(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Names and Identifiers
Name | captopril
|
Synonyms | captopril Captopril API Captopril (200 mg) Captopril Cardiovascular 1-(2-methyl-3-sulfanylpropanoyl)proline 1-[(S)-3-Mercapto-2-methylpropionyl]-L-proline (2s)-1-(3-mercapto-2-methylpropionyl)-l-proline (s,s)-1-(d-3-mercapto-2-methyl-1-oxopropyl)-l-proline Captopril,N-[(S)-3-Mercapto-2-methylpropionyl]-L-proline (2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylate 3-Mercapto-2-Methylpropanoic acid 1,2-diphenylethylaMine salt (MMPA) (2S)-1-[(2S)-3-Mercapto-2-methylpropionyl]-2-pyrrolidinecarboxylic acid (S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline
|
CAS | 62571-86-2
|
EINECS | 263-607-1 |
InChI | InChI=1/C9H15NO3S/c1-6(5-14)8(11)10-4-2-3-7(10)9(12)13/h6-7,14H,2-5H2,1H3,(H,12,13)/p-1/t6-,7+/m1/s1 |
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Physico-chemical Properties
Molecular Formula | C9H15NO3S
|
Molar Mass | 217.29 |
Density | 1.2447 (rough estimate) |
Melting Point | 104-108 °C (lit.) |
Boling Point | 427.0±40.0 °C(Predicted) |
Specific Rotation(α) | -129.5 º (c=1, EtOH) |
Flash Point | 212.068°C |
Water Solubility | soluble |
Solubility | Soluble in methanol, ethanol, acetone, dichloromethane or chloroform, soluble in water, insoluble in ether or hexane. |
Vapor Presure | 0mmHg at 25°C |
Appearance | White or white-like crystalline powder |
Color | white to off-white |
Merck | 14,1774 |
BRN | 477887 |
pKa | 3.7, 9.8(at 25℃) |
Storage Condition | room temp |
Stability | Stable. Incompatible with strong oxidizing agents. |
Sensitive | Sensitive to air |
Refractive Index | -127.5 ° (C=1.7, EtO |
MDL | MFCD00168073 |
Physical and Chemical Properties | Melting point 103-108°C specific optical rotation -129.5 ° (c = 1, EtOH) water-soluble solution
|
Use | For the treatment of hypertension and heart failure |
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Risk and Safety
Risk Codes | R43 - May cause sensitization by skin contact
R63 - Possible risk of harm to the unborn child
R36/37/38 - Irritating to eyes, respiratory system and skin.
R40 - Limited evidence of a carcinogenic effect
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Safety Description | S36/37 - Wear suitable protective clothing and gloves.
S37/39 - Wear suitable gloves and eye/face protection
S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
S36 - Wear suitable protective clothing.
S22 - Do not breathe dust.
|
WGK Germany | 2 |
RTECS | UY0550000 |
HS Code | 29339900 |
Toxicity | LD50 in mice (mg/kg): 1040 i.v.; 6000 orally (Keim) |
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Reference
Reference Show more | 1. Xin Li, Qi Zhang, Yingying Zhao, et al. Preparation and formulation optimization of captopril pulse tablets [J]. Pharmaceutical research 2018 37(09):25-28. 2. Wang Ningli, Wei jianteng, Wang Yong, etc. In vitro evaluation of angiotensin-converting enzyme inhibitory peptides from sweet gourd [J]. Food Science and Technology, 2017, 29 (9):224-226. 3. Lai Xingfei, Pan shunun, Zhang Wenji, Sun Lingli, Li Qiuhua, Chen Ruohong, Sun Shili, properties of ACE anti-hyperintensive activity, Process Biochemistry, Volume 92, 2020, 4. Chu, Xi, et al. "Crocin protects against cardiotoxicity induced by doxorubicin through TLR-2/NF-κB signal pathway in vivo and vitro." International immunopharmacology 84 (2020): 106548.https://doi.org/10.1016/j.intimp.2020.106548 5. [IF=7.46] Ying Zhang et al."A polydopamine-polyethyleneimine/quantum dot sensor for instantaneous readout of cell surface charge to reflect cell states."Sensor Actuat B- Chem. 2020 Dec;324:128696 6. [IF=5.279] Mengdi Chen et al."Novel Umami Peptide IPIPATKT with Dual Dipeptidyl Peptidase-IV and Angiotensin I-Converting Enzyme Inhibitory Activities."J Agr Food Chem. 2021;69(19):5463-5470 7. [IF=5.279] Yanbo Huang et al."Novel ACE Inhibitory Peptides Derived from Yeast Hydrolysates: Screening, Inhibition Mechanisms and Effects on HUVECs."J Agr Food Chem. 2021;69(8):2412-2421 8. [IF=5.275] Sui-Qun Yang et al."Separation and configurational assignment of stereoisomeric phenalenones from the marine mangrove-derived fungus Penicillium herquei MA-370."Bioorg Chem. 2021 Jan;106:104477 9. [IF=5.275] Hong-Lei Li et al."Structurally diverse alkaloids produced by Aspergillus creber EN-602, an endophytic fungus obtained from the marine red alga Rhodomela confervoides."Bioorg Chem. 2021 May;110:104822 10. [IF=3.943] Xi Chu et al."Crocin protects against cardiotoxicity induced doxorubicin through TLR-2/NF-κB signal pathway in vivo and vitro."Int Immunopharmacol. 2020 Jul;84:106548 11. [IF=3.757] Lai Xingfei et al."Properties of ACE inhibitory peptide prepared from protein in green tea residue and evaluation of its anti-hypertensive activity."Process Biochem. 2020 May;92:277 |
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Nature
Open Data Verified Data
white or white crystalline powder, there are similar garlic specific odor, salty taste. Soluble in methanol, ethanol, acetone, dichloromethane or chloroform, soluble in water, insoluble in ether or hexane. There are two kinds of crystal forms, which are homogenous crystals. Melting point 106 °c (stable) and melting point 84~86 °c (unstable); Or melting point 87~88 °c, then solidified, the second melting point of 104~105 °c.
Last Update:2024-01-02 23:10:35
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Preparation Method
Open Data Verified Data
L-proline was dissolved in an aqueous sodium hydroxide solution, cooled in an ice bath, and reacted by adding benzyl chloroformate in portions with vigorous stirring to obtain N-benzylcarbonyl-L-proline. N-benzylcarbonyl-L-proline was dissolved in a solution of dichloromethane, isobutylene and concentrated sulfuric acid, and the reaction was worked up to give N-benzylcarbonyl-L-proline tert-butyl ester. L-proline tert-butyl ester was obtained by dissolving it in absolute ethanol and hydrogenating it under normal pressure using palladium on carbon as catalyst. L-proline tert-butyl ester is dissolved in dichloromethane, dicyclohexylcarbodiimide is added, and then dichloromethane solution of 3-acetylmercapto-2-methylpropionic acid is added, after completion of the reaction, N-(3-acetylmercapto-2-methylpropionyl) L-prolyamino tert-butyl ester was obtained. This was added to a mixed solution of anisole and trifluoroacetic acid, the reactant was precipitated with diethyl ether-hexane, the precipitate was dissolved in acetonitrile, dicyclohexylamine was added, and the dicyclohexylamine salt of the (S.S.) L-proline derivative was worked up. The salt is in a mixed solution of potassium hydrogen sulfate and acetic acid ethanol, the separated organic layer is washed with water, concentrated to dryness, and the obtained material is crystallized with ethyl acetate-hexane to obtain optically active (S.S.) l-N-(3-acetyl thiol -2- D-methyl propionyl)-L-proline. The Proline derivative was dissolved in a solution of ammonia in methanol and maintained at room temperature, and the solvent was distilled off under reduced pressure. The resulting material was dissolved in water, chromatographed on an acid type ion exchange resin, and further treated to give captopril. Or a-based acrylic acid and thioacetic acid addition, to obtain a-methyl-p-acetyl mercaptoacetic acid, and then chloride sulfoxide chlorination to acid chloride, directly and proline in the role of sodium hydroxide, N-(3-acetylmercapto-2-methylpropionyl)-L-proline was obtained, and optical resolution was carried out by using dicyclohexylamine as a salt to obtain (S,S) body, and then the acetyl group was removed by ammonolysis, captopril was obtained.
Last Update:2022-01-01 09:10:30
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Standard
Authoritative Data Verified Data
This product is l-[(2S)-2-methyl-3-mercapto-propionyl] -L-proline. Calculated as dry, containing no less than 97.5% C9Hl5N03S.
Last Update:2024-01-02 23:10:35
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Trait
Authoritative Data Verified Data
- This product is white or white crystalline powder; There is a special odor similar to garlic.
- This product is soluble in methanol, ethanol or three gas methane, dissolved in water.
melting point
The melting point of this product (General 0612) is 104~110°C.
specific rotation
take this product, precision weighing, plus ethanol dissolution and quantitative dilution of about 20mg per lml solution, according to the law (General 0621), the specific rotation was from -126 ° to -132 °.
Last Update:2022-01-01 11:37:04
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Use
Open Data Verified Data
non-peptide angiotensin-converting enzyme inhibitors that act primarily on the renin-angiotensin-aldosterone system (RAA system). Inhibits angiotensin converting enzyme (ACE) of the RAA system and inhibits aldosterone secretion. It has obvious effects of lowering blood pressure and reducing cardiac load. Used for different types of hypertension, also effective for heart failure. For the treatment of various types of hypertension, especially severe hypertension, which is ineffective with conventional therapy.
Last Update:2022-01-01 09:10:31
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Differential diagnosis
Authoritative Data Verified Data
- take about 25mg of this product, add 2ml of ethanol to dissolve, add a small amount of sodium nitrite crystal and 10 drops of dilute sulfuric acid, shake, the solution shows red.
- the sample solution under the item of captopril disulfide was taken and diluted with the mobile phase to prepare a solution containing 0. A solution of 1mg was used as a test solution; A captopril control was additionally taken, dissolved in an appropriate amount of methanol, and then diluted with a mobile phase to prepare a solution containing about 0.1mg per 1 ml as a control solution. According to the chromatographic conditions of captopril disulfide, 20 u1 of the test solution and the reference solution were injected into the liquid chromatograph respectively, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the control solution.
- The infrared absorption spectrum of this product should be consistent with that of the control (Spectrum set 96).
Last Update:2022-01-01 11:37:04
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Safety
Open Data Verified Data
mouse LDso (mg/kg):1040 intravenously, 6000 orally.
Last Update:2022-01-01 09:10:31
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Exam
Authoritative Data Verified Data
captopril disulfide (impurity I)
operation in the dark. Take this product, precision weighing, plus mobile phase dissolution and quantitative dilution to make a solution containing about 0.5mg per lml, as a test solution (ready to use new system); Another impurity I reference substance, precision weighing, adding an appropriate amount of methanol to dissolve, and then quantitatively diluting with mobile phase to make a solution containing about 5ug per lml as a reference solution; Then taking captopril and impurity I reference, adding an appropriate amount of methanol to dissolve, diluted with mobile phase to make each about 0. A mixed solution of 1 mg and 15ug was used as the system suitability solution. According to the high performance liquid chromatography (General 0512) test, with the eighteen alkyl silane bonded silica gel as filler 0.01mol /L sodium dihydrogen phosphate solution-methanol-acetonitrile (70:25:5 )(PH adjusted to 3.0 with 81 acid) as mobile phase; Detection wavelength was 215nm; Column temperature 40°C. Take the system applicable solution 50 u1 and inject it into human Liquid Chromatograph. The resolution between captopril peak and impurity I peak should be greater than 4.0. The sample solution and the reference solution of 50 u1 were respectively injected into the liquid chromatograph, and the chromatogram was recorded. If there is a chromatographic peak in the chromatogram of the test solution that is consistent with the retention time of impurity I, the peak area shall be calculated according to the external standard method, and shall not exceed 1.0%.
sulfate
take this product L. 0g, check according to law (General rule 0802), compared with the standard potassium sulfate solution 5.0ml made of the control solution, not more concentrated (0.05%).
loss on drying
take this product, with phosphorus pentoxide as desiccant, at 60°C under reduced pressure drying to constant weight, weight loss should not exceed 0.5% (General rule 0831). 2.0g of this product shall be taken for ignition residue and inspected according to law (General rule 0841). The remaining residue shall not exceed 0.1%.
Heavy metals
take the residue left under the item of ignition residue, add 1 ml of nitric acid, and evaporate to dryness until the nitrogen oxide vapor is removed. Add 2ml of hydrochloric acid, dry on a water bath, then add 5ml of water, and evaporate to dryness, add water (15ml) and acetate buffer (pH 0821) (4ml), slightly warm to dissolve, add water (50ml), shake well, take 25ml, check according to law (General rule method 1), heavy metals should not be more than 20 parts per million.
zinc salt
take the remaining solution under the above heavy metal item 25ml, put it in a 50ml Nessler's colorimetric tube, add hydrochloric acid solution (1- 2 ) 4ml and potassium ferrocyanide solution 3ml, add water to the scale, shake, in case of turbidity, take 44mg of zinc sulfate (zns4/7h2o) with standard zinc solution, put it in a 100ml measuring flask, add water to dissolve and dilute to the scale, shake well, take 10ml of precision measurement, in another 100ml measuring flask, dilute to the scale with water and shake. Each 1 ml is equivalent to 10ug of Zn] 0.003% ml of the control solution should not be more concentrated ().
Last Update:2022-01-01 11:37:05
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Content determination
Authoritative Data Verified Data
take about 0.3g of this product, weigh it accurately, add 100ml of water, shake to dissolve, Add 10 ml of dilute sulfuric acid, and add potassium iodide l.Og and 2ml of starch indicator solution were titrated with potassium iodate titration solution (0.01667mol /L) to a microscopic blue color of the solution (no fading for 30 seconds), and the results of the titration were corrected with a blank test. Each 1 ml of potassium gallate titrant (0.01667mol/L) corresponds to 21.73mg of C9H15N03S.
Last Update:2022-01-01 11:37:06
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Category
Authoritative Data Verified Data
angiotensin-converting enzyme inhibitors.
Last Update:2022-01-01 11:37:06
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Storage
Authoritative Data Verified Data
light shielding, sealed storage.
Last Update:2022-01-01 11:37:06
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Captopril tablets
Authoritative Data Verified Data
This product contains captopril (C9H15N03S) should be 90.0% to 110.0% of the label.
trait
This product is white or white-like tablets, or sugar-coated tablets or film-coated tablets, white or white after removing the coating.
identification
- take an appropriate amount of fine powder of this product (about 50mg equivalent to captopril), add 4ml of ethanol, shake to dissolve captopril, filter, and filter the filtrate according to the identification (1) Test under captopril, the same reaction was shown.
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
examination
- The captopril disulfide (impurity I) was protected from light. Accurately weigh the appropriate amount of fine powder of this product (about 25mg equivalent to captopril), put it in a 50ml measuring flask, add the appropriate amount of mobile phase, ultrasonic for 15 minutes, let it cool, dilute to the scale with mobile phase, shake well, filter, take the continued filtrate as the test solution (used within 8 hours); Take the reference substance of impurity I, weigh the precision, add the appropriate amount of methanol to dissolve, A solution containing about 15ug per 1 ml was prepared as a control solution by quantitative dilution with mobile phase. If there is a peak in the chromatogram of the test solution consistent with the retention time of impurity I, the peak area shall be calculated according to the external standard method, not 3.0% of the labeled amount of captopril.
- Dissolution Test Method for Determination of dissolution and release (General rule 0931 method 2), using water as dissolution medium, speed of 75 rpm, after 20 minutes (for example, sugar-coated tablets, after 45 minutes), take the appropriate amount of solution, filter, and take the continued filtrate as the test solution; Take the appropriate amount of captopril reference, precision weighing, water was added to dissolve and quantitatively diluted to prepare a solution containing about Upg (12.5mg specification),28UG (25mg specification) or 56UG (50mg specification) per 1 ml as a control solution. The dissolution amount of each tablet was calculated according to the measurement method under the content measurement item. The limit is 80% of the labeled amount and shall be in accordance with the provisions.
- others shall be in accordance with the relevant provisions under the item of tablets (General rule 0101).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using eighteen alkyl silane bonded silica as filler; 0.Olmol/L sodium dihydrogen phosphate solution-methanol-acetonitrile (70:25:5)(pH adjusted to 3.0 with phosphoric acid) as mobile phase; The detection wavelength was 215mn; The column temperature was 40°C.
- determination Method: Take 20 tablets of this product (remove coating of sugar-coated tablets), precise weighing, fine grinding, precise weighing appropriate amount (about equivalent to captopril lOmg), put it in a 100ml measuring flask, and add appropriate amount of mobile phase, shake to dissolve captopril, dilute to scale with mobile phase, shake well, filter, take filtrate as test solution, take 20 u1 with precision, inject human liquid chromatograph, record chromatogram; in addition, the captopril reference product was precision weighed, dissolved and quantitatively diluted with mobile phase to make about 0 in 1 ml. lmg solution, the same method for determination. According to the external standard method to calculate the peak area, that is.
category
Same as Captopril.
specification
(1)12.5mg (2)25mg (3)50mg
storage
light shielding, sealed storage.
Last Update:2022-01-01 11:37:07
(S)-(-)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline(S)-(-)-1-(3-Mercapto-2-methylpropionyl)-L-proline - Compound captopril tablets
Authoritative Data Verified Data
This product contains captopril (C9H15N03S) and hydrochlorothiazide (C7H8CIN30482) should be 90.0% ~ 110.0% of the label amount.
prescription
captopril 10g
Hydrochlorothiazide 6G
Appropriate amount of excipients
Made into 1000 tablets
trait
This product is white or off-white.
identification
- take 1 tablet of this product, grind, add 5ml of water, shake well, add appropriate amount of basic sodium nitrosoferricyanide test solution, and then show purplish red.
- Take 3 tablets of this product, grind them, add 15ml of water, shake to dissolve captopril, filter, take filter residue to dry, put it in a test tube, add 10ml of sodium hydroxide test solution, shake to dissolve hydrogen thiazide, filter, take 3ml filtrate, boil for 5 minutes, let cool, add 5ml chromotropic acid test solution, and heat on water bath, should be blue purple.
- in the chromatogram recorded under the content determination item, the retention time of the two main peaks of the test solution should be consistent with the retention time of the corresponding two main peaks of the reference solution.
examination
- The captopril disulfide (captopril impurity I) was protected from light. Accurately weigh the appropriate amount of fine powder of this product (about 25mg equivalent to captopril), put it in a 50ml measuring flask, add the appropriate amount of mobile phase, ultrasonic for 15 minutes, let it cool, dilute to the scale with mobile phase, shake well, filter, take the continued filtrate as the test solution (use it within 8 hours, take the captopril impurity I reference substance, weigh it precisely, add the appropriate amount of methanol to dissolve, A solution containing about 15ug per 1 ml was prepared as a control solution by quantitative dilution with mobile phase. If there are chromatographic peaks in the chromatogram of the test solution that are consistent with the retention time of the captopril impurity I peak, the peak area shall be calculated according to the external standard method, not 3.0% of the labeled amount of captopril.
- Content uniformity take 1 tablet of this product, put it in a 100ml measuring flask, add appropriate amount of mobile phase, ultrasonic dissolve captopril and hydrochlorothiazide, let it cool, dilute it to the scale with mobile phase, shake it well, filtration, take and continue the filtrate as determined by the method under the content determination item, should comply with the provisions (General 0941).
- dissolution dissolution of this product, according to the dissolution and release determination method (General rule 0931 The first method), with hydrochloric acid solution (dilute hydrochloric acid 24-100) as the dissolution medium, speed is rpm, operate in accordance with the law, after 30 minutes, take 10ml of solution, filter, take the filtrate as a test solution: Another precision weigh captopril reference and hydrochlorothiazide reference, A mixed solution containing about 10ug of captopril and 6ug of hydrothiazide per 1 ml was prepared by dissolving and quantitatively diluting with a dissolution medium as a control solution. The dissolution amounts of captopril and hydrochlorothiazide in each tablet were calculated as measured by the method under the content determination item. The limit shall be 70% of the labeled amount and shall be in accordance with the regulations.
- others shall be in accordance with the relevant provisions under the item of tablets (General rule 0101).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using eighteen alkyl silane bonded silica gel as filler; 0.01mol/ L sodium dihydrogen phosphate solution-methanol-acetonitrile (70:25:5) mobile phase (pH adjusted to 3.0 with phosphoric acid); Detection wavelength was 215nm; Column temperature 40°C.
- determination of 20 tablets of this product, precision weighing, fine grinding, precision weighing an appropriate amount (about equivalent to 10mg of captopril), put in a 100ml measuring flask, add an appropriate amount of mobile phase, ultrasonic about 20 minutes to dissolve captopril and hydrochlorothiazide, cool, dilute to the scale with mobile phase, shake, filter, take the continued filtrate as the test solution, take 10ul with precision, note human liquid chromatograph, record chromatogram: Take the captopril pair: the control sample and hydrochlorothiazide, precision weigh, add mobile phase dissolution and quantitative dilution to make about 0 captopril per 1 ml. 0.06mg solution of lmg and hydrogen dust, the same method for determination. According to the external standard method to calculate the peak area, that is.
category
angiotensin-converting enzyme inhibitors.
storage
The samples were sealed and kept in a dry place at 30 ° C. Or lower.
Last Update:2022-01-01 13:43:17