Degradable duodenum bypass stent system and preparation method thereof

Abstract

The degradable duodenum bypass stent system comprises a tubular grid stent and a bypass membrane tube, one end of the bypass membrane tube is fixed to the tubular grid stent, the other end of the bypass membrane tube is a free end, the bypass membrane tube is communicated with the interior of the tubular grid stent, and the bypass membrane tube is arranged in the tubular grid stent. Anchor thorns capable of being embedded into a duodenum bulbar mucous membrane are arranged on the tubular grid stent; all components of the degradable duodenum bypass stent system are made of materials which can be degraded in the human digestive tract environment. All the components of the degradable duodenum bypass stent system are made of materials which can be degraded in the human digestive tract environment, the degraded components can be discharged out of the body through excrement, and then a secondary endoscopic extraction operation can be avoided.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to a degradable duodenal bypass stent system and a preparation method thereof. BACKGROUND

[0002] Obesity has become a major public health problem that needs to be solved globally. Although traditional weight loss surgery has definite therapeutic effect, it is more traumatic and has a high risk of postoperative complications. In this context, endoluminal interventional weight loss devices have become an important research direction due to their minimally invasive characteristics. In the current clinical application, the duodenal weight loss stent is a typical representative. The device uses a nickel-titanium alloy stent fixed in the duodenal bulb, and the end is connected to a long section of isolation bypass membrane tube. By guiding food to flow in the bypass membrane tube to reduce contact and absorption with the intestinal wall, the weight loss effect is achieved.

[0003] However, through clinical verification, the existing technology has the following significant limitations: 1. The necessity of secondary removal surgery: the metal stent implanted after the local tissue hyperplasia and embedding phenomenon is easy to occur, and it must be removed through a secondary endoscopic surgery, which not only increases the pain and treatment risk of the patient, but also significantly increases the medical cost.

[0004] 2. Potential risk of device displacement: due to the insufficient long-term biocompatibility of the metal stent with the tissue, the device may be displaced, which is difficult to remove through endoscopic surgery after displacement, and the removal requires surgical operation, which is more harmful.

[0005] In view of this, the present application is proposed. SUMMARY

[0006] The purpose of the present application is to provide a degradable duodenal bypass stent system and a preparation method, which avoids the problem that the existing metal stent needs to be removed through endoscopic surgery after implantation.

[0007] The present application is implemented as follows: In a first aspect, the present application provides a degradable duodenal bypass stent system, comprising a tubular mesh stent and a bypass membrane tube, one end of the bypass membrane tube is fixed with the tubular mesh stent, the other end is a free end, and the bypass membrane tube is in communication with the inside of the tubular mesh stent, and the tubular mesh stent is provided with an anchor spike capable of embedding the mucosa of the duodenal bulb; Each component of the degradable duodenal bypass stent system is made of a material that can be degraded in the human digestive tract environment.

[0008] In an optional embodiment, the tubular mesh stent has a self-expanding property.

[0009] In an optional embodiment, the tubular mesh stent is covered with a covering film.

[0010] In an optional embodiment, the degradable duodenal bypass stent system has a degradation period of 3 to 6 months in the human digestive tract environment. And / or, the degradation period of the tubular mesh stent in the human digestive tract environment is longer than that of the bypass film tube in the human digestive tract environment.

[0011] In an optional embodiment, the anchor spikes are arranged in 4-6 groups along the circumference of the tubular mesh stent, each group comprising two or more anchor spikes arranged in the axial direction. And / or, the tubular mesh stent is integrally formed with the anchor spikes.

[0012] In an optional embodiment, the length of the bypass film tube is 55-65 cm.

[0013] In an optional embodiment, the material of the tubular mesh stent is left-handed polylactic acid or polyglycolide. And / or, the material of the covering film and / or bypass film tube is polyglycolide.

[0014] In a second aspect, the present application provides a preparation method of the degradable duodenal bypass stent system according to any one of the preceding embodiments, comprising: Preparation of the tubular mesh stent; Preparation of the bypass film tube; Fixing the tubular mesh stent and the bypass film tube.

[0015] In an optional embodiment, the preparation of the tubular mesh stent comprises: first contour processing by laser engraving, and then heat setting to obtain the tubular mesh stent. And / or, the forming method of the bypass film tube is dip molding. And / or, further comprising a covering film, and the forming method of the covering film is dip molding.

[0016] The present application has the following advantages: The degradable duodenal bypass stent system in the present application comprises a tubular mesh stent at the proximal end, and the outer wall of the stent is provided with anchor spikes for embedding the duodenal bulb mucosa to initially fix the degradable duodenal bypass stent system. The distal end of the tubular mesh stent is fixed with the bypass film tube, which is preferably a flexible film bypass film tube. The proximal end of the flexible film bypass film tube seamlessly connects with the tubular mesh stent, and the other end is a free end for directly draining food from the stent cavity to the middle segment of the jejunum.

[0017] The degradable duodenal bypass stent system in the present application is made of materials that can be degraded in the human digestive tract environment, and after degradation, it can be excreted through feces, thereby avoiding secondary endoscopic removal surgery. BRIEF DESCRIPTION OF DRAWINGS

[0018] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following will briefly introduce the drawings needed to be used in the embodiments. It should be understood that the following drawings only show some embodiments of the present application, and therefore should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can also be obtained without creative labor on the basis of these drawings.

[0019] Figure 1 The structure of the degradable duodenal bypass stent system in the present application is shown in the figure.

[0020] Figure: 100-tubular mesh stent; 200-bypass membrane tube; 300-covering membrane. DETAILED DESCRIPTION

[0021] In order to make the purpose, technical solutions and advantages of the embodiments of the present application more clear, the technical solutions in the embodiments of the present application will be described clearly and completely. If the specific conditions are not specified in the embodiments, the conventional conditions or the conditions recommended by the manufacturer are used. If the reagents or instruments used are not specified by the manufacturer, they are all conventional products that can be purchased on the market.

[0022] The present application provides a degradable duodenal bypass stent system, which comprises a tubular mesh stent 100 and a bypass membrane tube 200. One end of the bypass membrane tube 200 is fixed to the tubular mesh stent 100, and the other end is a free end. The bypass membrane tube 200 is in communication with the inside of the tubular mesh stent 100. The tubular mesh stent 100 is provided with anchor spikes that can be embedded in the mucosa of the duodenal bulb to fix the degradable duodenal bypass stent system initially. The degradable duodenal bypass stent system in the present application is made of materials that can be degraded in the human digestive tract environment, and after degradation, it can be excreted through feces, thereby avoiding secondary endoscopic removal surgery.

[0023] The degradable duodenal bypass stent system in the present application comprises a tubular mesh stent 100 at the proximal end. The outer wall of the stent is provided with anchor spikes for embedding the mucosa of the duodenal bulb to fix the degradable duodenal bypass stent system initially. The distal end of the tubular mesh stent 100 is fixed to the bypass membrane tube 200. Preferably, the bypass membrane tube 200 is a flexible thin film bypass membrane tube 200. The proximal end of the flexible thin film bypass membrane tube 200 is seamlessly connected to the tubular mesh stent 100, and the other end is a free end, which is used to directly drain food from the stent cavity to the middle segment of the jejunum.

[0024] The degradable duodenal bypass stent system in the present application is made of materials that can be degraded in the human digestive tract environment, and after degradation, it can be excreted through feces, thereby avoiding secondary endoscopic removal surgery.

[0025] In an optional embodiment, the tubular mesh stent 100 has a self-expanding property. The duodenal bypass stent in the present application can be in a contracted state before implantation, reducing resistance during implantation. When the tubular mesh stent 100 reaches the duodenal bulb, the tubular mesh stent 100 can spontaneously recover to its original shape, which is the self-expanding property.

[0026] In an optional embodiment, the tubular mesh stent 100 is covered with a covering film 300, which can isolate the duodenal wall and the stent, preventing the duodenal inner wall from growing into the tubular mesh stent and causing blockage of the bypass film tube 200.

[0027] In an optional embodiment, the degradable duodenal bypass stent system has a degradation period of 3 to 6 months in the human digestive tract environment, which is consistent with the weight loss treatment period.

[0028] In an optional embodiment, the degradation period of the tubular mesh stent 100 in the human digestive tract environment is longer than that of the bypass film tube 200 in the human digestive tract environment, avoiding the degradation of the tubular mesh stent 100 first, while the bypass film tube 200 remains relatively intact, causing the entire bypass film tube 200 to move along the intestinal tract, resulting in local irritation or injury, and in severe cases, intestinal obstruction.

[0029] In an optional embodiment, the anchor spikes are arranged in 4-6 groups along the circumference of the tubular mesh stent 100, each group including two or more axially arranged anchor spikes; preferably, the multiple groups of anchor spikes are uniformly and symmetrically distributed along the circumference of the tubular mesh stent 100, maintaining the stability of the degradable duodenal bypass stent system.

[0030] In an optional embodiment, the tubular mesh stent 100 is integrally formed with the anchor spikes.

[0031] In an optional embodiment, the length of the bypass film tube 200 is 55-65 cm, so as to directly drain food from the stent cavity to the middle segment of the jejunum.

[0032] In an optional embodiment, the material of the tubular mesh stent 100 is left-handed polylactic acid or polyglycolide, which can have self-expanding property.

[0033] In an optional embodiment, the material of the covering film 300 and / or the bypass film tube 200 is polyglycolide.

[0034] The application also provides a preparation method of the degradable duodenal bypass stent system. Preparation of the tubular mesh stent 100; Preparation of the bypass membrane tube 200; Fixing the tubular mesh stent 100 and the bypass membrane tube 200.

[0035] In an optional embodiment, the preparation of the tubular mesh stent 100 comprises: first, contour processing by laser engraving, and then heat setting to obtain the tubular mesh stent 100. In an optional embodiment, the forming method of the bypass membrane tube 200 is dip molding. In an optional embodiment, a covering film 300 is further included, and the forming method of the covering film 300 is dip molding.

[0036] The features and performances of the application are further described in detail below in combination with embodiments.

[0037] Embodiment 1 The embodiment provides a preparation method of a degradable duodenal bypass stent system, and specifically comprises the following steps. 1. Preparation of the tubular mesh stent 100: PLGA with a LA proportion of 85% and a GA proportion of 15% and a specific viscosity of 5.0 dl / g is selected, and the PLGA is prepared into a thick-walled tube with an outer diameter of 10 mm, an inner diameter of 8 mm and a length of 30 mm through melt extrusion.

[0038] A UV laser precision machining system is used to engrave a rhombic grid pattern on the thick-walled tube to obtain a small-diameter stent with a grid wire diameter of 0.5 mm.

[0039] Heat setting: the engraved small-diameter stent is sleeved on a cylindrical core mold with a diameter of 35 mm. It is placed in a constant temperature oven at 60°C for 20 minutes to fully expand to the size of the core mold. Then it is quickly quenched in an ice water mixture to "remember" the expanded shape.

[0040] 2. Preparation of the bypass membrane tube 200: 2.1 Solution preparation: PLGA powder with a LA:GA ratio of 70:30 and a specific viscosity of 0.6 dL / g is accurately weighed and added to dichloromethane to obtain a PLGA-dichloromethane solution with a concentration of 5% w / v.

[0041] The solution was left to mix in a closed container on a magnetic stirrer or roller mixer at low speed, 50 rpm, for 36 hours until complete dissolution, forming a uniform, clear, viscous solution.

[0042] The prepared solution was degassed: the solution was placed in a vacuum desiccator and slowly evacuated for 3 hours at a vacuum of -0.08 MPa until no bubbles overflowed from the solution, obtaining the impregnation liquid. Due to the high viscosity of the solution, degassing requires patience and avoidance of violent boiling.

[0043] 2.2 Mandrel preparation: A mandrel of 23.5 mm was selected, the mandrel was thoroughly washed, dried and fixed on a motorized device that allowed uniform lifting / descending. The mandrel can be chosen as a cylindrical stainless steel or glass mandrel with a diameter slightly smaller than 25 mm. The choice of mandrel diameter must take into account the shrinkage of the cured film, which in the case of the PLGA / DCM system can reach 5-10%, so that, to obtain a cast film tube 200 with a diameter of 25 mm, a mandrel with a diameter of 23.5 mm was chosen.

[0044] 2.3 Dip coating: The degassed impregnation liquid was poured into an elongated glass container with an internal diameter slightly larger than the mandrel, in order to form a stable liquid column.

[0045] The mandrel was vertically immersed in the solution pool at a constant and slow speed and remained in the pool for about 20 seconds to allow the surface to be fully wetted and leveled.

[0046] Then, the mandrel was lifted out of the solution at a uniform speed.

[0047] 2.4 Solvent evaporation and curing: The wet cast film tube 200, together with the mandrel, was immediately transferred to a fume hood. The ambient temperature was controlled at 25-30°C and the relative humidity was <30%.

[0048] The cast film tube 200 was allowed to initially cure on the mandrel for 3 hours until it was not sticky to the touch.

[0049] 2.5 Drying and demolding: The initially cured cast film tube 200, together with the mandrel, was placed in a vacuum drying oven and slowly evacuated at room temperature to 30°C to further remove residual solvents, a process that took 36 hours.

[0050] After complete drying, the cast film tube 200 was carefully pried at one end with a sharp scalpel blade and then gently and uniformly peeled off the mandrel.

[0051] 3. Covering film preparation The preparation method of the covering film is the same as that of the flow diversion film tube 200, and the only difference is that the prepared tubular mesh stent 100 is used as a mandrel, and after drying, it can be unmolded.

[0052] 4. System assembly: The prepared flow diversion film tube 200 and the tubular mesh stent 100 with the covering film are connected and fixed by adhesion.

[0053] The assembled flow diversion film tube 200 and the tubular mesh stent 100 are subjected to ethylene oxide (EO) sterilization, thereby obtaining the degradable duodenal flow diversion stent system.

[0054] Comparative Example 1 The present comparative example provides a preparation method of a degradable duodenal flow diversion stent system, which specifically comprises the following steps: 1. Stent body preparation: Material: High molecular weight left-handed polylactic acid (PLLA) resin with intrinsic viscosity IV of 6.0 dL / g is selected. PLLA particles are prepared into a solid thick-walled tube with an outer diameter of 10 mm, an inner diameter of 9 mm, and a length of 30 mm by melt extrusion.

[0055] Laser engraving: An ultraviolet laser precision machining system is used to engrave a designed diamond mesh pattern on the above thick-walled tube, and the mesh wire diameter is 0.5 mm.

[0056] Heat setting: The engraved small diameter stent is sleeved on a cylindrical core mold with a diameter of 35 mm, and is placed in a constant temperature oven at 75°C for 15 minutes to fully expand to the size of the core mold. Then it is quickly quenched in an ice water mixture to "remember" the expanded shape.

[0057] 2. Film tube unit preparation: Material: PLGA with LA:GA=50:50 and intrinsic viscosity IV of 0.8 dL / g is selected.

[0058] The remaining preparation steps are the same as those of Example 1.

[0059] 3. Covering film preparation and system assembly are also the same as those of Example 1 The prepared PLAA-based stent control group is placed in the same in vitro degradation environment for parallel testing.

[0060] Test Example Focusing on the degradation performance comparison experiment report of the 3-month functional period 1. Test purpose To verify that the polylactide-co-glycolide (PLGA 85:15) as the stent body and the polylactide-co-glycolide (PLGA 70:30) as the membrane tube in the degradable duodenal bypass stent system described in the application achieve the ideal degradation time sequence of "membrane tube function failure first, stent support follow-up, and end-stage synchronous collapse" within a 3-month treatment cycle. And compared with the combination of "PLLA stent + PLGA 50:50 membrane tube", it shows the advantages of the embodiment in time sequence control and safety.

[0061] 2. Test materials and methods Example 1: PLGA (85:15) stent + PLGA (70:30) membrane tube Comparative Example 1: PLLA stent + PLGA (50:50) membrane tube Degradation environment: completely immerse the sample in a phosphate buffer solution (PBS) with pH = 7.4 to simulate the intestinal environment, and place it in a constant temperature shaker at 37°C for continuous shaking. Replace the PBS solution every week.

[0062] Test time points: 0, 2, 4, 8, 12 weeks (corresponding to 3 months).

[0063] Test indicators and methods: Molecular weight change: use GPC to measure the number average molecular weight (Mn) retention rate.

[0064] Mechanical property decay: Stent: measure the radial compression force (N).

[0065] Membrane tube: measure the tensile breaking strength (N).

[0066] 3. Test results and data Table 1: Comparison of molecular weight (Mn) retention rate (%)

[0067] Table 2: Comparison of mechanical property retention rate (%)

[0068] 4. Data analysis (1) The degradation time sequence of Example 1 (the formula of the application) perfectly fits the 3-month treatment cycle: 0-4 weeks (functional period): both the stent and the membrane tube maintain sufficient mechanical properties, the device functions are complete, and effective bypass is achieved.

[0069] Week 4-8 (functional transition period): The mechanical properties of the membrane tube decrease sharply after week 4, and completely fail before week 8. This means that food begins to mix with digestive juice, achieving a smooth and safe transition from "complete diversion" to "partial / stop diversion". At the same time, the stent still maintains 55% of the supporting force, effectively maintaining the device position and intestinal patency, preventing the risk of early migration or obstruction that may be caused by the failure of the membrane tube.

[0070] Week 8-12 (structural collapse period): The membrane tube has completely degraded. The mechanical properties of the stent continue to decrease, and only 20% remains at week 12, on the verge of structural collapse. This means that after the end of the treatment function, the device body quickly enters the tail of the degradation, without the need for long-term retention in the body.

[0071] (2) Comparative Example 1: Premature failure of the membrane tube: The PLGA (50:50) membrane tube degrades too quickly and basically loses its mechanical function at week 4. This means that the effective diversion treatment time may be less than a month, making it difficult to ensure adequate efficacy.

[0072] Risk of stent residue: The PLLA stent degrades extremely slowly and still maintains 80% of the original supporting force at week 12. When the membrane tube has already failed, a still solid stent network continues to be long-term retained in the intestinal tract, which no longer provides therapeutic benefits, but instead serves as a potential foreign body, continuously stimulating the intestinal tract, increasing the risk of tissue hyperplasia, inflammation, and even obstruction.

[0073] Conclusion: The duodenal flow diversion stent system of "PLGA (85:15) stent + PLGA (70:30) membrane tube" in Example 1 can achieve "functional timing", which is beneficial to achieve: 1. Functional integrity during the treatment period.

[0074] 2. Smooth transition of function in the later treatment period.

[0075] 3. Rapid collapse of structure after the end of treatment.

[0076] In contrast, the stent system in Comparative Example 1 has the dual risks of "insufficient function during the treatment period" and "residual structure after treatment".

[0077] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A biodegradable duodenal bypass stent system, characterized in that, It includes a tubular mesh support and a transfer membrane tube, one end of which is fixed to the tubular mesh support and the other end is free. The transfer membrane tube is connected to the interior of the tubular mesh support. The tubular mesh support is provided with anchors that can be embedded in the duodenal bulb mucosa. All components of the biodegradable duodenal bypass stent system are made of materials that can degrade in the human digestive tract environment.

2. The biodegradable duodenal bypass stent system according to claim 1, characterized in that, The tubular mesh support has self-expanding properties.

3. The biodegradable duodenal bypass stent system according to claim 1, characterized in that, The surface of the tubular mesh support is covered with a covering film.

4. The biodegradable duodenal bypass stent system according to claim 1, characterized in that, The degradation period of the tubular mesh stent in the human digestive tract environment is longer than that of the bypass membrane tube in the human digestive tract environment.

5. The biodegradable duodenal bypass stent system according to claim 1, characterized in that, The degradation cycle of the biodegradable duodenal bypass stent system in the human digestive tract environment is 3 to 6 months.

6. The biodegradable duodenal bypass stent system according to claim 1, characterized in that, The anchors are arranged in 4-6 groups along the circumference of the tubular mesh support, and each group includes two or more anchors arranged along the axial direction. And / or, the tubular mesh support is integrally formed with the anchor spike.

7. The biodegradable duodenal bypass stent system according to claim 1, characterized in that, The length of the transfer membrane tube is 55cm-65cm.

8. The biodegradable duodenal bypass stent system according to claim 1, characterized in that, The tubular mesh support is made of polylactic acid or polyglycolic acid; And / or, the material of the covering membrane and / or the transfer membrane tube is poly(lactic acid) lactide.

9. A method for preparing a biodegradable duodenal bypass stent system according to any one of claims 1-8, characterized in that, include: Fabrication of tubular mesh scaffolds; Preparation of the transfer membrane tube; The tubular mesh support and the transfer membrane tube are fixed in place.

10. The method for preparing the biodegradable duodenal bypass stent system according to claim 9, characterized in that, The preparation of the tubular mesh support includes: first, contour processing by laser engraving, and then heat setting to obtain the tubular mesh support; And / or, the forming method of the transfer membrane tube is dip-molding; And / or, it also includes a cover film, which is formed by dip molding.

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