Abstract: A catalyst for reducing nitrogen oxides in oxidizing and reducing atmospheres which contains iridium on a support material. Silicon dioxide or a dealuminized zeolite in the acid H form with a modulus of more than 20, preferably more than 100, or mixtures thereof are used as support materials. Iridium is deposited on the external surfaces of these support materials with average particle sizes between 10 and 30 nm. The catalyst is particularly suitable for treating exhaust gases from lean-burn gasoline engines or from diesel engines.
Type:
Application
Filed:
July 1, 1999
Publication date:
December 20, 2001
Inventors:
HANS VAN DEN TILLAART, JURGEN LEYRER, WOLFGANG STREHLAU, EGBERT LOX, THOMAS KREUZER, CARSTEN PLOG, RENATO ANDORF, NORBERT MARKERT, THOMAS STENGEL
Abstract: A method and a device for selective catalytic NOx reduction in oxygen-containing exhaust gases using ammonia and a reduction catalyst (9) are described, according to which gaseous ammonia is made available by heating a solid storage medium (2) in a container (1). The method and the device are suitable for use in motor vehicles in particular.
Type:
Application
Filed:
May 6, 1999
Publication date:
December 20, 2001
Inventors:
ARMIN MARKO, THOMAS WAHL, ULRICH ALKEMADE, FRANK BRENNER, MARC BAREIS, HORST HARNDORF
Abstract: A process for separating metal chlorides from a suspension of metal chlorides in chlorosilanes, in which the suspension is filtered under pressure in the absence of air and moisture forming a filter cake, which is granulated and passed to a dissolution zone where the metal chlorides are dissolved to form an aqueous metal chloride solution. The invention also relates to a filtration and dissolution apparatus for this process, and to an apparatus for introducing the crude reaction gas into a circulated suspension of metal chlorides in chlorosilanes, thus producing a feedstock for the process.
Abstract: An apparatus for the production of elongated carbonaceous article includes a chamber having at least one heating element, a catalyst and a device for generating a magnetic field in proximity to or around the catalyst. In operation, a carbon-containing precursor is introduced to the chamber to contact the catalyst with a sufficient amount of heat to cause the deposition of carbon on the catalyst. Continual deposition of carbon over time forms elongated carbon structures, such as carbon fibers and carbon nanotubes. By operating the device to magnetically confine the catalyst during the formation of the carbon structures, migration of catalyst is reduced or prevented thereby minimizing contaminants in the produced products and improving the useful life of the catalyst.
Type:
Application
Filed:
June 15, 2001
Publication date:
December 20, 2001
Applicant:
The Penn State Research Foundation
Inventors:
Avetik R. Harutyunyan, Leonid Grigorian
Abstract: An object of the present invention is to provide an effective and efficient process for the treatment of an inorganic salt containing an organic material which can solve various problems with the prior art, i.e., process for purifying an inorganic salt containing an organic material to an extent such that it can be recovered and re-used from the standpoint of environmental protection and utilization of resources. An inorganic salt containing an organic material is granulated or subjected to chemical treatment (mixed with an alkali and/or oxidizing agent), and then subjected to heat treatment so that it is purified.
Abstract: The present invention provides a method for combining sodium and aluminum into a single, substantially homogeneous alloy without the need to use potentially dangerous, toxic mercury compounds. The present invention also provides a catalytic alloy that is capable of dissociating water into hydrogen and oxygen, thereby allowing the hydrogen to be utilized as fuel.
Abstract: The deleterious effects of the passage of time on human skin (i.e., chronological aging of human skin) can be prevented and treated with the topical application of a retinoid, preferably retinol. We have found that some of the same pathways (namely the stress-activated pathways, SAPs) activated in photoaging of human skin (i.e., sun-induced premature skin aging) are similarly elevated in the skin of elderly people. We have also found that other pathways (namely the mitogen-activated ERK pathway) is depressed in the same skin. Treatment of chronologically-aged skin with a retinoid both inhibits degradation of dermal collagen and promotes procollagen synthesis. Biopsied sections from skin of elderly (80+ years old) show that a single treatment can increase epidermal thickness, improve the dermal collagen density, and promote the formation of rete pegs and dermal papillae (see FIG. 13), and can decrease the amount of c-Jun and increase the amounts of Types I and III procollagen (see FIG. 18).
Type:
Application
Filed:
February 24, 1998
Publication date:
December 20, 2001
Inventors:
JAMES VARANI, GARY J. FISHER, JOHN J. VOORHEES, SEWON KANG
Abstract: The sunscreen or makeup may be applied to a person who is wet, or even underwater, yet it will provide the full efficacy which it would have had had it been applied to the person when their skin was dry. In addition, it will be effective from the time that it is first applied, so no waiting period is required, as was the case for the so-called “water resistant” and “waterproof” sunscreens of the prior art.
Abstract: A daily perventive method reduces infection risk associated with artificial nails. When applied as a spray or gel soak to the nail and periungal areas, bacterial and fungal counts are significantly reduced. It is a well established medical fact that hand to hand contact is the #1 mode of transmission of infection. Artificial nails act as carriers when applied onto natural fingernails. Attached to the human hand they transmit bacteria one to another on personal contact. The porous composition of artificial nails along with additional gaps and separation created by natural nail growth; provides a template for which skin organisms are trapped and grow. Artificial nails attract water moisture on contact (bandwashing); remaining damp they act as a template which supports growth of organisms.
Abstract: A depigmenting and/or lightening composition is provided, wherein the composition contains N-ethyloxycarbonyl-4-para-aminophenol and at least one depigmenting agent selected from arbutin and its derivatives and/or ellagic acid and its derivatives, and its use in a method for depigmenting and/or lightening skin.
Abstract: The activity of NF-&kgr;B is modulated through the effects of GSK-3 on NF-&kgr;B activity. Inhibition or down-regulation of GSK-3 results in decreased NF-&kgr;B activity. Inappropriate activation of NF-&kgr;B has been linked to inflammation and hyperproliferative disorders. Development of modulatory strategies provide a novel therapeutic tool for the treatment or prevention of various diseases. Methods are also provided for enhanced killing of tumor cells through the sensitization action of GSK-3 inhibition, when administered in conjunction with apoptosis inducing ligands of TNFR1. Transgenic animals defective in GSK-3 function are also provided.
Type:
Application
Filed:
December 22, 2000
Publication date:
December 20, 2001
Inventors:
Klaus Hoeflich, James Woodgett, Juan Luo
Abstract: The present invention provides adenoviral vectors comprising cell status-specific transcriptional regulatory elements which confer cell status-specific transcriptional regulation on an adenoviral gene. A “cell status” is generally a reversible physiological and/or environmental state. The invention further provides compositions and host cells comprising the vectors, as well as methods of using the vectors.
Abstract: Slowly polymerizing polysaccharide hydrogels have been demonstrated to be useful as a means of delivering large numbers of isolated cells via injection. The gels promote engraftment and provide three dimensional templates for new cell growth. The resulting tissue is similar in composition and histology to naturally occurring tissue. This method can be used for a variety of reconstructive procedures, including custom molding of cell implants to reconstruct three dimensional tissue defects, as well as implantation of tissues generally.
Type:
Application
Filed:
January 20, 1998
Publication date:
December 20, 2001
Inventors:
LINDA G GRIFFITH, ANTHONY ATALA, CHARLES A. VACANTI, KEITH T. PAIGE
Abstract: Porcine cardiomyocytes and methods for using the cardiomyocytes to treat disorders characterized by insufficient cardiac function are described. The porcine cardiomyocytes are preferably embryonic porcine cardiomyocytes. The porcine cardiomyocytes can be modified to be suitable for transplantation into a xenogeneic subject, such as a human. For example, the porcine cardiomyocytes can be modified such that an antigen (e.g., an MHC class I antigen) on the cardiomyocyte surface which is capable of stimulating an immune response against the cardiomyocytes in a xenogeneic subject is altered (e.g., by contact with an anti-MHC class I antibody, or a fragment or derivative thereof) to inhibit rejection of the cardiomyocyte when introduced into the subject. In one embodiment, the porcine cardiomyocytes are obtained from a pig which is essentially free from organisms or substances which are capable of transmitting infection or disease to the recipient subject.
Abstract: A method for inducing differentiation of monocytes contained in an extracorporeal quantity of a subject's blood into functional dendritic antigen presenting cells is provided. The monocytes are first treated by exposure to physical perturbation, irradiation in the presence of a photoactivatable agent capable of forming photoadducts with cellular DNA components, and/or treatment with a DNA binding agent. The treated monocytes are then incubated for a period of time sufficient to maximize the number of functional dendritic cells in the treated cell population. Functional dendritic cells generated from induced monocytes are incubated together with disease effector agents to enhance the presentation of at least one disease-causing antigen expressed by the disease effector agents.
Abstract: The present invention provides compositions and method of use for the prevention and treatment of vascular-related disorders such as vascular re-occlusion or restenosis post-coronary intervention with balloon angioplasty or stent procedures and diseases associated with pathological angiogenesis such as cancer, ocular or inflammatory diseases. More specifically, compositions and methods of the present invention involve the combination of the garlic-derived or related compounds and antioxidants.
Abstract: The present method provides for an isolated peptide having an amino acid sequence corresponding to the amino acid sequence of a V-domain of a receptor for advanced glycation endproduct (RAGE). The present invention also provides for an isolated peptide having an amino acid sequence A-Q-N-I-T-A-R-I-G-E-P-L-V-L-K-C-K-G-A-P-K-K-P-P-Q-R-L-E-W-K (Seq. I.D. No. 1). The present invention provides for a pharmaceutical composition comprising a therapeutically effect amount of an isolated peptide having an amino acid sequence corresponding to the amino acid sequence of a V-domain of RAGE.
Type:
Application
Filed:
October 9, 1997
Publication date:
December 20, 2001
Inventors:
DAVID STERN, SHI DU YAN, ANN MARIE SCHMIDT, IRA LAMSTER
Abstract: A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-11 (GDF-11) chromosomally integrated into the germ cells of the animal is disclosed. Also disclosed are methods for making such animals, and methods of treating animals with antibodies or antisense directed to GDF-11. The animals so treated are characterized by increased muscle tissue.
Type:
Application
Filed:
December 6, 1999
Publication date:
December 20, 2001
Applicant:
THE JOHN HOPKINS UNIVERSITY SCHOOL OF MEDICINE
Abstract: A drug delivery composition for nasal administration is provided which comprises the antiviral agent ICAM-1 and a bioadhesive material. The bioadhesive material may be a chitosan solution, a liquid formulation comprising a polymeric material or a plurality of bioadhesive microspheres. The polymeric material is preferably gellan gum or alginate. The microspheres may comprise starch, chitosan, hyaluronic acid, or gelatin.
Abstract: Anti-human major histocompatibility complex (MHC) class II, HLA-DR-specific monoclonal antibodies which can induce apoptosis of HLA-DR positive cells are disclosed. The antibodies are used to specifically eliminate HLA-DR antigen positive tumor cells by cross-linking of HLA-DR. Also disclosed are methods for treating cancer using such antibodies, and compositions containing them.
Abstract: A method of immunotherapy stimulates the T cell CD28 surface molecule to enhance T cell proliferation and increase overall lymphokine levels or to increase cellular production of human TH1 lymphokines or both. Thee method is selective for the induction of activated T cell mediated immune responses and enhances immune function even in the presence of immunosuppresants.
Type:
Application
Filed:
June 7, 1995
Publication date:
December 20, 2001
Applicant:
THE REGENTS OF THE UNIVERSITY OF MICHIGAN
Inventors:
CRAIG B. THOMPSON, CARL H. JUNE, JEFFREY A. LEDBETTER, TULLIA LINDSTEN
Abstract: A new approach to immune system transplantation and other organ transplantation is described below. The invention describes the novel use of human tissues, or products derived from human tissues including but not limited to antigens, proteins, glycoproteins, and carbohydrates, taken from an individual patient, group or group of patients, to induce immunological tolerance to human antigens in other mammals. Mammals thus rendered tolerant to human antigens can subsequently serve as immune system donors, and as donors of other biological systems, to recipient humans. The invention also uniquely integrates experimentally documented observations from diverse fields of biological and medical research. The invention provides novel treatments for all cancers; for hereditary and acquired immunodeficiency disorders including AIDS; for failures of host immunological defenses including infectious diseases; for hereditary end acquired bone marrow failure syndromes; and for autoimmune diseases.
Abstract: A method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of Botulinum toxin types A, B, C, D, E, F and G.
Type:
Application
Filed:
July 11, 2001
Publication date:
December 20, 2001
Inventors:
K. Roger Aoki, Michael W. Grayston, Steven R. Carlson, Judith M. Leon
Abstract: A method of removing bacterial endotoxin from a pharmaceutical process solution is disclosed. In one embodiment, the method comprises treating the solution with a surfactant effective to dissociate the endotoxin from a pharmaceutical drug or vaccine substance in the solution, and then filtering the solution through a molecular cut-off filter having a pore size effective to retain the pharmaceutical drug or vaccine substance but allow the dissociated bacterial endotoxin to pass therethrough.
Type:
Application
Filed:
March 12, 2001
Publication date:
December 20, 2001
Inventors:
Bridget Kathleen Mapleson, Philip Sizer
Abstract: The anti-viral vaccine of the present invention is produced in transgenic plants and then administered through standard vaccine introduction method or through the consumption of the edible portion of those plants. A DNA sequence encoding for the expression of a surface antigen of a viral pathogen is isolated and ligated to a promoter which can regulate the production of the surface antigen in a transgenic plant. This gene is then transferred to plant cells using a procedure that results in its integration into the plant genome, such as through the use of an Agrobacterium tumenfaciens plasmid vector system. Preferably, the foreign gene is expressed in an portion of the plant that is edible by humans or animals. In a preferred procedure, the vaccine is administered through the consumption of the edible plant as food, preferably in the form of a fruit or vegetable juice which can be taken orally.
Type:
Application
Filed:
March 23, 2001
Publication date:
December 20, 2001
Applicant:
PRODIGENE, INC.
Inventors:
Charles Joel Arntzen, Dominic Man-Kit Lam
Abstract: Improved forms of vaccines which comprise proteosomes and protein antigens are described. Vaccines which contain influenza HA as the antigen are used for illustration as to demonstrate efficacy. Improvements in the preparation of the vaccines themselves and the proteosome component are also included.
Type:
Application
Filed:
February 15, 2001
Publication date:
December 20, 2001
Inventors:
Davis S. Burt, David Hugh Jones, George H. Lowell, Gregory Lee White, Kirkor Torossian, Louis F. Fries, Martin Plante
Abstract: Methods for treating a movement disorder by intracranial administration to a human patient of a therapeutically effective amount of a neurotoxin, such as a botulinum toxin type A.
Abstract: Methods for treating a movement disorder by intracranial administration to a human patient of a therapeutically effective amount of a neurotoxin, such as a botulinum toxin type A.
Abstract: Disclosed is a method of inhibiting the growth of tumors bearing IL13-specific receptors. Included among this class of tumors is glioblastoma multiform (GBM), a rapidly progressing brain tumor for which there is currently no effective treatment available. In the disclosed method, a chimeric cytotoxin comprising an IL13 receptor-binding moiety and a cytotoxic moiety is delivered into a mammalian subject having a tumor bearing IL13-specific receptors. All studied human GBM specimens abundantly express the IL13-specific tumor.
Abstract: The present invention provides a sustained release pheromone formation comprising the sex pheromone substance which is an aldehyde compound wherein the formation can prevent the degradation of the aldehyde compound and release the compound at an uniformed rate during the control term of the subjective pest insects. The sustained release pheromone formation is obtained by mixing an aliphatic derivative of which number of carbon atoms is equal to or less than that of the sex pheromone substance with a C10-18 aldehyde which is a sex pheromone and then filling the resulting liquid mixture in a plastic container.
Abstract: A microemulsion for use in personnel care products, home care products and fabric care products which is clear and has particle sizes that are less than the wavelength of light, said microemulsion comprising, as essential components; (a) a substantially water insoluble quaternary ammonium salt containing at least one long-chain aliphatic C8-24 hydrocarbon group; (b) an oil or hydrophobic organic compound that is not dispersible in water on its own; and (c) a dispersant capable of preventing component (b) from coalescing into particle sizes that are above the wavelength of light, wherein the weight ratio of component (a) to component (b) to component (c) is from 2:0.5:0.4 to about 0.5:2:0.8. A clear, indefinitely dilutable microemulsion is obtained by quenching the same in water.
Abstract: Delivery systems for whitening teeth are provided. The delivery system includes a strip of material sized to cover a front surface of a plurality of teeth and a layer of a tooth whitening substance in contact with the strip of material. The tooth whitening substance includes a gelling agent and a whitening active selected from the group consisting of peroxides, metal chlorites, perborates, percarbonates, peroxyacids, hypochlorites, and combinations thereof. The delivery system further includes a release liner having a coating thereon, wherein the release liner exhibits less affinity for the tooth whitening substance than the tooth whitening substance exhibits for itself and for the strip of material.
Type:
Application
Filed:
May 29, 2001
Publication date:
December 20, 2001
Inventors:
Paul Albert Sagel, Robert Stanley Dirksing, Frederick James Rohman
Abstract: An oil-in-water type emulsion cosmetic which contains (A) a hydrophilic surface active agent, (B) an oily component and (C) water, and weight ratio of the component (B) is 10 or more based on 1 of the component (A).
Abstract: The present invention relates to a process for increasing the persistence of at least one cosmetic and/or care effect of a cosmetic composition comprising an oily phase. This process comprises the incorporation into this oily phase of at least one linear or cyclic polyorganosiloxane which comprises at least two organosiloxy units and at least two side and/or end groups which are each capable of forming at least one hydrogen bond with one or more partner groups. The process may be applied, for example, to lipsticks, mascaras or eyeliners to increase the persistence of their coloring effect and/or gloss, to foundations, powders, blushers and eyeshadow to increase the persistence of the matt effect, and to care products such as moisturizing products, deodorants or antiperspirants to increase the persistence of their active care agents.
Abstract: A composition and method for producing the composition, which is effective as a virucide and a bactericide, yet safe and non-irritating to human skin. The compositions include fumaric acid, benzoic acid and “IRGASAN® DP 300” as the active ingredients, and can also include denatured ethyl alcohol.
Abstract: This invention pertains to a method that can control, treat, and prevent Diabetes Mellitus. The method includes means of administering a potent product, including mainly the active ingredient Linalool, in any one of several forms, alone or with other additives and catalysts, such as vitamin E to enable the body to handle and control, then correct the complications of Diabetes Mellitus. A modest percentage of users suffering from this disease can be cured completely while the majority of others improve remarkably and experience lower blood glucose and reduce the glycated hemoglobin HbAlc readings to what are medically acceptable and healthy levels. Others, who are vulnerable to the disease due to hereditary factors, or other reasons, can help prevent it. The method works in several ways, including activation of the pancreas and re-establishing the ability of body cells to utilize and handle better and well, the glucose in the blood, and regulate the level of natural insulin in the body.
Type:
Application
Filed:
January 2, 2001
Publication date:
December 20, 2001
Applicant:
DIABEX INC.
Inventors:
Osama Mansour Murad, Husni Abu Seir, Hafez Taji Farouqi
Abstract: The present invention is a system and method capable of improving the dietary fuel capabilities and metabolically impaired patients and correct an overutilization of free fatty acids associated with heart disease in diabetic and non-diabetic patients. The current invention is the treating of heart disease and cardiovasular disease using insulin pulses to a patient utilizing Chronic Intermittent Intravenous Insulin Therapy to achieve an increase dietary fuel capabilities and correct overutilization of free fatty acids associated with heart disease in both diabetic and non-diabetic patients.
Abstract: The present invention is a system and method capable of improving the entire metabolic process and through its multiplicity of effects on neurovascular reactivity, intraglomerular presure and hemodynamics, arresting the progression of overt diabetic nephropathy, improving intraglomerular hemodynamics, and thus arresting the progression of diabetic nephropathy and therefore reducing the risk of development of End Stage Renal Disease. The current system and method is for the treatment of kidney disease using insulin pulses to a patient utilizing Chronic Intermittent Intravenous Insulin Therapy to achieve the slowing, stopping or reversing of kidney disease in both diabetic and non-diabitic patient.
Abstract: The present invention is a system and method capable of increasing glucose oxidation in an affected area and therefore providing more energy for treating wounds, promoting healing and avoiding amputations in both diabetic and non-diabetic patients. The current invention is the treating of wounds, promoting healing and avoiding lower extremity amputations using insulin pulses to a patient utilizing Chronic Intermittent Intravenous Insulin Therapy to achieve an increase in glucose oxidation in tissues surrounding an affected area, therefore treating wounds, promoting healing and avoiding amputations in both diabetic and non-diabetic patients.
Abstract: The method of adjusting the saturation concentration of a drug in a transdermal composition for application to the dermis, which comprises mixing polymers having differing solubility parameters, so as to modulate the delivery of the drug. This results in the ability to achieve a predetermined permeation rate of the drug into and through the dermis. In one embodiment, a dermal composition of the present invention comprises a drug, an acrylate polymer, and a polysiloxane. The dermal compositions can be produced by a variety of methods known in the preparation of drug-containing adhesive preparations, including the mixing of the polymers, drug, and additional ingredients in solution, followed by removal of the processing solvents. The method and composition of this invention permit selectable loading of the drug into the dermal formulation and adjustment of the delivery rate of the drug from the composition through the dermis, while maintaining acceptable shear, tack, and peel adhesive properties.
Abstract: A method for the delivery of substances to a cell is disclosed. In a preferred embodiment, one administers continuous wave ultrasound or pulse-wave ultrasound to a cell bathed in a cocktail containing macromolecules and monitors the ultrasound using reflected echos of the ultrasound. One then observes incorporation of the substances into the cell. In a preferred embodiment of the present invention, macromolecules are combined in a cocktail solution comprising bubble micronuclei.
Type:
Application
Filed:
July 2, 1998
Publication date:
December 20, 2001
Inventors:
JAMES F. GREENLEAF, MARK E. BOLANDER, WILLIAM J. GREENLEAF
Abstract: The present invention is directed to a formulation comprising a lipid-regulating agent dissolved in at least one monoglyceride as the primary solvent medium for said agent. One or more emulsifiers may be added to the formulation.
Type:
Application
Filed:
December 18, 1998
Publication date:
December 20, 2001
Inventors:
JOHN M. LIPARI, DAWN M. RAYMOND, TOM REILAND, YESHWANT D. SANZGIRI
Abstract: The sustained release tablet of (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinolin-2(1H)-one (Z)-2-butenedioate (1:1) which is disclosed permits twice daily administration of (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinolin-2(1H)-one (Z)-2-butenedioate (1:1) to treat humans with Parkinson's disease.
Abstract: A pharmaceutical composition which is a solid pellet comprising an inert core, a benzimidazole in or on the core, a moisture resistant coating around the core, the moisture resistant coating comprising at least one hydrophobic material, and an enteric coating around the moisture resistant coating.
Type:
Application
Filed:
July 9, 2001
Publication date:
December 20, 2001
Inventors:
Yusuf Khwaja Hamied, Vinay G. Nayak, Geena Malhotra
Abstract: The invention is concerned with a pharmaceutical preparation for subcutaneous, parenteral administration, which contains bisphosphonic acids or their salts as the active substance, as well as the production of this preparation. By means of the preparation in accordance with the invention it is possible to administer locally relatively high concentrations of bisphosphonates without the occurrence of incompatibilities.
Type:
Application
Filed:
May 3, 2001
Publication date:
December 20, 2001
Inventors:
Rainer Bader, Petra Bastian, Achim Goepferich, Wolfgang Roedel, Gerhard Winter
Abstract: A composition for managing blood glucose levels is herein described. The composition comprises decocted tea and vanadate and does not cause the same side effects as vanadate and water mixtures known in the prior art. Specifically, the vanadate suspended in decocted tea does not cause diarrhea and in some cases stabilizes blood glucose at normal levels for several weeks after only a few treatments.
Abstract: Novel herbal extracts provide potent efficacy in the treatment of acne and furuncle. The formulated extracts of Momordica charantia L. are from either the whole plant or parts of the plant. The extracts have been formulated into aqueous solution, pads, and/or lotion. These formulations have been provided to treat acne and furuncle 2 to 3 times a day. It has demonstrated the ability to manage various grades of acne, from mild, moderate to severe, which include comedos, papules, pustules and nodules. Significant improvement is visible within five days. There are no observed either long-term or short-term side reactions.