TW509568B - Container for an inhalation anesthetic - Google Patents

Abstract

A pharmaceutical product. The pharmaceutical product includes a container constructed from a material containing polyethylene terephthalate and/or polyethylene isophthalate. The container defines an interior space. A volume of sevoflurane is contained in the interior space defined by the container.

Description

509568 A7 B7 V. Description of the Invention (1) This application is a follow-up to US Patent No. 09 / 205,460 filed on December 12, 1998, and the latter is US Patent No. 09 / 004,792 filed on 1998. 1. It is a subsequent part of US Patent No. 6,074,668, and a subsequent part of US Patent No. 09 / 004,876 filed in 1998.1.9. BACKGROUND OF THE INVENTION The present invention relates to containers for inhaled anesthetics and methods for storing inhaled anesthetics. In particular, the present invention is directed to a container made of a material that provides protection against vapor transmission through the wall of the container and does not react with the inhaled anesthetic contained therein. Inhalation anesthesia agents such as sevoflurane (fluoromethyl-2,2,2-trifluoro-1- (trifluoromethyl) ether), enflurane (2-chloro-1,1,2-trifluoroethyl) Difluoromethyl ether), isofluoro ether (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), methoxyfluoro ether (2,2-dichloro-1,1- Diethyl ethyl ether) and desflurane (2-difluoromethyl-1,2,2,2-tetrafluoroethyl ether) are usually filled in glass containers. Although these fluoroether preparations have been shown to be excellent anesthetics, fluoroether preparations and glass containers have been found to work under certain conditions, causing the degradation of fluoroether preparations. This effect is believed to be due to the presence of Lewis acid in the glass container material. Lewis acid is an empty space that accepts unpaired electron pairs, and therefore provides a possible space to react with the fluorinated fluorinated fluorenic acid (-C-0-C 4). Degradation of these fluorinating agents in the presence of Lewis acid may form degradation products such as hydrofluoric acid. The glass materials currently used with these fluoroethers are called Class III glass. This material contains silicon dioxide, calcium hydroxide, sodium hydroxide and alumina. Class III glass shields the transmission of vapours through the walls of the container, thus preventing the transmission of fluoroethers and other vapours into the container. However, the size of this paper is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 509568 A7 B7 V. Description of the invention (2) Glass materials such as alumina contained in Class III glass are directly exposed to The fluorinated ether is similar to Lewis acid, which promotes the degradation of the fluorinated ether. Degradation products such as hydrofluoric acid produced by this degradation may corrode the inner surface of the glass container, thereby exposing a larger amount of alumina to the fluoroether compound, and thus promoting further degradation of the fluoroether compound. In some cases, the resulting degradation products endanger the structural integrity of the glass container. Efforts are currently underway to suppress the reactivity of glass to various chemicals. For example, treating glass with sulfur has been found to protect the glass in some cases. However, it is important to understand that sulfur on glass surfaces is unacceptable in many applications. Furthermore, there is a danger that the glass container may break. For example, glass containers can break when dropped or subjected to sufficient force during use or transport and handling. This cracking may cause the medicine or the user to touch the contents of the glass container, and therefore, the inhaled anesthetic agent evaporates rapidly. Therefore, if the glass container contains an inhalation anesthetic such as sevoflurane, rupture of the container may require immediate removal of items around the ruptured container, such as the operating room or medical team. To avoid cracking, the exterior of glass, non-product contact surfaces are usually coated with polyvinyl chloride (PVC) or synthetic thermoplastic resins, such as Surlyn® (registered trademark of E.I. Du Pont De Nemours and Comp any). These will increase the cost of the container, and are not aesthetically pleasing. In particular, it cannot overcome the problems related to the degradation caused by the use of glass-filled fluoroether inhaled anesthetics. Therefore, it is necessary to provide a container made of a material other than glass to store, transport, and dispense inhaled anesthetics, thereby avoiding the disadvantages of the aforementioned glass. The preferred material does not contain Lewis acid, which promotes the degradation of inhaled anesthetics, provides shielding for the transmission of vapors into and out of the container, and increases the breakage of the container relative to the glass container. -5- This paper applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 509568 A7 B7 5. Description of the invention (3) Crack resistance. SUMMARY OF THE INVENTION The present invention is directed to pharmaceutical products. In the first specific example, the pharmaceutical product includes a container made of a material containing polyethylene terephthalate and / or polyethylene isophthalate. The container defines an internal space containing a volume of sevoflurane therein. A second specific example of the present invention is directed to a pharmaceutical product, in which a container defining an inner space has an inner surface adjacent to the two inner spaces. The inner surface of the container is made of a material containing polyethylene terephthalate and / or polyethylene isophthalate. The inside of the container contains one volume of sevoflurane. The invention also relates to a method for storing inhaled anesthetics. The method includes the step of providing a predetermined volume of sevoflurane. The container is also provided, and the container is composed of a material containing polyethylene terephthalate and / or polyethylene isophthalate. The container defines the interior space. A predetermined volume of sevoflurane is injected into the inner space of the container. Another specific example of the method of the present invention is to provide a predetermined volume of sevoflurane. In addition, the present invention provides a container having an inner surface that defines an interior space. The inner surface of the container is made of polyethylene terephthalate and / or polyethylene isophthalate. A predetermined volume of sevoflurane is injected into the inner space of the container. Fg of the drawings, to converge — For a more complete understanding of the present invention, it is necessary to refer to the drawings and read the following detailed description, in which: Figure 1 is a cross-sectional view of a pharmaceutical product constructed according to the present invention. Detailed description The pharmaceutical products constructed according to the present invention are generally shown in Figures 1-10. Pharmaceutical products -6- This paper size is applicable to Chinese National Standard (CNS) A4 (210 X 297 mm) V. Description of the invention (4 A7 B7

The object 10 includes a container 19 having an inner surface 14. The inner surface 14 defines a container 12 and two inner rooms 16 inside. 18 packs of inhaled anesthetic. The interior space of Yu Guzhai 12 Middle School. In a preferred embodiment of the present invention, hemp agent 18 is sevoflurane. The inhaled anesthetic 18 is a liquid and may include a liquid phase, a gas phase or a liquid phase, and a vapor phase. Figure 1 illustrates a liquid phase inhalation anesthetic i 8. ..... The purpose of the container 12 is to fill the inhaled anesthetic 18. In the specific example of the present invention shown in Fig. Β, the container 12 has a bottle shape. However, it needs to be understood that the container has a long time, structure and volume, all without departing from the spirit and scope of the present invention. For example, the container 12 can be constructed to deliver a large volume (tens or hundreds of liters) of inhaled anesthetic agent. The cross-section of the conveying trough can be 球形, spherical_off, and both are inseparable: the scope of the invention. The container 12 is preferably made of a material that minimizes the amount of vapor that enters or leaves the container 12, so that the amount of inhaled anesthetic 18 released from the internal space 16 of the container 12 can be minimized, and therefore from the outside of the container 2 The vapor transmission into the internal space 16 and therefore into the anesthetic 18, such as water vapor transmission, is minimal. The container 12 is also preferably composed of a material that does not promote inhalation of the anesthetic 18 to lower the feet. In addition, the container 12 is preferably made of a material with the least possibility of rupture during storage, transportation, and use of the container. It has been found that when a container made of a material containing polyethylenate is used to inhale the anesthetic 18, it can provide the required vapor shielding, chemical action and strength characteristics. Those skilled in the art should understand that there are many different types of polyethylenic acid ester polymers with different molecular weights, additives, and acetic acid ester content. These polymers can be divided into three different groups, namely homopolymers, copolymers and blends. It has been found that the comparison of the homopolymers of polyethylenic acid esters with copolymers and blends can apply the Chinese National Standard (CNS) A4 specifications (210X297 mm) to the paper size of the paper. 509568 A7 B7 V. Description of the invention (5 ) Teleportation provides better cover. Therefore, it is preferable that the material constituting the container 12 of the present invention contains a polyethylenate homopolymer. However, it is to be understood that certain copolymers and blends of polyethylenate can be used in conjunction with the present invention, as long as it can provide adequate shielding of vapors, such as inhaled anesthetics and water vapor transmission, as long as it provides the required strength And will not react with inhaled anesthetic 18. In addition to the required vapor-shielding properties of polyethylenic acid ester-containing materials, polyethylenic acid esters do not contain solid Lewis acid, and therefore do not promote fluorinated ethers in containers made of them. Threat of degradation of inhaled anesthetics. An example of the polyethoxylated acid related material of the present invention is HiPERTUFtm90000 polyester resin (trademark of Shell Chemical Co., Ltd.), a polyethylidene ester based on 2,6-dimethylphosphonate. Those skilled in the art should understand that other polyethylenic acid esters can be used without departing from the scope set in the patent scope of the subsidiary application of the present invention. Those skilled in the art should understand that polyethylenate is a polyester containing acetic acid. Other polyester materials believed to be useful in the present invention are polyethylene terephthalate (" PET "), that is, polyesters containing terephthalic acid, and polyethylene isophthalate ( "PEE)), which is an isophthalic acid-containing polyester. In addition, it is believed that polyester copolymers such as copolymers of two or more of PEN, PET and PEI can be used in the present invention. -In addition to the above polymer materials, it is believed that nanocomposites can be used in the present invention. Nanocomposite materials are well known to those skilled in related arts, and may contain various materials such as PET combined with limestone. Many nanocomposites have been shown to provide adequate vapor shielding properties. According to a first specific example of the present invention, the container 12 is composed of a single layer of material. Also -8- This paper size applies to China National Standard (CNS) A4 (210X297 mm) 509568

P, the trough device 12 is a homopolymer in its entire thickness f. As in the specific example described above, the container 12 is made of a material containing polyethylene terephthalate, PET, PEI, a diester copolymer, and / or a nanocomposite. In another specific example of the invention, the container 12 is multi-layered. As for the m-layer material used here, it will contain materials consisting of more than one layer of base material. One layer is composed of different materials, that is, materials with different chemical or structural properties, or materials with different performance characteristics. Materials, where the base materials are arranged one on top of the other, or are arranged alternately with each other, thus forming a single piece: (11) a coating with different materials, and a lining material combined with the lining, which is composed of different materials; and (Iv) Changes to any of the above are known. In another example of the present invention, the inner surface 14 of the container 12 is preferably composed of a material containing poly (vinylethylacetate), PET, PEI, a poly (vinyl acetate) copolymer, and / or a nano composite material. The surface of the container 14 in contact with the fluorinated ether inhaled anesthetic agent contains polyethylenic acid, pET, pEI, polyglycan copolymer and / or nanometer ... It is expected to obtain the required air shielding properties, and Minimize the degradation of fluoroether inhaled anesthetics.-In another embodiment of the present invention, the container 12 is composed of a material containing polymethylpentene. In a preferred embodiment, polycyclomethylpentene is used. The seal of the polymethylpentene material used in the invention is, "Daikyo Resin CZ", which is manufactured and distributed by Daikyo / Pharma-Gummi / West Group. This is a polycyclomethylvalerium material. In addition, the inner surface 14 of the container 12 is made of a material containing polymethylpentane and Greek. In another specific example, the inner surface 14 may be in the following form: (i) a lining position in a body defined by different materials such as glass; or (11) a coating applied on a body defined by different materials, or ( m) —Floor as above-9-A7

It is a multilayer material related to the purpose of poly (ethylene glycol): acid. Those skilled in this art should understand the work of polymethyl riding and polycyclomethylpentane. Other poly # hydrocarbon materials are believed to be useful in the present invention, including ethylene glycol (' EVQH ,,), and polyethylene. Poly-associated hydrocarbons are as follows: methylpentene, polycyclomethylpentene, polyester, and nanomaterials. Materials: In the example, the container 12 is composed of an ionic monomer resin. In addition, the inner surface 14 of the container 12 is made of a material containing an ionic monomer, such as SURLYN (R) ionomer resin manufactured by DuPont. As used herein, "ionic monomer resin" refers to an ionic cross-linked thermoplastic compound. In another specific example, the inner surface 14 may be in the form of: (i) a lining disposed in a body defined by different materials such as glass; or (ii) a coating applied on a body defined by different materials: or (ii) a layer as above The multi-layer materials related to Polygon® and nano composites. Those skilled in the art will appreciate that the coating can be applied to the interior surface of the guest 12 using a variety of known techniques. The preferred technique will depend on the material of the container 12 used, and (π) the coating material to be applied to the container 12. For example, if the container 12 is made of a known glass material, the coating can be applied to the inner surface of the container 2 by heating the container 12 to at least the melting point of the material to be coated. The coating material is then applied to the heated container 12 using various known techniques, such as a coating material sprayed by a spray. The temperature of the container 12 is then cooled below the melting point of the coating material, thereby forming the coating material into a single unbroken film or layer, i.e., the inner surface 14. In addition to the materials disclosed in this article, a coating can also be applied to the container 12 to improve the paper size. 10- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)

Pretend

Line 509568 A7 B7 V. Description of the invention (8) Provides additional vapor shielding properties. The coating can be applied to glass containers and containers composed of one or more materials disclosed herein. The coating is preferably applied so that it cannot be in direct contact with the inhalation anesthetic 18, even if the coating is not present on the inner surface 14 of the container 12, for example, polyvinyl chloride can be used to provide the desired vapor shielding properties. Other vapor barrier coatings can also be applied to the container 12, including polyvinyl alcohol (" PVOH "), silica, alumina, and aluminum foil. As shown in FIG. 1, the container 12 defines an opening 20. The opening 20 can assist in filling the container 12 and provide use of the contents of the container 12, so that the contents can be removed when the cross container 12 is needed. Another specific example of the present invention is described in FIG. 1, and the opening 20 is a bottle mouth. However, it should be understood that the opening 20 may have many known structures without departing from the scope of the present invention.

The lid 22 is constituted by a fluid-tight opening 20, so that the inhalation anesthetic 18 is fluid-tightly sealed in the container 12. The cover 22 may be composed of various known materials. However, it is preferred that the cover 22 be constructed of a material that minimizes the transmission of vapor and also minimizes the degradation of the inhaled anesthetic 16. In a preferred embodiment of the present invention, the cover 22 is made of a material containing polyethylenate and / or one of the materials described herein. In another embodiment of the present invention, the cover 22 has an inner surface 24 made of a material containing poly (ethylene glycol) ester and / or one of the materials described herein. In summary, it should be understood that the cover 22 and / or its inner gray surface 24 may be made of polypropylene, polyethyl, polyethylnaphthalate, polymethylvalerate, ionic monomer resin, polyethylene terephthalate Esters, polyethylene isophthalate, EVOH and combinations thereof. As in the container 12 described above, the lid 22 may be a substrate or may be multi-layered. The lid 22 and the container 12 are constructed so that the lid 22 can be screwed onto it. Containers of this type -11-This paper size is applicable to Chinese National Standard (CNS) A4 (210 X 297 mm) 509568 A7 B7 V. Description of invention (9) and cover are customary. Other specific examples of the lid 22 and the container 12 are also possible and can be easily understood by those skilled in the art. The different specific examples include (but are not limited to) caps that can "clamp" the container, caps that are adhesively fixed to the container, and caps that are fixed to the container using known mechanical devices such as metal sleeves. In a preferred embodiment of the present invention, the lid 22 and the container 12 are constructed so that the lid 22 can be separated from the container 12 under the permanent damage caused by the lid 22 or the container 12, so that the user can pour out the required volume from the container 12 After inhaling the anesthetic 18, the lid 22 may be sealed again with a lid 20 and the container 12 may contain other characteristics than those which are part of the present invention. For example, the container 12 may be constructed to contain a system for dispensing an inhaled anesthetic 18 into an anesthetic vaporizer. Grabenkort U.S. Patent No. 5,505,236 discloses this system.

The method of making the type of container used in the present invention is known in the art. For example, it is known that polyethenyl acetate needs to be dried to a water content of about 0.005% before processing to obtain the best physical properties of container 12 and lid 22. The preferred method for making the container 12 and the lid 22 used in the present invention is limited to injection stretch blow molding of a material containing polyethylene glycolate. A machine manufactured by Japan AOKI Technical Laboratory, Inc. is particularly useful for performing this molding operation. The material containing polyethylene terephthalate is injection molded into a preform, and then moved to a blow molding station where it is stretched and blown into a 4-mold container. The container is then heated and calcined in batches in a conductive oven. It has been found that the calcination of materials containing polyethylenic acid will increase the crystallinity of the materials to a level that cannot be achieved by blow molding alone. Increasing the crystallization results in a higher shielding of vapor transmission, so that the vapor shielding performance characteristics of the container 12 made of a calcined material containing polyethylenic acid ester can be improved. Adding crystals is also -12- This paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) 509568 A7 B7 V. Description of the invention (10) Reduce the total weight of container 12 (to achieve the strength of the selected container) Required weight), and the amount of material required to reach the intended container strength of container 12. Increasing the strength of the container can make the container bear a greater load during transportation, storage and use, so that the cracking of the container can be minimized. For example, when the container 12 is placed on top of another container, or when the container 12 or the cartons or trays of the container 12 are transported or stored in a stack, greater container strength is required. It should be noted that a container made of a calcined polyethylene resin containing less weight than a glass container with comparable strength characteristics is less likely to break than a comparable weight glass container, and the manufacturing cost is higher than that of glass with comparable performance characteristics The container is low. Lower container weights also reduce the cost of shipping such as containers. Furthermore, the container does not have the possibility of degradation of the fluoroether inhaled anesthetic contained in the glass container. The method of the invention comprises the step of providing a predetermined volume of inhaled anesthetic 18. In a preferred embodiment, the inhalation anesthetic 18 is sevoflurane. The present invention also provides a container 12 composed of one or more of the above materials. The method of the present invention also includes the step of placing a predetermined volume of inhaled anesthetic 18 into an inner space 16 defined by a container 12. Another specific example of the method of the present invention is to provide a predetermined volume of inhaled anesthetic 18 (preferably sevoflurane). The invention also provides a container 12. In particular, the container 12 defines two interiors 16 and is composed of a material containing one or more of the above materials, wherein the material is on the inner surface 14 of the container 12 and is a homogeneous property of the container 12 or a reference material The result of the inner surface 14 of one of the multilayer materials is as described above. The method includes the step of filling a predetermined volume of inhaled anesthetic 18 into an internal space defined by the container. It should be understood that the container 12 and its inner surface 14 can be composed of more than one of the above materials. -13- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 509568 A7

to make. In each specific example of the method of the present invention, the container 12 may define an opening 20 to provide the inner space 16 of the container η and the outer portion of the container 12: therefore. The specific examples of the present invention may further include the step of providing a cover material comprising the above-mentioned materials (cover 22). In the example, the cover M may include-or a variety of materials constituting the inner surface thereof. Make Wanfasang include an opening defined by the container 12 with a lid 22 <

Although the pharmaceutical products and methods of the present invention have been specifically discussed, those skilled in the art should understand that the present invention can be modified in various ways without departing from the disclosed invention and the claimed invention Spirit and scope. -14 ·

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Claims (1)

范围 、 Scope of patent application 1. An inhalation anesthetic product, comprising: a passenger vessel composed of a material selected from the group consisting of polyethylene terephthalate and polyethylene isophthalate; the passenger vessel is defined therein A constructed internal space, outside the patient's body and inhaled anesthetic; and a volume of sevoflurane contained in the internal space of the container. 2. If the inhaled anesthetic product according to item 1 of the patent application, wherein the container defines an opening therein, and the opening provides fluid transfer between the internal space defined by the container and the exterior of the container, the inhaled anesthetic product further includes a lid, The lid is constructed to seal an opening defined in the container, and the lid consists of a member selected from the group consisting of polypropylene; polyethylene; polyethylenate, polymethylpentene, ionic monomer resin, polyterephthalic acid. Material composition of ethylene glycol ester, polyethylene isophthalate, nano composite material and combination thereof. 3. If the inhaled anesthetic product according to item 1 of the patent application scope, wherein the container defines an opening therein, and the opening provides fluid transportation between the internal space defined by the container and the exterior of the container, the inhaled anesthetic product also includes an internal A surface cover configured to seal an opening defined in the container. The inner surface of the cover consists of a material selected from the group consisting of polypropylene; polyethylene; polyethylenate, polymethylpentene, and ionic monomers. Resin, polyethylene terephthalate, polyethylene isophthalate, nano composite materials and combinations of materials. — 4. An inhalation anesthetic product, comprising: a container defined within S, outside the patient's body, and a container for inhalation anesthesia, the container having an inner surface adjacent to the inner space, and the inner surface is comprised of It is selected from the group consisting of polyethylene terephthalate and polyisophthalic acid. 15- This paper is applicable to Chinese National Standard (CNS) A4 specifications (210 X 297 mm). Material composition; & as contained in this instrument-volume seven Qiqi. The inhalation anesthetic product of the patent No. 4 of the patent, wherein the opening of the container boundary ^ and the opening σ provides an internal space defined by the container and. Bu. 6. The fluid transport between the inhaled anesthetics is constructed to seal the opening defined in the container. The cap is made up of: = polyethylene; polyethylene terephthalate is called polyethylene terephthalate. Glycol vinegar, polyisoarsinic acid =, ionic early resin nano composite material and its material composition. ^ The inhaled anesthetic product according to item 4 of the patent application, wherein the container defines an opening therein with the opening. Provides the internal space defined by the container and the fluid transport between the outside of the container. The inhaled anesthetic product also includes an internal A surface cover configured to seal an opening defined in the container. The inner surface of the cover consists of a material selected from the group consisting of polypropylene; polyethylene; polyethylenate, polymethylpentene, and ionic monomers. Resin, poly (p-phenylene) 2-epoxyethylene glycol § said, I isobenzyl monocarboxylate, nano composite materials and combinations of materials. A method of storing an inhaled anesthetic in a patient's body, the method includes the steps of: providing a predetermined volume of sevoflurane; providing a capacity defining an internal space; the container is selected from the group consisting of And the material composition of polyethylene isophthalate: and fill the predetermined volume of sevoflurane in the interior defined by the weight container -16- 509568 8 8 8 8 A BCD . 8. A method of storing inhaled anesthetics outside the patient's body, the method comprising the steps of: providing a predetermined volume of sevoflurane; providing a container defining an internal space, the container having a space adjacent to the internal space defined by the container The inner wall of the container is composed of a material selected from the group consisting of polyethylene terephthalate and polyethylene isophthalate; and the predetermined volume of sevoflurane is filled in the container In the interior space. -17- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)