本发明涉及胃延长给药装置领域，特别是一种胃滞留装置。The present invention relates to the field of gastric prolonged drug delivery devices, in particular to a gastric retention device.
胃滞留装置设计用于给药到患者的胃中，通常以胶囊形式通过其他给药方法(例如，喂食管或胃管)吞咽或引入胃中。当胃中的胶囊溶解后，胃滞留装置扩张或展开到一定大小，该尺寸保留在胃中，并在所需的滞留期(例如三天、七天、两周等)内抵抗通过幽门括约肌。这需要在所需的滞留期内保持机械稳定性，同时释放一种或多种活性药物，且该胃滞留装置应在所需停留时间结束时从胃中排出，并易于从患者体内排出。Gastric retention devices are designed to be administered into a patient's stomach, typically in capsule form, to be swallowed or introduced into the stomach via other methods of administration (e.g., feeding tube or nasogastric tube). After the capsule dissolves in the stomach, the gastric retention device expands or unfolds to a size that remains in the stomach and resists passage through the pyloric sphincter for a desired retention period (e.g., three days, seven days, two weeks, etc.). This requires maintaining mechanical stability while releasing one or more active drugs during the desired retention period, and the gastric retention device should be expelled from the stomach at the end of the desired retention time and easily expelled from the patient's body.
如专利CN201680081222.8、专利CN201680075519.3、专利CN201780032420.X等公开了胃滞留装置，一般包括通常通过弹性中心部件、多个延长臂和连接两者之间的连接部件，为了使得胃滞留装置具有一定的滞留期，连接部件包括时间依赖性模块和肠溶模块，既在水性条件下以可预测的时间依赖性方式降解，例如，当胃滞留装置在胃中滞留期间，时间依赖性模块被设计成随时间逐渐降解、溶解、机械弱化或断裂。在达到所需的滞留期后，时间依赖性模块已降解、溶解、解离或机械弱化，或已经破裂，使得延长臂与弹性中心部件相分离或使得延长臂在胃肠道内可相对于弹性中心部件折叠，其程度达到胃滞留装置可以通过幽门瓣，离开胃环境并进入小肠，最终从体内排出。For example, patents CN201680081222.8, CN201680075519.3, and CN201780032420.X disclose gastric retention devices, which generally include a flexible central component, a plurality of extension arms, and a connecting component connecting the two. To ensure that the gastric retention device has a certain retention period, the connecting component includes a time-dependent module and an enteric-coated module. Both modules degrade in a predictable, time-dependent manner under aqueous conditions. For example, while the gastric retention device is retained in the stomach, the time-dependent module is designed to gradually degrade, dissolve, mechanically weaken, or break over time. After achieving the desired retention period, the time-dependent module has degraded, dissolved, dissociated, or mechanically weakened, or has broken, allowing the extension arms to separate from the flexible central component or to fold relative to the flexible central component within the gastrointestinal tract, to the extent that the gastric retention device can pass through the pyloric valve, exit the gastric environment, enter the small intestine, and ultimately be excreted from the body.
在胃滞留装置中，延长臂用于活性药物的负载，其选用的聚合物基质一般为非降解的、具有足够机械强度的聚合物。In gastric retention devices, the extended arm is used to load the active drug, and the polymer matrix selected is generally a non-degradable polymer with sufficient mechanical strength.
延长臂基质和连接部件的崩解材料相溶性相差较大，使得延长臂和连接部件进行熔融焊接时，无法保证焊接处的机械强度，容易导致胃滞留装置在胃内时，粘接处提前断裂，从而导致胃滞留装置提前排出。The compatibility of the disintegrating materials of the extension arm matrix and the connecting component is quite different, which makes it impossible to ensure the mechanical strength of the weld when the extension arm and the connecting component are melt-welded. This can easily lead to premature rupture of the bonding joint when the gastric retention device is in the stomach, thereby causing the gastric retention device to be expelled prematurely.
为此，需要提供一种胃滞留装置，解决现有连接部件和延长臂粘合力低，延长臂容易提前断裂的问题。Therefore, it is necessary to provide a gastric retention device to solve the problem that the existing connecting parts and the extension arm have low adhesion and the extension arm is prone to premature breakage.
为实现上述目的，本发明提供了一种胃滞留装置，包括：To achieve the above objectives, the present invention provides a gastric retention device comprising:
弹性中心部件；elastic centerpiece;
多个延长臂，所述延长臂轴向的两端分别为固定端和自由端；A plurality of extension arms, wherein the two axial ends of the extension arms are respectively a fixed end and a free end;
多个连接部件，所述连接部件包括第一端面、第二端面和连接两者之间的外侧面，所述第一端面与弹性中心部件粘接，所述第二端面与延长臂的固定端相粘接；a plurality of connecting components, each of the connecting components including a first end surface, a second end surface, and an outer side surface connecting the first end surface and the elastic center component, the second end surface being bonded to the fixed end of the extension arm;
所述连接部件包括崩解模块和粘接模块，所述崩解模块具有显露于连接部件外侧面的外露区域，所述粘接模块具有由第一端面连续延伸至第二端面的连续区域；The connecting component includes a disintegration module and an adhesive module, wherein the disintegration module has an exposed area exposed on the outer side of the connecting component, and the adhesive module has a continuous area extending continuously from the first end surface to the second end surface;
所述粘接模块用于增加连接部件和延长臂粘接处的粘接力以使得延长臂和弹性中心部件之间的断裂力至少为2.5N以上。The bonding module is used to increase the bonding force at the bonding point between the connecting component and the extension arm so that the breaking force between the extension arm and the elastic central component is at least 2.5N.
进一步，所述崩解模块的外露区域在连接部件的外侧面上占据至少30％的面积。外露区域的足够面积能够保证崩解模块在胃肠道环境时能够与外部环境充分接触，从而起到定时崩解或安全保护崩解的作用。Furthermore, the exposed area of the disintegration module occupies at least 30% of the area on the outer surface of the connecting component. The sufficient area of the exposed area can ensure that the disintegration module can fully contact the external environment in the gastrointestinal environment, thereby achieving the effect of timed disintegration or safety protection disintegration.
进一步，所述粘接模块在第二端面上至少占据20％的面积。粘接模块与延长臂固定端的接触面积越大，熔融粘接后，粘接效果越好。Furthermore, the bonding module occupies at least 20% of the area on the second end face. The larger the contact area between the bonding module and the fixed end of the extension arm, the better the bonding effect after melt bonding.
进一步，所述粘接模块和/或崩解模块为沿其轴向延伸的等截面模块。轴向延长保证了连接部件在轴向上机械强度的一致性。Furthermore, the bonding module and/or the disintegration module are modules of uniform cross-section extending along their axial direction. The axial extension ensures the consistency of the mechanical strength of the connecting component in the axial direction.
进一步，所述连接部件包括中心模块和多个侧面模块，多个所述侧面模块周向设置在中心模块的侧面上，Furthermore, the connecting component includes a central module and a plurality of side modules, wherein the plurality of side modules are circumferentially arranged on the side surfaces of the central module.
崩解模块和粘接模块的组合方式为以下方式中的一种：The disintegration module and the bonding module are combined in one of the following ways:
(A)所述崩解模块为中心模块，所述粘接模块为侧面模块，所述中心模块具有显露于侧面模块外侧面的所述外露区域；(A) The disintegration module is a central module, the bonding module is a side module, and the central module has the exposed area exposed on the outer side of the side module;
(B)所述粘接模块为中心模块，所述崩解模块为侧面模块，所述侧面模块的外侧面即为外露区域。(B) The bonding module is a central module, the disintegration module is a side module, and the outer side of the side module is the exposed area.
进一步，在方式(A)中，所述外露区域通过以下方式中的一种显露于连接部件的外侧面：Furthermore, in mode (A), the exposed area is exposed on the outer side of the connecting component by one of the following modes:
(1)所述中心模块的外露区域贴合于侧面模块外侧面所在面；(1) The exposed area of the central module is attached to the outer surface of the side module;
(2)多个所述侧面模块制备时完全包覆中心模块侧面，之后在所述侧面模块上开设有开槽，以显露中心模块的侧面形成所述外露区域。(2) When the plurality of side modules are prepared, they completely cover the side of the central module, and then grooves are opened on the side modules to expose the side of the central module to form the exposed area.
进一步，所述中心模块的侧面上具有向内侧凹陷的安装槽，所述侧面模块设于安装槽内。Furthermore, a side surface of the central module is provided with an inwardly recessed mounting groove, and the side modules are arranged in the mounting groove.
进一步，所述粘接模块包括两个子模块和所述连续区域，两个所述子模块分别位于第一端面和第二端面，所述崩解模块设置在两个子模块之间，两个子模块之间通过连续区域相连接。Furthermore, the bonding module includes two submodules and the continuous area. The two submodules are respectively located on the first end face and the second end face. The disintegration module is arranged between the two submodules. The two submodules are connected through the continuous area.
进一步，所述崩解模块上具有容纳结构，所述连续区域横穿容纳结构。Furthermore, the disintegration module has a containing structure, and the continuous area crosses the containing structure.
进一步，所述崩解模块包括时间依赖性崩解模块和/或肠溶崩解模块。Furthermore, the disintegration module includes a time-dependent disintegration module and/or an enteric disintegration module.
所述时间依赖性崩解模块既在水性条件下以在预定的时间内强度弱化，以使得延长臂相对于弹性中心部件断裂或可弯曲，从而控制胃滞留装置的在胃内的滞留时间，时间依赖性崩解模块的强度弱化方式可以为随时间逐渐降解、溶解、解离或机械弱化，延长臂断裂足够的数量后胃滞留装置可以通过幽门瓣，离开胃腔并进入小肠，最终从体内排出。The time-dependent disintegration module can weaken its strength within a predetermined time under aqueous conditions so that the extension arm breaks or becomes bendable relative to the elastic central component, thereby controlling the retention time of the gastric retention device in the stomach. The strength weakening of the time-dependent disintegration module can be gradual degradation, dissolution, dissociation or mechanical weakening over time. After a sufficient number of extension arms break, the gastric retention device can pass through the pyloric valve, leave the gastric cavity and enter the small intestine, and finally be discharged from the body.
所述肠溶崩解模块即为pH依赖崩解模块，用于为胃滞留装置提供安装机制，一旦胃滞留装置提前离开胃腔，进入到肠道时，肠溶崩解模块将根据小肠的高pH环境中迅速完成降解、溶解、解离或机械弱化，从而导致延长臂断裂，避免出现肠梗阻，使得胃滞留装置容易通过小肠。The enteric disintegration module is a pH-dependent disintegration module, which is used to provide an installation mechanism for the gastric retention device. Once the gastric retention device leaves the gastric cavity prematurely and enters the intestine, the enteric disintegration module will quickly complete degradation, dissolution, dissociation or mechanical weakening according to the high pH environment of the small intestine, thereby causing the extension arm to break, avoiding intestinal obstruction, and making it easier for the gastric retention device to pass through the small intestine.
进一步，所述崩解模块包括时间依赖性崩解模块和肠溶崩解模块，所述时间依赖性崩解模块和肠溶崩解模块沿轴向排列，所述粘接模块轴向延伸，所述粘接模块周向设置在时间依赖性崩解模块、肠溶崩解模块的侧面。Furthermore, the disintegration module includes a time-dependent disintegration module and an enteric disintegration module, the time-dependent disintegration module and the enteric disintegration module are arranged axially, the bonding module extends axially, and the bonding module is circumferentially arranged on the sides of the time-dependent disintegration module and the enteric disintegration module.
时间依赖性崩解模块和肠溶崩解模块沿轴向并排设置，粘接模块在时间依赖性崩解模块和肠溶崩解模块的侧面上轴向延伸，粘接模块能够对时间依赖性崩解模块和肠溶崩解模块进行粘合，因此此时在连接部件制备时，无需特别注意时间依赖性崩解模块和肠溶崩解模块之间的粘着性能。The time-dependent disintegration module and the enteric disintegration module are arranged side by side in the axial direction, and the bonding module extends axially on the sides of the time-dependent disintegration module and the enteric disintegration module. The bonding module can bond the time-dependent disintegration module and the enteric disintegration module. Therefore, when preparing the connecting parts, there is no need to pay special attention to the adhesion performance between the time-dependent disintegration module and the enteric disintegration module.
进一步，所述粘接模块包括50％以上的粘接材料；Furthermore, the bonding module comprises more than 50% bonding material;
所述时间依赖性崩解模块包括小于30％的粘接材料和大于70％的时间依赖崩解材料；The time-dependent disintegration module comprises less than 30% of a binding material and more than 70% of a time-dependent disintegration material;
所述肠溶崩解模块包括小于30％的粘接材料和大于70％的肠溶崩解材料。The enteric disintegrating module comprises less than 30% of a bonding material and more than 70% of an enteric disintegrating material.
时间依赖性崩解模块和肠溶崩解模块均包含部分粘接材料用于与粘接模块熔融粘接。The time-dependent disintegration module and the enteric disintegration module both contain some bonding materials for melt bonding with the bonding module.
进一步，所述粘接材料和延长臂的基质材料相同。相同材料具有良好的熔融性，保证连接模块和延长臂固定端的粘接力。Furthermore, the bonding material is the same as the matrix material of the extension arm, and the same material has good melting properties, thereby ensuring the bonding strength between the connecting module and the fixed end of the extension arm.
进一步，所述粘接材料包括聚己内酯、聚乳酸、聚乙交酯、聚乳酸-羟基乙酸共聚物、聚羟基脂肪酸酯和改性多糖中的一种或多种；Furthermore, the bonding material includes one or more of polycaprolactone, polylactic acid, polyglycolide, polylactic acid-glycolic acid copolymer, polyhydroxyalkanoate and modified polysaccharide;
所述时间依赖崩解材料包括聚乳酸、聚乳酸-羟基乙酸共聚物、聚乙交酯、聚己内酯、聚酸酐和聚正酯中的一种或多种；The time-dependent disintegrating material comprises one or more of polylactic acid, polylactic-co-glycolic acid, polyglycolide, polycaprolactone, polyanhydride and polyorthoester;
所述肠溶崩解材料包括醋酸羟丙甲纤维素琥珀酸酯、丙烯酸酯共聚物、醋酸邻苯二甲酸纤维素、虫胶和聚醋酸乙烯邻苯二酸酯中的一种或多种。The enteric disintegrating material includes one or more of hypromellose acetate succinate, acrylate copolymer, cellulose acetate phthalate, shellac and polyvinyl acetate phthalate.
进一步，所述连接部件通过熔融共挤、熔融注塑成型、压塑成型、二次烧结成型和三维打印中的一种或多种方法制备成型。Furthermore, the connecting component is prepared and formed by one or more methods selected from the group consisting of melt co-extrusion, melt injection molding, compression molding, secondary sintering molding and three-dimensional printing.
本发明另一方面公开了一种胃滞留装置，包括Another aspect of the present invention discloses a gastric retention device, comprising
弹性中心部件；elastic centerpiece;
多个延长臂，所述延长臂轴向的两端分别为固定端和自由端；A plurality of extension arms, wherein the two axial ends of the extension arms are respectively a fixed end and a free end;
多个连接部件，所述连接部件包括多个相熔融粘接的连接片，其中包括至少一个崩解连接片和两端的末端连接片，A plurality of connecting parts, wherein the connecting parts include a plurality of fusion-bonded connecting pieces, including at least one disintegrating connecting piece and end connecting pieces at both ends,
所述连接片中均包含由粘接材料，相邻连接片之间的粘接材料的质量分数百分比差值不超过50％，The connecting sheets all contain adhesive materials, and the difference in mass fraction of the adhesive materials between adjacent connecting sheets does not exceed 50%.
所述崩解连接片包含60％以上的崩解材料，The disintegrating connecting piece contains more than 60% of disintegrating material,
所述末端连接片包括60％以上的粘接材料，用于粘接延长臂的固定端，连接部件上多个连接片的设置使得延长臂和弹性中心部件之间的断裂力至少为2.5N。The end connecting piece comprises more than 60% of adhesive material and is used to bond the fixed end of the extension arm. The arrangement of multiple connecting pieces on the connecting component ensures that the breaking force between the extension arm and the elastic central component is at least 2.5N.
进一步，所述崩解连接片包括时间依赖性崩解连接片和/或肠溶崩解连接片。Furthermore, the disintegrating connecting tablet includes a time-dependent disintegrating connecting tablet and/or an enteric-coated disintegrating connecting tablet.
进一步，所述崩解连接片包括时间依赖性崩解连接片和肠溶崩解连接片，Furthermore, the disintegrating connecting tablets include time-dependent disintegrating connecting tablets and enteric disintegrating connecting tablets.
所述连接部件的多个连接片中包括至少两个位于时间依赖性崩解连接片和肠溶崩解连接片之间的中间连接片，所述时间依赖性崩解连接片包括至少60％时间依赖性崩解材料，所述肠溶崩解连接片包括至少60％肠溶崩解材料，所述中间连接片中包括至少60％粘接材料，紧贴时间依赖性崩解连接片的中间连接片含有不超过30％的时间依赖性崩解材料，紧贴肠溶崩解连接片的中间连接片含有不超过30％的肠溶崩解材料。The multiple connecting pieces of the connecting component include at least two intermediate connecting pieces located between the time-dependent disintegrating connecting piece and the enteric disintegrating connecting piece, the time-dependent disintegrating connecting piece includes at least 60% time-dependent disintegrating material, the enteric disintegrating connecting piece includes at least 60% enteric disintegrating material, the intermediate connecting piece includes at least 60% adhesive material, the intermediate connecting piece closely attached to the time-dependent disintegrating connecting piece contains no more than 30% time-dependent disintegrating material, and the intermediate connecting piece closely attached to the enteric disintegrating connecting piece contains no more than 30% enteric disintegrating material.
时间依赖性崩解连接片和肠溶崩解连接片之间通过中间连接片的缓冲，增强粘接强度，同时紧贴时间依赖性崩解连接片、肠溶崩解连接片的连接片分别含有部分对应的崩解材料，使得两者熔融状态下，相容性更好。The time-dependent disintegrating connecting tablet and the enteric disintegrating connecting tablet are buffered by the intermediate connecting tablet to enhance the bonding strength. At the same time, the connecting tablets close to the time-dependent disintegrating connecting tablet and the enteric disintegrating connecting tablet respectively contain part of the corresponding disintegrating material, so that the two are more compatible in the molten state.
进一步，所述至少两个中间连接片中，越靠近时间依赖性崩解连接片的中间连接片的时间依赖性崩解材料含量越高，越靠近肠溶崩解连接片的中间连接片的肠溶崩解材料含量越高。Furthermore, among the at least two intermediate connecting pieces, the intermediate connecting piece closer to the time-dependent disintegrating connecting piece has a higher content of time-dependent disintegrating material, and the intermediate connecting piece closer to the enteric disintegrating connecting piece has a higher content of enteric disintegrating material.
进一步，所述粘接材料包括聚己内酯、聚乳酸、聚乙交酯、聚乳酸-羟基乙酸共聚物、聚羟基脂肪酸酯和改性多糖中的一种或多种；Furthermore, the bonding material includes one or more of polycaprolactone, polylactic acid, polyglycolide, polylactic acid-glycolic acid copolymer, polyhydroxyalkanoate and modified polysaccharide;
所述时间依赖崩解材料包括聚乳酸、聚乳酸-羟基乙酸共聚物、聚乙交酯、聚己内酯、聚酸酐和聚正酯中的一种或多种；The time-dependent disintegrating material comprises one or more of polylactic acid, polylactic-co-glycolic acid, polyglycolide, polycaprolactone, polyanhydride and polyorthoester;
所述肠溶崩解材料包括醋酸羟丙甲纤维素琥珀酸酯、丙烯酸酯共聚物、醋酸邻苯二甲酸纤维素、虫胶和聚醋酸乙烯邻苯二酸酯中的一种或多种。The enteric disintegrating material includes one or more of hypromellose acetate succinate, acrylate copolymer, cellulose acetate phthalate, shellac and polyvinyl acetate phthalate.
进一步，所述粘接材料与延长臂的基质材料相同。Furthermore, the bonding material is the same as the matrix material of the extension arm.
进一步，相邻的连接片中，粘接材料相差不超过40％。Furthermore, in adjacent connecting sheets, the difference in bonding material does not exceed 40%.
本发明的另一方面公开一种胃滞留装置，包括：Another aspect of the present invention discloses a gastric retention device comprising:
弹性中心部件；elastic centerpiece;
多个延长臂，所述延长臂轴向的两端分别为固定端和自由端，；A plurality of extension arms, wherein the two axial ends of the extension arms are respectively a fixed end and a free end;
多个连接部件，Multiple connecting parts,
所述连接部件包括崩解模块和位于崩解模块两侧的粘接模块，所述延长臂的固定端、弹性中心部件分别与崩解模块两侧的粘接模块相粘接，所述连接部件的垂直横截面的面积为S，所述崩解模块和粘接模块的粘接处设有第一连接结构，以使得崩解模块和粘接模块在粘接处具有至少1.5S的接触面积，从而使得延长臂和弹性中心部件之间的断裂力至少为2.5N。The connecting component includes a disintegration module and bonding modules located on both sides of the disintegration module. The fixed end of the extension arm and the elastic center component are respectively bonded to the bonding modules on both sides of the disintegration module. The area of the vertical cross-section of the connecting component is S. The bonding point of the disintegration module and the bonding module is provided with a first connecting structure so that the disintegration module and the bonding module have a contact area of at least 1.5S at the bonding point, so that the breaking force between the extension arm and the elastic center component is at least 2.5N.
进一步，所述第一连接结构包括相匹配的凸缘和凹槽，所述凸缘的外侧面与凹槽的内侧面相接触以使得崩解模块和粘接模块在粘接处具有至少1.5S的接触面积。凸缘的两侧面和前侧面均与凹槽的内侧面相接触，有效提高接触面积。Furthermore, the first connection structure includes a matching flange and groove, with the outer side of the flange contacting the inner side of the groove to ensure that the disintegration module and the bonding module have a contact area of at least 1.5S at the bonding point. Both side surfaces and the front side of the flange contact the inner side of the groove, effectively increasing the contact area.
进一步，所述凸缘沿水平方向或竖直方向延伸设置。Furthermore, the flange is extended in a horizontal direction or a vertical direction.
进一步，所述凸缘的最大厚度处至少为0.2mm。凸缘的厚度保证了粘接模块和崩解模块粘接后的机械强度。Furthermore, the maximum thickness of the flange is at least 0.2 mm. The thickness of the flange ensures the mechanical strength of the bonding module and the disintegration module after bonding.
进一步，所述凸缘在延伸方向上的宽度d1，所述凸缘所在平面的连接部件宽度为d2，所述d1≥0.5d2。Furthermore, the width of the flange in the extension direction is d1, the width of the connecting component in the plane where the flange is located is d2, and d1 ≥ 0.5d2.
进一步，所述第一连接结构包括在崩解模块和粘接模块的粘接处相对面上错位间隔设置的多个凸缘，同侧相邻凸缘之间的间隔形成所述凹槽。Furthermore, the first connection structure includes a plurality of flanges arranged at intervals and staggered on opposite surfaces of the bonding portion of the disintegration module and the bonding module, and the intervals between adjacent flanges on the same side form the groove.
崩解模块和粘接模块上的凸缘相互错位设置，组装时，凸缘错位交叉定位与凹槽相匹配，之后进行熔融粘接，相互交叉错位的凸缘有助于提高粘接效果。The flanges on the disintegration module and the bonding module are staggered. During assembly, the flanges are staggered and cross-positioned to match the grooves, and then melt-bonded. The staggered flanges help improve the bonding effect.
进一步，所述崩解模块包括时间依赖性崩解模块和/或肠溶崩解模块。Furthermore, the disintegration module includes a time-dependent disintegration module and/or an enteric disintegration module.
进一步，所述崩解模块包括时间依赖性崩解模块和肠溶崩解模块，所述时间依赖性崩解模块和肠溶崩解模块之间设有第二连接结构，以使得时间依赖性崩解模块和肠溶崩解模块在粘接处具有至少5S的接触面积。Furthermore, the disintegration module includes a time-dependent disintegration module and an enteric disintegration module, and a second connecting structure is provided between the time-dependent disintegration module and the enteric disintegration module so that the time-dependent disintegration module and the enteric disintegration module have a contact area of at least 5S at the bonding point.
进一步，所述第二连接结构和第一连接结构的结构相同或不同。Furthermore, the second connection structure and the first connection structure have the same or different structures.
进一步，所述粘接材料和延长臂的基质材料相同。Furthermore, the bonding material and the matrix material of the extension arm are the same.
进一步，所述粘接模块包括50％以上的粘接材料，所述粘接材料与延长臂的基质材料粘接熔融；Furthermore, the bonding module comprises more than 50% of bonding material, and the bonding material is bonded and melted with the matrix material of the extension arm;
所述时间依赖性崩解模块包括小于30％的粘接材料和大于70％的时间依赖崩解材料；The time-dependent disintegration module comprises less than 30% of a binding material and more than 70% of a time-dependent disintegration material;
所述肠溶崩解模块包括小于30％的粘接材料和大于70％的肠溶崩解材料。The enteric disintegrating module comprises less than 30% of a bonding material and more than 70% of an enteric disintegrating material.
进一步，所述粘接材料包括聚己内酯、聚乳酸、聚乙交酯、聚乳酸-羟基乙酸共聚物、聚羟基脂肪酸酯和改性多糖中的一种或多种；Furthermore, the bonding material includes one or more of polycaprolactone, polylactic acid, polyglycolide, polylactic acid-glycolic acid copolymer, polyhydroxyalkanoate and modified polysaccharide;
所述时间依赖崩解材料包括聚乳酸、聚乳酸-羟基乙酸共聚物、聚乙交酯、聚己内酯、聚酸酐和聚正酯中的一种或多种；The time-dependent disintegrating material comprises one or more of polylactic acid, polylactic-co-glycolic acid, polyglycolide, polycaprolactone, polyanhydride and polyorthoester;
所述肠溶崩解材料包括醋酸羟丙甲纤维素琥珀酸酯、丙烯酸酯共聚物、醋酸邻苯二甲酸纤维素、虫胶和聚醋酸乙烯邻苯二酸酯中的一种或多种。The enteric disintegrating material includes one or more of hypromellose acetate succinate, acrylate copolymer, cellulose acetate phthalate, shellac and polyvinyl acetate phthalate.
进一步，所述连接部件包括通过三维打印或二次注塑依次成型的粘接模块、时间依赖性崩解模块、肠溶崩解模块和粘接模块，之后熔融成型。Furthermore, the connecting component includes a bonding module, a time-dependent disintegration module, an enteric disintegration module and a bonding module, which are sequentially molded by three-dimensional printing or secondary injection molding and then melt-molded.
上述技术方案具有以下有益效果：The above technical solution has the following beneficial effects:
本发明中一方面通过分别单独设置粘接模块和崩解模块，在不影响崩解模块本身机械性能的同时，保证延长臂与弹性中心部件的断裂力为2.5N以上，进而使得胃滞留装置能够在胃腔内保留充足的时间，且连接部件和延长臂之间的粘接力主要来自与粘接模块，崩解模块的材料和配方可以在更广泛的范围内选择，连续区域连续延伸穿过整个连接部件，有利于加强连接部件的整体性合机械强度。On the one hand, the present invention separately provides a bonding module and a disintegration module, thereby ensuring that the breaking force between the extension arm and the elastic central component is above 2.5N without affecting the mechanical properties of the disintegration module itself, thereby enabling the gastric retention device to remain in the gastric cavity for a sufficient time. The bonding force between the connecting component and the extension arm mainly comes from the bonding module, and the material and formula of the disintegration module can be selected from a wider range. The continuous region continuously extends through the entire connecting component, which is beneficial to enhancing the integrity and mechanical strength of the connecting component.
本发明的另一方面将连接部件设置由多个连接片组成，多个连接片熔融粘接有助于提高连接部件的粘结牢固性，且相邻连接片之间粘接材料含量相差不超过50％，避免相邻连接片之间材料相差过大，从而保证连接部件的机械强度，避免连接部件上出现应力集中的区域，有效提高连接部件整体的断裂力。On the other hand, the present invention provides a connecting component composed of multiple connecting sheets. The fusion bonding of the multiple connecting sheets helps to improve the bonding strength of the connecting component, and the difference in the adhesive material content between adjacent connecting sheets does not exceed 50%, avoiding excessive difference in material between adjacent connecting sheets, thereby ensuring the mechanical strength of the connecting component, avoiding the occurrence of stress concentration areas on the connecting component, and effectively improving the overall breaking force of the connecting component.
本发明的另一方面将连接部件设置为崩解模块和粘接模块，粘接模块与延长臂的固定端粘接以保证延长臂与连接部件的充分粘接力，且通过第一连接结构的设置，使得崩解模块和粘接模块的熔接结合面积至少为1.5S以上，从而加强增强后续熔融粘接的效果，使得两者之间的断裂力为2.5N以上，从而保证胃滞留装置在胃中能够滞留充分的时间。On the other hand, the connecting component is configured as a disintegration module and a bonding module. The bonding module is bonded to the fixed end of the extension arm to ensure sufficient bonding force between the extension arm and the connecting component. By setting the first connecting structure, the fusion bonding area of the disintegration module and the bonding module is at least 1.5S or more, thereby enhancing the effect of subsequent melt bonding and making the breaking force between the two greater than 2.5N, thereby ensuring that the gastric retention device can be retained in the stomach for a sufficient time.
图1为具体实施方式所述处于展开构型的胃滞留装置。FIG. 1 illustrates a gastric retention device according to an embodiment of the present invention in a deployed configuration.
图2为具体实施方式所述处于折叠构型的胃滞留装置。2 is a diagram of a gastric retention device in a collapsed configuration according to an exemplary embodiment.
图3为一种实施例所述的连接部件的示意图。FIG3 is a schematic diagram of a connecting component according to an embodiment.
图4为一种实施例所述的连接部件的示意图。FIG4 is a schematic diagram of a connecting component according to an embodiment.
图5为一种实施例所述的连接部件的立体示意图。FIG5 is a perspective schematic diagram of a connecting component according to an embodiment.
图6为一种实施例所述的连接部件的示意图。FIG6 is a schematic diagram of a connecting component according to an embodiment.
图7为一种实施例所述的连接部件的示意图。FIG. 7 is a schematic diagram of a connecting component according to an embodiment.
图8为一种实施例所述的连接部件的示意图。FIG8 is a schematic diagram of a connecting component according to an embodiment.
图9为一种实施例所述的连接部件的立体示意图。FIG9 is a perspective schematic diagram of a connecting component according to an embodiment.
图10为一种实施例所述的连接部件的示意图。FIG. 10 is a schematic diagram of a connecting component according to an embodiment.
图11为一种实施例所述的连接部件的立体示意图。FIG11 is a perspective schematic diagram of a connecting component according to an embodiment.
图12为一种实施例所述的连接部件的立体示意图。FIG12 is a perspective schematic diagram of a connecting component according to an embodiment.
图13为图12中连接部件沿线A-A的截面图。FIG13 is a cross-sectional view of the connecting component along line A-A in FIG12.
图14为一种实施例所述的连接部件的立体示意图。FIG14 is a perspective schematic diagram of a connecting component according to an embodiment.
图15为一种实施例所述的连接部件的立体示意图。FIG15 is a perspective schematic diagram of a connecting component according to an embodiment.
图16为一种实施例所述的连接部件的立体示意图。FIG16 is a perspective schematic diagram of a connecting component according to an embodiment.
图17为一种实施例所述的连接部件的立体示意图。FIG17 is a perspective schematic diagram of a connecting component according to an embodiment.
图18为一种实施例所述的连接部件的立体示意图。FIG18 is a perspective schematic diagram of a connecting component according to an embodiment.
图19为一种实施例所述的连接部件的立体示意图。FIG19 is a perspective schematic diagram of a connecting component according to an embodiment.
图20为一种实施例所述的连接部件的轴向剖面示意图。FIG20 is a schematic axial cross-sectional view of a connecting component according to an embodiment.
图21为一种实施例所述的连接部件的立体示意图。FIG21 is a perspective schematic diagram of a connecting component according to an embodiment.
图22为图21中连接部件端面的示意图。FIG22 is a schematic diagram of the end face of the connecting component in FIG21 .
图23为一种实施例所述的连接部件的立体示意图。FIG23 is a perspective schematic diagram of a connecting component according to an embodiment.
图24为一种实施例所述的连接部件的组合图。FIG. 24 is a diagram showing an assembly of connecting components according to an embodiment.
图25为图24连接部件的立体示意图。FIG25 is a perspective schematic diagram of the connecting component in FIG24 .
图26为折断测试装置的结构示意图。FIG26 is a schematic structural diagram of a fracture test device.
附图标记说明：
1、弹性中心部件；
2、延长臂；21、固定端；22、自由端；
3、连接部件；31、崩解模块；311、外露区域；312、通槽；313、时间
依赖性崩解模块；314、肠溶崩解模块；32、粘接模块；321、开槽；322、子模块；323、连续区域；33、安装槽；34、崩解连接片；341、时间依赖性崩解连接片；342、肠溶崩解连接片；35、末端连接片；36、中间连接片；37、第一连接结构；371、凸缘；372、凹槽；38、第二连接结构；
4、折断测试装置；41、固定台；42、下压板；43、测试件。Description of reference numerals:
1. Elastic center component;
2. Extension arm; 21. Fixed end; 22. Free end;
3. Connecting components; 31. Disintegration module; 311. Exposed area; 312. Through slot; 313. Time-dependent disintegration module; 314. Enteric disintegration module; 32. Adhesive module; 321. Slot; 322. Submodule; 323. Continuous area; 33. Mounting slot; 34. Disintegration connector; 341. Time-dependent disintegration connector; 342. Enteric disintegration connector; 35. End connector; 36. Intermediate connector; 37. First connecting structure; 371. Flange; 372. Groove; 38. Second connecting structure;
4. Fracture test device; 41. Fixing table; 42. Lower pressure plate; 43. Test piece.
现有技术中胃滞留装置以压缩的折叠构型被包含在胶囊壳或其它容器中，其可以由患者吞咽或者以其它方式能够被施用于胃以便不能吞咽的患者(例如，经过胃造口术管、饲管、胃管或其它对胃的施用途径)。Prior art gastric retention devices are contained in a capsule shell or other container in a compressed, folded configuration that can be swallowed by the patient or that can otherwise be administered to the stomach for patients who are unable to swallow (e.g., via a gastrostomy tube, feeding tube, nasogastric tube, or other route of administration to the stomach).
如图1中所示为胃滞留装置的展开构型。如图2所示为胃滞留装置的折叠构型。胃滞留装置包括弹性中心部件1、多个延长臂2和多个连接部件3，多个延长臂2周向环绕弹性中心部件1设置，至少一个延长臂2上负载有活性物质，延长臂2通过连接部件3与弹性中心部件1粘接。Figure 1 shows the deployed configuration of the gastroretentive device. Figure 2 shows the folded configuration of the gastroretentive device. The gastroretentive device comprises an elastic core member 1, a plurality of extension arms 2, and a plurality of connecting members 3. The plurality of extension arms 2 are circumferentially arranged around the elastic core member 1, at least one extension arm 2 is loaded with an active substance, and the extension arms 2 are bonded to the elastic core member 1 via the connecting members 3.
一旦填充有折叠胃滞留装置的胶囊壳或其它容器到达患者的胃中，则胶囊壳溶解并释放折叠的胃滞留装置。释放时，胃滞留装置恢复到其展开构型。展开构型的胃滞留装置的尺寸大于胃的幽门排出口，从而防止该胃滞留装置排出胃腔，当胃滞留装置滞留充足的时间后，连接部件3上的崩解材料崩解，使得该装置离开胃腔进入小肠。Once the capsule shell or other container filled with the folded gastric retention device reaches the patient's stomach, the capsule shell dissolves and releases the folded gastric retention device. Upon release, the gastric retention device returns to its expanded configuration. The gastric retention device in the expanded configuration is larger than the pyloric outlet of the stomach, thereby preventing the gastric retention device from exiting the stomach cavity. After the gastric retention device has been in the patient's stomach for a sufficient period of time, the disintegrating material on the connecting member 3 disintegrates, allowing the device to exit the stomach cavity and enter the small intestine.
当在胃中时，胃滞留装置与消化胃肠道的其它正常功能相容。胃滞留装置不干扰或妨碍食糜(部分消化的食物)或其它从胃中排出的胃内容物通过幽门括约肌进入十二指肠。When in the stomach, the gastric retention device is compatible with the other normal functions of the digestive gastrointestinal tract. The gastric retention device does not interfere with or prevent chyme (partially digested food) or other gastric contents from being expelled from the stomach through the pyloric sphincter and into the duodenum.
在一些实施例中，延长臂2上包括基质材料，基质材料用于构成延长臂2的主体，延长臂2上负载的活性物质为治疗剂或诊断剂。In some embodiments, the extension arm 2 includes a matrix material, which is used to constitute the main body of the extension arm 2. The active substance loaded on the extension arm 2 is a therapeutic agent or a diagnostic agent.
在一些实施例中，活性物质选自多西环素、多奈哌齐、伊维菌素、利培酮、西替利嗪和瑞舒伐他汀或其药学上可接受的盐。In some embodiments, the active substance is selected from doxycycline, donepezil, ivermectin, risperidone, cetirizine, and rosuvastatin, or a pharmaceutically acceptable salt thereof.
延长臂2的两端分别为固定端21和自由端22，延长臂2的固定端21通过连接部件3与弹性中心部件1相粘接。The two ends of the extension arm 2 are a fixed end 21 and a free end 22 . The fixed end 21 of the extension arm 2 is bonded to the elastic central component 1 through a connecting component 3 .
在本发明中，连接部件3被构造为经过降解、溶解、解离或机械弱化过程后使得延长臂2与弹性中心部件1相分离或可相对弯曲。口服胃滞留装置通过弹性中心部件1提供弹性力完成折叠构型至展开构型的转变。In the present invention, the connecting member 3 is configured to undergo degradation, dissolution, dissociation, or mechanical weakening, allowing the extension arms 2 to separate from or bend relative to the elastic core member 1. The oral gastric retention device utilizes the elastic force provided by the elastic core member 1 to transition from a folded configuration to an expanded configuration.
在一些实施例中，弹性中心部件1为弹性聚合物。In some embodiments, the elastic center member 1 is an elastic polymer.
在一些实施例中，弹性中心部件1包括弹性合金部件，弹性合金部件被构造为由马氏体转变为奥氏体以使得口服胃滞留装置由折叠构型转变为展开构型。In some embodiments, the resilient center member 1 comprises a resilient alloy member configured to transform from martensite to austenite to enable the oral gastroretention device to transform from a collapsed configuration to an expanded configuration.
相比于使用弹性聚合物，使用弹性合金部件具有较强的弹性模量，在胃内能够较好的抵抗来自胃的蠕动力，同时弹性记忆合金进入体内后，由于人体温度较高，记忆合金能够自然的从马氏体转变为奥氏体从而使得延长臂2展开形成展开构型，从而使得装置可以滞留在胃内。Compared with the use of elastic polymers, the use of elastic 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 elastic memory alloy enters the body, due to the high temperature of the human body, the memory alloy can naturally transform from martensite to austenite, thereby allowing the extension arm 2 to expand to form an expanded configuration, so that the device can remain in the stomach.
在本发明中，连接部件3包括第一端面、第二端面和连接两者的外侧面，第一端面与弹性中心部件1粘接，第二端面与延长臂2的固定端21相粘接。In the present invention, the connecting component 3 includes a first end face, a second end face and an outer side face connecting the two. The first end face is bonded to the elastic central component 1 , and the second end face is bonded to the fixed end 21 of the extension arm 2 .
如图3-15所示，连接部件3包括崩解模块31和粘接模块32，崩解模块31具有显露于连接部件3外侧面的外露区域311，粘接模块32具有由第一端面连续延伸至第二端面的连续区域323，粘接模块32的材料与延长臂2的材料具有良好熔融相容性，粘接模块32用于增加连接部件3和延长臂2粘接处的粘接力以使得延长臂2和弹性中心部件1之间的断裂力至少为2.5N以上。As shown in Figure 3-15, the connecting component 3 includes a disintegration module 31 and a bonding module 32. The disintegration module 31 has an exposed area 311 exposed on the outer side of the connecting component 3, and the bonding module 32 has a continuous area 323 extending continuously from the first end face to the second end face. The material of the bonding module 32 has good melting compatibility with the material of the extension arm 2. The bonding module 32 is used to increase the bonding force at the bonding point between the connecting component 3 and the extension arm 2 so that the breaking force between the extension arm 2 and the elastic center component 1 is at least 2.5N.
在一些实施例中，粘接模块32的材料选择与延长臂2的基质材料在熔融状态完全相容或部分相容。In some embodiments, the material of the bonding module 32 is fully or partially compatible with the matrix material of the extension arm 2 in a molten state.
在一些实施例中，粘接模块32的材料选择与延长臂2基质材料相同的材料，相同的材料具有完全的熔融相容性。In some embodiments, the material of the bonding module 32 is the same as the matrix material of the extension arm 2 , and the same materials have complete melting compatibility.
在一些实施例中，崩解模块31的外露区域311在连接部件3的外侧面上占据至少30％的面积。通过连接部件3的外露区域311的面积以控制崩解模块31的崩解速率和时间，从而起到定时崩解或安全保护崩解的作用。In some embodiments, the exposed area 311 of the disintegration module 31 occupies at least 30% of the area on the outer surface of the connecting component 3. The area of the exposed area 311 of the connecting component 3 is used to control the disintegration rate and time of the disintegration module 31, thereby achieving the effect of timed disintegration or safety protection disintegration.
在具体的实施例中，崩解模块31的外露区域311在连接部件3的外侧面上可以占据30-40％、30-60％、30-80％、30-100％、40-50％、40-50％、40-80％、40-100％、50-60％、50-80％、50-100％、60-70％、60-80％、60-100％、70-80％、70-90％、70-100％、80-90％、80-100％或90-100％的面积。In a specific embodiment, the exposed area 311 of the disintegration module 31 can occupy 30-40%, 30-60%, 30-80%, 30-100%, 40-50%, 40-50%, 40-80%, 40-100%, 50-60%, 50-80%, 50-100%, 60-70%, 60-80%, 60-100%, 70-80%, 70-90%, 70-100%, 80-90%, 80-100% or 90-100% of the area on the outer surface of the connecting part 3.
在一些实施例中，粘接模块32在第二端面上至少占据20％的面积。粘接模块32在第二端面上占有的面积用于增强连接部件3和延长臂2熔融粘接的牢固性。In some embodiments, the bonding module 32 occupies at least 20% of the area on the second end surface. The area occupied by the bonding module 32 on the second end surface is used to enhance the firmness of the melt bonding between the connecting component 3 and the extension arm 2.
在具体的实施例中，粘接模块32在第二端面上至少占据20-30％、20-50％、20-70％、20-80％、20-100％、30-40％、30-60％、30-80％、30-100％、40-50％、40-50％、40-80％、40-100％、50-60％、50-80％、50-100％、60-70％、60-80％、60-100％、70-80％、70-90％、70-100％、80-90％、80-100％或90-100％的面积。In a specific embodiment, the bonding module 32 occupies at least 20-30%, 20-50%, 20-70%, 20-80%, 20-100%, 30-40%, 30-60%, 30-80%, 30-100%, 40-50%, 40-50%, 40-80%, 40-100%, 50-60%, 50-80%, 50-100%, 60-70%, 60-80%, 60-100%, 70-80%, 70-90%, 70-100%, 80-90%, 80-100% or 90-100% of the area on the second end surface.
在一些实施例中，粘接模块32和/或崩解模块31为沿其轴向延伸的等截面模块。轴向延长保证了连接部件3在轴向上机械强度的一致性。In some embodiments, the bonding module 32 and/or the disintegration module 31 are modules with a uniform cross-section extending along the axial direction thereof. The axial extension ensures the consistency of the mechanical strength of the connecting component 3 in the axial direction.
如图3-11，14-15所示，在具体的实施例中，粘接模块32和崩解模块31均为沿其轴向延伸的等截面模块。崩解模块31和粘接模块32可以为圆形、三角形、多边形等其他各种等截面拉伸形状，轴向上的等截面拉伸能够保证连接部件3在轴向上机械强度的一致性。As shown in Figures 3-11 and 14-15, in a specific embodiment, both the bonding module 32 and the disintegration module 31 are modules of uniform cross-section extending along their axial direction. The disintegration module 31 and the bonding module 32 can have various other uniform cross-sectional stretched shapes, such as circular, triangular, polygonal, etc. The uniform cross-sectional stretching in the axial direction ensures the consistency of the mechanical strength of the connecting component 3 in the axial direction.
如图3-4所示，在一些实施例中，崩解模块31和粘接模块32分别上下或左右设置。As shown in FIG3-4 , in some embodiments, the disintegration module 31 and the bonding module 32 are respectively arranged vertically or horizontally.
在一些实施例中，连接部件3和延长臂2竖直截面相同，可以为圆形、多边形等其他形状，在本发明的实施例中，连接部件3和延长臂2的竖直截面的形状三角形。In some embodiments, the vertical cross-sections of the connecting component 3 and the extension arm 2 are the same, and may be circular, polygonal or other shapes. In an embodiment of the present invention, the vertical cross-sections of the connecting component 3 and the extension arm 2 are triangular.
在一些实施例中，连接部件3包括中心模块和多个侧面模块，多个侧边模块周向设置在中心模块的侧面上。In some embodiments, the connecting component 3 includes a central module and a plurality of side modules, and the plurality of side modules are circumferentially arranged on the sides of the central module.
如图5-9，14-15所示，中心模块为崩解模块31，侧面模块为粘接模块32，中心模块的侧面具有显露于侧面模块外侧面外露区域311。As shown in Figures 5-9 and 14-15, the central module is a disintegration module 31, the side modules are bonding modules 32, and the side of the central module has an exposed area 311 exposed on the outer side of the side modules.
如图5-6、9、14所示，在连接部件3的截面图中，中心模块的外露区域311贴合内切于侧面模块外侧面所在面。在图5-6中心模块为内切于侧面的圆形和六边形。As shown in Figures 5-6, 9 and 14, in the cross-sectional view of the connecting component 3, the exposed area 311 of the central module is inscribed in the surface of the outer side of the side module. In Figures 5-6, the central module is a circle and a hexagon inscribed in the side.
如图7-8、15所示，在连接部件3的截面图中，中心模块的侧面不与连接部件3的外侧面相切，制备时多个侧面模块组合先制备包覆中心模块侧面，然后在侧面模块上开设开槽321，以显露中心模块的侧面形成外露区域311，外露面积占据连接部件3外侧面的大小可以通过开槽321的面积来进行决定。崩解模块31位于中心，粘接模块32对崩解模块31起到一定的保护和加强的作用。As shown in Figures 7-8 and 15 , in the cross-sectional views of connecting component 3, the side surfaces of the central module are not tangent to the outer surface of connecting component 3. During preparation, multiple side modules are assembled to cover the sides of the central module. Then, slots 321 are formed in the side modules to expose the sides of the central module, forming exposed areas 311. The size of the exposed area relative to the outer surface of connecting component 3 is determined by the area of slots 321. Disintegration module 31 is located in the center, and bonding module 32 provides some protection and reinforcement for disintegration module 31.
如图5-9中，在一些实施例中，连接部件3可以将崩解模块31可以设置为侧面模块，粘接模块32设置为中心模块。As shown in FIG5-9 , in some embodiments, the connecting component 3 may configure the disintegration module 31 as a side module and the bonding module 32 as a central module.
如图10所示，在一些实施例中，中心模块为粘接模块32，此时侧面模块可以完全包覆中心模块侧面，此时崩解模块31的外露区域311在连接部件3的外侧面上占据100％的面积。As shown in FIG10 , in some embodiments, the central module is a bonding module 32 , and the side modules can completely cover the sides of the central module. In this case, the exposed area 311 of the disintegration module 31 occupies 100% of the area on the outer surface of the connecting component 3 .
如图11所示，在一些实施例中，中心模块的侧面上具有向内侧凹陷的安装槽33，侧面模块设于安装槽33内。安装槽33增强中心模块和侧边模块的相互接触面积，当制备连接部件3时，有助于提高中心模块和侧边模块之间的作用效果。As shown in FIG11 , in some embodiments, the side of the central module has an inwardly recessed mounting groove 33, and the side modules are disposed within the mounting groove 33. The mounting groove 33 increases the contact area between the central module and the side modules, which helps improve the interaction between the central module and the side modules when preparing the connecting member 3.
如图12-13所示，在一些实施例中，粘接模块32包括两个子模块322和连续区域323，两个子模块322分别位于第一端面和第二端面，崩解模块31设置在两个子模块322之间，两个子模块322之间具有连续区域323相连接，连续区域323横穿崩解模块31。崩解模块31上具有容纳结构，连续区域323横穿容纳结构。容纳结构可以为在崩解模块31侧面上的通槽312或者贯穿崩解模块31的通孔。容纳结构和连续区域323的配合使得崩解模块31和粘接模块32的配合更加的紧密。As shown in Figures 12-13, in some embodiments, the bonding module 32 includes two submodules 322 and a continuous region 323. The two submodules 322 are respectively located on the first end face and the second end face. The disintegration module 31 is arranged between the two submodules 322, and the two submodules 322 are connected by a continuous region 323, which crosses the disintegration module 31. The disintegration module 31 has a receiving structure, and the continuous region 323 crosses the receiving structure. The receiving structure can be a through groove 312 on the side of the disintegration module 31 or a through hole that penetrates the disintegration module 31. The cooperation between the receiving structure and the continuous region 323 makes the cooperation between the disintegration module 31 and the bonding module 32 more compact.
具体的，如图12-13所示，容纳结构为位于崩解模块31侧面的通槽312。连续区域323适配的嵌入通槽312内，加强了崩解模块31和粘接模块32的整体强度。12-13 , the receiving structure is a through groove 312 located on the side of the disintegration module 31 . The continuous area 323 is adaptively embedded in the through groove 312 , thereby enhancing the overall strength of the disintegration module 31 and the bonding module 32 .
在一些其他的实施例中，第二端面上具有与延长臂2固定端21相互卡合的连接结构，延长臂2的固定端21与延长臂2相互卡合定位后进行熔融粘接。In some other embodiments, the second end surface has a connection structure that engages with the fixed end 21 of the extension arm 2, and the fixed end 21 of the extension arm 2 and the extension arm 2 are engaged with each other and positioned and then melt-bonded.
在一些实施例中，崩解模块31包括时间依赖性崩解模块313和/或肠溶崩解模块314。In some embodiments, the disintegration module 31 includes a time-dependent disintegration module 313 and/or an enteric disintegration module 314 .
时间依赖性崩解模块313既在水性条件下以在预定的时间内强度弱化，以使得延长臂2相对于弹性中心部件1断裂或可弯曲，从而控制胃滞留装置的在胃内的滞留时间，时间依赖性崩解模块313的强度弱化方式可以为随时间逐渐降解、溶解、解离或机械弱化，延长臂2断裂足够的数量后胃滞留装置可以通过幽门瓣，离开胃腔并进入小肠，最终从体内排出。The time-dependent disintegration module 313 weakens its strength within a predetermined time under aqueous conditions so that the extension arm 2 breaks or becomes bendable relative to the elastic central component 1, thereby controlling the retention time of the gastric retention device in the stomach. The strength weakening mode of the time-dependent disintegration module 313 can be gradual degradation, dissolution, dissociation or mechanical weakening over time. After a sufficient number of extension arms 2 are broken, the gastric retention device can pass through the pyloric valve, leave the gastric cavity and enter the small intestine, and finally be discharged from the body.
肠溶崩解模块314即为pH依赖崩解模块，用于为胃滞留装置提供安全防护机制，一旦胃滞留装置提前离开胃腔，进入到肠道时，肠溶崩解模块314将根据小肠的高pH环境中迅速完成降解、溶解、解离或机械弱化，从而导致延长臂2断裂，避免出现肠梗阻，使得胃滞留装置容易通过小肠。The enteric disintegration module 314 is a pH-dependent disintegration module, which is used to provide a safety protection mechanism for the gastric retention device. Once the gastric retention device leaves the gastric cavity prematurely and enters the intestine, the enteric disintegration module 314 will quickly complete degradation, dissolution, dissociation or mechanical weakening according to the high pH environment of the small intestine, thereby causing the extension arm 2 to break, avoiding intestinal obstruction and making it easier for the gastric retention device to pass through the small intestine.
如图14所示，在一些实施例中，崩解模块31包括时间依赖性崩解模块313和肠溶崩解模块314，时间依赖性崩解模块313和肠溶崩解模块314沿轴向排列，粘接模块32轴向延伸，粘接模块32周向设置在时间依赖性崩解模块313、肠溶崩解模块314的侧面。时间依赖性崩解模块313、肠溶崩解模块314分别靠近连接部件3的第一端面和第二端面。As shown in FIG14 , in some embodiments, the disintegration module 31 includes a time-dependent disintegration module 313 and an enteric disintegration module 314. The time-dependent disintegration module 313 and the enteric disintegration module 314 are arranged axially. The bonding module 32 extends axially and is circumferentially disposed on the sides of the time-dependent disintegration module 313 and the enteric disintegration module 314. The time-dependent disintegration module 313 and the enteric disintegration module 314 are respectively located near the first and second end faces of the connecting component 3.
时间依赖性崩解模块313和肠溶崩解模块314沿轴向并排设置，粘接模块32在时间依赖性崩解模块313和肠溶崩解模块314的侧面上轴向延伸，粘接模块32能够对时间依赖性崩解模块313和肠溶崩解模块314进行粘合，因此此时在连接部件3制备时，无需特别注意时间依赖性崩解模块313和肠溶崩解模块314之间的粘合性能。The time-dependent disintegration module 313 and the enteric disintegration module 314 are arranged side by side in the axial direction, and the bonding module 32 extends axially on the sides of the time-dependent disintegration module 313 and the enteric disintegration module 314. The bonding module 32 can bond the time-dependent disintegration module 313 and the enteric disintegration module 314. Therefore, when preparing the connecting component 3, there is no need to pay special attention to the bonding performance between the time-dependent disintegration module 313 and the enteric disintegration module 314.
如图15所示，在一些实施例中，崩解模块31包括时间依赖性崩解模块313和肠溶崩解模块314，时间依赖性崩解模块313和肠溶崩解模块314沿轴向排列，制备时，先在时间依赖性崩解模块313和肠溶崩解模块314外侧面形成一层粘接模块32，之后再在粘接模块32的侧面上开设开槽321，以在时间依赖性崩解模块313和肠溶崩解模块314的侧面形成外露区域311。As shown in Figure 15, in some embodiments, the disintegration module 31 includes a time-dependent disintegration module 313 and an enteric disintegration module 314. The time-dependent disintegration module 313 and the enteric disintegration module 314 are arranged axially. During preparation, a layer of bonding module 32 is first formed on the outer side of the time-dependent disintegration module 313 and the enteric disintegration module 314, and then a groove 321 is opened on the side of the bonding module 32 to form an exposed area 311 on the side of the time-dependent disintegration module 313 and the enteric disintegration module 314.
在一些实施例中，粘接模块32包括50％以上的粘接材料，粘接材料与延长臂2的基质材料粘接熔融；In some embodiments, the bonding module 32 includes more than 50% of bonding material, and the bonding material is bonded and melted with the matrix material of the extension arm 2;
时间依赖性崩解模块313包括小于30％的粘接材料和大于70％的时间依赖崩解材料；The time-dependent disintegration module 313 includes less than 30% of a binding material and more than 70% of a time-dependent disintegration material;
肠溶崩解模块314包括小于30％的粘接材料和大于70％的肠溶崩解材料。The enteric disintegrating module 314 includes less than 30% of a binder material and more than 70% of an enteric disintegrating material.
时间依赖性崩解模块313和肠溶崩解模块314均包含部分粘接材料用于与粘接模块32熔融粘接。The time-dependent disintegration module 313 and the enteric disintegration module 314 both contain some bonding materials for melt-bonding with the bonding module 32 .
在一些其他的实施例中，粘接模块32、时间依赖性崩解模块313和肠溶崩解模块314的组分还可以包括其他添加剂，添加剂可以包括增塑剂、增溶剂、染色剂和亲水物质(增加亲水性，如PEG)或疏水物质等添加剂。In some other embodiments, the components of the bonding module 32, the time-dependent disintegration module 313 and the enteric disintegration module 314 may further include other additives, and the additives may include plasticizers, solubilizers, dyes and hydrophilic substances (to increase hydrophilicity, such as PEG) or hydrophobic substances and other additives.
在一些实施例中，粘接材料和延长臂2的基质材料相同。In some embodiments, the adhesive material and the matrix material of the extension arm 2 are the same.
在一些实施例中，粘接材料包括聚己内酯(PCL)、聚乳酸(PLA)、聚乙交酯(PGA)、聚乳酸-羟基乙酸共聚物(PLGA)、聚羟基脂肪酸酯(Polyhydroxyalkanoates)和改性多糖(modified polysaccharides)中的一种或多种；时间依赖崩解材料包括聚乳酸(PLA)、聚乳酸-羟基乙酸共聚物(PLGA)、聚乙交酯PGA()、聚己内酯(PCL)、聚酸酐(Polyanhydrides)和聚正酯(Polyorthoesters)中的一种或多种(PLGA)；肠溶崩解材料包括醋酸羟丙甲纤维素琥珀酸酯(HPMCAS)、丙烯酸酯共聚物(acrylate co-polymers)、醋酸邻苯二甲酸纤维素(cellulose acetate phthalate)、虫胶(shellac)和聚醋酸乙烯邻苯二酸酯(polyvinyl acetate phthalate)中的一种或多种。In some embodiments, the adhesive material includes one or more of polycaprolactone (PCL), polylactic acid (PLA), polyglycolide (PGA), polylactic-co-glycolic acid (PLGA), polyhydroxyalkanoates and modified polysaccharides; the time-dependent disintegrating material includes one or more of polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), polyglycolide PGA (), polycaprolactone (PCL), polyanhydrides and polyorthoesters (PLGA); the enteric disintegrating material includes one or more of hydroxypropyl methylcellulose acetate succinate (HPMCAS), acrylate co-polymers, cellulose acetate phthalate, shellac and polyvinyl acetate phthalate.
在一些实施例中，崩解模块31和粘接模块32通过熔融共挤、熔融注塑成型、压塑成型、二次烧结成型和三维打印中的一种或多种方法制备。In some embodiments, the disintegration module 31 and the bonding module 32 are prepared by one or more methods selected from the group consisting of melt coextrusion, melt injection molding, compression molding, secondary sintering molding, and three-dimensional printing.
其中，如图3-6、图9-11、所示的连接部件3可以通过熔融共挤、熔融注塑成型、压塑成型、二次烧结成型或三维打印制备。Among them, the connecting component 3 shown in Figures 3-6, 9-11 can be prepared by melt co-extrusion, melt injection molding, compression molding, secondary sintering molding or three-dimensional printing.
图7-8所示的连接部件3，通过熔融共挤、熔融注塑成型、压塑成型、二次烧结成型或三维打印制备成型后，再在连接部件3外侧面开设开槽321以显露外露区域311。The connecting component 3 shown in Figures 7-8 is prepared by melt co-extrusion, melt injection molding, compression molding, secondary sintering molding or three-dimensional printing, and then a groove 321 is opened on the outer side of the connecting component 3 to reveal the exposed area 311.
图11-12、图14-15所示的连接部件3可以通过熔融注塑成型、压塑成型、二次烧结成型或三维打印制备。The connecting component 3 shown in FIG. 11 - 12 and FIG. 14 - 15 can be prepared by melt injection molding, compression molding, secondary sintering molding or three-dimensional printing.
如图1-2、16-17所示，本发明另一方面公开了一种胃滞留装置，包括弹性中心部件1、多个延长臂2和多个连接部件3，延长臂2轴向的两端分别为固定端21和自由端22，连接部件3包括多个相熔融粘接的连接片，其中包括至少一个崩解连接片34和两端的末端连接片35。As shown in Figures 1-2 and 16-17, another aspect of the present invention discloses a gastric retention device, comprising an elastic central component 1, a plurality of extension arms 2 and a plurality of connecting components 3, wherein the axial ends of the extension arms 2 are respectively a fixed end 21 and a free end 22, and the connecting components 3 include a plurality of fusion-bonded connecting pieces, including at least one disintegrating connecting piece 34 and end connecting pieces 35 at both ends.
连接片中均包含由粘接材料，相邻连接片之间的粘接材料的质量分数百分比差值不超过50％。The connecting pieces all contain adhesive material, and the difference in mass fraction of the adhesive material between adjacent connecting pieces does not exceed 50%.
崩解连接片34包含60％以上的崩解材料，末端连接片35包括60％以上的粘接材料，用于粘接延长臂2的固定端21，连接部件3上多个连接片的设置使得延长臂2和弹性中心部件1之间的断裂力至少为2.5N。The disintegrating connecting piece 34 contains more than 60% disintegrating material, and the end connecting piece 35 includes more than 60% adhesive material, which is used to bond the fixed end 21 of the extension arm 2. The arrangement of multiple connecting pieces on the connecting part 3 makes the breaking force between the extension arm 2 and the elastic central part 1 at least 2.5N.
连接部件3的崩解连接片34用于控制连接部件3的定时崩解断裂或安全保护崩解，胃滞留装置在胃内滞留预定的时间后或提前进入小肠环境时，崩解连接片34开始崩解，从而使得延长臂2和弹性中心部件1相分离。The disintegrating connecting piece 34 of the connecting part 3 is used to control the timed disintegration and rupture or safety protection disintegration of the connecting part 3. When the gastric retention device stays in the stomach for a predetermined time or enters the small intestine environment in advance, the disintegrating connecting piece 34 begins to disintegrate, thereby separating the extension arm 2 and the elastic central part 1.
在一些实施例中，崩解连接片34包括时间依赖性崩解连接片341和/或肠溶崩解连接片342。In some embodiments, the disintegrating web 34 includes a time-dependent disintegrating web 341 and/or an enteric disintegrating web 342 .
时间依赖性崩解连接片341既在水性条件下以在预定的时间内强度弱化，以使得延长臂2相对于弹性中心部件1断裂或可弯曲，从而控制胃滞留装置的在胃内的滞留时间，时间依赖性崩解连接片341的强度弱化方式可以为随时间逐渐降解、溶解、解离或机械弱化，延长臂2断裂足够的数量后胃滞留装置可以通过幽门瓣，离开胃腔并进入小肠，最终从体内排出。The time-dependent disintegrating connecting piece 341 weakens in strength within a predetermined time under aqueous conditions so that the extension arm 2 breaks or bends relative to the elastic central component 1, thereby controlling the retention time of the gastric retention device in the stomach. The strength weakening of the time-dependent disintegrating connecting piece 341 can be gradual degradation, dissolution, dissociation or mechanical weakening over time. After a sufficient number of extension arms 2 are broken, the gastric retention device can pass through the pyloric valve, leave the gastric cavity and enter the small intestine, and finally be discharged from the body.
肠溶崩解连接片342块即为pH依赖崩解连接片，用于为胃滞留装置提供安全防护机制，一旦胃滞留装置提前离开胃腔，进入到肠道时，肠溶崩解模块314将根据小肠的高pH环境中迅速完成降解、溶解、解离或机械弱化，从而导致延长臂2断裂，避免出现肠梗阻，使得胃滞留装置容易通过小肠。The enteric disintegrating connecting piece 342 is a pH-dependent disintegrating connecting piece, which is used to provide a safety protection mechanism for the gastric retention device. Once the gastric retention device leaves the gastric cavity prematurely and enters the intestine, the enteric disintegrating module 314 will quickly complete degradation, dissolution, dissociation or mechanical weakening according to the high pH environment of the small intestine, thereby causing the extension arm 2 to break, avoiding intestinal obstruction and making it easier for the gastric retention device to pass through the small intestine.
在一些实施例中，崩解连接片34包括时间依赖性崩解连接片341和肠溶崩解连接片342。In some embodiments, the disintegrating web 34 includes a time-dependent disintegrating web 341 and an enteric disintegrating web 342 .
连接部件3的多个连接片中包括至少两个位于时间依赖性崩解连接片341和肠溶崩解连接片342之间的中间连接片36，时间依赖性崩解连接片341包括至少60％时间依赖性崩解材料，肠溶崩解连接片342包括至少60％肠溶崩解材料，中间连接片36中包括至少60％粘接材料，紧贴时间依赖性崩解连接片341的中间连接片36含有不超过30％的时间依赖性崩解材料，紧贴肠溶崩解连接片342的中间连接片36含有不超过30％的肠溶崩解材料。The multiple connecting pieces of the connecting component 3 include at least two intermediate connecting pieces 36 located between the time-dependent disintegrating connecting piece 341 and the enteric disintegrating connecting piece 342, the time-dependent disintegrating connecting piece 341 includes at least 60% time-dependent disintegrating material, the enteric disintegrating connecting piece 342 includes at least 60% enteric disintegrating material, the intermediate connecting piece 36 includes at least 60% adhesive material, the intermediate connecting piece 36 close to the time-dependent disintegrating connecting piece 341 contains no more than 30% time-dependent disintegrating material, and the intermediate connecting piece 36 close to the enteric disintegrating connecting piece 342 contains no more than 30% enteric disintegrating material.
时间依赖性崩解连接片341和肠溶崩解连接片342之间通过中间连接片36的缓冲，增强粘接强度，同时紧贴时间依赖性崩解连接片341、肠溶崩解连接片342的连接片分别含有部分对应的崩解材料，使得两者熔融状态下，相容性更好。The intermediate connecting piece 36 acts as a buffer between the time-dependent disintegrating connecting piece 341 and the enteric disintegrating connecting piece 342 to enhance the bonding strength. At the same time, the connecting pieces close to the time-dependent disintegrating connecting piece 341 and the enteric disintegrating connecting piece 342 respectively contain part of the corresponding disintegrating material, so that the two are more compatible in the molten state.
在一些实施例中，至少两个中间连接片36中，越靠近时间依赖性崩解连接片341的中间连接片36的时间依赖性崩解材料含量越高，越靠近肠溶崩解连接片342的中间连接片36的肠溶崩解材料含量越高。In some embodiments, among the at least two intermediate connecting pieces 36 , the intermediate connecting piece 36 closer to the time-dependent disintegrating connecting piece 341 has a higher content of time-dependent disintegrating material, and the intermediate connecting piece 36 closer to the enteric disintegrating connecting piece 342 has a higher content of enteric disintegrating material.
如图17所示，连接部件3包括六个连接片组成，其中包括两个位于端面的末端连接片35、时间依赖性崩解连接片341、肠溶崩解连接片342和两个中间连接片36，两个末端连接片35用于分别与弹性中心部件1和延长臂2相粘接。As shown in Figure 17, the connecting component 3 is composed of six connecting pieces, including two end connecting pieces 35 located on the end faces, a time-dependent disintegrating connecting piece 341, an enteric disintegrating connecting piece 342 and two intermediate connecting pieces 36. The two end connecting pieces 35 are used to bond to the elastic central component 1 and the extension arm 2 respectively.
时间依赖性崩解连接片341包括至少60％时间依赖性崩解材料和不超过30％的粘接材料，紧贴时间依赖性崩解连接片341的中间连接片36包括至少60％的粘接材料和不超过30％的时间依赖性崩解材料，肠溶崩解连接片342包括至少60％肠溶崩解材料和不超过30％的粘接材料，紧贴肠溶崩解连接片342的中间连接片36包括至少60％的粘接材料和不超过30％的肠溶崩解材料。The time-dependent disintegrating connecting sheet 341 includes at least 60% time-dependent disintegrating material and no more than 30% adhesive material, the intermediate connecting sheet 36 closely attached to the time-dependent disintegrating connecting sheet 341 includes at least 60% adhesive material and no more than 30% time-dependent disintegrating material, the enteric disintegrating connecting sheet 342 includes at least 60% enteric disintegrating material and no more than 30% adhesive material, the intermediate connecting sheet 36 closely attached to the enteric disintegrating connecting sheet 342 includes at least 60% adhesive material and no more than 30% enteric disintegrating material.
在一些实施例中，粘接材料包括聚己内酯、聚乳酸、聚乙交酯、聚乳酸-羟基乙酸共聚物、聚羟基脂肪酸酯和改性多糖中的一种或多种；时间依赖崩解材料包括聚乳酸、聚乳酸-羟基乙酸共聚物、聚乙交酯、聚己内酯、聚酸酐和聚正酯中的一种或多种；肠溶崩解材料包括醋酸羟丙甲纤维素琥珀酸酯、丙烯酸酯共聚物、醋酸邻苯二甲酸纤维素、虫胶和聚醋酸乙烯邻苯二酸酯中的一种或多种。In some embodiments, the bonding material includes one or more of polycaprolactone, polylactic acid, polyglycolide, polylactic acid-glycolic acid copolymer, polyhydroxyalkanoate and modified polysaccharide; the time-dependent disintegrating material includes one or more of polylactic acid, polylactic acid-glycolic acid copolymer, polyglycolide, polycaprolactone, polyanhydride and polyorthoester; the enteric disintegrating material includes one or more of hydroxypropyl methylcellulose acetate succinate, acrylate copolymer, cellulose acetate phthalate, shellac and polyvinyl acetate phthalate.
在一些实施例中，粘接材料与延长臂2的基质材料相同。In some embodiments, the adhesive material is the same as the matrix material of the extension arm 2 .
在一些实施例中，相邻的连接片中，粘接材料相差不超过40％。In some embodiments, the bonding material of adjacent connecting sheets differs by no more than 40%.
在一些实施例中，每个连接片的厚度可以为0.3-2mm，具体的厚度可以为0.3mm、0.5mm、0.86mm、1mm、1.28mm、1.5mm或2mm。连接部件3包括的多个连接片的厚度可以相同也可以不同。In some embodiments, the thickness of each connecting piece can be 0.3-2 mm, and the specific thickness can be 0.3 mm, 0.5 mm, 0.86 mm, 1 mm, 1.28 mm, 1.5 mm or 2 mm. The thickness of the multiple connecting pieces included in the connecting component 3 can be the same or different.
如图1-2，18-25，本发明的另一方面公开一种胃滞留装置，包括弹性中心部件1、多个延长臂2和多个连接部件3，延长臂2轴向的两端分别为固定端21和自由端22，延长臂2包括基质材料，连接部件3包括崩解模块31和位于崩解模块两侧的粘接模块32，延长臂2的固定端21、弹性中心部件1分别与崩解模块两侧的粘接模块32相粘接，连接部件3的垂直横截面的面积为S，崩解模块31和粘接模块32的粘接处设有第一连接结构37，以使得崩解模块31和粘接模块32在粘接处具有至少1.5S的接触面积，从而使得延长臂2和弹性中心部件1之间的断裂力至少为2.5N。As shown in Figures 1-2, 18-25, another aspect of the present invention discloses a gastric retention device, comprising an elastic central component 1, multiple extension arms 2 and multiple connecting components 3, the axial ends of the extension arm 2 are respectively a fixed end 21 and a free end 22, the extension arm 2 comprises a matrix material, the connecting component 3 comprises a disintegration module 31 and bonding modules 32 located on both sides of the disintegration module, the fixed end 21 of the extension arm 2 and the elastic central component 1 are respectively bonded to the bonding modules 32 on both sides of the disintegration module, the vertical cross-sectional area of the connecting component 3 is S, and a first connecting structure 37 is provided at the bonding point of the disintegration module 31 and the bonding module 32, so that the disintegration module 31 and the bonding module 32 have a contact area of at least 1.5S at the bonding point, so that the breaking force between the extension arm 2 and the elastic central component 1 is at least 2.5N.
在一些实施例中，第一连接结构37包括相匹配的凸缘371和凹槽372，凸缘371的外侧面与凹槽372的内侧面相接触以使得崩解模块31和粘接模块32在粘接处具有至少1.5S的接触面积。凸缘371的两侧面和前侧面均与凹槽372的内侧面相接触，有效提高接触面积。In some embodiments, the first connecting structure 37 includes a matching flange 371 and a groove 372. The outer side of the flange 371 contacts the inner side of the groove 372, so that the disintegration module 31 and the bonding module 32 have a contact area of at least 1.5S at the bonding point. Both the side surfaces and the front side of the flange 371 contact the inner side of the groove 372, effectively increasing the contact area.
在一些实施例中，凸缘371可以任意方向延伸，凸缘371的截面形状也可以为三角形、梯形、方形或者任意其他形状。In some embodiments, the flange 371 may extend in any direction, and the cross-sectional shape of the flange 371 may also be a triangle, a trapezoid, a square, or any other shape.
在一些实施例中，凸缘371沿水平方向或竖直方向延伸设置。In some embodiments, the flange 371 extends in a horizontal direction or a vertical direction.
如图18所示，在一些实施例中，第一连接结构37包括在崩解模块31和粘接模块32的粘接处相对面上错位间隔设置的多个凸缘371，同侧相邻凸缘371之间的间隔形成凹槽372，楔形凸缘371在宽度方向上水平延伸，多个楔形凸缘371由上至下间隔排列，崩解模块31的两侧面和粘接模块32的相对侧面上凸缘371和凹槽372互补。As shown in Figure 18, in some embodiments, the first connecting structure 37 includes a plurality of flanges 371 staggered and spaced apart on the opposite surfaces of the bonding point of the disintegration module 31 and the bonding module 32, and the intervals between adjacent flanges 371 on the same side form a groove 372. The wedge-shaped flanges 371 extend horizontally in the width direction, and the plurality of wedge-shaped flanges 371 are arranged at intervals from top to bottom. The flanges 371 and the grooves 372 on the two side surfaces of the disintegration module 31 and the opposite side surfaces of the bonding module 32 complement each other.
在一些实施例中，凸缘371的最大厚度处至少为0.2mm。凸缘371的厚度保证了粘接模块32和崩解模块31粘接后的机械强度。In some embodiments, the maximum thickness of the flange 371 is at least 0.2 mm. The thickness of the flange 371 ensures the mechanical strength of the bonding module 32 and the disintegration module 31 after bonding.
在具体的实施例中，凸缘371为三角形或梯形时，最大的厚度即为凸缘371的底边长度，凸缘371为方形时，最大的厚度即为凸缘371的侧边的竖直宽度。In a specific embodiment, when the flange 371 is triangular or trapezoidal, the maximum thickness is the length of the base of the flange 371 ; when the flange 371 is square, the maximum thickness is the vertical width of the side of the flange 371 .
在具体实施例中，凸缘371的最大厚度处具体可以为0.2mm、0.3mm、0.5mm、0.6mm、0.8mm、1.0mm、1.2mm、1.5mm。In a specific embodiment, the maximum thickness of the flange 371 can be 0.2 mm, 0.3 mm, 0.5 mm, 0.6 mm, 0.8 mm, 1.0 mm, 1.2 mm, or 1.5 mm.
如图19所示，在一些实施例中，崩解模块31的两侧上均具有方型凸缘371，凸缘371在宽度方向上水平延伸，凸缘371水平延伸至连接部件3的两侧面，粘接模块32上均具有相对应的凹槽372。图9中凸缘371的厚度h至少为0.2mm。As shown in FIG19 , in some embodiments, the disintegration module 31 has square flanges 371 on both sides. The flanges 371 extend horizontally in the width direction and extend horizontally to both sides of the connecting component 3. The bonding module 32 has corresponding grooves 372. In FIG9 , the thickness h of the flanges 371 is at least 0.2 mm.
如图20所示，在一些实施例中，崩解模块31上的凸缘371在连接部件3轴向上的竖直截面为梯形，凸缘371的最大厚度H至少为0.2mm。As shown in FIG. 20 , in some embodiments, the flange 371 on the disintegration module 31 has a trapezoidal vertical cross-section in the axial direction of the connecting component 3 , and the maximum thickness H of the flange 371 is at least 0.2 mm.
在一些实施例中，凸缘371在延伸方向上的宽度d1，凸缘371所在平面的连接部件3宽度为d2，d1≥0.5d2。In some embodiments, the width d1 of the flange 371 in the extension direction and the width d2 of the connecting component 3 on the plane where the flange 371 is located are d1 ≥ 0.5 d2 .
在本发明的具体的实施例中，凸缘371沿水平方向延伸，凸缘371在延伸方向上的长度d1可以为0.5d2、0.6d2、0.7d2、0.8d2、0.9d2或d2。In a specific embodiment of the present invention, the flange 371 extends in the horizontal direction, and the length d1 of the flange 371 in the extending direction may be 0.5d2, 0.6d2, 0.7d2, 0.8d2, 0.9d2 or d2.
如图21-22所示，在一些实施例中，崩解模块31的侧面上设有凸缘371，凸缘371在延伸方向上的宽度d1，凸缘371所在平面的连接部件3宽度为d2，d1≥0.5d2。As shown in Figures 21-22, in some embodiments, a flange 371 is provided on the side of the disintegration module 31. The width of the flange 371 in the extension direction is d1, and the width of the connecting component 3 on the plane where the flange 371 is located is d2, and d1≥0.5d2.
如图23所示，在一些实施例中，崩解模块31的侧面上设有三个的水平凸缘371，粘接模块32的对应侧面上具有形状相适应的凹槽372。As shown in FIG. 23 , in some embodiments, three horizontal flanges 371 are provided on the side of the disintegration module 31 , and corresponding side surfaces of the bonding module 32 have grooves 372 of corresponding shapes.
在一些实施例中，崩解模块31包括时间依赖性崩解模块313和/或肠溶崩解模块314。In some embodiments, the disintegration module 31 includes a time-dependent disintegration module 313 and/or an enteric disintegration module 314 .
时间依赖性崩解模块313既在水性条件下以在预定的时间内强度弱化，以使得延长臂2相对于弹性中心部件1断裂或可弯曲，从而控制胃滞留装置的在胃内的滞留时间，时间依赖性崩解模块313的强度弱化方式可以为随时间逐渐降解、溶解、解离或机械弱化，延长臂2断裂足够的数量后胃滞留装置可以通过幽门瓣，离开胃腔并进入小肠，最终从体内排出。The time-dependent disintegration module 313 weakens its strength within a predetermined time under aqueous conditions so that the extension arm 2 breaks or becomes bendable relative to the elastic central component 1, thereby controlling the retention time of the gastric retention device in the stomach. The strength weakening mode of the time-dependent disintegration module 313 can be gradual degradation, dissolution, dissociation or mechanical weakening over time. After a sufficient number of extension arms 2 are broken, the gastric retention device can pass through the pyloric valve, leave the gastric cavity and enter the small intestine, and finally be discharged from the body.
肠溶崩解模块314即为pH依赖崩解模块，用于为胃滞留装置提供安全防护机制，一旦胃滞留装置提前离开胃腔，进入到肠道时，肠溶崩解模块314将根据小肠的高pH环境中迅速完成降解、溶解、解离或机械弱化，从而导致延长臂2断裂，避免出现肠梗阻，使得胃滞留装置容易通过小肠。The enteric disintegration module 314 is a pH-dependent disintegration module, which is used to provide a safety protection mechanism for the gastric retention device. Once the gastric retention device leaves the gastric cavity prematurely and enters the intestine, the enteric disintegration module 314 will quickly complete degradation, dissolution, dissociation or mechanical weakening according to the high pH environment of the small intestine, thereby causing the extension arm 2 to break, avoiding intestinal obstruction and making it easier for the gastric retention device to pass through the small intestine.
在一些实施例中，崩解模块31包括时间依赖性崩解模块313和肠溶崩解模块314，时间依赖性崩解模块313和肠溶崩解模块314之间设有第二连接结构38，以使得时间依赖性崩解模块313和肠溶崩解模块314在粘接处具有至少5S的接触面积。In some embodiments, the disintegration module 31 includes a time-dependent disintegration module 313 and an enteric disintegration module 314, and a second connecting structure 38 is provided between the time-dependent disintegration module 313 and the enteric disintegration module 314 so that the time-dependent disintegration module 313 and the enteric disintegration module 314 have a contact area of at least 5S at the bonding point.
在一些实施例中，第二连接结构38和第一连接结构37的结构相同或不同。In some embodiments, the second connection structure 38 and the first connection structure 37 have the same or different structures.
如图24-25所示，在一些具体的实施例中，连接部件3包括两个位于两端的粘接模块32和位于其两者之间的时间依赖性崩解模块313和肠溶崩解模块314。As shown in FIG. 24-25 , in some specific embodiments, the connecting component 3 includes two bonding modules 32 located at both ends and a time-dependent disintegration module 313 and an enteric disintegration module 314 located therebetween.
第一连接结构37和第二连接结构38为相同的结构，粘接模块32、时间依赖性崩解模块313和肠溶崩解模块314上均具有多个楔形凸缘371，楔形凸缘371在宽度方向上水平延伸，多个楔形凸缘371由上至下间隔排列，楔形凸缘371之间的间隔为凹槽372，延长臂2的固定端21与连接部件3第二端面上的形状互补。The first connecting structure 37 and the second connecting structure 38 have the same structure. The bonding module 32, the time-dependent disintegration module 313 and the enteric disintegration module 314 all have multiple wedge-shaped flanges 371. The wedge-shaped flanges 371 extend horizontally in the width direction. The multiple wedge-shaped flanges 371 are arranged at intervals from top to bottom. The intervals between the wedge-shaped flanges 371 are grooves 372. The fixed end 21 of the extension arm 2 is complementary to the shape of the second end face of the connecting component 3.
在一些实施例中，粘接材料和延长臂2的基质材料相同。In some embodiments, the adhesive material and the matrix material of the extension arm 2 are the same.
在一些实施例中，粘接模块32包括50％以上的粘接材料，粘接材料与延长臂2的基质材料粘接熔融；时间依赖性崩解模块313包括小于30％的粘接材料和大于70％的时间依赖崩解材料；肠溶崩解模块314包括小于30％的粘接材料和大于70％的肠溶崩解材料。In some embodiments, the bonding module 32 includes more than 50% bonding material, and the bonding material is bonded and melted with the matrix material of the extension arm 2; the time-dependent disintegration module 313 includes less than 30% bonding material and more than 70% time-dependent disintegration material; the enteric disintegration module 314 includes less than 30% bonding material and more than 70% enteric disintegration material.
在一些实施例中，粘接材料包括聚己内酯、聚乳酸、聚乙交酯、聚乳酸-羟基乙酸共聚物、聚羟基脂肪酸酯和改性多糖中的一种或多种；时间依赖崩解材料包括聚乳酸、聚乳酸-羟基乙酸共聚物、聚乙交酯、聚己内酯、聚酸酐和聚正酯中的一种或多种；肠溶崩解材料包括醋酸羟丙甲纤维素琥珀酸酯、丙烯酸酯共聚物、醋酸邻苯二甲酸纤维素、虫胶和聚醋酸乙烯邻苯二酸酯中的一种或多种。In some embodiments, the bonding material includes one or more of polycaprolactone, polylactic acid, polyglycolide, polylactic acid-glycolic acid copolymer, polyhydroxyalkanoate and modified polysaccharide; the time-dependent disintegrating material includes one or more of polylactic acid, polylactic acid-glycolic acid copolymer, polyglycolide, polycaprolactone, polyanhydride and polyorthoester; the enteric disintegrating material includes one or more of hydroxypropyl methylcellulose acetate succinate, acrylate copolymer, cellulose acetate phthalate, shellac and polyvinyl acetate phthalate.
在一些实施例中，连接部件3包括通过三维打印或二次注塑依次成型的粘接模块32、时间依赖性崩解模块313、肠溶崩解模块314和粘接模块32，之后熔融成型。In some embodiments, the connecting component 3 includes a bonding module 32, a time-dependent disintegration module 313, an enteric disintegration module 314 and a bonding module 32, which are sequentially molded by three-dimensional printing or secondary injection molding and then melt-molded.
优选的，使用3D打印形成连接部件3，之后再进行熔融成型，使用3D打印可以灵活设置第一连接结构37和第二连接结构38上凸缘371的数量和大小，从而增加崩解模块31和粘接模块32之间的接触面积。Preferably, the connecting component 3 is formed by 3D printing and then melt-molded. 3D printing can flexibly set the number and size of the flanges 371 on the first connecting structure 37 and the second connecting structure 38, thereby increasing the contact area between the disintegration module 31 and the bonding module 32.
本发明中，延长臂2、连接部件3和弹性中心连接的牢固性通过折断/90°折弯测试进行测定，具体过程如下：In the present invention, the firmness of the connection between the extension arm 2, the connecting member 3 and the elastic center is determined by a break/90° bend test, and the specific process is as follows:
单个延长臂2通过连接部件3与弹性中心部件1熔融粘接后形成测试件43，如图26所示，使用折断测试装置4进行测试，折断测试装置4包括固定台41和下压板42，通过固定台41固定弹性中心部件1后，下压板42下压延长臂2的自由端22，测试当延长臂2与弹性中心部件1断裂或相对弯曲90°时的下压压力。A single extension arm 2 is melt-bonded with the elastic center component 1 through the connecting component 3 to form a test piece 43, as shown in Figure 26, and is tested using a fracture test device 4. The fracture test device 4 includes a fixed platform 41 and a lower pressure plate 42. After the elastic center component 1 is fixed by the fixed platform 41, the lower pressure plate 42 presses down the free end 22 of the extension arm 2 to test the downward pressure when the extension arm 2 and the elastic center component 1 are broken or bent 90° relative to each other.
为充分模拟胃滞留装置在胃中的环境，将测试件43在pH为1.2的模拟胃液中分别浸泡0d(天)、7d(天)、10d(天),在0d中测试件43浸泡2h,之后再进行折断/90°折弯测试，测试时下压板42上反馈得到的力分别记为F0、F7、F10。To fully simulate the environment of the gastric retention device in the stomach, the test piece 43 was immersed in simulated gastric fluid with a pH of 1.2 for 0 days, 7 days, and 10 days, respectively. The test piece 43 was immersed for 2 hours on the 0th day, and then a fracture/90° bending test was performed. During the test, the forces fed back on the lower pressure plate 42 were recorded as F0, F7, and F10, respectively.
在测试过程中，一般的在0d时，由于崩解材料还未充分溶解，在测试过程中首先进行断裂，此时测定的F0为延长臂2与弹性中心部件1之间的断裂力，而在模拟位于中浸泡7d、10d后，由于崩解材料溶解，连接部件3具有一定的柔软性，延长臂2可相对于弹性中心部件1弯曲，此时测定的F7、F10为延长臂2相对弹性中心部件1弯曲90°时压力。During the test, generally at 0 days, the disintegrating material has not yet fully dissolved and breaks first during the test. At this time, the measured F0 is the breaking force between the extension arm 2 and the elastic central component 1. After 7 days and 10 days of immersion in the simulated position, the disintegrating material dissolves and the connecting component 3 has a certain degree of flexibility. The extension arm 2 can bend relative to the elastic central component 1. At this time, the measured F7 and F10 are the pressures when the extension arm 2 is bent 90 degrees relative to the elastic central component 1.
本发明中，通过连接部件3的设置，使得延长臂2和弹性中心部件1之间的断裂力在第0d时为2.5N以上，从而使得胃滞留装置在胃腔内能够抵抗胃的蠕动压力，保持展开构型，避免胃滞留装置提前排出。In the present invention, by providing the connecting component 3, the breaking force between the extension arm 2 and the elastic central component 1 is greater than 2.5N at day 0, thereby enabling the gastric retention device to resist the peristaltic pressure of the stomach in the gastric cavity, maintain the expanded configuration, and prevent the gastric retention device from being discharged prematurely.
在另一些实施例中，在0天时，延长臂2和弹性中心部件1之间的断裂力为2.5-15.0N、3.0-15.0N、3.5-15.0N、4.0-15.0N、4.5-15.0N、5.0-15.0N、8-15.0N、10-15.0N或12-15.0N。In other embodiments, at day 0, the breaking force between the extension arms 2 and the elastic centerpiece 1 is 2.5-15.0N, 3.0-15.0N, 3.5-15.0N, 4.0-15.0N, 4.5-15.0N, 5.0-15.0N, 8-15.0N, 10-15.0N, or 12-15.0N.
为详细说明技术方案的技术内容、构造特征、所实现目的及效果，以下结合具体实施例并配合附图详予说明。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.
实施例1Example 1
本实施例提供一种胃滞留装置，包括弹性中心部件1、六个延长臂2和六个连接部件3，弹性中心部件1包括中心弹性金属(附图未显示)和包裹中心弹性金属的TPU聚合物外层，延长臂2使用聚己内酯制备。This embodiment provides a gastric retention device, including an elastic central component 1, six extension arms 2 and six connecting components 3. The elastic central component 1 includes a central elastic metal (not shown in the drawings) and a TPU polymer outer layer wrapping the central elastic metal. The extension arms 2 are made of polycaprolactone.
如图8所示，连接部件3包括时间依赖性崩解模块313和粘接模块32，时间依赖性崩解模块313和粘接模块32的体积比为4：1，此时，粘接模块32占据第二端面上20％的面积。As shown in FIG8 , the connecting component 3 includes a time-dependent disintegration module 313 and an adhesive module 32 . The volume ratio of the time-dependent disintegration module 313 to the adhesive module 32 is 4:1. At this time, the adhesive module 32 occupies 20% of the area on the second end surface.
其中，时间依赖性崩解模块313包括20％的聚己内酯和80％的聚乳酸-羟基乙酸共聚物，粘接模块32为100％的聚己内酯。The time-dependent disintegration module 313 includes 20% polycaprolactone and 80% polylactic acid-glycolic acid copolymer, and the bonding module 32 is 100% polycaprolactone.
制备时，连接部件3通过熔融注塑成型制备，时间依赖性崩解材料先混合熔融注入到第一模型中，形成时间依赖性崩解模块313，之后时间依赖性崩解模块313再放入到第二模型中，注入粘接材料，成型后粘接材料包覆时间依赖性崩解模块313的外侧面，最后在侧面上开槽321，去除部分粘接材料，以显露中心的时间依赖性崩解模块313的侧面，本实施例，设定时间依赖性崩解模块313的外露区域311占据外侧面30％的面积。During preparation, the connecting component 3 is prepared by melt injection molding, and the time-dependent disintegration material is first mixed and melted and injected into the first mold to form a time-dependent disintegration module 313. Then, the time-dependent disintegration module 313 is placed in the second mold and the adhesive material is injected. After molding, the adhesive material covers the outer side of the time-dependent disintegration module 313. Finally, a groove 321 is cut on the side to remove part of the adhesive material to reveal the side of the central time-dependent disintegration module 313. In this embodiment, the exposed area 311 of the time-dependent disintegration module 313 is set to occupy 30% of the area of the outer side.
实施例2-4Examples 2-4
本实施例提供一种胃滞留装置，与实施例1不同的是：通过控制时间依赖性崩解模块313和粘接模块32的体积比制备不同的连接部件3。This embodiment provides a gastric retention device, which is different from the first embodiment in that different connecting components 3 are prepared by controlling the volume ratio of the time-dependent disintegration module 313 and the bonding module 32 .
对比例1Comparative Example 1
一种胃滞留装置，与实施例1不同的是：连接部件包括36％的聚己内酯和64％的聚乳酸-羟基乙酸共聚物，完全混合后熔融注塑成型形成连接部件。A gastric retention device, which is different from Example 1 in that: the connecting component comprises 36% polycaprolactone and 64% polylactic acid-glycolic acid copolymer, which are completely mixed and then melt-injected to form the connecting component.
对比例2Comparative Example 2
一种胃滞留装置，与实施例1不同的是：连接部件包括两个粘接模块，时间依赖性崩解模块位于两个粘接模块之间，时间依赖性崩解模块包括20％的聚己内酯和80％的聚乳酸-羟基乙酸共聚物，粘接模块为100％的聚己内酯，其结构如图16所示，时间依赖性崩解模块和粘接模块的组分与实施例1相同。A gastric retention device, which differs from Example 1 in that: the connecting component includes two adhesive modules, the time-dependent disintegration module is located between the two adhesive modules, the time-dependent disintegration module includes 20% polycaprolactone and 80% polylactic acid-glycolic acid copolymer, and the adhesive module is 100% polycaprolactone. Its structure is shown in Figure 16. The components of the time-dependent disintegration module and the adhesive module are the same as those in Example 1.
对比例3Comparative Example 3
一种胃滞留装置，与实施例1不同的是：通过控制时间依赖性崩解模块和粘接模块的体积比使得粘接模块占据第二端面面积为15％。A gastric retention device, which differs from Example 1 in that the volume ratio of the time-dependent disintegration module and the bonding module is controlled so that the bonding module occupies 15% of the area of the second end surface.
实施例5Example 5
如图15，本实施例提供一种胃滞留装置，与实施例1不同的是：中心模块上包括依次成型的时间依赖性崩解模块313和肠溶崩解模块314，其中肠溶崩解模块314包括20％的聚己内酯和80％的醋酸羟丙甲纤维素琥珀酸酯。As shown in FIG15 , this embodiment provides a gastric retention device, which is different from Example 1 in that the central module includes a time-dependent disintegration module 313 and an enteric disintegration module 314 formed in sequence, wherein the enteric disintegration module 314 includes 20% polycaprolactone and 80% hydroxypropyl methylcellulose acetate succinate.
对比例4Comparative Example 4
本对比例提供一种胃滞留装置，制备与实施例5具有相同组分的两个粘接模块、时间依赖性崩解模块和肠溶崩解模块，按照粘接模块、时间依赖性崩解模块、肠溶崩解模块、粘接模块的顺序依次熔融粘接制备连接部件，之后制备胃滞留装置。This comparative example provides a gastric retention device, which is prepared by preparing two bonding modules, a time-dependent disintegration module, and an enteric disintegration module having the same components as in Example 5. The bonding module, the time-dependent disintegration module, the enteric disintegration module, and the bonding module are melt-bonded in this order to prepare a connecting component, and then the gastric retention device is prepared.
以实施例1-5和对比例1-4的方案制备的测试件进行折断/90°折弯测试，并记录断裂力和90°弯曲时的弯曲压力。The test pieces prepared according to the schemes of Examples 1-5 and Comparative Examples 1-4 were subjected to breaking/90° bending tests, and the breaking force and the bending pressure during 90° bending were recorded.
折弯测试结果如下表1。The bending test results are shown in Table 1.
其中，A为粘接模块占据第二端面的面积，B为外露区域占据连接部件侧面面积,折断测试时，测试件上的位置：连接部件本体，记为W1；连接部件端面和延长臂的粘接处，记为W2；时间依赖性崩解模块和粘接模块的粘接处，记为W3；时间依赖性崩解模块和肠溶崩解模块粘接处，记为W4。Among them, A is the area of the second end face occupied by the bonding module, B is the area of the side surface of the connecting component occupied by the exposed area, and during the fracture test, the positions on the test piece are: the connecting component body, denoted as W1; the bonding point between the end face of the connecting component and the extension arm, denoted as W2; the bonding point between the time-dependent disintegration module and the bonding module, denoted as W3; the bonding point between the time-dependent disintegration module and the enteric disintegration module, denoted as W4.
表1折断/90°折弯测试结果。
Table 1. Breaking/90° bending test results.
由表1可知，等截面延长设置的连接部件3上，粘接模块32占据的面积对连接部件3出的断裂力和折弯压力影响较大，粘接模块32体积比越高，断裂力越高，由实施例1和对比例1对比可知，在具有组分含量相同的连接部件3中，实施例1由于单独形成粘接材料大于50％的粘接模块32，其极大的加强了粘接处的粘接力，并增强了断裂力。由实施例1和对比例2对比可知，在实施例1中，由于粘接模块32在连接部件3上具有连续延伸的连续区域323，因此在折断试验中，实施例1连接部件3具有更高断裂力。由实施例5和对比例4对比可知，实施例5中，由于两个粘接模块32之间具有从第一端面到第二端面的连续区域323，提高了连接部件3的整体机械强度，也提高了时间依赖性崩解模块313和肠溶崩解模块314的粘接效果。As shown in Table 1, the area occupied by the bonding module 32 on the connecting component 3 with a uniform cross-section has a significant impact on the breaking force and bending pressure of the connecting component 3. The higher the volume ratio of the bonding module 32, the higher the breaking force. A comparison between Example 1 and Comparative Example 1 shows that, in connecting components 3 with the same component content, Example 1, due to the bonding module 32 comprising more than 50% of the bonding material, significantly strengthens the bonding strength at the bond point and enhances the breaking force. A comparison between Example 1 and Comparative Example 2 shows that in Example 1, due to the continuous region 323 extending continuously on the connecting component 3, the connecting component 3 of Example 1 has a higher breaking force in the fracture test. A comparison between Example 5 and Comparative Example 4 shows that in Example 5, due to the continuous region 323 extending from the first end face to the second end face between the two bonding modules 32, the overall mechanical strength of the connecting component 3 is improved, and the bonding effect of the time-dependent disintegration module 313 and the enteric disintegration module 314 is also improved.
实施例6Example 6
本实施例提供一种胃滞留装置，包括弹性中心部件1、六个延长臂2和六个连接部件3，弹性中心部件1包括中心弹性金属和包裹中心弹性金属的TPU聚合物外层，延长臂2使用聚己内酯制备。This embodiment provides a gastric retention device, including an elastic central component 1, six extension arms 2 and six connecting components 3. The elastic central component 1 includes a central elastic metal and a TPU polymer outer layer wrapping the central elastic metal, and the extension arms 2 are made of polycaprolactone.
如图16所示，连接部件3包括时间依赖性崩解连接片341和两个末端连接片35，时间依赖性崩解连接片341位于两个末端连接片35之间。As shown in FIG. 16 , the connecting component 3 includes a time-dependent disintegrating connecting piece 341 and two terminal connecting pieces 35 . The time-dependent disintegrating connecting piece 341 is located between the two terminal connecting pieces 35 .
其中，时间依赖性崩解连接片341包括30％的聚己内酯和70％的聚乳酸-羟基乙酸共聚物，两个末端连接片35均包括70％的聚己内酯和30％聚乳酸-羟基乙酸共聚物。The time-dependent disintegrating connecting piece 341 comprises 30% polycaprolactone and 70% polylactic acid-glycolic acid copolymer, and the two end connecting pieces 35 each comprise 70% polycaprolactone and 30% polylactic acid-glycolic acid copolymer.
制备时，不同连接片的材料分离混合熔融挤出形成塑料条，之后对应塑料条通过切片装置，分别切成对应厚度的连片，之后进行熔融粘接。During preparation, the materials of different connecting sheets are separated, mixed, melted and extruded to form plastic strips. The corresponding plastic strips are then cut into connecting sheets of corresponding thickness through a slicing device and then melt-bonded.
实施例7Example 7
本实施例提供一种胃滞留装置，与实施例6的不同点是：时间依赖性崩解连接片341包括30％的聚己内酯、60％的聚乳酸-羟基乙酸共聚物和10％的添加剂，末端连接片35包括60％的聚己内酯、30％聚乳酸-羟基乙酸共聚物和10％的添加剂。This embodiment provides a gastric retention device, which is different from Example 6 in that the time-dependent disintegrating connecting piece 341 includes 30% polycaprolactone, 60% polylactic acid-glycolic acid copolymer and 10% additives, and the terminal connecting piece 35 includes 60% polycaprolactone, 30% polylactic acid-glycolic acid copolymer and 10% additives.
实施例8Example 8
与实施例6的不同点是：时间依赖性崩解连接片341包括40％的聚己内酯和60％的聚乳酸-羟基乙酸共聚物，末端连接片35包括60％的聚己内酯和40％聚乳酸-羟基乙酸共聚物。The difference from Example 6 is that the time-dependent disintegrating connecting piece 341 comprises 40% polycaprolactone and 60% polylactic acid-glycolic acid copolymer, and the terminal connecting piece 35 comprises 60% polycaprolactone and 40% polylactic acid-glycolic acid copolymer.
实施例9Example 9
本实施例提供一种胃滞留装置，与实施例6的不同点是：时间依赖性崩解连接片341包括20％的聚己内酯、70％的聚乳酸-羟基乙酸共聚物和10％的添加剂，末端连接片35包括70％的聚己内酯、20％聚乳酸-羟基乙酸共聚物和10％的添加剂。This embodiment provides a gastric retention device, which is different from Example 6 in that the time-dependent disintegrating connecting piece 341 includes 20% polycaprolactone, 70% polylactic acid-glycolic acid copolymer and 10% additives, and the terminal connecting piece 35 includes 70% polycaprolactone, 20% polylactic acid-glycolic acid copolymer and 10% additives.
实施例10Example 10
本实施例提供一种胃滞留装置，与实施例6的不同点是：如图17所示，连接部件3由六个连接片熔融粘接组成，依次序分别为第一末端连接片35、时间依赖性崩解连接片341、第一中间连接片36、第二中间连接片36、肠溶崩解连接片342、第二末端连片。This embodiment provides a gastric retention device, which differs from Example 6 in that: as shown in Figure 17, the connecting component 3 is composed of six connecting pieces melt-bonded together, which are, in order, the first terminal connecting piece 35, the time-dependent disintegrating connecting piece 341, the first intermediate connecting piece 36, the second intermediate connecting piece 36, the enteric disintegrating connecting piece 342, and the second terminal connecting piece.
不同连接片的材料组分如下：The material compositions of different connecting pieces are as follows:
第一末端连接片35：70％的聚己内酯和30％聚乳酸-羟基乙酸共聚物；First terminal connecting piece 35: 70% polycaprolactone and 30% polylactic acid-glycolic acid copolymer;
时间依赖性崩解连接片341：30％的聚己内酯和70％的聚乳酸-羟基乙酸共聚物；Time-dependent disintegrating connecting tablet 341: 30% polycaprolactone and 70% polylactic acid-glycolic acid copolymer;
第一中间连接片36：70％的聚己内酯和30％聚乳酸-羟基乙酸共聚物；First intermediate connecting sheet 36: 70% polycaprolactone and 30% polylactic acid-glycolic acid copolymer;
第二中间连接片36：70％的聚己内酯和30％醋酸羟丙甲纤维素琥珀酸酯；Second intermediate connecting sheet 36: 70% polycaprolactone and 30% hypromellose acetate succinate;
肠溶崩解连接片342：30％的聚己内酯和70％的醋酸羟丙甲纤维素琥珀酸酯；Enteric disintegrating connecting tablet 342: 30% polycaprolactone and 70% hypromellose acetate succinate;
第二末端连接片35：70％的聚己内酯和30％的醋酸羟丙甲纤维素琥珀酸酯。The second terminal connecting piece 35 is composed of 70% polycaprolactone and 30% hypromellose acetate succinate.
对比例5Comparative Example 5
本对比例提供一种胃滞留装置，与实施例6不同的是：This comparative example provides a gastric retention device, which differs from Example 6 in that:
其中，时间依赖性崩解连接片包括30％的聚己内酯和70％的聚乳酸-羟基乙酸共聚物，末端连接片包括90％的聚己内酯和10％聚乳酸-羟基乙酸共聚物。The time-dependent disintegrating connecting piece comprises 30% polycaprolactone and 70% polylactic acid-glycolic acid copolymer, and the terminal connecting piece comprises 90% polycaprolactone and 10% polylactic acid-glycolic acid copolymer.
以实施例6-10和对比例2、对比例4、对比例5的方案制备的测试件进行折断/90°折弯测试，并记录断裂力和90°弯曲时的弯曲压力，The test pieces prepared according to the schemes of Examples 6-10 and Comparative Examples 2, 4, and 5 were subjected to breaking/90° bending tests, and the breaking force and the bending pressure at 90° bending were recorded.
结果如下表2。The results are shown in Table 2 below.
表2.折断/90°折弯测试结果。
Table 2. Break/90° bend test results.
其中，C为连接片片数；D为相邻连接片粘接材料含量的最大差值，以实施例6为例，时间依赖性崩解连接片含有30％的聚己内酯，末端连接片含有70％的聚己内酯，则D＝70％-30％＝40％。测试件上的位置：时间依赖性崩解连接片和末端连接片的粘接处，记为E1；末端连接片和延长臂的粘接处，记为E2；肠溶崩解连接片与中间连接片或末端连接片的粘接处，记为E3；肠溶崩解连接片和时间依赖性崩解连接片的粘接处，记为E4。Where C is the number of connecting sheets; D is the maximum difference in the adhesive content between adjacent connecting sheets. For example, in Example 6, the time-dependent disintegrating connecting sheet contains 30% polycaprolactone and the terminal connecting sheet contains 70% polycaprolactone, so D = 70% - 30% = 40%. The following locations on the test piece are used: the bonding point between the time-dependent disintegrating connecting sheet and the terminal connecting sheet is designated as E1; the bonding point between the terminal connecting sheet and the extension arm is designated as E2; the bonding point between the enteric disintegrating connecting sheet and the intermediate or terminal connecting sheet is designated as E3; and the bonding point between the enteric disintegrating connecting sheet and the time-dependent disintegrating connecting sheet is designated as E4.
由实施例6-9和对比例2可知，随着相邻连接片之间粘接材料的增加，相邻连接片的粘接材料含量差值越小，粘接的效果越好.由实施例10和对比例4对比可知，在时间依赖性崩解连接片341和肠溶崩解连接片342之间设置两个中间连接片36，两个中间连接片36使得时间依赖性崩解连接片341和肠溶崩解连接片342之间具有良好的粘接效果，提高连接部件3的断裂力。It can be seen from Examples 6-9 and Comparative Example 2 that as the amount of adhesive material between adjacent connecting sheets increases, the smaller the difference in the adhesive material content of adjacent connecting sheets, the better the bonding effect. As can be seen from the comparison between Example 10 and Comparative Example 4, two intermediate connecting sheets 36 are provided between the time-dependent disintegrating connecting sheet 341 and the enteric-coated disintegrating connecting sheet 342. The two intermediate connecting sheets 36 provide a good bonding effect between the time-dependent disintegrating connecting sheet 341 and the enteric-coated disintegrating connecting sheet 342, thereby improving the breaking force of the connecting component 3.
实施例11Example 11
本实施例提供一种胃滞留装置，包括弹性中心部件、六个延长臂和六个连接部件，弹性中心部件包括中心弹性金属和包裹中心弹性金属的TPU聚合物外层，延长臂使用聚己内酯制备。This embodiment provides a gastric retention device, including an elastic central component, six extension arms and six connecting components. The elastic central component includes a central elastic metal and a TPU polymer outer layer wrapping the central elastic metal. The extension arms are made of polycaprolactone.
如图19所示，连接部件3竖直截面的形状为类等边的三角形，三角的边长为3.3mm，连接部件3包括肠溶崩解模块314和粘接模块32，肠溶崩解模块314的两侧边设有凸缘371，设置凸缘371的厚度h为0.2mm，宽度d为1mm，通过控制凸缘371向前凸出的长度L，使得肠溶崩解模块314的侧面具有1.5S的表面积。As shown in Figure 19, the shape of the vertical cross-section of the connecting component 3 is an equilateral triangle with a side length of 3.3 mm. The connecting component 3 includes an enteric disintegration module 314 and a bonding module 32. Flanges 371 are provided on both sides of the enteric disintegration module 314. The thickness h of the flange 371 is set to 0.2 mm and the width d is set to 1 mm. By controlling the length L of the flange 371 protruding forward, the side of the enteric disintegration module 314 has a surface area of 1.5S.
其中，肠溶崩解模块314包括20％的聚己内酯和80％醋酸羟丙甲纤维素琥珀酸酯，粘接模块32为100％的聚己内酯。The enteric disintegrating module 314 includes 20% polycaprolactone and 80% hypromellose acetate succinate, and the bonding module 32 is 100% polycaprolactone.
实施例12Example 12
与实施例11的不同点在于，如图23所示，连接部件3包括肠溶崩解模块314和粘接模块32，肠溶崩解模块314的两侧边设有三个凸缘371，三个凸缘371的厚度均为0.2mm，通过凸缘371长度和宽度的设置，使得肠溶崩解模块314与占据模块的占据侧面具有3S的接触面积。图23中仅显示了肠溶崩解模块314单一侧面上的凸缘371。The difference from Example 11 is that, as shown in FIG23 , the connecting component 3 includes an enteric disintegration module 314 and an adhesive module 32. Three flanges 371 are provided on both sides of the enteric disintegration module 314. Each flange 371 has a thickness of 0.2 mm. The length and width of the flanges 371 are configured to provide a contact area of 3S between the enteric disintegration module 314 and the occupied side of the occupying module. FIG23 shows only the flange 371 on a single side of the enteric disintegration module 314.
实施例13Example 13
与实施例11的不同点在于，如图24-25所示，连接部件3包括依次包括相熔接的粘接模块32、时间依赖性崩解模块313、肠溶崩解模块314和粘接模块32。The difference from Example 11 is that, as shown in Figures 24-25, the connecting component 3 includes a bonding module 32, a time-dependent disintegration module 313, an enteric disintegration module 314 and a bonding module 32 which are fused in sequence.
时间依赖性崩解模块313和肠溶崩解模块314相对的两侧面上均设有间隔设置的多个凸缘371，两个粘接模块32的内侧面上设有凸缘371，相对的两侧的凸缘371错位交叉设置。Multiple flanges 371 are provided on opposite sides of the time-dependent disintegration module 313 and the enteric disintegration module 314 . Flanges 371 are provided on the inner sides of the two bonding modules 32 . The flanges 371 on the opposite sides are staggered and cross-arranged.
时间依赖性崩解模块313包括20％的聚己内酯和80％的聚乳酸-羟基乙酸共聚物。The time-dependent disintegrating module 313 includes 20% polycaprolactone and 80% poly(lactic-co-glycolic acid).
本实施例中，由于连接部件3本身体积较小，整个连接部件3可以通过3D打印设备进行立体打印成型，3D打印完成后，为进一步完善模块之间的粘接力，对连接部件3进行加热熔融，使得模块之间牢固粘接。In this embodiment, since the connecting component 3 itself is relatively small in size, the entire connecting component 3 can be three-dimensionally printed by a 3D printing device. After the 3D printing is completed, in order to further improve the bonding strength between the modules, the connecting component 3 is heated and melted so that the modules are firmly bonded.
3D打印设备可以灵活设置凸缘371的结构和形式，本实施例中如图24-25所示可以通过电脑设置第一连接结构37和第二连接结构38的接触面积为5S。The 3D printing device can flexibly set the structure and form of the flange 371. In this embodiment, as shown in Figures 24-25, the contact area between the first connecting structure 37 and the second connecting structure 38 can be set to 5S through a computer.
对比例6Comparative Example 6
一种胃滞留装置，与实施例11不同的是：肠溶崩解模块的侧面上不设置凸缘，粘接模块和肠溶崩解模块的接触粘接面积为S。A gastric retention device, which is different from Example 11 in that: no flange is provided on the side of the enteric disintegration module, and the contact bonding area between the bonding module and the enteric disintegration module is S.
对比例7Comparative Example 7
一种胃滞留装置，与实施例13不同的是：肠溶崩解模块和时间依赖性崩解模块之间的第二连接结构的设置，使得肠溶崩解模块和时间依赖性崩解模块的接触面积为3S，第一连接结构与实施例13的结构相同。A gastric retention device, which differs from Example 13 in that: the second connecting structure between the enteric disintegration module and the time-dependent disintegration module is set so that the contact area between the enteric disintegration module and the time-dependent disintegration module is 3S, and the first connecting structure is the same as the structure of Example 13.
以实施例11-13和对比例4、对比例6、对比例7的方案制备的测试件进行折断/90°折弯测试，并记录断裂力和90°弯曲时的弯曲压力，结果如下表3。The test pieces prepared according to the schemes of Examples 11-13 and Comparative Examples 4, 6, and 7 were subjected to breaking/90° bending tests, and the breaking force and bending pressure at 90° bending were recorded. The results are shown in Table 3 below.
表3.折断/90°折弯测试结果。
Table 3. Break/90° bend test results.
其中S1表示肠溶崩解模块和粘接模块的接触面积，S2为肠溶崩解模块和时间依赖性崩解模块的接触面积，测试件上的位置：肠溶崩解模块和粘接模块的粘接处，记为F1；粘接模块和延长臂的粘接处，记为F2；肠溶崩解模块和时间依赖性崩解模块的粘接处，记为F3。Wherein, S1 represents the contact area between the enteric disintegration module and the bonding module, S2 represents the contact area between the enteric disintegration module and the time-dependent disintegration module, and the positions on the test piece are: the bonding point between the enteric disintegration module and the bonding module, denoted as F1; the bonding point between the bonding module and the extension arm, denoted as F2; and the bonding point between the enteric disintegration module and the time-dependent disintegration module, denoted as F3.
由对比例7连接部件3制成的测试件43在模拟胃液中浸泡第3天时，连接部件3的肠溶崩解模块314和时间依赖性崩解模块313之间发生断裂分离。When the test piece 43 made of the connecting component 3 of Comparative Example 7 was immersed in the simulated gastric fluid for the third day, the enteric disintegration module 314 and the time-dependent disintegration module 313 of the connecting component 3 were broken and separated.
由实施例11-12和对比例6的对比可知，连接部件3上通过凸缘371的设置能够有效加强崩解模块和粘接模块32的粘接效果，提高机械强度。From the comparison between Examples 11-12 and Comparative Example 6, it can be seen that the provision of the flange 371 on the connecting component 3 can effectively enhance the bonding effect between the disintegration module and the bonding module 32 and improve the mechanical strength.
由实施例13和对比例7的对比可知，时间依赖性崩解模块313和肠溶崩解模块314之间通过凸缘371增大粘接面积，能够使得二者即使在成分相差较大的情况下，依然能够牢固连接。From the comparison between Example 13 and Comparative Example 7, it can be seen that the flange 371 increases the bonding area between the time-dependent disintegration module 313 and the enteric disintegration module 314, so that the two can still be firmly connected even when the ingredients are greatly different.
需要说明的是，在本文中，诸如第一和第二等之类的关系术语仅仅用来将一个实体或者操作与另一个实体或操作区分开来，而不一定要求或者暗示这些实体或操作之间存在任何这种实际的关系或者顺序。而且，术语“包括”、“包含”或者其任何其他变体意在涵盖非排他性的包含，从而使得包括一系列要素的过程、方法、物品或者终端设备不仅包括那些要素，而且还包括没有明确列出的其他要素，或者是还包括为这种过程、方法、物品或者终端设备所固有的要素。在没有更多限制的情况下，由语句“包括……”或“包含……”限定的要素，并不排除在包括所述要素的过程、方法、物品或者终端设备中还存在另外的要素。此外，在本文中，“大于”、“小于”、“超过”等理解为不包括本数；“以上”、“以下”、“以内”等理解为包括本数。It should be noted that, in this document, relational terms such as first and second, etc., are used solely to distinguish one entity or operation from another, and do not necessarily require or imply any actual relationship or order between these entities or operations. Furthermore, the terms "include," "comprise," or any other variations thereof are intended to encompass non-exclusive inclusion, such that a process, method, article, or terminal device comprising a series of elements includes not only those elements, but also other elements not explicitly listed, or elements inherent to such process, method, article, or terminal device. Without further limitation, elements defined by the phrase "include..." or "comprising..." do not exclude the presence of additional elements in the process, method, article, or terminal device comprising the elements. Furthermore, in this document, "greater than," "less than," "exceeding," etc., are understood to exclude the number itself; "above," "below," "within," etc., are understood to include the number itself.
尽管已经对上述各实施例进行了描述，但本领域内的技术人员一旦得知了基本创造性概念，则可对这些实施例做出另外的变更和修改，所以以上所述仅为本发明的实施例，并非因此限制本发明的专利保护范围，凡是利用本发明说明书及附图内容所作的等效结构或等效流程变换，或直接或间接运用在其他相关的技术领域，均同理包括在本发明的专利保护范围之内。Although the above embodiments have been described, those skilled in the art may make additional changes and modifications to these embodiments once they know the basic creative concepts. Therefore, the above descriptions are merely embodiments of the present invention and do not limit the scope of patent protection of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention's description and drawings, or directly or indirectly applied in other related technical fields, are also included in the scope of patent protection of the present invention.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410332241 | 2024-03-22 | ||
| CN202410332241.X | 2024-03-22 |
| Publication Number | Publication Date |
|---|---|
| WO2025195482A1true WO2025195482A1 (en) | 2025-09-25 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2025/083920PendingWO2025195482A1 (en) | 2024-03-22 | 2025-03-21 | Gastric retention apparatus |
| Country | Link |
|---|---|
| CN (1) | CN120154807A (en) |
| WO (1) | WO2025195482A1 (en) |
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