JP3319777B2 - Aseptic preparation method and device for intravenously administered drug solution - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a sterile regulating process of dilution or intravenous drug solution intravenous drug product solution, and an apparatus using this method. The invention is particularly directed to injecting a drug solution for intravenous administration into a medium for intravenous administration without using a needle.
On the adjustment process of the intravenous drug solution.

[0002]

BACKGROUND OF THE INVENTION Many drugs need to be liquid or diluted in an intravenous vehicle before they can be administered to a patient. These drugs are generally emergency drugs that need to be infused directly into the patient's vein to achieve the desired pharmacological effect. For example, it may be necessary to dilute the solution to obtain the required pharmacological composition (ie, steady state plasma levels, etc.) or to reduce the potential toxic effects of the drug. This means that cytotoxic drugs (mostly
This is particularly true if the injection is made without prior dilution, which can cause significant venous damage).

[0003] Potentially dangerous drugs are preferably brought into solution under the direct control of a hospital pharmacy. The solution is administered at the pharmacy and then administered to the patient.

[0004] The chemicals to be diluted are usually supplied in glass bottles or ampoules with rubber stoppers. They may be in the form of a dry powder or a concentrated liquid. These chemicals come from a variety of sources and vary in size,
Colors, dosages, qualities, additives, etc. also vary. The most standard vehicles for intravenous administration used for solubilizing or diluting drugs are 5% dextrose solution and 0.9% saline solution, the latter commonly called saline. .

These vehicles for intravenous administration are packaged in rigid containers such as glass bottles, semi-rigid containers made of plastic such as polypropylene, or collapsible soft containers made of, for example, polyvinyl chloride (PVC). You may.

Conventional techniques of dry chemical is prepared for intravenous administration drug solution initially comprising the step of injecting a portion of the intravenous medium in the ampoule. This step is called re-solution, since the powder form of the drug may be by lyophilization. Intravenous medium used in this re-solutionizing is to intravenous administration for medium final dilution is carried out may be taken from a container being enclosed, it is taken from another container Good
Or it may be taken from an ampoule.

First, a syringe is filled with a medium for intravenous administration , and then the needle of the syringe is pierced through a rubber stopper of the medicine container, and the medium for intravenous administration is introduced into the medicine container through the syringe.

[0008] The requirements that syringes, needles, and luer containers must meet are specified in a number of standards, particularly the ISO. These standards describe the specification of luer connectors that must be fully and leak-proof compatible with male and female connectors, for example, because they are attached to needles and syringes.

In general, a needle--a material used for re-solution as well as a material used for injection of a patient--is provided with a female luer connector. Therefore, a male luer or luer lock connector is usually attached to the syringe. Usually, a luer lock connector is preferred for emergencies. There are several patents for luer connectors; for example, US Patents 4,639,019 and 4,45.
2,473.

After mixing and dissolving the powders in the medicine container,
The solution is sucked back into the syringe, into a container for intravenous administration medium is already contained, is injected by a syringe through an addition hole, Ru diluted.

In the case of diluting the medicines contained in the ampoule, the medicines are shipped in the form of a solution, so that re-solution is generally unnecessary. The drug solution can be drawn directly into the syringe by breaking the neck of the ampoule and subsequently introduced into the intravenous administration medium through the addition hole of the container. Some dosage required for the patient for the desired pharmacological effect, part of the ampoule <br/> contents thereof, may require the entire amount, or the contents of one or more ampoules. In some cases, the container containing the intravenously administered drug solution must be pierced more than once to introduce the required dose into the container.

Usually, glass bottles and semi-rigid containers have only one injection hole made of a rubber stopper. Flexible containers, such as those made in Abbott, Baxter, McGow, USA or NPBI in the Netherlands, have two fill holes. One of these injection holes is for adding a drug to the intravenous administration medium . These injection holes usually consist of a rubber membrane separated from the intravenously administered drug solution by a PVC membrane. PVC film protects the intravenous drug solution from the components that may be leaking from the rubber contaminate intravenous drug solution. In addition, the PVC membrane protects the IV solution from particles that may be released from the rubber. It is desirable that these rubber films pass through the needle only once. if,
If the needle accidentally passes through the same location more than once, there is likely to be a leak at that location. Therefore, manufacturers usually
Unless absolutely necessary, he advises not to pass the needle through the rubber membrane more than once. The inner diameter of the needle used for diluting the chemical solution is moderate. That is, it cannot be too small or too large. The needle is the smallest diameter part in this system and also the main stenosis, so the smaller the needle, the more effort is needed by the person performing the dilution . However, the larger the needle diameter, the greater the damage to the rubber film. In addition, when the needle is larger, the chance of the rubber film coming out of the rubber film increases.

[0013] However, rubber particles in intravenous drug solution that has been diluted, unacceptable from a medical point of view. In short, the larger needle is more convenient, but requires less effort to perform the dilution, or occurred leaking from the injection hole of the container at the same time, the opportunity to rubber particles are mixed into the intravenous drug solution increases.

[0014] After dilution, the container is tested for particle matter and leakage. If there is a leak, the container is discarded.
Labeled tension packaged in a container, carry it to the ward, where after setting the dosing apparatus to the inspection, intravenous drug solution is administered to the patient.

There are several dangers associated with diluting or resolubilizing drugs. It derives from the fact that some drugs are extremely toxic, even in small quantities and are toxic if exposed for extended periods of time. This is especially true for cytotoxic drugs used to treat cancer. Most of them are themselves carcinogenic. Therefore, care is taken in hospitals to avoid inadvertent contact with these drugs. Spills, leaks and sprays are particularly problematic.

To avoid inadvertent contact, most hospitals have strict prescriptions, for example, based on guidelines set by the American Association of Hospital Pharmacists, or based on local rules or regulations. . In general, their prescriptions are based on special rules for working in special (vertical laminar flow) chambers with air filtration, wearing special protective clothing, and waste products and re-solutions , dilutions and waste generated from dilution. Become.

Spills, leaks and sprays may occur during dilution , transport to wards, administration to patients, and due to waste. This is particularly problematic in the process of dilution since the addition of the drug solution to the drip solution is performed with a needle. The needle penetrates the rubber and PVC membrane of the injection hole of the container. When the needle is removed from the container, there is often some leakage. This means that the closing of the rubber film is based on purely physical processes, unlike chemical processes. Thus, at the moment the needle is removed, a thin capillary remains in the membrane where the needle penetrated.

[0018] Typically, in these capillaries, derived from the outside of the needle, the liquid that may contain drug products slightly remains. Since the capillary is thin, if such pressure in the vessel for the volume of the added into the container drug product solution is increased, in particular, the liquid is sometimes slightly leak. Spray particles may be formed by increasing the pressure.

It is important, however, that the rubber breaks and the membrane breaks and remains in the container , which may leak from the container not only during dilution , but also during transport or administration in a ward. It is to recognize that there is not. Static in a soft container
The use of a needle to add a drug solution to a medium for intravenous administration can also break the container by accident, but is particularly dangerous because the entire drug may spill into the LAF chamber.

Another disadvantage with the use of needles is that the small inner diameter requires labor during dilution of the drug. Using a needle is awkward for the operator, especially when a large volume of chemical solution has to be injected. Finally, another disadvantage of this method is that the PVC membrane is perforated during the dilution and the intravenous
Administered drug solution and the rubber is that the direct contact. vein
It inner administered drug solution may be contaminated by the components in the rubber, or rubber might absorb chemicals or components intravenous drug solution in the opposite.

Several systems have been developed to improve the dilution of drug solutions in intravenous vehicles . For example, several types of two-point needles, commonly referred to as transfer needles, have been developed. Regarding this needle and the dilution process using this needle, for example, US Pat.
56.

US Pat. No. 4,614,267 describes a dedicated system in which a dedicated vial containing a drug solution is screwed into a container with an intravenous administration medium . US Patent 4,9
The 97,430, vein in the chemical liquid and the container in the chemical liquid bottle
Devices and connectors for direct connection of the internal administration media are described.

However, these systems generally have poor applicability. According to them, using one Tsunokusuri product solution containing the contents of the bottle and one intravenous medium containing vessel contents
Dilution is performed. Thus, these systems can only produce a fixed dose and a constant concentration of diluent drug solution.

However, for many drugs, especially cytotoxic drugs, the dosage must be determined based on the weight and / or skin condition of the patient. For that, a flexible rare
A release system is required, in which case the dosage and concentration of the drug must be easily adjusted to the patient's requirements while reducing the chance of spills, leaks, spray droplets, etc.

[0025]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a vehicle for intravenous administration of an arbitrary amount of a drug solution which overcomes many of the disadvantages of the above-described dilution method.
A method and apparatus for diluting with the body .

In particular, it is an object of the present invention to provide a method and apparatus for performing dilution without the use of needles or rubber dosing holes.

These and other objects, which will become apparent hereinafter, are contained in a foldable plastic container.
In a sterile intravenous administration medium
And by injecting an intravenous drug solution is, in a sterile preparation of intravenous drug solution, a collapsible plastic container fitted with a female luer connector or luer-lock connector via a seal capable of tubes, male
Using a syringe fitted with a luer connector, by connecting the male luer connector and the female luer connector or luer-lock connector, and connect the syringe and the tube, while it connects the male luer connector and the female luer connector or luer-lock connector ,
Inject the drug solution for intravenous administration in the syringe through the tube into the intravenous administration medium in the container, and then inject the tube .
Form a sealed part between the syringe and the container, and make the sealed part into two
Seal the tube by cutting and place the syringe in the container
And a method for aseptically preparing a drug solution for intravenous administration characterized by comprising the steps of:

[0028] Furthermore, the above object of the present invention, in a sterile intravenous device including a collapsible plastic container sterile static <br/> vein administration medium are enclosed, in the container
Against the connection has been sealed can of the tube, the female luer connector disposed on the upper Symbol tube or luer lock connectionist
It includes a coater, and intravenous drug product solution is encapsulated
The male luer connector and a female that came in to have a syringe
By connecting a luer connector or luer lock connector , it can be directly connected to the syringe
This is achieved by an intravenous administration device.

The drug product solution containing a syringe having a male luer connector that is connected to the female luer connector of the container is also part of the present invention.

According to a feature of the invention, the sealing of the tube is to cut the seal into two parts, thereby sealing the tube and separating the syringe from the container.

The disconnect connector may be connected to the syringe by integrating it with the female luer connector, or by placing it along the tube between the female luer connector and the container, or by placing it at the junction between the tube and the container. It is arranged in a liquid flow passage between the containers.

[0032] A clamp can be placed on the tube to block the flow in the tube. Alternatively, or in addition, a one-way valve (one-way check valve) can be attached to the tube so that liquid flow is only in the direction of the container. By covering the female luer connector, accidental touching and contamination can be prevented.

In the present invention, a foldable plastic container containing a medium for intravenous administration is used, to which a female luer connector or a luer lock connector is attached via a sealable tube. The luer connector, male luer connector of the dissolved drug product solution containing the syringe is connected directly to the container, in order that there is no need to use a needle chemicals liquid for injection into infusate. After injecting the drug solution into the container, the tube is sealed to provide a sealed intravenous drug solution .

[0034]

FIG. 1 shows a container with three injection holes.
The first injection hole is provided with a filling tube 2 and is used by the manufacturer to fill the intravenous administration medium 9.
This filling tube is sealed after completion of filling. The second injection hole has a dosing hole 3. This injection hole is a twisted administration hole. However, the administration hole may be in a known form, and is not particularly limited to the configuration shown in the drawing. The plug of the injection hole shown can be removed by twisting the upper wing.

After removing the plug, it can be used to connect the dosing device to the container . Through this injection hole, intravenously
The administered drug solution can be administered to the patient.

The third injection hole is provided with a tube 4, and further connected to a female luer connector 5 with a lid 6 and a disconnecting connector 7. The tube 4 is made of a sealable plastic material, for example PVC or polyethylene. The length of the tube must be small enough to be sealed, at least 2 cm, but is preferably as short as possible to minimize wasted space in the tube and avoid packaging problems.

The female luer connector 5 must conform to ISO standards, regional standards, etc., in order to tightly join the male luer connector or luer lock connector of the syringe. The female luer connector 5 is provided with a lid 6 to prevent accidental touching and contamination during use. In this embodiment, the luer connector 5 is integrated with a disconnect connector 7 as a means for blocking the tube. However, disconnect connector 7, the liquid flow
It may be anywhere in the passage and need not necessarily be integral with the female luer connector.

For example, FIG. 6 shows a disconnecting connector 7 housed in a tube 4 'at the joint with the container 1'.
It is shown. Or also disconnecting connector 7 "
May be located in the tube 4 "between the female luer connector 5 and the container 1. In each case, the disconnect connector will allow the solution in the container to escape through the luer connector prior to receiving the drug. The disconnecting connector may have a sleeve 7IV that couples to the tube or forms part of a luer connector, and a pin 7 "" which, when folded, opens the disconnecting connector. This pin can be bent by bending a tube or the like.

As can be seen from FIG. 4, after the contents of the syringe have been transferred, the tube 4 is sealed by being crushed and closed by a heat seal at 4a, cut at 4b, and sealed at 4b.
Form c.

In some applications, the one-way valve 8 is
It may be desirable to be between the lure connector 5 and the lure connector 5. The valve 8 allows the liquid flowing to the container to pass, but prevents the liquid from leaking from the container. For example, this valve, capacity
Prevent liquid leakage when removing the syringe from the container . this is,
It becomes necessary in the case of transferring one worth more than the contents of the syringe into the container. For the same purpose, a sliding clamp 10 (FIG. 8) is also used to temporarily block the tube.

FIG. 2 shows a container having two injection holes. The first injection hole has a dosing hole as shown in FIG. 1, while the second dosing hole has a tube with a female luer connector and a disconnect connector. The container is injected intravenously through the first injection hole.
The administration medium can be filled and twisted for sealing, or the intravenous administration medium can be filled through the second administration hole and sealed with a luer connector during the production.

FIG. 3 shows an intravenous administration container with only one injection hole. Capacity through the tube during manufacture
Fill the container with the liquid and attach the luer connector to the tube after filling. After diluting the chemical solution and sealing the tube,
Connect the intravenous device aseptically into tubes, veins
The drug solution for internal administration is administered to the patient. Methods for making aseptic connections are described in several patents. Equipment for aseptic connection is marketed in the United States by Hemonetics.

[0043] Generally, the filling, as long as necessary functions such as dilution and intravenous drug solution administered is executable, the combination of injection holes in the container may be that it would anything.

When the drug is a dry powder, a certain amount of the medium for intravenous administration is first introduced into the drug container or bottle using a syringe and a needle and dissolved therein, as described above. This stillness
The vehicle for intravenous administration may be taken from the container or ampoule containing the vehicle for intravenous administration . Also, by connecting the syringe to the luer connector, breaking the disconnecting connector and removing the intravenous administration medium from the container,
The medium for intravenous administration can be removed from the container of the present invention. Before disconnecting the syringe, the tube can be temporarily clamped off.

[0045] If it is necessary to use a needle, after dissolution, the blotted medicine products <br/> liquid into the syringe, connecting it directly to the female luer connector of the container with a male luer connector. Discard the needle. From beating disconnect connector, thoroughly mixed with the drug product solution in the infusion solution. After mixing
Seal the tube. Depending on the material of the tube, for example,
The tube can be sealed using one of several techniques, such as heat sealing or RF melting. This sealing can be performed using a standard device marketed in the United States by Sebra Corporation or the like.

The sealing portion can be cut from the center. Some of the original tube remains attached to infusion containers intravenous drug solution-filled, while another part is a female luer connector - remain attached to the side of the syringe. After separating the seal, both ends are blocked. The part attached to the syringe side can be discarded.

[0047] In the case of the ampoule and went into the bottle dissolving drug product solution, it can be used for dilution without dissolving process the same way.

[0048] Alternatively, the tube is not sealed.
During transport to the ward, and during the administration of intravenous drug solution to a patient, the syringe remains firmly attached to the infusion container.

The container tube, when sealed after dilution, as already mentioned, connected to the dosing device and the tube by an aseptic connection technology, to perform intravenous drug solution administered to the patient Can also be used. The dispensing device may be a standard one, equipped with a drip chamber or the like, or may be simply a tube for carrying the solution in a piggy bag manner with a standard intravenous drug administration device. .

The method of the present invention has several advantages over the conventional method of using a needle to introduce a drug solution into a medium for intravenous administration .

[0051] In this method, to fast because it is possible to connect the syringe and the container directly, it is convenient and safe. Because the needle is not used at all, so much the need without the pressure to inject the chemical liquid to the container, it is easy to fast to dilute. Also, as is often the case with soft containers when performing dilution with a needle, there is no chance that the container will be punctured. Needles are not stabbed by humans.

Furthermore, the chemical does not come into contact with the rubber film at any stage of the dilution , transportation or administration process. Thus, intravenous drug solution to will not be contaminated by rubber, nor rubber absorbs components from intravenous drug solution. Further, rubber is lost by omission mind rubber film, nor intravenous drug solution from being contaminated by the rubber particles.

However, the main advantage of this method is that the container is once again closed since the female luer connector is sealed after dilution . The membrane does not leak or drip with holes. This is a significant difference compared to the conventional method in which intravenous products delivered to a hospital are used in a ward with a needle passed through a rubber membrane.

Therefore, by performing dilution using the method of the present invention, chances such as leakage and spraying of aerosol generated when handling dangerous dilution in a hospital are reduced.

FIG. 9 shows a luer connector, that is, a male luer connector, for any of the ones shown in FIGS.
The structure of a syringe that is also attached to the female luer connector of the container is shown. However, in FIG. 9, the syringe solution has been injected into the container, and the syringe body 12 and the plunger 13 are visible.

[Brief description of the drawings]

[Figure 1] intravenous administration with a female luer connector
The side view of a container shows the state where the cap was removed.

FIG. 2 is a view similar to FIG. 1, but showing another embodiment of the present invention.

FIG. 3 is yet another view of a container showing an embodiment of the present invention.

FIG. 4 shows the sealing of a tube according to the invention.

FIG. 5 shows a sealed tube.

FIG. 6 is a diagram showing an arrangement of a disconnecting connector in a connection portion between a tube and a container .

FIG. 7 is a side view of a tube incorporating a disconnecting connector.

FIG. 8 is a perspective view showing a pinch clamp used in the tube shown in FIGS.

FIG. 9 is a partial structural view showing mounting of the syringe shown in FIGS.

[Explanation of symbols]

1: Intravenous container for administration 2: Filling tube 3: Administration hole 4: Tube 5: female luer connector 6: Lid 7: Disconnect Connector 7IV: Sleeve 8: one way valve 9: Intravenous administration medium 10: Clamp 11: Male luer connector 12: Syringe 13: Plunger

Continuation of the front page (56) References US Pat. No. 4,336,802 (US, A) French Patent Application Publication No. 659395 (FR, A1) British Patent Application Publication No. 1428373 (GB, A) (58) Fields Inquired (Int. Cl. ⁷ , DB name) A61J 3/00 312

Claims (9)

(57) [Claims] Claims 1. A wrapped plastic container containing
In a sterile intravenous administration medium
By injecting the intravenous drug solution are, in a sterile preparation of intravenous drug solution, a collapsible plastic container fitted with a female luer connector or luer-lock connector via a seal capable of tubing, the male luer connector Siri attached
Using the Nji, by connecting the male luer connector and the female luer connector or luer-lock connector, and connect the syringe and the tube, while it connects the male luer connector and the female luer connector or luer-lock connector, the vein in the syringe
Intravenous administration of drug solution for internal administration through a tube in a container
Injection medium , and then form a seal between the tube syringe and the container
And, to seal the tube by cutting the sealing portion into two, separating the syringe from the container, sterile adjustment <br/> preparation of intravenous chemical solution, comprising the steps. 2. A sterile intravenous administration medium is contained therein.
Sterile intravenous administration device including foldable plastic container
In, a sealable tube connected to the container, a female luer connector disposed on the tube or
A luer lock connector, has a, to accessory to a syringe for intravenous administration drug solution is contained
Male luer connector and female luer connector or lure
By connecting to the lock connector,
Intravenous characterized by being directly connectable to the
Dosing device. 3. The apparatus according to claim 1, further comprising a liquid between the syringe and the container.
Claim: Includes a disconnect connector located in the flow passage.
3. The sterile intravenous administration device according to 2. 4. The method according to claim 1 , wherein said disconnecting connector is a female arco.
Connector or luer lock connector
The sterile intravenous administration device according to claim 3. 5. The method according to claim 1 , wherein the disconnecting connector is a female arco.
Tube between the connector or luer lock connector and the container
4. The sterile vein of claim 3, wherein the vein is located along a vein.
Internal administration device. 6. The container according to claim 6, wherein said disconnecting connector comprises a container and a tube.
4. The aseptic bacterium of claim 3, wherein the germ is located at the junction of the lobes.
Intravenous administration device. 7. The apparatus according to claim 1, further comprising :
3. The aseptic as claimed in claim 2, comprising a clamp for cutting.
Intravenous administration device. 8. The apparatus according to claim 1, further comprising :
3. A one-way valve for passing only the liquid flow of
A sterile intravenous administration device according to the above. 9. The device according to claim 9, further comprising a female luer connector.
Is accidentally touched on the luer lock connector and becomes contaminated
3. The sterile device according to claim 2, further comprising a cap for preventing bleeding.
Intravenous administration device.