WO2010025632A1 - 一种利用水滑石作为载体对甾体类药物进行包合的方法 - Google Patents

一种利用水滑石作为载体对甾体类药物进行包合的方法 Download PDF

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WO2010025632A1
WO2010025632A1 PCT/CN2009/072173 CN2009072173W WO2010025632A1 WO 2010025632 A1 WO2010025632 A1 WO 2010025632A1 CN 2009072173 W CN2009072173 W CN 2009072173W WO 2010025632 A1 WO2010025632 A1 WO 2010025632A1
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hydrotalcite
solution
drug
preparing
body drug
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卫敏
李勇
陆军
段雪
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Beijing University of Chemical Technology
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Beijing University of Chemical Technology
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/44—Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids

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  • the present invention pertains to the field of utilizing an organic-inorganic composite material as a release device, and more particularly to a method for using a hydrotalcite as a carrier for inclusion in a body drug.
  • the present invention relates to constructing an intercalated hydrotalcite composite material and studying its behavior of inclusion and release of a body drug. Background technique:
  • Bimetallic composite hydroxides also known as Layered Double Hydroxides (LDHs)
  • LDHs Layered Double Hydroxides
  • micelles formed by prednisone wrapped with a block copolymer such as methyl isopropyl acrylate-ethyl acrylate-methacrylic acid copolymer
  • a block copolymer such as methyl isopropyl acrylate-ethyl acrylate-methacrylic acid copolymer
  • this structural system can effectively improve the sustained release properties of prednisone and reduce its toxicity.
  • hydrotalcite as a "molecular container” will make it a novel carrier for the storage and release of adrenocortical hormones, and at the same time contribute to the development of new and effective routes of administration for adrenal corticosteroids.
  • the general drug has been absorbed or degraded before reaching the colon and rectum; rectal administration (including suppositories or enema)
  • rectal administration including suppositories or enema
  • the enema is not only inconvenient to use, but also has a large individual difference in the colon, and the distribution is uneven.
  • the drug is limited to the rectum and the sigmoid colon, and cannot reach the transverse colon and the ascending colon.
  • suppositories it can only be used for treating rectal diseases or the whole body. Treatment, the purpose of colonic administration cannot be achieved.
  • OCTDDS colon-targeted oral colon-targeted drug delivery system
  • the colon is an important part of drug absorption. Although the surface area of the colon is smaller than that of the small intestine, the absorption rate of the drug is relatively small, but the absorption of the drug is partially compensated by the long residence time of the drug in the colon. In addition, the colon is more selective in absorption than the small intestine, and the hydrophobic drug can be absorbed through the mucosal cells, so that it is better absorbed in the colon.
  • the pH of the human gastrointestinal tract gradually increases from low to high, and the pH of the colon is relatively high, which is the physiological basis for colon-targeted administration of a pH-dependent drug delivery system.
  • pH-dependent drug delivery systems are primarily achieved by coating with pH sensitive materials. As an ideal colon-targeted coating material, it must have two conditions: one is tolerant to acidic gastric juice without being dissolved; the other is to be dissolved or eroded under neutral or weak alkali conditions at the end of the ileum.
  • the colon targeting performance of pH-dependent drug delivery systems is influenced by material solubility, film thickness, and residence time of the formulation in various segments of the gastrointestinal tract.
  • the solubility characteristics of the coating material in solutions of different pH have a great influence on the targeting of the preparation.
  • Guo Shengrong et al. methylated a part of the carboxyl group of the acrylic polymer Eudragit S to obtain a polymer that dissolved in a higher pH solution.
  • In vivo experiments demonstrated the effectiveness of methylated Eudragit S colon targeting. Guo Shengrong et al.
  • the object of the present invention is to provide a method for inclusion of a body drug by using hydrotalcite as a carrier, which utilizes a layered material hydrotalcite as a carrier to encapsulate a body drug and insert it into a layer of hydrotalcite to solve the body.
  • hydrotalcite as a carrier
  • the problem of targeted drug release in the large intestine such as Ponisone.
  • the invention utilizes the intercalability of hydrotalcite to encapsulate a body drug (such as prednisone, etc.) by a high polymer (methyl methacrylate-ethyl acrylate-methacrylic acid copolymer), and adopts coprecipitation.
  • the method involves inserting the encapsulated drug into the hydrotalcite layer and then examining the release of the target product in phosphate and citrate buffer solutions at different pH values.
  • step A Weigh 0.01-0.05 g of prednisone dissolved in 20 ml of acetone, and then transfer to step A at 1 ml/s-3 ml/s;
  • step E Add the nitrate mixed solution prepared in step C and the NaOH solution prepared in step D to step A under N 2 protection conditions at 1 ml/s to 3 ml/s (ie, step A after adding B) Solution), stirring, adjusting the pH range of the obtained solution to 10-11 with 1-5 mol/L NaOH, and removing C0 2 after crystallization at 40 °C-60 °C for 12-48 hours.
  • the deionized hot water is centrifugally washed to neutrality, and dried at 70 ° C - 100 ° C for 12-24 hours to obtain a compound compound intercalated hydrotalcite.
  • the method of filtering may include filtering using a 0.45 ⁇ filter membrane.
  • the invention has the advantages that the layered nanocarriers for constructing hydrotalcite are encapsulated and intercalated, and the prepared product can be better released at the colon, and the absorption of prednisone in the gastric juice is avoided.
  • Figure 2 is a graph showing the in vitro release of the intercalated product obtained under the conditions of the specific embodiment of the present invention.
  • the abscissa is time, the unit is: hour; the ordinate is the percent release.
  • the FT-IR spectrum was obtained on VECTOR 22 (Brook, Germany), and the sample was mixed with KBr and compressed, and scanned at room temperature under an air atmosphere.
  • the parameter indicators are: resolution of 4 cm - 1 and scanning range of 4000-400 cm.
  • Step A Weigh a certain amount of high polymer dissolved in 300 ml of deionized water to obtain a solution concentration of 3 X 10 - 4 M.
  • Step B Weigh 0.05 g of prednisone dissolved in 20 ml of acetone, then slowly transfer to the solution obtained in the step A, and stir at 40 ° C for 20 hours.
  • Step C 1.5414 g (0.006 mol) of solid Mg(N0 3 ) 2 *6H 2 0 and 1.1306 g (0.003 mol) of solid ⁇ 1( ⁇ 0 3 ) 3 ⁇ 9 ⁇ 2 0 dissolved in 50 mL removed C0 2 Deionized water (solution 1); Another 0.7202 g (0.018 mol) NaOH was dissolved in 50 mL of deionized water (solution 2) from which CO 2 was removed to prepare a NaOH solution.
  • Step D Under the condition of N 2 gas protection, the solution 2 and the solution 1 were respectively placed in two constant pressure hoppers in a three-necked flask, and while slowly stirring, slowly added to the solution obtained in the step A (after adding B) ), about 1 hour dripping.
  • Step E Adjust the pH range of the solution obtained in Step D to 10-11 with 1-5 mol/L NaOH, crystallize at 40 ° C for 48 hours, and then centrifuge with deionized hot water with CO 2 removed. Neutral, dried at 70 ° C - 100 ° C for 12 hours to obtain intercalated hydrotalcite products.
  • Step F Weigh 0.5 g of the product obtained in the above procedure and dissolve it in 200 ml of pH.
  • UV-vis As time goes on, the release of prednisone increases and its intensity increases accordingly.

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Description

一种利用水滑石作为载体对留体类药物进行包合的方法
技术领域：
本发明属于利用有机-无机复合材料作为释放器件的技术领域， 特别是 提供了一种利用水滑石作为载体对 体类药物进行包合的方法。本发明涉及 构筑一种插层结构水滑石复合材料并研究其对 体类药物进行包合释放的 行为。 背景技术：
随着近年来生命科学、 材料科学与纳米科学与相关技术的发展， 生物技 术药物与新型载体材料不断涌现， 微粒载体与纳米粒载体更加多种多样， 新 型给药系统的研究和应用进一步深入和普遍，促使 21世纪的药剂学将沿着细 胞、 亚细胞水平和分子水平深入发展。
双金属复合氢氧化物又称为水滑石 (Layered Double Hydroxides, 简写为 LDHs)是一种新型的多功能层状材料， 其化学稳定性良好， 具有强的抗热性 能， 在药物的缓释方面也有广泛的应用， 且 LDHs层板金属离子种类和比例 可调变， 层间阴离子具有可交换性。 利用此种性能可以将用嵌段共聚物 （如 异丙基丙烯酸甲酯-丙烯酸乙酯-甲基丙烯酸共聚物） 包合的泼尼松形成的胶 束共同插入水滑石层间， 形成超分子结构体系， 这种结构体系可有效提高泼 尼松的缓释性能， 降低其毒性。 水滑石作为 "分子容器"的功能， 将使其成 为肾上腺皮质激素类药物贮存和释放的新型载体， 同时有助于开发肾上腺皮 质激素类药物新的有效的给药途径
目前广泛使用的药物分子和药物制剂中，在体内对病变部位具有靶向性 分布很少。 这使那些药理作用强烈的药物， 在治疗过程中容易出现严重的毒 副反应。 因此， 设计出能够相对靶向分布于病变器官、 组织或细胞的药物分 子或给药系统 （drug delivery systems, DDS ) 一直是医药学家的追求。 对肠道疾病 （如溃疡性结肠炎和大肠癌） 的治疗， 目前主要是采用普通 的口服片剂、 栓剂、 灌肠剂等。 由于胃肠道环境因素十分复杂， 受这些复杂 环境因素的影响， 经口服用普通口服制剂后， 一般药物在到达结肠和直肠前 就已经被吸收或降解； 直肠给药 （包括栓剂或灌肠剂） 中， 例如灌肠剂不仅 使用不便而且药物在结肠的个体差异大， 分布不均匀， 药物只限于在直肠和 乙状结肠， 到达不了横结肠和升结肠； 对于栓剂而言， 只能用于治疗直肠疾 病或全身治疗， 无法实现结肠给药的目的。 而用口服结肠靶向给药后， 药物 在上消化道不释放， 在回盲部才开始崩解或溶蚀并释放出来， 从而使药物在 人体大肠发挥局部或全身治疗作用。 因此， 采用化学或制剂学手段， 将药物 构建成结肠靶向释放的口服结肠靶向给药系统（OCTDDS)的临床意义重大。
结肠是药物吸收的一个重要部位。 虽然结肠的表面积小于小肠， 药物的 吸收速率相对小些，但由于药物在结肠中停留时间长而可以使药物的吸收量 得到部分补偿。 另外， 结肠比小肠更具有选择吸收性， 疏水性药物可穿过黏 膜细胞而被吸收， 因而在结肠吸收较好。 人体胃肠道 pH由低到高逐渐递增， 其中结肠 pH相对较高， 这是结肠靶向给药 pH依赖型释药系统的生理基础。 目前， pH依赖型释药系统主要通过用 pH敏感性材料进行包衣的方法来实现。 作为理想的结肠靶向包衣材料， 其必须具备两个条件： 一是能耐受酸性胃液 而不被溶解； 二是在回肠末端的中性或弱碱条件下被溶解或蚀解。
pH依赖型释药系统的结肠靶向性能受到材料溶解度、衣膜厚度及制剂在 胃肠各段停留时间的影响。包衣材料在不同 pH的溶液中的溶解特性，对制剂 的靶向性有较大的影响。郭圣荣等将丙烯酸聚合物 Eudragit S的部分羧基甲基 化， 可得到在更高 pH的溶液中发生溶解的聚合物， 体内试验证明了甲基化 Eudragit S结肠靶向的有效性。 郭圣荣等合成了甲基丙烯酸甲酯 -甲基丙烯酸 共聚物 （PMMA-co-MAA)， 对采用了 PMMA-co-MAA的萘普生包衣微丸进 行研究， 证实了通过 PMMA-co-MAA包衣能把药物输送到结肠释药， 并对共 聚物 pH敏感性与酸值的关系进行了研究。 发明内容：
本发明的目的在于提供一种利用水滑石作为载体对 体类药物进行包 合的方法， 该方法利用层状材料水滑石作为载体对 体类药物进行包合后插 入水滑石层间， 解决了 体类药物波尼松等在大肠靶向释放的难题。
本发明利用水滑石的可插层性将 体类药物（如波尼松等）通过高聚物 (异丙基丙烯酸甲酯-丙烯酸乙酯-甲基丙烯酸共聚物） 包合后， 采用共沉淀 法将包合的药物插入到水滑石层间， 然后考察目标产物在不同 pH值的磷酸 盐和柠檬酸缓冲溶液中的释放情况。
共沉淀法：
A. 称取 0.15-0.60 g量的高聚物溶于 300ml去离子水中， 得到溶液的浓 度为 0.5-2.0 g/1;
B. 称取 0.01-0.05g的波尼松溶于 20ml丙酮中， 然后以 1 ml/s-3 ml/s转 移入步骤 A中；
C. 配制可溶性硝酸镁和可溶性硝酸铝的硝酸盐混合溶液， 其中二价金 属镁的离子浓度为 0.02-0.05 mol/l。
D. 配制 NaOH溶液；
E. 将步骤 C配制的硝酸盐混合溶液和步骤 D配制的 NaOH溶液在 N2 保护的条件下以 1 ml/s-3 ml/s滴加到步骤 A中 （即， 加入 B之后的步骤 A 的溶液）， 搅拌， 利用 1-5 mol/L的 NaOH将得到的溶液的 pH值范围调节至 10-11， 在 40°C-60°C下晶化 12-48小时后采用除去了 C02的去离子热水离心 洗涤至中性， 在 70°C-100°C下干燥 12-24小时， 得到 体类化合物插层水滑 石。
目标产物的释放
A. 取 0.05-0.10g 体类药物插层水滑石产物加入缓冲溶液中， 缓慢搅 拌； B. 每隔 0.5-4小时抽取 2 ml的溶液， 过滤后在紫外-可见光 （UV-vis ) 下检测溶液的波尼松的吸收强度。 所述过滤的方法可以包括使用 0.45μηι过 滤膜进行过滤。
将得到的插层水滑石和产物的释放溶液进行 X射线衍射 （XRD)、 傅里 叶变换红外光谱 （FT-IR) 和 UV-vis后的表征显示， 包合后的波尼松胶束成 功进入层间。经不同 pH值缓冲液释放的 UV-vis检测数据可以看出， 在酸性 环境下， 波尼松释放较缓慢， 而 pH在中性附近时， 波尼松释放比较快， 从 而实现了水滑石作为纳米载体靶向释放的功能。
本发明的优点在于：构筑水滑石的层状纳米载体对 体类药物进行包合 后插层， 制备的产物可以在结肠处得到较好的释放， 同时避免了波尼松在胃 液中被吸收。
附图说明- 图 1为本发明具体实施方式条件下得到的 XRD谱图； 横坐标为 2Θ, 单 位： 度； 纵坐标为强度。
图 2为本发明具体实施方式条件下得到的插层产物的体外释放的曲线； 横坐标为时间， 单位： 小时； 纵坐标为释放百分数。
具体实施方式：
通过下面实施例对本发明予以具体说明。
在以下实施例中， 使用如下方法测定各实施例中制得的产物：
以日本岛津 XRD-6000型 X射线衍射仪进行结构分析， Cu Κα光源（λ = 0.154 nm)， 电压 40 Kv， 电流 30 mA， 连续扫描， 扫描速度 5 min。
FT-IR光谱在 VECTOR 22 (德国布鲁克公司） 上获得， 样品与 KBr混 合后压片， 室温、 空气气氛下扫描。 参数指标为： 分辨率为 4 cm—1 , 扫描范 围 4000-400cm 。
Shimadzu UV-2501PC紫外一可见分光光度计用于插层产物中波尼松定 量和分子间作用力分析 (测试范围: 200~800nm， 最大吸收波长为 240nm)。 实施例 1
步骤 A. 称取一定量的高聚物溶于 300 ml的去离子水中，得到溶液的浓 度为 3 X 10— 4 M。
步骤 B. 称取 0.05 g的波尼松溶于 20 ml的丙酮中， 然后缓慢转移入步 骤 A得到的溶液中， 在 40°C搅拌 20小时。
步骤 C. 将 1.5414 g (0.006mol)的固体 Mg(N03)2*6H20 和 1.1306 g (0.003mol)的固体 Α1(Ν03)3·9Η20溶于 50 mL的除去了 C02的去离子水中 (；溶 液 1); 另将 0.7202 g (0.018mol)的 NaOH溶于 50 mL的除去了 C02的去离子 水中 (；溶液 2)配制 NaOH溶液。
步骤 D. 在 N2气保护的条件下， 将溶液 2和溶液 1分别置于三口瓶中 两个恒压漏斗中， 边剧烈搅拌， 边缓慢滴加入步骤 A得到的溶液中（加入了 B之后的）， 约 1小时滴完。
步骤 E. 利用 1-5 mol/L的 NaOH将步骤 D得到的溶液的 pH值范围调 节至 10-11， 在 40°C下晶化 48小时后采用除去了 C02的去离子热水离心洗 涤至中性， 70°C-100°C干燥 12小时， 得到插层水滑石产物。
由 XRD、 FT-IR谱图、 UV-vis可知， 高聚物包合波尼松后插入到水滑 石层间。
步骤 F. 把按上述步骤制得的产物称取 0.5 g分别溶于 200 ml的 pH为
4.8和 7.2的磷酸盐和柠檬酸的缓冲溶液中， 在 37°C下缓慢搅拌， 每隔 30分 钟抽取 2 ml的上述溶液，用 0.45μηι过滤膜过滤后在 UV-vis下检测其波尼松 的吸收强度。
由 UV-vis可知， 随着时间的推移， 波尼松的释放量增加， 其强度也会 相应增强。

Claims

权利要求书
1、 一种利用水滑石作为载体对 体类药物进行包合后插层的方法， 其 特征在于： 该方法利用水滑石的可插层性将 体类药物通过高聚物包合后， 采用共沉淀法将包合后的药物插入到水滑石层间， 然后考察目标产物在不同 pH值磷酸盐和柠檬酸缓冲溶液中的释放情况； 所述 体类药物为波尼松， 所述高聚物为异丙基丙烯酸甲酯-丙烯酸乙酯-甲基丙烯酸共聚物。
2、 按照权利要求 1所述的方法， 其特征在于： 所述的将 体类药物通 过高聚物包合的方法包括：
a、 采用共沉淀法制备 体类药物插层水滑石：
(a) , 称取 0.15-0.60 g量的高聚物溶于 300 ml的去离子水中， 得到浓度 为 0.5-2.0 g/1的溶液；
(b)、称取 0.01-0.05g的波尼松溶于 20 ml的丙酮中，然后以 1 ml/s-3 ml/s 的速度转移入步骤 （a) 中；
(c) ,配制可溶性硝酸镁和可溶性硝酸铝的硝酸盐混合溶液， 其中二价金 属镁的离子浓度为 0.02-0.05 M;
(d)、 配制 NaOH溶液；
(e) , 将步骤（c)配制的硝酸盐混合溶液和步骤（d)配制的 NaOH溶液 在 护的条件下以 1 ml/s-3 ml/s的速度滴加到步骤 （a) 中， 搅拌， 利用 1-5 mol/L的 NaOH将所得的溶液的 pH值范围调节至 10-11，在 40°C-60°C晶 化 12-48 小时后采用除去了 C02 的去离子热水离心洗涤至中性， 在 70°C-100°C下干燥 12-24小时， 得到 体类药物插层水滑石；
b、 目标产物的释放：
(a2), 取 0.05-0.10 g量的所述 体类药物插层水滑石加入所述缓冲溶液 中， 缓慢搅拌，
(b)、每隔 0.5-4小时的时间抽取 2 ml的（ a2 )中的溶液过滤后通过 UV-vis 检测其波尼松的吸收强度。
PCT/CN2009/072173 2008-09-05 2009-06-08 一种利用水滑石作为载体对甾体类药物进行包合的方法 Ceased WO2010025632A1 (zh)

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CN110522732A (zh) * 2019-09-04 2019-12-03 中国科学院上海硅酸盐研究所 一种超小纳米水滑石-肽核酸复合材料及其制备方法和应用
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Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000059629A1 (en) * 1999-04-06 2000-10-12 Japan Science And Technology Corporation Process for producing anion-layered double hydroxide intercalation compounds and products thus produced
WO2002047729A2 (en) * 2000-12-14 2002-06-20 Isis Innovation Limited Drug delivery system comprising a drug intercalated between a layered double hidroxide
CN1561963A (zh) * 2004-03-26 2005-01-12 北京化工大学 一种肠溶材料包覆抗炎药插层水滑石及其制备方法
CN1640395A (zh) * 2004-01-07 2005-07-20 北京化工大学 一种超分子插层结构缓释型卡托普利及其制备方法
US20050244439A1 (en) * 2004-04-30 2005-11-03 Eastman Kodak Company Composition comprising anionic clay layered host material with intercalated functional-active organic compound
CN1850275A (zh) * 2006-02-28 2006-10-25 北京化工大学 一种手性药物插层水滑石及其制备方法
CN100998872A (zh) * 2007-01-16 2007-07-18 北京化工大学 一种多肽药物插层水滑石及其制备方法
CN101366947A (zh) * 2008-09-05 2009-02-18 北京化工大学 一种利用水滑石作为载体对甾体类药物进行包合的方法

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000059629A1 (en) * 1999-04-06 2000-10-12 Japan Science And Technology Corporation Process for producing anion-layered double hydroxide intercalation compounds and products thus produced
WO2002047729A2 (en) * 2000-12-14 2002-06-20 Isis Innovation Limited Drug delivery system comprising a drug intercalated between a layered double hidroxide
CN1640395A (zh) * 2004-01-07 2005-07-20 北京化工大学 一种超分子插层结构缓释型卡托普利及其制备方法
CN1561963A (zh) * 2004-03-26 2005-01-12 北京化工大学 一种肠溶材料包覆抗炎药插层水滑石及其制备方法
US20050244439A1 (en) * 2004-04-30 2005-11-03 Eastman Kodak Company Composition comprising anionic clay layered host material with intercalated functional-active organic compound
CN1850275A (zh) * 2006-02-28 2006-10-25 北京化工大学 一种手性药物插层水滑石及其制备方法
CN100998872A (zh) * 2007-01-16 2007-07-18 北京化工大学 一种多肽药物插层水滑石及其制备方法
CN101366947A (zh) * 2008-09-05 2009-02-18 北京化工大学 一种利用水滑石作为载体对甾体类药物进行包合的方法

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