WO2023123994A1

WO2023123994A1 - Sodium carboxymethyl starch and injection thereof

Info

Publication number: WO2023123994A1
Application number: PCT/CN2022/104064
Authority: WO
Inventors: 施卫群
Original assignee: 施卫群
Priority date: 2021-12-28
Filing date: 2022-07-06
Publication date: 2023-07-06
Also published as: CN114053422A

Abstract

The present invention relates to a sodium carboxymethyl starch and an injection thereof, a preparation method for a sodium carboxymethyl starch and an injection thereof, and a use for preparing blood substitutes. The sodium carboxymethyl starch described in the present invention is a sodium carboxymethyl starch having a molecular weight of 151,000-420,000, a conductivity meter substitution degree of 0.1-1.1, a specific rotation of 185-198, and an intrinsic viscosity of 20-45, and can be used to prepare blood substitutes. The preparation method for the sodium carboxymethyl starch and the sodium carboxymethyl starch injection in the present invention is simple and convenient, economical and suitable for industrial production.

Description

Sodium Carboxymethyl Starch and Its Injection

technical field

The present invention relates to a kind of carboxymethyl starch sodium and its injection, manufacturing method and application thereof.

Background technique

Scientists from all over the world are looking for a plasma substitute that can safely increase blood volume, also known as plasma volume expander, which is a commonly used volume supplement in clinical practice. After administration, it can increase blood volume and temporarily maintain blood pressure. It is used to treat shock or hemorrhagic disease caused by massive bleeding, burns or other trauma, and to prevent circulatory disorders and microcirculation disorders caused by low blood volume. Reduced blood flow and oxygen supply eventually lead to organ failure. At present, the plasma volume expanders commonly used clinically at home and abroad are divided into crystalloids and colloids.

The main components of crystalloid are water and electrolyte, which is a solution of small molecules, and the diameter of solute particles is less than 1nm. Clinically, crystalloid is one of the basic resuscitation fluids used to correct water and electrolyte deficiency after blood and body fluid loss. Its main function is to replenish functional extracellular fluid, maintain a relatively stable internal environment (pH and crystal osmotic pressure), increase glomerular filtration rate, replenish circulating blood volume and maintain urine output to a certain extent.

After the crystalloid is injected, electrolytes and water can be distributed inside and outside the blood vessel according to the composition of the body fluid. Most of the crystalloid seeps out from the blood vessel to the extravascular tissue space quickly, 25% is distributed in the blood vessel, and 75% is distributed outside the blood vessel. Therefore, when crystalloid is used to supplement blood loss and expand blood vessel volume, the volume of crystalloid input is required to be 3 to 4 times the blood loss.

Crystalloids are divided into isotonic and hypertonic. The osmotic pressure of normal human plasma is 280-320mmoI/L, which is called hypertonic when the osmotic pressure of normal human plasma is 320mosm/L. Isotonic crystalloids commonly used in clinical practice mainly include normal saline, Ringer's solution, lactated Ringer's solution and sodium acetate Ringer's solution, and their osmotic pressures are all within the normal plasma osmotic pressure range. The hypertonic crystalloid used clinically is mainly 7.5% sodium chloride solution with an osmotic pressure of 2400mosm/L.

Colloid is a macromolecular substance with a diameter of solute particles ranging from 1 to 100 nm. It is difficult to pass through the capillary wall. The particles remain in the blood vessels to generate colloid osmotic pressure, and the liquid is retained in the blood vessels, thereby increasing and effectively maintaining blood volume. Colloids are divided into various natural colloids and synthetic colloids derived from blood plasma. The natural colloid commonly used clinically is mainly human serum albumin, and the artificial colloid mainly includes gelatin, dextran and carboxyethyl starch.

The relative molecular weight of albumin is relatively high, and the speed of permeating the membrane is relatively slow, so that the osmotic pressure of albumin colloid and the static pressure of capillaries are balanced, so as to maintain a normal and constant blood volume. At the same time, 1g of albumin in the blood circulation can Retain 18mL of water to increase circulating blood volume and maintain plasma colloid osmotic pressure. Albumin is "natural" and has long been considered the most beneficial colloid for patients. It has been widely used in the past and is often used as the gold standard for evaluating other colloids. However, after 1998, the clinical application of albumin was full of controversy. Until 2004, a multi-center controlled, randomized double-blind clinical trial called SAFE (Saline versus Albumin Fluid Evaluation) carried out in Europe, published in the New England Journal, became an important milestone in the evaluation of albumin effects. The results of this study confirmed that, compared with normal saline, 4% albumin expansion therapy did not increase the 28-day mortality of critically ill patients. So far, the safety of albumin for volume expansion therapy in critically ill patients has been affirmed. The US FDA also revoked the warning on albumin, and the prescription volume of albumin returned to the level before 1998. However, compared with other resuscitation solutions, the source of albumin is limited, the price is higher, and the advantage in effect is not obvious.

Dai Lianbao and Shi Weiqun invented a sodium carboxymethyl starch sodium chloride injection (ZL031155243) with a molecular weight of 0.5-150,000 and sodium carboxymethyl starch and a degree of substitution of 0.1-1.0 and its injection. Blood red blood cells and white blood cells, white blood cells can treat cancer after chemotherapy to supplement white blood cells in red blood cells have the function of carrying oxygen. Because carboxymethyl starch sodium sodium chloride injection is added in the blood, red blood cells are deformed and can treat diseases such as vasculitis and cerebral infarction. And acid-base balance plays a very important role in blood transfusion patients.

Contents of the invention

The object of the present invention is to provide a kind of sodium carboxymethyl starch and injection thereof.

The object of the present invention also provides a kind of configuration method of above-mentioned sodium carboxymethyl starch and injection thereof.

Another object of the present invention is to provide a kind of purposes of above-mentioned sodium carboxymethyl starch and injection thereof.

The sodium carboxymethyl starch of the present invention has a molecular weight of 151,000-420,000; a conductivity meter substitution degree of 0.1-1.1; a specific rotation of 185-198; and an intrinsic viscosity of 20-45. The recommended molecular weight is 151,000-360,000, especially sodium carboxymethyl starch with a molecular weight of 200,000-360,000.

The raw material sodium carboxymethyl starch with a molecular weight of 190,000-440,000 is configured into the original drug powder or slurry: the raw material sodium carboxymethyl starch is added to distilled water and spray-dried to make a powder; the raw material powder or slurry sodium carboxymethyl starch is added Distilled water is freeze-dried to make powder; raw material powder or paste sodium carboxymethyl starch is purified by adding ethanol, and alcohol is removed to make paste or powder.

Use distilled water to configure the above-mentioned original drug slurry or powder original drug into the injection solution of the following weight percentages: sodium carboxymethyl starch 3%-6%, add activated carbon 0.1%-3%, sodium chloride 0.6%-1.2%, The rest is distilled water; the recommended weight of sodium carboxymethyl starch is 4%-5%. After mixing, decolorize, the decolorization temperature is 70°C-110°C, and the time is 40 minutes-90 minutes. Filtrate through a sand rod or a titanium rod to remove activated carbon, so that the concentration of sodium carboxymethyl starch in the solution reaches 4.5%-6%. Adjust the pH value to 5-7, the recommended pH is 5.5-6.5, and then filter through micropores for canning, and then sterilize (120 degrees Celsius, 30 minutes) (Fo>12), or the original drug slurry or powder It is diluted with physiological saline and configured to be sodium starch glycolate injection containing 5-6.

Further say that above-mentioned sodium carboxymethyl starch powder or its slurry are made former medicine and adopt following three kinds of methods to obtain sodium carboxymethyl starch injection of the present invention:

Decolorize the powder or the slurry that has been evaporated to remove alcohol with activated carbon, filter, configure 3%-6% by weight sodium carboxymethyl starch injection with distilled water, add 0.7%-0.8% by weight sodium chloride solution, and adjust the pH of the solution Value to 5.5-6.5 filtration, sterilization;

Carboxymethyl starch sodium powder or slurry becomes solid after freeze-drying, and it is made into a 3%-6% carboxymethyl starch sodium solution, and activated carbon is added to filter through a sand rod or a titanium rod, and the solution concentration is adjusted to 5% with distilled water , adding 0.8% sodium chloride solid, adjusting the pH value of the solution to 5.5-6.5, filtering, bottling and sterilizing;

Sodium carboxymethyl starch powder or slurry is solidified with 95% ethanol solution, configured into a 3%-6% sodium carboxymethyl starch solution with distilled water, dealcoholized, decolorized with activated carbon, filtered, and the concentration of the solution is adjusted to 3% by weight -6%, 5% is recommended, after adding 0.7%-0.8% sodium chloride solution, adjust the pH value of the solution to 5.5-6.5, then filter through an acrylic membrane, and sterilize after bottling.

The carboxymethyl starch sodium sodium chloride and its injection solution of the present invention can not only be used to prepare blood substitutes, but also can increase the release of oxygen. It has a certain protective effect on kidney tissue, and has a certain effect on maintaining tissue oxygen supply under the state of blood loss. Positive effect, can safely increase blood volume, and has the function of carrying oxygen, which can be used instead of blood. Moreover, the production method is simple and economical, and is suitable for industrialized preparation of blood substitutes.

Description of drawings

Fig. 1. Hepatic HE staining diagram when the HCT of the control group was 25% (liver pair 25%).

Fig. 2. Hepatic HE staining diagram when the HCT of the control group was 50% (liver pair 50%).

Fig. 3. Hepatic HE staining diagram when HCT75% (liver pair 75%) in the control group.

Fig. 4. Hepatic HE staining diagram when the HCT of the experimental group was 100% (liver 1).

Fig. 5. Hepatic HE staining diagram when HCT75% (liver 2) of the experimental group.

Fig. 6. Hepatic HE staining diagram at HCT50% (liver 3) of the experimental group.

Fig. 7. Hepatic HE staining diagram when HCT 25% (liver 4) in the experimental group.

Fig. 8. Transmission electron micrographs of the kidneys in the control group when HCT was 25%.

Fig. 9. Transmission electron micrographs of the kidneys in the control group when HCT was 50%.

Fig. 10. Transmission electron micrographs of the kidneys in the control group when HCT was 75%.

Fig. 11 is a transmission electron micrograph of the kidney in the experimental group when HCT was 25%.

Fig. 12 is a transmission electron micrograph of the kidney at HCT50% of the experimental group.

Fig. 13 is a transmission electron microscope image of the kidneys in the experimental group when HCT was 75%.

Fig. 14 is a transmission electron micrograph of the kidney when HCT is 100%.

Fig. 15 is a transmission electron microscope image of the liver in the control group when HCT was 25%.

Fig. 16 is a transmission electron micrograph of the liver when HCT50% of the control group.

Fig. 17 is a transmission electron micrograph of the liver in the control group when the HCT was 75%.

Fig. 18 is a transmission electron microscope image of the liver in the experimental group when HCT was 25%.

Fig. 19 is a transmission electron micrograph of the liver when HCT50% of the experimental group.

Fig. 20 is a transmission electron microscope image of the liver in the experimental group when HCT75%.

Fig. 21 is a transmission electron micrograph of the liver when HCT is 100%.

Specific implementation method

The sample that adopts in the embodiment:

Sodium carboxymethyl starch injection of the present invention.

Hydroxyethyl starch 130/0.4 sodium chloride injection (HES 130), produced by Beijing Fresenius Kabi Pharmaceutical Co., Ltd.

Hydroxyethyl starch 200/0.4 sodium chloride injection (HES 200), produced by Beijing Fresenius Kabi Pharmaceutical Co., Ltd. Or 200 carboxymethyl starch sodium sodium chloride injection (CMS200), produced by Shanghai Changzheng Fumin Jinshan Pharmaceutical Co., Ltd.

Hydroxyethyl starch 40 sodium chloride injection (706 generation plasma), produced by Shandong Qidu Pharmaceutical Co., Ltd.

Carboxymethyl starch sodium sodium chloride injection (CMS120), produced by Shanghai Changzheng Fumin Jinshan Pharmaceutical Co., Ltd. The following examples will help to understand the present invention, but do not limit the content of the present invention.

Example 1

Commercially available raw material sodium carboxymethyl starch powder or slurry (usually the molecular weight of sodium carboxymethyl starch is 190,000-420,000) liquid is configured into a 3%-6% sodium carboxymethyl starch solution, and the solution is evaporated by distillation. of alcohol. Use an instrument to measure and confirm that the solution does not contain alcohol or contains a small amount of alcohol. Then add activated carbon, heat and heat to 100°C for decolorization, and then filter through a sand rod or titanium rod to meet the requirements of the injection to obtain the original drug sodium carboxymethyl starch. Configured as 5% sodium carboxymethyl starch injection, add 0.7%-0.8% sodium chloride solution, adjust the pH value of the solution to 5.5-6.5, then filter through an acrylic membrane, and carry out 15 days at 110°C after bottling. Sterilize in minutes to obtain a product with a conductivity meter substitution degree of 0.1-1.1; a specific rotation of 185-198; an intrinsic viscosity of 20-45 and a molecular weight of 15.1-350,000.

Example 2

The raw material liquid sodium carboxymethyl starch powder or slurry is freeze-dried to become a solid, configured into a 3%-6% sodium carboxymethyl starch solution, added activated carbon and filtered through a sand rod or a titanium rod, and the concentration of the solution is adjusted to 5% %. Add 0.8% sodium chloride solid to adjust the pH value of the solution to 5.5-6.5. Then the solution was filtered through an acrylic membrane to prepare 5% carboxymethyl starch sodium sodium chloride injection. After bottling, it is sterilized for 15 minutes under an environment of 110° C. to obtain a finished product.

Example 3

The raw material carboxymethyl starch sodium powder or slurry is solidified with 95% ethanol solution, and the solid is configured into a 3%-6% carboxymethyl starch sodium solution, alcohol is removed, and activated carbon is added to filter through a sand rod or a titanium rod. The solution concentration was adjusted to 5%. After adding 0.7%-0.8% sodium chloride solution, adjust the pH value of the solution to 5.5-6.5. Then the solution was filtered through an acrylic membrane to prepare 5% sodium carboxymethyl starch injection. After bottling, it is sterilized for 15 minutes under an environment of 110° C. to obtain a finished product.

The mensuration of embodiment 4 molecular weight and molecular weight distribution

Using chromatograph: Agilent 1260,

Chromatographic column: shodex SB-804, measuring range <1 million,

Detector: Wyatt laser light scattering instrument, DAWN HELEOS II; Wyatt differential detector, OPtilabrex,

experimental method

Dilute the sample concentration to 2mg/ml, inject 100ul,

Mobile phase: 0.9% Nacl+0.02% NaN3.

Flow rate: 0.500ml/min,

Detection wavelength: 663.6nm,

Temperature: room temperature,

Recording raw material liquid carboxymethyl starch sodium molecular weight is 41-42 ten thousand, and the carboxymethyl starch sodium molecular weight of the present invention after its purification is recorded as 290,000 carboxymethyl starch sodium (P50 is 46.02).

The measurement results show that the molecular weight of the raw material is higher than that of the original drug in the corresponding injection solution of the present invention.

The detection of five basic quality control items of embodiment 5

1. Determination of pH value of different injections

The pH value test results of sodium carboxymethyl starch injection of the present invention and commonly used artificial colloid resuscitation fluid are shown in Table 2.1

Table 2.1 pH value of different injection solutions

2. Crystal Osmolality Determination

Adopt Model-210 type crystal osmotic pressure instrument (Fiske company, the United States); Crystal osmotic pressure instrument detects sample tube (Fiske company, the United States)

The powder sodium injection osmotic pressure detection result of the present invention is as table 2.2

Table 2.2 Crystal osmotic pressure values of different injection solutions, the above values are in mOsm/kg

3. Determination of Plasma Viscosity

Determination of Viscosity of Carboxymethyl Starch Sodium Sodium Chloride Injection and Human Plasma by Capillary Viscometer

Using LBY-BX type blood rheometer (Prison Instruments Co., Ltd., Beijing, China);

HDB-1 constant temperature heater (Wu Nuosi Technology Co., Ltd., Beijing, China); several EP tubes.

The viscosity testing results of three kinds of Suan methyl starch sodium sodium chloride injection and healthy human plasma are as follows:

Table 2.3 Viscosity measurement values of different injection solutions, the above values are in mPa.s

Measuring Viscosity of Several Injections by Suspension Viscometer

Adopt BT-300 suspension wire blood viscometer (Bright Technology Co., Ltd., Beijing, China);

The measurement results are as follows:

Table 2.4 Viscosity measurements of different injections

Carboxymethyl starch sodium sodium chloride injection of the present invention and 706 generations of blood plasma five basic quality control items detection data are summarized in table 2.5 as follows:

Example 6 Preliminary Experiment of Drug Efficacy Evaluation under the Blood Dilution Model

The slurry form of the raw material sodium carboxymethyl starch is spray-dried into a solid, and the solid is used to form a 3%-4% sodium carboxymethyl starch solution. Add activated carbon and filter through a sand rod or titanium rod to adjust the concentration of the solution to 5%. After adding 0.7%-0.8% sodium chloride solution, adjust the pH value of the solution to 5.5-6.5. Then the solution was filtered through an acrylic membrane to prepare 5% sodium carboxymethyl starch injection. After bottling, it was sterilized at 110° C. for 15 minutes to obtain the sodium carboxymethyl starch injection of the present invention.

CMS120 Two Carboxymethyl Starch Sodium Injections and the Carboxymethyl Starch Sodium Injection of the Present Invention Preliminary Experiments for Drug Efficacy Evaluation under the Blood Dilution Model

Experimental animals: Beagle weighing 7-12kg, 8 male dogs, from the Experimental Animal Center of the Academy of Military Medical Sciences.

Drug samples to be tested:

Sodium carboxymethyl starch injection of the present invention.

CMS120 Carboxymethyl Starch Sodium Injection (CMS120) was provided by Shanghai Langyou Biotechnology Co., Ltd.

Hydroxyethyl starch 130/0.4 sodium chloride injection (Fresenius Kabi Deutschland GmbH, trade name: Wanwen or HES130), 0.9% sodium chloride injection: sodium pentobarbital, Beijing Chemical Reagent Company, chemically pure.

Pulse index continuous cardiac output monitoring equipment, referred to as PICCO (PULSION, Germany); tissue oxygen partial pressure detection equipment system (POG-203, Japan): 2-16PK ultracentrifuge (Sigma, the United States); ABL90co-ox blood gas Analyzer (RADIOMETER company, Denmark); MoorLAB laser Doppler blood flowmeter (Moor instruments Led, UK); LBY-N6B full-featured automatic blood rheometer (Beijing Prism Instrument Co., Ltd., China); 4420 colloid Osmometer (Wescor, USA); HEMAVET950 hematology analyzer (DREW, USA); liquid chip system (Luminex 200, Germany); automatic biochemical analyzer (Hitachi 7020, Japan). HEMOX™-ANALYSER (TCS Scientific Corp, USA).

Preparation and Pharmacodynamic Observation of Beagle Animal Model

1. Anesthesia and surgery

① Anesthesia: Beagle dogs were weighed and anesthetized with 3% pentobarbital sodium solution (1 mL/kg) via the superficial vein of the forelimb.

②Operation: After anesthesia, the limbs were fixed in the supine position, and the right jugular vein, right femoral vein and bilateral femoral arteries were separated. One femoral artery was cannulated for blood loss, the femoral vein was cannulated for fluid reinfusion, and the other femoral artery was cannulated for monitoring hemodynamics and other physiological indicators. The right jugular vein was used for mixed venous blood gas collection and cold saline injection. Stable for 10 minutes after the operation, record physiological indicators, and take 0.5 ml of arterial and venous blood to measure blood gas indicators, take 125mm ³ tissue blocks for HE staining section analysis and transmission electron microscopy, then perform bloodletting and fluid replacement, and repeat at the next blood collection point operate.

2. Preparation of acute hemodilution model

Prepare the acute isovolemic hemodilution model, which is divided into three steps for blood dilution. The first step is to reduce the hematocrit to 75% of the base value, the second step is to reduce the hematocrit to 50% of the base value, and the third step is to reduce the hematocrit to 50% of the base value. The capacity is reduced to 25% of the base value. Experimental Grouping Experiments were divided into two groups. In the experimental group, the experimental animals were infused with an equivalent amount of sodium carboxymethyl starch injection of the present invention after losing blood. In the control group, the experimental animals were infused with the same amount of normal saline injection after blood loss. At each hypoxic point, the maximum respiratory rate, blood pressure, arterial pressure, and central venous pressure were recorded.

①Normal saline group (control group);

3. sodium carboxymethyl starch injection group (experimental group) of the present invention

The influence of the sodium carboxymethyl starch injection of the present invention on the oxygen dissociation curve under the state of blood loss, and the histological changes under the same ischemia state. The results of the dog experiment show that the experimental drug can effectively maintain the animals under different degrees of blood loss (HCT is 75%, 50% and 25%). The oxygen dissociation curve in venous blood presents a curve shifting to the right in the state of massive blood loss. The reason why HCT is chosen as the parameter point is because in the state of blood loss, HCT can more accurately reflect the amount of blood loss. In the study, each group was compared Unified reference point.

Determination of pH value, oxygen partial pressure, oxygen saturation, carbon dioxide molecular pressure. The experimental data are as follows:

A represents arterial blood. V indicates venous blood.

Experimental group sodium carboxymethyl starch injection of the present invention arterial blood data (respiratory frequency 15 times/min, dog body weight 7KG)

The venous blood data of experimental group sodium carboxymethyl starch injection of the present invention Respiratory frequency 15 times/min

Control group arterial blood data Dog weight 10KG

Control group venous blood data Dog weight 10KG

Dog experiment result shows: sodium carboxymethyl starch injection of the present invention, (HCT is respectively 75%, 50% and 25%) maintenance tissue oxygen supply has certain positive effect under the state of blood loss in various degrees, can more effectively maintain Animals, in the state of blood loss (HCT were 75%, 50% and 25% respectively, the histological changes of the animals are shown in Figure 1-21.

Figure 1-3 is the control group B (liver, HCT25%): individual liver cells with mild watery degeneration, no necrosis, a small amount of lymphocyte infiltration, and mild inflammatory changes. Figure 4-7 is the experimental group A (liver tissue): the liver cell structure is basically normal.

Fig. 8-10 is contrast B group (HCT is respectively 25%, 50%, 75%) kidney transmission electron micrograph, foot process fusion, endothelial cell swelling, mitochondrial swelling; Fig. 18-21 is experimental group (HCT25%, 50%) , 75%) kidney transmission electron microscope, foot process fusion, swelling of endothelial cells.

Figures 11-13 are transmission electron micrographs of livers in control group B (HCT 25%, 50%, and 75%), showing swelling of liver cells, swelling of mitochondria, vacuoles and glycogen particles. Figures 14-17; Experimental group A (HCT 25%, 50%, 75%): swelling of liver cells, swelling of mitochondria, vacuoles, and no glycogen particles.

The experimental results also show that the medicament of the present invention has a certain protective effect on the tissue under the state of blood loss.

The experimental results show that: Beagle dog hemodilution model is relatively stable, controllable, suitable for evaluating the role of plasma substitutes. The result shows that the injection solution of the present invention has obvious anti-shock effect under the state of acute blood loss of a certain amount, and can change hypervolemia (raise blood pressure) simultaneously. It can more effectively maintain the oxygen dissociation curve in arterial and venous blood, and has a certain protective effect on tissues.

Claims

A sodium carboxymethyl starch and an injection thereof, characterized in that the molecular weight of the original drug sodium carboxymethyl starch is 151,000-360,000.
Carboxymethyl starch sodium and injection thereof as shown in claim 1, it is characterized in that described carboxymethyl starch sodium injection has the material composition of following percentage by weight: former drug carboxymethyl starch sodium 3%-6 %, sodium chloride 0.6%-1.2%, the rest is distilled water, and the pH value is 5.5-6.5; the molecular weight of the original drug carboxymethyl starch sodium is 151,000-420,000, and the conductivity meter substitution degree is 0.1-1.1, Specific rotation 185-198, intrinsic viscosity 20-45.
A kind of preparation method of sodium carboxymethyl starch as described in claim 1 or 2 and injection thereof, it is characterized in that the former medicine as described in claim 1 or 2 is that raw material sodium starch glycolate powder adopts following The above method is obtained:

The raw material carboxymethyl starch sodium is added with distilled water and spray-dried to make a powder; or the raw material carboxymethyl starch sodium is added with distilled water and then freeze-dried to make a powder; The original drug is made of sodium carboxymethyl starch.
Want 1 or 2 described carboxymethyl starch sodium and the preparation method thereof injection, it is characterized in that the preparation method of described injection: the former medicine of carboxymethyl starch sodium as claimed in claim 3 The physiological saline is diluted and configured to be sodium starch glycolate injection containing 5-6%.
Want 1 or 2 described sodium carboxymethyl starch and the preparation method thereof injection, it is characterized in that the preparation method of described injection:

The raw material sodium carboxymethyl starch is decolorized with activated carbon, filtered, and distilled water is used to form a sodium chloride solution containing 3%-6% by weight of the original drug and 0.7%-0.8% by weight, and the pH value of the solution is adjusted to 5.5-6.5 for filtration , bottling sterilization;

Or the raw material sodium carboxymethyl starch becomes solid after freeze-drying, and it is made into a 3%-6% sodium carboxymethyl starch solution, and activated carbon is added to filter through sand rods or titanium rods, and the concentration of the solution is adjusted to 5% with distilled water. 0.8% sodium chloride solid, adjust the pH value of the solution to 5.5-6.5, filter, bottle and sterilize;

Or the raw material sodium carboxymethyl starch is solidified with 95% ethanol solution, configured with distilled water to form a 3%-6% sodium carboxymethyl starch solution, dealcoholized, decolorized with activated carbon, filtered, and the concentration of the solution is adjusted to 3%-6% by weight After adding 0.7%-0.8% sodium chloride solution, adjust the pH value of the solution to 5.5-6.5, then filter through an acrylic membrane, and sterilize after bottling.
A kind of sodium carboxymethyl starch as claimed in claim 1 or 2 and injection thereof are used for preparing blood substitute.
The sodium carboxymethyl starch obtained by the method as claimed in claim 3, 4, 5 or 6 and injection thereof are used for preparing blood substitute.