CL059
L-Asparaginase
CAS: 9015-68-3
Molecular Formula: C14H17NO4S
CL059 - Names and Identifiers
| Name | L-Asparaginase |
| Synonyms | CL059 LASPAR crasnitin colaspase EC 3.5.1.1 ASPARAGINASE L-Asparaginase Sustanon Injection ADENOSINE DEAMINASE Asparaginase (Owenism) 1,2-Benzothiazol-3(2H)-one Asparaginase (usan 8ci 9ci) L-ASPARAGINE AMIDOHYDROLASE Asparaginase, L- (escherichia coli) Asparaginase from Escherichia coli,L-Asparagine Amidohydrolase |
| CAS | 9015-68-3 |
| EINECS | 232-765-3 |
| InChI | InChI=1/C15H16Cl3N3O2.C9H8O4/c1-2-4-20(15(22)21-5-3-19-10-21)6-7-23-14-12(17)8-11(16)9-13(14)18;1-6(10)13-8-5-3-2-4-7(8)9(11)12/h3,5,8-10H,2,4,6-7H2,1H3;2-5H,1H3,(H,11,12) |
CL059 - Physico-chemical Properties
| Molecular Formula | C14H17NO4S |
| Molar Mass | 295.35 |
| Specific Rotation(α) | D20 -30 to -32° |
| Appearance | suspension |
| Color | Crystals or powder |
| Merck | 13,841 |
| Storage Condition | 2-8°C |
| MDL | MFCD00130565 |
| Physical and Chemical Properties | Asparaginase is an enzyme preparation produced by microbial fermentation. It is a white crystalline powder, easily soluble in water, insoluble in organic solvents such as ethanol, acetone, chloroform, acetaldehyde, benzene, etc. It is slightly wet and stable to heat. It lasts for 15min at 500C, the activity decreases by 30%, and it is completely inactivated at 600C for less than 1h. Freeze-dried products can be stable for several months at 2 ~ 50C. However, the solution can only be stored for a few days and 200C for 7 days. 50C storage for 14 days did not reduce the enzyme activity. The optimum ph is 8.5 and the optimum temperature is 370C. This product is a drug that has a selective inhibitory effect on tumor cells. It is effective for solid tumors and leukemia, and has no cross-resistance with commonly used mercaptopurine, vincristine, cytarabine, methotrexate, etc. |
CL059 - Risk and Safety
| Risk Codes | R61 - May cause harm to the unborn child R42/43 - May cause sensitization by inhalation and skin contact. R63 - Possible risk of harm to the unborn child |
| Safety Description | S53 - Avoid exposure - obtain special instructions before use. S22 - Do not breathe dust. S36/37/39 - Wear suitable protective clothing, gloves and eye/face protection. S45 - In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.) S36/37 - Wear suitable protective clothing and gloves. |
| UN IDs | 3249 |
| WGK Germany | 3 |
| RTECS | CI9000000 |
| FLUKA BRAND F CODES | 10-21 |
| Hazard Class | 6.1(a) |
| Packing Group | II |
| Toxicity | TDLo ims-chd: 8145 iu/kg/1W:SYS CANCAR 34,780,74 |
CL059 - Nature
Open Data Verified Data
- this strain is an enzyme preparation produced by microbial fermentation, which is a white crystalline powder; Slightly wet. Soluble in water, insoluble in methanol, ethanol, acetone, chloroform, acetaldehyde, benzene and other organic solvents. On the thermal stability, 50 15min, the activity decreased by 30%,60th inactivation. The lyophilized product is stable for several months at 2-5 °c, but the solution can only be stored for several days: 20 °c for 7 days, 5 °c for 14 days does not reduce the activity of the enzyme. The optimum pH was 8.5, and the optimum temperature was 37. The molecular weights of the pure enzymes ranged from 130000 to 140000.
- day (Portal) asparaginase is an amidohydrolase. Tumor cells can not synthesize the necessary day (gate) of the winter amide for growth, must rely on the host supply, this product can make the day (gate) of the winter amide hydrolysis, so that the tumor cells lack days (gate) due to the growth inhibition of. Normal cells can synthesize asparagine, so it is less affected. Therefore, this product is a drug that has selective inhibitory effect on tumor cells. In animal experiments, the product is effective for solid tumors and leukemia, and has no cross resistance to commonly used mercaptopurine, methotrexate, vincristine, cytarabine and so on. The blood concentration after intramuscular injection is one tenth of that after intravenous injection. After intravenous injection, the duration of enzyme activity was different due to the source of the product, and the Half-Life was 3~24h. The enzyme is excreted from the urine, and there is no accumulation in the body.
Last Update：2024-01-02 23:10:35
CL059 - Preparation Method
Open Data Verified Data
Erwinia fermentation can also be used.
Last Update：2022-01-01 11:11:27
CL059 - Standard
Authoritative Data Verified Data
This product is asparagine monohydrate. The content of C4H8N2O3 shall not be less than 98.0% calculated as the dried product.
Last Update：2024-01-02 23:10:35
CL059 - Trait
Authoritative Data Verified Data
- This product is white or off-white crystalline or crystalline powder; Odorless.
- This product is soluble in hot water, almost insoluble in methanol, ethanol or ether; Soluble in dilute hydrochloric acid or sodium hydroxide solution.
specific rotation
take this product, precision weighing, add 3mol/L hydrochloric acid solution to dissolve and quantitatively dilute to make a solution containing about 20mg per lml, and determine according to law (General 0621), the specific rotation was 31 ° to ten 35 °.
Last Update：2022-01-01 11:31:03
CL059 - Introduction
See Chinese Pharmacopoeia
Last Update：2022-10-16 17:29:57
CL059 - Use
Open Data Verified Data
- Anti-tumor enzyme preparation. The remission rate of acute lymphoblastic leukemia was more than 50%. It has a certain effect on acute myeloid leukemia and acute monocytic leukemia, and has a good effect on malignant lymphoma. The advantage is that it is also effective for the case of recurrence after the treatment of common drugs. The disadvantage is that the single use is not only short remission period, but also easy to produce drug resistance. On the body's immune suppression, can be used for the treatment of Dermatomyositis.
- the usage and dosage can be used for intravenous injection, intravenous drip, intramuscular injection and intrathecal injection. General dose: 20~5000 units/kg, or 10000 N15000 units/mz, 3~7 times a week. Preferably, it is from 500 to 1000 units/kg per day. Can also be applied once a week, each time 2500 units/kg. Generally 3~4 weeks for a course of treatment. The total dose will depend on the purity and toxicity of the drug used. Intravenous injection with normal saline 20~40ml dilution, intravenous drip with 5% glucose solution or 0.9% sodium chloride injection dilution.
- formulation daily (Portal) asparaginase for injection: 1000 units or 2000 units per tablet.
Last Update：2022-01-01 11:11:27
CL059 - Differential diagnosis
Authoritative Data Verified Data
- take about lg of this product, add 10% sodium hydroxide solution 5ml, slightly heat to boiling, the generated vapor has ammonia odor and can make the wet red litmus test paper turn blue.
- take about 1 mg of this product, add 5ml of water to dissolve, add about 5mg of ninhydrin, heat, the solution appears purple.
- each 0.lg of this product and the asparagine reference product were added with 10ml of water, dissolved at a water temperature (not more than 40 ° C.), and allowed to cool, and used as a test solution and a reference solution. According to the chromatographic condition test under other amino acids, the position and color of the main spot of the test solution should be the same as that of the reference solution.
Last Update：2022-01-01 11:31:04
CL059 - Safety
Open Data Verified Data
- (1) Escherichia coli Day (phylum) asparaginase contains endotoxin, can cause Fever. Also often loss of appetite, Nausea, Vomit, Diarrhea, some patients Head Pain, dizziness, drowsiness, mental disorder. Because asparaginase can affect protein synthesis and interfere with lipid metabolism, some patients have low plasma protein, high or low blood lipids, azotemia and liver function damage. Some patients have myelosuppression, thrombocytopenia and leukopenia. Some patients with alopecia, proteinuria, pancreatitis. (2) can cause allergic reactions, before use must first do skin test, patients with allergic history should be very careful or not. (3) the purity and allergic reactions of different pharmaceutical factories and different batches of products are different, and the use should be careful. (4) teratogenic effect, early pregnancy disabled. (5) liver and kidney function serious damage should not be used. (6) after dissolution, it should not be placed for a long time to avoid loss of vitality. (7) abnormal toxicity of sodium chloride solution containing 44000 units of this product from the body weight of 20g ± lg of male mice tail injection of 0. 5ml 30min after the emergence of Dyspnea, convulsive symptoms. (8) There are reports of other diseases.
- keep in a cold-dark dry place.
Last Update：2022-01-01 11:11:28
CL059 - Exam
Authoritative Data Verified Data
transmittance of solution
take 0.4g of this product, add water 20ml to dissolve, according to UV-visible spectrophotometry (General rule 0401), measure the transmittance at 430nm wavelength, not less than 98.0%.
chloride
take l.Og of this product and check it according to law (General rule 0801). Compared with the control solution made of 5.0ml of standard sodium chloride solution, it should not be more concentrated (0.005%).
sulfate
take 2.0g of this product, add 25ml of water, heat and dissolve, cool, check according to law (General rule 0802), and compare with the control solution made of standard potassium sulfate solution, no more concentrated (0.005%).
other amino acids
take 0.25g of this product, put it in a 10ml measuring flask, and add an appropriate amount of water. Slightly warm to dissolve (not more than 40°C), cool, dilute to the scale with water, shake, as a test solution; Take 1ml of precision, put in 200ml measuring flask, dilute with water to scale, shake, as a control solution; Take another glutamic acid reference product 25mg, put it in a 10ml measuring flask, add appropriate amount of water to heat to dissolve, then add 1ml of test solution, dilute with water to scale, shake well as a system-suitable solution. According to the thin layer chromatography (General 0502) test, draw 5ul of each of the above three solutions, respectively, on the same silica gel G thin layer plate, with glacial acetic acid-water-n-butanol (1:1:2) for Development, spread at least 10cm, dry, heat at 110°C for 15 minutes, spray with 0.2% ninhydrin in n-butanol -2mol/L acetic acid solution mixture, heat at 110°C for about 10 minutes until spots appear, immediate review. The control solution should show a clear spot, and the system applicable solution should show two completely separated spots. If the test solution shows impurity spots, the color should not be deeper (0.5%) than the main spot of the control solution.
loss on drying
take this product, dry at 105°C for 3 hours, loss weight is 11.5% ~ 12.5% (General 0831).
ignition residue
not more than 0.1% (General rule 0841).
Iron Salt
take l.Og of this product, add 25ml of water to dissolve, and then check according to law (General rule 0807). Compared with the control solution made of 0.001% of standard iron solution, it shall not be deeper ().
ammonium salt
Take 10mg of this product, put it in a weighing bottle with a diameter of about 4cm, and add 1 ml of water to dissolve it. Take another 1.0 of standard ammonium chloride solution and put it in another same weighing bottle. Under the cap of the two weighing bottles, a piece of silver-manganese test paper with a side length of about 5mm moistened with 1 drop of water was pasted (the filter paper strip was dipped in 0.85% manganese sulfate-0.85% silver nitrate solution for 3-5 minutes, taken out and dried). Add 0.30g of magnesium oxide to each of the two weighing bottles, immediately close the plug, rotate and mix well at 40°C for 30 minutes, the gray color produced by the test paper shall not be deeper (0.1%) than that of the control test paper made of standard ammonium chloride solution.
Heavy metals
take l.Og of this product, add 23ml of water to heat and dissolve, add 2ml of acetate buffer (pH3.5), and check according to law (the first method of general rule 0821), containing heavy metals not more than 10 parts per million.
arsenic salt
take 2.0g of this product, add water 23ML and hydrochloric acid 5ml to dissolve, check according to law (General rule 0822 first law), should comply with the provisions (0.0001%).
Last Update：2022-01-01 11:31:05
CL059 - Content determination
Authoritative Data Verified Data
take this product about 0.15g, precision weighing, according to the nitrogen determination method (General 0704 first method), each 1 ml sulfuric acid titration solution (0.05mol/L) is equivalent to 6.606mg C4H8N203.
Last Update：2022-01-01 11:31:05
CL059 - Category
Authoritative Data Verified Data
amino acid drugs.
Last Update：2022-01-01 11:31:05
CL059 - Storage
Authoritative Data Verified Data
shade, seal, and store in a cool place.
Last Update：2022-01-01 11:31:06
CL059 - L-Asparagine Tablets
Authoritative Data Verified Data
This product contains asparagine (C4H8N203) should be 90.0% to 110.0% of the label children.
trait
This product is white tablet.
identification
take the appropriate amount of fine powder of this product, according to the identification test under the item of asparagine, show the same reaction.
examination
should be in accordance with the relevant provisions under The tablet item (General rule 0101).
Content determination
Take 10 tablets of this product, precision weighing, fine grinding, precision weighing take appropriate amount (about equivalent to asparagine, according to C4H8N203 0.15g), according to the method under the item of asparagine determination.
category
The same as asparagine.
specification
0.25g (as C4H8N203)
storage
shade, seal, and store in a cool place.
Last Update：2022-01-01 11:31:06
CL059 - L-asparaginase (E. Coli) for injection
Authoritative Data Verified Data
This product is a sterile lyophilized product of L-asparaginase (E. Coli) with appropriate amount of stabilizer and excipient. The titer of L-asparaginase (E. Coli) should be 85.0% to 115.0% of the labeled amount.
trait
This product is a white lyophilized cake or powder.
identification
- take this product, add water to dissolve and dilute to make a solution containing 1000 units per 1 ml, and test the identification (1) under the item of asparaginase (E. Coli), the same reaction should be shown.
- take this product, add mobile phase A to dissolve and dilute to make A solution containing about 100 units per lm, as A test solution, according to the identification under the item of asparaginase (Escherichia coli) (2) the same results should be shown in all trials.
examination
- pH value: Take 1 piece of this product, Add 10ml of water to dissolve, shake well, and measure according to law (General rule 0631). The pH value should be 6.5~7.5.
- the purity of this product is taken, and the mobile phase is dissolved and diluted to prepare a solution containing about 200 units per 1 ml as a test solution. Check according to the method of asparaginase (E. Coli), the purity should not be less than 95.0%.
- loss on drying: Take O.lg of this product, dry to constant weight at 105°C, and the weight loss shall not exceed 5.0% (General rule: 0831).
- abnormal toxicity take this product, and dissolve and dilute the solution containing 10 000 units per lml of sodium injection, and check according to law (General rule 1141), and shall comply with the regulations.
- bacterial endotoxin this product, according to the law to check (General 1143), each unit of L-asparaginase (E. Coli) containing endotoxin should be less than 0.015EU.
- sterile take this product, after dissolving with appropriate solvent, the membrane filtration method, according to the law inspection (General 1101), should comply with the provisions.
- In addition to a small amount of fibrous insolubles and slight opalescence allowed for visible foreign bodies, the other items shall comply with the relevant provisions under injection (General rule 0102).
titer determination
take 5 pieces of this product and add an appropriate amount of 0.1 mol/L phosphate buffer (pH 8.0) was dissolved, and the whole amount was transferred to the same measuring flask, diluted to the scale with the above buffer, and shaken. An appropriate amount is accurately taken, and a solution containing about 5 units per 1 ml is prepared by quantitative dilution with the above buffer, and the enzyme activity is measured and calculated according to the method of asparaginase (Escherichia).
category
Same as L-asparaginase (E. Coli).
specification
(1)5000 units (2) 10,000 units
storage
shading, closed, cold preservation.
Last Update：2022-01-01 11:31:07
CL059 - Reference Information
| EPA chemical substance information | information provided by: ofmpeb.epa.gov (external link) |
| biological activity | L-Asparaginase (L- ASNase) is a hydrolase that catalyzes the conversion of L-asparagine, for the study of acute lymphoblastic leukemia. L-asparaginase removal of L-asparagine from plasma results in inhibition of RNA and DNA synthesis and subsequent apoptosis. |
| Use | (day) asparaginase is an anti-tumor enzyme preparation. It has a certain effect on acute myeloid leukemia and acute monocytic leukemia. The curative effect on malignant lymphoma is also good, the remission rate of acute lymphatic leukemia is more than 50%, and it is also effective for recurrent cases after common drug treatment, but the single use is not only short remission period, and easy to produce drug resistance. It also has an inhibitory effect on the body's immunity. But Enterobacter (day) asparaginase contains endotoxin, can cause Fever, loss of appetite, Nausea, Vomit, Diarrhea, some patients Head Pain, dizziness, drowsiness, mental confusion, some patients have low plasma protein, blood lipid is too high or too low, azotemia and liver function damage, some patients have bone marrow suppression, platelets and white blood cells decreased. Some patients with alopecia, proteinuria, pancreatitis. Skin test must be done before use, so as not to cause allergic reactions, allergic history of patients should be very careful or not. The purity and allergic reactions of different pharmaceutical factories and different batches of products are different, and the use should be careful. Teratogenic effect, early pregnancy disabled. Liver and kidney function serious damage to avoid. It can be used for intravenous injection, intravenous drip, intramuscular injection and intrathecal injection. General dose: 20 ~ 5000U/kg, or 10000 ~ 15000U/m%<2, 3~7 times a week. From 500 to 1000U/kg per day, Preferred. Can also be applied once a week, each time 25000U/kg. Generally 3 to 4 weeks for a course of treatment. The total dose should be based on the purity and toxicity of the drug used. The intravenous injection was diluted with 20 to 40ml of normal saline, and the intravenous drip was diluted with 0.9% ml of 5% glucose solution or sodium chloride injection. for various causes of leukopenia, thrombocytopenia and aplastic anemia. |
| production method | strain culture Escherichia Coli A.S.1.357, beef juice medium 2.5 ml, peptone 1g, sodium chloride 0.5g and Agar 2 ~ g, in 370C, 24h test tube culture, eggplant flask culture 8H, cone flask culture 16H. Escherichia coli broth culture medium; 370C;2d → strain culture broth strain seed culture medium with 10% corn steep liquor inoculation amount 1%~ 1.5%, in 370C, aeration and stirring Culture 6~8H. Fermented corn steep liquor; 370C;6h → seed culture seed strain fermenter culture 10% corn steep liquor inoculum 8%, at 370C, aeration stirring Culture 6~8H, centrifugation, separation of fermentation broth, add 2 times the amount of fermentation liquid of acetone, pressure filtration, filter cake sieving, natural dry air dry bacterial powder. Seed strain corn steep liquor; 370C;7H → fermenter culture fermentation broth acetone → pressure filtration, air-dry cell extraction, Precipitation per kilogram of cell dry powder added 10L of boric acid buffer solution (0.01mol/L) pH 8, after stirring at 370C for 1.5H, cool down to 300C left or right, adjust pH 4.2~4.4 with acetic acid solution (5mol/L), press filtration, add 2 times the volume of acetone in the filtrate, let stand for 3~4H, until the precipitation is complete, filter, collect the precipitate, and dry to obtain dry crude enzyme. Boric acid buffer solution of dry cell; PH 8;370C → extract HAc; PH 4.3 → precipitation dry crude enzyme heat treatment 1g of crude enzyme was added into 20ml of glycine solution (3g/L, 0.3g) To adjust pH 8.8, the mixture was stirred for 1.5h, centrifuged, and the supernatant was collected, heated to 600C, and heat-treated for 30min. Discard the precipitate by centrifugation, add 2 volumes of acetone to the supernatant, precipitate the precipitate, centrifuge, collect the enzyme precipitate, add pH 8 phosphate buffer solution (0.01mol/L), and then discard the insoluble matter by centrifugation, the supernatant enzyme precipitation solution was obtained. Dry crude enzyme glycine; 600;30min → heat-treated enzyme solution refining, lyophilization to adjust pH8.8 enzyme solution, centrifugal discard branch precipitation, supernatant adjusted to pH7.7, polyethylene glycol (50% g/L) was added to the supernatant, so that the concentration of polyethylene glycol reached 160g/L(16%). When the temperature was 2 ~ 50C, it was placed for 4 ~ 5d, and there was precipitation, the precipitate was separated by centrifugation. Distilled water was added to dissolve it, 4 times the solution amount of acetone was added, and precipitation was repeated once in the same method. The precipitation was dissolved with Ph 6.4 phosphate buffer (0.05mol/L) to obtain a purified enzyme solution. The pH was adjusted to 5-5.2, polyethylene glycol (g/L) was added, and the treatment was repeated once. Then adjust the pH to 7.7, add polyethylene glycol (500g/L) to dissolve, under aseptic conditions, filter with 6# vertical melting funnel, pack, freeze-dry, then obtain (day) asparaginase finished product, each 10000U or 20000U. Enzyme solution poly-ethanol; Different pH treatment → sterile subpackage of refined pyogenase → freeze-dried (day) asparaginase lyophilized preparation |
| category | toxic substances |
| toxicity grade | low toxicity |
| Acute toxicity | intraperitoneal-rat LD50: 8204 mg/kg; Subcutaneous-rat LD50; 7568 mg/kg |
| flammability hazard characteristics | flammable; Combustion-induced irritating smoke |
| storage and transportation characteristics | ventilation and low temperature drying |
| fire extinguishing agent | dry powder, foam, sand, carbon dioxide, water mist |
| toxic substance data | information provided by: pubchem.ncbi.nlm.nih.gov (external link) |
Last Update：2024-04-09 21:11:58
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Spot supply
Product Name: Asparaginase (Owenism) Visit Supplier Webpage Request for quotationCAS: 9015-68-3
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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