CN1579421A - Freeze-dried powder of pig's lung surface matter, its preparation method and use - Google Patents
Freeze-dried powder of pig's lung surface matter, its preparation method and use Download PDFInfo
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- CN1579421A CN1579421A CNA031420672A CN03142067A CN1579421A CN 1579421 A CN1579421 A CN 1579421A CN A031420672 A CNA031420672 A CN A031420672A CN 03142067 A CN03142067 A CN 03142067A CN 1579421 A CN1579421 A CN 1579421A
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Abstract
The invention relates to pig lung surface active substance freeze-dry power and its manufacturing method and the application. The pig lung surface active substance freeze-dry powder disclosed in the invention is the preparation acquired by freezing the liquid made up of 5-10% of pig lung surface active substance, 2-5% of poly sorbus ester 80 and 85-93% sodium chloride injection. The preparation material resource is rich, the quality is table, the use and storage are convenient. It applies to new child and adult respiration pinch syndrome, it especially applies to respiration pinch syndrome caused by SARS.
Description
Technical field
The present invention relates to field of pharmaceutical preparations.Be specifically related to pig lung surface active substance freeze-dry and preparation method and application.
Background technology
(Pulmonary surfactant is to keep the indispensable material of normal lung function PS) to pulmonary surfactant.Pulmonary surfactant is made up of multiple components, DPPC (Dipalmitoylphosphatidylcholine) mainly provides the stability of alveolar, reduce the surface tension of alveolar, PG (Phosphati5dylglycerol) then help surfactant exhale and when air-breathing in IA heavy distribution.When exhaling, surfactant is dimer, and its hydrophilic area is outside, and hydrophobic region is together overlapped, surfactant function reduction at this moment, and alveolar tension force increases and forms the alveolar retraction force; And when air-breathing, accumulative dimer surfactant becomes single aggressiveness again, and its hydrophobic region is adsorbed in the surface of alveolar cell, hydrophilic area is towards the gas phase of alveolar, to reduce the surface tension of alveolar, help the increase of alveolar surface area, the enlargement gas exchange area.
Surfactant is synthetic in the cytoplasm of two type cells, protein then synthesizes at rough endoplasmic reticulum, after Golgi body glycosylation processing, be connected with surfactant, form the LamellarsShi corpusculum, be secreted into alveolar with the alveolar membrane fusion, the albumen in the surfactant is generally absorbed by macrophage, and phospholipid can heavily be absorbed into two type cells again and form the synthetic recirculation of phospholipid.Upgrade metabolism once in the average 5-10 of alveolar surfactant hour, and formed once circulation.
Protein in the pulmonary surfactant has various function, and SP-A is a hydrophilic protein, and according to its glycosylated degree, molecular weight does not wait from 28-30KD.Its function be in the presence of calcium in conjunction with DPPC, be gathered into liposome, also have simultaneously and suppress two type emiocytosis Lamellar corpusculums, increase the effect of taking in DPPC.Latest find proof SP-A has opsonic effect, helps macrophage phagocytic to invade the antibacterial of alveolar.SP-B is a hydrophobin, the polypeptide of forming by 79 aminoacid, SP-B can be produced by two type cells and bronchial epithelial cell, the initial SP-B that produces is the protein of 40KD, modify through enzyme action then and remove 20-23 amino acid whose signal peptide, 106-107 aminoacid formation SP-B of 176 aminoacid of N section and C end, but also not clear to its function at present.SP-C is hydrophobic polypeptide, produce by two type cells, form 4KD through post translational modification from the precursor protein of 21KD and contain 23 amino acid whose polypeptide, its hydrophobicity can combine with the lipid of the hydrophobic region of surfactant, and surfactant is linked together can distribute it at alveolar surface homogeneous phase.SP-D and SP-A are similar, are glycosylated hydrophilic proteins, and the about 43KD of size can bring into play conditioning, the anti-infective effect.
PN is owing to alveolar type II cells hypoplasia, and alveolar surfactant produces not enough, can cause dyspnea, threat to life, and mortality rate is higher.Adult respiratory distress is secondary to the complication after many serious diseases often, as severe infections, wound, surgical operation etc., in case find that patient has the property of carrying out dyspnea, anoxia and pulmonary edema are checked and are often found that these patients reduce with surfactant, adopt the capillary measure of attenuating lung can improve patient's symptom.
At present the pulmonary surfactant of treatment usefulness mainly contains synthetic and animal derived surfactant and isolating surfactant from the fetus amniotic fluid.In these three kinds of surfactants, synthetic owing to do not contain surfactant protein, its effect is undesirable, and cost is too high; And containing surfactant Protein S P-B and SP-C from the animal derived surfactant of pig or cattle, its therapeutic effect is better.
The Japanese achieved success with pulmonis Bovis seu Bubali PS treatment hyaline membrane disease of newborn (NRDS) first in 1980, later on states such as U.S., Europe, Japan adopt the PS preparation for treating in multiple source should disease in succession, obtain sure curative effect, the clinic trial that surpasses ten thousand examples so far makes the sick mortality rate of NRDS reduce to 10-20% from original 50-70%.The clinical practice that American scholar gives the credit to PS with the decline of the eighties U.S. neonatal mortality.In addition, acute and chronic pneumonopathy such as adult type respiratory distress syndrome (ARDS), heavy pneumonia, pneumorrhagia, asthma also have PS to lack, and with exogenous PS treatment certain curative effect is arranged also, so PS have broad clinical application prospect.
China does not still have the specific treatment method to NRDS and ARDS at present, and case fatality rate all more than 50-70%, has a strong impact on the rescue of China's prenatal and postnatal care work and NRDS and ARDS, and the clinicist presses for the pulmonary surfactant preparation.External PS preparation costs an arm and a leg, and treats a NRDS infant and needs more than 1000 dollar, treats patient ARDS and then needs thousands of dollars, therefore can't bear by import PS patient and his family.
Existing P S preparation is a suspensoid in the market in addition, make troubles for the storage of product, transportation, and the existence of water is affected the stability of product.
Summary of the invention
Technical problem to be solved by this invention is the defective that overcomes existing preparation, adopts the surfactant that extracts from the abundant Pulmonis Sus domestica of originating to make steady quality, use, store freeze-dried powder preparation easily.
The preparation that obtains after the solution lyophilizing that pig lung surface active substance freeze-dry disclosed by the invention is made up of following percentage ratio prescription:
Prescription:
5～10%w/v poractant alfa
2～5%v/v concentration is 5% polyoxyethylene sorbitan monoleate
85～93%v/v concentration is 0.9% sodium chloride injection
Poractant alfa of the present invention is a kind of phospholipoprotein complex that adopts the classical preparation method of general in the world phospholipid to extract from Pulmonis Sus domestica.Total phospholipids content is 56-75% in the described preparation, basal surface tension force γ
Min＜10mN/m, protein content is at 0.15-2.5%.
Owing to need make suspension when preparation of the present invention uses in tracheal intubation is injected lung, therefore add a small amount of polyoxyethylene sorbitan monoleate in the prescription and can keep suspension particle homodisperse.
Another technical problem to be solved by this invention is to provide the preparation method of above-mentioned pig lung surface active substance freeze-dry preparation.
The preparation of pig lung surface active substance freeze-dry preparation disclosed by the invention comprises the following steps:
1. the extraction of poractant alfa
(1) raw material is handled
The learn from else's experience fresh Pulmonis Sus domestica of quarantine use flushing with clean water, removes surface contaminants, is cut into small pieces, and Schweineseuche virus (FMDV) and pig Brucella are rechecked in sampling, and the Pulmonis Sus domestica of stripping and slicing is rubbed with electrical meat mincer, and homogenate is made in the pulverizing of reuse pulverizer.
(2) extract
Pulmonis Sus domestica homogenate is added normal saline stir, filter to remove through 10 eye mesh screens and organize impurity.Filtrate low-temperature centrifugation 10 minutes discards precipitation, gets supernatant, under cryogenic conditions centrifugal 60 minutes again, the flesh pink precipitation, should precipitate and use the normal saline suspendible, with method centrifuge washing 3 times, the light red precipitation, this promptly contains the poractant alfa of phospholipoprotein;
2. the preparation of freeze-dried powder preparation
Take by weighing poractant alfa by recipe quantity, add 0.9% sodium chloride injection, the high speed pulverization suspension is to milky, add polyoxyethylene sorbitan monoleate, stir evenly, behind the autoclaving, add 0.9% sodium chloride injection again, ultrasonic grinding, be diluted to total amount with sodium chloride injection, filter packing, lyophilization, promptly.
Relatively the apparent speckle of institute is consistent with reference standards lecithin through thin layer chromatography for product, lowest surface tension γ
Min＜10mN/m, protein content are between 0.15-2.5%, and total phospholipids is greater than 56.0%.
A technical problem more to be solved by this invention is to disclose the application of above-mentioned pig lung surface active substance freeze-dry preparation in preparation treatment neonate and adult respiratory distress syndrome medicine, is particularly useful for making the application in the respiratory distress syndrome medicine that the treatment atypical pneumonia causes.
Atypical pneumonia is called severe acute respiratory syndrome (Severe acute respiratory syndrome is called for short SARS) in the world.The clinical diagnosis standard (trying) of the atypical pneumonia case of delivering according to Ministry of Health of the People's Republic of China, the symptom of SARS and sign are for " to have heating (＞38 ℃) and following more than or; Cough is breathed and is quickened, tachypnea, respiratory distress syndrome, pulmonary rale, pulmonary consolidation Signs ".This standard also is to meet the SARS standard that The World Health Organization (WHO) delivers.The serious symptom SARS mainly shows as respiratory distress syndrome (ivrds), and clinical manifestation is an intra-alveolar edema, dyspnea.Clinical characters according to China SARS patient, cause acute lung injury behind the viral infection, carrying out property dyspnea appears in most critically ill patient generation acute respiratory distress syndromes (ARDS), and cause death, in fact rescuing SARS patient key is how to treat ARDS.Can tide over ARDS as the patient, case fatality rate will greatly reduce.
The coronavirus of SARS is exactly a kind of of pulmonary's actute infection, and it can reduce the alveolar cell surfactant, causes alveolar interstitial edema and dyspnea, causes blood oxygen level to reduce a series of serious consequences such as the respiratory function forfeiture of lung.
Present clinical research shows that the reason of SARS death mainly is that the respiratory failure that respiratory distress syndrome causes takes place.Virus has damaged the alveole cell and it produces the function of surfactant, has been full of moisture in the alveolar, and alveolar no longer includes respiratory function.The alternative medicine of pulmonary surfactant goes for the treatment of atypical pneumonia.In the recommendation therapeutic scheme and discharge diagnosis reference standard (trying) of atypical pneumonia case that Ministry of Public Health is delivered or suspected case, to the processing of critically ill patient with treat the present method of taking and mainly be to use respirator to help patient respiratory.Have clinical research to show abroad, use pulmonary surfactant that alveolar pO2 is raise, alveolar and arterial partial pressure of oxygen increase, and the storage that alleviates carbon dioxide is stayed, and lowers oxygen demand and do not re-use assisted ventilation unit.Owing to do not use assisted ventilation unit, reduced the Secondary cases lung loss that causes by assisted ventilation unit, as respiratory tract hemorrhage, diseases such as pneumothorax.Therefore, the treatment that pulmonary surfactant thing alternative medicine is applied to SARS not only can improve patient's respiratory function, reduce mortality rate, can also reduce the multiple SARS virus cross infection of using respirator to occur owing to patient, can be country simultaneously again and save the foreign exchange of buying the import respirator.
Carry out the acute toxicity test and the test of pesticide effectiveness with pig lung surface active substance freeze-dry preparation of the present invention:
1. acute toxicity test
Mice oral administration gavage poractant alfa, LD
50Greater than 5g/kg, mice is through lumbar injection, LD
50Greater than 3g/kg.
2. pharmacodynamics test
Make the NRDS model with 27 days premature labor rabbits of gestational age.In tracheal intubation was injected lung, 150mg/kg was administered once, the prolonged survival period of treatment group as a result with poractant alfa.Give the rabbit lung lavage of growing up with normal saline, through 7 lavations, make PS minimizing 86.7% in the lung, cause the rabbit that grows up that the ARDS performance takes place, then with the poractant alfa treatment, in tracheal intubation is injected lung, divide 3 dosage groups 100,150 and 200mg/kg, observed the result 8 hours: the treatment group calling is inhaled difficulty and is improved PaO
2Raise PaCO
2Descend, acidosis is corrected, and dynamic lung compliance and lung pathology change all and obviously improve.
The above results shows, preparation safety of the present invention, and toxicity is low, to the premature labor rabbit NRDS model energy significant prolongation time-to-live, improves the lung static compliance; Can improve anoxia, hypercapnia and acidosis fast and significantly to the rabbit ARDS models show of growing up, improve pulmonary dynamic compliance: two models show that all can alleviate lung pathology changes, and the result is consistent with bibliographical information.
Carry out stability test with pig lung surface active substance freeze-dry preparation of the present invention, investigate by different storage requirements.
One, influence factor's test
1. hot test: in 40 ℃ of calorstats
Get this product, put in 40 ℃ of calorstats, place after 5 days, 10 days, sampling analysis measuring, the result is as follows:
| The examination time (my god) | 0 | 5 | 10 |
| Outward appearance | Little yellow | Yellow | Yellow |
| Thin layer chromatography | Consistent with reference standard liquid thin layer point | The thin layer chromatography speckle is consistent with 0 day | |
| Content (total phospholipids) % | 66.58 | 67.38 | 66.00 |
2. high humility test: 25 ℃ of temperature, relative humidity 75%
Getting this product, to put relative humidity be in 75% the airtight vessel, under the condition that temperature is 25 ℃, to place after 5 days, 10 days, sampling analysis measuring, and the result is as follows:
| The examination time (my god) | 0 | 5 | 10 |
| Outward appearance | Little yellow | Little yellow | Little yellow |
| Thin layer chromatography | Consistent with reference standard liquid thin layer point | The thin layer chromatography speckle is consistent with 0 day | |
| Content (total phospholipids) % | 66.58 | 66.58 | 65.68 |
3. strong illumination test
Get this product, put with under the 4200Lux illuminance after 5 days, 10 days, sampling analysis measuring, the result is as follows:
| The examination time (my god) | 0 | 5 | 10 |
| Outward appearance | Little yellow | Little yellow | Little yellow |
| Thin layer chromatography | Consistent with reference standard liquid thin layer point | The thin layer chromatography speckle is consistent with 0 day | |
| Content (total phospholipids) % | 66.58 | 66.78 | 67.53 |
Two, accelerated test: 25 ℃ of temperature, relative humidity 60%
Get three lot numbers of this product, put relative humidity and be in 60% the airtight vessel, under the condition that temperature is 25 ℃, place after 1,2,3,6 month, sampling analysis measuring, the result is as follows:
| Lot number | The examination time (moon) | Appearance character | Thin layer chromatography | Content (total phospholipids) % |
| 20000523 | 0 | Little yellow | Consistent with reference substance | 67.09 |
| 1 | Little yellow | Speckle is consistent with 0 month | 67.12 | |
| 2 | Little yellow | Speckle is consistent with 0 month | 66.82 | |
| 3 | Little yellow | Speckle is consistent with 0 month | 67.48 | |
| 6 | The lyophilized products atrophy | |||
| 20000525 | 0 | Little yellow | Consistent with reference substance | 67.48 |
| 1 | Little yellow | Speckle is consistent with 0 month | 67.25 | |
| 2 | Little yellow | Speckle is consistent with 0 month | 66.48 | |
| 3 | Little yellow | Speckle is consistent with 0 month | 66.82 | |
| 6 | The lyophilized products atrophy | |||
| 20000527 | 0 | Little yellow | Consistent with reference substance | 66.58 |
| 1 | Little yellow | Speckle is consistent with 0 month | 65.88 | |
| 2 | Little yellow | Speckle is consistent with 0 month | 67.20 | |
| 3 | Little yellow | Speckle is consistent with 0 month | 67.72 | |
| 6 | The lyophilized products atrophy |
Three, long term test (2-8 ℃)
Get three lot numbers of this product, place 2-8 ℃ of refrigerator, place after 3,6,9,12,24 months, sampling analysis measuring, the result is as follows:
| Lot number | The examination time (moon) | Appearance character | Thin layer chromatography | Content (total phospholipids) % |
| 20000523 | 0 | Little yellow | Speckle is consistent with reference substance | 67.09 |
| 3 | Little yellow | Speckle is consistent with reference substance | 67.68 | |
| 6 | Little yellow | Speckle is consistent with reference substance | 67.15 | |
| 9 | Little yellow | Speckle is consistent with reference substance | 67.42 | |
| 12 | Little yellow | Speckle is consistent with reference substance | 67.05 | |
| 18 | Little yellow | Speckle is consistent with reference substance | 60.25 | |
| 24 | Little yellow | Speckle is consistent with reference substance | 61.25 | |
| ?20000525 | 0 | Little yellow | Speckle is consistent with reference substance | 67.48 |
| 3 | Little yellow | Speckle is consistent with reference substance | 67.48 | |
| 6 | Little yellow | Speckle is consistent with reference substance | 66.35 | |
| 9 | Little yellow | Speckle is consistent with reference substance | 67.38 |
| 12 | Little yellow | Speckle is consistent with reference substance | 67.90 | |
| 18 | Little yellow | Speckle is consistent with reference substance | 60.50 | |
| 24 | Little yellow | Speckle is consistent with reference substance | 62.00 | |
| ??20000527 | 0 | Little yellow | Speckle is consistent with reference substance | 66.58 |
| 3 | Little yellow | Speckle is consistent with reference substance | 67.22 | |
| 6 | Little yellow | Speckle is consistent with reference substance | 66.85 | |
| 9 | Little yellow | Speckle is consistent with reference substance | 67.48 | |
| 12 | Little yellow | Speckle is consistent with reference substance | 66.25 | |
| 18 | Little yellow | Speckle is consistent with reference substance | 61.85 | |
| 24 | Little yellow | Speckle is consistent with reference substance | 60.70 |
The aforementioned stable test shows that except that 40 ℃ of appearance colors of hot test were deepened, do not see had other variation to product of the present invention to thermally labile.This product is preserved under 2-8 ℃ of condition, uses stable in 2 years.
The more existing suspensoid of poractant alfa lyophilized formulations that the present invention adopts freeze-drying to make has following advantage:
1. contain a large amount of phospholipoproteins in the product, because of the anhydrous variation decomposes of ambient temperature of avoiding goes bad.
2. the product quality is dissolved the original characteristic of recovery medicinal liquid rapidly after loosening and adding water.
3. this product is difficult for oxidation, helps long term storage.
4. particle matter is than lacking with additive method production in the product made from freeze-drying, and opportunities for contamination reduces relatively.
The specific embodiment
Embodiment 1
1. the extraction of poractant alfa
(1) raw material is handled
The learn from else's experience fresh Pulmonis Sus domestica 100kg of quarantine use flushing with clean water, removes surface contaminants, is cut into small pieces, and Schweineseuche virus (FMDV) and pig Brucella are rechecked in sampling, and the Pulmonis Sus domestica of stripping and slicing is rubbed with electrical meat mincer, and homogenate is made in the pulverizing of reuse pulverizer.
(2) extract
Pulmonis Sus domestica homogenate is added normal saline 1000ml/kg stir, filter to remove through 10 eye mesh screens and organize impurity.Centrifugal 10 minutes of 4 ℃ of filtrates discard precipitation, get supernatant, again under 4 ℃ of conditions, centrifugal 60 minutes, get the flesh pink precipitation, should precipitate and use the normal saline suspendible, with method centrifuge washing 3 times, the light red precipitation, this promptly contains the poractant alfa of phospholipoprotein.
2. the preparation of freeze-dried powder preparation
Take by weighing poractant alfa 75g, add 0.9% sodium chloride injection 500ml, the high speed pulverization suspension is to milky, add polyoxyethylene sorbitan monoleate 36ml, stir evenly, behind the autoclaving, add 0.9% sodium chloride injection again, ultrasonic grinding is diluted to 1000ml with sodium chloride injection, filter packing, lyophilization, promptly get 500 bottles, every bottle of 2g, total phospholipids content 〉=56.0%, basal surface tension force＜10mN/m, protein content is at 0.15-2.5%.
The preparation of embodiment 2 freeze-dried powder preparations
Prescription:
Poractant alfa 80g
Concentration is 5% polyoxyethylene sorbitan monoleate 39ml
Concentration is 0.9% sodium chloride injection 1000ml
Preparation method is with embodiment 1.
Claims (5)
1, a kind of pig lung surface active substance freeze-dry preparation is characterized in that the preparation that obtains after the solution lyophilizing that said preparation is made up of following percentage ratio prescription:
Prescription:
5～10%w/v poractant alfa
2～5%v/v concentration is 5% polyoxyethylene sorbitan monoleate
85～93%v/v concentration is 0.9% sodium chloride injection
2, pig lung surface active substance freeze-dry preparation according to claim 1 is characterized in that described preparation total phospholipids content is 56-75%, and protein content is at 0.15-2.5%.
3, the preparation method of pig lung surface active substance freeze-dry preparation according to claim 1 is characterized in that the preparation of described freeze-dried powder preparation comprises the following steps:
1) extraction of poractant alfa
(1) raw material is handled
The learn from else's experience fresh Pulmonis Sus domestica of quarantine use flushing with clean water, removes surface contaminants, is cut into small pieces, and Schweineseuche virus and pig Brucella are rechecked in sampling, and the Pulmonis Sus domestica of stripping and slicing is rubbed with electrical meat mincer, and homogenate is made in the pulverizing of reuse pulverizer;
(2) extract
Pulmonis Sus domestica homogenate is added normal saline stir, filter to remove through 10 eye mesh screens and organize impurity.Filtrate low-temperature centrifugation 10 minutes discards precipitation, gets supernatant, under cryogenic conditions centrifugal 60 minutes again, the flesh pink precipitation, should precipitate and use the normal saline suspendible, with method centrifuge washing 3 times, the light red precipitation, this promptly contains the poractant alfa of phospholipoprotein;
2) preparation of freeze-dried powder preparation
Take by weighing poractant alfa by recipe quantity, add 0.9% sodium chloride injection, the high speed pulverization suspension is to milky, add polyoxyethylene sorbitan monoleate, stir evenly, behind the autoclaving, add 0.9% sodium chloride injection again, ultrasonic grinding, be diluted to total amount with sodium chloride injection, filter packing, lyophilization, promptly.
4, the application of pig lung surface active substance freeze-dry preparation according to claim 1 in preparation treatment neonate and adult respiratory distress medicine.
5, application according to claim 4 is characterized in that wherein said medicine can be used for the treatment of the respiratory distress syndrome that atypical pneumonia causes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031420672A CN1579421A (en) | 2003-08-05 | 2003-08-05 | Freeze-dried powder of pig's lung surface matter, its preparation method and use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031420672A CN1579421A (en) | 2003-08-05 | 2003-08-05 | Freeze-dried powder of pig's lung surface matter, its preparation method and use |
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| Publication Number | Publication Date |
|---|---|
| CN1579421A true CN1579421A (en) | 2005-02-16 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031420672A Pending CN1579421A (en) | 2003-08-05 | 2003-08-05 | Freeze-dried powder of pig's lung surface matter, its preparation method and use |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102242162A (en) * | 2011-06-13 | 2011-11-16 | 丹阳市永鑫电子工艺有限公司 | Method for preparing phosphatidylcholine from chicken lungs |
| CN102462699A (en) * | 2010-11-01 | 2012-05-23 | 台湾糖业股份有限公司 | Use of porcine lung extract as matrix metalloproteinase inhibitor |
| CN104382942A (en) * | 2014-11-05 | 2015-03-04 | 烟台东诚药业集团股份有限公司 | Novel process for preparing swine pulmonary surfactant suspension |
| CN107519205A (en) * | 2017-08-22 | 2017-12-29 | 昆明理工大学 | A kind of extracting method of animal pulmonary surfactant |
-
2003
- 2003-08-05 CN CNA031420672A patent/CN1579421A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102462699A (en) * | 2010-11-01 | 2012-05-23 | 台湾糖业股份有限公司 | Use of porcine lung extract as matrix metalloproteinase inhibitor |
| CN102462699B (en) * | 2010-11-01 | 2013-05-08 | 台湾糖业股份有限公司 | Use of porcine lung extract as matrix metalloproteinase inhibitor |
| CN102242162A (en) * | 2011-06-13 | 2011-11-16 | 丹阳市永鑫电子工艺有限公司 | Method for preparing phosphatidylcholine from chicken lungs |
| CN104382942A (en) * | 2014-11-05 | 2015-03-04 | 烟台东诚药业集团股份有限公司 | Novel process for preparing swine pulmonary surfactant suspension |
| CN107519205A (en) * | 2017-08-22 | 2017-12-29 | 昆明理工大学 | A kind of extracting method of animal pulmonary surfactant |
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