CN101505591A - Method for treatment and storage of blood and blood products using endogenous alloxazines and acetate - Google Patents

Method for treatment and storage of blood and blood products using endogenous alloxazines and acetate Download PDF

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CN101505591A
CN101505591A CNA200680045661XA CN200680045661A CN101505591A CN 101505591 A CN101505591 A CN 101505591A CN A200680045661X A CNA200680045661X A CN A200680045661XA CN 200680045661 A CN200680045661 A CN 200680045661A CN 101505591 A CN101505591 A CN 101505591A
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R·P·古德里奇
李俊之
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Terumo BCT Biotechnologies LLC
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    • A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock

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Abstract

Methods are provided for treatment and storage of blood and blood products using at least endogenous alloxazines and acetate. Methods include adding a blood component additive solution comprising at least an endogenous alloxazine and acetate to a fluid comprising at least one collected blood component.

Description

Utilize endogenous alloxazine and acetate to handle method with storage of blood and blood product
Cross reference to related application
The application is that the application number of submitting on February 28th, 2003 is 10/377, the part continuation application of 524 U. S. application, 10/377,524 is that the application number of submitting on June 2nd, 2000 is 09/586,147, the continuation application of the U. S. application of having abandoned at present, 09/586,147 is that the application number submitted July 20 in 1999 is 09/357,188, U.S. Patent number is 6,277 at present, the part continuation application of 337 U. S. application, 09/357,188 is that the application number submitted on July 21st, 1998 is 09/119,666, U.S. Patent number is 6 at present, the part continuation application of 258,577 U. S. application.The application number that the application also requires on December 6th, 2005 to submit is 60/597,506 U.S. Provisional Application No..
Technical field
The present invention relates generally to and is used for gathering and/or storing hematoblastic artificial dielectric, and described blood platelet is intended to be used for intravital, comprises the artificial dielectric that is used for reducing with hematoblastic pathogene associating.
Background technology
Collection utilizes various known methods to be typically the blood transfusion receptor from the whole blood of volunteering the blood donor and is separated into its component: erythrocyte, leukocyte, blood platelet and blood plasma.In these parts each all is stored in respectively under the specified conditions of every kind of blood constitutent, and is used for the treatment of many specific situations and morbid state.For example, the erythrocyte component is used to treat anaemia, and concentrated platelet component is used to control and loses blood and plasma component usually is used as hematoglobin protein, for example the source of coagulation factor.
In blood bank's scope, have infectious microorganism, for example the blood contamination of HIV, hepatitis and other virus and bacterium the people that must accept transfusion of whole blood to those or use various blood constitutents has formed serious health hazard.The filtering technique of blood may leak pollutant, and can not damage the cellular component of blood and effectively deactivation the sterilization process of infectious virus and other microorganisms also do not exist at present.
The loss function that another main problem is blood constitutent in storing process in blood bank.Blood platelet particularly after separating from other blood constitutents, need be suspended in the suitable storing solution or blood plasma again, so that improve or keep hematoblastic quality at least at memory period.
If blood platelet is to be stored in the blood plasma, they typically are stored in about 900-2100 * 10 3The concentration of/μ L.The hematoblastic side effect that blood transfusion has blood plasma is that the blood transfusion receptor may produce allergy and/or TRALI (acute lung injury that blood transfusion is relevant) to the component that is present in blood donor's blood plasma.Another considerable factor is a price.Blood plasma self can be used or sell and be used for the fractionation plasma protein and become coagulation factor or the like.
Therefore, the handlebar platelet storage is in the demand of artificial storing solution.If blood platelet is to be stored in the artificial storing solution, they also are typically to be stored in about 900-2100 * 10 3The concentration of/μ L.Several commercially available solution comprise PASIII (MacoPharma sale), PASII (Baxter sale) and CompoSol (Fresenius sale).Commercially available platelet storage solution comprises additive, for example phosphate, glucose, sodium, potassium, citric acid, magnesium, sulphate and acetate, and described additive is considered to strengthen hematoblastic metabolism at memory period.
In order to keep vigor, blood platelet must constantly produce enough adenosine triphosphates (ATP) to satisfy their energy requirement.Two paths are normally used for producing ATP, glycolysis and oxidative phosphorylation.In glycolysis, a glucose molecule is converted into two lactic acid molecules to produce two ATP molecules.In oxidative phosphorylation, glucose, fatty acid or amino acid enter citrate cycle and are converted into CO 2And water.This path needs the existence of the sufficient oxygen of supplying with, to be received in the proton that produces in the breakdown of glucose.It is more effective than glycolysis.Oxidative metabolism of substrates is to CO 2With 36 ATP molecules of water generates.
Have realized that to have under the state of vigor, blood platelet will not be must be to satisfy their energy requirement with the corresponding to mode of their longer-term storage.When giving enough oxygen, blood platelet produces the major part of their ATP by oxidation, but continues to produce lactic acid rather than transform all metabolizable glucoses by the oxidation path.When blood platelet is stored in blood plasma, lactic acid concn about 2.5mM that rises every day.See Murphy etc.; " at22 ℃ of Platelet Storage. ", Blood, 46 (2): 209-218 (1975); Murphy, ＂ Platelet Storagefor Transfusion ＂, Seminars in Hematology, 22 (3): 165-177 (1985).This causes the decline gradually of pH value.As described in the article of Murphy, when lactic acid reached about 20mM, beginning was that 7.2 pH value can reach 6.0.Because if the pH value drop to 6.1 or when lower platelet viability will irreversibly lose, be the pH value to the main qualification variable of platelet storage.
Therefore, the adjustment of pH value is a principal element in long-term platelet storage.In fact, the pH value of hematoblastic all units has all shown decline from about 7.0 initial value.Described decline mainly is the lactic acid that produces owing to by the human platelet glycoprotein glycolysis, and less degree is owing to come from the CO of oxidative phosphorylation 2Accumulative total.When the pH value descended, blood platelet changed shape from the disc to the sphere.When the pH value drops to approximately 6.0, they are become after blood transfusion be non-vigor in platelet morphology and physiological irreversible change.Therefore, an important goal in blood platelet is preserved is the decline that stops pH.
Relevant with the decline of pH value, the decline of the ATP total quantity of the unit's of observing blood platelet generation.Metabolism can with ATP exhaust the influence hematoblastic function because ATP is the requisite role of platelet adhesion reaction and platelet aggregation.At memory period, blood platelet is kept total ATP and has been found to be relevant with platelet viability in the ability that approaches normal level.
In platelet storage medium design, once comprised a kind of additive at the solution of the problems referred to above, described additive serves as two kinds of roles: the substrate of oxidative phosphorylation and offset the buffer of the acidizing effect of the lactic acid that produces at the memory period blood platelet.Acetate is found to be suitable substrate.In addition, its oxidation produces bicarbonate:
CH 3COOO+2O 2＝CO 2+HCO 3+H 2O
Therefore, use acetate can make two order ground usefulness, as the substrate that is used for oxidative phosphorylation with as buffer.This platelet storage solution is disclosed in the patent No. 5,344, and 752 and 5,376, in 524 the United States Patent (USP).
Another kind of additive is a useful substrate in blood and blood constitutent storage, comprises the compound that stimulates mitochondria activity.A kind of described suitable compound is an endogenous 7,8-dimethyl-10-ribityl isoalloxazine (vitamin b3), its metabolite and precursor.This mitochondria stimulus compound can comprise based on the endogenous derivative, described derivative is the synthetic derived analogs and the homolog of vitamin b3, can have or lack rudimentary (1-5) alkyl or halogenic substituent, and preserve its function and nontoxic basically.These are disclosed in the U.S. Patent application of application number 10/430,896.
It is believed that, keep hematoblastic vigor by stimulating mitochondria activity at these medicaments of memory period.FMN (FMN) that metabolism by vitamin b3 produces and flavin adenine dinucleotide (FAD) (FAD) are the key elements that transmits activity for electronics.What this activity was a large amount of is included in the mitochondrial respiratory.Therefore by the vitamin b3 that increases level is provided to cell, might strengthen mitochondrial respiratory and by oxidative phosphorylation rather than promote the generation of ATP by glycolysis.
Yet, up to now, during memory period or pathogene minimizing processing, be used in combination substrate that serves as oxidative phosphorylation substrate and two kinds of roles of buffer and the substrate that stimulates mitochondria activity, storage or the additive solution of keeping platelet viability are non-existent.Order of the present invention ground just is this solution.
Brief summary of the invention
Be a kind of blood constitutent storage or additive solution, it comprises at least a photosensitizer-like additive and acetate order of the present invention, and it can be used to collect, handle and/or the storage blood platelet.
Order of the present invention ground also is the method that the blood constitutent pathogene of a kind of blood or collection reduces, and it comprises to being reduced the blood of pathogene or endogenous photosensitizers that effective nontoxic quantity is added in blood constitutent or based on the derive mixture of sensitising agent and acetate of endogenous; With fluid-mixing is exposed under the light radiation of the described sensitising agent of enough activation, make whereby to the pathogen inactivated step of small part.
Description of drawings
Fig. 1 is the chart of comparison of the glucose consumption rate of a processing and untreated platelet storage 5 and 7 days.
Fig. 2 is the chart of comparison of the lactic acid production rate of a processing and untreated platelet storage 5 and 7 days.
Fig. 3 is the chart of the comparison that changes of the pH value of a processing and untreated platelet storage 5 and 7 days.
Processing of Fig. 4 and untreated platelet storage surpass 7 days O 2The chart of the comparison of consumption rate.
Processing of Fig. 5 and untreated platelet storage surpass 7 days CO 2The chart of the comparison of generation rate.
Fig. 6 is the chart of the comparison of a processing and the bicarbonate neutralizes rate of untreated platelet storage above 7 days.
Fig. 7 is the chart of the comparison of a processing and the blood platelet deformation extent of untreated platelet storage above 7 days.
Fig. 8 is one and is stored in blood platelet that surpasses 12 days in the solution that comprises vitamin b3 and acetate and the chart that is stored in the comparison of the blood platelet glucose consumption rate in the salt solution.
Fig. 9 is one and is stored in blood platelet that surpasses 12 days in the solution that comprises vitamin b3 and acetate and the chart that is stored in the comparison of the blood platelet lactic acid production rate in the salt solution.
Figure 10 is one and is stored in blood platelet that surpasses 12 days in the solution that comprises vitamin b3 and acetate and the chart that is stored in the hematoblastic Cytometric comparison in the salt solution.
Figure 11 has shown one embodiment of the present of invention, and it utilizes a series of bag that sensitising agent and additive stream are led to and will be reduced in the blood constitutent of pathogene.
Figure 12 has shown one embodiment of the present of invention, and it utilizes bags of blood to hold fluid, and fluid is reduced pathogene when the light radiation that described fluid is exposed to from light source.
Summary of the invention
The present invention relates generally to a kind of Storage and Processing solution for the blood constitutent use, and described blood constitutent is intended to for intravital.
As mentioned above, a kind of platelet storage solution that comprises acetate and riboflavin can increase blood platelet vigor during prolonged storage greatly. The pH value of described solution is preferably between about 5.0 and 7.4. A kind of solution like this can by the useful carrier as platelet concentrate, to allow memory period cell quality and metabolic keeping, allow to reduce quantity and the limit that extends storage period of blood plasma in the blood platelet of storage. This solution allows also that remaining blood plasma is reduced to about 20-60 milliliter/10 in platelet concentrate11Cell (mLs/1011Cells) standard level is about 75-100 milliliter/10 by comparison11Cell.
Except that longer-term storage, also have other factors can cause blood platelet to enter glycolysis, thereby gather lactic acid.An example that can cause blood platelet to gather the external treatment of lactic acid is deactivation or the program that reduces any pathogene, and described pathogene can be included in and will be given in receptor's the cell or periphery by blood transfusion.The mitochondrial damage that the method that the present minimizing of using may be present in the pathogen contamination in the blood constitutent can cause docking the cell that is subject to processing.For example ultraviolet light has shown mitochondrial damage.If mitochondria is damaged, cell can only be made ATP by glycolysis, causes gathering of in cell lactic acid, and reduces in the corresponding pH value of memory period.
Therefore order of the present invention ground also is a kind of solution that can be used to reduce the step of any pathogene, and described pathogene can be included in the blood constitutent of whole blood or collection.In such an embodiment, if a kind ofly be exposed to the light time and play the additive of sensitising agent effect, pollute pathogene to help to remove by the use of selectivity.Pathogene reduces solution can also comprise a kind of additive, for example serves as the substrate role's who is used for oxidative phosphorylation acetate, with among reducing step in pathogene and/or help keep the cell viability of cell afterwards.
If the pathogene of blood and/or blood constitutent reduces and to be supposed to, in the present invention, be exactly useful being exposed to the additive that the light time serves as sensitising agent.Described additive comprises endogenous photosensitizers.The example of described endogenous photosensitizers is an alloxazine, for example 7,8-dimethyl-10-ribityl isoalloxazine (vitamin b3), 7,8,10-lumifiavin (lumiflavin), 7,8-lumichrome (photopigment), isoalloxazine-adenine-dinucleotide (flavin adenine dinucleotide (FAD) [FAD]), alloxazine mononucleotide (having another name called FMN [FMN] and riboflavin-5-phosphoric acid salt), their metabolite and precursor.When using endogenous photosensitizers, particularly when described sensitising agent is not poisonous inherently or does not produce poisonous photoproducts after light radiation, after removing pollution, do not need to remove or purification step, and the product of handling is directly to return patient's body or to use for the patient of the result of treatment that needs it.Therefore, the fluid that reduced of pathogene will comprise the photoproducts of photosensitizer-like additive.
Accept the blood of pathogene minimizing or storage or component erythrocyte, blood platelet and/or the blood plasma that blood constitutent comprises whole blood or separated from whole blood.
Vitamin b3 and riboflavin derivative as sensitising agent with the purposes that reduces microorganism in the blood products respectively by United States Patent (USP), comprise 6,277,337,6,258,577,6,268120 and 6,828,323 descriptions.
Can use solution of the present invention to reduce or the pathogene of deactivation is included in unwanted any material in blood or the blood constitutent, no matter at first from external source or endogenous.Described material can include but not limited to virus (extracellular and cell in both), bacterium, phage, fungi, blood propagation parasite, prion and protozoa.
If expectation is to the inhibition of immunity or autoimmune response, for example, in the time of may having blood donor's leukocyte in the process that comprises erythrocyte, blood platelet or blood plasma blood transfusion, pathogene can also comprise leukocyte.
The material that can use method of the present invention to handle and/or store comprises for example blood platelet of the mitochondrial blood constitutent of having of whole blood or separation.
The method that is used to store whole blood or separate blood component of the present invention need be mixed riboflavin additive and acetate with wanting stored blood constitutent.Mixing can be added the vitamin b3 and the acetate of anhydrous or moisture form to whole blood or blood constitutent by simple, or by finishing to wanting stored whole blood or blood constitutent to add the solution that comprises vitamin b3 and acetate at least.Described vitamin b3 and acetate can add together or add respectively separately.
Described riboflavin additive can be used in the concentration between the per 35 ± 5mL solution of about 500 μ M.The concentration of acetate can be between the per 35 ± 5mL solution of about 140 ± 50mM, but also can be wideer scope.Can also add the salt solution that contains 0.9% sodium chloride of having an appointment.
Be used for if desired reducing or the processing of inactivating pathogens, comprise sensitising agent at least and perhaps acetate whole blood or gather the light radiation that blood constitutent is exposed to suitable wavelength, with the activation sensitising agent, use enough light radiation of the quantity of activation sensitising agent as mentioned above, but less than causing the significant non-specific damage of irradiated component or having disturbed the bioactive amount that has protein in fact.
The thrombocytopathy substance reduces if desired, and the light source that preferably is used to activate photosensitizer-like additive is the ultraviolet source of wide spectrum, and described light source is provided at the light of about 320nm.
When being exposed to the light time, vitamin b3 can be by disturbing duplicating or the direct pathogen kill pathogene of coming deactivation to exist of pathogene.The effect of sensitising agent may be from closely approaching to pathogen nucleic acid of the formation of singlet oxygen and sensitising agent, and this can be to come from being connected of sensitising agent and pathogen nucleic acid." nucleic acid " comprises ribonucleic acid (RNA) and DNA (deoxyribonucleic acid) (DNA).Occur in 7, chemical reaction between 8-dimethyl-10-ribityl isoalloxazine and the nucleic acid is considered to not be only to be undertaken by the process (being Type II mechanism) of singlet oxygen dependence, and would rather say so by the interaction (type i mechanism) of direct emulsion-substrate (sensitizer-substrate).Cadet etc. [J.Chem., 23:420-429 (1983)] clearly illustrate 7, and the effect of 8-dimethyl-10-ribityl isoalloxazine is because the non-singlet oxygen oxidation of guanosine residue.In addition, adenosine bases seems that to 7 8-dimethyl-10-ribityl isoalloxazine adds the effect sensitivity of ultraviolet light.This is important, because the adenosine residue is insensitive to the process that singlet oxygen relies on relatively.7,8-dimethyl-10-ribityl isoalloxazine seems not produce a large amount of singlet oxygens when being exposed to ultraviolet light, but by directly and substrate (for example, nucleic acid) interaction is brought into play its effect, and described and interaction substrate are by finishing with the electron transfer reaction of the emulsion material of excitation state.Because the indiscriminate damage of pair cell and protein mainly is to result from the singlet oxygen source, with use other photosensitizer compounds, the example that for example has the psoralen of significant Type II chemical reaction is compared, for 7, the path of this mechanism of 8-dimethyl-10-ribityl isoalloxazine allows at it bigger selectivity to be arranged on.
Photosensitizer-like additive and acetate can be added before blood constitutent is added to container or flow in irradiation or the storage container, perhaps can be added in the blood constitutent in container.As mentioned above, photosensitizer-like additive and acetate can also add in the blood constitutent as storing solution after pathogene reduces step.
Reduce step for pathogene, the additive solution of vitamin b3 is placed in the bag with being reduced the blood constitutent of pathogene and comprising at least, and described bag is that light-permeable light-permeable or enough at least is so that the content that allows sufficient radiation to reach them activates sensitising agent.The material that term " light-permeable " means container is fully transparent to the light radiation of the suitable wavelength that is used to activate photosensitizer-like additive.In the described additive solution that comprises vitamin b3 at least, vitamin b3 adds in the concentration of about at least 500 μ M.
The bag that comprises blood constitutent and vitamin b3 is illuminated, preferably arrives about 120J/cm greater than 1 2, the time, the absorption ratio that depends on irradiated blood constitutent was to guarantee that the fluid of all exposures all receives radiation basically between about 6 to about 10 minutes.
Acetate can add to before vitamin b3 is added in the irradiated blood products, also can add together with vitamin b3, perhaps added after irradiating step.Acetate is at least approximately concentration interpolation of the every 35mL solution of 106mM.Additive solution can also comprise physiological saline, and described physiological saline comprises about 0.9% sodium chloride.
Figure 11 has shown one embodiment of the present of invention, wherein will be reduced in the initial collected bags of blood 280 of blood constitutent of pathogene.The irradiation bag 284 that collection bag 280 enters into light-permeable is flowed out in blood constitutent subsequently, and irradiation bag 284 is equipped with import 282, can be via entering pipe 288 by import 282 interpolations from the vitamin b3 and/or the acetate of bag 286.Be exposed to as shown in figure 12 optical emitter 260 with back pkt. 284.
Selectable, acetate can add to after irradiating step in the blood products of pathogene minimizing, and the product that pathogene reduces can be transfused blood immediately or store in order to following use.Bag 284 can also be packed in advance comprising sensitising agent and acetate, and can be added to after this in the bag 284 from the fluid of bag 280.
As mentioned above, storing solution of the present invention also uses additive vitamin b3 and acetate.
Specific embodiments
Embodiment 1
Add the effect that acetate had for measuring on the blood platelet of having accepted pathogene minimizing step, blood platelet is suspended in the solution that comprises independent vitamin b3 or vitamin b3 and acetate, and is exposed to light.
These tests comprise two contrasts, and (150mL comprises 3-4 x 10 to have the hematoblastic control sample of high concentration 11Per 1 x 10 of blood platelet and 40mL blood plasma 11Cell) (on chart, be called as the storage of height (blood platelet) concentration) and standard storage contrast (250mL comprises 3-4 x10 11Blood platelet and 62-83mL blood plasma/3-4 x 10 11Blood platelet) (on chart, is called as standard storage contrast (or being untreated)).
This test also comprises blood platelet sample that two pathogene reduce (being called as processings (or processing) in chart).The sample of a processing comprise be suspended in 150mL comprise 50 μ M vitamin b3 and per 1 x 10 of 40mL blood plasma 113-4x 10 in the pathogene minimizing/storing solution of cell 11Blood platelet (in chart, being called as processing, vitamin b3) and sample comprise be suspended in 150mL comprise per 1 x 10 of 50 μ M vitamin b3 and 20mM acetate and 40mL blood plasma 113-4 x 10 in the pathogene minimizing/storing solution of cell 11Blood platelet (in chart, being called as processing, vitamin b3+acetate).The sample of two kinds of processing is exposed to the light of 6.24J/mL, and stores 7 days under standard platelet storage conditions.
Below Fig. 1-7 shown that handle and untreated hematoblastic metabolic direct and indirect measurement.
Fig. 1 is the comparison of processing and untreated platelet storage 5 and 7 days glucose consumptions.Can see, especially store 7 days after, compare with the blood platelet that vitamin b3 is handled separately, the platelet consumption that the pathogene of handling with vitamin b3 and acetate reduces less glucose.
Fig. 2 is the comparison of processing and untreated platelet storage 5 and lactic acid generation in 7 days.Especially after storage 7 days, compare with the blood platelet that vitamin b3 is handled separately, the blood platelet that the pathogene of handling with vitamin b3 and acetate reduces produces less lactic acid.
Fig. 3 is that pathogene minimizing/storing solution compares above the pH value variation of 7 days storage periods.The pH value that the blood platelet that the pathogene of handling with vitamin b3 and acetate behind the storage period above 7 days reduces has experienced pathogene minimizing/storing solution changes (or reduction) very slowly.At the 7th day, mean ph value was on 7.0.For the blood platelet in not having the pathogene minimizing/storing solution of acetate, the pH value is lower than 6.8.
Fig. 4 is that the blood platelet that pathogene reduces compares above the oxygen consumption of 7 days storage periods.Compare with two groups of contrast blood platelets, in 7 days storage periods, with vitamin b3 and acetate and vitamin b3 separately the pathogene of processing reduce hematoblastic oxygen consumption and constantly increase.Oxygen consumption is the sign of mitochondrial respiratory.Low pO 2Value reflects oxygen consumption and better mitochondria activity.
Fig. 5 is the comparison that platelet storage surpasses 7 days carbon dioxide generating.Carbon dioxide generating is measuring of a mitochondrial respiratory; Platelets consume oxygen of breathing and generation carbonic acid gas.Compare with the untreated blood platelet of contrast, the pathogene of handling with vitamin b3 and acetate reduces blood platelet generation more carbon dioxide.
Fig. 6 is the comparison that the 40mL in pathogene minimizing/storing solution remains the bicarbonate neutralizes effect of platelet storage above 7 days in the blood plasma.The platelet economy bicarbonate is to keep stable p H value.If because the generation pH value of lactic acid descends, more bicarbonates will be neutralized.Compare with the untreated blood platelet of contrast, in the blood platelet that the pathogene of handling with vitamin b3 and acetate reduces and less bicarbonate.
Fig. 7 is that the blood platelet percentage that extended configuration changes between 5 and 7 days of storage compares.Compare with the blood platelet that does not have acetate to handle, again, the blood platelet of handling with vitamin b3 and acetate has shown less alteration of form after storing 7 days.
As can seeing at Fig. 1-3, acetate be added on glucose consumption, lactic acid produces and pH value aspect has produced significant improvement, described glucose consumption, lactic acid produce and pH value is in the external blood platelet the most proactive index of restoring and survive.This effect combines with vitamin b3 with acetate and promotes that the effect of mitochondrial respiratory is consistent.
These data show that also the additive solution that comprises vitamin b3 and acetate allows the hematoblastic storage of high concentration when reducing plasma concentration and/or pathogene to reduce.This allows to gather more blood plasma in blood separation procedure, and reduces blood transfusion receptor's plasma exposure level.
Embodiment 2
Do a comparative study to observe the effect of acetate on 12 days blood platelet of storage.Described blood platelet is not exposed to light.
One group comprises 250mL concentration is 900-2100 x 10 3The hematoblastic sample of/μ L is suspended in the storing solution of the salt solution that has 1.85M sodium acetate and 500 μ M vitamin b3 comprising of 35mL.
It is 900-2100 x 10 that another group comprises 250mL concentration 3The hematoblastic sample of/μ L is suspended in 37mL and only comprises in the storing solution of salt solution.
Fig. 8 has compared blood platelet that is stored in the solution that comprises vitamin b3 and acetate and the hematoblastic glucose consumption rate that is stored in the solution that does not have vitamin b3 and acetate.After having stored 12 days, compare the less glucose that has been stored in platelet consumption in the solution that comprises vitamin b3 and acetate with the blood platelet in being stored in the solution that does not have vitamin b3 and acetate.
Fig. 9 has compared the hematoblastic production of lactic acid rate after storing 12 days.After having stored 12 days, to compare with the blood platelet in being stored in the solution that does not have vitamin b3 and acetate, the blood platelet that is stored in the solution that comprises vitamin b3 and acetate has produced less lactic acid.
Figure 10 has compared hematoblastic cell counting that is stored in the storing solution that comprises vitamin b3 and acetate and the hematoblastic cell counting that is stored in the solution that does not have vitamin b3 and acetate.Storage surpassed after 12 days, platelet storage the solution that comprises vitamin b3 and acetate be stored in the solution that does not have vitamin b3 and acetate in compare, do not show measurable influence for hematoblastic cell counting.
The result has shown the advantage of using the storing solution that comprises vitamin b3 and acetate.As seen in Fig. 8-10, to compare with the blood platelet in being stored in the solution that does not have vitamin b3 and acetate, the blood platelet of storing in the solution that comprises acetate and vitamin b3 can be stored blood platelet at least 12 days.

Claims (31)

1, a kind of fluid comprises:
The blood constitutent of at least a collection; With
The blood constitutent additive solution, this blood constitutent additive solution comprises
The endogenous alloxazine; With
Acetate.
2, fluid as claimed in claim 1, wherein said endogenous alloxazine is a vitamin b3.
3, fluid as claimed in claim 1, the blood constitutent of wherein said at least a collection comprises blood platelet.
4, fluid as claimed in claim 1, wherein said blood constitutent additive solution further comprises physiological saline.
5, fluid as claimed in claim 4, wherein said physiological saline are 0.9% sodium chloride.
6, fluid as claimed in claim 3 further comprises blood plasma.
7, fluid as claimed in claim 6, wherein the volume of blood plasma is at 20-80mL per 10 11Between the blood platelet of gathering.
8, fluid as claimed in claim 6, wherein the volume of blood plasma is at 30-60mL per 10 11Between the blood platelet of gathering.
9, fluid as claimed in claim 1, the blood constitutent of wherein said at least a collection has been reduced pathogene.
10, storage or additive solution comprise: endogenous alloxazine and acetate.
11, storage as claimed in claim 10 or additive solution, wherein said endogenous alloxazine is a vitamin b3.
12, storage as claimed in claim 10 or additive solution further comprise physiological saline.
13, storage as claimed in claim 12 or additive solution, wherein said physiological saline are 0.9% sodium chloride.
14, storage or additive solution basic composition is: endogenous alloxazine and acetate.
15, storage as claimed in claim 14 or additive solution, wherein said endogenous alloxazine is a vitamin b3.
16, storage as claimed in claim 15 or additive solution, wherein vitamin b3 is the concentration of the per 35 ± 5mL solution of about 500 μ M.
17, storage as claimed in claim 14 or additive solution, wherein acetate is the concentration of the per 35 ± 5mL solution of about 140 ± 50mM.
18, storage or additive solution consist of: vitamin b3, acetate and salt solution.
19, reduced the fluid of pathogene, basic composition is:
The blood or the blood constitutent of gathering; With
Pathogene reduces solution, and this pathogene reduces basic composition is of solution
The photoproducts of photosensitizer-like additive;
Acetate; With
Salt solution.
20, fluid as claimed in claim 19, the blood of wherein said collection or blood constitutent further basic composition is blood platelet and blood plasma.
21, fluid as claimed in claim 20, wherein blood plasma is at 20-80mL per 10 11Between the blood platelet of gathering.
22, fluid as claimed in claim 20, wherein blood plasma is at 30-60mL per 10 11Between the blood platelet of gathering.
23, fluid as claimed in claim 19, the photoproducts of wherein said photosensitizer-like additive is the photoproducts of endogenous photosensitizers.
24, pathogene reduces solution, comprises endogenous alloxazine and acetate.
25, pathogene as claimed in claim 24 reduces solution, further comprises salt solution.
26, pathogene as claimed in claim 24 reduces solution, and wherein said endogenous alloxazine further comprises vitamin b3.
27, pathogene reduces solution, consists of: vitamin b3, acetate and salt solution.
28, may comprise the blood of pathogene or gather the method that the pathogene of blood constitutent reduces, comprise:
(a) the mixture of effective nontoxic quantity and blood or gather blood constitutent and mix and prepare fluid-mixing, described mixture is gone up substantially by endogenous photosensitizers and acetate and is formed; With
(b) described fluid-mixing is exposed under the light radiation of enough activation sensitising agents, is reduced to the small part pathogene whereby.
29, method as claimed in claim 28, the blood constitutent of wherein said collection comprises blood platelet.
30, method as claimed in claim 28 further comprises to fluid-mixing and adds physiological saline.
31, method as claimed in claim 29, wherein said fluid-mixing further comprise quantity at 20-80mL per 10 11Blood plasma between the blood platelet of gathering.
32, method as claimed in claim 29, wherein said fluid-mixing further comprise quantity at 30-60mL per 10 11Blood plasma between the blood platelet of gathering.
CNA200680045661XA 2005-12-06 2006-12-01 Method for treatment and storage of blood and blood products using endogenous alloxazines and acetate Pending CN101505591A (en)

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US8835104B2 (en) 2007-12-20 2014-09-16 Fenwal, Inc. Medium and methods for the storage of platelets
EP2694131B1 (en) 2011-04-07 2019-08-28 Fenwal, Inc. Automated methods and systems for providing platelet concentrates with reduced residual plasma volumes and storage media for such platelet concentrates

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US5376524A (en) * 1991-04-01 1994-12-27 Thomas Jefferson University Platelet storage medium containing acetate and phosphate
US5234808A (en) * 1991-10-30 1993-08-10 Thomas Jefferson University Acetate addition to platelets stored in plasma
US5344752A (en) * 1991-10-30 1994-09-06 Thomas Jefferson University Plasma-based platelet concentrate preparations
US7094378B1 (en) * 2000-06-15 2006-08-22 Gambro, Inc. Method and apparatus for inactivation of biological contaminants using photosensitizers
TW590780B (en) * 2000-06-02 2004-06-11 Gambro Inc Additive solutions containing riboflavin
US6548241B1 (en) * 2000-11-28 2003-04-15 Gambro, Inc. Storage solution containing photosensitizer for inactivation of biological contaminants
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