TW562678B - Physiologically acceptable aqueous solutions and methods for their use - Google Patents

Abstract

Physiologically acceptable aqueous solutions and methods for their use are provided. The subject solutions comprise: electrolytes; a dymamic buffering system and an oncotic agent; and do not comprise a conventional biological buffer. The subject solutions find use in a variety of applications, particularly in those applications where at least a portion of a host's blood volume is replaced with a blood substitute.

Description

562678 A7 B7 V. Description of the invention 纟) Related application for reference This application is date of application July 2, 1997, application number 0/8 / 8 8 6, 9 2 1 (lawyer reference number 06537 / 0 1 2002 continuation) part of the continuous application; it is the application date of January 9, 1997, application serial number 08/780, 974 part of the serial application; it is the application serial number 08 / 364,699; part of the serial application with application serial number 08 / 253,384; it is part of the serial application with application serial number 08 / 071,533; the full text of the disclosure is incorporated herein by reference.刖 g TECHNICAL FIELD The technical field of the present invention is a substitute plasma solution. Background of the Invention Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the notes on the back before filling out this page) It is known that physiologically acceptable solutions have many different medical, biomedical, and other related fields. use. For example, physiologically acceptable solutions can be used as surrogate blood prizes in surgical applications where the amount of plasma replacement is very high. These applications include managing blood loss during surgery or trauma, or when it is necessary to maintain tissues, organs, groups of organs, or individuals at a low temperature or in a frozen state. These applications also include the use of a patient's blood flowing through an extracorporeal device, such as a cardiopulmonary bypass machine. Since the patient's circulatory system creates excess circulation space after installation of such a device, it must be compatible with The volume expansion of the substitute blood (ie, blood volume expander) of this paper is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) -4-562678 A7 B7 V. Description of the invention & . Physiologically acceptable solutions suitable for use as plasma dilators / substitutes must be completely miscible with the blood and have no incompatibilities in their components, such as: formation of deposits in small blood vessels that significantly block blood flow, The degree of destruction of the constituent elements is unacceptable (eg, cells, any area of the body), carrying reagents or generating water, destroying cells and tissues in the body, causing an ionic or molecular imbalance, or causing harmful physiological activities, such as : Improper acceleration or inhibition of heartbeat, nerve conduction or muscle contraction, etc. The first alternative plasma solution used in the past was derived from mammalian blood. Although this solution is quite successful, because it is derived from natural blood, it may contain many pathogenic sources, such as: viral pathogens (such as) Η Hepatitis IV, B and other pathogens (such as: Cruetzfeldt- Jakob) disease-related protein infectin). Therefore, substitute blood and substitute plasma solutions derived from natural blood have their disadvantages. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Therefore, a variety of artificial blood and substitute plasma solutions prepared from non-blood components are produced by bursts. Although the use of synthetic plasma-based solutions is increasing in many ways, none has proven to be suitable for all possible applications. There is therefore a need to continue to develop new physiologically acceptable aqueous solutions as appropriate substitute plasma. In particular, a solution has been developed that is suitable for cryogenic surgery applications, such as cardiac surgery. It is also necessary to develop a solution that can be autoclaved. Related Literature-5- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 562678 A7 B7 V. Description of the invention Please read the precautions on the back 1¾ before filling in the various physiologically acceptable solutions on this page ( In particular, substitute blood solutions) and methods have been used in US Patent Nos .. RE 3 4,0 7 7; 3,937,821; 4,00,4〇1; 4,061,736; 4'216,2 〇5; 4,663,166; 4,812,310; 4,908,35; 34,923,442; 4,927,80; 5'〇82,831; 5,084,377; 5 '130, 23〇; 5,171,526; 5,21〇, 〇83; 5,274,001; 5,374,624; and 5,407,428. Other documents describing physiologically acceptable solutions (including blood substitute solutions) printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs include: Bishop et al., Transplantation (1978) 25 · 235-239; Messmer et al., Characteristics, Effect and Side- Effect of plasma Substitutes, pp 51-70; Rosenberg, Proc. 12th Congr. Int. Soc. Blood Transf. (1969); Spahn, Anesth. Analg. (1994) 78: 1000-1021; Biomedical Advances In Agmg (Plenum Press) Chapter 19; Wagner et al., Clin. Pharm. (1 993) 1 2: 3 3 5; ATCC Catalogue of Bacteria & Bacteriophages (1 992) p 4 8 6; and 06-3 874- R8-Rev. May (1 987) Abbott Laboratories, North Chicago, IL 60064, USA. Other literature describing the many applications of this solution, including cryogenic applications, include: Bailes et al., Cryobiology (1990) 27 · 615- 696 (ρρ 622-623); Belzer et al., Transplantation (1985) 39: 118-121; This paper size applies to China National Standard (CNS) A4 (210 乂 297 mm) -6-562678 A7 B7 V. Invention Description 4)

Collins, Transplantation Proceedings (1977) 9.1529; Fischer et al., Transplantation (1 9 85) 3 9: 1 22; Kallerhoff et al.,

Transplantation (1 985) 39: 485; Leavitt et al., FASB J. (1 990) 4: A963; Ross et al., Transplantation (1 976) 2 1: 498; Segall et al. FASB J. (1991) 5: A396; Smith, Proc. Royal Soc. (1 956) 1 45.395; Waitz et al., FASB J. (1991) 5.

Lehninger, Biochemistry (2nd Ed., 1 975), pp 829ff has written book reviews on the composition of blood. SUMMARY OF THE INVENTION The present invention provides physiologically acceptable aqueous solutions and uses thereof. Title The solution contains: electrolyte; dynamic buffer system and swelling agent; its solution does not contain traditional biological buffers. This solution can be used in a variety of applications, especially for applications in which at least a portion of the host's blood volume is replaced with a substitute blood solution. Description of Specific Embodiments Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economics The present invention provides physiologically acceptable aqueous solutions and uses thereof. Title Solution contains: electrolyte; power buffer system and swelling agent; this solution optionally further contains at least one sugar and bicarbonate, and at least one of magnesium or sugar. This solution can be used in a variety of applications, especially for applications in which at least a portion of the host's blood is replaced with a substitute blood solution. In the detailed description of the present invention, the aqueous solution itself will be explained in detail before discussing various representative applications that can be applied to the solution. This paper size applies the Chinese National Standard (CNS) A4 specification (210 X297 mm) I-562678 A7 B7 V. Description of the invention Before further explaining the main invention, it should be noted that the invention is not limited to the following specific embodiments of the invention, because Certain specific embodiments may be modified and established, and are still included in the scope of the attached patent application. Also, the terminology used herein is for the purpose of describing particular embodiments and is not intended to limit the scope of the invention. Therefore, the scope of the present invention is based on the scope of the accompanying patent application. Unless otherwise specified, the specifications used in this document and the scope of the attached patent application, the singular `` a '', `` a '' and `` this '' include the plural reference meaning. Unless otherwise specified, all technical terms and scientific names used in this invention have the same meaning as those who are familiar with the technology to which the invention belongs. The aqueous solution heading this invention is a physiologically acceptable aqueous solution, meaning that the solution can be introduced into the blood circulation of the host without causing a toxic reaction. The p Η of the solution is between about 4 and 10, usually between about 4.5 and 9 and more usually between about 5 and 8.5. The solution contains several electrolytes, including: sodium, chloride, potassium, and # 5 ions, and selected magnesium ions. The concentration of sodium ions in the solution is between about 70 and 16O ', usually between about 110 and 150, and in some embodiments between 130 and 15 OmM. The chloride ion concentration in the solution is between about 70 and 170, usually between about 80 and 160, more usually between about 100 and 135 'and in some embodiments between about 1 1 0 to 125 m. Potassium ion concentration is in the physiological to subphysiological range, this' > physiological range "j means between about 3.5 to 5, usually between about 4 to 5 m Μ, and the subphysiological range This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) -8. Please read the notes on the back 1. Write to the Central Consumers Bureau of the Ministry of Economic Affairs, printed by the Consumer Cooperatives 562678 A7 _______B7__ 5. Description of the invention 纟) 〃 意Means between about 0 and 3.5, usually between about 2 and 3 mM, in many embodiments of the invention, the number of potassium ions is between about 1 and 5, usually between about 2 and 3 mM, In some embodiments, the amount of potassium ions may be higher than 5 mM and may be as high as about 5.5 mM or higher, but usually does not exceed about 5.5 mM. The solution also contains calcium ions, and the amount is between about 0.5 To 6 · 0 m Μ, in some embodiments between about 0.5 · 4 to 0, usually between about 2 · 0 to 2 · 5 mM, but in some embodiments between about 4 · 0 to 6 · 0, usually between about 4.5 to 6.0 m Μ. Furthermore, this solution may optionally contain magnesium. If magnesium ions At that time, its concentration is between about 0 to 10 mM, usually between about 0.3 to 3.0 ′ and more usually between about 0.3 to 45 mM. In certain embodiments, the title solution is The content of potassium and magnesium is increased. The content increase means that the amount of potassium ion concentration is between about 50 mM to 3.0M, usually between about 200mM to 2.5M, and more usually between about 1.0 to 2.0. Μ, magnesium ion concentration is between about 40 m Μ and 1.0 M, usually between about 1 m and 9 m and more usually between about 3 m and 7 m. (Please read the precautions on the back before filling this page) At the same time, it is discussed that there is an increase in the content of potassium and magnesium electrolytes in the solution (so-called, pressurized solution). An increase in content means that the number of potassium ions is between about 5 0mM to 3.0M, usually between about 200mM to 2.5M, and more usually between about 1.0 to 2.5M, and its magnesium ion concentration is between about 40m to 1.0M, usually Between about 1 to 9 M, and more usually between about 3 to 7 M. These solutions may further contain (in some specific embodiments) bicarbonate In which the bicarbonate presents—this paper size applies to the Chinese National Standard (CNS) A4 specification (210 × 297 mm) ~ " Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 562678 A7 _____B7 V. Description of the invention f ~ Quantity introduction At about 0.1 to 40 mM ', it is usually between about 0.5 to 30 mM and more usually between about 1 to 10 mM. The solution also contains a dynamic buffer system. The dynamic buffer system here means that the P Η 値 of the solution is maintained within a certain range in a living environment with a combination of one or more reagents. The composition of the preferred power buffer system reagent should be a biological component that normally maintains a living organism. The idea of such a dynamic buffer system is based on the researcher's discovery that compounds that are not buffering in nature in the biological scope (such as lactate, acetate or gluconate that can be metabolized in vivo) can be combined with other solutions The components react to maintain proper animal biology, even at low temperatures and near bloodless conditions. The power buffer system of the present invention relies on combining with oxygen and removing carbon dioxide (C02). The dynamic buffer system of the present invention does not have or does not have the capacity of a buffer solution outside the biological system, which means that the dynamic buffer solution is only in the living body, but cannot maintain the biological ρ Η range in a non-cellular environment. . The key component of the power buffer system of the present invention is a carboxylic acid, its salts or esters. Carboxylic acids, their salts or esters refer to compounds whose structural formula is generally represented by RC 0 OX, where R is alkyl, alkenyl or aryl, branched or linear, and contains 1 to 30 This carbon can be substituted, and one of its carbon chains should preferably consist of the following carbon chains: lactate, acetate, gluconate, citrate, pyruvate or other biological metabolites; and X is Hydrogen or sodium or other biocompatible, ionic substituents that can associate at the oxygen site. Depending on the need, this power buffer system can also contain a source of bicarbonate, usually sodium bicarbonate (NaHC03). When it exists, it applies the Chinese National Standard (cns) A4 specification (2l0X 297mm) ~ 7ι〇. ~ ^ (Please read the precautions on the back before filling this page) • Binding · Order 562678 A7 _ B7 5 、 Explanation of the invention a) The concentration of Na HC〇3 is between about · 1 m Μ to 40 m Μ, usually between about

• 5 mM to 30 mM, and more usually between about 1 mM to 10 mM. The solutions of the present invention do not include traditional biological buffers. '' Traditional buffer solution 〃 means a compound that maintains p Η in a specific range in solution, in vitro. '' Traditional biological buffer 〃 means a compound that maintains P 在 in the biological range 7-8 in a non-cellular system. Examples of traditional biological buffers include N-2-hydroxyethylhexahydropyridine-N > -2 monohydroxypropanesulfonic acid (Η EPES), 3-(N-morpholinyl) propanesulfonic acid ( MOPS), 2-([2-Hydroxy-1,1-bis (hydroxymethyl) ethyl] amino) ethane sulfonic acid (TES), 3- [N-Shen (hydroxy-methyl) ethylamine ] -2-Hydroxyethyl] -1 hexahydropyrrolpropanesulfonic acid (EPPS), ginseng [hydroxymethyl] monoamine methane (THAM), and ginseng [hydroxymethyl] methylamine methane (TRIS). Traditional biological buffers have ρ K 値 in the physiological range and their functions are most efficient in this range. Therefore, the functions of these buffers are not affected by general biological functions and are the strongest in non-cellular systems. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) The solution of the present invention does not contain traditional biological buffers, which has several medical advantages. For example, the concentration of traditional biological buffers required to maintain a living body ρ 比 is lower than that of traditional biological buffers. At the same time, traditional biological buffers may also cause toxicity problems. In addition, non-biological buffers allow the solution to be finally heat sterilized. Generally, the medical solution is preferably one which can be sterilized by heating before being used by a patient. The so-called, and finally, can be heat sterilized (or heat sterilized) represents a method of heating the solution at 120 ° C under high pressure. This paper applies the Chinese National Standard (CNS) A4 specification (210X297 mm). ^ Ministry of Economy Printed by the Consumer Standards Cooperative of the Central Bureau of Standards 562678 A7 _B7_____ V. Description of Invention 6) A process of about 15 minutes, 'that is, maintaining a period of time sufficient to kill all or substantially all bacteria under high temperature and high pressure' and make the solution All or substantially all viruses are inactive. This procedure is generally performed in an autoclave, commonly known as 'high temperature autoclaving.' The purpose of heat sterilization is to kill all infection vectors that may be present in the solution. Generally, the infection vector can withstand temperatures up to 100 ° C. The art world believes that heating the solution at 120 ° C for about 15 minutes under high pressure is sufficient to ensure sterilization. The solution also contains a swelling agent. This swelling agent contains molecules large enough to pass through window-shaped capillaries and enter the space between tissues in the body to avoid loss in circulation. One example of such a swelling agent is a plasma expander. The compounds that may be used as swelling agents in the title of the present invention may be natural or artificially synthesized, usually polymeric compositions, having an average molecular weight of at least about 40,000, usually at least about 100,000, and more usually at least about 2000, 0 0 0, wherein the swelling agent which can be used has a molecular weight of at least 3 0,0 0 0. Examples of swelling agents suitable for use in the solution of the present invention include protein compounds, such as: proteins (such as human blood proteases and crosslinked or high molecular weight heme), polysaccharides (such as polydextrose polymers, ); Organic polymers, such as: PVP, peg, etc .; and the like; Among them, non-antigenic polysaccharides are preferred. Polysaccharides suitable as swelling agents in the title solution include: hydroxyethyl starch, hydroxymethyl avar (1-4) or (1-6) polymers, D-glucose polymers, such as polydextrose avar ( 1-6) Bonding, cyclodextrin, hydroxypropyl starch, hydroxyacetyl starch, and the like. Certain specific examples of the title of the invention are specifically directed to hydroxyethyl powder. This paper size applies Chinese National Standard (CNS) A4 specifications (210〆297 mm) (Please read the precautions on the back before filling out this page) • Binding · Order-12- 562678 A7 B7 V. Description of Invention Read the note and then fill in the page. The average molecular weight of the hydroxyethyl starch suitable for the title of the present invention may be between 10'000d and 1,000,000d or higher, where the molecular weight is usually between about 40, 0000d to 1,000,000d 'is usually between about 100,000 to 9,000, and more usually between about 20,000 to 8,000. , 〇〇〇. The average molecular weight of the hydroxyethyl starch swelling agent in the preferred composition is preferably between about 50'000d to 1'000'd00'd, usually between 100,000 to 900'd, 000, and more usually between about 200,000 to 800,000. The degree of substitution is between about 4 and 10, the degree of substitution in some specific embodiments ranges from 7 to 10, some other specific embodiments range from 4 to 5, and in other specific embodiments range from 6 to 10. 7. Therefore, in some preferred solutions, hydroxyethyl starch will contain between about 6 and 7 hydroxyethyl groups per 10 glucose units. Another preferred type of solution is between about 4 and 5 hydroxyethyl groups per 10 glucose units. Another preferred type of solution contains between about 7 and 8 hydroxyethyl groups per 10 glucose units. The best swelling agent printed by the China Consumers' Standards Cooperative Bureau of the Ministry of Economic Affairs is Hetastarch (McGaw, Inc.), which is an artificial colloid derived from waxy starch, which is almost entirely composed of amylopectin It has hydroxyethyl ether on the glucose unit connected by α (1-4) and the degree of Mohr substitution is about .7 hydroxyethyl / glucose unit. The colloidal properties of the 6% Heida starch solution (w t / w t) are approximately equivalent to human hemagglutinin. Another particularly good swelling agent is Pentastarch, which has a Mohr substitution degree of about 0.4 5 hydroxyethyl / glucose units, and its -13- This paper size applies the Chinese National Standard (CNS) A4 Specifications (210X 297 mm) 562678 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention 纟 1) The average molecular weight (measured by the HP SEC method published by the 196 PDR) is about 15.0. 0, 000 to 3 50, 0 000 d, and 80% are between 1 0, 0 0 to 2, 0, 0, 000 d. Liyi's best swelling film agent is 'H e X astarch 〃', which has a Mohr substitution degree of about 0.64 hydroxyethyl / glucose units and an average molecular weight of about 220,00. 〇. In some specific embodiments, hydroxyethyl starch is a selected hydroxyethyl starch source portion, especially a portion selected by size. Generally, this portion has at least an average molecular weight of less than about 1,000, The part of 0.000 Daltons may be the part with an average molecular weight greater than about 50,000 Daltons. This can be prepared using conventional fractionation equipment. The concentration of the swelling agent in the solution is sufficient to achieve (using the above-mentioned sodium, calcium and magnesium chloride salts, organic ions of sodium and hexose organic salts) equivalent to the colloid osmotic pressure of normal human blood pressure, about 28 mmHg. Generally speaking, the amount of swelling agent in the solution is between about · 5 to 30, usually between about 1 to 25, and more usually between about 2 to 8%. When the swelling agent is hydroxyethyl starch, the amount present in the solution is between about 1 and 30, usually between about 2 and 15 and more usually between about 4 and 8%. One of the features of the present invention is that the solution contains two or more swelling agents with different expulsion rates. An additional advantage provided by the solution of the present invention containing two or more swelling agents with different depletion rates is that an individual with reduced circulating blood volume can maintain the colloid osmotic pressure of the blood for a long period of time while urging the individual to make plasma proteins by itself. Slower swelling artificial swelling agents include high molecular weight Heida starch (molecular weight 30,000 to 1,000, 000) and poly (please read the precautions on the back before filling this page) • Packing-order ml This paper size applies Chinese National Standard (CNS) A4 specification (21〇χ297 public shame) -14- 562678 A7 B7 V. Description of the invention 彳 2) Glucose 70, whose intravascular endurance rate is tested for 6 hours (

Messmer (1 9 89) Bodensee Symposium on Microcirculation (Hammersen &amp; Messmer, eds.), Karger, N.Y., pg. 59). Artificial swelling agents with a fast elimination rate include low molecular weight and medium molecular weight heida starch (average molecular weight 40, 000 to 2000, 000) and polydextrose 40, whose intravascular persistence rate is 2 — 3 hours (Mes smer (1989), supra). Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) The solution may contain one or more different selective reagents, which can make the solution suitable for special purposes. One optional reagent that can be included (and is usually added) is sugar. Sugars are usually hexoses, such as glucose, fructose, and galactose, and glucose is preferred. In the preferred embodiment of the present invention, nourishing hexose is used, and sugar mixtures may also be used. The sugar content in solution is usually (but not necessarily) a physiological quantity. "Physiological quantity" or "physiological level" means that the concentration of sugar is between 2 m and 50 m, and the glucose concentration is preferably 5 mM. Sometimes, the concentration of hexose can be increased as needed to reduce the fluid retained in the individual tissues. Therefore, if it is desired to avoid or limit edema in the individual to be treated, the range of hexose content can be expanded to 50 mM or higher, but usually not higher than 60, more usually not higher than 5 5mM, but when the agent is used as a frozen Except for protective agents. The solution of the present invention may contain blood coagulation factors to accelerate or promote the formation of blood clots. The preferred blood coagulation factors suitable for use in the solution of the present invention include: vitamin K, factor I, II, V, VII, VIII, VIIIC, IX, X, XI, XII, XIII, protein c, von Vebrand factor , Fergu's factor, Fryer factor and protein inhibitors. The concentration of blood coagulation factors is determined by the paper size of the paper to the Chinese National Standard (CNS) A4 (210X297 mm) -15- 562678 A7 B7 V. Description of the invention 纟 3) 谙 The person skilled in the art depends on individual treatment cases. For example, when vitamin K is administered, the concentration should be sufficient to supply the patient with 5 to 10 mg. The solution of the present invention may include an oxygen-containing component at a concentration so as not to cause poisoning to the individual. The amount of oxygenated components should generally be sufficient to provide increased oxygen to the tissues of the individual without poisoning the individual. 'v Amount of aerobic oxygen content refers to the content that can make quiescent individuals with circulatory and physiological damage survive and recover from trauma, illness or injury. For normal humans with normal body temperature, at least 5 to 6 m 10 2/100 m 1 blood is required. Oxygen-containing components include heme, recombinant heme, hemocyanin, chlorocrnorin, and erythrin extracted from human and non-human sources, and other natural respiratory pigments extracted from natural products or reconstituted with DNA or Isolated method maker. Such compounds can be modified by several methods commonly known in the art, including chemical cross-linking or covalent bonding with polyethylene glycol groups. If the oxygen component is heme, its concentration range is preferably between about 20 and 200 g / 1. It is printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) ) The solution may further contain one or more cryoprotectants. This cryoprotectant means any agent that can maintain the integrity of the tissue structure at a low temperature (such as: sub-zero temperature). In some specific embodiments, the cryoprotectant An agent capable of destroying at least a portion of the tightly crystallized water molecules is required so that the freezing point of an aqueous solution containing a cryoprotectant is lower than the freezing point of a similar solution containing no cryoprotectant. Useful cryoprotectants include: alcohols, especially low molecular weight aliphatic alcohols, usually c 1 to C 6 alcohols, more usually C 1 to C 4 alcohols, such as: methanol, ethanol, and the like; polyols , Including straight-chain, branched and cyclic polyols, usually low-molecular-weight, aliphatic, and many paper sizes. Applicable to China National Standard (CNS) A4 (210X 297 mm). -16- Central Bureau of Standards, Ministry of Economic Affairs Printed by the employee consumer cooperative 562678 A7 _ B7 V. Description of the invention ") Alcohols' include: glycols, triols, and other polyols, such as sugars (to be described in detail below), available polyols Classes include glycols, such as: ethylene glycol, propylene glycol, butanediol, triols, such as: glycerol; sugars, including erythrose, isoerythrose, nucleic acid sugar, arabinose, xylose, Lyxose, isomerose, latrose, glucose, mannose, gulose, idose, galactose, roose, erythrose, ribose, xylulose , Psicose, fructose, verbose, lattice sugar and disaccharides, such as: sucrose, milk Sugar and maltose, of which glucose is particularly preferred; other reagents such as dimethylamine, trimethylamine oxide (TMA〇), DMSO, urea, formamidine, dimethylformamide, etc. clathrates), silicon-containing reagents, such as: sand gardens, fluorocarbons and their derivatives; etc .; cryoprotectants can be added to the solution with pressure and / or appropriate surfactants, where the surfactants are refined in It is well known to those skilled in the art. The general content of such reagents is sufficient to provide the required cryoprotective effect, and the specific dosage of the reagents is determined according to the specific reagents used. When the reagent is a polyol (such as a diol), Its content is generally between about 0.2 to 1M or 0 to 30%. As for the propanediol, it is preferably between 0.2M and 0.6M, and the propanediol having a concentration of about 0.4M is For the solution according to the present invention for preserving low temperature organs and donors, 1,2-propanediol is the preferred adduct, but 1,3-propanediol can also be used. As for T The final concentration of Μ A〇 'Τ Μ A〇 in the solution is between 0.2 M to 7 If glycerin is used, it contains a concentration of about 0 to 40%, usually about 5 to 30%, and more usually 5 to 20%. If DMS0 is used, its content is about 0 to 40%, (Please read the notes on the back before filling out this page). The size of the paper for the binding and binding applies to the Chinese National Standard (CNS) A4 specification (21 〇X 297 mm) -17- 562678 A7 B7 V. Description of the invention (15 Usually between about 5 to 30%, and more usually between about 5 to 20%. If sugar (especially glucose) is used, the sugar content is between about 0.6M to about 1.4M. For some specific implementations For example, 1.0 M is preferred. In one of the preferred embodiments, the title solution of the present invention contains at least two of the following: magnesium ions, sugars (such as glucose), and medium to high molecular weight hydroxyethyl starch, and may contain both components. The following specific example solutions are particularly valued: Solution A High molecular weight heda starch (average molecular weight 350,000 to 9 00,000) C a η K + M g + + Lactate glucose 1 to 10% 1 to 6 m Μ 1 to 5 m Μ 0 to 10m Μ 1 to 40m Μ Ο to 50 mM (Please read the precautions on the north θ before filling out this page) Install the printed solution of the Consumer Cooperative of the Central Standard Bureau of the Ministry of Economic Affairs Β High molecular weight Heida Starch (average molecular weight 350,000 to 900,000) C a η κ + Mg &quot; Lactate 1 to 10% 1 to 6m Μ 1 to 5m Μ 〇 to 10m Μ 1 to 4 〇m Applicable to China National Standard (CNS) A4 specification (210X297 mm) _ 18 _ 562678 A7 B7 V. Description of the invention (16) Glucose bicarbonate cryoprotectant solution I. High molecular weight heda starch (average molecular weight 350,000 to C a + + K + M g + + lactate glucose bicarbonate glycerol 0 to 50 m M 5 to 10 m M 900,000) 1 to 10% 1 to 6 m M 1 to 5 m M 0 to 10 m M 1 to 40 m 〇 0 to 50m Μ 5 to 10m Μ 1 〇 to 2 〇% (Please read the notes on the back first Please fill in this page again) High-molecular-weight Heida starch (average molecular weight of 3 50,000 to C + + K h M g + + lactate bicarbonate glycerol 900,000) printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economy 1 to 6 m Μ 1 to 5 m Μ 0 to 10m Μ 1 to 40 m Μ 5 to 10m Μ 10 to 20% This paper size applies Chinese National Standard (CNS) Α4 specification (210 X 297 (Mm) -19- 562678 A7 B7 V. Description of the invention (17) III. 1 to 10% 1 to 6 m Μ 1 to 5 m Μ 0 to 10 m Μ 1 to 4 m 〇 0 to 50 m Μ 5 to 10 m Μ 5 to 15% 5 to 15% (Please read the notes on the back before filling out this page): Packing · High molecular weight heda starch (average molecular weight 350,000 to 900,000) C a η K + M g η Lactate Glucose Bicarbonate Glycerin DMS. Ordered by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs to prepare the title solution. Various ingredients were added. According to the statement, the solution may contain a source of carbonates, among which sodium bicarbonate can be regarded as a base solution free of 〃. The same components can be used to coagulate blood before high temperature and high pressure sterilization. In order to explain the present invention, it is essentially the same as that of the last stage of heat sterilization. Dry the compound in the lower part, adjust the required amount of sodium chloride and organic sodium salt, and be familiar with one of the techniques in the relevant aqueous solution. For the sake of convenience, you can pass the above without the participation of the final carbonate. Add bacterial solution to the plot, if you want to add factors or oxygen to form a `` matrix solution '' &lt; For those who continue to discuss under this section, the bacteria can be combined or sequenced from time to time. At the same time, the reagents (such as: traditional). At this time, autoclaving factors or oxygenated solution are added to the pre-composition for discussion. The invention description is provided to mix to achieve the normal Chinese paper standard (CNS) A4 specification (210X297 mm) -20- 562678 A7 B7 V. Description of the invention (18) The amount of sodium chloride in a physiological saline solution (as a diluent for the dry type mixture according to the present invention). The title solution is suitable for many different applications. The title solution is particularly useful in applications where it is necessary to replace at least a portion of the host's (or its tissues or organs) circulating blood volume with a replacement solution. Such applications include: Surgery 'including normalization of the host's temperature from the host Body temperature reduction surgery 'as substitute blood' for post-mortem maintenance of physiological integrity; as cryopreservation of tissues or organs; for local chemical perfusion; etc. The solution may be combined with oxygen or high-pressure oxygen as a circulating solution at normal body temperature or during a time when the body temperature of the individual is significantly lower than the normal temperature of the individual. For example, during donation of cadaveric organs during surgery and at low temperature, the blood of an individual can be replaced with the cold circulating solution of the present invention, wherein the solution can be circulated for a period of time to perfuse and maintain the individual and its organs intact during this process. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) The solution of the present invention can be administered to individuals with normal body temperature intravenously or intra-arterially. Under pressurized gas raised to 100% oxygen, or administered to an individual undergoing surgery, the individual's body temperature is much lower than the individual's normal temperature (whether or not using high-pressure oxygen). Although the solution is administered and circulated in the individual, various agents (such as a heart-suppressing agent) can also be directly administered to the individual's circulatory system, directly into the individual's myocardium, or added to the circulating solution of the present invention. Adding such ingredients can achieve the required physiological effects, such as maintaining the contractile activity of the heart, blocking the fibrillation of the heart, or completely suppressing the contractile activity of the myocardium or heart muscle. This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) -21-Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 562678 Α7 Β7 V. Description of the invention (19) The heartbeat inhibitor is a kind that can stop the heart muscle Contractile substances, including anesthetics (such as lidocaine, procaine, and nuevocaine), and monovalent cations (such as potassium ions) at a concentration sufficient to inhibit myocardial contraction. The potassium ion concentration sufficient to achieve this effect is usually higher than 15 mM, and the magnesium content may also be higher than about 0.5 μM. During recovery of the individual (after a period of sub-normal temperature or after supporting the individual under freezing maintenance with the solution according to the invention), the individual can be refilled with the solution mixture according to the invention and the blood retained by the individual or the donor's blood . When the individual is warming up, the blood is infused until the individual reaches an acceptable hematocrit, which is usually approximately 20% above the hematocrit. After an acceptable hematocrit is reached, the perfusion is stopped and the individual is resuscitated after the wound is sutured using conventional surgery. Generally, the solution according to the present invention is added to the freezing by an intravenous catheter (when the body temperature is normal) or a suction circulation device (such as a centrifugal pump, roller pump, peristaltic pump or other common and effective circulation pump) Individual. The circulatory device is connected to the individual via a cannula accurately inserted into the appropriate veins and arteries. After the solution is added to a frozen individual, it is usually added via an arterial cannula, removed from the individual via a venous cannula, and then discarded, stored, or recycled. The solution can be used in various surgical conditions and procedures. It can be applied to intensive neurosurgery, which requires a clear field of vision, and if necessary reduces the activity of the central nervous system, and performs this procedure on patients whose core temperature and / or brain temperature have substantially decreased. The solution can increase the concentration of oxygen in the pressurized state (which can be higher than the oxygen tension in the atmosphere by 100% oxygen) so that the individual (after losing a large amount of blood, this paper size applies the Chinese National Standard (CNS) A4 specification ( 210 × 297 mm) -22- (Please read the notes on the back before filling out this page) • Equipment · ^ Printed by the Consumers 'Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 562678 A7 B7 V. Description of the invention &amp; 〇)' Example: 2 0% ~ 98% of blood) body temperature remains normal. The individual is continuously or intermittently maintained at a high oxygen concentration until the individual can synthesize sufficient blood components to sustain life at atmospheric pressure and oxygen concentration. The solution according to the present invention can be used to maintain the temperature of an individual who has been threatened by a fatal injury at below normal body temperature and at a lower metabolic rate, until an appropriate life-saving or restorative surgical procedure is performed. In addition, the solution can be used to maintain a patient with a rare blood or tissue type until he or she seeks an appropriate anastomosis donor and is exchanged for a blood unit or other organ. The solution according to the present invention was unexpectedly found to be able to exchange substantially all circulating blood of a mammalian individual and to allow the individual to survive without the need to perfuse the blood into the individual. When the hematocrit of an individual is below 10%, all circulating blood of the mammalian individual is deemed to have been exchanged. The hematocrit may be less than 10% when provided to the individual 02, or may be substantially less than 10% in a high-pressure 02 chamber. The solution according to the present invention can naturally be used to maintain an individual with a hematocrit exceeding 10%. The exchange of all circulating blood in a mammalian individual can be performed while the mammalian individual's body temperature is maintained at its substantially normal body temperature. In addition, this process can be performed while the individual is cooling and lowering the mammalian individual's body temperature below its normal body temperature. Cooling can be done in an ice bath, ice salt slurry or cold felt. Cooling the solution according to the invention before subjecting the subject to a perfusion solution can further cool the subject. In the process of exchanging circulating blood for mammalian individuals according to the present invention, it is better to infuse the solution after the individual is cooled. The solution is delivered to the individual's circulatory system using an arterial catheter, and the blood and perfusate are sold from the individual with an intravenous catheter (Please read the notes on the back before filling in this page), τ This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 23- 562678 A7 B7 V. Invention description). All circulating blood of an individual is essentially removed in this manner, as determined by measuring the hematocrit of the venous catheter effluent. Perfusion can be stopped when all circulating blood of the individual has been removed. In addition, the process of obtaining all the circulating blood of the individual can be performed with the help of high pressure 02. The individual is placed in a high-pressure chamber pressurized with oxygen at a concentration exceeding 20% (preferably 100% oxygen). This high pressure chamber maintains a pressure to atmospheric pressure of 0.5 pounds per square inch to about twice the atmospheric pressure throughout the process. One of the specific embodiments is a process in which an individual is placed in a high pressure chamber (0.5 to 30 pounds per square inch [psi]) pressurized with 100% oxygen to a chamber pressure of about 0.77 to about 2 atmospheres. ). If necessary, the pressure in the high-pressure chamber can be reduced to atmospheric pressure when the wound is closed. Individuals thereafter remain at high pressure and high oxygen concentrations. The pressure is gradually reduced to a lower pressure but still high pressure. This pressure is preferably maintained for several hours to several days below 10 p s i to about 5 P s 1. Thereafter, the pressure is again lowered to less than 1 P s i to about 0.5 p s i, and it is maintained under this pressure for a period of time or more than one day. Printed by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) The solution can also be used to maintain the physiological integrity of organ donors immediately after brain death. The individual can be frozen, the individual's blood can be removed and exchanged for a circulating solution maintained below 37 ° C, or it can be circulated with a cooling solution according to the present invention. By using this solution, it is possible to minimize ischemia of living organs. The circulatory system of an individual is circulated at a low temperature with the cooling solution according to the present invention, regardless of whether the individual is placed in a hyperbaric oxygen chamber, the living organs can be maintained for a longer period of time, thus making the usable number of organs of donors waiting for transplant Greatly improved. This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 562678 Printed by A7 B7, Consumer Cooperatives of the China Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention. Adducts (especially propanediol and high-concentration glucose) strengthening solutions can reduce the temperature of donor organs (especially the donated heart) to below the freezing point (0 ° c) of water, and return from freezing to use The state of being able to maintain a coordinated systole. In addition, when using the solution according to the present invention and such a chewing compound, the temperature of an intact mammalian individual can be reduced below the freezing point of water (0 t), and restored from a frozen state to maintain coordinated cardiac contraction State even regains breathing and consciousness. Other official systems are also believed to maintain high biological integrity, ie, maintain a physiological state of longevity. The following examples are intended to be illustrative and not restrictive. EXPERIMENTS The following proposed examples are intended to provide a complete description for the average person familiar with the art and how to synthesize the invention, and are not intended to set limits on the scope of the inventor's invention. The data (for example: content, temperature, etc.) used are all directed towards ensuring its accuracy. However, in some embodiments, errors and deviations must be explained. Unless otherwise stated, parts represent weight parts, molecular weight is weight average molecular weight, temperature is in degrees Celsius, and pressure is atmospheric pressure or its vicinity. Example 1. Solution composition A · L solution composition. The composition of the L solution is as follows: Na + 14 3mM; Ca ++ 2 · 5mM; Mg ++ 0 · 45mM; K + 3 · 0 This paper size is applicable to China National Standard (CNS) A4 specification (210X 297 mm) _ 25-( Please read the notes on the back before filling in this page.) Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs and printed 562678 A7 _____B7_ V. Description of the invention b) mM; (: 1.124 ιΜ; glucose 5mM; and lactate 28 m M. The solution is filtered to remove insoluble matter, and placed in a high temperature and high temperature autoclave container at a temperature of 120. (: High temperature and high temperature autoclave for 15 minutes. Β · HL (Bi〇Time HextendTM-Lactate) Ingredients of the solution. 60 g / 1 high molecular weight heda starch was added to the L formulation. C · HLB (BioTime HextendTM-lactate monobicarbonate) solution. 5 m 1/1 of 1M NaHCCh was added to the HL solution. Solution OD · HL — Ingredients of DL (Bio Time HetadexTM — Lactate) solution. 6% Heda Starch in HL formulations are replaced with 6% Polydextrose 40. E • Ingredients of BioTime AlbextendTM solution. L Add 50 g / 1 protein to solution The ALB solution is an AL solution with 5 m 1/1 lM NaHC〇3. F · HL-the component of the heme solution. Adding 20-2 0 0g / i heme HL solution. G. L-the heme solution Ingredients. Add a solution of 20-200g / l heme in L. Example 2. Replace the blood with HL-DL solution. Female rats of 240 g were injected with 1 · m of ketamine, wood plowing and ashhip plowing. (Acepromazine) mixture for anesthesia. Place the animal on the platform and intubate from its right femoral artery and vein. For animals 10f please read the precautions on the back before filling out this page; &gt;-bound paper The scale is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) -26- 562678 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention h) m 1 HL — DL solution for equal volume perfusion, Until the hematocrit reaches 17.2%. Remove the cannula, adhere the blood vessels, and suture the incision. The animal is well tolerant to perfusion, eating normally and vigorously during the three-day experiment. Animals after the experiment Can fully recover and survive healthy. Example 3. Recovery of dogs treated with ice instead of blood. Male dogs of 26.8 kg were anesthetized with sodium pentobarbital and inserted through a tube. The dog was moved into the operating room, put on an oxygen mask to breathe oxygen, and was inserted with a venous catheter, a Foley catheter, an arterial catheter, and a Swan-Ganz catheter. After the 1 · v · injection of heparin, the right femoral artery was inserted. And veins for intubation. An esophageal tube is inserted into the esophagus and treated with an antacid. Place temperature sensors in the esophagus and rectum. Methyldehydrocortisol was injected via i · v ·. Wrap the animal in a cold hood and allow its surface to cool. The intubation of the animal is connected to the bypass circuit (including a blood mixing pump, an oxygen generator, a built-in heat exchanger, a second coaxial heat exchanger, and a funnel) for rapid blood treatment fluid replacement. The whole blood (2 2 5 m 1) was removed from the dog and stored for use in subsequent warming steps. Blood volume was quickly replaced with H L B solution. The bypass circuit (containing 1.0 liter of H L Β solution) connected to the animal was opened, and the core cooling process was started. Replace 3 3 liters of H L B solution. After substantially all the blood has been removed, a sufficient amount of blood is perfused with a 2 M K C 1 solution to stop the heart from contracting. When the temperature reaches the freezing point, the hematocrit is well below 1%. The temperature of the animal's esophagus was maintained below 10 ° C for a period of 4 hours and 5 minutes. The lowest temperature was recorded as 0 · 7 ° C. This paper size applies to China National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling out this page) • I Pack · Order -27- 562678 A7 B7 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Preparation 5. Description of the invention k) Allow the animal to warm up after the low temperature period. When the body temperature rises above 10 ° C, the previously collected venous effluent, whole blood, and donor blood are returned from the circuit; the hematocrit increases with the temperature. Add lidocaine and bicarbonate to restore heartbeat and breathing. When blood pressure and body temperature returned to normal, the animal's bypass circuit was closed, and protamine and Lasu were injected. Hours after warming, the animals regained consciousness and responded. The animals survived healthy after the experiment.实施 例 4。 Example 4. Recovery of baboons treated with blood on ice. Male baboons (scientific name Papio annahis) of 2 4 g were first injected with ketamine and Yasip through i · m · and then injected into Pandoso through 1 · v ·. Finally, anesthesia was fixed with pangulin (p a n c u r ο n i u m) bromide. Put an animal under an oxygen mask to breathe oxygen, and insert it into veins, foral, and arterial catheters. Wrap the animal in a cold hood and allow its surface to cool. The cannula was inserted into the right femoral artery and left and right femoral veins of the baboon after heparin injection. Place the temperature sensor in the esophagus, rectum and brain. Animals were used to measure E K G, somatosensory evoked potentials (SSEPs) and EEG in animals. Flumesonone was injected via 1.V. Connect the animal's cannula to the bypass circuit (including blood mixing pump, oxygen generator, built-in heat exchanger, second coaxial heat exchanger, and funnel) for rapid blood processing and blood replacement. The whole blood (300 m 1) was removed from the baboon, stored and used for subsequent warming. Blood volume was quickly replaced with 300 ml of physiological saline solution. Open the bypass circuit that connects the animals (including 2 liters of plasma plasma (Plasmalyte) (please read the precautions on the back before filling this page)-binding and binding paper size applicable to China National Standard (CNS) A4 specification (210X 297 male 28) 562678 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention ㊁ 6) 'Commercially available effective electrolyte solution)' began to cool the core. When the temperature of the esophagus is lower than 13 ° C, add another 2 L 3 1 2 · 5 g of mannitol blood prize quality liquid to the bypass circuit to replace the blood and plasma quality liquid mixture filled in the circuit. Save this diluted blood and use it in subsequent warm-up steps. Immediately afterwards, 10 liters of H L B solution was added to replace the plasma plasma. When the temperature reaches the freezing point, the hematocrit is well below 1%. The blood pump was stopped when the brain temperature reached 3.4 ° C and the temperature in the deep esophagus was below 2.8 ° C, and the animals were maintained in a standstill condition for 4 5 minutes. After this period, the cycle was resumed. After the hypothermia period, 4.2 L of H L B solution was input from the vein to allow the animals to warm up. When the body temperature rose to 15 ° C, 2 liters of plasma was added to the circuit to replace the H L B solution. Add mannitol (6.25 g / 1) to the plasma plasma of the circuit. In addition, the collected venous effluent, whole blood, donor blood, and fresh frozen plasma were input from the circuit; the hematocrit increased with temperature. Add 1 2 · 5 g of mannitol to the circuit. When the temperature of the esophagus and rectum approaches normal, the heartbeat returns and begins to breathe. When the blood pressure and body temperature are close to normal, the animal is injected with protamine through i.v., the animal's bypass circuit is closed, its cannula and catheter are removed, and its incision is sutured. The temperature deep in the animal's esophagus was below 15 ° C for 3 hours, and below 10 ° C for 2 hours and 17 minutes. The lowest recorded temperature was 2.8 ° C (Table 3). The next morning, the animal can sit upright in a cage, pick up a banana and eat it with apple juice. After the experiment, the animals can survive in a healthy way, and they will be sacrificed one week later (please read the precautions on the back before filling out this page) 29- 562678 Α7 Β7 V. Description of the invention) (Please read the precautions on the back before filling out this page) Example 5 The blood of patients undergoing cardiopulmonary bypass surgery was replaced with two solution systems. The patient is anesthetized 'cannulated and connected to a cardiopulmonary bypass device. The patient was then wrapped in a frozen hood to cool the surface to 30 °. The patient is then placed in a bypass circuit that has been previously treated with the ALB solution. The patient is core-cooled 'until the temperature deep in his esophagus reaches 20 ° C. Blood and 4 L of A L B solution were collected and immediately replaced with η L B solution. Maintain this cool body temperature during heart or brain surgery. The patient is then allowed to warm up, first replacing the η L Β solution with the A L Β solution, and then replacing it with the previously removed A L Β-blood solution. Add 5-10 mg of vitamin K. The use of the ALB solution as a depletion solution and blood collection has the advantage that the patient can use his own diluted blood for reperfusion when warming up, because protein can be regarded as a natural compound, so it can not affect the patient's own synthesis of protein Swelling agent that maintains blood under its ability. Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs, Example 6. H L -heme solution is used as an emergency substitute for blood in patients with bleeding. When the patient has severe blood loss, a perfusion solution containing 5 mg / 1 of blood coagulation factor vitamin K and 30 g / 1 of oxygenated hemoglobin H L can be used for perfusion. When the patient's blood pressure is stable and normal oxygen is delivered to the patient's tissue, it returns. Heda starch can be gradually removed from the patient's body while synthesizing its own protein, thereby maintaining a stable blood colloid osmotic pressure during recovery. This paper size applies to China National Standard (CNS) Α4 specifications (210, &lt; 297 mm) -30- 562678 A7 ____B7 V. Description of the invention Pan 8) The use of H L solution containing blood coagulation factors and oxygenated components can reduce or completely avoid the use of blood substitutes.实施 例 7。 Example 7. Six young female mice (2 7-2 62 g) were anesthetized with hemagglutination factor 0 in mammals with diluted red blood cells, and femoral arteries and veins were intubated. 40-60% of the blood was HL Solution replacement. After the hematocrit decreased to 16-22%, the animals were slowly injected with 6 ml of Trasylol® (10,000 KIU / ml) via i · ν ·. And cut off its tail from the tip 30mm. The average blood loss was 0.39 ± 0.06 (mean ± SEM) ml, and all animals except one survived for at least one day. Eight animals in the control group were given a similar H L solution, but T r a s y 1 ο 1 ® was not given. The average blood loss was 4 · 8 ± 0 · 5 4ml 'only two of the eight animals survived. Compared with the untreated animal group, the mortality of HL-treated animals without Trasylol® was significantly higher (P <0.02) and blood loss was significantly higher (P &lt; 0.0 0 2) ° Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling this page) Example 8. The H L Β solution was used as a dog's ice cold to replace blood. Place a dog of 2 5-30 kg on a partial cardiopulmonary bypass device. Cool the dog to the surface and core to near freezing point (1 to 3 t). The blood of the dog was replaced with a cryopreserved blood H L B solution according to the method of Example 1. Continuous blood transfusion during the warming period. The animal's temperature dropped to near freezing (below 4 ° C) and then returned to temperature. Replace the substitute blood with blood, warm up and resuscitate the animal. This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) -31-562678 Α7 Β7 V. Description of the invention &amp; 9) Preparation. The dog was inserted into the catheter through the right radial vein, and Pandoso was injected through 1 v, and then the endotracheal tube was installed and passed through isoflurane (or Flether) / 100% 02. Ringer'5 lactate-regulated droplets were initiated to titrate to dog arterial blood pressure (approximately 40 m 1 / h r 1 v). Place the dog on a cold hood and cool with recirculating ice water. A catheter was inserted at the right carotid artery to monitor blood pressure (CA P), and a three-necked piston was added to the line to allow arterial blood sampling every 10-60 minutes during the entire procedure. A foley catheter was inserted to collect urine, and urine volume was measured throughout the procedure. The King's wedge catheter with two lumens (7 F) was implanted from the right internal jugular vein or the right femoral vein, and then entered the pulmonary artery from the right ventricle. The insertion pressure (PAW) of the lung was measured from the distal port, and the central venous pressure (CVP) was measured from the proximal port. Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (CV P can be measured as needed, catheterized into one of the arm veins) to separate the left femoral artery from the vein and prepare for intubation. Animals were treated with heparin (approximately 5,000 u). A biomedicus venous return cannula (15-19 F) was inserted into the femoral vein and a Biomedicus arterial cannula (12-15 F) was inserted into the femoral artery. The activated clotting time (A C T) was measured every 45 minutes (until the blood was replaced) and heparin was adjusted to be greater than 400 s e c. Connect the thermocouple approximately at the midpoint of the esophagus and insert it into the stomach. Place a second thermocouple in the rectum. Connect E C G wire. 1 v was injected with 80 mg of solu-Deha-Conef (Up John, veterinary dehydrocortisol sodium succinate). The eyes were coated with Ternmycin (or Lacrylube) and DiGel (or Maalox, 20 ml) was infused from the esophagus. measuring. Measure the arterial blood gas, pΗ, and hematocrit of each blood sample, as well as certain electrolytes, enzymes, and other chemical properties. Monitoring food -32- (Please read the precautions on the back before filling this page) This paper size applies to China National Standard (CNS) Α4 specifications (210, &lt; 297 mm) 562678 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 ____ — B7 '~ * ----------------— ___ V. Description of Invention (30) Road And rectal temperature and blood temperature of arterial outflow and venous return. Monitor CAP, PAW, CVP, ECG, tracheal pressure. The temperature is displayed in numbers and stored in a computerized data collection system over time. Pressure and ECG are displayed as real-time waveforms or digital data and stored by a computer. Elements of a detour circuit. The circuit includes Biomedicus centrifugal blood, liquid pump and flow meter, Terumo hollow fiber membrane and oxygen device, and built-in heat exchanger, Shiley hard-shell vein reservoir with filter, and a second heat exchanger with an air brake (Electromedics) (As close as possible to the animal). The drain is located near the inlet of the venous reservoir and is closed with a control valve. Therefore, rapid and effective blood / substitute blood exchange can be performed. And there is an A-V shunt section, which can also circulate blood when not bypassing. The venous reservoir can be filled from a 1-liter separation funnel via a '' quick-fill inlet '' or a double infusion bag through a heart incision. The arterial line from the oxygen supply to the arterial intubation and A-V shunt is a 1/4 〃 line; the venous return, drain, and pump head lines are 3 〃 〃. This part contains sharp bends, then use thick-walled pipe or '' spiral wrap '' to wrap the pipe. The patient's pipeline is double-wrapped and the entire circuit (non-factory sterilized reservoir, second heat exchanger and oxygen supply) and six basic parts (pump head, flow meter section, center bypass ring, funnel, Infusion tubes and gas purifier tubes) are sterilized with ethylene oxide gas. Detour loop bracket. Pump ice water from one of the two 10 gallon insulated reservoirs to cool the oxygen supply and the second heat exchanger. The other reservoir supplies the cooling hood. At the beginning of the surgery, ice water was circulated through the cooling hood. (Please read the notes on the back before filling this page)-Binding. Order * k · This paper size is applicable to China National Standard (CNS) A4 specification (21〇 乂 297 mm) -33-562678 Α7 Β7 V. Description of the invention (31) At the beginning of the bypass, room temperature water is circulated through the loop heat exchanger. Add ice cubes to the reservoir to slowly reduce the temperature, which is sufficient to maintain the temperature difference between the esophagus and blood flow at 7-10 ° C ° After the blood is replaced (ie, the hematocrit is less than 4%), 'start to start the entire ice The flow of water. When warming, remove the ice cubes from the reservoir and turn on the heater. The thermostat of the heater is manually adjusted to limit the maximum temperature of the return temperature to 10 ° C higher than the return temperature of the pulse. The oxygen supply provides a sterile, filtered 100% 02. Substitute blood. The circuit was pre-loaded with 2 liters of solution L (Example 1) and recirculated through the A-V splitter to ensure temperature-gas balance. Connect the cannula to the arterial and bypass venous tubes, and clamp this line with a clip. Wrap the patient with a cooling hood until the surface cools down to a temperature of 35 ° C deep in the esophagus. Remove the clamp and begin to bypass the L-diluted blood solution at room temperature (approximately 25 ° C). At the beginning of cooling, gas anesthesia was terminated and the dogs were treated with 2.5% Pandoso. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) The blood flow is gradually cooled until the temperature of the animal's esophagus is 20 ° C. At this time, the vein is clamped at the inlet of the reservoir to return and Drain the blood from the drain while removing the L solution. During this exchange period, add 2 liters of L solution from the venous reservoir. When the content of the L solution drops to 250 m 1, gradually add about 6 liters of HLB until all blood is removed (observe HC T Less than 2%). Approximately 4 liters of blood / alternative blood mixture was collected in sterile bottles and retained for subsequent reperfusion. Discard very diluted blood mixture (approximately 5 1/2 liters). This paper size applies to Chinese National Standard (CNS) A4 specification (210 × 297 mm) -34- 562678 A7 _____B7 V. Description of the invention (32) After exchanging 4 liters (that is, after adding 2 liters of L solution and 2 liters of HLB solution ), Injecting 20 meq KC1 through the stop piston of the second heat exchanger to suppress the heartbeat. During the exchange, the inflow was adjusted to keep p A W below 5 m m H g and the outflow rate was equal to the inflow rate, that is, it was only possible to approach an equal volume of blood. At the end of the exchange, the final content of the reservoir was about 500 ml, PAW was less than 5 mmHg and CVP was less than 5 mm Hg. Adjust the flow rate to maintain an equal volume of blood (reservoir content, and increase in pressure, ie PAW &lt; 5mmHg and CVP &lt; 5 mm H g) 〇 When almost all the blood is removed (less than 4% Η C T with the naked eye), reduce the cold flow temperature to the freezing point (add ice cubes in the reservoir), and quickly cool the dog To the lowest temperature. When cooling the perfusion, whenever an HCT rise is detected, the 2 to 4 liter HLB solution is exchanged at a high speed to remove the blood mixture. Throughout the process, arterial blood samples are taken and blood gas, pH, HCT are monitored, and in some cases electrolytes and other blood chemicals are monitored. Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) After the substitute blood has been cooled for about 1-2 hours, the dog's body temperature is about 1-4 ° C ′ and it begins to warm up. When the dog is warmed, remove the ice cubes from the reservoir and heat its contents, i.e. the hood, with a heater. When the temperature of the esophagus reached 15 t, 4 L of the L solution containing 25 g of mannitol was first replaced with the H L B solution followed by 4 L of the collected blood mixture. Discard the effluent. Animals are transfused into the blood of their own storage or donors and gently warmed, with a temperature difference of less than 10 ° C and not more than 40 ° C. Heartbeat will reply naturally This paper size applies Chinese National Standard (CNS) A4 specification (210X 297mm) ~ Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 562678 A7 _____ B7 V. Description of the invention (33) or beating. When the temperature of the animal (esophagus and rectum) reaches about 3 5 t, the physiological characteristics will stabilize, and such characteristics can be supported by itself, and can be warmed by the extracorporeal circuit.实施 例 9。 Example 9. Heart-protected magnesium and potassium concentrated aqueous solutions are disclosed here as novel products, especially high-concentration K + and M g + + aqueous solutions that can be used with cold HLB instead of blood for individuals requiring cryo-surgery. Individuals who inhibit heartbeat, or provide better organ preservation for organ donors-such as the heart before transplantation. * This solution can be used with H L Β solution for total internal hypothermic flushing under ice-cold temperature to provide better protection of the heart during circulation suppression. The solution and H L Β can also be used as heartbeat inhibitors for standard cardiac surgery that does not include low temperature internal flushing, or preserved for transplanted hearts after low temperature flushing with a cooled H L Β solution. For the preparation of high-concentration Mg and K solutions, Mg S04 and K C 1 were used. Such compounds are currently approved for use in human patients by US F DA. However, Mg C 1 2 can replace Mg S04 and KOH can also be used to adjust the pH to approximately 7.8 (between 7.2-8.4). Other substances that can be used in high-concentration Mg and K solutions are KH C03, K2P04, potassium lactate, potassium citrate, potassium acetate, and potassium gluconate, as well as those containing K + and Mg +. To the solution, NaHCO3 was added. The final solution contained approximately 1.5M potassium and 0.5M magnesium. A LB solution containing 50 mM KC1 and 10 mM Mg S04 was prepared initially. Use approximately 1 to 2 m 1 of this solution with 1 v or arteries. The paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) · 36 _ (Please read the precautions on the back before filling this page): Equipment · 丨 Equipment 562678 A7 B7 V. Description of the invention (34) Injection to trigger a hamster heartbeat stop using a small amount of ice-cold blood. This volume is approximately equal to 30-50% of the hamster's blood volume. It was found in the experiment that this solution may cause the heartbeat to stop after intramuscular injection with Dajiu Medicine. Approximately 9.5 ml of a 50% solution of MgS04 · 7H20 (that is, about 2 Μ) and 27 m 1 2 Μ KC 1 were injected into an ice-cold dog (weighing about 25 kg, the estimated blood volume was about 1.8 liters, whose blood has been replaced by HLB), the effect of protecting the heart and the use of K and M g or a more diluted K / M g solution (that is, the concentrated K / M g solution is first dissolved in the oxygen supply reservoir It is significantly better in comparison with a solution of about 5,000 m 1 HLB solution and further diluted to 6.2 mM Mg + + and 17.4 mM K + in a circuit containing 850 m 1 of HL B solution. A solution containing approximately 0.75MMgS04 · 7H20 and 1.48M K C 1 -37 m 1 was injected into a bypass circuit assembly (heat exchanger) directly connected to the individual femoral artery. Based on dog experiments, this solution is expected to improve the protection of the heart for individuals replaced with low-temperature HLB. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page). Injecting a high concentration Mg + + / K + mixed solution of 0 · 1 m 1 into hamsters can effectively provide heart protection after flushing with HLB as a whole. The novel discovery described herein is the use of solutions containing extremely high concentrations of Mg and K to trigger safe and effective heart protection, which is an ice-cold individual whose blood is replaced with HLB. The therapeutic concentration of K + and Mg ++ is the aforementioned Chinese paper standard (CNS) A4 specification (210X 297 mm) -37- 562678 Α7 Β7 V. Description of the invention (35) Use or insert to protect the cold heart 1 〇 times or more (these two electrolytes) 〇 (Please read the precautions on the back before filling out this page) 1 · Use HL · B and concentrated μg / K solution to resuscitate the hamster. 55 g of female hamsters were anesthetized overnight with ketamine 〇 03 ^ 1 (100 mg / m 1 solution), and covered with crushed ice until the lower rectal temperature was about 130 ° C. Place the animal under a stereo microscope on a surgical table. The cannula was placed in the carotid artery and internal jugular vein. H L B solution was infused from the artery and the venous effluent was collected. The blood was replaced with ice-cold η l B solution. Approximately 65% of the blood was removed and the animal temperature dropped to 1 ° C. When the animal temperature dropped below 10 ° C, aeration with 1000% 02 was started. Approximately 7 m 1 or 2 blood volumes are required to replace circulating blood. At the time of termination of perfusion, a large medicine containing 0.21 MgS04-0.5M KC1 was given 90.2 m 1 (I · V ·). The heartbeat stopped immediately. Animals are kept in mind Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economy 5 h r s and 30 m 1 η. Blood was collected from the donated animals and then the animals were perfused with 3 ml of HB. The animal gradually warmed up, the heartbeat was normal, and breathing resumed. When recovering, the animal responds to stimuli such as light pressure on its abdomen or paws. 2. Anesthetize 70g hamsters with 0.03ml ketamine (100 mg / m1 solution) overnight and cover with crushed ice until the temperature of the lower intestine is about 13 ° C. The animals are placed on a surgical table under a stereo microscope. The cannula was placed in the carotid artery and internal jugular vein. The HLB solution (plus 50 mM glucose and 5 mM NaHCO3) was infused from the artery and the venous effluent was collected. The blood was replaced with ice-cold H L Β solution. This paper size applies to Chinese National Standard (CNS) A4 specifications (X 297 mm) -38- Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 562678 A7 B7 V. Description of the invention —) ^ Remove about 65% of the blood, The animal temperature dropped to 1 t. When the temperature of the animals reached below 10 C, ventilation with 100% 02 was started. Approximately 1 or 2 blood volumes are required to replace circulating blood. A solution containing 0.02 ml of 11 ^^ 1 304 and 0.1 ml of KC1 1M was diluted with 0.1 ml of HLB. Then 1 v was injected into this 0.2 2 m 1 solution. This is equivalent to inputting a mixed solution of 5 M K C 1 and 0 9 M M S04. 5 hours after the suppression cycle ', the blood was collected from the donated hamster and then the animals were perfused with 3 m 1 H L B. The animal gradually warms up, recovering heartbeat, breathing, and responsiveness. The resuscitation of 5 hours after the hamster's heart stopped using Mg / K concentrate was not reproducible. 3. 70 g female hamsters were banned from eating overnight. 1) 1 chloramine (100 mg / m 1 solution) was anesthetized and covered with crushed ice until the rectal temperature was about 13 ° C. The animal is placed under a stereo microscope on a surgical table. The cannula was placed in the carotid artery and internal jugular vein. H L B solution was infused from the arteries and venous effluent was collected. The blood was replaced with ice-cold η l B solution. Approximately 65% of the blood was removed and the animal temperature dropped to 1 ° c. When the animal temperature dropped to 10 t: aeration with 100% 02 was started. About _into 5 m 1. Then, a mixture of 0.5 M K C 1 and 0.9 M M S0 4 was injected from the artery. Then inject 1 m 1 of HLB to track this "cardioprotective agent," and track its movements in the circulatory system and tissues. Maintain inhibition of animal circulation for 1 hour. When gradually warming, infuse the animals with 4 m 1 of HLB and damage the animals. Blood. It is found that the hamsters are restored to the size of this paper. The Chinese National Standard (CNS) Α4 specification (210 X 297 mm) (please read the precautions on the back before filling this page)

-39-Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 562678 A7 B7 V. Description of the Invention (37) Heartbeat, E K G signal is normal, spontaneous breathing, response, regaining consciousness, upper right posture, and long-term survival. In the past, long-term survival was rarely achieved without the use of K / Mg concentrates for such experiments.实施 例 10。 Example 10. Using bicarbonate-containing H L B intermittent perfusion method During the period of cold blood replacement and suppression of circulation, it was found that some nerves took longer to recover than continuous H L Β solution circulation. This result can be improved in hamster experiments by reducing bicarbonate H L B and / or intermittent H L B perfusion to reduce acidosis. This also prevents stiffening and improves recovery of brain function (especially hamster reactivity after prolonged cardiac arrest). At the same time, it was found that the dogs with slow continuous perfusion of blood using cold H L Β instead of slow continuous perfusion had longer heartbeat periods than dogs with continuous perfusion. The presence of bicarbonate (5 μM) in hamsters has been found to help reduce acidosis after long-term termination of circulation. 1. · Anesthetize 60g hamsters with 0 · 03ml ketamine (100 mg / m 1 solution) overnight and cover them with crushed ice until the temperature of the lower rectum is about 13 ° C. Place the animal under a stereo microscope on a surgical table. The cannula was placed in the carotid artery and internal jugular vein. The Η LB solution (plus 50 mM glucose and 5 mM NaHCO3) was poured into the artery, and the venous effluent was collected. The blood was replaced with ice-cold H L Β solution. Approximately 65% of the blood was removed and the animal temperature dropped to 1 ° C. Ventilation was started when the animal temperature dropped below 10 ° C] _ 〇 〇% 〇2. Approximately 7 m 1 or 2 blood volumes are required to replace circulating blood. Plus 5 m Μ Na HC〇3 This paper size applies Chinese National Standard (CNS) A4 size (210X297 mm) (Please read the precautions on the back before filling this page) Order -40- 562678 Central Standard of the Ministry of Economic Affairs A7 B7 printed by the Bureau ’s Consumer Cooperatives V. Invention Description k) Adjust p Η to 8.5. After perfusion, the heartbeat was stopped with 0.5 m 1 to 50 m M K c 1 and 10 m M M g S04. After 4 hours and 40 minutes, the animals were reperfused with 2 ml HLB and then perfused with blood from the donor animals. Animals did not resume breathing and response. 2. In addition to 2 hours and 30 minutes after the suppression cycle, intermittent bicarbonate perfusion for 15 minutes was used to perform the above-mentioned experiment. 60 g of hamsters were banned from eating 0.03 ml of ketamine overnight, and anesthetized, and covered with crushed ice until the temperature of the lower rectum was about 13 ° C. The animals were placed on a surgical table under a stereo microscope. The cannula was placed in the carotid artery and internal jugular vein. H L B solution (plus glucose 5 OmM and 5 mM NaHC03) was perfused into the arteries and the venous effluent was collected. The blood was replaced with ice-cold H L B solution. Approximately 65% of the blood was removed and the animal temperature dropped to 1 ° C ° when the animal temperature dropped to 10%. (: Start with 100% 02 ventilation. Approximately 7 m 1 or 2 blood volumes are required to replace the circulating blood. Use an additional 5 m MH Na 3 to adjust the pH to HL of 8. 5 Β perfusion. After perfusion, the heartbeat was stopped with 0 · 5 m 1 to 50 m Μ KC 1 and 10 m Μ M g S〇4. 2 hours and

After 30 minutes, the animals were perfused with H L B for minutes (ie 2 m 1 H L B). After 4 hours and 40 m i η, reperfusion was performed with 2 m 1 H L B followed by rewarming with blood from donated animals. Animals resuscitate respiration and responsiveness. Heartbeat stopped for more than 5 hours.实施 例 11。 Example 1 1. Cryoprotectant solution 1. Prepare the solution (please read the precautions on the back before filling this page)-The size of the paper is applicable to the Chinese National Standard (CNS) A4 (21〇X297 mm) -41-562678 Α7 Β7 V. Description of the invention (39) a. Method 1 Prepare 50 ml of a 10% glycerol HLB solution, and pour 0.45 ml of HLB into a test tube. Then 5 ml of 100% glycerol was added. Shake the solution and pass through a filter of 0.2 μm or smaller. b. Method 2 Prepare 1 liter of 15% glycerol HLB: add HES60g / l, Na C 1 6 · 7 2 * g / l and adjust the volume to half of the final volume with deionized water (ie 50 0 m 1) . One chemical was sequentially added and shaken at a time to dissolve one chemical: MgCl2 · 09g / l; CaCl2 · 37g / 1; KC1 0.22g / l; glucose 0.9g / i; sodium lactate (60% syrup) 4.03ml / L; NaHC03.42g / l or 0.84g / l (extra bicarbonate helps reduce acidity). The volume was adjusted to 8 500 m 1 with deionized water. Add 150 m 1 100% glycerol. Filter through a 0.2 micron filter. * The amount of Na C 1 added is adjusted according to the amount of Na C 1 in the starch. Note: For every more than 5 OmM glucose, add 9 g / glucose and drop it.

JTU rn ~ L Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) 1. 10% glycerol / HLB solution cryoprotectant can restore some frozen hamsters to 60 g Female hamsters are banned from anaesthesia at 0 · 03 m 1 ketamine (100 mg / m 1 solution) overnight and covered with crushed ice until the temperature of the lower rectum is about 13 ° C. Place the animal under a stereo microscope on a surgical table. The cannula was placed in the carotid artery and internal jugular vein. Use 2 m 1 of ice-cold HLB solution for blood and then freeze protection with HLB plus 10% glycerol. The paper size is applicable to Chinese National Standard (CNS) A4 specification (21〇297 mm) -42- 562678 Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by Consumer Cooperative A7 B7 V. Description of Invention (40) Replacement of agent solution. A removes about 65% of the blood, and the temperature of the animal drops to 〇c. When the animal temperature dropped below 10, ventilation with 100% 02 was started. After perfusion of 5 m of the cryoprotectant solution, the heartbeat was stopped with 50 m M K c and 0 mM M g S 0 4 (丄 · 5 m 丄 L.v ·). The animals were placed in plastic bags and immersed in an ice bath of ~ 1 5 t. After 30 minutes, the rectal temperature was cooled to -2.2 ° C. The animals were thawed &apos; with HB and then reperfused with donor blood. After warming, the 'E K G signal is normal', and then breathing and reactivity return to normal. A large and intense lesion (microbleeding) was found in the brain after the anatomy of the nerves, indicating that the brain was frozen under this condition. However, the frozen animal was still able to restore responsiveness. 2.10% glycerol and 10% DMS in a cryoprotectant solution. 60 g of female hamsters were banned from eating overnight. Anesthetized with 1.03 m 1 ketamine (100 mg / m 1 solution) and covered with crushed ice until The temperature of the lower rectum is about 13 ° C. Place the animal under a stereo microscope on a surgical table. The cannula was placed in the carotid artery and internal jugular vein. Blood was replaced with 1.5 ml of ice-cold H L B solution followed by a solution of H L B plus 10% glycerol and 10% D M S0 cryoprotectant. Approximately 65% of the blood was removed and the animal temperature dropped to 1 ° C. When the animal temperature dropped below 10 ° C, aeration with 100% 02 was started. After perfusion of about 6 · 5—7 · Oml of cryoprotectant solution, use 5〇111] \ / [1 &lt; :(: 1 and 1〇111] \ / 1] \ / 1 to stop the heartbeat (1 · 5 m 1 i · v ·) ° Put the animals in plastic bags and immerse them in an ice bath at -1 5 ° C. After thawing with HLB and then donor blood and reperfusion, 'recover the original paper standards applicable_Home Standards (CNS ) Α4 specification (21QX 297 reading) -43-(Please read the precautions on the back before filling this page)

562678 A7 _ B7 V. Description of the Invention (4) Gastric heartbeat, breathing, and responsiveness. A large amount of severe damage (micro-bleeding) was found in the brain after neurodissection, indicating that the brain was frozen under this condition. However, the frozen animal was still able to recover its reactivity. All announcements and patent applications mentioned in this specification are hereby incorporated by reference in their entirety, and each announcement or patent application is deemed to be clear and individually displayed and incorporated herein by reference. Any reference cited is intended to be a disclosure of a prior application date and is not a denial of the invention based on the previous invention. Although the foregoing invention has been described in detail with examples and embodiments so that it can be understood clearly, for those of ordinary skill in the art, certain changes and improvements can be made to the invention with the scope of the attached patent application without departing from its principles or category. (Please read the precautions on the back before filling this page) Order 丨 # · Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs -44- This paper size applies to China National Standard (CNS) A4 (210X297 mm)

Claims (1)

562678 A8 B8 C8 D8 VI. Scope of patent application Annex II (A): See ^ Announcement No. 87 1 1 8863 Patent Application Chinese Application Patent Scope Replacement of the Republic of China January 24, 1992 Amendment 1. A physiologically acceptable An aqueous solution comprising: an electrolyte; a power buffer system; and at least one swelling agent, which is a weight fraction of an initial source of swelling agent, wherein the weight fraction ranges from 50,000 to 1,000,000 Daltons; wherein the solution contains magnesium, At least two of sugars and swelling agents of medium or high molecular weight, not more than 50 mM, and the solution does not contain biological buffers (please read the precautions on the back before filling this page) Printed by the Consumer Cooperative A8 B8 C8 D8 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 562678 6. Containing cryoprotectants outside the scope of patent applications. 6. The solution according to item 1 or 2 of the scope of patent application, wherein the swelling agent is a polysaccharide. 7. The solution according to item 1 or 2 of the patent application, wherein the polysaccharide is hydroxyethyl starch. 8. The solution according to item 7 of the application, wherein the hydroxyethyl starch is a medium molecular weight hydroxyethyl starch. 9. The solution according to item 7 of the patent application, wherein the hydroxyethyl starch is a high molecular weight hydroxyethyl starch. 10. The solution according to item 8 in the scope of patent application, wherein the hydroxyethyl starch has 6 to 7 hydroxyethyl groups per 10 monomer units, and the concentration of the hydroxyethyl starch is 2 to 8%, wherein the solution The contained glucose does not exceed 5 OmM 〇1 1 · As the solution in the scope of the patent application No. 8 wherein the hydroxyethyl starch has 4 to 5 hydroxyethyl groups per 10 monomer units, and its concentration is It is 2 to 8%, wherein the solution contains glucose not exceeding 5 Om Μ 〇 1 2 · As in the solution of the patent application No. 13 item, wherein the hydroxyethyl starch has 7 ~ per 10 monomer units 8 hydroxyethyl groups, and its concentration is 2 to 8%, wherein the solution contains glucose not exceeding 50 m Μ03. For the solution of item 1 or 2 of the patent application scope, wherein the electrolyte contains sodium , Potassium, calcium, chloride and magnesium. 1 4 · If you apply for the solution of item 1 or 2 in the scope of patent application, the paper size of the solution is applicable to China National Standard (CNS) A4 specification (210 × 297 mm) TiT (Please read the note on the back before filling in this page) 562678 A8 B8 C8 D8 6. Scope of patent application In addition, it contains clotting factors. 15. The solution according to item 1 or 2 of the scope of patent application, which is used as a plasma substitute solution in the host's circulatory system or a part thereof. 16. The solution according to claim 1 or 2, wherein the swelling agent is a low or medium molecular weight swelling agent. (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs -3-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)