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Ohtake S.,Aridis Pharmaceuticals, Llc | Wang Y.J.,Genentech
Journal of Pharmaceutical Sciences | Year: 2011

Trehalose, a disaccharide of glucose, has been reported to accumulate in many organisms that can withstand extended periods of inanimation. Since this discovery, the properties of trehalose have been examined extensively to understand its role and abundance in nature. The unique features of this sugar became clearer with each new finding which demonstrated its ability to sustain and preserve a wide array of biological molecules. Trehalose has been used in a variety of research applications and is contained in several commercially available therapeutic products, including Herceptin®, Avastin®, Lucentis®, and Advate®. Currently, there is a growing interest in the use of trehalose in solid dosage formulations, most notably in quick-dissolving tablets. Furthermore, trehalose has found its use in several food and cosmetic products, and new applications capitalizing on its unique properties are being developed and implemented in everyday-use products. As trehalose is an approved ingredient in all major markets, there is no significant barrier to its use. Extensive work with trehalose has been conducted in the three major industries, however with little overlap. Further understanding of the role of trehalose in the various applications may lead to an increase in the number of trehalose-containing products. © 2011 Wiley-Liss, Inc. Source


Ohtake S.,Aridis Pharmaceuticals, Llc | Koyama A.H.,Wakayama Medical University
Molecules | Year: 2010

Development of effective and environmentally friendly disinfectants, or virucidal agents, should help prevent the spread of infectious diseases through human contact with contaminated surfaces. These agents may also be used, if non-toxic to cells and tissues, as chemotherapeutic agents against infectious diseases. We have shown that arginine has a synergistic effect with a variety of virucidal conditions, namely acidic pH and high temperature, on virus inactivation. All of these treatments are effective, however, at the expense of toxicity. The ability of arginine to lower the effective threshold of these parameters may reduce the occurrence of potential toxic side effects. While it is clear that arginine can be safely used, the mechanism of its virus inactivation has not yet been elucidated. Here we examine the damages that viruses suffer from various physical and chemical stresses and their relations to virus inactivation and aggregation. Based on the relationship between the stress-induced structural damages and the infectivity of a virus, we will propose several plausible mechanisms describing the effects of arginine on virus inactivation using the current knowledge of aqueous arginine solution properties. © 2010 by the authors. Source


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 300.00K | Year: 2007

DESCRIPTION (provided by applicant): Cystic Fibrosis (CF) is an autosomal recessive disorder, which leads to the abnormal composition and physical properties of airway secretions in CF patients. Additionally, the lungs of CF patients are particularly susceptible to chronic bacterial infections with >80% of CF patients becoming chronically infected by 18 years of life with mucoid forms of Pseudomonas aeruginosa that over-produce the surface polysaccharide alginate. The long term goal of this project (which is outside the scope of this application) is to investigate the use of alginate specific monoclonal antibodies (mAb) as an immunotherapeutic to treat chronic P. aeruginosa lung infections in CF patients. The major hypothesis to be tested is whether alginate specific mAbs can be used to reduce P. aeruginosa lung infections and result in improvement in lung function. One key observation of P. aeruginosa infections in CF is that the infection fails to elicit opsonic/protective antibodies in patients. This ineffective immune response allows the organism to escape elimination by acquired host immune defenses and underlies the progressive decline in lung function. The alginate-specific human mAbs are both opsonic and protective against both mucoid strains of P. aeruginosa as well as classical non- mucoid strains isolated from patients with nosocomial infections. Preliminary data indicate that these human mAbs recognize an epitope on alginate that is defined by the highly charged carboxylic acid component of the uronic acid monomers that make up alginate, and represent a broadly reactive epitope that may be an effective target for immunotherapeutic intervention. In this application, we propose further preclinical development of alginate-based immunotherapeutics by preparing and testing the protective activities of a human mAb against acute P. aeruginosa pulmonary infection in wild-type (WT) mice and chronic P. aeruginosa oropharyngeal colonization and lung disease in transgenic CF mice. We will first develop cell culture processes to provide sufficient quantities of a mAb to perform preclinical testing in animal models and to determine whether the existing cell lines expressing mAb will be adequate to provide sufficient quantities for clinical testing. We will also investigate whether a mAb can be formulated and delivered optimally as a liquid in a mouse inhalation model. The studies proposed in this application are designed to further development of a human monoclonal antibody to treat chronic Pseudomonas aeruginosa lung infections of CF patients. At present, 80-95% of CF patients ultimately succumb to respiratory failure due to chronic P. aeruginosa infection and airway inflammation.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 599.83K | Year: 2009

DESCRIPTION (provided by applicant): Cystic Fibrosis (CF) is an autosomal recessive disorder, which leads to the abnormal composition and physical properties of airway secretions in CF patients. Additionally, the lungs of CF patients are particularly susceptible to chronic bacterial infections with gt80% of CF patients becoming chronically infected by 18 years of life with mucoid forms of Pseudomonas aeruginosa that over-produce the surface polysaccharide alginate. The long term goal of this project (which is outside the scope of this application) is to investigate the use of gallium nitrate as an anti-infective to treat chronic P. aeruginosa lung infections in CF patients. The major hypothesis to be tested is whether gallium nitrate can be used to reduce P. aeruginosa lung infections and result in improvement in lung function. One key observation of P. aeruginosa infections in CF is that the patients ultimately succumb to bacterial infections despite being on a regiment of antibiotics. It is believed that bacterial resistance is a major reason for treatment failure, allowing the organism to escape elimination by acquired host immune defenses and underlies the progressive decline in lung function. Gallium nitrate was found to be bactericidal in vitro against both Gram- and Gram+ bacteria, particularly against bacteria that are found to chronically colonize the lungs of CF patients, such as P. aeruginosa, Burkholderia cepacia and methycillin-resistant Staphylococcus aureus (MRSA). Galllium was protective against mucoid strains of P. aeruginosa isolated from patients with nosocomial infections. Preliminary data indicate that gallium is effective against bacterial resistant Pa strains as well as recent strains isolated from fresh sputum. In this application, we propose further preclinical development of gallium nitrate and testing the protective activities against acute P. aeruginosa pulmonary infection in wild- type (WT) mice. We will first develop an optimal aerosol formulation using a spray drying process, characterize the aerosol properties, and confirm that lead formulations can be efficiently delivered from conventional, commercially available inhalers. We will perform preclinical testing of optimized aerosol formulation in a mouse inhalation model to assess its residence time and biodistribution, followed by determination of the minimal protective dose in a bacterial challenge study. PUBLIC HEALTH RELEVANCE: The studies proposed in this application are designed to further development of a new anti-infective candidate gallium nitrate to treat chronic Pseudomonas aeruginosa lung infections of CF patients. At present, 80-95% of CF patients ultimately succumb to respiratory failure due to chronic P. aeruginosa infection and airway inflammation.


Patent
Aridis Pharmaceuticals, Llc | Date: 2012-08-14

This invention provides methods of spray drying pharmaceutical powders from a vibrating nozzle at low pressures. The method can effectively spray dry thick or viscous solutions or suspensions to provide small uniform particles. The invention includes dry particle compositions prepared by methods of low pressure spraying from vibrating nozzles.

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