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WO2004080427A2 - Methode de prevention et de traitement d'infections attaquant la muqueuse et d'aide a la readaptation ulterieure au moyen d'acide ascorbique applique localement - Google Patents

Methode de prevention et de traitement d'infections attaquant la muqueuse et d'aide a la readaptation ulterieure au moyen d'acide ascorbique applique localement Download PDF

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Publication number
WO2004080427A2
WO2004080427A2 PCT/US2004/007803 US2004007803W WO2004080427A2 WO 2004080427 A2 WO2004080427 A2 WO 2004080427A2 US 2004007803 W US2004007803 W US 2004007803W WO 2004080427 A2 WO2004080427 A2 WO 2004080427A2
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ascorbic acid
mucosa
formulation
acid formulation
individual
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PCT/US2004/007803
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WO2004080427A3 (fr
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Daniel J. Schneider
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Schneider Daniel J
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration

Definitions

  • the present invention generally relates to medical treatment. More specifically, the present invention relates to an ascorbic acid formulation and a method of preventing and treating mucous and/or serous membrane associated infections and inflammation, and afterwards assisting rehabilitation of pulmonary function, using the ascorbic acid formulation thereof.
  • Pneumonia is the leading cause of death during the immediately post-operative recovery period for all thoracic surgery cases given current standard techniques of pre- and post-operative respiratory care.
  • the overall frequency of bronchitis or pneumonia or other disease due to the pulmonary infections and inflammation is high in the general human population with bronchitis and pneumonia in the population over 55 years of age being the third leading cause of death.
  • mucosa associated infections and inflammation such as acute or chronic lung mucosa disease in the general population or lung infections post a thoracic surgery in a finite population and afterwards assisting rehabilitation of pulmonary function.
  • the mucosa consists of all internal surfaces of the human body that are indirectly exposed lo the external environment, some of which is readily visualized to those not trained in the art, such as that of the mouth, nose, anus and vagina; while some others are less easily visualized, such as the external surface of the sinuses and middle ear system, lacrimal system, salivary systems, lower respiratory system, bile and pancreatic collecting systems, esophageal-gastro-intestinal system, and genito-urinary systems.
  • Ascorbic acid also known as vitamin C, is a water-soluble metabolite. In its pure form, ascorbic acid occurs as a white or slightly yellow crystal or powder with an acid taste. Ascorbic acid is an antiscorbutic product. When exposed to air and light it gradually darkens. In the dry state, ascorbic acid is reasonably stable in air, while in solution its oxidation is accelerated at room temperature when exposed to air. Ascorbic acid is readily soluble in water, sparingly soluble in alcohol, and insoluble in chloroform, ether, and benzene. The chemical name of ascorbic acid is L-ascorbic acid. The molecular formula of ascorbic acid is C 6 H 8 O 6 , and the molecular weight is 175.13.
  • the present invention is directed to an ascorbic acid formulation and a method for preventing and/or treating mucosa associated infections and/or inflammation, i.e., lung infections, using the ascorbic acid formulation thereof. Also provided is a method for assisting rehabilitation of mucosa (i.e., pulmonary) function post the treatment.
  • mucosa i.e., pulmonary
  • an ascorbic acid formulation advantageously comprises ascorbic acid in such an amount that the total daily dose per individual ranges from about 1 mg/kg to about 250 mg kg when administered to mucosa of the individual.
  • a method for treating and thereafter assisting rehabilitation of an individual having a mucosa- associated lower respiratory system pathological condition advantageously includes administering a pharmaceutically effective amount of an ascorbic acid formulation to the pathologically afflicted lower respiratory system mucosa of the individual.
  • a method for treating and thereafter assisting rehabiUtation of an individual having a mucosa-associated upper respiratory system pathological condition advantageously includes administering a pharmaceutically effective amount of an ascorbic acid formulation directly to the pathologically afflicted upper respiratory system mucosa of the individual.
  • Figure 1 shows lung mucosa effects correlated to antibiotic and bronchodilator use as well as ascorbic acid aerosol inhalant treatment according to the present invention
  • Figure 2 shows respiratory remission and pulmonary function rehabilitation correlated to antibiotic and ascorbic acid aerosol inhalant treatment according to the present invention.
  • vitamin C deficiency results in pulmonary mucosa-associated pathokinetic dysfunction (i.e., active pathologic siege between an aggressive external agent and host defense mechanisms), manifest as abnormal tissue response and injury with increased predisposition to microbial colonization and invasion.
  • pathokinetic dysfunction i.e., active pathologic siege between an aggressive external agent and host defense mechanisms
  • Physiology functions of ascorbic acid upon which lung is dependent include: a) anti-oxidant in preventing oxidative damage of highly oxygenated lung tissue (Persson, et al., 1989; Benson, et al., 1985); b) collagen processing in strengthening, repairing and replacement of pulmonary epithelium (i.e., mucous membrane) (Brown, et al., 1997); c) apoproteins A and D processing in production of surfactant (i.e., an essential serous watery fluid from membrane secretion needed for ciliary efficiency in making mucous flow) (Fessler, et al., 1985; Jariwalla, et al., 1997); d) redox control of total RNA in gene expression (i.e., essential gene regulation of membrane function) (Alcain, et al., 1994); e) coenzymalic activity in protecting enzyme function through free radical mechanisms (Stone, 1972); f) enhancement of leukocyte function (i
  • This dietary habit strongly dosed abundant vitamin C directly onto the ancestral oral and adjoining upper respiratory mucosa by means of dedicated or required mastication, and by extension of oral-pharyngeal dosing effect provided a topical nutrition protection for the mucosa of both upper and lower respiratory systems, strengthening collagen, increasing surfactant production, and subduing pathogen colonization, thereby rendering a survival advantage by reducing the ancestor's susceptibility to pulmonary infections and related morbidity and mortality.
  • a strong ascorbic acid aerosol applied directly to the external surface of the lower respiratory system does not provide a surface ascorbic acid metabolic effect to strengthen respiratory system mucosa, increase surfactant production or subdue micro-organism colonization associated with acute and chronic pulmonary infections, the occurrence of which is not measurable as significantly reduced pulmonary infection signs and symptoms, such as increased mucolysis and mucous transport, improved pulmonary function, and rehabilitation of lung health.
  • HI Alternative Hypothesis
  • topical application of a strong (i.e. 300 mg in 3 ml aqueous solution) ascorbic acid aerosol applied directly to the external surface of the lower respiratory system does provide a surface ascorbic acid metabolic effect to strengthen respiratory system mucosa, does increase surfactant production and subdue micro-organism colonization associated with acute and chronic pulmonary infections, the occurrence of which is measurable as significantly reduced pulmonary infection signs and symptoms, such as increased mucolysis and mucous transport, improved pulmonary function, and rehabilitation of lung health.
  • a strong ascorbic acid aerosol applied directly to the external surface of the lower respiratory system does provide a surface ascorbic acid metabolic effect to strengthen respiratory system mucosa, does increase surfactant production and subdue micro-organism colonization associated with acute and chronic pulmonary infections, the occurrence of which is measurable as significantly reduced pulmonary infection signs and symptoms, such as increased mucolysis and mucous transport, improved pulmonary function, and rehabilitation of lung health.
  • P 0.05
  • Healthful therapeutic, rehabilitative and metabolic homeostasis is achieved in the infected mucosa.
  • Appropriate clinical trials will be conducted to explore a new dimension of respiratory care in which the new use of topically applied vitamin C could greatly reduce cost and suffering associated with lung disease, and assure long term stable pulmonary health and a high quality of extended life.
  • Three sequential steps to qualify and statistically quantify causal association among disease, its etiology and pathogenesis, and its remedy include: 1) observe, comprehensively articulate, and model biologically plausible causal-effect association(s); 2) design and execute Index Case experiments to reveal the statistical strength and level of significance of the suspected causal and remedial association(s) (i.e. Koch's postulates compliance, dose-response, observation consistency, temporality, specificity and sensitivity concordance); and then 3) design and execute clinical trials to test the experimentally revealed associations in appropriate reference populations and/or a general population base so as to confirm that the Index Case results are replicated in the general population.
  • Ascorbic acid used herein is not limited to the ascorbic acid per se, the term "ascorbic acid” shall refer to all related ascorbates with mucosa-associated biological activity, which include ascorbic acid and ascorbic acid derivatives having similar biological activity to that of ascorbic acid.
  • an inhalant formulation of ascorbic acid is prepared and used for these purposes.
  • Embodiments of other anatomically differentiated mucosa or serosa- associated infections are also included, such as the upper respiratory system, the mouth, the lacrimal system, the genito-urinary system, and the large intestine.
  • Differentiated topical formulations of ascorbic acid are prepared for topical application purposes on the above-mentioned anatomically differentiated mucosa and serosa locations.
  • an aqueous solution of between 200 mg and 300 mg of ascorbic acid made up to 3 ml of solution in sterile water was prescribed for therapeutic inhalation (i.e., respiratory mucosa topical application) by patients who suffer from lung infections.
  • the designed prescription was tested in a dose-response controlled experiment to evaluate topical vitamin C use for reduction of chronic and acute infection-related lung inflammation and associated asthmatic airway obstruction, and for follow-on long-term rehabilitation of lung function.
  • the controlled experiment was repeated several times on a human Index Case Subject who was afflicted with bronchiectasis and chronic bronchitis complicated by frequent acute bronchitis and occasional attendant pneumonia episodes, all associated with underlying mild primary immunodeficiency.
  • the experiment established a rational and safe regimen for the new use of vitamin C in reducing morbidity and antibiotic need in achieving cost- effective and potentially life-saving mucosa-associated lung infection treatment, including treatment of some forms of asthma, and certain upper respiratory mucosa- associated diseases.
  • Statistical analysis of the experiment results has established the high level of significance (p ⁇ 0.05) of the new use of vitamin C in mucosa-associated disease treatment regimen.
  • ascorbic acid formulations for lung application may be simply an aqueous inhalant hyper-tonic solution aerosolized to sufficiently small droplet size to deliver a total dose per application of about 200 to 300 mg of ascorbic acid uniformly distributed throughout the respiratory tree; or the inhalant may be formulated with other substances such as bronchodilators, antibiotics, or anti- inflammatory medications.
  • Formulations for the mouth include aqueous solutions and/or lozenges that deliver up to 1000 mg or more of ascorbic acid sustained over a period of time up to five minutes or more.
  • Formulations for the nasal, sinus, and pharynx may be aqueous solutions for nasal spray or drops that deliver up to 100 mg or more of ascorbic acid per dose and may be formulated with decongestanls and/or anti-histamine medications.
  • Formulations for muco-cutaneous lip and nose junction application may be aqueous-gel or lotion to deliver up to 100 mg or more of ascorbic acid per dose.
  • Formulations for genito-urinary mucosa topical application may be an aqueous isotonic solution to deliver a total dose per application of up to 1000 mg or more of ascorbic acid per dose such as an irrigant for application by means of a catheter.
  • Formulations for large bowel topical application may be aqueous isotonic solution for application of up to 3000 mg or more of ascorbic acid to the large bowel mucosa for up to 5 minutes or more per application by means of a retention enema or by means of special orally ingested tablets timed to release the ascorbic acid within the large bowel.
  • Formulations for small bowel mucosa topical application may be orally swallowed tablets timed to release up to 3000 mg or more of ascorbic acid delivered to the small bowel mucosa.
  • an ascorbic acid formulation advantageously comprises ascorbic acid in such an amount that the total daily dose per individual ranges from about 1 mg/kg of the weight of the individual to about 250 mg/kg of the weight of the individual when administered to mucosa of the individual.
  • the ascorbic acid formulation is in the form of aqueous solution, gel or lozenge. More preferably, the formulation in the form of aqueous solution is aerosolized and the formulation is an inhalant.
  • the ascorbic acid formulation further advantageously comprises active non-ascorbic acid ingredients such as bronchodilators, antibiotics, mucolytics, anti-inflammatory medications, decongestants, or anti-histamine medications, as well as adjunctive ingredients such as substances used to buffer, intensify or amend ascorbic acid.
  • active non-ascorbic acid ingredients such as bronchodilators, antibiotics, mucolytics, anti-inflammatory medications, decongestants, or anti-histamine medications, as well as adjunctive ingredients such as substances used to buffer, intensify or amend ascorbic acid.
  • the ascorbic acid formulation can be administered to all mucosa including upper and lower respiratory mucosa.
  • the upper respiratory mucosa includes all mucosa above and proximal to epiglottis. Representative examples include nasal mucosa, sinus mucosa, pharynx mucosa, mouth mucosa, and muco- cutaneous lip and nose junctions.
  • the lower respiratory mucosa includes all lung mucosa below and distal to epiglottis with examples including the lining of the trachea, bronchi, bronchioles, and alveoli, and the junction between the respiratory epithelial and lympho-cardiovascular endothelium.
  • a method for treating and thereafter assisting rehabilitation of an individual having a mucosa- associated lower respiratory system pathological condition advantageously includes administering a pharmaceutically effective amount of an ascorbic acid formulation to the pathologically afflicted lower respiratory system mucosa of the individual.
  • the individual can be a human or non-human subject.
  • the ascorbic acid formulation administered contains ascorbic acid in an amount of from about 100 mg to about 1000 mg per dose and is in the form of aqueous solution. More preferably, the aqueous solution is aerosolized and the ascorbic acid formulation is used as an inhalant.
  • the ascorbic acid formulation administered further contains active non-ascorbic acid ingredients such as bronchodilators, mucolytics, antibiotics, anti-inflammatory medications, decongestants, and anti-histamine medications, as well as adjunctive ingredients such as substances used to buffer, intensify or amend ascorbic acid.
  • active non-ascorbic acid ingredients such as bronchodilators, mucolytics, antibiotics, anti-inflammatory medications, decongestants, and anti-histamine medications, as well as adjunctive ingredients such as substances used to buffer, intensify or amend ascorbic acid.
  • mucosa-associated lower respiratory system pathological condition include bronchiectasis, bronchitis, pneumonia, asthma, chronic obstructive pulmonary disease (COPD), sarcoidosis, bronchiolitis obliterans, cystic fibrosis, primary immunodeficiency, influenza, common cold, and mucosa-associated lymphoma.
  • COPD chronic obstructive pulmonary disease
  • a method for treating and thereafter assisting rehabilitation of an individual having a mucosa-associated upper respiratory system pathological condition advantageously includes administering a pharmaceutically effective amount of an ascorbic acid formulation directly to the pathologically afflicted upper respiratory system mucosa of the individual.
  • the individual can be a human or non-human subject.
  • the ascorbic acid formulation administered contains ascorbic acid in an amount of from about 100 mg to about 1000 mg per dose and is in the form of aqueous solution, gel or lozenge. More preferably, the aqueous solution is aerosolized and the ascorbic acid formulation is used as an inhalant.
  • the ascorbic acid formulation administered further contains active non-ascorbic acid ingredients such as bronchodilators, antibiotics, mucolytics, anti-inflammatory medications, decongestants, and anti-histamine medications, as well as adjunctive ingredients such as substances used to buffer, intensify or amend ascorbic acid.
  • active non-ascorbic acid ingredients such as bronchodilators, antibiotics, mucolytics, anti-inflammatory medications, decongestants, and anti-histamine medications, as well as adjunctive ingredients such as substances used to buffer, intensify or amend ascorbic acid.
  • mucosa-associated upper respiratory system pathological condition include oral sores, gingivitis, oral papiUoma and verruca lesions, nasal papillomas, sore throat, enlarged lymph nodes, pharyngeal inflammation and swelling, and excessive mucous or phlegm production.
  • the lung infection experiment i.e., lower respiratory system vitamin C inhalant experiment
  • the mild primary immune deficiency co-morbidity of the Index Case increases experiment sensitivity without sacrifice of specificity, thereby enhancing the suitability of the Index Case as an experimental subject, both in terms of treatment and pulmonary function rehabilitation effects of topical application of vitamin C to respiratory mucosa.
  • the experiment results are statistically significant, which add new medical knowledge about the use of topical vitamin C in association with lung infection treatment.
  • the new knowledge provides grounds to mobilize clinical trials in target or reference populations placed in hazard by lung infections.
  • the knowledge also adds insight into the pathogenesis of respiratory and oral mucosa diseases causality associated with genus Homo sapiens 1 genetic aascorbogenesis (i.e., genetically determined inability to synthesize ascorbic acid), and thereby assists physician with prescription of improved treatment and prevention regimen for respiratory mucosa- associated diseases.
  • the new knowledge further makes an important contribution to medicine's ultimate goal which is to certify new and better medical practices that efficiently prevent, or at least reduce, chronic and/or acute morbidity and mortality.
  • the Lower Respiratory System Inhaled aerosol Experiment: The reported Index Case patient is a 70-year-old Caucasian male diagnosed with mild bronchiectasis and progressive chronic bronchitis who presented with a 43-year history of increasing chronic cough, sputum production, multiple episodes of acute bronchitis and occasional pneumonia requiring many repeated courses of antibiotic therapy. Contributing to his condition is a mild primary immunodeficiency. In 1 99, during a severe acute exacerbation of acute bronchitis complicated by pneumonia confirmed by X-ray imaging, empirical treatment with an ascorbic acid aerosol inhaled aerosol was administered as a solution of ascorbic acid in sterile water.
  • the patient quickly and dramatically responded to the inhaled aerosol treatment, and during a 3-year period following empirical initiation of the inhaled aerosol treatment, the patient's pulmonary disease reversed course, with statistically significant reduction of both frequency and severity of acute bronchitis events, no new pneumonia events, statistically significant reduction of chronic bronchitis symptoms, and statistically significant measurable rehabilitation of respiratory function including complete remission of restrictive disease as diagnosed by flow-volume loop spirometry.
  • the Index Case patient had suffered for many years from chronic oral sores (including aphthous ulcers, herpes simplex, and pemphigoid stomatitis), gingivitis, oral papiUoma and verruca lesions; nasal papillomas, and chronic sore throat productive of copious thick mucus consistent with his affliction with mild primary immunodeficiency. His lymph nodes at the juncture of the hard and soft palate would frequently become enlarged, firm and tender following episodes of certain oral lesions, with nodes following pemphigoid lesions occurring more often than following other lesions.
  • AU lesions including lymph node sweUing, have remained quiescent and in remission using maintenance of 1 to 2 lozenges per day, but some lesions, particularly buccal and palate mucosa papillomas and, pemphigoid, and verruca at the muco-cutaneous lip junction, recur if lozenge use is stopped for more than 5 to 15 days and promptly go into remission with several days of lozenge re-application. Due to relief enjoyed, the Index Case is not willing to stop using the lozenges to assess further exacerbation of oral lesions.
  • Ascorbic Acid Treatment Regimen for the Experiment The hypothesis implies that the treatment regimen for the experiment take into account the following considerations: 1) the dependent variables: symptoms and signs of pulmonary mucosa associated disease; 2) the Index Case as control: the subject exposed to physician prescribed independent variables (conventional pulmonary mucosa associated disease treatment) without complementary ascorbic acid aerosol inhalation; 3) the Index Case experiment: the subject exposed to physician prescribed independent variables (conventional pulmonary mucosa associated disease treatment) with complementary ascorbic acid aerosol inhalation added as the experimental independent variable; 4) measurement of dependant variable responses to independent variable manipulation shall be quantitative; 5) the Index Case Subject must have a long history of progressive chronic pulmonary mucosa associated disease; 6) ascorbic acid dose- response pattern, that is high concentration and long duration of exposure, should mimic that theorized for the paleopathological gene evolution condition; 7) the experimental ascorbic acid must be applied to the external surface (topical) of the respiratory mucosa; 8) the ascorbic acid should directly nourish
  • the Index Case Subject To assure that the array of the expected outcomes (dependent variables exposed to independent variables without the ascorbic acid erosol inhalant) is predictable and stable, the Index Case Subject must have a long history of progressive chronic pulmonary mucosa associated disease. Thus, the subject for the experiment was selected on the basis of his long standing 43 -year history of progressively worsening chronic bronchitis with frequent episodes of acute bronchitis complicated on many occasions with pneumonia confirmed by chest imaging. His disease commenced following a severe bout of lingular pneumonia which clinically left a residual mild bronchiectatic lesion. The progressive advance of his disease was slowed but never cured by frequent conventional antibiotic, mucolytic and bronchodilator therapy.
  • the subject At the time of initiation of the experiment, the subject always carried a course of antibiotics, an albuterol inhaler, and a supply of guiafenesin to respond quickly to any onset of renewed acute bronchitis, which recurred at an average rate of 8 times per year, 3 of which approximately 24 events during the years of 1995 to 1997 are representative as recorded in Table II.
  • the subject has never received steroid therapy.
  • the Subject experiences characterize the observed morbidity and observed conventional treatment independent variables associated with the dependent variables experienced by the Subject during his empirical and experimental treatment in which the ascorbic acid aerosol inhalant was added to the regimen and conventional treatment was applied in accordance with normal medical practice parameters as needed according to the Subject's condition.
  • the Subject was never denied conventional medication, nor was conventional medication withheld if indicated.
  • Dependent variables for mucosa associated pulmonary disease are symptoms and signs including sputum production, difficulty in clearing mucus, bronchiolar infection with inflammation, lung parenchyma infection with inflammation (pneumonia), fever, night sweats, impaired respiratory function, impaired exercise and activity tolerance, bronchiolar remodeling, etc. AU of these symptoms and signs were present in the Index Case Subject and are tabulated as lines 4 through 23 in Table 2.
  • the Subject's "control" state conventional treatment independent variables, including physician prescribed conventional treatment for management of the dependent variables in a combination of antibiotics, mucolytics, and bronchodilators, are identified in lines 24 through 27 in Table 2.
  • control state experimental independent variables for the Empirical and Experiment Events are the aerosol inhalation of the ascorbic acid in lines 28, 29 and 30 added (as needed in accordance with the Subject's condition and standards of conventional medical practice) to the physician prescribed conventional treatment as in the Control State in lines 24 through 27 in Table 2.
  • Dose-Response Assessment The dose-response design theory is: the historic condition at the time of aascorbogenic gene selection (at the historic time of genetic selection for the gene that no longer synthesized ascorbic acid in the Anthropoidea liver) required a dose-response pattern that provided an "ample” concentration of ascorbic acid for an "ample” time of exposure to achieve "ample” external nourishment of the upper respiratory mucosa as a highly efficient means to "feed” the metabolism of the mucous membrane assertively engaged in external dynamic, pathokinetic biota and oxidation siege, including facilitation of mucosa defense tissue responses (i.e.
  • the Index Case Since January 2001, the Index Case has been completely free of any acute infection events which would have required antibiotics treatment. The last, and most persistent, signs of chronic bronchitis were rales and mucous plugs, which were first to reappear on the occasion that the Index Case became careless and skipped some daily SI doses. On these occasions, the dosage was temporarily increased to two SI doses per day for several days, after which the rales and mucous plugs ceased to occur and the dose was returned to one dose per day for maintenance purposes.
  • the Alternative Hypothesis (HI) for the experiment is vaUd, which is topical application of a strong (i.e. approximately 300 mg in 3 ml aqueous solution) ascorbic acid aerosol applied directly to the external surface of the lower respiratory system does provide a surface ascorbic acid metabolic effect to strengthen respiratory system mucosa, does increase surfactant production and subdue micro-organism colonization associated with acute and chronic pulmonary infections, the occurrence of which is measurable as significantly reduced pulmonary infection signs and symptoms, increased mucolysis and mucous transport, improved pulmonary function, and rehabilitation of lung health.
  • a strong ascorbic acid aerosol applied directly to the external surface of the lower respiratory system does provide a surface ascorbic acid metabolic effect to strengthen respiratory system mucosa, does increase surfactant production and subdue micro-organism colonization associated with acute and chronic pulmonary infections, the occurrence of which is measurable as significantly reduced pulmonary infection signs and symptoms, increased mucolysis and mucous transport, improved pulmonary function, and rehabilitation of lung health.
  • ascorbic acid mucosa deficiency manifests as chronic and acute infections and associated reversible bronchiolar inflammation and obstruction is ameliorated by topical application of therapeutic doses of ascorbic acid; and therapeutic doses of ascorbic acid rehabilitate reversible pulmonary infection sequellae - topical ascorbic acid appUcation while repressing mucosa infections facilitates repairing of respiratory system tissue with improvement of pulmonary function and stabilization of respiratory health and well-being, including mental relief.
  • the ascorbic acid aerosol inhalant formulation is used to protect lower respiratory mucosa from colonization by infective agents, facilitate repairing of stress/injured mucosa to expedite treatment of pulmonary infections, facilitate mucolysis and clearance of mucous and mucous plugs, facilitate long term repairing of inflammation to reduce pathological remodeling bronchioles, and reverse dysfunction features of bronchioles that contribute to reduction of respiratory performance (e.g. features that contribute to complications of chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, etc.).
  • COPD chronic obstructive pulmonary disease
  • Clinical trials are currently designed and to be conducted in the near future to assess whether the ascorbic acid aerosol inhalant can improve pulmonary medicine management of chronic bronchitis while mailing a significant reduction in use of antibiotics for the general population in similar fashion to that observed in the Index case; whether the inhalant can improve cardio-thoracic pre- and post-surgery respiratory care to reduce post surgical morbidity and mortality; and expand knowledge about the mucosa-associated biochemical pathways, including possible toxicological effects, by which topically applied ascorbic acid acts on respiratory mucosa and on other human mucosa systems.
  • vitamin C can also be used in treatment of urinary tract mucosal infections, for example, as an infusion flooding the bladder mucosa by means of a catheter or as an intermittent irrigate to reduce complications in cases which require indwelling catheters. It is predicted that topically applied and dose-response regulated ascorbic acid can be used to treat all mucous and serous membrane infections and inflammation.
  • *Rx without other words means use of a lozenge compounded with up to 1 gm ascorbic acid. **Ag: refers to an aqueous formula with up to 5% ascorbic acid. ** ⁇ Q e ⁇ : re rs to gel formula with up to 5% ascorbic acid. 6 Common cold/flu: Experimental trials resulted in complete clearance of prodromal symptoms; thus flu shots discontinued in 2000.
  • SI Rx Schneider's Inhalant (SI) not yet formulated, although it was conceived as early as 1995. Antibiotics, bronchodilators, mucolytics and bed rest were conventional Rx.
  • SI Rx Schneider's Inhalant (SI) formulated in 1999 and cautiously tested in November 1999 per informed consent. Immediate reduction in expected morbidity noticed.
  • SI treatment experiments were repeated 8 times in 2000-2002. SI started at earliest URI symptoms and continued for 2 weeks.
  • Exacerbation Events Average of 8 events per year during the years 1995-1999. SI treatment reduced number of events to 2/year during the period of 1999-200 with 0 events occurring in 2003.
  • SI Schneider's Inhalant
  • SI is a sterile aqueous solution containing 250 mg ascorbic acid in 3 ml unit dose dispensed by means of a nebulizer as an aerosol.

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Abstract

L'invention concerne une préparation d'acide ascorbique qui contient de l'acide ascorbique dans des proportions telles que la dose quotidienne totale est comprise entre environ 100 mg et environ 5 000 mg lorsqu'elle est administrée sur la muqueuse. L'invention porte également sur des méthodes de traitement et d'aide à la réadaptation ultérieure d'une personne souffrant d'une pathologie du système respiratoire inférieur, par l'administration d'une dose efficace au plan pharmaceutique de ladite préparation d'acide ascorbique de l'invention sur la muqueuse du système respiratoire inférieur et/ou supérieur touché de la personne.
PCT/US2004/007803 2003-03-12 2004-03-12 Methode de prevention et de traitement d'infections attaquant la muqueuse et d'aide a la readaptation ulterieure au moyen d'acide ascorbique applique localement WO2004080427A2 (fr)

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US45413303P 2003-03-12 2003-03-12
US60/454,133 2003-03-12

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WO2004080427A2 true WO2004080427A2 (fr) 2004-09-23
WO2004080427A3 WO2004080427A3 (fr) 2005-05-06

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IT201900002623A1 (it) * 2019-05-17 2020-11-17 Neilos S R L Composizione per la prevenzione e/o il trattamento di affezioni della mucosa oro-faringea

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Publication number Priority date Publication date Assignee Title
IT201900002623A1 (it) * 2019-05-17 2020-11-17 Neilos S R L Composizione per la prevenzione e/o il trattamento di affezioni della mucosa oro-faringea
EP3738589A1 (fr) * 2019-05-17 2020-11-18 Neilos S.r.l. Composition pour la prévention et/ou le traitement de maladies de la muqueuse oropharyngienne

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