Deoxyribonuclease recombinant human

Cacia, J., Quan, C. P., Vasser, M., Sliwkowski, M. B., and Frenz, J., Protein sorting by high-performance liquid chromatography I. Biomimetic interaction chromatography of recombinant human deoxyribonuclease I on polyionic stationary phases, /. Chromatogr., 634, 229, 1993. 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Small amounts of surfactants may be used to prevent aggregation of proteins and may enhance the refolding process when the dried protein dissolves. Buffers may also help to prevent aggregation of the dissolved drug. Similarly, polymers may be used as aggregation inhibitors or to form matrices. Chan et al. [86] prepared crystalline powders of recombinant human deoxyribonuclease with high fractions of sodium chloride. These powders were formulated as adhesive mixtures on lactose and mannitol and showed improved aerosolization behaviour compared to the pure protein. 

Dosage form Pulmozyme Inhalation Solution is a sterile, preservative-free, highly purihed solution of recombinant human deoxyribonuclease I (dornase alfa). Each Pulmozyme single-use ampule will deliver 2.5 ml of the solution to the nebulizer bowl. The aqueous solution contains domase alfa l.Omg/ml. 

Shire, S. J. (1996), Stability, characterization and formulation of recombinant human deoxyribonuclease (Pulmozyme , Dornase Alpha), in Pearlman, R., and Wang, Y. J. Eds., Formulation, Characterization and Stability of Protein Drugs, Plenum Press, New York, pp. 393 126. 

Mucolytics Pulmozyme (Genentech) Dornase alfa (recombinant human deoxyribonuclease DNAse) In 2.5 mL ampoules Preservative-free. With 0.15mg/mL calcium chloride dihydrate and 8.77mg/mL sodium chloride... 

Chen B, Costantino HR, Liu J, Hsu CC, Shire SJ. Influence of calcium ions on the structure and stability of recombinant human deoxyribonuclease I in the aqueous and lyophilized states. J Pharm Sci 1999 88(4) 477 182. 

Jones AP, Wallis CE. Recombinant human deoxyribonuclease for cystic fibrosis. Cochrane Database Syst Rev. 2003 CD001127. 

B. Ferraiolo, and J. Mordenti. 1993. Altered pharmacokinetics of recombinant human deoxyribonuclease in rats due to the presence of a binding protein. Drug Metab. Dispos. 21 71-75. 

L Gonda. Inhalation therapy with recombinant human deoxyribonuclease I. Adi. Drug Dciiv. Rev. 19 37-46 (1996). 

B. W. Ramsey, 8. J. Aslley, M. L. Ailken, W, Burke, A. A. Colin, H. L, Dorian, J. D. hisenbe, K. L. Gibson, I. R. Harwood, D. V. Schidlow, et al. Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis. Am. jfeu Reqtir. Dm, /4 ]45-l Jl (1993k... 

Recombinant human deoxyribonuclease (Genentech Inc, South San Francisco, CA, USA). 

Ref. 12 describes the preparation of microspheres of lysozyme, insulin, albumin, and recombinant human deoxyribonuclease. Of these proteins, insulin powders demonstrated the highest degree of agglomeration. 

Dornase alfa is phosphorylated glycosylated recombinant human deoxyribonuclease. It is given daily by inhalation of a nebulised solution containing 2500 units (2.5 mg). It is of modest value only in patients with cystic fibrosis, whose genetic defect in chloride transport causes particularly viscous sputum. The blocked airways, as well as the sputum itself, are a trap for pathogens and the lysis of invading neutrophils leads to substantial levels of free and very viscous DNA within the CF airways. 

Shire, S.J. Stabihty characterization and formulation development of recombinant human deoxyribonuclease I [pulmozyme , (domase alpha)]. In Formulation, Characterization, Stability of Protein Drugs Pearlman, R., Wang, J., Eds. Plenum Press New York, 1996. 

Green, J.D. Pharmacological-toxicological (expert report on recombinant human deoxyribonuclease I (rhDNase pulmo-zyme ). Human Experimental Toxicology 1994, 13, S1-S42. 

Chan, H.-K. Clark, A. Gonda, I. Mumenthaler, M. Hsu, C. Spray dried powders and powder blends of recombinant human deoxyribonuclease (rhDNase) for aerosol delivery. Pharm. Res. 1997, 14, 431-497. 

Fig. 1 An example of excipient as carrier for drug particles. Scanning electron micrographs showing adhesion of recombinant human deoxyribonuclease I (rhDNase) particles to lactose (A) and mannitol (B).

Chan, H.-K. Gonda, 1. Solid state characterization of spray-dried powders of recombinant human deoxyribonuclease (rhDNase). J. Pharm. Sci. 1998, 87, 647-654. 

Cipolla, D.C. Clark, A.R. Chan, H.-K. Gonda, I. Shire, 59. S.J. Assessment of aerosol delivery systems for the recombinant human deoxyribonuclease I (rhDNase). STP Pharma Sciences 1994, 4, 50-62. 

Warming may have a beneficial effect. For instance, the temperature of fluids atomized in air-jet nebulizers decreases by approximately 10-15°C during use, resulting in bronchoconstriction in some asthma suffers.Bronchoconstriction, which is most marked at 5°C, disappears at 37°C and thus may be minimized by using an ultrasonic device. Furthermore, when solutions of drugs with low solubility are to be nebulized, ultrasonic nebulizers, which warm the solutions, may be preferable to air-jet devices, which cool them and may cause precipitation. However, the heat generated may harm heat-labile materials such as diethylenetriaminepentoacetic acid ( mTc-/DTPA), " proteins, and some antibiotic solutions. Thus, ultrasonic nebulizers are specifically prohibited for aero-solization of recombinant human deoxyribonuclease (rhDNase). ... 

Hsu CC, Wu SS, Walsh AJ. The preparation of recombinant human deoxyribonuclease powder comparative studies of spray drying versus lyofrftilization and application of microwave drying. In Strumillo C, Pakowski 2, cds. Drying 96. Vol B. Krakow, Poland Lodz Technical University, Dep. of Process and Environmental Engineering, 1996 1229-36. 

Bustami RT, Chan HK, Sweeney T, Dehghani F, and Foster NR. Generation of Fine Powders of Recombinant Human Deoxyribonuclease using the Aerosol Solvent Extraction System. Pharmaceutical Research 2003 20 2028—2035. 

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