JP2001079087A - Holder of container for injecting highly viscous injection-and injection container - Google Patents

Abstract

PROBLEM TO BE SOLVED: To make the holder of an injection container attached to the leading end of a glass cartridge in order to connect an injection needle suitable for a highly viscous injection. SOLUTION: A lure lock hub 4 consisting of a needle attaching part 11 and the collar ring 12 surrounding the periphery of the needle attaching part 11 is protruded outwardly from the leading end of an injection container and the collar ring 12 is projected over length equal to or more than the protruding length of the needle attaching part 11 and a screw used for screwing the injection needle fitted in the needle attaching part 11 and screwing the cap covering the needle attaching part 11 before the fitting of the injection needle is provided to the inner peripheral surface of the collar ring 12.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a holder and a container for a high-viscosity injection liquid injection container most suitable for enclosing a solution of sodium hyaluronate having an average molecular weight of 1.5 to 3 million used in the medical field. About.

[0002]

2. Description of the Related Art Hyaluronic acid was obtained from Karl in 1934.
It was first isolated and named from bovine vitreous by Karl Meyer. Since then, its presence has been found widely in connective tissues of mammals, such as the vitreous of the eye, as well as in the umbilical cord, skin, blood vessels, tendons, synovial fluid, cartilage and cockscomb. It is also known that a microorganism of the genus Streptococcus, which is a kind of lactic acid bacterium, is produced.

[0003] Hyaluronic acid is composed of D-glucuronic acid and N-
It is a linear anionic polymer having acetyl-D-glucosamine as a constituent unit, and is a kind of typical glucosaminoglycan together with chondroitin sulfate, heparin, ketalan sulfate and the like.

However, other glycosaminoglycans have relatively low molecular weights of tens of thousands or less and have a sulfate group in the structure, whereas hyaluronic acid has only a sulfate group. Not having an average molecular weight of 200
It is a huge molecule of more than 10,000.

[0005] Accordingly, a characteristic difference is shown in comparison of the physical properties with other proteoglycans in terms of high viscoelasticity and water retention derived from it. In the joint,
It is thought that it forms a complex with protein or proteoglycan as a main component of the synovial fluid and exhibits specific viscoelasticity, and thus functions as a shock absorber for joint lubrication and mechanical shock.

[0006] Focusing on such features, the variation (Ba)
Lazs) proposed the application of hyaluronic acid to joint diseases such as traumatic arthritis and osteoarthritis in 1942. Further, in 1958, a study of the vitreous of the eye found that hyaluronic acid plays an important role in the maintenance and function of vitreous tissue, and proposed that it be used for vitreous humor replacement after retinal detachment surgery. Against this background, the application of hyaluronic acid to pharmaceuticals has been widely studied.
As a result, it is currently on the market as an adjuvant for ophthalmic surgery and as a treatment for osteoarthritis of the knee and periarthritis of the shoulder in the orthopedic field.

[0007]

When such a drug is supplied in an ampoule, it is necessary to use a syringe to suck the sodium hyaluronate injection solution in the ampoule and then inject it into the joint cavity. Is normal.

However, sodium hyaluronate having an average molecular weight of as much as 1.5 to 3 million, in particular, increases in viscosity as its concentration increases, and a solution filled in an ampoule like a usual injection solution is injected with a syringe. There is a problem that it is extremely difficult to aspirate. Even if the container is changed from an ampoule to a vial, the difficulty of suction is the same.

Further, in the ampule cutting operation, which is a problem peculiar to the ampule-containing injection, there is a possibility that glass fragments may be mixed into the solution at the time of ampule cutting.

On the other hand, in recent medical syringes, so-called disposable syringes are used in order to prevent virus or microbial infection via the syringe. Further, so-called kit products in which a drug solution is filled into a disposable syringe have been developed for the purpose of, for example, reducing the burden at the time of preparing a drug at a medical institution and preventing the contamination of bacteria and foreign substances.

As a sodium hyaluronate solution injection prepared by filling a sodium hyaluronate solution into an injection container, Alzdispo (manufactured by Seikagaku Corporation), Healon (manufactured by Pharmacia) and the like are known.

However, Artz Dispo has a low molecular weight of 600,000 to 1,200,000 as an average molecular weight of the filled sodium hyaluronate, and naturally has a low viscosity, and the performance of the injection container is more compatible with high molecular weight sodium hyaluronate. is not. Healon is a high molecular weight sodium hyaluronate (1.9 million to 3.9 million), which is used as a surgical aid in the ophthalmic field. The filling amount of sodium hyaluronate is as small as 0.4 ml, The amount of the drug solution used in the surgical field is insufficient. Therefore, injection containers are also compatible with small quantities.

[0013] In addition, as a disposable syringe for filling a drug solution, an injection tube described in Japanese Patent Publication No. 62-58745 is known. When a high-viscosity drug solution is filled, slipping of fingers and feeling of resistance during administration are inevitable. Furthermore, as with other disposable syringes, there is room for study on countermeasures against bacterial and viral contamination by contact when the injection needle is attached.

[0014]

Means for Solving the Problems The present inventors have solved the above-mentioned problems by using an average molecular weight of 15 used in the medical field.
We have developed a holder for an injection container suitable for a high viscosity injection solution such as a solution of 100,000 to 3,000,000 sodium hyaluronate and an injection container using the same.

That is, according to the present invention, outwardly from the tip,
A luer lock hub consisting of a needle mounting portion and a color ring surrounding the needle mounting portion protrudes, and a color ring surrounding the needle mounting portion of the luer lock hub is equal to or greater than the needle mounting portion. The present invention provides a holder for a container for injection of a high-viscosity injection solution, characterized in that the holder protrudes from the container.

In the holder for a container for injection of a high-viscosity injection solution according to the present invention, the inner peripheral surface of the collar is screwed with a needle to be fitted into the needle mounting portion, and the needle mounting portion before the fitting of the needle is inserted. It is preferable to include a screw used for screwing a cap covering the cover.

The present invention also provides a high-viscosity injection container characterized in that a holder for the high-viscosity injection container is attached to a tip of a glass cartridge for enclosing the high-viscosity injection solution. It also provides.

The above-mentioned container for injection of a high-viscosity injection solution of the present invention comprises:
The high-viscosity injection liquid enclosed in the glass cartridge is prepared by combining sodium hyaluronate having an average molecular weight of 1.5 to 3,000,000 obtained by the microorganism fermentation method with 0.75 to 1.25 W /
The preferred embodiment includes a solution prepared by dissolving in a dissolution solution for injection at a concentration of V%.

[0019]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be further described with reference to the drawings.

As shown in FIG. 1, the injection container enclosing the sodium hyaluronate solution includes a glass cartridge 1, a front rubber stopper 2, an end rubber stopper 3, a luer lock hub 4, a finger grip 5, and a plunger rod 6. , Holder 13 and cap 7.

The glass cartridge 1 is a transparent glass cylinder, and a luer lock hub 4 is attached to the tip end of the glass cartridge 1 by fitting and locking a holder 13. The luer lock hub 4 is made of a transparent synthetic resin. By being transparent, it is possible to easily confirm removal of air bubbles in the syringe, which is peculiar to a high viscosity injection solution.

FIG. 3 is an enlarged view of the luer lock hub 4 and the holder 13. The luer lock hub 4 includes a needle mounting portion 11 protruding outward and a collar ring 12 surrounding the needle mounting portion 11.

The needle mounting section 11 has a discharge port 8. The collar ring 12 is for protecting the needle mounting portion 11 and is equal to or more than the needle mounting portion 11, and a finger or other object touches the needle mounting portion 11 when mounting an injection needle at a medical site. This can prevent microbial and virus contamination. Also,
On the inner peripheral surface of the collar ring 12, a screw into which an injection needle (not shown) to be fitted into the needle mounting portion 11 is screwed is formed.

The holder 13 has an internal space capable of receiving the front rubber stopper 2, and a groove 9 communicating with the discharge port 8 is formed on the inner surface.

The cap 7 is attached to the coloring ring 12 so as to cover the needle mounting portion 11, so that contamination of the needle mounting portion 11 before use can be prevented.
The cap 7 is screwed into the collar ring 12. In addition, if the cap 7 is partially fused to the color ring 12 and the fused portion is broken so that the syringe can be opened, the re-capped syringe can be easily identified after opening, and the time after opening can be reduced. This is preferable because accidents caused by erroneous use of the used syringe or used syringe can be prevented.

On the rear end side of the glass cartridge 1, a finger grip 5 is fitted and locked. This finger grip 5 is enlarged as shown in FIG. 4, and the finger-holding surface (the surface on the side of the glass cartridge 1) is subjected to a non-slip process by providing fine ridges 10. This non-slip processing is for making it easier to push the plunger rod 6 at the time of administration of the enclosed sodium hyaluronate solution.

Inside the glass cartridge 1 on the tip side,
A front rubber stopper 2 slidable in the axial direction while being in close contact with the inner surface of the glass cartridge 1 is fitted. On the other hand, from the rear end side of the glass cartridge 1, an endless stopper 3 attached to the tip of the plunger rod 6 is fitted in close contact with the inner surface of the glass cartridge 1. By pressing the plunger rod 6, the end rubber stopper 3 is slidable in the axial direction while being in close contact with the inner surface of the glass cartridge 1.

A sodium hyaluronate solution is sealed between the front rubber stopper 2 and the end rubber stopper 3.

This sodium hyaluronate solution is prepared by adding sodium hyaluronate having an average molecular weight of 1.5 to 3,000,000 obtained by a microorganism fermentation method to 0.75 to 1.25 W /
It is a solution prepared by dissolving in a solution for injection such as water for injection or physiological saline at a concentration of V%.

The sodium hyaluronate solution sealed between the front rubber stopper 2 and the end rubber stopper 3 is pushed out and administered by pushing the plunger rod 6. That is, when the plunger rod 6 is pushed and the end rubber stopper 3 is advanced in a state where the cap 7 is removed and the injection needle is attached to the needle attachment part 8 at the medical site, the front rubber stopper 2 is thereby passed through the sodium hyaluronate solution. Is pushed, and the front rubber stopper 2 is pushed into the holder 13. Then, when a part of the groove 9 on the inner surface of the holder 13 is exposed to the sealing area of the sodium hyaluronate solution, the sodium hyaluronate solution is pushed out to the discharge port 8 through the groove 9.

In order to improve the slidability of the front rubber stopper 2 during administration of the above-mentioned sodium hyaluronate solution and reduce the burden on the fingers, as shown in FIG. The outer peripheral edge has a corner shape. For the same reason, the outer peripheral surfaces of the front rubber stopper 2 and the end rubber stopper 3 and the inner peripheral surface of the glass cartridge 1 are each coated with silicon.

[0032]

EXAMPLES Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited to these examples.

Example 1 (Actual Volume Deviation Test) The actual volume deviation test of the injection of the present invention as shown in FIG. 1 to FIG.
It carried out according to 3). According to this, more than 2 ml and 5
0.5 ml for viscous liquids for medicinal solutions with the indicated amount of
It is customary to add an excess of ml. In the case of the injection of the present invention, 0.25 ml as the injection of the indicated amount of 2.5 ml
An actual volume deviation test was performed when 2.75 ml was added to which the excess amount was added, and the accuracy of filling the injection container, which is a component of the present invention, was confirmed.

That is, sodium hyaluronate having an average molecular weight of 1.5 to 3,000,000 obtained by a microbial fermentation method is dissolved in physiological saline at a concentration of 1.0 W / V%, and is used as a constituent of the present invention for injection. Ten injections of the present invention, each filled with 2.75 ml in a container, were prepared so that they could be distinguished from each other. This injection was dried in a drier at about 60 ° C. and allowed to cool in a desiccator. The filled weight was measured precisely, and then the injection container was disassembled and the drug solution was washed out.
After the empty injection container was dried, it was allowed to cool in a desiccator.
The weight of the empty container was precisely measured, and the weight of the drug solution was calculated from the filled weight and the weight of the empty container to determine the actual volume deviation.

The density of sodium hyaluronate is 1.00
Since it was 8, it was converted to capacity using 1.0. Table 1 shows the results.

[0036]

[Table 1]

According to the Japanese Pharmacopoeia, the average actual volume of 10 pills is 107% or less of the sum of the indicated amount and the excess amount. It is also stated that the actual volume of each injection is not less than the indicated amount, and one or less than 115% of the sum of the indicated amount and the excess amount.

From the results of this example, the injection of the present invention passed the actual volume deviation test of the Japanese Pharmacopoeia.

Example 2 (Difference in Test and Pushing Method of Discharge Amount of Chemical Solution) As in Example 1, sodium hyaluronate having an average molecular weight of 1.5 to 3,000,000 obtained by a microbial fermentation method was used.
It was dissolved in physiological saline at a concentration of 1.0 W / V%, and 2.7 ml was filled into an injection container as a component of the present invention.
Fluctuation of the amount of the drug solution discharged from the filled injection container due to the difference in how the plunger was pushed was tested. As the injection needle, 21G11 / 2 (manufactured by Terumo Corporation) was used.

The test was carried out by changing the pushing method of the plunger 10 times by three persons each. The breakdown of the ten trials is as follows. 3 times: until the plunger is firmly stopped 3 times: until the plunger is weakly pressed 4 times: assuming a normal injection case

Table 2 shows the results.

With any pushing method, the indicated amount (2.5 ml) could be discharged with a 0.2 ml overfill amount.

[0043]

[Table 2]

Example 3 (Determination of chemical solution discharge and tester difference) As in Example 1, sodium hyaluronate having an average molecular weight of 1.5 to 3,000,000 obtained by the microbial fermentation method was used.
It was dissolved in physiological saline at a concentration of 1.0 W / V%, and 2.7 ml was filled into a syringe as a component of the present invention. Fluctuations of the amount of the drug solution discharged from the filled injection container due to the difference in the tester were tested. The injection needle is 21G1
1/2 (manufactured by Terumo Corporation) was used.

The test was performed three times by 10 persons each.

The plunger was pushed assuming a normal injection case. Table 3 shows the results.

[0047]

[Table 3]

Regardless of the tester's difference, the indicated amount (2.5 ml) could be discharged with a 0.2 ml overfill amount.

Example 4 (Sterility test) In the same manner as in Example 1, sodium hyaluronate having an average molecular weight of 1.5 to 3,000,000 obtained by the microbial fermentation method was used.
It was dissolved in physiological saline at a concentration of 1.0 W / V%, and 2.7 ml was filled into a syringe as a component of the present invention. Assuming a medical site, in a general laboratory, an injection needle was attached to the filled injection container, and then a sterility test was performed on the drug solution discharged in a clean bench. Needle 2
1G11 / 2 (manufactured by Terumo Corporation) was used. The sterility test is
Using the medium subjected to the medium performance test, a part of the test solution was directly added to the medium and cultured, and the presence or absence of viable bacteria in the test solution was measured.

For the bacterial test, thioglycolic acid medium I for sterility test was used, and for the fungal test, glucose for sterility test was used.
Peptone medium was used. Culture conditions are 30 for bacterial tests.
7 days at 32 ° C. and 10 days at 20-25 ° C. for fungal testing. Table 4 shows the results.

[0051]

[Table 4]

[0052] In the mounting of the injection needle in the general laboratory, sterility was ensured in all cases.

[0053]

According to the present invention, if a necessary amount of a hyaluronic acid solution is sealed in a container for injection provided with the holder of the present invention from the beginning,
This eliminates the need for an ampule cut operation and a suction operation of a drug into a syringe, and prevents the glass pieces from being mixed into the drug solution during ampule cutting or the contaminants from the outside air from being mixed into the sodium hyaluronate solution.

In addition, the injection container provided with the holder of the present invention can be used for filling a higher-molecular-weight sodium hyaluronate than the conventionally used injection container filled with sodium hyaluronate. However, there is a great advantage in that the configuration is such that operability is not impaired and contamination of microorganisms and viruses can be prevented.

[Brief description of the drawings]

FIG. 1 is a sectional view showing an example of an injection container provided with a holder of the present invention, with a partial front view left.

FIG. 2 is an enlarged sectional view of a front rubber stopper.

FIG. 3 is an enlarged sectional view of a luer lock hub and a holder.

FIG. 4 is an enlarged sectional view of a finger grip.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Glass cartridge 2 Front rubber stopper 3 End rubber stopper 4 Luer lock hub 5 Finger grip 6 Plunger rod 7 Cap 8 Discharge port 9 Groove 10 Convex stripe 11 Needle mounting part 12 Coloring 13 Holder

Claims (4)

[Claims] 1. A luer lock hub comprising a needle mounting portion and a color ring surrounding the needle mounting portion projects outward from the distal end, and a color ring surrounding the needle mounting portion of the luer lock hub. A holder for a container for injection of a high-viscosity injection solution, characterized in that the holder protrudes at least as much as the needle mounting portion. 2. An inner peripheral surface of the collar is provided with a screw used for screwing an injection needle fitted into the needle attachment portion and screwing a cap for covering the needle attachment portion before the injection needle is fitted. The holder for a container for injection of a high-viscosity injection solution according to claim 1, wherein: 3. A high-viscosity injection solution, wherein the holder for the high-viscosity injection solution container according to claim 1 is attached to a tip of a glass cartridge for enclosing the high-viscosity injection solution. Container. 4. A high-viscosity injection solution enclosed in a glass cartridge is prepared by using an average molecular weight of 15 obtained by a microorganism fermentation method.
100,000 to 3,000,000 sodium hyaluronate is added to 0.75
The high viscosity injection solution container according to claim 3, wherein the solution is a solution prepared by dissolving in a solution for injection at a concentration of ~ 1.25 W / V%.