TW200950769A - New material used for package for sevoflurane - Google Patents

Abstract

The present invention relates to a use of a material made of cyclic olefin copolymers and graft copolymers of ethylene and octene for producing a container for holding anesthetic agents, and to a container comprising a container body and a container lip, wherein the internal surface material of said container is made of cyclic olefin copolymers and graft copolymers of ethylene and octene.

Description

200950769 VI. Description of the invention: [Technical field to which the invention pertains] The invention relates to the use of a cyclic olefin polymer, and a graft copolymer of ethylene and octene, for the manufacture of a container for storing an anesthetic agent. And a container comprising a container body and a container lid, wherein: the material of the inner surface of the body is composed of a combination of a cyclic olefin copolymer polymer and an ethyl octyl graft copolymer. [Prior Art] · ❹ Compound sevoflurane (Sevoflurane) [fluoromethyl-1,ll 3 3 3_hexafluoroisopropyl ether, ie (CF〇2CH〇CH2F] is a widely used 'inhalation type Anesthetics, usually packaged in glass, stainless steel containers, but it has been found that in some cases, sevoflurane interacts with glass containers to promote the decomposition of heptafluorocarbon. This interaction is thought to be due to seven tilts. In the presence of Lewis acid, it will decompose to produce decomposition products such as hydrofluoric acid. Currently, the common glass material is glass-type glass, which contains dioxin fossil, gas oxidation, hydroxide surface and oxidation. The oxidation of the cucurbit-type glass contained in the hexafluoride will cause the effect of Lewis acid when it is directly exposed to heptafluorocarbon, thereby promoting the decomposition of heptafluorocarbon. The decomposition products such as hydrogen acid generated by this decomposition reaction will be engraved with glass. The inner surface, so that more oxygen is exposed to the seven burns, which further promotes the decomposition of heptafluorocarbon, which affects the use of the product. People = have made efforts by using stable, not easy to produce Lewis acid Packaging container heptafluoro burn 'or Lewis acid employed is an amount sufficient to inhibit the suppression heptafluoro ^ & exploded' These have been given corresponding patent disclosure as

I 3 94584 200950769 CN 1152674C and CN llTfiRiRr1 # 聚乙烯 Polyethylene naphthalene (4) A: Polypropylene: c: 117 〇 516c Mainly choose materials such as resin to make a significant effect on the secondary polymer = stator polymer. There are ones that are stable and seven-reduced, and that inhibit degradation. However, the materials are not limited to the materials described in the above patents, and the more molecular materials used in the molecular materials technology, the more polymer materials are used. Yu Le (10) armored We also found some packaging materials suitable for sevoflurane in addition to the materials mentioned in the above patents. The preferred material is a cyclic olefinic copolymer high ((10), CyCl〇〇lefin c〇p〇lymer), this material does not contain the seven-burning fraction, (4), the seed (four) is made of silk Burning, do not need to add a Lewis acid inhibitor to inhibit the decomposition of heptafluorocarbon. The cyclic olefin copolymer polymer (10)) is a non-crystalline transparent copolymer polymer having a cyclic olefin structure, which is commercially available from Tai-Ti Company under the trade name TGPAS. The cyclic olefin copolymer is a new series of amorphous thermoplastic engineering plastics with high transparency, moisture barrier properties, HDT ' Heat Deflection Temperature, and chemical resistance. C0C has optical properties comparable to PMMA (polymethyl methacrylate, acrylic resin) and has higher heat resistance than pc (polycarbonate). It also has better dimensional stability V than PMMA and PC. It has the advantages of improving water vapor tightness, increasing rigidity, heat resistance, easy to impart, etc. - pre-cutting performance. TOPAS (COC) 8007 grade materials are mainly used to process a variety of bottles for narcotics and pharmaceuticals. These bottles can withstand all sterilization methods commonly used by people to sterilize, such as steam sterilization, ethylene oxide disinfection, electronics and R-ray sterilization, etc., therefore, ring 4 94584 200950769 olefin copolymerization polymer (C0C) has a wide range of applications in the field of pharmaceutical packaging materials. Compared with glass and stainless steel materials, it does not contain Lewis acid such as alumina or iron oxide, thus ensuring the storage stability of sevoflurane. T0PAS is highly secure and the specifications have been certified by the US fda. NamSA tests TOPAS (COC) 8007 samples according to the US Pharmacopoeia. Under FDA C to steroid use conditions, TOPAS (COC) 8007 is fully compliant with FDA requirements. ExactTMP 1 astomers © manufactured by ExxonMob i 1 e is a copolymer of ethylene and olefin, which is a very rich product containing butene, hexene and octene copolymer. The following characteristics: outstanding low temperature and temperature impact resistance; low specific gravity; clean; outstanding heat sealing performance; excellent compatibility with various base polymers; excellent flexibility and puncture resistance; extremely high inorganic filling; Elongation and high elasticity; embrittlement and discoloration caused by radiation resistance. ExactTM Plastomers, model: 乂 乂 ( (^ 5061, is an ethylene and octene graft copolymer (ethylene alpha octene ❹ copolymers). Compliance with FDA regulations: 21 CFR 177. 1520 "Olefin polymer" (c) 3. 2c, It can be applied to raw materials and articles that come into contact with food. When the temperature reaches hot filling or higher than 150°F (less than 212°F), and in the 21CFR: 176. 170(c) Table 2, the olefin is used under the conditions of ΗC. The polymeric article can be in contact with all food types in Table 1 of CFR CFR 176. 170(c). In our examples, packaging made of TOPAS (COC) 8007 and ExactTMP 1 astomers (EXACT 5 0 61) was also selected. The container holds sevoflurane. In the packaging container, T0PAS ((3) 08007 is used as the main material constituent component, and EXACT 5061 is used as an auxiliary component, the purpose is to improve the performance of the container against the fall 5 94584 200950769. [Invention] The present invention relates to one type. The container material is produced by a ring-shaped cigarette core: the product comprises:::, a polymer, a container of the dimerization molecule and a graft of ethylene and octene. Space; and in the defined space The container sucks eight anesthetic heptafluoropyrans. The inner wall of the crucible is composed of the inner wall adjacent to the inner space of the ring, and the grafted copolymer of ethylene and octene is: 00 < The internal space is placed in a predetermined amount of heptafluoride. The container is defined as an opening = in fluid communication, and 5 ^ 'the opening is such that the inner space and the external environment are σ 5 pieces, and the gasket is in the cover of the olefin (HDPE) The inside of the cover has a gasket material of polyparaphenylene to contact the fluid in the container. The gasket has a foaming material. The i has a C, SI (PET) film or a polyethylene (PE) mouth. In the cover of the test PP~ sheet to seal the inner space defined by the container in the present invention, a predetermined amount of heptaphane is placed in the inner space of the present invention. - The general bottle type can also be used for seven. Fluorocarbon, the container can be a olefin copolymer:: its shape and capacity. It has been found that the compatibility and strength properties of a five-hearted and conjugated graft copolymer are prepared in a ring-shaped packaging container. , can 'have the desired vapor barrier properties, chemical film, fun and other packaging materials. Read general Molding processing method

A packaging container prepared by grafting a copolymer of molecular material U ethylene and octene, 94584 200950769, is used to hold sevoflurane, has desired vapor barrier properties, and does not contain Lewis acid, so there is no The possibility of degrading the heptafluorocarbon contained in the container. An example of a cyclic olefin copolymer polymer which can be used in the present invention is the United States.

The Topas 8007 (COC), 8007 provided by Ticona Corporation represents a level, and those having ordinary knowledge in the art to which the present invention pertains can understand that other levels can be employed without departing from the scope defined by the scope of the present invention. A cyclic olefin copolymer polymer.接枝 The graft copolymer of ethylene and sage which can be used in the present invention is ExactTM Plastomers manufactured by ExxonMobil, model: EXACT 5061, which is an ethylene alpha octene copolymers ° heptafluorocarbon Burning is mainly used as an inhalant'. Therefore, the solution is a relatively volatile component. If the solution is decomposed, the decomposition products produced by it, such as hydrofluoric acid, are harmful to the human body once inhaled, so 'packaging in sevoflurane In addition to ensuring the high purity of the inhalant sevoflurane, it is necessary to ensure the stability of the sevoflurane solution. Further, the purity of the heptafluoroalkane of the present invention is higher than 99.95 wt%, preferably the purity is still 99.98 wt%. The above purity is calculated on the basis of no water. The advantage of the present invention is that the seven alkane encapsulated in a container made of TOPAS (COC) and ExactTM Plastomers (EXACT 5061) is stable, and the solution is stored in the new package at a high temperature of 4 ° C. stable. 1 The stable sevoflurane of the present invention has a moisture content of 15 〇 ppm to 1400 ppm, and 7 94584 200950769 · and is packaged or stored in a container made of TOPAS (COC) 8007 and ExaCtTM Plast 〇mers (ExACT 5061). In another embodiment, the moisture content is less than 140 ppm. The above moisture content is detected by the Karl-Fischer method. The sevoflurane has a purity of more than 99.95 wt%, even up to 99. 98 wt%, in the container at room temperature for 6 months or at 40 ° C, at a relative humidity of 20% for 6 months. It is generally desired that the present invention is not degraded in heptanethane in a packaging container made of a material such as TOPAS (COC) 8〇07 and ExactTM Plast〇mers (EXACT 5061) in the presence of a package or a base. The following examples are for illustrative purposes only and are not intended to limit the scope of the invention. [Embodiment] EXAMPLES Example 1 This example describes the preservation of sevoflurane having a water content between 150 ppm and 1400 ppm. Stability in containers made of TOPAS (COC) 8007 and ExactTM Plastomers ◎ (EXACT 5061). In a test that began in January 2000, the water content of Qirui was 165 ppm by the Karl-Fischer method. A sample of sevoflurane was placed in a TOPAS (COC) 8007 and , which had been previously dried at l〇5 °C for 2 hours.

Inside the container made of ExactTM Plastomers (EXACT 5061), seal and then place the sample at 40 ° C and maintain relative humidity at 75% relative humidity. The purity of sevoflurane was analyzed by gas chromatography at 6 months. The result was 99.959 wt%, and no decomposition occurred. Example 2 94584 200950769 This example describes the stability of heptafluoropyrene stored in a container made of TOPAS (COC) 6013 and ExactTM Plastomers (EXACT 5061) having a water content of between 150 ppm and 1400 ppm. In January 2008, the initial test was conducted to determine the water content of sevoflurane by the Karl-Fischer method to be 1300 ppm. Place a sample of sevoflurane in a container made of TOPAS (COC) 8007 and ExactTM Plastomers (EXACT 5061) that had been previously dried at 105 ° C for 2 hours, seal, and then place the sample at 40 ° Under C, the relative humidity is 75%. After 6 months, the purity of sevoflurane was analyzed by gas chromatography, and the result was 99.964 wt%, and no decomposition occurred. EXAMPLE 3 This example describes the stability of a heptafluorocarbonate having a water content of less than 140 ppm in a container made of TOPAS (COC) 8007 and ExactTM Plastomers (EXACT 5061). In a test started in January 2008, the water content of sevoflurane was measured by the Karl-Fischer method to be ❹80 ppm. A sample of sevoflurane was placed in a container made of TOPAS (COC) 8007 and Exac.tTM Plastomers.. (EXACT 5061) which had been previously dried at i〇5 °C for 2: hour, sealed and used. The thermoplastic film was packaged, and then the sample was placed at 40 ° C 'relative humidity 75%, maintaining the relative humidity around. After 6 months, the purity of sevoflurane was analyzed by gas chromatography, and the result was 99.959 wt%, and no decomposition occurred. Example 4. Additional information in the table below confirms the long-term stability of sevoflurane in containers made of TOPAS (COC) 8007 and ExactTM Plas "tomers (EXACT 5061) material 94584 200950769. The water content of sevoflurane is determined by the Karl Fischer method. The heptafluorocarbon is placed in 250 ml of t〇PAS (COC) 8007 and

V

Partial sevoflurane was tested for stability in a container made of ExactTM Plastomers (EXACT 5061) and then under certain conditions or at room temperature. The purity of sevoflurane (determined by gas chromatography) in all experiments indicated that no decomposition occurred. Container Type Production Prime Water Moisture Duration Conditions Final Product Results 2008.01 90 ppm 180 Days 25〇c/60% Humidity 99. 971% Does not decompose 250ml 2008.01 170 ppm 180 days 25〇C/60% Humidity 99. 964% No Decomposition 2008. 01 1100 ppm 180 days 25〇C/60% 99. 977% Not decomposed 〇〇 Although the invention has been described in detail for the purpose of illustration only, not a description . In the technical field of the present invention, the present invention is understood to be within the scope of protection of the present invention. Any change or change of 仃; [Graphic Drought-Ming] No 7»*> [Main component symbol description] None 94584

Claims (1)

200950769 VII. Patent application scope: 1. A material consisting of a cyclic olefin copolymer polymer and a graft copolymerization of ethylene and octene, which is used to manufacture a container for storing an anesthetic. 2. For the use of the scope of claim 1, wherein the anesthetic is a fluoroether inhalation anesthetic. 3. The use of the scope of claim 2, wherein the fluoroether is a sevoflurane (4) container comprising a container body and a container lid, characterized in that the material of the inner surface of the container body It is composed of a cyclic olefin copolymer polymer and a graft copolymer of ethylene and octane. 5. The container of claim 4, wherein the container lid is provided with a sealing gasket. 6. The container of claim 4, wherein the material of the container lid is rf? density polyethylene (HDPE). 7. The container of claim 5, wherein the material of the gasket is a polyethylene terephthalate (PET) film or a polyethylene (PE) foaming material. 8. A pharmaceutical product comprising: a container comprising a cyclic olefin copolymer polymer (referred to as COC, hereinafter the same) and a graft copolymer of ethylene and octene, the container defining an internal space, and A certain amount of fluoroquinone inhalation anesthetic is contained within the defined space. 9. If the pharmaceutical product of claim 8 is applied, the fluoroether is inhaled 11 94584 200950769 The anesthetic is heptafluorocarbon. 10. The pharmaceutical product of claim 8 wherein the container defines an opening that provides fluid communication between the interior space and the external environment; the dispensing product includes a cover with a gasket for the cover To seal the opening of the container, the material of the cover is high density polyethylene (HDPE). 11. The pharmaceutical product of claim 8 wherein the container defines an opening that provides fluid communication between the interior and the external environment; the dispensing product includes a cover having a gasket inside thereof The mat may be in contact with the fluid in the container at the top of the lid, wherein the material of the gasket is a polyethylene terephthalate (PET) film and a polyethylene (PE) foam material. . 12. A pharmaceutical product comprising: a container defining an interior space, the container having an inner surface adjacent the interior space, the inner surface comprising a cyclic olefin copolymer polymer (C0C) and ethylene and octane The graft copolymer of the olefin is composed of, and placed in a predetermined amount of sevoflurane in the internal space defined by the container. 13. A method of storing an inhaled anesthetic sevoflurane comprising the steps of: providing a predetermined amount of an anesthetic sevoflurane; providing a container defining an internal space I, the container comprising a cyclic olefin copolymer polymer (C0C) and A graft copolymer of ethylene and octene; and the predetermined amount of sevoflurane is placed in the interior space defined by the container. 14. The method of claim 17, wherein the container defines an opening that provides fluid communication between the interior and the external environment, the method comprising the steps of: 12 94584 200950769 provides a cover constructed to seal the opening defined by the container, the material of which is constructed of high density polyethylene (HDPE); the opening defined by the container is sealed with a lid. 15. The method of claim 11, wherein the container defines an opening that provides fluid communication between the interior and the external environment, the method comprising the steps of: providing a Constructing a cover for sealing the opening defined by the container, the inside of the cover having a gasket at the top of the cover for contacting the fluid in the container, the material of the gasket being a cyclic olefin copolymer a polymer (C0C) and a graft copolymer of ethylene and octene; and sealing the opening defined by the container with the gasketed cover. 16. A method of storing an inhaled anesthetic sevoflurane comprising the steps of: providing a predetermined amount of anesthetic sevoflurane; providing a container defining an interior space having an inner wall adjacent the interior space defined thereby, The inner wall of the container is composed of a cyclic olefin copolymer polymer (C0C) and a graft copolymer of ethylene and octene; and a predetermined amount of heptafluorocarbon is placed in the inner space defined by the container. 17. The method of claim 17, wherein the container defines an opening that provides fluid communication between the interior and the external environment, the method comprising the steps of: providing A cover for sealing the opening defined by the container, the material constituting the cover is high density polyethylene (HDPE). 18. The method of storing an inhaled anesthetic, in accordance with claim 16, wherein a lid having a gasket is provided, the lid being a lid for sealing the opening defined by the container of 13 94584 200950769, The gasket may be in contact with the fluid in the container at the top of the cover, the material of the gasket being a cyclic olefin copolymer polymer (C0C) and a graft copolymer of ethylene and octene, and the gasket with the gasket The lid seals the opening defined by the container. Ο 14 94584 200950769 IV. Designated representative map: There is no schema in this case (1) The representative representative figure of this case is: (). - (2) A brief description of the symbol of the representative figure: ©5. If there is a chemical formula in this case, please show the chemical formula that best shows the characteristics of the invention: This case does not represent the chemical formula Ο 94584