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WO2024225432A1 - Procédé de fabrication de préparation pharmaceutique lyophilisée de nicotinamide mononucléotide - Google Patents

Procédé de fabrication de préparation pharmaceutique lyophilisée de nicotinamide mononucléotide Download PDF

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Publication number
WO2024225432A1
WO2024225432A1 PCT/JP2024/016422 JP2024016422W WO2024225432A1 WO 2024225432 A1 WO2024225432 A1 WO 2024225432A1 JP 2024016422 W JP2024016422 W JP 2024016422W WO 2024225432 A1 WO2024225432 A1 WO 2024225432A1
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WO
WIPO (PCT)
Prior art keywords
nmn
freeze
vial
dried
solution
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Pending
Application number
PCT/JP2024/016422
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English (en)
Japanese (ja)
Inventor
巌 堤
文人 伊藤
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Seed Medical Pharmaceutical Co Ltd
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Seed Medical Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Seed Medical Pharmaceutical Co Ltd filed Critical Seed Medical Pharmaceutical Co Ltd
Priority to CN202480028593.4A priority Critical patent/CN121127247A/zh
Publication of WO2024225432A1 publication Critical patent/WO2024225432A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

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Classifications

    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/08—Radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals

Definitions

  • the present invention relates to a method for producing a freeze-dried NMN preparation.
  • NMN nicotinamide mononucleotide
  • NAD + nicotinamide adenine dinucleotide
  • One possible method for making NMN into a liquid is to manufacture the NMN formulation as a liquid at the time of production.
  • the NMN formulation there are several things to be aware of when handling the NMN formulation.
  • NMN is unstable in solution, it is necessary to keep NMN preparations frozen until the time of use. Therefore, an environment in which a frozen state can be maintained is necessary not only within the hospital, but also during distribution and storage, and sufficient care must be taken to keep NMN stable.
  • thawing must be done slowly over time, and thawing must begin in advance when administering to the subject, with the timing carefully timed so that thawing is complete just before administration.
  • NMN is not produced as a liquid, but rather dispensed into vials as a solution, and this solution is freeze-dried to precipitate NMN, it can be stored at room temperature for around 18 months, and the problem of instability of NMN as mentioned above does not occur, making it more convenient to handle.
  • NMN that has undergone normal freeze-drying processing cannot be said to be able to dissolve quickly in a solvent, or ideally, to a level that allows it to be administered intravenously in a short period of time.
  • Preparations other than NMN are freeze-dried to give them a cotton-like appearance, and such preparations are expected to dissolve more quickly than porous, blocky freeze-dried products, but no such manufacturing method has been known for NMN so far.
  • the present invention was made in consideration of these circumstances, and provides a method for producing a freeze-dried NMN preparation that is capable of producing a cotton-like freeze-dried NMN preparation that can be smoothly prepared just before use.
  • the manufacturing method of the NMN freeze-dried preparation of the present invention comprises (1) a solution preparation process for preparing a 5-200 mg/mL NMN (nicotinamide mononucleotide) solution, a dispensing process for dispensing an amount of NMN solution equivalent to 50 mg-200 mg or 600 mg-800 mg of NMN into a vial to a depth of 10-45 mm, a first process for holding the vial at -37 to -43°C for 8 hours, a second process for holding the vial at -27 to -33°C for 3 hours, a third process for holding the vial at -12 to -18°C for 99 hours, a fourth process for holding the vial at -3 to 3°C for 6 hours, and a fifth process for raising the temperature to 27 to 33°C under a pressure of 1 to 100 Pa to produce cotton-like NMN, a gas phase formation process for filling the upper space of the vial with a
  • the method for producing a freeze-dried NMN formulation according to the present invention is also characterized by the following points.
  • the specified gas is a mixture of nitrogen (N 2 ) and 1 to 50 v/v % argon (Ar).
  • the vial is a brown glass vial.
  • the method for producing the NMN freeze-dried preparation of the present invention includes a solution preparation step of preparing a 5-200 mg/mL NMN (nicotinamide mononucleotide) solution, a dispensing step of dispensing an amount of NMN solution equivalent to 50 mg-200 mg or 600 mg-800 mg of NMN into a vial to a depth of 10-45 mm, a first process of holding the vial at -37 to -43°C for 8 hours, a second process of holding the vial at -27 to -33°C for 3 hours, and a third process of holding the vial at -12 to -18°C for 99 hours.
  • NMN nicotinamide mononucleotide
  • the third process is to freeze-dry the NMN
  • the fourth process is to hold the NMN at -3 to 3°C for six hours
  • the fifth process is to raise the temperature to 27 to 33°C under a pressure of 1 to 100 Pa to produce cotton-like NMN.
  • the gas phase formation process is to fill the upper space of the vial with a specific gas
  • the sterilization process is to sterilize the cotton-like NMN with radiation. This makes it possible to provide a method for producing a cotton-like NMN freeze-dried preparation that can be smoothly prepared just before use.
  • the specified gas is a mixture of nitrogen ( N2 ) with 1 to 50 v/v% argon (Ar), preferably 1 to 30 v/v%, and more preferably 1 to 10 v/v% argon (Ar), it can suppress free radicals generated by exposure to radiation and prevent NMN from breaking down and changing into substances other than NMN.
  • the vial is made of brown glass, it is possible to prevent NMN from changing into substances other than NMN due to light.
  • the present invention provides a method for producing a freeze-dried NMN preparation that can produce a cotton-like freeze-dried NMN preparation that can be smoothly prepared just before use.
  • the manufacturing method for the NMN freeze-dried formulation comprises a solution preparation process, a dispensing process, a freeze-drying process, a gas phase formation process, and a sterilization process.
  • the solution preparation process is a process for preparing an NMN solution of 5 to 200 mg/mL.
  • NMN includes both ⁇ - and ⁇ -isomers.
  • ⁇ -NMN is a compound having the following structure, which is converted to nicotinamide adenine dinucleotide (NAD + ) in the body as described above and has the role of activating the sirtuin gene, which is known as a longevity gene.
  • NAD + nicotinamide adenine dinucleotide
  • the solvent for dissolving NMN (hereinafter also referred to as production water) is not particularly limited, and pure water, for example, can be used.
  • the solution concentration should be between 5 and 200 mg/mL. If it is less than 5 mg/mL, the amount of freeze-dried product produced per unit amount will be excessively small, which is undesirable. Also, if it is more than 200 mg/mL, it will be difficult to make the freeze-dried NMN into a flocculent form, which is undesirable.
  • the dispensing process involves dispensing an amount of NMN solution equivalent to 50mg to 200mg or 600mg to 800mg of NMN into a vial to a depth of 10 to 45mm.
  • the NMN solution is dispensed into glass vials in an amount equivalent to 50mg to 200mg (hereinafter referred to as the first range) or 600mg to 800mg (hereinafter referred to as the second range) of NMN.
  • the method of dispensing is not particularly limited, and may be done manually using a pipette, for example, or mechanically using a filling machine, etc.
  • the NMN equivalent amount of the dispensed NMN solution When the NMN equivalent amount of the dispensed NMN solution is in the first range, it has the effect of preparing cotton-like NMN with a coarser degree of crystal aggregation compared to the second case. Also, when the NMN equivalent amount is in the second range, it has the effect of preparing cotton-like NMN with a denser degree of crystal aggregation (the crystals are densely aggregated) compared to the first case.
  • the amount of NMN solution filled into the vial should be 10 to 45 mm deep, from the perspective of drying it into a cotton-like consistency in the freeze-drying process described below. If the dispensing depth in the vial is less than 10 mm, there will be partial unevenness in the density of the dried product, and it will not become uniformly cotton-like, which is undesirable, and if it exceeds 45 mm, drying will be difficult even if steps 1 to 5 described below are performed, which is also undesirable.
  • the material of the vial is not particularly limited as long as it can withstand freeze-drying, and glass or resin vials can be used.
  • the vial is colored or colorless as long as it is transparent, and colored or transparent vials such as brown bottles can also be used as long as the dissolution of NMN can be visually confirmed when water for injection is added to the vial.
  • the NMN freeze-dried preparation produced by the method for producing an NMN freeze-dried preparation according to this embodiment has a cotton-like freeze-dried product, making it extremely unlikely that any undissolved material will remain.
  • brown vials can be used without hesitation, the benefits of blocking ultraviolet rays provided by brown vials can be enjoyed.
  • the freeze-drying process involves freezing and drying the NMN solution in the vial. Freezing and drying can be carried out, for example, using a commercially available freeze dryer.
  • the freeze-drying process is carried out by carrying out the following steps 1 to 5 under a pressure of 1 to 100 Pa.
  • the first process involves adjusting the pressure of the NMN solution to 1 to 100 Pa at -37 to -43°C and holding it for 8 hours.
  • the second process involves holding it at -27 to -33°C for 3 hours, and the third process involves holding it at -12 to -18°C for 99 hours.
  • the fourth process is to stabilize the product at -3 to 3°C for six hours, and the fifth process is to raise the temperature to 27 to 33°C.
  • This secondary drying process completely removes moisture from the vial, and by suppressing hydrolysis, it is possible to transport and store the product at room temperature while maintaining its quality.
  • the gas phase formation process is a process in which a specific gas is filled into the upper space of a vial.
  • a gas mixture of nitrogen ( N2 ) and 1 to 50 v/v% argon (Ar) (hereinafter referred to as the mixed gas) is flowed into the upper space of the vial, filling it and sealing it.
  • the gas phase of freeze-dried preparations is generally formed using only nitrogen, but in the method for producing an NMN freeze-dried preparation according to this embodiment, the replacement gas is not only nitrogen ( N2 ), but also a mixed gas combining it with argon (Ar).
  • the sterilization process is a process in which the inside of the vial is sterilized. Sterilization in this process is carried out by radiation, for example, gamma rays or electron beams.
  • the manufacturing method for the NMN freeze-dried formulation includes the solution preparation process, dispensing process, freeze-drying process, gas phase formation process, and sterilization process, which makes it possible to produce a cotton-like NMN freeze-dried formulation, shortening the dissolution time and increasing the uniformity of the concentration during dissolution, making it possible to provide an optimal formulation for infusion.
  • NMN solution 5 mL was dispensed into a 10 mL brown glass vial using a pipette in a clean bench.
  • object to be dried this dispensed NMN solution will be referred to as the "object to be dried" regardless of whether it is in a liquid, solid, or dry state.
  • the NMN solution was frozen and dried using a freeze dryer. Specifically, the above vials were placed on a tray, and the tray was placed inside the chamber of the freeze dryer, and the door was closed.
  • the temperature inside the chamber was then lowered, and the material to be dried inside the vial was frozen while measuring its temperature to -37 to -43°C.
  • the pressure was reduced to 1-100 Pa, and the following first to fifth steps were carried out while maintaining this reduced pressure.
  • the material to be dried in the vial was heated to -27 to -33°C and held there for three hours (second process), and then held at -12 to -18°C for a further 99 hours to complete the primary drying (third process).
  • the material to be dried in the vial was kept at -3 to 3°C for 6 hours (fourth process), and then the temperature was raised to 33°C to complete the secondary drying (fifth process).
  • the material to be dried had a cotton-like appearance.
  • a gas mixture of nitrogen ( N2 ) and argon (Ar) with a volume ratio of 90:10 (nitrogen gas containing 10 v/v% argon) was supplied into the chamber and flowed into the upper space of the vial to fill it, followed by a gas phase formation process in which the vial was then sealed using a sealing shelf.
  • the sealed vials were removed from the freeze-dryer and the objects to be dried were sterilized using a radiation sterilization device by irradiating them with gamma rays at a dose of 25 kGy, resulting in an NMN freeze-dried preparation. It was confirmed that the NMN freeze-dried preparation still had a cotton-like shape even after this sterilization process was completed.
  • the manufacturing method for the NMN freeze-dried preparation according to this embodiment is a manufacturing method for an NMN freeze-dried preparation that can produce a cotton-like NMN freeze-dried preparation that can be smoothly prepared at the time of use.
  • Example 2 the freeze-dried preparation prepared by the method of Example 1 was used, and the amount of remaining NMN was quantified and evaluated by HPLC when pure nitrogen and a mixed gas of nitrogen and argon were used. The results are shown in Table 4.
  • Example 3-1 when only nitrogen was substituted, the remaining amount of NMN decreased by 4.2% to 95.8% due to the effects of gamma ray irradiation.
  • the mechanism of this phenomenon is not entirely clear at this time, but the inventors believe that it is due to the deterioration or decomposition of NMN caused by gamma ray irradiation.
  • Example 3-2 In contrast, when the mixture was replaced with one containing less than half the amount of argon, the effect on the remaining amount of NMN was suppressed even when ⁇ -rays were irradiated, and the remaining amount increased. In particular, compared to Example 3-1, which used pure nitrogen, it is extremely interesting that the remaining amount improved significantly by adding only 1% argon (Example 3-2).
  • Example 3-3 when the nitrogen was replaced with a mixed gas containing 90 v/v% nitrogen and 10 v/v% argon (Example 3-3), a mixed gas containing 70 v/v% nitrogen and 30 v/v% argon (Example 3-4), or a mixed gas containing 50 v/v% nitrogen and 50 v/v% argon (Example 3-5), the amount of remaining NMN increased in all cases compared to Example 3-1, where pure nitrogen was used.
  • Example 3-6 when the nitrogen was replaced with a mixed gas containing 30 v/v% and 70 v/v% argon (Example 3-6), the residual amount decreased compared to Example 3-1, where pure nitrogen was used.
  • the gas to be filled into the upper space of the vial in the gas phase formation process should be a mixture of nitrogen and argon, with the proportion of argon in the replacement gas (100 v/v%) being 1 to 50 v/v%, preferably 1 to 30 v/v%, and more preferably 1 to 10 v/v%.
  • the manufacturing method for the NMN freeze-dried preparation according to this embodiment is a method capable of manufacturing a cotton-like NMN freeze-dried preparation that can be smoothly prepared just before use.
  • the above-mentioned embodiment is merely an example of the present invention, and the present invention is not limited to the above-mentioned embodiment. Therefore, even if it is an embodiment other than the above-mentioned, various modifications can be made depending on the capacity, etc., as long as they do not deviate from the technical concept of the present invention.

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  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
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Abstract

L'invention fournit un procédé de fabrication de préparation pharmaceutique lyophilisée de nicotinamide mononucléotide (NMN) qui permet de fabriquer une préparation pharmaceutique lyophilisée de NMN floculant permettant une préparation sans incident au moment de la mise en œuvre.　Le procédé de fabrication de l'invention présente : une étape de préparation de solution au cours de laquelle une solution de NMN à 5 à 200mg/mL est préparée ; une étape de répartition au cours de laquelle une quantité de solution de NMN correspondant à 50mg à 200mg ou 600mg à 800mg de NMN est répartie dans une fiole à une profondeur de 10 à 45mm ; une étape de lyophilisation au cours de laquelle un premier traitement de maintien pendant 8 heures entre -37 et -43℃ , un second traitement de maintien pendant 3 heures entre -27 et -33℃, un troisième traitement de maintien pendant 99 heures entre -12 et -18℃, un quatrième traitement de maintien pendant 6 heures entre -3 et 3℃, et un cinquième traitement d'élévation de température jusqu'à 27 à 33°C, sont effectués vis-à-vis de ladite fiole sous une pression de 1 à 100Pa, et un NMN floculant est produit ; une étape de formation de phase gazeuse au cours de laquelle un gaz spécifique remplit un espace de partie supérieure de ladite fiole ; et une étape de stérilisation au cours de laquelle ledit NMN floculant est stérilisé au moyen d'un rayonnement radioactif.
PCT/JP2024/016422 2023-04-28 2024-04-26 Procédé de fabrication de préparation pharmaceutique lyophilisée de nicotinamide mononucléotide Pending WO2024225432A1 (fr)

Priority Applications (1)

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CN202480028593.4A CN121127247A (zh) 2023-04-28 2024-04-26 Nmn冷冻干燥制剂的制造方法

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JP2023074847 2023-04-28

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002529519A (ja) * 1998-11-16 2002-09-10 メドイミューン オンコロジー，インコーポレーテッド 安定な非晶質アミフォスチン組成物およびその製造法および使用法
JP2021038213A (ja) * 2019-08-30 2021-03-11 広東丸美生物技術股▲フン▼有限公司 アボカド抽出物及びその調製方法並びに老化防止化粧品における使用
WO2021222565A1 (fr) * 2020-04-30 2021-11-04 Oncour Pharma, Inc. Particules chargées négativement pour le traitement du choc cytokinique (cc) et du syndrome de détresse respiratoire aiguë (sdra)
WO2022114105A1 (fr) * 2020-11-27 2022-06-02 ミライラボバイオサイエンス株式会社 MONONUCLÉOTIDE β-NICOTINAMIDE DE GRANDE PURETÉ (NMN) ET SON PROCÉDÉ DE PRODUCTION
CN114835768A (zh) * 2022-05-19 2022-08-02 浙江省农业科学院 从果蔬中提取β-烟酰胺单核苷酸的方法及其纯化方法
CN115769894A (zh) * 2022-12-13 2023-03-10 福迈香港基因工程有限公司 一种含高活性nmn提取物的制备方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002529519A (ja) * 1998-11-16 2002-09-10 メドイミューン オンコロジー，インコーポレーテッド 安定な非晶質アミフォスチン組成物およびその製造法および使用法
JP2021038213A (ja) * 2019-08-30 2021-03-11 広東丸美生物技術股▲フン▼有限公司 アボカド抽出物及びその調製方法並びに老化防止化粧品における使用
WO2021222565A1 (fr) * 2020-04-30 2021-11-04 Oncour Pharma, Inc. Particules chargées négativement pour le traitement du choc cytokinique (cc) et du syndrome de détresse respiratoire aiguë (sdra)
WO2022114105A1 (fr) * 2020-11-27 2022-06-02 ミライラボバイオサイエンス株式会社 MONONUCLÉOTIDE β-NICOTINAMIDE DE GRANDE PURETÉ (NMN) ET SON PROCÉDÉ DE PRODUCTION
CN114835768A (zh) * 2022-05-19 2022-08-02 浙江省农业科学院 从果蔬中提取β-烟酰胺单核苷酸的方法及其纯化方法
CN115769894A (zh) * 2022-12-13 2023-03-10 福迈香港基因工程有限公司 一种含高活性nmn提取物的制备方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BUTREDDY ARUN, DUDHIPALA NARENDAR, JANGA KARTHIK YADAV, GADDAM RAJENDRA PRASAD: "Lyophilization of Small-Molecule Injectables: an Industry Perspective on Formulation Development, Process Optimization, Scale-Up Challenges, and Drug Product Quality Attributes", AAPS PHARMSCITECH, SPRINGER NEW YORK LLC, US, vol. 21, no. 7, 1 October 2020 (2020-10-01), US , XP093227276, ISSN: 1530-9932, DOI: 10.1208/s12249-020-01787-w *
KASPER JULIA CHRISTINA, FRIESS WOLFGANG: "The freezing step in lyophilization: Physico-chemical fundamentals, freezing methods and consequences on process performance and quality attributes of biopharmaceuticals", EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, ELSEVIER SCIENCE PUBLISHERS B.V., AMSTERDAM., NL, vol. 78, no. 2, 1 June 2011 (2011-06-01), NL , pages 248 - 263, XP093227271, ISSN: 0939-6411, DOI: 10.1016/j.ejpb.2011.03.010 *
KAWASAKI HIDENORI, SHIMANOUCHI TOSHINORI, KIMURA YUKITAKA: "Recent Development of Optimization of Lyophilization Process", JOURNAL OF CHEMISTRY, HINDAWI PUBLISHING CORPORATION, US, vol. 2019, 5 May 2019 (2019-05-05), US , pages 1 - 14, XP093227273, ISSN: 2090-9063, DOI: 10.1155/2019/9502856 *

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