DE102006014184A1 - Deactivating unwanted organisms in blood plasma, especially viruses, involves adding porphyrin to blood plasma immediately after extracting it from blood and irradiating mixture with xenon radiation - Google Patents

Abstract

The method involves adding a porphyrin to the blood plasma immediately after extracting it from blood and irradiating the mixture with xenon radiation. A chlorine e6 is used as the porphyrin, which is added to the blood in blood plasma filtering hydrophobic filter and irradiating the blood plasma exposed to porphyrin immediately after exiting the filter. An independent claim is also included for a device for deactivating unwanted organisms in blood plasma, especially viruses.

Description

The The invention relates first to a method for inactivating unwanted in blood plasma Organisms, in particular of viruses.

During the entire recovery and storage process of blood plasma must be ensured be that finally with highest Safety is not harmful organic matter in ready-to-use blood plasma more available are. Such organic components may be, for example: molecules, such as Proteins, lipids or DNA, or microorganisms, such as bacteria, Viruses and fungi or diseased cells, e.g. Cancer cells. The Elimination of such components is often by filters under Use of centrifuges performed. These procedures lead but not to a complete, So 100%, elimination of the ingredients. Because through these ingredients, even if they were so small, especially by microbes, such as z. As viruses, but a variety of life-threatening diseases can be caused an extraordinary urgent need for a method of the type mentioned.

Of the Invention is therefore based on the attempt to specify a method with which the blood plasma is treated so that certainly no active organic components, in particular viruses or the like, more are available.

In a comprehensive series of investigations, it was found that the combined application of two measures is fundamentally successful in this respect:
If the blood plasma is immediately mixed with a porphyrin during its extraction and irradiated with xenon radiation, then all organic components are inactivated. The blood plasma is z. B. absolutely free of viruses.

The Effect of the new method is based on the following biological mechanism back to lead: Will the porphyrin or chlorin e6-added blood plasma with xenon rays irradiated, then from O2 becomes a singlet O2, whereby the highest oxidation effect is reached. It has been found that this effect is even stronger than with the use of radicals or peroxides.

It it was further found that when using a chlorin e6 a particularly small amount of this porphyrin is sufficient to the achieve the desired effect with certainty.

Particularly advantageous, in particular very safe, economical and effective, the method is applicable when the porphyrin or chlorin e6 is already added to the blood in a hydrophobic filter filtering out the blood plasma and the plasma exchanged with porphyrin or chlorin e6 immediately after exiting the hydrophobic filter is irradiated. Such filter methods or filter arrangements, also using special hollow fiber filters, have become known, for example, from the publications DE 297 13 774 U1 . DE 197 33 407 A1 . DE 20014311 U1 , WO 2000062840 A1, WO 2002013888 A1. and US 20020183678 A1 , Such a filtering method or such a filter arrangement is also the subject of the hitherto unpublished German patent application DE 102005035528 ,

Under Use of the above-mentioned methods and devices in continuation proposed the invention that the porphyrin or chlorin e6 is added to the blood plasma by the hydrophobic filter with the Porphyrin or chlorin e6 wetted or soaked and then the blood through the filter is passed. As a result, the method according to the invention in a very good practice integrated for the production of blood plasma, and any impurities of blood plasma from the outside are completely locked out.

If irradiated with porphyrin or chlorin e6 added blood plasma dropwise becomes, then the blood plasma in a sense in a delay line, while a certain, also controllable period of time and in a very Compact volume shape all around and thus very effectively irradiated. In addition, will the blood plasma in the aforementioned method according to the state of Technique drop-shaped so that integration of the new method into the abovementioned very proven Procedure possible without problems is.

In continuation The invention can control the irradiation time and in particular increase, by the porphyrin or chlorin e6 staggered blood plasma after its exit from the hydrophobic filter in a buffer recorded and irradiated in this buffer.

Around Keeping the entire system closed will make the blood plasma immediate passed after irradiation in a collection container.

Of the The invention is further based on the desire, a device to indicate inactivation of organisms unwanted in blood plasma, with which the blood plasma is treated so that certainly no active organic constituents, in particular viruses or the like, more are available.

• a) ein Vorratsbehälter mit einer Mischung aus frisch gewonnenem, Blutplasma und Porphyrin, insbesondere Chlorin e6,
• b) eine Bestrahlungskammer zur Aufnahme der Mischung,
• c) eine Verzögerungsstrecke und/oder ein Zwischenspeicher für die Mischung in der Bestrahlungskammer,
• d) eine Strahlungsquelle für Xenon-Strahlen zur Bestrahlung der Mischung in der Bestrahlungskammer,
• e) ein Sammelbehälter für das bestrahlte Blutplasma.

Such a device for inactivating undesirable in blood plasma organisms, esp especially of viruses, may include the following structure:

• (a) a reservoir containing a mixture of fresh blood plasma and porphyrin, in particular chlorin e6,
• b) an irradiation chamber for receiving the mixture,
• c) a delay line and / or a buffer for the mixture in the irradiation chamber,
• d) a source of xenon radiation for irradiating the mixture in the irradiation chamber,
• e) a collection container for the irradiated blood plasma.

Becomes a device for obtaining blood plasma according to the above Prior art used, then one from the blood, the blood plasma filter out, hydrophobic filter as a reservoir for the mixture from blood plasma and porphyrin or chlorin e6 serve.

One Such hydrophobic filter can in particular as a U-shaped hollow fiber filter be formed, whose membranes with porphyrin or chlorin e6 wetted or soaked are.

to easy control of the irradiation time and thus the intensity can be one delay path be arranged in the form of a drip path. It can also be a cache in the form of a surface filter to be ordered. This area filter may be in place or in addition be arranged to the drip path, in particular record the drops and in a thin one area Bring volume shape. Then can in particular, both the drops and the soaked with droplets surface filter be irradiated with the same radiation source with xenon beams.

at the already mentioned Integration can be hydrophobic filters and the area filter in a common filter housing be arranged, which also include the irradiation chamber or can serve as such.

It has been shown to be a device for irradiation very successful is when the xenon rays have a wavelength of 300 to 800 microns, preferably about 630 microns.

Of another has proven a device in which the distance the radiation source to the blood plasma is 30 to 40 mm. in this connection is taken into account, that the effectively effective radiation dose is dependent not only on the Radiation density of the radiation source, but also of the irradiation time and the distance of the radiation source and finally the radiation transmission the radiation chamber, here z. B. the filter housing.

to Ensuring the distance between the radiation source and the To be irradiated blood plasma can be a special, possibly stepless serve adjustable spacer. This spacer can z. B. in an upper attachment of said filter housing or be integrated into the attachment of the radiation source.

The Radiation source can be formed very different in itself, as long as the radiation dose is sufficient. So it can almost come from several individual punctate or flat Radiation sources exist. A very effective irradiation will achieved when the radiation source is substantially as open, closed or overlapping and level ring is formed and the blood plasma only by gravity through the interior, especially through the Center, led to the ring is. Then the radiation concentrates on the interior, the center of the ring and thus exclusively and from all sides to the blood plasma located there, so that can be operated with a relatively low radiation dose.

If required or required, you can even two or more such rings may be arranged parallel to each other. Is the ring open, so not completely closed on the circumference or to Overlapping part, so he can for assembly first leading a blood plasma Line, z. B. below the filter housing, record in its interior. Subsequently can he, for. B. around the serving as an irradiation chamber filter housing, high led and in a certain, possibly adjustable distance to the blood plasma be attached.

A The aforementioned device can be mounted conveniently and safely. by the radiation source and / or a mixture containing reservoir or optionally the filter housing serving for this purpose and if necessary, the collection container are releasably secured together on a sturdy holder. Such a Holder can be adapted to different shapes or dimensions, in particular for receiving different, closed devices with storage and collection containers, comprise a vertical bar on which the radiation source and / or the reservoir or the filter housing and / or optionally the collecting container in height adjustable is attached or are. Similar Holders and rods are from the aforementioned prior art for mounting a Filter arrangement previously known.

To protect the environment and in particular of persons from the xenon radiation, it may be provided that the radiation source is directed outwards completely or at least radially covered by a protective shield. Such a shield may be internally at least partially mirrored. For gapless radial shielding, an annular shield between two overlapping peripheral regions may have a nearly tangential opening for passage of a conduit. Such a shield may be attached to the radiation source or directly to the rod and combined with an above-mentioned spacer.

In the drawing is an embodiment of Invention shown, now closer is described.

1 shows a device for irradiation of blood plasma according to the invention, in side view and in a slightly schematic representation.

2 shows the section II-II in 1 omitting the parts under the filter housing, on a larger scale.

The device 1 after 1 includes a filter container 2 , in its upper inner area 2a a U-shaped hydrophobic hollow fiber filter 3 is stored, which consists of a vielzähligen fiber bundle. Through a supply line 4 can be supplied to the interiors of the hollow fibers blood B, a first derivative 5 serves for discharging the cavities passing cellular blood components in a collecting container, not shown.

Inside the lower area 2 B of the filter container 2 extends over the entire clear, round cross-section of a woven surface filter 6 with the mesh size 20 to 40 μm. Below the surface filter 6 are in the ground 7 of the filter container 2 a supply line 8th and a derivative 9 appropriate. The derivative 9 serves to remove the through the membranes of the hollow fiber filter 3 squat blood plasma 10 , initially in the form of drops 10a centrally from the hollow fiber filter 3 can drip out, then under gravity the area filter 6 penetrates and over the derivative 9 a collection container 11 is supplied. The supply line 8th is used in particular for supplying superheated steam for sterilization.

The filter container 2 is at the top of the range 2a over a clamp 12 detachable and adjustable in height H1 with a vertical rod 13 a keeper 14 connected, over a foot 15 stable on the ground 16 rests. The collection container 11 is over a hook 17 in height H2 adjustable on the rod 13 suspended

The lower inner area 2 B of the filter container 2 serves as irradiation chamber and is therefore well permeable to xenon radiation. Appropriately, the entire filter container 2 completely transparent. A xenon-emitting radiation source 18 comprises an annular radiator 19 that is around the bottom area 2 B and thus also around the surface filter 6 around and at a distance A of about 30 to 40 mm from the drop 10a extends. The ring-shaped radiator 19 is not closed, but has at its periphery a radial passage 20 on. The wavelength of the xenon beams is approximately between 300 to 800 .mu.m, in particular about 630 microns. The radiation source 18 includes a clamp 21 with which it is adjustable in height H3 with the vertical rod 13 connected is.

the clamp 21 can be rotated and longitudinally adjustable to the annular radiator 19 exactly concentric to those in the field 2 B falling drops 10a and the area filter 6 Align so that the xenon radiation can be used most safely and effectively. Via an electrical plug cable 22 is the radiation source 18 can be connected to the usual power supply with 230 Volt voltage.

To shield the environment against the intense xenon rays is all around the spotlight 19 a protective shield 23 arranged. Such a shield 23 is in 1 for the sake of clarity only indicated by dash-dotted lines and in 2 drawn only as a dash. It is particularly useful when the xenon rays are directed not only toward the center of the ring, but also radially outward. However, this is always somewhat the case due to some unavoidable axial scattering and reflection of the radial ring radiation. Will this ring-shaped shield 23 inside at least partially mirrored, so in addition to the optical shield, a substantial concentration of the rays in the direction of the ring center and thus to be irradiated blood plasma out. As a result, a significant energy savings can be achieved.

A protective shield 23 can, similar to the passage 20 on the annular radiator 19 , at its periphery for the purpose already mentioned an opening 24 for maintaining the radial optical shielding effect preferably in the region of a significant overlap of two peripheral regions 25 and 26 arranged and thus only approximately tangentially accessible. The protective shield 23 Can be easily mounted either on the spotlight 19 or at the terminal 21 or also with its own clamp separately on the rod 13 be attached.

The irradiation procedure is, for example, as follows:
First, the hollow fibers of the hydrophobic hollow fiber filter 3 wetted with chlorin e6. Then it will be Blood B through the supply line 4 into the internal cavities of the hydrophobic hollow fiber filter 3 in the filter container 2 directed. Inside the hollow fiber filter 3 The cellular components of blood B will stay behind and be drained by the drainage 5 directed into a collection container, not shown.

The blood plasma and other unwanted microorganisms, in particular viruses, in short: the contaminated blood plasma 10 , penetrates by gravity through the membranes of the hollow fibers, accumulates with chlorin e6 and collects in the form of drops 10a in the middle of the lower area 2 B of the filter container 2 and above the area filter 6 ,

The contaminated and chlorin e6-enriched blood plasma 10 drips on the surface filter 6 that the drops 10a absorbs it, distributes it in the area and holds it for a while in order to act as a sort of buffer. The one around the falling drops 10a and the area filter 6 arranged around annular radiator 19 irradiates both the individual falling drops 10a as well as with blood plasma 10 impregnated surface filters 6 with xenon rays.

By irradiating the mixture of contaminated blood plasma and chlorin e6 with xenon rays, unwanted organisms, in particular viruses, are inactivated, so that finally by the discharge 9 in the collection container 11 absorbed blood plasma 10 ' especially completely free of viruses.

During the irradiation process, the protective shield shields 23 the environment from the intense xenon rays safely off. Because both the spotlight 19 as well as the protective shield 23 have an opening on the periphery, namely passage 20 and opening 24 , can be used when mounting z. As the lines 8th and 9 be performed laterally through these openings, so that the entire radiation source 18 always on her holder 14 can remain. It needs after passing through the lines 8th and 9 on the bar 13 just slightly upwards to the bottom area 2 B of the filter housing 2 to be moved when the filter housing 2 first attached. Alternatively it can be provided that the radiation source 18 remains firmly mounted and during assembly, the filter housing 2 from above into the spotlight 19 introduced and then the clamp 12 is pulled tight.

1

contraption

2

filter container

2a

upper Area

2 B

lower Area

3

hydrophobic filter

4

supply

5

derivation

6

surface filter

7

ground

8th

supply

9

derivation

10

blood plasma with chlorin e6

10 '

irradiated blood plasma

10a

drops

11

Clippings

12

clamp

13

Rod

14

holder

15

foot

16

ground

17

hook

18

radiation source

19

spotlight

20

Passage

21

clamp

22

patching

23

shield

24

opening

25

peripheral region

26

peripheral region

A

distance

B

blood

H1

height

H2

height

H3

height

Claims (26)

Method for inactivating organisms undesirable in blood plasma, in particular of viruses, characterized in that the blood plasma is mixed with a porphyrin as soon as it is obtained from blood (B) and the mixture ( 10 . 10a ) is irradiated with xenon rays. Method according to claim 1, characterized in that that a chlorin e6 is used as porphyrin. A method according to claim 1 or 2, characterized in that the porphyrin already the blood (B) in a filtering out the blood plasma, hydrophobic filter ( 3 ) and the porphyrin-added blood plasma ( 10 . 10a ) immediately after exiting the hydrophobic filter ( 3 ) is irradiated. Process according to claim 3, characterized records that the porphyrin is the blood plasma ( 10 . 10a ) is added by the hydrophobic filter ( 3 ) is impregnated with the porphyrin and then the blood (B) through the filter ( 3 ). Method according to one of claims 1 to 4, characterized in that the added with porphyrin blood plasma drop-shaped ( 10a ) is irradiated. Method according to one of claims 1 to 5, characterized in that the porphyrin-added blood plasma ( 10 ) after its exit from the hydrophobic filter ( 3 ) in a cache ( 6 ) and stored in this cache ( 6 ) is irradiated. Method according to one of claims 1 to 6, characterized in that the blood plasma ( 10 ' ) immediately after irradiation in a collecting container ( 11 ). Contraption ( 1 ) for inactivating organisms undesirable in blood plasma, in particular of viruses, characterized by the following arrangement: a) a storage container ( 3 ) with a mixture ( 10 ) from freshly obtained, blood plasma and porphyrin, b) an irradiation chamber ( 2 B ) for receiving the mixture, c) a delay line ( 10a ) and / or a cache ( 6 ) for the mixture ( 10 ) in the irradiation chamber ( 2 B ), d) a radiation source ( 18 . 19 ) for xenon radiation for irradiating the mixture ( 10 ) in the irradiation chamber ( 2 B ), e) a collecting container ( 11 ) for the irradiated blood plasma ( 10 ' ). Device according to claim 8, characterized in that a hydrophobic filter (13) filtering out of the blood (B) the blood plasma ( 3 ) as a reservoir for the mixture ( 10 ) from blood plasma and porphyrin. Device according to claim 9, characterized in that the hydrophobic filter ( 3 ) is designed as a U-shaped hollow fiber filter. Device according to claim 9 or 10, characterized in that the hydrophobic filter ( 3 ) is wetted or impregnated with porphyrin. Device according to one of claims 8 to 11, characterized that the delay line is designed as a drip path. Device according to one of claims 8 to 12, characterized in that the temporary storage as a surface filter ( 6 ) is trained. Device according to claim 13, characterized in that the hydrophobic filter ( 3 ) and the area filter ( 6 ) in a common filter housing ( 2 ) are arranged. Apparatus according to claim 14, characterized in that the common filter housing ( 2 ) also the irradiation chamber ( 2 B ). Device according to one of claims 8 to 15, characterized that the xenon rays have a wavelength of 300 to 800 microns. Device according to claim 16, characterized in that that the xenon rays a wavelength from above 630 microns have. Device according to one of claims 8 to 17, characterized in that the distance (A) of the radiation source ( 19 ) to the blood plasma is 30 to 40 mm. Device according to claim 18, characterized in that that a spacer is used to ensure the distance (A). Device according to one of claims 8 to 19, characterized in that the radiation source ( 18 . 19 ) essentially as an open, closed or overlapping and horizontally arranged ring ( 19 ) is formed and the blood plasma ( 10 ) only under gravity through the center of the ring ( 19 ) is guided. Device according to one of claims 8 to 20, characterized in that the radiation source ( 18 ) and / or a reservoir containing the mixture or, if appropriate, the filter ( 3 ) and, where appropriate, the collecting container ( 11 ) together on a sturdy holder ( 14 ) are releasably attached. Apparatus according to claim 21, characterized in that the holder ( 14 ) a vertical rod ( 13 ) at which the radiation source ( 18 ) and / or the reservoir or the filter ( 3 ) and / or optionally the collecting container ( 11 ) in height (H1, H2, H3) is adjustably attached or are. Device according to one of claims 8 to 22, characterized in that the radiation source ( 18 . 19 ) to the outside through a protective shield ( 23 ) is covered. Contraption ( 14 ) according to claim 23, characterized in that the protective shield ( 23 ) inside is at least partially mirrored. Apparatus according to claim 23 or 24, since characterized in that the annular shield ( 23 ) between two overlapping peripheral areas ( 25 . 26 ) a tangential opening ( 24 ) having. Device according to one of claims 23 to 25, characterized in that the protective shield ( 23 ) at the radiation source ( 18 ) or on the rod ( 13 ) is attached.