Gel-like composition, reagent, and method for storing reagent

Abstract

A gel-like composition of the present disclosure contains gelatin, a stabilizer, an aqueous medium, and at least one of saccharides in an amount of 1 mass%-30 mass% and salts in an amount of 250 mM-2 M with respect to the total mass of the composition. The content of the stabilizer is 0.5 mass%-5 mass% with respect to the total mass of the composition.

Description

Gel composition, reagent and method for storing reagent

[0001] The present disclosure relates to a gel composition, a reagent, and a method for storing a reagent.

[0002] For example, various reagents are used in contexts such as biochemical experiments, clinical tests, and treatment. After being produced at a factory, reagents are stored under temperature-controlled conditions before being shipped to users.

[0003] Patent Document 1 discloses a method for stably storing a reagent, in which gelatin is present in a solution containing an immunoassay reagent bound with an antibody or an antigen. According to Patent Document 1, the method enables stable storage of the immunoassay reagent and prevents an aqueous solution from adhering to wall surfaces during transportation. In addition, Patent Document 2 discloses a particle composition containing particles having an antigen or antibody immobilized thereon, lactose, glycine, and water. According to Patent Document 2, storing the particles having an antigen or antibody immobilized thereon in a solution containing lactose, glycine, and water improves the stability of the antigen or antibody, enabling continuous and stable immunoassay. Furthermore, Patent Document 3 discloses an antibody dilution composition containing agar, carrageenan, or a mixture thereof. According to Patent Document 3, the use of this antibody dilution composition can improve the accuracy of immunological analysis.

[0004] Patent Document 1: Japanese Unexamined Patent Publication No. Hei 5-180836 Patent Document 2: Japanese Unexamined Patent Publication No. 2017-181492 Patent Document 3: Japanese Unexamined Patent Publication No. 2007-333723

[0005] Incidentally, reagents are manufactured in containers, stored in those containers, and transported to the user. Furthermore, once transported to the user, the reagents may be stored in their containers until use. Thus, the reagents are stored in their containers from manufacturing to use, but condensation may occur on the inner wall of the container during storage. Condensation alters the amount of reagent in the container, and repeated condensation and drying can alter the reagent's composition. Therefore, preventing condensation on the inner wall of the container is desirable in experiments, tests, and treatments using reagents. However, there is no knowledge about which reagents will cause condensation, and there has been a problem in that it is not possible to suppress condensation in the target reagent. Therefore, this disclosure aims to provide a composition, a reagent, and a method for storing reagents that can suppress the occurrence of condensation.

[0006] As a result of diligent research to achieve the above-mentioned objectives, we have found that condensation is significantly observed in compositions containing gelatin and a stabilizer in an amount of 0.5% to 5% by mass relative to the total mass of the composition, and that the occurrence of condensation can be suppressed by including at least one of sugars and salts. Based on these findings, we have completed this disclosure. This disclosure encompasses the following:

[0007] <1> A gel-like composition comprising gelatin, a stabilizer, an aqueous medium, and at least one of 1% to 30% by mass of sugars and 250 mM (mol / l; the same applies hereinafter) to 2 M (mol / l; the same applies hereinafter) of salts, wherein the content of the stabilizer is 0.5% to 5% by mass of the total mass of the composition. <2> The gel-like composition according to <1>, wherein the content of the stabilizer is 1% to 5% by mass of the total mass of the composition. <3> The composition according to <1> or <2>, wherein the stabilizer is albumin. <4> The gel-like composition according to any one of <1> to <3>, wherein the composition does not contain the sugars and contains 250 mM to 2 M of the salt. <5> The gel-like composition according to any one of <1> to <3>, wherein the composition does not contain the salt and contains 1% to 30% by mass of the sugars based on the total mass of the composition. <6> The gel-like composition according to any one of <1> to <3>, wherein the composition contains 250 mM to 2 M of the salt and 1% to 30% by mass of the sugars relative to the total mass of the composition. <7> The gel-like composition according to any one of <1> to <6>, wherein the gelatin content is 0.1% to 10% by mass relative to the total mass of the composition. <8> A reagent comprising the gel-like composition according to any one of <1> to <7> and a container containing the composition. <9> The reagent according to <8>, wherein the composition is contained in an amount of 5% to 50% by volume relative to the capacity of the container. <10> The reagent according to <8>, further comprising a solid support contained in the container. <11> A method for storing a reagent, comprising a reagent preparation step of preparing the reagent according to any one of <8> to <10> and a storage step of storing the reagent obtained in the reagent preparation step. <12> The method for storing a reagent according to <11>, wherein the storage step is performed under temperature conditions of 2°C to 10°C.

[0008] According to the gel-like composition, reagent, and method for storing the reagent described herein, the occurrence of condensation can be suppressed.

[0009] The embodiments of this disclosure are described below. The description is illustrative and does not limit the scope of this disclosure.

[0010] In the following embodiments, the components (including elemental steps, etc.) are not essential unless otherwise explicitly stated. The same applies to numerical values ​​and their ranges, and these do not limit the disclosure. For example, the disclosure allows for additions, omissions, substitutions, and changes to numbers, quantities, locations, ratios, materials, compositions, types, and sequences, etc., without departing from the intent of the disclosure.

[0011] In this disclosure, numerical ranges indicated using "~" include the numbers before and after "~" as the minimum and maximum values, respectively. In numerical ranges described in stages in this disclosure, the upper or lower limit of one numerical range may be replaced with the upper or lower limit of another numerical range described in stages. Also, in numerical ranges described in this disclosure, the upper or lower limit of that numerical range may be replaced with the values ​​shown in the examples. In this disclosure, each component may contain multiple types of the corresponding substance. If multiple types of the substance corresponding to each component exist in the composition, the content or amount of each component means the total content or amount of the multiple types of substances present in the composition, unless otherwise specified. The term "process" in this specification includes not only independent processes but also processes that cannot be clearly distinguished from other processes, as long as the intended purpose of the process is achieved.

[0012] <Gel-like composition> The gel-like composition of this disclosure contains gelatin, a stabilizer, an aqueous medium, and at least one of sugars and salts at a concentration of 250 mM to 2 M relative to the total mass of the composition, wherein the content of the stabilizer is 0.5% to 5% relative to the total mass of the composition. In a composition containing gelatin and a stabilizer at a concentration of 0.5% to 5% relative to the total mass of the composition, condensation was significantly observed. However, by including at least one of sugars and salts at a concentration of 250 mM to 2 M relative to the total mass of the composition, the occurrence of condensation is suppressed.

[0013] The gel-like compositions of this disclosure are not particularly limited, but can be applied to immunoassay reagent compositions that include a solid support on which an antibody or antigen is immobilized as an immunoassay component. However, the gel-like compositions of this disclosure are not limited to immunoassay reagent compositions, but can be applied to a wide range of reagent compositions used in biochemical experiments, clinical trial compositions used in clinical trials, or disease treatment compositions used for the treatment of various diseases.

[0014] -Gelatin- In this disclosure, gelatin refers to the general term for water-soluble proteins obtained when collagen is treated with hot water. Gelatin is a heterogeneous substance, unlike a homogeneous substance consisting of a single molecule. One form of gelatin that can be used is gelatin derived from tissues such as the skin, bones, and tendons of animals such as cows and pigs, or gelatin derived from tissues such as the scales and skin of fish. In this disclosure, the gelatin may be manufactured from these tissues according to a standard method, or a commercially available product may be used. To manufacture gelatin, first, inorganic substances such as calcium phosphate contained in the above-mentioned tissues are removed using dilute hydrochloric acid. The resulting osein, mainly composed of collagen, is subjected to acid treatment or alkali treatment (also called lime treatment). After that, a gelatin solution is extracted from the treated material using hot water. Gelatin can be manufactured by purifying the obtained gelatin solution by filtration, ion exchange treatment, etc., concentrating it, and drying it. Examples of commercially available gelatin include GLS250 gelatin solution from Nitta Gelatin Co., Ltd., pigskin gelatin (Type A), bovine bone gelatin (Type B), and fish gelatin (Type A). Type A is prepared from ocene treated with acid, and Type B is prepared from ocene treated with alkali. The gel-like composition of this disclosure exhibits a gel-like state due to the aforementioned gelatin.

[0015] In this disclosure, in addition to gelatin prepared as described above or commercially available products, chemically modified gelatin derivatives may also be used, in which functional groups such as amino groups, imino groups, carboxyl groups, mercapto groups, and hydroxyl groups are introduced to gelatin using well-known methods.

[0016] In the compositions of this disclosure, the gelatin content is not particularly limited, but for example, it can be 0.1% by mass or more and 10% by mass or less based on the total mass of the composition, preferably 0.5% by mass or more and 8% by mass or less, and more preferably 1% by mass or more and 5% by mass or less. By setting the gelatin content of the composition within this range, the fluidity of the composition can be moderately reduced, preventing the composition from scattering and preventing it from adhering to the inner wall surface of the container even when vibration is applied while the composition is contained in a container.

[0017] -Stabilizer- In this disclosure, a stabilizer is a component for maintaining the activity of proteins such as antibodies, antigens, and enzymes contained in immunoassay reagents, clinical test reagents, therapeutic reagents, etc., using the composition of this disclosure. Examples of stabilizers include albumins such as bovine serum albumin (BSA), human serum albumin (HSA), chicken egg white-derived albumin, mouse serum-derived albumin, rat serum-derived albumin, porcine serum-derived albumin, and sheep serum-derived albumin, as well as caseins such as sodium caseinate and calcium caseinate. Albumin is preferred, and bovine serum albumin is more preferred.

[0018] In the compositions of this disclosure, the content of the stabilizer is 0.5% by mass or more and 5% by mass or less based on the total mass of the composition, and is particularly preferably 1% by mass or more and 5% by mass or less, and more preferably 1% by mass or more and 3% by mass or less. By setting the content of the stabilizer in the compositions of this disclosure to this range, the activity of proteins such as antibodies, antigens, and enzymes contained in immunoassay reagents, clinical test reagents, therapeutic reagents, etc. using the compositions of this disclosure can be maintained for a long period of time. In particular, even if the content of the stabilizer in the compositions of this disclosure is within this range, the occurrence of condensation can be suppressed.

[0019] -Aqueous Media- In this disclosure, the aqueous media is not particularly limited as long as the main component is water, and examples include aqueous solutions containing a buffering compound. "Aqueous" means that the main component is water, specifically that 50% by mass or more is water, preferably 55% by mass or more is water, more preferably 60% by mass or more is water, and even more preferably 65% ​​by mass or more is water. In other words, as long as it contains water within the above range, it is included in the aqueous media even if it contains other compounds (inorganic compounds and organic compounds). Specifically, examples of aqueous media include water, physiological saline, PBS, Tris-HCl, TBS, Good's buffer, etc. Examples of buffering agents included in Good's buffer include MES, Bis-Tris, ADA, PIPES, Bis-Tris-Propane, ACES, MOPS, MOPSO, BES, TES, HEPES, HEPPS, Tricinene, Bicine, and TAPS. The pH of the aqueous medium (25°C ± 1°C) is set appropriately depending on the type of buffering agent used, but is for example in the range of 5.5 to 11.1, preferably in the range of 5.5 to 9.0, and more preferably in the range of 6.0 to 7.5. pH is a value measured by a pH meter. The concentration of the buffering agent included in the aqueous medium is for example in the range of 10 mM to 1 M, preferably in the range of 20 mM to 500 mM, and more preferably in the range of 30 mM to 100 mM.

[0020] - Sugars - In this disclosure, sugars include monosaccharides, disaccharides, oligosaccharides, polysaccharides, and sugar derivatives. The compositions of this disclosure may contain at least one sugar selected from the group consisting of monosaccharides, disaccharides, oligosaccharides, polysaccharides, and sugar derivatives.

[0021] Examples of monosaccharides include tetrasaccharides such as erythrose, threose, and erythrulose; pentoses such as ribose, lyxose, xylose, arabinose, apiose, ribulose, and xylulose; hexoses such as allose, talose, gross, glucose, altrose, mannose, idose, galactose, psicose, fructose, sorbose, and tagatose; and heptoses such as sedoheptulose and coliose.

[0022] Examples of disaccharides include trehalose, isotrehalose, kordibiose, sophorose, nigerose, laminaribiose, maltose, cellobiose, isomaltose, gentibiose, lactose, sucrose, melibiose, palatinose, agarobiose, xylobiose, lactulose, and rutinose.

[0023] Examples of oligosaccharides include trisaccharides such as raffinose, gentianose, cellotriose, maltotriose, and melenitose; tetrasaccharides such as stachyose; and oligosaccharides such as xylooligosaccharides, isomaltoligosaccharides, gentiooligosaccharides, fructooligosaccharides, chitosan oligosaccharides, chitin oligosaccharides, and cellooligosaccharides.

[0024] Examples of polysaccharides include curdlan, cyclodextrin, pectin, starch, agarose, amylose, amylopectin, arabinan, arabinogalactan, alginic acid, inulin, galactan, xylan, chitin, chitosan, glycogen, glucomannan, keratan sulfate, colomic acid, cellulose, dextran, pectin, pectic acid, heparan sulfate, heparin, mannan, lichenan, levan, lentinan, etc. Examples of sugar derivatives include deoxy sugars such as deoxyribose, fucose, and rhamnose; uronic acids such as glucuronic acid, galaxuronic acid, iduronic acid, mannuronic acid, and guluronic acid; and amino sugars such as glucosamine, galactosamine, fucosamine, and mannosamine.

[0025] In this disclosure, the sugars are preferably one or more selected from the group consisting of monosaccharides and disaccharides, from the viewpoint of solubility in aqueous media, and among these, one or more selected from the group consisting of lactose, trehalose, sucrose, glucose and fructose are more preferred.

[0026] The sugar content in the composition of this disclosure is 1% by mass or more and 30% by mass or less of the total composition, but is preferably 1% by mass or more and 20% by mass or less, and more preferably 1% by mass or more and 10% by mass or less. When the composition of this disclosure contains sugars, the occurrence of condensation as described above can be suppressed by having a sugar content of 1% by mass or more. Furthermore, if the sugar content is too high, the viscosity of the solution will increase and crystals will be more likely to precipitate, so a sugar content of 30% by mass or less is advantageous in terms of solubility.

[0027] -Salt- In this disclosure, the salt may be either an inorganic salt or an organic salt, but an inorganic salt is particularly preferred. The inorganic salt is not particularly limited, but salts of mineral acids such as sulfuric acid, hydrochloric acid, and phosphoric acid, or salts of carbonate with alkali metals or alkaline earth metals are preferred. Specifically, examples include sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium sulfate, potassium sulfate, magnesium sulfate, calcium sulfate, sodium bisulfate, potassium bisulfate, monosodium phosphate, disodium phosphate, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, magnesium carbonate, calcium carbonate, etc. In particular, in the compositions of this disclosure, it is preferable to use at least one salt selected from the group consisting of sodium chloride, potassium chloride, magnesium chloride, and calcium chloride as the salt.

[0028] The salt content in the composition of this disclosure is 250 mM or more and 2 M or less relative to the total composition, but is preferably 250 mM or more and 1.5 M or less, and more preferably 300 mM or more and 1000 mM or less. When the composition of this disclosure contains salt, a salt content of 250 mM or more can suppress the occurrence of condensation as described above. Furthermore, if the salt content is too high, the viscosity of the solution increases and crystals are more likely to precipitate, so a salt content of 2 M or less is advantageous in terms of solubility.

[0029] - Sugars and Salts - The compositions of this disclosure may contain either the sugars and the salts described above, or both. That is, the compositions of this disclosure may contain no sugars from the sugars and salts described above, but contain 250 mM to 2 M of salt. Alternatively, the compositions of this disclosure may contain no salts from the sugars and salts described above, but contain 1% to 30% by mass of sugars based on the total mass of the composition. Furthermore, the compositions of this disclosure may contain 250 mM to 2 M of salt and 1% to 30% by mass of sugars based on the total mass of the composition. In particular, from the viewpoint of suppressing the occurrence of condensation described above, it is most preferable for the compositions of this disclosure to contain both the sugars and salts described above.

[0030] -Other Components- In addition to the gelatin, stabilizers, aqueous media, sugars, and salts described above, the compositions of this disclosure may contain various other components. For example, the compositions of this disclosure may include a solid support on which an antibody or antigen is immobilized as an immunoassay component. The solid support is not particularly limited, but particles are an example.

[0031] The particles are not particularly limited, and typical examples include glass beads, polystyrene beads, magnetic particles, microplates, and latex. Specifically, known magnetic silica particles used in immunoassays can be cited as examples of magnetic particles. Magnetic silica particles consist of a silica matrix in which a superparamagnetic metal oxide with an average particle size of 1 nm to 15 nm is dispersed. Examples of superparamagnetic metal oxides with an average particle size of 1 nm to 15 nm that exhibit superparamagnetism include oxides of iron, cobalt, nickel, and their alloys, but iron oxide is particularly preferred due to its excellent sensitivity to magnetic fields. One type of superparamagnetic metal oxide may be used alone, or two or more types may be used in combination.

[0032] The antigens are not particularly limited and specifically include antigens used in the following immunoassays. Antigens include nucleotide chains (oligonucleotide chains, polynucleotide chains); chromosomes; peptide chains (e.g., C-peptide, angiotensin I, etc.); proteins (e.g., procalcitonin, immunoglobulin A (IgA), immunoglobulin E (IgE), immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin D (IgD), β2-microglobulin, albumin, their degradation products, serum proteins such as ferritin); enzymes (e.g., amylase (e.g., pancreatic type, salivary gland type, type X, etc.)); Lucaly phosphatases (e.g., hepatic, ossicular, placental, small intestinal, etc.), acid phosphatases (e.g., PAP, etc.), γ-glutamyl transferases (e.g., renal, pancreatic, hepatic, etc.), lipases (e.g., pancreatic, gastric, etc.), creatine kinases (e.g., CK-1, CK-2, mCK, etc.), lactate dehydrogenases (e.g., LDH1-LDH5, etc.), glutamate oxaloacetate transaminases (e.g., ASTm, ASTs, etc.), glutamate pyruvate transaminases (e.g., ALTm, ALTs, etc.), choline esters [Enzymes (e.g., ChE1-ChE5, etc.), leucine aminopeptidases (e.g., C-LAP, AA, CAP, etc.), renin, protein kinases, tyrosine kinases, etc.) and inhibitors of these enzymes; hormones (e.g., PTH, TSH, insulin, LH, FSH, prolactin, etc.); receptors (e.g., receptors for estrogen, TSH, etc.); ligands (e.g., estrogen, TSH, etc.); bacteria (e.g., Mycobacterium tuberculosis, Streptococcus pneumoniae, Neisseria diphtheriae, Neisseria meningitidis, Neisseria gonorrhoeae, Staphylococcus aureus, Streptococcus, Enterobacteriaceae, Escherichia coli) Microorganisms such as Helicobacter pylori; viruses (e.g., rubella virus, herpesvirus, hepatitis virus, ATL virus, AIDS virus, influenza virus, adenovirus, enterovirus, poliovirus, EB virus, HAV, HBV, HCV, HIV, HTLV, etc.); fungi (e.g., Candida, Cryptococcus, etc.), spirochetes (e.g., Leptospira, Treponema pallidum, etc.); Chlamydia; microorganisms such as Mycoplasma; proteins or peptides or glycogen antigens derived from such microorganisms;Allergens that cause allergies such as bronchial asthma, allergic rhinitis, and atopic dermatitis (e.g., house dust, dust mites such as house dust mites and house dust mites, pollen from trees such as cedar, cypress, barnyard grass, ragweed, timothy grass, sweet vernal grass, and rye, animals such as cats, dogs, and crabs, foods such as rice and egg whites, fungi, insects, wood, drugs, chemicals, etc.); lipids (e.g., lipoproteins); proteases (e.g., trypsin, plasmin, serine proteases, etc.); tumor marker protein antigens (e.g., PSA, PGI, PGII, etc.); glycosylation antigens (e.g., AFP (e.g., L1 to L3, etc.), hCG (hCG family), transferrin, IgG, thyroglobulin, Decay-accelerating factor (DAF), carcinoembryonic antigens (e.g., etc.)); Examples include: CEA, NCA, NCA-2, NFA, etc.), CA19-9, PIVKA-II, CA125, prostate-specific antigen, tumor marker glycan antigens with special glycans produced by cancer cells, ABO glycan antigens, etc.; glycans (e.g., hyaluronic acid, β-glucan, glycans possessed by the above glycan antigens, etc.); proteins that bind to glycans (e.g., hyaluronic acid-binding protein, β-glucan-binding protein, etc.); phospholipids (e.g., cardiolipin, etc.); lipopolysaccharides (e.g., endotoxin, etc.); chemical substances (e.g., T3, T4, e.g., tributyltin, nonylphenol, 4-octylphenol, di-n-butyl phthalate, dicyclohexyl phthalate, benzophenone, octachlorostyrene, di-2-ethylhexyl phthalate, and other environmental hormones); various drugs administered or inoculated into the human body and their metabolites; aptamers; and nucleic acid-binding substances.

[0033] Antibodies are not particularly limited and specifically include antibodies used in immunoassays. Examples of antibodies include antibodies against proteins, antibodies against hormones, antibodies against peptide chains, antibodies against glycosylated antigens, and other antigens mentioned above. Antibodies also include proteolytic enzymes such as papain and pepsin, or degradation products such as Fab and F(ab')2 fragments produced by chemical degradation.

[0034] One method for immobilizing antigens or antibodies onto particles is to physically adsorb the antigens or antibodies onto the particles as described above. From the viewpoint of more efficiently immobilizing antigens or antibodies onto particles, it is preferable to bind at least one organic compound selected from the group consisting of glutaraldehyde, albumin, carbodiimide, streptavidin, biotin, and alkylalkoxysilane having a functional group to the surface of the particles and immobilize the antigens or antibodies via them.

[0035] In the compositions of this disclosure, the mass ratio of particles immobilized with antigens or antibodies is not particularly limited, but is preferably 0.0001% to 50% by mass, and particularly preferably 0.001% to 20% by mass, relative to the total mass of the composition. A mass ratio of 0.0001% by mass or more of the particles is preferable because it makes the particles easy to handle and improves workability. On the other hand, a mass ratio of 50% by mass or less of the particles is preferable because it provides sufficient stability.

[0036] The compositions of this disclosure may further contain chelating agents, surfactants, preservatives, etc., and may include sodium azide, glycerol, 2-mercaptoethanol, dithiothreitol, etc. Examples of chelating agents include ethylenediaminetetraacetic acid (EDTA), hydroxyethylethylenediaminetriacetic acid (HEDTA), dihydroxyethylethylenediaminediacetic acid (DHEDDA), diethylenetriaminepentaacetic acid (DTPA), and EDTA metal salts. Examples of surfactants include nonionic surfactants such as sorbitan fatty acid esters, glycerin fatty acid esters, decaglycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyethylene glycol fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene phytosterols, polyoxyethylene phytostanols, polyoxyethylene alkylphenyl ethers, polyoxyethylene castor oil, hydrogenated castor oil, and polyoxyethylene lanolin; anionic surfactants such as polyoxyethylene alkyl ether acetates and polyoxyethylene alkyl ether sulfates; and amphoteric surfactants such as betaine acetate. Examples of preservatives include sodium azide, salicylic acid, and benzoic acid.

[0037] <Reagents> The reagents of this disclosure include the composition of this disclosure described above and a container containing the composition. A commonly used glass or resin reagent container can be used as the container. Such resins may be either thermoplastic resins or thermosetting resins. Examples of thermoplastic resins include polyethylene, polypropylene, polystyrene, polymethyl methacrylate, polyvinyl chloride, polyethylene terephthalate, styrene-acrylonitrile copolymer, styrene-maleic anhydride copolymer, styrene-acrylic acid copolymer, styrene-methyl methacrylate copolymer, ethylene-propylene copolymer, ethylene-acrylic acid copolymer, and ethylene-acrylic acid ester copolymer. Examples of thermosetting resins include unsaturated polyester resins, epoxy resins, and epoxy-acrylate resins.

[0038] Such containers are not particularly limited, but examples include cryotubes (manufactured by Thermo Fisher Scientific K.K.), centrifuge tubes (manufactured by Corning International K.K.), microtubes (manufactured by Eppendorf K.K.), screw tubes (manufactured by Maruemu Co., Ltd.), and PCR tubes (manufactured by Nippon Genetics Co., Ltd.).

[0039] In the reagents of this disclosure, the composition described above is not particularly limited, but is preferably contained in an amount of 5% to 50% by volume relative to the volume of the container, more preferably 5% to 25% by volume, and even more preferably 5% to 10% by volume. In the reagents of this disclosure, when the amount of the composition contained is within the above range, the occurrence of condensation can be reliably suppressed.

[0040] In particular, the reagent of this disclosure preferably further comprises a solid support contained in a container. Examples of the solid support include the particles described above. That is, among the compositions of this disclosure, it is particularly preferable that the reagent of this disclosure comprises a composition containing a solid support such as particles contained in a container. In this case, because the composition of the reagent of this disclosure contains gelatin, the solid support such as particles can be prevented from adhering to the inner wall of the container due to vibration, and the occurrence of condensation as described above can be suppressed.

[0041] <Method for storing reagents> The method for storing reagents according to this disclosure includes a reagent preparation step of preparing the reagents described above, and a storage step of storing the reagents obtained in the reagent preparation step. According to the method for storing reagents according to this disclosure, the occurrence of condensation on the inner wall of the reagent container can be suppressed during the storage step. In the method for storing reagents according to this disclosure, the storage step may be the period from the completion of the reagent preparation step until the reagents reach the user. In addition, the storage step may also include the period until the user uses the reagents.

[0042] The specific period of the storage step is not particularly limited, but may be several months, 1 month, 2 weeks, 1 week, or 5 days counting from the end of the reagent preparation step. According to the reagent storage method of the present disclosure, the occurrence of condensation can be suppressed during these periods.

[0043] In the reagent storage method of the present disclosure, the temperature conditions for the storage step may be appropriately set according to the type of reagent and the like. For example, the temperature may be 2°C or higher and 10°C or lower, 2°C or higher and 8°C or lower, or 2°C or higher and 5°C or lower. According to the reagent storage method of the present disclosure, the occurrence of condensation can be suppressed even when the temperature condition during storage falls within this range.

[0044] In the reagent storage method of the present disclosure, the reagent preparation step refers to the step of producing the reagent of the present disclosure described above. Therefore, this reagent preparation step can also be referred to as a reagent production step. Specifically, in the reagent preparation step, the composition of the present disclosure described above is prepared, the obtained composition is dispensed into a container, and the container is sealed. To prepare the composition of the present disclosure, first, at least one selected from gelatin, a stabilizer, a saccharide and a salt is mixed into an aqueous medium, and if necessary, a solid phase carrier such as particles is dispersed therein. To dispense the obtained composition into a container, for example, a predetermined amount of the composition can be dispensed into the container using an automatic dispenser or the like.

[0045] Hereinafter, the present disclosure will be described in more detail by way of Examples, but the technical scope of the present disclosure is not limited to the following Examples.

[0046] [1. Preparation of gelatin-containing reagent] A solution containing bovine serum albumin (manufactured by Sigma-Aldrich Japan K.K.; a stabilizer), sodium chloride (manufactured by Fujifilm Wako Pure Chemical Corporation; a salt), lactose (manufactured by Fujifilm Wako Pure Chemical Corporation; a saccharide), and 3% by mass gelatin (manufactured by Nitta Gelatin Inc.; pig skin gelatin type A; gel-like gelatin) was prepared with 50 mM MES (manufactured by Dojindo Laboratories), followed by heating and dissolution at 37°C. Then, 40 µL of the obtained solution was placed in a 0.5 mL sample tube (manufactured by Eppendorf Co., Ltd.) and sealed.

[0047] Furthermore, the reagents of Examples 1 to 8 and the reagents of Comparative Examples 1 to 10 were prepared. All of these reagents commonly used MES as an aqueous medium and contained bovine serum albumin; the concentrations of 3% by mass gelatin, bovine serum albumin, sodium chloride and lactose were as shown in Table 1.

[0048] [2. Evaluation of Condensation After Refrigerated Storage] The reagents of Examples 1 to 8 and Comparative Examples 1 to 10 prepared in the above 1. were stored at 8°C for 4 weeks, and condensation formed on the inner wall of the sample tube was evaluated. Specifically, after storage as described above, condensation formed on the inner wall of the sample tube was wiped off with Kimwipes (manufactured by Nippon Paper Crecia Co., Ltd.), and the amount of condensation was calculated according to the following formula. Amount of condensation = {(mass of reagent before refrigerated storage − mass of reagent after refrigerated storage) / mass of reagent before refrigerated storage} × 100%

[0049] Condensation intensity (rated "-" to "+++") was evaluated based on the amount of condensation calculated by the above formula. When the amount of condensation calculated by the above formula was less than 0.1% by mass, the rating was "-"; when the amount of condensation was 0.1% by mass or more and less than 5% by mass, the rating was "+"; when the amount of condensation was 5% by mass or more and less than 10% by mass, the rating was "++"; when the amount of condensation was 10% by mass or more, the rating was "+++". For the reagents of Examples 1 to 8 and the reagents of Comparative Examples 1 to 10, the composition and the amount of condensation are summarized in Table 1.

[0050]

[0051] First, when comparing Comparative Example 1 and Comparative Example 9 among the results shown in Table 1, it was found that in a reagent containing gelatin in gel form, condensation occurs when bovine serum albumin accounts for 0.5% by mass relative to the total mass of the composition. Furthermore, when comparing Comparative Example 1 and Comparative Example 10, it was found that no condensation occurs in a reagent that does not contain gelatin in gel form. Furthermore, when comparing Comparative Example 1 and Comparative Example 5, it was found that the higher the concentration of bovine serum albumin, the more significant the occurrence of condensation. From these results, a novel finding was obtained that in a reagent containing gelatin in gel form, when the reagent contains 0.5% by mass or more of a stabilizer such as bovine serum albumin relative to the total mass of the composition, condensation occurs on the inner wall of the container.

[0052] Next, comparing the results shown in Table 1, Example 1 and Comparative Example 1 showed that condensation occurred in the reagent containing gelatin and a stabilizer such as bovine serum albumin at a concentration of 0.5% by mass or more relative to the total mass of the composition. However, it was found that the presence of 300 mM sodium chloride could suppress the occurrence of condensation. Furthermore, considering the results of Comparative Examples 2, 5, 6, 2, 3, and 4 comprehensively, it was found that the effect of sodium chloride in suppressing condensation is dependent on the sodium chloride concentration. These results indicate that the effect of suppressing condensation can be achieved when the sodium chloride concentration is between 250 mM and 2 M.

[0053] Next, comparing the results shown in Table 1, Example 5 and Comparative Example 1 showed that condensation occurred in the reagent containing gelatin and a stabilizer such as bovine serum albumin at a concentration of 0.5% by mass or more relative to the total mass of the composition. However, it was found that the occurrence of condensation could be suppressed by coexisting with 1% by mass of lactose relative to the total mass of the composition. Furthermore, considering the results of Comparative Examples 3, 7, 5, 6, and 7 comprehensively, it was found that the effect of lactose in suppressing condensation is dependent on the lactose concentration. These results indicate that the effect of suppressing condensation can be achieved when the lactose concentration is between 1% by mass and 30% by mass relative to the total mass of the composition.

[0054] Next, we compare Example 8 with Examples 2 and 6 from the results shown in Table 1. The reagent containing 300 mM sodium chloride but no lactose (Example 2) and the reagent containing 1% by mass lactose but no sodium chloride (Example 6) showed a "+" condensation intensity, whereas the reagent containing 300 mM sodium chloride and 1% by mass lactose (Example 8) showed a "-" condensation intensity. Considering these results along with the results of Comparative Examples 4 and 8, it became clear that a reagent containing 250 mM to 2 M sodium chloride and 1% to 30% by mass lactose relative to the total mass of the composition can more reliably suppress the occurrence of condensation.

[0055] The disclosure of Japanese Patent Application No. 2025-044033, filed on 18 March 2025, is incorporated herein by reference in its entirety. All documents, patent applications, and technical standards described herein are incorporated herein by reference to the same extent as if each individual document, patent application, and technical standard were specifically and individually noted to be incorporated by reference.

Claims

1. A gel-like composition containing gelatin, a stabilizer, an aqueous medium, and at least one of sugars and salts at a concentration of 250 mM to 2 M, in an amount of 1% to 30% by mass relative to the total mass of the composition, wherein the amount of the stabilizer is 0.5% to 5% by mass relative to the total mass of the composition.

2. The gel-like composition according to claim 1, wherein the content of the stabilizer is 1% by mass or more and 5% by mass or less based on the total mass of the composition.

3. The gel-like composition according to claim 1, wherein the stabilizing agent is albumin.

4. The gel-like composition according to claim 1, wherein the composition does not contain the sugars and contains the salt in an amount of 250 mM or more and 2 M or less.

5. The gel-like composition according to claim 1, wherein the composition does not contain the salt and contains 1% by mass or more and 30% by mass or less of the sugars based on the total mass of the composition.

6. The gel-like composition according to claim 1, wherein the composition contains 1% by mass or more and 30% by mass or less of the sugars based on the total mass of the salt (250 mM or more and 2 M) and the composition.

7. The gelatin content according to claim 1, wherein the gelatin content is 0.1% by mass or more and 10% by mass or less based on the total mass of the composition.

8. A reagent comprising a gel-like composition according to any one of claims 1 to 7, and a container containing the gel-like composition.

9. The reagent according to claim 8, wherein the gel-like composition is contained in an amount of 5% to 50% by volume relative to the volume of the container.

10. The reagent according to claim 8, further comprising a solid-phase support contained in the container.

11. A method for storing reagents, comprising: a reagent preparation step of preparing a reagent according to any one of claims 8 to 10; and a storage step of storing the reagent obtained in the reagent preparation step.

12. The method for storing reagents according to claim 11, wherein the storage step is performed under temperature conditions of 2°C to 10°C.

Images