WO2010038656A1 - Agent prophylactique et thérapeutique pour la septicémie - Google Patents

Agent prophylactique et thérapeutique pour la septicémie Download PDF

Info

Publication number
WO2010038656A1
WO2010038656A1 PCT/JP2009/066593 JP2009066593W WO2010038656A1 WO 2010038656 A1 WO2010038656 A1 WO 2010038656A1 JP 2009066593 W JP2009066593 W JP 2009066593W WO 2010038656 A1 WO2010038656 A1 WO 2010038656A1
Authority
WO
WIPO (PCT)
Prior art keywords
glucopyranosyl
sepsis
group
cyclo
glucose
Prior art date
Application number
PCT/JP2009/066593
Other languages
English (en)
Japanese (ja)
Inventor
益浩 西村
直応 澁谷
公雄 吉柳
徹也 福永
雅子 土居
望 田村
光 渡邊
朗子 山本
友之 西本
Original Assignee
株式会社林原生物化学研究所
株式会社大塚製薬工場
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 株式会社林原生物化学研究所, 株式会社大塚製薬工場 filed Critical 株式会社林原生物化学研究所
Publication of WO2010038656A1 publication Critical patent/WO2010038656A1/fr

Links

Classifications

    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
    • C07H3/06—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages

Definitions

  • the present invention relates to a preventive and therapeutic agent for sepsis and its use.
  • Sepsis is caused by bacterial infections such as pneumonia and peritonitis, and bacterial infections caused when the immune system is reduced by chemotherapy for malignant tumors.
  • bacterial infections such as pneumonia and peritonitis
  • bacterial infections caused when the immune system is reduced by chemotherapy for malignant tumors.
  • Symptoms such as fever, tachypnea, tachycardia, and leukocytosis appear, and if progressed, circulatory failure such as impaired consciousness and blood pressure decrease, and organ dysfunction such as renal / lung / liver / coagulation dysfunction. If severe, it leads to acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation syndrome (DIC), etc., leading to the worst results such as cardiac arrest and death due to septic shock.
  • ARDS acute respiratory distress syndrome
  • DIC disseminated intravascular coagulation syndrome
  • Treatment methods for sepsis include fluid resuscitation, antibiotics intended to suppress lipopolysaccharide (LPS) production, and nonsteroidal anti-inflammatory drugs that suppress inflammatory reactions.
  • LPS lipopolysaccharide
  • nonsteroidal anti-inflammatory drugs that suppress inflammatory reactions.
  • administration of vasopressors that improve hypotension, steroids that suppress inflammation, blood coagulation inhibitors, and the like are performed in clinical settings.
  • Xigris (Digris Drotrecogin alfa, activated: Eli Lilly, USA), which is known as a therapeutic agent for sepsis, is an active protein C preparation and has an effect of suppressing cell apoptosis as well as an effect of inhibiting blood coagulation. It is ineffective for patients with sepsis and is restricted to use only for patients with severe sepsis.
  • cyclic oligosaccharides mainly used as food additives include ⁇ -, ⁇ - and ⁇ - ⁇ cyclodextrins in which 6 to 8 molecules of glucose are linked by ⁇ -1,4 bonds to form a cyclic structure. It has been known. There is a report that these ⁇ -cyclodextrin, ⁇ -cyclodextrin and ⁇ -cyclodextrin have an effect on sepsis (see Patent Document 1 below). However, ⁇ - and ⁇ -cyclodextrins have a problem of hemolysis (see Non-Patent Document 1 and Non-Patent Document 2 below), and ⁇ -cyclodextrin has nephrotoxicity.
  • ⁇ -cyclodextrin, ⁇ -cyclodextrin and ⁇ -cyclodextrin cannot be said to sufficiently satisfy the demand as a therapeutic agent for sepsis.
  • the present invention has been made in view of the above-described problems of the prior art, and its main purpose is to provide a preventive and therapeutic agent for sepsis that has a sufficient therapeutic effect on sepsis and has no side effects. It is to be.
  • the present inventor has intensively studied to achieve the above-mentioned purpose.
  • cyclic tetrasaccharides composed of glucose, cyclic pentasaccharide and derivatives thereof which have not been used as a therapeutic agent for sepsis, have a sufficiently strong effect on sepsis from an early stage, Furthermore, it has been found that there are almost no side effects such as hemolysis and nephrotoxicity, and the present invention has been completed here.
  • a prophylactic and therapeutic agent for sepsis comprising as an active ingredient at least one component selected from the group consisting of a cyclic tetrasaccharide having glucose as a constituent sugar, a cyclic pentasaccharide having glucose as a constituent sugar, and derivatives thereof.
  • Item 2. The preventive and therapeutic agent for sepsis according to Item 1, which is an injectable aqueous preparation or a solid agent for dissolution upon use. 4).
  • Item 4. The prophylactic and therapeutic agent for sepsis according to Item 3, which is used for intravenous administration. 5).
  • a prophylactic and therapeutic agent for sepsis containing at least one component selected from the group consisting of a cyclic tetrasaccharide having glucose as a constituent sugar, a cyclic pentasaccharide having glucose as a constituent sugar, and derivatives thereof; Methods for preventing and treating sepsis. 8).
  • the sepsis preventive and therapeutic agent of the present invention contains, as an active ingredient, at least one selected from the group consisting of a cyclic tetrasaccharide having glucose as a constituent sugar, a cyclic pentasaccharide having glucose as a constituent sugar, and derivatives thereof. .
  • a cyclic tetrasaccharide having glucose as a constituent sugar is a compound in which four glucoses are linked to form a ring
  • a cyclic pentasaccharide having glucose as a constituent sugar is a compound in which five glucoses are connected in a ring. is there.
  • CNN is a compound found by Gregory El Cote et al. (European Journal of Biochemistry, 226, 641 (1994)), and then Hayashibara Biochemical Research Institute Co., Ltd. As a result, a mass production method from starch was realized. CNN itself exhibits high solubility (dissolves 46.1 g in 100 g water at 20 ° C.), low sweetness (27% sweetness of sugar), and good pH stability and heat stability. As for the use of CNN, there are reports that some medical uses are expected, but the prevention and treatment effects of sepsis are not known at all.
  • CMM is a compound found by Hayashibara Biochemical Laboratories Co., Ltd. and described in JP-A-2005-95148.
  • CMM like CNN, is a compound that exhibits high solubility and stability, and its use is currently under investigation, but there is no report on the prevention and treatment effects of sepsis.
  • ICG5 a cyclic pentasaccharide, is a compound found by Hayashibara Biochemical Laboratories Co., Ltd. and is described in WO2006 / 35725. ICG5 is a compound that has almost no sweetness and exhibits high solubility and stability, and its use is currently under investigation, but there is no report on the effect of preventing and treating sepsis.
  • cyclic tetrasaccharide and cyclic pentasaccharide can also be used as derivatives in which hydrogen atoms of one or more hydroxyl groups in the glucose residues constituting these cyclic sugars are substituted with various substituents.
  • a derivative is not particularly limited, and a derivative having an arbitrary substituent can be used. Examples thereof include acylated derivatives; etherified derivatives; sulfur-containing derivatives;
  • acylated derivative a lower alkanoyl group having an alkyl group having about 1 to 6 carbon atoms such as an acetylated derivative, a propionylated derivative, a butyrylated derivative, a pentanoylated derivative, a hexanoylated derivative, a heptanoylated derivative, etc.
  • etherified derivatives include lower alkyl ether derivatives having about 1 to 6 carbon atoms such as methyl ether, ethyl ether, propyl ether, butyl ether, pentyl ether, hexyl ether and the like.
  • Examples of sulfur-containing derivatives include sulfonated derivatives.
  • Examples of carbohydrate derivatives include those in which sugars such as glucose are ether-bonded to form a branched chain.
  • carbohydrate derivatives of CNN are described in WO2002 / 72594, and carbohydrate derivatives of CMM are This is described in JP-A-2007-84462.
  • cyclic tetrasaccharide cyclic pentasaccharide and derivatives thereof can be used singly or in combination of two or more.
  • the agent for preventing and treating sepsis according to the present invention can be made into various preparation forms containing the above-mentioned active ingredients.
  • a liquid agent in particular an aqueous preparation for injection
  • a suitable example a liquid agent
  • the aqueous medium in the injectable aqueous preparation include water or a medium containing water.
  • water sterilized water, preferably sterilized water that does not contain a pyrogen, is usually used.
  • the medium containing water may be a known solvent used in pharmaceutical preparations, and examples thereof include physiological saline, PBS (phosphate buffered physiological saline), and lactic acid-containing Ringer's solution.
  • additives usually used in the art can be appropriately used.
  • additives include isotonic agents, buffering agents, soothing agents, and the like.
  • isotonic agent include sugars such as glucose, sorbitol and mannitol, sodium chloride, glycerin, propylene glycol, polyethylene glycol and the like.
  • buffer include borate buffer, phosphate buffer, citrate buffer, tartaric acid buffer, and acetate buffer.
  • soothing agents include polyhydric alcohols such as albumin, glycerin and propylene glycol, lidocaine hydrochloride, benzyl alcohol and the like.
  • the agent for preventing and treating sepsis of the present invention may contain various pH adjusters that are usually used in the art in order to adjust the pH.
  • the pH adjuster may be an acid or a base.
  • the acids include ascorbic acid, hydrochloric acid, gluconic acid, acetic acid, lactic acid, boric acid, phosphoric acid, sulfuric acid, tartaric acid, and citric acid.
  • the base include potassium hydroxide, calcium hydroxide, sodium hydroxide, magnesium hydroxide, monoethanolamine, diethanolamine, triethanolamine and the like.
  • amino acids such as glycine, histidine, and ⁇ -aminocaproic acid can be used.
  • the aqueous injection preparation of the present invention can be produced by a conventional method.
  • a component contained in the injectable aqueous preparation according to the present invention (hereinafter referred to as a contained component) is dissolved in an aqueous medium.
  • the order of mixing the components is not particularly limited. All the components may be mixed at the same time, or only some of the components may be dissolved in the aqueous medium first, and then the remaining components may be dissolved. Good.
  • the total concentration of active ingredients in the injectable aqueous preparation of the present invention that is, the total concentration of cyclic tetrasaccharide, cyclic pentasaccharide, and derivatives thereof is, for example, 0.1 to 70 W / V% (mass / volume%) Degree.
  • the obtained solution is usually subjected to sterilization such as filtration sterilization using a membrane filter, autoclaved autoclaving, heat sterilization such as intermittent sterilization.
  • sterilization such as filtration sterilization using a membrane filter, autoclaved autoclaving, heat sterilization such as intermittent sterilization.
  • the solution thus obtained preferably has a pH of about 6-8.
  • the obtained aqueous preparation is sealed after filling in a container such as an infusion bag or ampoule.
  • a commonly used additive may be used as necessary, and it may be processed into a solid agent that is dissolved and used in an aqueous medium, that is, a “solid agent for use when dissolved”.
  • solid preparation for use at the time of use can be prepared, for example, by drying the above-mentioned aqueous preparation for injection in a solution state by a known drying method such as freeze-drying or drying under reduced pressure to form a powder or granules.
  • the solid preparation includes, for example, sterilized water; physiological saline; infusion containing electrolytes, sugars, amino acids, vitamins, trace elements, and the like.
  • the total concentration of the active ingredient of the present invention is, for example, 0.1 to 70 W / It can be dissolved at the time of use so as to be about V% (mass / volume%).
  • the aqueous preparation for injection according to the present invention is filled with the above-described solid solution for use in one room of a multi-chamber container and sterilized water in another room; physiological saline; electrolyte, carbohydrate, amino acid, vitamin, trace element
  • the preparation may be in the form of being filled with an infusion solution containing, etc. and mixed and dissolved before use.
  • Administration Method There are no particular limitations on the administration method of the prophylactic and therapeutic agent for sepsis according to the present invention, and administration is performed according to the dosage form, patient age, sex, other conditions, disease severity, and the like.
  • the dose varies depending on the patient's symptoms, age, etc., but it is desirable to administer the amount of the active ingredient in the range of usually about 0.001 to 1 g, preferably about 0.01 to 0.8 g per kg body weight per day.
  • an administration method for example, in the case of an aqueous preparation for injection, it is administered alone, intravenously, intraarterially, intramuscularly, intradermally, subcutaneously, intrathecally, intraperitoneally, or the like.
  • the injectable aqueous preparation can be mixed with an infusion solution, and can be administered intravenously as a mixture of the injectable aqueous preparation and the infusion solution according to the present invention.
  • the infusion to be mixed with the injectable aqueous preparation is not particularly limited, and generally commercially available or normal infusion is used.
  • infusion examples include glucose injection, xylitol injection, D-mannitol injection, fructose injection, physiological saline, dextran 40 injection, dextran 70 injection, amino acid injection, Ringer's solution, lactated Ringer's solution Sugar, electrolytes, amino acids, and general vitamin solutions.
  • sepsis preventive and therapeutic agent of the present invention sepsis can be prevented and treated without causing side effects such as hemolysis.
  • the active ingredient has a short half-life, it can be administered to patients with rapidly-advanced sepsis as needed to avoid unnecessary exposure to the drug and prevent the transition to severe sepsis. Can do.
  • Example 1 50 g of CNN (produced by Hayashibara Biochemical Laboratories), which is a cyclic tetrasaccharide composed of glucose, is injected with 0.1 g of calcium chloride, 0.15 g of potassium chloride, 3.0 g of sodium chloride and 1.55 g of sodium lactate. It melt
  • CNN produced by Hayashibara Biochemical Laboratories
  • Example 2 10 g of CNN (manufactured by Hayashibara Biochemical Laboratories) was dissolved in 100 mL of PBS (phosphate buffered saline). After aseptic filtration, it was dried by freeze-drying to form a powder, which was filled in 1-g glass vials, sealed, dissolved at the time of use, and used as an injection for prevention and treatment of sepsis.
  • PBS phosphate buffered saline
  • Example 3 10 g of CNN (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.) was dissolved in 100 mL of water for injection, and this was sterilized by filtration and then dried by lyophilization to obtain a powder. This was pre-filled with 100 mL of physiological saline in the lower chamber and filled into the upper chamber of a plastic multi-chamber container sterilized by autoclaving according to a conventional method to prepare a sepsis prevention and treatment agent kit product.
  • CNN manufactured by Hayashibara Biochemical Laboratories Co., Ltd.
  • Example 4 5 g of CNN (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.) was dissolved in 50 mL of water for injection, and this was sterilized by filtration and then lyophilized to a powder. This product is filled with 300 mL of amino acid infusion in the upper chamber and 600 mL of sugar / electrolyte in the lower chamber and filled into a small chamber of a plastic multi-chamber container sterilized by high-pressure steam according to a conventional method. It was.
  • Example 5 Injection of 5 g of CMM (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.), a cyclic tetrasaccharide composed of glucose, 0.02 g of calcium chloride, 0.03 g of potassium chloride, 0.6 g of sodium chloride and 0.31 g of sodium lactate It melt
  • CMM manufactured by Hayashibara Biochemical Laboratories Co., Ltd.
  • Example 6 5 g of CMM (produced by Hayashibara Biochemical Laboratories Co., Ltd.) was dissolved in 100 mL of PBS (phosphate buffered saline). After aseptic filtration, it was dried by freeze-drying to form a powder, which was filled in 1-g glass vials, sealed, dissolved at the time of use, and used as an injection for prevention and treatment of sepsis.
  • PBS phosphate buffered saline
  • Example 7 2 g of CMM (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.) was dissolved in 100 mL of water for injection, and this was sterilized by filtration and dried by lyophilization to obtain a powder. This was prefilled in the lower chamber with 100 mL of physiological saline and filled into the upper chamber of a plastic multi-chamber container that was autoclaved in accordance with a conventional method to obtain a kit product for preventing and treating sepsis.
  • CMM manufactured by Hayashibara Biochemical Laboratories Co., Ltd.
  • Example 8 1 g of CMM (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.) was dissolved in 50 mL of water for injection, and this was sterilized by filtration and dried by lyophilization to obtain a powder.
  • This product is filled with 300 mL of amino acid infusion in the upper chamber and 600 mL of sugar / electrolyte in the lower chamber and filled into a small chamber of a plastic multi-chamber container sterilized by high-pressure steam according to a conventional method. It was.
  • Example 9 Injection of 10 g of ICG5 (produced by Hayashibara Biochemical Laboratories Co., Ltd.), a cyclic pentasaccharide containing glucose as a constituent sugar, 0.02 g of calcium chloride, 0.03 g of potassium chloride, 0.6 g of sodium chloride and 0.31 g of sodium lactate It melt
  • Example 10 ICG5 (produced by Hayashibara Biochemical Laboratories Co., Ltd.) 30 g, calcium chloride 0.01 g, potassium chloride 0.015 g, sodium chloride 0.3 g and sodium lactate 0.155 g were dissolved in 30 mL of water for injection, and water for injection was added. The total volume was 50 mL. This was sterilized by filtration to produce an injection solution.
  • Example 11 25 g of ICG5 (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.) was dissolved in 100 mL of water for injection, and this was sterilized by filtration and then lyophilized to a powder. This was prefilled in the lower chamber with 100 mL of physiological saline and filled into the upper chamber of a plastic multi-chamber container that was autoclaved in accordance with a conventional method to obtain a kit product for preventing and treating sepsis.
  • ICG5 manufactured by Hayashibara Biochemical Laboratories Co., Ltd.
  • Example 12 5 g of ICG5 (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.) was dissolved in 50 mL of water for injection, and this was sterilized by filtration and dried by lyophilization to obtain a powder.
  • This product is filled with 300 mL of amino acid infusion in the upper chamber and 600 mL of sugar / electrolyte in the lower chamber and filled into a small chamber of a plastic multi-chamber container sterilized by high-pressure steam according to a conventional method. It was.
  • Example 13 5 g of CNN (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.) and 5 g of ICG5 (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.) were dissolved in 50 mL of water for injection. .
  • This product is filled with 300 mL of amino acid infusion in the upper chamber and 600 mL of sugar / electrolyte in the lower chamber and filled into a small chamber of a plastic multi-chamber container sterilized by high-pressure steam according to a conventional method. It was.
  • control group was treated in the same manner as the CNN group except that 1 mL / kg of the injection solution having the composition of Example 1 containing no CNN was administered as a test solution.
  • the survival rate (%) of each group every 4 hours after LPS administration is shown in Table 1 below.
  • the CNN group administered with the sepsis prevention and treatment agent of Example 1 showed a higher survival rate than the comparative group administered with ⁇ -cyclodextrin. From this, it was confirmed that CNN, which is an active ingredient of the sepsis prevention and treatment agent of the present invention, has a preventive effect on sepsis, suggesting that it can be used effectively from the initial stage.
  • Example 5 2 mL / kg of the injection solution obtained in Example 5 was administered as a test solution within the tail vein within 10 seconds after a fasting day and night (hereinafter referred to as fasting until the end of the experiment). Furthermore, in order to induce septic shock immediately after that, a physiological saline solution (20 mg / mL) of an endotoxin Escherichia coli 0111: B4-derived lipopolysaccharide (hereinafter “LPS”) was administered at a dose of 1 mL / kg. It was administered intraperitoneally within 10 seconds.
  • LPS an endotoxin Escherichia coli 0111: B4-derived lipopolysaccharide
  • the ICG5 group was treated in the same manner as the CMM group except that 1 mL / kg of the injection solution obtained in Example 9 was administered as a test solution.
  • control group was treated in the same manner as the CMM group except that 1 mL / kg of the injection solution having the composition of Example 1 containing no CNN was administered as the test solution.
  • the survival rate (%) of each group every 4 hours after LPS administration is shown in Table 2 below.
  • the CNN group was intraperitoneally administered with a physiological saline solution of LPS (20 mg / mL) at a dose of 1 mL / kg within 10 seconds after fasting all day and night (hereinafter referred to as fasting until the end of the experiment). . Further 2 hours later, 1 mL / kg of the injection solution obtained in Example 1 as a test solution was administered into the tail vein within 10 seconds. Separately, inflammatory cytokines were measured to confirm that sepsis occurred at the time of administration of the test solution.
  • control group was treated in the same manner as the CNN group except that 1 mL / kg of the injection solution having the composition of Example 1 containing no CNN was administered as the test solution.
  • the survival rate (%) of each group every 4 hours after LPS administration is shown in Table 3 below.
  • CNN group showed a higher survival rate than the control group. From this, it was confirmed that CNN which is an active ingredient of the sepsis prevention and treatment agent of the present invention has a therapeutic effect after infection of sepsis.
  • Test example 4 Effect of CNN on erythrocyte hemolysis (comparison with ⁇ -cyclodextrin and effect of CNN concentration) Blood blood components and plasma were separated by centrifugation (2000 rpm ⁇ 15 min) of 25 mL of blood (cardiac blood sampling: heparin-treated) for 30 male and female 4 to 6 month old Syrian hamsters at room temperature. Further, the uppermost part of the blood cell layer (buffy coat; leukocyte layer) was removed with a Pasteur pipette.
  • PBS (0.15 M NaCl + 10 mM phosphate buffer, pH 7.4) was added thereto, the blood cells were suspended and centrifuged again (2000 rpm ⁇ 15 min), and this operation was repeated three times to obtain erythrocytes. This was suspended in 25 mL of PBS to obtain a hamster erythrocyte suspension of 6.07 ⁇ 10 10 cells / mL.
  • CNN does not show the strong erythrocyte hemolytic action seen in ⁇ -cyclodextrin.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Hematology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)

Abstract

La présente invention concerne un agent prophylactique et thérapeutique pour la septicémie qui renferme au moins un composant choisi dans le groupe constitué d’un tétrasaccharide cyclique dont un saccharide constituant est le glucose, d’un pentasaccharide cyclique dont un saccharide constituant est le glucose et de dérivés du tétrasaccharide cyclique et du pentasaccharide cyclique en tant que principe actif. L’agent prophylactique et thérapeutique pour la septicémie peut prévenir et traiter une septicémie sans provoquer d’effet secondaire indésirable quelconque tel qu’une hémolyse.
PCT/JP2009/066593 2008-10-03 2009-09-25 Agent prophylactique et thérapeutique pour la septicémie WO2010038656A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2008258709A JP2011256111A (ja) 2008-10-03 2008-10-03 敗血症の予防及び治療剤
JP2008-258709 2008-10-03

Publications (1)

Publication Number Publication Date
WO2010038656A1 true WO2010038656A1 (fr) 2010-04-08

Family

ID=42073420

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2009/066593 WO2010038656A1 (fr) 2008-10-03 2009-09-25 Agent prophylactique et thérapeutique pour la septicémie

Country Status (3)

Country Link
JP (1) JP2011256111A (fr)
TW (1) TW201018469A (fr)
WO (1) WO2010038656A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016193917A (ja) * 2010-12-01 2016-11-17 ジ オーストラリアン ナショナル ユニバーシティ ヒストン阻害

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03133931A (ja) * 1989-10-18 1991-06-07 Ueno Seiyaku Oyo Kenkyusho:Kk 抗ショック剤
JP2005095148A (ja) * 2003-08-28 2005-04-14 Hayashibara Biochem Lab Inc 環状マルトシルマルトース及び環状マルトシルマルトース生成酵素とそれらの製造方法並びに用途
WO2006035725A1 (fr) * 2004-09-27 2006-04-06 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Isocyclomaltooligosaccharide, isocyclomaltooligosaccharide synthase, procedes de synthese de ces composes, et utilisation de ces composes
WO2006115067A1 (fr) * 2005-04-20 2006-11-02 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Fluide pour dialyse peritoneale
WO2007013122A1 (fr) * 2005-07-28 2007-02-01 Humanitas Mirasole S.P.A. Hemofiltres pour detoxification sanguine
JP2008056631A (ja) * 2006-09-01 2008-03-13 Chisso Corp 硫酸化環状四糖またはその塩

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03133931A (ja) * 1989-10-18 1991-06-07 Ueno Seiyaku Oyo Kenkyusho:Kk 抗ショック剤
JP2005095148A (ja) * 2003-08-28 2005-04-14 Hayashibara Biochem Lab Inc 環状マルトシルマルトース及び環状マルトシルマルトース生成酵素とそれらの製造方法並びに用途
WO2006035725A1 (fr) * 2004-09-27 2006-04-06 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Isocyclomaltooligosaccharide, isocyclomaltooligosaccharide synthase, procedes de synthese de ces composes, et utilisation de ces composes
WO2006115067A1 (fr) * 2005-04-20 2006-11-02 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Fluide pour dialyse peritoneale
WO2007013122A1 (fr) * 2005-07-28 2007-02-01 Humanitas Mirasole S.P.A. Hemofiltres pour detoxification sanguine
JP2008056631A (ja) * 2006-09-01 2008-03-13 Chisso Corp 硫酸化環状四糖またはその塩

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GREGORY L. C. ET AL.: "Enzymically Produced Cyclic a-1,3-Linked and a-1,6-Linked Oligosaccharides of d-Glucose.", EUROPEAN JOURNAL OF BIOCHEMISTRY, vol. 226, no. 2, 1994, pages 641 - 648 *
HIDETOSHI ARIMA: "Cyclodextrin no Saranaru Kanosei o Motomete", JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY, vol. 63, no. 3, 2003, JAPAN, pages 125 - 128 *
HIROSHI NISHIMOTO ET AL.: "Cyclodextrin Yudotai ni yoru Macrophage kara no NO Sansei no Yokusei", ABSTRACTS OF ANNUAL MEETING OF PHARMACEUTICAL SOCIETY OF JAPAN, vol. 120, no. 4, 2000, pages 21 *
KEIICHI MOTOYAMA: "Endotoxin Shock Yokuseizai toshite no Dimethyl Acetyl-§-Cyclodextrin no Yuko Riyo", JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY, vol. 68, no. 3, May 2008 (2008-05-01), JAPAN, pages 196 - 201 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016193917A (ja) * 2010-12-01 2016-11-17 ジ オーストラリアン ナショナル ユニバーシティ ヒストン阻害

Also Published As

Publication number Publication date
JP2011256111A (ja) 2011-12-22
TW201018469A (en) 2010-05-16

Similar Documents

Publication Publication Date Title
US5608038A (en) Highly concentrated immunoglobulin preparation and method for its production
EP0216362B1 (fr) Préparations stables lyophilisées contenant un complexe de platine anti-cancéreux
EP2540284B1 (fr) Compositions et méthodes pour des formulations de polysaccharides stabilisés
JP6888091B2 (ja) スルホニル尿素系薬の医薬組成物及びその調製方法
JP7443443B2 (ja) 関節を治療するための組成物及びキット
EP2827862B1 (fr) Formulations de bendamustine
CZ234898A3 (cs) Zdokonalené koncentrované injekční a infusní roztoky pro intravazální použití
KR100720886B1 (ko) 주사용 실로스타졸 수성 제제
RU2015134583A (ru) Фармацевтические композиции, содержащие доноры нитроксила
CA3043979A1 (fr) Nouvelles formulations de composes de la famille des beta-lactamines substitues par une amidine, a base de cyclodextrines modifiees et d'agents acidifiants, leur preparation et leur utilisation en tant que compositions pharmaceutiques antimicrobiennes
JP7254101B2 (ja) 複数回使用のトラセミド組成物
JPH11240835A (ja) 安定なプロスタグランジンｅ１−含有注射剤組成物
JPH06199691A (ja) 安定化スーパーオキシドジスムターゼ組成物
JP3597239B2 (ja) 安定な点眼剤
EA008776B1 (ru) Жидкая стабильная композиция оксазафосфорина с месной
WO2010038656A1 (fr) Agent prophylactique et thérapeutique pour la septicémie
WO2013026694A1 (fr) Compositions pharmaceutiques comprenant du voriconazole
JP7423028B2 (ja) ボルテゾミブを含有する凍結乾燥医薬組成物
US11931376B1 (en) Methods for the treatment of chronic kidney disease
JP5019923B2 (ja) プラノプロフェン含有医薬組成物
JP2772878B2 (ja) マクロファージ活性化組成物
JP4275394B2 (ja) 注射用シロスタゾール水性製剤
US5071838A (en) Treatment of shock by cyclodextrins and their derivatives
JP5652963B2 (ja) 腹膜肥厚抑制剤
JPH07267863A (ja) プロスタグランジンまたはその類縁化合物を含有する注射用組成物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09817689

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

NENP Non-entry into the national phase

Ref country code: JP

122 Ep: pct application non-entry in european phase

Ref document number: 09817689

Country of ref document: EP

Kind code of ref document: A1