connection at the other end of the flexible connector.

[0018] Furthermore, the flexible connector and the extension arm are connected by embedded welding, embedded clamping, bonding and winding binding. The embedded welding ensures the fixing effect of the flexible connector and the extension arm.

[0019] Furthermore, a reinforcing piece is provided on the flexible connecting piece, and the reinforcing piece is embedded in the extension arm. The reinforcing piece can enhance the connection and fixing relationship between the flexible connecting piece and the extension arm.

[0020] Furthermore, the reinforcement piece is extended along the axial direction of the extension arm, and the reinforcement piece is extended axially to further enhance the strength of the extension arm in the axial direction.

[0021] Further, the elastic core component includes a memory alloy component, the flexible connector is fixed to the memory alloy component or the flexible polymer shell, and the memory alloy component is configured to transform from martensite to austenite to enable the oral gastroretention device to transform from a folded configuration to an unfolded configuration.

[0022] Compared with the use of polymers, the use of memory alloy components has a stronger elastic modulus and can better resist the peristaltic force from the stomach in the stomach. At the same time, after the memory alloy enters the body, due to the high temperature of the human body, the memory alloy can naturally transform from martensite to austenite, so that the extension arm can be expanded to form an expanded configuration, so that the device can remain in the stomach.

[0023] Furthermore, the elastic central component also includes a flexible polymer shell, the memory alloy component is fixed in the flexible polymer shell, and one end of the flexible connector is connected to the flexible polymer shell or the memory alloy component.

[0024] The flexible polymer shell fixes and protects the memory alloy component, the memory alloy component is fixed in the flexible polymer shell, the flexible connector is fixed to the memory alloy component or the flexible polymer shell, the flexible polymer has a certain softness after molding, and does not affect the folding of the memory alloy component. The flexible connector connects the flexible polymer shell or the memory alloy component. When some connecting components are weakened and broken prematurely, the flexible connector will still keep the extension arm on the gastric retention device.

[0025] Another aspect of the present invention provides an oral gastric retention device comprising:

[0026] a flexible center member;

[0027] A plurality of extension arms, wherein the plurality of extension arms are arranged circumferentially around the elastic central component, and at least one of the extension arms is loaded with an active substance;

[0028] A connecting component, one end of the extension arm is connected to the elastic central component through the connecting component, and the connecting component is constructed to separate the extension arm from the elastic central component after being weakened;

[0029] A flexible connector, each of the extension arms is connected to at least one other extension arm via the flexible connector, so that the plurality of extension arms have the same residence time;

[0030] The oral gastroretention device comprises a folded configuration and an unfolded configuration, and the oral gastroretention device completes the transformation from the folded configuration to the unfolded configuration by providing elastic force through an elastic central component.

[0031] Furthermore, the flexible connector is in the form of a line, a wire bundle, a belt or a mesh structure.

[0032] Furthermore, at least one of the flexible connectors is provided between two adjacent extension arms, and the flexible connector connects the two adjacent extension arms. The extension arms are connected by the flexible connector, and after a single extension arm is separated from the elastic central component in advance, its two adjacent extension arms are connected to the separated extension arm by the flexible connector, so as to avoid the premature emptying of the extension arm, so that the separated extension arm can have a sufficient residence time in the stomach, and ensure that the medicine thereon can be fully released in the stomach.

[0033] Furthermore, the flexible connecting member includes at least one annular connecting line, which is arranged around the elastic central component and is connected to each of the extension arms.

[0034] The annular connecting line connects all the drug carriers in series, effectively avoiding the premature detachment of the extension arms. When the strength of all the connecting parts is weakened and broken, all the extension arms are separated from the elastic central part together.

[0035] Furthermore, when the oral gastric retention device is in an expanded configuration, the length of the flexible connector has a redundant amount.

[0036] At the same time, when part of the extension arm is separated from the elastic central component in advance, the redundant length of the line reduces the lateral pulling force of the separated extension arm on the adjacent extension arm, thereby reducing the influence of the extended arm separated in advance on the adjacent extension arm.

[0037] Furthermore, the flexible connector and the extension arm are connected by embedded welding, embedded clamping or bonding.

[0038] Furthermore, a reinforcement piece is provided on the flexible connecting piece, and the reinforcement piece is embedded in the extension arm.

[0039] Furthermore, the reinforcement member is extended along the axial direction of the extension arm.

[0040] Further, the elastic center member includes a memory alloy member configured to transform from martensite to austenite to enable the oral gastroretention device to transform from a folded configuration to an expanded configuration.

[0041] Furthermore, the elastic central component also includes a flexible polymer shell, and the memory alloy component is fixed in the flexible polymer shell.

[0042] Another aspect of the present invention provides a gastroretentive dosage form, comprising any one of the above-mentioned oral gastroretentive devices in a folded configuration and a capsule shell for housing the oral gastroretentive device.

[0043] The above technical solution has the following beneficial effects:

[0044] In the present invention, a flexible connector is added to the oral gastric retention device, and the flexible connector does not affect the folding and unfolding of the oral gastric retention device. When part of the extension arm is prematurely weakened and broken due to the connection component or prematurely separated from the elastic central component due to uneven force in the stomach, due to the connection of the flexible connector, the separated extension arm will still remain on the gastric retention device, and because the gastric retention device still has a relatively complete unfolded configuration, it can still be maintained in the stomach at this time. Therefore, the extension arm separated in advance in the present invention will not be emptied from the stomach in advance, so that the extension arm can retain the same retention time in the stomach, avoiding premature emptying of the extension arm, and the active substances on the extension arm can be fully released in the stomach, effectively improving the utilization rate of the active substances. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 FIG. 1 is a block diagram of the oral gastric retention device described in Example 1 in an expanded configuration without the flexible connector connected.

[0046] Figure 2 FIG. 1 is a block diagram of the oral gastroretention device described in Example 1 in a folded configuration without the flexible connector connected.

[0047] Figure 3 A top view of the oral gastric retention device in the deployed configuration described in Example 1.

[0048] Figure 4 A top view of the oral gastric retention device in the deployed configuration described in Example 3.

[0049] Figure 5 A top view of the oral gastric retention device in the expanded configuration described in Example 4.

[0050] Figure 6 A top view of the oral gastric retention device in the deployed configuration described in Example 5.

[0051] Figure 7 A top view of the oral gastric retention device in the deployed configuration described in Example 6.

[0052] Figure 8 A top view of the oral gastric retention device in the expanded configuration described in Example 7.

[0053] Fig. 9 A structural diagram of the oral gastric retention device in the expanded configuration described in Example 9, without the flexible connector connected.

[0054] Fig.10 A perspective view of the oral gastroretention device of Example 9 in the deployed configuration without the flexible connector attached.

[0055] Fig.11 This is a structural diagram of the oral gastric retention device in a folded configuration as described in Example 9, connected to a flexible connector.

[0056] Fig.12 Schematic diagram of the oral gastric retention device in the expanded configuration described in Example 9.

[0057] Fig.13 This is a schematic diagram of the embedding of the extension arm and the additional component described in Example 10.

[0058] Fig.14 A bottom view of the oral gastric retention device described in Example 11 in the expanded configuration.

[0059] Fig.15 A bottom view of the oral gastric retention device described in Example 12 in the expanded configuration.

[0060] Fig.16 A structural diagram of the oral gastric retention device in the expanded configuration described in Example 15, without the flexible connector connected.

[0061] Fig.17 An exploded view of the oral gastroretention device of Example 15 in the deployed configuration without the flexible connector attached.

[0062] Fig.18 This is a bottom structural diagram of the oral gastric retention device in the expanded configuration described in Example 15.

[0063] Fig.19 This is a structural diagram of the gastric retentive dosage form described in Example 16.

[0064] Description of reference numerals:

[0065] 10. Elastic center component; 11. Memory alloy component; 12. Ribs; 13. Flexible polymer shell; 14. Memory alloy wire; 20. Extension arm; 21. Slit; 22. Connecting groove; 30. Connecting component; 40. Flexible connector; 41. Flexible filament; 42. Wiring structure; 43. Flexible connecting net; 44. Ring connecting line; 45. Reinforcement; 46. Connecting belt. DETAILED DESCRIPTION

[0066] The present invention provides an oral gastric retention device, comprising:

[0067] a flexible center member;

[0068] A plurality of extension arms, the plurality of extension arms are arranged circumferentially around the elastic central component, and the extension arms are loaded with active substances;

[0069] A connecting component, one end of the extension arm is connected to the elastic central component through the connecting component, and the connecting component is constructed to separate the extension arm from the elastic central component after being weakened;

[0070] A flexible connector, each of the extension arms is connected to the elastic central component or other extension arms through the flexible connector so that the plurality of extension arms have the same residence time,

[0071] The oral gastroretentive device comprises a folded configuration and an expanded configuration, and the elastic central member is configured to provide a force for the oral gastroretentive device to transform from the folded configuration to the expanded configuration.

[0072] Another aspect provides an oral gastric retention device comprising:

[0073] a flexible center member;

[0074] A plurality of extension arms, the plurality of extension arms are arranged circumferentially around the elastic central component, and the extension arms are loaded with active substances;

[0075] A connecting component, one end of the extension arm is connected to the elastic central component through the connecting component, and the connecting component is constructed to separate the extension arm from the elastic central component after being weakened;

[0076] A flexible connector, each of the extension arms is connected to at least one other extension arm via the flexible connector, so that the plurality of extension arms have the same residence time;

[0077] The oral gastroretentive device comprises a folded configuration and an expanded configuration, and the elastic central member is configured to provide a force for the oral gastroretentive device to transform from the folded configuration to the expanded configuration.

[0078] In the oral gastric retention device provided by the present invention, the number of extension arms is at least 4. The length of the extension arms can be designed so that when the oral gastric retention device is in the expanded configuration, the minimum width of at least one plane projection is greater than 2 cm. Since the width of the human pylorus is 2 cm, the oral gastric retention device will be retained in the stomach when it is greater than 2 cm. Only when the extension arms are separated and broken and lose the expanded configuration can the oral gastric retention device be emptied from the stomach.

[0079] In some embodiments, the folded configuration is that the extension arms gather together in the same direction to reduce the projection size of the gastric retention device in the horizontal plane, thereby facilitating the preparation of the gastric retention device into an easy-to-swallow dosage form.

[0080] In some embodiments, the active substance is a diagnostic agent or a therapeutic agent.

[0081] In some embodiments, a protruding rib is provided at a connection between the elastic central component and the extension arm, and the rib is connected to the extension arm via a connecting component.

[0082] In some embodiments, the strength weakening process is a process in which the connecting component undergoes degradation, dissolution, dissociation or mechanical weakening. The connecting component can achieve the above process by selecting a material that degrades, dissolves or dissociates in the human stomach.

[0083] Furthermore, the flexible connector is in the form of a line, a wire bundle, a belt or a mesh structure.

[0084] In some embodiments, the wire harness includes a plurality of flexible thin wires, the middle portions of the plurality of connecting wires pass through the same cluster sleeve, and the two ends of the connecting wires are respectively connected to two adjacent extension arms.

[0085] In some embodiments, the diameter of the flexible filament is 0.5 mm-3 mm.

[0086] In some embodiments, the filaments of the present invention are made of high-toughness and high-elasticity filaments that are not prone to breakage, thereby ensuring the consistency of the retention time of the extension arm in the stomach.

[0087] In some embodiments, the flexible connector and the extension arm are connected by one of embedded welding, embedded clamping, bonding and winding binding, wherein:

[0088] Embedded fusion connection method: prefabricate or open a transverse connection hole on the extension arm, and pass the flexible connector through the connection hole; laser heat and melt the connection hole part of the extension arm, so that the flexible thin wire is connected and fixed to the extension arm.

[0089] Embedded card connection method: a transverse card hole is prefabricated or opened on the extension arm, and one end of the flexible connector is embedded in the card hole and engaged with the card hole.

[0090] Adhesive connection method: an adhesive is provided on the flexible connector and / or the extension arm, and the two are bonded and fixed by the adhesive.

[0091] The connecting component of the present invention is made of water-soluble and / or degradable polymers and their blends, including but not limited to: polyvinyl pyrrolidone, polyvinyl alcohol, polyorthoester, polyhydroxybutyrate and mixtures thereof.

[0092] The memory alloy component of the present invention is made of nickel-titanium memory alloy.

[0093] The material of the flexible polymer shell in the present invention can be selected from at least one material of polypropylene, polystyrene, polyvinyl chloride, synthetic rubber, phenolic resin, chloroprene rubber, nylon, polyacrylonitrile, PVB, silicone, acrylonitrile-butadiene-styrene, high-density polyethylene, polycarbonate, polycaprolactone, polylactic acid, nylon, acrylic acid, polyethylene terephthalate, polybutylene terephthalate, acetal, polyimide, polyurethane and epoxy resin.

[0094] 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.

[0095] Example 1

[0096] The present embodiment discloses an oral gastric retention device, comprising an elastic central component 10, a plurality of extension arms 20, a connecting component 30 and a plurality of flexible connectors 40, wherein the plurality of extension arms 20 are circumferentially arranged around the elastic central component 10, and active substances are loaded on the extension arms 20; one end of the extension arm 20 is connected to the elastic central component 10 through the connecting component 30, and the connecting component 30 is configured to separate the extension arm 20 from the elastic central component 10 by degradation, dissolution, dissociation or mechanical weakening; the oral gastric retention device comprises a folded configuration and an unfolded configuration, and the elastic central component 10 is configured to provide power for the oral gastric retention device to change from the folded configuration to the unfolded configuration.

[0097] In this embodiment, the elastic central component 10 is a memory alloy component 11, and the memory alloy component 11 has a protruding rib 12, and the rib 12 is connected to the extension arm 20 through a connecting component 30. Figure 1-2 The memory alloy component 11 has six protruding ribs 12 , and each rib 12 is connected to an extension arm 20 .

[0098] Attached Figure 1 and attached Figure 2They are respectively the expanded configuration and the folded configuration of the gastric retention device before the flexible connector 40 is connected.

[0099] like Figure 3 As shown, in this embodiment, the flexible connector 40 uses a linear flexible filament 41, and two adjacent extension arms 20 are connected by one flexible filament 41, and the flexible filament 41 and the extension arm 20 are embedded and fused.

[0100] In this embodiment, after the gastric retention device enters the human stomach, the ambient temperature rises, and the memory alloy component 11 is transformed from martensite to austenite so that the oral gastric retention device is transformed from a folded configuration to an unfolded configuration. The memory alloy component 11 is used as the elastic center component 10, which has a strong elastic modulus and can better resist the pressure from the stomach wall. The extension arms 20 are connected by flexible thin wires. When a single extension arm 20 is separated from the elastic center component in advance, its two adjacent extension arms 20 still connect the separated extension arms 20. Avoid the emptying of the extension arm 20 alone, so that the extension arm 20 can have a sufficient residence time in the stomach to ensure that the drug thereon is effectively released.

[0101] The preparation of this embodiment can be carried out by the following steps, including:

[0102] (1) First, prepare the main body of the gastric retention device, which includes an elastic central component 10, a plurality of extension arms 20 and a connecting component 30;

[0103] (2) prefabricating or opening a transverse connecting hole on the extension arm 20, and passing the flexible filament 41 through the connecting hole;

[0104] (3) The connection hole on the extension arm 20 is melted by laser heating so that the flexible thin wire is connected and fixed to the extension arm 20.

[0105] The prefabricated connection hole on the extension arm 20 may also be in the form of a connection groove, a connection seam, etc. After the flexible filament 41 passes through, it can be melted and sealed.

[0106] Example 2

[0107] This embodiment discloses an oral gastric retention device, which is different from Embodiment 1 in that two adjacent extension arms are connected by two parallel flexible filaments, and multiple flexible filaments are connected together to improve the connection strength of the extension arms.

[0108] Example 3

[0109] This embodiment discloses an oral gastric retention device, which is different from the embodiment 1 in that:

[0110] like Figure 4As shown, two adjacent extension arms 20 include three flexible filaments 41, and the middle parts of the three flexible filaments are bundled by a bundling sleeve to form a harness structure 42. The harness structure 42 can bundle the middle part to prevent the flexible filaments 41 from being entangled with each other and affecting the deployment of the deployment configuration of the oral gastric retention device.

[0111] Example 4

[0112] like Figure 5 This embodiment discloses an oral gastric retention device. Different from the embodiment 1, the flexible connecting member is a flexible connecting belt 46 having a certain width, and the flexible connecting belt connects two adjacent extension arms 20.

[0113] Example 5

[0114] This embodiment discloses an oral gastric retention device, which is different from the embodiment 1 in that Figure 6 As shown, the flexible connector 40 is a flexible connector mesh 43. The mesh structure can increase the connection points between the flexible connector 40 and the extension arm 20, and has a better fixing effect on the separated extension arm 20.

[0115] Example 6

[0116] This embodiment discloses an oral gastric retention device. Different from the embodiment 1, the flexible connector 40 is a long line with redundant length, such as Figure 7 As shown, the flexible connector 40 is a flexible thread 41, which is connected to the extension arm 20. The flexible thread 41 still has redundancy when the gastric retention device is in the expanded configuration.

[0117] Example 7

[0118] See also Figure 8 The present embodiment discloses an oral gastric retention device, comprising an elastic central component 10, a plurality of extension arms 20, a connecting component 30 and a flexible connector 40, wherein the plurality of extension arms 20 are circumferentially arranged around the elastic central component 10, and the extension arms 20 are loaded with active substances; one end of the extension arm 20 is connected to the elastic central component 10 through the connecting component 30, and the connecting component 30 is configured to separate the extension arm 20 from the elastic central component 10 by degradation, dissolution, dissociation or mechanical weakening, and the oral gastric retention device comprises a folded configuration and an unfolded configuration, and the elastic central component 10 is configured to provide power for the oral gastric retention device to change from the folded configuration to the unfolded configuration.

[0119] In this embodiment, the elastic central component 10 uses a memory alloy component 11, and the flexible connecting member 40 includes an annular connecting wire 44, which is arranged around the memory alloy component 11 and is connected to each extension arm 20.

[0120] The extension arms 20 can be connected to form an integral structure through a ring-shaped connecting line 44 . When all the connecting components 30 are weakened and separated, all the extension arms 20 are separated from the elastic central component 10 together.

[0121] Example 8

[0122] This embodiment discloses an oral gastric retention device, which is different from Embodiment 7 in that when the number of annular connecting lines is two, multiple annular connecting lines are arranged in concentric circles, and each annular connecting piece is connected to the extension arm.

[0123] Example 9

[0124] See also Figure 9-12 The present embodiment discloses an oral gastric retention device, comprising an elastic central component 10, a plurality of extension arms 20, a connecting component 30 and a plurality of flexible connecting members 40, wherein the plurality of extension arms 20 are circumferentially arranged around the elastic central component 10, and the extension arms 20 are loaded with active substances; one end of the extension arm 20 is connected to the elastic central component 10 through the connecting component 30, and the connecting component 30 is configured to separate the extension arm 20 from the elastic central component 10 by degradation, dissolution, dissociation or mechanical weakening, and the oral gastric retention device comprises a folded configuration and an unfolded configuration, and the elastic central component 10 is configured to provide power for the oral gastric retention device to change from the folded configuration to the unfolded configuration.

[0125] In this embodiment, the elastic central component 10 is a memory alloy component 11 , which is wrapped and fixed in a flexible polymer shell 13 and forms six ribs 12 . The six ribs 12 are connected to the extension arm 20 through a connecting component 30 .

[0126] Specifically, the memory alloy component 11 may include three cross-arranged memory alloy wires 14 , and then the polymer of the shell is injected through a mold molding method to wrap the memory alloy wires 14 with the flexible polymer shell 13 .

[0127] The model forming method can be: three memory alloy wires are placed crosswise in the model, and then the shell polymer in a molten state is injected and then cooled, and the shell polymer completely wraps the memory alloy wires.

[0128] Figure 9-11 It is a structural diagram without the flexible connector 40 connected.

[0129] like Fig.12 The flexible connecting member 40 includes six flexible filaments 41 , and two adjacent extension arms 20 are connected by the flexible filaments 41 .

[0130] The flexible polymer shell 13 fixes and protects the memory alloy component 11. The flexible polymer shell 13 has a certain degree of softness and does not affect the folding of the memory alloy component 11. The flexible polymer shell 13 is connected to the extension arm 20. When the partial connection component 30 is weakened and broken prematurely, the flexible connector 40 still keeps the extension arm 20 on the gastric retention device.

[0131] Example 10

[0132] See also Fig.13 This embodiment discloses an oral gastric retention device. The difference from the first embodiment is that a reinforcing member 45 is provided on the flexible connecting member 40 . The reinforcing member 45 is embedded in the extension arm 20 . The reinforcing member 45 is extended along the axial direction of the extension arm 20 .

[0133] In this embodiment, the reinforcing member 45 is a slender reinforcing sheet, and the flexible connecting member 40 is a flexible filament 41. Fig.13 As shown, a slit 21 extending along the axial direction is preset on the bottom surface of the extension arm 20, and a connecting groove 22 is preset. The reinforcing sheet connected by the flexible filament 41 is placed in the slit 21, and the flexible filament 41 corresponds to the connecting groove 22. Thereafter, the connecting groove 22 and the slit 21 are melted by laser heating, so that the reinforcing piece 45 is embedded in the extension arm 20.

[0134] In other embodiments, the reinforcing sheet may be in other special shapes, such as a wavy sheet extending axially along the extension arm.

[0135] Embodiment 11

[0136] See also Fig.14 The present embodiment discloses an oral gastric retention device, comprising an elastic central component 10, a plurality of extension arms 20, a connecting component 30 and a plurality of flexible connecting members 40, wherein the plurality of extension arms 20 are circumferentially arranged around the elastic central component 10, and the extension arms 20 are loaded with active substances; one end of the extension arm 20 is connected to the elastic central component 10 through the connecting component 30, and the connecting component 30 is configured to separate the extension arm 20 from the elastic central component 10 by degradation, dissolution, dissociation or mechanical weakening, and the oral gastric retention device comprises a folded configuration and an unfolded configuration, and the elastic central component 10 is configured to provide power for the oral gastric retention device to change from the folded configuration to the unfolded configuration.

[0137] In this embodiment, the elastic central component 10 is a memory alloy component 11 . The memory alloy component 11 has six ribs 12 . The six ribs 12 are connected to the extension arm 20 through a connecting component 30 .

[0138] Specifically, in this embodiment, the flexible connector 40 includes six flexible filaments 41 , which correspond one to one with the extension arms 20 , one end of the flexible filament 41 is connected to the memory alloy component 11 , and the other end of the flexible filament 41 is connected to the bottom surface of the extension arm 20 .

[0139] In this embodiment, when the connecting component 30 is broken and separated in advance, the extension arm 20 is separated from the memory alloy component 11, and the separated extension arm 20 is still retained on the gastric retention device due to the connection of the flexible filament 41. Therefore, the extension arm 20 has a common residence time in the stomach, and when the gastric retention system breaks and separates enough connecting components 30, the extension arm 20 and the memory alloy component 11 are emptied by the stomach.

[0140] Meanwhile, in this solution, the extension arms 20 are not connected to each other, and the separation of a single extension arm 20 will not affect the force of the remaining extension arms 20, thus ensuring the normal breakage of the remaining extension arms 20.

[0141] When the connecting component 30 is weakened and broken enough, the oral gastric retention device can no longer stay in the stomach and is discharged through the stomach. At this time, the extension arm 20 connected to the flexible connecting member 40 is also discharged.

[0142] Example 12

[0143] like Fig.15 As shown, this embodiment discloses an oral gastric retention device, which is different from the embodiment 11 in that, specifically, in this embodiment, a flexible connector 40 including six wire harness structures 42 is included, and the wire harness structure 42 specifically includes three flexible filaments 41. The middle parts of the three flexible filaments are bundled by a bundle sleeve to form a wire harness structure 42. The wire harness structure can bundle the middle part to prevent the flexible filaments 41 from being entangled with each other, which affects the deployment of the deployment configuration of the oral gastric retention device. One end of the three flexible filaments 41 is connected to the bottom surface of the extension arm 20, and the other end is connected to the memory alloy component 11. The three flexible filaments 41 are connected to the extension arm 20 in sequence along the axial direction.

[0144] Embodiment 13

[0145] This embodiment discloses an oral gastric retention device, which is different from Embodiment 11 in that the flexible connector is in the form of a connecting belt.

[0146] Embodiment 14

[0147] This embodiment discloses an oral gastric retention device, which is different from Embodiment 11 in that the flexible connector is in the form of a flexible connecting net.

[0148] In the oral gastric retention devices disclosed in Examples 11-14, the length of the flexible connecting line can be set to still have a redundant amount when the retention device is in the gastric expanded configuration.

[0149] Embodiment 15

[0150] like Figure 16-18 The present embodiment discloses an oral gastric retention device, comprising an elastic central component 10, a plurality of extension arms 20, a connecting component 30 and a plurality of flexible connecting members 40, wherein the plurality of extension arms 20 are circumferentially arranged around the elastic central component 10, and the extension arms 20 are loaded with active substances; one end of the extension arm 20 is connected to the elastic central component 10 through the connecting component 30, and the connecting component 30 is configured to separate the extension arm 20 from the elastic central component 10 by degradation, dissolution, dissociation or mechanical weakening, and the oral gastric retention device comprises a folded configuration and an unfolded configuration, and the elastic central component 10 is configured to provide power for the oral gastric retention device to change from the folded configuration to the unfolded configuration.

[0151] In this embodiment, specifically, the memory alloy component 11 may include three cross-arranged memory alloy wires 14 , and then the flexible polymer shell 13 may be wrapped around the memory alloy wires 14 by a mold forming method.

[0152] Specifically, in this embodiment, the flexible connector 40 includes six flexible filaments 41, and the six flexible filaments 41 correspond to the extension arms 20 one by one. One end of the flexible filament 41 is connected to the flexible polymer shell 13, and the other end of the flexible filament 41 is connected to the extension arm 20. The flexible filament 41 can be embedded in the flexible polymer shell when it is cooled and formed. When the cooling and forming is completed, the flexible filament is connected to the flexible polymer shell.

[0153] In this embodiment, when the connecting component 30 is broken and separated in advance, the extension arm 20 is separated from the memory alloy component 11, and the separated extension arm 20 is still retained on the gastric retention device due to the connection of the flexible filament 41. Therefore, the extension arm 20 has a common residence time in the stomach, and when the gastric retention system breaks and separates enough connecting components 30, the extension arm 20 and the memory alloy component 11 are emptied by the stomach.

[0154] Meanwhile, in this solution, the extension arms 20 are not connected to each other, and the separation of a single extension arm 20 will not affect the force of the remaining extension arms 20, thus ensuring the normal breakage of the remaining extension arms 20.

[0155] When the connecting component 30 is weakened and broken enough, the oral gastric retention device can no longer stay in the stomach and is discharged through the stomach. At this time, the extension arm 20 connected to the flexible connecting member 40 is also discharged.

[0156] like Fig.18In this embodiment, the two ends of the flexible filament 41 are connected to the outer side surfaces of the extension arm 20 and the elastic central component 10 in the folded configuration of the oral gastric retention device, so as to prevent the flexible filament 41 from affecting the transformation of the configuration of the oral gastric retention device.

[0157] Example 16

[0158] See also Fig.19 This embodiment discloses a gastroretentive dosage form, comprising an oral gastroretentive device as in Example 1 in a folded configuration and a capsule housing containing the oral gastroretentive device. Fig.19 The flexible connector is not shown.

[0159] In the present invention, a flexible connector 40 is added to the oral gastric retention device. The flexible connector 40 does not affect the folding and unfolding of the oral gastric retention device. When part of the extension arm 20 is separated from the elastic central component 10 in advance due to premature weakening and rupture of the connecting component 30, the separated extension arm 20 is still maintained on the gastric retention device due to the connection of the flexible connector 40, so that the active drug on the extension arm 20 can be fully released in the stomach, effectively improving the utilization rate of the drug on the extension arm 20.

[0160] 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.

[0161] 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. An oral gastric retention device, characterized in that include: a flexible center member; A plurality of extension arms, wherein the plurality of extension arms are arranged circumferentially around the elastic central component, and at least one of the extension arms is loaded with an active substance; A connecting component, one end of the extension arm is connected to the elastic central component through the connecting component, and the connecting component is constructed to separate the extension arm from the elastic central component after being weakened; A flexible connector, each of the extension arms is connected to the extension arm of the elastic central component through the flexible connector so that the plurality of extension arms have the same residence time; The oral gastroretention device comprises a folded configuration and an unfolded configuration, and the oral gastroretention device completes the transformation from the folded configuration to the unfolded configuration by providing elastic force through an elastic central component.

2. The oral gastric retention device according to claim 1, wherein: The flexible connecting piece is in the form of a line, a wire bundle, a belt or a mesh structure.

3. The oral gastric retention device according to claim 1, wherein: The flexible connectors correspond to the extension arms one by one, and the flexible connectors connect the extension arms and the elastic central component.

4. The oral gastric retention device according to claim 1, wherein: When the oral gastroretention device is in the expanded configuration, the length of the flexible connecting member has a redundant amount.

5. The oral gastric retention device according to claim 1, wherein: The flexible connector and the extension arm are connected by one of the following methods: embedded welding, embedded clamping, bonding and winding binding.

6. The oral gastric retention device according to claim 1, wherein: The flexible connecting piece is provided with a reinforcing piece, and the reinforcing piece is embedded in the extension arm.

7. The oral gastric retention device according to claim 6, wherein: The reinforcement piece is extended along the axial direction of the extension arm.

8. The oral gastric retention device according to claim 1, wherein: The resilient center member includes a memory alloy member configured to transform from martensite to austenite to enable the oral gastroretention device to transform from a folded configuration to an expanded configuration.

9. The oral gastric retention device according to claim 8, wherein: The elastic central component further comprises a flexible polymer shell, the memory alloy component is fixed in the flexible polymer shell, and one end of the flexible connector is connected to the flexible polymer shell or the memory alloy component.

10. An oral gastric retention device, characterized in that include: a flexible center member; A plurality of extension arms, wherein the plurality of extension arms are arranged circumferentially around the elastic central component, and at least one of the extension arms is loaded with an active substance; A connecting component, one end of the extension arm is connected to the elastic central component through the connecting component, and the connecting component is constructed to separate the extension arm from the elastic central component after being weakened; A flexible connector, each of the extension arms is connected to at least one other extension arm via the flexible connector, so that the plurality of extension arms have the same residence time; The oral gastroretention device comprises a folded configuration and an unfolded configuration, and the oral gastroretention device completes the transformation from the folded configuration to the unfolded configuration by providing elastic force through an elastic central component.

11. The oral gastric retention device according to claim 10, wherein: The flexible connecting piece is in the form of a line, a wire bundle, a belt or a mesh structure.

12. The oral gastric retention device of claim 10, wherein: At least one flexible connector is provided between two adjacent extension arms, and the flexible connector connects the two adjacent extension arms.

13. The oral gastric retention device of claim 10, wherein: The flexible connecting member comprises at least one annular connecting line, which is arranged around the elastic central component and is connected to each of the extension arms.

14. The oral gastric retention device of claim 10, wherein: When the oral gastroretentive device is in the expanded configuration, the length of the flexible connector has a redundant amount.

15. The oral gastric retention device of claim 10, wherein: The flexible connector and the extension arm are connected by one of the following methods: embedded welding, embedded clamping, bonding and winding binding.

16. The oral gastroretentive device of claim 10, wherein: The flexible connecting piece is provided with a reinforcing piece, and the reinforcing piece is embedded in the extension arm.

17. The oral gastroretentive device of claim 16, wherein: The reinforcement piece is extended along the axial direction of the extension arm.

18. The oral gastroretentive device of claim 1, wherein: The resilient center member includes a memory alloy member configured to transform from martensite to austenite to enable the oral gastroretention device to transform from a folded configuration to an expanded configuration.

19. The oral gastroretentive device of claim 18, wherein: The elastic core component further includes a flexible polymer shell, and the memory alloy component is fixed in the flexible polymer shell.

20. A gastric retentive dosage form, characterized in that The invention comprises the oral gastroretentive device according to any one of claims 1 to 19 in a folded configuration and a capsule shell for housing the oral gastroretentive device.

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