WO2022009973A1 - Composition à teneur en tarc, et procédé d'amélioration de stabilité de conservation de tarc - Google Patents

Composition à teneur en tarc, et procédé d'amélioration de stabilité de conservation de tarc Download PDF

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WO2022009973A1
WO2022009973A1 PCT/JP2021/025902 JP2021025902W WO2022009973A1 WO 2022009973 A1 WO2022009973 A1 WO 2022009973A1 JP 2021025902 W JP2021025902 W JP 2021025902W WO 2022009973 A1 WO2022009973 A1 WO 2022009973A1
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tarc
surfactant
composition
sodium
type
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PCT/JP2021/025902
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English (en)
Japanese (ja)
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建午 藤村
智之 臼井
明子 松本
由香 鈴木
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積水メディカル株式会社
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Priority to JP2022535400A priority Critical patent/JPWO2022009973A1/ja
Publication of WO2022009973A1 publication Critical patent/WO2022009973A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Definitions

  • the present invention relates to a composition containing TARC. More specifically, the present invention relates to a composition capable of stably storing TARC for a long period of time.
  • the present invention also relates to a TARC measuring method and kit, a TARC storage stability improving method, and a TARC adsorption inhibitor.
  • Thymus and activated-regulated chemokine (hereinafter, may be referred to as TARC) is a CC chemokine ligand 17 (CCL17), which is a kind of chemokine having a leukocyte migration action.
  • TARC attracts Th2 cells, which are one of the lymphocytes, to the lesion site, causing IgE production and infiltration / activation of eosinophils. By enhancing the allergic reaction in this way, TARC is considered to exacerbate the symptoms of atopic dermatitis (Non-Patent Document 1).
  • TARC is important to promptly and surely sedate the inflammation of atopic dermatitis.
  • TARC is in good agreement with the severity of atopic dermatitis compared to serum IgE levels, peripheral blood eosinophil counts, and serum LDH levels, which have been used as indicators of the pathology of other atopic dermatitis. It is considered to reflect the disease situation more sensitively (Non-Patent Document 2). Therefore, by using TARC as a biomarker, when selecting or changing a therapeutic agent for atopic dermatitis, the severity can be objectively and quickly grasped and the effect can be determined.
  • the calibration sample is a sample containing a component to be measured, which is used for purposes such as an internal standard or a concentration calibration standard (calibrator).
  • a calibration sample that is stable with respect to the passage of time and temperature is required.
  • the calibration sample is preferably in a fluid liquid state (hereinafter, may be referred to as “liquid”) because of its ease of operation.
  • biological activity for example, antigenicity to a specific antibody, binding activity to a specific binding partner possessed by an antibody or lectin, physiological activity possessed by a peptide hormone or the like, enzyme activity).
  • biological activity for example, antigenicity to a specific antibody, binding activity to a specific binding partner possessed by an antibody or lectin, physiological activity possessed by a peptide hormone or the like, enzyme activity.
  • Patent Document 1 As a method for storing the calibration sample in liquid form, which is intended for use in an immunological measurement method, a method for stabilizing an antigen by coexisting casein and / or whey protein in the calibration sample (Patent Document 1).
  • Patent Document 2 A method of stabilizing insulin in the coexistence of a bile acid amide derivative (Patent Document 2) and a method of stabilizing a soluble interleukin-2 receptor (sIL-2R) in the coexistence of a chelating agent are known (Patent Document 3).
  • sIL-2R soluble interleukin-2 receptor
  • An object of the present invention is to provide a TARC-containing composition having high storage stability.
  • the present inventors have attempted to prepare a TARC-containing composition having high storage stability. Then, when TARC is added to a solution containing at least one surfactant selected from the group consisting of a cationic surfactant and an anionic surfactant, the stability of TARC is improved. I found it.
  • the present invention is based on such findings. Specifically, the present invention is as follows. ⁇ 1> A composition containing TARC (Thymus and activation-regulated chemokine). The composition comprising TARC and at least one surfactant selected from the group consisting of cationic and anionic surfactants and in liquid form. ⁇ 2> The composition according to ⁇ 1>, which is a sample solution for calibration for measuring TARC.
  • ⁇ 3> The composition according to ⁇ 1> or ⁇ 2>, which is filled in a storage container.
  • ⁇ 4> The composition according to ⁇ 3>, wherein the storage container is plastic or glass.
  • ⁇ 5> The composition according to any one of ⁇ 1> to ⁇ 4>, wherein the concentration of TARC is 10 pg / mL to 1 ⁇ g / mL with respect to the composition.
  • ⁇ 6> The composition according to any one of ⁇ 1> to ⁇ 5>, wherein the concentration of the surfactant is 0.00001% by mass to 1% by mass with respect to the composition.
  • the cationic surfactant is an alkylamine salt type or a quaternary ammonium salt type cationic surfactant.
  • composition according to any one of ⁇ 1> to ⁇ 6> wherein the anionic surfactant is a cholic acid type, a sulfate type, a carboxylic acid type, or a sulfonic acid type anionic surfactant.
  • the anionic surfactant is a cholic acid type, a sulfate type, a carboxylic acid type, or a sulfonic acid type anionic surfactant.
  • the concentration of TARC is 2000 pg / mL with respect to the composition, the residual rate of TARC after storage at 10 ° C. for 6 hours in a glass container is 55% or more, ⁇ 1> to ⁇ 9.
  • the cationic surfactant is lauryltrimethylammonium chloride or coconatamine acetate.
  • ⁇ 13> A TARC measurement kit comprising the composition according to any one of ⁇ 1> to ⁇ 11>.
  • a method for improving the storage stability of TARC which comprises a step of contacting TARC with a solution containing at least one surfactant selected from the group consisting of a cationic surfactant and an anionic surfactant. .. ⁇ 15>
  • the method for improving storage stability of TARC according to ⁇ 14> which comprises a step of adjusting the concentration of TARC to be 10 pg / mL to 1 ⁇ g / mL with respect to the solution.
  • the cationic surfactant is an alkylamine salt type or a quaternary ammonium salt type cationic surfactant.
  • the storage stability of TARC according to any one of ⁇ 14> to ⁇ 16>, wherein the anionic surfactant is a cholic acid type, a sulfate type, a carboxylic acid type, or a sulfonic acid type anionic surfactant. How to improve.
  • the cationic surfactant is lauryltrimethylammonium chloride or coconatamine acetate.
  • the TARC according to any one of ⁇ 14> to ⁇ 17>, wherein the anionic surfactant is sodium collate, sodium lauryl sulfate, sodium lauroylmethylalanine, or ⁇ -naphthalene sulfonic acid formarin condensate sodium salt.
  • the anionic surfactant is sodium collate, sodium lauryl sulfate, sodium lauroylmethylalanine, or ⁇ -naphthalene sulfonic acid formarin condensate sodium salt.
  • An inhibitor for adsorbing TARC to a container in a solution containing TARC which comprises at least one surfactant selected from the group consisting of a cationic surfactant and an anionic surfactant.
  • the adsorption inhibitor contained as an active ingredient.
  • ⁇ 20> The adsorption inhibitor according to ⁇ 19>, wherein the concentration of TARC in the solution containing TARC is 10 pg / mL to 1 ⁇ g / mL with respect to the solution.
  • the cationic surfactant is an alkylamine salt type or a quaternary ammonium salt type cationic surfactant.
  • the cationic surfactant is lauryltrimethylammonium chloride or coconatamine acetate.
  • TARC-containing composition having high storage stability, particularly a TARC-containing calibration sample. Therefore, according to the present invention, TARC in a biological sample can be accurately quantified, and the severity of atopic dermatitis can be accurately grasped.
  • TARC means Symus and activated-regulated chemokine (CCL17).
  • TARC is a type of chemokine that has leukocyte migration activity.
  • TARC has the function of attracting Th2 cells, which are one of the lymphocytes, to the lesion site to produce IgE or infiltrate and activate eosinophils.
  • the measurement of TARC can be performed using a known method, for example, an immunological method.
  • Immunological methods include ELISA, enzyme immunoassay, surface plasmon resonance method, latex aggregation immunoassay (LTIA), chemical luminescence immunoassay, electrochemical luminescence immunoassay, fluorescent antibody method, radioimmunoassay, Western blot method, immunochromatography method, high performance liquid chromatography method (HPLC method) and the like can be mentioned.
  • TARC contained in the composition of the present invention a commercially available product may be used, or a product prepared or purified by itself may be used.
  • TARC contained in the composition of the present invention one prepared in vitro may be used, or one extracted from a living body may be used.
  • TARC concentration The concentration of TARC contained in the composition of the present invention is not limited to the following, but is preferably 10 pg / mL to 1 ⁇ g / mL with respect to the composition in consideration of the stability of TARC. It is preferably 50 pg / mL to 500 ng / mL, more preferably 100 pg / mL to 100 ng / mL, and most preferably 100 pg / mL to 50 ng / mL.
  • the anionic surfactant means a surfactant in which the hydrophobic group portion is ionized into negative (negative) ions when dissolved in water.
  • a surfactant having a hydrophilic group that does not ionize when dissolved in water is referred to as a nonionic surfactant, and a surfactant in which the hydrophobic group portion is ionized into a positive (positive) ion is a cation.
  • a surfactant that exhibits the properties of an anionic surfactant in the alkaline region and the properties of a cationic surfactant in the acidic region is referred to as a sex surfactant, and is referred to as an amphoteric surfactant.
  • an alkylamine salt type, a quaternary ammonium salt type and the like are preferable.
  • anionic surfactant cholic acid type, sulfate ester (sulfate) type, carboxylic acid type, sulfonic acid type and the like are preferable.
  • alkylamine salt type of the cationic surfactant examples include amines containing 1 to 3 alkyl groups having 8 to 22 carbon atoms such as monododecylamine, monooctadecylamine, dioctadecylamine, and trioctadecylamine, and hydrochloric acid.
  • Inorganic acids such as sulfuric acid or salts with lower carboxylic acids such as acetic acid, lactic acid and citric acid.
  • dodecylamine hydrochloride [CAS number: 929-73-7, manufactured by Tokyo Kasei Kogyo Co., Ltd.]
  • coconut amine acetate [CAS number: 61790-57-6, product name: acetamine 24, Kao Corporation Company-made]
  • stearylamine acetate [CAS number: 2190-04-7, product name: acetamine 86, made by Kao Corporation] and the like.
  • the quaternary ammonium salt type includes ammonium containing 1 to 3 alkyl groups having 8 to 22 carbon atoms such as dodecyltrimethylammonium, octadecyltrimethylammonium, hexadecyltrimethylammonium, didecyldimethylammonium, and benzylmethyltetradecylammonium.
  • Examples include salts with chlorine, bromine and the like.
  • lauryltrimethylammonium chloride [CAS number: 112-00-5, product name: Coatamine (registered trademark) 24P, manufactured by Kao Co., Ltd.], dodecyltrimethylammonium bromide [CAS number: 1119-94-4, Tokyo Chemical Industry Co., Ltd.], Octadecyltrimethylammonium chloride [CAS number: 112-03-8, Tokyo Chemical Industry Co., Ltd.], Distearyldimethylammonium chloride [CAS number: 107-64-2, Product name: Coatamine ( Registered trademark) D86P, manufactured by Kao Co., Ltd.] and the like.
  • the cholic acid types of anionic surfactants include sodium deoxycholic acid [CAS number: 302-95-4, manufactured by Fujifilm Wako Co., Ltd.] and sodium cholic acid [CAS number: 361-09-1, Fuji. Film Wako Co., Ltd.] and the like.
  • Examples of the sulfate ester (sulfate) type include higher alcohol sulfate esters such as dodecyl sulfate ester, polyoxyethylene alkyl ether sulfate esters such as polyoxyethylene dodecyl ether sulfate ester, and salts with sodium and ammonium.
  • sodium dodecyl sulfate [CAS number: 151-21-3, manufactured by Sigma-Aldrich], ammonium lauryl sulfate [CAS number: 2235-54-3, Latemul (registered trademark) AD-25, Kao Co., Ltd.
  • Higher alcohol sulfate ester salts such as [manufactured by], polyoxyethylene alkyl ether sulfate ester salts such as polyoxyethylene lauryl ether sulfate sodium [CAS number: 68585-34-2, product name: Emar 20C, manufactured by Kao Co., Ltd.] Can be mentioned.
  • Examples of the carboxylic acid type include dodecanoic acid (lauric acid), tetradecanoic acid (myristic acid), hexadecanoic acid (palmitic acid), octadecanoic acid (stearic acid), and cis-9-octadecenoic acid (oleic acid) having 8 to carbon atoms.
  • Examples thereof include salts of 22 higher fatty acids and the like with alkali metals such as sodium and potassium. Specifically, for example, sodium laurate [CAS number: 629-25-4, manufactured by Fujifilm Wako Co., Ltd.], sodium myristate [CAS number: 822-12-8, manufactured by Fujifilm Wako Co., Ltd.], palmitic acid.
  • sulfonic acid type examples include alkylbenzene sulfonic acid such as dodecylbenzene sulfonic acid, naphthalene sulfonic acid such as dibutylnaphthalene sulfonic acid, formalin condensate of naphthalene sulfonic acid, sulfosuccinic acid such as dioctylsulfosuccinic acid, and salts such as sodium.
  • alkylbenzene sulfonic acid such as dodecylbenzene sulfonic acid
  • naphthalene sulfonic acid such as dibutylnaphthalene sulfonic acid
  • formalin condensate of naphthalene sulfonic acid sulfosuccinic acid
  • sulfosuccinic acid such as dioctylsulfosuccinic acid
  • salts such as sodium.
  • sodium laurylbenzene sulfonate [CAS number: 25155-30-0, manufactured by Fujifilm Wako Co., Ltd.]
  • ⁇ -naphthalene sulfonic acid formarin condensate sodium salt [CAS number: 9084-06-4, product. Name: Demol (registered trademark) RN, manufactured by Kao Co., Ltd.]
  • sodium dioctylsulfosuccinate [CAS number: 577-11-7, product name: Neocol (registered trademark) SW, manufactured by Daiichi Kogyo Co., Ltd.]
  • anionic surfactants or cationic surfactants are handled by various detergent makers and reagent makers, and commercially available products can be purchased and used.
  • anionic surfactants or cationic surfactants may be used alone or in combination of two or more.
  • the cationic or anionic surfactants used in the compositions of the present invention are coconutamine acetate, lauryltrimethylammonium chloride, sodium sulphonate, sodium dodecyl sulfate, sodium lauroylmethylalanine, or ⁇ -.
  • Sodium salt of sodium phthalene sulfonic acid formalin condensate is more preferable.
  • lauryltrimethylammonium chloride, sodium colate, sodium dodecyl sulfate, or sodium lauroylmethylalanine is used
  • lauryltrimethylammonium chloride, coconatamine acetate, or ⁇ is further preferred to use sodium salt of sodium naphthalene sulfonic acid formalin condensate.
  • surfactants it is possible to use other types of surfactants in addition to the anionic surfactants or cationic surfactants as long as the effects of the present invention are not impaired, it is preferable not to use them. ..
  • an anionic surfactant and a cationic surfactant can be used in combination, it is preferable to use only one of them without using them in combination.
  • the order of addition of the cationic surfactant or the anionic surfactant and TARC is not particularly limited as long as the effect of the present invention can be obtained.
  • the concentration of the cationic or anionic surfactant is not limited to the following, but is preferable with respect to the composition in consideration of the stability of TARC. Is 0.00001% by mass to 1% by mass, more preferably 0.0001% by mass to 1% by mass, still more preferably 0.001% by mass to 0.5% by mass, and most preferably 0.001% by mass to 0. It is 1% by mass.
  • the composition of the present invention is preferably filled in a storage container.
  • the material of the storage container is not particularly limited as long as the effects of the present invention can be obtained and can be sealed, but at least a part or all of the contact portion with the composition is a plastic [for example, an olefin resin or a styrene resin.
  • Acrylic resin Acrylic resin, polyester resin, polycarbonate resin, fluororesin, chlorine resin (polyvinyl chloride, etc.), polyamide resin, polyacetal resin, polyphenylene ether resin (modified polyphenylene ether, etc.), polyallylate, polysulfone, Polyimide-based resins, cellulose-based resins (cellulose acetate, etc.), hydrocarbon-based resins (including halogen atom-substituted products), etc.], metals (aluminum, etc.), glass, etc.
  • plastic or glass is preferable from the viewpoint of manufacturing, transporting, and storing the calibration sample, and among the plastics, an olefin resin is preferable, and polypropylene is more preferable.
  • the storage container may be made of a single material or two or more kinds of materials, but is preferably made of a single material.
  • the storage container can include a container body portion and a cap. In this case, the container body portion and the cap may be made of different materials. Further, it is preferable that the storage container, particularly the main body portion, has transparency to the extent that the content liquid can be seen from the outside.
  • the storage container may be of either a hard type or a soft type, and examples thereof include ampoules, vials, soft bags, injection containers, and glass bottles.
  • the storage container is preferably in the form of a plastic eye drop bottle including a container body portion and a cap portion, particularly in the form of a cylindrical eye drop bottle, from the viewpoint of ease of use and stability of TARC.
  • the storage container should be a glass ampoule or a form including a glass container body and a cap, particularly a cylindrical glass container and a form including a rubber cap, for ease of use and TARC. Preferred from the viewpoint of stability.
  • composition The composition of the present invention can be used as a sample solution for calibration in the measurement of TARC.
  • the sample solution for calibration means a sample solution containing a substance to be measured at a constant concentration, which is used for accurate measurement of the substance to be measured, and is used as a standard substance, a calibrator, a control, and a sample solution. Internal standard substances, etc. are applicable.
  • Examples of the form of supplying the composition of the present invention include a form in which TARC and an anionic surfactant or a cationic surfactant are mixed with a solvent and prepared in a solution state in advance.
  • "using a composition” means using a composition in order to accurately measure TARC.
  • a liquid composition containing TARC is used as a sample solution for calibration ( Means to be used as a reference material, calibrator, control, and internal standard material, etc.).
  • the pH of the composition of the present invention is, for example, 4.0 to 9.5, 5.0 to 9.0, 6.0 to 8.5, 6.5 to 8.0, or 7.0 to 8. It is 0.
  • the pH can be adjusted using a pH adjusting reagent well known to those skilled in the art, such as sodium hydroxide or hydrochloric acid.
  • composition of the composition of the present invention is not particularly limited as long as the effect of the present invention is not impaired. If TARC is measured by an immunological measurement method, the effects of the present invention are not impaired, and the reactions constituting the measurement system such as antigen-antibody reaction, labeling reaction for detection with biotin / avidin, and enzyme reaction It does not have to interfere with all or part of it.
  • Various components commonly used in immunological measurement methods such as acetic acid, citric acid, phosphoric acid, PBS (phosphate buffered saline), HEPES, MES, Tris, glycine, boric acid, carbonic acid and good buffer.
  • buffers components that promote antigen-antibody reactions (polymers such as polyethylene glycol and polyvinylpyrrolidone), glycoproteins and peptides (BSA, casein, etc.), amino acids, salts (sodium chloride, potassium chloride, etc.), sugars (sho) Sugar, cyclodextrin, etc.), preservatives (sodium azide, ProClin300, etc.) and the like can be appropriately selected and used according to the purpose. It is preferable to use PBS having a pH of 6.5 to 8.0.
  • improved storage stability means that most of the TARC contained in the solution containing TARC is not decomposed for a long period of time and the structure is not changed. Alternatively, by maintaining the TARC in the solution without adsorbing it, it means that there is no big difference between the initial value of TARC in the solution and the measured value after storage. More specifically, “improvement of storage stability” or “improvement of storage stability” means, for example, 80% or more of TARC contained in a solution containing TARC having a concentration of 10 pg / mL to 1 ⁇ g / mL. In the solution after storage in a plastic container for 28 days at 37 ° C. by being maintained at 37 ° C.
  • TARC for 28 days without decomposition, structural changes or adsorption to the container. It can mean that the measured value of TARC is 80% or more of the initial value.
  • "improvement of storage stability” or “improvement of storage stability” means that, for example, 90% or more of TARC contained in a solution containing TARC having a concentration of 10 pg / mL to 1 ⁇ g / mL is 4 ° C. Measurement of TARC in the solution after storage in a plastic container at 4 ° C. for 28 days at 4 ° C. by being maintained without decomposition, structural changes or adsorption to the container for 28 days. It can mean that the value is 90% or more of the initial value.
  • improved of storage stability or “improvement of storage stability” means that, for example, 55% or more of TARC contained in a solution containing TARC having a concentration of 10 pg / mL to 1 ⁇ g / mL is 10 ° C.
  • the measured value of TARC in the solution after storage in a glass container at 10 ° C. for 6 hours It can mean that it becomes 55% or more of the initial value.
  • the biological sample for measuring TARC is not particularly limited as long as TARC can be measured, but blood, serum, or plasma is preferably used. If necessary, the biological sample may be pretreated.
  • the biological sample is preferably a biological sample taken from a human.
  • the composition of the present invention can be used to easily and accurately measure TARC.
  • the TARC measurement kit include a kit using an immunological method.
  • the TARC measurement kit of the present invention can contain a reagent for measuring the concentration of TARC in a human body by an immunological method. Immunological methods include ELISA, enzyme immunoassay, surface plasmon resonance method, latex aggregation immunoassay (LTIA), chemical luminescence immunoassay, electrochemical luminescence immunoassay, fluorescent antibody method, radioimmunoassay, Western blot method, immunochromatography method, high performance liquid chromatography method (HPLC method) and the like can be mentioned.
  • the TARC measurement kit of the present invention can be used to grasp the severity of atopic dermatitis in determining the treatment method or drug selection of atopic dermatitis and the effect of the treatment.
  • the TARC measurement kit of the present invention may also include an instruction manual or the like.
  • the TARC measurement kit may include any component, such as a buffer, a stabilizer, a sample diluent, a pH regulator, a reaction vessel, and the like.
  • the method for improving the storage stability of TARC of the present invention includes a step of contacting TARC with a solution containing a cationic surfactant or an anionic surfactant.
  • TARC may be added after the cationic or anionic surfactant is added to the solution, or after the TARC is added to the solution, the cationic or anionic surfactant is added. It may be added.
  • the solution is preferably a buffer such as PBS, HEPES, MES, CHES and Tris. It is more preferable to use PBS having a pH of 6.5 to 8.0.
  • the concentration of TARC contained in the solution is not limited to the following, but is preferably 10 pg / mL to 1 ⁇ g / mL in consideration of the stability of TARC. , More preferably 50 pg / mL to 500 ng / mL, still more preferably 100 pg / mL to 100 ng / mL, and most preferably 100 pg / mL to 50 ng / mL.
  • an alkylamine salt type, a quaternary ammonium salt type and the like are preferable.
  • anionic surfactant cholic acid type, sulfate ester (sulfate) type, carboxylic acid type, sulfonic acid type and the like are preferable.
  • alkylamine salt type of the cationic surfactant examples include amines containing 1 to 3 alkyl groups having 8 to 22 carbon atoms such as monododecylamine, monooctadecylamine, dioctadecylamine, and trioctadecylamine, and hydrochloric acid.
  • Inorganic acids such as sulfuric acid or salts with lower carboxylic acids such as acetic acid, lactic acid and citric acid.
  • dodecylamine hydrochloride [CAS number: 929-73-7, manufactured by Tokyo Kasei Kogyo Co., Ltd.]
  • coconut amine acetate [CAS number: 61790-57-6, product name: acetamine 24, Kao Corporation Company-made]
  • stearylamine acetate [CAS number: 2190-04-7, product name: acetamine 86, made by Kao Corporation] and the like.
  • the quaternary ammonium salt type includes ammonium containing 1 to 3 alkyl groups having 8 to 22 carbon atoms such as dodecyltrimethylammonium, octadecyltrimethylammonium, hexadecyltrimethylammonium, didecyldimethylammonium, and benzylmethyltetradecylammonium. Examples thereof include salts such as chlorine and bromine.
  • lauryltrimethylammonium chloride [CAS number: 112-00-5, product name: Coatamine (registered trademark) 24P, manufactured by Kao Co., Ltd.], dodecyltrimethylammonium bromide [CAS number: 1119-94-4, Tokyo Chemical Industry Co., Ltd.], Octadecyltrimethylammonium chloride [CAS number: 112-03-8, Tokyo Chemical Industry Co., Ltd.], Distearyldimethylammonium chloride [CAS number: 107-64-2, Product name: Coatamine ( Registered trademark) D86P, manufactured by Kao Co., Ltd.] and the like.
  • the cholic acid types of anionic surfactants include sodium deoxycholic acid [CAS number: 302-95-4, manufactured by Fujifilm Wako Co., Ltd.] and sodium cholic acid [CAS number: 361-09-1, Fuji. Film Wako Co., Ltd.] and the like.
  • Examples of the sulfate ester (sulfate) type include higher alcohol sulfate esters such as dodecyl sulfate ester, polyoxyethylene alkyl ether sulfate esters such as polyoxyethylene dodecyl ether sulfate ester, and salts with sodium and ammonium.
  • sodium dodecyl sulfate [CAS number: 151-21-3, manufactured by Sigma-Aldrich], ammonium lauryl sulfate [CAS number: 2235-54-3, Latemul (registered trademark) AD-25, Kao Co., Ltd.
  • Higher alcohol sulfate ester salts such as [manufactured by], polyoxyethylene alkyl ether sulfate ester salts such as polyoxyethylene lauryl ether sulfate sodium [CAS number: 68585-34-2, product name: Emar 20C, manufactured by Kao Co., Ltd.] Can be mentioned.
  • Examples of the carboxylic acid type include dodecanoic acid (lauric acid), tetradecanoic acid (myristic acid), hexadecanoic acid (palmitic acid), octadecanoic acid (stearic acid), and cis-9-octadecenoic acid (oleic acid) having 8 to carbon atoms.
  • Examples thereof include salts of 22 higher fatty acids and the like with alkali metals such as sodium and potassium. Specifically, for example, sodium laurate [CAS number: 629-25-4, manufactured by Fujifilm Wako Co., Ltd.], sodium myristate [CAS number: 822-12-8, manufactured by Fujifilm Wako Co., Ltd.], palmitic acid.
  • sulfonic acid type examples include alkylbenzene sulfonic acid such as dodecylbenzene sulfonic acid, naphthalene sulfonic acid such as dibutylnaphthalene sulfonic acid, formalin condensate of naphthalene sulfonic acid, sulfosuccinic acid such as dioctylsulfosuccinic acid, and salts such as sodium.
  • alkylbenzene sulfonic acid such as dodecylbenzene sulfonic acid
  • naphthalene sulfonic acid such as dibutylnaphthalene sulfonic acid
  • formalin condensate of naphthalene sulfonic acid sulfosuccinic acid
  • sulfosuccinic acid such as dioctylsulfosuccinic acid
  • salts such as sodium.
  • sodium laurylbenzene sulfonate [CAS number: 25155-30-0, manufactured by Fujifilm Wako Co., Ltd.]
  • ⁇ -naphthalene sulfonic acid formarin condensate sodium salt [CAS number: 9084-06-4, product. Name: Demol (registered trademark) RN, manufactured by Kao Co., Ltd.]
  • sodium dioctylsulfosuccinate [CAS number: 577-11-7, product name: Neocol (registered trademark) SW, manufactured by Daiichi Kogyo Co., Ltd.], etc. Be done.
  • the cationic or anionic surfactants used in the compositions of the present invention are coconutamine acetate, lauryltrimethylammonium chloride, sodium sulphonate, sodium dodecyl sulfate, sodium lauroylmethylalanine, or ⁇ -.
  • Sodium salt of sodium phthalene sulfonic acid formalin condensate is more preferable.
  • lauryltrimethylammonium chloride, sodium colate, sodium dodecyl sulfate, or sodium lauroylmethylalanine is used, and in the case of glass containers, lauryltrimethylammonium chloride, coconatamine acetate, or ⁇ .
  • -It is further preferred to use sodium salt of sodium naphthalene sulfonic acid formalin condensate.
  • the concentration of the cationic surfactant or the anionic surfactant is not limited to the following, but the composition is made in consideration of the stability of TARC. On the other hand, it is preferably 0.00001% by mass to 1% by mass, more preferably 0.0001% by mass to 1% by mass, still more preferably 0.001% by mass to 0.5% by mass, and most preferably 0.001. It is from mass% to 0.1% by mass.
  • TARC adsorption inhibitor contains a cationic surfactant or an anionic surfactant.
  • a TARC adsorption inhibitor containing a cationic surfactant or an anionic surfactant may be added before contacting the storage container with the solution containing TARC, and the cationic surfactant as an adsorption inhibitor may be added to the TARC solution.
  • An agent or anionic surfactant may be added and added to the storage container.
  • MEGA-9 Ingredient name: n-Nonanoyl-N-methyl-D-glucamine, Dojin Chemical Laboratory Co., Ltd. Ingredient name: Sodium dodecyl, Fuji Film Wako Co., Ltd. ⁇ SDS component name: sodium lauryl sulfate, Sigma Aldrich Co., Ltd. ⁇ Energol (registered trademark) L-30AN Ingredient name: lauroylmethylalanine sodium, Lion Specialty Chemicals Co., Ltd.
  • Example 1 Storage stability test results in a plastic eye drop bottle >> The storage stability of TARC in plastic eye drop bottles was tested.
  • the test method and evaluation method are as follows. A solution having the following composition was used as the storage solution. ⁇ PBS (pH 7.2) ⁇ 1% by mass BSA -Surfactant (concentration, product name, type are listed in Table 1)
  • TARC liquid preservation solution 0.5 mL was dispensed into plastic eye drop bottles and stored at 37 ° C for 28 days or at 4 ° C for 28 days. TARC concentrations were tested at 500 pg / mL, 2000 pg / mL, and 10000 pg / mL.
  • Measurement method was performed by a latex immunoturbidimetry method using two types of antibodies.
  • the composition of the reagent and the measurement method are shown below. The measurement was performed by a Hitachi automated analyzer using the first reagent and the second reagent.
  • -First reagent 100 mM MOPS-NaOH (pH 7.5) 500 mM NaCl 0.5% BSA ⁇
  • Second reagent Anti-human TARC monoclonal antibody sensitized latex (2 types) 5 mM MOPS-NaOH (pH 7.0)
  • the anti-human TARC monoclonal antibody was obtained by a method well known to those skilled in the art using a commercially available TARC antigen.
  • TARC antigens include CCL17, thymus and activated chemokine (Shenandoah Biotechnology, Inc.), CCL17 / TARC, Human (LifeSpan Biossyence, Inc., Inc., Inc.). Further, a combination of monoclonal antibodies capable of sandwich measurement against the TARC antigen was selected by a method well known to those skilled in the art.
  • the anti-human TARC monoclonal antibody sensitized latex was prepared with reference to the method described in JP-A-2017-18137. First, 120 ⁇ L of the first reagent was added to 2.4 ⁇ L of the liquid storage solution of TARC of each concentration. After heating at 37 ° C.
  • the change in absorbance for 5 minutes was measured at a main wavelength of 570 nm and a sub-wavelength of 800 nm.
  • the amount of change in the measured absorbance was converted to the TARC concentration using a calibration curve obtained by measuring a standard substance having a known concentration.
  • TARC residual rate (%) of the TARC concentration in the liquid storage solution of each TARC after storage at 37 ° C for 28 days or at 4 ° C for 28 days using the following formula. was calculated.
  • TARC residual rate (%) TARC concentration (pg / mL) of each TARC liquid storage solution after storage at 37 ° C for 28 days or 4 ° C for 28 days in an eye drop bottle / TARC concentration of TARC liquid storage solution immediately after preparation (TARC concentration) pg / mL) x 100
  • the surfactants and concentrations used under each condition are shown in Table 1, and the evaluation results are shown in Tables 2 and 3.
  • the TARC residual rate (%) was calculated based on the average value of the three experiments.
  • Condition 6 is a compound shown in Patent Document 2, and has an effect of improving storage stability with respect to insulin, but has a slight effect of improving storage stability with respect to TARC.
  • the residual rate after 28 days was 80% or more for any of the surfactants. .. This is because under conditions 7 to 10, the addition of an anionic surfactant or a cationic surfactant could prevent the adsorption of TARC on the wall surface of the container, or could suppress the structural change of TARC during storage. It was thought that it was a tame.
  • the TARC concentration is 2000 pg / mL and 10000 pg / mL
  • the conditions 1 in which the surfactant is not added the conditions 2 to 5 in which the nonionic surfactant is added, and the condition 6 in which the amphoteric surfactant is added are met.
  • the residual rate was equal to or higher than that.
  • the residual rate after 28 days was 65.7% under the condition 1 in which the surfactant was not added, which was a low result.
  • the residual rate after 28 days was 92.0 to 100.5%, and any of the surfactants
  • the survival rate after 28 days was significantly improved. This is because under conditions 7 to 10, the addition of an anionic surfactant or a cationic surfactant could prevent the adsorption of TARC on the wall surface of the container, or could suppress the structural change of TARC during storage. It was thought that it was a tame. From the above, it was shown that the coexistence of an anionic surfactant or a cationic surfactant and TARC improves the storage stability of TARC during storage of a plastic instillation bottle.
  • Example 2 Storage stability test results in glass vials >> The storage stability of TARC in glass vials was tested. The test method and evaluation method are as follows. A solution having the following composition was used as the storage solution. ⁇ PBS (pH 7.2) ⁇ 1% by mass BSA -Surfactant (concentration, product name, type are listed in Table 4)
  • TARC liquid preservation solution 0.5 mL was dispensed into a glass container and stored at 10 ° C. for 6 hours. As a control, a sample before dispensing in a glass container was also used for measurement. TARC concentrations were tested at 2000 pg / mL and 10000 pg / mL.
  • TARC Residual Rate (%) was calculated using the following formula for the TARC concentration of each TARC liquid storage solution after storage at 10 ° C. for 6 hours.
  • TARC residual rate (%) TARC concentration of each TARC liquid storage solution after storage in a glass container at 10 ° C. for 6 hours (pg / mL) / TARC concentration of TARC liquid storage solution before dispensing in a glass container (pg / mL) ⁇ 100
  • the surfactants and concentrations used under each condition are shown in Table 4, and the evaluation results are shown in Table 5.
  • the TARC residual rate (%) was calculated based on the average value of the three experiments.
  • the residual rate after 6 hours was 42.7% under the condition 1 in which the surfactant was not added, which was a low result.
  • the residual rate after 6 hours was 48.6 to 52.5%, which was hardly improved.
  • the residual rate after 6 hours was improved with any of the surfactants, and particularly under condition 12, 93.7%. It was greatly improved.
  • TARC-containing composition having high storage stability, particularly a TARC-containing calibration sample.

Abstract

L'invention a pour objet de fournir une composition à teneur en TARC (thymus et chimiokine régulée par activation) dotée d'une stabilité de conservation élevée.　À cet effet, l'invention concerne une composition qui contient des TARC. Plus précisément, cette composition contient des TARC, et au moins une sorte d'agent tensio-actif choisie dans un groupe constitué d'un agent tensio-actif cationique et d'un agent tensio-actif anionique, et se présente sous forme liquide.
PCT/JP2021/025902 2020-07-10 2021-07-09 Composition à teneur en tarc, et procédé d'amélioration de stabilité de conservation de tarc WO2022009973A1 (fr)

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WO2002061119A1 (fr) * 2001-01-31 2002-08-08 Asahi Kasei Kabushiki Kaisha Compositions pour analyse de glycoproteines
JP2003344388A (ja) * 2002-05-24 2003-12-03 Nippon Koden Corp 赤血球溶血剤、白血球分類用試薬および試薬
JP2008539434A (ja) * 2005-04-28 2008-11-13 アボット・ラボラトリーズ 心臓トロポニンの安定化
US20130171659A1 (en) * 2011-12-28 2013-07-04 Abbott Japan Co., Ltd. Methods of prognosis and diagnosis of rheumatoid arthritis
CN104181291A (zh) * 2014-08-21 2014-12-03 深圳北京大学香港科技大学医学中心 一种通过tarc/ccl17评估特异性皮炎病情的诊断方法
WO2015076284A1 (fr) * 2013-11-21 2015-05-28 協和メデックス株式会社 Stabilisant et procédé de stabilisation des lipoprotéines haute densité contenues dans le sérum sanguin ou le plasma sanguin
WO2016143351A1 (fr) * 2015-03-11 2016-09-15 プリマハム株式会社 Procédé de détection de cannabinoïde
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WO2016143351A1 (fr) * 2015-03-11 2016-09-15 プリマハム株式会社 Procédé de détection de cannabinoïde
WO2018101389A1 (fr) * 2016-11-30 2018-06-07 東洋紡株式会社 Procédé de mesure du taux de glycation de l'hémoglobine

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