Opening globule core for distal end release of gastrointestinal sleeve, method of preparation and use thereof

Abstract

This disclosure provides a release sphere core for distal end release of a gastrointestinal sleeve, a method for preparing the same, and its use, and belongs to the art of medical devices. The release sphere core for distal end release of a gastrointestinal sleeve comprises a filler, an adhesive, and a disintegrant in a mass ratio of 50-90:10-50:0-20, wherein the filler comprises at least one of starch, microcrystalline cellulose, and an inorganic salt, and the adhesive comprises at least one of water, ethanol, hypromellose, carboxymethylcellulose or a salt thereof, methylcellulose, and syrup. By utilizing the peristalsis of the gastrointestinal tract and the gravitational action of the release spheres themselves, the sleeve body is driven to move within the gastrointestinal tract until the sleeve is fully deployed, and after the sleeve body has automatically deployed, the release sphere core can be detached from the sleeve body by controlling the composition of the release sphere core, thereby completing the gastrointestinal sleeve installation operation. This method is easy to operate, significantly reduces the time required for gastrointestinal sleeve installation, and minimizes the risk of infection and radiation exposure.

Description

TECHNICAL FIELD

[0001] The present disclosure belongs to the technical field of medical devices, and specifically relates to a release pellet core for releasing the distal end of a gastrointestinal sleeve, a preparation method and use thereof.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS The present disclosure claims priority to the Chinese patent application filed with the China National Intellectual Property Administration on September 7, 2023, with the application number 202311152577X and the title "A release pellet core for releasing the distal end of a gastrointestinal sleeve, a preparation method and use thereof", the entire content of which is incorporated herein by reference. BACKGROUND ART

[0003] With the deepening and development of the understanding of obesity, it has been recognized that obesity is not merely weight gain, but is accompanied by a series of chronic disease syndromes such as type 2 diabetes, hypertension, sleep apnea or polycystic ovary syndrome. As a person becomes overweight or obese, the risk of various chronic diseases in adults increases. It not only causes severe cerebrovascular diseases or abnormal endocrine metabolism, but may also cause disorders of the respiratory, digestive or motor system, and is associated with the occurrence of various malignant tumors. In addition, obesity has become an important factor affecting people's mental health and social interaction, and also leads to an increase in economic burden. Obesity-related chronic diseases are serious in China.

[0004] According to the WHO criteria, a BMI of 30kg / m 2The above criteria are used to determine obesity, and the obesity rate among adults in China increased approximately eightfold from 1980 to 2015. According to the "Beijing Municipal Primary and Secondary School Nutrition and Health Status Report (2017)," the overweight rate among students surveyed in Beijing in 2017 was 15.9%, and the obesity rate was 16.9%, with the combined overweight and obesity rate reaching 32.8%, the same level as in the United States. Over the past 20 years, both the overweight and obesity rates among the Chinese population have increased significantly, surpassing many developed countries. Currently, the main treatment methods for obesity include diet, exercise and behavioral interventions, drug therapy, and weight-loss surgery. These methods have the problem of being difficult to continue due to their relatively long duration, and the weight-loss effect of diet, exercise, and behavioral interventions is only 3-5%. Weight-loss drugs can provide additional weight-loss effects, but according to the US electronic medical record database, both the prescription rate and the continued use rate of weight-loss drugs are very low due to drug side effects. While weight-loss surgery offers good therapeutic effects for the above-mentioned conditions, irreversible tissue damage, a certain mortality rate, and postoperative complications (e.g., gastrointestinal leakage, anastomotic stricture, or dumping syndrome) are unavoidable. In recent years, researchers have focused on a method that applies the principle of gastric bypass surgery to weight-loss surgery, placing a sleeve in the duodenum-jejunum and using the sleeve to block contact between yogurt and the intestinal tract, thereby reducing intestinal absorption and achieving weight loss.

[0005] CN109152570 discloses a method for inserting a sleeve under endoscopy. However, this method requires manual operation of the connection between the distal end of the sleeve and the distal cap, and the injection of fluid into the sleeve to smoothly stretch and mold it into the gastrointestinal tract. This method is complex, takes a relatively long time to insert the sleeve, and requires operation under X-ray, significantly increasing the risk of infection and radiation damage. Therefore, there is an urgent need for a new method for releasing gastrointestinal sleeves that can solve the above problems.

[0006] In light of this, we provide this disclosure. [Overview of the project]

[0007] The present disclosure aims to provide a small sphere core for releasing the distal end of a gastrointestinal sleeve, a method for preparing the same, and a method for using the same, which can be automatically deployed in the gastrointestinal tract, is easy and simple to operate, and significantly reduces the time required for the installation of the gastrointestinal sleeve.

[0008] The embodiments of this disclosure are implemented as follows.

[0009] In a first embodiment, the disclosure provides an open sphere core for opening the distal end of a gastrointestinal sleeve. The open sphere core for opening the distal end of a gastrointestinal sleeve comprises a filler, an adhesive, and a disintegrant in a mass ratio of 50-90:10-50:0-20, wherein the filler comprises at least one of starch, microcrystalline cellulose, and an inorganic salt.

[0010] The adhesive comprises water, ethanol, hypromellose, carboxymethylcellulose or its salt, methylcellulose, and at least one of the following:

[0011] In an optional embodiment, the inorganic salt comprises at least one of calcium sulfate, calcium hydrogen phosphate, calcium carbonate, and barium sulfate.

[0012] Preferably, the barium sulfate is one of the following: elutriated barium sulfate, type I barium sulfate, and type II barium sulfate.

[0013] More preferably, the barium sulfate is expecular barium sulfate or type II barium sulfate.

[0014] In an optional embodiment, the filler comprises one of two combinations: a combination of microcrystalline cellulose and calcium carbonate, or a combination of microcrystalline cellulose and barium sulfate, and preferably comprises a combination of microcrystalline cellulose and barium sulfate.

[0015] Preferably, the mass ratio of the filler to the adhesive is 56.2 to 86.9:13.1 to 42.2.

[0016] In an optional embodiment, the disintegrant comprises at least one of cross-linked sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, and sodium chloride.

[0017] In an optional embodiment, the mixture further includes auxiliary materials, the mass ratio of the filler to the auxiliary materials being 50-90:0.01-5.

[0018] Preferably, the auxiliary material includes at least one of an antioxidant, a preservative, and a fragrance.

[0019] In a second embodiment, the disclosure provides a method for preparing an open sphere core for opening the distal end of a gastrointestinal sleeve according to any one of the embodiments described above. The preparation method comprises mixing raw materials in a predetermined proportion and then press molding, the press molding method being one of a wet granulation compression method, a direct press molding method and a mold press method.

[0020] Preferably, the press molding method is a wet granulation compression method or a mold press method, and more preferably, a wet granulation compression method.

[0021] In a third embodiment, the disclosure provides a gastrointestinal sleeve comprising a sleeve body and an open sphere core for opening the distal end of a gastrointestinal sleeve according to any one of the above embodiments, wherein the open sphere core is fixed within an open sphere having a chamber, and the sleeve body comprises a proximal end and a distal end, the distal end being connected to the open sphere core.

[0022] In an optional embodiment, the dry connection force between the open microbulb core and the distal end of the gastrointestinal sleeve is greater than 2.5 N, preferably greater than 5 N.

[0023] Preferably, the wet connection force between the open microbulb core and the distal end of the gastrointestinal sleeve is less than 1.5 N, and more preferably less than 1 N, after 2 hours in a wet state.

[0024] In a fourth aspect, the present disclosure provides the use of a release pellet core for releasing the distal end of a gastrointestinal sleeve according to any one of the above embodiments, or a gastrointestinal sleeve according to the above embodiments, in the preparation of a product for reducing gastrointestinal absorption.

[0025] The beneficial effects of the examples of the present disclosure are as follows.

[0026] The present disclosure provides a release pellet core for releasing the distal end of a gastrointestinal sleeve, a preparation method and use thereof. In the release process, natural peristalsis of the intestinal tract is utilized to drive the expansion of the sleeve, and by controlling the composition of the release pellet core, after the release pellet core is completely deployed, mucus at the distal end of the intestinal tract is utilized to disintegrate the release pellet core, causing it to lose its structure and mechanical properties, so that the connection between the sleeve and the release pellet core can be released. No additional operations by medical staff are required in the whole process. The operation method is simple, which can greatly shorten the time required for placing the gastrointestinal sleeve, and reduce the infection risk and the harm of X-ray exposure.

[0027] In order to more clearly describe the technical solutions of the examples of the present disclosure, the drawings used in the description of the examples are briefly described below. The drawings described only show some examples of the present disclosure, and are not intended to limit the scope. Those skilled in the art can obtain other related drawings based on these drawings without inventive effort. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] [Figure 1] It is a schematic structural diagram of the gastrointestinal sleeve according to the present disclosure. [Figure 2] It is a schematic diagram showing the introduction process of the gastrointestinal sleeve according to the present disclosure. [Figure 3] It is a digital gastrointestinal angiography photograph taken 4 hours after releasing the gastrointestinal sleeve according to Test Example 2 of the present disclosure. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0029] The embodiments of this disclosure will be described in detail below using examples. As those skilled in the art will see, the following examples are for illustrative purposes only and do not limit the scope of this disclosure. In the examples, where specific conditions are not specified, it is possible to perform the procedures under conventional conditions or conditions recommended by the manufacturer. For reagents or instruments where the manufacturer is not specified, commercially available conventional products may be used.

[0030] The endpoints and any values ​​of the ranges disclosed herein are not limited to those specific ranges or values, and these ranges or values ​​should be understood to include values ​​close to those ranges or values. In the case of numerical ranges, one or more new numerical ranges can be obtained by combinations of the endpoints of each range, combinations of the endpoints of each range and individual specific values, and combinations of individual specific values, and these numerical ranges should also be considered to be specifically disclosed herein.

[0031] This disclosure provides an open sphere core for opening the distal end of a gastrointestinal sleeve. The open sphere core comprises a filler, an adhesive, and a disintegrant in a mass ratio of 50-90:10-50:0-20.

[0032] The filler comprises at least one of starch, microcrystalline cellulose, and an inorganic salt.

[0033] The adhesive comprises water, ethanol, hypromellose, carboxymethylcellulose or its salt, methylcellulose, and at least one of the following:

[0034] Currently, in the installation process of gastrointestinal sleeves, a method of injecting fluid to deploy the sleeve is often used. However, the time required for fluid injection and sleeve deployment is relatively long, resulting in a longer installation time and increased difficulty of the operation. In view of this, the inventors propose a method of installing an open sphere core in the gastrointestinal sleeve. This sphere core can automatically deploy the sleeve body within the gastrointestinal tract due to its own weight. Therefore, the gastrointestinal sleeve can be installed directly, eliminating the need to wait a long time for the sleeve to fully deploy, making the operation easier. However, since this open sphere core cannot be used without sterilization, it is generally sterilized using substances such as ethylene oxide. In general, the disintegration effect of the open sphere core changes significantly after sterilization, especially for sustained-release structures or disintegrating granules.

[0035] For example, a product that normally disintegrates in about two hours will not disintegrate even after 24 hours if sterilized with ethylene oxide. Therefore, ensuring that the open microsphere core still maintains relatively good disintegration performance after sterilization is key to whether this product can achieve the above-mentioned effect of "not having to wait a long time for the sleeve to fully unfold and being easier to operate."

[0036] The inventors have found that by using a method of compounding fillers, adhesives, and disintegrants, and by selecting the composition and mixing ratio of the raw materials, the prepared open sphere cores can still maintain relatively good disintegration performance even after sterilization. The disintegration action in this disclosure mainly comprises two aspects. One is the acceleration of disintegration by capillary action, specifically, the open sphere core has numerous capillaries and voids, and when it comes into contact with water, water enters the interior of the open sphere core through these hydrophilic channels, and the open sphere core is lubricated and disintegrates due to strong water absorption, and the disintegration action of cellulose derivatives is often involved in this mechanism. The other is erosion, specifically, when the open sphere core comes into contact with intestinal fluid in the duodenum, soluble components in the open sphere core, such as disintegrants, dissolve when they come into contact with water, forming erosive pores, which causes the core to break down into fine granules, and after dissolution, form "holes", accelerating disintegration.

[0037] In an optional embodiment, the inorganic salt comprises at least one of calcium sulfate, calcium hydrogen phosphate, calcium carbonate, and barium sulfate.

[0038] Preferably, the barium sulfate is one of the following: expecular barium sulfate, type I barium sulfate, and type II barium sulfate. Because barium sulfate has developing ability, when barium sulfate is selected as a packing material, the open sphere core according to this disclosure has developing ability, and when placed in the digestive tract, the position of the open sphere core within the digestive tract can be observed more clearly, thereby making it possible to determine whether or not the digestive tract sleeve has been delivered to a predetermined position.

[0039] More preferably, the barium sulfate is expecular barium sulfate or type II barium sulfate.

[0040] In an optional embodiment, the filler includes one of two combinations: a combination of microcrystalline cellulose and calcium carbonate, or a combination of microcrystalline cellulose and barium sulfate. The combination of microcrystalline cellulose and barium sulfate is preferred.

[0041] Preferably, the mass ratio of the filler to the adhesive is 56.2 to 86.9:13.1 to 42.2.

[0042] In an optional embodiment, to further control the separation time between the open spherical core and the sleeve body, the mass ratio of the filler, adhesive, and disintegrant is 50-90:10-50:0.01-20.

[0043] Preferably, the mass ratio of the filler, adhesive, and disintegrant is 56.2-86.9:13.1-42.2:0.01-15.6.

[0044] Preferably, the disintegrant comprises at least one of cross-linked sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, and sodium chloride.

[0045] In an optional embodiment, the mass ratio of the filler, adhesive, disintegrant, and auxiliary material is 50-90:10-50:0-20:0.01-5.

[0046] Preferably, the mass ratio of the filler, adhesive, disintegrant, and auxiliary material is 56.2-86.9:13.1-42.2:0.01-15.6:0.01-3.

[0047] Preferably, the auxiliary material includes at least one of an antioxidant, a preservative, and a fragrance.

[0048] In a second embodiment, the disclosure provides a method for preparing an open sphere core for opening the distal end of a gastrointestinal sleeve according to any one of the embodiments described above. The preparation method comprises mixing raw materials in a predetermined proportion and then press molding, the press molding method being one of a wet granulation compression method, a direct press molding method and a mold press method.

[0049] Preferably, the press molding method is a wet granulation compression method or a mold press method, and more preferably, a wet granulation compression method. Specifically, the process can be carried out by referring to a conventional press molding method.

[0050] In a third embodiment, the disclosure provides a gastrointestinal sleeve 100. As shown in Figure 1, the gastrointestinal sleeve 100 includes a sleeve body 110 and an open globule core for opening the distal end of the gastrointestinal sleeve according to any one of the embodiments described above, wherein the open globule core is fixed within an open globule 120 having a chamber, and the open globule 120 is connected to the sleeve body 110 via the open globule core, and the sleeve body 110 includes a proximal end and a distal end, the distal end being connected to the open globule core. Furthermore, referring to Figure 2, the process of separating the open globule core and the sleeve body 110 is shown from left to right. First, the gastrointestinal sleeve 100 is introduced into the duodenal bulb via the introduction tube. The release globule core is driven by gravity to expand the sleeve body 110 away from the duodenal bulb. Then, the introduction tube detaches from the sleeve body 110, and the release globule core further drives the sleeve body 110 to expand completely. Finally, the release globule core disintegrates, the release globules 120 detach from the sleeve body 110, and the introduction of the gastrointestinal sleeve 100 is completed.

[0051] In an optional embodiment, to ensure the final separation effect, the dry connection force between the open globule core and the distal end of the gastrointestinal sleeve is greater than 2.5 N, preferably greater than 5 N.

[0052] Preferably, the wet connection force between the open microbulb core and the distal end of the gastrointestinal sleeve is less than 1.5 N, and more preferably less than 1 N, after 2 hours in a wet state.

[0053] In a fourth embodiment, the disclosure provides the use of an open microbulb core of a gastrointestinal sleeve or a gastrointestinal sleeve according to any one of the above embodiments in the preparation of a product that reduces gastrointestinal absorption.

[0054] Example 1 This embodiment provides an open sphere core for opening the distal end of a gastrointestinal sleeve, comprising a filler, an adhesive, and a disintegrant.

[0055] Here, the filler consisted of 2 g of microcrystalline cellulose and 2 g of type II barium sulfate. The adhesive consisted of 2 g of water and 0.12 g of carboxymethylcellulose. The disintegrant was 0.1 g of cross-linked carboxymethylcellulose sodium.

[0056] After mixing the above raw materials in the above proportions, wet granulation press molding was performed, with a press molding parameter of 0.4 MPa. After ethylene oxide sterilization, an open sphere core was obtained.

[0057] This embodiment further provides a gastrointestinal sleeve including a sleeve body, the sleeve body including a proximal end and a distal end. The open sphere core described above is sterilized with ethylene oxide and then connected and fixed to the distal end.

[0058] Example 2 This embodiment provides an open sphere core for opening the distal end of a gastrointestinal sleeve, comprising a filler, an adhesive, and a disintegrant.

[0059] Here, the filler consisted of 2 g of microcrystalline cellulose and 2 g of expecular barium sulfate. The adhesive consisted of 1.2 g of water and 1 g of carboxymethylcellulose. The disintegrant was 0.1 g of cross-linked carboxymethylcellulose sodium. After mixing the above raw materials in the above proportions, wet granulation press molding was performed in the same manner as in Example 1, followed by ethylene oxide sterilization to obtain open sphere cores.

[0060] This embodiment further provides a gastrointestinal sleeve including a sleeve body, the sleeve body including a proximal end and a distal end. The open globule core described above is sterilized and then connected and fixed to the distal end.

[0061] Example 3 This embodiment provides an open sphere core for opening the distal end of a gastrointestinal sleeve, comprising a filler, an adhesive, and a disintegrant.

[0062] Here, the filler consisted of 1 g of microcrystalline cellulose and 2 g of type II barium sulfate. The adhesive consisted of 1.2 g of water and 2 g of carboxymethylcellulose, and the disintegrant was 0.3 g of cross-linked carboxymethylcellulose sodium. After mixing the above raw materials in the above proportions, wet granulation press molding was performed in the same manner as in Example 1, followed by ethylene oxide sterilization to obtain open sphere cores.

[0063] This embodiment further provides a gastrointestinal sleeve including a sleeve body, the sleeve body including a proximal end and a distal end. The open globule core described above is sterilized and then connected and fixed to the distal end.

[0064] Example 4 This embodiment provides an open sphere core for opening the distal end of a gastrointestinal sleeve, comprising a filler, an adhesive, and a disintegrant.

[0065] Here, the filler consisted of 2 g of microcrystalline cellulose and 2 g of type II barium sulfate. The adhesive consisted of 1.2 g of water and 0.2 g of carboxymethylcellulose, and the disintegrant was 0.3 g of cross-linked carboxymethylcellulose sodium. After mixing the above raw materials in the above proportions, wet granulation press molding was performed in the same manner as in Example 1, followed by ethylene oxide sterilization to obtain open sphere cores.

[0066] This embodiment further provides a gastrointestinal sleeve including a sleeve body, the sleeve body including a proximal end and a distal end. The open globule core described above is sterilized and then connected and fixed to the distal end.

[0067] Example 5 This embodiment provides an open sphere core for opening the distal end of a gastrointestinal sleeve, comprising a filler, an adhesive, and a disintegrant.

[0068] Here, the filler consisted of 0.5 g of microcrystalline cellulose and 3.5 g of type II barium sulfate. The adhesive consisted of 1 g of water and 0.12 g of carboxymethylcellulose, and the disintegrant was 0.1 g of sodium chloride. After mixing the above raw materials in the above proportions, wet granulation press molding was performed in the same manner as in Example 1, followed by ethylene oxide sterilization to obtain open sphere cores.

[0069] This embodiment further provides a gastrointestinal sleeve including a sleeve body, the sleeve body including a proximal end and a distal end. The open globule core described above is sterilized and then connected and fixed to the distal end.

[0070] Example 6 This embodiment provides an open sphere core for opening the distal end of a gastrointestinal sleeve, comprising a filler, an adhesive, and a disintegrant.

[0071] Here, the filler consisted of 1 g of microcrystalline cellulose and 3 g of expecular barium sulfate. The adhesive consisted of 1 g of water and 0.12 g of carboxymethylcellulose, and the disintegrant was 0.1 g of sodium chloride. After mixing the above raw materials in the above proportions, press molding was performed using a mold press method, followed by ethylene oxide sterilization to obtain an open sphere core.

[0072] This embodiment further provides a gastrointestinal sleeve including a sleeve body, the sleeve body including a proximal end and a distal end. The open globule core described above is sterilized and then connected and fixed to the distal end.

[0073] Example 7 This embodiment provides an open sphere core for opening the distal end of a gastrointestinal sleeve, comprising a filler, an adhesive, and a disintegrant.

[0074] Here, the filler consisted of 2.5 g of microcrystalline cellulose and 2 g of type II barium sulfate. The adhesive consisted of 1.2 g of water and 0.5 g of carboxymethylcellulose, and the disintegrant was 0.1 g of sodium chloride. After mixing the above raw materials in the above proportions, direct press molding was performed, followed by ethylene oxide sterilization to obtain open sphere cores.

[0075] This embodiment further provides a gastrointestinal sleeve including a sleeve body, the sleeve body including a proximal end and a distal end. The open globule core described above is sterilized and then connected and fixed to the distal end.

[0076] Example 8 This embodiment provides an open sphere core for opening the distal end of a gastrointestinal sleeve, comprising a filler, an adhesive, and a disintegrant.

[0077] Here, the filler consisted of 2 g of microcrystalline cellulose and 2.8 g of type II barium sulfate. The adhesive consisted of 1 g of water, 0.2 g of ethanol, and 0.12 g of carboxymethylcellulose, and the disintegrant was 0.3 g of cross-linked carboxymethylcellulose sodium. After mixing the above raw materials in the above proportions, direct press molding was performed, 0.2 g of sodium chloride was added and press molding was performed again, followed by ethylene oxide sterilization to obtain an open sphere core.

[0078] This embodiment further provides a gastrointestinal sleeve including a sleeve body, the sleeve body including a proximal end and a distal end. The open globule core described above is sterilized and then connected and fixed to the distal end.

[0079] Comparative Example 1 This comparative example provided a gastrointestinal sleeve and differed from Example 1 only in that it did not contain a disintegrant in the raw materials for preparing the open microbulb core.

[0080] Comparative Example 2 This comparative example provided a gastrointestinal sleeve and differed from Example 2 only in that it did not contain a disintegrant in the raw materials for preparing the open microbulb core.

[0081] Comparative Example 3 This comparative example provided a gastrointestinal sleeve and differed from Example 3 only in that it did not contain a disintegrant in the raw materials for preparing the open microbulb core.

[0082] Comparative Example 4 This comparative example provided a gastrointestinal sleeve and differed from Example 4 only in that it did not contain a disintegrant in the raw materials for preparing the open microbulb core.

[0083] Comparative Example 5 This comparative example provided a gastrointestinal sleeve and differed from Example 5 only in that it did not contain a disintegrant in the raw materials for preparing the open microbulb core.

[0084] Comparative Example 6 This comparative example provided a gastrointestinal sleeve and differed from Example 6 only in that it did not contain a disintegrant in the raw materials for preparing the open microbulb core.

[0085] Comparative Example 7 This comparative example provided a gastrointestinal sleeve and differed from Example 7 only in that it did not contain a disintegrant in the raw materials for preparing the open microbulb core.

[0086] Comparative Example 8 This comparative example provided a gastrointestinal sleeve and differed from Example 8 only in that it did not contain a disintegrant in the raw materials for preparing the open microbulb core.

[0087] Comparative Example 9 This comparative example differs from Example 1 only in that it provides an open globular core for a gastrointestinal sleeve and uses dried starch as a disintegrant.

[0088] Comparative Example 10 This comparative example differs from Example 2 only in that it provides an open microbulb core for a gastrointestinal sleeve and uses cross-linked polyvinylpyrrolidone as a disintegrant.

[0089] Comparative Example 11 This comparative example differs from Example 3 only in that it provides an open microbulb core for a gastrointestinal sleeve and uses low-substituted hydroxypropyl cellulose as a disintegrant.

[0090] Test Example 1 The disintegration time in physiological saline, the connection force in the dry state, and the connection force in the wet state of the gastrointestinal sleeves produced in Examples 1-8 and Comparative Examples 1-11 were measured.

[0091] The measurement method was as follows:

[0092] 1. Disintegration time: Measurement was performed in accordance with the disintegration time testing method described in the 2020 edition of the "Pharmacopoeia of the People's Republic of China" (0921).

[0093] 2. Method for measuring connection force in dry state: The released ball and the sleeve body were each clamped in a universal material testing machine, and tension was applied at a speed of 20 mm / min until the released ball detached from the sleeve body, and the maximum tensile force was recorded.

[0094] 3. Method for measuring connection force in a wet state: The released ball was placed in physiological saline solution and shaken at 40 rpm for 2 hours using a shaker with a water bath at 37±2℃. Then, the released ball and the sleeve body were clamped in a universal material testing machine, and tension was applied at a speed of 20 mm / min until the released ball detached from the sleeve body, and the maximum tensile force was recorded.

[0095] The measurements yielded the results shown in Table 1.

[0096] [Table 1]

[0097] As can be seen from Table 1, the open sphere core according to the embodiment of this disclosure has a shorter collapse time, superior collapse capability, contributes to the automatic deployment of the sleeve body, facilitates the use of the sleeve, and does not cause prolonged blockage of the sleeve body.

[0098] Test Example 2 The digestive tract sleeves prepared in Examples 1-3 and Comparative Example 1 were placed inside Bama fragrant pigs. The disintegration time of the free sphere cores prepared in Examples 1-3 and Comparative Example 1 within the pigs was tested, and the time it took for the free spheres and sleeve body to detach within the animal was measured using X-ray imaging. The results are shown in Figure 3. As shown in Figure 3, the free spheres according to the examples of this disclosure can be made to detach from the sleeve body within the animal by controlling the composition and mixing ratio of their raw materials. In contrast, the free spheres according to Comparative Example 1 could not disintegrate and could not detach from the sleeve body, so the photograph shows a dark shadow where the free sphere core and sleeve body remained connected, which is unfavorable for use in digestive tract sleeves.

[0099] The foregoing describes preferred embodiments of the Disclosure and does not limit the Disclosure. For those skilled in the art, the Disclosure may have various modifications and changes. Any modifications, equivalent substitutions, or improvements made, provided they do not deviate from the spirit and principles of the Disclosure, shall fall within the scope of the Disclosure. [Industrial applicability]

[0100] The release sphere core for releasing the distal end of a gastrointestinal sleeve according to this disclosure can be automatically deployed within the gastrointestinal tract, is easy and simple to operate, significantly reduces the time required for the installation of the gastrointestinal sleeve, and has excellent utility value. [Explanation of Symbols]

[0101] 100 Gastrointestinal Sleeves 110 Sleeve body 120 Release Small Ball

Claims

1. It includes fillers, adhesives, and disintegrants having a mass ratio of 50-90:10-50:0-20. The filler comprises at least one of starch, microcrystalline cellulose, and an inorganic salt. The adhesive comprises water, ethanol, hypromellose, carboxymethylcellulose or its salt, methylcellulose, and at least one of syrup. A small globular core for releasing the distal end of a gastrointestinal sleeve, characterized by the following features.

2. The inorganic salt comprises at least one of calcium sulfate, calcium hydrogen phosphate, calcium carbonate, and barium sulfate. Preferably, the barium sulfate is one of the following: elutriated barium sulfate, type I barium sulfate, and type II barium sulfate. More preferably, the barium sulfate is expecular barium sulfate or type II barium sulfate. The opening sphere core for opening the distal end of a gastrointestinal sleeve according to feature 1.

3. The filler comprises one of two combinations: a combination of microcrystalline cellulose and calcium carbonate, or a combination of microcrystalline cellulose and barium sulfate, preferably a combination of microcrystalline cellulose and barium sulfate. Preferably, the mass ratio of the filler to the adhesive is 56.2 to 86.9:13.1 to 42.

2. The release sphere core for releasing the distal end of a gastrointestinal sleeve according to feature 2.

4. The disintegrant comprises at least one of cross-linked sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, and sodium chloride. The opening sphere core for opening the distal end of a gastrointestinal sleeve according to feature 1.

5. The mixture further contains auxiliary materials, and the mass ratio of the filler to the auxiliary materials is 50 to 90:0.01 to 5. A release globule core for releasing the distal end of a gastrointestinal sleeve, as described in claim 1 or 4.

6. The aforementioned auxiliary material includes at least one of an antioxidant, a preservative, and a fragrance. The release sphere core for releasing the distal end of a gastrointestinal sleeve according to feature 5.

7. A method for preparing an open globule core for opening the distal end of a gastrointestinal sleeve according to any one of claims 1 to 6, The preparation method includes mixing raw materials in a predetermined proportion and then press molding, and the press molding method includes one of the following: wet granulation compression method, direct press molding method, and mold press method. Preferably, the press molding method is a wet granulation and compression method or a mold press method, and more preferably, a wet granulation and compression method. A method for preparing an open globule core for opening the distal end of a gastrointestinal sleeve, characterized by the following features.

8. The invention comprises a sleeve body and an open sphere core for opening the distal end of a gastrointestinal sleeve according to any one of claims 1 to 6, wherein the open sphere core is fixed within an open sphere having a chamber, and the sleeve body includes a proximal end and a distal end, the distal end being connected to the open sphere core. A gastrointestinal sleeve characterized by the following features.

9. The dry connection force between the open globule core and the distal end of the gastrointestinal sleeve is greater than 2.5 N, preferably greater than 5 N. Preferably, the wet connection force between the open microbulb core and the distal end of the gastrointestinal sleeve is less than 1.5 N after 2 hours in a wet state, and more preferably less than 1 N. The gastrointestinal sleeve according to feature 8.

10. In a product for reducing gastrointestinal absorption, use of an open spherical core for opening the distal end of a gastrointestinal sleeve according to any one of claims 1 to 6, or a gastrointestinal sleeve according to claim 8 or 9, which has been sterilized with ethylene oxide.

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