WO2017188016A1 - Récipient pour contenir un complexe l-carnosine-zinc cristallin, et procédé pour tenir ledit récipient - Google Patents

Récipient pour contenir un complexe l-carnosine-zinc cristallin, et procédé pour tenir ledit récipient Download PDF

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Publication number
WO2017188016A1
WO2017188016A1 PCT/JP2017/015206 JP2017015206W WO2017188016A1 WO 2017188016 A1 WO2017188016 A1 WO 2017188016A1 JP 2017015206 W JP2017015206 W JP 2017015206W WO 2017188016 A1 WO2017188016 A1 WO 2017188016A1
Authority
WO
WIPO (PCT)
Prior art keywords
crystalline
zinc complex
carnosine zinc
storage container
resin
Prior art date
Application number
PCT/JP2017/015206
Other languages
English (en)
Japanese (ja)
Inventor
平野　直樹
守 梶山
健次 田中
Original Assignee
株式会社トクヤマ
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 株式会社トクヤマ filed Critical 株式会社トクヤマ
Priority to KR1020187028481A priority Critical patent/KR102415182B1/ko
Priority to CN201780022717.8A priority patent/CN109071093B/zh
Publication of WO2017188016A1 publication Critical patent/WO2017188016A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D81/00—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents
    • B65D81/24—Adaptations for preventing deterioration or decay of contents; Applications to the container or packaging material of food preservatives, fungicides, pesticides or animal repellants
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D85/00—Containers, packaging elements or packages, specially adapted for particular articles or materials
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine

Definitions

  • the present invention relates to a novel storage container for storing a crystalline L-carnosine zinc complex, and a novel storage method for the crystalline L-carnosine zinc complex using the storage container. More specifically, the present invention relates to a novel storage container for storing a crystalline L-carnosine zinc complex, which is a drug substance, without additives such as excipients, and a novel storage method using the storage container.
  • glass, pottery, stainless steel, resin, paper, etc. are used as packaging materials, not limited to pharmaceutical products.
  • active pharmaceutical ingredients it is common to use a polyolefin represented by polyethylene as a primary container.
  • this olefin the thing which reduced additives, such as antioxidant and a chlorine supplement agent as much as possible from the problem of contamination, or the high purity olefin which does not contain the said additive is used.
  • polyolefins low-carbon substances (low molecular weight polymers) in polyolefins may be mixed as impurities for some reason in pharmaceuticals, and as a method to prevent them as much as possible, especially as packaging polyolefins for antibiotics, Polyolefins have been developed in which substances having a low carbon number are reduced as much as possible (see Patent Document 1). Polyolefins are generally used as storage containers for active pharmaceutical ingredients, and therefore, those having a very low content of low molecular weight polymers compared to other resins are being investigated.
  • a crystalline L-carnosine zinc complex (generic name: polaprezinc, hereinafter sometimes simply referred to as “polaprazinc”), which is an active pharmaceutical ingredient, Following formula (1)
  • n is an integer indicating a repeating unit.
  • the solution of the crystalline L-carnosine zinc complex after storage may become cloudy.
  • the crystalline L-carnosine zinc complex after storage is diluted with dilute hydrochloric acid. It has been found that a turbid component that cannot be seen before storage is generated when dissolved in (this turbid component is sometimes simply referred to as “turbidity problem”). Such a phenomenon is the same as that observed when antibiotics are stored in ordinary polyethylene and polypropylene containers as described in Patent Document 1, and this cloudy product is a low molecular weight polymer. Assumed.
  • the present inventors examined the use of a storage container made of polyolefin having a low content of a low molecular weight polymer, which is assumed to be a causative substance of the turbidity problem.
  • the turbidity problem cannot be solved even by the method described in Patent Document 1 when the storage object is a crystalline L-carnosine zinc complex.
  • the polyolefin described in Patent Document 1 has a very low content of low molecular weight polymer, which is a causative substance of turbidity, compared to other resins, and it is difficult to further reduce the content of low molecular weight polymer. It was thought that there was.
  • an object of the present invention is to provide a storage container that can stably and easily store a crystalline L-carnosine zinc complex that is useful as an active pharmaceutical ingredient without any change.
  • the present inventor has conducted intensive research to solve the above problems.
  • the crystalline L-carnosine zinc complex is a high molecular weight substance having a large molecular weight as compared with, for example, cefazolin sodium salt exemplified in Patent Document 1.
  • the crystalline L-carnosine zinc complex differs in the behavior of the resin that makes up the storage container compared to other active pharmaceutical ingredients, and the material of the storage container is selected based on the same criteria as other active pharmaceutical ingredients. I can't do it. That is, when a low molecular weight polymer with very high mobility moves to the container surface, the crystalline L-carnosine zinc complex, which is a high molecular weight substance, actively takes in this low molecular weight polymer. Even a storage container having a sufficiently small amount is presumed to affect the storage of the crystalline L-carnosine zinc complex.
  • the present invention is a container for storing a crystalline L-carnosine zinc complex, wherein the portion in contact with the crystalline L-carnosine zinc complex is at least one polarity selected from the group consisting of a cyano group, a hydroxyl group, and an ester group
  • a storage container for crystalline L-carnosine zinc complex characterized in that it is formed of a resin having a group in the molecule.
  • the resin is preferably polyacrylonitrile, polyethylene terephthalate, or ethylene-vinyl alcohol copolymer.
  • the method for preserving the crystalline L-carnosine zinc complex of the present invention includes at least one selected from the group consisting of a cyano group, a hydroxyl group, and an ester group without bringing the crystalline L-carnosine zinc complex into contact with the polyolefin.
  • the crystalline L-carnosine zinc complex is preserved by contacting with a resin having a polar group in the molecule.
  • the crystalline L-carnosine zinc complex which is a high molecular weight substance
  • its form is not changed and the problem of turbidity does not occur. Therefore, since the crystalline L-carnosine zinc complex useful as a drug substance can be stored for a long period of time, the industrial utility value is high.
  • the present invention relates to a storage container for storing a crystalline L-carnosine zinc complex.
  • the storage of the crystalline L-carnosine zinc complex means that after the crystalline L-carnosine zinc complex is produced, the crystalline L-carnosine zinc complex taken out from the container used for production or purification is preserved.
  • the storage container of the present invention is a container for storing the crystalline L-carnosine zinc complex for at least several minutes to several months. In the following examples and comparative examples, in order to make the difference in effect more prominent, those stored for 1 month in an atmosphere of 45 ° C. and 75% RH were evaluated.
  • the storage container of the present invention is not limited to the expiration date of one month (it can be used for one month or more, and can be used for less than one month).
  • the crystalline L-carnosine zinc complex to be stored is the product itself, that is, the drug substance. According to the study by the present inventor, the reason is not clear, but only when the crystalline L-carnosine zinc complex, which is an active ingredient containing no excipient, is stored in a container made of polyolefin or the like, the problem of turbidity occurs. I found it to happen. Therefore, a tablet or granular preparation in which the crystalline L-carnosine zinc complex is mixed with an excipient is not an object to be stored in the storage container of the present invention. However, tablets and granular preparations can also be stored in the storage container of the present invention.
  • the crystalline L-carnosine zinc complex to be preserved does not contain an excipient as described above, but the impurities present in the production of the crystalline L-carnosine zinc complex are It may be included.
  • the object of the present invention is that the purity of the crystalline L-carnosine zinc complex is 99.50% by mass or more, preferably 99.70% by mass or more, and more preferably 99.85% by mass or more.
  • a substance having a purity of 100% by mass is also an object of the present invention.
  • Such a crystalline L-carnosine zinc complex can be produced by a known method. Specifically, it can be produced by the method described in Japanese Patent Publication No. 7-116160.
  • the material of the portion in contact with the crystalline L-carnosine zinc complex uses a specific resin.
  • the resin in contact with the crystalline L-carnosine zinc complex must be a resin having in the molecule at least one polar group selected from the group consisting of a cyano group, a hydroxyl group, and an ester group.
  • a resin having a polar group a low-molecular-weight polymer that is easy to move (although it is estimated that this low-molecular-weight polymer also has a polar group) becomes difficult to move to the surface of the container. It is estimated that it will be easy to stay.
  • a resin having a polar group has a relatively high glass transition point and low molecular mobility. Therefore, it is considered that the movement of the low molecular weight polymer is small, and even if it comes into contact with the crystalline L-carnosine zinc complex, which is a high molecular weight substance, the low molecular weight polymer is not easily incorporated into the crystalline L-carnosine zinc complex. It is thought that there is not.
  • the resin in contact with the crystalline L-carnosine zinc complex is polyacrylonitrile, polyethylene terephthalate, or ethylene-vinyl alcohol copolymer.
  • this bag-like product can be composed of a commercially available film.
  • Hytron BX film polyacrylonitrile film
  • Hytron PG film polyethylene terephthalate film
  • PET / ⁇ -1230 film polyethylene terephthalate film manufactured by Fujimori Kogyo Co., Ltd.
  • PET / ⁇ -1230 film ethylene-vinyl alcohol copolymer film manufactured by Fujimori Kogyo Co., Ltd.
  • a laminated film made of a plurality of resins may be used as long as the material in contact with the crystalline L-carnosine zinc complex uses the specific resin.
  • Such a laminated film is preferable because the advantages of each resin can be imparted to the storage container.
  • the method for storing the crystalline L-carnosine zinc complex in the storage container is not particularly limited.
  • crystalline L-carnosine zinc complex may be placed in the bag-shaped storage container and the opening may be closed by means such as heat sealing or insulation locking.
  • the crystalline L-carnosine zinc complex may be put in a bag-like storage container made of the above resin and further stored in a hard storage container made of another material. That is, only the material of the portion in direct contact with the crystalline L-carnosine zinc complex needs to be composed of the above material.
  • the crystalline L-carnosine zinc complex may be stored under an inert gas such as nitrogen gas or argon gas, or may be stored under reduced pressure so that no gas is present. You can also
  • Example 1 10 g of crystalline L-carnosine zinc complex was stored in a commercially available polyacrylonitrile film bag having a contact area of 400 cm 2 and stored at 45 ° C. and 75% RH for 1 month.
  • This bag in which the resin in contact with the crystalline L-carnosine zinc complex is polyacrylonitrile, is made of Nihon Matai's film “Hytron BX” (polyethylene terephthalate with an outer layer of 12 ⁇ m thickness and polyacrylonitrile with an inner layer of 30 ⁇ m thickness).
  • a laminated body is processed into a bag shape.
  • 1 g of crystalline L-carnosine zinc complex after storage was dissolved in 10 ml of diluted hydrochloric acid and storage stability was evaluated, it was a colorless and clear liquid. The light transmittance of this solution was 99.99%.
  • Example 2 The same evaluation as in Example 1 was performed except that a polyethylene terephthalate film was used in place of the polyacrylonitrile film of Example 1.
  • This bag in which the resin in contact with the crystalline L-carnosine zinc complex is polyethylene terephthalate, is made of Tamapoly's film “Hitron PG”; the outer layer is made of polyethylene terephthalate with a thickness of 12 ⁇ m, and the inner layer is made of polyethylene terephthalate with a thickness of 30 ⁇ m.
  • This laminate is processed into a bag shape.
  • the evaluation result of storage stability was a colorless and clear liquid.
  • the portion of the storage container in contact with the crystalline L-carnosine zinc complex had a light transmittance of 99.95%.
  • Example 3 In Example 2, the same operation as in Example 2 was carried out except that polyethylene terephthalate, which is a resin in contact with the crystalline L-carnosine zinc complex, was changed to a polyethylene terephthalate film made by another company. The transmittance was evaluated. The results are shown in Table 1.
  • Example 4 In Example 2, the same operation as in Example 2 was performed except that polyethylene terephthalate, which is a resin in contact with the crystalline L-carnosine zinc complex, was changed to an ethylene-vinyl alcohol copolymer (inner layer resin). The light transmittance of the solution was evaluated. The results are shown in Table 1.
  • Example 3 (Comparative Examples 1 to 3)
  • various polyolefins having different contents of low molecular weight substances having 12 to 26 carbon atoms were used in place of the polyacrylonitrile bags.
  • Table 2 shows the content of low molecular weight compounds having 12 to 26 carbon atoms in the polyolefin in the portion in contact with the crystalline L-carnosine zinc complex.
  • Table 2 shows the results of the transmittance of the solution after storage.
  • polyolefins have a small amount of low molecular weight in the n-hexane extract, but there are many eluates into polaprezinc and the light transmittance is lowered. That is, even if the amount of the low molecular weight material is reduced, the problem of turbidity cannot be solved.

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  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Food Science & Technology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Packages (AREA)
  • Packaging Of Annular Or Rod-Shaped Articles, Wearing Apparel, Cassettes, Or The Like (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Abstract

La présente invention concerne un récipient destiné à contenir un complexe L-carnosine-zinc cristallin, lequel récipient destiné à contenir le complexe L-carnosine-zinc cristallin est caractérisé en ce qu'une partie destinée à venir en contact avec le complexe L-carnosine-zinc cristallin est formée à partir d'une résine ayant au moins un groupe polaire, sélectionné parmi le groupe comprenant un groupe cyano, un groupe hydroxyle et un groupe ester dans la molécule.
PCT/JP2017/015206 2016-04-27 2017-04-13 Récipient pour contenir un complexe l-carnosine-zinc cristallin, et procédé pour tenir ledit récipient WO2017188016A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
KR1020187028481A KR102415182B1 (ko) 2016-04-27 2017-04-13 결정성 l-카르노신 아연 착체의 보존 용기 및 보존 방법
CN201780022717.8A CN109071093B (zh) 2016-04-27 2017-04-13 结晶性l-肌肽锌络合物的保存容器及保存方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2016088805A JP6659442B2 (ja) 2016-04-27 2016-04-27 結晶性ｌ−カルノシン亜鉛錯体の保存容器
JP2016-088805 2016-04-27

Publications (1)

Publication Number Publication Date
WO2017188016A1 true WO2017188016A1 (fr) 2017-11-02

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PCT/JP2017/015206 WO2017188016A1 (fr) 2016-04-27 2017-04-13 Récipient pour contenir un complexe l-carnosine-zinc cristallin, et procédé pour tenir ledit récipient

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JP (1) JP6659442B2 (fr)
KR (1) KR102415182B1 (fr)
CN (1) CN109071093B (fr)
TW (1) TW201803542A (fr)
WO (1) WO2017188016A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007314467A (ja) * 2006-05-25 2007-12-06 Takahashi Gakuen 脳血管性認知症の予防または治療用飲食物、その包装または容器ならびに脳血管性認知症の予防または治療薬
JP2011001324A (ja) * 2009-06-22 2011-01-06 Sawai Pharmaceutical Co Ltd ポラプレジンク含有口腔内崩壊錠
US20160101048A1 (en) * 2014-10-09 2016-04-14 Richard J. Di Rocco +l-carnosine zinc formulations and methods of use

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3294920B2 (ja) 1993-10-27 2002-06-24 アロカ株式会社 超音波画像記録再生装置
JP2002068981A (ja) 2000-08-22 2002-03-08 Hamari Chemicals Ltd 末期ガン患者の食欲不振および味覚異常を改善する医薬
JP2004267384A (ja) * 2003-03-07 2004-09-30 Niccon Kohsan Co Ltd 医療用容器の製造方法および医療用容器
US20090310890A1 (en) * 2005-06-15 2009-12-17 Fujimori Kogyo Co., Ltd. Duplex-Chamber Package
JP6124141B2 (ja) * 2011-09-01 2017-05-10 三菱瓦斯化学株式会社 酸素吸収剤組成物及びそれを用いた酸素吸収剤包装体
EP2826643B1 (fr) 2012-03-14 2018-08-08 Bridgestone Corporation Pneumatique
CN104812837A (zh) * 2012-12-05 2015-07-29 日本瑞翁株式会社 树脂组合物以及使用其的医疗用药剂容器

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007314467A (ja) * 2006-05-25 2007-12-06 Takahashi Gakuen 脳血管性認知症の予防または治療用飲食物、その包装または容器ならびに脳血管性認知症の予防または治療薬
JP2011001324A (ja) * 2009-06-22 2011-01-06 Sawai Pharmaceutical Co Ltd ポラプレジンク含有口腔内崩壊錠
US20160101048A1 (en) * 2014-10-09 2016-04-14 Richard J. Di Rocco +l-carnosine zinc formulations and methods of use

Also Published As

Publication number Publication date
TW201803542A (zh) 2018-02-01
KR20180134874A (ko) 2018-12-19
KR102415182B1 (ko) 2022-07-01
CN109071093A (zh) 2018-12-21
JP6659442B2 (ja) 2020-03-04
CN109071093B (zh) 2020-06-23
JP2017197215A (ja) 2017-11-02

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