JPH04246364A - Injection cylinder for two-layer type injector - Google Patents

Abstract

PURPOSE:To suppress the turbidity at the time of dissolving lyophilized powder with a soln. to the extent of having no troubles in use by providing a specific difference between the concn. of the silicone coatings of the coating layers applied on the inside wall of an injection cylinder with which a lyophilized liquid chemical comes into contact and the inside wall of the injection cylinder with which the liquid chemical does not substantially come into contact. CONSTITUTION:The coating layer subjected to a coating treatment with a silicone oil soln. having <=0.3% (W/V) concn. is formed on the inside wall part of the injection cylinder 3 with which the lyophilized liquid chemical comes into contact and the coating layer which is subjected to the coating treatment with the silicone oil soln. having >=1% (W/V) concn. is formed on the inside wall part of the injection cylinder 3 with which the liquid chemical does not substantially come into contact. A silicone oil which is dissolved in a liquefied gas, such as hydrocarbon fluoride, having high volatility is used for the silicone oil soln. The coating method includes a method for spraying the silicone oil soln., a method for sucking the soln. from an injection hole formed in the needle juncture 2 of the injection cylinder 3, a method for sinking the injection cylinder 3 into a silicone oil soln. tank, etc.

Description

[Detailed description of the invention]

0001

[Industrial Application Field] The present invention is characterized in that the lyophilized powder of a medicinal solution freeze-dried in the syringe and the solution are stored in the syringe in a separated state, and when used, the lyophilized powder and the solution are stored in the syringe. This invention relates to a syringe barrel of a two-layer syringe for mixing and preparing a solution with a solution and injecting the same, in which a step is provided in the silicon coating concentration on the inner wall of the syringe barrel so that turbidity does not occur during mixing and preparation. Specifically, a freeze-dried powder obtained by freeze-drying a drug solution in an inverted syringe barrel with the needle connection side facing downward is stored in the bottom of the syringe barrel, and the freeze-dried powder is stored at the bottom of the syringe barrel. The space is partitioned by a first elastic gasket inserted into the syringe barrel, and the solution of the freeze-dried powder is divided between the first gasket and a second elastic gasket inserted into the syringe barrel. It is stored between the
The syringe barrel of a two-layer syringe has a plunger rod attached to the second gasket, and the silicone coating concentration on the inner wall of the syringe barrel, which is in contact with the drug solution to be freeze-dried, is lowered, and the silicone coating on the inner wall of the syringe barrel, where the drug solution does not substantially come into contact with, is reduced. The present invention relates to a syringe having a coating concentration that is used for coating ordinary syringes.

0002

[Prior Art] There are various dosage forms of pharmaceuticals.
In the case of aqueous preparations such as injections, it is preferable to take the form of a final solution at the time of formulation, but some drugs are often unstable in a dissolved state. Therefore, in the case of such drugs, a method is generally used in which they are dissolved before use, that is, a method of dissolving them before use is used. Furthermore, some drugs may not be obtained as crystals or may have high hygroscopicity, and in such cases, drugs are often used in the form of lyophilized powder. In the case of injections, the commonly used method is to put freeze-dried powder into a vial or the like, dissolve it by injecting a solution, and suck it up with a syringe needle. However, it is more convenient to store the solution and the lyophilized powder in the syringe barrel from the beginning, and when using it during surgery, it is necessary to take into account keeping it in a sterile state. Therefore, there is a method in which the drug and solution are placed in the syringe from the beginning and dissolved in the syringe immediately before use. In other words, the drug in the form of freeze-dried powder is placed in the bottom of the syringe on the needle connection side. Put the drug solution into the side of the syringe where the plunger rod is attached, separate the drug storage part and the solution storage part in an appropriate way, and mix the solution and drug in an appropriate way to dissolve the drug. A method has been proposed to
992, JP-A-60-72561, Japanese Utility Model Publication No. 14465-1980, etc.).

0003

[Problems to be Solved by the Invention] However, freeze-dried powder tends to be charged with static electricity, and the amount is often very small, so it is difficult to accurately put it into a syringe barrel. Therefore, in order to improve these disadvantages, a method of performing freeze-drying within a syringe barrel may be considered. On the other hand, the inner wall of the syringe barrel is usually coated with a silicone oil solution having a concentration of 1 to 5% (W/V) in order to smooth the movement of the gasket and plunger rod. However, when a drug solution to be freeze-dried is placed in a silicone-coated syringe at the concentration mentioned above and the freeze-dried powder obtained by freeze-drying is dissolved in a solution, it becomes cloudy, making it unsuitable for use as a pharmaceutical product. There was a problem that disappeared. The purpose of the present invention is to apply a silicone coating to the inner wall of the syringe barrel to maintain smooth movement of the gasket and plunger rod, while also preventing turbidity from occurring when the freeze-dried powder is dissolved with a dissolving solution. The point is to suppress it to the extent that it does not exist.

0004

[Means for Solving the Problems] In order to achieve the above object, the present invention provides a freeze-dried powder obtained by freeze-drying a drug solution in an inverted syringe barrel with the needle connection side facing downward. The body is placed in the bottom of the syringe barrel, the storage space for the freeze-dried powder is partitioned off by a first elastic gasket inserted into the syringe barrel, and the solution of the freeze-dried powder is A syringe barrel of a two-layer syringe, which is stored between the first gasket and an elastic second gasket inserted into the syringe barrel, and further has a plunger rod attached to the second gasket, is freeze-dried. 0.3% (W/V) on the inner wall of the syringe barrel that is in contact with the drug solution.
The inner wall of the syringe barrel is coated with a silicone oil solution with a concentration of 1% (W/
V) A coating layer was formed by coating with a silicone oil solution having a concentration above.

[0005]

[Operation] As a result of various studies on the causes of turbidity when lyophilized powder is dissolved in a dissolving solution, it was found that the cause of turbidity was silicone coating. Therefore, we conducted extensive research on the silicone coating concentration that would not cause turbidity. Table 1 below shows the relationship between silicone oil solution concentration, turbidity, and sliding force obtained through experiments during the research process. As is clear from the results of this experiment, it has been found that substantially no turbidity occurs when the concentration is 0.3% (W/V) or less. Furthermore, even if the concentration of silicone coating is reduced in the area containing the drug solution to be freeze-dried, that is, the inner wall portion of the syringe barrel that comes into contact with the drug solution, there is virtually no effect on the movement of the gasket and plunger rod. I found it.

[0006]

[Effects of the Invention] Therefore, by providing the above-mentioned difference in the silicone coating concentration of the coating layer applied to the inner wall of the syringe barrel, the movement of the gasket and plunger rod can be maintained in a smooth state, while the syringe barrel can be maintained smoothly. It has become possible to suppress turbidity when the freeze-dried powder obtained by freeze-drying the drug solution and the solution are dissolved in the syringe barrel before use to a level that does not interfere with use.

[0007]

Embodiments Hereinafter, embodiments of the present invention will be explained based on the drawings. 1 to 4 show a two-layer syringe, in which an elastic tube is inserted into a cylindrical syringe barrel 3 with a needle connection 2 for the syringe needle 1 through an opening 3a formed at the other end of the syringe barrel 3. Two strong gaskets, a first gasket 4 and a second gasket 5, are slidably inserted. This first gasket 4
The second gasket 5 is made of a cylindrical halogenated butyl rubber having a diameter slightly larger than the inner diameter of the syringe 3, and when inserted into the syringe 3, there is a gap between the inner wall of the syringe 3 and the inner wall of the syringe 3. Configured to provide a fluid-tight seal. Two chambers 3A, 3 are partitioned in a fluid-tight manner by a first gasket 4 and a second gasket 5.
In B, the first chamber 3A located on the needle connection part 2 side contains freeze-dried powder a obtained by freeze-drying the drug solution in the syringe barrel 3 in an inverted position with the needle connection part 2 side facing downward. On the other hand, the second chamber 3B located on the opening 3a side stores a dissolving liquid b for dissolving the freeze-dried powder a. The second gasket 5 located on the opening 3a side of the syringe barrel 3 includes:
A plunger rod 6 for slidingly operating the second gasket 5 in the direction of the cylinder axis of the syringe barrel 3 is removably screwed and fixed to the tip of the plunger rod 6. A thumb rest 7 is formed that is flatter than the inner diameter. Further, a flange portion 8 projecting outward in the diametrical direction is integrally formed at the end of the outer circumferential surface of the syringe barrel 3 on the side of the opening 3a, and furthermore, at an intermediate portion of the syringe barrel 3 in the direction of the cylinder axis, A raised portion 3C that bulges outward in the radial direction is formed, and the first chamber 3A of the syringe barrel 3 is formed on the inner surface of the raised portion 3C.
A bypass passage 9 for communicating and connecting the second chamber 3B and the second chamber 3B is exposed. The length of this bypass passage 9 in the cylinder axis direction is:
The length of the first gasket 4 located on the side of the needle connection part 2 in the cylinder axis direction is slightly longer than that of the first gasket 4, and as shown in FIG. When located within the area, the solution b in the second chamber 3B is passed through the bypass passage 9 to the first chamber 3A.
It is designed to lead inward. Further, on the outer circumferential surface of the syringe barrel 3, a holder 10 made of synthetic resin is provided on a cylindrical portion located between the collar portion 8 and the raised portion 3C, which is detachably attached to the cylindrical portion. . This holder 10 is divided into two parts along an imaginary plane passing through the cylinder axis of the syringe barrel 3, and the end portion located on the opening 3a side of the syringe barrel 3 and the joint surface of the two divided holder parts 10A, 10B. Male and female connecting portions 10a and 10b, which elastically fit into each other from the diametrical direction of the syringe barrel 3, are integrally formed at each of two locations on the end portion located on the needle connecting portion 2 side. Also, at the end of the divided holder parts 10A and 10B of this holder 10 located on the opening 3a side of the syringe barrel 3, a pair of support pieces 11a and 11b that protrude outward in the diametrical direction than the collar part 8 is provided. On the other hand, the end portion located on the needle connecting portion 2 side has a shape that is similar to the support pieces 11a, 11b of the first finger hook portion 11 when viewed in the direction of the cylinder axis. A pair of support pieces 1 having the same shape
A second finger hook 12 consisting of 2a and 12b is integrally formed. Among the support pieces 11a and 11b of the first finger hook part 11,
A pair of semi-cylindrical portions 13A and 13B are integrally provided on the end face of the syringe barrel 3 located on the opening 3a side, and are enclosed in the collar portion 8. Furthermore, a plunger is provided in both semi-cylindrical portions 13A and 13B. A stopper 14 made of synthetic resin and externally wrapped around the rod 6 is fitted and held in a detachable manner from the direction of the axis of the cylinder. Further, a stopper 15 made of halogenated butyl rubber is inserted into the injection hole formed in the needle connection part 2 of the syringe barrel 3, which is pierced by the injection needle 1 attached to the needle connection part 2. In the two-layer syringe constructed in this manner, the inner wall portion of the syringe barrel 3 that comes into contact with the drug solution to be freeze-dried is coated with a silicone oil solution having a concentration of 0.3% (W/V) or less. On the other hand, a coating layer coated with a silicone oil solution having a concentration of 1% (W/V) or more is formed on the inner wall portion of the syringe barrel 3, which is not substantially in contact with the drug solution. There is. The silicone oil solution is prepared by dissolving silicone oil to a desired concentration in a highly volatile liquefied gas such as fluorocarbon (fluorocarbon). A specific example of the coating treatment method will be described in detail later, but as a general method for manufacturing the syringe barrel 3 of the present invention, first, the syringe barrel 3 is coated with a silicone oil solution having a concentration of 0.3% (W/V) or less. coating the entire inner wall of
Next, the inner wall part of the syringe barrel 3 other than the drug solution storage part was coated with 1% (W
/V) or more. Of course, only the inner wall portion of the syringe barrel 3 in the drug storage portion is coated with a silicone oil solution with a concentration of 0.3% (W/V) or less, and then the inner wall portion of the syringe barrel 3 other than the drug solution storage portion is coated with a silicone oil solution of 1% (W/V) or less. Although coating may be performed with a silicone oil solution having a concentration of W/V) or higher, the former method is simpler. In addition, as a coating method,
Examples include a method of spraying the silicone oil solution, a method of suctioning it from an injection hole formed in the needle connection part 2 of the syringe barrel 3, and a method of submerging the syringe barrel 3 in a silicone oil solution tank. Furthermore, the area to be coated with a silicone oil solution with a concentration of 0.3% (W/V) or less is the inner wall portion of the syringe barrel 3 that comes in contact with the drug solution to be freeze-dried; When the freeze-dried powder a obtained by freeze-drying and the solution b are dissolved in the syringe barrel 3 before use, if the turbidity does not interfere with use, the coating area will be in contact with the freeze-dried drug solution. It may be slightly smaller than the surface area of the inner wall of the cylinder 3. From a practical standpoint, it is preferable to coat the inner wall portion, including the inner wall portion where the chemical liquid may be scattered, with a silicone oil solution having a concentration of 0.3% (W/V) or less. With the needle connection part 2 of the syringe barrel 3 thus obtained facing down, the injection hole of the needle connection part 2 is inserted into the rubber stopper 15.
The syringe is sealed and inverted, and the drug solution is put into the syringe barrel 3 and freeze-dried. Next, after inserting the first gasket 4 into the syringe barrel 3, the solution b is added, and the upper end side is sealed with the second gasket 5. In use, the plunger rod 6 is attached to the second gasket 5, and the injection needle 1 is attached to the needle connection part 2 of the syringe barrel 3. Of course, plunger rod 6
may be attached to the second gasket 5 from the beginning. Next, a specific example of the coating method will be described. [First Example] As shown in FIGS. 5A and 5B, the syringe barrel 3 was placed upside down with the needle connection part 2 on top, and in this state it was inserted through the opening 3a. Using the nozzle 16, a silicone oil solution with a concentration of 0.1% (W/V) [silicone oil (SH-200 manufactured by Toray Dow Corning Co., Ltd.)
A solution prepared by dissolving Freon 113 (using Freon TF manufactured by Mitsui-DuPont Fluorochemicals)]
Apply by spraying. Next, a nozzle 18 with a partition 17 at the tip so that the solution does not come into contact with the liquid to be freeze-dried is inserted through the opening 3a of the syringe barrel 3, and a silicone oil solution with a concentration of 3% (W/V) ( A 0.1% solution (prepared in the same manner as the 0.1% solution) is applied to the inner wall portion of the syringe barrel 3 that is not substantially in contact with the drug solution, and then dried. [Second embodiment] As shown in (a) and (b) of FIG.
．． In a tank 19 containing a silicone oil solution with a concentration of 1% (W/V) (prepared in the same manner as in the first embodiment),
Slightly sink the syringe barrel 3 in an inverted position with the needle connection part 2 on top, and draw suction through the injection hole formed in the needle connection part 2 of the syringe barrel 3 to the needle connection part 2 inside the syringe barrel 3. The silicone oil solution in the tank 19 is pumped up to the maximum level. Next, the tank 19 is
% (W/V) of silicone oil solution (the first
After replacing the syringe barrel 3 with the tank 20 containing the syringe (prepared in the same manner as in the example) and slightly submerging the syringe barrel 3 in an inverted position with its needle connection portion 2 facing upward, the needle connection portion 2 of the syringe barrel 3 is formed. Aspirate from the injection hole. At this time, the silicone oil solution in the tank 20 is pumped up to just before the part that comes into contact with the chemical solution to be freeze-dried, while the pumping position is detected by the optical sensor 21, and then the syringe barrel 3 is taken out from the tank 20 and subjected to drying processing. Next, the inventor conducted an experiment to show the relationship between the concentration of silicone oil solution, turbidity, and sliding force. In this experiment, a 10% aqueous solution of mannitol was used as an example of the chemical liquid to be freeze-dried, and purified water was used as an example of the solution. Further, the needle connection part 2 of the syringe barrel 3 prepared by the method of the first embodiment or the second embodiment is sealed with a rubber cover, and the syringe barrel 3 is held upside down with the needle connection part 2 facing down. Add a 10% aqueous solution of mannitol and freeze-dry. Next, a first gasket 4 made of halogenated butyl rubber is attached to the inside of the syringe barrel 3, purified water is added, a second gasket 5 made of halogenated butyl rubber is attached, and 10% of mannitol is added.
% aqueous solution and purified water were prepared. Then, the degree of turbidity generated when the freeze-dried powder of a 10% aqueous solution of mannitol was dissolved in purified water, and the resistance force (sliding force) when pushing down the plunger rod 6 were investigated. The experimental results are shown in Table 1.

[0008]

[Table 1]

[0009] In the table, in the degree of turbidity, "-" indicates that no turbidity is observed, "+" indicates that turbidity has occurred, and "±" indicates a state that does not pose a problem in actual use. shows. In the sliding force, "-" indicates that the plunger rod 6 is pushed down smoothly, "+" indicates that the resistance is large, and "±" indicates a resistance that does not pose a problem in actual use. From this experimental result, the chemical contact area was reduced to 0.3% (
Silicon coating is applied at a concentration of 1% (W/V) or lower, and the non-contact area is coated with silicon at a concentration of 1% (W/V) or higher, preferably 1 to 1% (W/V).
When silicon coating is applied at a concentration of 5% (W/V),
It has been found that the syringe barrel 3 which is the object of the present invention can be obtained.

[Other Examples] ■ In the above-mentioned example, the silicon coating concentration on the inner wall of the syringe barrel 3 that comes into contact with the drug solution was specified to be 0.3% (W/V) or less, but if the amount of the drug solution is small In some cases, even without silicone coating, there is virtually no impediment to the movement of the gaskets 4, 5 and the plunger rod 6. In other words, 0.3% (W/V
) shall include 0%. (2) Application of the syringe barrel 3 of the present invention is not limited by the type of medicinal solution, but can be applied to all medicinal solutions that are used after being freeze-dried. ■ In the above example, silicone oil was added to liquefied gas such as fluorocarbon (fluorocarbon) to create a silicone oil solution with a predetermined concentration. However, instead of using fluorocarbon, silicone oil was added to water. A suspended product may also be used. Furthermore, the silicone oil to be used is not particularly limited as long as it can be applied to the inside of the syringe, and examples include dimethylpolysiloxane and cyclic polydimethylsiloxane. ■ In the above embodiment, the solution in the second chamber 3B is guided to the freeze-dried powder in the first chamber 3A through the bypass channel 9 provided in the syringe barrel 3, but the first gasket 4
It may be implemented by providing a valve structure for guiding the solution in the second chamber 3B to the freeze-dried powder in the first chamber 3A during the pushing operation of the plunger rod 6. In short, any structure may be used as long as it can guide the solution in the second chamber 3B to the freeze-dried powder in the first chamber 3A during the pushing operation of the plunger rod 6. (2) Of course, the present invention can also be applied to a syringe barrel of a two-layer syringe that does not have the holder 10 and stopper 14 described in the above embodiments. Further, the shapes, materials, dimensions, etc. of the syringe barrel 3, both gaskets 4 and 5, and the plunger rod 6 can be changed in various ways depending on the conditions of use.

[0011] Note that although reference numerals are written in the claims for convenience of comparison with the drawings, the present invention is not limited to the structure of the accompanying drawings by such entry.

[Brief explanation of the drawing]

FIG. 1 is a cross-sectional side view showing a two-layer syringe of the present invention.

[Figure 2
】Cross-sectional side view showing the process of mixing freeze-dried powder and solution

[Figure 3] Overall perspective view

[Figure 4] Overall exploded perspective view

[Fig. 5] (A) and (B) are explanatory diagrams showing the first embodiment of the silicon coating treatment method.

[Fig. 6] (A) and (B) are explanatory diagrams showing a second embodiment of the silicon coating treatment method.

[Explanation of symbols]

2. Syringe needle connection part 3. Syringe barrel 4 First gasket 5 Second gasket 6 Plunger rod a Freeze-dried powder b Dissolution solution

Claims (1)

[Claims] Claim 1: Freeze-dried powder (a) obtained by freeze-drying a drug solution in a syringe barrel (3) in an inverted position with the syringe needle connection part (2) side facing downward. ), and the storage space for this freeze-dried powder (a) is
The lyophilized powder (
The solution (b) of a) is stored between the first gasket (4) and an elastic second gasket (5) inserted into the syringe barrel (3), and gasket(
5) is a double-layered syringe barrel with a plunger rod (6) attached to the inner wall of the syringe barrel (3), which is in contact with the drug solution to be freeze-dried, with a concentration of 0.3% (W/V) or less. A coating layer coated with a silicone oil solution having a concentration of 1% (W/V) or more is formed on the inner wall of the syringe barrel (3), which is not substantially in contact with the drug solution. A syringe barrel of a double-layered syringe.