WO2016138793A1 - 一种一次性经鼻脑靶向给药装置 - Google Patents

一种一次性经鼻脑靶向给药装置 Download PDF

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Publication number
WO2016138793A1
WO2016138793A1 PCT/CN2015/100089 CN2015100089W WO2016138793A1 WO 2016138793 A1 WO2016138793 A1 WO 2016138793A1 CN 2015100089 W CN2015100089 W CN 2015100089W WO 2016138793 A1 WO2016138793 A1 WO 2016138793A1
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Prior art keywords
catheter
nasal
drug delivery
delivery device
syringe
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PCT/CN2015/100089
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English (en)
French (fr)
Inventor
钱明心
何仁扬
施俊巍
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苏州同力生物医药有限公司
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Publication of WO2016138793A1 publication Critical patent/WO2016138793A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/06—Sprayers or atomisers specially adapted for therapeutic purposes of the injector type

Definitions

  • the utility model relates to a disposable nasal brain targeted drug delivery device.
  • nasal olfactory area is the only place in the human body where the nerve cells are in direct contact with the surrounding environment.
  • the nerve cells (olfactory nerve, trigeminal nerve) pathway, intercellular space or microvascular pathway directly connected to the venous sinus of the brain can realize the drug.
  • how to effectively deliver drugs through the nasal-brain route such as the central nervous system, while avoiding excessive absorption directly into the peripheral circulation through the nasal mucosa is a difficult problem to be solved.
  • Patent CN101600417A discloses a nasally administered dopamine galenical gel formulation which enhances the bioavailability of transnasal targeted absorption of a drug by a lipophilic system.
  • Patent CN102370623A discloses a method for preparing liquid lipid microparticles for targeted administration via the nasal brain.
  • Patent CN102174080A discloses a polypeptide obtained by phage display technology for modifying a pharmaceutical carrier to achieve a targeted delivery effect through the nasal brain.
  • Patent CN1839799A discloses a method for modifying a drug carrier by a lectin to increase the residence time of the drug in the nasal cavity, thereby achieving a targeted effect of nasal and nasal administration.
  • Patent CN201280021497 discloses a nasal drug delivery device which is an intranasal aerosolization of a hydrofluoroalkane propellant and passes through a nozzle. The drug plume is delivered to the nasal olfactory area and absorbed into the brain, and the proportion of the drug into the olfactory area is more than 64.2%.
  • the nasal olfactory region drug delivery device of the prior art also has the following disadvantages: 1) Although the nozzle of the drug delivery device can deliver the drug to the nasal olfactory region, the nozzle cannot extend into the nasal olfactory region, so the drug cannot be completely It is sent to the nasal olfactory area. As in the prior art, only about 64% of the medicine can be sent to the nasal olfactory area, which causes waste of medicine and causes unnecessary economic loss to the patient. 2) The drug delivery device is not pre-packaged design. It needs to be refilled and dispensed every time. It is cumbersome to operate and wastes time.
  • the technical problem to be solved by the utility model is to overcome the deficiencies of the prior art and provide a disposable nasal brain targeted drug delivery device.
  • a disposable nasal-targeted drug delivery device comprising an applicator comprising a catheter and a spray head disposed at one end of the catheter, the dispenser further comprising a lumen
  • the one end of the catheter may extend through the total nasal passage of the human body into the nasal olfactory region above the horizontal position corresponding to the middle turbinate
  • the applicator further includes a syringe disposed in the syringe
  • the inner cavity of the syringe is divided into pressure sensitive membranes of a plurality of chambers independent of each other and rupturing under pressure, the other end of the conduit being connected to one of the plurality of chambers and the tube of the conduit
  • the chamber is in communication with a chamber to which it is coupled, the dispenser further comprising a soluble membrane for separating the lumen of the catheter from the chamber to which it is attached and which may partially or completely dissolve upon contact with the formulation.
  • the soluble membrane is disposed at the junction of the syringe and the catheter.
  • the applicator further includes a nasal cavity adapter disposed at the one end of the catheter for buffering direct stimulation of the catheter to the nasal mucosa.
  • the nasal cavity adapter is substantially conically wrapped around the outer circumference of the catheter, and the material of the nasal cavity adapter is selected from one of medical silicone, neoprene, butadiene rubber, natural rubber, nitrile rubber, and ethylene propylene diene rubber. Kind.
  • the catheter is a hose having an outer diameter of 0.1 to 50 mm.
  • the material of the catheter is selected from the group consisting of medical silicone, latex, plastic, and thermoplastic elastomer (TPE).
  • the spray head has one or more holes having a diameter of 0.1 to 1000 ⁇ m.
  • the pores have a diameter of from 1 to 100 microns.
  • the syringe includes a syringe having the lumen and a piston disposed within the syringe, the syringe being provided with an opening, the other end of the catheter being coupled to the opening.
  • the drug delivery device further includes a plurality of preparation components pre-packaged in the plurality of chambers, respectively, wherein the preparation component stored in the chamber to which the catheter is connected is a preparation component that cannot dissolve the soluble membrane
  • the formulation component stored in at least one of the chambers in the other chamber contains a formulation component that dissolves the soluble membrane.
  • the chambers are 2 to 3.
  • the preparation component for dissolving the soluble film may be a solvent
  • the other preparation component may be a biologically active substance selected from the group consisting of small-molecule non-peptide non-protein drugs, peptide/protein drugs, natural animals and plants, and One or more of an extract and a diagnostic agent.
  • the small molecule non-peptide non-protein drug is selected from the group consisting of atropine and its derivatives, phosphatidine, bisphosphorus, bisphosphorus, bispyridinium, bispyridinium, temozolomide, nitrosourea, Etoposide, platinum, irinotecan, capecitabine, methotrexate, gemcitabine, topotecan, cytarabine (cytarabine), thiotepa, vincristine, procarbazine, morphine, fentanyl, oxycodone, butorphanol, tramadol, granisetron, endo Citronone, tropisetron, palonosetron, definizrin, sumatriptan, zolmitriptan, rizatriptan, naratriptan, ergotamine, triazolam, melatonin , carbamazepine, midazolam, donepezil, thiophene,
  • the peptide/protein drug is selected from the group consisting of insulin, growth hormone, somatostatin, growth hormone releasing peptide, vasopressin, desmopressin, terry vasopressin, glucagon, calcitonin, interference , erythropoietin, interleukin, parathyroid hormone (PTH1-34), parathyroid hormone (PTH1-84), parathyroid hormone PTH-related peptide, GLP-1, vasopressin, bright Propirin, granulocyte colony-stimulating factor, prolactin, human menopausal gonadotropin, chorionic gonadotropin, follicle stimulating hormone, luteinizing hormone, leptin, bevacizumab, rituximab A combination of one or more of rituximab, nerve growth factor, stem cell growth factor, keratinocyte growth factor, thioredoxin, cyclosporin, and analogs thereof.
  • the natural flora and fauna and the extract thereof are selected from the group consisting of Asarum, borneol, wind, Nepeta, Radix Puerariae, Hedyotis diffusa, Schisandra, Gardenia, Azalea, Sophora, Green Walnut, Rutin, Ginkgo, Shichangpu, Ginseng One or more combinations of saponins, velvet antler, St. John's wort, Basil, Albizia, Bupleurum, Angelica, Cistanche, and Astragalus.
  • the diagnostic agent is a contrast agent.
  • the solvent is selected from the group consisting of water, physiological buffer, decyl benzoate, cottonseed oil, N, N-dimethylacetamide, ethanol, glycerin, peanut oil, polyethylene glycol, poppy seed oil, propylene glycol, safflower oil, sesame oil, soybean oil, rapeseed oil, gum arabic, aluminum monostearate, carboxymethyl Cellulose, sodium carboxymethyl cellulose, polyoxyethylene 35 castor oil, sodium deoxycholate, egg lecithin, hydrolyzed gelatin, lecithin, polyoxyethylene fatty acid, Tween 80, Tween 20, polyvinylpyrrolidone, ten Sodium dialkyl sulfonate, sorbitol, cyclodextrin, benzoic acid, sodium benzoate, salicylic acid, sodium salicylate, p-aminobenzoic acid, urethane, urea, amide, acetamide, borax, potassium io
  • the drug delivery device of the utility model adopts a disposable device design, which eliminates the cumbersome steps of repeated cleaning and disinfection of the drug delivery device, and further reduces the potential hidden danger of cross-contamination.
  • the catheter of the drug delivery device of the present invention can penetrate into the nasal olfactory region to achieve brain targeted administration.
  • the catheter of the drug delivery device of the present invention is provided with a spray head, which atomizes the preparation to fully contact the nerves of the nasal olfactory region, thereby improving the bioavailability of brain targeted administration.
  • Figure 1 is a schematic view showing the structure of a drug delivery device of the present invention
  • a disposable nasal-targeted drug delivery device includes a drug applicator including a catheter 2 and a spray head 4 disposed at one end of the catheter 2, the applicator further comprising a lumen
  • the syringe 1 for storing the preparation, the end of the catheter 2 provided with the spray head 4 can extend through the total nasal passage of the human body into the nasal olfactory area above the horizontal position corresponding to the middle turbinate, and the applicator further comprises a syringe set.
  • the applicator further includes a soluble membrane 9 for separating the lumen of the catheter 2 from the chamber to which it is attached and which may partially or completely dissolve upon contact with the formulation.
  • the soluble membrane 9 is placed at the junction of the syringe 1 and the catheter 2.
  • the applicator of the present invention further includes a nasal adapter 6 disposed at one end of the catheter 2 provided with the spray head 4 for buffering the direct stimulation of the catheter 2 to the nasal mucosa.
  • the nasal cavity adapter 6 is conically wrapped around the outer circumference of the catheter 2, and the material of the nasal cavity adapter 6 is selected from one of medical silicone, neoprene, butadiene rubber, natural rubber, nitrile rubber, and ethylene propylene diene rubber. .
  • the catheter 2 of the present invention is a hose having an outer diameter of 0.1 to 50 mm and a material selected from the group consisting of medical silicone, latex, plastic, and thermoplastic elastomer (TPE).
  • TPE thermoplastic elastomer
  • the spray head 4 of the present invention has one or more holes 5 having a diameter of 0.1 to 1000 ⁇ m. It is preferably 1 to 100 ⁇ m.
  • the syringe 1 includes a syringe 101 having a lumen and a piston 102 disposed within the syringe 101.
  • the syringe 101 is provided with an opening, and one end of the catheter 2 is attached to the opening.
  • the drug delivery device of the present invention further comprises a plurality of preparation components pre-packaged in a plurality of chambers respectively, wherein the preparation component stored in the chamber to which the catheter 2 is connected is a preparation component which cannot dissolve the soluble membrane 9, and is in other chambers.
  • the formulation component stored in at least one of the chambers is a formulation component capable of dissolving the soluble membrane 9.
  • the preparation component of the dissolved soluble membrane 9 may be a solvent, and other preparation components may be biologically active substances selected from the group consisting of small molecule non-peptide non-protein drugs, peptide/protein drugs, natural plants and animals, and extraction thereof. One or more of the substance and the diagnostic agent.
  • the pressure sensitive membrane 3 divides the lumen of the syringe 101 into two chambers, a first chamber 7 and a second chamber 8, respectively, which are connected to the second chamber 8. Among them, the solvent is stored in the first chamber 7, and the components stored in the second chamber 8 cannot dissolve the soluble film 9.
  • the first chamber 7 and the second chamber 8 are each stored with a preparation component, and the solvent that dissolves the soluble membrane 9 is stored in the first chamber 7, and when the administration is required, the catheter 2 is provided with the spray head 4.
  • One end extends through the main nasal passage of the human body into the nasal olfactory area above the horizontal position corresponding to the middle turbinate, and then the piston 102 of the syringe 1 is pushed by hand to squeeze the preparation component in the first chamber 7, and the pressure sensitive membrane 3 is broken by force.
  • the preparation components in the first chamber 7 and the second chamber 8 are mixed, and the soluble membrane 9 is dissolved in the solvent to connect the second chamber 8 with the lumen of the catheter 2, and the piston 102 is further pushed to deliver the mixed mixture.
  • Disposable drug delivery device The drug delivery device adopts a simple design and is prepared by a relatively inexpensive and easy-to-use and safe material, thereby eliminating the cumbersome steps of repeated cleaning and disinfection of the drug delivery device, and further reducing the potential hidden danger of cross-contamination.
  • Multi-chamber design Through a plurality of independent chamber designs, the solvent-free preparation and the solvent system are independently stored, and the medicine has a good stable expiration date in the drug delivery device.
  • Pre-package design Prior to use, the pressure-sensitive membrane is broken by inward pushing the piston to connect the chamber of the originally separated storage solvent and the chamber for storing the solvent-free preparation, so that the precise pre-packaged solvent-free
  • the preparation and the solvent can be uniformly mixed in a short time, and can be directly used for administration, and the process of the traditional drug delivery and drug dispensing is avoided, and is especially suitable for the occasions requiring rapid administration such as hospital first aid, battlefield neurotoxic gas detoxification and the like.
  • Catheter for nasal administration Due to the narrowing of the nasal passages of the human body, the general drug delivery device cannot be probed into the deep part of the nasal passage for administration. Most drugs can't enter the nasal olfactory area, and it is impossible to achieve the purpose of nasal brain targeted administration.
  • the drug delivery device of the utility model is equipped with a biocompatible and soft nasal adapter, so that the drug delivery position can reach the horizontal position of the total nasal passage close to the nasal olfactory region, thereby greatly increasing the target of the drug into the local olfactory region. To the dose, the waste of the drug into the peripheral circulation through the nasal mucosa is avoided, and the peripheral side effects of the drug are also minimized.
  • the porous design of the spray head a spray head containing a large number of micropores is attached to the tip of the catheter, and under a certain pressure of injecting, the drug can be aerosolized as much as possible to make it fully contact with the nerves of the nasal olfactory region. Improve the bioavailability of brain targeted drug delivery.

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Abstract

一次性经鼻脑靶向给药装置，包括给药器，给药器包括导管(2)及设置在导管(2)的一端的喷雾头(4)，给药器还包括具有内腔的且用于存放制剂的注射器(1)，导管(2)的设有喷雾头(4)的一端可经人体的总鼻道伸入到中鼻甲对应的水平位置以上的鼻腔嗅区，给药器还包括设置在注射器(1)内将注射器(1)的内腔分隔成彼此独立的多个腔室(7,8)的且在压力作用下发生破裂的压力敏感膜(3)，导管(2)的另一端与多个腔室(7,8)中的一个连接且导管(2)的管腔和与其连接的腔室(8)连通，给药器还包括用于将导管(2)的管腔和与其连接的腔室(8)隔开且在接触制剂后可部分或全部溶解的可溶性膜(9)。该给药装置能够将制剂高效递送到鼻腔嗅区，进而直接吸收入脑，在中枢神经系统发挥治疗作用。

Description

一种一次性经鼻脑靶向给药装置 技术领域
本实用新型涉及一种一次性经鼻脑靶向给药装置。
背景技术
在治疗脑部疾病如多发性硬化症、帕金森病、癫痫症、阿滋海默病、脑部肿瘤、艾滋病及其它传染性疾病和急性中毒时，医学上一直存在着一个难题，即：如何克服血脑屏障，使药物能够迅速进入中枢神经系统（central nervous system, CNS）内以发挥药效作用。目前临床上应用较多的方法是通过可逆性开启血脑屏障，鞘内注射以及颈动脉注射给药，使药物透过并进入中枢神经系统。但是，这些方法在操作技术上要求高、安全风险大，在应用上受到一定制约。基于鼻腔的特殊结构，通过鼻腔给药治疗脑部疾病具有非侵入性、脑生物利用度高、可以绕过首次通过代谢和体循环和血脑屏障等优点，且方便操作。
在最近几年，许多研究都证明了只要通过恰当的手段，药物直接通过鼻腔进入脑是完全可行的。鼻腔嗅区是人体中唯一一处神经细胞与周围环境直接接触的位置，通过神经细胞（嗅神经、三叉神经）通路、细胞间隙通路或与脑部静脉窦直接相连的微血管通路均能实现药物经鼻脑靶向的传递。但如何将药物有效地通过鼻腔-脑的途径递送如中枢神经系统，而避免过多的通过鼻腔粘膜直接吸收进入外周循环是一个有待解决的难题。
已有大量的研究聚焦于通过制剂的改变来提高药物经鼻-脑途径的吸收效率，包括增加药物在鼻腔的滞留时间、提高鼻腔粘膜的通透性、药物分子修饰、改变药物的粒径、用脂质体增加药物的渗透性等方法，也形成了不少专利。专利CN101600417A公开了一种经鼻施用的多巴胺盖伦凝胶制剂，通过亲脂性系统提高药物的经鼻脑靶向吸收的生物利用度。专利CN102370623A公开了一种液态脂质微粒的制备方法用于经鼻脑靶向给药。专利CN102174080A公开了通过噬菌体展示技术获得的一个多肽，用于修饰药物载体以实现经鼻脑靶向给药效果。专利CN1839799A公开了一种通过凝集素修饰药物载体，以增加药物在鼻腔中滞留时间，从而实现经鼻脑靶向给药效果的方法。也有专利着眼于通过给药装置来实现经鼻脑靶向递送药物的目的，专利CN201280021497公开了一种鼻药递送装置，该装置通过氢氟烷烃推进剂是鼻内剂型气雾化，并通过喷嘴将药物羽流递送至鼻腔嗅区，从而吸收入脑，其药物进入嗅区的比例为64.2%以上。
但现有技术中的鼻腔嗅区给药装置还存在有以下缺点：1）给药装置的喷嘴虽然能将药物送至鼻腔嗅区，但喷嘴不能伸入到鼻腔嗅区，所以不能将药物全部送至鼻腔嗅区，如现有技术中，只能将64%左右的药物送至鼻腔嗅区，造成药物的浪费，也会给病患造成不必要的经济损失。2）给药装置不是预封装设计，每次给药都需重新装药、配药，操作比较繁琐，也浪费时间，特别是对于医院急救、战场神经性毒气解毒等需要快速给药的场合，很有可能会因为装药、配药时间的浪费而不能对病患进行及时处理。3）因每次给药都需重新配药、给药使得储存药物的容器需要经常打开，容易使药物发生变质而不能使用，特别是对于一些存储稳定性低的药物容易造成浪费。4）每次给药都要进行清洗、消毒的繁琐步骤，若清洗、消毒不彻底容易造成交叉污染。
发明内容
本实用新型所要解决的技术问题是克服现有技术的不足，提供一种一次性经鼻脑靶向给药装置。
为解决以上技术问题，本实用新型采用如下技术方案：
一种一次性经鼻脑靶向给药装置，包括给药器，所述给药器包括导管及设置在所述导管的一端的喷雾头，所述给药器还包括具有内腔的且用于存放制剂的注射器，所述导管的所述一端可经人体的总鼻道伸入到中鼻甲对应的水平位置以上的鼻腔嗅区，所述给药器还包括设置在所述注射器内将所述注射器的内腔分隔成彼此独立的多个腔室的且在压力作用下发生破裂的压力敏感膜，所述导管的另一端与所述多个腔室中的一个连接且所述导管的管腔和与其连接的腔室连通，所述给药器还包括用于将所述导管的管腔和与其连接的腔室隔开且在接触制剂后可部分或全部溶解的可溶性膜。
进一步地，所述可溶性膜设置在所述注射器和所述导管的连接处。
进一步地，所述给药器还包括设置在所述导管的所述一端、用于缓冲所述导管对于鼻腔粘膜的直接刺激的鼻腔适配器。
所述鼻腔适配器基本成锥形包裹于所述导管的外周，所述鼻腔适配器的材料选自医用硅胶、氯丁橡胶、顺丁橡胶、天然橡胶、丁晴橡胶、三元乙丙橡胶中的一种。
进一步地，所述导管为软管，其外径为0.1~50毫米。
所述导管的材料选自医用硅胶、乳胶、塑料、热塑性弹性体（TPE）中的一种。
进一步地，所述喷雾头具有1个或1个以上的直径为0.1~1000微米的孔。
优选地，所述孔的直径为1~100微米。
进一步地，所述注射器包括具有所述内腔的注射筒及设置在所述注射筒内的活塞，所述注射筒上设置有开口，所述导管的所述另一端连接在所述开口上。
进一步地，所述给药装置还包括分别预封装在所述多个腔室中的多种制剂成分，其中连接有所述导管的腔室内存放的制剂成分为不能溶解所述可溶性膜的制剂成分，其他腔室内的至少一个腔室内存放的制剂成分中含有溶解所述可溶性膜的制剂成分。
进一步地，所述腔室为2~3个。
上述中，溶解所述可溶性膜的制剂成分可以为溶剂，其他制剂成分可以为生物活性物质，所述生物活性物质选自小分子非肽非蛋白质药物、肽类/蛋白质药物、天然动植物及其提取物、诊断剂中的一种或一种以上。
所述小分子非肽非蛋白质药物选自阿托品及其衍生物、解磷定、双解磷、双复磷、双吡啶单肟、双吡啶双肟、替莫唑胺（temozolomide）、亚硝脲类药物、依托泊苷（etoposide）、铂类药物、伊立替康（irinotecan）、卡培他滨（capecitabine）、甲氨蝶呤（methotrexate）、吉西他滨（gemcitabine）、拓扑替康（topotecan）、阿糖胞苷（cytarabine）、噻替哌（thiotepa）、长春新碱（vincristine）、丙卡巴肼（procarbazine）、吗啡、芬太尼、羟考酮、布托啡诺、曲马多、格拉司琼、恩丹西酮、托烷司琼、帕洛诺司琼、吲地司琼、舒马曲坦、佐米曲普坦、利扎曲坦、那拉曲坦、麦角胺、三唑仑、褪黑素、卡马西平、咪达唑仑、多奈哌齐、硫必利、头孢克洛、依诺沙星、阿昔洛韦、齐多夫定、去羟肌苷、那韦拉平、茚地那韦、丹曲林、地高辛、苯海索、吡哌立登、右美沙芬、纳洛酮、倍他司丁、萘甲唑啉、地尔硫卓、曲尼司特、洛哌丁胺、双氯芬酸、倍氯美松、氯苯吡胺、西地那非、伐地那非、氰钴胺、非那雄胺、肾上腺素、5-FU、低分子量肝素、他克莫司中的一种或一种以上的组合。
所述肽类/蛋白质药物选自胰岛素、生长激素、生长抑素、生长激素释放肽、血管加压素、去氨加压素、特里加压素、胰高血糖素、降钙素、干扰素、促红细胞生成素、白细胞介素、甲状旁腺素（PTH1-34）、甲状旁腺素(PTH1-84)、甲状旁腺素PTH相关肽、GLP-1、后叶加压素、亮丙瑞林、粒细胞集落刺激因子、促乳素、人绝经期促性腺激素、绒毛膜促性腺激素、促卵泡激素、促黄体生成素、瘦素、贝伐珠单抗（bevacizumab）、利妥昔单抗（rituximab）、神经生长因子、干细胞生长因子、角化细胞生长因子、硫氧还蛋白、环孢菌素以及它们的类似物中的一种或一种以上的组合。
所述天然动植物及其提取物选自细辛、冰片、防风、荆芥、葛根、白花蛇舌草、五味子、枸杞子、映山红、苦参、青核桃、芦丁、银杏、石菖蒲、人参、皂苷、鹿茸、贯叶连翘、巴戟天、合欢花、柴胡、当归、肉苁蓉、黄芩中的一种或一种以上的组合。
所述诊断剂为造影剂。
所述溶剂选自水、生理缓冲液、苯甲酸卞酯、棉籽油、N, N-二甲基乙酰胺、乙醇、甘油、花生油、聚乙二醇、罂粟籽油、丙二醇、红花油、芝麻油、大豆油、菜籽油、阿拉伯胶、单硬脂酸铝、羧甲基纤维素、羧甲基纤维素钠、聚氧乙烯35蓖麻油、脱氧胆酸钠、蛋卵磷脂、水解明胶、卵磷脂、聚氧乙烯脂肪酸、吐温80、吐温20、聚乙烯吡咯烷酮、十二烷基磺酸钠、山梨醇、环糊精类、苯甲酸、苯甲酸钠、水杨酸、水杨酸钠、对氨基苯甲酸、乌拉坦、尿素、酰胺、乙酰胺、硼砂、碘化钾中的一种或一种以上的组合。
由于上述技术方案的实施，本实用新型与现有技术相比具有如下优点：
本实用新型给药装置采用一次性装置设计，免除了给药装置的重复清洗、消毒的繁琐步骤，更降低了交叉污染的潜在隐患。
本实用新型给药装置的导管能够深入到鼻腔嗅区，实现脑靶向给药。
本实用新型给药装置的导管上设有喷雾头，喷雾头将制剂雾化使之充分与鼻腔嗅区神经接触，提高脑靶向给药的生物利用度。
附图说明
图1为本实用新型给药装置的结构示意图；
图中数字所表示的名称为：
1.注射器；101、注射筒；102、活塞；2、导管；3、压力敏感膜；4、喷雾头；5、孔；6、鼻腔适配器；7、第一腔室；8、第二腔室；9、可溶性膜。
具体实施方式
下面结合说明书附图对本实用新型作进一步描述。
如图1所示，一种一次性经鼻脑靶向给药装置，包括给药器，给药器包括导管2及设置在导管2的一端的喷雾头4，给药器还包括具有内腔的且用于存放制剂的注射器1，导管2的设有喷雾头4的一端可经人体的总鼻道伸入到中鼻甲对应的水平位置以上的鼻腔嗅区，给药器还包括设置在注射器1内将注射器1的内腔分隔成彼此独立的多个腔室且在压力作用下发生破裂的压力敏感膜3，导管2的另一端与多个腔室中的一个连接且导管2的管腔和与其连接的腔室连通，给药器还包括用于将导管2的管腔和与其连接的腔室隔开且在接触制剂后可部分或全部溶解的可溶性膜9。
本例中，可溶性膜9设置在注射器1和导管2的连接处。
本实用新型的给药器还包括设置在导管2的设有喷雾头4的一端、用于缓冲导管2对于鼻腔粘膜的直接刺激的鼻腔适配器6。具体地，鼻腔适配器6成锥形包裹于导管2的外周，鼻腔适配器6的材料选自医用硅胶、氯丁橡胶、顺丁橡胶、天然橡胶、丁晴橡胶、三元乙丙橡胶中的一种。
本实用新型的导管2为软管，其外径为0.1~50毫米，其材料选自医用硅胶、乳胶、塑料、热塑性弹性体（TPE）中的一种。
本实用新型的喷雾头4具有1个或1个以上的直径为0.1~1000微米的孔5。优选为1~100微米。
本例中，注射器1包括具有内腔的注射筒101及设置在注射筒101内的活塞102，注射筒101上设置有开口，导管2的一端连接在开口上。
本实用新型的给药装置还包括分别预封装在多个腔室中的多种制剂成分，其中连接有导管2的腔室内存放的制剂成分为不能溶解可溶性膜9的制剂成分，其他腔室内的至少一个腔室内存放的制剂成分为能够溶解可溶性膜9的制剂成分。
上述中，溶解可溶性膜9的制剂成分可以为溶剂，其他制剂成分可以为生物活性物质，所述生物活性物质选自小分子非肽非蛋白质药物、肽类/蛋白质药物、天然动植物及其提取物、诊断剂中的一种或一种以上。
本例中，压力敏感膜3将注射筒101的内腔分隔成二个腔室，分别为第一腔室7和第二腔室8，导管2与第二腔室8相连。其中，溶剂存放于第一腔室7内，第二腔室8内存放的制剂成分不能溶解可溶性膜9。
本实用新型的给药装置的工作原理：
第一腔室7和第二腔室8均存放有制剂成分，而可溶解可溶性膜9的溶剂存放于第一腔室7内，当需给药时，将导管2的带有喷雾头4的一端经人体的总鼻道伸入到中鼻甲对应的水平位置以上的鼻腔嗅区，然后用手推注射器1的活塞102挤压第一腔室7内的制剂成分，压力敏感膜3受力破裂，第一腔室7内和第二腔室8内的制剂成分混合，同时可溶性膜9遇溶剂溶解将第二腔室8与导管2的管腔连通，进一步推活塞102将混合后的混合物送至导管2内，然后经过喷雾头4雾化后送至鼻腔嗅区，进而直接吸入脑，在中枢神经系统发挥治疗作用。
本实用新型的给药装置具有如下优点：
1）一次性给药装置：给药装置采用简洁的设计，并用相对廉价易得又安全的材料制备，免除了给药装置的重复清洗、消毒的繁琐步骤，更降低了交叉污染的潜在隐患。
2）多腔室设计：通过多个独立的腔室设计，实现了不含溶剂的制剂与溶剂系统独立保存，保证药物在给药装置内有良好的稳定的有效期。
3）预封装设计：在使用前，通过向内推活塞使得压力敏感膜破裂从而连通原本分隔的储存溶剂的腔室和储存不含溶剂的制剂的腔室，使得精确预分装的不含溶剂的制剂和溶剂能够在很短时间内混合均匀，直接用于给药，避免传统给药器吸药配药的过程，尤其适用于医院急救、战场神经性毒气解毒等需要快速给药的场合。
4）导管用于鼻腔给药：由于人体鼻道狭窄，一般给药装置无法探入鼻道深部进行给药。绝大部分药物都无法进入鼻腔嗅区，更无法实现鼻腔脑靶向的给药目的。本实用新型给药装置通过导管配上生物相容性好、质地柔软的鼻腔适配器，使得给药位置能够深入到总鼻道接近鼻腔嗅区的水平位置，大大提高了药物进入局部嗅区的靶向剂量，避免了药物经鼻粘膜吸收入外周循环的浪费，同时也最大程度降低了药物的外周副作用。
5）喷雾头的多孔设计：在导管顶端接上一个含有大量微孔的喷雾头，在一定推注压力之下，能够将药物尽可能的气雾化，使之充分与鼻腔嗅区神经接触，提高脑靶向给药的生物利用度。
以上对本实用新型做了详尽的描述，其目的在于让熟悉此领域技术的人士能够了解本实用新型的内容并加以实施，并不能以此限制本实用新型的保护范围，凡根据本实用新型的精神实质所作的等效变化或修饰，都应涵盖在本实用新型的保护范围内。

Claims (10)

  1. 一种一次性经鼻脑靶向给药装置，包括给药器，所述给药器包括导管及设置在所述导管的一端的喷雾头，其特征在于：所述给药器还包括具有内腔的且用于存放制剂的注射器，所述导管的所述一端可经人体的总鼻道伸入到中鼻甲对应的水平位置以上的鼻腔嗅区，所述给药器还包括设置在所述注射器内将所述注射器的内腔分隔成彼此独立的多个腔室的且在压力作用下发生破裂的压力敏感膜，所述导管的另一端与所述多个腔室中的一个连接且所述导管的管腔和与其连接的腔室连通，所述给药器还包括用于将所述导管的管腔和与其连接的腔室隔开且在接触制剂后可部分或全部溶解的可溶性膜。
  2. 根据权利要求1所述的一次性经鼻脑靶向给药装置，其特征在于：所述可溶性膜设置在所述注射器和所述导管的连接处。
  3. 根据权利要求1所述的一次性经鼻脑靶向给药装置，其特征在于：所述给药器还包括设置在所述导管的所述一端、用于缓冲所述导管对于鼻腔粘膜的直接刺激的鼻腔适配器。
  4. 根据权利要求1所述的一次性经鼻脑靶向给药装置，其特征在于：所述导管为软管，其外径为0.1~50毫米。
  5. 根据权利要求1所述的一次性经鼻脑靶向给药装置，其特征在于：所述喷雾头具有1个或1个以上的直径为0.1~1000微米的孔。
  6. 根据权利要求5所述的一次性经鼻脑靶向给药装置，其特征在于：所述孔的直径为1~100微米。
  7. 根据权利要求1所述的一次性经鼻脑靶向给药装置，其特征在于：所述给药装置还包括分别预封装在所述多个腔室中的多种制剂成分，其中连接有所述导管的腔室内存放的制剂成分为不能溶解所述可溶性膜的制剂成分，其他腔室内的至少一个腔室内存放的制剂成分中含有溶解所述可溶性膜的制剂成分。
  8. 根据权利要求7所述的一次性经鼻脑靶向给药装置，其特征在于：所述溶解所述可溶性膜的制剂成分为溶剂，所述不能溶解所述可溶性膜的制剂成分为小分子非肽非蛋白质药物、肽类/蛋白质药物、天然动植物及其提取物、诊断剂中的一种。
  9. 根据权利要求1或7所述的一次性经鼻脑靶向给药装置，其特征在于：所述腔室为2~3个。
  10. 根据权利要求1所述的一次性经鼻脑靶向给药装置，其特征在于：所述注射器包括具有所述内腔的注射筒及设置在所述注射筒内的活塞，所述注射筒上设置有开口，所述导管的所述另一端连接在所述开口上。
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CN204446845U (zh) * 2015-03-03 2015-07-08 苏州同力生物医药有限公司 一种一次性经鼻脑靶向给药装置
CN115068795A (zh) * 2022-07-28 2022-09-20 纳索菲德(上海)制药技术有限公司 向鼻内喷射药液的喷雾头及其装置

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