WO2022057905A1 - Oral retention device and preparation method therefor - Google Patents

Oral retention device and preparation method therefor Download PDF

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Publication number
WO2022057905A1
WO2022057905A1 PCT/CN2021/119120 CN2021119120W WO2022057905A1 WO 2022057905 A1 WO2022057905 A1 WO 2022057905A1 CN 2021119120 W CN2021119120 W CN 2021119120W WO 2022057905 A1 WO2022057905 A1 WO 2022057905A1
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WO
WIPO (PCT)
Prior art keywords
drug
retention device
dental
oral
tablet
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PCT/CN2021/119120
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French (fr)
Chinese (zh)
Inventor
董良昶
陈溪山
吴刚
Original Assignee
上海汉都医药科技有限公司
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Application filed by 上海汉都医药科技有限公司 filed Critical 上海汉都医药科技有限公司
Priority to CN202180064047.2A priority Critical patent/CN116322602A/en
Priority to EP21868727.5A priority patent/EP4215175A4/en
Priority to JP2023517740A priority patent/JP2023541319A/en
Publication of WO2022057905A1 publication Critical patent/WO2022057905A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J7/00—Devices for administering medicines orally, e.g. spoons; Pill counting devices; Arrangements for time indication or reminder for taking medicine
    • A61J7/0092—Devices for administering medicines orally, e.g. spoons; Pill counting devices; Arrangements for time indication or reminder for taking medicine for holding medicines in, or fixing medicines on, a tooth, e.g. holder containing medicines fixed on a tooth

Definitions

  • the invention relates to the field of medical devices, in particular to an oral retention device and a preparation method thereof.
  • Patent application US10/668,274 and patent application CN1997421A disclose an oral medicine-containing container based on the mechanism of electric control of drug release. Moreover, the drug-containing container and the electric control system claimed in the patent are difficult to implement. There is no example in the patent specification, and it does not explain how to use the electric control drug release mechanism to realize the controlled release of the osmotic pump tablet as the drug storage device, so as to achieve the above Drug absorption in the gastrointestinal tract, so as to achieve long-term stable blood drug concentration.
  • CN1925823A discloses a dental bracket for attaching fluoride pills to teeth to improve the treatment and/or prevention of dental caries.
  • the patent application does not involve drug absorption in the upper gastrointestinal tract and long-term stable blood drug concentration, nor does it involve the method of tablet insertion.
  • Chinese patent application CN105873631A discloses an oral retention device that requires an electronic pump or a mechanical pump as an external force for drug delivery, and does not involve a tablet insertion method.
  • the tablet In the way of inserting the tablet from the front to the back (from the incisor to the molar), the tablet is easy to slip out from the front of the device (the side of the incisor), and the patient is prone to suffocation due to accidentally swallowing the dropped tablet.
  • the present invention provides a novel oral retention device that allows the tablet to remain in the oral cavity and not easily fall off.
  • the present invention provides an oral retention device in which the tablet is inserted from the back to the front. Since the rear side is close to the throat, there are oral tissues such as buccal fat pad tip and pterygomandibular fold that block the tablet, so that the tablet does not remain in the oral device. It will fall off and will not cause suffocation due to accidental swallowing.
  • a first aspect of the present invention provides an oral retention device.
  • the oral retention device includes a dental engagement member and a medicated member, the dental engagement member is connected to the drug loaded member, wherein the dental engagement member is used for bridging and mating with the teeth in the mouth cavity , the drug-carrying member can accommodate at least one tablet and is used to keep the tablet in the oral cavity.
  • the dental anastomosis member and the drug-carrying member are connected at their respective sides; and/or, the drug-carrying member is a mesh structure or a non-mesh structure, and the drug-carrying member has a mesh structure or a non-mesh structure.
  • the shape of the cross section is a circle, an ellipse, a polygon, or a special-shaped closed-loop or open-loop structure, or a combination thereof.
  • the cross section is a cross section perpendicular to the long axis direction of the dental engaging member (the long axis direction of the dental engaging member is substantially equal to the horizontal plane formed after the dental engaging member is matched with the teeth in the oral cavity).
  • the drug-carrying member includes at least one ring body and at least one limiting member, or the drug-carrying member is composed of at least one limiting member; wherein, the ring body has a space for inserting a tablet
  • the structure of the limiting member is used to limit the tablet in the drug-carrying member.
  • the opening faces the molars in a horizontal direction formed by the molars and the incisors, so that the tablet is inserted from the molars to the incisors in the horizontal direction; or, the openings are perpendicular to the incisors. It is arranged in the horizontal direction, and the tablet is inserted from top to bottom in the horizontal direction perpendicular to the Insert horizontally from buccal to lingual.
  • the horizontal direction described herein is basically equivalent to the horizontal direction in which the longest axis of the dental anastomosis member is located when the oral retention device is placed horizontally, and is also basically equivalent to the horizontal direction in which the oral retention device is matched with the teeth in the oral cavity of the subject through the dental anastomotic member.
  • the form of the tablet of the present invention does not change with time, and it is an osmotic pump tablet.
  • the osmotic pump tablet contains active drugs and excipients.
  • the component of the active drug is one of levodopa or its ester, carbidopa, baclofen, acyclovir, valacyclovir, ganciclovir, metformin and gabapentin, or levodopa or one or both of its esters and carbidopa.
  • the tablet is a film-controlled tablet, the controlled release film is a water-insoluble cellulose acetate excipient, and the tablet core is supported by an insoluble excipient skeleton or a booster layer. When the tablet completely releases the drug in the oral cavity, the appearance of the tablet is The top is still a full tablet shape.
  • the ring body is an open ring body or a closed ring body.
  • the closed-loop body is a circular, elliptical, polygonal or special-shaped closed-loop body;
  • the open-loop body is a circular, elliptical, polygonal or special-shaped open-loop body with missing parts (non-closed).
  • the limiting member is an arc-shaped hollow or solid shape, or the limiting member is formed by connecting a closed-loop body and a semicircle perpendicular to the closed-loop body; and/or, the The limiting member is adjacent to the ring body, or the limiting member is spaced from the ring body.
  • the abutments are integrally formed or connected together by connecting structures.
  • the number of the stopper is one, and the stopper is located on the side of the incisor in the horizontal direction; and/or, the number of the ring body is one, and the ring body It is located on the side of the molars in the horizontal direction formed by the molars and the incisors.
  • the tooth-fitting member can fit with any one or more teeth in the oral cavity, and/or the length of the tooth-fitting member is the length of 2-5 teeth.
  • the teeth are mandibular permanent teeth.
  • Mandibular molars are preferred. Most preferably first molars and second molars, or first molars, second molars and second premolars, or first molars, second molars and third molars, or first molars, second molars, third molars Tri-molars and second premolars.
  • the dental engaging members are prepared according to the size and shape of individual teeth.
  • the dental engaging member wraps, engages, snaps into, or inserts the teeth to which it engages.
  • the material of the oral retention device is a stable material for oral cavity, and the stable material for oral cavity is selected from oral stable metal or thermoplastic elastomer.
  • the oral-stable metal is selected from one of dental titanium, stainless steel, cobalt-chromium alloy, cobalt-chromium-molybdenum alloy or precious metal;
  • the thermoplastic elastomer is selected from polycaprolactone, ethylene-vinyl acetate copolymer , HDPE, polypropylene, polyacrylate, polyurethane, silicone polymers, polyester, poly(styrene-ethylene-butylene-styrene), poly(styrene-butadiene-styrene), poly A copolymer of one or both of (styrene-isoprene-styrene).
  • the material of the dental anastomosis member and the drug-carrying member is cobalt-chromium alloy.
  • a second aspect of the present invention provides a method of manufacturing the oral retention device of the first aspect of the present invention.
  • the method is selected from any of 3D printing, injection molding or impression molding.
  • the method for preparing the oral retention device of the first aspect of the present invention is 3D printing, which includes the following steps:
  • the design software add the plan of the saved drug-carrying component, and assemble the plan of the integrated oral retention device with the plan of the dental anastomosis component, and export the 3D printable file;
  • the design software is preferably 3Shape Dental System ;
  • the 3D printing preferably uses a laser sintering process
  • the step (1) it also includes: (0) in the software, design and save the plan of the drug-carrying member according to the data of the tablet size, the software is preferably SolidWorks or Zhongwang 3D platform design software; and /or, in the design software, design the plan of the dental anastomosis member according to the data of the subject's tooth size;
  • the data of the tablet size and/or the data of the subject's teeth are obtained by scanning the tablet and/or the subject's teeth or the subject's tooth model using a scanner, and the tooth model is obtained by traditional impression taking techniques prepared, the scanner is preferably a 3Shape scanner.
  • “3Shape” The intraoral scanner scans the size data of the tablet, and then, import the data into the "SolidWorks” software, design a plan for the drug-carrying component that can load the drug part, create and save the plan as a "standard attachment”file; use “3Shape” "The intraoral scanner scans the subject's teeth, and the data is imported into the “3Shape Dental System” software, and the dental anastomotic components are designed according to the tooth data; on the "3Shape Dental System” software, "standard accessories” are added and assembled with the dental anastomotic components.
  • the 3D printing preferably uses a laser sintering process.
  • the 3D printing is basically the same as the working principle of an ordinary printer.
  • the 3D printer is equipped with different "printing materials” such as metal, ceramics, plastic, sand, etc. After the printer is connected to the computer, the "printing materials" can be superimposed layer by layer through the computer control, and finally the blueprint on the computer can be turned into a real thing.
  • 3D printing refers to the technical principles of ordinary printers, in which the process of layered processing is very similar to inkjet printing. This printing technology is called 3D stereo printing technology. Many different technologies exist for 3D printing, which differ in the way the materials are available, and build up in different layers to create parts.
  • 3D printing Common materials for 3D printing are nylon glass fiber, polylactic acid, ABS resin, durable nylon material, gypsum material, aluminum material, titanium metal, titanium alloy, stainless steel, silver-plated, gold-plated, cobalt-chromium alloy, cobalt-chromium-molybdenum alloy or rubber materials, etc.
  • the advantage of 3D printing is that the operation can be automated, the production speed is fast, the design blueprint in the computer can be directly and accurately converted into a physical model, and it is also suitable for small-scale custom manufacturing.
  • the method of making the oral retention device of the first aspect of the present invention is injection molding comprising the steps of:
  • the tooth model is prepared by traditional impression taking technology or the subject's tooth data is obtained and printed by oral scanning technology;
  • the material of the dental anastomosis component model, the drug-carrying component model and the oral retention device model is dental wax, and/or the material of the tooth model is gypsum or resin.
  • Injection molding also known as injection molding, is a molding method of injection and molding, that is, at a certain temperature, the completely molten material is stirred by a screw, injected into the mold cavity with high pressure, and cooled and solidified to obtain a molded product Methods.
  • This method is suitable for mass production of complex-shaped parts, and is one of the important processing methods.
  • the advantages of the injection molding method are that the production speed is fast, the efficiency is high, the operation can be automated, there are many varieties of colors, the shape can be from simple to complex, the size can be from large to small, and the size of the product is accurate, the product is easy to replace, and it can be formed into complex shapes. Parts, injection molding is suitable for mass production and complex shape products and other molding processing fields.
  • the method of making the oral retention device of the first aspect of the present invention is impression molding, comprising:
  • the drug-carrying component was designed according to the tablet size; the dental anastomosis component was prepared with polycaprolactone (PCL) as the material, and the drug-carrying component was prepared with cobalt-chromium alloy as the material; the dental anastomosis component and the drug-carrying component were assembled into a complete oral retention device.
  • PCL polycaprolactone
  • a traditional injection molding process is used to prepare a drug-carrying member capable of loading an osmotic pump sheet; then the thermoplastic sheet is heated and softened to prepare a dental anastomosis member, and the softened dental anastomosis member is embedded with the drug-carrying member at the same time. After cooling, an integrated oral retention device is formed and taken out from the oral cavity.
  • the reagents and raw materials used in the present invention are all commercially available.
  • the positive and progressive effect of the present invention is that: an oral retention device in which the insertion direction of the tablet is from the throat to the incisors is provided. Because the rear side of the oral retention device is close to the throat, the tablet is not easy to fall off in the oral cavity due to the blocking effect of the oral mucosal tissue. .
  • the tablet is inserted into the oral cavity retention device to form a drug-device composition, and the drug-device composition is fixed on the matching teeth in the oral cavity, so that the drug can be continuously released within a certain period of time. After holding for 0-24 hours, the drug-device composition is taken out, replaced with a new tablet, and the drug-device composition is re-fixed on the matching teeth in the oral cavity, so that the drug can be continuously and stably released.
  • FIG. 1 is a tablet post-insertion oral retention device according to an embodiment of the present invention, which is composed of a dental anastomosis member 11 and a drug-carrying member 41, wherein the drug-carrying member 41 is composed of a stopper 21 and a ring body 31, and the ring body 31 There is an opening 311 thereon.
  • FIG. 2 shows a tablet front-insertion oral retention device according to an embodiment of the present invention, which is composed of a dental anastomosis member 12 and a drug-carrying member 42 , wherein the drug-carrying member 42 is composed of a stopper 22 and a ring body 32 , and the ring body 32 There is an opening 321 thereon.
  • the tablet post-insertion oral retention device is formed by connecting the dental anastomosis member 11 and the drug-carrying member 41 .
  • the dental engagement member 11 can be in close contact with the teeth in the oral cavity of the subject, and the drug-carrying member 41 is sized to accommodate at least one tablet and retain the tablet in the oral cavity.
  • the dental anastomosis member 11 and the drug-carrying member 41 are both made of cobalt-chromium alloy, and the dental anastomosis member 11 and the drug-carrying member 41 are connected at their respective sides.
  • the drug-carrying member includes a ring body 31 and a limiter 21 at the end.
  • the ring body 31 is a circular closed-loop body and has an opening 311 for inserting a tablet.
  • the stopper and the ring body are arranged at intervals, and are respectively connected to the dental anastomosis member 11; It can also be produced in one piece with the ring body and the dental engagement member.
  • the opening 311 opens toward the molars in the horizontal direction formed by the molars and the incisors (the ring body 31 is located in the horizontal direction close to the molars.
  • the dental anastomosis member 11 is anastomosed with the mandibular first molars, second molars and/or third molars in the oral cavity of the subject, and wraps the teeth through anastomosis.
  • the oral retention device of this embodiment after the tablet is loaded in the oral cavity, even if the drug immediate-release layer is rapidly dissolved by vigorous gargling, the tablet can be fixed firmly and will not slip out of the device.
  • Example 2 Cobalt-chromium alloy front insertion oral retention device
  • the tablet front-insertion oral retention device is formed by connecting the dental anastomosis member 12 and the drug-carrying member 42 .
  • the dental engagement member 12 can be in close contact with the teeth in the oral cavity of the subject, and the medicated member 42 is sized to receive at least one tablet and retain the tablet in the oral cavity.
  • the dental anastomosis member 12 and the drug-carrying member 42 are both made of cobalt-chromium alloy, and the dental anastomosis member 12 and the drug-carrying member 42 are connected at their respective sides.
  • the drug-carrying member 42 includes a ring body 32 and a limiter 22 at the end.
  • the ring body 32 is a circular closed ring body and has an opening 321 for inserting a tablet.
  • the stopper and the ring body are arranged at intervals, and are respectively connected to the dental anastomosis member 11; It can also be produced in one piece with the ring body and the dental engagement member.
  • the opening 321 opens toward the incisors in the horizontal direction formed by the molars and the incisors (the ring body 32 is located on the side of the molars in the horizontal direction formed by the molars and the incisors, that is, the position of the ring body 32 is higher than the position of the limiting member 22 .
  • the dental anastomosis member 11 is anastomosed with the mandibular first molars, second molars and/or third molars in the oral cavity of the subject, and wraps the teeth through anastomosis.
  • the tablet may slip from the device during the rapid dissolution of the drug immediate release layer, and the tablet may also slip out of the device during wearing. Slipped, but still has a certain use value.
  • Step 1 Scan the size data of the tablet by the "3Shape Dental System” scanner. Then, through the “SolidWorks” software, a drug-carrying member capable of loading drug parts is designed, created and saved as a "Standard Attachment” file. Each time an oral retention device is designed in the "3Shape Dental System” software, a "standard accessory” is added and assembled with the dental anastomotic component to form an integrated oral retention device.
  • Step 2 Perform an intraoral or dental model scan:
  • the scanning can be performed using a conventional mouth scanner in the field, such as 3Shape Mouth scanner or conventional scanner such as Qscan type dental scanner, so scanning software such as 3Shape can be used
  • a conventional mouth scanner in the field such as 3Shape Mouth scanner or conventional scanner such as Qscan type dental scanner, so scanning software such as 3Shape can be used
  • the oral scanner or Qscan type dental scanner comes with its own system software.
  • Step 3 Device Design
  • Step 4 3D Print/Sand Polish Clean.
  • the cobalt-chromium alloy post-insertion oral retention device prepared in this embodiment includes a dental anastomosis member 11 and a drug-loading member; In close contact with the teeth in the oral cavity, the drug-carrying member can accommodate at least one tablet and keep the tablet in the oral cavity.
  • the tablet may be a controlled release formulation, preferably an osmotic pump tablet.
  • the osmotic pump tablet contains an active drug and excipients, and the active drug is composed of levodopa or its ester, carbidopa, baclofen, acyclovir, valacyclovir, ganciclovir, metformin and one of gabapentin, or one or both of levodopa or its esters and carbidopa.
  • the shape of the cross section of the drug-carrying member is a circular closed loop.
  • the drug-carrying member may be a mesh structure or a non-mesh structure.
  • the drug-carrying member includes at least one ring body 31 and at least one limiter 21 at the end, and the ring body 31 forms an opening 311 into which the tablet can be inserted.
  • the limiting piece is in the shape of a circular arc hollow.
  • the opening faces the molars in a horizontal direction formed by the molars and the incisors, and the tablet is inserted from the molars to the incisors in the horizontal direction.
  • the dental plaster model of the patient/volunteer is prepared by the traditional impression taking technique; then the dental wax model is manually prepared on the plaster model by using the dental wax as the material through the traditional manual process; The injection molding process was used to prepare the oral retention device.
  • Example 5 Cobalt-chromium alloy front insertion oral retention device prepared by 3D printing
  • the oral retention device shown in FIG. 2 is prepared by the same method as in Example 3. Only in step 3 f, the positions of the ring body of the drug-carrying member and the stopper are opposite to those in Example 3.
  • the ring body 32 of the drug-carrying member 42 forms an opening 321 into which the tablet can be inserted.
  • the opening opens toward the incisor in the horizontal direction formed by the molar and the incisor, and the tablet is inserted from the incisor to the molar in the horizontal direction.
  • the tablet may be a controlled release formulation, preferably an osmotic pump tablet.

Abstract

Disclosed are an oral retention device and a preparation method therefor. The oral retention device comprises a tooth fitting component and a drug loading component. The tooth fitting component is connected to the drug loading component. The tooth fitting component is used for bridging a tooth in the oral cavity and matching same and the tooth. The drug loading component can accommodate at least one tablet, and is used for making the tablet retained in the oral cavity. The preparation method for the oral retention device is selected from any one of 3D printing, injection molding, or stamp molding. When the tablet is inserted into the oral retention device of the present invention, a drug-device combination product can be formed, the drug-device combination product is fixed onto the fitting teeth in the oral cavity, and the tablet is not easy to fall off in the oral cavity, so that the medicine can be continuously released within a certain time, the tablet can be replaced, and the medicine is continuously and stably released.

Description

一种口腔滞留装置及其制备方法A kind of oral retention device and preparation method thereof
本申请要求申请日为2020/9/17的中国专利申请2020109803114的优先权。本申请引用上述中国专利申请的全文。This application claims the priority of Chinese patent application 2020109803114 with an application date of 2020/9/17. This application cites the full text of the above Chinese patent application.
技术领域technical field
本发明涉及医疗器械领域，特别涉及一种口腔滞留装置及其制备方法。The invention relates to the field of medical devices, in particular to an oral retention device and a preparation method thereof.
背景技术Background technique
许多活性药物成分，包括左旋多巴(Levodopa,LD)或其酯、卡比多巴(Carbidopa,CD)、巴氯芬、阿昔洛韦、伐昔洛韦、更昔洛韦、二甲双胍、加巴喷丁等，其吸收窗口限制在上胃肠道。将这些活性药物成分制备成常规的缓释剂型不仅会导致生物利用度降低，而且会导致不能实现延长的治疗覆盖。现有技术中已经揭示许多技术来延长活性药物成分在胃中的滞留时间。这些技术是：扩张(US4,735,804、US5,002,772和US6,685,962等)、膨胀(US4,434,153、US5,750,585、US5,972,389、US6,120,803、US6,660,300B1、US2007/0196396A1和US9,439,851等)、漂浮(US4,167,558、US5,232,704和US6,261,601等)、筏形成(raft-forming)(US4,140,760、US5,068,109等)、下沉(US4,193,985、US4,900,557等)和黏膜黏附(US6,207,197和US11/204,106等)。上述技术的成功非常有限，特别是当使用这些技术的口服剂型在禁食状态下给药时。Many active pharmaceutical ingredients, including levodopa (Levodopa, LD) or its esters, carbidopa (Carbidopa, CD), baclofen, acyclovir, valacyclovir, ganciclovir, metformin, gabapentin etc., its absorption window is limited to the upper gastrointestinal tract. Formulation of these active pharmaceutical ingredients into conventional sustained-release dosage forms results not only in reduced bioavailability, but also in the inability to achieve prolonged therapeutic coverage. Numerous techniques have been disclosed in the prior art to prolong the residence time of active pharmaceutical ingredients in the stomach. These techniques are: dilation (US4,735,804, US5,002,772 and US6,685,962 etc.), inflation (US4,434,153, US5,750,585, US5,972,389, US6,120,803, US6,660,300B1, US2007/0196396A1 and US9,439,851 etc.), floating (US4,167,558, US5,232,704, and US6,261,601, etc.), raft-forming (US4,140,760, US5,068,109, etc.), sinking (US4,193,985, US4,900,557, etc.) and Mucoadhesion (US6,207,197 and US11/204,106 etc.). The above techniques have had very limited success, especially when oral dosage forms using these techniques are administered in the fasted state.
因此，需要一种新的药物控释***，其能够提供对这些活性药物成分的长时间暴露，且它们的吸收窗口被限制在上胃肠道。通过口腔滞留装置和这些药物组合成药械组合物，形成口腔滞留给药***，能够提供吸收窗口限制在上胃肠道这些药物的长时间暴露。Therefore, there is a need for a new drug controlled release system that can provide prolonged exposure to these active pharmaceutical ingredients and whose absorption window is limited to the upper gastrointestinal tract. By combining the oral retention device and these drugs into a drug-device composition, an oral retention drug delivery system is formed, which can provide an absorption window to limit the prolonged exposure of these drugs in the upper gastrointestinal tract.
目前口腔滞留装置的相关研究不多，专利申请US10/668,274和专利申 请CN1997421A公开了一种基于电动控制药物释放机理的口腔含药装容器，通过电力控制药物释放，其没有涉及药片的***问题。而且该专利声称的含药容器和电动控制***实施起来困难，该专利说明书中也没有实例，没有说明如何运用电动控制药物释放机理实现以渗透泵片作为存药装置的控制释放，以达到在上胃肠道的药物吸收，从而达到长期稳定的血药浓度。At present, there are not many related researches on oral retention devices. Patent application US10/668,274 and patent application CN1997421A disclose an oral medicine-containing container based on the mechanism of electric control of drug release. Moreover, the drug-containing container and the electric control system claimed in the patent are difficult to implement. There is no example in the patent specification, and it does not explain how to use the electric control drug release mechanism to realize the controlled release of the osmotic pump tablet as the drug storage device, so as to achieve the above Drug absorption in the gastrointestinal tract, so as to achieve long-term stable blood drug concentration.
另外，CN1925823A公开了一种牙齿托架，用于将氟化物药丸体附着于牙齿，以提高龋齿的治疗和/或预防。该专利申请不涉及上胃肠道的药物吸收和长期稳定的血药浓度，也不涉及药片***方式。In addition, CN1925823A discloses a dental bracket for attaching fluoride pills to teeth to improve the treatment and/or prevention of dental caries. The patent application does not involve drug absorption in the upper gastrointestinal tract and long-term stable blood drug concentration, nor does it involve the method of tablet insertion.
另外，中国专利申请CN105873631A公开了一种需要以电子泵或机械泵作为外力动力给药的口腔滞留装置，不涉及药片***方式。In addition, Chinese patent application CN105873631A discloses an oral retention device that requires an electronic pump or a mechanical pump as an external force for drug delivery, and does not involve a tablet insertion method.
从前往后***药片(由门牙往磨牙方向)方式，药片易从装置前面(门牙侧)滑出，且病人容易因误吞脱落的药片而导致窒息。In the way of inserting the tablet from the front to the back (from the incisor to the molar), the tablet is easy to slip out from the front of the device (the side of the incisor), and the patient is prone to suffocation due to accidentally swallowing the dropped tablet.
发明内容SUMMARY OF THE INVENTION
为了解决活性药物成分在胃中的滞留时间短而导致生物利用度低的缺陷的技术问题，本发明提供一种使药片滞留于口腔而不易脱落的新的口腔滞留装置。具体地，本发明提供了一种药片的***方式为由后向前的口腔滞留装置，因后侧靠近咽喉，有颊脂垫尖和翼下颌皱襞等口腔组织阻挡，使药片在口腔装置中不脱落，不会由于误吞导致窒息。In order to solve the technical problem of low bioavailability due to short residence time of active pharmaceutical ingredients in the stomach, the present invention provides a novel oral retention device that allows the tablet to remain in the oral cavity and not easily fall off. Specifically, the present invention provides an oral retention device in which the tablet is inserted from the back to the front. Since the rear side is close to the throat, there are oral tissues such as buccal fat pad tip and pterygomandibular fold that block the tablet, so that the tablet does not remain in the oral device. It will fall off and will not cause suffocation due to accidental swallowing.
本发明的第一方面，提供了一种口腔滞留装置。所述口腔滞留装置包括一牙齿吻合构件和一载药构件，所述牙齿吻合构件与所述载药构件连接，其中，所述牙齿吻合构件用于桥接口腔内的牙齿并与所述牙齿相匹配，所述载药构件可容纳至少一药片，并用于使所述药片滞留于口腔中。A first aspect of the present invention provides an oral retention device. The oral retention device includes a dental engagement member and a medicated member, the dental engagement member is connected to the drug loaded member, wherein the dental engagement member is used for bridging and mating with the teeth in the mouth cavity , the drug-carrying member can accommodate at least one tablet and is used to keep the tablet in the oral cavity.
在优选的实施例中，所述牙齿吻合构件与所述载药构件于各自的侧部相连；和/或，所述载药构件为网状结构或非网状结构，所述载药构件的横截面的形状为圆形、椭圆形、多边形或异形的闭环或开环结构，或者其组合。所 述横截面为垂直于所述牙齿吻合构件长轴方向(所述牙齿吻合构件长轴方向基本等同于所述牙齿吻合构件与口腔中的牙齿匹配后构成的水平面)的横截面。In a preferred embodiment, the dental anastomosis member and the drug-carrying member are connected at their respective sides; and/or, the drug-carrying member is a mesh structure or a non-mesh structure, and the drug-carrying member has a mesh structure or a non-mesh structure. The shape of the cross section is a circle, an ellipse, a polygon, or a special-shaped closed-loop or open-loop structure, or a combination thereof. The cross section is a cross section perpendicular to the long axis direction of the dental engaging member (the long axis direction of the dental engaging member is substantially equal to the horizontal plane formed after the dental engaging member is matched with the teeth in the oral cavity).
在优选的实施例中，所述载药构件包括至少一环体和至少一限位件，或，所述载药构件由至少一限位件构成；其中，所述环体具有可供药片***的开口，所述限位件的结构用于将药片限制于载药构件中。In a preferred embodiment, the drug-carrying member includes at least one ring body and at least one limiting member, or the drug-carrying member is composed of at least one limiting member; wherein, the ring body has a space for inserting a tablet The structure of the limiting member is used to limit the tablet in the drug-carrying member.
在优选的实施例中，所述开口在由磨牙与门牙形成的水平方向上朝向磨牙，用于使药片在所述的水平方向从磨牙往门牙方向***；或，所述开口在垂直于所述的水平方向上设置，所述药片在垂直于所述的水平方向从上往下***；或，所述开口在垂直于所述的水平方向上朝向颊侧，所述药片在垂直于所述的水平方向从颊侧往舌侧***。本文所述的水平方向基本等同于口腔滞留装置水平放置时牙齿吻合构件最长轴所处的水平方向，也基本等同于当口腔滞留装置通过牙齿吻合构件与受试者口腔内的牙齿匹配后，所述口腔滞留装置及其牙齿吻合构件最长轴所处的水平方向。In a preferred embodiment, the opening faces the molars in a horizontal direction formed by the molars and the incisors, so that the tablet is inserted from the molars to the incisors in the horizontal direction; or, the openings are perpendicular to the incisors. It is arranged in the horizontal direction, and the tablet is inserted from top to bottom in the horizontal direction perpendicular to the Insert horizontally from buccal to lingual. The horizontal direction described herein is basically equivalent to the horizontal direction in which the longest axis of the dental anastomosis member is located when the oral retention device is placed horizontally, and is also basically equivalent to the horizontal direction in which the oral retention device is matched with the teeth in the oral cavity of the subject through the dental anastomotic member. The horizontal direction in which the longest axis of the oral retention device and its dental anastomotic member is located.
优选地，本发明的药片形态不会随时间的改变而变化，其为渗透泵片。在优选的实施例中，所述渗透泵片含活性药物和辅料。所述活性药物的成分为左旋多巴或其酯、卡比多巴、巴氯芬、阿昔洛韦、伐昔洛韦、更昔洛韦、二甲双胍和加巴喷丁中的一种，或左旋多巴或其酯和卡比多巴中的一种或两种。所述药片是一种膜控型药片，控释膜为不溶于水的醋酸纤维素类辅料，片芯由不溶性辅料骨架支撑或者助推层支撑，当药片在口腔完全释药药物后，药片外观上仍然是一个完整的药片形状。Preferably, the form of the tablet of the present invention does not change with time, and it is an osmotic pump tablet. In a preferred embodiment, the osmotic pump tablet contains active drugs and excipients. The component of the active drug is one of levodopa or its ester, carbidopa, baclofen, acyclovir, valacyclovir, ganciclovir, metformin and gabapentin, or levodopa or one or both of its esters and carbidopa. The tablet is a film-controlled tablet, the controlled release film is a water-insoluble cellulose acetate excipient, and the tablet core is supported by an insoluble excipient skeleton or a booster layer. When the tablet completely releases the drug in the oral cavity, the appearance of the tablet is The top is still a full tablet shape.
优选地，所述环体为开环体或闭环体。Preferably, the ring body is an open ring body or a closed ring body.
优选地，所述闭环体为圆形、椭圆形、多边形或异形的闭环体；所述开环体为缺少部分的(非封闭)的圆形、椭圆形、多边形或异形的开环体。Preferably, the closed-loop body is a circular, elliptical, polygonal or special-shaped closed-loop body; the open-loop body is a circular, elliptical, polygonal or special-shaped open-loop body with missing parts (non-closed).
在优选的实施例中，所述限位件为圆弧形镂空状或实心状，或所述限位件由一个闭环体和一个垂直于闭环体的半圆连接而成；和/或，所述限位件与 所述环体邻接，或，所述限位件与所述环体间隔设置。In a preferred embodiment, the limiting member is an arc-shaped hollow or solid shape, or the limiting member is formed by connecting a closed-loop body and a semicircle perpendicular to the closed-loop body; and/or, the The limiting member is adjacent to the ring body, or the limiting member is spaced from the ring body.
优选地，所述邻接为一体成型，或通过连接结构连接到一起。Preferably, the abutments are integrally formed or connected together by connecting structures.
在优选的实施例中，所述限位件的数目为一个，所述限位件位于所述的水平方向靠门牙一侧；和/或，所述环体的数目为一个，所述环***于由磨牙与门牙形成的水平方向靠磨牙一侧。In a preferred embodiment, the number of the stopper is one, and the stopper is located on the side of the incisor in the horizontal direction; and/or, the number of the ring body is one, and the ring body It is located on the side of the molars in the horizontal direction formed by the molars and the incisors.
优选地，所述牙齿吻合构件可以与口腔内任意一个或者多个牙齿相吻合，和/或，所述牙齿吻合构件的长度为2～5颗牙的长度。Preferably, the tooth-fitting member can fit with any one or more teeth in the oral cavity, and/or the length of the tooth-fitting member is the length of 2-5 teeth.
优选地，所述牙齿为下颌恒牙。优选下颌磨牙。最优选为第一磨牙和第二磨牙，或，第一磨牙、第二磨牙和第二前磨牙，或，第一磨牙、第二磨牙和第三磨牙，或第一磨牙、第二磨牙、第三磨牙和第二前磨牙。Preferably, the teeth are mandibular permanent teeth. Mandibular molars are preferred. Most preferably first molars and second molars, or first molars, second molars and second premolars, or first molars, second molars and third molars, or first molars, second molars, third molars Tri-molars and second premolars.
优选地，所述牙齿吻合构件根据个体牙齿尺寸、形状制备。所述牙齿吻合构件包裹、嵌入、卡入或***与其相吻合的牙齿。Preferably, the dental engaging members are prepared according to the size and shape of individual teeth. The dental engaging member wraps, engages, snaps into, or inserts the teeth to which it engages.
优选地，所述的口腔滞留装置的材质为口腔用稳定性材料，所述口腔用稳定性材料选自口腔稳定性金属或热塑性弹性体。Preferably, the material of the oral retention device is a stable material for oral cavity, and the stable material for oral cavity is selected from oral stable metal or thermoplastic elastomer.
优选地，所述口腔稳定性金属选自牙科用钛、不锈钢、钴铬合金、钴铬钼合金或贵金属中的一种；所述热塑性弹性体选自聚己内酯、乙烯-醋酸乙烯共聚物、高密度聚乙烯、聚丙烯、聚丙烯酸酯、聚氨酯、硅聚合物、聚酯、聚(苯乙烯-乙烯-丁烯-苯乙烯)、聚(苯乙烯-丁二烯-苯乙烯)、聚(苯乙烯-异戊二烯-苯乙烯)的一种或两种的共聚物。Preferably, the oral-stable metal is selected from one of dental titanium, stainless steel, cobalt-chromium alloy, cobalt-chromium-molybdenum alloy or precious metal; the thermoplastic elastomer is selected from polycaprolactone, ethylene-vinyl acetate copolymer , HDPE, polypropylene, polyacrylate, polyurethane, silicone polymers, polyester, poly(styrene-ethylene-butylene-styrene), poly(styrene-butadiene-styrene), poly A copolymer of one or both of (styrene-isoprene-styrene).
更优选地，所述牙齿吻合构件和载药构件的材质为钴铬合金。More preferably, the material of the dental anastomosis member and the drug-carrying member is cobalt-chromium alloy.
本发明的第二个方面，提供了一种制备本发明的第一个方面的口腔滞留装置的方法。所述方法选自3D打印、注塑成型或印模成型中的任一种。A second aspect of the present invention provides a method of manufacturing the oral retention device of the first aspect of the present invention. The method is selected from any of 3D printing, injection molding or impression molding.
所述制备本发明的第一个方面的口腔滞留装置的方法为3D打印，其包括以下步骤：The method for preparing the oral retention device of the first aspect of the present invention is 3D printing, which includes the following steps:
(1)在设计软件中，添加保存的载药构件的方案，并与牙齿吻合构件的方案组装成一体化的口腔滞留装置的方案，导出可3D打印的文件；所 述设计软件优选3Shape Dental System；(1) In the design software, add the plan of the saved drug-carrying component, and assemble the plan of the integrated oral retention device with the plan of the dental anastomosis component, and export the 3D printable file; the design software is preferably 3Shape Dental System ;
(2)将所述可3D打印的文件导入3D打印机并打印所述口腔滞留装置；所述3D打印优选使用激光烧结工艺；(2) importing the 3D printable file into a 3D printer and printing the oral retention device; the 3D printing preferably uses a laser sintering process;
较佳地，在所述步骤(1)前还包括：(0)在软件中，根据药片尺寸的数据设计载药构件的方案并保存，所述软件优选SolidWorks或中望3D平台设计软件；和/或，在所述设计软件中，根据受试者的牙齿尺寸的数据设计牙齿吻合构件的方案；Preferably, before the step (1), it also includes: (0) in the software, design and save the plan of the drug-carrying member according to the data of the tablet size, the software is preferably SolidWorks or Zhongwang 3D platform design software; and /or, in the design software, design the plan of the dental anastomosis member according to the data of the subject's tooth size;
更佳地，所述药片尺寸的数据和/或所述受试者牙齿的数据使用扫描仪扫描药片和/或受试者牙齿或受试者牙齿模型获得，所述牙齿模型通过传统取模技术制备，所述扫描仪优选为3Shape
Figure PCTCN2021119120-appb-000001
扫描仪。 More preferably, the data of the tablet size and/or the data of the subject's teeth are obtained by scanning the tablet and/or the subject's teeth or the subject's tooth model using a scanner, and the tooth model is obtained by traditional impression taking techniques prepared, the scanner is preferably a 3Shape
Figure PCTCN2021119120-appb-000001
scanner.
在一个具体的实施例中，使用“3Shape
Figure PCTCN2021119120-appb-000002
”口内扫描仪扫描药片的尺寸数据，然后，将数据导入“SolidWorks”软件，设计能够装载药品部分的载药构件的方案，创建并保存该方案为“标准附件”文件；使用“3Shape
Figure PCTCN2021119120-appb-000003
”口内扫描仪扫描受试者牙齿，数据导入到“3Shape Dental System”软件，根据牙齿数据设计牙齿吻合构件；在“3Shape Dental System”软件上，添加“标准附件”并与牙齿吻合构件组装成一体化的口腔滞留装置，导出可3D打印的文件；将所述可3D打印的文件导入3D打印机并打印所述口腔滞留装置。所述3D打印优选使用激光烧结工艺。 In a specific embodiment, "3Shape
Figure PCTCN2021119120-appb-000002
"The intraoral scanner scans the size data of the tablet, and then, import the data into the "SolidWorks" software, design a plan for the drug-carrying component that can load the drug part, create and save the plan as a "standard attachment"file; use "3Shape"
Figure PCTCN2021119120-appb-000003
"The intraoral scanner scans the subject's teeth, and the data is imported into the "3Shape Dental System" software, and the dental anastomotic components are designed according to the tooth data; on the "3Shape Dental System" software, "standard accessories" are added and assembled with the dental anastomotic components. importing the 3D printable file into a 3D printer and printing the oral retention device. The 3D printing preferably uses a laser sintering process.
其中，所述3D打印与普通打印机工作原理基本相同。3D打印机内装有金属、陶瓷、塑料、砂等不同的“打印材料”，打印机与电脑连接后，通过电脑控制可以把“打印材料”一层层叠加起来，最终把计算机上的蓝图变成实物。3D打印参照了普通打印机的技术原理，其中分层加工的过程与喷墨打印十分相似，这种打印技术称为3D立体打印技术。3D打印存在着许多不同的技术，它们的不同之处在于以可用的材料的方式，并以不同层构建创建部件。3D打印常用材料为尼龙玻纤、聚乳酸、ABS树脂、耐用性尼龙材料、石膏材料、铝材料、金属钛、钛合金、不锈钢、镀银、镀金、钴铬合金、钴 铬钼合金或橡胶类材料等。3D打印的优点在于操作可实现自动化、生产速度快、直接和较精确地将计算机中的设计蓝图转成实物模型，也适用于小规模的定制生产制造。Wherein, the 3D printing is basically the same as the working principle of an ordinary printer. The 3D printer is equipped with different "printing materials" such as metal, ceramics, plastic, sand, etc. After the printer is connected to the computer, the "printing materials" can be superimposed layer by layer through the computer control, and finally the blueprint on the computer can be turned into a real thing. 3D printing refers to the technical principles of ordinary printers, in which the process of layered processing is very similar to inkjet printing. This printing technology is called 3D stereo printing technology. Many different technologies exist for 3D printing, which differ in the way the materials are available, and build up in different layers to create parts. Common materials for 3D printing are nylon glass fiber, polylactic acid, ABS resin, durable nylon material, gypsum material, aluminum material, titanium metal, titanium alloy, stainless steel, silver-plated, gold-plated, cobalt-chromium alloy, cobalt-chromium-molybdenum alloy or rubber materials, etc. The advantage of 3D printing is that the operation can be automated, the production speed is fast, the design blueprint in the computer can be directly and accurately converted into a physical model, and it is also suitable for small-scale custom manufacturing.
在另外的实施例中，所述制备本发明的第一个方面的口腔滞留装置的方法为注塑成型，其包括以下步骤：In further embodiments, the method of making the oral retention device of the first aspect of the present invention is injection molding comprising the steps of:
(1)根据牙齿模型制备牙齿吻合构件模型；(1) Prepare a dental anastomosis component model according to the tooth model;
(2)根据药片尺寸制备载药构件模型；(2) Prepare a drug-carrying component model according to the tablet size;
(3)获得牙齿吻合构件和载药构件一体化的口腔滞留装置模型；(3) Obtaining an oral retention device model integrating the dental anastomosis component and the drug-carrying component;
(4)通过传统注塑工艺制备个性化的口腔滞留装置；(4) Preparation of personalized oral retention device by traditional injection molding process;
较佳地，所述牙齿模型通过传统取模技术制备或通过口腔扫描技术获得受试者的牙齿数据并打印；Preferably, the tooth model is prepared by traditional impression taking technology or the subject's tooth data is obtained and printed by oral scanning technology;
更佳地，所述牙齿吻合构件模型、载药构件模型和口腔滞留装置模型的材质为牙蜡，和/或，所述牙齿模型的材质为石膏或树脂。More preferably, the material of the dental anastomosis component model, the drug-carrying component model and the oral retention device model is dental wax, and/or the material of the tooth model is gypsum or resin.
注塑成型又称注射模塑成型，其是一种注射兼模塑的成型方法，即在一定温度下，通过螺杆搅拌完全熔融的材料，用高压射入模腔，经冷却固化后，得到成型品的方法。该方法适用于形状复杂部件的批量生产，是重要的加工方法之一。注塑成型方法的优点是生产速度快、效率高，操作可实现自动化，花色品种多，形状可以由简到繁，尺寸可以由大到小，而且制品尺寸精确，产品易更新换代，能成形状复杂的制件，注塑成型适用于大量生产与形状复杂产品等成型加工领域。Injection molding, also known as injection molding, is a molding method of injection and molding, that is, at a certain temperature, the completely molten material is stirred by a screw, injected into the mold cavity with high pressure, and cooled and solidified to obtain a molded product Methods. This method is suitable for mass production of complex-shaped parts, and is one of the important processing methods. The advantages of the injection molding method are that the production speed is fast, the efficiency is high, the operation can be automated, there are many varieties of colors, the shape can be from simple to complex, the size can be from large to small, and the size of the product is accurate, the product is easy to replace, and it can be formed into complex shapes. Parts, injection molding is suitable for mass production and complex shape products and other molding processing fields.
在另外的实施例中，所述制备本发明的第一个方面的口腔滞留装置的方法为印模成型，其包括：In further embodiments, the method of making the oral retention device of the first aspect of the present invention is impression molding, comprising:
根据药片尺寸设计载药构件；以聚已内酯(PCL)为材料制备牙齿吻合构件，以钴铬合金为材料制备载药构件；将牙齿吻合构件和载药构件组装成完整的口腔滞留装置。The drug-carrying component was designed according to the tablet size; the dental anastomosis component was prepared with polycaprolactone (PCL) as the material, and the drug-carrying component was prepared with cobalt-chromium alloy as the material; the dental anastomosis component and the drug-carrying component were assembled into a complete oral retention device.
在一个具体的实施例中，首先采用传统注塑工艺制备能够装载渗透泵片 的载药构件；然后将热塑片加热软化后制备成牙齿吻合构件，同时将软化的牙齿吻合构件与载药构件嵌合，冷却后形成一体化的口腔滞留装置，从口腔取出。In a specific embodiment, a traditional injection molding process is used to prepare a drug-carrying member capable of loading an osmotic pump sheet; then the thermoplastic sheet is heated and softened to prepare a dental anastomosis member, and the softened dental anastomosis member is embedded with the drug-carrying member at the same time. After cooling, an integrated oral retention device is formed and taken out from the oral cavity.
在符合本领域常识的基础上，上述各优选条件，可任意组合，即得本发明各较佳实例。On the basis of conforming to common knowledge in the art, the above preferred conditions can be combined arbitrarily to obtain preferred examples of the present invention.
本发明所用试剂和原料均市售可得。The reagents and raw materials used in the present invention are all commercially available.
本发明的积极进步效果在于：提供了一种药片的***方向为由咽喉向门牙的口腔滞留装置，因口腔滞留装置的后侧靠近咽喉，在口腔粘膜组织阻挡的作用下药片在口腔中不易脱落。将药片***口腔滞留装置中形成药械组合物，药械组合物固定于口腔中相吻合的牙齿上，实现药物在一定时间内持续释放。保持0～24小时后取出药械组合物，更换新的药片，重新将药械组合物固定于口腔中相吻合的牙齿上，使药物持续稳定释放药物。The positive and progressive effect of the present invention is that: an oral retention device in which the insertion direction of the tablet is from the throat to the incisors is provided. Because the rear side of the oral retention device is close to the throat, the tablet is not easy to fall off in the oral cavity due to the blocking effect of the oral mucosal tissue. . The tablet is inserted into the oral cavity retention device to form a drug-device composition, and the drug-device composition is fixed on the matching teeth in the oral cavity, so that the drug can be continuously released within a certain period of time. After holding for 0-24 hours, the drug-device composition is taken out, replaced with a new tablet, and the drug-device composition is re-fixed on the matching teeth in the oral cavity, so that the drug can be continuously and stably released.
附图说明Description of drawings
图1为本发明一实施例的药片后插式口腔滞留装置，其由牙齿吻合构件11和载药构件41组成，其中，载药构件41由限位件21和环体31组成，环体31上有开口311。FIG. 1 is a tablet post-insertion oral retention device according to an embodiment of the present invention, which is composed of a dental anastomosis member 11 and a drug-carrying member 41, wherein the drug-carrying member 41 is composed of a stopper 21 and a ring body 31, and the ring body 31 There is an opening 311 thereon.
图2为本发明一实施例的药片前插式口腔滞留装置，其由牙齿吻合构件12和载药构件42组成，其中，载药构件42由限位件22和环体32组成，环体32上有开口321。FIG. 2 shows a tablet front-insertion oral retention device according to an embodiment of the present invention, which is composed of a dental anastomosis member 12 and a drug-carrying member 42 , wherein the drug-carrying member 42 is composed of a stopper 22 and a ring body 32 , and the ring body 32 There is an opening 321 thereon.
附图标记说明：Description of reference numbers:
11：后插式口腔滞留装置的牙齿吻合构件11: Dental anastomosis component of the rear-insertion oral retention device
21：后插式口腔滞留装置的限位件21: The limiter of the rear-inserted oral retention device
31：后插式口腔滞留装置的环体31: Ring body of the rear insertion oral retention device
311：后插式口腔滞留装置的环体上的开口311: Opening in the ring body of the rear insertion oral retention device
41：后插式口腔滞留装置的载药构件41: The drug-carrying member of the rear-insertion oral retention device
12：前插式口腔滞留装置的牙齿吻合构件12: Dental anastomosis component of the front insertion oral retention device
22：前插式口腔滞留装置的限位件22: The limiter of the front-inserted oral retention device
32：前插式口腔滞留装置的环体32: Ring body of the front insertion oral retention device
321：前插式口腔滞留装置的环体上的开口321: Opening in the ring body of a front insertion oral retention device
42：前插式口腔滞留装置的载药构件42: The drug-carrying member of the front-inserted oral retention device
具体实施方式detailed description
下面列举较佳实施例，并结合附图来更清楚完整地说明本发明。应注意到：除非另有说明，否则在这些实施例中阐述的部件和步骤的相对布置和数值不限制本发明的范围。The preferred embodiments are listed below, and the present invention will be more clearly and completely described with reference to the accompanying drawings. It should be noted that the relative arrangements and numerical values of the components and steps set forth in these embodiments do not limit the scope of the invention unless otherwise indicated.
实施例1 钴铬合金后插式口腔滞留装置Example 1 Cobalt-chromium alloy post-insertion oral retention device
图1所示的实施例中，所述药片后插式口腔滞留装置由牙齿吻合构件11和载药构件41连接而组成。所述牙齿吻合构件11可与受试者口腔内的牙齿密合，所述载药构件41的尺寸使其可容纳至少一药片，并使所述药片滞留于口腔中。所述牙齿吻合构件11和载药构件41均由钴铬合金制备而得，所述牙齿吻合构件11与所述载药构件41于各自的侧部相连接。所述载药构件包括一环体31和一位于末端的限位件21，所述环体31为圆形闭环体，具有可供药片***的开口311。所述限位件与所述环体为间隔设置，各自连接在牙齿吻合构件11上；在另一方案中，所述限位件可以与所述环体一体成型后固定在牙齿吻合构件上，也可以与所述环体和所述牙齿吻合构件一体成型制备。口腔滞留装置通过牙齿吻合构件与受试者口腔内的牙齿匹配后，所述开口311在由磨牙与门牙形成的水平方向上开口朝向磨牙(所述环体31位于所述的水平方向靠磨牙一侧，即环体31的位置较限位件21的位置更接近磨牙)，所述药片在所述的水平方向从磨牙往门牙方向***。所述限位件为圆弧形镂空状，其结构用于将药片限制于载药构件。所述牙齿吻合构件11与 受试者口腔内下颌第一磨牙、第二磨牙和/第三磨牙吻合，通过吻合包裹牙齿。In the embodiment shown in FIG. 1 , the tablet post-insertion oral retention device is formed by connecting the dental anastomosis member 11 and the drug-carrying member 41 . The dental engagement member 11 can be in close contact with the teeth in the oral cavity of the subject, and the drug-carrying member 41 is sized to accommodate at least one tablet and retain the tablet in the oral cavity. The dental anastomosis member 11 and the drug-carrying member 41 are both made of cobalt-chromium alloy, and the dental anastomosis member 11 and the drug-carrying member 41 are connected at their respective sides. The drug-carrying member includes a ring body 31 and a limiter 21 at the end. The ring body 31 is a circular closed-loop body and has an opening 311 for inserting a tablet. The stopper and the ring body are arranged at intervals, and are respectively connected to the dental anastomosis member 11; It can also be produced in one piece with the ring body and the dental engagement member. After the oral retention device is matched with the teeth in the oral cavity of the subject through the dental anastomosis member, the opening 311 opens toward the molars in the horizontal direction formed by the molars and the incisors (the ring body 31 is located in the horizontal direction close to the molars. side, that is, the position of the ring body 31 is closer to the molars than the position of the limiting member 21), the tablet is inserted from the molars to the incisors in the horizontal direction. The limiting member is in the shape of a circular arc hollow, and its structure is used to limit the tablet to the drug-carrying member. The dental anastomosis member 11 is anastomosed with the mandibular first molars, second molars and/or third molars in the oral cavity of the subject, and wraps the teeth through anastomosis.
在口腔中佩戴装载药片后的本实施例的口腔滞留装置，即使经过激烈漱口使药物速释层快速溶解，药片也能固定牢固，不会从装置中滑落。Wearing the oral retention device of this embodiment after the tablet is loaded in the oral cavity, even if the drug immediate-release layer is rapidly dissolved by vigorous gargling, the tablet can be fixed firmly and will not slip out of the device.
实施例2 钴铬合金前插式口腔滞留装置Example 2 Cobalt-chromium alloy front insertion oral retention device
图2所示的实施例中，所述药片前插式口腔滞留装置由牙齿吻合构件12和载药构件42连接而组成。所述牙齿吻合构件12可与受试者口腔内的牙齿密合，所述载药构件42的尺寸使其可容纳至少一药片，并使所述药片滞留于口腔中。所述牙齿吻合构件12和载药构件42均由钴铬合金制备而得，所述牙齿吻合构件12与所述载药构件42于各自的侧部相连。所述载药构件42包括一环体32和一位于末端的限位件22，所述环体32为圆形闭环体，具有可供药片***的开口321。所述限位件与所述环体为间隔设置，各自连接在牙齿吻合构件11上；在另一方案中，所述限位件可以与所述环体一体成型后固定在牙齿吻合构件上，也可以与所述环体和所述牙齿吻合构件一体成型制备。所述开口321在由磨牙与门牙形成的水平方向上开口朝向门牙(所述环体32位于由磨牙与门牙形成的水平方向靠磨牙一侧，即环体32的位置较限位件22的位置更接近门牙)，所述药片在由磨牙与门牙形成的水平方向从门牙往磨牙方向***。所述限位件为圆弧形镂空状，所述限位件的结构用于将药片限制于载药构件。所述牙齿吻合构件11与受试者口腔内下颌第一磨牙、第二磨牙和/第三磨牙吻合，通过吻合包裹牙齿。In the embodiment shown in FIG. 2 , the tablet front-insertion oral retention device is formed by connecting the dental anastomosis member 12 and the drug-carrying member 42 . The dental engagement member 12 can be in close contact with the teeth in the oral cavity of the subject, and the medicated member 42 is sized to receive at least one tablet and retain the tablet in the oral cavity. The dental anastomosis member 12 and the drug-carrying member 42 are both made of cobalt-chromium alloy, and the dental anastomosis member 12 and the drug-carrying member 42 are connected at their respective sides. The drug-carrying member 42 includes a ring body 32 and a limiter 22 at the end. The ring body 32 is a circular closed ring body and has an opening 321 for inserting a tablet. The stopper and the ring body are arranged at intervals, and are respectively connected to the dental anastomosis member 11; It can also be produced in one piece with the ring body and the dental engagement member. The opening 321 opens toward the incisors in the horizontal direction formed by the molars and the incisors (the ring body 32 is located on the side of the molars in the horizontal direction formed by the molars and the incisors, that is, the position of the ring body 32 is higher than the position of the limiting member 22 . closer to the incisors), the tablet is inserted from the incisors to the molars in the horizontal direction formed by the molars and the incisors. The limiting member is in the shape of a circular arc hollow, and the structure of the limiting member is used to limit the tablet to the drug-carrying member. The dental anastomosis member 11 is anastomosed with the mandibular first molars, second molars and/or third molars in the oral cavity of the subject, and wraps the teeth through anastomosis.
在口腔中佩戴装载药片后的本实施例的口腔滞留装置，在经过激烈漱口的情况下，药物速释层快速溶解过程中，药片有可能从装置中滑落，佩戴过程中也可能从装置中滑落，但仍具有一定使用价值。Wearing the oral retention device of this embodiment after the tablet is loaded in the oral cavity, in the case of vigorous gargling, the tablet may slip from the device during the rapid dissolution of the drug immediate release layer, and the tablet may also slip out of the device during wearing. Slipped, but still has a certain use value.
实施例3 3D打印制备钴铬合金后插式口腔滞留装置Example 3 3D printing preparation of cobalt-chromium alloy post-insertion oral retention device
本实施例的钴铬合金后插式口腔滞留装置的制备方法包括以下步骤：The preparation method of the cobalt-chromium alloy post-insertion oral retention device of the present embodiment comprises the following steps:
步骤1：通过“3Shape Dental System”扫描仪扫描药片的尺寸数据。然后，通过“SolidWorks”软件，设计能够装载药品部分的载药构件，创建并保存为“标准附件”文件。每次在“3Shape Dental System”软件中设计口腔滞留装置时，添加“标准附件”并与牙齿吻合构件组装成一体化的口腔滞留装置。Step 1: Scan the size data of the tablet by the "3Shape Dental System" scanner. Then, through the "SolidWorks" software, a drug-carrying member capable of loading drug parts is designed, created and saved as a "Standard Attachment" file. Each time an oral retention device is designed in the "3Shape Dental System" software, a "standard accessory" is added and assembled with the dental anastomotic component to form an integrated oral retention device.
步骤2：进行口腔内或牙齿模型扫描：Step 2: Perform an intraoral or dental model scan:
a.打开扫描软件；a. Open the scanning software;
b.新建患者，新建病例；b. New patients and new cases;
c.选择研究模型；c. Select the research model;
d.进行下颌扫描；d. Perform a jaw scan;
e.进行上颌扫描；e. Perform a maxillary scan;
f.进行咬合关系扫描；f. Scan the occlusal relationship;
g.后处理文件，确认所有磨牙和前磨牙的数据扫描完整，无缺陷。上下牙咬合扫描准确；g. Post-process files to confirm that all molar and premolar data scans are complete and free of defects. The upper and lower occlusal scanning is accurate;
h.保存3OXZ或STL格式文件。h. Save 3OXZ or STL format files.
本步骤中，扫描可使用本领域常规口扫仪例如3Shape
Figure PCTCN2021119120-appb-000004
口扫仪或常规扫描仪例如Qscan型齿科扫描仪，因此可使用扫描软件例如3Shape
Figure PCTCN2021119120-appb-000005
口扫仪或Qscan型齿科扫描仪自带***软件。 In this step, the scanning can be performed using a conventional mouth scanner in the field, such as 3Shape
Figure PCTCN2021119120-appb-000004
Mouth scanner or conventional scanner such as Qscan type dental scanner, so scanning software such as 3Shape can be used
Figure PCTCN2021119120-appb-000005
The oral scanner or Qscan type dental scanner comes with its own system software.
步骤3：装置设计Step 3: Device Design
a.打开设计软件；a. Open the design software;
b.新建订单；b. New order;
c.选中牙位；c. Select the tooth position;
d.选择基底冠设计；d. Select the basal crown design;
e.导入口腔扫描牙齿数据(STL文件)，进行个性化磨牙吻合构件的设计；e. Import oral scanned tooth data (STL file) to design personalized molar anastomosis components;
f.添加“标准附件”并与牙齿吻合构件组装成一体化的口腔滞留装置， 开口在由磨牙与门牙形成的水平方向上开口朝向磨牙，使药片在由磨牙与门牙形成的水平方向并可从磨牙往门牙方向***。f. Add a "standard accessory" and assemble it with the dental anastomosis member to form an integrated oral retention device, with the opening facing the molars in the horizontal direction formed by the molars and the incisors, so that the tablet can be removed from the horizontal direction formed by the molars and the incisors. The molars are inserted towards the front teeth.
g.设计完成，导出3OXZ或STL格式文件文件。g. After the design is completed, export the file in 3OXZ or STL format.
本步骤中，可使用本领域常规设计软件例如3Shape Dental System设计软件。In this step, conventional design software in the field such as 3Shape Dental System design software can be used.
步骤4：3D打印/打磨抛光清洁。Step 4: 3D Print/Sand Polish Clean.
a.CAM程序输入；a. CAM program input;
b.EOS激光熔铸；b. EOS laser casting;
c.打磨抛光，装置如图1所示；c. Grinding and polishing, the device is shown in Figure 1;
d.清洁；d. Clean;
e.成品检验。e. Finished product inspection.
如图1所示，本实施例制备的钴铬合金后插式口腔滞留装置包括牙齿吻合构件11和载药构件；牙齿吻合构件11与载药构件于各自的侧部相连接，牙齿吻合构件可与口腔内的牙齿密合，载药构件可容纳至少一药片，并使药片滞留于口腔中。药片可为控释制剂，优选为渗透泵片。所述渗透泵片含活性药物和辅料，所述活性药物的成分为左旋多巴或其酯、卡比多巴、巴氯芬、阿昔洛韦、伐昔洛韦、更昔洛韦、二甲双胍和加巴喷丁中的一种，或左旋多巴或其酯和卡比多巴中的一种或两种。载药构件横截面的形状为圆形闭环。载药构件可为网状结构或非网状结构。载药构件包括至少一环体31和至少一位于末端的限位件21，环体31形成可供药片***的开口311。限位件为圆弧形镂空状。开口在由磨牙与门牙形成的水平方向上朝向磨牙，药片在所述水平方向上从磨牙往门牙方向***。As shown in FIG. 1 , the cobalt-chromium alloy post-insertion oral retention device prepared in this embodiment includes a dental anastomosis member 11 and a drug-loading member; In close contact with the teeth in the oral cavity, the drug-carrying member can accommodate at least one tablet and keep the tablet in the oral cavity. The tablet may be a controlled release formulation, preferably an osmotic pump tablet. The osmotic pump tablet contains an active drug and excipients, and the active drug is composed of levodopa or its ester, carbidopa, baclofen, acyclovir, valacyclovir, ganciclovir, metformin and one of gabapentin, or one or both of levodopa or its esters and carbidopa. The shape of the cross section of the drug-carrying member is a circular closed loop. The drug-carrying member may be a mesh structure or a non-mesh structure. The drug-carrying member includes at least one ring body 31 and at least one limiter 21 at the end, and the ring body 31 forms an opening 311 into which the tablet can be inserted. The limiting piece is in the shape of a circular arc hollow. The opening faces the molars in a horizontal direction formed by the molars and the incisors, and the tablet is inserted from the molars to the incisors in the horizontal direction.
实施例4 注塑成型钴铬合金口腔滞留装置的制备Example 4 Preparation of injection molding cobalt-chromium alloy oral retention device
首先通过传统取模技术制备患者/志愿者的牙齿石膏模型；然后通过传统手工工艺，以牙蜡为材料，在石膏模型上手工制备牙蜡模型；最后以钴铬烤 瓷合金为材料，通过传统注塑工艺制备口腔滞留装置。Firstly, the dental plaster model of the patient/volunteer is prepared by the traditional impression taking technique; then the dental wax model is manually prepared on the plaster model by using the dental wax as the material through the traditional manual process; The injection molding process was used to prepare the oral retention device.
实施例5 3D打印制备得到的钴铬合金前插式口腔滞留装置Example 5 Cobalt-chromium alloy front insertion oral retention device prepared by 3D printing
如图2所示的口腔滞留装置，其通过同实施例3的方法制备得到，仅在步骤3的f中，载药构件的环体与限位件的位置与实施例3的相反。载药构件42的环体32形成可供药片***的开口321，开口在由磨牙与门牙形成的水平方向上开口朝向门牙，药片在所述水平方向上从门牙往磨牙方向***。药片可为控释制剂，优选为渗透泵片。The oral retention device shown in FIG. 2 is prepared by the same method as in Example 3. Only in step 3 f, the positions of the ring body of the drug-carrying member and the stopper are opposite to those in Example 3. The ring body 32 of the drug-carrying member 42 forms an opening 321 into which the tablet can be inserted. The opening opens toward the incisor in the horizontal direction formed by the molar and the incisor, and the tablet is inserted from the incisor to the molar in the horizontal direction. The tablet may be a controlled release formulation, preferably an osmotic pump tablet.

Claims (10)

  1. 一种口腔滞留装置，其特征在于，所述口腔滞留装置包括一牙齿吻合构件和一载药构件，所述牙齿吻合构件与所述载药构件连接，其中，所述牙齿吻合构件用于桥接口腔内的牙齿并与所述牙齿相匹配，所述载药构件可容纳至少一药片，并用于使所述药片滞留于口腔中。An oral retention device, characterized in that the oral retention device comprises a dental anastomosis member and a drug-carrying member, the dental anastomosis member is connected to the drug-carrying member, wherein the dental anastomosis member is used for bridging an oral cavity teeth inside and matched with the teeth, the medicated member can accommodate at least one tablet and is used to retain the tablet in the oral cavity.
  2. 如权利要求1所述的口腔滞留装置，其特征在于，所述牙齿吻合构件与所述载药构件于各自的侧部相连接；和/或，所述载药构件为网状结构或非网状结构，所述载药构件的横截面的形状为圆形、椭圆形、多边形或异形的闭环或开环结构；The oral retention device of claim 1, wherein the dental anastomosis member and the drug-carrying member are connected at respective side portions; and/or the drug-carrying member is a mesh structure or non-mesh The shape of the cross section of the drug-loading member is a circular, elliptical, polygonal or special-shaped closed-loop or open-loop structure;
    优选地，所述载药构件包括至少一环体和至少一限位件，或，所述载药构件由至少一限位件构成；其中，所述环体具有可供药片***的开口，所述限位件的结构用于将药片限制于载药构件中；Preferably, the drug-carrying member includes at least one ring body and at least one limiting member, or the drug-carrying member is composed of at least one limiting member; wherein, the ring body has an opening into which the tablet can be inserted, so the The structure of the limiter is used to limit the tablet in the drug-carrying member;
    更优选地，所述开口在由磨牙与门牙形成的水平方向上朝向磨牙，用于使药片在所述的水平方向从磨牙往门牙方向***；或，所述开口在垂直于所述的水平方向上设置，所述药片在垂直于所述的水平方向从上往下***；或，所述开口在垂直于所述的水平方向上朝向颊侧，所述药片在垂直于所述的水平方向从颊侧往舌侧***。More preferably, the opening faces the molars in a horizontal direction formed by the molars and the incisors, so that the tablet is inserted in the horizontal direction from the molars to the incisors; or, the openings are perpendicular to the horizontal direction. Set on the upper side, the tablet is inserted from top to bottom in the horizontal direction perpendicular to the said opening; or, the opening is facing the buccal side in the Insert buccal to lingual.
  3. 如权利要求2所述的口腔滞留装置，其特征在于，所述药片为渗透泵片；优选地，所述渗透泵片含活性药物和辅料，所述活性药物的成分为左旋多巴或其酯、卡比多巴、巴氯芬、阿昔洛韦、伐昔洛韦、更昔洛韦、二甲双胍和加巴喷丁中的一种或多种，或左旋多巴或其酯和卡比多巴中的一种或两种。The oral retention device according to claim 2, wherein the tablet is an osmotic pump tablet; preferably, the osmotic pump tablet contains an active drug and auxiliary materials, and the active drug is composed of levodopa or its ester. , one or more of carbidopa, baclofen, acyclovir, valacyclovir, ganciclovir, metformin, and gabapentin, or levodopa or its esters and carbidopa one or both.
  4. 如权利要求2所述的口腔滞留装置，其特征在于，所述环体为开环体或闭环体；优选地，所述环体为圆形、椭圆形、多边形或异形的闭环体或开环体。The oral retention device according to claim 2, wherein the ring body is an open-loop body or a closed-loop body; preferably, the ring body is a circular, elliptical, polygonal or special-shaped closed-loop body or an open-loop body body.
  5. 如权利要求2所述的口腔滞留装置，其特征在于，所述限位件为圆弧形镂空状或实心状，或，所述限位件由一个闭环体和一个垂直于闭环体的半圆连接而成；和/或，所述限位件与所述环体邻接，或，所述限位件与所述环体间隔设置；优选地，所述邻接为一体成型，或通过连接结构连接到一起。The oral retention device according to claim 2, wherein the limiting member is a hollow or solid arc-shaped, or the limiting member is connected by a closed-loop body and a semicircle perpendicular to the closed-loop body and/or, the stopper is adjacent to the ring body, or the stopper is spaced from the ring body; preferably, the abutment is integrally formed, or connected to the ring body through a connecting structure Together.
  6. 如权利要求2所述的口腔滞留装置，其特征在于，所述限位件的数目为一个，所述限位件位于由磨牙与门牙形成的水平方向靠门牙一侧；和/或，所述环体的数目为一个，所述环***于由磨牙与门牙形成的水平方向靠磨牙一侧。The oral retention device according to claim 2, wherein the number of the limiting member is one, and the limiting member is located on the side of the incisor in the horizontal direction formed by the molars and the incisors; and/or, the The number of ring bodies is one, and the ring body is located on the side of the molars in the horizontal direction formed by the molars and the incisors.
  7. 如权利要求1所述的口腔滞留装置，其特征在于，所述牙齿吻合构件可以与口腔内任意一个或者多个牙齿相吻合，和/或，所述牙齿吻合构件的长度为2～5颗牙的长度；较佳地，所述牙齿为下颌恒牙，优选下颌磨牙，更优选为下颌的第一磨牙和第二磨牙，或，第一磨牙、第二磨牙和第二前磨牙，或，第一磨牙、第二磨牙和第三磨牙，或第一磨牙、第二磨牙、第三磨牙和第二前磨牙。The oral retention device according to claim 1, wherein the dental anastomosis member can be fitted with any one or more teeth in the oral cavity, and/or the tooth engagement member has a length of 2 to 5 teeth Preferably, the teeth are mandibular permanent teeth, preferably mandibular molars, more preferably mandibular first molars and second molars, or, first molars, second molars and second premolars, or, first molars A molar, a second molar and a third molar, or a first molar, a second molar, a third molar and a second premolar.
  8. 如权利要求1所述的口腔滞留装置，其特征在于，所述牙齿吻合构件包裹、嵌入、卡入或***与其相吻合的牙齿。6. The oral retention device of claim 1, wherein the dental engagement member wraps, engages, snaps into, or inserts the teeth it engages with.
  9. 如权利要求1～8任一项所述的口腔滞留装置，其特征在于，所述的口腔滞留装置的材质为口腔用稳定性材料，所述口腔用稳定性材料选自口腔稳定性金属或热塑性弹性体；The oral retention device according to any one of claims 1 to 8, wherein the material of the oral retention device is a stable material for oral cavity, and the stable material for oral cavity is selected from oral stable metal or thermoplastic elastomer;
    优选地，所述口腔稳定性金属选自牙科用钛、不锈钢、钴铬合金、钴铬钼合金或贵金属中的一种，所述热塑性弹性体选自聚己内酯、乙烯-醋酸乙烯共聚物、高密度聚乙烯、聚丙烯、聚丙烯酸酯、聚氨酯、硅聚合物、聚酯、聚(苯乙烯-乙烯-丁烯-苯乙烯)、聚(苯乙烯-丁二烯-苯乙烯)、聚(苯乙烯-异戊二烯-苯乙烯)的一种或两种的共聚物；Preferably, the oral-stable metal is selected from one of dental titanium, stainless steel, cobalt-chromium alloy, cobalt-chromium-molybdenum alloy or precious metal, and the thermoplastic elastomer is selected from polycaprolactone, ethylene-vinyl acetate copolymer , HDPE, polypropylene, polyacrylate, polyurethane, silicone polymers, polyester, poly(styrene-ethylene-butylene-styrene), poly(styrene-butadiene-styrene), poly (Styrene-isoprene-styrene) one or two copolymers;
    更优选地，所述牙齿吻合构件和载药构件的材质为钴铬合金。More preferably, the material of the dental anastomosis member and the drug-carrying member is cobalt-chromium alloy.
  10. 一种如权利要求1～9任一项所述的口腔滞留装置的制备方法，其特 征在于，所述方法选自3D打印、注塑成型或印模成型中的任一种；A method for preparing an oral retention device according to any one of claims 1 to 9, wherein the method is selected from any one of 3D printing, injection molding or impression molding;
    其中，所述3D打印包括以下步骤：Wherein, the 3D printing includes the following steps:
    (1)在设计软件中，添加保存的载药构件的方案，并与牙齿吻合构件的方案组装成一体化的口腔滞留装置的方案，导出可3D打印的文件，所述设计软件优选3Shape Dental System；(1) In the design software, add the plan of the saved drug-carrying component, and assemble the plan of the integrated oral retention device with the plan of the dental anastomosis component, and export the 3D printable file, the design software is preferably 3Shape Dental System ;
    (2)将所述可3D打印的文件导入3D打印机并打印所述口腔滞留装置；所述3D打印优选使用激光烧结工艺；(2) importing the 3D printable file into a 3D printer and printing the oral retention device; the 3D printing preferably uses a laser sintering process;
    较佳地，在所述步骤(1)前还包括：(0)在软件中，根据药片尺寸的数据设计载药构件的方案并保存，所述软件优选SolidWorks或中望3D平台设计软件；和/或，在所述设计软件中，根据受试者的牙齿尺寸的数据设计牙齿吻合构件的方案；Preferably, before the step (1), it also includes: (0) in the software, design and save the plan of the drug-carrying member according to the data of the tablet size, the software is preferably SolidWorks or Zhongwang 3D platform design software; and /or, in the design software, design the plan of the dental anastomosis member according to the data of the subject's tooth size;
    更佳地，所述药片尺寸的数据和/或所述受试者牙齿的数据使用扫描仪扫描药片和/或受试者牙齿或牙齿模型获得，所述牙齿模型通过传统取模技术制备，所述扫描仪优选为3Shape
    Figure PCTCN2021119120-appb-100001
    扫描仪；     More preferably, the data of the tablet size and/or the data of the subject's teeth are obtained by scanning the tablet and/or the subject's teeth or dental models with a scanner, and the dental models are prepared by traditional imposing techniques, so The scanner is preferably 3Shape
    Figure PCTCN2021119120-appb-100001
    scanner;
    其中，所述注塑成型包括以下步骤：Wherein, the injection molding comprises the following steps:
    (1)根据牙齿模型制备牙齿吻合构件模型；(1) Prepare a dental anastomosis component model according to the tooth model;
    (2)根据药片尺寸制备载药构件模型；(2) Prepare a drug-carrying component model according to the tablet size;
    (3)获得牙齿吻合构件和载药构件一体化的口腔滞留装置模型；(3) Obtaining an oral retention device model integrating the dental anastomosis component and the drug-carrying component;
    (4)通过传统注塑工艺制备个性化的口腔滞留装置；(4) Preparation of personalized oral retention device by traditional injection molding process;
    较佳地，所述牙齿模型通过传统取模技术制备或通过口腔扫描技术获得受试者的牙齿数据并打印；Preferably, the tooth model is prepared by traditional impression taking technology or the subject's tooth data is obtained and printed by oral scanning technology;
    更佳地，所述牙齿吻合构件模型、载药构件模型和口腔滞留装置模型的材质为牙蜡，和/或，所述牙齿模型的材质为石膏或树脂。More preferably, the material of the dental anastomosis component model, the drug-carrying component model and the oral retention device model is dental wax, and/or the material of the tooth model is gypsum or resin.
PCT/CN2021/119120 2020-09-17 2021-09-17 Oral retention device and preparation method therefor WO2022057905A1 (en)

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Citations (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4140760A (en) 1976-11-09 1979-02-20 Reckitt & Colman Products Limited Pharmaceutical compositions for use in the suppression of gastric reflux
US4167558A (en) 1976-02-13 1979-09-11 Hoffmann-La Roche Inc. Novel sustained release tablet formulations
US4193985A (en) 1977-03-30 1980-03-18 A/S Alfred Benzon Multiple-units drug dose
US4434153A (en) 1982-03-22 1984-02-28 Alza Corporation Drug delivery system comprising a reservoir containing a plurality of tiny pills
US4735804A (en) 1985-05-10 1988-04-05 Merck & Co., Inc. Drug delivery device which can be retained in the stomach for a controlled period of time
US4900557A (en) 1984-08-30 1990-02-13 Troponwerke Gmbh & Co. Kg Pellet formulation
US5002772A (en) 1988-05-31 1991-03-26 Pfizer Inc. Gastric retention system for controlled drug release
US5068109A (en) 1987-04-08 1991-11-26 Farma Food A/S Antacid composition
US5232704A (en) 1990-12-19 1993-08-03 G. D. Searle & Co. Sustained release, bilayer buoyant dosage form
US5750585A (en) 1995-04-04 1998-05-12 Purdue Research Foundation Super absorbent hydrogel foams
US5972389A (en) 1996-09-19 1999-10-26 Depomed, Inc. Gastric-retentive, oral drug dosage forms for the controlled-release of sparingly soluble drugs and insoluble matter
US6120803A (en) 1997-08-11 2000-09-19 Alza Corporation Prolonged release active agent dosage form adapted for gastric retention
US6207197B1 (en) 1997-05-24 2001-03-27 West Pharmaceutical Services Drug Delivery & Clinical Research Centre Limited Gastroretentive controlled release microspheres for improved drug delivery
US6261601B1 (en) 1997-09-19 2001-07-17 Ranbaxy Laboratories Limited Orally administered controlled drug delivery system providing temporal and spatial control
US6660300B1 (en) 1998-03-19 2003-12-09 Bristol-Myers Squibb Co. Method of use of a biphasic controlled release delivery system for high solubility pharmaceuticals and method
US6685962B2 (en) 1999-11-29 2004-02-03 Yissum Research Development Company Of The Hebrew University Of Jerusalem Gastroretentive controlled release pharmaceutical dosage forms
CN1925823A (en) 2004-03-04 2007-03-07 厄耳他拉登脱产品股份有限公司 Dental brackets for retaining a medicament-rekeasing pellet
CN1997421A (en) 2003-02-06 2007-07-11 安迪·沃尔夫 Oral devices and methods for controlled drug delivery
US20070196396A1 (en) 2004-02-11 2007-08-23 Rubicon Research Private Limited Controlled release pharmaceutical compositions with improved bioavailability
KR101424763B1 (en) * 2013-12-31 2014-08-01 현기봉 Apparatus for providing oral medicines
US20150238292A1 (en) * 2011-04-08 2015-08-27 Innovative Products, Inc. Dental prosthetic device with remoldable base and medicant delivery system
CN105873631A (en) 2013-11-05 2016-08-17 辛纳吉勒公司 Devices and methods for continuous drug delivery via the mouth
US9439851B2 (en) 2004-03-25 2016-09-13 Sun Pharma Advanced Research Company Ltd. Gastric retention system
WO2019223753A1 (en) * 2018-05-23 2019-11-28 上海汉都医药科技有限公司 Controlled-release system of active pharmaceutical ingredient and preparation method therefor
CN212973560U (en) * 2020-09-17 2021-04-16 上海汉都医药科技有限公司 Oral cavity detention device

Patent Citations (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4167558A (en) 1976-02-13 1979-09-11 Hoffmann-La Roche Inc. Novel sustained release tablet formulations
US4140760A (en) 1976-11-09 1979-02-20 Reckitt & Colman Products Limited Pharmaceutical compositions for use in the suppression of gastric reflux
US4193985A (en) 1977-03-30 1980-03-18 A/S Alfred Benzon Multiple-units drug dose
US4434153A (en) 1982-03-22 1984-02-28 Alza Corporation Drug delivery system comprising a reservoir containing a plurality of tiny pills
US4900557A (en) 1984-08-30 1990-02-13 Troponwerke Gmbh & Co. Kg Pellet formulation
US4735804A (en) 1985-05-10 1988-04-05 Merck & Co., Inc. Drug delivery device which can be retained in the stomach for a controlled period of time
US5068109A (en) 1987-04-08 1991-11-26 Farma Food A/S Antacid composition
US5002772A (en) 1988-05-31 1991-03-26 Pfizer Inc. Gastric retention system for controlled drug release
US5232704A (en) 1990-12-19 1993-08-03 G. D. Searle & Co. Sustained release, bilayer buoyant dosage form
US5750585A (en) 1995-04-04 1998-05-12 Purdue Research Foundation Super absorbent hydrogel foams
US5972389A (en) 1996-09-19 1999-10-26 Depomed, Inc. Gastric-retentive, oral drug dosage forms for the controlled-release of sparingly soluble drugs and insoluble matter
US6207197B1 (en) 1997-05-24 2001-03-27 West Pharmaceutical Services Drug Delivery & Clinical Research Centre Limited Gastroretentive controlled release microspheres for improved drug delivery
US6120803A (en) 1997-08-11 2000-09-19 Alza Corporation Prolonged release active agent dosage form adapted for gastric retention
US6261601B1 (en) 1997-09-19 2001-07-17 Ranbaxy Laboratories Limited Orally administered controlled drug delivery system providing temporal and spatial control
US6660300B1 (en) 1998-03-19 2003-12-09 Bristol-Myers Squibb Co. Method of use of a biphasic controlled release delivery system for high solubility pharmaceuticals and method
US6685962B2 (en) 1999-11-29 2004-02-03 Yissum Research Development Company Of The Hebrew University Of Jerusalem Gastroretentive controlled release pharmaceutical dosage forms
CN1997421A (en) 2003-02-06 2007-07-11 安迪·沃尔夫 Oral devices and methods for controlled drug delivery
US20070196396A1 (en) 2004-02-11 2007-08-23 Rubicon Research Private Limited Controlled release pharmaceutical compositions with improved bioavailability
CN1925823A (en) 2004-03-04 2007-03-07 厄耳他拉登脱产品股份有限公司 Dental brackets for retaining a medicament-rekeasing pellet
US9439851B2 (en) 2004-03-25 2016-09-13 Sun Pharma Advanced Research Company Ltd. Gastric retention system
US20150238292A1 (en) * 2011-04-08 2015-08-27 Innovative Products, Inc. Dental prosthetic device with remoldable base and medicant delivery system
CN105873631A (en) 2013-11-05 2016-08-17 辛纳吉勒公司 Devices and methods for continuous drug delivery via the mouth
KR101424763B1 (en) * 2013-12-31 2014-08-01 현기봉 Apparatus for providing oral medicines
WO2019223753A1 (en) * 2018-05-23 2019-11-28 上海汉都医药科技有限公司 Controlled-release system of active pharmaceutical ingredient and preparation method therefor
CN212973560U (en) * 2020-09-17 2021-04-16 上海汉都医药科技有限公司 Oral cavity detention device

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP4215175A4

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