JPH11262514A - Bicarbonate containing chemical container package and carbon dioxide gas partial pressure controlling agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a bicarbonate containing chemical container package which is stable in long-team preservation and of a comparatively low price. SOLUTION: This bicarbonate containing chemical container has a water vapor and gas permeable plastic container 1 filled with a bicarbonate containing liquid chemical 3 and a water vapor and gas hardly permeable plastic package 2 to pack this container 1, and has the carbon dioxide gas partial pressure controlling agent 4, and, if necessary, carbon dioxide gas or carbon dioxide gas containing gas in the space between the plastic container 1 and the plastic package 2.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a chemical liquid container package capable of stably storing a liquid preparation containing bicarbonate for a long period of time.

[0002]

2. Description of the Related Art Usually, many drugs, except for very limited ones such as sodium chloride, are unstable against a temporal load of water, oxygen, light, etc. Glass containers have been used since ancient times. However, recently, due to the development of pharmacology, container materials, manufacturing methods, manufacturing machines, and the like, the use of plastic containers that are easy for industrial waste disposal and easy for medical staff to use has been increasing.

However, when the above-mentioned plastic container is used as a container for containing a preparation containing bicarbonate,
It has the following disadvantages.

[0004] Bicarbonate generates water and carbon dioxide gas over time to produce carbonate. In a closed system such as a glass ampoule, bicarbonate, carbonate, water and carbon dioxide gas are expressed by the following formula. It is known that the equilibrium relationship is maintained.

[0005]

Embedded image

On the other hand, when the above-mentioned preparation containing bicarbonate is filled in a plastic container usually used for medical treatment, the plastic container easily transmits carbon dioxide gas and water vapor, so that the plastic container is generated from bicarbonate. The generated carbon dioxide gas and water (steam) evaporate out of the container through the container wall. Therefore, the equilibrium relationship of the above formula (1) is such that carbonates are generated by tilting to the right side, and the original purpose of the compounding cannot be achieved, or the pH of the drug solution after dissolving the powder formulation increases, resulting in the stability of the drug. There are adverse effects such as impairing the properties.

[0007] International Publication No. WO 94/16663 discloses, in order to solve the above-mentioned problem, to provide (1) carbonic acid in the space between a plastic container filled with a powder preparation containing bicarbonate and a plastic packaging material containing the same. Filling with gas, (2) the presence of a carbon dioxide generating type deoxidizing material,
(3) A technique is described which employs at least one means of causing a desiccant in which carbon dioxide is saturatedly adsorbed. However, this method is intended only for a powder preparation containing bicarbonate, and does not describe any method for stabilizing a liquid preparation containing bicarbonate.

On the other hand, there is also a need for a liquid preparation which is sealed under aseptic conditions from the viewpoint of hygiene such as prevention of contamination during preparation.
Among them, a liquid preparation containing a bicarbonate, for example, a sodium hydrogen carbonate aqueous solution has a disadvantage that it is decomposed to generate carbon dioxide gas, and the pH of the preparation rises. With respect to a package for stabilizing such a bicarbonate-containing liquid preparation, a plastic container is accommodated or packaged in a gas-impermeable secondary packaging material, and a space between the container and the secondary packaging material is provided. (Japanese Patent Application Laid-Open Nos. 5-49675, 5-261141, and 6-339512) have also been developed. This technique suppresses the progress of the reversible decomposition reaction of the bicarbonate-containing liquid preparation by forming a carbon dioxide atmosphere in the space, thereby suppressing the increase in the pH of the liquid preparation (that is, stabilization). It is intended.

[0009] However, according to the above-mentioned technology, there is a possibility that slow gas permeation from the secondary packaging material may occur in the case of long-term storage and the like, and a secondary packaging material having a high barrier performance may be used. Such secondary packaging materials are expensive and their types are limited. Furthermore, in order to improve the impact resistance and reduce the occurrence of pinholes, it is necessary to increase the thickness of the packaging material.However, thickening an expensive material is more economically disadvantageous and is not practical. is there.

In the above-mentioned Japanese Patent Application Laid-Open No. 5-49675, a carbon dioxide-generating type oxygen absorber is present in the space between the plastic container and the secondary packaging material, and the oxygen in the space and the container is converted into carbon dioxide. A technique is also described in which the carbon dioxide is converted and dissolved in the liquid preparation to lower the pH of the liquid preparation. However, the carbon dioxide generating type oxygen scavenger has a disadvantage that it is expensive. In addition, when using a carbon dioxide-generating type oxygen absorber, water and oxygen are required for a reaction to generate carbon dioxide, but in such a case, if a secondary packaging material having a barrier performance not so high is used, It is difficult to sufficiently achieve the effect of using an oxygen scavenger. That is, in general, a film having a low barrier performance has higher permeability of carbon dioxide gas than oxygen, and even when a carbon dioxide-generating type oxygen absorber is used, oxygen is substantially removed from the outside of the secondary packaging material. It is difficult to enter, and there is not much oxygen inside the secondary packaging material, and as a result, there is not much reaction for generating carbon dioxide gas, and the effect of increasing the carbon dioxide gas concentration in the space cannot be sufficiently exhibited. . Therefore, it is difficult to say that even the method disclosed in this publication sufficiently solves the above-mentioned adverse effects.

[0011]

SUMMARY OF THE INVENTION An object of the present invention is to provide a bicarbonate-containing chemical liquid container package which solves the above-mentioned problems, is stable for long-term storage, and is relatively inexpensive. I do.

[0012]

That is, the present invention provides a steam and gas permeable plastic container filled with a liquid preparation containing bicarbonate, and a steam and gas permeable plastic packaging material containing the container. In the space between the plastic container and the plastic packaging material, a carbon dioxide partial pressure control agent having carbon dioxide adsorbed in advance and, if necessary, carbon dioxide or a carbon dioxide-containing gas are present. The present invention relates to a bicarbonate-containing chemical solution container package.

According to the chemical liquid container package of the present invention, the carbon dioxide partial pressure control agent is present in the space between the container and the packaging material,
The control agent can release carbon dioxide gas to increase the concentration of carbon dioxide gas in the container, thereby suppressing the decomposition of bicarbonate in the liquid preparation, and achieving the original purpose of HCO containing bicarbonate. ^3- supply can be achieved. Also,
By suppressing the decomposition of bicarbonate, an increase in the pH of the liquid preparation can be suppressed, and the liquid preparation becomes stable even after long-term storage.

Further, the carbon dioxide partial pressure control agent used in the present invention does not require water and oxygen in the space to increase the carbon dioxide gas concentration, unlike the case where a carbon dioxide generating type oxygen scavenger is used. Therefore, unlike the case where a carbon dioxide-generating type oxygen scavenger is used, even if a material having a medium gas barrier property is used as a packaging material, the concentration of carbon dioxide in the container can be increased. Materials with medium gas barrier properties are inexpensive compared to high performance materials with high gas barrier properties, so even if the thickness is increased to reduce pinholes and the impact resistance is improved, Is economically advantageous.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION A package containing a bicarbonate-containing drug solution of the present invention is typically a water vapor and gas permeable plastic container filled with a bicarbonate-containing liquid preparation, and the packaging or packaging of the plastic container. It is provided with a water vapor and gas impervious plastic packaging material to be contained, and furthermore, a carbon dioxide partial pressure control agent in which carbon dioxide is previously adsorbed in a space between the plastic container and the plastic packaging material, and if necessary. Carbon dioxide or a gas containing carbon dioxide.

FIG. 1 shows an embodiment of the bicarbonate-containing chemical liquid container package of the present invention. In FIG. 1, reference numeral 1 denotes a water vapor and gas permeable plastic container for containing a bicarbonate-containing liquid preparation. Reference numeral 2 denotes a water vapor and gas impervious plastic packaging material containing the plastic container 1. Reference numeral 3 indicates a liquid preparation containing bicarbonate. Reference numeral 4 indicates a tablet-form carbon dioxide partial pressure control agent. In FIG. 1, the control agent is contained in a small bag 5 and is present in a space between a plastic container and a packaging material.

FIG. 1 shows a mere example of the bicarbonate-containing chemical liquid container package of the present invention, and the present invention includes other embodiments as described later.

Hereinafter, the bicarbonate-containing chemical liquid container package of the present invention will be described in more detail.

1. Liquid Formulation Containing Bicarbonate The bicarbonate used in the present invention is not particularly limited, and examples thereof include sodium bicarbonate, potassium bicarbonate, and ammonium bicarbonate, and other bicarbonates may be used. These may be used in combination of at least two or more. Of these bicarbonates, sodium bicarbonate is particularly preferred.

The bicarbonate-containing liquid preparation is obtained by dissolving, dispersing or suspending the above-mentioned bicarbonate in water, and is not particularly limited as long as the bicarbonate requires a liquid preparation. Not something. Such bicarbonate-containing liquid preparations include, for example, antidote containing bicarbonate, artificial kidney dialysate, peritoneal dialysate, infusion, root canal enlargement (for dental use), artificial cerebrospinal fluid, intraocular fluid Perfusion fluid, heart perfusion fluid, myocardial protection fluid,
Peritoneal washings, organ preservation solutions, and the like.

The liquid preparation may contain other drugs in addition to the bicarbonate. Examples of other drugs contained in the liquid preparation include sugars such as glucose, fat emulsions, amino acids, vitamins, sodium chloride, potassium chloride, and calcium chloride.

2. Plastic containerThe plastic container for filling the bicarbonate-containing liquid preparation is not particularly limited as long as the object of the present invention can be achieved.For example, heat sealing around the stacked sheets is performed. It may be a bag obtained, or a container obtained by blow molding.
Further, the plastic container usually has a mouth member.

As a material of the plastic container, for example, a plastic material having a property of transmitting water vapor and gas, which is commonly used as a plastic container for pharmaceutical preparations, can be preferably used.

Specifically, water vapor and gas permeable polyethylene (eg, LDPE, LLDPE, HDP
E, etc.), polyolefin polymers such as polypropylene,
Examples include an ethylene-vinyl acetate copolymer and a polyamide.

In the present invention, a multilayer film combining these materials can also be used.

The shape of the plastic container for filling the bicarbonate-containing liquid preparation of the present invention is not particularly limited, and may be any shape depending on the purpose of use.
Generally, the plastic container has one structure.
It may consist of a room. Alternatively, for example, the plastic container may have a structure including at least two chambers that can communicate with each other via a weak seal portion.

The capacity of the plastic container for filling the bicarbonate-containing liquid preparation of the present invention is not particularly limited, and an arbitrary capacity may be adopted depending on the purpose of use.

[0028] 3. Plastic wrapping material The plastic wrapping material (also referred to as a secondary wrapping material) used in the present invention may be any of those generally used in this field without particular limitation, and may have a so-called gas barrier property. As long as it is not particularly limited, a wide range can be used. In particular, it is preferable to use a plastic material that is less permeable to water vapor and gas than the above-mentioned plastic containers, that is, a plastic material having poor water vapor and gas permeability (hereinafter sometimes simply referred to as “gas poor permeability”). .

Among the gas-impermeable plastic materials,
Although there are high-performance materials and medium-performance materials, both materials can be used in the present invention. As a high-performance material, generally, the gas permeability during drying is 10 ml /
(M ² · 24 h · atm), and a material having a medium performance is generally 10 to 200 m
1 / (m ² · 24 h · atm) In the present invention, even when a material having a medium performance is used, the concentration of carbon dioxide in the space can be controlled. In particular, in applications where it is necessary to improve the impact resistance by increasing the film thickness, an inexpensive medium-performance material can be used, which is economically advantageous.

Specifically, the plastic packaging material may be, for example, aluminum laminate, polyethylene terephthalate, nylon, polyvinyl alcohol, polyvinylidene chloride, ethylene-
And vinyl alcohol copolymers. Further, in the present invention, a multilayer film in which these are combined can also be used. When used as a multilayer film, it can be used in combination with a water vapor and gas permeable film such as polyethylene or polypropylene described above. PET / PVA / LLDPE, O
PP / Ny / EVOH / LLDPE and the like.

The shape or capacity of these plastic packaging materials is also appropriately selected according to the purpose of use. If the plastic container and the carbon dioxide partial pressure control agent can be packaged and a certain space can be formed, There is no particular limitation.

[0032] 4. The volume of the space portion of the space portion container and packaging material is the content liquid are those may vary depending on the type of, but is not particularly limited as long as the volume sufficient to carbon dioxide partial pressure control agent can accommodate.

[0033] 5. Carbon dioxide partial pressure control agent Carbon dioxide partial pressure control agent used in the present invention,
Typically, when reversibly absorbing and releasing carbon dioxide gas and present in a closed space such as the space between the plastic container and the plastic packaging material of the present invention, the carbon dioxide in the closed space is It means a substance whose concentration can be controlled, and is clearly distinguished from the carbon dioxide-generating type oxygen scavenger described in JP-A-5-49675, which generates carbon dioxide in the presence of water and oxygen. In the present invention, when the carbon dioxide partial pressure in the space between the plastic container and the plastic packaging material decreases, the carbon dioxide partial pressure control agent releases carbon dioxide to compensate for this, and the carbon dioxide partial pressure in the space is reduced. Keep or increase the carbon dioxide partial pressure.

The carbon dioxide partial pressure control agent is not particularly limited as long as it can absorb and release carbon dioxide gas reversibly and can control the concentration of carbon dioxide gas in the closed space as described above. Examples include zeolite, activated carbon, ion exchange resin, styrene amino resin, carbodiimide, polyethyleneimine, etc., on which gas has been adsorbed. These can be used alone or in combination of two or more. Among them, zeolite, activated carbon and ion exchange resin are preferred, zeolite is more preferred in terms of adsorption amount, and activated carbon is more preferred in terms of cost. The form of these zeolites, activated carbon, ion-exchange resin, styrene amino resin, carbodiimide, polyethyleneimine and the like is not particularly limited, but may be, for example, a powder form, a tablet form obtained by compressing and molding the powder.

These carbon dioxide partial pressure control agents are prepared by subjecting zeolite, activated carbon, ion exchange resin, styrene amino resin, carbodiimide, polyethyleneimine, and the like to appropriate pretreatment such as vacuum heating and drying, and leaving them in a carbon dioxide gas atmosphere. By doing so, the carbon dioxide gas can be adsorbed, preferably by leaving it until the carbon dioxide gas is saturated and adsorbed.

The carbon dioxide gas may be saturatedly adsorbed on zeolite, activated carbon, ion exchange resin, styrene amino resin, carbodiimide, polyethyleneimine, or the like, or may be adsorbed in an amount less than the saturated adsorption amount.

These carbon dioxide partial pressure control agents include:
Various shapes such as a powder and a tablet are included. The control agent such as a powder or a tablet may be put in the space as it is, or may be stored in a gas-permeable small bag such as paper, a polyethylene bag having air permeability in advance, and the small bag is placed in the space. Is also good.

The control agent only needs to be present in the space between the plastic container and the packaging material, and may be in a form other than the tablet form.
Alternatively, it may be bonded on a plastic packaging material. Alternatively, the carbon dioxide partial pressure control agent may not be bonded or the like, and may be movable in the space between the plastic container and the packaging material.

Further, a film or sheet coated with zeolite or the like in which carbon dioxide is adsorbed is also included in the carbon dioxide partial pressure control agent of the present invention. Such a film or sheet is, for example, a method of uniformly mixing zeolite or the like with a molten plastic such as polyethylene, forming a film by an inflation method, or a method of applying zeolite to a film of a plastic such as polyethylene with an adhesive. Can be manufactured.

The amount of the carbon dioxide partial pressure control agent used is
It is sufficient that the amount is sufficient to provide a carbon dioxide partial pressure effective for suppressing the decomposition of the bicarbonate-containing liquid preparation. For example, it is sufficient that carbon dioxide in an amount that keeps the concentration of carbon dioxide in the space constant for three months is held in the carbon dioxide partial pressure control agent to be used. For example, bicarbonate 5-30
0.5 to 5 g, in particular 1 to 20 ml of a liquid formulation by weight
It is preferable to use 2 to 2 g.

Conventionally, the carbon dioxide-generating type oxygen absorber used to increase the carbon dioxide concentration in the atmosphere in the package requires water and oxygen to generate carbon dioxide, and the carbon dioxide concentration in the package is low. Even so, carbon dioxide could not be generated without the presence of oxygen. On the other hand, the carbon dioxide partial pressure control agent used in the present invention is characterized in that carbon dioxide is generated and absorbed to control the atmosphere in the package, regardless of whether oxygen exists inside the package. Are better.

Therefore, the present invention also provides the carbon dioxide partial pressure control agent itself as described above.

6 Manufacturing method of package of the present invention The bicarbonate-containing chemical liquid container package of the present invention can be manufactured, for example, according to the following method.

First, a liquid preparation containing bicarbonate is filled in a water vapor and gas permeable plastic container, and the container is sealed in a conventional manner. Thereafter, the plastic container is packaged together with a carbon dioxide partial pressure control agent using a plastic packaging material that is impervious to water vapor and gas. Packaging can be performed, for example, by putting a plastic container filled with a bicarbonate-containing liquid preparation in a bag-shaped plastic packaging material in advance and a carbon dioxide partial pressure control agent. Finally, the plastic packaging material is hermetically sealed by, for example, fusing.

In addition to the above, in the present invention, before sealing the plastic packaging material, the space between the container and the packaging material is filled with carbon dioxide or a carbon dioxide-containing gas, for example, a mixed gas of carbon dioxide and air. It is also possible.

[0046]

The present invention will be described in more detail with reference to the following examples.

Examples 1 to 4 20 ml of a 7% aqueous sodium hydrogen carbonate solution was filled into a plastic ampule (LDPE density: about 0.9, thickness: about 500 μm, volume: about 30 ml) made of LDPE, and sealed by a conventional method. The ampoule is packed with a gas-impermeable wrapping material (both having a volume of 60 m
l). The carbon dioxide partial pressure control agent, the amount used, and the type of packaging material are as shown in Table 1 below.

The carbon dioxide partial pressure control agent was produced as follows. First, 2 g of zeolite or activated carbon is filled in a polyethylene pouch at 0 atm, 1 atm.
Vacuum heating and drying were performed at 10 ° C. for 24 hours. Next, the mixture was cooled to room temperature, and carbon dioxide gas was impregnated at 1 atm for 1 hour, and then adjusted gas (CO ₂ 20%, air 80
%) For 1 hour to obtain a carbon dioxide partial pressure control agent having carbon dioxide adsorbed thereon.

After enclosing a mixed gas of 40% carbon dioxide and 60% air in the packaging material, the packaging material was sealed to obtain a package of the drug solution container of the present invention as shown in FIG.

Comparative Example 1 A container containing a liquid preparation was packaged with a packaging material shown in Table 1, and the above-mentioned Example 1 was used except that the carbon dioxide partial pressure control agent was not present.
In the same manner as in Nos. To 4, a chemical liquid container package was obtained.

[0051]

[Table 1]

[Formulation stability test] The liquid medicine container packages of the liquid preparations obtained in the above Examples 1 to 4 and Comparative Example 1 were stored at 40 ° C and 75% RH, respectively, immediately after production, and one month after storage. , 2 months and 3 months later, the pH of the solution was measured. Table 2 shows the results.

[0053]

[Table 2]

From Table 2, it can be seen that, when the carbon dioxide partial pressure control agent was used, the fluctuation of the pH of the solution was small and the stability of the liquid preparation was excellent as compared with the case where the carbon dioxide partial pressure control agent was not used. I understand. Also, OPP / Ny / E
When a medium-performance gas-impermeable plastic such as VOH / LLDPE is used as a packaging material, PET /
When a high-performance gas-impermeable plastic such as PVA / LLDPE was used, it was inferior, but showed sufficient stability.

Example 5 In a compartment of a plastic bag (thickness: about 260 μm) consisting of two compartments having a partition wall made of polyethylene and capable of communicating,
The following chemicals were filled and closed, respectively, and sterilized with hot water shower (pH after sterilization in each room after mixing: 7.24). This was put together with a carbon dioxide partial pressure control agent in a packaging material having poor gas permeability. Carbon dioxide partial pressure control agent
Three zeolites (6 g in total) used in Example 1 were used, and the same film as in Example 2 was used as a packaging material.

After enclosing a mixed gas of 40% carbon dioxide and 60% air in the packaging material (space volume: 400 ml), the packaging material was sealed to obtain the package of the drug solution container of the present invention.

[Medicinal solution formulation] In the first room 300 ml, the following components containing calcium chloride dihydrate 0.17 g magnesium chloride hexahydrate 0.22 g glucose 0.61 g in the second room 700 ml Containing sodium chloride 7.15 g potassium chloride 0.13 g sodium hydrogen carbonate 1.94 g potassium phosphate dihydrate 0.15 g

[0058]

The carbon dioxide partial pressure control agent used in the present invention is capable of equilibrium adsorption and desorption of carbon dioxide, so that the amount of carbon dioxide released can be adjusted according to the concentration of carbon dioxide in the system. Therefore, there is an advantage that the carbon dioxide concentration in the space between the container and the packaging material can be easily kept constant as compared with the method of simply filling the space with the carbon dioxide gas or the method using the carbon dioxide generating type oxygen scavenger.

In the present invention, the gas barrier property of the packaging material does not have to be high because a sufficient amount of carbon dioxide to be released is adsorbed by the carbon dioxide partial pressure control agent such as zeolite.

Thus, according to the present invention, a liquid preparation containing a bicarbonate can be stably held in a plastic container without causing denaturation, deterioration, etc. of the liquid preparation containing the bicarbonate, thereby achieving the purpose of blending the bicarbonate. I can make it.

Further, according to the conventional technology of setting the space between the plastic container and the secondary packaging material to a carbon dioxide gas atmosphere, in order to achieve the purpose of stabilizing the preparation, a high-performance gas-impermeable material is required. A film was required, and thus an expensive film having a certain thickness had to be used. According to the present invention, the gas permeability is relatively thin (about 70 μm).
Even if an inexpensive medium-performance gas-impermeable film of 0 ml / (m ² · 24 h · atm) or more is used, the preparation can be sufficiently stabilized. In addition, it is possible to appropriately select a film from among inexpensive gas-impermeable films having medium performance, according to conditions such as use and transportation of the package. In addition, gas-impermeable films with medium performance
In general, since it is cheaper than a high-performance hardly permeable film, it is possible to practically use a material whose film thickness is increased and pinholes are hardly generated.

[Brief description of the drawings]

FIG. 1 is a schematic view showing an example of a drug solution container package of the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Water vapor and gas permeable plastic container 2 Water vapor and gas impervious plastic packaging material 3 Bicarbonate containing liquid preparation 4 Carbon dioxide partial pressure control agent 5 Sachet

Claims (8)

[Claims] 1. A water vapor and gas permeable plastic container filled with a liquid preparation containing bicarbonate, and a water vapor and gas impervious plastic wrapping material for packaging the container, further comprising the plastic container and the plastic A bicarbonate-containing chemical liquid container package, characterized in that a carbon dioxide partial pressure control agent having carbon dioxide adsorbed in advance is present in a space with the packaging material. 2. The bicarbonate according to claim 1, wherein the carbon dioxide partial pressure control agent is at least one selected from the group consisting of zeolite, activated carbon, ion exchange resin, styrene amino resin, carbodiimide, and polyethylene imine. Containing chemical solution container package. 3. The bicarbonate-containing chemical container package according to claim 2, wherein zeolite is used as the carbon dioxide partial pressure control agent. 4. The bicarbonate-containing chemical liquid container package according to claim 2, wherein activated carbon is used as the carbon dioxide partial pressure control agent. 5. The package according to claim 1, wherein the bicarbonate is sodium bicarbonate. 6. The bicarbonate-containing drug solution is a bicarbonate-containing antidote, an artificial kidney dialysate, a peritoneal dialysate, an infusion,
The bicarbonate-containing drug solution according to claim 1, which is selected from the group consisting of a root canal enlargement agent, an artificial cerebrospinal fluid, an intraocular perfusion solution, a heart perfusion solution, a cardioplegic solution, a peritoneal lavage solution, and an organ preservation solution (for dental use). Container packaging. 7. The bicarbonate-containing chemical liquid container package according to claim 1, wherein the space between the plastic container and the plastic packaging material is further filled with carbon dioxide or a carbon dioxide-containing gas. . 8. Reversible absorption and release of carbon dioxide gas,
Zeolite, activated carbon, ion exchange resin, styrene amino resin, which can control the concentration of carbon dioxide in a closed space,
A carbon dioxide partial pressure control agent comprising at least one selected from the group consisting of carbodiimide and polyethyleneimine.