CN1990880B - Non-zymocyte drug sensitive batten preparation method - Google Patents
Non-zymocyte drug sensitive batten preparation method Download PDFInfo
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- CN1990880B CN1990880B CN200510112029XA CN200510112029A CN1990880B CN 1990880 B CN1990880 B CN 1990880B CN 200510112029X A CN200510112029X A CN 200510112029XA CN 200510112029 A CN200510112029 A CN 200510112029A CN 1990880 B CN1990880 B CN 1990880B
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Abstract
The invention discloses a non-fermentative bacteria drug sensitivity lath. The antibiotic on lath is prepared according to clinical requirement and regulation, and anti- oxidation agent is added into it to prolong its storage period. The product can direct clinical medication and is very great value of clinical application.
Description
Technical field:
The invention belongs to the biologic product technology field.Be specifically related to a kind of non-zymocyte (MP) drug sensitive batten and preparation method thereof.
Background technology:
Over nearly 20 years, owing to extensively use miscellaneous antibacterials in large quantities clinically, drug-resistance of bacteria is more and more general, and the bacterium that has is anti-2-7 kind medicine simultaneously, and the wide-scale distribution of Resistant strain is brought very big difficulty to clinical treatment.The clinical diagnosis and treatment means are brought in constant renewal in addition, though improved diagnosis and result of treatment, have also brought more cross infection chance, make modulation on immune status be tending towards low.Especially noticeable is that very big transition have taken place infection type, and be among the variation, in order to adapt to this new variation, the research fresh condition, solve the new problem that constantly occurs, formed a new subject gradually--clinical microbiology (Clinical Microbiology).
In the last few years, hospital infection (Nosocomial infection) more and more becomes one of problem that people extremely pay close attention to.So-called hospital infection is meant that patient occurred in the while in hospital and the just infection of morbidity soon of leaving hospital, but does not comprise that patient has begun before being admitted to hospital or be in infection in latent period when being admitted to hospital.So the infection of the characteristics of hospital infection in appearing at hospital environment, and take place popular, so can be referred to as hospital acquired infections (Hospital acquired infection) again.Nineteen eighty-three, 11, the 295 routine patients of 21 hospitals, the incidence average out to 8.4% of hospital infection were investigated by the Ministry of Health.Though the state of an illness of generation hospital infection has and gently has heavily, has all increased extra misery, economical load and misfortune to patient, also can increase the weight of the burden of medical treatment and nursery work simultaneously owing to the prolongation hospital stays, influence sick bed and have enough to meet the need.The disease that serious hospital infection often makes patient is suffered from can not reach the curative effect of expection, even produces sequela or the death that is difficult to treat.According to an incomplete statistics data report of the U.S., have 5% hospital infection takes place among its inpatient approximately, the average 4～5d that is in hospital that prolongs has 100,000 people's death every year approximately in hospital infection, estimate annual since hospital infection to consume 20 more surplus hundred million dollars.
From causing the microorganism of hospital infection, no doubt some is still the pathogenic very strong microorganism that we are familiar with, they are everlasting and cause that complication infects after the some diseases, but the pathogenic agent kind of hospital infection in recent years has the trend of considerable change, it was the gram-positive cocci of main pathogen originally that Gram-negative bacteria has replaced, wherein non-zymocyte section and pseudomonas account for the 60%-65% of hospital infection, and are mainly many drug tolerant bacterias.Wherein major part is human body normal microflora, fungi and virus, and also there are some reports the parasite aspect.
With regard to entire society, hospital is a susceptible host, because the patient of hypoimmunity concentrates (comprising infant and the elderly), the continual renovation of diagnostic means (as the application of endoscope, intubate, conduit etc.), though improved diagnosis and result of treatment, also increased the chance of cross infection.Owing to use microbiotic widely, the continuous transition of bacterium have encouraged the existence and the development of nosocomial infection, and the clinical microbiology most important character of today is to change to the hospital infection aspect.
Microorganism identification and susceptibility analytical system are the high-tech in-vitro diagnosis products that is mainly used in clinical labororatory, and be significant to auxiliary clinical each section office's diagnoses and treatment.At present in the world, Rapid identification and the susceptibility analysis of bacterium obtained very big progress, microorganism automatization testing product has progressively substituted manual inspection.
At present, like product mainly contains in the world: the MicroScan automatic microbe of the VITEK-AMS microbiological analysis system of French biology-Mei Liai company, U.S. Dade-MicroScan company is identified and the SENSTITRE fluorescent method fast microbiological of antibiotics susceptibility test system and Britain Trek Diagnostic System Ltd. is identified and the susceptibility analytical system.Their principle of work is close, mainly be difference according to the bacterium physico-chemical property, adopt photoelectric colorimetry (susceptibility is a turbidimetry), measure bacterial growth and decompose substrate and cause pH value to change and the different colours that produces and turbidity change and judge response situation, thereby provide the identification and susceptibility result.
At present, for adapting to the demand of specialty of clinical labororatory to microorganism identification susceptibility equipment, have higher requirement to the function of microflora product in market, the microniological proudcts that development and operation is easy, the evaluation scope is wide, susceptibility MIC value is accurately practical, also can provide experimental result have fast become a kind of an urgent demand.
Though the microbial identification system of BIOLOG company is the Identifying micro-organisms bacterial classification comparatively exactly, but lacking susceptibility (microbiotic MIC) detects, and when doing the clinical expansion of Micro biological Tests product, the general system that all requires possesses two kinds of functions of MIC (minimal inhibitory concentration) value of identifying bacterial classification and detect antibiotics simultaneously, to instruct clinical application.For meeting the need of market, and in competition, occupy advantage.
And the drug sensitive batten kind of product is less now, can not satisfy the drug sensitive test of all kinds bacterium, antibiotic concentration gradient is less in the lath in addition, and major part is reported sensitivity, medium sensitivity and resistance result qualitatively only, and can accurately not report out quantitative MIC value.
Summary of the invention:
Technical problem to be solved by this invention is to overcome above-mentioned weak point, a kind of susceptibility fast and accurately of research and design detection system.
The invention provides a kind of non-zymocyte (ME) drug sensitive batten.
Susceptibility of the present invention detects to be tested based on following principle:
Linear relationship according to each medicine growth slope and MIC (minimal inhibitory concentration), select the extent of dilution of proper number, the bacteria suspension that adds bacterium to be checked, after 4-15h is hatched, use photoelectricity than turbid principle, can obtain the slope of bacterium to be checked in each concentration, compare with positive control hole deviation rate, and calculate the compound slope of bacterium to be checked, obtain the MIC value through regression analysis, and obtain the result of corresponding sensitivity (S), medium sensitivity (I) and resistance (R) according to the NCCLS standard.
On the other hand, the inventor improves the stability of drug sensitive batten through great deal of experimental.Because in drug sensitive batten of the present invention, added microbiotic, because oxidation very easily takes place the performance of microbiotic own, just can lose efficacy in the short period of time, storage has caused very big influence to drug sensitive batten.Therefore the present invention selects for use antioxidant to add the preservation period that prolongs drug sensitive batten in the drug sensitive batten.
Antioxidant (AOA) also be scavenging agent, be startup and hyperplasia (spreading) process that a class can suppress or block free chain reaction, reduce number of free radical, delay the old process of sorrow, the compound antioxidant and the free radical that improve vitality are a pair of paradox.The molecular structure of antioxidant is more special, and its electronics is single arrangement, and it can provide in the electronics and free radical, and self can not be formed with the material of harm, and chain reaction can not take place yet, and reaches oxidation resistant purpose by removing free radical.How antioxidant works
1. normal Sauerstoffatom has 4 pairs of electronics, and the body eubolism can make atom lose an electronics, has so just formed free radical, and free radical mainly makes oneself pairing by the electronics of grabbing on other his molecule.
2. when free radical is captured an electronics from cytolemma after, just produced another new free radical, and begun chain reaction.
3. electronics is captured chain reaction erosion cytolemma, and the forfeiture that causes the cell integrity is that cancer and other disease have been opened convenience.
4. because its specific molecule structure, antioxidant can provide that an electronics is given free radical and self can not form the deleterious Hazardous substances that can cause chain reaction.
Common antioxidant has VC, VE, selenium, germanium, veronal, glycine, sodium bisulfite, tea-polyphenol class, spice extract.
Amino acid and dipeptide amino acid such as methionine(Met), tryptophane, phenylalanine, proline(Pro) etc. can both with metal ion-chelant, so their good auxiliary antioxidants.In recent years, the food scientist finds that the L-Ala end is that 9 kinds of dipeptides of nitrogen are all stronger than any amino acid whose resistance of oxidation.Wherein the strongest with L-Ala-Histidine, L-Ala-tyrosine, 3 kinds of dipeptides resistance of oxidation of L-Ala-tryptophane especially, be worth exploitation energetically.
Spice extract is as far back as the thirties in 20th century, and people study the antioxygenation of spice with regard to beginning.To the fifties, the scientific research personnel analyzes 32 kinds of spices, find antioxidant property wherein best be Rosmarinus officinalis and Salvia japonica Thunb..This series products contains multiple antioxidant components such as flavonoid, terpenoid, organic acid more, can cut off greasy autoxidation chain, chelated metal ions, and play and the organic acid synergistic function.Rosmarinus officinalis (Rosmarinus officinalisL.) is a Labiatae, belongs to evergreen perennial filling and wants the incense drug Maki thing of tool high anti-oxidation ability.Its resistance of oxidation comes from the aldehydes matter (phenolics) that includes, serve as main wherein with phenolic diterpenes, as Salvin (carnosicacid), carnosol (carnosol), rosmarinic acid rosemary extract Nantural non-toxics such as (rosmarinic acid), anti-oxidation efficacy is higher than natural antioxidantss such as existing VC, VE, tea-polyphenol far away, resistance of oxidation than the oxygenant BHT of synthetic and BHA is strong more than 4 times, and its Stability Analysis of Structures, is difficult for decomposing.Therefore rosemary antioxidant is a natural antioxidant of new generation, has thoroughly avoided the toxic side effect of synthetized oxidation preventive agent and the characteristics of pyrolytic decomposition.
The inventor selects the use of antioxidant by following test:
1, experimental technique
Adopted veronal, glycine and Rosmarinus officinalis to be configured to the aqueous solution and the aqueous solution that does not add antioxidant respectively and added that microbiotic is mid-to become drug sensitive batten, stored for-10 ℃ as antioxidant.Selection standard bacterial strain 29213 adds drug sensitive batten to be tested, and the microbiotic MIC value of testing 4 kinds of laths for the first time is all in specialized range.First month carried out one-time detection weekly, from per two months per two weeks carrying out one-time detection, carries out one-time detection after six months every other month, to all losing efficacy to all microbiotic.Every kind of lath of each test is tested ten times altogether.
2, lath working method (clinical setting during use)
(1), get 27853 usefulness reason salt solution and dispose 0.5 Maxwell bacteria suspension, bacteria suspension and cultured solution of broth are diluted (being that every 12ml meat soup adds the 60ul bacteria suspension) by 1: 200 times.
(2), the bacterium liquid that configures is added in the drug sensitive batten with pipettor, every hole adds 100ul.
(3), lath being placed 35 ℃ of incubators cultivated 24 hours.
(4), read the lath result, be growth if become turbid in the hole, if haze-free for not growing, every kind of first concentration value of not growing the hole of microbiotic is correct MIC value.
3, experimental result
This experiment has been carried out 1 year altogether, and experimental result is as shown in the table:
4, interpretation of result
Test-results shows:
(1), use veronal, glycine antioxidant, inefficacy has just appearred in lath some microbiotic after two months, shows that these two kinds of microbiotic not only prolong the preservation period of susceptibility, can influence antibiotic performance on the contrary, has shortened the period of storage of lath.So two kinds of antioxidants can not be selected for use.
(2), use the rosemary antioxidant microbiotic just to have some microbiotic to occur losing efficacy later at ten months, obviously long than the lath shelf time that does not add antioxidant.So using Rosmarinus officinalis is feasible as the preservation period that antioxidant adding drug sensitive batten prolongs drug sensitive batten.
On the basis of above-mentioned test, the present invention has selected rosemary antioxidant for use, strengthens the stability of drug sensitive batten, prolongs the preservation period of drug sensitive batten.
Another object of the present invention has provided the preparation method of non-zymocyte drug sensitive batten, and this method comprises the following steps:
(1) configuration microbiotic diluent
It is stand-by as antibiotic diluent to add (Alecrim antioxidant) concentration in the distilled water and be 100,000 of distilled water/to 1,000,000/be configured to the aqueous solution;
(2) packing
It is stand-by that the diluent that configures is packed as every test tube 15ml;
(3) configuration stoste
Require the various antibiotic initial stostes of configuration according to dilution;
(4) packing liquid material
According to the requirement of various lath concentration dilution, the microbiotic stoste of step (3) is joined in step (2) test tube that corresponding branch installs.
(5) application of sample packing lath
Use to divide assembling system in the corresponding position in 96 holes to specified drug sensitive batten application of sample, every hole adds 50ul;
(6) lath drying
Above-mentioned lath vacuum-drying 16-18 hour;
(7) packing
Above-mentioned antibiotic concentration dilution requires:
Stoste: the initial soln of medicine after preparation
(once) diluent: 10 times of gained solution of stoste dilution, promptly 100ul stoste and 900ul solvent form
(secondary) redilution liquid: 10 times of gained solution of diluent redilution, promptly 100ul diluent and 900ul solvent form
Lath of the present invention is behind the bacterium bacteria suspension that carries out bacterium operation adding 100ul, and the microbiotic ultimate density is as follows in the lath: (unit is: ug/ml)
Annotate: be the scope between medicaments insensitive and resistance between the shade.(with reference to the NCCLS2002 standard)
Product of the present invention is compared with existing Micro biological Tests product, has more the clinical application directive significance, can reduce growing of Resistant strain, and reduces various infection in the institute.Statistical analysis system can be according to different statistical condition, in one period, analysis on the epidemiology is made in each lesion of hospital, this crowd zone and surrounding area, and the effect of monitoring is played in the control of the variation of special Resistant strain and disease, bigger clinical value is arranged.
Embodiment:
Example:
The MP drug sensitive batten is an example, and the technological process of production of producing 250 products in batches is as follows:
1, the configuration Rosmarinus officinalis aqueous solution
Taking by weighing 0.03 gram Rosmarinus officinalis (Rosmarinus officinalis ultimate density be 100,000/) fully is dissolved in the 1500ml deionized water.
Or take by weighing 0.3 gram Rosmarinus officinalis (Rosmarinus officinalis ultimate density be ten thousand/) and fully be dissolved in the 1500ml deionized water.
Or take by weighing 0.003 gram Rosmarinus officinalis (Rosmarinus officinalis ultimate density be 1,000,000/) and fully be dissolved in the 1500ml deionized water.
2,, evenly divide then to install in 96 test tubes that disinfect every pipe packing 15ml with the solution autoclaving that configures.
3, dispose the initial liquid of each microbiotic.
Concentration according to following table disposes each antibiotic initial liquid:
4, dispose each hole antibiotic solution
According to following table the antibiotic concentration dilution table add in the stand-by 15ML test tube of 96 packing of lath by the volume that shows in the table.
Non-zymocyte (No. four plates) MP
Remarks:
1, above unit all is ul
2. black matrix look word table shows with 10 times of stoste dilutions: i.e. 100ul stoste+900ul water diluent.
3, italics is represented with 10 times of diluent redilution: i.e. 100ul diluent liquid+900ul water
4, application of sample packing lath
96 cuvette cartridges that 5, will configure are adding on the model machine, use to add model machine to specified drug sensitive batten application of sample, and every hole adds 50ul.(to move the branch assembling system earlier before this; Whole procedure approximately needs 3 hours).
6, lath drying
The vacuum pump that the lath that application of sample is good is put into drying room carries out vacuum to be drained, and lath can drying finish after 24 hours.
7, lath packing
The lath that drying is good is delivered to make-up room from drying room through pass-through and is packed.
8, lath storage
The lath that packing finishes is put into-20 ℃ of refrigerators and is carried out freezing preservation.
Claims (2)
1. the preparation method of non-zymocyte drug sensitive batten is characterized in that this method comprises the following steps:
(1) disposes antibiotic diluent
Add rosemary antioxidant in the distilled water, the concentration of adding be 100,000 of distilled water/to 1,000,000/, be configured to the aqueous solution, stand-by as antibiotic diluent;
(2) packing
It is stand-by that the diluent that configures is packed as every test tube 15ml;
(3) configuration stoste
Concentration requirement according to following table disposes various antibiotic stostes:
(4) packing liquid material
According to following table the antibiotic concentration dilution table add in the stand-by 15ML test tube of 96 packing of step (2) by the volume that shows in the table;
Described stoste is the initial soln of medicine after preparation;
Described diluent: 10 times of gained solution of stoste dilution, promptly 100ul stoste and 900ul solvent form
Redilution liquid: 10 times of gained solution of diluent redilution, promptly 100ul diluent and 900ul solvent form:
Microbiotic name location solution title consumption ul
A1 -- --
B1 -- --
No. 17 medicines
No. 17 medicine stostes 180 of C1
Ciprofloxacin
No. 17 medicine stostes 90 of D1
No. 17 medicine stostes 45 of E1
No. 17 medicine diluents 225 of F1
No. 17 medicine diluents 112 of G1
No. 17 medicine diluents 56 of H1
Microbiotic name location solution title consumption ul
No. 25 medicine stostes 640 of A2
No. 25 medicine stostes 320 of B2
No. 25 medicine stostes 160 of C2
No. 25 medicines
No. 25 medicine stostes 80 of D2
The husky star of oxygen oxygen
No. 25 medicine stostes 40 of E2
No. 25 medicine diluents 200 of F2
No. 25 medicine diluents 100 of G2
No. 25 medicine diluents 50 of H2
Microbiotic name location solution title consumption ul
No. 2 medicine stostes 192 of A3
No. 2 medicine stostes 96 of B3
No. 2 medicine stostes 48 of C3
No. 2 medicines
No. 2 medicine diluents 360 of D3
Gentamicin
No. 2 medicine diluents 180 of E3
No. 2 medicine diluents 90 of F3
No. 2 medicine diluents 45 of G3
No. 2 medicine diluents 23 of H3
Microbiotic name location solution title consumption ul
No. 3 medicine stostes 144 of A4
No. 3 medicine stostes 72 of B4
No. 3 medicine stostes 36 of C4
No. 3 medicines
No. 3 medicine diluents 180 of D4
Amikacin
No. 3 medicine diluents 90 of E4
No. 3 medicine diluents 45 of F4
No. 3 medicine redilution of G4 liquid 230
No. 3 medicine redilution of H4 liquid 112
Microbiotic name location solution title consumption ul
No. 21 medicine stostes 768 of A5
No. 21 medicine stostes 384 of B5
No. 21 medicine stostes 192 of C5
No. 21 medicines
No. 21 medicine stostes 93 of D5
Tobramycin
No. 21 medicine stostes 48 of E5
No. 21 medicine diluents 240 of F5
No. 21 medicine diluents 120 of G5
No. 21 medicine diluents 60 of H5
Microbiotic name location solution title consumption ul
No. 5 medicine stostes 288 of A6
No. 5 medicine stostes 144 of B6
No. 5 medicines
No. 5 medicine stostes 72 of C6
Piperacillin
No. 5 medicine stostes 36 of D6
No. 5 medicine diluents 180 of E6
No. 5 medicine diluents 90 of F6
No. 5 medicine diluents 45 of G6
No. 5 medicine diluents 23 of H6
Microbiotic name location solution title consumption ul
No. 31 medicine stostes 288 of A7
No. 31 medicine stostes 144 of B7
No. 31 medicine stostes 72 of C7
No. 31 medicines
No. 31 medicine stostes 36 of D7
Aztreonam
No. 31 medicine diluents 180 of E7
No. 31 medicine diluents 90 of F7
No. 31 medicine diluents 45 of G7
No. 31 medicine diluents 23 of H7
Microbiotic name location solution title consumption ul
No. 18 medicine stostes 768 of A8
No. 18 medicine stostes 384 of B8
No. 18 medicine stostes 192 of C8
No. 18 medicines
No. 18 medicine stostes 96 of D8
Imipenum
No. 18 medicine stostes 48 of E8
No. 18 medicine diluents 240 of F8
No. 18 medicine diluents 120 of G8
No. 18 medicine diluents 60 of H8
Microbiotic name location solution title consumption ul
No. 9 medicine stostes 144 of A9
No. 9 medicines
No. 9 medicine stostes 72 of B9
Ceftazime
No. 9 medicine stostes 36 of C9
No. 9 medicine diluents 180 of D9
No. 9 medicine diluents 90 of E9
No. 9 medicines
No. 9 medicine diluents 45 of F9
Ceftazime
No. 9 medicine diluents 23 of G9
No. 9 medicine diluents 12 of H9
Microbiotic name location solution title consumption ul
No. 8 medicine stostes 144 of A10
No. 8 medicine stostes 72 of B10
No. 8 medicines
No. 8 medicine stostes 36 of C10
Cefoperazone
No. 8 medicine diluents 180 of D10
No. 8 medicine diluents 90 of E10
No. 8 medicine diluents 45 of F10
No. 8 medicine diluents 23 of G10
No. 8 medicine diluents 12 of H10
Microbiotic name location solution title consumption ul
No. 10 medicine stostes 288 of A11
No. 10 medicine stostes 144 of B11
No. 10 medicine stostes 72 of C11
No. 10 medicines
No. 10 medicine stostes 36 of D11
Ceftriaxone
No. 10 medicine diluents 180 of E11
No. 10 medicine diluents 90 of F11
No. 10 medicine diluents 45 of G11
No. 10 medicine diluents 23 of H11
Microbiotic name location solution title consumption ul
No. 40 medicine stostes 576 of A12
No. 40 medicine stostes 288 of B12
No. 40 medicine stostes 144 of C12
No. 40 medicines
No. 40 medicine stostes 72 of D12
Cefepime
No. 40 medicine stostes 36 of E12
No. 40 medicine diluents 180 of F12
No. 40 medicine diluents 90 of G12
No. 40 medicine diluents 45 of H12
(5) application of sample packing lath
Use to divide assembling system in the corresponding position in 96 holes to specified drug sensitive batten application of sample, every hole adds 50ul;
(6) lath drying
Above-mentioned lath vacuum-drying 16-18 hour;
(7) packing.
2. want the preparation method of 1 described a kind of non-zymocyte drug sensitive batten according to right, the non-zymocyte drug sensitive batten that it is characterized in that making by this method is behind the bacterium bacteria suspension that carries out bacterium operation adding 100ul, and the microbiotic ultimate density is as follows in the lath: unit is: ug/ml
MP lath susceptibility concentration gradient
It between the shade of last table the scope between medicaments insensitive and resistance.
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|---|---|---|---|
| CN200510112029XA CN1990880B (en) | 2005-12-27 | 2005-12-27 | Non-zymocyte drug sensitive batten preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510112029XA CN1990880B (en) | 2005-12-27 | 2005-12-27 | Non-zymocyte drug sensitive batten preparation method |
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| Publication Number | Publication Date |
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| CN1990880A CN1990880A (en) | 2007-07-04 |
| CN1990880B true CN1990880B (en) | 2010-12-08 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2462387Y (en) * | 2001-01-21 | 2001-11-28 | 张同军 | Density gradient medicine sensitive test strip |
| CN2544282Y (en) * | 2002-04-26 | 2003-04-09 | 莱芜钢铁集团有限公司医院 | Mountable/dismountable microquantity dilute drug sensitivity reagent box |
| WO2004110412A1 (en) * | 2003-06-18 | 2004-12-23 | Lipofoods, S.L. | Microcapsules for the administration of active ingredients |
-
2005
- 2005-12-27 CN CN200510112029XA patent/CN1990880B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2462387Y (en) * | 2001-01-21 | 2001-11-28 | 张同军 | Density gradient medicine sensitive test strip |
| CN2544282Y (en) * | 2002-04-26 | 2003-04-09 | 莱芜钢铁集团有限公司医院 | Mountable/dismountable microquantity dilute drug sensitivity reagent box |
| WO2004110412A1 (en) * | 2003-06-18 | 2004-12-23 | Lipofoods, S.L. | Microcapsules for the administration of active ingredients |
Non-Patent Citations (2)
| Title |
|---|
| 董文波.细菌药敏最低抑菌浓度微孔检测板的研制.衡阳医学院学报28 2.2000,28(2),第166页右栏第一段至169页倒数第一段. |
| 董文波.细菌药敏最低抑菌浓度微孔检测板的研制.衡阳医学院学报28 2.2000,28(2),第166页右栏第一段至169页倒数第一段. * |
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Address after: Kangshi road Kangqiao Industrial Zone Pudong New Area town Shanghai City No. 31 200010 Cambridge Patentee after: Upper starfish one hundred Bioisystech Co., Ltd Address before: 201103 No. 1351, Shanghai, Wuzhong Road Patentee before: Shanghai Fosun Biolog Biotechnology Co., Ltd. |
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Granted publication date: 20101208 Termination date: 20191227 |
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