CA1254838A - Prolonged storage of red blood cells - Google Patents
Prolonged storage of red blood cellsInfo
- Publication number
- CA1254838A CA1254838A CA000483917A CA483917A CA1254838A CA 1254838 A CA1254838 A CA 1254838A CA 000483917 A CA000483917 A CA 000483917A CA 483917 A CA483917 A CA 483917A CA 1254838 A CA1254838 A CA 1254838A
- Authority
- CA
- Canada
- Prior art keywords
- red blood
- blood cells
- suspension medium
- solution
- adenine
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/18—Erythrocytes
Abstract
ABSTRACT
The present invention discloses a hypotonic suspension medium and a method for prolonged storage of red blood cells at about 4°C. The suspension medium comprises about 80-150 mM glucose, 30-80 mM mannitol, 6-90 mM potassium citrate, 1-5 mM adenine and 10-200 mM
ammonium chloride or acetate in an aqueous solution having a pH of about 6.8 to 7.2 and an osmolarity of about 180-220 milli-osmolar. The suspension medium and the method of the present invention allow viable storage of red blood cells at about 4°C up to 125 days or more.
The present invention discloses a hypotonic suspension medium and a method for prolonged storage of red blood cells at about 4°C. The suspension medium comprises about 80-150 mM glucose, 30-80 mM mannitol, 6-90 mM potassium citrate, 1-5 mM adenine and 10-200 mM
ammonium chloride or acetate in an aqueous solution having a pH of about 6.8 to 7.2 and an osmolarity of about 180-220 milli-osmolar. The suspension medium and the method of the present invention allow viable storage of red blood cells at about 4°C up to 125 days or more.
Description
2 BACKGROUND OF THE INVENTION
3 Technical Field
4 The present invention is related to preservation of red blood cells in substantially physiologically native 6 state. More particularly, the present invention is 7 related to a novel suspension medium for storage of human 8~ red blood cells at about 4~C in a condition suitable for 9 ~1ood transfusion. The novel suspension medium of the ~present invention makes it feasible to substantially inc~rease~ the storage time of the red blood cells than was 12 heretofore possible.
::
13 Prior Art 14 ~ Storage or preservation of red blood cells in a ;15~suspension medium at about 4 C according to standard 16~b~lood bank procedure is well known. As ar as known to ::
~ 17 ~the; ~Applicants there are no literature referenee~
, .:
::
:
, 1 reporting the effects of either hypotonic suspension 2 or the addition of penetrating salts, e.g., ammonium 3 salts as related to the keeping quality of red blood 4 cells.
, It has been observed, however, that, during 6 continued refrigerated storage, human red cells undergo a 7 shape change with the development of spicules which may 8 ultimately bud off into small vesicles. This reduces the 9 surface area of the red cell, presumably rendering it less flexible and less able to pass through the 11 filtration system in the spleen. This in turn leads to 12 the removal of cells from the circulation within a few 13 minutes following transfusion. Acceptable standards for 14 transfusable red cells require that at least 70% of the cells must still be circulating 24 hours following 16 transfusion.
17 The present invention overcomes the limitations and 18 problems associated with the prior art process. It was 19 reasoned that increasing the surface tension of the cells by osmotic swelling would theoretically tend to forestall 21 the development of spicules. Therefore, a suspension 22 medium of suitable osmolarity and membrane permeability ~ was developed which could preserve the red blood cel1s at 24 q~C for extended period of time in a condition suitable ~or transfusion in accordance with standards established for transfusion of red blood cells (~BCs). It was discovered that inclusion of certain penetratlng compounds, such as ammonium salts, preferably ~IHI~C
and NH4 COOCH3, in a suspension medium not only avoids the deleterious effect~s of low ionic concentration, but also provides certain positive benefits as described more fully infra.
SUMMARY OF_THE INVENTION
It is, therefore, an object of the present invention to provide a suspension medium for red blood cells which substantially increases the storage time of the suspended RBCs at about 4C while maintaining the transfusion quality of the stored RBCs.
It is a further object of the present invention to provide a method of storing RBCs Yor an extended period of time at 4C than is possible by conventional processes while maintaining the suitability of such stored RBCs for transfusion in humans.
Thus the present invention provides a suspension medium for prolonged storage o~ red blood cells at about 4C, consisting essentially of an aqueous solution containing about 80-150 mM glucose, 30-80 mM mannitol, 6 90 mM potassium citrate, 1-5 mM adenine and 40-95 mM of a phosphate salt, said solution having an osmolarity of about 180-220 milli-osmolar and having 10-200 mM of a penetrating salt, the pH of said solution being about 6.8 to 7,2 wherein said red blood cells can be viably stored.
In another aspect the invention provides a method of preserving red blood cells for extended period of time at about 4~C, comprising suspending said oells in an aqueous solution consisting essentially of about 80-150 mM
glucose, 30-80 mM mannitol, 6-90 mM potassium citrate, 1-5 mM adenine and 40-95 mM of a phosphate salt, said solution having an osmolarity of about 180-220 milli-osmolar and having 10-200 mM of a penetrating salt, the pH of said solution~being about 6.8 to 7.2 allowing viable storage of said red blood cells.
Other objects and advantages will become apparent as the description of the invention proceeds.
1~ ' "`" ' '`' ~ ' ~
, , ~ ~.D~
____ _ ___ l~ese and other objects, eatures and many of the attendant advantages of the invention will be better undexstood upon a reading of the following detailed description when considered in connection with the accompanying drawings whereinO
Fig. 1 shows ATP content in human RBCs (percent of original value) as a function of storage time at 4C in various suspending media.
Fig 2 shows percent ln _ vo survival of human RBCs after torage at various time intervals at 4C in different suspending media.
Without being bound to any particular theory or e~planation, it is postulated that in order to forestall :
the development oE undesirable spicules in the RBCs during refrigexated storage in conventional suspension media, increasing the surface tension of the cells by osmotic swelling may be necessary. The cells are, therefore, suspended in a medium of about 180~220 mOsm (m~ osmolar), more particularly in a medium of about ~ ' ~z~
200 mOsm. The pH of the suspension medium is maintairl~d in a range oE about 6.8 to 7.2, preferably around 7Ø
Since this involved a reduction in ionic concentration which could lead to an increase in membrane permeability, normal ionic concentration of the cells is maintained by a unique composition employing certain penetrating, ionizable salts in the suspension medium, preferable among such salts being ammonium acetate and ammonium chlorid~ at about 10-200 mM concentration, preferably at about 50 mM
concentration. OE course, suitable cations other than ammonium and suitable anions other than acetate and chloride could also be advantageously utilized so long as such salts meet the criteria and objects of the present invention~ An example of such salt is methyl amine hydrochloride. The other constituents o~ the suspending medium are those conventionally used and comprise potassium phosphate, mannitol, adenine, bovine serum albumln, inosine, pyruvate, potassium citrate and glucose at suitabIe concentrations, for instance the concentration o~ glucose could be about 80-150 mM, mannitol about 30-80 mM, pot~assium citrate about 6-90 r~M, adenine about 1-5 mM. Mono and dibasic potassium phosphate concentration is adjusted to maintain the pH at about 6.8 to 7.2 of the suspension medium at about 180~220 mOsm.
, .
3~3 The term "substantial.ly prolonged" or "extended"
storage and the liXe simply means that viable preservation or storage of RBCs for a period oE time greater than that possible by utilizing hereto-Eore known blood bank procedure and conven-tional suspending media is obtainecl.
DESCRIPTION OF SPECIFIC EM:BODIMENT
A typical composition of the suspending medium in accordance with the present invention comprises an aqueous solution containing:
gLucose 110 mM adenine 2 mM
mannitol 55 mM ammonium chloride 50 mM
potassium citrate 7.9 mM
potassium phosphate dibasic 25.8 mM
potassium phosphate monobasic 14.7 mM
Other such compositions can be easily prepared so long as the pH is about 7.0 and the osmolarity is in the range of about 200 m0sm.
Red cells which have been separated from their phasma in the normal course of component manuEacture are ,~
~ ' .
3~
-- 7 ~
resuspended in an approxima-tel~ equal volume of this suspending medium~ ~e cell suspension is then stored at about 4 + 2C according to standard blood bank procedure which is described in "Clinical Practice of Blood Transfusion" editors: Petz ~ Swisher, Churchill-Livingston publishers, N~Y., 1981. ~apter 11, page 281 of the reference shows viability date of preserved RUCs by conventional techniques.
When stored in a suspension medium in accordance with the present invention, there is a progressive increase in adenosine triphosphate (ATP) over the first four to five weeks of storage. ATP levels tend to be correlated with red cell survival following transfusion.
At four weeks the ATP levels range from 115~ to as high as 250~ with an average of 165~ of the initial ~alue. The ATP level then falls steadily with further storage, reaching the original value at around eleven weeks and falling to 50~ of original value at approximately sixteen weeks .
Table 1 shows various components and solute concentrations of suspension media in which red cells were stored for up to 16 weeks. It should be noted that solution ~20, which is the preferred suspending medium in ~.~
.
~s~
accordance with -the present inven-tion, maintains red cell ATP at a higher level for a longer time than any other ~ s ~hown in Fig. 1.
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;.t, .-t- t- t-t~ I ., i Figure :l shows ATP values at 4, 8, 10, 12, L~ and 16 weeks for cells suspended in a) an isotonic po-tassium citrate, phosphate, mannitol, glucose, adenine solution, corresponding to solution #7 in Table l; b) the same solution as (a) with ammonium acetate added, corresponding to solution #:L4 in Table l; c) the same solution as (a) with some potassium citrate removed to make it hypotonic, corresponding to solution #12 in Table l; d) the same hypotonic solution as (c) with the addition of ammonium acetate, corresponding to solution #13 in Table 1; 3) ~he same hypotonic solution as (c) with the addition of ammonium chloride, corresponding to solution #20 in Table 1. The results indicate that there are benefits from both the hypotonicity and the addition of ammonium salts. The benefits of hypotonicity may be associated with the postponement o~ spicule ~ormation but the reasons for increase in ATP levels is unknown. The mechanism by which the ammonium salts of the present invention when incorporated in the suspension medium increase ATP is also unknown.
Figure 2 demonstrates the 24 hour ln vivo survival igures for red cells stored in solution ~c~ for ~periods ranging up -to 125 days.
It may be noted that i-t is unlikely that a hypotonic cell suspension containing ammonium chloride would be acceptable ~or transfusion~ I~ere~ore, it is ~.
,, ..
3i~
recommended that, prior to transfusion, the cells should be sedimented by centriEugation and the cells resuspencled in a transfusable solution and -then transfused.
The hemo].ysis of RBCs stored in accordance with the present invention is from about 0.3 to 3.8%.
It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and the scope of the appended claims.
, :
::
13 Prior Art 14 ~ Storage or preservation of red blood cells in a ;15~suspension medium at about 4 C according to standard 16~b~lood bank procedure is well known. As ar as known to ::
~ 17 ~the; ~Applicants there are no literature referenee~
, .:
::
:
, 1 reporting the effects of either hypotonic suspension 2 or the addition of penetrating salts, e.g., ammonium 3 salts as related to the keeping quality of red blood 4 cells.
, It has been observed, however, that, during 6 continued refrigerated storage, human red cells undergo a 7 shape change with the development of spicules which may 8 ultimately bud off into small vesicles. This reduces the 9 surface area of the red cell, presumably rendering it less flexible and less able to pass through the 11 filtration system in the spleen. This in turn leads to 12 the removal of cells from the circulation within a few 13 minutes following transfusion. Acceptable standards for 14 transfusable red cells require that at least 70% of the cells must still be circulating 24 hours following 16 transfusion.
17 The present invention overcomes the limitations and 18 problems associated with the prior art process. It was 19 reasoned that increasing the surface tension of the cells by osmotic swelling would theoretically tend to forestall 21 the development of spicules. Therefore, a suspension 22 medium of suitable osmolarity and membrane permeability ~ was developed which could preserve the red blood cel1s at 24 q~C for extended period of time in a condition suitable ~or transfusion in accordance with standards established for transfusion of red blood cells (~BCs). It was discovered that inclusion of certain penetratlng compounds, such as ammonium salts, preferably ~IHI~C
and NH4 COOCH3, in a suspension medium not only avoids the deleterious effect~s of low ionic concentration, but also provides certain positive benefits as described more fully infra.
SUMMARY OF_THE INVENTION
It is, therefore, an object of the present invention to provide a suspension medium for red blood cells which substantially increases the storage time of the suspended RBCs at about 4C while maintaining the transfusion quality of the stored RBCs.
It is a further object of the present invention to provide a method of storing RBCs Yor an extended period of time at 4C than is possible by conventional processes while maintaining the suitability of such stored RBCs for transfusion in humans.
Thus the present invention provides a suspension medium for prolonged storage o~ red blood cells at about 4C, consisting essentially of an aqueous solution containing about 80-150 mM glucose, 30-80 mM mannitol, 6 90 mM potassium citrate, 1-5 mM adenine and 40-95 mM of a phosphate salt, said solution having an osmolarity of about 180-220 milli-osmolar and having 10-200 mM of a penetrating salt, the pH of said solution being about 6.8 to 7,2 wherein said red blood cells can be viably stored.
In another aspect the invention provides a method of preserving red blood cells for extended period of time at about 4~C, comprising suspending said oells in an aqueous solution consisting essentially of about 80-150 mM
glucose, 30-80 mM mannitol, 6-90 mM potassium citrate, 1-5 mM adenine and 40-95 mM of a phosphate salt, said solution having an osmolarity of about 180-220 milli-osmolar and having 10-200 mM of a penetrating salt, the pH of said solution~being about 6.8 to 7.2 allowing viable storage of said red blood cells.
Other objects and advantages will become apparent as the description of the invention proceeds.
1~ ' "`" ' '`' ~ ' ~
, , ~ ~.D~
____ _ ___ l~ese and other objects, eatures and many of the attendant advantages of the invention will be better undexstood upon a reading of the following detailed description when considered in connection with the accompanying drawings whereinO
Fig. 1 shows ATP content in human RBCs (percent of original value) as a function of storage time at 4C in various suspending media.
Fig 2 shows percent ln _ vo survival of human RBCs after torage at various time intervals at 4C in different suspending media.
Without being bound to any particular theory or e~planation, it is postulated that in order to forestall :
the development oE undesirable spicules in the RBCs during refrigexated storage in conventional suspension media, increasing the surface tension of the cells by osmotic swelling may be necessary. The cells are, therefore, suspended in a medium of about 180~220 mOsm (m~ osmolar), more particularly in a medium of about ~ ' ~z~
200 mOsm. The pH of the suspension medium is maintairl~d in a range oE about 6.8 to 7.2, preferably around 7Ø
Since this involved a reduction in ionic concentration which could lead to an increase in membrane permeability, normal ionic concentration of the cells is maintained by a unique composition employing certain penetrating, ionizable salts in the suspension medium, preferable among such salts being ammonium acetate and ammonium chlorid~ at about 10-200 mM concentration, preferably at about 50 mM
concentration. OE course, suitable cations other than ammonium and suitable anions other than acetate and chloride could also be advantageously utilized so long as such salts meet the criteria and objects of the present invention~ An example of such salt is methyl amine hydrochloride. The other constituents o~ the suspending medium are those conventionally used and comprise potassium phosphate, mannitol, adenine, bovine serum albumln, inosine, pyruvate, potassium citrate and glucose at suitabIe concentrations, for instance the concentration o~ glucose could be about 80-150 mM, mannitol about 30-80 mM, pot~assium citrate about 6-90 r~M, adenine about 1-5 mM. Mono and dibasic potassium phosphate concentration is adjusted to maintain the pH at about 6.8 to 7.2 of the suspension medium at about 180~220 mOsm.
, .
3~3 The term "substantial.ly prolonged" or "extended"
storage and the liXe simply means that viable preservation or storage of RBCs for a period oE time greater than that possible by utilizing hereto-Eore known blood bank procedure and conven-tional suspending media is obtainecl.
DESCRIPTION OF SPECIFIC EM:BODIMENT
A typical composition of the suspending medium in accordance with the present invention comprises an aqueous solution containing:
gLucose 110 mM adenine 2 mM
mannitol 55 mM ammonium chloride 50 mM
potassium citrate 7.9 mM
potassium phosphate dibasic 25.8 mM
potassium phosphate monobasic 14.7 mM
Other such compositions can be easily prepared so long as the pH is about 7.0 and the osmolarity is in the range of about 200 m0sm.
Red cells which have been separated from their phasma in the normal course of component manuEacture are ,~
~ ' .
3~
-- 7 ~
resuspended in an approxima-tel~ equal volume of this suspending medium~ ~e cell suspension is then stored at about 4 + 2C according to standard blood bank procedure which is described in "Clinical Practice of Blood Transfusion" editors: Petz ~ Swisher, Churchill-Livingston publishers, N~Y., 1981. ~apter 11, page 281 of the reference shows viability date of preserved RUCs by conventional techniques.
When stored in a suspension medium in accordance with the present invention, there is a progressive increase in adenosine triphosphate (ATP) over the first four to five weeks of storage. ATP levels tend to be correlated with red cell survival following transfusion.
At four weeks the ATP levels range from 115~ to as high as 250~ with an average of 165~ of the initial ~alue. The ATP level then falls steadily with further storage, reaching the original value at around eleven weeks and falling to 50~ of original value at approximately sixteen weeks .
Table 1 shows various components and solute concentrations of suspension media in which red cells were stored for up to 16 weeks. It should be noted that solution ~20, which is the preferred suspending medium in ~.~
.
~s~
accordance with -the present inven-tion, maintains red cell ATP at a higher level for a longer time than any other ~ s ~hown in Fig. 1.
\
\
: . ' ~' ' `
- 9~ i~ t3~ ~ ~ o . . P n ~
I ~ o~
~ - ~ n I ~ ,, >a ~
I O O O O ~ O O O O O O O O O O O O O ~ " ~ o l ; ~o ~o _ I ~ ~
l .~ IT~ D ~J
n o ~ n r.
n O o o _ ~ .----- ~ E~ _ _ ~ J r~ O
~ ~ ~ ~-~ Oq r~
. . ... I ; , - ~ N
~ JI ~ ~ W ~ n ~ O O, o, ~nI I t) I c~ cn CO ~~ co o~ C~ ~ o~ C~ o) O~ 0~ 0~ ~ co co Oo Oo 0~ ; co O I g _ . ~ n I . .... . .. . ~ . ....... .... .. . _ ~ J~ l , O I O
_ . ~ a j ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~_ t- ~ t~ ~ I
! ~ I
~1 _ ~, 1~ ~o~O O~OWO~ 11~ ~ ~t 0 ~0 WO ~00 0 ~0 0 _ _ _ . , _ l~ " ~ :~ I
O ~n O O ~ n ~ I
O o oO o O O , I
~ n _ - - -- - ! -- -I '-!--' I ; _ _ _ ~ ,- - , . ' . ~! l O C ~ ~ , , , :~
o o ~ o ~ I
~n . .
_ . . __~ . _ o l W ~ !
t ~ ~ O . - ~
I ~ ~ r~ ~ ~ ~ ~ ~ ~ w w w ~ ~ w ~ w ~.7 ~ ~ w l t-- ~~ t~Pl ~~ ~~ t~ ~ ~ t-~ ~ t~ ~ /-- ~ o o I
I o o o ~ O O O O O O O O O O O O O O O ~ o ~o ~
! 'o ~3 l ~_ __ _ I
;.t, .-t- t- t-t~ I ., i Figure :l shows ATP values at 4, 8, 10, 12, L~ and 16 weeks for cells suspended in a) an isotonic po-tassium citrate, phosphate, mannitol, glucose, adenine solution, corresponding to solution #7 in Table l; b) the same solution as (a) with ammonium acetate added, corresponding to solution #:L4 in Table l; c) the same solution as (a) with some potassium citrate removed to make it hypotonic, corresponding to solution #12 in Table l; d) the same hypotonic solution as (c) with the addition of ammonium acetate, corresponding to solution #13 in Table 1; 3) ~he same hypotonic solution as (c) with the addition of ammonium chloride, corresponding to solution #20 in Table 1. The results indicate that there are benefits from both the hypotonicity and the addition of ammonium salts. The benefits of hypotonicity may be associated with the postponement o~ spicule ~ormation but the reasons for increase in ATP levels is unknown. The mechanism by which the ammonium salts of the present invention when incorporated in the suspension medium increase ATP is also unknown.
Figure 2 demonstrates the 24 hour ln vivo survival igures for red cells stored in solution ~c~ for ~periods ranging up -to 125 days.
It may be noted that i-t is unlikely that a hypotonic cell suspension containing ammonium chloride would be acceptable ~or transfusion~ I~ere~ore, it is ~.
,, ..
3i~
recommended that, prior to transfusion, the cells should be sedimented by centriEugation and the cells resuspencled in a transfusable solution and -then transfused.
The hemo].ysis of RBCs stored in accordance with the present invention is from about 0.3 to 3.8%.
It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and the scope of the appended claims.
, :
Claims (10)
IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A suspension medium for prolonged storage of red blood cells at about 4°C, consisting essentially of an aqueous solution containing about80-150 mM glucose, 30-80 mM mannitol, 6-90 mM potassium citrate, 1-5 mM
adenine and 40-95 mM of a phosphate salt, said solution having an osmolarity of about 180-220 milli-osmolar and having 10-200 mM of a penetrating salt, the pH of said solution being about 6.8 to 7.2 wherein said red blood cells can be viably stored.
adenine and 40-95 mM of a phosphate salt, said solution having an osmolarity of about 180-220 milli-osmolar and having 10-200 mM of a penetrating salt, the pH of said solution being about 6.8 to 7.2 wherein said red blood cells can be viably stored.
2. A method of preserving red blood cells for extended period of time at about 4°C, comprising suspending said cells in an aqueous solution consisting essentially of about 80-150 mM glucose, 30-80 mM mannitol, 6-90 mM potassium citrate, 1-5 mM adenine and 40-95 mM of a phosphate salt, said solution having an osmolarity of about 180-220 milli-osmolar and having 10-200 mM of a penetrating salt, the pH of said solution being about 6.8 to 7.2 allowing viable storage of said red blood cells.
3. The suspension medium of Claim 1 wherein said penetrating salt is selected from the group consisting of ammonium chloride and ammonium acetate.
4. The suspension medium of claim 3 containing about 110 mM glucose, 55 mM mannitol, 7.9 mM potassium citrate, 2 mM adenine and 50 mM ammonium chloride or acetate.
5. The suspension medium of claim 4 wherein the pH is maintained at a value of about 7.0 by adjusting the pH with suitable amounts of mono or dibasic potassium phosphate.
6. The suspension medium of claim 5 wherein the osmolarity is about 200 mOsm.
7. The method of claim 2 wherein said penetrating salt is selected from the group consisting of ammonium chloride and ammonium acetate.
8. The method of claim 7 containing about 110 mM
glucose, 55 mM mannitol, 7.9 mM potassium citrate, 2 mM
adenine and 50 mM ammonium chloride or acetate.
glucose, 55 mM mannitol, 7.9 mM potassium citrate, 2 mM
adenine and 50 mM ammonium chloride or acetate.
9. The method of claim 8 wherein the pH is maintained at a value of about 7.0 by adjusting the pH
with suitable amounts of mono or dibasic potassium phosphate.
with suitable amounts of mono or dibasic potassium phosphate.
10. The method of claim 9 wherein the osmolarity is about 200 mOsm.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/632,242 US4585735A (en) | 1984-07-19 | 1984-07-19 | Prolonged storage of red blood cells |
| US632,242 | 1984-07-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1254838A true CA1254838A (en) | 1989-05-30 |
Family
ID=24534708
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000483917A Expired CA1254838A (en) | 1984-07-19 | 1985-06-13 | Prolonged storage of red blood cells |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4585735A (en) |
| EP (1) | EP0187816B1 (en) |
| JP (1) | JPS61502750A (en) |
| AT (1) | ATE66814T1 (en) |
| AU (1) | AU569958B2 (en) |
| CA (1) | CA1254838A (en) |
| DE (1) | DE3584010D1 (en) |
| DK (1) | DK168079B1 (en) |
| FI (1) | FI84135C (en) |
| IL (1) | IL75707A (en) |
| NO (1) | NO167075C (en) |
| WO (1) | WO1986000809A1 (en) |
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0687062B2 (en) * | 1985-05-10 | 1994-11-02 | 株式会社京都医科学研究所 | How to prevent glycolysis in blood |
| US4675185A (en) * | 1985-12-06 | 1987-06-23 | Baxter Travenol Laboratories, Inc. | Solution for stabilizing red blood cells during storage |
| JPS6360931A (en) * | 1986-08-29 | 1988-03-17 | Noboru Sato | Solution for preserving blood or blood preparation and preservation of blood or blood preparation using said solution |
| US5045446A (en) * | 1988-08-26 | 1991-09-03 | Cryopharm Corporation | Lyophilization of cells |
| IL90188A0 (en) * | 1988-05-18 | 1989-12-15 | Cryopharm Corp | Process and medium for the lyophilization of erythrocytes |
| US4874690A (en) * | 1988-08-26 | 1989-10-17 | Cryopharm Corporation | Lyophilization of red blood cells |
| IL95912A (en) * | 1989-10-06 | 1998-08-16 | American Nat Red Cross | Method for prolonging the shelf life or red blood cells |
| US5250303A (en) * | 1989-10-06 | 1993-10-05 | The American National Red Cross | Procedure for storing red cells with prolonged maintenance of cellular concentrations of ATP and 2,3 DPG |
| DE3938907C2 (en) * | 1989-11-24 | 1999-11-04 | Dade Behring Marburg Gmbh | Means for storing and suspending cells, in particular erythrocytes |
| US5147776A (en) * | 1990-02-26 | 1992-09-15 | University Of Iowa Research Foundation | Use of 2,5-anhydromannitol for control of pH during blood storage |
| US5545516A (en) * | 1990-05-01 | 1996-08-13 | The American National Red Cross | Inactivation of extracellular enveloped viruses in blood and blood components by phenthiazin-5-ium dyes plus light |
| EP0509083B1 (en) * | 1990-11-07 | 1997-07-16 | Baxter International Inc. | Red blood cell storage solution |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2532183C3 (en) * | 1975-07-18 | 1982-03-04 | Behringwerke Ag, 3550 Marburg | Polyionic isotonic saline solution for the preservation of erythrocytes or for the perfusion and preservation of organs intended for transplantation |
| JPS56139419A (en) * | 1980-03-31 | 1981-10-30 | Kuraray Co Ltd | Erythrocytic preservative and erythrocytic pharmaceutical for preservation |
| FR2542617B2 (en) * | 1982-07-09 | 1986-06-06 | Rgl Transfusion Sanguine Centr | PROTECTIVE SOLUTION FOR THE PRESERVATION OF FUNCTIONAL CELLS |
-
1984
- 1984-07-19 US US06/632,242 patent/US4585735A/en not_active Expired - Lifetime
-
1985
- 1985-06-13 CA CA000483917A patent/CA1254838A/en not_active Expired
- 1985-06-21 WO PCT/US1985/001185 patent/WO1986000809A1/en active IP Right Grant
- 1985-06-21 AT AT85903530T patent/ATE66814T1/en not_active IP Right Cessation
- 1985-06-21 DE DE8585903530T patent/DE3584010D1/en not_active Expired - Lifetime
- 1985-06-21 AU AU46052/85A patent/AU569958B2/en not_active Expired
- 1985-06-21 JP JP60503050A patent/JPS61502750A/en active Granted
- 1985-06-21 EP EP85903530A patent/EP0187816B1/en not_active Expired - Lifetime
- 1985-07-03 IL IL75707A patent/IL75707A/en not_active IP Right Cessation
-
1986
- 1986-03-11 NO NO86860913A patent/NO167075C/en unknown
- 1986-03-14 DK DK119986A patent/DK168079B1/en not_active IP Right Cessation
- 1986-03-18 FI FI861137A patent/FI84135C/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| US4585735A (en) | 1986-04-29 |
| AU4605285A (en) | 1986-02-25 |
| DE3584010D1 (en) | 1991-10-10 |
| EP0187816A1 (en) | 1986-07-23 |
| FI861137A0 (en) | 1986-03-18 |
| DK168079B1 (en) | 1994-02-07 |
| NO167075B (en) | 1991-06-24 |
| AU569958B2 (en) | 1988-02-25 |
| FI84135B (en) | 1991-07-15 |
| DK119986A (en) | 1986-03-14 |
| EP0187816A4 (en) | 1988-04-06 |
| NO860913L (en) | 1986-03-11 |
| EP0187816B1 (en) | 1991-09-04 |
| DK119986D0 (en) | 1986-03-14 |
| JPS61502750A (en) | 1986-11-27 |
| WO1986000809A1 (en) | 1986-02-13 |
| FI861137A (en) | 1986-03-18 |
| ATE66814T1 (en) | 1991-09-15 |
| IL75707A0 (en) | 1985-11-29 |
| JPH0572888B2 (en) | 1993-10-13 |
| FI84135C (en) | 1991-10-25 |
| NO167075C (en) | 1991-10-02 |
| IL75707A (en) | 1989-02-28 |
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