JPH06510067A - Starch-iodine preservation of blood, tissues and biological fluids - 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] Starch-iodine preservation technology for blood, tissues and biological fluids The present invention relates to the processing and storage of blood and blood derivatives, the treatment of other body tissues and cells, processing and preparation of tissue cultures and tissue culture products, and experimentation Concerning the preparation of reagents, standards and samples. According to the present invention, iodine and starch complexes with body or starch components, such as amylose and amylopectin, and Similar iodine-bonded polysaccharides and their derivatives (all of which are specifically mentioned in the text) (hereinafter referred to as "starch") is used in the processing of biological materials. after that as an additive or as a bed or film of solid albumin, starch, povidone, etc. Physiologically compatible reducing agents such as ascorbate on solid supports in filters to remove the final traces of biolethal iodine. Therefore, the present invention , bacteria, Chlamydia, Rickettsia, Mycoplasma and other potential to kill or inactivate pathogenic microorganisms and remove all biolethal iodine. used for

The present invention relates to the processing and preparation of human blood, tissues, etc. and other animal blood, tissues, etc. It is intended to be manufactured. Generally, the field of the invention is in the practice of medicine and veterinary medicine; Examples of parts include applications in similar fields of medical practice, veterinary medicine, for the benefit of patients. It is related to.

Background technology Iodine was officially recognized by the US Pharmacy Act in 1930, and chicken iodine ( Iodine (chicken agent) and liniment agent (iodine glue agent) It was also officially recognized. Clinicians and microbiologists have a large amount of experimental data and The purpose is described. Despite the success achieved with iodine, it was not initially put into practical use. Iodine has been found to have unsuitable properties, for example, iodine has an unpleasant odor. Things, etc. In addition, iodine stains the skin with a strong yellow-brown color, and in the presence of starch causes a blue stain on laundry, combines with iron and other metals, and the solution is unstable. , is irritating to animal tissues, and is toxic. Yoo in the past 100 years Nasty side effects, open wound pain and the possibility of algic reactions are associated with these unsuitable treatments. In order to avoid oxidation, a large number of iodine compounds (and and iodine preparations). In this regard, the ideal shape is De Fois ultimately succeeded. New products that have all or most of the benefits of iodophors New iodine complexes, such as povidone-iodine, are described in this application.

Details of killing of living cells by 12 molecules (or reaction products produced in aqueous solution) Although it is not known, iodine is thought to react in the following way: (1) bases that are part of certain amino acids (e.g. phosphorus 2, histidine, arginine) reacts with the functional N-H functional group of nucleotides (adenine, cytosine, and anine) to produce the corresponding N-iodo derivative. This reaction results in hydrogen bonding. Critical positions are blocked, resulting in lethal damage to the protein structure.

(2) Disulfide (-8-8 −) Bonding of protein chains by bridges (an important element in protein synthesis) That's how it gets lost.

(3) Reacts with the phenol group of the amino acid tyrosine to form mono- or short derivatives. generate. In this case, most of the iodine atoms in the ortho position are phenol Provides a form of steric hindrance to the hydrogen bond of the OH group.

(4) Reacts with the carbon-carbon double bond (C=C) of unsaturated fatty acids. This is a lipid resulting in changes in physical properties and membrane immobilization.

Iodine is consumed by protein substances, and its efficacy as a disinfectant is Decreased by the use of preservatives. This is due to the reducing action of the material being disinfected (sterilized). As a result, it converts iodine to non-sterilizing iodide. Therefore, the effective Not only is the storage of urin reduced, but also the balance of iodide is affected.

Together these effects reduce the proportion of free molecular iodine, an effective antimicrobial agent.

Iodine, which is widely used in human medicine, is a skin disinfectant (e.g. for skin preparation). Preparation for surgery, surgical disinfection of hands, disinfection of the entire genital area before delivery and skin cleaning before infection and blood transfusion. disinfection). Iodine preparations are also used for treatment, such as in the treatment of infected and burned skin. It is a strong stimulant. Iodine is used in medical devices, e.g. catguts, catheters. knives, blades, ampoules, plastic products, rubber products, brushes, etc. Also used to sterilize dosing vials and thermometers.

Adsorbs or binds to purified plant carbon as a blood contact agent with bactericidal and bacteriostatic properties. The use of oxidizing iodine, which contains ``compounds that combine molecules of oxidizing iodine,'' Does National Patent No. 4.898,572 mention an autotransfusion device? No explanation given.

Therefore, iodine can be used without the sometimes severe limitations inherent in its use. If you are infected, you may be infected with intestinal bacteria, viruses, bacterial viruses, and protozoan cysts. An excellent product with a wide range of actions, including almost all important microorganisms related to human health. It is a fast-acting disinfectant. Mycobacteria and Bacillus and Clostridium Spores of the genus Paramium can also be killed by iodine. Furthermore, iodine is deadly It also exhibits fungal and trichomocidal activity. Complete sterilization of various classes or microorganisms Different amounts of iodine are required to do this. However, within the same class, There is little published data on the bactericidal action of the base. In particular, spores and will Published sterilization times vary widely.

Many authors have looked at the literature and analyzed data to determine the effectiveness of iodine and other halogens. An attempt has been made to summarize the bactericidal properties of water. The most important conclusion is that = (1 ) Standard eradication of enteric bacteria, amoebic cysts and enteric viruses (i.e. 25 99.999% eradication in 10 minutes at °C) were 0.2, 3.5 and 14, respectively. ．． Requires 5 ppm residual work 2.

(2) On a weight basis, iodine is more complete in a wide range of water conditions than other halogens. It can inactivate all viruses.

(3) In the presence of organic and inorganic nitrogen substances, iodine reacts with side effects that hinder its bactericidal properties. It is the fungicide of choice because it does not cause any harmful effects.

(4) Iodine is used compared to chlorine and bromine to disinfect water and provide free residue. A minimum ■/L dosage is sufficient.

(5) I2 is 2 to 3 times as much as HOI as a herbicide and 6 times as a sporicidal agent, but Hot is at least 40 times more virucidal than I2. The behavior of this is On the one hand, the high diffusivity of molecular iodine through the cell wall of the envelope and spores, and on the other hand, the high diffusivity of HO This is explained by the high oxidizing power of I.

Along these lines, see Gottardi, W., “Iodine and Iodi ne Compounds in Disinfection, 5terili zation, and Preservation, “Th1rd Editi” on Block, Seymour S, Ed, Lea & Fedige r, Ph1ladel'phia, 1983.

The classic blue starch-iodine complex is well known and is a reaction between iodine and starch. is used as an indicator reaction in various types of iodine analysis.

It is also known that starch-iodine complexes have certain biocidal activities. However, extensive research on this activity has not been identified.

Starch-iodine bridge that absorbs moisture from wounds and provides a source of iodine Solid beads of beads are also well known, for example Holloway, G., Al. len, Jr.; Johansen, Kaj　H.; Barnes, Robert tW,;Pierce,Pierce,George E,,”Multice inter trial of cadexomer 1odine to tr eat venous 5tasis ulcer”, Western Jou rnal of Medicine, V, 151 nl, p35 (4), Ju ly.

See 1989. Cadexomer (for treatment of venous stasis ulcers mentioned above) Cadexome r) Iodine is a starch polymer with iodine bonded to the polymer. It is a bead. This type of polymeric beet kills bacteria with its iodine and is effective against open wounds and Used to treat venous stasis ulcers. Cadexomer iodine (trademark rlOD O3ORBJ, trademark rPER3TORP CARBOTECJ, Perstor p, Sweden) is dextrano? - similar to (dextranomer) This is a starch polymer bead with 0.0% iodine added to the polymer. 9% by weight combined It is. When fluid comes into contact with these beads, 1 g of cadexomer iodine An amount of approximately 6 ml of fluid and bacteria within the fluid are absorbed. It's connected Uron acts as a disinfectant in this environment.

Somewhat limited instructions have been published for the use of starch-iodine. example For example, Rocha patent No. 5U1204575 by Glushankof Sl, et al. starch, aluminum sulfate to make drinking water from released reservoirs in wilderness conditions. describes a composition for the purification and purification of water containing ionium, iodine and activated charcoal. Ru. Suspension of starch in potassium permanganate, followed by its potassium permanganate A starch-based disinfectant prepared by treatment with an iodine solution of Compositions are disclosed in Rocha Patent No. 979363 and by Tatarov PG, et al. No. 821207. The product of Glushankof et al. , containing or coated with iodine and aluminum sulfate It appears to be a solid bed of charcoal.

Contains slurried starch, iodine, potassium iodide and sodium bicarbonate. A protective coating for storage fruits and vegetables with It is described in the patents 5U959733 and 820928.

Disinfectant iodine-starch was developed by Mochnacz, W. et al. odstvo, 1980, 11. p, 37; Zh, Vet, 1981. A bstr, No. 38226 (bactericidal agent, disinfectant, antiseptic, fungicide, fungistatic agent) , amyliodine) as an antiviral and antiviral agent (C AS registration number + 7553-56-2).

John, ansson, J, A, O, CA: 92 (24) 203621a .

Australian patent AU506419.800103 describes dextrin oxy Describes the production of ethylated iodine phore disinfectants (CA: 86 (24) 17 7326nSUS4010259).

Alferov, V.V., et al., CA: 82 (9) 52180; Tr, U. zb, Naucho-ISSled, In5t, Vet, 1973. V, 21 iodinol sperm disinfectant and starch in ゜238-40 describes starch-iodine treated sperm and disinfection of sperm with starch-iodine complexes. Ru.

Also, in CA: 82 (7) 39339, “Iodine during artificial fertilization of animals” "Use of Le", A11ev, N, Ya; Rakhimov, ni, ni,; Alfer .

v, V, V, Pu1atov, T,, Tr, Uzb, Nauchno-Summer 5sl ed, In5t, Yet, 1973. Please refer to V21.241-3.

CA: 68 (10) 43119s, “Iodized High Polymers and Medical and Veterinary Their use in medicine”, Mokhnach, V. O., Botan.

1odonol, Mecl, Vet, 1967.5-20, polyvinyl alcohol Complexes of iodine with coals, starches and polymers are mentioned.

CA: 67 (14) 67490m, "Sterilizing water filter", Panzer.

Hans W, P; Brown, Jerry Hugh, French Patent 146 No. 2968 describes the purification of water by filtration and sterilization with iodine. water The use of soluble organic iodine compounds for the purification of is, of course, well known. More One of the most common water purification agents is tetraglycine hydroperiodide. , it is widely used because it is effective against Nardsia spp. Iodine is swimming pool It is also used to treat swimming pools, but it is used to irritate the eyes and stain pool walls yellow. undesirable.

People who handle blood and other invasively obtained body fluid samples are at risk of infection from those samples. be. People at risk should be treated by doctors, nurses, clinical technicians who collect their samples, Technicians who handle materials and use samples during analysis and testing; sample collection and testing; Persons handling equipment and devices; Persons witnessing the disposal of sample collection devices; Used devices; from those who received the equipment to those who ultimately put the equipment into a high temperature furnace.

The danger is that almost all experienced insurance management experts agree that Epstein bar virus (EBV) and/or cytomegalovirus (CMV) (the latter is probably a ubiquitous pathogenic virus). As big as that. Handles insurance administration workers and blood and fluid sampling equipment Other pathogenic viruses to which people are exposed include hepatitis, human immunodeficiency virus (HI) V) as well as many non-life-threatening viruses.

Other microorganisms that are often present in blood and blood products or fractions and pose a significant risk is the bacterium Yersinia enterocolitiC. a, which is an important contaminant responsible for acute bacterial gastroenteritis, Salm.

nella and Campylobacter. Y, enterocol It has been reported that there has been a significant increase in infections related to blood transfusions ( Tpple, et al., Transfusion 30.3. p, 207 (1990)) oY, enterocolitica and other relatively low-temperature plants. Bacteria that grow, such as 5 taphylococcus epidermid is and Logionella pneumophila are important in blood products. pose a threat.

Protein substances can destroy the bactericidal action of iodine and iodophors such as PVP-1. It is generally recognized that it can be destroyed. This element in the presence of large amounts of biological material It has been considered the main obstacle to the use of iodine and iodophors. albumin has extremely high performance in deactivating the bactericidal power of iodine and iodophors. It is recognized that For example, Buff et al. , and.

it M, L,, Winton J, R,, Appl, Environ Mic robiol, 57 (5), 1991.1379-1385) reported the results of using iodine to kill viruses, but the water contained no protein. Adding quality materials reduces the effectiveness of iodine. Bovine serum albumin is iodine depletion of the virus more effectively than with a single concentration of fetal bovine serum or liver sediment. Inhibits activation. Buff et al. also found that sodium thiosulfate effectively neutralized free iodine. It says what to do.

In addition to the risk of transmitting infectious diseases through blood and blood products, various stages of manufacturing and processing Bacterial growth in blood and blood products on the floor A pyrogenic factor is introduced, but the pyrogen is removed before the blood product is used therapeutically. There must be. Molecules such as povidone-I2 are used early in the processing of blood products. The introduction of urin significantly reduces or eliminates the pyrogen load of the final formulation or both.

Protozoa cause many diseases, some of which have medical and economical significance. It's important. Examples of such protozoa are the genus Plasmodium, e.g. Plasmodium vivax, Plasmodium vivax, Plasmodium ovale, Plasmodium vivax (these (which causes malaria), Trypanosoma (which causes Chagas disease), and Leishmania (which causes various types of leishmaniasis). Method of the invention are effective in eliminating these causative microorganisms in blood and blood products. .

Generally, the present invention relates to donated blood and products made from blood, tissues and fluids. Viruses, bacteria, Chlaminia sp., Rickettsia sp., Mycoplasty It can be applied to the loading of Suma genus and other potentially pathogenic microorganisms.

Among the important potential pathogens to which this invention applies are those found in animal body fluids and tissues. Cytomegalovirus (CMV), the most ubiquitous pathogenic microorganism I have lupes virus. Herpesviruses include herpes simplex, herpes zoster, and sexually transmitted diseases is extremely large, causing monocytosis, eye infections, birth defects and 2.3 tumors. represents a group of viruses. The present invention relates to human immunodeficiency virus (HIV). ) is also effective in preventing infection. Blood products are safer now than they were 10 years ago. With current knowledge and technology, it is difficult to completely eliminate HIV-contaminated blood and blood products. Total elimination is also impossible.

The term "blood" as used herein specifically refers to "whole blood" or a specific blood derivative. , for example, whole blood and blood, unless otherwise referred to as blood fractions, components or blood products. means fractions, components and products of blood (blood products). Hence the term "blood" blood at the point of collection or at all stages of processing, as described in the text. This applies to blood derivatives in Blood derivatives are blood cell concentrates (erythrocytes, blood platelets, etc.), blood components such as plasma and serum and albumin and blood factors refers to products prepared from blood such as blood and blood factors. Body tissue and body structure Cell means all tissues, organs or cells of an animal or the fluid containing tissues, organs or cells. Taste. Therefore, in a broad sense, the tissues and cells of the body are blood and blood cells. blood, but for the most part, for the sake of brevity, blood is a separate component of the present invention. Treat it as a request. Examples of body tissues and cells are semen, bone marrow, kidneys, heart valves, hips, and tendons. Includes bands, skin, allografts or xenografts and prosthetics. Tissue and cell culture Nutrient means the cells and tissues grown on rented land and the medium itself; Does not contain nutrients used for culture. An example of cultured tissue is skin tissue cultured for burn injuries. , cells and cell production regulated by standard biological and/or genetic engineering techniques. It is a thing. The experimental reagents and standards used herein refer to human or animal fluids, cells, or a reagent or standard made from or consisting of a tissue. Example of the product are blood cell panels, control serum and chemical controls used for reference blood. test Tissue and fluid samples taken include blood, urine, sputum, cell smears, and the like. for The term "donor" generally refers to the source of such samples. Although it does not apply to individuals, the terminology ``donor'' is used here in a more general sense to donate blood, tissue, Used to include the individual from whom the cell or fluid is obtained.

When tissue is transplanted onto rented land for the propagation of its cells, the process is called tissue culture. , the transplantation of individual cells onto borrowed land is called cell culture. However, both methods The term "tissue culture" is often used interchangeably unless the accompanying reason is particularly important. Called. The common usage of this term is used herein.

Tissue cultured cells are not only nutrient-rich, but also contain the amount and type of resident microorganisms that are tolerated. is extremely weak in many ways with strict requirements regarding highly susceptible to bacterial and/or viral infections.

In general, the precise specification of the exact materials needed to propagate a given cell line cell growth using serum-based or serum-containing compounds. A common practice is to add the necessary nutritional serum during growth. Orchids from adult animals Although serum is appropriate in some cases, safe propagation and high purity of many cell lines are critical. If necessary, fetal bovine serum (FBS) is required. However, F.B.S. Freedom from infectious agents is guaranteed even without the use of FBS produced in quantity Each lot of is contaminated with infectious bovine viral diarrhea (BVD) virus. stop Infectious bovine rhinotracheitis (IBR) and parainfluenza 3 (PI3) infections are extremely common. It is very common. At best, the pool of raw serum probably contains at least 104 Contains infectious BVD virus particles. Serum filtration removes infectious microorganisms in serum. Although a common step in unloading, significant amounts of serum components are Damaged by filtration when macromolecules are adsorbed to filters or sheared. There is a risk of falling. The shear of macromolecules during filtration is generally caused by tangential flow filtration. Occurs when turbulence occurs. Removal of BVD virus from serum by filtration It is currently extremely difficult to obtain reliable results.

The presence of indeterminate viruses in cell culture is well recognized, and culture is In the case of similar lineages, the production of human virus vaccines poses significant risks.

This is one of the reasons for the increasing use of bovine cell leases. However, these leased lands are It is not a state without virus contamination. Calf Kidney (CK) and Calf Teimaru (CT ) cells are often infected with non-cytopathic mucosal disease virus (MDV), Although the cysts appeared morphologically healthy, almost all were infected with BVD antiserum and rabbit anti-false serum. They showed fluorescence when combined.

The risk of infection from whole blood is well known. The biggest tragedy in medical care these days is that many believers infection, and hemophiliacs often require transfusions of HIV-containing blood.

The risk of infection from red blood cell concentrates is similar to the comparable risk associated with whole blood.

The teaching of the prior art is that both elemental (diatomic) and complex iodine are The fluid used for the reaction with urin, in the body, e.g. blood, packed or concentrated cells. This suggests that it is not an effective and reliable disinfectant.

Various drugs and blood processing methods are cited below. These are all well-known methods. As such, the steps in these methods are fully described in the literature. The following documents are Sources for general technical background and detailed references to the literature on specialized methods. °TECHNIC to provide L MANI:, jL o! lb+A merican Aoocia+ion ofRlood Banke++, 9+h Ed, (1985) :) ILA TEC) INIQUES FOR BLOOD BANKERR, ^me+1can 8++ ociation of Blood Bankui f1984):D +velopmenN in BiolBica 5tanр={di xition, Volt, 1-57.5. Ka+get, Baul: CLI NICAL 11tMUNOCHEMISTRY, The`+ne+1can Aociation lo “Cl1nical Chemiu+y, MEDI CINE, VolS, I-2,5 scientific `me"1ca n, N+v Yo+: Ca++ of ttu 5URGICAL PATI ENT, Voltl-2,5 scientific Amer Amamo ≠ Mr. AN+ v Yolk:CURRENT PROTOCOLS IN MOLECL:L ARBIOLOGY, G+e+ne Publishing@A++oeia 1! + and Withy-1nle+tcienc+, John Will Disclosure of iy & 5ont New York invention The present invention provides a method for disposing a liquid composition containing bacteria, viruses or other pathogenic organisms in the liquid phase. or react the liquid with solid starch-iodine filaments. Contact the liquid with starch-iodine by passing it through a filter or column. The present invention includes a method of treating a liquid composition in which the liquid composition is sterilized by sterilizing the liquid composition. starch Iodine is present in essentially all of the wide variety of starches available from a variety of sources. starch molecules, or polysaccharide components of starch and their derivatives, or starch It can be iodine complexed with a similar polysaccharide to which it binds. These formations Among these, amylose and aminopectin are the most widely used.

Then, if you need to ensure that all iodine is removed, dilute the solution with iodine. Come to PVP. Does the device have a third floor (layer) between the first and second floors? Subsaturated, preferably subtrace, amounts of iodine or another iodine such as cross-linked povidone Excess iodine can be removed by passing it in contact with albumin containing an iodine-absorbing material. can. Similarly, reducing sugars, such as ascorbate, sodium sulfite, etc. Agents can be added to remove the last traces of oxidizing iodine. reducing sugar, asco Rubic acid (vitamin C) and its salts, and sodium sulfite are physiologically acceptable. is a well-known and readily available reducing agent that can be used. However, physiologically tolerated Any reducing agent that can be used can be used.

The present invention is implemented in a method of sterilizing biological materials. The steps of the method include the components of the biological material. The biological material is treated with starch-iodine prior to separation of said biological material prior to separation of said components. The starch-iodine concentration is 0.1-5% by weight. before that A derivative of the material obtained from the process is prepared and optionally also treated with starch-iodine. to provide the derivative with 0.1-5% by weight of starch-iodine. In addition, the derivative by addition of a physiologically acceptable reducing agent or by contacting with cross-linked PVP. Reduce or eliminate residual iodine. These methods include, for example, whole blood, plasma, tissue , culture nutrients, sperm cells, packed red blood cells and cells with liquid or cells. Applicable to biological fluids that do not contain water.

The present invention also provides a step of collecting plasma from a donor, adding 0.1 to 5% by weight to the plasma. Sufficient starch-iodine is mixed to obtain a starch-iodine concentration and the plasma and said starch-iodine for at least 2 minutes to remove infectious and disease-causing substances in the plasma. inactivate or kill the pathogenic microorganisms and, optionally, process the resulting mixture. Contact with cross-linked PVP or albumin or add physiologically acceptable reducing agent Plasma from which oxidized iodine has been removed from the mixture is injected into the patient to be treated. a method of treating a patient with plasma, the method comprising the step of: administering plasma to a patient;

The present invention also provides a liquid treatment device for killing microorganisms. The device is An upper reservoir section that holds the liquid during use, a lower reservoir section that collects the liquid, and fine particles. in the form of a liquid container having a structure defining a first bed and a second bed of material; One bed consists of substantially insoluble starch-iodine and the second bed consists of substantially insoluble P. These first and second beds, consisting of VP or albumin, pass the liquid through each bed. The structure is such that it passes through in contact with the surface of the particles being formed. The first floor is from the bridge best mode of implementation The third layer then consists of a substantially insoluble PV filtered hydrogen oxide particulate material. Applicable The device may include a layer of particulate material comprising an iodine reducing agent. to the liquid reservoir One first bed may be provided with a layer of soluble denoprone-iodine. 1st floor and All or some of these layers can be provided after the second bed.

One method of sterilizing tissue for transplantation according to the present invention is to sterilize tissue for transplantation into a patient. A tissue that is acceptable for maintained for a period sufficient to extract at least half of the unbound water naturally present in the tissue Then, a starch-iodine solution was introduced into the vacuum chamber to replace the vacuum extracted water. It consists of reconstituting the solution into the tissue. Optionally, iodine can be added to tissues, e.g. For example, cleaning with a reducing agent such as ascorbic acid or its salts or sodium sulfite. or removed by reconfiguration.

Brief description of the drawing FIG. 1 shows that a liquid material according to the invention is prepared from starch-iodine and (a) iodine adsorbent. contact with one or both of the iodine reducing agent and/or (b) an iodine reducing agent; and In particular, it shows an apparatus for providing other materials for processing biological materials.

FIG. 2 is an enlarged illustration of an apparatus for processing solid tissue samples.

Starch-iodine can be produced in any of a number of ways. Very small amount Substantially pure densities that contain other biological materials or are essentially free of contaminants. Pun is commercially available. Included in the term "starch" used in the general sense of Amylose and amylopectin, which are components of starch, are also available in high purity. The drug is used to treat disorders in which patients require transport of blood cells. At the same time, again Later, the sample is added in excess of the amount needed to kill or inactivate all microorganisms. Plump-iodine is added. Starch-iodine is, for example, 0.01 to 1 0% by weight, preferably 0.1-5% by weight. Starch-iodine is used in medicine Prepared blood cells or plasma or other biological material that is sufficient to kill microorganisms. , for a period of time that does not denature or damage the biological material, i.e. for at least 1/2 minute. Make it happen. Generally, contact for one hour or less is desirable. Therefore, the contact time is 1/2~ The resulting mixture for one hour is then treated with cross-linked PVP, or albumin-like Iodine is removed by contacting with an iodine absorber. If necessary, then absorb the reducing agent. Add enough iodine to reduce all remaining iodine. Contact with iodine absorbers The material to be treated is coated with a layer of substantially solid, insoluble albumin, i.e., a bed or filter. Preferably, this is done by passing it through a filter. The second process may be performed if necessary. Do this to ensure total sterilization. Similarly, the product or the treated primary product A process similar to the second process is performed regarding quality.

Similarly, the addition of a reducing agent to a material undergoing treatment transforms that material into a material with active reducing sites. The liquid material is passed through a layer of substantially insoluble material that is in equilibrium with the liquid material being treated or treated. partially dissolved in or made readily available to the liquid reducing portion. It is done by. For example, a bed of beads or fibers exposing reducing sugar moieties on the surface Convenient to use.

FIG. 1 shows the liquid material according to the invention as starch-iodine and (a) iodine-absorbing material. and/or (b) contacting with the iodine-reducing material and providing other materials. In particular, it refers to a device for processing biological fluids. The device shown schematically can be of various constructions. As far as the invention is concerned, the only important structure is the arrangement of the layers. be.

Apparatus 10 can be viewed as a filtration funnel or column. person skilled in the art As I understand, the difference between a filter and a column is that they both filter the composition and It is meaningless in that it brings the body into contact with a solid material. The filter is definitely made of material. Only a portion must be removed. For example, filters and columns can be used to allows small particles to pass through but retains large cells, or only liquids and very small particles pass. The device 10 includes a cylinder partially defining a reservoir portion 12. Consisting of 12 parts. The reservoir can be made as large or as small as required. can. The illustrated construction of the device 10 includes a second small cylindrical tube portion 14; A conical transition zone connecting two cylindrical parts is conventional in the manufacture of funnels. Consists of 16 parts. However, if the device has a reservoir or funnel portion of a particular size, Otherwise, it is meaningless to specify the shape.

Device 10 defines a first layer 20 and a second layer. The first layer 2o is substantially insoluble It consists of starch-iodine. This layer is described as consisting of particulate material.

an underlying layer or another support (e.g., fibers or particles bonded to or disposed within the layer) solid insoluble starch in the form of a layer (or bed) of particles supported directly by a support particles of starch-iodine, such as cross-linked starch-iodine, are contemplated. first layer 2 0 may contain some insoluble starch-iodine. bonded by heat and pressure Also within the scope of this invention are frits made of particles that are Starch-iodine is albumin The albumin layer can be generated in situ by iodination of the albumin layer, or the albumin layer can be generated by presynthesized densities. It can also be made from pun-iodine.

The second layer 22 is downstream of the first layer 20, i.e. the liquid to be treated is in the first layer After passing through the second layer. The second layer is an insoluble iodine absorber, e.g. Kepovidone, insolubilized albumin, or an iodine reducing agent, or a mixture of both, or It consists of a multi-sublayer structure of an iodine absorber sublayer and an iodine reducing agent. The second layer is Free-standing frits or other structures or provided by supports or other layers Can be done. The essential function of the device 10 is to collect the liquid to be treated together with cells and other particles. first pass through the starch-iodine layer, with or without, and then absorb the liquid. Contact with a collecting agent to remove iodine and/or contact with a reducing agent to reduce iodine. It is to restore it. Therefore, those layers provide adequate contact between the liquid and each layer or bed. Very deep or very thin, adjacent to each other or spaced apart because they need to touch each other has.

The device 10 is suitable for treating liquids to kill microorganisms therein. A concise model of Figure 1. In the example shown formally, the liquid container defined by the entire device holds the liquid to be processed. an upper part or liquid inlet reservoir section. This is a very small reservoir or Comes with a large reservoir. This reservoir is placed at a very long distance from the floor or layer. This is generally not convenient. The device 10 has a lower part for recovering the treated liquid. Equipped with a purification or recovery section. Between these parts there are a first bed and a second bed of particulate material. defined by a suitable structure. The first bed or layer is substantially insoluble starch-iodine. Consists of urin. The second bed is substantially insoluble albumin or other iodine absorbent; and/or an iodine reducing agent. Those beds are the surface of the particles that form each bed. Structured to allow liquid to pass through in close contact with a surface. The most common iodine absorption The agent is a cross-linked pohidone.

Preferably, the device 10 further comprises a third layer 24 between the first and second layers.

The third layer consists of substantially insoluble povidone hydrogen peroxide particulate material. third layer Its presence scavenges and regenerates iodine, significantly increasing the bactericidal activity of iodine.

A fourth layer 26 of particulate iodine reducing agent is in the form of a sublayer within the second layer 22. A second layer is provided downstream of the second layer to reduce residual iodine from I2 to iodide or If reduction occurs early on, add a safety step to ensure all oxidizable iodine is removed. Give back.

In the present application, soluble starch-iodine is added on top of the first layer 20 in the liquid reservoir. A fifth layer 28 of starch-iodine is provided to dissolve a substantial amount of starch-iodine in the liquid. and provides a large reservoir of more available iodine in the liquid.

The first and second layers are essential for the integrity and proper functioning of the device; After these layers, several further layers or additives are applied as they are the first and second layers. It can be provided as long as it does not interfere with the combination function of the two layers.

The above layers are (not necessarily (although not) all are supported. Floor thickness can be the same or significantly different . It is easy to calculate the contact time in the column and provide a suitable bed of material to the column. It's simple.

The floor is made of carriers such as frosted glass, charcoal, ion exchange resins, cellulose derivatives, etc. It consists of active materials such as starch-iodine, reducing agents, etc. attached to the particles. fine particles The child material essentially consists of particles with a diameter of 10 to 100 μ, but with a suitable flow rate. Sizes that provide close contact are available. human or mammal For the production of biological materials for transfusion or for the production of transplanted or transfused biological materials between - The use of iodine and a physiologically acceptable reducing agent is part of the invention. Transfer ( Blood transfusion) material or transplanted tissue: 0.01 to 10% by weight, preferably 0.1 to 5% by weight After sterilization with a starch-iodine solution with a concentration of Original. The liquid material is processed in any suitable manner as described above. Solid tissue samples are simply Process by injection or vacuum injection.

FIG. 2 is an enlarged schematic diagram of an apparatus for processing solid tissue samples. The device can withstand vacuum forces. It consists of a chamber system 100 that can be moved. Cylinder 1 shown merely in exemplary form 02 is an end cover which is closed at each end with end covers 104 and 106. Bar 106 is removable to provide access to the interior of the chamber. For example, Portion 108 of cover 106 slips into cylinder 102 and attaches an O-ring, etc. Can be sealed using a vacuum tight seal. Vacuum line 110 causes a vacuum to be applied to the chamber via valve 112 and line 114. valve 122 and An input line 120 connected to line 124 facilitates the introduction of liquid into the chamber. let A platform secured to end cover 106 supports tissue sample 130. I can do it. Place the tissue sample in the chamber, evacuate the chamber, introduce liquid, and The water in the sample is substantially replaced by the introduced liquid.

Tissues for transplantation are processed to kill microorganisms, i.e., to maintain a physiological Place the tissue acceptable to the tissue in a vacuum chamber and evacuate the chamber to remove the tissue present in the tissue. Maintain the vacuum long enough to extract at least half of the unbound water that was Starch-iodine was introduced into the vacuum chamber and the solution was added to the tissue instead of the vacuum-extracted water. Sterilize by reconstituting the liquid. The tissue thus treated is then physiologically acceptable. immerse in a solution of iodine reducing agent. Alternatively, evacuate the chamber again and remove the tissue. A starch-iodine solution is extracted from the starch, and a solution of a physiologically acceptable iodine reducing agent is added to the It is introduced into the empty space and saturates the tissue to reduce residual iodine.

As a method for sterilizing blood derivatives, the present invention provides a method for sterilizing blood by starch-yolk prior to separation of blood components. Treated with urin to add 0.01 to 10% by weight, preferably 0.01 to 10% by weight of blood. 1-5% by weight ALB-1 of 100% is provided, a blood derivative is prepared from the process, and the derivative is denatured. Treatment with pun-iodine gives the derivative 0.01 to 10% by weight, preferably 0.01 to 10% by weight. 1～ 5% by weight of iodine followed by addition or bridging of a physiologically acceptable reducing agent. The derivative is treated to reduce or remove residual iodine by contacting with PVP. consists of doing.

Infectious bacterial microorganisms are removed from the donor and placed in tissues and tissues before being implanted into the recipient individual. Starch-iodine is thought to be inert when used in a solution sprayed into the organ. . The spray solution is 0.01 to 10% by weight, preferably 0.01% to 10% by weight. 1-5% by weight (10 0-500 ppm I2), optimally at a concentration of 0.25-2% by weight of molecular iodine compounds. Contains. After a certain period of time, most of the unreacted molecular iodine compounds are washed away and the remaining Any molecular iodine compound that is distilled is removed by e.g. the ascorbate or other reducing agent. is absorbed into proteins or converted to inert iodide using Therefore, it does not significantly impede acceptance by recipient individuals.

When the material to be purified is a liquid or cells contained in a liquid, the above treatment involves A bed of starch-iodine solid particles of appropriate size (e.g. solids on a porous support) or through a liquid and/or fine particles in a liquid. carried out by contacting the cells with particles or starch-iodine membranes or surfaces. be able to. When particle beds are used in cell-containing liquids, the particles can trap or trap cells. must be large enough to allow intimate contact without binding. the The liquid then comes into contact with the solid starch-iodine phase and passes through the layer to maintain complete bactericidal action. It is proved. The liquid then passes through or comes into intimate contact with the cross-linked PVP. absorbs molecular iodine from the liquid. Finally, if necessary, ascorbate Add a reducing agent such as

In the practice of this aspect of the invention, the liquid or cell-containing liquid is solid denopone-iodine. bring into contact with. This converts the liquid into a settling bed of starch-iodine particles in most cases. This can be done most efficiently by leading to a fluidized or packed bed; The method is generally not suitable for treating cell-containing liquids. The cell-containing liquid is stored in a liquid container. Treated by mixing particles or passing a liquid over the surface of the starch-iodine material. Understand. Starch-iodine is washed and its iodine content is regenerated during use. be able to.

Generally reducing sugars (or mixtures of reducing sugars), ascorbic acid, ascorbate, A solution of a reducing agent such as a sulfite (e.g. sodium sulfite), etc. The concentration is 0.001-1%) or as appropriate, unless otherwise specified. It is rare.

Iodine is extracted by solvent extraction with solvents that are inert to blood and biological materials. It can also remove urin. N-hebutane is a good solvent for iodine and is Low exposure has little effect on blood and blood cells. cottonseed oil, corn Oils, etc. are generally biologically inert to blood and blood cells and are suitable for iodine. It is a solvent that The solvent extraction involves thoroughly mixing blood and solvent in a suitable container, Decant the hydrophobic phase from the top and blood or biological fluid from the bottom. be collected. The method is safe, free of pathogenic microorganisms, and contains no additives other than iodine. We provide high quality whole blood for transfusion that does not contain added chemicals.

Industrial applicability The present invention can be used in medicine, pharmacy and veterinary medicine.

Continuation of front page (51) Int, C1,5 identification symbol Internal office reference number C02F 1150 5 20 Z 7158-4D532 H7158-4D I

Claims (19)

[Claims] 1. In plasma or other carrier liquids for the treatment of disabled patients whose patients require transfusion of blood cells. A drug consisting of blood cells of 0.01 to 10% by weight of the drug. Pun-iodine in excess of the amount necessary to kill or inactivate all microorganisms. Starch used in the production of the drug, characterized in that it is added to the drug. Iodine. 2. Sterilized with starch-iodine with a concentration of 0.01 to 10% by weight and optionally After that, a reducing agent is added to reduce residual iodine, and biological materials for transplantation or blood transfusion are used in humans. or a device used in the manufacture of biological material for transfusion from an animal to another human or animal. Pumpkin-iodine and a physiologically acceptable reducing agent. 3. (a) Treating the biological material with starch-iodine before separating its components; and adding 0.01 to 10% by weight of starch-iodine to the biological material before separation of the components. Step of providing concentration; (b) preparing a derivative of the material obtained in step (a); (c) preparing a derivative of the material obtained in step (a); Starch-iodine treatment to give the derivative 0.01-10% by weight starch-iodine and optionally, (d) providing the residual by reduction, absorption or solvent extraction. A method for extinguishing biological materials, comprising the step of removing iodine. 4. 4. The method of claim 3, wherein the biological material is whole blood. 5. 4. The method according to claim 3, wherein the biological material is plasma. 6. 4. The method of claim 3, wherein the biological material is body tissue. 7. 4. The method of claim 3, wherein the biological material is tissue culture nutrients. 8. 4. The method according to claim 3, wherein the red blood cells are filled with biological material. 9. 4. The method of claim 3, wherein the biological material is a liquid containing cells. 10. From the process of collecting plasma from a donor and injecting the plasma into the patient being treated, in the treatment of patients by giving the plasma a concentration of 0.01 to 10% by weight. the plasma and starch-iodine to at least Contact for 1/2 minute to inactivate or kill infectious and pathogenic microorganisms in plasma. Optionally, the resulting mixture may then be coated with cross-linked PVP, solid starch, or sufficient contact with albumin or addition of a physiologically acceptable reducing agent. further comprising the step of removing biolethal iodine from the mixture by Characteristic patient plasma therapy. 11. An upper reservoir part that holds a liquid that kills microorganisms during use, and a lower part that collects the liquid. A liquid container having a structure defining a purification section and a first bed and a second bed of particulate matter. The first bed consists essentially of insoluble starch-iodine and the second bed consists essentially of insoluble starch-iodine. the first bed and the second bed are substantially insoluble in PVP or albumin; passing the fluid through or contacting the surfaces of the particles forming a bed; A liquid processing device for killing microorganisms, characterized by having a structure. 12. Claims characterized in that the substantially insoluble PVP is cross-linked PVP 12. The apparatus according to paragraph 11. 13. Further, another layer is provided between the first layer and the second layer, and the another layer is substantially Claim 11, characterized in that it is made of insoluble PVP hydrogen peroxide particulate material. Apparatus described in section. 14. A further particulate material layer is provided below the second layer, the further layer containing iodine. 12. The device according to claim 11, characterized in that it comprises a reducing agent. 15. A further soluble starch-iodine layer is provided on the first layer of the liquid reservoir. 12. A device according to claim 11, characterized in that the device includes: 16. The insoluble starch-iodine particles of the first layer are physically removed by the material layer of the fiber chamber. 12. The device of claim 11, wherein the device is 17. (a) Placing physiologically acceptable tissue in a vacuum chamber for transplantation into a patient step; (b) evacuating the vacuum chamber and applying the vacuum in the vacuum chamber to the non-condensate originally present in the tissue; maintaining the combined water for a period long enough to extract at least half of the combined water; and (c) Vacuum extraction is performed by introducing an albumin-iodine solution into the vacuum chamber. The method further comprises a step of reconstituting the solution in the tissue instead of water. Sterilization of tissue for transplantation. 18. Furthermore, the treated tissue is placed in a solution of a physiologically acceptable iodine reducing agent. 18. The method according to claim 17, comprising the step of dipping. 19. After the step (c), further (d) evacuate the vacuum chamber to remove starch-iodine. extracting the solution and (ε) a physiologically acceptable iodine reducing agent in said vacuum chamber. A technique to reduce residual iodine by introducing solution into the tissue and saturating the tissue with the solution. 18. A method according to claim 17, characterized in that the method comprises: