Patency capsule and preparation method therefor

Abstract

The present application relates to the technical field of medical instruments, and specifically to a patency capsule and a preparation method therefor. The patency capsule comprises: a first disintegration body; second disintegration bodies, which are connected to two ends of the first disintegration body; a radiopaque marker, which is disposed in the first disintegration body and / or the second disintegration bodies, and is formed by means of extrusion molding of a mixture of barium sulfate and polymer medical plastics; and a waterproof film, which is plated on outer surfaces of the first disintegration body and the second disintegration bodies, and is provided with notch portions. The patency capsule of the present application uses an X-ray opaque marker as the radiopaque marker; after the patency capsule disintegrates in a patient's body, determination of the location or state of disintegration can be made via abdominal radiography, thereby determining the location of capsule retention in the patient, simplifying the complicated preparation and usage processes of existing patency capsules; moreover, the radiopaque marker is formed by means of extrusion molding of a mixture of barium sulfate and polymer medical plastics, solving the problem of powdered barium sulfate ionizing easily to produce barium ions and thus causing harm to a human body.

Description

Pathfinder capsule and preparation method thereof

[0001] This application claims priority to the Chinese patent application filed with the State Intellectual Property Office on June 26, 2023, with application number 202310763567.3 and application name “Pathfinder Capsule and Its Preparation Method”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present application relates to the field of medical device technology, and in particular to a pathfinder capsule and a preparation method thereof. Background Art

[0003] Since its clinical application, capsule endoscopy has played a vital role in the diagnosis of small intestinal diseases, lesion location determination, and treatment efficacy assessment. However, some patients with Crohn's disease, small intestinal tumors, intestinal obstruction, or long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) may experience capsule retention during capsule endoscopy. Capsule retention occurs when the capsule remains in the digestive tract for more than two weeks. It primarily occurs in the small intestine, with a few cases occurring in the esophagus, stomach, and colon. Although most patients with capsule retention are asymptomatic, some are at risk of developing intestinal obstruction or even perforation, necessitating prevention. However, there is currently no effective method to completely prevent capsule retention. Conventional preventive measures, such as a thorough medical history and imaging assessment during capsule endoscopy to determine the presence of intestinal obstruction, can assess the risk of capsule retention. However, this approach is only applicable during the capsule endoscopy itself; pre-procedural imaging screening has no significant effect in reducing capsule retention.

[0004] Another solution to this problem involves using biodegradable pathfinder capsules to pre-emptively identify patients requiring gastrointestinal endoscopy, thus preventing capsule retention. The pathfinder capsules are the same size and shape as standard capsule endoscopes. If the pathfinder capsule cannot be completely expelled, capsule endoscopy is generally considered inappropriate. Furthermore, after the pathfinder capsule remains in the body of a patient with gastrointestinal stenosis for a certain period of time, plugs at one or both ends of the capsule dissolve in the moist environment of the digestive tract, allowing the decomposed fragments to pass through the stricture and be expelled.

[0005] The existing pathfinder capsule consists of two parts: a capsule body and a radio detector. The capsule body is identical in shape and size to a gastrointestinal capsule endoscope, primarily composed of a degradable lactose material. It contains barium that can be developed under X-rays and a radio frequency sensor, but does not contain the same lenses and electronic components as a gastrointestinal capsule endoscope. This pathfinder capsule has time indicators at both ends. When it becomes stuck in a narrow part of the body, the time indicator on the capsule body can dissolve under the action of digestive fluid, causing the entire capsule body to degrade. However, the pathfinder capsule contains a radio frequency sensor and a barium developer, and the preparation process is relatively complicated. Furthermore, the barium developer is barium sulfate powder. After the capsule body decomposes, the powdered barium sulfate will ionize into a small amount of barium ions in the digestive fluid, which can be harmful to the human body.

[0006] Therefore, it is particularly important to prepare a pathfinder capsule that is safe, simple, and has obvious indications.

[0007] Application Contents

[0008] In view of this, the present application provides a pathfinder capsule and a preparation method thereof, which simplifies the existing pathfinder capsule preparation process and the complicated process during use, and improves the safety when using barium sulfate as a developer.

[0009] In a first aspect, the present application provides a pathfinder capsule, comprising:

[0010] First disintegration subject;

[0011] A second disintegrating body connected to both ends of the first disintegrating body;

[0012] A developing marker is disposed in the first disintegrating body and / or the second disintegrating body; the developing marker is extruded from a mixture of barium sulfate and a high molecular weight medical plastic; and

[0013] The waterproof film is plated on the outer surfaces of the first disintegrating body and the second disintegrating body, and a notch is provided in the waterproof film at the end of the second disintegrating body away from the first disintegrating body.

[0014] In conjunction with the first aspect, the pathfinder capsule has at least one of the following features:

[0015] (1) The first disintegrating body is cylindrical in shape;

[0016] (2) The second disintegrating body is hemispherical, and the diameter of the hemispherical shape is the same as that of the cylindrical shape;

[0017] (3) The total length of the pathfinder capsule is 20 mm to 30 mm;

[0018] (4) The diameter of the pathfinder capsule is 8 mm to 15 mm;

[0019] (5) The thickness of the waterproof film is 0.5 μm to 20 μm;

[0020] (6) The diameter of the notch is 2 mm to 10 mm.

[0021] In combination with the first aspect, the first disintegrating body is composed of at least one of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate.

[0022] In conjunction with the first aspect, the pathfinder capsule has at least one of the following features:

[0023] (1) The mass content of the anhydrous lactose in the first disintegrating body is 0% to 60%;

[0024] (2) the mass content of the microcrystalline cellulose in the first disintegrating body is 0% to 40%;

[0025] (3) The mass content of the citric acid in the first disintegrating body is 10% to 50%;

[0026] (4) The mass content of the sodium bicarbonate in the first disintegrating body is 10% to 50%;

[0027] (5) The mass content of the magnesium stearate in the first disintegrating body is 0.5% to 5%.

[0028] In conjunction with the first aspect, the pathfinder capsule has at least one of the following features:

[0029] (1) The mass proportion of the barium sulfate in the imaging marker is 20% to 60%;

[0030] (2) The polymer medical plastic includes but is not limited to one or more of PVC, TPE, and TPU;

[0031] (3) The first disintegrating body and / or the second disintegrating body is provided with a receiving cavity, and the developing marker is accommodated in the receiving cavity;

[0032] (4) The directions and distances of the imaging markers are regularly related when the pathfinder capsule is not decomposed.

[0033] In combination with the first aspect, the second disintegrating body is composed of at least one of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinyl pyrrolidone, and magnesium stearate.

[0034] In conjunction with the first aspect, the pathfinder capsule has at least one of the following features:

[0035] (1) The mass content of the glyceryl behenate in the second disintegrating body is 5% to 50%;

[0036] (2) The mass content of the anhydrous lactose in the second disintegrating body is 20% to 50%;

[0037] (3) The mass content of the microcrystalline cellulose in the second disintegrating body is 20% to 50%;

[0038] (4) The mass content of the polyvinyl pyrrolidone in the second disintegrating body is 5% to 10%;

[0039] (5) The mass content of the magnesium stearate in the second disintegrating body is 0.5% to 2%.

[0040] In conjunction with the first aspect, the pathfinder capsule has at least one of the following features:

[0041] (1) The waterproof film is a parylene film;

[0042] (2) The thickness of the waterproof film is 0.5 μm to 20 μm.

[0043] In a second aspect, the present application provides a method for preparing a pathfinder capsule, the method comprising the following steps:

[0044] Weigh 1.5 g to 5 g of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate in proportion, mix uniformly to obtain a first mixture, place the mixture in a tablet press, and compress at a first pressure to obtain a cylindrical first disintegrating body;

[0045] Weighing 0.1-1 g of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinyl pyrrolidone, and magnesium stearate in proportion, mixing uniformly to obtain a second mixture, placing the mixture into a tablet press, and pressing at a second pressure to obtain a hemispherical second disintegrating body; wherein the first disintegrating body and / or the second disintegrating body is provided with a receiving cavity;

[0046] A developing marker is obtained by extrusion injection molding barium sulfate and a polymer plastic, and the developing marker is placed in the receiving cavity. The ends of the first disintegrating body and the second disintegrating body are bonded together with an adhesive and air-dried. The weight proportion of the barium sulfate in the developing marker is 20% to 60%.

[0047] A 0.5 μm to 20 μm waterproof film is formed on the outer surfaces of the first and second disintegrating bodies by vapor deposition, and a notch with a diameter of 2 mm to 10 mm is provided in the waterproof film at the end of the second disintegrating body away from the first disintegrating body.

[0048] In conjunction with the second aspect, the method for preparing the pathfinder capsule has at least one of the following characteristics:

[0049] (1) The mass content of the anhydrous lactose in the first mixture is 0% to 60%;

[0050] (2) the mass content of the microcrystalline cellulose in the first mixture is 0% to 40%;

[0051] (3) The mass content of the citric acid in the first mixture is 10% to 50%;

[0052] (4) The mass content of the sodium bicarbonate in the first mixture is 10% to 50%;

[0053] (5) The mass content of magnesium stearate in the first mixture is 0.5% to 5%;

[0054] (6) the first pressure is 0.5T to 5T, and the application time of the first pressure is 1min to 10min;

[0055] (7) The mass content of the glyceryl behenate in the second mixture is 5% to 50%;

[0056] (8) The mass content of the anhydrous lactose in the second mixture is 20% to 50%;

[0057] (9) The mass content of the microcrystalline cellulose in the second mixture is 20% to 50%;

[0058] (10) The mass content of the polyvinyl pyrrolidone in the second mixture is 5% to 10%;

[0059] (11 The mass content of magnesium stearate in the second mixture is 0.5% to 2%;

[0060] (12) the second pressure is 0.5T to 5T, and the application time of the second pressure is 1min to 10min;

[0061] (13) The adhesive is a bioglue, UV curing glue or ethyl cellulose solution.

[0062] After adopting the above scheme, the beneficial effects are:

[0063] The pathfinder capsule and preparation method provided in the present application use a plurality of X-ray-opaque development markers extruded from a mixture of barium sulfate and a polymer medical plastic as the development markers of the pathfinder capsule. If the patient has problems such as intestinal stenosis, the disintegration position or disintegration state of the pathfinder capsule can be determined by taking an abdominal X-ray after the pathfinder capsule decomposes in the patient's body, and then the capsule retention position of the patient can be determined, thereby simplifying the existing pathfinder capsule preparation process and the complicated process during use. At the same time, the development marker is extruded from a mixture of barium sulfate and a polymer medical plastic, and the barium sulfate will not exist alone and be exposed in the patient's body, thereby solving the problem that barium sulfate is easily ionized into barium ions in a powder state, which is harmful to the human body. BRIEF DESCRIPTION OF THE DRAWINGS

[0064] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following is a brief introduction to the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0065] FIG1 is a cross-sectional view of a pathfinder capsule provided by the present application;

[0066] FIG2 is a cross-sectional view of a first disintegrating body of a pathfinder capsule provided in the present application;

[0067] FIG3 is a cross-sectional view of another pathfinder capsule provided by the present application;

[0068] FIG4 is a cross-sectional view of another pathfinder capsule provided by the present application;

[0069] FIG5 is a cross-sectional view of a development marker of a pathfinder capsule provided by the present application;

[0070] FIG6 is a flow chart of the preparation method of the pathfinder capsule provided in this application.

[0071] Figure ID:

[0072] 1-first disintegrating body; 12-accommodating cavity; 2-second disintegrating body; 3-waterproof film; 31-notch; 4-developable marker. DETAILED DESCRIPTION

[0073] In order to better understand the technical solution of the present application, the embodiments of the present application are described in detail below with reference to the accompanying drawings.

[0074] It should be clear that the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application.

[0075] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments and are not intended to limit the present application. The singular forms "a", "an", "the" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms unless the context clearly indicates otherwise.

[0076] It should be understood that the term "and / or" as used herein is merely a description of the relationship between associated objects, indicating that three possible relationships exist. For example, "A and / or B" can represent: A exists alone, A and B exist simultaneously, or B exists alone. Furthermore, the character " / " in this document generally indicates that the associated objects are in an "or" relationship.

[0077] It should be noted that the directional words such as "upper", "lower", "left", and "right" described in the embodiments of the present application are described based on the angles shown in the accompanying drawings and should not be understood as limiting the embodiments of the present application. In addition, in the context, it should be understood that when it is mentioned that an element is connected to another element "on" or "under", it can not only be directly connected to the other element "on" or "under", but also be indirectly connected to the other element "on" or "under" through an intermediate element.

[0078] Since its clinical application, capsule endoscopy has played a vital role in the diagnosis of small intestinal diseases, lesion location determination, and treatment efficacy assessment. However, some patients with Crohn's disease, small intestinal tumors, intestinal obstruction, or long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) may experience capsule retention during capsule endoscopy. Capsule retention occurs when the capsule remains in the digestive tract for more than two weeks. It primarily occurs in the small intestine, with a few cases occurring in the esophagus, stomach, and colon. Although most patients with capsule retention are asymptomatic, some are at risk of developing intestinal obstruction or even perforation, necessitating prevention. However, there is currently no effective method to completely prevent capsule retention. Conventional preventive measures, such as a thorough medical history and imaging assessment during capsule endoscopy to determine the presence of intestinal obstruction, can assess the risk of capsule retention. However, this approach is only applicable during the capsule endoscopy itself; pre-procedural imaging screening has no significant effect in reducing the rate of capsule retention.

[0079] Another solution to this problem involves using biodegradable pathfinder capsules to pre-emptively identify patients requiring gastrointestinal endoscopy, thus preventing capsule retention. The pathfinder capsules are the same size and shape as standard capsule endoscopes. If the pathfinder capsule cannot be completely expelled, capsule endoscopy is generally considered inappropriate. Furthermore, after the pathfinder capsule remains in the body of a patient with gastrointestinal stenosis for a certain period of time, plugs at one or both ends of the capsule dissolve in the moist environment of the digestive tract, allowing the decomposed fragments to pass through the stricture and be expelled.

[0080] The existing pathfinder capsule consists of two parts: a capsule body and a radio detector. The capsule body is identical in shape and size to a gastrointestinal capsule endoscope, primarily composed of a degradable lactose material. It contains barium that can be developed under X-rays and a radio frequency sensor, but does not contain the same lenses and electronic components as a gastrointestinal capsule endoscope. This pathfinder capsule has time indicators at both ends. When it becomes stuck in a narrow part of the body, the time indicator on the capsule body can dissolve under the action of digestive fluid, causing the entire capsule body to degrade. However, the pathfinder capsule contains a radio frequency sensor and a barium developer, and the preparation process is relatively complicated. Furthermore, the barium developer is barium sulfate powder. After the capsule body decomposes, the powdered barium sulfate will ionize into a small amount of barium ions in the digestive fluid, which can be harmful to the human body.

[0081] Therefore, it is particularly important to prepare a pathfinder capsule that is safe, simple, and has obvious indications.

[0082] In view of this, the present application provides a pathfinder capsule, as shown in Figures 1 to 4, which includes:

[0083] First disintegration body 1;

[0084] The second disintegrating body 2 is connected to both ends of the first disintegrating body 1;

[0085] The developing marker 4 is disposed in the first disintegrating body 1 and / or the second disintegrating body 2; the developing marker 4 is formed by extrusion of a mixture of barium sulfate and a high molecular medical plastic; and

[0086] The waterproof film 3 is plated on the outer surfaces of the first disintegrating body 1 and the second disintegrating body 2 , and a notch 31 is formed in the waterproof film 3 at the end of the second disintegrating body 2 away from the first disintegrating body 1 .

[0087] In the above scheme, the pathfinder capsule uses a plurality of X-ray-opaque development markers 4 extruded from a mixture of barium sulfate and high-molecular medical plastics as the development markers 4 of the pathfinder capsule. If the patient has problems such as intestinal stenosis, after the pathfinder capsule decomposes in the patient's body, the development markers 4 can be observed by taking an abdominal X-ray to determine the disintegration position or disintegration state of the pathfinder capsule, and then the capsule retention position of the patient can be determined, which simplifies the existing pathfinder capsule preparation process and the complicated process during use; at the same time, the development markers 4 are extruded from a mixture of barium sulfate and high-molecular medical plastics, and the barium sulfate will not be exposed to the patient's body alone, which solves the problem that barium sulfate is easily ionized into barium ions in a powder state and causes harm to the human body.

[0088] In some embodiments, the pathfinder capsule is composed of a first disintegrating body 1, a second disintegrating body 2, a developing marker 4, and a waterproof film 3. The second disintegrating body 2 is connected to both ends of the first disintegrating body 1; the developing marker 4 is disposed within the first disintegrating body 1 and / or the second disintegrating body 2; the developing marker 4 is extruded from a mixture of barium sulfate and a high-molecular-weight medical plastic; and the waterproof film 3 is plated on the outer surfaces of the first disintegrating body 1 and the second disintegrating body 2, with a notch 31 being provided in the waterproof film 3 disposed at the end of the second disintegrating body 2 away from the first disintegrating body 1.

[0089] In some embodiments, a pathfinder capsule includes a cylindrical first disintegrating body 1 having a accommodating cavity 12, a hemispherical second disintegrating body 2 connected to both ends of the first disintegrating body 1, and a waterproof film 3 coated on the outer surfaces of the first disintegrating body 1 and the second disintegrating body 2. A developing marker 4 is disposed within the first disintegrating body 1 and / or the second disintegrating body 2. The waterproof film 3 at both ends of the pathfinder capsule is provided with a notch 31. It is understood that when the pathfinder capsule enters the human body, if the patient suffers from intestinal stenosis or other problems, when the pathfinder capsule becomes stuck, the water-insoluble waterproof film 3 can prevent the first disintegrating body 1 from directly reacting. The notch 31 in the waterproof film 3 on the second disintegrating body 2 allows digestive fluid to react with the second disintegrating body 2. Only after the second disintegrating body 2 has reacted completely can the digestive fluid react with the first disintegrating body 1. In other words, the present application can control the reaction rate of the second disintegrating body 2 by the size of the notch 31, thereby achieving precise control of the pathfinder capsule's disintegration time to ensure that the test results are obtained within the specified time.

[0090] It should be noted that the development marker 4 of the present application is arranged in the first disintegrating body 1 and / or the second disintegrating body 2 , and the first disintegrating body 1 and / or the second disintegrating body 2 is provided with a receiving cavity 12 , and the development marker can be accommodated in the receiving cavity 12 .

[0091] As an optional technical solution of the present application, as shown in Figures 1 and 2, a accommodating cavity 12 is provided in the first disintegrating body 1, and the accommodating cavity 12 is not provided in the second disintegrating body 2, and the imaging marker 4 is accommodated in the accommodating cavity 12 of the first disintegrating body 1. And the shape, volume and opening position of the accommodating cavity 12 can be set. Exemplarily, the accommodating cavity 12 can be axially arranged through the first disintegrating body 1, and the diameter of the through hole can be set according to the number and size of the imaging marker 4 to accommodate the imaging marker 4; or, the accommodating cavity 12 is a blind hole opened at one end of the first disintegrating body 1, and the depth of the blind hole is less than the height of the first disintegrating body 1; or, the accommodating cavity 12 is a blind hole opened at both ends of the first disintegrating body 1, and the two blind holes are not connected; at the same time, the cross-sectional shape of the accommodating cavity 12 can be circular, triangular, rectangular or other polygonal, which is not limited here. It can be understood that a developing marker 4 is set in the first disintegration body 1. When the pathfinder capsule is embedded in the patient's body, the notch 31 of the waterproof film 3 on the second disintegration body 2 allows the digestive fluid to react with the second disintegration body 2. After the second disintegration body 2 reacts completely, the digestive fluid can react with the first disintegration body 1, thereby releasing the developing marker 4 in the first disintegration body 1. At this time, the disintegration position or disintegration state of the pathfinder capsule can be determined by observing the developing marker 4 through abdominal X-ray, and then the capsule retention position of the patient can be determined.

[0092] As another optional technical solution of the present application, as shown in Figure 3, the second disintegrating body 2 is provided with a receiving cavity 12 on the end face facing the first disintegrating body 1, and the first disintegrating body 1 is not provided with a receiving cavity 12, and the imaging marker 4 is accommodated in the receiving cavity 12 of the second disintegrating body 2. The shape, volume and opening position of the receiving cavity 12 can be set. Exemplarily, the receiving cavity 12 is a blind hole opened on the end face of the second disintegrating body 2, and the depth of the blind hole is less than the height of the second disintegrating body 2; at the same time, the cross-sectional shape of the receiving cavity 12 can be circular, triangular, rectangular or other polygonal, which is not limited here. It can be understood that the imaging marker 4 is provided in the second disintegrating body 2. When the pathfinder capsule is embedded in the patient's body, the notch 31 of the waterproof film 3 on the second disintegrating body 2 allows the digestive fluid to react with the second disintegrating body 2, thereby releasing the imaging marker 4 in the second disintegrating body 2. At this time, the disintegration position or disintegration state of the pathfinder capsule can be determined by observing the imaging marker 4 through abdominal X-ray, thereby determining the patient's capsule retention position. Compared with the previous technical solution, the development marker 4 is arranged in the second disintegrating body 2, which can shorten the time (28 to 32 hours) to determine whether the pathfinder capsule has decomposed, thereby shortening the treatment time.

[0093] As another optional technical solution of the present application, as shown in FIG4 , both the first disintegrating body 1 and the second disintegrating body 2 are provided with a accommodating cavity 12, and the shape, volume and opening position of the accommodating cavity 12 can be set. For the first disintegrating body 1, for example, the accommodating cavity 12 can be set through the axial direction of the first disintegrating body 1, and the diameter of the through hole can be set according to the number and size of the imaging markers 4 to accommodate the imaging markers 4; or, the accommodating cavity 12 is a blind hole opened at one end of the first disintegrating body 1, and the depth of the blind hole is less than the height of the first disintegrating body 1; or, the accommodating cavity 12 is a blind hole opened at both ends of the first disintegrating body 1, and the two blind holes are not connected. Moreover, for the second disintegrating body 2, for example, the accommodating cavity 12 is also a blind hole opened at the end face of the second disintegrating body 2, the depth of the blind hole is less than the height of the second disintegrating body 2, and the cross-sectional shape of the accommodating cavity 12 can be circular, triangular, rectangular or other polygonal, which is not limited here. It is understandable that when the pathfinder capsule becomes entrapped in the patient's body, the notch 31 of the waterproof film 3 on the second disintegrating body 2 allows the digestive fluid to react with the second disintegrating body 2, thereby releasing the imaging marker 4 in the second disintegrating body 2. At this time, the disintegration position or disintegration state of the pathfinder capsule can be determined by observing the imaging marker 4 through abdominal X-ray, thereby determining the patient's capsule retention position; only after the second disintegrating body 2 has reacted completely, the digestive fluid can react with the first disintegrating body 1 and release the imaging marker 4 in the first disintegrating body 1. Compared with the above scheme, according to the state of the imaging marker 4 in the second disintegrating body 2, it is possible to determine whether the pathfinder capsule has decomposed (28 to 32 hours) through abdominal X-ray, which shortens the judgment time; and the imaging marker 4 is set in both the first disintegrating body 1 and the second disintegrating body 2, so that after the pathfinder capsule becomes entrapped, the number of imaging markers 4 is greater and the indication is obvious, thereby improving the judgment accuracy during abdominal X-ray.

[0094] It should be noted that when the pathfinder capsule has not decomposed, the directions of the imaging markers 4 and the distances between them observed through abdominal X-rays are all regularly related. Regular correlation means that the imaging markers 4 are arranged according to preset rules in the first disintegration body 1 and / or the second disintegration body 2. For example, multiple imaging markers 4 are arranged parallel to each other in the first disintegration body 1, and one or more imaging markers 4 are arranged parallel to each other in each accommodating cavity of the second disintegration body 2, or multiple imaging markers 4 of the first disintegration body 1 and imaging markers 4 in each accommodating cavity of the second disintegration body 2 are arranged parallel to each other and their distances are limited by the position of the accommodating cavity. When the pathfinder capsule decomposes, the imaging markers 4 are scattered in the digestive tract. At this time, the directions of the imaging markers 4 and the distances between them are no longer regularly related. That is, when taking an abdominal X-ray, it can be determined that the pathfinder capsule has been decomposed only when it is observed within a specified time that the directions of the imaging markers 4 and the distances between them are no longer regularly related.

[0095] The placement of the imaging marker 4 in the pathfinder capsule can be selected according to actual needs and is not limited here. Preferably, the present application takes the imaging marker 4 being accommodated in the accommodation cavity 12 of the first disintegrating body 1 as an example for description.

[0096] The imaging markers 4 used in this application can have various shapes, including but not limited to those shown in FIG5 , such as solid spherical particles, hollow spherical particles, rectangular particles, hollow rectangular particles, pyramidal particles, hollow pyramidal particles, etc., or other polygonal shapes. These shapes can be selected based on actual needs and are not limited here. Preferably, the imaging markers 4 can be prepared as particles without sharp corners to further improve the safety of the pathfinder capsule.

[0097] As another optional technical solution of the present application, the imaging marker 4 can be mixed evenly with the components of the first disintegrating body 1 and / or the second disintegrating body 2 and then pressed together to form a first disintegrating body 1 and / or second disintegrating body 2 without a cavity, or the imaging marker 4 can be pressed into a position in the middle of the first disintegrating body 1 and / or the second disintegrating body 2. The selection can be made according to actual needs and is not limited here. However, it is also necessary to ensure that when the pathfinder capsule has not decomposed, the direction and distance between the imaging markers 4 observed by abdominal radiography are regularly related.

[0098] In the present application, the diameter of the notch portion 31 is 2 mm to 10 mm. Optionally, the diameter of the notch portion 31 can be 2 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, etc., or other values ​​within the range. It can be selected according to actual needs and is not limited here. If the diameter of the notch portion 31 is too large, the contact area between the second disintegration body 2 and the digestive fluid is too large, which will shorten the disintegration time of the second disintegration body 2; if the diameter of the notch portion 31 is too small, the contact area between the second disintegration body 2 and the digestive fluid is too small, which will prolong the disintegration time of the second disintegration body 2. It is understandable that a diameter of the notch portion 31 that is too large or too small will affect the degradation time of the pathfinder capsule, and thus it is impossible to accurately control the disintegration time of the pathfinder capsule. Therefore, the diameter of the notch 31 of the present application is in the range of 2mm to 10mm, preferably in the range of 5mm to 8mm, which can ensure that the second disintegrating body 2 is not completely disintegrated within 30h. After 30h, the first disintegrating body 1 begins to contact the digestive fluid, and it can be degraded within 0 to 50h, so that the total disintegration time of the pathfinder capsule is 30h to 80h. During this time, the imaging marker 4 can be observed by taking an abdominal X-ray, which proves that the pathfinder capsule cannot be discharged smoothly and has been degraded. It can be judged that the patient has gastrointestinal obstruction, stenosis or Crohn's disease and other problems, and this patient cannot undergo gastrointestinal capsule endoscopy. If the imaging marker 4 cannot be observed within 30h to 80h, it proves that the pathfinder capsule has been discharged, and it can be judged that the patient does not have gastrointestinal obstruction, stenosis or Crohn's disease and other problems, and this patient can undergo gastrointestinal capsule endoscopy.

[0099] It should be noted that when the imaging marker 4 is set in the second disintegration body 2, since the degradation time of the second disintegration body 2 is 0 to 30 hours (greater than 0 hours), it is understandable that at 28 to 32 hours (usually around 30 hours), scattered imaging markers 4 can be observed through abdominal X-ray, proving that the pathfinder capsule cannot be discharged smoothly and has been degraded, and it can be judged that the patient has gastrointestinal obstruction, stenosis or Crohn's disease and other problems, and this patient cannot undergo gastrointestinal capsule endoscopy; if at 28 to 32 hours (usually around 30 hours), regular imaging markers 4 are observed through abdominal X-ray, proving that the degradation site of the second disintegration body 2 has not reached the location of the imaging marker 4 (that is, the second disintegration body 2 has not completely disintegrated), then combined with the pathfinder The position of the pathfinder capsule in the digestive tract is used to comprehensively judge whether the patient can undergo a gastrointestinal capsule endoscopy. For example, if the pathfinder capsule is located in the colon, it means that the patient does not have gastrointestinal obstruction, stenosis or Crohn's disease, and this patient can undergo a gastrointestinal capsule endoscopy. If the pathfinder capsule is located in the small intestine, it proves that the pathfinder capsule is incarcerated, and it can be judged that the patient has gastrointestinal obstruction, stenosis or Crohn's disease, and this patient cannot undergo a gastrointestinal capsule endoscopy. If no scattered development markers 4 are observed through abdominal X-ray within 28 to 32 hours (usually around 30 hours), it proves that the pathfinder capsule has been expelled, and it can be judged that the patient does not have gastrointestinal obstruction, stenosis or Crohn's disease, and this patient can undergo a gastrointestinal capsule endoscopy.

[0100] When the imaging marker 4 is set in the first disintegration body 1 and the second disintegration body 2 at the same time, since the degradation time of the second disintegration body 2 is 0 to 30 hours (greater than 0 hours), it is understandable that at 28 to 32 hours (usually around 30 hours), through abdominal X-ray, it is observed that the imaging marker 4 is no longer regularly correlated (the imaging marker 4 of the second disintegration body 2 is scattered and no longer regularly correlated with the imaging marker 4 of the first disintegration body 1), proving that the pathfinder capsule cannot be discharged smoothly and the second disintegration body 2 has been degraded, it can be judged that the patient has gastrointestinal obstruction, stenosis or Crohn's disease and other problems, and this patient cannot undergo gastrointestinal capsule endoscopy; if at 28 to 32 hours (usually around 30 hours), regularly correlated imaging markers 4 are observed through abdominal X-ray, proving that the degradation part of the second disintegration body 2 is If the position of the imaging marker 4 has not been reached, the current position of the pathfinder capsule is used to comprehensively judge whether the patient can undergo gastrointestinal capsule endoscopy. For example, if the pathfinder capsule is located in the colon, it means that the patient does not have gastrointestinal obstruction, stenosis or Crohn's disease, and the patient can undergo gastrointestinal capsule endoscopy. If the pathfinder capsule is located in the small intestine, it proves that the pathfinder capsule is incarcerated, and it can be judged that the patient has gastrointestinal obstruction, stenosis or Crohn's disease, and the patient cannot undergo gastrointestinal capsule endoscopy. If no scattered imaging markers 4 can be observed through abdominal X-ray within 28 to 32 hours (usually around 30 hours), it proves that the pathfinder capsule has been expelled, and it can be judged that the patient does not have gastrointestinal obstruction, stenosis or Crohn's disease, and the patient can undergo gastrointestinal capsule endoscopy.

[0101] The pathfinder capsule of this application is used for examination before capsule endoscopy, so as to understand whether the patient has the above-mentioned intestinal stenosis and other problems, and then determine whether the patient can undergo gastrointestinal capsule endoscopy. Therefore, it is necessary to control the size of the pathfinder capsule to make it similar to the size of the capsule endoscope, so as to better simulate the journey of the capsule endoscope after entering the human body, so as to achieve more accurate detection results. Specifically:

[0102] The total length of the pathfinder capsule is 20mm to 30mm, and the diameter of the pathfinder capsule is 8mm to 15mm. Optionally, the total length can be 20mm, 21mm, 22mm, 23mm, 24mm, 25mm, 26mm, 27mm, 28mm, 29mm, 30mm, etc., and the diameter can be 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, etc., or other values ​​within the range. The selection can be based on actual needs and is not limited here. If the pathfinder capsule is too large or too small, it will not be able to effectively simulate the entry process of the capsule endoscope. It may become blocked in the digestive tract due to its large size, or it may be directly expelled due to its small size, reducing the accuracy of predicting whether the patient has the aforementioned intestinal stenosis and other problems. Furthermore, if the pathfinder capsule is too large or too small, its disintegration time will be affected, making it impossible to ensure that the test results are obtained within the specified time.

[0103] The waterproof film 3 is formed by vapor deposition on at least part of the surface of the first disintegrating body 1 and the second disintegrating body 2. The waterproof film 3 used in this application is a parylene film. The thickness of the waterproof film 3 is 0.5μm to 20μm. Optionally, the thickness can be 0.5μm, 5μm, 10μm, 15μm, 20μm, etc., or other values ​​within the range. It can be selected according to actual needs and is not limited here. If the thickness of the waterproof film 3 is too thick, the preparation cost of the pathfinder capsule increases; if the thickness of the waterproof film 3 is too thin, the waterproof film 3 is easily damaged during entry into the human body, and thus cannot effectively isolate the digestive fluid, causing the digestive fluid to react with the first disintegrating body 1 in advance. After the first disintegrating body 1 degrades, the imaging marker 4 is released, resulting in patients without gastrointestinal obstruction, stenosis or Crohn's disease and other problems also observing the imaging marker 4 when taking abdominal radiographs, affecting the detection accuracy of the pathfinder capsule.

[0104] The first disintegrating body 1 is composed of at least one of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate. Preferably, the first disintegrating body 1 is composed of a combination of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate. More preferably, the mass content of anhydrous lactose is 0% to 60%, the mass content of microcrystalline cellulose is 0% to 40%, the mass content of citric acid is 10% to 50%, the mass content of sodium bicarbonate is 10% to 50%, and the mass content of magnesium stearate is 0.5% to 5%.

[0105] The imaging marker 4 is extruded from a mixture of barium sulfate and a polymer medical plastic, wherein the polymer medical plastic includes, but is not limited to, one or more of PVC, TPE, and TPU. The mass proportion of barium sulfate in the imaging marker 4 is 20% to 60%, and the mass proportion of the polymer medical plastic in the imaging marker 4 is 40% to 80%. Optionally, the mass proportion of barium sulfate in the imaging marker 4 can be 20%, 30%, 40%, 50%, 60%, or other values ​​within the range, and can be selected based on actual needs and is not limited here. If the mass proportion of barium sulfate in the imaging marker 4 is too small, the indication function of the imaging marker 4 will be unclear when taking an abdominal X-ray. If the mass proportion of barium sulfate in the imaging marker 4 is too large, the barium sulfate will be easily exposed to the surface of the imaging marker 4 during extrusion molding of the barium sulfate and the polymer medical plastic, and will easily ionize into barium ions, thereby causing harm to the human body.

[0106] The composition of the second disintegrating body 2 includes at least one of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinyl pyrrolidone, and magnesium stearate. Preferably, the composition of the second disintegrating body 2 is a combination of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinyl pyrrolidone, and magnesium stearate. The mass content of glyceryl behenate is 5% to 50%, the mass content of anhydrous lactose is 20% to 50%, the mass content of microcrystalline cellulose is 20% to 50%, the mass content of polyvinyl pyrrolidone is 5% to 10%, and the mass content of magnesium stearate is 0.5% to 2%.

[0107] It should be noted that the waterproof film 3 used in this application is insoluble in water, that is, after the second disintegrating body 2 and the first disintegrating body 1 are degraded, the remaining waterproof film 3 can be discharged through the human body's metabolic process, and also has no side effects on the human body.

[0108] It can be understood that the pathfinder capsule prepared with the above materials has no side effects on the human body after degradation, even if the patient has gastrointestinal obstruction, stenosis or Crohn's disease, and the indication effect of the developing marker 4 is obvious when taking abdominal X-rays.

[0109] In some embodiments, as shown in FIG6 , the method for preparing the above-mentioned safe, simple, and clearly indicated pathfinder capsule comprises the following steps:

[0110] Step S10, weighing 1.5 g to 5 g of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate in proportion, mixing the mixture to obtain a first mixture, placing the mixture into a tablet press, and pressing the mixture at a first pressure to obtain a cylindrical first disintegrating body 1;

[0111] Step S20, weighing 0.1 g to 1 g of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinyl pyrrolidone, and magnesium stearate in proportion, mixing the mixture to obtain a second mixture, placing the mixture into a tablet press, and pressing the mixture under a second pressure to obtain a hemispherical second disintegrating body 2; wherein the first disintegrating body 1 and / or the second disintegrating body 2 is provided with a receiving cavity 12;

[0112] In step S30, barium sulfate and a polymer plastic are extruded and injection molded to obtain a developing marker 4, which is then placed in the receiving cavity 12. The ends of the first disintegrating body 1 and the second disintegrating body 2 are bonded together with an adhesive and air-dried. The weight percentage of barium sulfate in the developing marker 4 is 20% to 60%.

[0113] In step S40, a waterproof film 3 with a thickness of 0.5 μm to 20 μm is formed on the outer surfaces of the first disintegrating body 1 and the second disintegrating body 2 by vapor deposition, and a notch 31 with a diameter of 2 mm to 10 mm is provided on the waterproof film 3 at the end of the second disintegrating body 2 away from the first disintegrating body 1.

[0114] As an optional technical solution of the present application, a specific description is given by taking the arrangement of the accommodating cavity 12 in the first disintegrating body 1 as an example:

[0115] Step S10: Weigh 1.5 g to 5 g of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate in proportion, mix them evenly to obtain a first mixture, and then put it into a tablet press. After pressing at a first pressure, a cylindrical first disintegrating body 1 having a receiving cavity 12 is obtained.

[0116] In step S10, the mass of the first mixture is 1.5 g to 5 g. Optionally, the mass of the first mixture can be 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g, 4 g, 4.5 g, 5 g, etc., or other values ​​within the range. The mass can be selected according to actual needs and is not limited here. If the mass of the first mixture is too large, too much powder is used for pressing, which will cause the size of the first disintegration body 1 obtained by pressing to be too large or the compaction density to be too high, which will prolong the degradation time of the first disintegration body 1. If the mass of the first mixture is too small, too little powder is used for pressing, which will cause the size of the first disintegration body 1 obtained by pressing to be too small or the compaction density to be too low, which will shorten the degradation time of the first disintegration body 1.

[0117] The mass content of anhydrous lactose in the first mixture is 0% to 60%, the mass content of microcrystalline cellulose is 0% to 40%, the mass content of citric acid is 10% to 50%, the mass content of sodium bicarbonate is 10% to 50%, and the mass content of magnesium stearate is 0.5% to 5%.

[0118] It can be understood that the above-mentioned ratio of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate is selected, the first mixture is placed in a cylindrical mold of a tablet press, and a first pressure is applied to obtain a cylindrical first disintegrating body 1 having a accommodating cavity 12. Specifically, the first pressure is 0.5T to 5T, and the time for applying the first pressure is 1min to 10min. Optionally, the first pressure can be 0.5T, 1T, 1.5T, 2T, 2.5T, 3T, 3.5T, 4T, 4.5T, 5T, etc., and the time for applying the first pressure can be 1min, 2min, 3min, 4min, 5min, 6min, 8min, 10min, etc., or other values ​​within the range. It can be selected according to actual needs and is not limited here. If the pressure of the first pressure is too high or the application time is too long, the compaction density of the prepared first disintegration body 1 is too high, and the reaction rate of the digestive fluid and the first disintegration body 1 is slow, which will extend the disintegration time of the first disintegration body 1; if the pressure of the first pressure is too low or the application time is too short, the first disintegration body 1 does not reach the required size after the pressing is completed, and the compaction density of the prepared first disintegration body 1 is too low, and the reaction rate of the digestive fluid and the first disintegration body 1 is fast, which will shorten the disintegration time of the first disintegration body 1.

[0119] Step S20: weigh 0.1 g to 1 g of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinyl pyrrolidone, and magnesium stearate in proportion, mix them evenly to obtain a second mixture, and then put it into a tablet press. After pressing under a second pressure, a hemispherical second disintegrating body 2 is obtained.

[0120] In step S20, the mass of the second mixture is 0.1g to 1g. Optionally, the mass of the second mixture can be 0.1g, 0.3g, 0.5g, 0.7g, 0.8g, 0.9g, 1g, etc., or other values ​​within the range. The mass can be selected according to actual needs and is not limited here. If the mass of the second mixture is too large, too much powder is used for pressing, which will cause the size of the second disintegration body 2 obtained by pressing to be too large or the compaction density to be too high, which will prolong the degradation time of the second disintegration body 2. If the mass of the second mixture is too small, too little powder is used for pressing, which will cause the size of the second disintegration body 2 obtained by pressing to be too small or the compaction density to be too low, which will shorten the degradation time of the second disintegration body 2.

[0121] The mass content of glyceryl behenate in the second mixture is 5% to 50%, the mass content of anhydrous lactose is 20% to 50%, the mass content of microcrystalline cellulose is 20% to 50%, the mass content of polyvinyl pyrrolidone is 5% to 10%, and the mass content of magnesium stearate is 0.5% to 2%.

[0122] It is understood that the above-mentioned proportion of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinyl pyrrolidone, and magnesium stearate is selected, the second mixture is placed in a hemispherical mold of a tablet press, and a second pressure is applied to obtain a hemispherical second disintegrating body 2. Specifically, the second pressure is 0.5T to 5T, and the application time of the second pressure is 1min to 10min. Optionally, the second pressure can be 0.5T, 1T, 1.5T, 2T, 2.5T, 3T, 3.5T, 4T, 4.5T, 5T, etc., and the application time of the second pressure can be 1min, 2min, 3min, 4min, 5min, 6min, 8min, 10min, etc., or other values ​​within the range can be selected according to actual needs and are not limited here. If the pressure of the second pressure is too high or the application time is too long, the compaction density of the prepared second disintegration body 2 is too high, and the reaction rate of the digestive fluid and the second disintegration body 2 is slow, which will extend the disintegration time of the second disintegration body 2; if the pressure of the second pressure is too low or the application time is too short, the second disintegration body 2 does not reach the required size after the pressing is completed, and the compaction density of the prepared second disintegration body 2 is too low, and the reaction rate of the digestive fluid and the second disintegration body 2 is fast, which will shorten the disintegration time of the second disintegration body 2.

[0123] In step S30, barium sulfate and polymer plastic are extruded and injection molded to obtain a developing marker 4, and the developing marker 4 is placed in the accommodating cavity 12. The edges of the first disintegrating body 1 and the second disintegrating body 2 are bonded together with an adhesive and dried. The weight proportion of barium sulfate in the developing marker is 20% to 60%.

[0124] In step S30, the adhesive layer used to connect the first disintegrating body 1 and the second disintegrating body 2 can be one or more of biological glue, UV curing glue, or ethyl cellulose solution. The mass proportion of barium sulfate in the imaging marker 4 is 20% to 60%. Optionally, the mass proportion of barium sulfate in the imaging marker 4 can be 20%, 30%, 40%, 50%, 60%, etc., or other values ​​within the range. It can be selected according to actual needs and is not limited here. If the mass proportion of barium sulfate in the imaging marker 4 is too small, the indication function of the imaging marker 4 will be unclear when taking an abdominal X-ray. If the mass proportion of barium sulfate in the imaging marker 4 is too large, the barium sulfate will be easily exposed to the surface of the imaging marker 4 during extrusion molding of the barium sulfate and the polymer medical plastic, and it will easily ionize into barium ions, which will cause harm to the human body.

[0125] In step S40, a waterproof film 3 with a thickness of 0.5 μm to 20 μm is formed on the outer surfaces of the first disintegrating body 1 and the second disintegrating body 2 by vapor deposition, and a notch 31 with a diameter of 2 mm to 10 mm is provided on the waterproof film 3 at the end of the second disintegrating body 2 away from the first disintegrating body 1.

[0126] In step S40, the waterproof film 3 is made of parylene film. The specific steps are as follows: the assembled pathfinder capsule is placed in a fixed fixture, and a micron-level waterproof film 3 with a thickness of 0.5 to 20 μm is formed on the surface of the uniformly rotating capsule by vapor deposition. This waterproof film 3 has water-insoluble properties and can effectively isolate the first disintegrating body 1 and part of the second disintegrating body 2 from contact with the digestive fluid.

[0127] After the above preparation steps, the pathfinder capsule of the present application can be obtained. During actual use, the pathfinder capsule passes through the esophagus from the mouth and enters the digestive system. At this time, if the patient does not have the above-mentioned intestinal stenosis and other problems, the pathfinder capsule will be excreted with the patient's feces, and no imaging marker 4 will be observed when an abdominal X-ray is taken within the specified time.

[0128] If a patient has intestinal stenosis or other problems as described above, when the pathfinder capsule is blocked in the digestive system, the notch 31 of the waterproof film 3 on the second disintegrating body 2 allows the second disintegrating body 2 to come into contact with digestive fluids, pepsin, and trypsin, slowly disintegrating. At this point, the water-insoluble waterproof film 3 prevents the first disintegrating body 1 from reacting, allowing the first disintegrating body 1 to remain intact. This reaction continues until the second disintegrating body 2 is completely degraded, a reaction time of more than 30 hours. After 30 hours, when the second disintegrating body 2 is essentially disintegrated, the digestive fluid can contact and react with the ends of the first disintegrating body 1, gradually degrading the first disintegrating body 1. The citric acid and sodium bicarbonate in the first disintegrating body 1 react with water, generating small bubbles of carbon dioxide, which accelerates the disintegration of the first disintegrating body 1 and releases the imaging marker 4 in the first disintegrating body 1. This reaction time is 0 to 50 hours, so the imaging marker 4 can be observed on abdominal radiographs within 30 to 80 hours.

[0129] The following further describes the decomposition process of the pathfinder capsule by setting the accommodating cavity 12 in the first disintegrating body 1 in combination with specific embodiments:

[0130] Example 1:

[0131] (1) 5 g of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate in a mass ratio of 36:31:15:15:3 were mixed into a first mixture and placed into a tablet press mold. The mixture was maintained at a pressure of 5 T for 5 minutes, and the mold was opened to obtain a cylindrical first disintegrating body having a receiving cavity.

[0132] (2) Weigh 1 g of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinylpyrrolidone (PVPK-90), and magnesium stearate in a mass ratio of 10:50:30:9:1, mix them into a second mixture, and place it into a hemispherical mold of a tablet press. Hold the pressure at 5 T for 5 minutes, open the mold, and take out the compressed hemispherical second disintegrating body.

[0133] (3) barium sulfate and polymer plastic are extruded and injection molded to obtain a developing marker, and the developing marker is placed in the receiving cavity, and the ends of the first disintegrating body and the second disintegrating body are attached to each other with biological glue and dried; wherein the mass proportion of barium sulfate in the developing marker is 60%;

[0134] (4) A 10 μm waterproof film is formed on the outer surfaces of the first disintegrating body and the second disintegrating body by vapor deposition, and a notch with a diameter of 10 mm is provided in the waterproof film at the end of the second disintegrating body away from the first disintegrating body, finally obtaining a pathfinder capsule with a total length of 25 mm and a diameter of 11.5 mm.

[0135] Example 2:

[0136] Different from Example 1, the total mass of the first mixture is 3 g, and the total mass of the second mixture is 0.5 g.

[0137] Example 3:

[0138] Different from Example 1, the total mass of the first mixture is 1.5 g, and the total mass of the second mixture is 0.1 g.

[0139] Example 4:

[0140] Different from Example 1, the total mass of the first mixture is 0.5 g, and the total mass of the second mixture is 0.05 g.

[0141] Example 5:

[0142] Different from Example 1, the total mass of the first mixture is 7 g, and the total mass of the second mixture is 2 g.

[0143] Example 6:

[0144] Different from Example 1, the first pressure applied to the first mixture is 2.5T, and the second pressure applied to the second mixture is 2.5T.

[0145] Example 7:

[0146] Different from Example 1, the first pressure applied to the first mixture is 0.5T, and the second pressure applied to the second mixture is 0.5T.

[0147] Example 8:

[0148] Different from Example 1, the first pressure applied to the first mixture is 0.1T, and the second pressure applied to the second mixture is 0.1T.

[0149] Example 9:

[0150] Different from Example 1, the first pressure applied to the first mixture is 7T, and the second pressure applied to the second mixture is 7T.

[0151] Example 10:

[0152] The difference from Example 1 is that the diameter of the notch is 6 mm.

[0153] Example 11:

[0154] The difference from Example 1 is that the diameter of the notch is 2 mm.

[0155] Example 12:

[0156] The difference from Example 1 is that the diameter of the notch is 1 mm.

[0157] Example 13:

[0158] The difference from Example 1 is that the diameter of the notch is 12 mm.

[0159] test:

[0160] Prepare artificial gastric juice: take 16.4 mL of dilute hydrochloric acid, add 800 mL of water and 10 g of pepsin, and dilute with water to 1000 mL; wherein, the dilute hydrochloric acid is 234 mL of concentrated hydrochloric acid diluted with water to 1000 mL, to obtain 9.5% to 10.5% dilute hydrochloric acid.

[0161] Prepare artificial intestinal fluid: dissolve 6.8 g of potassium dihydrogen phosphate in 500 ml of water and adjust the pH to 6.8 with 0.4% sodium hydroxide solution. Dissolve 10 g of pancreatic enzyme (meeting pharmacopoeia requirements) in an appropriate amount of water. Mix the two solutions and dilute with water to 1000 ml to obtain artificial intestinal fluid.

[0162] Take 500 ml of artificial gastric juice and artificial intestinal juice and put them into the beaker of the disintegration instrument. Use the up and down swing of the disintegration instrument to replace gastrointestinal peristalsis. After the pathfinder capsule has been swung in the artificial gastric juice for 2 hours, take it out and put it into the artificial intestinal juice. Continue to swing it, observe the time when the development marker in the artificial intestinal juice appears, and record it.

[0163] Test results:

[0164] According to the test results of Examples 1 to 9, when the total mass of the ingredients for preparing the second disintegrating body is within the range of 0.1g to 1g and the second pressure is within the range of 0.5T to 5T, and the total mass of the ingredients for preparing the first disintegrating body is within the range of 1.5g to 5g and the first pressure is within the range of 0.5T to 5T, the degradation time of the obtained pathfinder capsule is within 30h to 80h. If the total mass of the ingredients for preparing the first disintegrating body or the second disintegrating body or the preparation pressure is not within the above range, the time for obtaining the predicted results will be affected;

[0165] Similarly, according to the test results of Examples 1 and 10 to 13, the reaction rate of the second disintegrating body can also be controlled by adjusting the size of the notch, thereby achieving precise control of the disintegration time of the pathfinder capsule, so that the degradation time of the pathfinder capsule is within 30 hours to 80 hours. If the diameter of the notch is too large or too small, the degradation time of the pathfinder capsule will be affected, and thus the precise control of the pathfinder capsule disintegration time cannot be achieved.

[0166] In summary, the pathfinder capsule of the present application is prepared using the above-mentioned preparation parameters. When used on patients, the test results can be obtained within 30 to 80 hours, preventing the test results from being affected by premature degradation or long degradation time of the pathfinder capsule in the patient's body, thereby improving the accuracy of the prediction results.

[0167] It should be noted that the detection time can be determined according to the location of the imaging marker. If the imaging marker is set in the first disintegration body, the detection can be carried out within 30 to 80 hours. If the imaging marker is set in both the first and second disintegration bodies, the detection can be carried out within 28 to 32 hours.

[0168] As another optional technical solution of the present application, a specific description is given by taking the arrangement of the accommodating cavity 12 in the second disintegrating body 2 as an example:

[0169] Step S10: Weigh 1.5 g to 5 g of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate in proportion, mix them evenly to obtain a first mixture, and then put it into a tablet press. After pressing at a first pressure, a cylindrical first disintegrating body 1 is obtained.

[0170] In step S10, the mass of the first mixture is 1.5 g to 5 g. Optionally, the mass of the first mixture can be 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g, 4 g, 4.5 g, 5 g, etc., or other values ​​within the range. The mass can be selected according to actual needs and is not limited here. If the mass of the first mixture is too large, too much powder is used for pressing, which will cause the size of the first disintegration body 1 obtained by pressing to be too large or the compaction density to be too high, which will prolong the degradation time of the first disintegration body 1. If the mass of the first mixture is too small, too little powder is used for pressing, which will cause the size of the first disintegration body 1 obtained by pressing to be too small or the compaction density to be too low, which will shorten the degradation time of the first disintegration body 1.

[0171] The mass content of anhydrous lactose in the first mixture is 0% to 60%, the mass content of microcrystalline cellulose is 0% to 40%, the mass content of citric acid is 10% to 50%, the mass content of sodium bicarbonate is 10% to 50%, and the mass content of magnesium stearate is 0.5% to 5%.

[0172] It can be understood that the above-mentioned proportion of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate are selected, the first mixture is placed in a cylindrical mold of a tablet press, and a first pressure is applied to obtain a first disintegrating body 1. Specifically, the first pressure is 0.5T to 5T, and the application time of the first pressure is 1min to 10min. Optionally, the first pressure can be 0.5T, 1T, 1.5T, 2T, 2.5T, 3T, 3.5T, 4T, 4.5T, 5T, etc., and the application time of the first pressure can be 1min, 2min, 3min, 4min, 5min, 6min, 8min, 10min, etc., or other values ​​within the range. It can be selected according to actual needs and is not limited here. If the pressure of the first pressure is too high or the application time is too long, the compaction density of the prepared first disintegration body 1 is too high, and the reaction rate of the digestive fluid and the first disintegration body 1 is slow, which will extend the disintegration time of the first disintegration body 1; if the pressure of the first pressure is too low or the application time is too short, the first disintegration body 1 does not reach the required size after the pressing is completed, and the compaction density of the prepared first disintegration body 1 is too low, and the reaction rate of the digestive fluid and the first disintegration body 1 is fast, which will shorten the disintegration time of the first disintegration body 1.

[0173] Step S20: weigh 0.1 g to 1 g of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinyl pyrrolidone, and magnesium stearate in proportion, mix them evenly to obtain a second mixture, and then put it into a tablet press. After pressing under a second pressure, a hemispherical second disintegrating body 2 with a receiving cavity 12 is obtained.

[0174] In step S20, the mass of the second mixture is 0.1g to 1g. Optionally, the mass of the second mixture can be 0.1g, 0.3g, 0.5g, 0.7g, 0.8g, 0.9g, 1g, etc., or other values ​​within the range. The mass can be selected according to actual needs and is not limited here. If the mass of the second mixture is too large, too much powder is used for pressing, which will cause the size of the second disintegration body 2 obtained by pressing to be too large or the compaction density to be too high, which will prolong the degradation time of the second disintegration body 2. If the mass of the second mixture is too small, too little powder is used for pressing, which will cause the size of the second disintegration body 2 obtained by pressing to be too small or the compaction density to be too low, which will shorten the degradation time of the second disintegration body 2.

[0175] The mass content of glyceryl behenate in the second mixture is 5% to 50%, the mass content of anhydrous lactose is 20% to 50%, the mass content of microcrystalline cellulose is 20% to 50%, the mass content of polyvinyl pyrrolidone is 5% to 10%, and the mass content of magnesium stearate is 0.5% to 2%.

[0176] It is understood that by selecting the above-mentioned proportion of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinyl pyrrolidone, and magnesium stearate, placing the second mixture into a hemispherical mold of a tablet press, and applying a second pressure, a hemispherical second disintegrating body 2 having a receiving cavity 12 can be obtained. Specifically, the second pressure is 0.5T to 5T, and the second pressure is applied for a time of 1 min to 10 min. Optionally, the second pressure can be 0.5T, 1T, 1.5T, 2T, 2.5T, 3T, 3.5T, 4T, 4.5T, 5T, etc., and the second pressure can be applied for a time of 1 min, 2 min, 3 min, 4 min, 5 min, 6 min, 8 min, 10 min, etc., or other values ​​within the range. It can be selected according to actual needs and is not limited here. If the pressure of the second pressure is too high or the application time is too long, the compaction density of the prepared second disintegration body 2 is too high, and the reaction rate of the digestive fluid and the second disintegration body 2 is slow, which will extend the disintegration time of the second disintegration body 2; if the pressure of the second pressure is too low or the application time is too short, the second disintegration body 2 does not reach the required size after the pressing is completed, and the compaction density of the prepared second disintegration body 2 is too low, and the reaction rate of the digestive fluid and the second disintegration body 2 is fast, which will shorten the disintegration time of the second disintegration body 2.

[0177] In step S30, barium sulfate and polymer plastic are extruded and injection molded to obtain a developing marker 4, and the developing marker 4 is placed in the accommodating cavity 12. The edges of the first disintegrating body 1 and the second disintegrating body 2 are bonded together with an adhesive and dried. The weight proportion of barium sulfate in the developing marker is 20% to 60%.

[0178] In step S30, the adhesive layer used to connect the first disintegrating body 1 and the second disintegrating body 2 can be one or more of biological glue, UV curing glue, or ethyl cellulose solution. The mass proportion of barium sulfate in the imaging marker 4 is 20% to 60%. Optionally, the mass proportion of barium sulfate in the imaging marker 4 can be 20%, 30%, 40%, 50%, 60%, etc., or other values ​​within the range. The selection can be based on actual needs and is not limited here. If the mass proportion of barium sulfate in the imaging marker 4 is too small, the indication function of the imaging marker 4 will be unclear when taking an abdominal X-ray. If the mass proportion of barium sulfate in the imaging marker 4 is too large, the barium sulfate will be easily exposed to the surface of the imaging marker 4 during extrusion molding of the barium sulfate and the polymer medical plastic, and it will easily ionize into barium ions, which will cause harm to the human body.

[0179] In step S40, a waterproof film 3 with a thickness of 0.5 μm to 20 μm is formed on the outer surfaces of the first disintegrating body 1 and the second disintegrating body 2 by vapor deposition, and a notch 31 with a diameter of 2 mm to 10 mm is provided on the waterproof film 3 at the end of the second disintegrating body 2 away from the first disintegrating body 1.

[0180] In step S40, the waterproof film 3 is made of parylene film. The specific steps are as follows: the assembled pathfinder capsule is placed in a fixed fixture, and a micron-level waterproof film 3 with a thickness of 0.5 to 20 μm is formed on the surface of the uniformly rotating capsule by vapor deposition. This waterproof film 3 has water-insoluble properties and can effectively isolate the first disintegrating body 1 and part of the second disintegrating body 2 from contact with the digestive fluid.

[0181] After the above preparation steps, the pathfinder capsule of the present application can be obtained. During actual use, the pathfinder capsule passes through the esophagus from the mouth and enters the digestive tract system. At this time, since the degradation time of the second disintegration body 2 is 0 to 30 hours (greater than 0 hours), it can be understood that at 28 to 32 hours (usually around 30 hours), scattered imaging markers 4 can be observed through abdominal X-rays, proving that the pathfinder capsule cannot be discharged smoothly and has been degraded, and it can be judged that the patient has gastrointestinal obstruction, stenosis or Crohn's disease and other problems, and this patient cannot undergo digestive tract capsule endoscopy; if at 28 to 32 hours (usually around 30 hours), regular-related imaging markers 4 are observed through abdominal X-rays, proving that the degradation site of the second disintegration body 2 has not reached the imaging marker 4 (that is, the second disintegration body 2 is not complete). If the pathfinder capsule is located in the colon, it is determined whether the patient can undergo gastrointestinal capsule endoscopy based on the location of the pathfinder capsule in the digestive tract. For example, if the pathfinder capsule is located in the colon, it means that the patient does not have gastrointestinal obstruction, stenosis or Crohn's disease, and the patient can undergo gastrointestinal capsule endoscopy. If the pathfinder capsule is located in the small intestine, it proves that the pathfinder capsule is incarcerated, and the patient can be judged to have gastrointestinal obstruction, stenosis or Crohn's disease, and the patient cannot undergo gastrointestinal capsule endoscopy. If no scattered development markers 4 are observed through abdominal X-ray within 28 to 32 hours (usually around 30 hours), it proves that the pathfinder capsule has been expelled, and the patient can be judged to have no gastrointestinal obstruction, stenosis or Crohn's disease, and the patient can undergo gastrointestinal capsule endoscopy.

[0182] The following further describes the decomposition process of the pathfinder capsule by setting the accommodating cavity 12 in the second disintegrating body 2 in combination with specific embodiments:

[0183] Example 14:

[0184] (1) 5 g of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate in a mass ratio of 36:31:15:15:3 were mixed into a first mixture and placed into a tablet press mold. The mixture was maintained at a pressure of 5 T for 5 minutes, and the mold was opened to obtain a first cylindrical disintegrating body.

[0185] (2) Weigh 1 g of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinylpyrrolidone (PVPK-90), and magnesium stearate in a mass ratio of 10:50:30:9:1, mix them into a second mixture, and place it into a hemispherical mold of a tablet press. Hold the pressure at 5 T for 5 minutes, open the mold, and take out the compressed hemispherical second disintegrating body with a receiving cavity.

[0186] (3) barium sulfate and polymer plastic are extruded and injection molded to obtain a developing marker, and the developing marker is placed in the receiving cavity, and the ends of the first disintegrating body and the second disintegrating body are attached to each other with biological glue and dried; wherein the mass proportion of barium sulfate in the developing marker is 60%;

[0187] (4) A 10 μm waterproof film is formed on the outer surfaces of the first disintegrating body and the second disintegrating body by vapor deposition, and a notch with a diameter of 10 mm is provided in the waterproof film at the end of the second disintegrating body away from the first disintegrating body, finally obtaining a pathfinder capsule with a total length of 25 mm and a diameter of 11.5 mm.

[0188] Example 15:

[0189] Different from Example 14, the total mass of the first mixture is 3 g, and the total mass of the second mixture is 0.5 g.

[0190] Example 16:

[0191] Different from Example 14, the total mass of the first mixture is 1.5 g, and the total mass of the second mixture is 0.1 g.

[0192] Example 17:

[0193] Different from Example 14, the total mass of the first mixture is 0.5 g, and the total mass of the second mixture is 0.05 g.

[0194] Example 18:

[0195] Different from Example 14, the total mass of the first mixture is 7 g, and the total mass of the second mixture is 2 g.

[0196] Example 19:

[0197] Different from Example 14, the first pressure applied to the first mixture is 2.5T, and the second pressure applied to the second mixture is 2.5T.

[0198] Example 20:

[0199] Different from Example 14, the first pressure applied to the first mixture is 0.5T, and the second pressure applied to the second mixture is 0.5T.

[0200] Example 21:

[0201] Different from Example 14, the first pressure applied to the first mixture is 0.1T, and the second pressure applied to the second mixture is 0.1T.

[0202] Example 22:

[0203] Different from Example 14, the first pressure applied to the first mixture is 7T, and the second pressure applied to the second mixture is 7T.

[0204] Example 23:

[0205] Different from Example 14, the diameter of the notch is 6 mm.

[0206] Example 24:

[0207] Different from Example 14, the diameter of the notch is 2 mm.

[0208] Example 25:

[0209] Different from Example 14, the diameter of the notch is 1 mm.

[0210] Example 26:

[0211] The difference from Example 14 is that the diameter of the notch is 12 mm.

[0212] test:

[0213] Prepare artificial gastric juice: take 16.4 mL of dilute hydrochloric acid, add 800 mL of water and 10 g of pepsin, and dilute with water to 1000 mL; wherein, the dilute hydrochloric acid is 234 mL of concentrated hydrochloric acid diluted with water to 1000 mL, to obtain 9.5% to 10.5% dilute hydrochloric acid.

[0214] Prepare artificial intestinal fluid: dissolve 6.8 g of potassium dihydrogen phosphate in 500 ml of water and adjust the pH to 6.8 with 0.4% sodium hydroxide solution. Dissolve 10 g of pancreatic enzyme (meeting pharmacopoeia requirements) in an appropriate amount of water. Mix the two solutions and dilute with water to 1000 ml to obtain artificial intestinal fluid.

[0215] 500 ml of artificial gastric juice and artificial intestinal juice were placed in the beaker of the disintegration apparatus. The up and down swing of the disintegration apparatus was used to replace gastrointestinal peristalsis. After the pathfinder capsule was swung in the artificial gastric juice for 2 hours, it was taken out and placed in the artificial intestinal juice. The swinging was continued. The time for the appearance of the development marker in the artificial intestinal juice was observed and recorded.

[0216] Test results:

[0217] According to the test results of Examples 14 to 26, when the total mass of the components for preparing the second disintegrating body is within the range of 0.1g to 1g and the second pressure is within the range of 0.5T to 5T, and when the total mass of the components for preparing the first disintegrating body is within the range of 1.5g to 5g and the first pressure is within the range of 0.5T to 5T, the developed marker can be observed within 0 to 30 hours. If the total mass of the components for preparing the first disintegrating body or the second disintegrating body or the preparation pressure is not within the above range, the time to obtain the predicted result will be affected.

[0218] Similarly, the test results of Examples 14 and 23-26 show that the reaction rate of the second disintegrating body can be controlled by adjusting the size of the notch, thereby precisely controlling the disintegration time of the pathfinder capsule and ensuring that the observation time of the developing marker is within 0-30 hours. If the notch diameter is too large, the degradation time of the pathfinder capsule will be affected, making it impossible to precisely control the disintegration time of the pathfinder capsule.

[0219] In summary, the pathfinder capsule of the present application is prepared using the above-mentioned preparation parameters. When used on patients, the test results can be obtained within 28 to 32 hours, preventing the test results from being affected by premature degradation or long degradation time of the pathfinder capsule in the patient's body, thereby improving the accuracy of the prediction results.

[0220] Finally, it should be noted that the above embodiments are intended only to illustrate the technical solutions of this application and are not intended to limit them. Although this application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they may modify the technical solutions described in the aforementioned embodiments or replace some or all of the technical features therein with equivalents. However, such modifications or replacements do not deviate from the essence of the corresponding technical solutions within the scope of the technical solutions of the embodiments of this application.

Claims

1. A pathfinder capsule, characterized in that: include: The first disintegration subject; A second disintegrating body connected to both ends of the first disintegrating body; A developing marker is disposed in the first disintegrating body and / or the second disintegrating body; the developing marker is formed by extrusion of a mixture of barium sulfate and a polymer medical plastic; and The waterproof film is plated on the outer surfaces of the first disintegrating body and the second disintegrating body, and the waterproof film disposed at the end of the second disintegrating body away from the first disintegrating body is provided with a notch.

2. The pathfinder capsule according to claim 1, characterized in that: The pathfinder capsule has at least one of the following features: (1) The shape of the first disintegrating body is cylindrical; (2) The shape of the second disintegrating body is hemispherical, and the diameter of the hemispherical shape is the same as that of the cylindrical shape; (3) The total length of the pathfinder capsule is 20 mm to 30 mm; (4) The diameter of the pathfinder capsule is 8 mm to 15 mm; (5) The thickness of the waterproof film is 0.5 μm to 20 μm; (6) The diameter of the notch is 2 mm to 10 mm.

3. The pathfinder capsule according to claim 1, characterized in that: The first disintegrating body is composed of at least one of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate, and magnesium stearate.

4. The pathfinder capsule according to claim 3, characterized in that: The pathfinder capsule has at least one of the following features: (1) The mass content of the anhydrous lactose in the first disintegrating body is 0% to 60%; (2) the mass content of the microcrystalline cellulose in the first disintegrating body is 0% to 40%; (3) The mass content of the citric acid in the first disintegrating body is 10% to 50%; (4) The mass content of the sodium bicarbonate in the first disintegrating body is 10% to 50%; (5) The mass content of the magnesium stearate in the first disintegrating body is 0.5% to 5%.

5. The pathfinder capsule according to claim 1, characterized in that: The pathfinder capsule has at least one of the following features: (1) The mass proportion of the barium sulfate in the imaging marker is 20% to 60%; (2) The polymer medical plastic includes but is not limited to one or more of PVC, TPE, and TPU; (3) The first disintegrating body and / or the second disintegrating body is provided with a receiving cavity, and the developing marker is received in the receiving cavity; (4) The directions and distances of the imaging markers are regularly related when the pathfinder capsule is not decomposed.

6. The pathfinder capsule according to claim 1, characterized in that: The second disintegrating body is composed of at least one of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinyl pyrrolidone, and magnesium stearate.

7. The pathfinder capsule according to claim 6, characterized in that: The pathfinder capsule has at least one of the following features: (1) The mass content of the glyceryl behenate in the second disintegrating body is 5% to 50%; (2) The mass content of the anhydrous lactose in the second disintegrating body is 20% to 50%; (3) The mass content of the microcrystalline cellulose in the second disintegrating body is 20% to 50%; (4) The mass content of the polyvinyl pyrrolidone in the second disintegrating body is 5% to 10%; (5) The mass content of the magnesium stearate in the second disintegrating body is 0.5% to 2%.

8. The pathfinder capsule according to claim 1, characterized in that: The pathfinder capsule has at least one of the following features: (1) The waterproof film is a parylene film; (2) The thickness of the waterproof film is 0.5 μm to 20 μm.

9. A method for preparing a pathfinder capsule, characterized in that: The preparation method of the pathfinder capsule comprises the following steps: Weigh 1.5 g to 5 g of anhydrous lactose, microcrystalline cellulose, citric acid, sodium bicarbonate and magnesium stearate in proportion, mix them evenly to obtain a first mixture, put them into a tablet press, and press them under a first pressure to obtain a cylindrical first disintegrating body; Weighing 0.1 g to 1 g of glyceryl behenate, anhydrous lactose, microcrystalline cellulose, polyvinyl pyrrolidone, and magnesium stearate in proportion, mixing evenly to obtain a second mixture, and then putting the mixture into a tablet press, and pressing under a second pressure to obtain a hemispherical second disintegrating body; wherein the first disintegrating body and / or the second disintegrating body is provided with a containing cavity; The barium sulfate and the polymer plastic are extruded and injection molded to obtain a developing marker, and the developing marker is placed in the receiving cavity. and using a binder to adhere the ends of the first disintegrating body and the second disintegrating body and air-dry them; wherein the mass proportion of the barium sulfate in the developing marker is 20% to 60%; A 0.5-20 μm waterproof film is formed on the outer surfaces of the first disintegration body and the second disintegration body by vapor deposition, and the waterproof film at the end of the second disintegration body away from the first disintegration body is provided with a notch with a diameter of 2-10 mm.

10. The method for preparing the pathfinder capsule according to claim 9, characterized in that: The method for preparing the pathfinder capsule has at least one of the following characteristics: (1) The mass content of the anhydrous lactose in the first mixture is 0% to 60%; (2) the mass content of the microcrystalline cellulose in the first mixture is 0% to 40%; (3) The mass content of citric acid in the first mixture is 10% to 50%; (4) The mass content of the sodium bicarbonate in the first mixture is 10% to 50%; (5) The mass content of magnesium stearate in the first mixture is 0.5% to 5%; (6) the first pressure is 0.5T to 5T, and the application time of the first pressure is 1min to 10min; (7) The mass content of glyceryl behenate in the second mixture is 5% to 50%; (8) The mass content of the anhydrous lactose in the second mixture is 20% to 50%; (9) The mass content of the microcrystalline cellulose in the second mixture is 20% to 50%; (10) The mass content of polyvinyl pyrrolidone in the second mixture is 5% to 10%; (11 The mass content of magnesium stearate in the second mixture is 0.5% to 2%; (12) the second pressure is 0.5T to 5T, and the application time of the second pressure is 1min to 10min; (13) The adhesive is biological glue, UV curing glue or ethyl cellulose solution.

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