- Biotransformation of cortisone with Rhodococcus rhodnii: Synthesis of new steroids
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Cortisone is a steroid widely used as an anti-inflammatory drug able to suppress the immune system, thus reducing inflammation and attendant pain and swelling at the site of an injury. Due to its numerous side effects, especially in prolonged and high-dose therapies, the development of the pharmaceutical industry is currently aimed at finding new compounds with similar activities but with minor or no side effects. Biotransformations are an important methodology towards more sustainable industrial processes, according to the principles of “green chemistry”. In this work, the biotransformation of cortisone with Rhodococcus rhodnii DSM 43960 to give two new steroids, i.e., 1,9β,17,21-tetrahydoxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11,20-dione and 1,9β,17,20β,21- pentahydoxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11-one, is reported. These new steroids have been fully characterized.
- Bertolasi, Valerio,Buzzi, Raissa,Costa, Stefania,Pedrini, Paola,Semeraro, Bruno,Summa, Daniela,Vertuani, Silvia,Zappaterra, Federico
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- Photodegradation of prednisolone under UVB solar irradiation. Role of photogenerated ROS in the degradation mechanism
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The use of biologically active substances with anti-inflammatory properties such as corticosteroids has increased considerably in the last few decades. Particularly, the compound we are interested in, prednisolone (Predn), is a glucocorticoid with high biological activity. This compound absorbs UV radiation and may participate in photochemical processes, which can result in its own decomposition. These processes could result in the formation of free radicals or reactive oxygen species (ROS). On these grounds, the kinetic and mechanistic aspects of the direct photodegradation of Predn have been studied in aqueous medium under different atmospheric conditions by stationary and time-resolved techniques. The mechanism involved in the photodegradation has been elucidated. Predn is capable of generating the excited triplet state 3Predn? as a result of UVB light absorption. In the presence of oxygen, 3Predn? allows the formation of ROS, of which O2(1Δg) (ΦΔ = 0.014), H2O2 and the radical OH stand out. The latter is generated from the spontaneous dismutation of O2- and subsequent homolytic cleavage, photochemically promoted, of H2O2. Predn undergoes unimolecular photodegradation reactions under an inert argon atmosphere. In this study we found that in the presence of oxygen, the Predn photo-consumption is improved. This implies that the attack by ROS involves a very important additional contribution to the photodegradation of Predn under aerobic conditions.
- Cacciari, R. Daniel,Reynoso, Eugenia,Montejano, Hernán A.,Biasutti, M. Alicia
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- Preparation method of prednisone
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The invention discloses a preparation method of prednisone, and belongs to the technical field of preparation and processing of medicines. According to the method, hydrocortisone acetate is used as aninitial raw material, and the prednisone is prepared through three steps of oxidation, biological fermentation dehydrogenation and hydrolysis. According to the preparation method of prednisone, the defects of a traditional process are overcome, the target product is high in purity, good in quality stability, high in yield, low in production cost and mild in reaction condition, a highly toxic cyanide reagent is prevented from being used, and the method is easy and convenient to operate, suitable for industrial production and wide in market prospect.
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Paragraph 0012; 0029; 0032-0033; 0036-0037; 0040
(2021/03/05)
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- Δ1-dehydrogenation and C20 reduction of cortisone and hydrocortisone catalyzed by rhodococcus strains
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Prednisone and prednisolone are steroids widely used as anti-inflammatory drugs. Development of the pharmaceutical industry is currently aimed at introducing biotechnological processes and replacing multiple-stage chemical syntheses. In this work we evaluated the ability of bacteria belonging to the Rhodococcus genus to biotransform substrates, such as cortisone and hydrocortisone, to obtain prednisone and prednisolone, respectively. These products are of great interest from a pharmaceutical point of view as they have higher anti-inflammatory activity than the starting substrates. After an initial lab-scale screening of 13 Rhodococcus strains, to select the highest producers of prednisone and prednisolone, we reported the 200 ml-batch scale-up to test the process efficiency and productivity of the most promising Rhodococcus strains. R. ruber, R. globerulus and R. coprophilus gave the Δ1-dehydrogenation products of cortisone and hydrocortisone (prednisone and prednisolone) in variable amounts. In these biotransformations, the formation of products with the reduced carbonyl group in position C20 of the lateral chain of the steroid nucleus was also observed (i.e., 20β-hydroxy-prednisone and 20β-hydroxy-prednisolone). The yields, the absence of collateral products, and in some cases the absence of starting products allow us to say that cortisone and hydrocortisone are partly degraded.
- Costa, Stefania,Fantin, Giancarlo,Semeraro, Bruno,Summa, Daniela,Zappaterra, Federico
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- THERAPEUTIC FOR HEPATIC CANCER
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A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
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- Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
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Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
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- Mild and selective deprotection method of acetylated steroids and diterpenes by dibutyltin oxide
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Dibutyltin oxide (DBTO) was first utilized for the deacetylation of steroid and diterpene esters. The results showed the deprotection of acetylated steroids and diterpenes separately with moderate catalysis dibutyltin oxide in methanol selectively removed part acetyl groups of these substrates, whereas several functional groups of the steroids and diterpenes were retained and neither isomerization nor degradation of these substrates was observed. It seems that the acetyl groups with lower steric hindrance or near carbonyl, alkoxy, or hydroxyl groups can be cleaved by the reaction, whereas the acetyl groups with higher steric hindrance or without carbonyl, alkoxy, or hydroxyl groups neighboring were retained under the same conditions. One of the interesting results obtained was the selective hydrolysis of the 3β-O-acetyl group in the presence of the 6β group in 3β,6β-Di-O-acetyl-5α-hydroxypregn-16-en-20-one. This allows for subsequent introduction of one unit at C-3 and the other unit at C-6. This procedure is useful for the synthesis of a series of closely related isomers of 3β,5α,6β-trihydroxypregn-16-en-20-one and other widespread polyhydroxysteroids in marine organisms and some terrestrial species.
- Wang, Shao-Min,Zhang, Yan-Bing,Liu, Hong-Min,Yu, Guo-Bin,Wang, Ke-Rang
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- LIQUID PHARMACEUTICAL FOR ORAL DELIVERY
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A liquid pharmaceutical for oral delivery wherein at the time of use, a solid unit dosage form is added to the liquid wherein the unit dosage form is comprised of a substrate soluble in the liquid and a particulate pharmaceutically active material in a pharmaceutically effective amount. At the time of use, the unit dosage form is added to the liquid, without requiring measurement of the liquid, and the entire liquid is consumed to provide for oral delivery of the pharmaceutically effective amount of material.
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- Method for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor
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Methods for reducing or preventing transplant rejection in the eye of an individual are described, comprising: a) performing an ocular transplant procedure; and b) implanting in the eye a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer.
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- Porous drug matrices and methods of manufacture thereof
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Drugs, especially low aqueous solubility drugs, are provided in a porous matrix form, preferably microparticles, which enhances dissolution of the drug in aqueous media. The drug matrices preferably are made using a process that includes (i) dissolving a drug, preferably a drug having low aqueous solubility, in a volatile solvent to form a drug solution, (ii) combining at least one pore forming agent with the drug solution to form an emulsion, suspension, or second solution and hydrophilic or hydrophobic excipients that stabilize the drug and inhibit crystallization, and (iii) removing the volatile solvent and pore forming agent from the emulsion, suspension, or second solution to yield the porous matrix of drug. Hydrophobic or hydrophilic excipients may be selected to stabilize the drug in crystalline form by inhibiting crystal growth or to stabilize the drug in amorphous form by preventing crystallization. The pore forming agent can be either a volatile liquid that is immiscible with the drug solvent or a volatile solid compound, preferably a volatile salt. In a preferred embodiment, spray drying is used to remove the solvents and the pore forming agent. The resulting porous matrix has a faster rate of dissolution following administration to a patient, as compared to non-porous matrix forms of the drug. In a preferred embodiment, microparticles of the porous drug matrix are reconstituted with an aqueous medium and administered parenterally, or processed using standard techniques into tablets or capsules for oral administration.
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- Application of Curvularia sp to the hydrolysis of steroid pivalates
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As glucocorticoids have alkali - sensitive hydroxyacetylic side chain, conventional methods of removing of 21 - pivalates groups are risky. In this paper we described the hydrolysis of pivalates of some glucocorticoids by fungi imperfecti: Curvularia lunata, Curvularia tuberculata, Cylindrocladium simplex Meyer and Cunninghamella elegans. The highest yield of hydrolysis was found in the case of hydrocortisone and prednisolone pivalates with Curvularia lunata and Curvularia tuberculata. The other two tested enzymes gave in all studied cases null or extremely poor results.
- Kruszewska,Chmielowiec,Uszycka-Horawa
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p. 809 - 810
(2007/10/03)
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- Mucosal adhesive device for long-acting delivery of pharmaceutical combinations in oral cavity
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Mucosal adhesive devices are provided for use in the oral cavity for therapy against infections. The devices are dosage units which comprise a combination of antimicrobial agents such as antifungal agents and anti-inflammatory agents, optionally also a local anesthetic. The dosage units yield a gradual and relatively constant release of the pharmaceuticals over at least a 12-hour period.
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- Process and intermediates for the preparation of 17 alphahydroxyprogesterones and corticoids from an enol steroid
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This invention discloses an improved process for the production of corticoids from 17α-hydroxy steroids utilizing peroxymonosulfate.
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- Amine containing ester prodrugs of corticosteroids
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Novel solution stable ester prodrugs of corticosteroids of the formula STR1
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- Amine containing ester prodrugs of corticosteroids
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Novel solution stable ester prodrugs of corticosteroids of the formula STR1
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- Sulfonate containing ester prodrugs of corticosteroids
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Novel solution stable ester prodrugs of corticosteroids of the formula STR1 and their salts.
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- Sulfonate containing ester prodrugs of corticosteroids
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Novel solution stable ester prodrugs of corticosteroids of the formula STR1 and their salts.
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- Water-soluble steroid compounds
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Beta-cyclodextrin forms a water-soluble complex or inclusion compound with steroid compounds having a molecular structure smaller than the interior cavity in the doughnut-shaped molecular structure of beta-cyclodextrin. The resulting inclusion compounds can be used for a variety of applications including aqueous topical ophthalmic preparations and topical dermatological ointments.
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- Radiolytic degradation scheme for 60Co-irradiated corticosteroids
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The cobalt 60 radiolytic degradation products have been identified in the following corticosteroids: cortisone, cortisone acetate, hydrocortisone, hydrocortisone acetate, hydrocortisone sodium succinate, isoflupredone acetate, methylprednisolone, methylprednisolone acetate, prednisolone, prednisolone acetate, and prednisone. Two major types of degradation processes have been identified: loss of the corticoid side chain the D-ring to produce the C-17 ketone and conversion of the C-11 alcohol, if present, to the C-11 ketone. Minor degradation products derived from other changes affecting the side chain are also identified in several corticosteroids. These compounds are frequently associated in corticosteroids as process impurities or degradation compounds. No new radiolytic compounds unique to 60Co-irradiation have been found. The majority of corticosteroids have been shown to be stable to 60Co-irradiation. The rates of radiolytic degradation ranged from 0.2 to 1.4%/Mrad.
- Kane,Tsuji
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- Novel N-nitroso compounds, compositions containing such compounds, processes for their preparation and methods of treatment therewith, and novel intermediates
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This invention relates to novel N-halogenoalkyl-N-nitroso carbamates and N 4 halogenalkyl-N 4 -nitroso allophanates of steroid compounds, having an anti-tumor activity, and to the preparation thereof. The invention is also concerned with pharmaceutical compositions containing the said compounds, and methods of treatment therewith.
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