Directional adjustment assembly for in vivo deployment of temporary implants and applications thereof

Abstract

This invention provides a directional adjustment component for deploying temporary implants in the body and its application. The directional adjustment component includes a gravity regulator for carrying the implant and a capsule disposed on one side of the gravity regulator. A drug-loading area is provided on the side of the gravity regulator away from the capsule. The drug-loading area has a vent that can be sealed or opened and communicates with the capsule. The capsule includes a main capsule, a first reactant cavity for holding a first reactant, and a second reactant cavity for holding a second reactant. The main capsule and the second reactant cavity are separated by a second soluble isolation device, and the second reactant cavity and the first reactant cavity are separated by a first soluble isolation device. The first and second reactants can react to generate gas. The directional adjustment component of this application can accurately and rapidly orient the implant while also rapidly expelling it from the body.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and more specifically, to a directional adjustment component for deploying temporary implants in vivo and its application. Background Technology

[0002] In recent years, the global biopharmaceutical market has developed rapidly, showing a high-speed growth trend. An increasing number of large-molecule biopharmaceuticals have been developed for the treatment of various major diseases such as infectious diseases, diabetes, and cancer. However, large-molecule biopharmaceuticals present several challenges. On the one hand, their large molecular weight, complex structure, and strong hydrophilicity make it difficult to penetrate multiple biological barriers in the body. On the other hand, these drugs have poor stability and are easily metabolized and broken down by gastric acid, enzymes, and enterohepatic circulation. Traditional oral and transdermal administration routes result in low bioavailability of large-molecule biopharmaceuticals, leading to a relatively limited clinical administration method, primarily injection. While injection can effectively improve the bioavailability of large-molecule biopharmaceuticals, it can cause discomfort, pain, and fear in patients, and may even lead to skin necrosis and infection at the injection site, thus reducing patient adherence.

[0003] Therefore, there is an urgent need for a new type of drug delivery system. Summary of the Invention

[0004] The present invention aims to provide a directional adjustment component for deploying temporary implants in vivo and its application therein, which can rapidly self-locate while reducing the time spent in vivo.

[0005] The embodiments of the present invention can be implemented as follows:

[0006] In a first aspect, the present invention provides a directional adjustment assembly for deploying a temporary implant in the body, comprising a gravity regulator for carrying the implant and a capsule disposed on one side of the gravity regulator, wherein a drug-loading area is disposed on the side of the gravity regulator away from the capsule, and an exhaust port that is connected to the capsule and can be sealed or opened is disposed on the drug-loading area; the capsule comprises a main capsule, a first reactant cavity for holding a first reactant and a second reactant cavity for holding a second reactant, wherein the main capsule and the second reactant cavity are separated by a second soluble isolation device, and the second reactant cavity and the first reactant cavity are separated by a first soluble isolation device; the first reactant and the second reactant are capable of reacting to generate gas.

[0007] In an optional embodiment, the gravity regulator is made of at least one of polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA), poly(glycolide-lactide) copolymer (PGLA), and poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG).

[0008] And / or, the axial length of the gravity regulator is 2-5 mm, the length in the direction perpendicular to the axis is 5-16 mm, and the mass of the gravity regulator is greater than the mass of the capsule.

[0009] In an optional embodiment, the capsule is made of at least one of polyurethane (PU), polyvinyl chloride (PVC), polyamide (PA), polyethylene (PE), and polyethylene terephthalate (PET).

[0010] And / or, after the first reactant and the second reactant react to generate gas, the height of the capsule is 10-20 mm.

[0011] In an optional embodiment, the first soluble isolation device is soluble under a first preset condition; the second soluble isolation device is soluble under a second preset condition.

[0012] And / or, the first soluble isolation device dissolves before the second soluble isolation device;

[0013] And / or, the second soluble isolation device is a device that isolates solids and liquids but allows air to pass through.

[0014] In an optional embodiment, the gravity regulator includes an upper gravity regulator layer and a lower gravity regulator layer that are fixed to each other. The capsule has an opening, which is fitted onto the gravity regulator. The capsule at the edge of the opening is fixed between the upper gravity regulator layer and the lower gravity regulator layer.

[0015] Alternatively, the capsule may have an opening, which is fitted onto the gravity regulator, and a soluble elastic ring may be fitted onto the opening to fix the capsule to the gravity regulator.

[0016] Alternatively, the gravity regulator may have an annular groove along its circumference, and the capsule may have an opening, which is fitted onto the gravity regulator, and the capsule at the opening may have a snap ring for engaging with the annular groove.

[0017] Secondly, the present invention provides a self-orienting microneedle unit, comprising an orientation adjustment component as described in any of the foregoing embodiments and a microneedle substrate that can be separated from the gravity regulator, wherein the microneedle substrate is located within the drug loading area and covers the outlet of the vent hole, and microneedles for drug loading are disposed on the microneedle substrate.

[0018] In an optional embodiment, the microneedle substrate is made of at least one of polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), and polyacrylamide (PAM).

[0019] And / or, the method for preparing the microneedle substrate includes: solidifying the raw material liquid on the surface of the gravity regulator to form the microneedle substrate.

[0020] And / or, the microneedle includes a microneedle body and a drug loaded in the microneedle.

[0021] In an optional embodiment, the drug includes at least one of growth hormone, parathyroid hormone, antibody, chemotherapeutic agent, insulin, glucagon-like peptide, immunosuppressant, vaccine or antiparasitic agent.

[0022] And / or, the microneedles are made of a biodegradable material;

[0023] And / or, the microneedle includes a microneedle base and a microneedle tip, with the drug loaded at the microneedle tip.

[0024] Thirdly, the present invention provides a swallowable microneedle device, comprising: a self-orienting microneedle unit as described in any one of the foregoing embodiments and a capsule for encapsulating the self-orienting microneedle unit.

[0025] In an optional embodiment, there are two or more self-orienting microneedle units, and the self-orienting microneedle units are separated by partitions.

[0026] And / or, the capsule is capable of dissolving under a third preset condition to release the self-directing microneedle unit.

[0027] The beneficial effects of the orientation adjustment component, self-orienting microneedle unit, and swallowable microneedle device for deploying temporary implants in vivo provided by the embodiments of the present invention include:

[0028] In this application, when the directional adjustment component first enters the body, the vent is blocked by the drug or drug substance in the drug-carrying area. After reaching the designated area of ​​the intestine, such as the colon, the first reactant and the second reactant can react and generate gas, so that the capsule and the gravity regulator together form a structure similar to a roly-poly toy, which can quickly form orientation in the colon area. At the same time, the peristaltic contraction wave of the intestine can squeeze the microneedles on the microneedle base against the intestinal wall, and the microneedles penetrate the mucosa so that the drug carried can act on the intestinal wall. Subsequently, the microneedle base and the gravity regulator detach from the vent located in the drug-carrying area and are exposed, so that the capsule is quickly expelled from the body along with the gravity regulator after venting. Attached Figure Description

[0029] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings 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 should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0030] Figure 1 This is a schematic diagram of the self-directing microneedle unit in this application (the capsule is not inflated).

[0031] Figure 2 This is a schematic diagram of the structure of the self-directing microneedle unit in this application (capsule inflation);

[0032] Figure 3 This is a schematic diagram of the cyst structure in this application;

[0033] Figure 4 The working mechanism of the self-oriented microneedle unit in this application;

[0034] Figure 5 This is a schematic diagram of the first connection method between the capsule and the gravity regulator in this application;

[0035] Figure 6 for Figure 5 A partial schematic diagram;

[0036] Figure 7 This is a schematic diagram of a second connection method between the capsule and the gravity regulator in this application;

[0037] Figure 8 This is a schematic diagram of a third connection method between the capsule and the gravity regulator in this application;

[0038] Figure 9 This is a schematic diagram of the microneedles and gravity regulator in this application;

[0039] Figure 10 This is a schematic diagram of the shape of the microneedle in this application;

[0040] Figure 11 This is a schematic diagram of the swallowable microneedle device in this application;

[0041] Figure 12 This is a schematic diagram showing the position of the swallowable microneedle device in this application;

[0042] Figure 13 This is a schematic diagram of the swallowable microneedle device for Comparative Example 1.

[0043] Icons: 100-Self-orienting microneedle unit; 101-Capsule; 102A-First reactant container cavity; 102-First soluble isolation device; 102B-Second reactant container cavity; 103-Second soluble isolation device; 107-Vent hole; 108-Gas; 104-Gravity regulator; 104-1-Upper layer of gravity regulator; 104-2-Lower layer of gravity regulator; 101-1-Capsule at the opening edge; 102-1-Soluble elastic ring; 102-2-Annular groove; 105-Microneedle base; 106-Microneedle; 106B-Bottom of microneedle; 106A-Tip of microneedle; 106D-Drug; 200-Capsule; 300-Separator. Detailed Implementation

[0044] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The components of the embodiments of the present invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0045] Therefore, the following detailed description of the embodiments of the invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the invention without inventive effort are within the scope of protection of the invention.

[0046] It should be noted that similar labels and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.

[0047] In the description of this invention, it should be noted that if terms such as "upper," "lower," "inner," or "outer" are used to indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship in which the product of this invention is usually placed, they are only for the convenience of describing this 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 this invention.

[0048] Furthermore, the terms "first" and "second" are used only to distinguish descriptions and should not be interpreted as indicating or implying relative importance.

[0049] It should be noted that, where there is no conflict, the features in the embodiments of the present invention can be combined with each other.

[0050] To improve the bioavailability of the macromolecular drug 106D, implantable 106D delivery pumps can be used, but these require semi-permanent implantation and still have many limitations associated with intravenous injection. Using microneedles for 106D delivery presents challenges in positioning, as the microneedles struggle to penetrate the intestinal wall. Conventional directional adjustment devices, on the other hand, have limited directional capabilities and are difficult to expel, resulting in long retention times in the body.

[0051] To address the aforementioned problems, embodiments of the present invention provide a directional adjustment component for deploying temporary implants in the body, such as... Figure 1-3 As shown, the device includes a gravity regulator 104 for carrying the implant and a capsule 101 disposed on one side of the gravity regulator 104. A drug-loading area is provided on the side of the gravity regulator 104 away from the capsule 101. The drug-loading area is provided with an exhaust port 107 that is connected to the capsule 101 and can be sealed or opened. The capsule 101 includes a main capsule 101, a first reactant container 102A for holding a first reactant, and a second reactant container 102B for holding a second reactant. The main capsule 101 and the second reactant container 102B are separated by a second soluble isolation device 103. The second reactant container 102B and the first reactant container 102A are separated by a first soluble isolation device 102. The first reactant and the second reactant can react to generate gas 108.

[0052] The above structure enables rapid orientation of temporary implants, specifically, such as... Figure 4As shown, in the initial stage of entering the body, the vent 107 of the directional adjustment component is blocked by the drug 106D or drug 106D substance in the drug-carrying area. After reaching the designated area of ​​the intestine, such as the colon, the first soluble isolation device 102 and the second soluble isolation device 103 dissolve. The first reactant and the second reactant can react to generate gas 108. The gas 108 enters the capsule 101 and expands the capsule 101, so that the volume of the capsule 101 gradually increases. Together with the gravity regulator 104, it forms a structure similar to a roly-poly toy, which can quickly form orientation in the colon area, keep the drug-carrying area parallel to the direction of the intestine, and use the peristaltic contraction wave of the intestine to squeeze the drug-carrying area against the inner wall of the intestine, so that the drug 106D carried in the drug-carrying area acts on the inner wall of the intestine. After the drug 106D in the drug-carrying area acts on the intestinal wall, it will detach from the intestine. At this time, the vent 107 located in the drug-carrying area will be exposed, allowing the gas 108 in the sac 101 to be discharged through the vent 107. The volume of the air sac gradually decreases, which is conducive to the rapid passage of the directional regulation component through the intestine and its discharge from the body, and can shorten the retention time of the directional regulation component in the body.

[0053] It should be noted that the first soluble isolation device 102 and the second soluble isolation device 103 can separate the two sides of the capsule 101 by means of lines, rings, clamps, etc. The standard for separation of the first soluble isolation device 102 is that liquid cannot pass through, and the standard for separation of the second soluble isolation device 103 is that solid, which is the second reactant, can not pass through or only a small amount can pass through without affecting the expansion of the capsule 101. In some embodiments, the second reactant can be a solid, and the first reactant can be a liquid.

[0054] The first and second reactants can contain acids and bases. However, it should be noted that since they act on the intestines, the first and second reactants must be safe for consumption, and the gas 108 produced must not affect human health. For example, the acid can be citric acid, and the base can be sodium bicarbonate or potassium bicarbonate, etc.

[0055] In an optional embodiment, the gravity regulator 104 is a biodegradable polymer, and its material can be at least one of polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA), poly(glycolide-lactide) copolymer (PGLA), and poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG).

[0056] In an optional embodiment, the axial length of the gravity regulator 104 is 2-5 mm, and the length in the direction perpendicular to the axis is 5-16 mm, preferably 8-13 mm. The mass of the gravity regulator 104 is greater than the mass of the capsule 101, which helps to ensure that its center of gravity is low, so that it can quickly contact the intestinal wall when it reaches the drug-carrying area in the intestine.

[0057] The gravity regulator 104 can be formed by injection molding or casting, and its shape is preferably circular.

[0058] In an optional embodiment, the capsule 101 is made of at least one of polyurethane (PU), polyvinyl chloride (PVC), polyamide (PA), polyethylene (PE), and polyethylene terephthalate (PET).

[0059] In an optional embodiment, after the first reactant and the second reactant react to generate gas 108, the height of the capsule 101 is 10-20 mm, which, in conjunction with the gravity regulator 104, facilitates rapid orientation.

[0060] In an optional embodiment, the first soluble isolation device 102 can dissolve under a first preset condition; the second soluble isolation device 103 can dissolve under a second preset condition. Specifically, the dissolution conditions of the first soluble isolation device 102 and the second soluble isolation device 103 can be the same, or they can be dissolved at different locations by utilizing environmental conditions (such as the pH difference between the proximal and distal ends of the intestine) so that the airbag can function, thereby achieving precise positioning and drug 106D delivery. However, since the first reactant and the second reactant only need to release enough gas 108 to inflate the airbag, the amount used is small. In order to enable the first reactant and the second reactant to react quickly and fully, preferably, the first soluble isolation device 102 dissolves before the second soluble isolation device 103. After the first soluble isolation device 102 dissolves, the first reactant and the second reactant can react. The second soluble isolation device 103 dissolves after the reaction is completed or nearly completed, so that the second reactant container cavity 102B and the first reactant container cavity 102A are connected.

[0061] In an optional embodiment, the second soluble isolation device 103 is a structure that isolates solids and liquids but allows air to pass through, so that while maintaining sufficient contact between the first reactant and the second reactant, the generated gas 108 can pass through the second soluble isolation device 103 as soon as possible and be transferred into the capsule 101, thus preventing the second reactant holding chamber 102B and the first reactant holding chamber 102A from being burst due to excessive gas 108.

[0062] In an optional embodiment, the gravity regulator 104 includes an upper gravity regulator layer 104-1 and a lower gravity regulator layer 104-2 fixed to each other. The capsule 101 has an opening, which is fitted onto the gravity regulator 104. The capsule 101 at the edge of the opening is fixed between the upper gravity regulator layer 104-1 and the lower gravity regulator layer 104-2. Figure 5-6 As shown. The bladder 101-1 at the edge of the opening can be fixed to the upper layer 104-1 of the gravity regulator by adhesive bonding or other optional methods.

[0063] In an optional embodiment, the capsule 101 has an opening, which is fitted onto the gravity adjuster 104. A dissolvable elastic ring 102-1 is fitted onto the opening to fix the capsule 101 to the gravity adjuster 104. Figure 7 As shown.

[0064] In an optional embodiment, the gravity regulator 104 is provided with an annular groove 102 along the circumference, and the capsule 101 is provided with an opening. The opening is fitted onto the gravity regulator 104, and the capsule at the opening is provided with a snap-fit ​​ring for engaging within the annular groove. Figure 8 As shown.

[0065] The present invention also provides a self-orienting microneedle unit 100, such as... Figure 1-3 and Figure 9 As shown, it includes the orientation adjustment component described in any of the foregoing embodiments and a microneedle substrate 105 that can be separated from the gravity regulator 104. The microneedle substrate 105 is located in the drug loading area and covers the outlet of the vent 107. Microneedles 106 for drug loading are provided on the microneedle substrate 105.

[0066] After the balloon is filled with gas 108, it forms a roly-poly-like structure together with the gravity regulator 104. This structure allows for rapid orientation in the colonic region, ensuring that the drug-loading area and the microneedle base 105 remain parallel to the intestinal direction. The peristaltic contractions of the intestine compress the microneedles 106 on the microneedle base 105 against the intestinal wall, allowing the microneedles 106 to penetrate the mucosa and deliver the drug 106D to the intestinal wall. As the microneedle base 105 absorbs water in the intestine, the adhesion between it and the gravity regulator 104 gradually decreases. After the microneedles 106 penetrate the mucosa, while the microneedles are fixed, the intestine continues to contract and peristalsis. Under external force, the microneedle base 105 detaches from the gravity regulator 104. At this point, the vent 107 in the drug-loading area is exposed, allowing the balloon 101 to release gas and be quickly expelled from the body along with the gravity regulator 104.

[0067] The microneedle base 105 is responsible for supporting and fixing the microneedle array 106 and providing reliable support for the precise insertion of the microneedle array 106 into the tissue. The shape of the microneedles 106 can be selected as needed, such as... Figure 10 As shown.

[0068] The microneedle 106 array contains a biological agent for treatment, which includes one or more of growth hormone, parathyroid hormone, antibody, chemotherapeutic agent, insulin, glucagon-like peptide, immunosuppressant, vaccine or antiparasitic agent.

[0069] In an optional embodiment, the microneedle substrate 105 is made of at least one of PVA (polyvinyl alcohol), PVP (polyvinyl ketone), and polyacrylamide.

[0070] In an optional embodiment, the preparation method of the microneedle substrate 105 includes: solidifying the raw material liquid on the surface of the gravity regulator 104 to form the microneedle substrate 105. The microneedle substrate 105 prepared in this manner has a certain adhesion to the gravity regulator 104, ensuring that the microneedle substrate 105 and the gravity regulator 104 will not detach before the microneedle 106 penetrates the mucosa, and can detach after the microneedle 106 penetrates the mucosa. In some embodiments, water-absorbing pores can be provided on the surface of the microneedle substrate to improve the water absorption rate of the microneedle substrate.

[0071] In an optional embodiment, the microneedle 106 includes a microneedle 106 body and a drug 106D loaded in the microneedle 106.

[0072] In an optional embodiment, the drug 106D includes at least one of growth hormone, parathyroid hormone, antibody, chemotherapeutic agent, insulin, glucagon-like peptide, immunosuppressant, vaccine or antiparasitic agent; the drug 106D is usually a biological agent, but in some special cases, it may be other types of drug 106D.

[0073] In an optional embodiment, the microneedles 106 are made of a biodegradable material; the microneedle array 106 is used for drug delivery and insertion into the intestine, and may be composed of one or more biodegradable materials such as polyethylene glycol diacrylate, polylactide copolymer, PCL, hyaluronic acid (HA), PVA, hydroxypropyl cellulose and chitosan (CS), and prepared by a molding process. The specific structure of the microneedles 106 may include barbs or not, and the shape may also be selected as needed.

[0074] In an optional embodiment, the microneedle 106 includes a microneedle base 106B and a microneedle tip 106A, with the drug 106D loaded on the microneedle tip 106A.

[0075] This invention also provides a swallowable microneedle 106 device, comprising: a self-orienting microneedle unit 100 as described in any one of the foregoing embodiments, and a capsule 200 for encapsulating the self-orienting microneedle unit 100, such as... Figure 11 As shown.

[0076] By compressing the capsule 101 inside the capsule 200, oral administration is facilitated, the drug loading capacity is greatly increased, and the self-directing microneedle 106 unit is prevented from being exposed to gastric juice.

[0077] In an optional embodiment, there are two or more self-orienting microneedle units 100, and the self-orienting microneedle units 100 are separated by a partition 300 to prevent adjacent microneedles 106 from sticking together. The partition 300 can be rice paper or the like.

[0078] In an optional embodiment, the capsule 200 is capable of dissolving under a third preset condition to release the self-directing microneedle unit 100. At least a portion of the capsule 200 dissolves upon exposure to a selected pH in the intestine to release the self-directing microneedle unit 100, such as... Figure 12 As shown.

[0079] It should be noted that in the embodiments of this application, the first preset condition, the second preset condition, and the third preset condition can be the same or different. They are usually the pH of a specified location in the intestine. If the first preset condition, the second preset condition, and the third preset condition are the same, the dissolution time can also be adjusted by adjusting the material of the corresponding structure. For example, the first soluble isolation device dissolves faster than the second soluble isolation device, so as to achieve the purpose of dissolving the first soluble isolation device first and the second soluble isolation device dissolving later. Specifically, in some embodiments, the first soluble isolation device dissolves about 1 minute after the capsule dissolves and the second soluble isolation device dissolves about 5 minutes after the capsule dissolves.

[0080] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0081] Examples 1-6

[0082] Embodiments 1-6 of this application provide a self-orienting microneedle unit 100, such as Figure 1-6 As shown in Figures 9 and 11, the device includes a cylindrical gravity modulator 104 (made of PCL) for carrying the implant, a capsule 101 (made of PU) disposed on one side of the gravity modulator 104, and a microneedle substrate 105 (made of PVA / PVP blend) that can be separated from the gravity modulator 104.

[0083] The gravity regulator 104 has a drug-carrying area on the side away from the capsule 101. The drug-carrying area has an exhaust port 107 that is connected to the capsule 101 and can be blocked or opened. The capsule 101 includes a main capsule 101, a first reactant holding cavity 102A for holding a first reactant, and a second reactant holding cavity 102B for holding a second reactant. The main capsule 101 and the second reactant holding cavity 102B are separated by a second soluble isolation device 103. The second reactant holding cavity 102B and the first reactant holding cavity 102A are separated by a first soluble isolation device 102. The first soluble isolation device 102 dissolves before the second soluble isolation device 103. The first reactant and the second reactant can react to generate gas 108.

[0084] The gravity regulator 104 includes an upper gravity regulator 104-1 and a lower gravity regulator 104-2 that are fixed to each other. The capsule 101 has an opening that is fitted onto the gravity regulator 104, and the capsule 101-1 at the edge of the opening is fixed between the upper gravity regulator 104-1 and the lower gravity regulator 104-2.

[0085] The microneedle substrate 105 is located within the drug-loading area and covers the outlet of the vent 107. Microneedles 106 for drug loading are provided on the microneedle substrate 105.

[0086] The dimensions of the inflated capsule 101 and the dimensions of the gravity regulator 104 in each embodiment are shown in Table 1.

[0087] Comparative Example 1

[0088] This comparative example provides a self-orienting microneedle unit 100, including a cylindrical gravity regulator 104 (made of PCL) for carrying the implant, a capsule 101 (made of 3D printed resin OBJ-04057, with a wall thickness of 1mm) disposed on one side of the gravity regulator 104, and a microneedle substrate 105 (made of PVA / PVP blend) that can be separated from the gravity regulator 104. It does not include structures such as a first reactant container 102A, a second reactant container 102B, or an exhaust port 107. Specifically, as shown... Figure 13 As shown.

[0089] Table 1

[0090]

[0091] The self-orienting microneedle unit 100 in the above embodiments and comparative examples were tested. The test methods are as follows, and the test results are shown in Table 2.

[0092] Self-orientation time t1: The self-orienting microneedle unit 100 is placed on a stationary horizontal platform. In the initial state, the axis of the self-orienting microneedle unit 100 is vertical and the gravity regulator 104 is located above the capsule 101. The process of their release until a stable state is recorded using a camera, and each frame of the image is exported to determine the self-orientation time.

[0093] Self-orientation accuracy p: 50 self-orientation microneedle units 100 are placed on a horizontal vibrator (70 rpm). The initial state of the self-orientation microneedle unit 100 is that the axis is vertical and the gravity adjuster 104 is above the capsule 101. The motion is recorded by a camera for 10 seconds. If the axis is vertical and the gravity adjuster 104 is below the capsule 101, it is recorded as self-orientation; otherwise, it is recorded as self-orientation failure. The self-orientation accuracy p = (number of self-orientation successful microneedle 106 robots) / 50.

[0094] The tissue penetration depth d of the microneedle 106 robot: After fixing the colon tissue with Cy5.5-labeled insulin loaded on the tip of the microneedle 106A for 10 minutes, the microneedle 106 punctured the colon tissue in an ex vivo state, and the puncture depth of the microneedle 106 was observed by confocal microscopy; the microscope height was adjusted to locate the position with the strongest fluorescence as the initial position of the microneedle 106 hole, and then adjusted in the opposite direction to locate another position with the weakest fluorescence as the final position of the microneedle 106 hole.

[0095] Separation time t2: A 1% (w / v) agarose gel was prepared to simulate the colon wall. The agarose gel was heated until completely dissolved and incubated at 60°C for 5 min. It was then transferred into a cell culture dish (35 mm in diameter) at a height of 10 mm and allowed to cool and solidify. Self-oriented microneedle units 100 were inserted into the gel, and PBS phosphate buffer (pH=7.4) was slowly added to submerge the microneedle substrate 105. The mixture was incubated at 37°C on a shaker (60 rpm) for different times. The separation of the gravity regulator 104 and the microneedle 106 array was recorded using a camera to determine the separation time t2.

[0096] Excretion time t3: Pigs, whose digestive system has a similar physiological structure to that of humans, were used as the research subjects. However, since the gastric peristalsis time of pigs differs greatly from that of humans, a gastroscope was used to insert the self-directed microneedle unit 100 into the duodenum of the pigs and the excretion time t3 of the self-directed microneedle unit 100 was recorded.

[0097] Table 2

[0098]

[0099] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention.

Claims

1. A directional adjustment assembly for deploying temporary implants in vivo, characterized in that, The device includes a gravity regulator for carrying an implant and a capsule disposed on one side of the gravity regulator. A drug-loading area is provided on the side of the gravity regulator away from the capsule. The drug-loading area has a vent that can be sealed or opened and communicates with the capsule. The capsule includes a main capsule, a first reactant cavity for holding a first reactant, and a second reactant cavity for holding a second reactant. The main capsule and the second reactant cavity are separated by a second soluble isolation device, and the second reactant cavity and the first reactant cavity are separated by a first soluble isolation device. The first and second reactants can react to generate gas; the first soluble isolation device dissolves before the second soluble isolation device. The gravity regulator has an axial length of 2-5 mm and a length of 5-16 mm in the direction perpendicular to the axis. The mass of the gravity regulator is greater than the mass of the capsule. After the first reactant and the second reactant react to generate gas, the height of the capsule is 10-20 mm.

2. The orientation adjustment component for deploying temporary implants in vivo according to claim 1, characterized in that, The gravity regulator is made of at least one of PCL, PLA, PGA, PGLA, and PLGA-PEG.

3. The orientation adjustment component for deploying temporary implants in vivo according to claim 1, characterized in that, The capsule is made of at least one of PU, PVC, PA, PE and PET.

4. The orientation adjustment component for deploying a temporary implant in vivo according to claim 1, characterized in that, The first soluble isolation device is soluble under a first preset condition; the second soluble isolation device is soluble under a second preset condition. And / or, the second soluble isolation device is a device that isolates solids and liquids but allows air to pass through.

5. The orientation adjustment component for deploying a temporary implant in vivo according to claim 1, characterized in that, The gravity regulator includes an upper gravity regulator layer and a lower gravity regulator layer that are fixed to each other. The capsule has an opening, which is fitted onto the gravity regulator. The capsule at the edge of the opening is fixed between the upper gravity regulator layer and the lower gravity regulator layer. Alternatively, the capsule may have an opening, which is fitted onto the gravity regulator, and a soluble elastic ring may be fitted onto the opening to fix the capsule to the gravity regulator. Alternatively, the gravity regulator may have an annular groove along its circumference, and the capsule may have an opening, which is fitted onto the gravity regulator, and the capsule at the opening may have a snap ring for engaging with the annular groove.

6. A self-orienting microneedle unit, characterized in that, The device includes the orientation adjustment component as described in any one of claims 1-5 and a microneedle substrate that can be separated from the gravity regulator, the microneedle substrate being located within the drug loading area and covering the outlet of the vent hole, and the microneedle substrate being provided with microneedles for drug loading.

7. The self-orienting microneedle unit according to claim 6, characterized in that, The microneedle substrate is made of at least one of PVA, PVP and PAM; And / or, the method for preparing the microneedle substrate includes: solidifying the raw material liquid on the surface of the gravity regulator to form the microneedle substrate; And / or, the microneedle includes a microneedle body and a drug loaded in the microneedle.

8. The self-orienting microneedle unit according to claim 7, characterized in that, The drug includes at least one of growth hormone, parathyroid hormone, antibody, chemotherapy agent, insulin, glucagon-like peptide, immunosuppressant, vaccine or antiparasitic agent; And / or, the microneedles are made of a biodegradable material; And / or, the microneedle includes a microneedle base and a microneedle tip, with the drug loaded at the microneedle tip.

9. A swallowable microneedle device, characterized in that, include: A self-orienting microneedle unit as described in any one of claims 6-8 and a capsule for encapsulating the self-orienting microneedle unit.

10. The swallowable microneedle device according to claim 9, characterized in that, There are two or more self-orienting microneedle units, and the self-orienting microneedle units are separated by partitions. And / or, the capsule is capable of dissolving under a third preset condition to release the self-directing microneedle unit.

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