WO2007110052A2

WO2007110052A2 - Method for inactivating unwanted organisms in blood plasma, especially viruses

Info

Publication number: WO2007110052A2
Application number: PCT/DE2007/000525
Authority: WO
Inventors: Gerd Heim
Original assignee: Heim, Heidrun
Priority date: 2006-03-24
Filing date: 2007-03-21
Publication date: 2007-10-04
Also published as: WO2007110052A3; DE102006014184A1

Abstract

In order to inactivate with complete reliability the viruses and the like present in blood plasma immediately when it is obtained, it is proposed to add a porphyrin, in particular a chlorin e6, to the blood plasma immediately when it is obtained from blood (B), and to irradiate the mixture (10, 10a) with xenon rays. An apparatus with a special irradiation apparatus is likewise proposed for this purpose.

Description

Method for inactivating organisms undesirable in blood plasma, in particular of viruses

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

During the entire process of obtaining and storing blood plasma, it must be ensured that, finally, no harmful organic components are more readily present in the ready-to-use blood plasma. Such organic constituents may be, for example: molecules such as proteins, lipids or DNA, or microorganisms such as bacteria, viruses and fungi or diseased cells such as e.g. Cancer cells. The elimination of such ingredients is often accomplished by filters using centrifuges. However, these methods do not lead to a truly complete, so 100%, elimination of the components. Because of these ingredients, even if they are so small, especially by microbes such. As viruses, but a variety of life-threatening diseases can be caused, there is an extremely urgent need for a method of the type mentioned.

The invention is therefore based on the desire to provide a method by which the blood plasma is treated so that certainly no active organic ingredients, such as viruses or the like, are more present.

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 attributed to the following biological mechanism: If xenon radiation is applied to the blood plasma mixed with porphyrin or chlorin e6, then 02 becomes a singlet O2, which achieves the highest oxidation effect. It has been found that this effect is even stronger than with the use of free radicals or peroxides. It has also been found that when using a chlorin e6, a particularly small amount of this porphyrin is sufficient to 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 filtering out of the blood plasma hydrophobic or hydrophilic filter and the porphyrin or chlorin e6 staggered blood plasma immediately after the Exit from the hydrophobic or hydrophilic 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 filter method or such a filter arrangement is also the subject of the hitherto unpublished German patent application DE 102005035528.

Using the above-mentioned methods and devices, it is proposed in the continuation of the invention that the porphyrin or chlorin e6 be added to the blood plasma by wetting or impregnating the hydrophobic or hydrophilic filter with the porphyrin or chlorin e6 and then the blood through the filter is directed. As a result, the method according to the invention is integrated into a very good method for obtaining blood plasma, and any contamination of the blood plasma from the outside is completely excluded.

If the blood plasma staggered with porphyrin or chlorin e6 is irradiated drop-shaped, then the blood plasma is effectively irradiated all around and thus very effectively in a delay line, during a certain, also controllable period of time and in a very compact volume form. In addition, the blood plasma in the aforementioned method according to the prior art is obtained drop-shaped, so that an integration of the new method in the aforementioned, very good practice is possible without problems. In continuation of the invention, the irradiation time can be controlled and in particular increased by the porphyrin or chlorin e6 offset blood plasma is taken after its exit from the hydrophobic or hydrophilic filter in a buffer and irradiated in this buffer.

To keep the entire system closed, the blood plasma is sent to a collection container immediately after irradiation.

The invention is further based on the desire to provide a device for inactivating undesirable in blood plasma organisms, with which the blood plasma is treated so that certainly no active organic ingredients, such as viruses or the like, are more present.

Such a device for inactivating blood-plasma-undesired organisms, in particular viruses, may include the following structure:

a) a reservoir with a mixture of freshly obtained, 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 radiation source for xenon -Radiation for irradiating the mixture in the irradiation chamber, e) a collection container for the irradiated blood plasma.

If a device for obtaining blood plasma according to the above-mentioned prior art is used, then a hydrophobic or hydrophilic filter filtering out of the blood the blood plasma can serve as a reservoir for the mixture of blood plasma and porphyrin or chlorin e6.

Such a hydrophobic or hydrophilic filter can be designed in particular as a U-shaped hollow fiber filter whose membranes are wetted or impregnated with porphyrin or chlorin e6. For easy control of the irradiation time and thus the intensity of a delay line may be arranged in the form of a drip path. It is also possible to arrange a buffer in the form of a surface filter. This surface filter can be arranged instead of or in addition to the drip path, in particular take up the drops and bring them into a thin, flat volume shape. In particular, both the droplets and the droplet-saturated surface filter with the same radiation source can be irradiated with xenon beams.

In the integration already mentioned, the hydrophobic or hydrophilic filter and the area filter can be arranged in a common filter housing, which can also comprise or serve as the irradiation chamber.

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

Furthermore, a device has proven in which the distance of the radiation source to the blood plasma is 30 to 40 mm. It should be noted that the effectively effective radiation dose is dependent not only on the radiation density of the radiation source, but also on the irradiation time and the distance of the radiation source and finally also on the radiation permeability of the radiation chamber, here z. B. the filter housing.

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

The radiation source can be designed very differently per se, as long as the radiation dose is sufficient. Thus, it can consist of several individual almost punctiform or planar radiation sources. A very effective irradiation is achieved if the radiation source is designed substantially as an open, closed or overlapping and horizontally arranged ring and the blood plasma is guided only by gravity through the interior, in particular through the center, of the ring. Then the radiation concentrates on the interior, the center of the ring and thus exclusively and from all sides on the blood plasma located there, so that it is possible to work with a relatively low radiation dose.

If desired or required, even two or more such rings may be arranged parallel to each other. If the ring is open, ie not completely closed on the circumference or partially overlapping, it can firstly be used for mounting a blood plasma leading line, for B. below the filter housing, record in its interior. Then he can, for. B. around the filter housing serving as the irradiation chamber, guided high and fixed in a certain, possibly adjustable distance to the blood plasma.

An aforementioned device can be conveniently and safely mounted by the radiation source and / or a reservoir containing the mixture or optionally the filter housing serving therefor and optionally the collecting container are releasably secured together on a sturdy holder.

Such a holder may comprise a vertical rod to adapt to different shapes or dimensions, in particular for receiving different, closed devices with storage and collecting containers, at which the radiation source and / or the reservoir or the filter housing and / or optionally the collecting container is mounted adjustable in height or are. Similar holders and rods are previously known from the aforementioned prior art for mounting a filter assembly.

To protect the environment and in particular of persons from the xenon beams, it can be provided that the radiation source is covered to the outside to be completely or at least radially by a protective shield. Such a shield may be internally at least partially mirrored. For gap-free radial shielding, an annular protective shield can have an almost tangential opening for passing through a line between two overlapping circumferential areas. 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, an embodiment of the invention is shown, which will now be described in more detail.

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

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

The device 1 according to FIG. 1 comprises a filter container 2, in whose upper inner region 2a a U-shaped hydrophobic or hydrophilic hollow fiber filter 3 is mounted, which consists of a multiplicity of fiber bundles. Through a supply line 4, the interior of the hollow fibers B blood are supplied, a first derivative 5 serves to discharge the cavities passing cellular blood components in a collecting container, not shown.

In the interior of the lower region 2b 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 microns. Below the surface filter 6, a supply line 8 and a discharge line 9 are in the bottom 7 of the filter container 2 attached. The discharge line 9 is used for discharging the squirted through the membranes of the hollow fiber filter 3 blood plasma 10, which can drip initially in the form of drops 10a centrally from the hollow fiber filter 3 out, then penetrates the surface filter 6 under gravity and fed via the discharge line 9 to a collecting container 11 becomes. The supply line 8 is used in particular for supplying superheated steam for sterilization.

The filter container 2 is detachably connected at the upper end of the area 2a via a clamp 12 and adjustably connected at the height H1 to a vertical bar 13 of a holder 14 which rests on the floor 16 in a stable manner via a foot 15. The collecting container 11 is suspended via a hook 17 in height H2 adjustable on the rod 13 The lower inner region 2b of the filter container 2 serves as an irradiation chamber and is therefore designed to be well permeable to xenon radiation. Appropriately, the entire filter container 2 is formed completely transparent. A xenon-emitting radiation source 18 comprises an annular radiator 19 which extends around the lower region 2b and thus also around the surface filter 6 and at a distance A of about 30 to 40 mm from the droplet 10a. The annular radiator 19 is not closed, but has a radial passage 20 at its periphery. The wavelength of the xenon beams is approximately between 300 to 800 .mu.m, in particular about 630 microns. The radiation source 18 comprises a clamp 21 with which it is adjustably connected to the vertical bar 13 at the height H3.

The clamp 21 may be rotatable and longitudinally adjustable in order to align the annular radiator 19 exactly concentric with the drops 10a falling in the region 2b and the surface filter 6, so that the xenon radiation can be exploited in a highly secure and effective manner. About an electrical patch cord 22, the radiation source 18 is connected to the usual power supply with 230 volts voltage.

To shield the environment against the intense xenon rays around the radiator 19, a protective shield 23 is arranged. Such a protective shield 23 is indicated in FIG. 1 for the sake of clarity only by dash-dotted lines and is drawn in FIG. 2 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. If the protective shield 23, which is annular in this case, is internally mirrored at least in part, then, in addition to the optical shielding, substantial bundling of the rays in the direction of the center of the ring and thus of the blood plasma to be irradiated is achieved. As a result, a significant energy savings can be achieved.

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

The irradiation procedure is, for example, as follows:

First, the hollow fibers of the hydrophobic or hydrophilic hollow fiber filter 3 are wetted with chlorin e6. Then blood B is passed through the feed line 4 into the inner cavities of the hydrophobic or hydrophilic hollow fiber filter 3 in the filter container 2. Inside the hollow fiber filter 3, the cellular components of the blood B remain behind and are passed through the discharge line 5 into a collection container, not shown.

The blood plasma and other unwanted microorganisms, in particular viruses, in short: the contaminated blood plasma 10, penetrates under gravity through the membranes of the hollow fibers, thereby enriching itself with chlorine e6 and collecting in the form of drops 10a in the middle of the lower region 2b of the Fiiterbehälters 2 and above the surface filter. 6

The contaminated and chlorin e6 enriched blood plasma 10 drips onto the surface filter 6, which absorbs the drops 10a, distributed in the area and held for a while, so as to serve as a buffer. The annular radiator 19 arranged around the falling drops 10a and the surface filter 6 irradiates both the individual falling drops 10a and the surface filter 6 soaked with blood plasma 10 with xenon beams.

By irradiating the mixture of contaminated blood plasma and chlorin e6 with xenon beams, undesired organisms, in particular viruses, are inactivated, so that the blood plasma 10 'finally taken up by the discharge 9 into the collection container 1 is in particular completely free of viruses.

During the irradiation process, the optical shield 23 shields the environment from the intense xenon rays safely. Since both the radiator 19 and the shield 23 have an opening on the periphery, namely passage 20 and Opening 24, can be used when mounting z. B. the lines 8 and 9 are performed laterally through these openings, so that the entire radiation source 18 can always remain on its holder 14. It needs after passing through the lines 8 and 9 on the rod 13 only slightly up to the lower portion 2b of the filter housing 2, to be moved when the filter housing 2 is first attached. Alternatively it can be provided that the radiation source 18 remains fixed and during assembly, the filter housing 2 is inserted from above into the radiator 19 and then the terminal 12 is tightened.

Reference numerals:

1 device

2 filter containers

2a upper area

2b lower area

3 hydrophobic or hydrophilic filter

4 supply line

5 derivative

6 area filters

7 soil

8 supply line

9 derivation

10 blood plasma with chlorin e6

10 'irradiated blood plasma

10a drops

11 collection containers

12 clamp

13 staff

14 holders

15 feet

16 floor

17 hooks

18 radiation source

19 spotlights

20 passage 21 clamp

22 plug cable

23 protective shield

24 opening

25 peripheral area

26 peripheral area

A distance

B blood

H1 height

H2 height

H3 height

Claims

claims

1. A method for inactivating undesirable in blood plasma organisms, in particular of viruses, characterized in that the blood plasma immediately upon its recovery from blood (B) with a porphyrin and the mixture (10, 10a) is irradiated with xenon beams.

2. The method according to claim 1, characterized in that a chlorin e6 is used as the porphyrin.

3. The method according to claim 1 or 2, characterized in that the porphyrin already the blood (B) in a blood plasma filtering out, hydrophobic or hydrophilic filter (3) is added and the porphyrin-added blood plasma (10, 10a) immediately after Exit from the hydrophobic or hydrophilic filter (3) is irradiated.

4. The method according to claim 3, characterized in that the porphyrin is added to the blood plasma (10, 10a) by the hydrophobic or hydrophilic filter (3) is impregnated with the porphyrin and then the blood (B) through the filter (3). is directed.

5. The method according to any one of claims 1 to 4, characterized in that the porphyrin staggered blood plasma is drop-shaped (10a) is irradiated.

6. The method according to any one of claims 1 to 5, characterized in that the added with porphyrin blood plasma (10) after its emergence from the hydrophobic or hydrophilic filter (3) in a buffer (6) and irradiated in this buffer (6) becomes.

7. The method according to any one of claims 1 to 6, characterized in that the blood plasma (10 ') immediately after the irradiation in a collecting container (11) is passed.

8. Device (1) for inactivating undesirable in blood plasma organisms, in particular of viruses, characterized by the following arrangement:

a) a reservoir (3) with a mixture (10) of freshly obtained, blood plasma and porphyrin,

b) an irradiation chamber (2b) for receiving the mixture,

c) a delay line (10a) and / or a buffer store (6) for the mixture (10) in the irradiation chamber (2b),

d) a radiation source (18, 19) for xenon radiation for irradiating the mixture (10) in the irradiation chamber (2b),

e) a collecting container (11) for the irradiated blood plasma (10 ').

9. The device according to claim 8, characterized in that from the blood (B) the blood plasma herausfiltemder, hydrophobic or hydrophilic filter (3) serves as a reservoir for the mixture (10) of blood plasma and porphyrin.

10. The device according to claim 9, characterized in that the hydrophobic or hydrophilic filter (3) is designed as a U-shaped hollow fiber filter.

11. The device according to claim 9 or 10, characterized in that the hydrophobic or hydrophilic filter (3) is wetted or impregnated with porphyrin.

12. Device according to one of claims 8 to 11, characterized in that the delay line is designed as a drip path.

13. Device according to one of claims 8 to 12, characterized in that the buffer is designed as a surface filter (6).

14. The apparatus according to claim 13, characterized in that the hydrophobic or hydrophilic filter (3) and the surface filter (6) are arranged in a common filter housing (2).

15. The apparatus according to claim 14, characterized in that the common filter housing (2) and the irradiation chamber (2b).

16. Device according to one of claims 8 to 15, characterized in that the xenon beams have a wavelength of 300 to 800 microns.

17. The apparatus according to claim 16, characterized in that the xenon beams have a filing length of about 630 microns.

18. 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.

19. The apparatus according to claim 18, characterized in that to ensure the distance (A) is a spacer.

20. Device according to one of claims 8 to 19, characterized in that the radiation source (18, 19) substantially 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.

21. Device according to one of claims 8 to 20, characterized in that the radiation source (18) and / or a mixture containing reservoir or optionally the filter (3) and optionally the collecting container (11) together on a sturdy holder (14 ) are releasably attached.

22. The apparatus according to claim 21, characterized in that the holder (14) comprises a vertical rod (13) on which the radiation source (18) and / or the reservoir or the filter (3) and / or optionally the collecting container (13). 11) in height (M, H2, H3) is adjustably mounted or are.

23. Device according to one of claims 8 to 22, characterized in that the radiation source (18, 19) is covered to the outside by a protective shield (23).

24. Device (14) according to claim 23, characterized in that the protective shield (23) is internally at least partially mirrored.

25. Device according to claim 23 or 24, characterized in that the annular protective shield (23) has a tangential opening (24) between two overlapping circumferential areas (25, 26).

26. Device according to one of claims 23 to 25, characterized in that the protective shield (23) on the radiation source (18) or on the rod (13) is attached.