JP5109918B2 - Multi-chamber formulation - Google Patents

Description

  The present invention relates to a multi-chamber container preparation, and more particularly to a multi-chamber container preparation in which a drug and a solution are separated and stored in order to dissolve and prepare an unstable drug in an aqueous solution in use.

  As a β-lactam antibiotic having an excellent antibacterial property, the following formula (1)

Is known, or a salt thereof (for example, hydrochloride).

  However, since cefotiam dihydrochloride (hereinafter abbreviated as cefotiam hydrochloride) is generally poor in stability in aqueous solution, it needs to be dissolved in a solvent such as water for injection at the time of injection administration. There was a fault that it was bad. For this reason, it takes time to dissolve, and even after dissolution, a uniform solution cannot be prepared. Therefore, when the solution is administered intramuscularly, necrosis, whitening, browning, bleeding of the administration site muscle cells There was a problem that local effects such as appeared. Therefore, a preparation with improved dissolution time and improved safety has been desired for many years.

  In order to solve these problems, by adding a non-toxic carbonate (for example, sodium carbonate) to cefotiam hydrochloride, carbon dioxide gas is generated when cefotiam hydrochloride is dissolved, and due to the stirring effect of the carbon dioxide gas, It has been practiced to reduce the dissolution rate of cefotiam hydrochloride and adjust the pH of the dissolved solution after dissolution (Japanese Patent Publication No. 56-36174). As such a preparation, a vial preparation and a multi-chamber container preparation are commercially available.

  In such a vial preparation, a preparation containing cefotiam hydrochloride and sodium carbonate is usually contained in the vial, and water for injection, physiological saline or glucose injection is injected into the vial before use, and cefotiam hydrochloride and carbonate carbonate are injected into the vial. Administered after dissolving sodium. The multi-chamber container preparation contains a medicine containing cefotiam hydrochloride and sodium carbonate in the first chamber, and a physiological saline solution or a glucose injection solution is contained in the second chamber partitioned by the isolation means capable of communicating with the first chamber. Etc. are accommodated. In the case where the first chamber and the second chamber are plastic bags, the first chamber and the second chamber are opened by communicating with each other by a predetermined method such as pressing the isolation means by hand. After cefotiam and sodium carbonate are dissolved in the physiological saline solution or glucose injection solution in the second chamber, an infusion channel is introduced from the discharge part at the bottom of the multi-chamber container to perform infusion.

  However, in the case of a multi-chamber container formulation including a plastic bag, the carbon dioxide gas generated from sodium carbonate excessively increases the pressure in the plastic container, which often makes it difficult to adjust the drip rate. Also, carbon dioxide gas bubbles may enter the drip flow path and further enter the blood vessel. For this reason, it is necessary for a medical worker to check the infusion rate frequently, or to start the infusion after sufficiently storing the chemical in the infusion tube of the infusion channel at the start of infusion. It was.

  In the clinical use of the multi-chamber container formulation, the generation of carbon dioxide gas has become a major problem in this way, in addition to cefotiam hydrochloride, carbonates such as imipenem / cilastatin sodium, ceftazidime, cefmenoxime hydrochloride, cefpyrom sulfate, etc. The same problem occurs in a multi-chamber container preparation containing bicarbonate, and a multi-chamber container preparation that does not generate carbon dioxide gas is desired.

International Publication No. 96/025136

  The problem of the present invention is that it takes time to dissolve a drug in a solution at the time of use, a multi-chamber container preparation in which the problem of generation of gas at the time of dissolution and a complicated process for the multi-chamber container are required. First, it is to provide a method for producing an engineering advantage.

  As a result of intensive studies to solve these problems, the present inventors have dissolved a drug such as cefotiam hydrochloride using a solution containing a pH adjusting agent without using carbonate and hydrogen carbonate. Has found that the dissolution time is shortened and the generation of gas is prevented, and the present invention has been achieved.

  That is, the present invention includes (1) a multi-chamber container preparation having at least two chambers partitioned by a separating means capable of communication, a first chamber containing a medicine not containing carbonate and bicarbonate, and pH adjustment A second chamber in which a solution containing the agent is stored, and the first chamber and the second chamber communicate with each other, whereby the solution stored in the second chamber is transferred to the first chamber and stored in the first chamber. A multi-chamber container preparation characterized in that the prepared medicine is easily dissolved in a solution, (2) a multi-chamber container preparation having at least two chambers partitioned by a separating means capable of communicating, and containing no carbonate And a second chamber containing a solution containing one or several compounds selected from the group consisting of inorganic salts, acids and bases, wherein the first chamber and the second chamber are By communicating, the solution contained in the second chamber is (1) The multi-chamber container preparation described in (1) above, in which the medicine contained in the first chamber is easily dissolved in the solution, and (3) has two chambers partitioned by a separating means that can communicate with each other. In the multi-chamber container preparation, the first chamber containing a drug that does not contain carbonate or hydrogen carbonate and that shows acidity in an aqueous solution, and a solution containing one or several basic compounds were contained. Including the second chamber, the first chamber and the second chamber communicate with each other, so that the solution stored in the second chamber is transferred to the first chamber, and the drug stored in the first chamber is easily transferred to the solution. A multi-chamber container preparation characterized by dissolving, (4) the above-mentioned agent that does not contain carbonate and bicarbonate and is acidic in an aqueous solution is an acid addition salt of β-lactam antibiotics (3) The multi-chamber container preparation according to (3), (5) the acid addition salt of the β-lactam antibiotic is (4) The multi-chamber container preparation according to (4) above, which is otiam, ceftazidime hydrochloride, cefmenoxime hydrochloride, cefpirome sulfate, or imipenem silastatin sodium, (6) does not contain the carbonate and bicarbonate, and exhibits acidity in an aqueous solution The multi-chamber container preparation according to (3) above, wherein the drug cefotiam hydrochloride is contained in the first chamber, and 0.05 to 0.72 g of disodium hydrogen phosphate is contained in the second chamber with respect to 1 g of cefotiam hydrochloride, (7) The multi-chamber container preparation according to (3), wherein at least one of the first chamber or the second chamber is a plastic bag, and (8) the multi-chamber container preparation is any of a double bag, a prefilled syringe, or a solution kit. The multi-chamber container preparation according to the above (3), having at least two chambers, and (9) at least two chambers partitioned by a separating means capable of communication, wherein the first chamber and the second chamber are In the method for producing a multi-chamber container preparation in which the solution stored in the second chamber is transferred to the first chamber by communicating and the drug stored in the first chamber is easily dissolved in the solution, the first chamber Is a method for producing a multi-chamber container preparation characterized in that a medicine containing no carbonate or bicarbonate is contained in the second chamber and a solution containing one or several kinds of pH adjusting agents is contained in the second chamber. .

  The multi-chamber container of the present invention is a container having at least two chambers partitioned by an isolating means that can communicate with each other. Specifically, the interior is called a double bag and is made of a plastic made up of a plurality of chambers partitioned by partition walls. A double bag (JP-A-8-215285, JP-A-8-257102, JP-A-8-280775, etc.) or a container containing a medicine and a container containing a solution can be communicated with each other. An integrated solution kit product (Japanese Patent No. 2551318, International Publication No. 96/25136, etc.) may be used. Furthermore, it may be a syringe (Japanese Patent Publication No. 32-8743, Japanese Patent No. 2642582, etc.) in which an interior called a double chamber type prefilled syringe is partitioned by a partition wall.

  The first chamber 1 and the second chamber 2 of the double bag (FIG. 1) are formed of, for example, a plastic sheet mainly composed of polyethylene, preferably made of aluminum foil laminate, polyethylene terephthalate and polyethylene. A plastic sheet is used. As the weak seal portion forming sheet, for example, a low-temperature softening plastic piece is used. The weak seal portion is formed by sandwiching between the plastic sheets forming the first chamber 1 and the second chamber 2 and heat-sealing. Is done.

  The lysate kit product includes, for example, a container in which a drug is sealed and a container in which a lysate is sealed connected by a connecting member including means for communicating the two containers (FIGS. 2 and 3), Alternatively, a plastic drug container and a plastic container in which a solution is sealed are directly joined and provided with isolation means (FIG. 4) capable of communicating with the joint. In the dissolution kit product shown in FIG. 2 or FIG. 3, the material used is not particularly limited as long as it is a material used for a normal medical infusion bag or the like. It is preferable that the container containing the dissolution liquid is made of plastic. In the solution kit product (PLW) shown in FIG. 4, the first chamber 1 and the second chamber 2 are not particularly limited as long as they are materials used for normal medical infusion bags, etc., but mainly polyethylene or polypropylene. It is preferable to use the following plastic. Moreover, the junction part of the 1st chamber 1 and the 2nd chamber 2 may be joined by the weak seal, for example.

  The prefilled syringe (FIG. 6) is usually formed by partitioning the first chamber 1 and the second chamber 2 with a gasket 81 in a cylindrical portion 8 made of polyolefin or glass.

  In the present invention, the communicating isolation means defines the inside of the multi-chamber container, and a mechanism in which the first chamber and the second chamber are communicated by a method such as applying an external force by an operator during use. It is. In the plastic double bag (FIG. 1), the separating means that can communicate with each other is that the weak seal forming sheet that partitions the first chamber 1 and the second chamber 2 presses the outer wall of the first chamber 1. It is a mechanism that peels and communicates between the two chambers.

  In the lysate kit product shown in FIG. 2, the isolation means capable of communicating is that the double-ended needle 41 is punctured into the first chamber 1 and the second chamber 2 by pushing down the upper end 42 while the second chamber 2 is fixed. This is a mechanism for communicating between the two chambers. Further, in the solution kit product shown in FIG. 3, the isolation means that can be communicated is that the double-ended needle 41 is punctured into the first chamber 1 and the second chamber 2 by rotating the rotating portion 43, and the two chambers are separated. This is a mechanism for communication. Further, in the dissolution kit product shown in FIGS. 4 and 5, the communicating isolation means is that the projecting piece 6 is rotated by rotating the cap member 7, and the notch 61 is a communication hole at the bottom of the first chamber 1. It is a mechanism that allows the two chambers to communicate with each other by being fitted to 15. In the prefilled syringe shown in FIG. 6, the isolation means that can communicate with each other is that when the plunger 82 is pushed in, the gasket 81 that divides the two chambers moves to the position of the injection groove 83, and further the plunger is pushed in, so that the second This is a mechanism for transferring the solution stored in the chamber 2 to the first chamber 1 through the injection groove 83. The multi-chamber container shown in FIGS. 1-6 shows an example of this invention, Comprising: This invention is not restrict | limited by these drawings.

  In the present invention, the pH adjuster is a compound that is added to the solution to keep the drug solution pH after dissolution at a constant value between about 2 and 8. Usually, when the drug is acidic, the pH adjuster is basic. When a compound is used and the drug is basic, an acidic compound is used as the pH adjuster. The basic compound used in the present invention is a compound that exhibits basicity in an aqueous solution, and examples thereof include basic inorganic salts other than carbonates and hydrogencarbonates, bases, and the like. The basic inorganic salt may be either a monoacid salt or a plurality of acid salts, preferably a salt such as an alkali metal or alkaline earth, and more preferably a salt such as sodium or potassium. The acid constituting the basic inorganic salt may be either a strong acid or a weak acid. Examples of the strong acid include phosphoric acid, sulfuric acid, hydrochloric acid, and the like. Examples of the weak acid include hydrogen phosphate, dihydrogen phosphate, and acetic acid. And boric acid. Specific examples of the basic inorganic salt include phosphates or hydrogen phosphates such as alkali metals and alkaline earths. Among these, sodium dihydrogen phosphate, trisodium phosphate, potassium dihydrogen phosphate, Etc. are preferable. Examples of the base include sodium hydroxide, potassium hydroxide, ammonia, sodium lactate, sodium acetate, potassium acetate and the like. Among these, it is particularly preferable to use sodium hydroxide and sodium acetate. The acidic compound used in the present invention is a compound that exhibits acidity (preferably, pH 5 or lower) in an aqueous solution, and examples thereof include acidic inorganic salts or acids other than carbonates and hydrogencarbonates. The acidic inorganic salt may be either a monoacid salt or a multiple acid salt, preferably a salt of an alkali metal, an alkaline earth, or the like, and more preferably a salt of sodium, potassium, or the like. The acid constituting the acidic inorganic salt may be either a strong acid or a weak acid. Examples of the strong acid include phosphoric acid, sulfuric acid, hydrochloric acid, and the like. Examples of the weak acid include hydrogen phosphate, dihydrogen phosphate, acetic acid, Examples include boric acid. Specific examples of the inorganic salt include hydrogen phosphates such as alkali metals and alkaline earths. Among these, disodium hydrogen phosphate, dipotassium hydrogen phosphate and the like are particularly preferable. Examples of the acid include organic acids such as citric acid, tartaric acid, lactic acid, and glacial acetic acid, and inorganic acids such as phosphoric acid, hydrochloric acid, sulfuric acid, dilute sulfuric acid, and boric acid. Among them, citric acid and hydrochloric acid are particularly used. It is preferable.

  In the present invention, the total amount of the pH adjusting agent is usually about 0.5 to 2.5 equivalents, preferably about 1 to 2 equivalents, per 1 equivalent of the drug. When the drug is cefotiam hydrochloride, the total amount of the pH adjusting agent relative to cefotiam hydrochloride is usually about 0.5 to 2.5 equivalents, preferably about 1 to 2 equivalents, with respect to 1 equivalent of the drug. That is, since 2 mol of hydrochloric acid is added to 1 mol of cefotiam in cefotiam hydrochloride, the monoacid base is about 2 to 4 mol per mol of cefotiam hydrochloride, and the diacid base is about 1 to 2 mol per mol of cefotiam hydrochloride. It is preferable to use moles. Furthermore, the pH adjuster for cefotiam hydrochloride preferably contains disodium hydrogen phosphate. In this case, the content of disodium hydrogen phosphate in the solution is usually 0.05 to 0.72 g per preparation.

  The solution used in the present invention is a solution in which the pH adjusting agent is dissolved in water for injection, physiological saline solution, 5% glucose injection solution or the like that is usually used as a solution for injection.

  Furthermore, the solution of the present invention contains a pH adjusting agent in an amount such that the pH value after dissolving the drug is about 2-8.

  In the present invention, the drug concentration after dissolution is generally preferably about 0.25 g titer / 100 mL to 10 g titer / 100 mL, and more preferably about 0.25 g titer / 100 mL to 1 g titer / 100 mL. It is. The cefotiam hydrochloride concentration after dissolution is preferably about 0.5 g titer / 100 mL to 2 g titer / 100 mL, and more preferably about 0.5 g titer / 100 mL to 1 g titer / 100 mL. That is, the volume of the solution is usually about 10 to 400 mL, preferably about 50 to 200 mL, more preferably about 100 mL with respect to about 1 g of drug titer.

  In addition to the acid or base usually used as a pH adjuster, the dissolution solution of the present invention can be used in addition to amino acids, ethanolamine, sodium chloride, sodium citrate, disodium succinate, diethanolamine, maltose. , Meglumine or the like may be added. Further, other appropriate additive components such as a stabilizer and a solubilizer may be added.

  In the present invention, in the first chamber, in addition to one or more drugs selected from the group consisting of cefotiam hydrochloride, imipenem / cilastatin sodium, ceftazidime, cefmenoxime hydrochloride, and cefpyrom sulfate, if necessary, the above inorganic Except for one or several compounds selected from salts, acids and salts, appropriate additive components such as commonly used pharmaceutical additives, ie, stabilizers, solubilizers, etc. may be added. However, the amount of these added components is limited to such an amount that does not deviate from the stable pH range of the drug after being dissolved in the dissolving solution.

  The multi-chamber container preparation containing no carbonate or bicarbonate of the present invention does not generate carbon dioxide gas even if the drug is dissolved by communicating the isolation means, and the drug is produced at a speed equal to or higher than that of the conventional product. Can be dissolved. In addition, an extremely clear solution without turbidity and coloration can be obtained. Bubbles are prevented from being mixed into the infusion channel into which the drug is introduced, and a chemical solution that is very safe for clinical use can be quickly prepared. In addition, it is known that carbonate generally reacts with calcium ions contained in infusions and the like to easily form a precipitate, but in the present invention, this precipitate does not form. Furthermore, since the drug and the pH adjuster are separately stored from production to just before use, there is no possibility that the drug reacts with the pH adjuster and decomposes or deteriorates. A long-term stable preparation can be obtained, storage management at a medical institution, etc. is easy, cost reduction, and convenience can be improved.

  Furthermore, the present invention makes it possible to adjust the pH more strictly, and it is possible to prevent vasculitis, vascular pain, and the like by bringing it closer to a physiological pH. Furthermore, in the preparation of the preparation, the conventional preparation had to be separately powdered aseptically with the powdered powder preparation and additives such as carbonate, and filled in each container. Since a step of aseptic powdering is not required, and a particularly complicated step is not required, a useful multi-chamber container preparation can be provided at a low cost. In addition, since the present invention does not generate gas and bubbles do not adhere to the wall of the multi-chamber container, it can be confirmed accurately that the drug has dissolved.

  The present invention will be specifically described below with reference to examples.

Example 1
As shown in FIG. 1 , a three-layered sheet (front sheet 13) in which the inner layer is polyethylene (hereinafter referred to as PE), the intermediate layer is silica-deposited polyethylene terephthalate, and the outer layer is PE, and the inner layer is polyethylene and the intermediate layer is aluminum. Foil, heat-sealing two sheets of a three-layer structure sheet (rear sheet 14) whose outer layer is polyethylene terephthalate, leaving a weak seal forming part, forming a bag-like container, and filled with 1 g of cefotiam hydrochloride, A weak seal portion forming sheet 31 is point-welded to the PE side of the rear sheet 14, and a front sheet is overlapped on this to seal a narrow belt-like portion having a width of about 5 mm on both side edges and the weak seal portion forming sheet. Chamber 1 (inner dimensions: 10 × 10 cm, capacity 30 mL) was formed.

  Separately, a weak seal portion forming sheet 32 is sandwiched between PE cylindrical sheets, the weak seal portion forming sheet protrudes about 5 mm from the cylindrical sheet, and the seal width is 5 mm above and below the weak seal portion forming sheet 32. Heat sealed so that it becomes narrower, 267 mg sodium hydroxide equivalent to twice the equivalent ratio to cefotiam hydrochloride is added to 100 mL of physiological saline, filled with the mixed solution, and then discharged to the open end of the cylindrical sheet 22 was inserted and heat-sealed to form a second chamber 2 (inner dimensions: 12 × 10 cm, capacity 130 mL).

  Next, the tubular sheet of the second chamber 2 is sandwiched between two unsealed plastic sheets of the first chamber 1 so that a part of the cylindrical sheet overlaps and heat-sealed. A chamber container preparation (inner dimensions: 22 cm × 20 cm) was obtained. In the connecting portion between the first chamber and the second chamber, the overlapping portion of the sheet in the first chamber 1 and the cylindrical sheet in the second chamber 2 is strongly sealed, but the sheets in the first chamber and the second chamber are weakly sealed. The sheet was weakly sealed with the part forming sheet and could be peeled off. The first chamber 1 contained a part (about 20 mL) of gas.

  (Example 2) In the same manner as in Example 1, 1 g of cefotiam hydrochloride was filled and sealed in the first chamber of the multi-chamber container, and 237 mg of disodium hydrogen phosphate equivalent to the same equivalent was added to 100 mL of physiological saline 100 ml of cefotiam hydrochloride. In addition, the mixed solution was filled and sealed in the second chamber to obtain a multi-chamber container preparation of the present invention.

(Example 3)
An aqueous solution containing 1 g of cefotiam hydrochloride was filled into a 20 mL vial (FIG. 4, first chamber 1) and freeze-dried, and then a rubber stopper was sealed to obtain a vial preparation. Separately, 237 mg of disodium hydrogen phosphate equivalent to 1 g of cefotiam hydrochloride is added to 100 mL of physiological saline, mixed, and then filled into a plastic bag (FIG. 2, second chamber 2). The second chamber was formed by welding. Finally, both were integrated by the connecting member 4 (FIG. 2) to obtain the multi-chamber container preparation of the present invention. At the time of use, by pushing down the upper end portion 42 of the coupling member 4, the double-ended needle 41 is punctured into the puncture portions 13 and 23 of each chamber, the two chambers are communicated, and the entire container is turned upside down, so that the second chamber The second solution was moved to the first chamber, and the cefotiam hydrochloride in the first chamber was dissolved.

(Experimental example 1)
Regarding the multi-chamber container preparation of the present invention (Example 1), its solubility and pH after dissolution are commercially available (1 g bag S for intravenous injection of pansporine (dissolved solution: physiological saline, manufactured by Takeda Pharmaceutical Co., Ltd.)) Compared with. That is, for each of the 6 preparations obtained in Example 1 and the commercial product, the outer wall of the first chamber of the double bag was pressed by hand, the weak seal was peeled off, and cefotiam hydrochloride was dissolved in the solution, The dissolution time and the pH after dissolution were measured. The determination of the end of dissolution was made visually. The results are shown in Table 1.

  As is apparent from Table 1, the multi-chamber container preparation of the present invention is dissolved in the same dissolution time as that of a commercial product containing sodium carbonate. Moreover, compared with the average pH 6.1 of a commercial item, the average pH of the product of the present invention is 6.5, which is closer to a physiological pH. This is because when a carbonate or bicarbonate is used as a pH adjuster, as in the case of a commercial product of this experimental example, it is alkaline for a drug that is stable in an acidic range, when left for a long time, or for changes in temperature. This is presumably because the pH needs to be adjusted to the acidic side to some extent from the physiological pH in consideration of the possibility of pH fluctuation to the side. Since the multi-chamber container preparation of the present invention does not use carbonate and bicarbonate, it can be adjusted to a pH value closer to a physiological pH value.

(Experimental example 2)
The stability of the cefotiam hydrochloride solution of the multi-chamber container formulation of the present invention (FIG. 1) was tested. That is, the first chamber 1 of the preparation obtained in Example 1 and a commercially available product (1 g bag S for intravenous injection of pansporin (dissolved solution: physiological saline, manufactured by Takeda Pharmaceutical Co., Ltd.)) was pressed by hand to separate the partition wall. 3 was opened, and 10 mL each of a solution in which cefotiam hydrochloride was dissolved in the dissolution solution and a solution in which the drug substance was dissolved in physiological saline were placed in a brown glass centrifuge tube, left at room temperature and 45 ° C. for 120 minutes, and HPLC The cefotiam hydrochloride concentration was calculated by the method, and the ratio to the cefotiam hydrochloride concentration at 0 hours was defined as the residual rate. The results are shown in Table 2.

  As is apparent from Table 2, Example 1 of the present invention obtained results comparable to those of commercially available products or drug substances in terms of drug stability after dissolution in the solution.

(Experimental example 3)
In the cefotiam hydrochloride multi-chamber container preparation of the present invention, the amount of gas generated after the isolation means was opened was compared with a commercially available product. That is, with respect to the preparation (FIG. 1) obtained in Example 1 and a commercially available product (1 g bag S for intravenous injection of pansporine (dissolved solution: physiological saline, manufactured by Takeda Pharmaceutical Co., Ltd.)), the gas in the container was syringed. The container was sealed and then sealed, and then the container was manually pressed from the outside to open the partition wall. After standing still for a while, the amount of gas generated was measured. The results are shown in Table 3. As a result of measuring the generated gas by gas chromatography, it was confirmed that it was carbon dioxide gas (FIG. 7).

It is a figure which shows an example of the multi-chamber container formulation of this invention. It is a figure which shows another example of the multi-chamber container formulation of this invention. It is a figure which shows another example of the multi-chamber container formulation of this invention. It is a figure which shows another example of the multi-chamber container formulation of this invention. It is explanatory drawing of the 1st chamber shown in FIG. It is a figure which shows another example of the multi-chamber container formulation of this invention. It is a gas chromatogram of Experimental example 3 of this invention.

Explanation of symbols

1. First chamber 11. Drug 12. Upper end 13. Puncture unit 14. 1. Communication hole Second chamber 21. Solution 22. Discharge unit 23. Puncture unit 31. Weak seal portion forming sheet 32. 3. Sheet for forming weak seal part Coupling member 41. Double-ended needle 42. Upper end 43. 4. Rotating unit 5. Container hanging part Protruding piece 61. Notch 7. Cap member 8. Cylindrical container 81. Gasket 82. Plunger 83. Injection groove

Claims (6)

In a multi-chamber container formulation having two chambers separated by means of isolation that can communicate, from the group consisting of cefotiam hydrochloride, ceftazidime hydrochloride, cefmenoxime hydrochloride, cefpirome sulfate, and imipenem silastatin sodium , which do not contain carbonate and bicarbonate A first chamber containing one selected β-lactam antibiotic , and one selected from the group consisting of sodium dihydrogen phosphate, trisodium phosphate, potassium dihydrogen phosphate, sodium hydroxide and sodium acetate Or a second chamber containing a solution containing a plurality of basic compounds , the first chamber and the second chamber communicating with each other, whereby the solution stored in the second chamber is transferred to the first chamber, A multi-chamber container preparation characterized in that the drug contained in the first chamber is easily dissolved in the solution. The multi-chamber container preparation according to claim 1, wherein the β-lactam antibiotic is cefotiam hydrochloride. The multi-chamber container preparation according to claim 1, wherein the basic compound is disodium hydrogen phosphate. The β-lactam antibiotic is cefotiam hydrochloride, the basic compound is disodium hydrogen phosphate, and contains 0.05 to 0.72 parts by weight of disodium hydrogen phosphate with respect to 1 part by weight of cefotiam hydrochloride. 2. The multi-chamber container preparation according to 1. The multi-chamber container preparation according to claim 1, wherein at least one of the first chamber or the second chamber is a plastic bag. The multi-chamber container preparation according to claim 1, wherein the multi-chamber container preparation has a form of any one of a double bag, a prefilled syringe, and a dissolution kit.

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