RU2794106C1 - Container for lyophilization of blood, its components and biological material - Google Patents

Abstract

FIELD: medical equipment.

SUBSTANCE: invention relates to devices and methods used in transfusiology for lyophilization of blood, its components, blood products and their storage and transfusion. The container is made of tubular or sheet (roll) waterproof film material in the form of a flattened container, the open edges of which are welded with at least two sealed seams, two opposite sides of the container are sealed with sealed seams with built-in fittings and (or) tubes communicating with the internal cavity. On the one hand, the container is provided with at least one fitting with a pierceable membrane closed with a detachable protective element. On the other hand, the container is provided with a tube having a ramification of lines provided with clamps, one or two of which are provided with a polymeric two-channel needle(s) with a removable cap(s) having a channel for liquid, one line is provided with a luer-lock connection with a cap, one or two lines are provided with a fitting(s) containing a pierceable membrane with detachable protective elements, one line has a hermetically sealed end. The container is provided with two or more lyophilization tubes closed with separable protective elements. The inner diameter of the lyophilization tubes is 2 to 10 mm. The container has a rectangular shape with rounded corners. The container has a volume ranging from 300 to 3.000 ml.

EFFECT: significant reduction in the time of lyophilization of blood, its components and biological material, increased productivity and reduced labor and energy costs per 1 unit of the finished product, maintaining tightness and no deformation at temperatures ranging from minus 85°C to plus 50°C, ensuring the sterility of the process of obtaining sterile lyophilized blood, its components or blood products at all production stages, namely, the transfer of blood or its components into the device, freezing and lyophilization, storage, rehydration, transfusion to the recipient.

3 cl, 3 dwg

Description

The invention relates to medical equipment, namely to devices and methods used in transfusiology for lyophilization of blood, its components, blood products and their storage and transfusion.

Lyophilization is a widely used physical processing method based on the process of dehydration of various products, including medicinal substances, vaccines, biological objects, etc. The advantages of such drying are high stability, prolonged shelf life, minimal changes in properties, uniformity and rapid rehydration of the drug to an usable form. In this form, preparations are easy to transport, long-term and safe to store without the need for refrigeration.

The transfusion of donor blood and its components is an integral part of the provision of specialized medical care both in peacetime and during emergencies and military operations. It is used in complex operations, severe injuries, childbirth, treatment of patients with various oncological and hematological diseases, liver diseases and many other cases. Despite a number of advantages of lyophilized blood components, most of the blood and its components are stored in a liquid or frozen state, which requires special expensive storage conditions and significantly complicates their transportation, storage and use under unsuitable conditions.

Freeze-drying of blood and its components, in particular plasma and cryoprecipitate, was widely used at Blood Transfusion Stations in the USSR and the Russian Federation, currently similar products are produced in Belarus (State Republican Scientific and Practical Center for Transfusiology and Medical Biotechnology), in Germany LyoPlas N-w (German Red Cross) and in France Lyophilized Plasma (FLYP) (French Military Blood Institute [CTSA]), lyophilization of plasma and cryoprecipitate is carried out in open glass vials, which requires protection from microorganisms both at the preparatory stage in special clean rooms under aseptic conditions, and at the drying stage .

Analogues of the claimed device are polymeric containers of various purposes and types: "Compoplast", "KPK", "Gemasin", "CompoFlex", "CompoSelect", "KPV" and others. The main purpose of these devices is the preparation of donor blood / or its components, storage and transportation, washing, freezing and thawing, secondary fractionation and transfusion. However, these containers are not intended for lyophilization of blood and its components in them.

Known double container for hemocomponents, which consists of two containers connected around the perimeter of one of the sides. The opposite side of the first container contains a tube, and the second one contains fittings and a tube equipped with a filter, a clamp and a polymer needle. In this case, the first container is made of a waterproof film material, the second container has one surface made of a waterproof, and the other one is made of a water-repellent and vapor-permeable material. The lyophilized hemocomponent, having opened the seam that isolates the second container from the first one, is transferred to the first container for storage, rehydration and transfusion. A method for using a double container is also presented. The quality of the lyophilized and rehydrated hemocomponent is preserved and the likelihood of microbial contamination is reduced (RU 2743609, IPC A61J 1/05, publ. 20.02.2021).

The closest technical solution to the claimed invention is a container for lyophilization and transfusion of hemocomponents, which allows in a single closed sterile system to lyophilize the hemocomponent, store, transport, rehydrate and transfuse the rehydrated lyophilizate of the hemocomponent. The container is made of film material in the form of a flattened container with connecting elements necessary to perform the listed functions. One surface of the container is made of a water-, gas- and vapor-permeable material, the other is made of a water-repellent, gas- and vapor-permeable material. At least one tube is hermetically inserted into the container at one end, the other end of which is connected in a certain sequence through a splitter to several tubes ending in connecting elements of various purposes. The quality is preserved and the probability of microbial contamination of the hemocomponent recovered from the lyophilizate is achieved (RU 2740839, IPC A61J 1/05, publ. 20.01.2021).

The disadvantage of analogue RU 2743609 and prototype RU 2740839 is that a long lyophilization time is required (more than 4-5 days when lyophilizing a standard plasma dose of 300 ml), which is excessively labor- and energy-intensive per 1 unit of the finished product.

The technical result of the claimed invention is to significantly reduce the time of lyophilization of blood, its components and biological material, increase productivity and reduce labor and energy costs per 1 unit of the finished product, maintain tightness and no deformation in the temperature range from minus 85°C to plus 50°C , ensuring the sterility of the process of obtaining sterile lyophilized blood, its components or blood products at all production stages, namely the transfer of blood or its components into the device, freezing and lyophilization, storage, rehydration, transfusion to the recipient.

The essence of the invention lies in the fact that the container for lyophilization of blood, its components and biological material is made of a tubular or sheet (roll) waterproof film material in the form of a flattened container, the open edges of which are welded with at least two sealed seams, two opposite sides of the container welded with sealed seams with built-in fittings and (or) tubes communicating with the internal cavity. Moreover, on the one hand, the container is provided with at least one fitting with a pierceable membrane closed with a detachable protective element. On the other hand, the container is provided with a tube having a branching of lines, provided with clamps, one or two of which are provided with a polymer (s) two-channel (s) needle (s) with a removable cap (s), having a channel for liquid, one line is provided with a luer-lock connection with a cap, one or two lines are provided with a fitting(s) containing a pierceable membrane with detachable protective elements, one line has a hermetically sealed end. The container is provided with two or more lyophilization tubes closed with separable protective elements. The inner diameter of the lyophilization tubes is 2 to 10 mm. The container has a rectangular shape with rounded corners. The container has a volume ranging from 300 to 3000 ml.

In FIG. 1 shows a general view of the container for lyophilization (example 1), in Fig. 2 shows a general view of the lyophilization container (Example 2), FIG. 3 - special sealer/clamp, heating element and tube ends.

Example 1. Container for lyophilization of blood, its components and biological material The container for lyophilization of blood, its components and biological material (Fig. 1) is made of tubular or sheet (roll) waterproof film material in the form of a flattened container, the open edges of which are welded along at least two sealed seams. Two opposite sides of the container are welded with sealed seams with built-in fittings and (or) tubes communicating with the internal cavity. Moreover, on the one hand, the container is provided with at least one fitting 1 with a pierceable membrane closed by a detachable protective element. On the other hand, the container is equipped with a tube having a branching of lines 2, one of which is equipped with a polymer two-channel needle 3 with a removable cap, having a channel for liquid, one line is equipped with a luer-lock connection 4 with a cap, one or two lines are equipped with (s) fitting ( s) containing a pierceable membrane with separable security elements 5, one line has a hermetically sealed end 6. The container is provided with two or more lyophilization tubes closed with a separable security element 7 without a pierceable membrane. The inner diameter of the lyophilization tubes is 2 to 10 mm. The container has a rectangular shape with rounded corners. The container has a volume ranging from 300 to 3000 ml.

Example 2. Container for lyophilization of blood, its components and biological material The container for lyophilization of blood, its components and biological material (Fig. 2) is made of a sleeve or sheet (roll) waterproof film material in the form of a flattened container, the open edges of which are welded along at least two sealed seams. Two opposite sides of the container are welded with sealed seams with built-in fittings and (or) tubes communicating with the internal cavity. Moreover, on the one hand, the container is provided with at least one fitting 1 with a pierceable membrane closed by a detachable protective element. On the other hand, the container is equipped with a tube having a branching of lines 2, two of which are equipped with polymeric two-channel needles 3 with removable caps, having a channel for liquid, one line is equipped with a luer-lock connection 4 with a cap, one or two lines are equipped with (s) fitting ( s) containing a pierceable membrane with separable security elements 5, one line has a hermetically sealed end 6. The container is provided with two or more lyophilization tubes closed with a separable security element 7 without a pierceable membrane. The inner diameter of the lyophilization tubes is 2 to 10 mm. The container has a rectangular shape with rounded corners. The container has a volume ranging from 300 to 3000 ml.

Unlike RU 2743609 and RU 2740839, the claimed invention does not require the obligatory presence of at least one surface of the container made of "film material of porous processed cellulose paper or polymeric non-woven "paper", from which the surfaces of known containers are made, has a water-repellent property and is necessary for lyophilization hemocomponents gas and vapor permeability. The use in RU 2740839 "one or more, preferably two layers, especially paper, increases the strength of the proposed container and maintains the level of gas and vapor permeability required for lyophilization."

The claimed invention can be made both from a tubular film material, the open edges of which are sealed with a sealed seam with fittings and (or) tubes, and a sheet (roll) film material, sealed with a sealed seam along the edges and also having the necessary fittings and (or) tubes . In the manufacture of the container, two, three or more welds can be used. Welded seams are made to limit and protect the internal cavity of the container from the adverse effects of the external environment.

Two opposite sides of the container are welded with a sealed seam with built-in fittings and (or) tubes communicating with the internal cavity, and on the one hand the container is equipped with one, two or more fittings 1 with a pierceable membrane closed by a detachable protective element, as well as a tube with branching lines 2, one or two of which are provided with a polymer (s) two-channel (s) needle (s) 3 with a removable cap, having a channel for the liquid, one line is provided with a luer-lock connection 4 with a cap, one or two lines are provided with ( ny) fittings containing a pierced membrane with detachable protective elements 5, one line has a hermetically sealed end 6.

A distinctive feature of the claimed container from the previously known ones is that the container is equipped with two or more tubes for lyophilization, closed with separable protective elements 7, the inner diameter of the tubes is from 2 to 10 mm, preferably 5-7 mm. These tubes are intended for the direct lyophilization process, providing communication between the inner chamber of the bag and freeze drying.

The sterility of lyophilization in the claimed container is ensured by the presence of a special sealer/clamp 8 in the freeze dryer (Fig. 3) and the presence of a sterilization system in the dryer, preferably by the gas method, or by any other available method, ensuring sterilization without destruction of the polymer material and the lyophilized substance, and providing proper aseptic conditions. The sealer/clamp 8 consists of two metal plates with a heating element 9, one or both of which move towards each other, thereby squeezing the ends of the lyophilization tubes 10 with a force that does not allow air to penetrate through the inner lumen of the tubes. Plates 8 work in two modes: directly as a scourer when the heating of the plates is turned on and as a clamp when the plate is turned off.

The lyophilization and transfusion process consists of four steps.

Stage 1: transfusion of native, preserved or thawed blood or its components from a standard container, as well as the introduction of a cryoprotectant solution (if necessary) into the declared container using connectors, fittings, line 3-6 adapters (located on line 2). After the transfer of blood or its components, as well as the introduction of a cryoprotectant solution (if necessary) into the declared container, line 2 is sealed using a mobile or stationary plastic line sealer and removed.

Stage 2: lyophilization of blood or its components in the declared container.

The container is placed in a lyophilic dryer, special tubes for lyophilization below the detachable protective elements 7 are pinched with a clip-sealer of plastic lines to prevent air from entering through them, but they are not sealed. Protective elements 7 are removed from the ends of the line. Drying closes, the inner chamber is disinfected. The sealing clamp rises, freeing access through line 7 to the declared container. The lyophilization process is carried out according to the specified parameters, upon completion of which the line 7 is sealed and sealed with a clamp-sealer.

At the end of drying, the lyophilizate moves by shaking inside the container towards the fittings of line 1 and can be hermetically sealed along line 11.

Stage 3: rehydration of the lyophilizate for its intended use in the proposed container is carried out with a solution and a transfusion system for transfusion by connecting to one of the two fittings 1 with a pierceable membrane and a closed detachable protective element.

Stage 4: transfusion (transfusion) to the recipient from the proposed container of the rehydrated lyophilizate is carried out using a transfusion system for transfusion by connecting to one of the two fittings 1 with a pierceable membrane and a closed detachable protective element.

Conducted experimental studies on lyophilization by the proposed method in the claimed device with a standard dose of 300 ml and a layer thickness of not more than 8 mm made it possible to achieve the task in less than 24 hours, which is much more efficient and faster (4-5 days for the invention of RU 2743609 and RU 2740839) for products with similar tasks and other principles for their implementation. The result of the claimed device is the production of sterile lyophilized blood, its components or blood products, the possibility of their long-term storage without creating special storage and transportation conditions, rehydration at the place of demand while maintaining acceptable quality and safety indicators with the possibility of further clinical use or other purposes.

Claims (3)

1. A container for lyophilization of blood, its components and biological material, made of tubular or sheet waterproof film material in the form of a flattened container, the open edges of which are welded with at least two sealed seams, two opposite sides of the container are sealed with sealed seams with built-in fittings and (or ) tubes communicating with the internal cavity, and on the one hand, the container is equipped with at least one fitting with a pierceable membrane closed by a detachable protective element, on the other side, the container is equipped with a tube having a branching of lines equipped with clamps, one or two of which are equipped with (we ) polymer(s) two-channel(s) needle(s) with a removable cap(s) having a channel for liquid, one line is equipped with a luer-lock connection with a cap, one or two lines are provided(s) with a fitting (s) containing a pierceable membrane with separable protective elements, one line has a hermetically sealed end, the container is equipped with two or more lyophilization tubes closed with separable protective elements, the inner diameter of the lyophilization tubes is from 2 to 10 mm. 2. A container for lyophilization of blood, its components and biological material according to claim 1, characterized in that it has a quadrangular shape with rounded corners. 3. A container for lyophilization of blood, its components and biological material according to claim 1, characterized in that it has a volume in the range from 300 to 3000 ml.

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