WO2023186155A1

WO2023186155A1 - Digestive tract simulation capsule and preparation method therefor

Info

Publication number: WO2023186155A1
Application number: PCT/CN2023/085787
Authority: WO
Inventors: 宋宏姣; 段晓东
Original assignee: 上海安翰医疗技术有限公司
Priority date: 2022-03-31
Filing date: 2023-03-31
Publication date: 2023-10-05
Also published as: CN114712527B; CN114712527A

Abstract

The present application provides a digestive tract simulation capsule and a preparation method therefor. The digestive tract simulation capsule comprises a core layer located in the middle, and a coating layer wrapping the core layer. The core layer is composed of a pharmaceutical excipient and a disintegrant, the pharmaceutical excipient and the disintegrant being both dissolved in a digestive juice; the coating layer is composed of a filler, a sustained-release agent, an adhesive, a flow enhancer and a lubricant, the adhesive being composed of a water-soluble polymer. Under the action of the digestive juice, the adhesive is dissolved so as to form pore microchannels communicating the inside and the outside of the coating layer. The digestive tract simulation capsule is simple, easy to implement, safe and harmless, and a patient can use the digestive tract simulation capsule to detect the smoothness of small intestine before capsule endoscopy examination, thereby providing a powerful support for clinical use of the capsule endoscope.

Description

Digestive tract simulation capsule and preparation method thereof

This application claims priority to the Chinese patent application number 202210334012.2, titled "Digestive tract simulation capsule and preparation method thereof" submitted on March 31, 2022, the entire content of which is incorporated into this application by reference.

Technical field

The present invention relates to the technical field of digestive tract simulation capsules, and in particular to a digestive tract simulation capsule and a preparation method thereof.

Background technique

As the longest organ in the digestive tract, the small intestine is free in the peritoneum and bound by the mesentery to form multiple complex intestinal loops. Small bowel disease has traditionally been diagnosed through small bowel barium meal, angiography, and radionuclide scans. However, due to the special anatomical location of the small intestine, traditional examination techniques face great difficulties, resulting in diagnostic results that suffer from problems such as low positive rate, rough positioning, inaccurate characterization, and many complications.

The advent of capsule endoscopy has made up for the shortcomings of traditional diagnostic methods. It has the advantages of painlessness, non-invasiveness, no cross-infection and convenient examination. It can be used as the first choice examination method for digestive tract diseases, especially small intestinal diseases. However, with the rise of capsule endoscopy, capsule endoscopy retention is an unavoidable problem. Moreover, due to the structural characteristics of the small intestine, retention of capsule endoscopy usually occurs in the small intestine. Existing studies have shown that the overall retention rate of capsule endoscopy is 1-2%.

technical problem

In order to prevent capsule endoscopy from being retained in the intestinal tract, current methods include: excluding patients with a history of digestive tract diseases through consultation or excluding subjects with digestive tract diseases or dysfunction through imaging methods. Even so, it is still difficult to avoid retention during capsule endoscopy.

Technical solutions

In view of this, in order to detect the safety of patients swallowing a capsule endoscope and prevent the capsule endoscope from being retained in the human body, this application provides a digestive tract simulation capsule used to detect the smoothness of the small intestine before performing capsule endoscopy and its The preparation method provides strong support for the clinical use of capsule endoscopy.

In response to the above problems, the present invention provides a digestive tract simulation capsule, which includes a tablet core layer located in the middle and a coating layer surrounding the tablet core layer. The tablet core layer is composed of pharmaceutical excipients and a disintegrant. The pharmaceutical excipient and disintegrant are both soluble in digestive juice; the coating layer is composed of a second filler, a sustained-release agent, a second binder, a second glidant, a second lubricant and an indicator. ; The second adhesive is composed of water-soluble polymers. Under the action of digestive juice, the second adhesive dissolves to form a channel in the coating layer that connects the inside and outside of the coating layer.

Further, in the coating layer, the content of each component in the coating layer in terms of mass percentage is:

Second filler: 30-55wt%; sustained release agent 40-65wt%; second binder 2-10wt%; second glidant 0.1-5%; second lubricant 0.1-1%; indicator 1 -15wt%.

Further, the indicator is a medical plastic particle with an indicator color.

Further, in the core layer of the tablet, the content of the pharmaceutical excipient is 70-90wt% in terms of mass percentage, and the content of the disintegrant is 10-30wt%.

Further, the pharmaceutical excipients in the core layer of the tablet mainly consist of a first filler, a first binder, a first glidant, a first lubricant and a disintegrant. In terms of mass percentage, each component is in the The components of the tablet core layer are: first filler 55-80wt%; first binder 2-10wt%; first glidant 0.1-5wt%; first lubricant 0.1-1wt%; disintegrant 10 -30wt%.

Further, the first filler and the second filler each include one or more of starch, sucrose, dextrin, lactose, pregelatinized starch, cellulose and inorganic salts; the first sticky The mixture and the second adhesive include one or more of hypromellose and povidone K30; the first glidant and the second glidant include micronized silica gel and talc powder. and one or more of silica; the first lubricant and the second lubricant include magnesium stearate.

Further, the disintegrant is selected from one or more of croscarmellose sodium, croscarmellose sodium, cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose. .

Further, the thickness of the coating layer is 2-5 mm, and the thickness of the tablet core layer is 3-10 mm.

Furthermore, the disintegration time of the digestive tract simulation capsule is 30-80 hours.

This application also provides a method for preparing the digestive tract simulation capsule according to claim 1, which includes the following steps: weighing 55-80wt% of the filler; 2-10wt% of the binder; 0.1-5wt% of the glidant; Lubricant 0.1-1wt%; disintegrant 10-30wt%, each component is pressed to form the tablet core layer;

Weigh the filler: 30-55wt%; sustained release agent 40-65wt%; adhesive 2-10wt%; glidant 0.1-5%; lubricant 0.1-1%; indicator 1-15wt%, wrap the After the core layer, the tablet is pressed to form a coating layer.

The above description is only an overview of the technical solution of the present invention. In order to have a clearer understanding of the technical means of the present invention, it can be implemented according to the content of the description, and in order to make the above and other objects, features and advantages of the present invention more obvious and understandable. , the following is a detailed description of the preferred embodiments, together with the accompanying drawings.

beneficial effects

In this application, the second filler provides skeleton support for the coating layer, and the coating layer contains brightly colored indicators (such as medical plastic particles with indicator colors). The adhesive in the coating layer reacts when encountering It dissolves in the digestive juice, especially the water in the digestive juice, and forms tiny pores in the coating layer, providing a path for the digestive juice to contact the core layer of the tablet. Moreover, the sustained-release agent controls the sustained-release time of the coating layer, thereby ensuring that the digestive tract simulation capsule basically maintains the shape of the capsule within a predetermined time. Moreover, this application does not require additional pores to provide passages, but utilizes tiny pores formed after the second binder is dissolved in water to allow digestive juices to pass through the coating layer. The structure is simple, the preparation process is simpler, the disintegration time of the digestive tract simulation capsule can be controlled more accurately, and the disintegration time is not affected by the pH value of the digestive tract.

Description of drawings

In order to explain the technical solutions of the embodiments of the present invention more clearly, the drawings required to be used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and therefore do not It should be regarded as a limitation of the scope. For those of ordinary skill in the art, other relevant drawings can be obtained based on these drawings without exerting creative efforts.

Figure 1 is a schematic structural diagram of the digestive tract simulation capsule of the present application.

Figure 2 is a schematic diagram of partial dissolution of the coating layer.

Figure 3 is a schematic diagram of the core layer of the tablet being expanded and the coating layer being partially stretched.

Figure 4 is a schematic diagram of the coating layer being broken.

Embodiments of the invention

Specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. Obviously, the described embodiments are only some of the embodiments of the present invention, but not all of the embodiments. Based on the description of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the scope of protection of the present invention.

In the description of the present invention, unless otherwise explicitly stipulated and limited, the terms "setting", "installation", "connection", etc. should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection. Ground connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium. For those of ordinary skill in the art, the specific meanings of the above terms can be understood on a case-by-case basis.

The terms "upper", "lower", "left", "right", "front", "back", "top", "bottom", "inner", "outer", etc. indicate an orientation or positional relationship based on the attached The orientation or positional relationship shown in the figures, or the orientation or positional relationship in which the invention product is customarily placed when used, is only for the convenience of description and to simplify the description, and does not indicate or imply that the device or component referred to must have a specific orientation. , are constructed and operated in specific orientations and therefore should not be construed as limitations of the invention.

Furthermore, the terms "first", "second", "third", etc. are only used to distinguish elements with similar properties, but do not indicate or imply relative importance or a specific order.

Furthermore, the terms "includes," "includes," or any other variations thereof, are intended to cover a non-exclusive inclusion of elements in addition to those listed and may also include other elements not expressly listed.

Based on the external size and shape of the capsule endoscope, this application provides a simple, safe and harmless digestive tract simulation capsule that patients can judge independently. Before capsule endoscopy, the patient is asked to swallow a simulated capsule similar in quality, shape, and volume to determine the smoothness of the simulated capsule in the digestive tract. If the simulated capsule is retained in the intestine (or stays in the intestine for longer than a predetermined time), it can degrade and be excreted from the body.

Figure 1 shows a schematic structural diagram of the digestive tract simulation capsule of the present application. As shown in FIG. 1 , the digestive tract simulation capsule 100 includes a tablet core layer 110 located in the middle and a coating layer 120 wrapping the tablet core layer 110 .

The core layer 110 of the tablet is composed of pharmaceutical excipients and a disintegrant. Both the pharmaceutical excipients and the disintegrant are soluble in digestive juices. The content of the pharmaceutical excipients is 70-90wt%, and the content of the disintegrant is 10-30wt%. In one embodiment, the pharmaceutical excipients of the tablet core layer 110 mainly consist of a first filler, a first binder, a first glidant and a first lubricant. Wherein, the first filler includes one or more of starch, sucrose, dextrin, lactose, pregelatinized starch, cellulose (the cellulose can be microcrystalline cellulose and/or ethyl cellulose) and inorganic salts. species, wherein the inorganic salt may be calcium sulfate and/or calcium hydrogen phosphate. Moreover, the first filler can be digested under the action of digestive enzymes in the digestive juice. In terms of mass percentage, the first filler accounts for 55-80 wt% of the total content of the core layer 110 of the tablet. The first binder may include hypromellose and/or povidone K30 (polyvinylpyrrolidone, PVPK30) water-soluble polymer compound. The first adhesive has excellent solubility and physiological compatibility. On the one hand, it can bind the first filler and the like, and on the other hand, it can also be dissolved in digestive juice (water). In terms of mass percentage, the first adhesive agent has excellent solubility and physiological compatibility. A binder accounts for 2-10 wt% of the total content of the core layer 110. The first flow aid may include one or more of micronized silica gel, talcum powder and silica to facilitate tableting and molding of the tablet core layer 110. In terms of mass percentage, the first flow aid occupies the tablet core layer 110. 0.1-5wt% of the total content. The first lubricant may be magnesium stearate, etc., and the first lubricant accounts for 0.1-1 wt% of the total content of the core layer 110 in terms of mass percentage.

In a preferred embodiment of the present application, the disintegrant is selected from croscarmellose sodium (CCMC-Na), croscarmellose sodium (CMS-Na), cross-linked polyvinylpyrrolidone (PVPP) and low-substituted hydroxypropyl cellulose (L-HPC), etc. The so-called disintegrant refers to a substance that enables the core layer 110 of the tablet to be broken into fine particles in the digestive juice. In this application, the disintegrant is a cold water-soluble anionic starch derivative. It has super water absorption due to its hydrophilic groups in its structure, especially carboxymethyl and sodium carboxymethyl. (up to 200 times the original volume) and the characteristics of rapid water absorption and expansion. Add an appropriate amount of disintegrant to the solid preparation. Its strong and rapid water absorption characteristics can introduce water into the solid preparation to increase the capillary pores, increase the contact between water and the solid preparation, and improve the water absorption and swelling effect. This will repeatedly absorb, swell, and absorb water. ..., the complete solid preparation will be quickly disintegrated into fine particles or powder.

In the embodiment of the present application, the coating layer 120 is mainly composed of a second filler, a sustained-release agent, a second adhesive, a second glidant, a second lubricant, and the like. Further, the coating layer 120 also includes an indicator, which is a brightly colored medical plastic particle. In terms of mass percentage, the indicator accounts for 1-15 wt% of the total content of the coating layer 120 . The second filler can be one of starch, sucrose, dextrin, lactose, pregelatinized starch, cellulose (the cellulose can be microcrystalline cellulose and/or ethyl cellulose) and inorganic salts, or A variety of inorganic salts may be calcium sulfate and/or calcium hydrogen phosphate, and the second filler accounts for 30-55 wt% of the total content of the coating layer 120 in terms of mass percentage. In this embodiment, the sustained-release agent includes one or more of glyceryl behenate, carnauba wax, stearyl alcohol, stearic acid, hydrogenated castor oil, or triglyceride. In terms of mass percentage, the sustained-release agent The releasing agent accounts for 40-65wt% of the total content of the coating layer 120. The addition of a sustained release agent can slow down the dissolution speed of the coating layer 120 . Preferably, the sustained-release agent can be glyceryl behenate. Glyceryl behenate is a lipid sustained-release matrix, which is obtained by esterification of behenic acid and glycerol. The main components are behenic acid monoglyceride, behenic acid monoglyceride, and behenic acid monoglyceride. Diglyceryl behenate and triglyceride behenate. The second binder can be a water-soluble polymer compound such as hypromellose or povidone K30 (polyvinylpyrrolidone, PVPK30), which will dissolve in the digestive juice. In terms of mass percentage, the second binder Accounting for 2-10wt% of the total content of the coating layer 120. The second glidant may include one or more of micronized silica gel, talcum powder and silica to facilitate the tableting of the coating layer 120. In terms of mass percentage, the second glidant accounts for the coating layer 120. 0.1-5wt% of the total content can increase the hardness of the coating layer 120. The second lubricant may be magnesium stearate, and in terms of mass percentage, the second lubricant accounts for 0.1-1 wt% of the total content of the coating layer 120 . In other embodiments, the indicator may also be other bioincompatible, non-toxic and harmless materials, such as bioincompatible dyes, etc.

Furthermore, the indicator in the coating layer 120 may also include a developer to display its specific location in the human body under the action of an external device.

In one embodiment, the coating layer 120 is composed of barium sulfate, calcium hydrogen phosphate, glyceryl behenate, povidone K30, and magnesium stearate. The thickness of the coating layer 120 is 2-5mm. The amount of disintegrant in the tablet core layer 110 is 10-30wt%. By controlling the thickness of the coating layer 120 and the amount of disintegrant in the tablet core layer 110, the gastrointestinal tract simulation capsule can be made to disintegrate after 30 hours.

In this application, among the components of the coating layer 120, the second adhesive will dissolve relatively quickly in the digestive juice, and the sustained-release agent will not swell or corrode in water to ensure the integrity of the basic shape of the coating layer 120. . Therefore, within a certain period of time, the skeleton of the coating layer 120 remains basically intact, which can better simulate the appearance of the capsule endoscope. At the same time, because some components in the coating layer 120 are dissolved, for example, the adhesive is dissolved in the digestive juice, tiny pores are formed in the coating layer 120 so that the outside of the coating layer 120 is connected to the tablet core layer 110 through the pores. The digestive juice, especially the water in the digestive juice, can reach the core layer 110 through the pores. As shown in FIG. 2 , some components are dissolved and the digestive juice enters the tablet core layer 110 . In FIG. 2 , the digestive tract simulation capsule 100 is located in the intestinal lumen 130 , and the direction pointed by the arrow is the direction in which liquid flows through the coating layer 120 and into the tablet core layer 110 .

When the tablet core layer 110 encounters digestive juice, it absorbs water and expands. As the degree of expansion increases, the coating layer 120 located on the outer layer is gradually opened, that is, the schematic diagram of the coating layer being opened is shown in Figure 3. As the tablet core layer 110 further expands and the coating layer 120 is finally broken by the tablet core layer 110, the simulated capsule 100 disintegrates. Figure 4 is a schematic diagram of the disintegration of the simulated capsule in the digestive tract. In FIG. 4 , the tablet core layer 110 is dissolved and broken into fragments 112 of fine particles in the digestive juice, and the coating layer 120 is broken to form coating layer fragments 122 . At this time, the indicator can be excreted out of the body along with the excrement, and the patient can clearly see the fragments of these medical plastic particles in the excrement. By observing the color of excreta (such as feces), patients can independently determine whether the digestive tract simulation capsule has disintegrated, thereby determining whether capsule endoscopy is suitable for use.

In this application, compared with the technical solution of using other chemical substances such as methylene blue as indicators, the use of colored medical plastic particles has good bioincompatibility and is almost not absorbed by the human body and is excreted from the body. In contrast, if methylene blue is used as an indicator, it will have adverse side effects during clinical use. After methylene blue enters the human digestive tract, part of the methylene blue may be methylated, and a small amount of methylene blue may be excreted in the feces through bile. Excretion, and part of the methylene blue is absorbed by the intestines when exposed to the intestinal environment and excreted in the urine. Clinical judgment is mainly based on the prototype of methylene blue in urine. However, the methylene blue prototype excreted in urine is small and takes a long time to be excreted, which greatly increases the examination time.

In the above-mentioned digestive tract simulation capsule 100, the coating layer 120 provides skeleton support, and the coating layer 120 contains brightly colored medical plastic particle indicators. The second filler in the coating layer 120 provides support. Povidone The second binder such as K30 provides a passage for the digestive juice to enter the tablet core layer 110, and the sustained-release agent controls the sustained-release time of the coating layer 120 so that it can basically maintain the shape of the capsule within a certain period of time. Therefore, this application does not require additional holes to provide access, has a simple structure, and a simpler manufacturing process. It can control the disintegration time of the digestive tract simulation capsule more accurately, and the disintegration time is not affected by the pH value of the digestive tract.

The above-mentioned digestive tract simulation capsule 100 of the present application adopts powder direct compression technology, specifically: the tablet core layer is pressed first, and then the coating layer is pressed.

First, various materials for the tablet core layer are weighed, placed in a mixer and stirred evenly, and then tableted in a tablet press to form the tablet core layer 110 .

Next, various materials of the coating layer 120 are weighed and placed in a mixer to make them uniform. After wrapping the tablet core layer 110 in the center, the tablet core layer 110 is pressed in a tablet press.

When the digestive tract simulation capsule 100 is taken orally, the digestive juice contacts the coating layer 120 . After a certain period of time, the digestive juice, especially the water in the digestive juice, infiltrates into the tablet core layer 110. After the disintegrant in the tablet core layer 110 absorbs a large amount of liquid, the volume increases rapidly, causing the coating layer 120 to rupture and destroying the entire digestive tract. Simulate capsule 100 degradation. By adjusting the thickness of the coating layer 120 and the amount of disintegrant in the tablet core layer 110, the gastrointestinal tract simulation capsule can be disintegrated within a specified time. In this application, the thickness of the coating layer 120 is controlled to be 2-5 mm, the amount of disintegrant in the tablet core layer 110 is controlled to be 10-30 wt%, and the disintegration time is controlled to be 30-80 hours. Moreover, in this embodiment, in order to better realize the simulation effect of the gastrointestinal tract simulation capsule 100, the thickness of the core layer 110 is controlled to 3-10 mm, thereby ensuring that the diameter of the gastrointestinal tract simulation capsule 100 (the core layer 110 The sum of the thickness and the thickness of the coating layer 120) is similar to the diameter of the capsule endoscope. In a preferred embodiment, the thickness of the core layer 110 is 3-5 mm.

The method of use is as follows: the patient eats easily digestible food and prepares the intestines the day before the gastrointestinal simulation capsule examination. After the digestive tract is cleansed, swallow one digestive tract simulation capsule with water. Observe whether the simulated capsule is completely discharged from the body within the specified time. If completely excluded, the patient can undergo capsule endoscopy. If bright-colored plastic particles are found in the patient's excrement after the specified time, the patient will not be suitable for capsule endoscopy.

In this application, the disintegration process of the digestive tract simulation capsule is made faster by adding a disintegrant. The disintegration time of the digestive tract simulation capsule can be controlled by adjusting the thickness of the coating layer and the amount of disintegrant in the tablet core layer. The coating layer contains colored medical plastic particles to facilitate patients' independent judgment and can be used in the civilian field. At the same time, this application adopts powder direct pressing technology, and the preparation process is simple and easy to implement. The disintegration time of the digestive tract simulation capsule can be controlled more accurately, and the disintegration time is not affected by the pH of the digestive tract.

Example 1:

Tablet core layer: calculated as a percentage of the total mass of the tablet core layer, 51.5wt% lactose, 20wt% starch, 5wt% polyvinylpyrrolidone K30, 5wt% silica, 1wt% magnesium stearate, 17.5wt% croscarmellidone Cellulose sodium (CCMC-Na).

Coating layer: Based on the percentage of the total mass of the coating layer, 30wt% calcium hydrogen phosphate, 52.5wt% glyceryl behenate, 6wt% polyvinylpyrrolidone K30, 0.5wt% silicon dioxide, 1wt% magnesium stearate, 10wt% medical plastic particles.

Thickness of coating layer: 4mm

Chip core layer thickness: 5mm

Processing method: dry powder direct compression, first compress the tablet core layer and then the coating layer

Disintegration time: 30-40h.

Example 2:

Tablet core layer: calculated as a percentage of the total mass of the tablet core layer, 51.5wt% lactose, 25wt% starch, 7wt% polyvinylpyrrolidone K30, 0.5wt% silica, 1wt% magnesium stearate, 15wt% croscarmellidone Cellulose sodium (CCMC-Na).

Coating layer: calculated as a percentage of the total mass of the coating layer, 48.5wt% calcium hydrogen phosphate, 40wt% glyceryl behenate, 5wt% polyvinylpyrrolidone K30, 0.5wt% silicon dioxide, 1wt% magnesium stearate, 5wt% medical plastic particles.

Thickness of coating layer: 5mm

Chip core layer thickness: 3mm

Disintegration time: 40-50h.

Example 3:

Tablet core layer: Based on the percentage of the total mass of the tablet core layer, 60wt% lactose, 20wt% starch, 8.5% polyvinylpyrrolidone K30, 0.5% silica, 1% magnesium stearate, 10% croscarmellose Sodium chloride (CCMC-Na).

Coating layer: Based on the percentage of the total mass of the coating layer, 35% ethyl cellulose, 47.5% glyceryl behenate, 2wt% polyvinylpyrrolidone K30, 0.4wt% silicon dioxide, 0.1wt% magnesium stearate , 15wt% medical plastic particles.

Thickness of coating layer: 5mm

Chip core layer thickness: 3mm

Disintegration time: 50-80h.

Example 4:

Tablet core layer: calculated as a percentage of the total mass of the tablet core layer, 80wt% lactose, 8.5wt% polyvinylpyrrolidone K30, 0.5wt% silica, 1%wt magnesium stearate, 10wt% croscarmellose sodium

Coating layer: Based on the percentage of the total mass of the coating layer, 34wt% starch, 60wt% glyceryl behenate, 3.5wt% polyvinylpyrrolidone K30, 0.5wt% silicon dioxide, 1wt% magnesium stearate, 1wt% Medical plastic pellets.

Among them, the thickness of the core layer: 5mm

Coating layer thickness: 4mm

Disintegration time: 50-80h.

Example 5:

Tablet core layer: calculated as a percentage of the total mass of the tablet core layer, 58.5wt% lactose, 10wt% polyvinylpyrrolidone K30, 0.5wt% silica, 1wt% magnesium stearate, 30wt% croscarmellose sodium

Coating layer: calculated as a percentage of the total mass of the coating layer, 45wt% starch, 40wt% ethyl cellulose, 3.5wt% polyvinylpyrrolidone K30, 0.5wt% silicon dioxide, 1wt% magnesium stearate, 10wt% medical Plastic particles.

Among them, the thickness of the core layer: 5mm

Coating layer thickness: 4mm

Disintegration time: 20-30h.

Comparative example 1:

A digestive tract simulation capsule system is provided, including a digestive tract simulation capsule and a radio detector. The system has exactly the same shape and size as capsule endoscopy. It is mainly composed of degradable lactose materials and does not contain lenses or other electronic components. It contains barium and wireless radio frequency sensors that can be developed under X-rays. There are time indicators at both ends of the digestive tract simulation capsule. When incarceration occurs in a narrow part, the time indicator of the simulation capsule can dissolve under the action of digestive juice, causing the entire simulation capsule to degrade. However, this method is complicated in process, the patient has poor independent judgment, and X-rays radiate to the human body to a certain extent, and requires external equipment assistance, which is relatively complicated.

Comparative example 2:

A sustained-release tablet for digestive tract emptying function detection is provided. The sustained-release tablet includes a skeleton tablet core composed of a mixture of insoluble pharmaceutical excipients, a coating layer made of edible wax, and a single hole channel for controlling the dissolution time of the sustained-release tablet. . The sustained-release tablet can remain stable during normal human evacuation time.

However, once the side of the pore is impacted, the sustained-release tablet will be difficult to dissolve in the digestive tract. The positioning of this sustained-release tablet in the intestine requires the assistance of X-rays, which radiates certain radiation to the human body and has low accuracy.

Comparative example 3:

A digestive tract pathfinding capsule is provided, which includes an outer membrane made of slow-release enteric material and a support material soluble in digestive juice; the cavity of the outer membrane capsule contains urine that can be absorbed by the human body and discharged. Liquid color change indicator (methylene blue).

The methylene blue indicator used has adverse side effects in clinical use, and after oral administration of methylene blue, the methylene blue prototype is excreted in the urine in a small amount and for a long time, which greatly increases the examination time.

The above are only specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any person familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed in the present invention. All are covered by the protection scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the appended claims.

Industrial applicability

The coating layer 120 of this application provides skeleton support, and the coating layer 120 contains brightly colored indicator medical plastic particles. The calcium hydrogen phosphate in the tablet core layer 110 provides support. Polyvinylpyrrolidone K30 in the coating layer 120 is The digestive juice provides a passage into the tablet core layer 110, and glyceryl behenate controls the sustained release time of the coating layer 120 so that it can basically maintain the shape of the capsule within a certain period of time. Therefore, this application does not require additional holes to provide access, has a simple structure, and can control the disintegration time of the digestive tract simulation capsule more accurately, and the disintegration time is not affected by the pH value of the digestive tract.

Claims

A digestive tract simulation capsule, characterized in that the digestive tract simulation capsule includes a tablet core layer located in the middle and a coating layer surrounding the tablet core layer, and the tablet core layer is composed of pharmaceutical excipients and disintegrants, The pharmaceutical excipients and disintegrants are both soluble in digestive juice; the coating layer is composed of a second filler, a sustained release agent, a second binder, a second glidant, a second lubricant and an indicator. ; The second adhesive is composed of water-soluble polymers. Under the action of digestive juice, the second adhesive dissolves to form a channel in the coating layer that connects the inside and outside of the coating layer.
The digestive tract simulation capsule according to claim 1, characterized in that: in the coating layer, the content of each component in the coating layer in terms of mass percentage is:

Second filler: 30-55wt%; sustained release agent 40-65wt%; second binder 2-10wt%; second glidant 0.1-5%; second lubricant 0.1-1%; indicator 1 -15wt%.
The digestive tract simulation capsule according to claim 1, wherein the indicator is a medical plastic particle with an indicator color.
The digestive tract simulation capsule according to claim 1, characterized in that: in the tablet core layer, the content of the pharmaceutical excipients is 70~90wt% in terms of mass percentage, and the content of the disintegrating agent is 10-30wt%.
The digestive tract simulation capsule according to claim 4, characterized in that: the pharmaceutical excipients of the tablet core layer mainly consist of a first filler, a first binder, a first glidant, a first lubricant and a disintegrating agent. The composition of the solution, in terms of mass percentage, the components of each component in the core layer of the tablet are: 55-80wt% of the first filler; 2-10wt% of the first binder; 0.1-5wt of the first glidant %; first lubricant 0.1-1wt%; disintegrant 10-30wt%.
The digestive tract simulation capsule according to claim 5, characterized in that: the first filler and the second filler include starch, sucrose, dextrin, lactose, pregelatinized starch, cellulose and inorganic salts one or more of; the first adhesive and the second adhesive include one or more of hypromellose and povidone K30; the first glidant and The second glidant includes one or more of micronized silica gel, talc and silicon dioxide; the first lubricant and the second lubricant include magnesium stearate.
The digestive tract simulation capsule according to claim 5, characterized in that: the disintegrant is selected from the group consisting of croscarmellose sodium, croscarmellose sodium, cross-linked polyvinylpyrrolidone and low Substitute one or more of the hydroxypropyl celluloses.
The digestive tract simulation capsule according to claim 1, characterized in that: the thickness of the coating layer is 2-5 mm, and the thickness of the core layer is 3-10 mm.
The digestive tract simulation capsule according to claim 1, characterized in that: the disintegration time of the digestive tract simulation capsule is 30-80 hours.
A method for preparing digestive tract simulation capsules according to claim 1, characterized in that it includes the following steps:

Weigh 55-80wt% filler; 2-10wt% binder; 0.1-5wt% glidant; 0.1-1wt% lubricant; 10-30wt% disintegrant, and press each component to form a tablet. core layer;

Weigh the filler: 30-55wt%; sustained release agent 40-65wt%; adhesive 2-10wt%; glidant 0.1-5%; lubricant 0.1-1%; indicator 1-15wt%, wrap the After the core layer, the tablet is pressed to form a coating layer.