Gastric retention device for oral administration

Abstract

The present disclosure relates to a gastric retention device for oral administration. The gastric retention device includes a collapsible central member, a plurality of elongate limb members, and a plurality of connecting members. The collapsible central member includes a plurality of ribs including at least one superelastic alloy. The elongate limb members are radially connected to the collapsible central member, wherein the plurality of elongate limb members correspond to the plurality of ribs. Each connecting member connects one elongate limb member to the collapsible central member. The ribs are expandable from a folded first state to a deployed second state to deploy the elongate limb component. At least one of the elongate limb components is configured to store a releasable drug. The connecting members are configured to transition from a rigid first state to a free second state to allow independent movement of the elongate limb members relative to the collapsible central member.

Description

Technical Field

[0001] The present invention relates to a gastric retention device for oral drug delivery. Background Art

[0002] Medical adherence to treatment regimens that require long-term adherence to medication is often poor. Adherence rates are lowest in primary and secondary prevention, where the conditions to be prevented or treated are often asymptomatic and medication regimens have no immediate practical effect. Current approaches to improving adherence, such as patient-directed interventions and advice, have yielded only limited improvements.

[0003] Drug treatment options such as invasive drug delivery methods and drug formulations are often less popular due to their invasiveness, while oral drug delivery is widely accepted because it is more convenient and cheaper. However, the transit time of drugs through the human gastrointestinal tract is only about 24 to 48 hours, including about 1 to 2 hours in the stomach, about 3 hours in the small intestine, and about 6 to 12 hours in the large intestine. Therefore, when a single dose is administered, it is impossible to achieve a single dose action period longer than the transit time.

[0004] A method for oral dosage forms to achieve a dosing frequency over a prolonged duration is to incorporate a self-expanding structure into the dosage form that physically prevents the dosage form from leaving the stomach cavity. Conventionally, the self-expanding structure is made entirely of superelastic materials (such as elastomers). However, using only polymers to create such structures has multiple disadvantages.

[0005] It is worth noting that in order to prevent the dosage form from leaving the stomach cavity by itself, it needs to have a minimum bending modulus to resist being squeezed through the pyloric sphincter connecting the stomach and duodenum. Polymers have relatively low bending moduli, so if polymers are used in a self-expanding structure, the cross-section of the structure needs to be large enough to achieve the minimum bending modulus, which results in a certain limit on the minimum volume of the structure. This limits the minimum size of the drug, making it unsuitable for patients with difficulty swallowing or young children.

[0006] Another disadvantage of using polymers as shape memory materials is that there are a limited number of polymers that meet the minimum flexural modulus requirement while also meeting other material property requirements, such as biocompatibility, melt processability for low-cost large-scale production, sufficient surface energy to bond with other parts of the dosage form, and high creep resistance to allow the self-expanding structure to rebound to its original shape after long-term storage.

[0007] Therefore, there is a need to solve at least one of the above problems or provide a useful alternative. Summary of the invention

[0008] According to a first aspect of the present invention, there is provided a gastric retention device for oral administration, comprising:

[0009] Foldable central superelastic alloy component;

[0010] A plurality of elongated limb members capable of carrying active substances, wherein the active substances are therapeutic agents or diagnostic agents,

[0011] wherein each of the plurality of elongated limb members is connected to the foldable central superelastic alloy member via a connecting member,

[0012] wherein the foldable central superelastic alloy component is elastically deformed when the gastroretention device is in a folded configuration, and the foldable central superelastic alloy component rebounds when the gastroretention device is in an expanded configuration, and

[0013] Wherein, the connecting component undergoes degradation, dissolution, dissociation or mechanical weakening, thereby causing the gastric retention device to lose the shape of the deployed configuration.

[0014] The gastric retention device may have a folding force of at least 0.5N in the expanded configuration.

[0015] The expanded configuration of the gastric retention device may have a expanded diameter of at least 2 cm.

[0016] The gastric retention device can be configured to maintain the shape of the expanded configuration for at least 24 hours.

[0017] The foldable central superelastic alloy component may include at least one material selected from the following group: nitinol (Ni-Ti), brass (Cu-Zn), copper aluminum nickel (Cu-Al-Ni) alloy, gold cadmium (Au-Cd) alloy, gold copper zinc (Au-Cu-Zn) alloy, indium thallium (In-Tl) alloy, cobalt nickel aluminum (Co-Ni-Al) alloy, copper aluminum beryllium zirconium (Cu-Al-Be-Zr) alloy, copper aluminum beryllium chromium (Cu-Al-Be-Cr) alloy, copper aluminum beryllium gadolinium (Cu-Al-Be-Gd) alloy, copper aluminum nickel hafnium (Cu-Al-Ni-Hf) alloy, copper tin (Cu-Sn) alloy. Gold, copper-zinc-silicon (Cu-Zn-Si) alloy, copper-zinc-aluminum (Cu-Zn-Al) alloy, copper-zinc-tin (Cu-Zn-Sn) alloy, iron-manganese-silicon (Fe-Mn-Si) alloy, iron-platinum (Fe-Pt) alloy, manganese-copper (Mn-Cu) alloy, nickel-iron-gallium (Ni-Fe-Ga) alloy, nickel-titanium-hafnium (Ni-Ti-Hf) alloy, nickel-titanium-palladium (Ni-Ti-Pd) alloy, nickel-manganese-gallium (Ni-Mn-Ga) alloy, nickel-manganese-gallium-copper (Ni-Mn-Ga-Cu) alloy, nickel-manganese-gallium-cobalt (Ni-Mn-Ga-Co) alloy, titanium-niobium (Ti-Nb) alloy.

[0018] The foldable central superelastic alloy component can be securely fixed within an outer skin component.

[0019] The at least 80% of the folding force may be provided by the foldable central superelastic alloy component.

[0020] The connection component may be connected to the outer skin component.

[0021] The outer surface layer component can be made of at least one material selected from the following group: polypropylene, polystyrene, polyvinyl chloride, synthetic rubber, phenolic resin or bakelite, chloroprene rubber, nylon, polyacrylonitrile, PVB, silicone, acrylonitrile-butadiene-styrene, high-density polyethylene, polycarbonate, acrylic, polyethylene terephthalate, polybutylene terephthalate, acetal, polyimide, polyurethane and epoxy resin.

[0022] The gastroretentive device may further include a housing for containing the gastroretentive device in the folded configuration, wherein the housing is configured to degrade, dissolve, separate, or mechanically weaken to allow the gastroretentive device to recoil and assume the expanded configuration.

[0023] According to a second aspect of the present invention, there is provided a gastric retention device for oral administration, comprising:

[0024] Foldable central shape memory alloy component;

[0025] A plurality of elongated limb members capable of carrying an active substance, the active substance being a therapeutic agent or a diagnostic agent,

[0026] wherein each of the plurality of elongated limb members is connected to the foldable central shape memory alloy member via a connecting member,

[0027] wherein the foldable central shape memory alloy component undergoes a phase transformation from a martensite phase to an austenite phase in its crystal structure, thereby enabling the gastric retention device to transform from a folded configuration to an expanded configuration, and

[0028] The connecting component degrades, dissolves, dissociates, or mechanically weakens, thereby causing the gastric retention device to lose the shape of the deployed configuration.

[0029] The gastric retention device can have a folding force of at least about 0.5N in the expanded configuration.

[0030] The expanded configuration of the gastric retention device may have a expanded diameter of at least 2 cm.

[0031] The gastric retention device can be configured to maintain the shape of the expanded configuration for at least 24 hours.

[0032] The foldable central shape memory alloy component may include at least one material selected from the following group: Ni-Ti, Ni-Ti-Hf, Ni-Ti-Pd, Ni-Fe-Ga, Ni-Mn-Ga, Ni-Mn-Ga-Cu, Ni-Mn-Ga-Co, Ag-Cd, Co-Ni-Al, Co-Ni-Ga, Cu-Al-Be-X (X: Zr, B, Cr, Gd), Cu-Al-Ni, Cu-Al-Ni-Hf, Cu-Sn, Cu-Zn, Cu-Zn-X (X=Si, Al, Sn), Fe-Mn-Si, Fe-Pt, Mn-Cu, Ti-Nb.

[0033] The foldable central shape memory alloy component is securely fixed within an outer skin component.

[0034] At least 80% of the folding force is provided by the foldable central shape memory alloy component.

[0035] The connecting member may be connected to the outer skin member.

[0036] The outer surface layer component can be made of at least one material selected from the following group: polypropylene, polystyrene, polyvinyl chloride, synthetic rubber, phenolic resin or bakelite, chloroprene rubber, nylon, polyacrylonitrile, PVB, silicone, acrylonitrile-butadiene-styrene, high-density polyethylene, polycarbonate, acrylic, polyethylene terephthalate, polybutylene terephthalate, acetal, polyimide, polyurethane and epoxy resin.

[0037] According to a third aspect of the present invention, there is provided a gastric retention device for oral administration, comprising:

[0038] a foldable central member comprising a plurality of ribs, wherein the ribs comprise at least one superelastic alloy;

[0039] a plurality of elongated limb members radially connected to the foldable central member, the plurality of elongated limb members corresponding to the plurality of ribs; and

[0040] A plurality of connecting members, each connecting member connecting one of the elongated limb members to the foldable central member,

[0041] wherein the ribs are expandable from a folded first state to an unfolded second state to unfold the elongated limb member,

[0042] wherein at least one of the elongated limb members is configured to release a drug stored thereon, and

[0043] The connecting members are configured to transition from a rigid first state to a free second state to allow the elongated limb members to move independently relative to the foldable central member.

[0044] The free second state may include the connecting members in a flexible state to allow the elongated limb members to flex relative to the foldable central member.

[0045] The free second state may include disconnection of the connecting members to separate the elongated limb members from the foldable central member.

[0046] The connecting member may include a material that undergoes hydrolysis to transform the connecting member from a rigid first state to a free second state.

[0047] The superelastic alloy may include at least one material selected from the following group: nitinol (Ni-Ti), brass (Cu-Zn), copper aluminum nickel (Cu-Al-Ni) alloy, gold cadmium (Au-Cd) alloy, gold copper zinc (Au-Cu-Zn) alloy, indium thallium (In-Tl) alloy, cobalt nickel aluminum (Co-Ni-Al) alloy, cobalt nickel gallium (Co-Ni-Ga) alloy, copper aluminum beryllium zirconium (Cu-Al-Be-Zr) alloy, copper aluminum beryllium chromium (Cu-Al-Be-Cr) alloy, copper aluminum beryllium gadolinium (Cu-Al-Be-Gd) alloy, copper aluminum nickel hafnium (Cu-Al-Ni-Hf) alloy, copper tin (Cu-Sn) alloy, copper zinc silicon (Cu-Zn-Si) alloy, copper zinc aluminum (Cu-Zn-Al) alloy, copper zinc tin (Cu-Zn) alloy. Sn) alloy, iron-manganese-silicon (Fe-Mn-Si) alloy, iron-platinum (Fe-Pt) alloy, manganese-copper (Mn-Cu) alloy, nickel-iron-gallium (Ni-Fe-Ga) alloy, nickel-titanium-hafnium (Ni-Ti-Hf) alloy, nickel-titanium-palladium (Ni-Ti-Pd) alloy, nickel-manganese-gallium (Ni-Mn-Ga) alloy, nickel-manganese-gallium-copper (Ni-Mn-Ga-Cu) alloy, nickel-manganese-gallium-cobalt (Ni-Mn-Ga-Co) alloy, and titanium-niobium (Ti-Nb) alloy.

[0048] The superelastic alloy may be a shape memory alloy.

[0049] The shape memory alloy may include at least one material selected from the following group: Ni-Ti, Ni-Ti-Hf, Ni-Ti-Pd, Ni-Fe-Ga, Ni-Mn-Ga, Ni-Mn-Ga-Cu, Ni-Mn-Ga-Co, Ag-Cd, Co-Ni-Al, Co-Ni-Ga, Cu-Al-Be-X (X: Zr, B, Cr, Gd), Cu-Al-Ni, Cu-Al-Ni-Hf, Cu-Sn, Cu-Zn, Cu-Zn-X (X=Si, Al, Sn), Fe-Mn-Si, Fe-Pt, Mn-Cu, Ti-Nb.

[0050] The foldable central member may further include an outer skin member, and wherein the ribs are securely secured within the outer skin member.

[0051] The connecting member may connect each elongate limb member to the outer skin member.

[0052] The outer surface layer component can be made of at least one material selected from the following group: polypropylene, polystyrene, polyvinyl chloride, synthetic rubber, phenolic resin or bakelite, chloroprene rubber, nylon, polyacrylonitrile, PVB, silicone, acrylonitrile-butadiene-styrene, high-density polyethylene, polycarbonate, acrylic, polyethylene terephthalate, polybutylene terephthalate, acetal, polyimide, polyurethane and epoxy resin.

[0053] The gastric retention device may further include a housing for housing the foldable central member and the elongated limb members, wherein the housing is configured to dissolve to expand the ribs from a folded first state to an unfolded second state to unfold the elongated limb members. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] The embodiments of the present invention are provided as examples only and will be better understood and easily appreciated by those skilled in the art through the following written description and accompanying drawings, in which:

[0055] Figure 1A Shown is a schematic diagram of a gastric retention device in a deployed configuration according to one embodiment.

[0056] Figure 1B Shown Figure 1A Schematic diagram of a gastric retention device in a folded configuration.

[0057] Figure 1C Shown Figure 1A Schematic diagram of a gastric retention device in a storage configuration.

[0058] Figure 2A Shown is a schematic diagram of a gastric retention device in a deployed configuration according to another embodiment.

[0059] Figure 2B Shown Figure 2A Schematic diagram of a gastric retention device in a folded configuration.

[0060] Figure 3A Shown is a schematic diagram of a gastric retention device in a deployed configuration according to another embodiment.

[0061] Figure 3B Shown Figure 3A Schematic diagram of a gastric retention device in a folded configuration.

[0062] Figure 4AShown is a schematic diagram of a gastric retention device in a deployed configuration according to another embodiment.

[0063] Figure 4B Shown Figure 4A A transparent schematic diagram of the internal components of a gastric retention device.

[0064] Figure 4C Shown Figure 4A Schematic diagram of a gastric retention device in a folded configuration.

[0065] Figure 5A Shown is a schematic diagram of a semi-finished foldable central component according to one embodiment.

[0066] Figure 5B Shown is a schematic diagram of a semi-finished foldable central component according to another embodiment.

[0067] Figure 5C Shown is the use of Figure 5B Schematic diagram of the two foldable central parts of the semi-finished product.

[0068] Fig. 6A Shown is a perspective view of an upper portion of an outer covering component of a gastric retention device according to one embodiment.

[0069] Figure 6B Shown Figure 3A Top view of the upper part.

[0070] Figure 6C Shown Fig. 6A Side view of the upper part.

[0071] Fig.6D Shown Fig. 6A The upper part of the device is provided with a superelastic alloy wire.

[0072] Fig. 6E Shown is the use of Fig. 6A Schematic diagram of the two foldable central parts completed above.

[0073] Fig. 7A Shown is the Figure 4A A test fixture for testing the gastric retention device.

[0074] Figure 7B Shown is the use of Fig. 7A A bar graph of the test results for tests performed on the test fixture. DETAILED DESCRIPTION

[0075] 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.

[0076] Figure 1A A schematic diagram of a gastric retention device 100 is shown in a deployed configuration according to one embodiment. Figure 1B Shows Figure 1A Schematic diagram of a gastric retention device in a folded configuration. Figure 1C Shows Figure 1A Schematic diagram of a gastric retention device in a storage configuration.

[0077] The gastric retention device 100 includes a foldable central member 102 and three elongated limb members 104 radially connected to the foldable central member 102. The foldable central member 102 includes three ribs 106 made of at least one superelastic alloy. Figure 1A As shown, three elongated limb members 104 correspond to three ribs 106. The positions and longitudinal axes of the elongated limb members 104 correspond to the positions and longitudinal axes of the ribs 106, respectively. Figure 1B and 1C As shown, the elongated limb member 104 has a triangular prism shape, thereby allowing the elongated limb member 104 to fit tightly when the gastric retention device 100 is in a folded configuration, thereby facilitating storage and oral administration. The rib 106 can be folded from a first state (such as Figure 1B and 1C ) to expand to a second state (as shown) Figure 1A ), to unfold the elongated limb members 104, causing the gastric retention device 100 to transform from a folded configuration to an expanded configuration. The gastric retention device 100 has an expanded diameter of at least 2 cm and a folding force of at least 0.5 N in the expanded configuration.

[0078] The gastroretentive device also includes three connecting members 108. Each connecting member 108 connects one elongated limb member 104 to the foldable central member 102. At least one elongated limb member 104 is configured to provide gastroretentive drug delivery at a predetermined rate by releasing an active substance or drug (e.g., a therapeutic agent or a diagnostic agent) stored thereon at a predetermined rate.

[0079] The connecting member 108 is configured to transform from a rigid first state to a free second state to allow the elongated limb members 104 to be independently movable relative to the foldable central member 102. The connecting member 108 includes a material that can be hydrolyzed to transform the connecting member 108 from the rigid first state to the free second state. Specifically, the connecting member 108 undergoes degradation, dissolution, separation, or mechanical weakening in the gastric environment, causing the gastric retention device 100 to lose its rigidity and shape and pass through the patient's gastric cavity. In one embodiment, the connecting member 108 loses its rigidity and becomes flexible in the free second state to allow the elongated limb members 104 to bend relative to the foldable central member 102. In another embodiment, the connecting member 108 breaks in the free second state to separate the elongated limb members 104 from the foldable central member 102.

[0080] like Figure 1C As shown, the gastric retention device 100 further includes a housing 110, which contains the foldable central component 102 and the elongated limb component 104 for storage and oral administration. After oral administration, the housing 112 will degrade, dissolve, separate or mechanically weaken in the body, and the ribs 106 will rebound from the folded first state to the unfolded second state to unfold the elongated limb component 104, so that the gastric retention device 100 is transformed from the folded configuration to the unfolded configuration, so that the gastric retention device 100 can be retained in the patient's stomach for a longer time, such as 24 hours or more.

[0081] In one embodiment, the rib 106 includes at least one superelastic alloy, wherein the superelastic alloy includes at least one material selected from the following group: nitinol (Ni-Ti), brass (Cu-Zn), copper aluminum nickel (Cu-Al-Ni) alloy, gold cadmium (Au-Cd) alloy, gold copper zinc (Au-Cu-Zn) alloy, indium thallium (In-Tl) alloy, cobalt nickel aluminum (Co-Ni-Al) alloy, cobalt nickel gallium (Co-Ni-Ga) alloy, copper aluminum beryllium zirconium (Cu-Al-Be-Zr) alloy, copper aluminum beryllium chromium (Cu-Al-Be-Cr) alloy, copper aluminum beryllium gadolinium (Cu-Al-Be-Gd) alloy, copper aluminum nickel hafnium (Cu-Al) alloy. -Ni-Hf) alloy, copper-tin (Cu-Sn) alloy, copper-zinc-silicon (Cu-Zn-Si) alloy, copper-zinc-aluminum (Cu-Zn-Al) alloy, copper-zinc-tin (Cu-Zn-Sn) alloy, iron-manganese-silicon (Fe-Mn-Si) alloy, iron-platinum (Fe-Pt) alloy, manganese-copper (Mn-Cu) alloy, nickel-iron-gallium (Ni-Fe-Ga) alloy, nickel-titanium-hafnium (Ni-Ti-Hf) alloy, nickel-titanium-palladium (Ni-Ti-Pd) alloy, nickel-manganese-gallium (Ni-Mn-Ga) alloy, nickel-manganese-gallium-copper (Ni-Mn-Ga-Cu) alloy, nickel-manganese-gallium-cobalt (Ni-MnGa-Co) alloy, and titanium-niobium (Ti-Nb) alloy.

[0082] The rib 106 may also be made of a shape memory alloy, which includes at least one material selected from the following group: Ni-Ti, Ni-Ti-Hf, Ni-Ti-Pd, Ni-Fe-Ga, Ni-Mn-Ga, Ni-Mn-Ga-Cu, Ni-Mn-Ga-Co, Ag-Cd, Co-Ni-Al, Co-Ni-Ga, Cu-Al-Be-X (X: Zr, B, Cr, Gd), Cu-Al-Ni, Cu-Al-Ni-Hf, Cu-Sn, Cu-Zn, Cu-Zn-X (X=Si, Al, Sn), Fe-Mn-Si, Fe-Pt, Mn-Cu, Ti-N.

[0083] Shape memory alloys belong to the family of superelastic alloys. One shape memory alloy suitable for ribs 106 has an austenite transformation completion temperature (Af) that is slightly lower than normal body temperature. At temperatures below Af (e.g., 30°C), shape memory alloys are in the martensite phase and have ductile plasticity. However, when shape memory alloys are heated to a temperature above Af, they become superelastic and will return to their initial unfolded state. During production and storage, the shape memory alloys are in the martensite phase, so the gastric retention device 100 can maintain its folded configuration without a restraining structure such as the housing 110. After oral administration of the gastric retention device 100, the temperature of the shape memory alloy increases due to the internal heat of the patient's body. This causes the shape memory alloy to undergo a transformation from the martensite phase to the austenite phase, thereby allowing the elongated limb member 104 to unfold to maintain the gastric retention device 100 in the patient's gastric cavity.

[0084] Figure 2A A schematic diagram of a gastric retention device 200 is shown in a deployed configuration according to another embodiment. Figure 2B Shows Figure 2A A schematic diagram of a gastric retention device is shown in a collapsed configuration.

[0085] The gastroretentive device 200 includes a foldable central member 202 and six elongated limb members 204 radially connected to the foldable central member 202. The foldable central member 202 includes six ribs 206, which are made of superelastic alloy wire. The gastroretentive device 200 also includes six connecting members 208 for connecting each elongated limb member 204 to the foldable central member 202. At least one elongated limb member 204 is configured to store an active substance or drug, such as a therapeutic agent or a diagnostic agent, for gastroretentive drug delivery. The connecting members 208 are configured to transition from a rigid first state to a free second state to allow the elongated limb members 204 to move independently relative to the foldable central member 202.

[0086] Figure 3A A schematic diagram of a gastric retention device 300 in a deployed configuration is shown according to another embodiment. Figure 3B Shows Figure 3A Schematic diagram of a gastric retention device 300 in a folded configuration.

[0087] The gastroretentive device 300 includes a foldable central member 302 and six elongated limb members 304 radially connected to the foldable central member 302. The foldable central member 302 includes six ribs 306, which are made of superelastic alloy strips. The gastroretentive device 300 also includes six connecting members 308 for connecting each elongated limb member 304 to the foldable central member 302. At least one elongated limb member 304 is configured to store an active substance or drug, such as a therapeutic agent or a diagnostic agent, for gastroretentive drug delivery. The connecting members 308 are configured to transition from a rigid first state to a free second state to allow the elongated limb members 304 to move independently relative to the foldable central member 302.

[0088] Figure 4A A schematic diagram is shown of a gastric retention device 400 in a deployed configuration according to one embodiment. Figure 4B Shows Figure 4A A transparent cross-sectional view of the internal components of the gastric retention device 400. Figure 4C Shows Figure 4A Schematic diagram of a gastric retention device 400 in a folded configuration.

[0089] The gastric retention device 400 includes a foldable central member 402 and a plurality of elongated limb members 404 radially connected to the foldable central member 402. Figure 4B As shown, the foldable central member 402 includes an outer skin member 406 and a plurality of ribs 408 made of superelastic alloy wires that are securely fixed within the outer skin member 406. The gastric retention device 400 also includes a plurality of connecting members 410 for connecting each elongated limb member 404 to the outer skin member 406.

[0090] The outer surface layer component 406 includes a soft and foldable material and is made of at least one material selected from the following group: polypropylene, polystyrene, polyvinyl chloride, synthetic rubber, phenolic resin or Bakelite, neoprene, nylon, polyacrylonitrile, PVB, silicone, acrylonitrile-butadiene-styrene, high-density polyethylene, polycarbonate, acrylic, polyethylene terephthalate, polybutylene terephthalate, acetal, polyimide, polyurethane and epoxy resin.

[0091] The main function of the outer skin component 406 is to cover the elongated limb component 404. In one embodiment, at least 80% of the folding force is provided by the foldable central component 402, and the remaining less than 20% of the folding force is provided by the outer skin component 406. Therefore, when selecting the material of the outer skin component 406, many materials can be used to manufacture the outer skin component 406 because the creep resistance, bending modulus and degradation time of the material are not the main considerations.

[0092] In one embodiment, the outer skin component 406 is formed by applying a polymer to the superelastic alloy rib 408 by injection molding or casting. It should be noted that the rib 408 is not limited to the shape of a metal wire, and the rib 408 may also include other shapes such as a ribbon or strip. The outer skin component 406 can be molded on the rib 408 of any of these shapes so that the rib 408 is firmly fixed in the outer skin component 406.

[0093] Figure 5A A schematic diagram of a semi-finished product of a foldable central member 500 according to one embodiment is shown. Figure 5B A schematic diagram of a semi-finished product of a foldable central component 502 of another embodiment is shown. Three superelastic alloy wires 504 made of Nitinol are fixed in a first mold in an overlapping manner. A thermoplastic polymer is injected into the first mold to form an inner component in the overlapping area of ​​the superelastic alloy wires 504, such as Figure 5A and 5B The injection molded component 506 shown in FIG. 5 is used to fix the relative position of the superelastic alloy wire 504. Figure 5B As shown, the first mold can also be made to first form an injection molded component 508 with a thermoplastic polymer at the distal end of the superelastic alloy wire 504. Next, the semi-finished product is transferred to a second mold, and the thermoplastic polymer is injected into the second mold to complete the foldable central component.

[0094] Figure 5C Shows the use Figure 5B Schematic diagram of two foldable central parts 510, 512 prepared from a semi-finished product. The foldable central part 510 is made of the same polymer, while the foldable central part 512 is made of a different polymer. For example, in the foldable central part 512, a first polymer with high hardness can be used to form an injection molded part 506 at the overlapping area of ​​the superelastic alloy wire 504 to fix the relative position of the superelastic alloy wire 504, a second polymer is used to form an injection molded part 508 at the distal end of the superelastic alloy wire 504 for forming a firm connection with the connecting part, and a third polymer with low hardness is used to form an injection molded part 514 covering the length of the superelastic alloy wire 504 to allow bending of the superelastic alloy wire 504.

[0095] In one embodiment, a thermoplastic polymer is first injected into a first mold to form the injection molded part 506, and then the superelastic alloy wire 504 is placed into the injection molded part 506 to be fixed in place.

[0096] In one embodiment, the injection molded parts 506, 508, 514 can be manufactured by casting instead of injection molding. Thermoplastic polymer is poured into the first mold or the second mold and hardened by cooling or curing.

[0097] It should be noted that the ribs are not limited to Figure 5A and 5B While shown in the shape of wires, the ribs may also include other shapes, such as ribbons or strips.

[0098] Fig. 6A A perspective view of an upper portion 602 of an outer covering component of a gastric retention device is shown according to one embodiment. Figure 6B Shows Fig. 6A A top view of the upper portion 602. Figure 6C Shows Fig. 6A A side view of the upper portion 602.

[0099] The upper portion 602 includes a slot 604 for receiving an internal superelastic alloy, in this embodiment, three superelastic alloy wires. Figure 6C As shown, the groove 604 has different depths to ensure that the superelastic alloy wire is in a horizontal state at the corresponding depth. Fig. 6A and 6B The cutout 606 shown in the figure is used to visually guide the assembly sequence of placing the superelastic alloy wire in the slot 604 of the upper part 602. The upper part 602 also includes a notch 608, which will form a stronger bond between the upper part and the lower part when the lower part is fused with the upper part.

[0100] Fig.6D Shows Fig. 6A The upper portion 602 is provided with a superelastic alloy wire. Three superelastic alloy wires 610 are provided in the groove 604 of the upper portion 602.

[0101] Fig. 6E Shows the use Fig. 6A Schematic diagram of two foldable central parts 612, 614 completed with an upper part 602. The foldable central parts 612, 614 include an upper part 602 and a lower part 616 connected to each other. The upper part 602 and the lower part 616 of the foldable central part 612 are made of the same polymer, while the upper part 602 and the lower part 616 of the foldable central part 614 are made of different polymers.

[0102] In one embodiment, the upper portion 602 and the lower portion 616 are made by injection molding or casting. A thermoplastic polymer is injected into a first mold to form the upper portion 602. The superelastic alloy wire 610 is placed in the groove 604 formed in the upper portion 602. Then, the upper portion 602 with the superelastic alloy wire 610 in the groove 604 is placed in a second mold, and then a thermoplastic polymer is injected into the second mold to form the lower portion 616 by secondary molding, thereby forming the foldable central parts 612, 614.

[0103] In one embodiment, the groove for accommodating the superelastic alloy wire may be formed in the lower portion 616 instead of in the upper portion 602. In another embodiment, the groove for accommodating the superelastic alloy wire 610 may be formed between the upper portion 602 and the lower portion 616.

[0104] In one embodiment, the lower portion 616 formed by overmolding of the second mold extends to cover the distal end 620 of the upper portion 602 , such that the connection component of the gastric retention device is connected to the lower portion 616 .

[0105] In one embodiment, the connecting member and the elongated limb member of the gastric retention device are manufactured by hot melt extrusion. The material is fed into a hot melt extruder and filaments are extruded in the desired cross-sectional shape and then cut into appropriate lengths to form the connecting member and the elongated limb member.

[0106] In one embodiment, the connecting member and the elongated limb member are manufactured by injection molding. The materials are first mixed into solid particles, which can be achieved by hot-melt extrusion of the mixed materials to produce extruded filaments, and then granulating the extruded filaments. The solid particles can also be formed by dissolving the materials in a suitable solvent to form a solution and pouring the solution on a flat surface to form a sheet, and then breaking the sheet to form solid particles. The solid particles are then fed into an injection molding device to form the connecting member and the elongated limb member that can carry the drug.

[0107] In one embodiment, the connecting component and the elongated limb component are manufactured by casting. First, the materials are mixed to form a casting solution, and then the casting solution is poured into a mold in the shape of the connecting component and the elongated limb component, and hardened by cooling or curing to form the connecting component and the elongated limb component.

[0108] In one embodiment, the foldable central member can be connected to the connecting member and the elongated limb member by heat bonding. The foldable central member and the elongated limb member to which the connecting member is already connected are placed in a mold, and heat is applied at the boundary between the foldable central member and the connecting member to fuse them together. A thrust force can be applied to the distal end portion of the elongated limb member to press the connecting member against the foldable central member to obtain a stronger bond. Heating can be performed by laser, heating element in the mold, etc. It should be noted that the foldable central member and the connecting member can also be connected by other methods, such as solvent bonding and using adhesives.

[0109] Fig. 7A Shows the Figure 4A The gastric retention device 400 is tested on a test fixture 700 . Figure 7B Shows the use Fig. 7A The test fixture 700 includes a funnel 702 having a 20 mm opening at the bottom, thereby simulating the pyloric opening of the stomach in a patient. The test fixture 700 is used to determine the peak pressure required to push the gastroretention device 400 through the bottom opening. Specifically, the gastroretention device 400 is placed into the funnel 702, and each elongated limb member of the gastroretention device 400 is placed in a groove 704 of the funnel 702. The gastroretention device 400 is then pressed through the funnel 702 using a probe, and the peak pressure is recorded.

[0110] The lateral force test simulates the situation where the gastric retention device 400 leaves the pyloric opening laterally, and the planar force test simulates the situation where the gastric retention device 400 leaves the pyloric opening in plane. The four gastric retention devices 400 tested include: no nitinol wire, and nitinol wires with cross-sectional areas of 0.20 mm, 0.30 mm, and 0.40 mm, and the peak pressures required to push the gastric retention device through the bottom opening are 0.6 N, 2.2 N, 4.1 N, and 4.9 N, respectively.

[0111] An embodiment of the present invention provides a gastric retention device 100 for oral administration. The gastric retention device 100 includes a plurality of ribs 106, which are generally made of at least one superelastic alloy having a high bending modulus. Therefore, the superelastic alloy ribs 106 with a relatively small volume can achieve the bending force required to keep the gastric retention device 100 in the stomach. This can facilitate the flexible design of the gastric retention device 100.

[0112] For example, when using similar superelastic alloy materials, only the length of the rib 106 needs to be changed to make gastric retention devices 100 of different sizes and shapes. Small gastric retention devices 100 are easier to swallow and can be used to treat small animals or patients with small gastrointestinal tracts, such as children. The superelastic alloy rib 106 can also easily adjust the bending force because only the cross-sectional area of ​​the bend of the superelastic alloy rib 106 needs to be adjusted. Therefore, gastric retention devices 100 with the same size and shape have different bending forces of the superelastic alloy rib 106 due to the use of superelastic alloy ribs 106 with different cross-sectional areas, and thus have different retention abilities in the stomach.

[0113] Example 1: Preparation of a foldable central component

[0114] Fig. 6E The foldable central part 614 is made as follows:

[0115] 1. Cut the 0.30 mm diameter Nitinol wire into a length of 17 mm.

[0116] 2. The upper portion 602 is produced by injection molding Lubrizol's PC-3575A into a first mold.

[0117] 3. The cut 0.30 mm diameter Nitinol wire is then carefully placed into the upper portion 602 .

[0118] 4. The entire component with the Nitinol wire is then placed into a second mold and injected with Lubrizol’s PC-3575A to form part 614.

[0119] In step 2, Nitinol wires of different diameters may be used, such as 0.10 mm, 0.20 mm, or 0.40 mm, etc.

[0120] Example 2: Preparation of Gastric Retention Device

[0121] The production process of a gastric retention device using the foldable central member 614 is as follows:

[0122] 1. 99g HPMC-AS-HG from Shin-Etsu, 99g PCL and 2g silica were mixed until homogeneous. The homogeneous powder was then fed into the feeder of the Thermo Scientific Pharma 11 twin-screw extruder and a custom-made triangular die was used to achieve triangular extrusion. After extrusion, the triangular filaments were cut into 3mm segments to form connecting parts;

[0123] 2. 99g of barium sulfate, 99g of PCL and 2g of silicon dioxide were mixed until homogeneous. The homogeneous powder was then loaded into the feeder of the Thermo Scientific Pharma 11 twin-screw extruder and a customized triangular die was used to achieve triangular extrusion. After extrusion, the triangular filaments were cut into 10mm segments to form elongated limb components without active substances;

[0124] 3. The foldable central member 614, the connecting members and the elongated limb members are then loaded into a custom mold and the different components are heat-fused together by laser to form the gastric retention device;

[0125] 4. The gastric retention device is then folded and placed into a size 0 capsule shell.

[0126] Example 3: Retention time in animal experiments

[0127] Two types of central foldable members were produced using the method of Example 1. One type was prepared using 0.30 mm diameter Nitinol wire, while the other was prepared without using any Nitinol wire. Each foldable central member was then made into three gastric retention devices according to the method of Example 2. The prepared samples are shown in the following table.

[0128] Female Panamanian pigs weighing between 30 kg and 45 kg were then given one device each. Ten minutes after administration, the pigs were examined daily by fluoroscopy to determine whether the gastric retention device was still in the stomach. The day on which the gastric retention device was not retained in the stomach was the retention period. The retention period results for the gastric retention device are shown in the table below.

[0129] Device 1 2 Super elastic alloy parts none 0.30mm Nitinol wire Central Area PC-3575A PC-3575A Detention period (d) 1.3±0.5 5.3±0.9

[0130] Without departing from the spirit or scope of the present invention as broadly described, as shown in the specific embodiments, those skilled in the art will appreciate that many changes and / or modifications may be made to the present invention, and those skilled in the art may make many changes and / or modifications to the present invention. Therefore, the present embodiments are considered to be illustrative in all aspects, rather than restrictive.

Claims

1. A gastric retention device for oral administration, characterized in that include: Foldable central super elastic alloy component, a plurality of elongated limb members capable of carrying active substances, wherein the active substances are therapeutic agents or diagnostic agents, wherein each of the plurality of elongated limb members is connected to the foldable central superelastic alloy member via a connecting member, wherein the foldable central superelastic alloy member is elastically deformed when the gastroretention device is in a folded configuration, and the foldable central superelastic alloy member rebounds when the gastroretention device assumes an expanded configuration, and Wherein, the connecting component undergoes degradation, dissolution, dissociation or mechanical weakening, thereby causing the gastric retention device to lose the shape of the deployed configuration.

2. The gastric retention device according to claim 1, characterized in that The gastric retention device has a folding force of at least 0.5N in its expanded configuration.

3. The gastric retention device according to claim 1, characterized in that wherein the gastric retention device has a deployed diameter of at least 2 cm in an expanded configuration.

4. The gastric retention device according to claim 1, wherein: wherein the gastric retention device is configured to maintain a shape in the expanded configuration for at least 24 hours.

5. The gastric retention device according to claim 1, wherein: The foldable central superelastic alloy component includes at least one material selected from the following group: nitinol, brass, copper-aluminum-nickel alloy, gold-cadmium alloy, gold-copper-zinc alloy, indium-thallium alloy, cobalt-nickel-aluminum alloy, cobalt-nickel-gallium alloy, copper-aluminum-beryllium-zirconium alloy, copper-aluminum-beryllium-chromium alloy, copper-aluminum-beryllium-gadolinium alloy, copper-aluminum-nickel-hafnium alloy, copper-tin alloy, copper-zinc-silicon alloy, copper-zinc-aluminum alloy, copper-zinc-tin alloy, iron-manganese-silicon alloy, iron-platinum alloy, manganese-copper alloy, nickel-iron-gallium alloy, nickel-titanium-hafnium alloy, nickel-titanium-palladium alloy, nickel-manganese-gallium alloy, nickel-manganese-gallium-copper alloy, nickel-manganese-gallium-cobalt alloy, and titanium-niobium alloy.

6. The gastric retention device according to claim 1, wherein: The foldable central superelastic alloy component is firmly fixed in an outer surface component.

7. The gastric retention device according to claim 6, characterized in that At least 80% of the folding force is provided by the foldable central superelastic alloy component.

8. The gastric retention device according to claim 6, wherein: The connecting component is connected to the outer skin component.

9. The gastric retention device according to claim 6, characterized in that The outer surface layer component is made of at least one material selected from the following group: polypropylene, polystyrene, polyvinyl chloride, synthetic rubber, phenolic resin or bakelite, chloroprene rubber, nylon, polyacrylonitrile, PVB, silicone, acrylonitrile-butadiene-styrene, high-density polyethylene, polycarbonate, acrylic, polyethylene terephthalate, polybutylene terephthalate, acetal, polyimide, polyurethane and epoxy resin.

10. The gastric retention device according to claim 1, wherein: Also included is a housing for containing the gastroretention device in the folded configuration, wherein the housing is configured to degrade, dissolve, separate, or mechanically weaken to allow the gastroretention device to recoil and assume the expanded configuration.

11. A gastric retention device for oral administration, characterized in that include: Foldable central shape memory alloy component; A plurality of elongated limb members capable of carrying an active substance, the active substance being a therapeutic agent or a diagnostic agent, wherein each of the plurality of elongated limb members is connected to the foldable central shape memory alloy member via a connecting member, wherein the foldable central shape memory alloy component undergoes a phase transformation from a martensite phase to an austenite phase in its crystal structure, thereby allowing the gastric retention device to transform from a folded configuration to an expanded configuration, and The connecting component degrades, dissolves, dissociates, or mechanically weakens, thereby causing the gastric retention device to lose the shape of the deployed configuration.

12. The gastric retention device according to claim 11, wherein: The gastric retention device has a folding force of at least about 0.5N in its expanded configuration.

13. The gastric retention device according to claim 11, wherein: wherein the gastric retention device has a deployed diameter of at least 2 cm in an expanded configuration.

14. The gastric retention device according to claim 11, wherein: wherein the gastric retention device is configured to maintain a shape in the expanded configuration for at least 24 hours.

15. The gastric retention device according to claim 11, wherein: The foldable central shape memory alloy component includes at least one material selected from the following group: Ni-Ti, Ni-Ti-Hf, Ni-Ti-Pd, Ni-Fe-Ga, Ni-Mn-Ga, Ni-Mn-Ga-Cu, Ni-Mn-Ga-Co, Ag-Cd, Co-Ni-Al, Co-Ni-Ga, Cu-Al-Be-X (X = Zr, B, Cr, Gd), Cu-Al-Ni, Cu-Al-Ni-Hf, Cu-Sn, Cu-Zn, Cu-Zn-X (X = Si, Al, Sn), Fe-Mn-Si, Fe-Pt, Mn-Cu, Ti-Nb.

16. The gastric retention device according to claim 11, wherein: The foldable central shape memory alloy component is firmly fixed in an outer skin component.

17. The gastric retention device according to claim 16, wherein: At least 80% of the folding force is provided by the foldable central shape memory alloy component.

18. The gastric retention device of claim 16, wherein: The connecting component is connected to the outer surface component.

19. The gastric retention device of claim 16, wherein: The outer surface layer component is made of at least one material selected from the following group: polypropylene, polystyrene, polyvinyl chloride, synthetic rubber, phenolic resin or bakelite, chloroprene rubber, nylon, polyacrylonitrile, PVB, silicone, acrylonitrile-butadiene-styrene, high-density polyethylene, polycarbonate, acrylic, polyethylene terephthalate, polybutylene terephthalate, acetal, polyimide, polyurethane and epoxy resin.

20. A gastric retention device for oral administration, characterized in that include: a foldable central member comprising a plurality of ribs, wherein the ribs comprise at least one superelastic alloy; a plurality of elongated limb members radially connected to the foldable central member, the plurality of elongated limb members corresponding to the plurality of ribs; and a plurality of connecting members, each connecting member connecting an elongated limb member to the foldable central member, wherein the ribs are expandable from a folded first state to an unfolded second state to unfold the elongated limb member, wherein at least one of the elongated limb members is configured to release a drug stored thereon, and The connecting members are configured to transition from a rigid first state to a free second state to allow the elongated limb members to move independently relative to the foldable central member.

21. The gastric retention device of claim 20, wherein: The free second state includes the connecting members being in a flexible state to allow the elongated limb members to flex relative to the foldable central member.

22. The gastric retention device of claim 20, wherein: The free second state includes disconnection of the connecting members to separate the elongated limb members from the foldable central member.

23. The gastric retention device of claim 20, wherein: The connecting element comprises a material which, upon hydrolysis, transforms the connecting element from a rigid first state to a free second state.

24. The gastric retention device of claim 20, wherein: The superelastic alloy includes at least one material selected from the following group: nitinol, brass, copper-aluminum-nickel alloy, gold-cadmium alloy, gold-copper-zinc alloy, indium-thallium alloy, cobalt-nickel-aluminum alloy, cobalt-nickel-gallium alloy, copper-aluminum-beryllium-zirconium alloy, copper-aluminum-beryllium-chromium alloy, copper-aluminum-beryllium-gadolinium alloy, copper-aluminum-nickel-hafnium alloy, copper-tin alloy, copper-zinc-silicon alloy, copper-zinc-aluminum alloy, copper-zinc-tin alloy, iron-manganese-silicon alloy, iron-platinum alloy, manganese-copper alloy, nickel-iron-gallium alloy, nickel-titanium-hafnium alloy, nickel-titanium-palladium alloy, nickel-manganese-gallium alloy, nickel-manganese-gallium-copper alloy, nickel-manganese-gallium-cobalt alloy, and titanium-niobium alloy.

25. The gastric retention device of claim 20, wherein: The superelastic alloy is a shape memory alloy.

26. The gastric retention device of claim 25, wherein: The shape memory alloy includes at least one material selected from the following group: Ni-Ti, Ni-Ti-Hf, Ni-Ti-Pd, Ni-Fe-Ga, Ni-Mn-Ga, Ni-Mn-Ga-Cu, Ni-Mn-Ga-Co, Ag-Cd, Co-Ni-Al, Co-Ni-Ga, Cu-Al-Be-X (X = Zr, B, Cr, Gd), Cu-Al-Ni, Cu-Al-Ni-Hf, Cu-Sn, Cu-Zn, Cu-Zn-X (X = Si, Al, Sn), Fe-Mn-Si, Fe-Pt, Mn-Cu, Ti-Nb.

27. The gastric retention device of claim 20, wherein: wherein the foldable central member further comprises an outer skin member, and wherein the ribs are securely secured within the outer skin member.

28. The gastric retention device of claim 27, wherein: The connecting member connects each elongated limb member to the outer skin member.

29. The gastric retention device of claim 27, wherein: The outer surface layer component is made of at least one material selected from the following group: polypropylene, polystyrene, polyvinyl chloride, synthetic rubber, phenolic resin or bakelite, chloroprene rubber, nylon, polyacrylonitrile, PVB, silicone, acrylonitrile-butadiene-styrene, high-density polyethylene, polycarbonate, acrylic, polyethylene terephthalate, polybutylene terephthalate, acetal, polyimide, polyurethane and epoxy resin.

30. The gastric retention device of claim 20, wherein: Also included is a housing for housing the foldable central member and the elongated limb members, wherein the housing is configured to be dissolved to expand the ribs from the folded first state to the unfolded second state to unfold the elongated limb members.

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