CA2121834C - A container for receiving and separating a fluid, preferably blood plasma, into its ingredients - Google Patents
A container for receiving and separating a fluid, preferably blood plasma, into its ingredientsInfo
- Publication number
- CA2121834C CA2121834C CA002121834A CA2121834A CA2121834C CA 2121834 C CA2121834 C CA 2121834C CA 002121834 A CA002121834 A CA 002121834A CA 2121834 A CA2121834 A CA 2121834A CA 2121834 C CA2121834 C CA 2121834C
- Authority
- CA
- Canada
- Prior art keywords
- container
- valve
- sections
- projection
- valve members
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D21/00—Separation of suspended solid particles from liquids by sedimentation
- B01D21/26—Separation of sediment aided by centrifugal force or centripetal force
- B01D21/262—Separation of sediment aided by centrifugal force or centripetal force by using a centrifuge
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
- A61J1/1412—Containers with closing means, e.g. caps
- A61J1/1418—Threaded type
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
- A61M2202/0445—Proteins
- A61M2202/0447—Glycoproteins
- A61M2202/045—Fibrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
- A61M2202/0445—Proteins
- A61M2202/0447—Glycoproteins
- A61M2202/0452—Factor VIII
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
- A61M2202/0445—Proteins
- A61M2202/0447—Glycoproteins
- A61M2202/0454—Fibrinase, i.e. Factor XIII
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2221/00—Applications of separation devices
- B01D2221/10—Separation devices for use in medical, pharmaceutical or laboratory applications, e.g. separating amalgam from dental treatment residues
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/25125—Digestion or removing interfering materials
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
Abstract
A container for receiving and separating blood plasma into its ingredients comprises two sealingly coupled sections (1 and 2). One container section (2) and the adjacent portion of the other container section are made of solid material, and the two container sections are screwed together. The container sections (1 and 2) comprise their respective chambers (29 and 30) far receiving their respective fluid ingredients, and these chambers are interconnected through a connecting channel (31) through the abutting portions, at which the container sections (1 and 2) are screwed together. A valve seat (21, 27) is shaped at each: end of the connecting channel (31) for each valve member (22, 16) for a sealing closing of the chambers (29, 30) in the separated state of the container sections (1, 2). The valve members (22, 16) comprise mutually abutting projections (23, 12) ensuring a distance between the valve members (22, 16) exceeding the distance between the associated valve seats (27, 21) in the coupled state of the container sections (1, 2), but being smaller than the distance between the associated valve seats (27, 21) in a position during a separating movement of the container sections (1, 2). Furthermore, retaining means (15, 16) are provided for ensuring that the valve members (22, 19) do not engage the valve seats (27, 21) in the coupled state of the container sections (1, 2).
Description
,~ '~~ ~~1~9753 ~ ~ ~ ~ ~ ~ ~ ~~rr~~c~zroo~z~
_ 1 Title; A container for receiving, arid separatinr~ a fluid.
preferably blood plasma, into its ingredients.
Technical Field The invention relates to a container for receiving and separating a fluid, preferably blood plasma) into its ingredients, where said container comprises two sealing-ly coupled sections.
Backg_,round Art w It is known inter alia from tJS-PS No. 4,714,4S7 to uti-line the plasma fraction in blood for the preparation of 7.5 so-called tissue glue. According to the publication the coagulation factors, such as fibrinogen, fibronectine, factor VT'Il, and factor XIII are precipitated from the plasma frantion. These coagulation factors are precipi-tated for;instance by cryoprecipitation or by means of a precipitation-promoting agent such as ethan~1. The pre-cipitated precipitate includes mainly fibrinogen and is used as tissue glue, such as ~.n cona~ection with opera-tion wounds, by the addition of a suitable enzyme, such as thrombine. Like in natur e) the fibrinogen and throm-2~ 'tine form tpgether fibrin, ~rahich is a.n iz~soluble netwozk of fibre-like material constituting ~ kind 'of tissue glue interconnecting the wound surfaces during a healing process: On account of the latter effect; a concentrate o~ coagulation factors containing mainly fibrinogen turned out to gios'sess a fav~urable effect on the healing process after an operation. For short, the concentrate of coagulation fact~rs is below xefeared to as fibrino-gen, as said fibrinogen is the main ingredient thereof.
Several methods are today used for separating plasma from blood. The separating process can be performed by means of filters or centrifuging techniques or by way of combir~ations thereof . The methods are usually known as 2~.21~~4 vv~ ~3io~~s~ ~c-fi~~c9~/o,~~.,z~
z °°plasmapheresis". The methods have been developed be-cause it is often sufficient to give the patients a plasma transfusion, whereby it is unnecessary also to remove slowly regenerating blood cells from the donor.
The precipitation of fibrinogen from plasma has pre-viously been performed in closed bag systems. The preci-pitation into such bags (blood bags) necessitated pro-duction of particular means for securing the bags in a for centrifugal bowl) in which the centrifuging is to be performed. In addition) it is difficult to separatewthe fibrinogen from the plasma in a reliable mariner. The flexibility of the blood bags often results in the viscous fibrinogen loosening from the bag and mixing with a remaining plasma in the bag, whereby the concen-tration is substantially reduced. The latter problems have had the effect fha~t these methods are not used by way of routine today.
DescriQtion of the Invention The container'according to the present invention is characterised i~a that at least ono container section and the adjacent.poztion of the other container section are made substantially of solid material, that the two con-taixaer sections ' can be separated, wherelay the sections remain sealingly conaneoted during the separating move_ went away from orie ano'th~r ) that the container sections compriso their respective chamber for receiving their 3Q respective fluid~ingre'~iont, th'af the chambers are in-tercoxinected thxs~ugh a connecting channel defined by . mutually abutting portions of each container section, ' v that a valve'sea.t is shaped a each end of the connect-ing chanxaei for each valve member,for a sealing closing ' of the chambers in the separated state of the container sections, that the valve members comprise mutually abut-ting projections ensuring a distance between the valve members exceeding the distance between the associated . -; v. :'; ..:, . , ~. . -~:~ .:.: ,, . ..
.... ~~ ~~~~9~~~ ~ ~ 2 ~. ~ 3 4 PCT/13~92/OfD~29 _ 3 valve seats in the coupled state of the container sec-tions, but being smaller than the distance between the associated valve~seats in a position during the separat-ing movement of the container sections, and that retain-s ing means are provided for ensuring that the valve.mem-bers do net engage the valve seats in the coupled state of th.e container sections.
The resulting container is well-suited for use during the precipitation of fibrinogen from plasma. In addi-tion, the container allows a sterile storing of the~'~two separated fractions in their respective separate con-tainer section. In this manner) the fibrinogen can be stored separately in a refrigerator until it is heated to liquid state immediately before its use and trans-ferred to a syringe so as to be used as tissue glue. The suitability of the container is partly due to the fact that one container section is made of solid material, whereby the fibrinogen can be precipitated on a solid bottom) and partly due to the fact that the container sectaons can be separa ed and are automatically closed during the separating movement, whereby the plasma and the fibrinogen are easily placed in their respective container secti:on., As the dis'tanae between the valve m~mbexs is smaller than the distame between the valve seats in a position during the s~parat-ing movement of the container sections) the valve ynembers close the operi~.ngs into e~.ch container section before said con-tainer sections are completely separated during the last 30' step 'of the epa'rating movement. In this manner,' the sealing closing, of the container sections can be per-formed autom~ati~ally without rendering it possible to handle.the container in an incorrect manner.
Accordiaig to the invention the projections of the valve members may comprise co-operating and releasable snap-ping means ensuring that the valve members remain coupled together in the coupled state of the container ~O 93/09753 1'~'/I~~C92/4~~.'~29 's sections. In this manner, a predetermined resistance is ensured against a separation of the valve members during the separating movement of the container sections in such a manner that the valve members are caused to en-gage their respective valve seats under a predetermined load, whereby said valve members can enter the engage-ment,by way of friction and be retained in said engage-ment with the valve seats by the friction. In addition, one valve member can be supported at a distance from the associated valve seat by means of the other valve member and retaining means associated therewith. w The retaining means may according to the invention ad-vantageously comprise a retaining projection placed at 25 least on one valve member) said retaining projection extending away from the other valve membex and engaging by way of friction adjacent portions of the correspond-ing container section.
The'valve members may according to-the invention be as-sociated with their respective bi~.sed spring adapted to press said valve memhexs into a sealing engagement with the valve spats dining the separation of the container sections. In, this manner, an additional. pressing force is ean,sured for the valve members against the valve seats d,u~ing and after the separatixag procedure.
According to the invention the retaining prpjection on at least one valve member may advantageously comprise a 30' recess for a 'ca~-operati'on by way of frict~.on with a pro jectiorn on the wall of the corresponding container sec-tion opposite the salve seat:
Moreover according o the invention the container sec dons may be coupled together by means of co-operating threads, whereby the coupling and separation of the con ta mer sections can be performed in a particularly simply manner:
,.-~,, '6~l~ 9311?9753 PCfI DIC92/0032~
Furthermore according to the invention,. means may pre-ferably be provided for feeding fluid into the container under sterile conditions and for removing fluid ingre-dients also under sterile conditions from at least one 5 of the separated container sections through' the wall thereof. As a result it is possible to remove especially the fibrinogen from the container section in question without open:.ng the valve .
Finally according to the invention the opposing projec-tions of the valve members may comprise a recess on'one projection, said recess telescopically receiving the other projection) and the snapping means may be formed by a circumferential rib placed on one projection and engaging a circumferential groove on the other projec-tion with the result that the valve members are retained relative to one another in a particularly simple manner.
Brief l~escri,gtion of the Drawines The invention is described in grater detail below with reference to the accompanying drawing) 3.n which Fig; I. is a. side and substantially sectional view of a c~ntainer acaogdin~ to the invention, Fig. 2 alluatrates on a larger scale the lower portion of the container c~f Fig, ~,, 3Q Fig. 3 coxraspoxads to Fig. 2) but in a position d'urin'g the se~arating,moVernent of the two sections of the con-Miner, Fig. 4 corresponds to Fig. ~) but illustrating the two 3~ comp~.etely separated container sections, and Fig. 5 is a diagrammatic, sectional view of another em-bodiment of a container according to the invention.
~JVO 93/097S3 ~ ~ ~ ~ ~ ~ ~ , ~~C'flI~K92lO,i~;~~9 _ 6 Best Mode fox Carrying Out the Tnvention The container of Figs. 1 to 4 comprises two container b sections designated the general reference numerals 1 and 2. The upper container section 1 comprises a cohvention-al bottomless blood bag 3, cf. Fig. 1, welded at the lower open end 4 between a rotationally symmetrical mouth portion 5 abutting the inner side of the blood bag and a sleeve-shaped tube portion 6 abutting the outer Z0 side of said b):ood bag. The mouth portian S.continues through a shoulder portion 7 into a tubular portion provided with a thread 9 on the outside.
The lower seond container section 2 is screwed on the thread 9 of the mouth portion 5, cf. the drawing. The entire lower conta~:ner section 2 is rotationally sym-metrically shaped and comprises a tubular portion 10 provided with an internal thread 11. The internal thread 11 engages the thread 9 on the upper container section.
The tubular portion 10 continues through a shoulder por-t3:~n 12 into a cylindrical portion 13. The free end of the cylindrical portion is closed by mans of a bottom member T4. The bottom member 14 comprises a disk with a circumferent~,al .flame 15' abutting the inmer side of the cylindrical portion 13. The bottom member comprises furthermore a central) rotationally symmetrical projec-tion 15 projecting artto the intsr3,or of the second con-tainer section 2. A first valve anember 16 is ret~.ined on the latter projec ion by way of friction, said valve member also being'rotationally symmetrically shaped:
The firet va-lve'member T6 comprises a tubular portion 17 ' engaging the projection 7:5 on the bottom member 14. The cylindric~.l portion continues into a conical portion 1~
in turn continuing into a comparatively narrower cylin-dr'lcal portion 19, The cylindrical portion 19 forms a projection of the valve member 16. The projection 19 is narrower than the cylindrical portion 17 engaging the ,~--~. , 'W~ 93/09753 ~ ~ ~ ~ S ~ ~ P~T/bK92/0032~
projection 15 of the bottom member 14. Along the tran-sition area between the broad cylindrical portion 17 and the conical portion 18) the first valve member 16 is adapted to co-operate sealingly with the adjacent inner side of the threaded tubular portion 10 on the lower container section 2. Thus the area in question of the inner side of the tubular portion 1~ forms a valve seat 21 for the first valve member. The valve seat 21 and the valve member 16 are besides formed in such a manner that they co-operate with one another by way of friction.
A second valve member 22 is telescopically received on the narrow projection 19 of the first valve member 16.
Thus the second valve member 22 comprises a cylindrical projection 23 surrounding the projection 19 on the first valve member 16: 7~nternally, the cylindrical projection 23 compr~.ses a transverse wall 24. hike the first valve member 16, the second valve member 22 comprises a conic-al portion 25 expanding in a direction away from the 2a projecta.on 23 of the end farthest from the valve member ~,6 and ending a,t- a-cylindrical portion 26. The transi-tic~n axes between the conical portion 25 and the cylxn-drical portion 26 is adapted to coy-operate in a sealing manner with bheinne~ side of the mouth p~rtion 5 of the upger container sea ion 1 on the inaaer side of the / threaded tubular portion 8 of said mouth portion. The portion in question of the mouth portion fox~ns thus a valve seat 27: for the second valve membex 2?. The valve seat 2? and the valve tn~ember 22 are adapted to co-oper ate with one anot~her'by'way of ~riction.~
The end of the second valve member 22 facing the inte-ridr of the blood. bag 3 is closed'by means of a conical cap 28 glued hereon.
As illus~Crated in the drawing, the telescopically co-operating projections 19 and 23) respectively, of the two valve members 16 and 22 are of such a length that ~~ 9~ro~~s~ ~~-r~~~~c~~oo~,~z~
2~~I~3~4' the two valve members 16 and 22 in the position shown in Figs. 1 and 2 are retained inside their respective con-tainer section 2 and 1 at a distance from the associated valve seats 21 and 27, said valve members in Figs. 1 and 2 being supported by the projection 15 on the lower con-b tamer section 2. As a result, an open connection exists between the interiors of the two container sections 1 and 2, Thus an open connection exists between a first chamber 29 inside the upper container section 1 and a chamber 30 inside the lower container section.2 through a connecting channel 31. Tha connecting channel 31'~is defined by the tubular portions 8 and 10, respectively, of the two container sections 1 and 2. As clearly illu-strated in Fig. 4, the projection 19 on the first valve member 16 comprises a circumferential rib 32. Corre-spandingly) the projection 23 on the second valve member 22 comprises on the ~,nner side a circumferential groove 33. The rib 32 and the groove 33 are adapted to snap-engage one another in such a manner that the second vaJ.ve membex 22 remains positioned on the first valve member 16 in the position ref Fig. 1 and is only released by a predetermined force in the axial direction thereof.
The di~tance'.between the two valve anembers 16 and 22 in tha engaging position of the rib 32 and the groove 33 is 'cf such a siza, cf. fig. 3,, that the 'valve members I6 and 22 engaga their associated salve seats 21 and 27) :re~p~ctively', ~,rlaen the two container sections 1 and 2 have been partially unscrewed one another, but are still engaging one another'thzough their th~ea'ds 9 and 11. As' also illustrated in Fig. 3) the first valve member 16 is I paxtially disengaging the projection 15 on the bottom ~oxtion'I4 of the lower container section 2 in the posi f~:an in which the:valve members 16 and 22 have fully 35. engaged their valve seats 21 and 27. The engagement of the valve members 16 and 22 by means of the rib 32 and the groove 33 has the effect that the valve members 16 and 22 remain coupled together until they have been ,~~, VN~ 93!Q9753 ~ ~ ~ ~ ~ ~ ~ P~.'TlDK92/~D03~9 pulled into position relative to their valve seats 21 and 27.
A continued unscrewing of the two container sections 1 and 2 relative to one another has the result"that the two valve members 16 and 22 are pulled out of their en-gagement, cf. Fig. 4) and left sealingly engaging their respective valve seats 21 and 27.
As illustrated 3.n the drawing) the first container sec-tion comprises a tubing 34 for the feeding of plasma to the first container section 1. The container section comprises furthermore a tubing 35 allowing feeding under sterile conditions thrcaugh a conventional filter of an agent, such as alcohol) fo'r instance ethanol, for an acceleration of the precipitation of a concentrate of coagulation factors ire the container.
A rubber msmb~ane 37 is furthermore provided within the 2p shoulder portion 12 ova the second container section, said rubber .membrane allowing ~xsuction of concentrate from the second:con~ainer section 2 by means of a sy ring~.:
- 25 Beyond assisting in fastening the blood bag 3 on the mouth portion 5 of the upper container sect~,on 1, the outer sleeve-shaped tube porfiion 6 serves also to pro-~~,de the container faith a pleasant appearance, said tube portio~r, 6 abutting the~ broad cyla;ndrical portion 13 on 3~ the second.con~ainex section 2~when the two container y ~dcbi~ns are screwed tightly together.
'When the container according to the invention is used, plasma is filled tluerein through the tubing 14. After 35 addi a.on of uitabl~'agents for accel:exating the preci pitation coagulation factors, the precipitation process is initiated in-a conventionally known manner, such as by way of cryoprecipitation. Subsequently, the container W~ 93/09p3 PCf/I)K92100:~~9 4. '~
is subjected to a centrifuging in such a manner that the very viscous concentrate is placed in the second chamber 50 of the container inside the second container section 2. When the concentrate has been collected in the second 5 container section 2, the container is turned 3n such a r manner that the container section 1 with the blood bag 3 faces downwards. As a result, the blood plasma flows into the blood bag 3 while the concentrate of fibrinogen or coagulation factors remain in the container section 2 10 now being the upper section. Then the two container sec-tions 1 and 2 are separated by being unscrewed one ono-ther. As the two container sections gradually reach the position shown in Fig. 3 during their separating move-ment) the two valve members 16 and 22 are pulled into a tight engagement with their respective valve seats 22 and 27. A continued unscre~;ing during the last step of the mutual separating movement of the two container sec-tions causes the two va~.ve members 16 and 22 to be pulldd out of their engagement. Finally) the two con-tamer sectia~s 1 and 2 reach the completely separated state shown ire Fig. 4) said state allowing the sections to be handled separately according to desire. The con-tainer section ~ containing the concentrate can be placed in an refrigerator until the'concentrate is to be used. 3~Then -the coa~~entrate as to be used, it is heated until it is sufficiently liquid for being sucked out through the rubber membrane ~7.
Fig. 5 is a ~.iagraBamatic view of a second embodiment of the invention, where parts corresponding~to the emboli ment of Figs . 1 , 0 4 have been provided with the same I ~efegence numerals,, The contain~x of Fig. 5 comprises °
also twto container sections 1 and 2, These container secti.orrs 1 and 2 are screwed together by means of a short thread: Therefore) a sterile-closing membrane 40 is provided about the connection place) said membrane being diagrammatically indicated. The membxane 40 is broken when the two container sections 1 and 2 are ,-~-~ ) Wt~ 93l09753 ~ PCTlI~K92100329 pulled a short distance apart after having been un-screwed one another. &;ach container section 1 and 2 com-prises a valve member 19 and 22 co-operating with their respective valve seat 21 and 27. lBoth valve members 19 and 22 comprise projections 41 and 42 facing away from their valve seats, said projections being received~in their respective guide tubing 43 and 44) respectively. A
spring 45 and 46 is arranged about each projection 41 and 42, said springs biasing the valve members 19 and 22 forwards towards their valve seats 21 and 27.~ The valve members 19 and 22 comprise furthermore projections' 47 and 48 projecting forwards towards one another and abut-zing one another ,in the position shown in Fig. S so as.
to keep the valve members 19 and 22 in contact with the ends of the guide tubings 43 and 44 at a distance from the valve seats 2l and 27. The separation of the two contaa.ner sections 2 and 2 aativa es the springs 45 and 46 to press the valve members against their respective valve seats 21 and 27 , the two abutting paro j ections 47 and 48 being of such a length that the valve seats en-gage ~ne another before the membrane 40 is broken.
The embodimen t of the-'container shown in Fig. 5 is used ih the same ynanner as stated above( The container according to the invention is easily pro-drxced from injection moulded parts, and as far as the embodiment of Figs : 1 to 4 is concerned the two valve members 16 and 22 are assembled before the blood bag 3 is glued onto~the mouth potion 5. Before the second val~cre xnember 22 i~ secured to 'the first valve member 16 , said first halve znemb~r is mounted on the proj ection 15 on the bot~nrn member 14, which' is subsequently glued ont~ the second container section 2) The blood bag 3 is, as mentioned; fastened by way of gluing, but it can also be fastened by way of welding. both the second container section 2 and the valve members 16 and 22 as well.as the mouth portion 5 of the first container section. 1 and the 'W~ 93!097S3 ~ ~ ~ ~ ~ ~ ~ PC f/DK92l~n'~=~9 r sleeve-shaped tube portion 6 are made of a solid plastic material, which may be of any suitable nature) such as polyvinyl chloride.
The invention has been described with reference to pre-ferred embodiments. Many modifications may, however, be carried out without thereby deviating from the scope of the invention. The container of Figs. 1 to ~E may for instance be of another shape than the rotationally sym- Q
metrical shape. Suitable sealing means may furthermore be provided in order to ensure the necessary sealing.
The described container is preferably intended for use in connection with blood plasma, but it may, of course, also be used for other fluids with ingredients available in states allowing the described separation.
_ 1 Title; A container for receiving, arid separatinr~ a fluid.
preferably blood plasma, into its ingredients.
Technical Field The invention relates to a container for receiving and separating a fluid, preferably blood plasma) into its ingredients, where said container comprises two sealing-ly coupled sections.
Backg_,round Art w It is known inter alia from tJS-PS No. 4,714,4S7 to uti-line the plasma fraction in blood for the preparation of 7.5 so-called tissue glue. According to the publication the coagulation factors, such as fibrinogen, fibronectine, factor VT'Il, and factor XIII are precipitated from the plasma frantion. These coagulation factors are precipi-tated for;instance by cryoprecipitation or by means of a precipitation-promoting agent such as ethan~1. The pre-cipitated precipitate includes mainly fibrinogen and is used as tissue glue, such as ~.n cona~ection with opera-tion wounds, by the addition of a suitable enzyme, such as thrombine. Like in natur e) the fibrinogen and throm-2~ 'tine form tpgether fibrin, ~rahich is a.n iz~soluble netwozk of fibre-like material constituting ~ kind 'of tissue glue interconnecting the wound surfaces during a healing process: On account of the latter effect; a concentrate o~ coagulation factors containing mainly fibrinogen turned out to gios'sess a fav~urable effect on the healing process after an operation. For short, the concentrate of coagulation fact~rs is below xefeared to as fibrino-gen, as said fibrinogen is the main ingredient thereof.
Several methods are today used for separating plasma from blood. The separating process can be performed by means of filters or centrifuging techniques or by way of combir~ations thereof . The methods are usually known as 2~.21~~4 vv~ ~3io~~s~ ~c-fi~~c9~/o,~~.,z~
z °°plasmapheresis". The methods have been developed be-cause it is often sufficient to give the patients a plasma transfusion, whereby it is unnecessary also to remove slowly regenerating blood cells from the donor.
The precipitation of fibrinogen from plasma has pre-viously been performed in closed bag systems. The preci-pitation into such bags (blood bags) necessitated pro-duction of particular means for securing the bags in a for centrifugal bowl) in which the centrifuging is to be performed. In addition) it is difficult to separatewthe fibrinogen from the plasma in a reliable mariner. The flexibility of the blood bags often results in the viscous fibrinogen loosening from the bag and mixing with a remaining plasma in the bag, whereby the concen-tration is substantially reduced. The latter problems have had the effect fha~t these methods are not used by way of routine today.
DescriQtion of the Invention The container'according to the present invention is characterised i~a that at least ono container section and the adjacent.poztion of the other container section are made substantially of solid material, that the two con-taixaer sections ' can be separated, wherelay the sections remain sealingly conaneoted during the separating move_ went away from orie ano'th~r ) that the container sections compriso their respective chamber for receiving their 3Q respective fluid~ingre'~iont, th'af the chambers are in-tercoxinected thxs~ugh a connecting channel defined by . mutually abutting portions of each container section, ' v that a valve'sea.t is shaped a each end of the connect-ing chanxaei for each valve member,for a sealing closing ' of the chambers in the separated state of the container sections, that the valve members comprise mutually abut-ting projections ensuring a distance between the valve members exceeding the distance between the associated . -; v. :'; ..:, . , ~. . -~:~ .:.: ,, . ..
.... ~~ ~~~~9~~~ ~ ~ 2 ~. ~ 3 4 PCT/13~92/OfD~29 _ 3 valve seats in the coupled state of the container sec-tions, but being smaller than the distance between the associated valve~seats in a position during the separat-ing movement of the container sections, and that retain-s ing means are provided for ensuring that the valve.mem-bers do net engage the valve seats in the coupled state of th.e container sections.
The resulting container is well-suited for use during the precipitation of fibrinogen from plasma. In addi-tion, the container allows a sterile storing of the~'~two separated fractions in their respective separate con-tainer section. In this manner) the fibrinogen can be stored separately in a refrigerator until it is heated to liquid state immediately before its use and trans-ferred to a syringe so as to be used as tissue glue. The suitability of the container is partly due to the fact that one container section is made of solid material, whereby the fibrinogen can be precipitated on a solid bottom) and partly due to the fact that the container sectaons can be separa ed and are automatically closed during the separating movement, whereby the plasma and the fibrinogen are easily placed in their respective container secti:on., As the dis'tanae between the valve m~mbexs is smaller than the distame between the valve seats in a position during the s~parat-ing movement of the container sections) the valve ynembers close the operi~.ngs into e~.ch container section before said con-tainer sections are completely separated during the last 30' step 'of the epa'rating movement. In this manner,' the sealing closing, of the container sections can be per-formed autom~ati~ally without rendering it possible to handle.the container in an incorrect manner.
Accordiaig to the invention the projections of the valve members may comprise co-operating and releasable snap-ping means ensuring that the valve members remain coupled together in the coupled state of the container ~O 93/09753 1'~'/I~~C92/4~~.'~29 's sections. In this manner, a predetermined resistance is ensured against a separation of the valve members during the separating movement of the container sections in such a manner that the valve members are caused to en-gage their respective valve seats under a predetermined load, whereby said valve members can enter the engage-ment,by way of friction and be retained in said engage-ment with the valve seats by the friction. In addition, one valve member can be supported at a distance from the associated valve seat by means of the other valve member and retaining means associated therewith. w The retaining means may according to the invention ad-vantageously comprise a retaining projection placed at 25 least on one valve member) said retaining projection extending away from the other valve membex and engaging by way of friction adjacent portions of the correspond-ing container section.
The'valve members may according to-the invention be as-sociated with their respective bi~.sed spring adapted to press said valve memhexs into a sealing engagement with the valve spats dining the separation of the container sections. In, this manner, an additional. pressing force is ean,sured for the valve members against the valve seats d,u~ing and after the separatixag procedure.
According to the invention the retaining prpjection on at least one valve member may advantageously comprise a 30' recess for a 'ca~-operati'on by way of frict~.on with a pro jectiorn on the wall of the corresponding container sec-tion opposite the salve seat:
Moreover according o the invention the container sec dons may be coupled together by means of co-operating threads, whereby the coupling and separation of the con ta mer sections can be performed in a particularly simply manner:
,.-~,, '6~l~ 9311?9753 PCfI DIC92/0032~
Furthermore according to the invention,. means may pre-ferably be provided for feeding fluid into the container under sterile conditions and for removing fluid ingre-dients also under sterile conditions from at least one 5 of the separated container sections through' the wall thereof. As a result it is possible to remove especially the fibrinogen from the container section in question without open:.ng the valve .
Finally according to the invention the opposing projec-tions of the valve members may comprise a recess on'one projection, said recess telescopically receiving the other projection) and the snapping means may be formed by a circumferential rib placed on one projection and engaging a circumferential groove on the other projec-tion with the result that the valve members are retained relative to one another in a particularly simple manner.
Brief l~escri,gtion of the Drawines The invention is described in grater detail below with reference to the accompanying drawing) 3.n which Fig; I. is a. side and substantially sectional view of a c~ntainer acaogdin~ to the invention, Fig. 2 alluatrates on a larger scale the lower portion of the container c~f Fig, ~,, 3Q Fig. 3 coxraspoxads to Fig. 2) but in a position d'urin'g the se~arating,moVernent of the two sections of the con-Miner, Fig. 4 corresponds to Fig. ~) but illustrating the two 3~ comp~.etely separated container sections, and Fig. 5 is a diagrammatic, sectional view of another em-bodiment of a container according to the invention.
~JVO 93/097S3 ~ ~ ~ ~ ~ ~ ~ , ~~C'flI~K92lO,i~;~~9 _ 6 Best Mode fox Carrying Out the Tnvention The container of Figs. 1 to 4 comprises two container b sections designated the general reference numerals 1 and 2. The upper container section 1 comprises a cohvention-al bottomless blood bag 3, cf. Fig. 1, welded at the lower open end 4 between a rotationally symmetrical mouth portion 5 abutting the inner side of the blood bag and a sleeve-shaped tube portion 6 abutting the outer Z0 side of said b):ood bag. The mouth portian S.continues through a shoulder portion 7 into a tubular portion provided with a thread 9 on the outside.
The lower seond container section 2 is screwed on the thread 9 of the mouth portion 5, cf. the drawing. The entire lower conta~:ner section 2 is rotationally sym-metrically shaped and comprises a tubular portion 10 provided with an internal thread 11. The internal thread 11 engages the thread 9 on the upper container section.
The tubular portion 10 continues through a shoulder por-t3:~n 12 into a cylindrical portion 13. The free end of the cylindrical portion is closed by mans of a bottom member T4. The bottom member 14 comprises a disk with a circumferent~,al .flame 15' abutting the inmer side of the cylindrical portion 13. The bottom member comprises furthermore a central) rotationally symmetrical projec-tion 15 projecting artto the intsr3,or of the second con-tainer section 2. A first valve anember 16 is ret~.ined on the latter projec ion by way of friction, said valve member also being'rotationally symmetrically shaped:
The firet va-lve'member T6 comprises a tubular portion 17 ' engaging the projection 7:5 on the bottom member 14. The cylindric~.l portion continues into a conical portion 1~
in turn continuing into a comparatively narrower cylin-dr'lcal portion 19, The cylindrical portion 19 forms a projection of the valve member 16. The projection 19 is narrower than the cylindrical portion 17 engaging the ,~--~. , 'W~ 93/09753 ~ ~ ~ ~ S ~ ~ P~T/bK92/0032~
projection 15 of the bottom member 14. Along the tran-sition area between the broad cylindrical portion 17 and the conical portion 18) the first valve member 16 is adapted to co-operate sealingly with the adjacent inner side of the threaded tubular portion 10 on the lower container section 2. Thus the area in question of the inner side of the tubular portion 1~ forms a valve seat 21 for the first valve member. The valve seat 21 and the valve member 16 are besides formed in such a manner that they co-operate with one another by way of friction.
A second valve member 22 is telescopically received on the narrow projection 19 of the first valve member 16.
Thus the second valve member 22 comprises a cylindrical projection 23 surrounding the projection 19 on the first valve member 16: 7~nternally, the cylindrical projection 23 compr~.ses a transverse wall 24. hike the first valve member 16, the second valve member 22 comprises a conic-al portion 25 expanding in a direction away from the 2a projecta.on 23 of the end farthest from the valve member ~,6 and ending a,t- a-cylindrical portion 26. The transi-tic~n axes between the conical portion 25 and the cylxn-drical portion 26 is adapted to coy-operate in a sealing manner with bheinne~ side of the mouth p~rtion 5 of the upger container sea ion 1 on the inaaer side of the / threaded tubular portion 8 of said mouth portion. The portion in question of the mouth portion fox~ns thus a valve seat 27: for the second valve membex 2?. The valve seat 2? and the valve tn~ember 22 are adapted to co-oper ate with one anot~her'by'way of ~riction.~
The end of the second valve member 22 facing the inte-ridr of the blood. bag 3 is closed'by means of a conical cap 28 glued hereon.
As illus~Crated in the drawing, the telescopically co-operating projections 19 and 23) respectively, of the two valve members 16 and 22 are of such a length that ~~ 9~ro~~s~ ~~-r~~~~c~~oo~,~z~
2~~I~3~4' the two valve members 16 and 22 in the position shown in Figs. 1 and 2 are retained inside their respective con-tainer section 2 and 1 at a distance from the associated valve seats 21 and 27, said valve members in Figs. 1 and 2 being supported by the projection 15 on the lower con-b tamer section 2. As a result, an open connection exists between the interiors of the two container sections 1 and 2, Thus an open connection exists between a first chamber 29 inside the upper container section 1 and a chamber 30 inside the lower container section.2 through a connecting channel 31. Tha connecting channel 31'~is defined by the tubular portions 8 and 10, respectively, of the two container sections 1 and 2. As clearly illu-strated in Fig. 4, the projection 19 on the first valve member 16 comprises a circumferential rib 32. Corre-spandingly) the projection 23 on the second valve member 22 comprises on the ~,nner side a circumferential groove 33. The rib 32 and the groove 33 are adapted to snap-engage one another in such a manner that the second vaJ.ve membex 22 remains positioned on the first valve member 16 in the position ref Fig. 1 and is only released by a predetermined force in the axial direction thereof.
The di~tance'.between the two valve anembers 16 and 22 in tha engaging position of the rib 32 and the groove 33 is 'cf such a siza, cf. fig. 3,, that the 'valve members I6 and 22 engaga their associated salve seats 21 and 27) :re~p~ctively', ~,rlaen the two container sections 1 and 2 have been partially unscrewed one another, but are still engaging one another'thzough their th~ea'ds 9 and 11. As' also illustrated in Fig. 3) the first valve member 16 is I paxtially disengaging the projection 15 on the bottom ~oxtion'I4 of the lower container section 2 in the posi f~:an in which the:valve members 16 and 22 have fully 35. engaged their valve seats 21 and 27. The engagement of the valve members 16 and 22 by means of the rib 32 and the groove 33 has the effect that the valve members 16 and 22 remain coupled together until they have been ,~~, VN~ 93!Q9753 ~ ~ ~ ~ ~ ~ ~ P~.'TlDK92/~D03~9 pulled into position relative to their valve seats 21 and 27.
A continued unscrewing of the two container sections 1 and 2 relative to one another has the result"that the two valve members 16 and 22 are pulled out of their en-gagement, cf. Fig. 4) and left sealingly engaging their respective valve seats 21 and 27.
As illustrated 3.n the drawing) the first container sec-tion comprises a tubing 34 for the feeding of plasma to the first container section 1. The container section comprises furthermore a tubing 35 allowing feeding under sterile conditions thrcaugh a conventional filter of an agent, such as alcohol) fo'r instance ethanol, for an acceleration of the precipitation of a concentrate of coagulation factors ire the container.
A rubber msmb~ane 37 is furthermore provided within the 2p shoulder portion 12 ova the second container section, said rubber .membrane allowing ~xsuction of concentrate from the second:con~ainer section 2 by means of a sy ring~.:
- 25 Beyond assisting in fastening the blood bag 3 on the mouth portion 5 of the upper container sect~,on 1, the outer sleeve-shaped tube porfiion 6 serves also to pro-~~,de the container faith a pleasant appearance, said tube portio~r, 6 abutting the~ broad cyla;ndrical portion 13 on 3~ the second.con~ainex section 2~when the two container y ~dcbi~ns are screwed tightly together.
'When the container according to the invention is used, plasma is filled tluerein through the tubing 14. After 35 addi a.on of uitabl~'agents for accel:exating the preci pitation coagulation factors, the precipitation process is initiated in-a conventionally known manner, such as by way of cryoprecipitation. Subsequently, the container W~ 93/09p3 PCf/I)K92100:~~9 4. '~
is subjected to a centrifuging in such a manner that the very viscous concentrate is placed in the second chamber 50 of the container inside the second container section 2. When the concentrate has been collected in the second 5 container section 2, the container is turned 3n such a r manner that the container section 1 with the blood bag 3 faces downwards. As a result, the blood plasma flows into the blood bag 3 while the concentrate of fibrinogen or coagulation factors remain in the container section 2 10 now being the upper section. Then the two container sec-tions 1 and 2 are separated by being unscrewed one ono-ther. As the two container sections gradually reach the position shown in Fig. 3 during their separating move-ment) the two valve members 16 and 22 are pulled into a tight engagement with their respective valve seats 22 and 27. A continued unscre~;ing during the last step of the mutual separating movement of the two container sec-tions causes the two va~.ve members 16 and 22 to be pulldd out of their engagement. Finally) the two con-tamer sectia~s 1 and 2 reach the completely separated state shown ire Fig. 4) said state allowing the sections to be handled separately according to desire. The con-tainer section ~ containing the concentrate can be placed in an refrigerator until the'concentrate is to be used. 3~Then -the coa~~entrate as to be used, it is heated until it is sufficiently liquid for being sucked out through the rubber membrane ~7.
Fig. 5 is a ~.iagraBamatic view of a second embodiment of the invention, where parts corresponding~to the emboli ment of Figs . 1 , 0 4 have been provided with the same I ~efegence numerals,, The contain~x of Fig. 5 comprises °
also twto container sections 1 and 2, These container secti.orrs 1 and 2 are screwed together by means of a short thread: Therefore) a sterile-closing membrane 40 is provided about the connection place) said membrane being diagrammatically indicated. The membxane 40 is broken when the two container sections 1 and 2 are ,-~-~ ) Wt~ 93l09753 ~ PCTlI~K92100329 pulled a short distance apart after having been un-screwed one another. &;ach container section 1 and 2 com-prises a valve member 19 and 22 co-operating with their respective valve seat 21 and 27. lBoth valve members 19 and 22 comprise projections 41 and 42 facing away from their valve seats, said projections being received~in their respective guide tubing 43 and 44) respectively. A
spring 45 and 46 is arranged about each projection 41 and 42, said springs biasing the valve members 19 and 22 forwards towards their valve seats 21 and 27.~ The valve members 19 and 22 comprise furthermore projections' 47 and 48 projecting forwards towards one another and abut-zing one another ,in the position shown in Fig. S so as.
to keep the valve members 19 and 22 in contact with the ends of the guide tubings 43 and 44 at a distance from the valve seats 2l and 27. The separation of the two contaa.ner sections 2 and 2 aativa es the springs 45 and 46 to press the valve members against their respective valve seats 21 and 27 , the two abutting paro j ections 47 and 48 being of such a length that the valve seats en-gage ~ne another before the membrane 40 is broken.
The embodimen t of the-'container shown in Fig. 5 is used ih the same ynanner as stated above( The container according to the invention is easily pro-drxced from injection moulded parts, and as far as the embodiment of Figs : 1 to 4 is concerned the two valve members 16 and 22 are assembled before the blood bag 3 is glued onto~the mouth potion 5. Before the second val~cre xnember 22 i~ secured to 'the first valve member 16 , said first halve znemb~r is mounted on the proj ection 15 on the bot~nrn member 14, which' is subsequently glued ont~ the second container section 2) The blood bag 3 is, as mentioned; fastened by way of gluing, but it can also be fastened by way of welding. both the second container section 2 and the valve members 16 and 22 as well.as the mouth portion 5 of the first container section. 1 and the 'W~ 93!097S3 ~ ~ ~ ~ ~ ~ ~ PC f/DK92l~n'~=~9 r sleeve-shaped tube portion 6 are made of a solid plastic material, which may be of any suitable nature) such as polyvinyl chloride.
The invention has been described with reference to pre-ferred embodiments. Many modifications may, however, be carried out without thereby deviating from the scope of the invention. The container of Figs. 1 to ~E may for instance be of another shape than the rotationally sym- Q
metrical shape. Suitable sealing means may furthermore be provided in order to ensure the necessary sealing.
The described container is preferably intended for use in connection with blood plasma, but it may, of course, also be used for other fluids with ingredients available in states allowing the described separation.
Claims (8)
1. A container for receiving and separating a fluid, preferably blood plasma, into its ingredients, where said container comprises two sealingly coupled sections, characterised in that at least one container section (2) and the adjacent portion (5, 6) of the other container section (1) are made substantially of solid material, that the two container sections (1, 2) can be separated, whereby the sections (1,2) remain sealingly connected during the separating movement away from one another, that the container sections (1, 2) comprise their respective chamber (29 and 30) for receiving their respective fluid ingredient, that the chambers (29, 30) are interconnected through a connecting channel {31) defined by mutually abutting portions (8, 10) of each container section (1, 2), that a valve seat (21, 27) is shaped at each end of the connecting channel (31) for each valve member (22, 16) for a sealing closing of the chambers (29, 30) in the separated state of the.container sections (1, 2), that the valve members (22, 16) comprise mutually abutting projections (23, 48; 19, 47) ensuring a distance between the valve members (22, 16) exceeding the distance between the associated valve seats (27, 21) in the coupled state of the container sections (1, 2), but being smaller than the distance between the associated valve seats (27, 21) in a position during the separating movement of the container sections (1, 2), and that retaining means (15, 17; 41, 43, 44, and 46) are provided for ensuring that the valve members (22, 19) do not engage the valve seats (27, 21) in the coupled state of the container sections (1, 2).
2. A container as claimed in claim 1, characterised in that the projections (19, 23) of the valve members (16, 22) comprise co-operating and releasable snapping means (32, 33) ensuring that the valve members (16, 22) remain coupled together in the coupled state of the container sections (2, 1).
3. A container as claimed in claim 1 or 2, characterised in that the retaining means (15, 17) comprise a retaining projection (17) placed at least on one valve member (16), said regaining projection extending away from the other valve member (22) and engaging by way of friction adjacent portions of the corresponding container section (2).
4. A container as claimed in claim 1 or 2, characterised in that the valve members (16, 22) are associated with their respective biased spring (45, 46) adapted to press said valve members (16, 22) into a sealing engagement with the valve seats (21, 27) during the separation of the container sections (2, 1).
5. A container as claimed in claim 3, characterised in that the retaining projection (17) on at least one valve member (16) comprises a recess for a co-operation by way of friction with a projection (15) on the wall (14) of the corresponding container section (2) opposite the valve seat (21).
6. A container as claimed in one or more of the preceding claims 1 to 5, characterised in that the container sections (1, 2) are coupled together by paeans of co-operating threads (9, 11).
7. A container as claimed in one or more of the preceding claims 1 to 6, characterised in that means (36, 37) are provided for feeding fluid into the container under sterile conditions and for removing fluid ingredients also under sterile conditions from at least one of the separated container sections (1, 2) through the wall thereof.
8. A container as claimed in one or more of the preceding claims 2 to 5, characterised in that the opposing projections (19) 23) of the valve members (16, 22) comprise a recess on one projection (23), said recess telescopically receiving the other projection (19), and that the snapping means (32) 33) are formed by a circumferential rib (32) placed on one projection and engaging a circumferential groove (33) on the other projection.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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DK1848/91 | 1991-11-11 | ||
DK184891A DK167517B1 (en) | 1991-11-11 | 1991-11-11 | CONTAINER FOR INCLUSION AND SEPARATION OF A FLUID, PRETTY BLOOD PLASMA, IN ITS INGREDIENTS |
PCT/DK1992/000329 WO1993009753A1 (en) | 1991-11-11 | 1992-11-10 | A container for receiving and separating a fluid, preferably blood plasma, into its ingredients |
Publications (2)
Publication Number | Publication Date |
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CA2121834A1 CA2121834A1 (en) | 1993-05-27 |
CA2121834C true CA2121834C (en) | 1999-08-17 |
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Application Number | Title | Priority Date | Filing Date |
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CA002121834A Expired - Fee Related CA2121834C (en) | 1991-11-11 | 1992-11-10 | A container for receiving and separating a fluid, preferably blood plasma, into its ingredients |
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EP (1) | EP0612238B1 (en) |
JP (1) | JP3249821B2 (en) |
KR (1) | KR100191138B1 (en) |
CN (1) | CN1031316C (en) |
AT (1) | ATE128857T1 (en) |
AU (1) | AU662182B2 (en) |
BR (1) | BR9206732A (en) |
CA (1) | CA2121834C (en) |
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DE (1) | DE69205438T2 (en) |
DK (2) | DK167517B1 (en) |
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FI (1) | FI105774B (en) |
GR (1) | GR3018561T3 (en) |
HU (1) | HU213814B (en) |
IL (1) | IL103694A (en) |
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NZ (1) | NZ245080A (en) |
PL (1) | PL171122B1 (en) |
SK (1) | SK279337B6 (en) |
WO (1) | WO1993009753A1 (en) |
ZA (1) | ZA928655B (en) |
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1991
- 1991-11-11 DK DK184891A patent/DK167517B1/en not_active IP Right Cessation
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1992
- 1992-11-09 IL IL10369492A patent/IL103694A/en not_active IP Right Cessation
- 1992-11-10 DK DK92923715T patent/DK0612238T3/en active
- 1992-11-10 MX MX9206451A patent/MX9206451A/en not_active IP Right Cessation
- 1992-11-10 PL PL92303540A patent/PL171122B1/en unknown
- 1992-11-10 BR BR9206732A patent/BR9206732A/en not_active IP Right Cessation
- 1992-11-10 KR KR1019940701467A patent/KR100191138B1/en not_active IP Right Cessation
- 1992-11-10 CZ CZ941120A patent/CZ281922B6/en not_active IP Right Cessation
- 1992-11-10 DE DE69205438T patent/DE69205438T2/en not_active Expired - Fee Related
- 1992-11-10 NZ NZ245080A patent/NZ245080A/en not_active IP Right Cessation
- 1992-11-10 JP JP50889193A patent/JP3249821B2/en not_active Expired - Fee Related
- 1992-11-10 AU AU29425/92A patent/AU662182B2/en not_active Ceased
- 1992-11-10 ZA ZA928655A patent/ZA928655B/en unknown
- 1992-11-10 CA CA002121834A patent/CA2121834C/en not_active Expired - Fee Related
- 1992-11-10 HU HU9401344A patent/HU213814B/en not_active IP Right Cessation
- 1992-11-10 AT AT92923715T patent/ATE128857T1/en not_active IP Right Cessation
- 1992-11-10 US US08/240,641 patent/US5462716A/en not_active Expired - Lifetime
- 1992-11-10 SK SK542-94A patent/SK279337B6/en unknown
- 1992-11-10 EP EP92923715A patent/EP0612238B1/en not_active Expired - Lifetime
- 1992-11-10 WO PCT/DK1992/000329 patent/WO1993009753A1/en active IP Right Grant
- 1992-11-10 ES ES92923715T patent/ES2079899T3/en not_active Expired - Lifetime
- 1992-11-11 CN CN92114309A patent/CN1031316C/en not_active Expired - Fee Related
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1994
- 1994-05-10 NO NO19941733A patent/NO306234B1/en unknown
- 1994-05-10 FI FI942165A patent/FI105774B/en not_active IP Right Cessation
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1995
- 1995-06-06 US US08/472,039 patent/US5746979A/en not_active Expired - Fee Related
- 1995-06-06 US US08/473,550 patent/US5658533A/en not_active Expired - Fee Related
- 1995-06-06 US US08/469,571 patent/US5674458A/en not_active Expired - Fee Related
- 1995-12-29 GR GR950402583T patent/GR3018561T3/en unknown
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