Oral administration device, method of manufacturing the same, and use

Abstract

The present invention discloses an oral administration device, a method for manufacturing the same, and its use. The oral administration device comprises a core assembly and a fixation device, the core assembly comprising a integrally formed molar anastomosis functional region and a drug-loading functional region, the molar anastomosis functional region comprising a first section close to the drug-loading functional region and a second section away from the drug-loading functional region, one end of the first and second sections connected to each other and the other end being an open end, forming a U-shaped structure, the first and second sections used to anastomose with the buccal and lingual sides of a tooth, respectively, the drug-loading functional region comprising a first ring and a second ring arranged coaxially, the fixation device used to enhance the fixation effect of the core assembly to the tooth, and the fixation device is a stator or a fixation layer. When the oral administration device is used, it offers high rigidity, safety, and comfort, and has little impact on facial appearance.

Description

Technical Field

[0001] This application claims the priority of Chinese Patent Application No. 2023103663509 with an application date of April 4, 2023 and Chinese Patent Application No. 2023207303692 with an application date of April 4, 2023. This application incorporates the full text of the above-mentioned Chinese patent applications by reference.

[0002] Specifically, the present invention relates to an oral administration device, a method for manufacturing the same, and its use.

Background Art

[0003] In the case of pharmaceutical active ingredients whose absorption region is limited to the upper digestive tract, such as levodopa, carbidopa, baclofen, acyclovir, etc., conventional sustained-release formulations have problems of low bioavailability and insufficient therapeutic range. Existing technologies for extending the gastric retention time of drugs (including expansion, swelling, floating, raft formation, sedimentation, mucosal adhesion) have a very limited extension effect, especially when administered on an empty stomach. Also, in the case of local oral mucosal administration, conventional liquid or semi-solid formulations such as sprays, gargles, ointments, etc. have a short retention time in the oral cavity and cannot obtain a sustained drug delivery effect. Therefore, there is a need for a drug delivery system that enables long-term exposure of drug components and is suitable for drugs with an absorption region in the upper digestive tract or drugs that require local oral administration. A drug delivery device is loaded with a drug and combined with a fixing device to be fixed in the oral cavity to form a drug controlled-release system, providing long-term exposure of drugs with a limited absorption region in the upper digestive tract.

[0004] Regarding oral administration devices, patent applications US10668274 and CN1997421A disclose oral drug containers based on an electrically controlled drug release mechanism, but the drug containers and electrical control systems disclosed in these patents are difficult to realize. CN105873631A discloses an oral drug delivery device that requires an electronic or mechanical pump as an external power source to achieve drug delivery. Furthermore, CN1925823A discloses a dental bracket for attaching fluoride pellets to teeth to improve the treatment or prevention of dental caries, but this patent application does not concern drug absorption in the upper gastrointestinal tract. Furthermore, patent application CN109908461A discloses an oral administration device applicable to dentures, orthodontic appliances, or oral implants, which is suitable for drug delivery to the oral mucosa, but does not concern drug absorption in the upper gastrointestinal tract. The above-mentioned published patent applications do not involve drug absorption that requires external force, relies on dentures, orthodontic appliances, or has an absorption end in the upper gastrointestinal tract.

[0005] CN114191307A and CN212973560U disclose an oral retention device for holding tablets in the oral cavity, providing long-term exposure to drugs whose absorption range is limited to the upper gastrointestinal tract, and obtaining stable blood drug concentrations over a long period. The oral retention device takes into account that the tablet is inserted from back to front near the throat and blocked by oral tissues such as the tip of the buccal fat pad, so that the tablet is less likely to fall out even when the device is worn. At the same time, the tooth anastomosis member of the oral retention device is customized to fit the patient's teeth and stabilize the fit. However, in patients with clinically short tooth crowns, small buccal space, or special oral conditions, large amplitudes of oral movement may result in insufficient retention of the oral retention device, increasing the risk of tilting or detachment.

[0006] The oral administration devices described above not only fail to consider the firmness of fit under specific oral conditions, but their complex structure and large size may also result in poor comfort and safety, as well as potentially significant impact on facial appearance during wear. [Overview of the Initiative]

[0007] To address the problem in conventional technology where some patients may experience the risk of drug delivery devices becoming dislodged after actions such as opening their mouths wide, the present invention provides an oral administration device, a method for manufacturing the same, and its use. Specifically, the present invention provides an oral administration device comprising a core assembly and a fixing device, which can stably hold the oral administration device and tablet in the mouth, preventing them from falling out due to oral movements, and allowing the tablet to be inserted from back to front. By wearing the oral administration device, patients can achieve long-term release of drugs whose absorption area is limited to the upper gastrointestinal tract, as well as drug delivery via the oral mucosa or localized drug release within the oral cavity. At the same time, the oral administration device is highly comfortable to wear and has little impact on facial appearance.

[0008] This invention solves the above technical problems by primarily employing the following technical solutions.

[0009] The present invention provides an oral administration device comprising a core assembly and a fixing device, wherein the core assembly comprises an integrally formed molar anastomosis functional region and a drug-loading functional region. When the oral administration device is fixed in the oral cavity, the drug-loading functional area is located in the space between the teeth and the cheek, or in the space between the teeth and the tongue. The molar anastomosis functional region includes a first section close to the drug-loading functional region and a second section away from the drug-loading functional region, with one end of the first and second sections connected to each other and the other end being an open end, forming a U-shaped structure, and the first and second sections are used to anastomose with the buccal and lingual sides of the tooth, respectively, and are used to fix the drug-loading functional region to the tooth. The drug-loading functional region comprises a first ring and a second ring arranged coaxially, and an axial clamp space formed between the first ring and the second ring is used to secure the drug. The aforementioned fixing device is a stator or fixing layer used to enhance the fixing effect of the core assembly to the teeth, If the aforementioned fixing device is a stator, When the oral administration device is used, the lingual, buccal, and occlusal surfaces of the stator anastomose with the corresponding lingual, buccal, and occlusal surfaces of the tooth, covering the outer surface of the tooth, and the stator simultaneously covers the molar anastomosis functional area. If the fixing device is a fixed layer, The fixed layer is attached to the outer surfaces of the first and second sections that come into contact with the teeth.

[0010] In the present invention, the first ring and the second ring are preferably located on the buccal side of the first or second molar.

[0011] In the present invention, the stator and the molar anastomosis functional region are preferably connected by mechanical assembly, mechanical connection, or adhesive bonding.

[0012] Here, the mechanical assembly is preferably embedded, with slots provided at positions corresponding to the drug-loading functional area of ​​the stator to enable removable fixation between the stator and the core assembly, and the embedding means that the molar anastomosis functional area is embedded in the spaces formed on both sides of the stator.

[0013] Here, the mechanical connection is preferably by welding, riveting, or bolting.

[0014] Here, the adhesive is preferably one or more of a pressure-sensitive adhesive, a starch adhesive, a latex, an epoxy resin, and a polyurethane acrylate.

[0015] In the present invention, the fixed layer is preferably also attached to other outer surfaces of the first section and the second section.

[0016] In the present invention, the first ring is close to the open end of the molar anastomosis functional region, and the second ring is away from the open end of the molar anastomosis functional region. Preferably, the first ring and the second ring are solid or hollow annular structures.

[0017] Here, the hollow annular structure is either a closed ring or an open ring.

[0018] Here, the shape of the annular structure is preferably one or more of the following: circular, elliptical, and polygonal.

[0019] Here, the annular structures of the first ring and the second ring are preferably circular in shape, the hollow area of ​​the first ring is preferably smaller than the hollow area of ​​the second ring, and the tablet can be inserted from the second ring into the first ring.

[0020] In the present invention, the material of the core assembly is preferably one of titanium, stainless steel, cobalt-chromium alloy, cobalt-chromium-molybdenum alloy, or a precious metal, more preferably a cobalt-chromium alloy, and all of the materials of the core assembly meet the standards for materials used in dentistry.

[0021] In the present invention, the material of the stator is preferably one or more of the following: polyvinyl chloride, polyethylene terephthalate, polyethylene terephthalate-1,4-cyclohexanedimethanol terephthalate, polyurethane, polyamide, ethylene-vinyl acetate copolymer, polycaprolactone, high-density polyethylene, polypropylene, epoxy acrylate, methacrylate, and polyurethane acrylate, and more preferably polyethylene terephthalate or ethylene-vinyl acetate copolymer, and all of the materials of the stator meet medical grade standards.

[0022] In the present invention, the material of the fixing layer is preferably one or more of polyvinyl chloride, polyethylene terephthalate, polyethylene terephthalate-1,4-cyclohexanedimethanol, polyurethane, polyamide, ethylene-vinyl acetate copolymer, polycaprolactone, high-density polyethylene, polypropylene, cellulose acetate, hydroxypropyl cellulose, and copovidone. More preferably, it is polyethylene terephthalate or copovidone. All of the materials of the fixing layer meet the medical grade standards.

[0023] In the present invention, the thickness of the fixing layer is preferably 0.01 mm to 1 mm.

[0024] In the present invention, the number of teeth covered by the stator can be adjusted according to the state of the teeth or the firmness of wearing. The length of the stator is preferably the length corresponding to 4 to 16 teeth in the upper or lower jaw, and more preferably the length corresponding to 5 to 9 teeth in the upper or lower jaw.

[0025] In the present invention, the length of the molar occlusion functional area is preferably the length corresponding to 2 to 5 teeth in the lower jaw.

[0026] Here, it should be understood by those skilled in the art that the length is such that the stator or the molar occlusion functional area can wrap the number of teeth and does not exceed the number of teeth in the target range.

[0027] In one preferred embodiment, the stator is connected to the molar occlusion functional area by an embedding method. Slots are provided at positions corresponding to the drug loading functional area of the stator to achieve detachable fixation of the stator and the core assembly. The length of the molar occlusion functional area corresponds to the lengths of the first and second premolars and the first and second molars in the lower jaw. The first ring and the second ring are circular closed rings.

[0028] In one preferred embodiment, the stator is connected to the molar anastomotic functional region by an implantation method, the length of the molar anastomotic functional region corresponds to the lengths of the mandibular first and second premolars and the first and second molars, and the first and second rings are elliptical closed rings.

[0029] In one preferred embodiment, the stator is connected to the molar anastomotic functional region by an implantation method, the length of the molar anastomotic functional region corresponding to the lengths of the maxillary second premolar and the first, second, and third molars, and the first and second rings are circular closed rings.

[0030] In one preferred embodiment, the stator is connected to the molar anastomotic functional region by bonding with a pressure-sensitive adhesive, the length of the molar anastomotic functional region corresponding to the lengths of the first, second, and third molars, and the first and second rings are polygonal closed rings.

[0031] In one preferred embodiment, the fixed layer is attached to the entire outer surface of the first section and the second section of the U-shaped structure, the length of the molar anastomosis functional area corresponds to the lengths of the mandibular first and second premolars and the first and second molars, and the first and second rings are circular closed rings.

[0032] In one preferred embodiment, a pair of clamp walls are symmetrically arranged along the direction of the open end of the molar anastomosis functional region on the first ring.

[0033] The present invention also provides a method for manufacturing an intraoral administration device, which includes the steps of: if the fixing device is a stator, combining the stator to cover the integrally formed first section and second section; and if the fixing device is a fixing layer, attaching the fixing layer to the integrally formed first section and second section.

[0034] In the present invention, the method for manufacturing the core assembly is preferably laser melting casting, injection molding, or stamping molding.

[0035] Here, the laser fusion casting step preferably includes: acquiring oral data of the subject by scanning the subject's oral cavity or by taking an oral impression and then scanning a plaster model after it has been manufactured; designing the drug-bearing functional area and the posterior anastomosis functional area of ​​the core assembly using 3D design software and dental design software, respectively, and combining them in the dental design software to generate a design file for the core assembly; and manufacturing the core assembly by laser fusion casting, grinding, polishing, and cleaning.

[0036] Here, the injection molding step preferably includes: taking an oral mold from a subject and manufacturing a plaster model; manufacturing a dental wax model on the plaster model using dental wax as the material; and manufacturing a core assembly by a conventional injection molding process.

[0037] In the present invention, the method for manufacturing the stator preferably includes lamination, stamping, cutting, or 3D printing.

[0038] Here, the lamination step preferably involves heating and softening the stator material in a laminating machine, then vacuuming it so that the stator material covers the dental model and the molar anastomosis functional area.

[0039] Here, the stamping step preferably involves heating and softening the stator material to cover the subject's teeth and molar anastomosis functional area.

[0040] In the present invention, the raw materials for the stator are preferably as described above.

[0041] In the present invention, the method for manufacturing the fixed layer preferably includes immersion, spraying, or lamination.

[0042] Here, the immersion step preferably involves: dissolving the raw material of the fixed layer, immersing the molar anastomosis functional region in the raw material solution of the fixed layer, removing it, and drying it to form a film.

[0043] Here, the spraying step preferably involves dissolving the raw material for the fixed layer, applying it to the molar anastomosis functional area by spraying, and drying it to form a film.

[0044] Here, the lamination step preferably involves heating and softening the raw material of the fixed layer, covering the molar anastomosis functional area, and then cooling it.

[0045] In the present invention, the raw material for the fixed layer is preferably as described above.

[0046] In the present invention, the method for forming the stator and the covering structures of the first and second sections is preferably mechanical assembly, mechanical connection, or adhesive bonding.

[0047] Here, the mechanical assembly is preferably embedded.

[0048] If the aforementioned combination method is mechanical assembly, the stator is bonded to the tooth model and core assembly during the molding process to naturally form a slot-like structure, and at the same time, a buckle design may be designed for the molar anastomosis function portion as needed.

[0049] Here, the form of the mechanical connection is preferably welding, riveting, or bolting.

[0050] Here, the application location of the adhesive is preferably the outer surface used for contact with the teeth in the first and second sections, and more preferably the entire outer surface of the first and second sections.

[0051] Here, the coating thickness of the adhesive is preferably less than 1.0 mm.

[0052] The present invention provides the use of the oral drug delivery device, characterized in that, when the fixing device is a stator, the lingual, buccal, and occlusal surfaces of the stator anastomose with the lingual, buccal, and occlusal surfaces of the tooth, cover the outer surface of the tooth, position the drug-loading functional area in the space between the tooth and the cheek, or position the drug-loading functional area in the space between the tooth and the tongue, and cover the molar anastomosis functional area with the stator. If the fixing device is a fixed layer, the drug-carrying functional area is located in the space between the teeth and the cheek, or in the space between the teeth and the tongue.

[0053] As long as it does not violate common sense in the art, the above preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0054] The reagents and raw materials used in this invention are commercially available.

[0055] The positive progressive effects of this invention are: The present invention provides an oral administration device that anastomoses with teeth in the oral cavity and has an extremely low risk of dislodgement. By inserting a tablet from the rear to the front of the drug delivery device into the drug-loading functional area of ​​the drug delivery device and fixing the oral administration device after the tablet has been combined with the corresponding tooth in the oral cavity, sustained drug release can be achieved. The drugs include, but are not limited to, drugs whose absorption range is limited to the upper gastrointestinal tract and drugs that act locally in the oral cavity.

[0056] The oral administration device of the present invention does not require external power, does not require adjustment of the patient's teeth, and is easy to insert. The oral administration device of the present invention is highly robust and safe when inserted, preventing accidental ingestion or choking due to the drug delivery device loosening and falling out. The oral administration device of this application has little impact on the appearance of the patient's face when inserted, is aesthetically pleasing when inserted, and also offers excellent comfort when inserted. [Brief explanation of the drawing]

[0057] [Figure 1] This is a schematic diagram of the structure of each component of the oral administration device according to Embodiment 1 of the present invention, which consists of a core assembly 1 and a fixing member 2, where the core assembly 1 includes a molar anastomosis functional area 11 and a drug-loading functional area 12, and the drug-loading functional area 12 consists of a first ring 121 and a second ring 122. [Figure 2] This is a schematic diagram of the core assembly structure of the oral administration device according to Example 1 of the present invention. [Figure 3] This is a schematic diagram of the structure of a stator when the fixing device for the oral administration device in Embodiment 1 of the present invention is a stator. [Figure 4] This is a cross-sectional view along plane AA in Figure 1. [Figure 5] This is a schematic diagram of the structure of the oral administration device of Example 2. [Figure 6] This is a schematic diagram of the structure of the oral administration device of Example 3. [Figure 7] This is a schematic diagram of the structure of the oral administration device of Example 6. [Figure 8] Figure 7 is a cross-sectional view along the BB plane. [Figure 9] This is a schematic diagram of the structure of the oral administration device of Example 9. Brief explanation of symbols: 1-core assembly, 2-fixing device, 201-lingual side of fixing device, 202-buccal side of fixing device, 203-occlusal surface of fixing device, 11-molar anastomosis functional area, 12-drug loading functional area, 121-first ring, 122-second ring, 123-clamp wall. [Modes for carrying out the invention]

[0058] The present invention will be further described below with reference to examples, but this does not limit the present invention to the scope of the above examples. In the following examples, experimental methods for which specific conditions are not described are selected according to conventional methods and conditions or according to the product description.

[0059] Example 1 This embodiment is an intraoral administration device that covers the entire mandibular teeth, and as shown in Figure 1, comprises a core assembly 1 and a fixing device 2, the fixing device 2 being a stator, a schematic diagram of the structure of the core assembly 1 is shown in Figure 2, a schematic diagram of the structure of the fixing device 2 is shown in Figure 3, and a cross-sectional view of the intraoral administration device is shown in Figure 4. The lingual side 201, buccal side 202, and occlusal surface 203 of the fixing device anastomose with the lingual, buccal, and occlusal surfaces of the teeth, covering the outer circumferential surface of the teeth, and the fixing device 2 simultaneously covers the molar anastomosis functional area 11. The core assembly 1 consists of a molar anastomosis functional area 11 and a drug-loading functional area 12, the molar anastomosis functional area 11 can be closely fitted to the mandibular first and second premolars and first and second molars in the oral cavity of the subject, and the size of the drug-loading functional area 12 is such that it can accommodate at least one tablet and be fixed in the oral cavity. The fixation device 2 is in close contact with the entire mandibular teeth of the subject and with the molar anastomosis functional area 11, fixing the core assembly 1 and the tablet in the oral cavity. The molar anastomosis functional area 11 and the drug-loading functional area 12 are made of cobalt-chromium alloy and are connected on each side. The drug-loading functional area 12 includes a first ring 121 and a second ring 122, which are circular closed rings, and the tablet is inserted through the second ring 122 and blocked by the first ring 121. The molar anastomosis functional area 11 and the fixation device 2 are combined using an embedded mechanical assembly method, and a slot is provided in the fixation device 2 at a position corresponding to the drug-loading functional area 12, enabling detachable fixation between the fixation device 2 and the core assembly 1. Fixation device 2 is made of colorless, transparent polyethylene terephthalate and covers all 14 lower teeth. After the core assembly 1 and fixation device 2 are combined, they are fitted to the teeth in the subject's mouth.

[0060] The oral administration device of this embodiment can be securely fitted into the oral cavity after filling with a tablet, and the tablet is fixed in the oral cavity. The stator, core assembly, and tablet do not tilt or come loose due to movement in the oral cavity, providing a very comfortable fit with minimal impact on facial appearance.

[0061] Example 2 This embodiment is an intraoral administration device covering 10 mandibular teeth, as shown in Figure 5, and comprises a core assembly 1 and a fixing device 2, the fixing device 2 being a stator. The core assembly 1 consists of a posterior anastomosis functional area 11 and a drug-loading functional area 12. The posterior anastomosis functional area 11 can be in close contact with the mandibular first and second premolars and first and second molars in the subject's oral cavity, and the size of the drug-loading functional area 12 is such that it can accommodate at least one tablet and be fixed in the oral cavity. The fixing device 2 is in close contact with a portion of the subject's mandibular teeth (including from the left canine to the right second molar) and in close contact with the posterior anastomosis functional area 11 to fix the core assembly 1 and the tablet in the oral cavity. The posterior anastomosis functional area 11 and the drug-loading functional area 12 are made of cobalt-chromium alloy, and the posterior anastomosis functional area 11 and the drug-loading functional area 12 are connected on their respective sides. The drug-loading functional area 12 includes a first ring 121 and a second ring 122, the first and second rings 121 and 122 being elliptical closed rings, and a pair of clamp walls 123 are symmetrically positioned on the first ring 121 along the direction of the open end of the molar anastomosis functional area, suitable for insertion of non-cylindrical tablets, the tablets being inserted through the second ring 122 and blocked by the first ring 121. The molar anastomosis functional area 11 and the fixation device 2 are combined in an embedded mechanical assembly manner, with slots provided in the fixation device 2 at positions corresponding to the drug-loading functional area 12, enabling detachable fixation between the fixation device 2 and the core assembly 1. The fixation device 2 is made of colorless, transparent polyethylene terephthalate and covers 10 teeth from the left mandibular canine to the right second molar, and after the core assembly 1 and the fixation device 2 are combined, they are fitted to a portion of the mandibular teeth in the subject's oral cavity.

[0062] The oral administration device of this embodiment can be securely fitted into the oral cavity after filling with a tablet, and the tablet is fixed in the oral cavity. The stator, core assembly, and tablet do not tilt or come loose due to movement in the oral cavity, providing a very comfortable fit with minimal impact on facial appearance.

[0063] Example 3 This embodiment is an intraoral administration device covering seven mandibular teeth, as shown in Figure 6, and includes a core assembly 1 and a fixing device 2, the fixing device 2 being a stator. The core assembly 1 consists of a posterior anastomosis functional area 11 and a drug-loading functional area 12. The posterior anastomosis functional area 11 can be in close contact with the first and second mandibular premolars and first and second molars in the subject's oral cavity, and the size of the drug-loading functional area 12 is such that it can accommodate at least one tablet and fix the tablet in the oral cavity. The fixing device 2 is in close contact with a portion of the subject's mandibular teeth (including a total of seven teeth from the right incisor to the right second molar) and also in close contact with the posterior anastomosis functional area 11 to fix the core assembly 1 and the tablet in the oral cavity. The posterior anastomosis functional area 11 and the drug-loading functional area 12 are made of cobalt-chromium alloy, and the posterior anastomosis functional area 11 and the drug-loading functional area 12 are connected on their respective sides. The drug-loading functional area 12 includes a first ring 121 and a second ring 122, both of which are circular, closed rings suitable for inserting cylindrical tablets. The tablets are inserted through the second ring 122 and blocked by the first ring 121. The molar anastomosis functional area 11 and the fixation device 2 are combined using an implantable mechanical assembly method, with slots provided in the fixation device 2 at positions corresponding to the drug-loading functional area 12, enabling detachable fixation between the fixation device 2 and the core assembly 1. The fixation device 2 is made of a colorless, transparent ethylene-vinyl acetate copolymer and covers a total of seven teeth from the incisors to the second molars on the right side of the mandible. After the core assembly 1 and the fixation device 2 are combined, they fit into a portion of the mandibular teeth in the subject's oral cavity.

[0064] When the oral administration device of this embodiment is placed in the oral cavity, the medication is fixed in the oral cavity after filling with tablets, making it less likely to fall out. The feeling of wearing it is not significantly different from that of Examples 1 and 2, and at the same time, because fewer teeth are covered, the feeling of wearing it and the impact on facial appearance are superior to those of Examples 1 and 2.

[0065] Example 4 The difference between this embodiment and Embodiment 1 is that the oral administration device covers all of the maxillary teeth, and the molar anastomosis functional area 11 can closely adhere to the maxillary second premolar and the first, second, and third molars in the subject's oral cavity; the rest is the same as Embodiment 1.

[0066] The oral administration device of this embodiment can be securely fitted into the oral cavity after filling with a tablet, and the tablet is fixed in the oral cavity. The stator, core assembly, and tablet do not tilt or come loose due to movement in the oral cavity, providing a very comfortable fit and having minimal impact on facial appearance.

[0067] Example 5 The differences between this embodiment and Embodiment 1 are that the core assembly 1 is 3 teeth long and can be designed for subjects with molar deficiencies, the first ring 121 and the second ring 122 are polygonal closed rings, the molar anastomosis functional part 11 and the fixation device 2 are joined by pressure-sensitive adhesive, the joining position is the entire outer surface of the molar anastomosis functional part 11 and the adhesive thickness is 0.1 mm. The fixation device 2 is made of a colorless, transparent ethylene-vinyl acetate copolymer. Otherwise, it is the same as Embodiment 1.

[0068] The oral administration device of this embodiment can be securely fitted into the oral cavity after filling with a tablet, and the tablet is fixed in the oral cavity. The stator, core assembly, and tablet do not tilt or come loose due to movement in the oral cavity, providing a very comfortable fit and having minimal impact on facial appearance.

[0069] Example 6 A schematic diagram of the structure of the oral administration device of this embodiment is shown in Figure 7, and includes a core assembly 1 and a fixing device 2, the fixing device 2 being a fixing layer, and a cross-sectional view of the oral administration device is shown in Figure 8. The core assembly 1 consists of a molar anastomosis functional area 11 and a drug-loading functional area 12, the molar anastomosis functional area 11 can be fitted tightly to the mandibular first and second premolars and first and second molars in the oral cavity of a subject. The drug-loading functional area includes a first ring 121 and a second ring 122, the first ring 121 and the second ring 122 are circular closed rings suitable for inserting cylindrical tablets, the tablets are inserted through the second ring 122 and blocked by the first ring 121. The size of the drug-loading functional area 12 allows for the accommodation of at least one tablet and the fixation of the tablet in the oral cavity. The fixation device 2 is attached to the entire outer surface of the first and second sections of the U-shaped structure, and the molar anastomosis functional area 11 and the drug-bearing functional area 12 are made of cobalt-chromium alloy, and the molar anastomosis functional area 11 and the drug-bearing functional area 12 are connected on their respective sides. The fixation device 2 is made of colorless, transparent polyethylene terephthalate, which is softened by heating, then covers the surface of the molar anastomosis functional area 11, and after cooling, the excess material is trimmed off. The thickness of the fixation device 2 is 0.3-0.5 mm, and after the core assembly 1 and the fixation device 2 are combined, they are matched to the subject's teeth.

[0070] The oral administration device of this embodiment can be securely fitted into the oral cavity after filling with a tablet, and the tablet is fixed in the oral cavity. The fixing layer, core assembly, and tablet do not tilt or come loose due to movement in the oral cavity, providing a very comfortable fit and having minimal impact on facial appearance.

[0071] Example 7 The difference between this embodiment and Embodiment 6 is that the fixing device 2 is made of light blue polycaprolactone, and the thickness of the fixing device 2 is 0.8 to 1 mm; otherwise, it is the same as Embodiment 6.

[0072] The oral administration device of this embodiment can be more securely fitted in the oral cavity after filling with a tablet, and the tablet can be fixed in the oral cavity. However, because the thickness of the fixing device is greater, the oral administration device of this embodiment is not as securely fitted as in embodiment 6, is less comfortable, and has a greater impact on facial appearance compared to embodiment 6.

[0073] Example 8 The difference between this embodiment and Embodiment 6 is that the core assembly 1 and the fixing device 2 are bonded and connected with a pressure-sensitive adhesive, the bonding position is the part where the molar anastomosis functional part and the tooth come into contact, the adhesive thickness is 0.1 mm, and the fixing device 2 is a colorless, transparent polypropylene film with a thickness of 0.02 to 0.04 mm; otherwise, it is the same as Embodiment 6.

[0074] The oral administration device of this embodiment can be securely fitted into the oral cavity after filling with a tablet, and the tablet can be fixed in the oral cavity. However, because the thickness of the fixing layer is thin and the surface of the fixing layer material is smooth, the fit of the oral administration device of this embodiment is not as secure as that of embodiments 6 and 7, and the fit is not as comfortable as that of embodiments 6 and 7.

[0075] Example 9 The oral administration device of this embodiment is as shown in Figure 9 and includes a core assembly 1 and a fixing device 2, which are symmetrical on both sides. The fixing device 2 is a stator, and the two core assemblies 1 consist of a posterior anastomosis functional area 11 and a drug-loading functional area 12. The posterior anastomosis functional area 11 can be fitted tightly to the maxillary first and second premolars and first and second molars in the subject's oral cavity, and the size of the drug-loading functional area 12 is such that it can accommodate at least one tablet and fix the tablet in the oral cavity. The fixing device 2 fits tightly to the entire maxillary teeth of the subject and tightly to the posterior anastomosis functional area 11 to fix the core assembly 1 and the tablet in the oral cavity. The posterior anastomosis functional area 11 and the drug-loading functional area 12 are made of cobalt-chromium alloy and are connected on their respective sides. The drug-loading functional area 12 includes a first ring 121 and a second ring 122, which are circular, closed rings suitable for inserting cylindrical tablets. The tablets are inserted through the second ring 122 and blocked by the first ring 121. The molar anastomosis functional area 11 and the fixation device 2 are combined using an implantable mechanical assembly method. Slots are provided in the fixation device 2 at positions corresponding to the drug-loading functional area 12, enabling detachable fixation between the fixation device 2 and the core assembly 1. The fixation device 2 is made of colorless, transparent polyethylene terephthalate and covers all maxillary teeth. After the core assembly 1 and the fixation device 2 are combined, they are matched to the teeth in the subject's oral cavity.

[0076] The oral administration device of this embodiment can be securely fitted into the oral cavity after filling with a tablet, and the tablet is fixed in the oral cavity. The stator, core assembly, and tablet do not tilt or come loose due to movement in the oral cavity, providing a very comfortable fit and minimizing impact on facial appearance.

[0077] Example 10 The cobalt-chromium alloy core assembly is manufactured by laser melting casting, and the stator is manufactured by lamination. The specific steps are as follows:

[0078] Step 1: Obtain oral data of the subject by scanning the subject's mouth or by taking an impression of the mouth, creating a plaster model, and scanning it. Step 2: Use 3D design software and dental design software to design the drug-delivery functional area and posterior anastomosis functional area of ​​the core assembly, respectively, and then combine them in the dental design software to generate the core assembly design file. Step 3: The cobalt-chromium alloy core assembly is manufactured by laser melting, grinding, polishing, and cleaning. Step 4: The core assembly is fitted onto the subject's dental impression, the polyethylene terephthalate is heated and softened in a laminating machine, the dental impression is vacuumed to remove excess material, and then polished. The device is then removed from the dental impression to obtain an intraoral administration device, which fits the subject's teeth.

[0079] Example 11 The cobalt-chromium alloy core assembly is manufactured by injection molding, and then laminated to produce a drug delivery device. The specific steps are as follows:

[0080] Step 1: Take an impression of the subject's mouth and create a plaster model. Step 2: Using dental wax as the material, create a dental wax model on top of a plaster model. Step 3: The core assembly is manufactured using a conventional injection molding process with a cobalt-chromium ceramic alloy as the material. Step 4: The core assembly is mounted onto a plaster dental model, the polyurethane is heated and softened in a laminating machine, the dental model is vacuumed, excess material is trimmed and polished, and then it is removed from the dental model to obtain an intraoral administration device combining the core assembly and stator.

[0081] Example 12 The cobalt-chromium alloy core assembly is manufactured by injection molding and then laminated to produce a drug delivery device. The specific steps are as follows:

[0082] Step 1: Take an impression of the subject's mouth and create a plaster model. Step 2: Using dental wax as the material, create a dental wax model on top of a plaster model. Step 3: Manufacture a drug delivery device using a cobalt-chromium ceramic alloy as the material and a conventional injection molding process. Step 4: The core assembly is fitted to the corresponding tooth of the subject, the polycaprolactone material is heated and softened to cover the subject's tooth and the molar-fitting functional area of ​​the core assembly, and after cooling, the core assembly is removed from the tooth to obtain an oral administration device.

[0083] Comparative Example 1 The oral administration device in this comparative example is as shown in Figure 2 and includes only the core assembly 1 of Example 1.

[0084] Effect Example 1 The secure fit of the oral administration devices in Examples 1, 3, 6, and Comparative Example 1 was tested, and the secure fit scores are shown in Table 1. Here, 1: Not secure: Comes off very easily with basic oral movements such as opening the mouth or talking after insertion. 2: Relatively not secure: May loosen, tilt, or come off with basic oral movements such as opening the mouth or talking after insertion. 3: Basically secure: Only easily comes off with large oral movements. 4: Secure: Only tilts or loosens with large oral movements, but does not come off. 5: Very secure: Does not loosen, tilt, or come off even with basic or large oral movements.

[0085] [Table 1]

[0086] As can be seen from Table 1, Examples 1, 3, and 6 of this application employ a combination of a fixing device and a core assembly. Compared to Comparative Example 1, which uses only a core assembly, the mounting rigidity is superior, and it can be seen that using a stator as a fixing device results in a more secure mounting than using a fixed layer.

[0087] Effect Example 2 The comfort of wearing the oral administration devices of Examples 1, 3, 6, and Comparative Example 1 was tested, and the comfort scores are shown in Table 2 below. Here, 1 point: Extremely uncomfortable, with a clear foreign body sensation or irritation, unacceptable. 2 points: Uncomfortable, with a clear foreign body sensation or irritation, not very acceptable. 3 points: A foreign body sensation or irritation, slightly affecting oral function, but acceptable. 4 points: Relatively comfortable, with no clear foreign body sensation or irritation, and basically no effect on oral function. 5 points: Highly comfortable, with little foreign body sensation or irritation, and no effect on oral function.

[0088] [Table 2]

[0089] As can be seen from Table 2, Examples 1, 3, and 6 of the present invention employ a combination of a fixing device and a core assembly, resulting in a better fit compared to Comparative Example 1, which employs only a core assembly.

[0090] Effect Example 3 The impact on facial appearance when wearing the oral administration devices of Examples 1, 3, 6, and Comparative Example 1 was tested, and the scores are shown in Table 2 below. 1 point: The greatest impact on facial appearance, unacceptable. 2 points: Relatively large impact on facial appearance, not very acceptable. 3 points: Affects facial appearance, but acceptable. 4 points: Small impact on facial appearance. 5 points: Almost no difference in facial appearance before and after wearing.

[0091] [Table 3]

[0092] As can be seen from the table above, Examples 1, 3, and 6 of the present invention employ a combination of a fixing device and a core assembly, and compared to Comparative Example 1, which employs only a core assembly, they have a similar effect on the appearance of the face when the oral administration device is worn. In other words, the oral administration devices of the examples of the present invention have a similar level of aesthetic appearance when worn as the comparative example.

[0093] While the above describes specific embodiments of the present invention, those skilled in the art should understand that these are provided only as examples, and these embodiments can be modified in various ways without departing from the principles and essence of the present disclosure. Accordingly, the scope of protection of the present invention is limited by the appended claims.

Claims

1. Oral administration device, The device includes a core assembly and a fixing device, the core assembly including an integrally formed molar anastomosis functional region and a drug-carrying functional region. When the oral administration device is fixed in the oral cavity, the drug-loading functional area is located in the space between the teeth and the cheek, or in the space between the teeth and the tongue. The molar anastomosis functional region includes a first section close to the drug-loading functional region and a second section away from the drug-loading functional region, with one end of the first and second sections connected to each other and the other end being an open end, forming a U-shaped structure, and the first and second sections are used to anastomose with the buccal and lingual sides of the tooth, respectively, and are used to fix the drug-loading functional region to the tooth. The drug-loading functional region includes a first ring and a second ring arranged coaxially, and the axial clamp space formed between the first ring and the second ring is used to secure the drug. The aforementioned fixing device is a stator or fixing layer used to enhance the fixing effect of the core assembly to the teeth, If the aforementioned fixing device is a stator, When the oral administration device is used, the lingual, buccal, and occlusal surfaces of the stator anastomose with the corresponding lingual, buccal, and occlusal surfaces of the tooth, covering the outer surface of the tooth, and the stator simultaneously covers the molar anastomosis functional area. If the fixing device is a fixed layer, An oral administration device characterized in that the fixed layer is attached to the outer surfaces of the first section and the second section that come into contact with the teeth.

2. The stator and the molar anastomosis functional area are connected by mechanical assembly, mechanical connection, or adhesive bonding. and / or the fixing layer is also attached to other outer surfaces of the first section and the second section. The oral administration device according to claim 1, characterized in that the first ring is close to the open end of the molar anastomosis functional area, the second ring is away from the open end of the molar anastomosis functional area, and the first ring and the second ring are solid or hollow annular structures.

3. The mechanical assembly is embedded, and slots are provided at positions corresponding to the drug-loading functional area of ​​the stator, thereby enabling detachable fastening of the stator and the core assembly. and / or the mechanical connection is welded, riveted or bolted, and / or the adhesive is one or more of the following: pressure-sensitive adhesive, starch adhesive, latex, epoxy resin, and polyurethane acrylate. and / or, the hollow annular structure is a closed ring or an open ring, and / or, the shape of the annular structure is one or more of the shapes of a circle, an ellipse, and a polygon. The oral administration device according to claim 2, characterized in that the annular structures of the first ring and the second ring are both circular in shape, and the hollow area of ​​the first ring is smaller than the hollow area of ​​the second ring.

4. The material of the core assembly is one of titanium, stainless steel, cobalt-chromium alloy, cobalt-chromium-molybdenum alloy, or a precious metal, preferably a cobalt-chromium alloy. and / or, the stator material is one or more of the following: polyvinyl chloride, polyethylene terephthalate, polyethylene terephthalate-1,4-cyclohexanedimethanol terephthalate, polyurethane, polyamide, ethylene-vinyl acetate copolymer, polycaprolactone, polyethylene, polypropylene, epoxy acrylate, methacrylate, and polyurethane acrylate, preferably polyethylene terephthalate or ethylene-vinyl acetate copolymer. And / or, the length of the stator is such that it corresponds to 4 to 16 teeth in the upper or lower jaw, preferably 5 to 9 teeth in the upper or lower jaw. The oral administration device according to any one of claims 1 to 3, characterized in that the length of the molar anastomosis functional area corresponds to the length of 2 to 5 teeth of the mandible.

5. The material of the fixed layer is one or more of the following: polyvinyl chloride, polyethylene terephthalate, polyethylene terephthalate-1,4-cyclohexanedimethanol, polyurethane, polyamide, ethylene-vinyl acetate copolymer, polycaprolactone, high-density polyethylene, polypropylene, cellulose acetate, hydroxypropylcellulose, and copolyvidone, preferably polyethylene terephthalate or copolyvidone. The oral administration device according to any one of claims 1 to 4, characterized in that the thickness of the fixed layer is 0.01 mm to 1 mm.

6. The stator and the molar anastomosis functional region are connected by an implantation method, the length of the molar anastomosis functional region corresponds to the length of the mandibular first and second premolars and the first and second molars, and the first ring and the second ring are circular closed rings. Alternatively, the stator and the molar anastomosis functional region are connected by an implantation method, the length of the molar anastomosis functional region corresponds to the lengths of the mandibular first and second premolars and the first and second molars, and the first and second rings are elliptical closed rings. Alternatively, the stator and the molar anastomosis functional region are connected by an implantation method, the length of the molar anastomosis functional region corresponds to the length of the maxillary second premolar and the first, second, and third molars, and the first ring and the second ring are circular closed rings. Alternatively, the stator and the molar anastomosis functional region are connected by bonding with a pressure-sensitive adhesive, the length of the molar anastomosis functional region corresponds to the lengths of the first, second, and third molars, and the first and second rings are polygonal closed rings. Alternatively, the fixed layer is attached to the entire outer surface of the first section and the second section of the U-shaped structure, the length of the molar anastomosis functional area corresponds to the lengths of the mandibular first and second premolars and the first and second molars, and the first and second rings are circular closed rings. Alternatively, the oral administration device according to any one of claims 1 to 5, characterized in that a pair of clamp walls are symmetrically arranged along the direction of the open end of the molar anastomosis functional region on the first ring.

7. A method for manufacturing an oral administration device according to any one of claims 1 to 6, characterized in that, if the fixing device is a stator, it is combined in such a way that it covers the first section and the second section which are integrally formed with the stator, and if the fixing device is a fixing layer, it is attached to the outer surface of the first section and the second section which are integrally formed with the fixing device.

8. The method for manufacturing the core assembly includes laser melting casting, injection molding, or stamping molding. and / or the method for manufacturing the stator includes lamination, stamping, cutting, or 3D printing. and / or, a method for producing the fixed layer includes immersion, spraying, or lamination. The method for manufacturing an oral administration device according to claim 7, characterized in that the method for forming the stator and the covering structures of the first and second sections is mechanical assembly, mechanical connection, or adhesive bonding.

9. In the method for manufacturing the stator, The lamination step involves heating and softening the stator material in a laminator so that it covers the tooth model and the molar anastomosis functional area, followed by vacuuming. Alternatively, the stamping step is a step of heating and softening the stator material to cover the subject's teeth and the molar anastomosis functional area. and / or, in the manufacture of the fixed layer, The immersion step involves dissolving the raw material for the fixed layer, immersing the molar anastomosis functional region in the raw material solution for the fixed layer, removing it, and drying it to form a film. Alternatively, the spraying step involves dissolving the raw material for the fixed layer, then spraying it onto the molar anastomosis functional area and drying it to form a film. Alternatively, the lamination step involves heating and softening the raw material of the fixed layer, covering the molar anastomosis functional area with it, and then cooling it. and / or, the mechanical assembly is embedded, and / or the mechanical connection is welded, riveted or bolted, and / or, the application location of the adhesive is the outer surface used for contact with the teeth in the first section and the second section, preferably the entire outer surface of the first section and the second section. The method for manufacturing an oral administration device according to claim 7 and / or 8, characterized in that the coating thickness of the adhesive is less than 1.0 mm.

10. If the fixing device is a stator, the lingual, buccal, and occlusal surfaces of the stator anastomose with the corresponding lingual, buccal, and occlusal surfaces of the tooth, covering the outer surface of the tooth, and the drug-carrying functional area is positioned in the space between the tooth and the cheek, or the drug-carrying functional area is positioned in the space between the tooth and the tongue, and the stator covers the molar anastomosis functional area. The use of the oral administration device according to any one of claims 1 to 6, characterized in that, when the fixing device is a fixed layer, the drug-carrying functional area is positioned in the space between the teeth and the cheek, or the drug-carrying functional area is positioned in the space between the teeth and the tongue.

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