WO2011145660A1 - Composition d'émulsion d'huile dans l'eau contenant du propofol - Google Patents

Composition d'émulsion d'huile dans l'eau contenant du propofol Download PDF

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WO2011145660A1
WO2011145660A1 PCT/JP2011/061452 JP2011061452W WO2011145660A1 WO 2011145660 A1 WO2011145660 A1 WO 2011145660A1 JP 2011061452 W JP2011061452 W JP 2011061452W WO 2011145660 A1 WO2011145660 A1 WO 2011145660A1
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propofol
fatty acid
oil
emulsion composition
mass
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PCT/JP2011/061452
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English (en)
Japanese (ja)
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泰之 泉
幸三 永田
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富士フイルム株式会社
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Publication of WO2011145660A1 publication Critical patent/WO2011145660A1/fr

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    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives

Definitions

  • the present invention relates to a propofol-containing oil-in-water emulsion composition.
  • Propofol (chemical name 2,6-diisopropylphenol) is an oil-soluble drug that is almost insoluble in water, so it has been used as a fat emulsion in the form of an intravenous general anesthetic and recently an intravenous sedative. .
  • This fat emulsion has features such as rapid induction of anesthesia, rapid arousal, less nausea after awakening, and vomiting, and has been widely used in surgical operations. It is also used for purposes.
  • propofol fat emulsion has been reported to have many side effects such as strong vascular pain occurring frequently during intravenous injection (see British (Journal of Anaethsia, 1991, Vol.67, pp.281-284).
  • a method for relieving this vascular pain a method of intravenous injection after cooling to 4 ° C., a method of intravenous injection mixed with lidocaine hydrochloride or naphthostat mesylate, and a narcotic such as fentanyl are intravenously administered several minutes before administration.
  • Various methods are known including a method for performing such a method. However, even if these methods are used alone, there is no sufficient effect, and each method itself is complicated and lacks convenience.
  • the oily component used in the oil phase of the fat emulsion is changed from conventional soybean oil to a mixture of soybean oil and medium-chain fatty acid triglyceride in a mass ratio of 50:50, thereby reducing pain during injection. (See Anesth Analg 1997, Vol.85, pp.1399-1403).
  • WO 2004/052354 pamphlet discloses a propofol preparation for mixing a local anesthetic such as lidocaine at the time of use. It has been proposed to utilize specific phospholipids, phospholipid derivatives or fatty acids.
  • International Publication No. 2006/112276 pamphlet discloses a propofol-containing fat emulsion containing propofol, an oil component and an emulsifier in predetermined amounts to reduce vascular pain, and having an average particle size of emulsified particles of 180 nm or less. The propofol-containing fat emulsion is described as having excellent emulsion stability without containing an emulsion stabilizer or the like.
  • an object of the present invention is to provide a propofol-containing oil-in-water emulsion composition in which vascular pain at the time of injection is sufficiently reduced.
  • propofol-containing oil-in-water emulsion composition comprising propofol, an oily component containing 30% by mass or more of a medium-chain fatty acid triglyceride having an average number of carbon atoms in the fatty acid chain of 9.9 or less, water, and a surfactant. object.
  • [3] The propofol-containing oil-in-water emulsion composition according to [1] or [2], wherein the average carbon number of the fatty acid chain of the medium chain fatty acid triglyceride is 8.2 or less.
  • [4] The propofol-containing oil-in-water emulsion composition according to any one of [1] to [3], wherein the content of medium chain fatty acid triglyceride in the oil component is 45% by mass or more.
  • [5] The propofol-containing oil-in-water emulsion composition according to any one of [1] to [4], wherein the content of medium-chain fatty acid triglyceride in the oil component is 45% by mass to 55% by mass.
  • the propofol-containing oil-in-water emulsion composition of the present invention includes propofol, an oily component containing 30% by mass or more of a medium chain fatty acid triglyceride having an average number of carbon atoms of a fatty acid chain of 9.9 or less, water, and a surfactant. ,including.
  • propofol-containing oil-in-water that can sufficiently reduce vascular pain at the time of injection by containing 30% by mass or more of medium-chain fatty acid triglycerides having an average fatty acid chain carbon number of 9.9 or less in the oil component.
  • Type emulsion compositions can be provided.
  • the propofol-containing oil-in-water emulsion composition is sometimes simply referred to as “emulsion composition” or “composition”.
  • the term “process” is not limited to an independent process, and is included in this term if the intended action of this process is achieved even when it cannot be clearly distinguished from other processes. .
  • a numerical range indicated by using “to” indicates a range including the numerical values described before and after “to” as the minimum value and the maximum value, respectively.
  • “w / v%” used for the blending amount (concentration) of each component constituting the emulsion composition of the present invention is “the mass of each component (g) / the volume of the total composition 100 mL”. means.
  • Propofol is a general name for 2,6-diisopropylphenol, and as described in, for example, JP-A-2002-179562, a general anesthetic or a sedative is used in the pharmaceutical field. It is a known compound that can be used as such. The solubility of the compound in water is considerably lower when used at its effective dosage compared to other drugs with a similar effective dosage.
  • the propofol is generally present in an amount of 0.1 w / v% to 5 w / v% in the total emulsion composition.
  • the emulsion composition of the present invention contains a medium chain fatty acid triglyceride as an oil component.
  • the medium chain fatty acid triglyceride means an oil or fat having an average carbon number of fatty acid chains constituting the triglyceride contained in the medium chain fatty acid triglyceride of 12 or less.
  • fatty acid triglycerides having an average fatty acid chain carbon number of 9.9 or less are used as medium chain fatty acid triglycerides.
  • the average carbon number of the fatty acid in the medium-chain fatty acid triglyceride is the number of carbon atoms (for example, caprylic acid in the fatty acid chain constituting the triglyceride contained in the medium-chain fatty acid triglyceride). 8 if present, and 10) if capric acid, the weighted average by the composition ratio of the constituent fatty acids.
  • the average carbon number of the fatty acid chain of the medium-chain fatty acid triglyceride is preferably 8.8 or less, more preferably 8.6 or less, and even more preferably 8.2 or less. Preferably, it is 8.0 or less.
  • the medium fatty acid triglyceride used in the present invention is not particularly limited as long as the average carbon number of the constituent fatty acid chain is within the above-mentioned range, and examples thereof include fatty acids having 6 to 12 carbon atoms. .
  • These constituent fatty acids in the medium-chain fatty acid triglyceride may be saturated or unsaturated.
  • the medium chain fatty acid triglyceride is mainly composed of a triglyceride of a saturated fatty acid having 6 to 12 carbon atoms.
  • the medium-chain fatty acid triglyceride may be derived from natural vegetable oils or may be a synthetic fatty acid triglyceride. You may use these individually or in combination of 2 or more types.
  • the medium chain fatty acid triglyceride may be used alone if the average carbon number of the constituent fatty acid chain is within the above-mentioned range, and two or more kinds of medium chain fatty acids having different average carbon numbers of the constituent fatty acid chain may be used. It may be a mixture of triglycerides. When two or more kinds of medium chain fatty acid triglycerides are mixed, the average number of carbon atoms of the constituent fatty acids may be within the above-described range as a whole of the mixture of medium chain fatty acid triglycerides.
  • Examples of the medium chain fatty acid triglyceride that can be used in the present invention include those that meet the standard of “medium chain fatty acid triglyceride” of “Pharmaceutical Additives Standard 2003 (Pharmaceutical Daily)”.
  • As commercial products of medium-chain fatty acid triglycerides trade names: “COCONARD” (COCONARD TM , Kao), “ODO TM ” (Nisshin Oil Co., Ltd.), “Miglyol” (Myglyol TM , SASOL), or “Panasate” (Panasate TM , Nippon Oil & Fats Co., Ltd.).
  • cocoonades cocoonado RK, cocoonado MT, and the like
  • miglyol 810 and the like each correspond to a medium chain fatty acid triglyceride having an average fatty acid carbon number of 9.9 or less.
  • the medium chain fatty acid triglyceride in the present invention is contained in the oil component at 30% by mass or more based on the total mass of the oil component. If the medium-chain fatty acid triglyceride is less than 30% by mass, it cannot be said that the effect of alleviating vascular pain is sufficient, and the effect of the present invention cannot be obtained. From the viewpoint of the effect of alleviating vascular pain, the proportion of medium-chain fatty acid triglycerides in the oil component is preferably 45% by mass or more, more preferably 70% by mass or more, and further preferably 95% by mass or more. preferable. When mixing 2 or more types of medium chain fatty acid triglycerides, the total amount after mixing may be 30% by mass or more in the oil component.
  • the oil component in the emulsion composition is a mixture with other oil components such as a long chain fatty acid triglyceride (for example, soybean oil). It is preferable that In the case of such a mixture, the medium-chain fatty acid triglyceride is preferably 80% by mass or less, more preferably 45% by mass or more and 55% by mass or less of the oil component from the viewpoint of the stability of the emulsion composition. .
  • the emulsion composition may contain an oil component other than the medium chain fatty acid triglyceride without particular limitation as long as it is a pharmaceutically acceptable oil component.
  • the “oil component” broadly means a component that can constitute an oil phase in an oil-in-water emulsion composition.
  • oily components in the present invention include, for example, vegetable oils (that is, natural triglycerides), long-chain fatty acid triglycerides such as chemically synthesized triglycerides, or animal oils; mineral oils; synthetic oils; essential oils; ester oils, etc., or mixtures thereof Is mentioned.
  • the oily component in the present invention does not include propofol, a surfactant described later, and fatty acids and salts thereof.
  • the other oily component is preferably a long-chain fatty acid triglyceride from the viewpoint of use in injections.
  • the “long-chain fatty acid triglyceride” means an oil or fat having an average carbon number of fatty acid chains constituting the triglyceride to be contained is larger than 12.
  • the fatty acid constituting the fatty acid chain of the long-chain fatty acid triglyceride may be a saturated fatty acid or an unsaturated fatty acid.
  • long-chain fatty acid triglycerides include vegetable oils corresponding to natural triglycerides and chemically synthesized triglycerides.
  • soybean oil is a vegetable oil obtained from the seed of a plant belonging to the leguminous soybean genus, and can be obtained from the seed using a known extraction method or a known purification method. For example, those that meet the standards of “soybean oil” described in the Japanese Pharmacopoeia can be used.
  • soybean oils examples include “Japanese Pharmacopoeia Soybean Oil” (Kaneda), “Soybean Oil YM” (Nisshin Oilio), SR-SOYBEAN-LQ- (JP) (Croda Japan) .
  • Examples of chemically synthesized triglycerides include 2-linoleoyl-1,3-dioctanoylglycerol.
  • the long-chain fatty acid triglyceride when contained in the present emulsion composition, it can be less than 70% by mass, preferably 20% to 65% by mass, based on the total mass of the oil component. From the viewpoint of stability, specifically, it is particularly preferably 55% by mass or less, particularly more than 45% by mass and less than 55% by mass based on the total mass of the oil component.
  • the content of the long-chain fatty acid triglyceride is more than 44% by mass and less than 55% by mass with respect to the total mass of the oil component, and is combined with the medium chain fatty acid triglyceride of 45% to 55% by mass of the total mass of the oil component Is particularly preferable from the viewpoint of the stability of the emulsion composition.
  • oil components can be used alone or in combination of two or more.
  • each component used together does not need to be selected from the same group, such as vegetable oil, medium chain fatty acid triglyceride, animal oil, or mineral oil, but should select from a different group. Is possible.
  • the oil component is preferably 2 to 30 w / v%, more preferably 5 to 25 w / v%, based on the total volume of the emulsion composition. If it is 2 w / v% or more, a sufficient concentration of drug can be contained in the emulsion composition, and if it is 30 w / v% or less, the stability of the emulsion composition is not impaired, and each is preferable.
  • the emulsion composition of the present invention contains a surfactant to constitute an emulsion composition containing propofol.
  • a phospholipid can be included as a surfactant from the viewpoint of the stability of the emulsion composition.
  • Examples of the surfactant include phospholipids, and examples of phospholipids include lecithin, which is a natural phospholipid.
  • Examples of lecithin include egg yolk lecithin, egg yolk phosphatidylcholine, soybean lecithin, soybean phosphatidylcholine, hydrogenated egg yolk lecithin hydrogenated with them, hydrogenated egg yolk phosphatidylcholine, hydrogenated soybean lecithin or hydrogenated soybean phosphatidylcholine.
  • the surfactant may be a chemically synthesized phospholipid.
  • Examples of the chemically synthesized phospholipids include phosphatidylcholine (dipalmitoylphosphatidylcholine, dimyristoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoylphosphatidylcholine, etc.), phosphatidylglycerol (dipalmitoylphosphatidylglycerol, dimyristoylphosphatidylglycerol, distearoylphosphatidylglycerol, Dioleoyl phosphatidylglycerol), phosphatidylethanolamine (dipalmitoyl phosphatidylethanolamine, dimyristoyl phosphatidylethanolamine, distearoyl phosphatidylethanolamine, dioleoylphosphatidylethanolamine, etc.).
  • phosphatidylcholine dipalmitoylphosphatidylcholine, dimyristoylphosphatid
  • surfactants include pharmaceutically acceptable nonionic surfactants and pharmaceutically acceptable ionic surfactants.
  • examples of such other surfactants include, for example, poloxamer and pluronic surfactants, polycamines (tetronic surfactants), polyoxyethylene sorbitan esters, polyvinyl pyrrolidone, desoxycholic acids, gelatin , Polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, albumins, polyoxyethylene hydroxystearate (for example, SolutollutHS-15, BASF Japan Ltd.), and the like.
  • the surfactant in the present invention preferably contains a phospholipid from the viewpoint of biocompatibility.
  • lecithin such as egg yolk lecithin, egg yolk phosphatidylcholine, soybean lecithin or soybean phosphatidylcholine is more preferable, and egg yolk lecithin is particularly preferable.
  • the content of the surfactant is not particularly limited as long as the oil-in-water emulsion composition can be formed, but it is preferably 0.4 to 10 w / v% with respect to the total volume of the emulsion composition. 0.5 to 7 w / v% is more preferable, and 0.6 to 2 w / v% is particularly preferable. If it is 0.4 w / v% or more, the stability of the obtained emulsion composition is sufficient, and if it is 10 w / v% or less, there is almost no need to consider the influence at the time of administration to the administration subject.
  • the emulsion composition of the present invention can be prepared by a method known in the art (emulsification dispersion method). For example, it is possible to use a method of emulsifying (precise emulsifying) a crude emulsion obtained by mixing an aqueous phase and crude oil and roughly emulsifying the mixture using a suitable high-pressure emulsifier. The rough emulsification is more specifically described in, for example, T.K. K. Using a homomixer such as a homomixer, it can be carried out usually at 5000 rpm / min for 5 minutes or more. An ultrasonic homogenizer can also be used.
  • emulsification dispersion method for example, it is possible to use a method of emulsifying (precise emulsifying) a crude emulsion obtained by mixing an aqueous phase and crude oil and roughly emulsifying the mixture using a suitable high-pressure emulsifier.
  • the fine emulsification can be performed using a high-pressure homogenizer, an ultrasonic homogenizer, or the like.
  • a high-pressure homogenizer it can be carried out generally by passing it about 1 to 50 times, preferably about 1 to 20 times under a pressure condition of about 200 kg / cm 2 or more.
  • These mixing and emulsifying operations may be performed at room temperature, or may be performed by employing a slight heating operation (usually about 40 to 80 ° C.).
  • a stabilizer for improving emulsification stability may be further added separately from the surfactant described above.
  • examples of such stabilizers include fatty acids and salts thereof, and these can be used alone or in combination of two or more.
  • fatty acids preferably used in the present invention include fatty acids having 12 to 18 carbon atoms, such as lauric acid, myristic acid, palmitic acid, oleic acid, stearic acid, isostearic acid, and linoleic acid. , ⁇ -linolenic acid, ⁇ -linolenic acid and the like.
  • fatty acid salts include salts with metals such as sodium and potassium, salts with basic amino acids such as L-arginine, L-histidine and L-lysine, and salts with alkanolamines such as triethanolamine. Etc.
  • the type of salt is appropriately selected depending on the type of fatty acid used and the like, but a metal such as sodium is preferable from the viewpoints of solubility and dispersion stability.
  • the content of the stabilizer in the emulsion composition is not particularly limited, but from the viewpoint of the stability of the emulsion composition, it is 0.01 w / v% to 0.1 w / v% with respect to the volume of the emulsion composition. It is preferably 0.02 w / v% to 0.09 w / v%.
  • the emulsion composition of the present invention may further be added with appropriate amounts of various additives known to be added and blended into this type of emulsion composition, if desired.
  • various additives known to be added and blended into this type of emulsion composition, if desired. it can.
  • the additive include an antioxidant, an antibacterial agent, a pH adjuster, and an isotonic agent.
  • antioxidant examples include sodium metabisulfite (also acting as an antibacterial agent), sodium sulfite, sodium bisulfite, potassium metabisulfite, potassium sulfite, sodium thiosulfate and the like.
  • antibacterial agent examples include sodium caprylate, methyl benzoate, sodium metabisulfite (also acting as an antioxidant), sodium edetate, and the like.
  • pH adjuster hydrochloric acid, acetic acid, lactic acid, malic acid, citric acid, sodium hydroxide and the like can be used.
  • tonicity agents include glycerin; sugars such as glucose, fructose, and maltose; sugar alcohols such as sorbitol and xylitol; salts such as sodium chloride and magnesium chloride.
  • the oil-soluble substance can be used by being mixed in advance with an oil-based component constituting the emulsion composition.
  • the water-soluble substance can be mixed with water for injection or added and blended in the aqueous phase of the resulting emulsion.
  • this emulsion composition can be made into a product by filtering and sterilizing according to a conventional method.
  • a filtration method for example, a known method using a membrane filter may be applied, and as a sterilization method, for example, high pressure steam sterilization (for example, 121 ° C., 12 minutes), hot water immersion sterilization, shower sterilization, and the like are known. The method described above may be applied.
  • the pH of the emulsion composition can usually be pH 5.0 to 9.0, preferably pH 6.0 to 8.0.
  • the vascular pain alleviation effect at the time of injection of this emulsion composition can be evaluated by, for example, the propofol concentration in the aqueous phase. That is, it is known that there is a correlation between the concentration of free propofol present in the aqueous phase and the incidence of vascular pain, and a mixture of soybean oil and medium-chain fatty acid triglycerides in a mass ratio of 50:50 was used as the oil phase. It has been reported that the factor that reduces vascular pain in fat emulsions is thought to be a decrease in the concentration of free propofol present in the aqueous phase. (Propofol Archives No.6, http://www.maruishi-pharm.co.jp/med/masuika/propo1/index.php).
  • the fatty acid composition was measured by the following method for Coconut RK, Coconut ML (above, Kao) or Miglyol 810 (Sasol), which are medium chain fatty acid triglycerides. 0.030 g of a sample was collected, 1.5 mL of a 0.5 mol / L sodium hydroxide methanol solution was added, and saponification was performed by heating at 100 ° C. for 9 minutes. Methyl esterification was performed by adding 2.0 mL of boron trifluoride methanol complex methanol solution and heating at 100 ° C. for 7 minutes.
  • Purified egg yolk lecithin was added to the oil phase and mixed, then the aqueous phase was added, and the mixture was coarsely emulsified by applying ultrasonic waves for 4 minutes with an ultrasonic homogenizer (US-600T, Nippon Seiki Seisakusho). This was passed once under the condition of 245 MPa using a high-pressure emulsifier (Starburst Minilab Machine, Sugino Machine Co.). This was autoclaved using an autoclave (Autoclave SP200, Yamato Scientific Co., Ltd.) to prepare an emulsion composition.
  • an autoclave Autoclave SP200, Yamato Scientific Co., Ltd.
  • Measurement method B Using a dialysis device (RED Device, Thermo Fisher Scientific), 0.5 mL of each measurement target emulsion composition (sample) and an aqueous glycerin solution (the same glycerin concentration as the glycerin concentration of each measurement target emulsion composition) 0.3 mL was brought into contact with the dialysis membrane. In this state, after shaking at 25 ° C.
  • the trends in the aqueous phase propofol concentration were the same between the measurement method A and the measurement method B, although the measurement values were different.
  • the medium chain fatty acid triglyceride having a fatty acid chain having an average carbon number of 9.9 or less is contained in an oil component in an amount of 30% by mass or more, the fatty acid chain having an average carbon number of 10.0 or more
  • Comparative Example 1 containing medium chain fatty acid triglyceride having a ratio of 25% by mass in the oil component of medium chain fatty acid triglyceride the aqueous phase propofol concentration could be reduced.
  • the aqueous phase propofol concentration of the emulsion compositions of Examples 1 to 4 was lower than the aqueous phase propofol concentration of Comparative Example 3. Comparing the aqueous phase propofol concentration measured by the measuring method A with the aqueous phase propofol concentration measured by the measuring method B for the sample having a mass ratio of 50% in the oil component of the medium chain fatty acid triglyceride, the value of the measuring method A is It was 87% to 91% of the value of the measuring method B, and averaged 89%. From this, a value corresponding to the measuring method A of Comparative Example 3 is estimated to be about 11.6.
  • the average carbon number of the fatty acid chain in the medium-chain fatty acid triglyceride is 9.9 or less, and such medium-chain fatty acid triglyceride is 30% by mass or more in the oil component.
  • the containing emulsion composition can reduce the aqueous phase propofol concentration. Therefore, according to this invention, the vascular pain of the propofol containing oil-in-water emulsion composition can be relieved compared with a prior art.

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Abstract

La présente invention concerne une composition d'émulsion d'huile dans l'eau contenant du propofol qui contient : du propofol ; un composant huileux qui contient au moins 30 % en masse de triglycérides à chaîne moyenne, dont les chaînes d'acide gras ont un nombre de carbone moyen de 9,9 ou moins ; de l'eau ; et un tensioactif.
PCT/JP2011/061452 2010-05-21 2011-05-18 Composition d'émulsion d'huile dans l'eau contenant du propofol WO2011145660A1 (fr)

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JP2010150324A JP5591603B2 (ja) 2010-05-21 2010-06-30 プロポフォール含有水中油型エマルション組成物

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015132985A1 (fr) * 2014-03-03 2015-09-11 丸石製薬株式会社 Composition d'émulsion contenant du sévoflurane
CN107823138A (zh) * 2017-12-14 2018-03-23 广州白云山汉方现代药业有限公司 一种脂肪酸甘油三酯乳剂及其制备方法
WO2020017578A1 (fr) * 2018-07-18 2020-01-23 テクノガード株式会社 Agent d'injection contenant un médicament à base d'oxycam

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002523356A (ja) * 1998-08-19 2002-07-30 アールティーピー・ファーマ・インコーポレーテッド プロポフォールの注射可能水性分散物
JP2003535884A (ja) * 2000-06-16 2003-12-02 スカイファーマ・カナダ・インコーポレーテッド プロポフォールの改善された注射可能な分散物
WO2004052354A1 (fr) * 2002-12-06 2004-06-24 Otsuka Pharmaceutical Factory, Inc. Emulsions grasses contenant du propofol
WO2006112276A1 (fr) * 2005-04-13 2006-10-26 Otsuka Pharmaceutical Factory, Inc. Emulsion grasse contenant du propofol

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0662771A (ja) * 1992-08-20 1994-03-08 Nippon Oil & Fats Co Ltd 中鎖脂肪含有豆腐様食品

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002523356A (ja) * 1998-08-19 2002-07-30 アールティーピー・ファーマ・インコーポレーテッド プロポフォールの注射可能水性分散物
JP2003535884A (ja) * 2000-06-16 2003-12-02 スカイファーマ・カナダ・インコーポレーテッド プロポフォールの改善された注射可能な分散物
WO2004052354A1 (fr) * 2002-12-06 2004-06-24 Otsuka Pharmaceutical Factory, Inc. Emulsions grasses contenant du propofol
WO2006112276A1 (fr) * 2005-04-13 2006-10-26 Otsuka Pharmaceutical Factory, Inc. Emulsion grasse contenant du propofol

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015132985A1 (fr) * 2014-03-03 2015-09-11 丸石製薬株式会社 Composition d'émulsion contenant du sévoflurane
CN107823138A (zh) * 2017-12-14 2018-03-23 广州白云山汉方现代药业有限公司 一种脂肪酸甘油三酯乳剂及其制备方法
WO2020017578A1 (fr) * 2018-07-18 2020-01-23 テクノガード株式会社 Agent d'injection contenant un médicament à base d'oxycam

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