WO2004112778A1 - Preparation de cisplatine et procede de production de ladite preparation - Google Patents

Preparation de cisplatine et procede de production de ladite preparation Download PDF

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Publication number
WO2004112778A1
WO2004112778A1 PCT/JP2004/009066 JP2004009066W WO2004112778A1 WO 2004112778 A1 WO2004112778 A1 WO 2004112778A1 JP 2004009066 W JP2004009066 W JP 2004009066W WO 2004112778 A1 WO2004112778 A1 WO 2004112778A1
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WO
WIPO (PCT)
Prior art keywords
cisplatin
light
oxygen
shielding
plastic container
Prior art date
Application number
PCT/JP2004/009066
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English (en)
Japanese (ja)
Inventor
Fujio Inoue
Masamitsu Izumi
Hideshi Okamoto
Original Assignee
Otsuka Pharmaceutical Factory, Inc.
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 Otsuka Pharmaceutical Factory, Inc. filed Critical Otsuka Pharmaceutical Factory, Inc.
Publication of WO2004112778A1 publication Critical patent/WO2004112778A1/fr

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Classifications

    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/282—Platinum compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a cisplatin formulation and a method for producing the same.
  • cisplatin which is one of the anticancer drugs, is originally extremely unstable in aqueous solution and causes rapid decomposition of the complex. It is known that it is stable in a low pH range of about pH 2-3, that is, stable at high concentrations.
  • cisplatin aqueous solution JP-A-3-24017 which can be injected at pH 3.0-6.0 by addition of citrate, and stable cisplatin aqueous solution (pH of about 5.0-7.5) by adding a chloride ion source ( JP-A-3-21252) has also been reported.
  • aqueous cisplatin aqueous solutions were filled exclusively in glass vials as sealed containers to prevent decomposition and deactivation by light, oxygen, heat and the like.
  • the aqueous cisplatin solution contained in the sealed container is generally contained in a glass vial in the form of a high-concentration solution, and when used, a required amount is extracted from the container containing the aqueous cisplatin solution and added to, for example, a drip solution to dilute the solution. Prepared and administered.
  • glass containers have the drawback that they are easily broken, heavy and difficult to dispose of.
  • cisplatin and a liquid containing it may accidentally adhere to the skin of a worker (medical worker), or the worker may drop, splash, etc.
  • An object of the present invention is to provide a cis-bratin preparation which can stably contain cis-bratin and can prevent the inactivation of cis-bratin for a long period of time by eliminating all the drawbacks found in the prior art. It is in.
  • Another object of the present invention is to provide a cisplatin preparation having excellent storage stability as described above, which is easy to handle and has a risk of causing harmful effects, tissue damage, etc. to workers during handling. It is an object of the present invention to provide a cisplatin preparation which can be safely avoided.
  • the present inventors have conducted intensive studies in order to achieve the above object, and as a result, have found that a specific cisplatin injection solution is contained in a light-shielding oxygen-paria plastic container and the force of allowing oxygen to exist in the container. After storing in a container made of permeable oxygen-permeable plastic, further wrap it in a light-shielding wrapping material and allowing oxygen to exist in the wrapping material, or storing it in a non-light-shielding oxygen-barrier plastic container, and then using a light-shielding wrapping material It has been found that a new formulation product meeting the above objectives can be provided when packaging and the presence of oxygen in the container. The present invention has been completed as a result of further studies based on these findings.
  • the present invention provides the invention described in the following item 1.-18.
  • a cisplatin preparation comprising a cisplatin injection solution contained in a light-shielding plastic container, wherein the cisbratin injection solution is a pH 4.5-6.5 solution containing 0.45 w / v% or more of chlorine ion.
  • Item 2 The cisplatin preparation according to Item 1, wherein the light-shielding plastic container blocks light of 450 nm or less.
  • Item 3 The preparation according to Item 1, wherein the cisplatin injection solution is contained in a light-shielding plastic container in an amount of 100 to "! OOOmL.
  • a cisplatin preparation comprising a cisplatin injection solution contained in a light-shielding plastic container, wherein the cisbratin injection solution is a pH 4.5-6.5 solution containing 0.45 w / v% or more of chloride ions.
  • Item 5 The cisplatin formulation according to Item 4, wherein the light-shielding plastic container blocks light of 450 nm or less.
  • Item 6 The preparation according to Item 4, wherein the cisplatin injection solution is contained in a light-shielding plastic container in an amount of 100 to 1000 mL.
  • Item 7 A cisplatin preparation in which a non-light-shielding plastic container containing cisplatin injection solution is packaged with a light-shielding packaging material, wherein the cisplatin injection solution contains chloride ions.
  • a packaged cisplatin formulation A packaged cisplatin formulation.
  • Item 8 The packaged cisplatin preparation according to Item 7, wherein the light-shielding packaging material blocks light of 450 nm or less.
  • Item 9 The preparation according to Item 7, wherein the cisplatin injection solution is contained in a plastic container in an amount of 100 to 1000 mL.
  • a cisplatin preparation comprising a non-light-shielding plastic container containing a cisplatin injection solution and a light-shielding packaging material, wherein the cis-bratin injection solution has a pH of 4.5-6.5 containing 0.45 w / v% or more of chloride ions. Liquid, the plastic container has oxygen permeability, the light-shielding packaging material blocks light of 470 nm or less and has an oxygen barrier property, and oxygen is not contained in the packaging material.
  • An existing packaged cisplatin formulation comprising a non-light-shielding plastic container containing a cisplatin injection solution and a light-shielding packaging material, wherein the cis-bratin injection solution has a pH of 4.5-6.5 containing 0.45 w / v% or more of chloride ions. Liquid, the plastic container has oxygen permeability, the light-shielding packaging material blocks light of 470 nm or less and
  • Item 11 The wrapped cisplatin preparation according to Item 10, wherein the light-shielding packaging material blocks light of 450 nm or less.
  • Item 12 The packaged cisplatin formulation according to Item 10, wherein the oxygen is sterile oxygen or dust-free oxygen.
  • Item 13 The formulation according to Item 10, wherein the cisplatin injection solution is contained in a plastic container in an amount of 100 to 1000 mL.
  • Item 14 A cisplatin preparation in which a non-light-shielding plastic container containing the cisplatin injection solution is packaged with a light-shielding packaging material, wherein the cis-bratin injection solution has a pH of 4.5 to 6.5 containing 0.45 w / v% or more of chloride ions.
  • a liquid the plastic container has oxygen barrier properties, oxygen is present in the container, and the light-shielding packaging material blocks light of 470 nm or less.
  • Item 15 The packaged cisplatin preparation according to Item 14, wherein the light-shielding packaging material blocks light of 450 nm or less.
  • Item 16 The packaged cisplatin formulation according to Item 14, wherein the oxygen is sterile oxygen or dust-free oxygen.
  • Cisplatin injection solution is contained in a plastic container in a volume of 100 to 1000 mL.
  • Item 15 The preparation according to Item 14, wherein
  • Item 18 Preparing a cisplatin injection solution of pH 4.5-6.5 containing 0.45 w / v% or more of chloride ions, storing the injection solution in a non-light-shielded oxygen-permeable plastic container, and then allowing the container to air or A method for producing a packaged cisplatin formulation, wherein the package is packaged with a light-shielding packaging material that blocks light of 470 nm or less together with oxygen and has oxygen barrier properties.
  • the cisplatin preparation of the present invention is based on the adoption of the constitution described in each of the above items, and particularly, based on the fact that cisplatin injection solution is contained in a plastic container and oxygen is present in the container. Is easy to break and easy to use, and ensures that the risk of health care workers being exposed to cisplatin during the practical use of cisplatin preparations is avoided. Moreover, the cisplatin preparation of the present invention surprisingly prevents the inactivation of cisplatin, which is an active ingredient, by adopting the above constitution, and has an excellent stability that it can be stored for a long period of time. are doing.
  • the present invention also provides a method for producing such a cisbratin preparation product of the present invention, and also provides a method for stably storing a cisplatin injection solution and a method for safely using the cisbratin injection solution. .
  • the cisplatin injection solution contained in the plastic container is a solution containing a predetermined amount of chloride ion together with cisbratin as an active ingredient and having PH 4.5-6.5.
  • the solvent (diluent) constituting the injection solution can be appropriately selected from various solvents capable of dissolving or diluting cisplatin.
  • the concentration of cisbratin (concentration after diluting cisbratin with a diluent) in the c- cisbratin injection solution which can be exemplified by physiological saline or aqueous sodium chloride solution, is not particularly limited. mg / mL to around 1.0 mg / mL, preferably around 0.01 mg / mL to 0.2 mg / mL, more preferably around 0.01 mg / mL to
  • Chloride ions contained in the injection solution are supplied by sodium chloride when, for example, an aqueous solution of sodium chloride is used as the above-mentioned solvent, but compounds that give chloride ions are particularly limited to sodium chloride.
  • potassium chloride, calcium chloride, N-methyldalcamine hydrochloride, choline chloride and the like may be used. These are necessary Accordingly, the predetermined amount can be added to and mixed with the above-mentioned injection solution or a solvent for the preparation thereof.
  • the chloride ion concentration in the prepared injection solution is usually 0.45 w / v%
  • the chlorine concentration is calculated by converting the weight (g) of the compound that gives chlorine to 10 OmL of the solvent into the weight (g) of chloride ion (in C).
  • the use of cisplatin injection as described above generally provides the following advantages. In other words, when cisplatin is administered by injection, the dose per body surface area of the patient is calculated in advance, and this amount is usually administered after dilution with a relatively large volume of diluent. The reason is that cisplatin has side effects such as nephrotoxicity and must be diluted with a large amount of diluent to promote its excretion. Use of the cisplatin injection in the present invention is preferable in terms of excretion of cisplatin.
  • the cisplatin injection according to the present invention is also suitable for performing such low-dose chemotherapy.
  • the cisplatin injection solution further contains, for example, amino acids such as glycine and arginine, ninatrium hydrogen phosphate, sodium dihydrogen phosphate, hydrochloric acid, and water as pH adjusting components for adjusting the pH to 4.5 to 6.5.
  • An acid such as sodium oxide or an alkali may be appropriately added.
  • inorganic salts such as sodium lactate, sodium citrate and sodium salt, and saccharides such as mannitol can be added for osmotic pressure adjustment.
  • various additives known to be added and compounded in the field of antiseptics, such as glucose, can also be added.
  • the plastic container when the preparation of the present invention contains the cisplatin injection solution in a light-shielding plastic container (first invention), a light-shielding plastic that blocks light of 470 nm or less is used. Any container can be used. This container does not matter whether it is oxygen-permeable or oxygen-barrier.
  • the preparation of the present invention is a plastic container containing a cisplatin injection solution and further packaged with a light-shielding wrapping material (second invention), it may be non-light-shielding. It does not matter whether it is transient.
  • oxygen permeability the oxygen permeability coefficient, 0.005X l0- l 7 ⁇ 255X10- l 7 m 2 / Pa 'sec, preferably 0.5 X 10- 1 7 shall be used when the range of ⁇ 94 X 10- 1 7 m 2 / Pa ⁇ sec £
  • oxygen barrier property is have a oxygen permeability of less than the oxygen permeability coefficient Shall be used in such cases.
  • the oxygen permeability coefficient is measured by the following method. That is, after the inside of the plastic container to be measured is sufficiently purged with nitrogen and sealed, the container is allowed to stand still in a thermostat at a predetermined temperature (50) filled with air. After a certain period (two weeks), the gas in the container is removed. Collect the sample, analyze its gas composition by gas chromatography, and calculate the oxygen permeability coefficient of the container according to the following equation.
  • Oxygen permeability coefficient P (m 2 / Pa ⁇ sec) (XrXo) ⁇ V ⁇ I / [Xa ir -7 "(Xi 2 + Xo 2 ) / 2] ⁇ P. ⁇ A ⁇ t
  • V Container volume (m 3 )
  • A Container surface area (m 2 )
  • the plastic container of the present invention that is, the light-shielding plastic container of the first invention and the non-light-shielding plastic container of the second invention can both be manufactured according to a conventional method.
  • various non-light-shielding plastic containers are commercially available, and such various commercially available products can be used in the present invention.
  • plastic bags are preferred.
  • a bag produced by a method of forming a polyolefin film into a bag shape by sealing the periphery thereof in a conventional manner can be mentioned.
  • the film used here preferably has a thickness of usually about 150 to 450 m.
  • any of various plastic containers used in the medical field can be used in the present invention.
  • the container may be in the form of a plastic bottle or in the form of a plastic bag.
  • the material of the plastic container is not limited to polyolefin in a bag according to the above method, for example, polyethylene, ethylene-vinyl acetate copolymer, polypropylene, etc., and a polymer or a film thereof obtained by blending or laminating each of the above polymers at an appropriate ratio. And so on.
  • the material of the plastic bag is a heat-fusible thermoplastic polymer such as high-density, low-density or linear low-density polyethylene, polypropylene, ethylene-vinyl alcohol copolymer, and polystyrene. preferable.
  • the bag may be made of a multi-layer film in which a suitable resin layer is further formed on the outside of the polyolefin, for example, in addition to the polyolefin single-layer film and the laminate film.
  • a suitable resin layer is further formed on the outside of the polyolefin, for example, in addition to the polyolefin single-layer film and the laminate film.
  • the resin that forms an appropriate resin layer include polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polyacrylonitrile, polyamide (nylon), polycarbonate, polyfluoroethylene (Teflon), and cyclic resin. Olefin copolymer, polystyrene and the like. These resins are generally heat-fusible, so if they are used to form a multilayer film, they may be heat-sealed.
  • An example of a particularly preferred multilayer film suitable for a bag-shaped container obtained by heat-sealing is a multilayer film in which a polyolefin is disposed in the innermost layer.
  • the multilayer film include a three-layer film in which the inner and outer layers are polyethylene, an intermediate layer of polypropylene and polystyrene, and a three-layer film in which the inner and outer layers are polyolefins such as polyethylene and polypropylene, and the intermediate layer is a cyclic olefin copolymer. Films and the like can be mentioned.
  • the cyclic olefin copolymer a commercially available product such as ethylene / tetracyclododecene copolymer can be used.
  • the shape and size of the plastic container are not particularly limited and can be arbitrarily determined as long as the above-mentioned cisplatin injection solution can be accommodated therein.
  • the light-shielding plastic container is typically composed of the non-light-shielding plastic container described above.
  • the light-shielding plastic container is selected from those capable of cutting light of 470 nm or less, more preferably 450 nm or less. This light-shielding property can be determined according to a general method using a Hitachi spectrophotometer U-2810.
  • the volume of the cisplatin injection solution contained in the plastic container is generally in the range of about 50 mL to about 3 L, preferably in the range of about 100-1000 mL, and more preferably in the range of about 100-500 mL.
  • cisplatin injection is usually administered by instillation to a living body, and in consideration of this, it is preferable to adjust the pH to a value that does not cause too much pain to the living body at the time of administration.
  • the above cisplatin injection solution is used. It is desirable to adjust the pH to the range of 5.5-6.5.
  • the above cisplatin injection solution can be stored in a plastic container according to a conventional method. Specifically, a cisplatin injection solution adjusted to an appropriate pH is injected into a plastic container, and the container is sealed (sealed), whereby the cisplatin preparation product containing the cisplatin injection solution of the present invention in a plastic container is sealed. Can be prepared.
  • a cisplatin injection solution adjusted to an appropriate pH is injected into a plastic container, and the container is sealed (sealed), whereby the cisplatin preparation product containing the cisplatin injection solution of the present invention in a plastic container is sealed.
  • the cisplatin preparation product of the present invention when an oxygen-paria light-shielding plastic container is used as the plastic container, it is important that oxygen is present in the container.
  • the injection operation is performed in air or in the presence of oxygen, and the container is sealed so that a head space is provided in the container.
  • the air or oxygen used is particularly subjected to aseptic treatment, and is preferably subjected to Z or dust-free treatment.
  • the packaged cisplatin preparation according to the second invention of the present invention contains a cisplatin injection solution prepared in the same manner as described above in a non-light-shielding plastic container.
  • the container can be manufactured by packaging the container with a light-shielding packaging material.
  • the light-shielding packaging material to be used may be an oxygen-permeable or oxygen-barrier material as long as it has a light-shielding property.
  • the term "light-shielding property" used in the light-shielding packaging material refers to light having a wavelength of 470 nm or less, preferably 450 nm or less, as in the case of the light-shielding plastic container. Means to do.
  • the term “oxygen barrier property” used for light-shielding packaging materials means a property that does not substantially transmit oxygen.
  • the light-shielding packaging material having the oxygen-parity property various types of conventionally known materials may be used. Specifically, for example, an aluminum foil, a laminated film using an aluminum vapor-deposited film, and the like can be given.
  • the material of the light-shielding packaging material may be a combination of an aluminum material such as the above-mentioned aluminum foil or aluminum vapor-deposited film and an ethylene-vinyl alcohol copolymer.
  • a combination of a material having an oxygen barrier property, such as a silica-deposited film or an ethylene vinyl alcohol copolymer, and a light-shielding printing film used for a vitamin injection is also used as the light-shielding packaging material. be able to.
  • linear polyethylene is used as the innermost layer, and aluminum foil is dry-laminated on the outer layer, and polyethylene terephthalate is coated on the outer layer (outermost layer).
  • Thiickness of about 40 m or more can be exemplified.
  • the shape and size of the packaging material are not particularly limited on the premise that plastic containers can be accommodated and packaged. Generally, it is desirable that the size is about 1.2-3 times the capacity of the plastic container.
  • the packaging material may be provided with a perforation for forming a hanging hole at an upper portion so that when the cisplatin injection solution is used, the injection solution can be administered without removing the packaging material.
  • both the non-light-shielding plastic container and the light-shielding packaging material have oxygen permeability, it is not particularly necessary because air (oxygen) can freely flow into the container.
  • air oxygen
  • air or oxygen must be present inside it.
  • the container has oxygen barrier properties, it is in the container, and if the packaging material has oxygen barrier properties, it is in the packaging material. Presence of air or oxygen.
  • the injection operation is performed in the air or in the presence of oxygen.
  • a method of sealing so as to provide a head space in the container.
  • a method for causing air or oxygen to be present in the oxygen-paria packaging material specifically, a method in which a container is packaged in air or in the presence of oxygen can be mentioned.
  • the air or oxygen used is particularly subjected to aseptic treatment and / or dust-free treatment. These aseptic treatments and dust-free treatments can be carried out according to ordinary methods.
  • the intended packaged pharmaceutical product of the present invention can be obtained.
  • FIG. 1 A preferred embodiment of the packaged pharmaceutical product of the present invention utilizing a plastic bag is shown in the attached drawing (FIG. 1).
  • a plastic bag 2 in which a cisplatin injection solution 1 is sealed is packaged with a light-shielding packaging material 4 together with oxygen 3.
  • the packaging with the packaging material in the packaged cisplatin formulation product in a plastic container according to the second invention of the present invention for example, the above-mentioned method is described on the outside (front and back) of a plastic container.
  • a mode in which a light-shielding film using an aluminum material or the like is arranged and the peripheral portion of the film is heat-sealed with a container or bonded (bonded) with an appropriate adhesive is also included. That is, such a mode of covering with a light-shielding film is also included in the second invention of the present invention.
  • This embodiment includes not only an embodiment in which the entire plastic container is covered with a light-shielding film, but also an embodiment in which, for example, only the portion of the container containing the cisplatin injection solution is covered with a light-shielding film.
  • the second invention of the present invention includes an embodiment in which at least a part of such a container is covered with a light-shielding film.
  • a preferred specific example of an embodiment in which at least a part of the container is covered for example, in the case of a bag 2 having the form shown in FIG. 1, for example, the entire outer surface of the portion containing the cisplatin injection solution 1 or the portion thereof And the entire surface outside the portion including the port portion is covered.
  • the production of the cisplatin preparation in a plastic container of the present invention filling of the cisplatin injection solution into the container, sterilization, packaging with a packaging material, and the like are performed by a known ordinary method. For example, it can be carried out in the same manner as in known amino acid infusions in plastic containers.
  • FIG. 1 is a schematic diagram showing one embodiment of the packaged cisplatin preparation of the present invention, wherein 1 is a cisplatin injection solution, 2 is a non-light-shielding plastic bag, 3 is oxygen, and 4 is light-shielding packaging. The materials are indicated respectively.
  • FIG. 2 is a cross-sectional view of the plastic container (bag) used for the production of the packaged cisbratin preparation of the present invention shown in Examples 3 and 4, and the cross-section is shown in FIG. This corresponds to the cross section taken along line XX of the plastic bag 2.
  • 5 indicates an oxygen-permeable plastic film
  • 6 indicates a light-shielding film
  • 7 indicates air existing in a space interposed between the films.
  • FIG. 3 is a cross-sectional view showing one embodiment of the cisplatin preparation of the present invention shown in Example 6.
  • This cross section corresponds to the X-X line cross section of the oxygen-permeable plastic bag 2 shown in FIG. 1 as in FIG. 5 indicates an oxygen-permeable plastic film, and 6 indicates a light-shielding film.
  • the inner preparation is made of linear polyethylene (thickness: 50jtz). m), the second layer is aluminum foil (thickness: 15 m), and the outermost layer is polyethylene terephthalate (thickness: 50 m).
  • a packaged cisplatin formulation of the present invention was obtained.
  • the obtained preparation in a container was stored under the conditions of 40 "C and 75% RH for 6 months, and the appearance and pH of the liquid in the container were observed and measured with time (after 1, 3 and 6 months). .
  • the preparation in a container prepared as described above was prepared by using linear polyethylene (thickness: 50 m) for the innermost layer, aluminum foil (thickness: 15 m) for the second layer, and polyethylene terephthalate (thickness: 50 wm) for the outermost layer.
  • the packaged cisplatin formulation of the present invention was obtained by enclosing it in a layer made of a light-shielding aluminum laminate together with dust-free oxygen.
  • the obtained preparation (packaged product form) is stored under storage conditions of 60t :, 75% RH for 4 weeks, and over time (after 1, 2 and 4 weeks), the appearance and pH of the liquid in the container are measured as described above. Same as Example 1 was observed and measured. The results are shown in Table 2 below.
  • the innermost layer is linear polyethylene (thickness: 50 m)
  • the second layer is aluminum foil (thickness: 15 m)
  • the innermost layer is linear polyethylene (thickness: 50 wm), and the second layer is aluminum foil (thickness). : 15j m>, outermost layer of polyethylene terephthalate (thickness: 50 im)
  • the layered light-shielding aluminum laminate was heat-sealed and covered with a light-shielding film to obtain a packaged product-form cisplatin formulation in a plastic container of the present invention.
  • the preparation in a container prepared in this way is the innermost layer of linear polyethylene (thickness: 50 m), the second layer is aluminum foil (thickness: 15 m), and the outermost layer is polyethylene terephthalate (thickness: 50 m) Was sealed together with dust-free oxygen in a three-layer light-shielding aluminum laminate bag to obtain a packaged cisplatin preparation of the present invention.
  • the residual ratio (%) in the cisplatin content is defined as a relative value (%) with respect to the measured value of the cisplatin content in the sample at the start of the test (the measured value of the cisplatin content in the sample after storage for a predetermined time). And expressed as a percentage of the value divided by the reference value.
  • LLDPE Linear low density polyethylene
  • a 20 w / w% light-shielding pigment (manufactured by Toyo Ink Co., Ltd.) was kneaded into the resin to obtain a light-shielding resin, and was extruded to obtain a light-shielding film. lOOii m)). Two sheets of the obtained light-shielding film were stacked, and the periphery thereof was heat-sealed to prepare an oxygen-permeable plastic bag having light-shielding properties.
  • the light-shielding properties of this product were measured by Hitachi Spectrophotometer U-2810, and as a result, it was confirmed that the product blocked light of 470 nm or less.
  • the oxygen permeability coefficient of this compound was 50 X10- 1 7 m 2 / Pa ⁇ sec.
  • the cisplatin injection solution prepared in Example 1 was filtered and filtered through a 0.2-im membrane filter, and sealed, to obtain a cisplatin formulation in a plastic container.
  • the pH of the cisplatin injection solution in the container immediately after this production was 5.85.
  • the obtained cisplatin preparation in a container is stored under storage conditions of 40 and 75% RH for 6 months, and the appearance and pH of the liquid in the container are observed and measured over time (after 1, 3 and 6 months). As a result, the same results as those shown in Table 1 were obtained.

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Abstract

La présente invention se rapporte à des préparations de cisplatine comportant une solution pour injection de cisplatine contenue dans un contenant en plastique bloquant tout rayonnement lumineux. L'invention se rapporte à des préparations dans lesquelles la solution pour injection de cisplatine est une solution ayant un pH compris entre 4,5 et 6,5 et contenant des ions chlorure en quantité représentant au moins 0,45 % de la masse volumique, le contenant en plastique utilisé ayant une propriété de blocage du rayonnement lumineux telle que, par exemple, un rayonnement de longueur d'onde inférieur ou égal à 470 nm est bloqué tandis que ledit contenant est perméable à l'oxygène. L'invention se rapporte également à des préparations de cisplatine associées à un contenant en plastique ne bloquant pas le rayonnement lumineux, ladite solution pour injection de cisplatine étant présente dans ledit contenant qui est rempli d'un matériau de conditionnement bloquant le rayonnement lumineux. Ces préparations facilitent la manipulation, elles peuvent être utilisées en toute sécurité du fait qu'elles éloignent absolument tout danger de dégât tissulaire de la peau du personnel médical lors de la manipulation, et elles présentent une excellente stabilité au stockage, du fait d'une réduction de leur désactivation ou de leur détérioration.
PCT/JP2004/009066 2003-06-20 2004-06-21 Preparation de cisplatine et procede de production de ladite preparation WO2004112778A1 (fr)

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JP2003175911A JP2006342058A (ja) 2003-06-20 2003-06-20 プラスチック製容器入りシスプラチン製剤
JP2003-175911 2003-06-20

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006103691A1 (fr) * 2005-03-28 2006-10-05 Dabur Pharma Ltd. Préparations pharmaceutiques stables d’agents antitumoraux contenant du platine(ii)
EP1967188A1 (fr) * 2005-12-29 2008-09-10 Nipro Corporation Preparation pharmaceutique de solution aqueuse contenant un complexe de platine

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2022174863A (ja) * 2021-05-12 2022-11-25 ゼネラルパッカー株式会社 輸液バッグの酸素濃度測定方法および輸液バッグ

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0321252A (ja) * 1988-11-14 1991-01-30 Bristol Myers Squibb Co シスプラチン高張液

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0321252A (ja) * 1988-11-14 1991-01-30 Bristol Myers Squibb Co シスプラチン高張液

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KOHO FUMIHARU: "Shin plastic-sei vial (CZ Vial) no hyoka", MEDICINE AND DRUG JOURNAL, vol. 29, no. 6, June 1993 (1993-06-01), pages 1211 - 1214, XP002984974 *
ZIESKE P.A. ET AL.: "Characterization of cisplatin degradation as affected by pH and light", AM. J. HOSP. PHARM., vol. 48, no. 7, July 1991 (1991-07-01), pages 1500 - 1506, XP002984975 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006103691A1 (fr) * 2005-03-28 2006-10-05 Dabur Pharma Ltd. Préparations pharmaceutiques stables d’agents antitumoraux contenant du platine(ii)
EP1967188A1 (fr) * 2005-12-29 2008-09-10 Nipro Corporation Preparation pharmaceutique de solution aqueuse contenant un complexe de platine
EP1967188A4 (fr) * 2005-12-29 2009-11-04 Nipro Corp Preparation pharmaceutique de solution aqueuse contenant un complexe de platine
JP5157454B2 (ja) * 2005-12-29 2013-03-06 ニプロ株式会社 白金錯体を含有する水溶液医薬製剤

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