CN103565736A - Hydroxyethyl starch 130 sodium acetate Ringer injection and preparation method thereof - Google Patents
Hydroxyethyl starch 130 sodium acetate Ringer injection and preparation method thereof Download PDFInfo
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- CN103565736A CN103565736A CN201310494294.3A CN201310494294A CN103565736A CN 103565736 A CN103565736 A CN 103565736A CN 201310494294 A CN201310494294 A CN 201310494294A CN 103565736 A CN103565736 A CN 103565736A
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- Prior art keywords
- injection
- sodium acetate
- hetastarch
- chloride
- needle
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/718—Starch or degraded starch, e.g. amylose, amylopectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0026—Blood substitute; Oxygen transporting formulations; Plasma extender
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
Abstract
The invention relates to a hydroxyethyl starch 130 sodium acetate Ringer injection and a preparation method thereof. The hydroxyethyl starch 130 sodium acetate Ringer injection is prepared from hydroxyethyl starch 130, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate, hydrochloric acid and water for injection. The preparation method comprises the concrete steps of adding the water for injection into the hydroxyethyl starch 130 to prepare a water solution of the hydroxyethyl starch 130, heating until the hydroxyethyl starch 130 is thoroughly dissolved, then, adding active carbon for a needle, slightly boiling, decarburizing and filtering to obtain a hydroxyethyl starch 130 filtrate; adding the water for injection into sodium chloride, potassium chloride, calcium chloride, magnesium chloride and sodium acetate, stirring and heating to enable sodium chloride, potassium chloride, calcium chloride, magnesium chloride and sodium acetate to be dissolved, adding active carbon for the needle, boiling, decarburizing and filtering to obtain a sodium acetate Ringer filtrate; mixing the hydroxyethyl starch 130 filtrate and the sodium acetate Ringer filtrate, adding the water for injection to enable the volume to be constant, adjusting the pH value, finely filtering, encapsulating, sealing and sterilizing. Chloride ions and sodium ions in the injection are closer to those in the plasma of a human body and can be used for maintaining the stability of internal environments including electrolyte, acid and base of an organism, so that the injection is safer and more effective in clinical application.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, particularly a kind of hetastarch
130sodium acetate ringer's injection and preparation method thereof.
Background technology
Blood plasma substitute is by improving plasma colloid osmotic pressure, expanding ECBV, to remain hemodynamic stable.Hydroxyethyl starch solution is used as blood plasma substitute, has been widely used in clinically, is mainly used in prevention and treats the molten amount of low blood and shock.
At present, it is domestic that to take the blood plasma substitute compound preparation that hetastarch is primary raw material be mainly hetastarch sodium chloride injection, and the chloride ion and the sodium ion that in this blood plasma substitute, in 0.9% saline as solvent, contain 154mmol/L, apparently higher than the content of normal sodium (135mmol/L~145mmol/L normal range) and chlorine (95mmol/L~105mmol/L normal range) in blood plasma.Research shows, excessive infusion normal saline sodium chloride solution due to chloride ion overload ion space change, may cause high chlorine metabolic acidosis.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of hetastarch sodium acetate ringer's injection and preparation method thereof, this injection chloride ion and sodium ion and human plasma are more approaching, can maintain body electrolyte and acid-base homeostasis, clinical use is safer, effective.
Technical solution of the present invention is:
A kind of hetastarch
130sodium acetate ringer's injection, is comprised of following effective ingredient:
Hetastarch
13060g;
Sodium chloride 5.7g~6.3g;
Potassium chloride 0.38g~0.42g;
Calcium chloride 0.127g~0.140g
Magnesium chloride 0.19g~0.21g;
Sodium acetate 3.515g~3.885g;
Hydrochloric acid 0.2g~0.5g;
Water for injection adds to 1000g.
A kind of hetastarch
130the preparation method of sodium acetate ringer's injection, its concrete steps are as follows:
1.1, take 60g hetastarch
130, add water for injection to make hetastarch
130content is 8%~10% hetastarch
130aqueous solution, heats 70 ℃~80 ℃ stirrings it is dissolved, and after dissolving completely, adds needle-use activated carbon to account for hetastarch
130the needle-use activated carbon of the moistening of aqueous solution quality 0.19%~0.21%, 100 ℃ of micro-boiling after 15min~20min, place and are cooled to 70 ℃~80 ℃, and decarbonization filtering, obtains hetastarch
130filtrate;
1.2, taking 5.7g~6.3g sodium chloride, 0.38g~0.42g potassium chloride, 0.127g~0.140 calcium chloride, 0.19g~0.21g magnesium chloride, 3.515g~3.885g sodium acetate adds 50g~70g water for injection to obtain sodium acetate Green solution, 50 ℃~60 ℃ of agitating heating are dissolved it completely, add needle-use activated carbon to account for the needle-use activated carbon of the moistening of sodium acetate Green solution quality 0.19%~0.21%, 100 ℃ are boiled after 8min~12min, placement is cooled to 28 ℃~30 ℃, decarbonization filtering, obtains sodium acetate Green filtrate;
1.3, hetastarch step 1.1 being made
130sodium acetate Green filtrate that filtrate and step 1.2 make is mixed, and adds water for injection to be settled to 1000g, and with salt acid for adjusting pH value 5.0~7.5, sampling detects, qualified after, medicinal liquid is by 0.22 μ m filter fine straining, filtrate embedding sealing by fusing;
1.4,115 ℃~120 ℃ sterilizing 25min~35min;
1.5, lamp inspection qualified after, packing warehouse-in.
The needle-use activated carbon of described moistening is formulated by 0.2g~0.5g needle-use activated carbon and 100g water for injection.
Beneficial effect of the present invention:
(1), hetastarch
130be the narrowest middle molecular ethoxyl starch preparation of a kind of distribution, replace low its metabolic degradation rate that makes of level and raise, in tissue, hetastarch declines, and less on coagulation impact, safety obviously increases.
(2), sodium acetate can be used as energy the same as fatty acid used, 2/3rds enter cardiac muscle, skeletal muscle and brain cell, 1/3rd enter hepatocyte, at intracellular plastochondria, enter tricarboxylic acid cycle (TCA), generate and wait a mole bicarbonate ion performance cushioning effect, final carbon dioxide and the water of generating, due to acetic acid many places metabolism in vivo, even also seldom accumulate during extracorporeal circulation, therefore for maintaining the stable advantage that has more of acid-base balance in body.
(3), using acetic acid Green injection as carrier solution, hetastarch
130cl in acetic acid ringer's injection
-ion concentration compares hetastarch
130sodium chloride injection, closer to normal physiological scope, meanwhile, contains and approaches physiological water product Ca
2+, Mg
2+, K
+, Na
+, the electrolyte such as acetate ion, can maintain the stable of border in body electrolyte and soda acid, clinical use is safer.
(4), chloride ion content approaches blood plasma biological value in acetic acid Green injection, sodium acetate can produce HCO in vivo in addition
3, and performance buffer capacity, after a large amount of infusions, blood electrolyte concentration change is more stable.
(5) technique is simple, easy to operate.First by active carbon moistening, then add hetastarch
130in aqueous solution or sodium acetate Green solution, avoided active carbon more directly to add decolouring and adsorb impurity easily causing damage, can fully guarantee the accurate consumption of activated carbon, time hetastarch sodium acetate ringer's injection color and clarity better.
The specific embodiment
Embodiment 1
Hetastarch
13060g;
Sodium chloride 6.3g;
Potassium chloride 0.38g;
Calcium chloride 0.140g
Magnesium chloride 0.19g;
Sodium acetate 3.885g;
Hydrochloric acid 0.2g;
Water for injection adds to 1000g;
1.1, take 60g hetastarch
130, add water for injection to make hetastarch
130content is 10% hetastarch
130aqueous solution, heats 70 ℃ of stirrings it is dissolved, and after dissolving completely, adds needle-use activated carbon to account for hetastarch
130the needle-use activated carbon of the moistening of aqueous solution quality 0.21%, the needle-use activated carbon of described moistening refers in every 100g water for injection and contains 0.5g needle-use activated carbon, and 100 ℃ of micro-boiling after 20min are placed and are cooled to 70 ℃, and decarbonization filtering, obtains hetastarch
130filtrate;
1.2, taking 6.3g sodium chloride, 0.38g potassium chloride, 0.140 calcium chloride, 0.19g magnesium chloride, 3.885g sodium acetate adds 70g water for injection to obtain sodium acetate Green solution, 50 ℃ of agitating heating are dissolved it completely, add needle-use activated carbon to account for the needle-use activated carbon of the moistening of sodium acetate Green solution quality 0.21%, the needle-use activated carbon of described moistening refers in every 100g water for injection and contains 0.5g needle-use activated carbon, 100 ℃ are boiled after 8min, placement is cooled to 28 ℃, decarbonization filtering, obtains sodium acetate Green filtrate;
1.3, hetastarch step 1.1 being made
130sodium acetate Green filtrate that filtrate and step 1.2 make is mixed, and adds water for injection to be settled to 1000g, adds 0.2g salt acid for adjusting pH value 5.0~7.5, and sampling detects, qualified after, medicinal liquid is by 0.22 μ m filter fine straining, filtrate embedding sealing by fusing;
1.4,115 ℃ of sterilizing 35min;
1.5, lamp inspection qualified after, packing warehouse-in.
Embodiment 2
Hetastarch
13060g;
Sodium chloride 5.7g;
Potassium chloride 0.42g;
Calcium chloride 0.127g
Magnesium chloride 0.21g;
Sodium acetate 3.515g;
Hydrochloric acid 0.5g;
Water for injection adds to 1000g;
1.1, take 60g hetastarch
130, add water for injection to make hetastarch
130content is 8% hetastarch
130aqueous solution, heats 80 ℃ of stirrings it is dissolved, and after dissolving completely, adds needle-use activated carbon to account for hetastarch
130the needle-use activated carbon of the moistening of aqueous solution quality 0.19%, the needle-use activated carbon of described moistening refers in every 100g water for injection and contains 0.2g needle-use activated carbon, and 100 ℃ of micro-boiling after 15min are placed and are cooled to 70 ℃, and decarbonization filtering, obtains hetastarch
130filtrate;
1.2, taking 5.7g sodium chloride, 0.42g potassium chloride, 0.127 calcium chloride, 0.21g magnesium chloride, 3.515g sodium acetate adds 50g water for injection to obtain sodium acetate Green solution, 60 ℃ of agitating heating are dissolved it completely, add needle-use activated carbon to account for the needle-use activated carbon of the moistening of sodium acetate Green solution quality 0.19%, the needle-use activated carbon of described moistening refers in every 100g water for injection and contains 0.2g needle-use activated carbon, 100 ℃ are boiled after 12min, placement is cooled to 30 ℃, decarbonization filtering, obtains sodium acetate Green filtrate;
1.3, hetastarch step 1.1 being made
130sodium acetate Green filtrate that filtrate and step 1.2 make is mixed, and adds water for injection to be settled to 1000g, adds 0.5g salt acid for adjusting pH value 5.0~7.5, and sampling detects, qualified after, medicinal liquid is by 0.22 μ m filter fine straining, filtrate embedding sealing by fusing;
1.4,120 ℃ of sterilizing 25min;
1.5, lamp inspection qualified after, packing warehouse-in.
Embodiment 3
Hetastarch
13060g;
Sodium chloride 6.0g;
Potassium chloride 0.4g;
Calcium chloride 0.134g
Magnesium chloride 0.2g;
Sodium acetate 3.7g;
Hydrochloric acid 0.3g;
Water for injection adds to 1000g;
1.1, take 60g hetastarch
130, add water for injection to make hetastarch
130content is 9% hetastarch
130aqueous solution, heats 75 ℃ of stirrings it is dissolved, and after dissolving completely, adds needle-use activated carbon to account for hetastarch
130the needle-use activated carbon of the moistening of aqueous solution quality 0.20%, the needle-use activated carbon of described moistening refers in every 100g water for injection and contains 0.4g needle-use activated carbon, and 100 ℃ of micro-boiling after 18min are placed and are cooled to 75 ℃, and decarbonization filtering, obtains hetastarch
130filtrate;
1.2, taking 6.0g sodium chloride, 0.4g potassium chloride, 0.134 calcium chloride, 0.2g magnesium chloride, 3.7g sodium acetate adds 60g water for injection to obtain sodium acetate Green solution, 55 ℃ of agitating heating are dissolved it completely, add needle-use activated carbon to account for the needle-use activated carbon of the moistening of sodium acetate Green solution quality 0.2%, the needle-use activated carbon of described moistening refers in every 100g water for injection and contains 0.4g needle-use activated carbon, 100 ℃ are boiled after 10min, placement is cooled to 29 ℃, decarbonization filtering, obtains sodium acetate Green filtrate;
1.3, hetastarch step 1.1 being made
130sodium acetate Green filtrate that filtrate and step 1.2 make is mixed, and adds water for injection to be settled to 1000g, adds 0.3g salt acid for adjusting pH value 6.8, and sampling detects, qualified after, medicinal liquid is by 0.22 μ m filter fine straining, filtrate embedding sealing by fusing;
1.4,118 ℃ of sterilizing 30min;
1.5, lamp inspection qualified after, packing warehouse-in.
After testing, hetastarch
130content and sodium acetate content are as shown in table 1.
Clinical research: 120 routine patients use hetastarch
130sodium acetate ringer's injection (embodiment 3) is used hetastarch with 120 routine patients
130sodium chloride injection (matched group) is as shown in table 1 for safety and the validity comparison of general anesthesia patients undergoing noncardiac surgery volume treatment.
Before and after table 1 embodiment 3 infuses with matched group, vim and vigour and electrolytic condenser are
Hetastarch
130the pH of sodium acetate ringer's injection, residue alkali (SBE), bicarbonate (HCO
3 -) amplitude of variation is starkly lower than matched group, with before infusion relatively blood gas index tend towards stability, in group before and after infusion relatively without significant difference, and matched group contrasts rear three indexs and all has reduction, difference has statistical significance, and between two groups, rate of change compares that also there were significant differences.Hetastarch
130the pH of sodium acetate ringer's injection is 5.5~7.5, and matched group pH is 4.0~5.5.
In embodiment 3 because of containing NaCl 6g/L, KCl 0.4g/L, CaCl
20.134g, MgCl
20.2g/L; Sodium acetate 3.7g/L, after infusion, blood potassium, calcium, magnesium abnormal rate was are starkly lower than matched group, and between two groups of calcium, potassium, magnesium difference and rates of change, there were significant differences.In embodiment 3, chloride ion content is that 109mmol/L approaches blood plasma biological value, and sodium acetate can produce HCO in vivo in addition
3, and performance buffer capacity, after a large amount of infusions, blood electrolyte concentration change is more stable.
With comparison before infusion, blood chlorine difference rate of change and abnormal rate was after infusion, embodiment 3 is aobvious is better than matched group, and matched group, the content of 0.9% its chloride ion of sodium chloride solution is 154mmol/L, far above blood plasma chloride ion content 95 mmol/L~105mmol/L, studies have shown that a large amount of infusion 0.9% sodium chloride solutions, can produce Introduced cases hyperchloremia, and hyperchloremia persistent period >6 hour, the liquid infusion of isodose, matched group Hb and HCT decline obviously, with the molten powder of ethoxy
130sodium acetate ringer's injection is compared difference statistical significance.
Comparative example 1
The needle-use activated carbon of the moistening in embodiment 3 steps 1.1, step 1.2 is substituted to the other the same as in Example 3 with the needle-use activated carbon of non-moistening.After testing, hetastarch
130content and sodium acetate content are as shown in table 1.
Table 2 active carbon adds method to investigate result
? | Hetastarch 130Content | Sodium acetate content | pH | Solution colour and clarity |
Embodiment 3 | 98.5% | 99.6% | 6.8 | Achromaticity and clarification |
Comparative example 1 | 96.8% | 97.5% | 6.8 | Micro-Huang |
Add moistening active carbon successful and be better than non-moistening active carbon.
Claims (3)
1. a hetastarch
130sodium acetate ringer's injection, is characterized in that:
By following effective ingredient, formed:
Hetastarch
13060g;
Sodium chloride 5.7g~6.3g;
Potassium chloride 0.38g~0.42g;
Calcium chloride 0.127g~0.140g
Magnesium chloride 0.19g~0.21g;
Sodium acetate 3.515g~3.885g;
Hydrochloric acid 0.2g~0.5g;
Water for injection adds to 1000g.
2. a kind of hetastarch as claimed in claim 1
130the preparation method of sodium acetate ringer's injection, is characterized in that:
Concrete steps are as follows:
1.1, take 60g hetastarch
130, add water for injection to make hetastarch
130content is 8%~10% hetastarch
130aqueous solution, heats 70 ℃~80 ℃ stirrings it is dissolved, and after dissolving completely, adds needle-use activated carbon to account for hetastarch
130the needle-use activated carbon of the moistening of aqueous solution quality 0.19%~0.21%, 100 ℃ of micro-boiling after 15min~20min, place and are cooled to 70 ℃~80 ℃, and decarbonization filtering, obtains hetastarch
130filtrate;
1.2, taking 5.7g~6.3g sodium chloride, 0.38g~0.42g potassium chloride, 0.127g~0.140 calcium chloride, 0.19g~0.21g magnesium chloride, 3.515g~3.885g sodium acetate adds 50g~70g water for injection to obtain sodium acetate Green solution, 50 ℃~60 ℃ of agitating heating are dissolved it completely, add needle-use activated carbon to account for the needle-use activated carbon of the moistening of sodium acetate Green solution quality 0.19%~0.21%, 100 ℃ are boiled after 8min~12min, placement is cooled to 28 ℃~30 ℃, decarbonization filtering, obtains sodium acetate Green filtrate;
1.3, hetastarch step 1.1 being made
130sodium acetate Green filtrate that filtrate and step 1.2 make is mixed, and adds water for injection to be settled to 1000g, and with salt acid for adjusting pH value 5.0~7.5, sampling detects, qualified after, medicinal liquid is by 0.22 μ m filter fine straining, filtrate embedding sealing by fusing;
1.4,115 ℃~120 ℃ sterilizing 25min~35min;
1.5, lamp inspection qualified after, packing warehouse-in.
3. hetastarch according to claim 2
130the preparation method of sodium acetate ringer's injection, is characterized in that: the needle-use activated carbon of described moistening is formulated by 0.2g~0.5g needle-use activated carbon and 100g water for injection.
Priority Applications (2)
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CN201310494294.3A CN103565736A (en) | 2013-10-21 | 2013-10-21 | Hydroxyethyl starch 130 sodium acetate Ringer injection and preparation method thereof |
CN201410556484.8A CN104306396A (en) | 2013-10-21 | 2014-10-20 | Hydroxyethyl starch 130 sodium lactate ringer injection and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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CN201310494294.3A CN103565736A (en) | 2013-10-21 | 2013-10-21 | Hydroxyethyl starch 130 sodium acetate Ringer injection and preparation method thereof |
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CN103565736A true CN103565736A (en) | 2014-02-12 |
Family
ID=50039019
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CN201310494294.3A Withdrawn CN103565736A (en) | 2013-10-21 | 2013-10-21 | Hydroxyethyl starch 130 sodium acetate Ringer injection and preparation method thereof |
CN201410556484.8A Pending CN104306396A (en) | 2013-10-21 | 2014-10-20 | Hydroxyethyl starch 130 sodium lactate ringer injection and preparation method thereof |
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CN201410556484.8A Pending CN104306396A (en) | 2013-10-21 | 2014-10-20 | Hydroxyethyl starch 130 sodium lactate ringer injection and preparation method thereof |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107596443A (en) * | 2016-07-11 | 2018-01-19 | 复旦大学附属华山医院 | A kind of non-invasive traceable biomaterial and preparation method thereof |
CN114748500A (en) * | 2022-05-06 | 2022-07-15 | 辽宁金品生物科技有限公司 | Hydroxyethyl starch injection and preparation method thereof |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN107802596A (en) * | 2017-11-30 | 2018-03-16 | 哈尔滨珍宝制药有限公司 | A kind of hydroxyethyl starch injection liquid composition and preparation method and application |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1813795A (en) * | 2005-12-06 | 2006-08-09 | 山东诚创医药技术开发有限公司 | Medicinal composition |
CN101444526B (en) * | 2008-12-30 | 2012-06-27 | 杭州民生药业有限公司 | Pharmaceutical composition |
CN103006555B (en) * | 2013-01-05 | 2014-08-06 | 四川美大康佳乐药业有限公司 | Hydroxyethyl starch injection and preparation method thereof |
-
2013
- 2013-10-21 CN CN201310494294.3A patent/CN103565736A/en not_active Withdrawn
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2014
- 2014-10-20 CN CN201410556484.8A patent/CN104306396A/en active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107596443A (en) * | 2016-07-11 | 2018-01-19 | 复旦大学附属华山医院 | A kind of non-invasive traceable biomaterial and preparation method thereof |
CN114748500A (en) * | 2022-05-06 | 2022-07-15 | 辽宁金品生物科技有限公司 | Hydroxyethyl starch injection and preparation method thereof |
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Application publication date: 20140212 |