Oral apparatus for injection administration in digestive tract

Abstract

Disclosed is an oral apparatus for injection administration in the digestive tract, comprising a housing, a trigger assembly, and an administration assembly. The housing comprises a top cover at the upper part thereof, a middle housing placed in the middle, and a base located at the bottom. The material density of the middle housing is less than the material density of the base, so that the apparatus is in the shape of a roly-poly toy. The trigger assembly comprises a soluble fixing member, an elastic member, and a transmission member. The administration assembly comprises a microneedle and a drug. The apparatus provided by the present invention, by means of an arranged liquid storage bag, greatly increases the drug loading capacity and can theoretically achieve a drug loading capacity of 50 mg, which is a significant improvement over the prior art.

Description

Devices for oral administration or intragastric injection

[0001] Cross-references to related applications

[0002] This application claims priority to patent application No. CN2024109680343, filed on July 18, 2024, entitled “Device for Oral Administration via Injection into the Digestive Tract”, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] This invention relates to the field of pharmaceutical technology, and more specifically to a device for administering medication orally or via injection into the digestive tract. Background Technology

[0004] Oral administration is the most common method of drug delivery, with advantages such as convenience and good patient compliance. However, oral formulations are not very suitable for large biological molecules due to factors such as the need to pass through the highly acidic environment of the intestine. At present, large biological molecules such as insulin, peptides, antibodies, and vaccines cannot be delivered orally and are generally administered by injection. However, patient compliance with injection is low, and some patients have a fear of needles. In addition, injection administration generally requires professional medical staff to perform, which is inconvenient and limits the application of such drugs.

[0005] Microneedling is a form of injection that creates drug delivery channels on the skin surface after needle insertion, effectively promoting transdermal drug absorption. Compared to oral administration, which relies on the digestive tract for absorption, microneedling offers faster absorption and higher drug utilization, along with advantages such as being minimally invasive, painless, and convenient. Combining microneedling with oral administration—by embedding microneedles within capsules to achieve the rapid absorption effect of injection via oral administration—is an ideal drug delivery method that has attracted widespread attention in research and clinical applications.

[0006] The biggest drawback of oral capsule microneedles is their low drug loading capacity. In particular, the overall drug loading capacity of solid microneedles is difficult to exceed the milligram level. Liquid microneedles generally only contain the drug liquid in the conical needle tip of the microneedle, and the drug loading capacity is also relatively small. Therefore, there is an urgent need to develop a device that can deliver drugs orally into the digestive tract with a large drug loading capacity. This device can also eliminate injection pain, increase patient compliance, and achieve the absorption efficiency of injection through oral administration. Summary of the Invention

[0007] To address the technical problems in the prior art, the present invention provides a device for oral administration via injection into the digestive tract. Specifically, the present invention mainly includes the following:

[0008] This invention provides a device for oral administration via injection into the digestive tract, comprising a housing, a triggering component, and a drug delivery component, wherein:

[0009] The outer casing includes a top cover at its upper part, an intermediate shell in the middle part, and a base at its bottom. The material density of the intermediate shell is less than that of the base, thereby making the device roly-poly-shaped.

[0010] The triggering component includes a soluble fixing component, an elastic component, and a transmission component;

[0011] The drug delivery component includes microneedles and drugs.

[0012] In some embodiments, the device for oral administration via injection into the digestive tract according to the present invention further includes a reservoir, the top surface of which is connected to the transmission member, the bottom surface of which is connected to a microneedle, and the bottom surface of which has an opening communicating with the microneedle below it.

[0013] In some embodiments, according to the present invention, the device for oral administration via injection into the digestive tract includes a top cover that is an arc-shaped cover made of a soluble material, an intermediate shell that is a hollow frustum with an opening at the lower end and convex arc-shaped sides around the frustum, and a base that is a hollow inverted frustum with openings at the top and bottom and convex arc-shaped sides around the inverted frustum.

[0014] In some embodiments, according to the present invention, the device for oral administration via injection into the digestive tract includes a transmission component comprising an outer cylinder and a guide post. The outer cylinder is a hollow cylinder with an open top. The guide post is vertically disposed at the center of the outer cylinder, and a first through hole is provided at the upper end of the guide post. The elastic component is a spring, which is fitted onto the guide post. Two second through holes are provided on the top surface of the intermediate shell, and the two second through holes are symmetrically disposed on both sides of the guide post. The fixing component is a soluble thread, which passes through the first through hole and the two second through holes and is bound together.

[0015] In some embodiments, the device for oral administration via injection into the digestive tract according to the present invention includes a microneedle comprising a needle hub, a needle tip, and a needle cap. The needle tip is a hollow frustum or pyramidal shape, and the needle cap is fitted over the lower part of the needle tip to seal the needle tip. The shape and size of the needle cap are adapted to the needle tip, and the shape of the needle cap is a hollow cone or pyramidal shape.

[0016] In some embodiments, the device for oral administration via injection into the digestive tract according to the invention, wherein the reservoir is made of an elastic material, and the pressure A generated by the elastic member, the deformation resistance B of the reservoir, and the resistance C of the microneedle to tissue penetration satisfy the conditions: A>B>C, and A>B+C.

[0017] In some embodiments, the device for oral administration via injection into the digestive tract according to the present invention includes an annular adhesive layer at the bottom of the outer shell, the annular adhesive layer being fixed to the bottom surface of the base, the shape and size of the adhesive layer being adapted to the bottom surface of the base, and the material of the adhesive layer including a viscous polymer and optional adjuvant drugs.

[0018] In some embodiments, the device for oral administration via injection into the digestive tract according to the present invention includes a water-resistant membrane at the bottom of the outer shell, the water-resistant membrane being an insoluble thin film material and having a thickness of 50-100 μm.

[0019] In some embodiments, the device for oral administration via injection into the digestive tract according to the present invention, wherein the microneedle is configured as an integrally formed soluble solid microneedle module, the soluble solid microneedle module being filled with a solid drug or coated with a solid drug, thereby enabling flexible switching between solid and liquid drug administration through a modular design.

[0020] In some embodiments, the device for oral administration via injection into the digestive tract according to the present invention, wherein the needle hub and needle tip are made of insoluble or poorly soluble materials, and the needle cap is made of a soluble material selected from at least one of the following: sodium hyaluronate, sodium carboxymethyl cellulose, pullulan, polyvinyl alcohol, water-soluble polysaccharides, hydroxypropyl methylcellulose, carboxymethyl cellulose, dextran, alginate, starch and gelatin blends, polyvinylpyrrolidone-polyvinyl alcohol, poly(methyl vinyl ether-co-maleic anhydride), trehalose, polyethylene glycol diacrylate, polyethylene glycol, methacrylamide gelatin, and methacrylamide hyaluronic acid.

[0021] The beneficial effects of this invention include:

[0022] 1. By setting up a reservoir, the present invention greatly increases the drug loading capacity, theoretically achieving a drug loading capacity of 50mg, which is a significant improvement compared to existing devices that administer drugs orally via injection into the digestive tract;

[0023] 2. By setting a stainless steel base, the center of gravity is lowered as much as possible, similar to a roly-poly toy, ensuring that the bottom of the drug delivery device always faces downwards, thus ensuring safe and reliable drug delivery. Attached Figure Description

[0024] Figure 1 is a cross-sectional view of the overall structure of an exemplary microneedle of the present invention inside the outer shell.

[0025] Figure 2 is an exemplary cross-sectional view of the overall structure of the present invention when a portion of the microneedles extends outside the outer shell.

[0026] Figure 3 is a cross-sectional view of the overall structure of an exemplary liquid storage bladder of the present invention when it is squeezed.

[0027] Figure 4 is an exploded view of an exemplary overall device of the present invention.

[0028] Figure 5 is a side view of an exemplary housing of the present invention.

[0029] Figure 6 is a three-dimensional schematic diagram of a microneedle exemplified by the present invention.

[0030] Figure 7 is a three-dimensional schematic diagram of an exemplary transmission component of the present invention.

[0031] Figure 8 is a three-dimensional schematic diagram of an exemplary intermediate shell of the present invention.

[0032] Figure 9 shows the pressure field distribution of shells with different shapes as examples of the present invention.

[0033] Figure 10 shows the velocity field distribution of shells with different shapes as examples of the present invention.

[0034] Figure 11 shows the velocity field resistance values ​​of different shaped shells exemplified by the present invention.

[0035] Figure 12 is a comparison diagram of a soluble thread before and after dissolution, as exemplified by the present invention.

[0036] Figure 13 is a sample image of an exemplary high center of gravity device of the present invention.

[0037] Figure 14 is a sample image of an exemplary low center of gravity device of the present invention.

[0038] Figure 15 is a schematic diagram of the changes in blood glucose concentration in the animal experiment of Example 2 of the present invention.

[0039] Figure 16 is a schematic diagram of the percentage change in blood glucose in animal experiments in Example 2 of the present invention.

[0040] Figure 17 is a comparative schematic diagram of injection and subcutaneous injection using the device of Example 1 of the present invention.

[0041] Explanation of reference numerals in the attached drawings: 1000. Outer shell; 1100. Top cover; 1200. Intermediate shell; 1210. Second through hole; 1220. First step; 1300. Base; 1310. Second step; 1400. Adhesive layer; 1500. Water-resistant membrane; 2000. Triggering component; 2100. Fixing component; 2200. Elastic component; 2300. Transmission component; 2310. Outer cylinder; 2320. Guide post; 2321. First through hole; 3000. Drug delivery component; 3100. Microneedle; 3110. Needle seat; 3120. Needle tip; 3130. Needle cap; 3200. Reservoir. Detailed Implementation

[0042] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0043] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that the upper and lower limits of the range and each intermediate value between them are specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0044] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. While only preferred structures and materials have been described herein, any structures and materials similar to or equivalent to those described herein may be used in the implementation or testing of this invention.

[0045] Furthermore, the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., used in the specification and claims to indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, are merely for the convenience of describing the invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the invention. In addition, terms such as "first," "second," etc., are also used to describe various elements, areas, parts, etc., and do not specifically refer to any order or sequence, and should not be considered as limitations. It should be understood that such terms can be replaced under appropriate conditions, and the embodiments of the invention described herein can operate in orientations other than those described or exemplified herein.

[0046] In this invention, the term "fixed connection" includes both detachable and non-detachable fixed connections. Detachable fixed connections include bolted connections, while non-detachable fixed connections include welding.

[0047] Example 1

[0048] As shown in Figures 1-8, this embodiment provides a device for oral administration via injection into the digestive tract, including a housing 1000, a triggering component 2000, and a drug delivery component 3000.

[0049] The outer shell 1000 is the casing covering the trigger component 2000 and the drug delivery component 3000. To ensure smooth movement of the outer shell 1000 within the digestive tract, three different shapes of the outer shell 1000 were designed for comparison. Using CFD (Computational Fluid Dynamics) technology, resistance calculations and simulations were performed to optimize the resistance of the three shapes. As shown in Figures 9-11, shape 3 has the lowest resistance. However, because the upper part of shape 3 is a sharp cone, the internal space is small and cannot meet the requirements for installing mechanical structures and drugs. Therefore, considering all factors, shape 1, i.e., an oval or egg-shaped structure with a flat bottom, is the optimal solution.

[0050] The outer casing 1000 includes a top cover 1100, a middle casing 1200, and a base 1300. The top cover 1100 is located at the top of the outer casing 1000 and is an arc-shaped cover plate with a higher center and lower ends. The middle casing 1200 is located in the middle of the outer casing 1000 and is preferably a hollow frustum-shaped structure with an open bottom. More preferably, the hollow frustum-shaped structure has convex arc-shaped sides around its perimeter. The top cover 1100 and the middle casing 1200 can be fixedly connected or detachably connected. The fixed connection can be adhesive, and the detachable connection can be threaded. The base 1300 is located at the bottom of the outer casing 1000 and is preferably a hollow inverted frustum-shaped structure with open top and bottom. More preferably, the hollow inverted frustum-shaped structure has convex arc-shaped sides around its perimeter.

[0051] The bottom opening of the base 1300 is preferably circular, and the bottom surface of the base has an annular structure. The base 1300 and the intermediate housing 1200 can be movably connected, and the movable connection can be a threaded connection or a snap-fit ​​connection, preferably a threaded connection.

[0052] Furthermore, the height of the outer shell 1000 is preferably 15-20 mm, and the maximum diameter of the middle shell 1200 is preferably 13-18 mm.

[0053] The center of gravity has a decisive impact on the uprightness of the device. Experiments were conducted on different materials for each component of the outer shell 1000, demonstrating that lowering the center of gravity of the outer shell 1000 by making the material density of the middle shell 1200 less than that of the base 1300 allows the entire device to quickly stand upright, as shown in Figure 14. The base 1300, made of stainless steel, can quickly regain its upright position due to its lower center of gravity, as shown in Figure 13. Conversely, the base 1300, made of resin, cannot stand upright independently due to its higher center of gravity. Through precise design and a low center of gravity, the entire device resembles a self-righting toy, ensuring that the base 1300 always faces downwards. This allows for automatic positioning of the injection microneedles on the gastric mucosa, enabling drug delivery via the digestive tract into the stomach.

[0054] The base 1300 is preferably made of stainless steel, more preferably food-grade stainless steel. Food-grade stainless steel will not leach various alloys and harmful substances in acidic or alkaline solutions. Austenitic or ferritic stainless steel can be selected, such as 1Cr18Ni9Ti, 0Cr19Ni9, 1Cr18Ni9, 1Cr17Ni2, etc. The main component of gastric acid is dilute hydrochloric acid. Under normal circumstances, the pH of gastric acid is 1.8-3.5, and it can be as low as 0.9 when fasting for a long time. At a human body temperature of 36.5℃, this concentration of dilute hydrochloric acid is difficult to corrode ordinary stainless steel, and the harmful elements produced are basically negligible.

[0055] The triggering component 2000 includes a fixing component 2100, an elastic component 2200, and a transmission component 2300. The triggering component 2000 is used to drive the drug delivery component 3000 to administer the drug. The fixing component 2100 is made of a soluble material that gradually dissolves upon contact with a liquid. The fixing component 2100 is preferably a soluble thread. The elastic component 2200 is an elastic member, which can be a spring, a sheet, etc. The elastic component 2200 is preferably a cylindrical helical spring. The elasticity of a spring is generally greater than that of a sheet, and a cylindrical helical spring is convenient for fixed installation. The elastic component 2200 is initially in a compressed state when installed. The transmission component 2300 transmits the elastic force of the elastic component 2200 to the drug delivery component 3000, pushing part of the drug delivery component 3000 out of the outer shell 1000 for injection. The spring is placed inside the transmission component 2300. The transmission component 2300 includes an outer cylinder 2310 and a guide post 2320. The outer cylinder 2310 is preferably a hollow cylinder with an open top. Preferably, the outer diameter of the outer cylinder 2310 is slightly smaller than the inner diameter of the intermediate shell 1200, so that the transmission component 2300 can move freely up and down within the outer shell 1000. The guide post 2320 is vertically arranged at the center of the outer cylinder 2310. The guide post 2320 can be in the shape of a cylinder, square prism, polyhedral prism, etc., preferably a cylinder. The outer diameter of the guide post 2320 is slightly smaller than the inner diameter of the spring, so that the spring can be fitted onto the guide post 2320, making the spring less prone to movement and maintaining stability. The height of the guide post 2320 is higher than the height of the outer cylinder 2310, and the height of the guide post 2320 is less than the height of the spring in its natural state. A first through hole 2321 is horizontally arranged at the upper end of the guide post 2320, so that the fixing component 2100 can pass through it.

[0056] Furthermore, the top surface of the intermediate housing 1200 is provided with two second through holes 1210, which penetrate the top surface. The two second through holes 1210 are symmetrically arranged on both sides of the guide post 2320. The second through holes 1210 can be circular, semi-circular, elliptical, etc. The fixing member 2100 passes through the first through hole 2321 and the two second through holes 1210 and is fixed together. The fixing method can be selected according to the structure and material of the fixing member 2100, such as plug-in, snap-fit, or binding. The fixing member 2100 fixes the transmission member 2300 to the intermediate housing 1200, so that the spring is kept in a compressed state.

[0057] Furthermore, an annular first step 1220 is provided on the inner wall of the intermediate shell 1200. Preferably, the inner and outer diameters of the first step 1220 are the same as the inner and outer diameters of the outer cylinder 2310. When the spring is in the initial compressed state, the upper surface of the outer cylinder 2310 abuts against the first step 1220 to keep the spring position stable.

[0058] Furthermore, the soluble filaments are preferably made of PVA as the main material, as shown in Figure 12. PVA is a water-soluble polymer that is non-toxic and harmless, and has a certain toughness and strength, which can firmly fix the compression spring. Moreover, PVA filaments will dissolve when they come into contact with water, thereby quickly releasing the compressed spring.

[0059] Furthermore, the top cover 1100 is made of a soluble material, and its main components are soluble components, including but not limited to modified starch, gelatin, polyvinyl alcohol and other polymer materials. The main function of the top cover 1100 is to protect the soluble thread from premature dissolution after the drug delivery device is swallowed, and at least to prevent leakage at the top cover before it reaches the stomach. The dissolution time of the top cover 1100 can be set as needed.

[0060] The drug delivery assembly 3000 includes microneedles 3100 and drugs. The microneedles 3100 include a needle hub 3110, a needle tip 3120, and a needle cap 3130. The type of drug can be selected according to the patient's condition. The needle hub 3110 is preferably a cylindrical structure with an open top. One or more needle tips 3120 are disposed on the bottom surface of the needle hub 3110. The needle tip 3120 can be a hollow frustum or prismatic structure. The central channel of the needle tip 3120 serves as a drug flow channel and is connected to the needle hub 3110. Both the needle hub 3110 and the needle tip 3120 can store drug solution, further increasing the drug loading capacity.

[0061] Furthermore, the upper end face of the needle holder 3110 is provided with an annular folded edge. Preferably, the outer diameter of the folded edge of the needle holder 3110 is the same as the outer diameter of the outer cylinder 2310. The inner wall of the bottom end of the base 1300 is provided with a second step 1310 that is adapted to the needle holder 3110. The inner diameter of the second step 1310 is larger than the diameter of the cylindrical hollow cylinder of the needle holder 3110, and the outer diameter of the second step 1310 is larger than the outer diameter of the folded edge of the needle holder 3110, so that the needle holder 3110 can move freely up and down within the outer shell 1000. The inner diameter of the second step 1310 is smaller than the outer diameter of the folded edge of the needle holder 3110, so that the second step 1310 blocks the folded edge of the needle holder 3110 to prevent the microneedle 3100 from sliding out of the outer shell 1000.

[0062] The needle cap 3130 is fitted under the needle tip 3120 to seal the needle tip 3120. The shape and size of the needle cap 3130 are adapted to the needle tip 3120. The shape of the needle cap 3130 can be a hollow cone or pyramid. The pointed end of the needle cap 3130 is used to puncture the tissue. The needle cap 3130 is made of a soluble material, while the needle hub 3110 and the needle tip 3120 are made of insoluble or poorly soluble materials. The middle of the needle tip 3120 is a liquid delivery channel. After the needle cap 3130 punctures the tissue, the drug solution is injected into the tissue through the middle channel of the needle tip 3120. After the acupuncture injection is completed, the needle cap 3130 can dissolve on its own. After dissolution, the entire microneedle 3100 no longer has a sharp head, avoiding damage to the mucous membrane during the expulsion process.

[0063] Needle cap 3130 can be manufactured by molding. The material of needle cap 3130 is a soluble material. The material of needle cap 3130 should meet the following requirements: 1) good biocompatibility and non-toxic, and has been used in clinical practice; 2) stable material properties that do not affect drug activity; 3) sufficient mechanical strength to penetrate the skin without breaking; 4) wide application and strong plasticity; 5) able to dissolve in the skin and control the drug release rate.

[0064] The raw materials for preparing the needle cap 3130 include, but are not limited to, the following: sodium hyaluronate (HA), sodium carboxymethyl cellulose (CMC-Na), pullulan, polyvinyl alcohol (PVA), water-soluble polysaccharides, hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), dextran, alginate, starch and gelatin blend, polyvinylpyrrolidone-polyvinyl alcohol (PVP-PVA), poly(methyl vinyl ether-co-maleic anhydride) (PMVE / MA), trehalose, PEGDA, polyethylene glycol (PEG), methacrylamide gelatin (GELMA), and methacrylamide hyaluronic acid (HAMA). It can be one or a combination of the above materials, with sodium hyaluronate (HA) being preferred. HA is a safe and reliable biomaterial and drug carrier with good biocompatibility, high viscoelasticity, plasticity, and permeability. HA with different relative molecular masses has different mechanical properties, and different relative molecular weights of HA can be selected according to actual needs when preparing microneedles. Currently, HA is widely used in the preparation of microneedles. When administered via microneedles, HA can dissolve rapidly in tissue fluid and undergo biodegradation in vivo.

[0065] The needle hub 3110 and the needle tip 3120 are made of insoluble or poorly soluble materials, and can be selected from at least one or a combination of high-toughness resins, such as polyethylene, polyvinyl chloride, polycarbonate, polystyrene and light-curing adhesives, or metals, such as stainless steel.

[0066] The spring is kept in a compressed state by the control of the soluble thread. After the soluble thread melts, the spring releases pressure and pushes the transmission component 2300. The transmission component 2300 pushes the needle seat 3110 downward, thereby pushing the microneedle tip 3120 out of the outer shell 1000 for drug injection.

[0067] The number of needle tips can be one or more, evenly distributed in an array on the needle base. In this embodiment, there are three needle tips. The dissolution time of the needle tips varies from 5 minutes to 24 hours depending on the material used. The needle tip length is preferably 2-3.5 mm, and more preferably 2.5 mm.

[0068] Furthermore, a water-resistant membrane 1500 is provided on the bottom surface of the base 1300 to prevent external liquids from entering the outer shell 1000 and dissolving the needle cap 3130. When the microneedle 3100 moves downward, the needle cap 3130 pierces the water-resistant membrane 1500 and continues to move into the tissue. The material of the water-resistant membrane 1500 includes, but is not limited to, high molecular materials such as polyethylene, paraffin mixture, polytetrafluoroethylene, rubber, and polyolefins. The thickness of the water-resistant membrane 1500 is preferably 50-100 μm.

[0069] Furthermore, the drug delivery assembly 3000 is also equipped with a reservoir 3200, which stores liquid medication, greatly increasing the drug loading capacity of the drug delivery device. The upper end of the reservoir 3200 is connected to the transmission component 2300, and the lower end of the reservoir 3200 is connected to the microneedle seat 3110. The reservoir 3200, transmission component 2300, and microneedle seat 3110 can be fixedly connected or detachably connected. The fixed connection can be adhesive. Preferably, the upper and lower surfaces of the reservoir 3200 are circular. Preferably, the outer diameter of the upper surface of the reservoir 3200 is slightly smaller than the outer diameter of the bottom surface of the transmission component 2300, and the outer diameter of the lower surface of the reservoir 3200 is slightly smaller than the outer diameter of the folded edge of the needle seat 3110, so that the two ends of the reservoir 3200 abut more stably and reliably when compressed and expanded.

[0070] The reservoir 3200 has an opening on its bottom surface, preferably circular. This circular opening allows the medication stored in the reservoir to flow into the microneedle 3100 below, significantly increasing the device's drug loading capacity. The maximum drug loading capacity can reach 50mg, far exceeding that of devices that only store medication within the microneedle. Preferably, the diameter of the opening on the bottom surface of the reservoir 3200 is slightly smaller than the inner diameter of the cylinder of the needle holder 3110, to facilitate smoother flow of the medication from the reservoir into the microneedle.

[0071] Furthermore, the reservoir 3200 is preferably a conical cylinder that is thicker at both ends and thinner in the middle, which provides more compression space, increases the deformation of the reservoir, and facilitates the squeezing of the liquid in the reservoir 3200 into the microneedle 3100.

[0072] The reservoir 3200 is made of an elastic material. Under the compression of the upper spring, it can deform and inject the drug solution inside the reservoir 3200 into human tissue through the lower microneedle channel. The reservoir 3200 is preferably made of medical-grade silicone rubber. Silicone rubber has high elasticity and excellent biocompatibility. It is non-irritating and non-toxic to human tissue. It can maintain its original elasticity and softness during contact with body fluids and tissues and will not be degraded. It is a very stable inert material.

[0073] By analyzing the forces involved in the acupuncture process, it can be seen that the entire acupuncture process involves three forces: the elastic downward pressure of the spring (A), the deformation resistance of the reservoir (B), and the resistance of the microneedle to the tissue (C). To complete the required injection action, it is necessary to ensure that A > B > C and A > B + C. In this embodiment, a precision force measuring device was used to measure and compare the three forces. The data for the three forces are A = 0.741 kgf, B = 0.293 kgf, and C = 0.011 kgf, respectively. It can be seen from the data that the designed device fully meets the required force conditions.

[0074] Furthermore, an annular adhesive layer 1400 is provided at the bottom of the base 1300. The adhesive layer 1400 is fixed to the bottom surface of the base 1300. The shape and size of the adhesive layer 1400 are adapted to the bottom surface of the base 1300. Preferably, the inner and outer diameters of the adhesive layer 1400 are consistent with the inner and outer diameters of the annular opening on the bottom surface of the base 1300.

[0075] The adhesive layer 1400 serves two purposes: 1. as an auxiliary fixation method; 2. the adhesive layer contains hemostatic Chinese medicine components, promoting the healing of acupuncture wounds. In this embodiment, mechanical measurements show that the maximum adhesive force of the adhesive layer is 0.005 kgf, and the weight of the capsule device is 8-10 g. During swallowing, the esophageal wall is in a naturally vertical state. Since the adhesive force is less than the gravity, in positions such as the vertical esophagus, the adhesive force cannot overcome gravity to fix the drug delivery device to the esophageal wall, and the drug easily "slides" into the stomach for adhesion and fixation. Furthermore, the low center of gravity of the base 1300 further ensures that the base of the drug delivery device is fixed to the stomach wall. The fixation of the drug delivery device is mainly achieved by the low center of gravity of the outer shell, which is positioned at the bottom of the stomach by gravity. At the same time, the adhesive layer 1400 assists in fixation. During swallowing, the esophageal wall is always vertical. Without the action of gravity, the adhesive layer 1400 at the bottom alone cannot fix the drug delivery device to the esophageal wall, thus avoiding the device being fixed to the vertical esophageal wall.

[0076] Furthermore, the adhesive layer 1400 material includes, but is not limited to, extracts of traditional Chinese medicines such as Panax notoginseng and Bletilla striata that have anti-inflammatory and hemostatic effects, as well as adhesive polymers such as carbomer and hydroxypropyl methylcellulose.

[0077] As the drug delivery device slides down the esophageal wall into the stomach, due to the low center of gravity of the base 1300, it stops at the lateral bend at the bottom of the stomach. The adhesive layer 1400 adheres to the stomach wall, and the top cover 1100 gradually dissolves until tissue fluid enters the outer shell 1000. The soluble filaments begin to dissolve, the spring is released, and the spring pushes the transmission component 2300, the reservoir 3200, and the microneedle 3100 downwards until the edge of the microneedle base 3110 abuts against the second step 1310. At this point, the microneedle tip 3120 extends beyond the outer shell 1000 and pierces the stomach wall. Since the stomach wall is about 3-4 mm thick and the needle tip is about 2.5 mm thick, the needle tip will not pierce the stomach wall but will only pierce under the mucus layer. Furthermore, there are few sensory nerves in the digestive tract, so it will not cause pain to the patient. The spring continues to press the reservoir, thereby deforming the reservoir and squeezing the drug liquid in the reservoir into the microneedle, thus accelerating the drug flow rate.

[0078] To further expand its applicability, this device can flexibly switch between solid and liquid drug delivery through modular design. The microneedle 3100 can be made into a one-piece molded dissolvable solid microneedle. The dissolvable solid microneedle is filled with solid drug inside or coated with solid drug on the surface. When the microneedle 3100 comes into contact with tissue fluid, it can dissolve and release the drug.

[0079] A common method for fabricating solid microneedles is to first dissolve biological drugs in water to prepare an aqueous solution. Then, dissolve solidifiable and soluble materials, such as hyaluronic acid, gelatin, and modified polyvinyl alcohol, in this drug-containing aqueous solution. The mixture is then poured into a microneedle mold for filling, drying, and demolding, resulting in a soluble drug-containing solid microneedle. After insertion into the skin, the needle, composed of soluble materials, gradually dissolves in the tissue fluid, releasing the drug simultaneously to achieve the therapeutic purpose. Furthermore, the soluble solid microneedle preferably has a pointed tip for easy tissue insertion.

[0080] The top surface of the intermediate shell 1200 prevents the spring from sliding out of the upper part of the outer shell 1000. Furthermore, the second step 1310 on the inner wall of the base 1300 blocks the microneedle hub 3110, preventing the spring, transmission component 2300, reservoir 3200, and microneedle hub 3110 inside the outer shell 1000 from sliding out, thus avoiding harm to the human body. The needle cap 3130 is soluble and dissolves on its own after injection, without damaging the mucous membrane. Additionally, the entire device has a closed elliptical structure, and the metal components inside the outer shell 1000 do not directly contact tissue. After injection, the entire device is excreted through the digestive tract. Moreover, some drugs containing metal or even electronic devices have been used clinically without showing any risk of harm to the human body.

[0081] Example 2

[0082] In this embodiment, an animal experiment was conducted using a beagle as an experimental animal, with insulin as a model drug, using the device in Example 1 as an example. The results are shown in Figures 15-17. The overall efficacy (change in blood glucose concentration and change in blood glucose percentage) is comparable to that of subcutaneous injection. Therefore, the feasibility of in vivo injection using the device in Example 1 is verified.

[0083] Although the invention has been described with reference to exemplary embodiments, it should be understood that the invention is not limited to the disclosed exemplary embodiments. Various adjustments or changes may be made to the exemplary embodiments described in this specification without departing from the scope or spirit of the invention. The scope of the claims should be interpreted in the broadest possible sense to cover all modifications and equivalent structures and functions.

Claims

1. A device for oral injection administration within the digestive tract, characterized in that, The device comprises a shell (1000), a trigger assembly (2000) and a drug delivery assembly (3000), wherein: The shell (1000) comprises a top cover (1100) on the upper part, an intermediate shell (1200) in the middle part and a base (1300) in the bottom part, the material density of the intermediate shell (1200) is less than that of the base (1300), so that the device is like a "Tumbler". The trigger assembly (2000) comprises a soluble fixed component (2100), an elastic component (2200) and a transmission component (2300). The drug delivery assembly (3000) comprises a microneedle (3100) and a drug.

2. The device for oral injection into the digestive tract according to claim 1, wherein The drug delivery assembly (3000) further comprises a liquid storage bag (3200), the top surface of the liquid storage bag (3200) is connected with the transmission component (2300), the bottom surface of the liquid storage bag (3200) is connected with the microneedle (3100), and the bottom surface of the liquid storage bag (3200) is provided with an opening which is in communication with the microneedle (3100) below.

3. The device for oral injection into the digestive tract according to claim 1, wherein The top cover (1100) is an arc-shaped cover plate, the material of the top cover (1100) is soluble material, the intermediate shell (1200) is a hollow circular truncated cone with an open lower end, the outer side of the circular truncated cone is convex, and the base (1300) is a hollow inverted circular truncated cone with an open upper and lower end, the outer side of the inverted circular truncated cone is convex.

4. The device for oral injection into the digestive tract according to claim 1, wherein The transmission component (2300) comprises an outer cylinder (2310) and a guide column (2320), the outer cylinder (2310) is a hollow cylinder with an open upper end, the guide column (2320) is vertically arranged in the center of the outer cylinder (2310), and the upper end of the guide column (2320) is provided with a first through hole (2321); the elastic component (2200) is a spring, the spring is sleeved on the guide column (2320); two second through holes (1210) are arranged on the top surface of the intermediate shell (1200), the two second through holes (1210) are symmetrically arranged on both sides of the guide column (2320), and the fixed component (2100) is a soluble thread, the fixed component (2100) passes through the first through hole (2321) and the two second through holes (1210) and is tied together.

5. The device for oral injection into the digestive tract according to claim 1, wherein The microneedle (3100) comprises a needle seat (3110), a needle tip (3120) and a needle cap (3130), the needle tip (3120) is a hollow circular truncated cone or a hollow prismatic truncated cone, the needle cap (3130) is sleeved on the lower part of the needle tip (3120) to seal the needle tip (3120), the shape and size of the needle cap (3130) are matched with those of the needle tip (3120), and the needle cap (3130) is a hollow circular cone or a hollow prismatic cone.

6. The device for oral injection into the digestive tract according to claim 2, wherein The liquid storage bag (3200) is made of elastic material, and the pressure A generated by the elastic component, the deformation resistance B of the liquid storage bag (3200) and the resistance C of the microneedle (3100) penetrating into the tissue satisfy the condition: A>B+C.

7. The device for oral injection into the digestive tract according to claim 1, wherein The bottom of the shell (1000) is provided with an annular adhesive layer (1400), which is fixed on the bottom surface of the base (1300), the adhesive layer (1400) is matched with the bottom surface of the base (1300) in shape and size, and the material of the adhesive layer (1400) comprises a high-molecular adhesive and optional auxiliary drugs.

8. The device for oral injection into the digestive tract according to claim 1, wherein The bottom of the shell (1000) is provided with a water barrier film (1500), which is a non-soluble film material, and the thickness of the water barrier film (1500) is 50-100 μm.

9. The device for oral injection into the digestive tract according to claim 5, wherein The microneedle (3100) is provided as an integrally formed soluble solid microneedle module, the inside of the soluble solid microneedle module is filled with solid drugs or coated with solid drugs on the surface, so as to realize the switching of solid drugs and liquid drugs through the modular design.

10. The device for oral injection into the digestive tract according to claim 5, wherein The needle seat (3110) and the needle tip (3120) are made of non-soluble or hardly soluble materials, and the needle cap (3130) is made of soluble materials selected from at least one of the following: sodium hyaluronate, sodium carboxymethyl cellulose, pullulan, polyvinyl alcohol, water-soluble polysaccharide, hydroxypropyl methyl cellulose, carboxymethyl cellulose, dextran, alginate, starch and gelatin blend, polyvinylpyrrolidone-polyvinyl alcohol, poly(methyl vinyl ether-co-maleic anhydride), trehalose, polyethylene glycol diacrylate, polyethylene glycol, methacrylated gelatin, methacrylated hyaluronic acid.

Images