CN1042474A - Pectin plasma substitute and preparation method - Google Patents

Pectin plasma substitute and preparation method Download PDF

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Publication number
CN1042474A
CN1042474A CN 88109696 CN88109696A CN1042474A CN 1042474 A CN1042474 A CN 1042474A CN 88109696 CN88109696 CN 88109696 CN 88109696 A CN88109696 A CN 88109696A CN 1042474 A CN1042474 A CN 1042474A
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Prior art keywords
pectin
plasma substitute
preparation
weight concentration
water
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CN 88109696
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于绍津
乐凤瑞
牟清华
杨群昌
杨卫东
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MEDICINES RESEARCH CENTER JINAN MILITARY REGION
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MEDICINES RESEARCH CENTER JINAN MILITARY REGION
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Priority to CN 88109696 priority Critical patent/CN1042474A/en
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Abstract

A kind of pectin plasma substitute and preparation method, it is characterized in that the comminuted plants fruit soaked with cold sour water and hot-pressing processing after transfer its pH value with aqueous alkali, it is formulated to add inorganic salt, glucose, water for injection again with the refining repeatedly pectin that obtains of organic alcohol, ion exchange resin, few, the good water solubility of impurity is arranged, the advantage that be not subjected to the blood group restriction in use, production technology is easy, cost is low, has no side effect, can be widely used in clinical injection, rescue all kinds of shock patients etc.

Description

Pectin plasma substitute and preparation method
The present invention relates to medical supplies, say so in more detail about being raw material, through pectin plasma substitute and the preparation method that is used to inject blood plasma substitute after the processed with the plant gum that contains in the fruit.
Known in fruit, as Fructus Mali pumilae, Fructus Citri grandis, Fructus Caricae, Fructus Jujubae, pears, Fructus Crataegi, Fructus Vitis viniferae, certain herbaceous plants with big flowers dish etc., contain a kind of material that is called pectin, its basic chemical structure formula is
Figure 881096962_IMG1
Molecular weight is generally between 10000-400000.This high molecular weight pectin matter, a class is low-molecular-weight, lower molecular weight, the mixing pectin of higher molecular weight through obtaining after the hydrolysis process, generally can be used for fresh-keeping, beverage of food-processing industry, food etc., and can be used for the pectin of medical supplies, the pectin that especially can be used for blood plasma substitute, because require quality height, the narrow range of molecular weight requirement, impurity few, preparation technology is strict, so never be widely used clinically.Hartman utilizes pectin as blood plasma substitute as far back as nineteen forty-one with regard to suggestion, though the animal hemorrhagic shock is had good curative effect, when a large amount of and quick the input, can cause vomiting, also have cumulative toxicity in various degree.Its shortcoming mainly is because gained pectin product purity is low, range of molecular weight distributions is big, esterification degree is low, poorly water-soluble.
Present inventors through studying with keen determination, find that the fruit with plant is a raw material in order to solve above-mentioned shortcoming, carry out merceration, heat with diluted acid water and carry, make with extra care and can obtain the pectin plasma substitute of excellent performance, so far finished the present invention.
Promptly the purpose of this invention is to provide a kind of pectin plasma substitute that can be used for clinical use, do not have irritated reaction, ametaboly reaction in use, do not have and accumulate the pectin plasma substitute of toxication phenomenon, no transfusion reaction.
Second purpose of the present invention provides a kind of raw material wide material sources, production technology is easy, cost the is low pectin plasma substitute preparation method with pectin.
The 3rd purpose of the present invention for all kinds shock patients such as losing blood property of rescue provide a kind of be not subjected to blood group restriction, should be acute strong, can be prefabricated, store, transportation, pectin plasma substitute safe in utilization, effective.
In order to achieve the above object, the present invention is achieved in that
In sterilization container, add
(a) weight concentration is 0.5~1.5% pectin,
(b) weight concentration is 0.80~1.0% butter,
(c) weight concentration is 0.09~1.2% glucose
(d) transferring its pH value is 3.5~5.5
Use water for injection formulated then.
Employed pectin has plant pectins such as apple pectin, pomelo-pectin, Fructus Chaenomelis pectin, zizyphus pectin, certain herbaceous plants with big flowers dish pectin, melonidum glue, hawthorn pectin in pectin plasma substitute of the present invention, and what generally use is apple pectin.
Prepare sodium chloride that the employed inorganic salt of pectin plasma substitute of the present invention is an injection, potassium chloride, calcium chloride, magnesium chloride etc., general what use is sodium chloride.
Employed plant pectin is preparation like this among the present invention:
(a) at first fruit is pulverized, the acidic aqueous solution that adds 0.1~1.2% weight concentration of 1~6 times of fruit weight in the comminuted plants fruit soaked 30~720 minutes,
(b) be that 105~130 ℃, pressure are 0.1~2kg/cm in temperature 2Condition under carry out hot-pressing processing, separate solution and residue after the hot-pressing processing then,
(c) transferring the pH value of separation solution with aqueous alkali is 3.0~5.4,
(d), get final product to such an extent that be used for the pectin of plasma substitute with the refining repeatedly separation solution of activated carbon, organic alcohol, ion-exchange resin.
The employed aqueous alkali of preparation pectin is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and its weight concentration is 4~32%.
When the hydrolysis separation solution of refining pectin, employed organic alcohol is methanol, ethanol, propanol, generally use is ethanol.
At refining pectin, the employed water of preparation pectin plasma substitute is water for injection.
Pectin plasma substitute by method preparation of the present invention, have that molecular weight ranges is narrow, impurity is few, good water solubility, determined curative effect, safety is big, it is acute strong not to be subjected to blood group to limit, answer in use, can be prefabricated, storage, transportation, production technology is easy, cost is low advantage, can be widely used in clinical rescue all kinds shock and prophylactic treatment coronary heart disease etc.
The present invention give further instruction in order to illustrate better below by embodiment.
Embodiment 1
Take by weighing and spend 141.35 kilograms of skin Fructus Mali pumilaes, 170 liters of the aqueous hydrochloric acid solutions of adding 0.5% after pulverizing are in the enamelled vessel of packing into, at 105 ℃ of temperature, pressure 0.2kg/cm 2Condition under, handled 40 minutes, adjusting pH value with 10% sodium hydroxide solution then is 5.2, removing impurities makes to contain amount of alcohol and reach 52% precipitation glue.The pectin of crude product adds 2 times of water dissolutioies, and reuse cation exchange resin post is made with extra care, and purified pectin is through dewatering, be drying to obtain the pectin that the pectin plasma substitute is used, its [η] NaCl65.0, M18082, [α] 25 D233.53 ,-OCH 38.75%, E 1% 5cm0.193.
Embodiment 2
Take by weighing 84.55 kilograms of Pyrus ussuriensis var.Ovoidea, pulverize the back and add 93 liters of 1.0% aqueous hydrochloric acid solutions, in the rustless steel container of packing into, at 130 ℃ of temperature, 2kg/cm 2The condition of pressure under handled 15 minutes, be 5.4 with 5% sodium hydroxide solution adjust pH then, removing impurities, other treatment conditions are with embodiment 1, its [η] NaCl67.0 of the pectin that obtains, M18526, [α] 25 D236.31 ,-OCH 38.58%, E 1% 5cm0.124
Embodiment 3
Take by weighing 84.55 kilograms of Guoguang apples, other treatment conditions are with embodiment 1, its [η] NaCl77.6 of the pectin that obtains like this, M20835[α] 25 D233.61, E 1% 5cm0.135.
Embodiment 4
Get that handle, calyx, seed are cleaned, gone to Fructus Crataegi, 1000 grams of weighing add 2000 milliliters of 0.4% aqueous hydrochloric acid solutions, merceration was 110 ℃ in temperature after 12 hours, pressure 0.4kg/cm 2Condition under hot pressing 25 minutes, filter cleaner, transfer its pH value 5.2 with 10% sodium hydrate aqueous solution then, leave standstill removing impurities after 4 hours, mother solution adds ethanol to be made solution contain amount of alcohol to reach 54%, purify through separating gel, refining by cation exchange column, separating and dehydrating is drying to obtain pectin plasma substitute pectin.
Embodiment 5
630 gram sodium chloride and calcium chloride 23 grams, potassium chloride 21 grams, glucose 77 are restrained; and to transfer to pH value be 4.0; be dissolved in the full dose water for injection, take out 200 milliliters and make diluent, add pectin 882 grams that embodiment 1 obtains; be warming up to 80 ℃; add grain active carbon 560 grams, stirred 10 minutes, complement to 70000ml with water for injection; after filtration after the assay was approved, packing, aseptic process, get final product.
Embodiment 6
With pectin 1512 grams of embodiment 2, other conditions are with embodiment 5.
Comparative example 1
Get apple slice, be dipped in the distilled water, and boiled 7 hours at 100 ℃, immersion is filtered and evaporation and concentration, then by the ethanol precipitation of 1: 1 ratio adding 96%.Precipitate adds water dissolution and adds aqueous hydrochloric acid solution again and make and be acid, and then adds ethanol precipitation.The precipitation that is obtained is dissolved with sodium hydroxide once more and is neutralized.Precipitate washs after drying with ethanol and ether, promptly gets the pectin powder of light brown odorless.
It is as follows that the pectin plasma substitute that is obtained by embodiment 5, embodiment 6, comparative example 1 is used for clinical effect:
Clinically be used to give example surplus anti-treatment kind shock, hemodilution, the coronary heart disease etc. 300, all received satisfied effect.Example surplus treatment traumatic shock, hemorrhagic shock, toxic shock, the burn shock 170, wherein severe shock accounts for 52.1%, after using low molecule apple pectin plasma substitute 500~2500ml, clinical indices points out most patients' circulatory function and shock sign all can be improved rapidly, carry out definitiveness simultaneously with sum and handle, shock can obtain correcting in a few hours.Circulatory function improvement rate is 96.9%, and the shock recovery success rate is 92.6%.Systolic pressure average out to 69.8 ± 2.5(Sx) mmHg before the medication, all go up rapidly after the medication to average be 102.2 ± 1.8(Sx) mmHg, promoted 46.42%; Breathe, heart rate is also corresponding improves; Urine is measured 91.3% patient to be increased to some extent, and microcirculation obviously improves.Still find no anaphylaxis, allergy and accumulate disease sign, also do not see bleeding tendency and infusion reaction.Even when importing fast with the speed pressurization vein of per minute 80ml, patient does not also have discomfort or untoward reaction; Liver function, kidney merit all take an evident turn for the better; Hemogram and biochemical analysis are also within normal range.
The equal no change of hemodilution patient's circulatory function and heart rate has all successfully been implemented operation.Example surplus the micromolecule apple pectin plasma substitute treatment coronary heart disease 30, clinical effectiveness is better than comparative example 1 and revolves sugared acid anhydride.Clinical outstanding behaviours is that subjective symptoms is improved, brain, physical exertion increase.
Clinical case 1
Liu * *, the woman, 66 years old, the diffuse peritonitis toxic shock, blood pressure does not detect when being admitted to hospital, and pulse, breathing are respectively 120 and 40 times/minute, and urine does not have.Import the apple pectin plasma substitute fast with per minute 30~40ml speed vein, in a few days twice input total amount is 2500ml, patient's success of recovering, blood pressure reaches 110/80mmHg, and pulse, breathing improve, and the urine amount reaches per hour more than the 80ml, microcirculation obviously improves, and healing is left hospital.
Clinical case 2
The palace * *, the man, 23 years old, hypovolemic shock was when being admitted to hospital, continue to drop to 78/60mmHg through the fluid-supplement therapy blood pressure, import apple pectin plasma substitute 500ml fast with the speed vein of per minute 25ml, it is clear-headed that patient's mind is changeed, and extremity warm, blood pressure stabilization is at 110/70~120/80mmHg, so that recovery from illness is left hospital.
Clinical case 3
In * *, man, 32 years old, traumatic shock, multiple fracture.When being admitted to hospital, blood pressure 50/0mmHg, the urine amount does not have.All invalid through transfusion and pressor agent treatment, promptly with the speed of the per minute 66ml quick vein input apple pectin plasma substitute 1500ml that pressurizes, blood pressure promptly gos up to 120/80mmHg, sb.'s illness took a favorable turn, and extremity warm, and arteries and veins is strong clearly, the urine amount increases, and blood pressure is more steady, and microcirculation improves.
Clinical case 4
Open * *, the man, 58 years old, the retired veteran cadre, because of coronary heart disease is admitted to hospital, every day quiet micromolecule apple pectin plasma substitute 500ml, 10 is a course of treatment, stops a week, has carried out second course of treatment again.Patient's subjective symptoms is obviously improved, and brain, physical exertion increase, and recovery from illness is left hospital.Visit after 8 years, patient is not obviously outbreak again, more is not in hospital, and all are normal.
The description of the drawings
Fig. 1 is the infrared spectrum of apple pectin
Fig. 2 is the NMR (Nuclear Magnetic Resonance) spectrum of apple pectin

Claims (6)

1, a kind of pectin plasma substitute wherein contains plant gum, inorganic salt, saccharide, water, it is characterized in that by
(a) weight concentration of pectin is 0.5~1.5%,
(b) weight concentration of butter is 0.8~1.0%,
(c) weight concentration of glucose is 0.09~1.2%,
(d) pH value is 3.5~5.5
The rest is water forms.
2, pectin plasma substitute according to claim 1 is characterized in that the pectin that uses is apple pectin, pomelo-pectin, certain herbaceous plants with big flowers dish pectin, Fructus Caricae pectin, zizyphus pectin, melonidum glue, hawthorn pectin etc.
3, pectin plasma substitute according to claim 1 is characterized in that the inorganic salt that uses is sodium chloride, potassium chloride, calcium chloride, magnesium chloride.
4, a kind of pectin plasma substitute is characterized in that in the comminuted plants fruit with the preparation method of pectin
(a) acidic aqueous solution that adds 0.1~1.2% weight concentration of pulverizing 1~6 times of fruit weight soaked 30~720 minutes,
(b) be that 105~130 ℃, pressure are 0.1~2kg/cm in temperature 2Condition under heat-treat, separate solution and residue after the hot-pressing processing then,
(c) transferring the pH value of separation solution with aqueous alkali is 3.0~5.4,
(d) with the refining repeatedly separation solution of activated carbon, organic alcohol, ion-exchange resin.
5, the preparation method of pectin according to claim 1 is characterized in that the aqueous alkali that uses is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and its weight concentration is 4~32%.
6, the preparation method of pectin according to claim 4 is characterized in that employed organic alcohol is methanol, ethanol, propanol.
CN 88109696 1988-11-10 1988-11-10 Pectin plasma substitute and preparation method Pending CN1042474A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999059602A1 (en) * 1998-05-15 1999-11-25 Chaoying Zhao Novel pharmaceutical composition for use in emergency treatment and preparation method thereof
WO2002083157A1 (en) * 2001-04-18 2002-10-24 Jianchuan Ma Blood group-free human blood plasma and the preparation method thereof
CN102344260A (en) * 2011-06-14 2012-02-08 昆山市瑞捷精密模具有限公司 Composition for drying gypsum and preparation method of gypsum mold
CN106674376A (en) * 2017-01-29 2017-05-17 吕小萍 Extraction technology of SHIDI zizyphus pectin

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999059602A1 (en) * 1998-05-15 1999-11-25 Chaoying Zhao Novel pharmaceutical composition for use in emergency treatment and preparation method thereof
EA003369B1 (en) * 1998-05-15 2003-04-24 Чаоын Жао Novel pharmaceutical composition for use in emergency treatment and preparation method thereof
AP1185A (en) * 1998-05-15 2003-07-04 Chaoying Zhao Novel pharmaceutical composition for the use in emergency treatment and preparation method thereof.
US6986905B1 (en) 1998-05-15 2006-01-17 Chaoying Zhao Pharmaceutical compositions for treating and saving and the method for the preparation thereof
WO2002083157A1 (en) * 2001-04-18 2002-10-24 Jianchuan Ma Blood group-free human blood plasma and the preparation method thereof
CN102344260A (en) * 2011-06-14 2012-02-08 昆山市瑞捷精密模具有限公司 Composition for drying gypsum and preparation method of gypsum mold
CN106674376A (en) * 2017-01-29 2017-05-17 吕小萍 Extraction technology of SHIDI zizyphus pectin

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