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Cyclosporin A

Immunosuppressants Pharmacological effects Pharmacokinetics Indications Drug interactions Side effects Chemical properties Production methods
Cyclosporin A
Cyclosporin A structure
CAS No.
59865-13-3
Chemical Name:
Cyclosporin A
Synonyms
CL285;Neoral;Atopica;s7481f1;Cipol N;Restasis;Lo-27400;ol27-400;Optimmune;sandimmun
CBNumber:
CB5163816
Molecular Formula:
C62H111N11O12
Formula Weight:
1202.61
MOL File:
59865-13-3.mol

Cyclosporin A Properties

Melting point:
148-151°C
alpha 
D20 -244° (c = 0.6 in chloroform); D20 -189° (c = 0.5 in methanol)
Boiling point:
838.63°C (rough estimate)
Density 
0.9913 (rough estimate)
refractive index 
1.6500 (estimate)
Flash point:
87℃
storage temp. 
2-8°C
solubility 
ethanol: 30 mg/mL
pka
13.32±0.70(Predicted)
form 
solid
color 
white
Water Solubility 
Soluble in dimethyl sulfoxide and ethanol. Insoluble in water.
Merck 
14,2752
BRN 
3647785
InChIKey
PMATZTZNYRCHOR-CGLBZJNRSA-N
CAS DataBase Reference
59865-13-3(CAS DataBase Reference)
EWG's Food Scores
4
NCI Dictionary of Cancer Terms
cyclosporine
Proposition 65 List
Ciclosporin (Cyclosporin A; Cyclosporine)
EPA Substance Registry System
Cyclosporin A (59865-13-3)
SAFETY
  • Risk and Safety Statements
Symbol(GHS) 
GHS07,GHS08,GHS02
Signal word  Danger
Hazard statements  H302-H350-H360-H225-H302+H332-H319-H362
Precautionary statements  P301+P312a-P501a-P201-P280-P301+P312+P330-P308+P313-P210-P305+P351+P338-P202-P260-P263-P264-P270-P405-P501
Hazard Codes  T,Xn,F
Risk Statements  45-60-22-40-36-20/21/22-11
Safety Statements  53-45-36/37-24/25-22-26-16
RIDADR  UN 1648 3 / PGII
WGK Germany  3
RTECS  GZ4120000
HS Code  29419090
Toxicity LD50 in mice, rats, rabbits (mg/kg): 107, 25, >10 i.v.; 2329, 1480, >1000 orally (Ryffel)

Cyclosporin A price More Price(21)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich 239835 Cyclosporin A 59865-13-3 100mg $86 2019-12-02 Buy
Sigma-Aldrich 1158504 Cyclosporine United States Pharmacopeia (USP) Reference Standard 59865-13-3 50mg $1080.45 2019-12-02 Buy
TCI Chemical C2408 Cyclosporin A >97.0%(HPLC)(N) 59865-13-3 1g $368 2020-06-24 Buy
TCI Chemical C2408 Cyclosporin A >97.0%(HPLC)(N) 59865-13-3 100mg $62 2020-06-24 Buy
Alfa Aesar J63191 Cyclosporin A, 99+% 59865-13-3 1g $185 2020-06-24 Buy

Cyclosporin A Chemical Properties,Uses,Production

Immunosuppressants

Cyclosporin A is a lipophilic cyclic peptide compounds separated by certain Hyphomycetes fungi, such as Cylindrocarpon lucidum and Tolypocladium inflatumculture medium. In 1980s, as an immunosuppressant, it has been widely used in the world, is now used for a variety of tissues and organ transplant to prevent rejection reaction and to treat autoimmune diseases.
Cyclosporin A is a strong immunosuppressant, inhibits the onset of the reaction in cell media, reversibly inhibits T cell proliferation, does not inhibit the generation of blood cells, does not affect the function of the phagocyte. As compared with other inhibitors, fewer advantages are induce or aggravate infection, mainly used in clinical kidney, liver, heart, lung, bone marrow transplant anti-rejection, can be combined with adrenal corticosteroids, but not in combination with other immunosuppressive agents. Also used in certain autoimmune diseases (such as systemic lupus erythematosus, lupus nephritis, rheumatoid arthritis, autoimmune hemolytic anemia). Try to uveitis, severe aplastic anemia, refractory idiopathic thrombocytopenic purpura, psoriasis, etc.

Pharmacological effects

Cyclosporin A can reversibly selectively alter T-lymphocyte function, prevent transcription of lymphokine gene, interfere transfer of original information, inhibit the release of interleukin-2, interferon and other immune factors, affect humoral immunity and immune cells, inhibit killing viability of NK cell; inhibit differentiation and proliferation of lymphocyte in the antigen or mitogen stimulation. But no activity on bone marrow, very small effect on B cells, at therapeutic doses no significant inhibiting effect on granulocyte survival. Oral absorption is slow and incomplete, only 4% to 60%, an average is 30% of the administered dose; relative bioavailability is 20% to 50%. After 2~8h of oral administration reach its peak, with an average of 3.5h. Significant individual differences, such as the relative bioavailability of renal transplant patients is 5% to 89%, liver transplant patients is 8% to 60%. This product is fat-soluble drug, meals and eating food can increase the absorption of fat. Bile deficiency, stagnation, slow gastric emptying, increased gastric peristalsis, pancreatic dysfunction and steatorrhea, all affect absorption of the product.

Pharmacokinetics

Oral absorption is irregular and big differences in different individual, bioavailability is 30%, but can be increased with the extended duration of treatment and the increased dose. After liver transplantation, patients with liver disease or disorder of the gastrointestinal absorption may be reduced . Binding rate this product with plasma proteins is up to about 90%, mainly in combination with lipoproteins. Oral peak time is 3 to 4 hours, whole blood concentration is 2 to 9 times of plasma, adult plasma T1/2 is 19 (10-27) hours, while the child is only 7 (7 to 19) hours. This product is metabolized in the liver, by biliary excretion through feces, only 6% by renal excretion, of which about 0.1% is excreted in the primary form.
The above information is edited by the Chemicalbook of Liu Yujie.

Indications

For prevention of a variety of tissue and organ transplant rejection and treatment of some autoimmune diseases, also used in kidney disease, aplastic anemia, refractory ulcerative colitis. In dermatology, for stubborn and intractable skin diseases, the best effect is severe psoriasis (including vulgaris, pustular, erythrodermic and joint disease); good efficacy on skin disorders including Behcet disease, gangrenous pyoderma, lichen planus, acquired epidermolysis bullosa psychosis; moderate efficacy on disease including alopecia, atopic dermatitis, chronic actinic dermatitis, light class of reticulocyte cell histiocytosis, adult linear IgA bullous dermatitis, pemphigus, bullous pemphigoid (the latter two illness should be in combination with corticosteroids). In addition, Cyclosporine A has effect on systemic lupus erythematosus, dermatomyositis, systemic sclerosis, AIDS, ichthyosis, cutaneous T-cell lymphoma, pityriasis rubra pilaris, generalized missed acrodermatitis, palmoplantar pus blister disease, male pattern baldness, vitiligo, progressive necrotizing xanthogranulomatous, generalized granuloma annulare, lichen myxedema, papular mucin calm disease, hyperthyroidism.

Drug interactions

1, In addition to corticosteroids, this product should be avoided in combination with any other immunosuppressive agents.
2, The inactivation of product is mainly in the liver metabolic, any drugs which can affect the liver enzyme activities can affect the metabolism of the product, such as erythromycin, josamycin, doxycycline, ketoconazole, H2 receptor antagonists , calcium antagonists, androgens, oral contraceptives affect activity of cytochrome P-450 liver cell, increase the risk of toxicity of this product.
3, Carbamazepine, phenytoin, phenobarbital, isoniazid, rifampin, et al. can make the plasma concentration of this product decrease.
4, Aminoglycoside antibiotic, trimethoprim-sulfamethoxazole, TMP, amphotericin B, cephalosporins, mechlorethamine, nonsteroidal anti-inflammatory drug, mannitol, furosemide, et al increase nephrotoxicity of cyclosporine .
5, Calcium and increased calcium are disabled when using this product, and cannot be vaccinated.
6, Long-term in combination with glucocorticoid can trigger diabetes, hypertension, ulcer disease and osteoporosis, and can increase the toxicity of this product.
7, Before used Cyclosporin A, other immunosuppressive agents are used, patients have overall decreased immunity and are easy to be infected.

Side effects

1, Kidney toxicity: accounted for about 13%, may have glomerular thrombosis, tubular obstruction, mitochondrial swelling, proteinuria, tubular urine; occasionally hyperuricemia, hyperkalemia, elevated serum creatinine, blood urea nitrogen rise, little or no urine.
2, Liver toxicity: hypoproteinemia, hyperbilirubinemia, serum alkaline phosphatase and lactate dehydrogenase elevated, when the serum concentration of the drug is greater than 200ng/ml most likely to occur, especially in the original hepatitis or liver dysfunction.
3, Nervous system: usually presents exercise-induced spinal cord syndrome, cerebellar ataxia, mental confusion, tremors, abnormal feeling, etc.
4, Gastrointestinal reactions: common anorexia, nausea, and vomiting. Other reactive hypertension, hirsutism. When administered intravenously, rare serious allergic reactions such as chest facial flushing, breathing difficulties, asthma, heart palpitations; once presents the above symptoms, should be discontinued immediately and anti-shock first aid.

Chemical properties

From-15 ℃ of acetone to obtain white needle crystallization, melting point 148~151 ℃, [α] D20-244 ° (C = 0.6, chloroform). Soluble in methanol, ethanol, acetone, ether or chloroform, slightly soluble in water and saturated hydrocarbons. Acute toxicity LD50 mouse, rat, rabbit (mg/kg): 107, 25, > 10 intravenous injection; 2329,1480,> 1000 oral.

Production methods

Used Tolypocladium inflatum Gams as production strains. 50L seed medium is added into 75 L tank, inoculated with 5 × 109 spores, Ph = 5.4-4.3, cultured for 72 h, to obtain first order seed liquid. 500L fermentation medium is added into 750 L fermentation tank, inoculated with above first order seed liquid, cultured for 6 days to give second order seed liquid. 3000L fermentation medium is added into 4500L fermentation tank, fermentation for 12 days to give fermented cyclosporine toxicity. An equal volume of ethyl acetate is added into the fermentation broth, organic layer was separated, evaporated under reduced pressure to give the crude product. Melting process, can obtain Cyclosporin A and Cyclosporin C component, wherein Cyclosporin A production is about 150~200 mg/L, Cyclosporin C is about 50~100 mg/L.

Chemical Properties

White or almost white powder

Chemical Properties

White crystalline solid or powder.

Uses

An immunosuppressant that has revolutionized organ transplantation through its use in the prevention of graft rejection. A group of nonpolar cyclic oligopeptides with immunosupppressant activity.

Uses

prothrombogenic agent

Uses

Cyclosporin A is a hydrophobic cyclic peptide isolated from several fungal species including Cylindrocarpon, Fusarium, Trichoderma and Tolypocladium. Cyclosporin A inhibits T-cell activation and has been marketed since 1983 as an immunosuppressant in post-allogeneic organ transplant. Cyclosporin A acts by binding to the protein, cyclophilin (immunophilin), in T-lymphocytes causing inhibition of calcineurin (protein phosphatase 2B). Cyclosporin A reduces transcription of interleukin 2, and inhibits lymphokine production, interleukin release and NO synthesis induced by interleukin 1α, lipopolysaccharides and TNFα.

Definition

ChEBI: A cyclic nonribosomal peptide of eleven amino acids; an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the patient's immune system, and therefore the risk of organ rejection. Also causes reversible inhibiti n of immunocompetent lymphocytes in the G0- and G1-phase of the cell cycle.

Indications

brand name

Gengraf (Abbott); Neoral (Novartis); Restasis (Allergan); Sandimmune (Novartis) [Names previously used: Cyclosporin A; Cyclosporin.].

General Description

White prismatic needles (from acetone) or white powder.

Air & Water Reactions

Slightly water soluble .

Reactivity Profile

Cyclosporin A is an amide. Amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).

Health Hazard

SYMPTOMS: Symptoms of exposure to Cyclosporin A include hepatotoxicity, nephrotoxicity, hyperkalemia, hyperuricemia, convulsions, renal dysfunction, tremor, hirsutism, hypertension, gum hyperplasia, cramps, acne, headache, diarrhea, nausea, vomiting, abdominal discomfort, paresthesia, flushing, leukopenia, lymphoma, sinusitis and gynecomastia. In 2% or less of persons exposed, it has caused allergic reactions, anemia, anorexia, confusion, conjunctivitis, edema, fever, brittle fingernails, gastritis, hearing loss, hiccups, hyperglycemia, muscle pain, peptic ulcer, thrombocytopenia and tinnitus. Rare reactions include anxiety, chest pain, constipation, depression, hair breaking hematuria, joint pain, lethargy, mouth sores, myocardial infarction, night sweats, pancreatitis, pruritus, swallowing difficulty, tingling, upper gastrointestinal bleeding, visual disturbance, weakness and weight loss. It has caused kidney and liver damage. An increased susceptibility to infection may occur. Other symptoms include gastrointestinal disturbance, rashes and angioedema.

Fire Hazard

Flash point data for Cyclosporin A are not available; however, Cyclosporin A is probably combustible.

Pharmacology

Cyclosporine has no direct effect on keratinocytes and is not a mitotic inhibitor. Cyclosporine inhibits cytokine release, which results in a decreased recruitment of APCs into the epidermis and decreases immunoreactivity of lesions. Potential long-term side effects preclude cyclosporine’s use in all but very severe and recalcitrant psoriasis. Cyclosporine can be combined with lowdose methotrexate.

Side effects

Cyclosporine’s main side effects, even at low doses, are hypertension and nephrotoxicity. Age, baseline blood pressure, and baseline creatinine levels are predictors of higher risks of side effects. Glomerular filtration rate (GFR) is a more sensitive test than creatinine for evaluating renal function, and a baseline is recommended in any high-risk patient. Longterm treatment with CSA may induce interstitial fibrosis and glomerular sclerosis, with more pronounced changes directly associated with duration of therapy. It should be administered only by dermatologists experienced in its use.

Safety Profile

Confirmed carcinogen producing Hodghn's dlsease. Experimental reproductive effects. Poison by intraperitoneal and intravenous routes. Moderately toxic by ingestion. Human systemic effects by ingestion: increased body temperature, cyanosis. Mutation data reported. When heated to decomposition it emits toxic fumes of NOx.

Potential Exposure

Cyclosporin A is a fungal metabolite; an amide immunosuppressant drug used in various surgeries.

Carcinogenicity

Cyclosporin A is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.

Shipping

UN3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials.

Incompatibilities

Amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents such as hydrideds and active metals. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as such as phosphorus pent- oxide or thionyl chloride generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).

Waste Disposal

t is inappropriate and possibly dangerous to the environment to dispose of expired or waste drugs and pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quantities shall carefully take into consider- ation applicable DEA, EPA, and FDA regulations. If possi- ble return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged, and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Cyclosporin A Preparation Products And Raw materials

Raw materials

Preparation Products


Cyclosporin A Suppliers

Global( 387)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Alpha Biopharmaceuticals Co., Ltd
0086-411-39042497
0086-411-39042693 sales@alphabiopharm.com China 921 58
Henan DaKen Chemical CO.,LTD.
+86-371-55531817
info@dakenchem.com CHINA 21821 58
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com CHINA 22626 55
ATK CHEMICAL COMPANY LIMITED
+86 21 5161 9050/ 5187 7795
+86 21 5161 9052/ 5187 7796 ivan@atkchemical.com CHINA 24723 60
Shanghai Zheyan Biotech Co., Ltd.
18017610038
zheyansh@163.com CHINA 3623 58
career henan chemical co
+86-371-86658258
sales@coreychem.com CHINA 30045 58
Shanghai Arbor Chemical Co., Ltd.
021-60451682
021-60451683 act@arborchemical.com CHINA 906 58
Biochempartner
0086-13720134139
candy@biochempartner.com CHINA 968 58
Chengdu Biopurify Phytochemicals Ltd.
18080483897
maggie@biopurify.com CHINA 2645 58
Chemwill Asia Co.,Ltd.
86-21-51086038
86-21-51861608 chemwill_asia@126.com;sales@chemwill.com;chemwill@hotmail.com;chemwill@gmail.com CHINA 23977 58

View Lastest Price from Cyclosporin A manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2019-12-25 Cyclosporin A
59865-13-3
US $0.00-0.00 / KG 1g 99% 2000tons Shaanxi Dideu Medichem Co. Ltd
2019-07-22 cyclosporine A
59865-13-3
US $1.00 / g 1g 99% 100 Kilogram/Kilograms per Month in stock Cangzhou Wanyou New Material Technology Co.,Ltd
2018-08-17 Cyclosporin A
59865-13-3
US $1.00 / KG 1G 98% 100KG career henan chemical co

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