JPH05502241A - Antibacterial preservation of plasma - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Antibacterial preservation of plasma Background of the invention This invention relates to the processing and preservation of plasma and plasma derivatives and to the treatment and storage of plasma-derived microorganisms. protection of technicians, nurses and doctors, and of the ultimate recipient patient, from infection by Regarding.

The following terms used throughout the definition and specification may have alternative or different meanings: Unless otherwise specified or clear from the context, no term used as having the stated meaning. You will be welcomed and understood.

Tissue culture: Tissue culture is the cultivation of cells and tissues grown or enhanced in a culture medium. Nutrients intended for use in tissue culture are Not included. Examples of cultured tissues cultured for use in burn victims It is skin tissue. prepared by standard biological and/or genetic engineering techniques. Cells grown and products of cells are other examples of tissue culture.

Laboratory Reagents, Standards and Samples, Laboratory Reagents and Standards It is produced from or contains human and animal body fluids. means the reagents and standards that Examples of such products are control serum and plasma chemistry. This is a stark contrast.

Toner ``Donor J'' term or from which such specimens are usually obtained does not apply, while the term ``toner j'' has a more general meaning here. used as including individuals from which plasma is obtained for any purpose in and such terms may be used to connote even unwilling donors. Dew. When applying the invention to animals, the donor is a mammal or a mammalian fetus. Maybe.

Povidone (USP) is used as it is used in the United States Pharmacopoeia Act and is Identifying suitable polyvinylpyrrolidone for use in acceptable solutions .

Molecular Iodine Compound: The term "molecular iodine compound" is used in this patent to refer to molecular iodine, Valid in molecular form as I, diatomic iodine, I2, or typically diatomic iodine containing iodine or reacting with the sample or reacting in its presence. means or includes a compound or mixture of compounds that produces iodine, such as used as. Povidone-iodine is a prime example of such a compound.

Povidone-iodine: Povidone-iodine is a complex of polyvinylpyrrolidone and molecular iodine It is. Povidone-iodine complexes of the type considered have been described in the literature. Purchased and sold by The Purdue-Frederick Co. has been done.

When a percentage concentration is referred to in relation to povidone-iodine, that percentage is Expresses the percentage by weight of povidone-iodine, relative to which povidone-iodine based on the weight of the solution or substance added. Thus, 1% by weight (Wlo) Povidone iodine in solution gives IW concentration of 11000 pp I2 Sufficient povidone iodine was dissolved to yield a concentration of 10 bohiton iodine. Show that. In many instances, povidone-iodine is present in solution, e.g., at a pH of about 15. , it can be added as a 10% solution in water, or it can be added as a powder or in other forms. It's okay. Povidone-iodine powder is approximately 85% PVP, 10% I2 and 5% iodine. Contains urides. A 10% solution of this powder contains 1% free, available iodine. Contains CGershenfeId, Am, J, Surgery 94.93 8 (1957)), Povidonyo used in the experiments mentioned later. The ratio of polyvinylpyrrolidone to iodine in the code product is 1 part active iodine. Povidone iodine at 8°5 parts per uranium. The product is also as iodide about Contains 0.5 part of inert iodine. A typical stock solution is 10% (10,000pp rn 12), 5% (5,000ppm 12) and 1% (100ppm i t).

In such cases mentioned, the ratio of povidone to iodine is higher than about 85 to 1. Additive povidone (polyvinylpyrrolidone) or increase the ratio of PVP to I2 It is added so that The concentration of povidone iodine in such a composition is I 2 povidone iodine to 8.5 to I Concentration of povidone iodine added like PVP degree, that is, i, oooppm I2.

Nutrients: The nutrients used here are derived from animal sources such as fetal bovine serum (FBS). derived in whole or in part from pathogenic microorganisms or toxic or Substances that may become contaminated from other sources with pyrogen-producing microorganisms means. The point is that nutrients are free from the microorganisms that proliferate. is distinct from tissue culture media and, when added to tissue media, contains nutritional compounds. The medium is inoculated or Supports the propagation of desired cellular components maintained in the culture medium.

Survival 10. (Viable): The word viability used here is , capable of self-replication under appropriate circumstances, e.g. tissues, bacteria, protozoa. Refers to cells or microorganisms that can reproduce or reproduce, such as animals.

Persons handling plasma or its components, e.g. serum, cryoprecipitate, etc., must be aware of pathogens in the sample. Risk of infection from the body. People exposed to such risks should not handle specimens. A physician, nurse, or clinical technician who handles the specimen and analyzes or tests the specimen. technicians, those handling sampling and testing equipment and equipment used for They also include a series of individuals participating in the disposal of sampling equipment, and the equipment used. from the person who produces the equipment to the person who ultimately processes the equipment, usually in a specially designed high temperature furnace. Including.

The risk of contracting disease is particularly great when handling pooled plasma. all Plasma pools contain infectious microorganisms and anyone handling pooled plasma must At some point you will contract one or more diseases from the plasma. The first stage of processing, and For example, if there is long-term indirect contact with the pooled plasma during the initial pool and spin-down, These engineers will eventually become infected with hepatitis. disease in pooled plasma The danger of disease from the original substance and the possibility of eventually becoming infected with the pathogen or at least being a carrier. The certainty that the result will be a long-standing problem in the blood hang industry I haven't been able to find a suitable solution.

The risks to health care workers are substantial and Tondo Health Care Worker Kaebstein Bar Virus (EBV) and/or by the fact that they carry Tomegalovirus (CMV). The latter is perhaps the most ubiquitous of the pathogenic viruses. health Care workers and people handling plasma and body fluid sup- plying and handling equipment should Pond pathogenic viruses, as well as many less life-threatening viruses, , including hepatitis and human immunodeficiency virus (HIV).

may contaminate plasma and plasma products or fractions. Another organism that does not exist and poses a serious danger is the bacterium Ernoniaensis. It is Yersinia enterocolitica.

Shigella (E) is the cause of acute bacterial gastroenteritis. and comparable species Salmone lIa and Campylo It surpasses Campylobacter. Blood transfusion of Enterocolitis bacterium A serious increase in related infections, Tipple, etc., Transfus ion 30°3, p, 207 (+990). en Terocolichi and other lXcutilia that grow at relatively low temperatures, such as T. Staphylococcus dermidis (Staphylococcus pidermis) and cashier Legionella pneumophila lia) potentially pose a serious risk in plasma products.

Bacterial infections are a continuing concern in the blood bank industry. Indeed, the import National Surveillance System for Blood-related Bacterial Infections Required Editorial, Transfusion 30. 3. p, I93 (1990).

Notomegalovirus (CMV), perhaps the most ubiquitous pathogenic microorganism, or animals found in body fluids and tissues.

CMV is often associated with life-threatening illness in individuals with suppressed immune systems. associated with pneumonia, and can be a factor causing or contributing to it, and pneumonia. , can be the main cause of neurological diseases, febrile diseases, eye diseases and hepatitis. C-IV Infection is a serious limiting factor in transfusion of fluid and plasma from individuals to pond individuals. blood The recipient of the plasma runs a significant risk of CMV infection, and that risk may be due to the recipient's immune system or external factors. suppressed or immunosuppressed to prevent rejection of organs or cells in the body Doubly so when it exists for a reason.

The herpesvirus genus, the CMV or component of it, causes cold sores, herpes zoster, associated with sexually transmitted diseases, mononucleosis, eye infections, birth defects and possibly some cancers or Represents a very large group of viruses that are related. These subfamilies are specific It is of great importance. Alpha subfamily is used for cold pain, blisters, and eye and brain sensations. HVI (herpesvirus alone), which causes infections, causes genital ulcers HV2 (herpes virus alone 2), and water @ healing, herpes zoster and brain sensation Contains HV3 (HV varicella zoster), which causes infection. Beta subfamily is that The main part contains HV5, which is the CMV mentioned above. The subfamily Gammaidae causes infectious mononucleosis. HV4 (Eps), which causes and is associated with herxotrine lymphoma and cancer of the nasopharynx. tine-pearl).

In addition to the risk of transmitting infectious diseases through plasma, the various stages of production and processing Bacterial growth in the plasma product at introduced and they must be removed before the product can be used in therapy. Must be.

Nutrients for tissue culture always contain pathogenic microorganisms that must be removed or treated. If so, it destroys or greatly impairs the value of nutrients in tissue culture. one In general, the exact substances needed to grow a given cell line can be precisely defined. It is therefore not possible to use serum-based or serum-containing media. It is also common practice to add nutrient serum as necessary during cell growth.

Bovine serum from adult animals may be appropriate in some cases and However, for the safe growth of many cell lines, false fetal serum (FBS) (sometimes fetal Bovine serum (called Fe2) is required and high purity is important. be. However, even the use of FBS does not guarantee freedom from infectious agents. do not have. Indeed, commercially produced FBS is VD) virus and infectious bovine rhinotracheitis (BR), paralyzed Infection with Influenza influenzae 3 (PI3) is very common. At best, raw serum The pool probably contains at least 10' infectious BVD virus particles per milliliter. Probably includes children. Serum filtration is a common method to reduce the presence of infectious microorganisms in serum. step or if a large amount of serum components are drawn into the filter or Serum quality can be damaged by filtration if particulates are cut off. during filtration Particle cutting is generally used when lateral flow filtration is used and turbulence occurs. It happens. Reliable evidence for the removal of BVD virus from serum using filtration It is currently very difficult to obtain such results.

The use of elemental iodine as a preservative dates back to 1839. . It is used today for various medicinal purposes. Iodine and various The combination with solubilized polymers creates a class of new compositions known as iodophors. ・It is satisfied by a single alcohol or water iodine solution Monopolize the market once. For example, polyethylene glycol mono(nonylphenyl ) ether, or non-ionic, such as poly(vinyl-pyrrolidone) (PVP) The surfactant and iodine form a complex. The complex contains free iodine in aqueous solution. It functions by rapidly promoting the release of They are bacteria, yeast, and yeast. It shows good activity against mother bacteria, protozoa and many viruses, and certainly against humans. and of all preservative preparations suitable for use directly on animals and tissues. Among them, povidone-iodine alone can kill all kinds of pathogens, and they are Gram-positive and Gram-negative bacteria, mycobacteria, fungi, yeasts, and rus and protozoa. Many bacteria are killed in 15 to 30 seconds of contact. It will be done. These iodophors are generally non-toxic, non-11Fl & non-toxic, non-sensitizing and Non-corrosive to all metals (except silver and iron alloys).

Iodine and iodine-containing compounds and preparations, for example, as preservatives, As drugs that are treated in different combinations in the prevention and treatment of diseases and in various Used intensively in medicine as a therapeutic agent in thyroid diseases and other abnormalities. It will be done. Iodine binds to proteins partly through chemical reactions and partly by adsorption. It is a highly reactive substance. Therefore, its antibacterial action is effective in serum, blood, urine, It is inherently weakened when organic substances such as milk are present. But in the middle However, in the absence of such interference, the non-selective bactericidal action is strong and rapid. You Saturated aqueous solutions of the element exhibit antibacterial properties. However, because of the low iodine content in water, For solubility (33 mg/l 00 ml at 25°C).

Reactions with bacteria or with externally present substances result in a solution of their active contents. , rapidly decrease. Iodide ions often increase the solubility of iodine in water Added to make a difference. This increase results in the formation of triiodide, 12 + I- = Ix - Therefore it happens. Aqueous solutions of iodine and iodide at pH less than 8 are primarily fluorocarbons. triatomic iodine I2 and triiodide I. The ratio of I2 and I3 is Depends on iodide concentration. Pharmaceutical povidone iodine preparation aerosol spray , gauze pads, lubricating gels, creams, solutions, irrigation preparations, suppositories, mouthwashes, perineum including cleaning solutions, shampoos and skin cleaners and scrubs. Povidonyo Administer preparations against the skin and membranes, such as the tunica vaginalis, and on infected wounds and and localized to the surgical incision.

An important solubilizer and carrier for iodine is polyvinylpyrrolidone (PVP). One grade of it is identified as Povidone USP. povidoneyo PVP-iodine is widely used externally by humans as a preservative.

Such products are marketed as BetadineTM and IsodineTM. It is. Povidone-iodine products and the preparation of such products are produced by GAF Co Rice for Hosmer and 51gg1a transferred to rporatic+n National patent number 2. 707. No. 701, No. 2,826,532 and No. 2. 9 00. 305 and numerous GAF Corporation publications. has been done. For example, Tableting with Povidone f JsP (+981) and PVP See (1982).

Povidone iodine powder contains approximately 85% PVP, 10% I2 and 5% iodide.

A 10% solution of this powder contains 1% free, available iodine (Gershen feld, Am, J., Surgery 94, 93B (1957)).

Under normal conditions, PVP is stable as a solid and in solution. Pv One of the most attractive properties of P is its binding ability. This property has enormous commercial This made it possible to use it in applications. Small amounts of PVP or apparently individual colloidal particles Due to its adsorption as a thin layer on the surface of Stabilizes the suspension. One of the most widely studied and best characterized PVs The P complex is of PVP-iodine. For example, hydrogen triiodide and PVP It forms a complex that is so stable that it has no appreciable vapor pressure.

It is better than iodine tincture as a fungicide.

The properties of iodine and povidone-iodine as disinfectants have been shown in some antiseptic applications. It is well known that this will be further reduced. It is non-sterile from iodine Due to the reduction effect of the substances to be sterilized resulting in their conversion to iodide.

Thus, not only is the available iodine store depleted, but the triiodide equilibrium is or similarly affected. Both of these effects are due to free molecular iodine, an actual antibacterial agent. Decrease the percentage of povidone-iodine preparations or contaminated with liquid substrates (e.g., plasma). In addition, when dyed, bohydride causes an increase in the equilibrium concentration of free molecular iodine. There is a dilution effect characteristic of the iodine type. The latter effect and the extent to which it compensates for the other two effects It depends on the content of the reducing substance. Thus, whole blood contains free molecular iodine. A strong decrease in concentration occurs, while in the presence of plasma it practically changes. There remains no.

Durmaz, et at, Mikrobiyol, Bul, 22 ( 3), 1988 (abstract): Gottardi W, Hyg , Med, 12 (4), 1987.150-154゜Nutritional Bouillon Hemoglobin and plasma had almost no inactivating activity, but 1g hemoglobin was free. 50 mg of NaI was inactivated.　　　　　Is the experiment using human red blood cells an experiment? It showed that it happened quickly. The best antibacterial efficacy in clinical use is relatively This is achieved in a load-free situation. Povidone-iodine on healthy skin Developed a strong and sometimes long-lasting bactericidal effect against bacteria.

Lacey, R, W, J Appl Bacteriol 46 (3), 1979.443-450. .

The bactericidal effect of diluted povidone-iodine solution is inversely proportional to the concentration of povidone-iodine solution and Restricted to the greatest extent by blood, phlegm, fat and glove powder. Ta. Zamora J: Surgery (St Louis) 98 (1 ), 1985. 25-29; 2 amora.

Am, J, Surgery, 151. p, 400 (+986). Also , Waheed 5heikh, Current Therapeutic R e5earch 40. See also No. 6.1096 (1986) . Van Den Broek, et at, Antimicrobial Agents and Chemotherapy, 1982.593-59 7, povidone-iodine is almost left behind due to interaction with microorganisms in the liquid phase. (Also, Abdulla et al. h, et al, Arzneim, -Forsch, /Drug Res , 31(f), Nr, 5.828) o Ninneman et al., J. of [mmunol, 81.1265 (1981) reported that povidone-iodine was absorbed within serum albumin, and Povidone-iodine or povidone-iodine is known to be bound to albumin. It was found that the bactericidal effect of the enzyme was not destroyed by albumin binding. Its activities Whether albumin pohytone iodine remains active or povitone iodine Don-iodine and/or iodine can be released from the albumin-bohyton-iodine complex. It has not been determined whether it will be removed.

The prior art teaches that elemental (diatomic) iodine, +3 also complex iodine, e.g. VI” It also provides effective and reliable sterilization in plasma or plasma derivatives. This suggests that it is not a drug.

Various medical and plasma handling methods will be presented later. These are very well known methods and the steps in these methods are fully explained in the literature. ing. The following references are for general background and to specific method literature. THCHNICAL MANIJAL of prepared for detailed reference the American As5ocation of Blood Ba nkers, 9th Ed, (1985): HLA TECHNIQUES FORBLOOD BANKERS, American As5ociatio n of Blood Bankers (+984); Developme nts in Biological 5 standardization, V ols, 1-57.3. Karger, Ba5el: CLIN[CAL I MMUNOcHEMIsTRY, The American Ass.

ciaeion for C11nical Che+n1stry; ME DrCINE, Vols, 2゜5cientific American, New York: CARE of the 5URGICAL PATIE NT, Vols, 1-2.5 scientific American, Ne w York: CLIRRENT PROTOCOLS IN MOLECU LARBIOLOGY, Greene Publishing As5ocia tes and Wiley- [interscience, John Wiley y & 5ons, New York Summary of the invention In particular, the invention is embodied in a method for treating a patient with blood plasma, the step of collecting plasma from the patient and then entering the plasma into the patient to be treated. The steps include: The improvements of this invention range from 0.1W10 to 2W10. ( 100 to 2. Molecular iodine compounding to yield a concentration of OOOppm If) The preferred range is about 0.25W10. or approximately 0.5 W10 (250 to 500 pprn +2), and at least about one-half minute sufficient to inactivate or destroy infectious pathogenic microorganisms. an additional step of contacting said plasma with said molecular iodine compound during include. The time of contact is not critical, e.g. up to 24 hours or more. Longer contact times result in increased bactericidal efficacy. However, generally , an effective bactericidal effect is obtained in a short period of one to two minutes of contact.

In particular, the invention provides a culture medium for inhibiting the growth of microorganisms in tissue culture media. Embodied in a method of processing plasma-containing nutrients for. This invention The plasma component of nutrients, either as is or after mixing with other nutrient components, is /'O to 2W10, preferably about 0.25W/○ to o, 5W10 (2 mixed with molecular iodine compounds to give a concentration of 50 to 500 ppm r2). a further step for inactivating or destroying infectious pathogenic microorganisms; contacting the nutrient with the molecular iodine compound for a sufficient period of at least about one-half minute; and then placing the nutrients into the tissue culture medium. nothing.

This invention is particularly applicable to commercial articles, i.e. nutrients for use in tissue culture media. and become concrete. Nutrients inactivate or inactivate infectious pathogenic microorganisms. is 0.0 enough to destroy it. IWlo to 2W10, preferably about 025W10 or 0. Povidone at a concentration of 5W10 (250 to 50 oppm12) A serum-containing fluid that contains iodine, which is introduced as iodine, and the said nutrient increases viability. and free from viable microorganisms.

The invention is particularly realized in a method for designing cell lines, including 0. IWlo to 2W10, preferably about o.

At a concentration of 25W10 to 0.5W10 (250 to 500ppm +2) is sufficient to arrest or inhibit cell line proliferation or kill the cell line. Tissue culture nutrition that supports cell replication based on nutrients that are insufficient to kill The addition of povidone-iodine to the nutrients and the ability of such compositions to be produced by cell lines. and harvesting the composition of interest after it has been revealed.

The invention inter alia provides a method for providing a liquid with sufficient iodine on its surface to expose a liquid to sufficient iodine. The solid povidone iodine containing a certain amount of water is brought into contact with the liquid to be purified to remove the Killing pathogenic microorganisms and removing liquid from contact with solid povidone-iodine Embodied in a method for purifying plasma by. The method is further To regenerate the iodine content, the surface of solid povidone-iodine is treated with iodine during use. It may also include reacting.

The invention is particularly embodied in a method of treating a patient, the steps of collecting plasma from a person and storing it by cooling or freezing. step, heating, and thawing the plasma if it has been frozen. and placing two biological materials into the patient.

Plasma is 0. The concentration of IWlo to 2W10 is preferably about 0.25W10. or about 0.5W10, treated with a molecular iodine compound like Motaras, and for at least about 2 minutes, sufficient to inactivate or destroy infectious pathogenic microorganisms. The molecular iodine compound is allowed to contact the plasma for 1 minute. plasma and povidone The mixing with iodine is carried out in three substeps, namely: Initially, povidone iodine is introduced into the plasma at a concentration of about 0.1 to 2W10, preferably The range is about 0.25W10 to about 0.5W10: second, about 1/2 minute or maintaining the plasma in contact with povidone-iodine for a longer period and thirdly , reintroducing povidone-iodine into the plasma at a concentration of about 0.1W10 to 2W10. , the preferred range is about 0.25W10 to about 0.5W10. For storage Preferably, the plasma is mixed with povidone-iodine before refrigeration and/or freezing. , this step is performed at a lower temperature, e.g. 4°C to 6°C1 or after melting. It may be done.

The invention is particularly embodied in a method of sterilizing plasma derivatives, which Concentration of W10 to 2W10, preferred range is about 0.25W/○ to about 0.5 W10, the plasma was treated with povidone-iodine into the plasma before separation of its components. to prepare plasma derivatives from the previous step and from the next previous step. Povidone iodine was added to the plasma derivative at a concentration of about 0.1W10 to 2W10. The preferred range is from about 0.25W10 to about 0.5W. It is 10.

In one preferred embodiment, the method of treating a patient with plasma comprises obtaining plasma from a donor. and the subsequent step of introducing plasma into the patient to be treated. and added to provide a povidone to iodine ratio of at least about 12:1. The povidone iodine obtained is mixed with plasma, preferably it is about 15 :1 to 30:1 and optionally amounts to about 60.1 and about 0.1W10. is sufficient to provide an iodine concentration of about 2W10, preferably it is about 0. ．． 25W/○ to 0.5W10 (250 to 500ppm 12) , and added to provide a povidone to iodine ratio of at least about 12,1 povidone allows contact of said povidone-iodine with said plasma, preferably is about 15:1 to 30:l and optionally reaches 60:l, which to inactivate or destroy infectious pathogenic microorganisms in plasma before injecting it into a patient. for at least about one-half minute.

In another embodiment, about 0.1W10 to about 2W/○, preferably about Povide of 0.25W10 to 0.5W10 (250 to 500pm T2) Preferably from 17 l to 30.1 l at a concentration that results in an iodine concentration of , added to provide a povidone to iodine ratio of at least about 12 to 1. With povidone, the nutrients are mixed with povidone-iodine and thereby made viable. produces nutrients that are free of both viable cells and viable microorganisms at least approximately enough to inactivate or destroy infectious pathogenic microorganisms, such that by allowing contact of said povidone-iodine with said nutrients for one-half minute. Nutrients for culture media to prevent microbial growth in tissue culture media or processed.

In another embodiment, the invention provides methods for inactivating infectious pathogenic microorganisms therein. from about 03IW10 to about 2W10 sufficient to oxidize or destroy povidone-iodine. in an amount sufficient to generate a concentration of at least about 12:1, preferably 15:1. Povidone was added to give a povidone to iodine ratio of 30:l. Tissue culture consisting essentially of serum-containing fluid containing iodine introduced as don-iodine Free from viable cells and viable microorganisms for use in culture media. is a commercially available product consisting essentially of nutrients that are free from both microorganisms and viable microorganisms. Povidone-iodine is preferred produces a povidone-iodine concentration of about 0.25W10 to about 0.5W10. Fully implemented.

Sufficient to arrest or prevent the growth of a cell line or to kill a cell line is insufficient and is insufficient to prevent the cell line from expressing the compound. sea urchin, from about 0.1W10 to about 2W10, preferably about O25, based on the culture medium. Povidone-iodine of W10 to 05W10 (250 to 500 ppm Is) For tissue culture nutrients that support cell line replication at concentrations that yield Preferably between about 151 and 30, sufficient to protect the cell line from destruction. 1 and optionally up to about 60:1, at least about 12:1 of povidone iodine. povidone iodine added to give a combination, and the synthesis by harvesting such compounds or after they have been expressed by a cell line. The invention is also embodied in methods of controlling cell lines.

Another embodiment of the invention is a method of sterilizing plasma derivatives, comprising: Bidon iodine, preferably about 0°25W10 to 0.5W10 (such as 250 Ishi sooppm ■2) is about 0.1W10 to about 2W10. preferably from 15:1 to 30:1, at least about! 2 vs l povi Povidone-iodine with povidone added to give a ratio of don to iodine (b) treating the blood plasma from step (a) before separation of its components; (C) preparing a serum derivative; treatment with bidone-iodine to provide povidone-iodine in the derivative from about 0.1W10 to about 2W10, preferably about 0.25W10 to 0.2W10. 5W10 (250 or s ooppm T2) Includes giving.

In the method of separating plasma factors by alcohol fractionation I, the improvement is that Includes attachment of povidone iodine to plasma 71a for higher yields and sharper fractions. Povidone-iodine, so as to give a differential of about 0 ．． 01W10 to about 2W10, preferably about 0.25W/○ to 0.5W1 At a concentration that gives 0 (250 to 500 ppm r2), at least about 12:1, preferably between 15:l and 30:l Povidone ioj− with povidone added to give the ratio of bidone to iodine 7 will also be disclosed. The concentration in plasma is preferably about 0.25 W/○ to about 0.25 W/○. It is 5W10.

An improvement in the method of separation of plasma fractions by cryoprecipitation is that The addition of povidone-iodine to the plasma of and about 0.01W/○ to about 2W10 bohidons to give sharper separation. The concentration to provide iodine is at least about 12 to 1, preferably 151 to 30. Povidone with povidone added to give a povidone to iodine ratio in plasma of Bidoun-iodine is also disclosed. The concentration in plasma is preferably about 0.25W10. It is about 0.5W/○.

The known value of povidone as a plasma expander is that it is free from pathogenic organisms. This is an element in an improved method for preparing blood plasma products.

Diagnostic testing without changing test results, with one exception: increased iodine The plasma derivatives used in the present invention are blood g1 derivatives or may be prepared from plasma.

Description of the preferred embodiment A number of non-limiting exemplary embodiments of this invention are set forth below, and are by way of example only. It is clearly indicated that the invention is not intended to limit the scope of the invention.

Surprisingly, about 0.1. Wlo to 2W10, the preferred range being about 0. For example, povidone iodine in plasma at a concentration of 25W10 to about 0.5W10. Molecular iodine compounds such as It was discovered that it did not result in hemolytic reactions or other changes in the plasma.

In general, conventional diagnostic procedures cannot be continued without any modifications to accommodate the presence of iodine. You may be Bohiton iodine is used as a laboratory standard for plasma preparations. It is an effective preservative solution used as described above.

Molecular iodine, such as povidone iodine, at a concentration of about 0.1W10 to 2W10 and preferably in the range of about o25W10 to 0.5W10 in plasma. Plasma is processed according to the invention by entering the plasma. Preferably all In embodiments, povidone-iodine has a molecular weight of at least about 12.1, preferably about J5. ] to 30. :L and Rendong have a povidone to iodine ratio of about 601. Exists. For example, the concentration of 0.25W/○ in plasma is 1. and other pathogens.

To our great surprise, iodine to the extent that it reduces or eliminates microbial activity Iodine reacts with other reducing agents in plasma Before, microbial killing is effective without altering the essential properties of plasma. certain In addition, the addition of Bocht-short is followed by a cryoprecipitation reaction and subsequent separation, e.g. of factors such as fib-1 nectin, fib-o nectin, and factor More complete alcohol separation, cleaner separation and higher factor yield Accompanied by nato.

The pooled plasma process is useful for many plasma products, especially those found at low concentrations in plasma. are an important and essential part of the production of those components and fractions that are treated. Worker - and potentially the risk of infection to the user of the product due to the large number of donor samples or pooled. Inevitably, any size of pooled plasma Lots that contain significant amounts of microbial contamination and that are exposed to such products are presents a serious risk of infection to cars and technicians. Plasma and plasma products Pathogenic microorganisms in the plasma should be removed preferably early in the plasma collection and pooling process. During the period, about 0. 1W10 to 2W10, preferably about 0.25W10 to about For example, povidone-iodine is present in plasma at concentrations in the range of 0.5 W/○. By adding molecular iodine, “ 'Can be removed.

Substantial amounts of plasma within or from hangs from individual toners, sometimes Use of purified plasma to replace blood lost in emergency and surgical procedures The blood is frozen and stored as fresh frozen blood W (FFP). That industry and outside Are physicians aware of the significant risks in using FFP or are there safe alternatives? Therefore, a large amount of FFP is used, exceeding 1 million units per year. There is. about 0.1W/○ to 2W10, preferably such that ton iodine is added. making an otherwise hazardous product completely safe. 1 of this invention One result is that millions of bound, enormous amounts of plasma, previously known as FFP. Once too dangerous to use, it now saves lives without the risk of infection. This means that it can be used for

In plasma and serum, 6+ and 70 log kills of vSv, i.e. total kills. . Table 1 and ■ show the effectiveness of the described method in whole blood and plasma.

Consecutive defeat＞＞＞till/J　2明! l 3% PVP C-15' 1. 67 2. 02 2% PVP C- 152,03,031% PVP C-152,333,043% PVP C -15+0.25% PVP-I' 5.33 8+5 2X PVP C-1 5+0.25% PVP-I 5.0 g+6 1X PVP C-15+0. 25% PVP-I 4.67 8+7 3% PVP C-15+0.10% PVP-14,’33’5.58 2% PVP C-15+O, LOX P VP I 4.33 6.339 1% PVP C-15+0.10? (PV P-r 4.33 5.331o 39g pvp c-3o13. 33 4 ．． 33II 2% PVP C-303,04,33121% PVP C- 303,335,0133% pvp C-30+0.25% PVP-16, 678+14 2% PVP C-30+0.25% PVP (7,338+1 5 1% PVP C-30+0.25% PVP-48+ 8+16 3% PVP C-30+0.10% PVP-14,56,67172% PVP C-30+0.10% PVP-14,676,5181% PVP C-30 +0.10% PVP-I 5.0 6.3319 3% PVP K-26- 28' 3.67 5.6720 2% PVP K-26-283,55,3 32+ 1% PVP K-26-284,05,00223% PVP K- 26-28+0.25% PVP (8+8+23 2X PVP K-26-2 8+0.25% PVP-I 8-1- 8+24 1% PVP K-26- 28+0.25% PVP-I8+8+25 3% PVP K-26-28+ 0.10% PVP-15,08+26 2% PVP K-26-28+0. 10% PVP-14,677,0271% PVP K-26-28+0.1 0% PVP-14,56,5I C-15 is GAF Corporation It is polyvinylpyrrolidone with a molecular weight of 12,500 manufactured by.

2 PVP-1 is Pu containing approximately 85% PVP, IO% J, and 5% iodide. povidone yo manufactured by rdue-Frederick Company It is powder.

3 C-30 is GAF Corpora tion with a molecular weight of 50,000 Polyvinyl pyrrolidone manufactured by

4 K-26-28 is a GA with a molecular weight between 40,000 and 50,000. Polyvinyl pyrrolidone manufactured by F Corporation .

PVP inhibits bacteria and viruses, making it an effective plasma expander. Very important benefits arise from the use of povidone-iodine in the treatment of plasma for killing. brought to you. Thus, both the quantity and quality of the plasma product or the method ahead of the treatment essentially increases compared to

In the course of research for the present invention, an interesting discovery was made regarding borJ hinyl pyro ton alone. It was seen. Polyvinylpyrrolidone alone or a virus that increases by 5 logs in body fluids It was discovered that it is possible to become extinct. This anti-antiviral effect and the effect of iodine It is not yet known whether there is a synergistic effect.

cryoprecipitation reaction or produced from individual toner plasma or from pooled plasma Good too. The risk of infection associated with the preparation and use of cryoprecipitation derived products is substantially eliminated by light. Cryoprecipitate is basically cryoprecipitate from which may be processed by processing whole plasma or plasma, or both, derived from . Alternatively or in addition to such pretreatment, cryoprecipitate can be prepared using the present invention. May be treated to kill bacteria and viruses. For example, Pobi Molecular iodine such as don-iodine or about 0°1W10 to 2W10, preferably Bacteria and viruses at concentrations ranging from about 0.25W10 to about 0.5W10. into the plasma in sufficient quantities to kill the virus.

The plasma is then frozen. If the resulting cryoprecipitate is dissolved, the cryoprecipitate , increased yield of fibrinoid poppy, fibronectin and factor II. The product is free of microorganisms.

For example, higher than IWlo or 2W10 and up to about 5W10 a high concentration of bohiton iodine, or 15 to 1 or more, preferably about 15 :Increase in Bochthon or factor ■ to a povidone to iodine ratio of 1 to 30 I may cause precipitation of yields a valuable process and is free from microbial contamination.

Similarly, other plasma fractions and plasma from other species have similar deafness. May be processed.

Plasma factors separated by alcohol fractionation, such as factor Higher yields and sharper separation if full separation liquid or Bohi 1-Short is included. separated by

In addition, of course, both the resulting components are free of microbial contamination.

In addition to molecular iodine compounds or nutrients containing Fetal Uno Serum (FB:S) or FBS. When exposed to infectious agents, infectious agents are inactivated. Pohitonyoto is approximately 0.1W/○ 2W/○, preferably in the range of about 0.25W10 to about 0.5W10 FBS or FBS-containing nutrients, or or other serum-containing nutrients. After a period of time, molecular iodination The compound is absorbed and the nutrients are sold and shipped as commercial items. Does not interfere with culture growth after being used in tissue or tissue culture media.

Bohiton iodine does not inhibit antibody function and thus is effective against bacteria or viruses. monoclonal antibodies and other It can be effectively used as a sterilizing agent for genetically engineered products.

industrial applications This invention finds applications in medical and veterinary science.

summary Do not destroy the effectiveness of plasma (to kill pathogenic microorganisms, Disclosed is the processing and storage of plasma and plasma derivatives using plasma.

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Claims (20)

[Claims] 1. Plasma or plasma derivative compositions for treating patients requiring transfusions of plasma or plasma-derived compositions. or the use of povidone-iodine for the manufacture of plasma-derived therapeutic compositions, the use of povidone-iodine comprising: Vidone-iodine provides povidone-iodine concentrations of 0.1 W/O to 2 W/O. be sufficiently added to the plasma or plasma-derived composition and to eliminate infectious pathogenic microorganisms in the plasma. contact with something for at least one-half minute long enough to inactivate or destroy it Permitted to be placed in, use. 2. The plasma povidone iodine concentration is between 0.25 W/O and 0.5 W/O. Manufacture according to claim 1. 3. The preparation according to claim 2, wherein the povidone to iodine ratio is at least 15:1. . 4. The preparation according to claim 1, wherein the povidone to iodine ratio is at least 15:1. . 5. Nutrients for culture media to prevent microbial growth in tissue culture media A method for treating the nutrients with povidone iodine at 0.1 W/O to 2 W/O. mixing with povidone iodine at a concentration such as to produce a concentration of iodine; Furthermore, it is free with respect to viable cells and viable microorganisms. sufficient to inactivate or destroy infectious agents to produce certain nutrients allowing contact of the povidone-iodine and the nutrient for at least 1/2 minute; A method, including steps. 6. Povidone was added to give a povidone to iodine ratio of at least 12:1. 6. The method according to claim 5, wherein: 7. 0.1 W/O, sufficient to inactivate or destroy infectious agents within it. and povidone-iodine in an amount to produce a povidone-iodine concentration of 2 W/O. contains a serum-containing fluid containing iodine, which is introduced as a Nutrients for use in tissue culture media that are free from viable microorganisms. 8. Povidone iodine in nutrients of at least 0.25 W/O 8. The method of claim 7, wherein the method is introduced to produce a code concentration. 9. Sufficient to arrest or prevent cell line proliferation, but kill cell lines. and insufficient to prevent the cell line from expressing the compound. Povidone-iodine concentrations from 0.1 W/O to 2 W/O were added per minute, based on the culture medium. Povidone-iodine is a tissue culture nutrient that supports cell line replication at concentrations that occur. and by the cell line after such compounds have been expressed by the cell line. harvesting said compound produced by said method. 10. (a) Plasma is treated with 0.1 W/O to 2 W/O in the plasma before separation of its components. Step of treating with povidone iodine to give povidone iodine of W/O; ( b) preparing a plasma derivative from step (a); and (c) Treating the derivative from step (a) with povidone-iodine to eliminate 0 in the derivative. ．． Plasma derivation comprising providing 1 W/O to 2 W/O of povidone-iodine A method for sterilizing things. 11. Improvements have been made in the method of separation of plasma factors by alcohol fractionation. 0.01 W/O to 0.5 W in plasma to give higher yields and sharper fractionation. Add povidone-iodine to the plasma before fractionation at a concentration giving povidone-iodine of /O A method including: 12. Nutrients for culture media to prevent microbial growth in tissue culture media A method of treating raw material with a povidone-iodine concentration of 0.1 W/O to 2 W/O. providing a povidone to iodine ratio of at least 12 to 1 at a concentration such that A step of mixing povidone-iodine and the above nutrients with povidone added to teps and, in addition, thereby both viable cells and viable microorganisms. inactivates or destroys infectious pathogens to produce nutrients that are free from contacting said povidone-iodine with said nutrients for at least one-half minute sufficient to and allowing touching. 13. 0.1 W/O sufficient to inactivate or destroy infectious agents therein at least in an amount sufficient to produce a povidone-iodine concentration of 1 to 2 W/O. Povidone with povidone given to give a povidone to iodine ratio of 12:1 Tissue culture consisting essentially of serum-containing fluid containing iodine introduced as iodine Free from viable cells and viable microorganisms for use in culture media is derived from nutrients that are present in viable cells and viable microorganisms Commercial goods that are free with respect to both living things. 14. the povidone to iodine ratio is at least 15 to 1, and the povidone iodine is added to give an iodine concentration of 250 ppm to 500 ppm. The commercial article according to claim 13. 15. Sufficient to arrest and prevent the growth of a cell line, but kill the cell line and even insufficient to prevent the cell line from expressing the compound. Sufficiently, a povidone-iodine concentration of 0.1 W/O to 2 W/O, based on the medium. For tissue culture media that support cell line replication at concentrations that produce Povidone-iodine ratio of at least 12 to 1 is sufficient to protect cell lines from destruction. Add povidone-iodine with povidone added to give a harvesting the compound after the compound is expressed by the cell line. Methods for controlling strains. 16. (a) Giving 0.1 W/O to 2 W/O povidone-iodine in plasma providing a povidone to povidone iodine ratio of at least 12 to 1 in sufficient quantities to Separate its components with povidone iodine using povidone added to (b) preparing a derivative of the plasma from step (a); a step of manufacturing; (c) Treating the derivative from step (a) with povidone-iodine so that the derivative has no odor. and administering 0.1 W/O to 2 W/O povidone iodine. How to sterilize derivatives. 17. In the method of separating plasma factors by alcohol fractionation, the improvement is that Includes addition of povidone-iodine to previous plasma for higher yields and sharper Give 0.01W/O to 2W/O povidone iodine to give a good fractionation. at a concentration such that the plasma povidone to iodine ratio is at least 12:1. With povidone, povidone-iodine is added to give the method. 18. The concentration of povidone iodine in plasma is 0.25W/O to 0.5W/0. 24. The method of claim 23. 19. In the method of separating plasma fractions by cryoprecipitation reaction, the improvement is that cryoprecipitation Including the addition of povidone-iodine to the plasma before the reaction, resulting in higher yields and more Add 0.1 W/O to 2 W/O povidone iodine to give sharp fractionation. povidone to iodine in plasma at a concentration of at least 12 to 1 such that The method in which povidone-iodine is added to give a proportion of povidone. 20. The concentration of povidone iodine in plasma is 0.25 W/O to 0.5 W/O. 20. The method of claim 19.