JP2010538008A - Calcium glycerophosphate for treating and preventing respiratory diseases or symptoms - Google Patents

Abstract

Calcium glycerophosphate has been found to be effective in treating and preventing respiratory diseases, disorders and / or symptoms. The disease, disorder, and / or symptom is associated with symptoms of obstruction or restraint of the respiratory airway. The disease, disorder and / or symptom is respiratory inflammatory disease, respiratory stenosis or nasal inflammatory disease such as asthma, chronic obstructive pulmonary disease (COPD), emphysema, reactive airway dysfunction disease (RADS), Rhinitis, bronchitis, bronchiolitis, nasal congestion, sinusitis, tonsillitis or laryngitis, postnasal drip (PND) and related complications, inflammatory and non-degranulated mast cell activity, goblet Any stimulating dyspnea, restraint or obstruction that causes mucus secretion from the cells; airway narrowing or blockage or mucus interference; sleep apnea, snoring, inflammatory or non-inflammatory responses to allergens or stimulants in the air or non-air May be nasal or non-nasal airway inflammation or irritation causing problems in any area of the body; and physical damage to the respiratory system. Methods, compositions and devices are described for using calcium glycerophosphate to treat and prevent respiratory diseases, disorders and / or symptoms.

Description

BACKGROUND OF THE INVENTION Respiratory diseases, disorders and / or symptoms are common in both developed and developing countries. They represent a large percentage of the total number of days related to sickness-related absences. The prevalence associated with respiratory diseases, disorders and / or symptoms has not decreased.

  Therefore, there is a need to develop relatively inexpensive means for treating and preventing respiratory diseases, disorders and / or symptoms. Preferably, such means are non-toxic, not harmful and have no significant side effects.

(Summary of the invention)
It has been found herein that calcium glycerophosphate is effective in treating and preventing respiratory diseases, disorders and / or symptoms.

  In one aspect, the invention relates to a method for treating or preventing a respiratory disease, disorder and / or condition in a subject. The method includes administering to the subject's respiratory system an effective amount of calcium glycerophosphate in a composition formulated for oral or nasal administration.

In another general aspect, the invention relates to a composition for treating or preventing a respiratory disease, disorder and / or condition in a subject. The composition comprises an effective amount of calcium glycerophosphate, and nasal drops, nasal sprays, gels, nasal washes, rapidly dissolving tablets, inhalation powders, oral inhalation solutions or suspensions, syrups, mechanical intermittent liquid pulser (eg Water-Pik ^(TM)), inhalers, ventilator, transpiration craters (Transpirator), atomizer, nebulizer, a nebulizer, an air mask, aspirator (insufflator), direct physical Formulated for oral or nasal administration to the respiratory system of the subject by means such as mechanical or mechanical use (eg, swabs).

  In yet another general aspect, the invention relates to a device for treating or preventing respiratory diseases, disorders and / or symptoms in a subject. The device includes an effective amount of calcium glycerophosphate and a means for administering the effective amount of calcium glycerophosphate to the respiratory system of the subject.

  In other aspects, features and advantages of the invention will be apparent from the following disclosure, including the detailed description of the invention and preferred embodiments thereof and the appended claims.

Detailed Description of the Invention

(Detailed Description of the Invention)
Calcium glycerophosphate has already been shown to function as an anti-inflammatory substance on the epidermis and epithelial cells, and as a wound healing agent in addition to the epidermal cells, and soft tissues of the gums and mucous membranes of other parts of the body, such as the vagina . This test has been extended to its use on the nasal mucosa and other parts of the respiratory system.

  Unless defined otherwise, all technical and chemical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Alternatively, certain terms used herein have the meanings as set forth in the specification. All patents, published patents and publications cited herein are hereby incorporated by reference as if fully set forth herein. It should be noted that the singular includes the meaning of the plural as used herein or in the claims appended hereto, unless expressly specified otherwise.

  As used herein, the term “subject” refers to a mammal that is the subject of treatment, observation or experiment. Examples of test subjects can be humans, livestock animals (beef and dairy cows, sheep, poultry, etc.), or pet animals (dogs, cats, cows, etc.).

  As used herein, the term “respiratory system” refers to any part of the airway, ie the passage of air from the breathing nose to the alveoli. The respiratory system includes organs involved in breathing, such as the nose, throat, larynx, trachea, bronchi and lungs.

  As used herein, the term “respiratory system disease, disorder and / or condition” refers to any disease, disorder and / or condition related to obstructive or restrictive symptoms of the respiratory system. Respiratory obstructive symptoms include any condition that impedes the rate of air flow into and out of the lungs. Respiratory restrictive symptoms include any condition that reduces the functional capacity of the lungs. Airway obstruction or restraint can cause symptoms such as wheezing, shortness of breath, difficulty breathing, chest tightness, and coughing. Respiratory diseases, disorders and / or symptoms include, for example, airway inflammatory disease, airway stenosis, or nasal inflammatory disease.

  Examples of respiratory diseases, disorders and / or symptoms include asthma; chronic obstructive pulmonary disease (COPD); emphysema, reactive airway disease (RADS); rhinitis; bronchitis; bronchiolitis; Sinusitis; tonsillitis; laryngitis; postnasal drip (PND) and any and all complications dependent on it; inflammatory degranulated and non-degranulated mast cell activity; dyspnea, respiratory restraint and Any stimulus that causes mucus secretion from goblet cells or others that cause respiratory obstruction; airway narrowing or airway obstruction or mucus interference with the airway; sleep apnea; snoring; inflammation in any airborne or other allergen or irritant Nasal or other airway inflammation or irritation caused by other body area problems; physical damage to the respiratory system, such as nosebleed, surgical treatment, trauma damage; Every breath disease caused by in or seasonal allergen or irritant, disorder and / or condition, but any swelling or the like of the tissue caused by any of the above can be cited, without limiting thereto.

  As used herein, the term “asthma” refers to a chronic condition characterized in most cases by reversible airway disorders and / or stenosis. In response to one or more triggers for asthma, the airways become inflamed and covered with excess amounts of mucus. Asthma triggers include environmental stimulants, such as allergens (ragweed, house dust, animal hair, pollen, etc.), cold air, hot air, humidity, temperature or humidity changes, upper respiratory tract infections, exercise, intense work, physical or mental Stress, smoke, viral diseases such as, but not limited to, those caused by common colds. The term “asthma” may or may not involve mast cells, degranulation and mucus exudation, whether an exacerbant has been identified, or whether the cause is in the air. Included are those caused by any cause of asthma whose primary effect is cellular inflammation and / or irritation. The term “asthma” should be covered in the widest scope and encompass all dyspnea to the extent that acute is hardly perceivable.

  Examples of asthma include bronchial asthma, infantile asthma, allergic asthma, atopic asthma, steroid intractable asthma, non-allergic asthma, intrinsic asthma, extrinsic asthma, aspirin asthma, heart asthma, exercise-induced asthma, Examples include, but are not limited to, infectious asthma, any asthma initiated by airway restraint or stenosis.

  As used herein, the term “chronic obstructive pulmonary disease” or “COPD”, also known as chronic obstructive airway disease (COAD), is also characterized by airflow limitation in the airway that is not fully reversible. Showing progressive respiratory disease. COPD includes permanent or temporary stenosis of the small bronchus that slows forced expiration. Examples of COPD include a range of chronic bronchitis, emphysema, and other disorders where etiological or more specific terms cannot be applied. COPD can be caused by preserved meat containing other airborne irritants such as coal dust, asbestos or solvents, and nitrite, but most often is smoking.

  As used herein, the term “reactive airway disease (RAD)” refers to an advanced asthma-like symptom after a single exposure to a trigger, such as irritating vapors, smoke or smoke. In certain embodiments of the invention, the term “RAD” includes an asthma-like symptom of an infant that may be confirmed to be asthmatic when sufficiently grown to undergo a diagnostic test.

  As used herein, the term “rhinitis” refers to any disease, disorder and / or condition that causes inflammation of the nasal mucosa. Examples of rhinitis include, but are not limited to, allergic rhinitis, hay fever, acute rhinitis, chronic rhinitis, abnormal hypertrophic rhinitis, nasal septum curvature, and the like. Symptoms of rhinitis include, but are not limited to, runny nose, nasal congestion, and postnasal drip. According to a recent trial completed in the United States, more than 50 million Americans currently have rhinitis. Rhinitis has been shown to adversely affect not only the nose, throat and eyes. It is also related to sleep problems and ear problems, and also related to learning problems. Possible causes of the appearance of rhinitis include food reactions, anatomical defects, immune deficiency disorders, ciliary movement disorders, environmental triggers, emotional triggers, occupational triggers, hormone-like triggers, etc. It is not limited.

As used herein, the term “calcium glycerophosphate” or “CGP”, also known as “glycerophosphate calcium”, refers to a compound having the molecular formula of C ₃ H ₇ CaO ₆ P in its anhydrous form. “CGP” can also exist as hydrates, including monohydrates and dihydrates. Examples of calcium glycerophosphate include three isomers of CGP, namely β-glycerophosphate calcium salt ((HOCH ₂ ) ₂ CHOPO ₃ Ca) and D (+) and L (−)-α-glycerophosphate calcium salt (HOCH ₂ CH ( OH) CH ₂ OPO ₃ Ca), or any combination of two or more thereof, but is not limited thereto.

  Calcium glycerophosphate can be synthesized using methods known to those skilled in the art. Calcium glycerophosphate can also be obtained from various commercial products. The commercial CGP products include AkPharma Inc. (Pleasantville, NJ 08232), Astha Laboratories Pvt. Ltd. (B-4, Industrial Estate, Sanathnagar, Hyderabad-18, India), and Seppic Inc. (30 Two Bridges Road Can be purchased from Fairfield, NJ 07004), but is not limited to these.

  As used herein, the term “treatment”, “treat” or “treatment” refers to the prevention of exacerbation of a disease, disorder or condition when the patient suffers from such disease, disorder or condition. Preferably refers to the maintenance of at least the starting state, and more preferably the alleviation of the disease, disorder or condition, and even more preferably the resolution of the disease, disorder or condition.

  As used herein, the term “prophylaxis”, “prevent” or “prevention” refers to a disease, disorder or symptom that the disease, disorder or symptom does not develop, delays onset, Or it refers to the case where some kind of treatment is performed before such a disease, disorder or symptom develops so that it develops but has a low degree of onset.

  As used herein, the term “treatment” or “prevention” in the broad sense with respect to a disease, disorder, or symptom refers to any medical practice performed on them, as well as diagnosis, treatment, prevention, prognosis, etc. Refers to all acts of

  When used to treat or prevent respiratory diseases, disorders and / or symptoms, calcium glycerophosphate is a palliative agent used during the appearance or seizure of the disease, disorder and / or symptoms, eg, asthma As a palliative agent for the relief of the appearance or seizure. Calcium glycerophosphate can also be used as a control agent used for long-term control to prevent the appearance of symptoms or the occurrence of seizures. Since controlling or preventing seizures is equally important with respect to improving or alleviating the seizures, it is essentially a treatment of diseases, disorders and / or symptoms of the respiratory system itself. One skilled in the art can use a suitable dose of calcium glycerophosphate for the treatment or prevention of respiratory diseases, disorders and / or symptoms.

  As used herein, the term “effective amount” refers to a tissue system, animal or human that includes alleviation of the symptoms of the disease or disorder being treated, as sought by a researcher, veterinarian, physician or other physician. Means the amount of active compound or pharmaceutical agent that elicits a biological or pharmaceutical response. Administration of an effective amount of calcium glycerophosphate to a subject results in a beneficial effect that can be observed clinically. Clinically observable beneficial effects are to the extent that the observable diseases, disorders and / or symptoms of the respiratory system are protected from further progression or worsening or less than not administering the composition of the invention. It can be a state of progress. In addition, the clinically observable beneficial effect means that when the composition of the present invention is administered to a test subject before the respiratory disease, disorder and / or symptoms can be observed, the respiratory disease, A disorder and / or symptom can be a condition in which onset is prevented or develops to a lesser extent than subsequent administration of the composition of the invention. In one embodiment of the invention, the effective amount of calcium glycerophosphate is about 10%, 20%, 30%, 40%, 50%, 60% greater than that shown by test subjects not receiving an effective amount of calcium glycerophosphate. Relieve or ameliorate respiratory disease, disorder and / or symptoms in a subject to any degree of%, 70%, 80%, or 90%.

  Methods for determining therapeutically and prophylactically effective amounts of calcium glycerophosphate according to embodiments of the present invention are known in the art. A useful assay to ascertain an effective amount (eg, a therapeutically effective amount) for a predetermined use is to measure the extent of recovery from the target disease. The actual amount administered will depend on the individual to be treated. This amount is preferably optimized so that the desired effect can be obtained without significant side effects. Determination of a prophylactically or therapeutically effective amount is within the ability of those skilled in the art. A prophylactically or therapeutically effective amount of any compound can be estimated using either a cell culture assay or any suitable animal model. An animal model is used to achieve the desired concentration range and route of administration. Moreover, such information can be used to determine useful doses and routes for administration in humans.

The therapeutic effect and toxicity of the compound is determined by standard pharmaceutical methods in cell cultures or experimental animals (eg, ED ₅₀ , effective therapeutic dose for 50% of the total; and LD ₅₀ , overall lethal dose of up to 50% ). The dose ratio between therapeutic and toxic effects is a therapeutic index and can be expressed as the ratio ED ₅₀ / LD ₅₀ . Pharmaceutical compositions that exhibit high therapeutic indices are preferred. Data obtained from cell culture assays and animal studies can be used to formulate a range of doses for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED ₅₀ with little or no toxicity. Such dosage may vary within this range depending on the dosage form employed, patient sensitivity and route of administration. Guidance on specific doses and delivery methods is provided in publications known to those skilled in the art. This exact dose is chosen by the individual physician in view of the patient's symptoms to be treated. Dosage and administration are adjusted to provide sufficient levels of the active moiety or to achieve the desired effect.

An effective amount of CGP is in any dose range from micro-dose to mega-dose. Because CGP is non-toxic, not harmful, and has no known side effects, Megadose CGP can be used effectively. Microdose CGP can be used effectively because both Ca ²⁺ and glycerophosphate anions are signaling molecules that can exhibit biological effects at very low levels.

  In embodiments of the invention, an effective amount of CGP is about 0.05% -15% (w / w), preferably about 0.5% -10% (w / w); most preferably about 1% -5% (w / w) is administered to the subject in a composition containing CGP. At high levels tested, for example, about 7.5% (w / w) and higher, it has been discovered that calcium glycerophosphate can help stop bleeding from the nose, possibly due to the calcium effect on blood clotting. However, the amount of CGP in the composition is not limited to about 0.05% -15% (w / w).

  In one aspect, embodiments of the invention relate to methods of treating or preventing respiratory diseases, disorders and / or symptoms in a subject. The method includes administering an effective amount of calcium glycerophosphate to a subject's respiratory system, wherein the calcium glycerophosphate is in a composition formulated for oral or nasal administration in a subject. To the respiratory system. The composition formulated for oral or nasal administration may be a liquid, solid, gel, syrup, powder, or mist formulation.

Calcium glycerophosphate can be administered to the subject's respiratory system by one or more means for oral or nasal administration depending on the type of respiratory disease, disorder and / or condition. For example, in the case of asthma, COPD or the like, an atomizer type inhaler such as MDI, BDI or nebulizer may be used for inhalation. For example, in the case of rhinitis, absorption and inhalation may be used for administration. Examples of means applicable to oral or nasal administration include nasal sprays, spray nasal drops, nasal rinses, instantly dissolving tablets, inhalable powders, oral inhalable solutions or suspensions, syrups, mechanical intermittent liquids pulsar (e.g. Water-Pik ^(TM)), inhalers, ventilator, transpiration aerator, atomizer, nebulizer, air masks, aspirator, direct physical or mechanical application means, for example include a swab, and However, it is not limited to these.

  Inhalation is commonly used as a method of administration via the nasal passages, airways, nasal passages and the like. In the preparation for administration into the respiratory tract, the respiratory tract absorption preparation, or the nasal absorption preparation, it is usually preferable to prepare a pharmaceutical solution or a fine powder (dry powder) in a mist form. In general, the formed medicinal solution can be inhaled by a nebulizer, and the medicinal substance processed into a powder is used together with the medicinal substance filled therein to form a gas spray type, MDI (quantitative injection type) It can be inhaled by means of an inhaler) or exhalation system, DPI (Dry Powder Inhaler).

There are currently two types of powder inhalers used for rapid and deep inhalation: “Dry Powder Inhaler (DPI)” and Delayed Inhalation “Metered Injection Inhaler (MDI)”. DPI is further divided into three categories: multi-dose containers (multi-dose reservoir), such as the product available from AstraZeneca TURBUHALER ^(TM); a plurality of single doses (multi-unit dose), for example, purchased from GSK Product ACCUHALER ^™ / FLOVENT DISKUS ^™ ; as well as unit-dose that can be purchased from many manufacturers.

  The inhaler refers to a kit including a mouthpiece and a cartridge (tube). Usually, both ends of the tube are sealed with aluminum foil. Prior to use, the tube is attached to the mouthpiece to penetrate the aluminum foil to allow inhalation of the powdered medicinal substance inside.

  On the other hand, absorption of a solution of a pharmaceutical substance can be achieved by means of a nebulizer or an inhaler, an artificial inhaler. Nebulizers flow pharmaceutical substance aerosols through the air at a slow rate, thus making absorption of the pharmaceutical substance easier.

  How often and for how long a calcium glycerophosphate is administered to a subject depends on the respiratory disease, disorder and / or symptom to be treated or prevented, as well as factors related to the subject, such as Depends on age, weight, health, etc. Calcium glycerophosphate may be administered on a regimen of multiple doses per day. The calcium glycerophosphate can be administered to the subject at multiple intervals during the day, for example after waking up, after breakfast, after lunch, after dinner and until bedtime. Calcium glycerophosphate can be administered during the onset or seizure of respiratory diseases, disorders and / or symptoms to provide relief of symptoms such as wheezing, shortness of breath, dyspnea, chest compressions, and cough. Calcium glycerophosphate may also be administered to a subject prior to symptom onset or seizure to control or prevent the onset or seizure of symptoms and signs associated with the onset or seizure of symptoms.

  The dose of calcium glycerophosphate is not limited to a specific value. The dose is suitably varied depending on the target disease, symptoms (range), age,% or absence of complication (s) and the like. For example, the dose is usually about 100 μg to about 1000 mg, preferably about 500 μg to about 100 mg, and most preferably about 1 mg to about 40 mg of anhydrous CGP per adult per administration. As used herein, “anhydrous CGP” refers to a CGP preparation containing at least about 88% (w / w) CGP free of residual or acquired moisture. Anhydrous CGP used in embodiments of the present invention meets food chemical standards (FCC) standards that loss on drying (LOD) does not exceed 12%. As used herein, “per dose” can be per inhalation, per nostril, per spray, per tablet, and the like. In one embodiment of the invention, the dose is an about 400 mg solution / suspension formulation containing about 2% by weight dry CGP per administration. In another embodiment of the invention, the dose is an about 400 mg solution / suspension formulation containing about 3.75% by weight dry CGP per dose. Dry CGP contains about 95-98% anhydrous CGP that is equilibrated with moisture. However, the dose of CGP is not limited to the above range, and may be in any range that does not pose a risk of life or death of the body.

  Without being bound by theory, calcium glycerophosphate can be used to treat or prevent at least partially respiratory diseases, disorders and / or symptoms due to the anti-inflammatory effects of CGP. . Inflamed airway epithelium results in respiratory diseases, disorders and / or symptoms. Various findings suggest that glycerophosphate functions to promote epidermal cell regeneration, see eg US2004 / 0037766. Rapid repair and replacement of epidermal cells provides, among other things, enhanced ceramide synthesis, which accelerates skin surface repair and ensures that irritant substances infiltrate between vulnerable cell walls. Provides preventable enhancement of cell-cell adhesion. This should be distinguished from the potential function that calcium ions modify the permeability of the cell membrane itself, ie the ability of calcium ions to reduce membrane porosity at high concentrations. Reduction, prevention, suppression or prevention of respiratory inflammation provides relief or prevention of symptoms. The beneficial effects of CGP are also, at least in part, its ability to prevent or reduce acid irritation and cytotoxicity in the upper and lower respiratory tract, and / or its ability to promote high ciliary activity, such as certain cilia This may be due to the ability to modulate the phosphorylation state of the protein. This is believed to be that the beneficial effects of newly discovered CGP on the respiratory system of embodiments of the present invention are achieved synergistically between calcium ions and glycerophosphate. This synergistic effect differs from the function of calcium ions or glycerophosphate alone.

  Calcium glycerophosphate is non-toxic, not harmful and has no known side effects. Therefore, the method of embodiments of the present invention is particularly desirable for pediatric patients, elderly patients, pregnant women or patients who frequently require palliative and / or preventive medications for diseases, disorders and / or symptoms of the respiratory system. It can be rare. Oral or nasal administration of the compositions of the present invention is non-invasive and can be administered repeatedly.

  In certain embodiments, calcium glycerophosphate can be administered in combination with one or more other palliative and / or prophylactic agents for respiratory diseases, disorders, and / or symptoms. Thus, embodiments of the invention include compositions comprising calcium glycerophosphate and one or more other palliative and / or prophylactic agents for respiratory diseases, disorders and / or symptoms, and the subject Relevant to methods of using the composition to treat or prevent respiratory diseases, disorders and / or symptoms in The calcium glycerophosphate and other agents can be administered sequentially, either simultaneously or sequentially. Other drugs can be administered to the test subject via such routes that are commonly used for such other pharmaceutical substances. However, it is not necessary to administer other palliative and / or prophylactic agents in a substantial percentage with respect to illustrations of embodiments of the invention. Calcium glycerophosphate, as a single active pharmaceutical ingredient, is effective for treating or preventing respiratory diseases, disorders and / or symptoms.

  Examples of such palliative and / or prophylactic agents include β-2 agonists, α agonists, bronchodilators, glucocorticoids, leukotriene modifiers, mast cell stabilizers, antimuscarinic / anticholinergic agents, methylxanthine, Examples include, but are not limited to, histamine, omalizumab, methotoxalate, and tianepine, albuterol, cromolyn.

Other embodiments of the present invention employ compositions comprising calcium glycerophosphate and one or more analgesics, and compositions for treating or preventing respiratory diseases, disorders and / or symptoms in a subject. Regarding the method. Illustrative of the composition, but include the following, without limiting thereto; nasal detergent / decongestants ^{(NasoCell (registered trademark))} CGP and general retail as (OTC) To treat respiratory diseases, disorders and / or symptoms caused by colds, hay fever, airborne or seasonal allergens or irritants, including analgesics such as ibuprofen, acetaminophen, aspirin, naproxen, capsaicin, etc. Pharmaceutical product. The amount of CGP in the composition is sufficient to provide a single dose (which may be 2-4 NasoCell sprays) to provide a nasal rinse and / or decongestant. May be preferred. The amount of analgesic in the composition can be effective to relieve colds, general headaches associated with hay fever, sinus pain, eye pain and the like.

  Nasal administration of the composition of the present invention can provide for faster relief of symptoms associated with colds, pollen and the like. Administration by nasal membrane absorption is quantitatively more effective than for the same digested analgesic, which must pass through the digestive system for subsequent absorption with compositional damage that may occur due to the digestive process Can reach the bloodstream more quickly over time. Furthermore, due to the low osmolarity of NasoCell, the composition can more easily adhere to the epithelial nasal cells and is more readily absorbed from the cell wall into the bloodstream.

  The compositions of the present invention include currently marketed drugs, such as diphenhydramine, ephedrine, pseudoephedrine, and the like, that are free of any undesirable general anticholinergic side effects at certain sites in the body or at other sites. It provides a unique combination of effective nasal lavage, nasal cleansing, anti-inflammatory, anti-swelling (swelling) and analgesia without any associated psychogenic effects. The composition is safe to use in large quantities, even when operating or mechanically operating.

  In another general aspect, embodiments of the present invention provide compositions for treating or preventing respiratory diseases, disorders and / or symptoms in a subject. The composition comprises an effective amount of calcium glycerophosphate, wherein the composition comprises a nasal spray, a spray nasal drop, a nasal wash, an instantly soluble tablet, an inhalable powder, an oral inhalation solution or suspension A respiratory system to be tested by means of an inhaler, ventilator, nebulizer, translator, atomizer, nebulizer, air mask, inhaler, means for direct physical or mechanical application, eg cotton swabs, etc. Formulated for oral or nasal administration.

  The composition of embodiments of the present invention may be produced by methods similar to those known to those skilled in the art, such as conventional mixing, disintegration, rendering for granulation, sugar-coated tablet preparation, starch syrup, emulsification, encapsulation, encapsulation, It can be produced using lyophilization. One or more excipients can be added to the composition. Excipients that can be used are inert to calcium glycerophosphate and as long as the use is approved as a pharmaceutical additive, there is no restriction on such excipients. Examples of suitable excipients include, but are not limited to: monosaccharides such as galactose, mannose, sorbose; disaccharides such as lactose, sucrose and trehalose; polysaccharides such as Starch, raffinose, dextran, etc .; sugar alcohols (eg, glycerol, erythritol, arabitol, xylitol, sorbitol, mannitol, etc.); glycols (eg, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, etc.); cellulosic polymers (eg, Hydroxycellulose, hydroxypropylcellulose); insoluble additives (crystalline cellulose, chitosan, calcium carbonate, talc, titanium oxide or silica (silicon oxide), and mixtures thereof .

  Compositions of embodiments of the present invention can be formulated to have a pH of about 4.5-10, such as about 4.5-6.0, about 6.0-8.0, or about 8.0-10.0. Note that the nasal pH varies widely within normal nasal cells to 4.5-6.5 and as high as 8.3 in rhinitis. However, the pH for compositions of embodiments of the present invention is not limited to the range of about 4.5-10 or nasal pH.

  The composition of the embodiment of the present invention can further contain a preservative. Preferably, the preservative is food grade or pharmaceutical grade. Examples of suitable preservatives include methyl paraben, ethyl paraben, butyl paraben, propyl paraben, sorbic acid and other cosmetic preservatives commonly used in cosmetics such as creams and lotions and certain bath products, It is not limited to these. Preservatives are preferably present in an amount sufficient to prevent the growth of microorganisms such as bacteria, fungi, or yeast.

  Compositions of embodiments of the present invention can also include adhesion molecules or substances that allow the composition to adhere to airway tissue for extended periods of time, i.e., provide sustained release of CGP into the airways. Adhesion factors are achieved by multiple interactions, physical interactions or chemical interactions such as electrostatic interactions, hydrogen bonds or hydrophobic interactions. In a preferred embodiment, the adhesion molecule or substance extends the contact time of CGP in the nasal cavity. Any suitable adhesion molecule or substance known to those skilled in the art can be used in the compositions for embodiments of the present invention. In one embodiment, the adhesion molecule or substance is a polysaccharide. In a preferred embodiment, the adhesion molecule is chitosan and the cationic polysaccharide is obtained from a crustacean shellfish. A universal transmucosal delivery system based on chitosan can be purchased from West Drug Delivery [Lionville, PA 19353 (US)] and used in the present invention.

  In preferred embodiments, the compositions of the invention are formulated as powders, gels, microspheres, or suspensions, ie, liquids that contain CGP in an amount that exceeds the solubility of CGP in the liquid. CGP has limited solubility in water, ie about 1% by weight. Administration of CGP in a powder, gel, microsphere, or suspension formulation results in a local amount of CGP that exceeds its solubility, ie, insoluble CGP accumulates on the mucosa of the respiratory system. Since insoluble CGP slowly dissolves in the mucosa, the sustained release of CGP into the cells inside the airways is achieved without the need for any additional auxiliary adhesion material. If desired, powder, gel, microsphere, or suspension formulations may include adhesion molecules, ie “stickers”, or substances that further enhance the attachment of CGP to the airway mucosal surface.

  A formulation that provides sustained release of CGP is desirable, for example, when it is desired to provide a sustained and steady level of CGP in the respiratory system, for example, when the formulation is used for prophylaxis. In one embodiment, the method of an embodiment of the invention comprises administering a formulation that provides prolonged release of CGP to the respiratory tract to the respiratory system of the subject. In a preferred embodiment, CGP is released into the respiratory tract during 3-8 hours.

  In another embodiment, the composition for embodiments of the present invention comprises an absorption enhancer that improves the absorption of CGP in the respiratory tract, eg, beyond the mucosa of the respiratory tract. There are many ways in which absorption enhancers can work. For example, the properties of the mucus layer may be altered by opening intimate junctions between cells, or membrane fluidity may be increased. Any suitable absorption enhancer known to those skilled in the art can be used in the compositions for embodiments of the present invention. Formulations that provide improved absorption of CGP are used, for example, in cases where it is desired to provide immediate and high levels of CGP to the respiratory system, such as for the treatment of symptoms appearing or during seizures If preferred. In one embodiment, the method of an embodiment of the invention comprises administering to the respiratory system of the subject a formulation that provides improved absorption of CGP into the respiratory tract.

  Compositions according to embodiments of the invention can be formulated into various forms suitable for oral or nasal administration by techniques known to those skilled in the art. For example, forms suitable for spray or exhaled compatible formats, including microparticles such as dry powders, can be used for intratracheal administration or trans-respiratory absorption. The dry powder can be produced by means selected from the group consisting of a dish crusher, a bead crusher, a jet crusher, a wet impingement crusher (ultimizer), a motor, a millstone, spray-dried and a supermarine liquid. The aerodynamic average particle size of the dry powder can be optimized for administration, for example, allowing the powder to float freely in a stream of air so that it can settle and adhere to the exposed mucosal cell membranes. For airway administration, the aerodynamic average particle size of the dry powder is usually about 0.01 to about 50 μm, preferably about 0.1 to about 30 μm, more preferably about 0.1 to about 10 μm in diameter. For pulmonary administration, it is preferred to produce such particles having an aerodynamic average particle size of about 3 μm or 3 μm or less, considering delivery into the alveoli, but the invention is not so limited. The powder can be inhaled or inhaled. They can be dispensed by any kind of “puff” container including means for dispensing unmetered or metered quantities.

  The composition for embodiments of the present invention can be associated with an aerosol system, such as an aerosol spray can. Aerosol systems include, for example, containers containing the propellant contained therein. The propellant comprises the active ingredient CGP and conventional additives such as lactose. The propellant formulation determines the aerosol output characteristics such as particle distribution, delivery rate, viscosity, and the like. Such aerosol systems can be manufactured using methods known to those skilled in the art with reference to this disclosure.

  The composition for embodiments of the present invention may also be an aqueous solution / suspension, which is suitable for nasal administration or inhalation, for example, direct nasal lavage, liquid or spray. The solution is atomized into very low molecular particles with a size range of 1-10 μm. Aerosol finely distributed in the atomized solution can be inhaled. Detailed information regarding aerosol inhalants is available, for example, from the pharmacopoeia, eg, Japanese Pharmacopoeia, US Pharmacopoeia, etc., which is incorporated herein by reference. The aqueous solution / suspension may be sprayed under manual operation, such as with a squeezable bottle or plunger, or may be present in a pressurized container.

  The composition according to embodiments of the present invention may further be a gel or cream for nasal application, in which case the ingredients are suitable to increase the viscosity to the desired level in addition to those described above. Has a stabilizing substance. Examples of such stabilizing substances include, but are not limited to, carboxymethylcellulose sodium gum (CMC gum), guar gum, xanthan gum and the like. The composition according to embodiments of the present invention may further comprise a fatty acid of plant or animal origin, such as butyric acid.

  In certain embodiments of the invention, the composition comprises about 1-5% (w / w) CGP; one or more acceptable wetting agents such as glycerol, sorbitol and / or the like; one or more acceptable A bacteriostatic / antifungal agent obtained, such as methylparaben, grapefruit seed extract and the like; an aqueous solution / suspension comprising one or more flavoring or aroma substances such as vanilla, eucalyptus and the like, and purified sterile water. Such compositions are used in the respiratory system by direct nasal lavage or nasal or oral inhalation.

  In another specific embodiment of the invention, the composition comprises about 6-10% (w / w) CGP; one or more acceptable wetting agents such as glycerol, sorbitol and / or the like; Acceptable bacteriostatic / antifungal agents such as methylparaben, grapefruit seed extract, etc .; one or more flavors or fragrances such as vanilla, eucalyptus; purified sterile water; stabilizers or thickeners; and An aqueous solution / suspension containing adhesion molecules. Such compositions are applied to the nasal cavity as nasal drops.

  In another aspect, the present invention provides an apparatus for treating or preventing a respiratory disease, disorder and / or condition in a subject. The device includes an effective amount of calcium glycerophosphate and a means for administering an effective amount of calcium glycerophosphate to the subject's respiratory system. It is understood that such a device may be in any form as long as it is intended to facilitate administration of calcium glycerophosphate to the respiratory system. The means for administering to the respiratory system is a means selected from the group consisting of means for administering to the lung, means for trans-respiratory administration, means for trans-airway absorption, and means for nasal absorption including.

  Examples of means for administering to the respiratory tract include inhalers, ventilators, translators, atomizers (e.g., means for applying a squirt / mist from a container such as a squeeze bottle or pressurized container), nebulizers, These include, but are not limited to, air masks, inhalers, and means for direct physical or mechanical application. In certain embodiments, the means for administering to the respiratory tract is a metered dose inhaler (MDI), a dry powder inhaler (DPI), a nebulizer, a means for directly washing the nose, a cotton swab, and the like.

  Illustrative means for administering to the lung include, but are not limited to, inhalers and bronchoscopes, their bronchoscope systems available from Olympus Corporation.

Example 1
Efficacy of calcium glycerophosphate in sensitized Brown-Norway rats An animal model of asthma can be used to demonstrate the effectiveness of CGP against asthma. The Brown-Norway (BN) rat model of airway hyperresponsiveness (AHR) may have characteristics similar to human allergic asthma, such as early and late responses after allergen challenge and generation of IgE responses to allergic sensitization [Haczku et al., Immunology. 85 (4): 598-603 (1995)]. Such BN AHR rats are treated with sensitization and ovo, according to methods similar to those described in Eur J. Pharmacol. 7; 293 (4): 401-12 (1995) or Haczku et al. (1995) as described above. It could be produced by exposure to albumin (OVA). CGP can be administered to BN AHR rats before or after stimulation with OVA. Airway reactivity can be measured before or after CGP administration.

Brown Norway rats (8-10 weeks old; body weight: 150-300 g) were grown and maintained in accordance with standards / guidelines established by the Institute for Laboratory Animal Care and Approval (“AAALAC”). These rats were sensitized by subcutaneous neck injection with aluminum hydroxide (4 mg) and ovalbumin (OVA; Sigma, grade V) (1 mg) in saline (1 ml) without pyrogens. Sensitized by administration. Bordetella pertussis vaccine containing 3 x 10 ⁹ bacteria inactivated by heating was used as an adjuvant for intraperitoneal injection. As a control, the same solution described above without ovalbumin was injected intraperitoneally, thus providing a negative control. Approximately 10-15 days after sensitization, airway irritation was induced by immunizing the rats with 5-10% OVA aerosolized with a nebulizer for 5-10 minutes. Aerosol exposure was connected to a nebulizer that generated aerosol mist that was pumped into the exposure chamber by an air flow supplied by a small animal ventilator set at 60 strokes / min with a pump dose of 10 ml. This can be accomplished by placing the rat in a plexiglass chamber.

  CGP can be administered to the rats either by nasal inhalation (using an aerosol or powder) or by intubation (liquid, aerosol, inhaler) either before or after airway irritation is induced.

  The airway reactivity of the rat can be measured. Anesthetized, tracheostomy, ventilated rats were followed for their airflow, transpulmonary pressure and blood pressure. Lung tolerance is calculated simultaneously using known methods, for example software programs (LabView, National Instruments, Austin, TX). Bronchoalveolar lavage (BAL) fluid was collected. BAL was performed 4 times using phosphate buffered saline (5 ml) (PBS; 137 mM NaCl, 10 mM sodium phosphate buffer (pH 7.4), 2.7 mM KCl). The total number of cells in the BAL fluid can be determined using an erythrocytometer, and the percentage of eosinophils in the BAL fluid can be determined by differential cell counting.

  OVA inoculation induces a statistically significant increase in the infiltration of inflammatory cells consisting mainly of eosinophils in the airways. To measure the ability of CGP to suppress the increase of eosinophils in BAL fluid in response to OVA inoculation The effectiveness of CGP can be examined at various doses, various formulations, various pH, etc. using a suitable control formulation.

Example 2
Efficacy of calcium glycerophosphate in an allergic rhinitis animal model An animal model of rhinitis can be used to demonstrate the effectiveness of CGP against rhinitis. Methods are known for creating animal models of rhinitis. For example, a mouse model of allergic rhinitis can be created by topical sensitization of mice with Dermatophagoides pteronyssinus (Kim et al., Otolaryngol Head Neck Surg. 2007 May; 136 (5): 720-5); and A rhinitis guinea pig model can be created by intranasal sensitization by instillation of pine pollen extract (Mizutani et al., Jpn J Pharmacol. 2001 Jun; 86 (2): 170-82).

  CGP can be administered to animal models of rhinitis via any desired means, such as inhalation or spray. Measure signs of rhinitis, nasal mucosal eosinophilia, serum total IgE, cytokines, and eosinophilia before or after CGP administration in BAL fluid in animal models to assess CGP efficacy did.

Example 3
Applying calcium glycerophosphate to human subjects with respiratory symptoms further exploring the effectiveness of calcium glycerophosphate for treating or preventing respiratory diseases, disorders and / or symptoms to the human body It was.

  CGP is repeated several times, sweetening / wetting ingredients (sorbitol, glycerin) with varying levels (0.5 wt-7.5 wt%), suitable food / drug grade fungistatic and fungistatic (methylparaben and chloride) Benzalkonium), and some flavors (peppermint, spearmint, and orange) were introduced into samples of varying concentrations of cleaning solutions or spray products.

  The first human subject for the laboratory / home study was a 77-year-old elderly with good general health. The test subject has a history of infant asthma and is currently not presenting as a symptom except rarely having seizures in middle age, and a nasal septum fold that blocks ~ 60% of one nostril for several years All that happened before. The subject has a childhood history of allergies to ragweed, house dust, horse hair, etc., which are not currently presenting as symptoms. The subject had experienced rhinorrhea (PND) and nasal congestion (mucus, nasal septum) for several decades as an adult. The subject experienced a cough that lasted several weeks after a seasonal flu or cold, and sometimes lasted for months. The subject was experiencing chronic coughing and chronic cough from PND, even if the subject was not after a respiratory illness belonging to bronchitis. This sometimes results in the inconvenience that the subject has to leave the group in order to clean the throat somewhere, such as exhaling mucus that causes voice dying or reflex swallowing. The subject was breathing mouths almost without exception during infancy due to nasal obstruction. The subject does not experience “shortness of breath” in terms of vital capacity, but occasionally breathes from the nose and mouth in adults due to occasional slightly problematic nose breathing that requires active conscious involvement. Went.

Forced nasal irrigation experiment Subjects were forced to wash nasal once a day for about 2 weeks. This forced nasal wash was performed on the skin and usually in the nasal cavity with a shower. CGP aqueous solutions or suspensions at various concentrations, e.g. about 7.5%, 3.75%, 2.5%, 2%, 1.5% by weight, using a sealed plastic bottle with an internal stem feed, on one side Poured into the nose and drained from the other nose. This procedure was repeated for each nostril side. Some products were swallowed nasally and were approximately 2 ounces of fluid per nostril.

  About 0-10 minutes after lavage, the subject experienced significant drainage from the beginning to the end of the nasal passage, considerable coughing, and considerable nasal wetting. The test subject expelled some swallow. During approximately 10-20 minutes after lavage, the subject experienced 90% reduced drainage, nasal opening and drying, and easy breathing. Within about 20-60 minutes after the wash, the subject had an open nasal passage, was dry, had a clearer voice, and coughing was reduced by about 90% compared to the previous condition. Felt. Between about 1 hour and 12/24 hours after lavage, subjects experienced easy breathing with no runny nose and cough and open airways. The subject was able to breathe naturally through the mouth and nose without the need for active conscious involvement. The subject's lower airway pathway was completely open.

Spray / mist experiments The subjects applied CGP into their nostrils with spray or mist. A closed small plastic bottle with an internal stem feed configured to deliver the liquid component as a mist was used. Usually a single application was made in the morning. Each application is performed with two sprays per nostril, changing left and right, with inhalation or inspiration of deep breaths completely simultaneously so as to aspirate the product from the nose to the airways. The spray is also used directly through the mouth to the throat, sometimes with one or two sprays / applications. The average spray delivery contained about 200 mg CGP formulation per squeeze. The formulation contained about 2% to about 3.75% by weight of dry CGP.

  The test subject experienced no preliminary water pressure and no recovery from it, but experienced the same effect with the spray nasal drops as the cleaning solution. CGP exerted its mitigation effect almost immediately upon application, which lasted for approximately 4-8 hours after application. Spray / mist application was repeated sometimes in the afternoon or as needed. A single spray per nostril during sleep was found to provide better nighttime breathing. Spray / mist application is better, easy to operate, easy to carry and more suitable for daily use.

  Following administration of CGP to the respiratory system via either forced nasal lavage or spray / mist, subjects are subject to about 95-98% reduction in postnasal drip, upright and activity, or sputum The subjects experienced daily discomfort, complete cessation of cough, no restraint, or worst, minimal constriction, and extended breathing from the subject's nose.

  In addition to the usual application of CGP to prevent or control signs associated with the respiratory system, subjects used CGP to relieve signs during the appearance of airway / upper airway symptoms. One morning during an initial product trial, after the subject ceased using CGP for approximately 24 hours, the subject was found to show the following signs associated with the airway / upper airway: nasal Obstruction, throat irritation due to postnasal drip, hoarseness and cough, faint breathing, and slight shortness of breath. The signs did not reach the state of asthma attack, but the subject experienced significant discomfort. At approximately 10:45 A.M., subjects applied a double dose of NasoCell (1.75 wt% CGP) by nasal inhalation in each nostril. At approximately 11:30 AM, the subject's symptoms improved further. The test subjects then self-administered another dose of NasoCell in each nostril. At about 12:50 PM, it was found that the signs of the test subjects had almost completely disappeared. The subject ate during lunch, but showed no dyspnea. At approximately 2:30 PM, the subject's symptoms were completely resolved. The subject's throat disappeared with any obstruction and breathing sound, and the airway expanded. The subject's nasal passages expanded again and the voice disappeared from the early morning hoarseness characteristic of postnasal drip symptoms. This subject should note that after several weeks of use, further reduced usage is necessary to “maintain” and this includes all of the usage, omitting several days. It is.

Example 4
Application of calcium glycerophosphate to human subjects with asthma This example describes a study on the effectiveness of calcium glycerophosphate to treat or prevent asthma in human subjects. A CGP composition similar to that described in Example 3 containing about 2% (w / w) CGP was used in this study. A second human subject, a 44-year-old male with a history of asthma, participated in the study.

  Subjects intentionally stopped using Advair Diskus (steroids) for approximately two weeks. The “mold smell” of the indoor environment caused by rain for several days and high humidity days caused allergies to the mold. Second, the allergy caused the subject's asthma. The subject felt a slight drop in airflow for several days, but refrained from using the albuterol inhaler (asthma emergency medication) during the day and used it only during severe wakefulness at night. The subject had to use an albuterol inhaler three nights before the night described below.

  In the middle of the night, at approximately 8:30 P.M., the subject experienced dyspnea and wheezing, which indicated the onset of an asthma attack. At approximately 8:35 PM, the subject received two sprays of the CGP composition in each nostril and sprayed the CGP composition once into the subject's mouth for inhalation. The average spray delivery contained about 200 mg of composition. At approximately 8:40 PM, the subject repeated a single oral inhalation and the subject experienced mild relief that did not feel the urgent need to use an albuterol inhaler. At approximately 8:52 PM, the test subject received two additional oral inhalations of the composition. At approximately 8:55 PM, the subject observed that the subject's wheezing and chest pain were alleviated by about 80% or more. All rinsed nasal fluid returned. At approximately 8:58 PM, the subject felt a gradual improvement and experienced no breathing difficulties. At approximately 9:05 PM, the subject felt good, but wanted complete relaxation and increased airflow. Subjects inhaled the composition once into each nostril; interrupted until full breathing and then performed two deep oral inhalations of the composition at approximately 9:07 PM. At approximately 9:27 PM, the subject felt refreshed and felt substantially returned to normal. At about 9:37 P.M., the test subject felt improved. At approximately 10:16 P.M., the subject felt complete (100%) recovery. At approximately 11:00 PM, the test subject went to bed without feeling uneasy. The subject did not experience wakefulness due to shortness of breath and did not use an inhaler during the night. About 8:00 AM the next day, the subject complained of some chest pain. Instead of using two puffs of albuterol at the start of the day as the subject normally does, the subject used a CGP composition. The test subject applied two sprays of the composition into each nostril and applied two sprays of the composition to the subject's mouth for inhalation. The subject felt symptomatic relief and felt that it was not necessary to use an albuterol inhaler.

  As will be appreciated by those skilled in the art, changes may be made to the above-described embodiments without departing from the broad concept of the invention. Accordingly, it is to be understood that the invention is intended to embrace modifications within the spirit and scope of the invention as defined by the appended claims, and is not limited to the specific embodiments disclosed.

Claims (30)

A method of treating or preventing a respiratory disease, disorder and / or condition in a subject comprising administering an effective amount of calcium glycerophosphate to the subject's respiratory system, wherein the calcium glycerophosphate is administered orally. Or a method of administration to the respiratory system of a subject in a composition formulated for nasal administration. The method of claim 1, wherein the respiratory disease, disorder, and / or symptom is associated with obstructive or restrictive symptoms of the respiratory airway. 2. The method of claim 1, wherein the respiratory disease, disorder and / or condition is a respiratory airway inflammatory disease, a respiratory airway stenosis or a nasal inflammatory disease. Respiratory system diseases, disorders and / or symptoms include asthma, chronic obstructive pulmonary disease (COPD), emphysema, reactive airway disease (RADS), rhinitis, bronchitis, bronchiolitis, stenosis, sinusitis, Tonsillitis, or laryngitis, postnasal drip (PND) and related complications, inflammatory and non-degranulated mast cell activity, any stimulation of mucus secretion from goblet cells, dyspnea, restraint, obstruction Airway constriction or blockage, or mucus interference with the respiratory tract; sleep apnea, snoring, inflammatory or non-inflammatory response to allergens or stimulants in the air or non-air; nose or nose caused by problems in any area of the body Selected from the group consisting of non-respiratory inflammation or irritation, physical damage to the respiratory system, respiratory diseases, disorders and / or symptoms caused by airborne or seasonal allergens or irritants The method of claim 1, wherein. The asthma is bronchial asthma, infantile asthma, allergic asthma, atopic asthma, steroid intractable asthma, non-allergic asthma, intrinsic asthma, extrinsic asthma, aspirin asthma, heart asthma, exercise-induced asthma and infectious 5. The method of claim 4, wherein the method is selected from the group consisting of asthma. 5. The method of claim 4, wherein the rhinitis is selected from the group consisting of allergic rhinitis, hay fever, acute rhinitis, chronic rhinitis, abnormal hypertrophic rhinitis, and nasal septal curvature. 5. The method of claim 4, wherein the physical injury is nosebleed, surgical treatment or trauma. The calcium glycerophosphate is administered in a powder, gel, microsphere, or suspension formulation, and the formulation provides sustained release of calcium glycerophosphate into the airways of a subject, where the sustained release. The method of claim 1, wherein the sex is due to the amount of calcium glycerophosphate in the local environment of the respiratory system being higher than the amount that can be dissolved. The method of claim 1, wherein the calcium glycerophosphate is administered in a formulation that provides improved absorption of calcium glycerophosphate into the respiratory tract of the subject. The calcium glycerophosphate is a nasal spray, nasal spray, nasal wash, quick-dissolving tablet, inhalable powder, solution or suspension for oral inhalation, syrup, mechanical intermittent liquid pulser, inhaler 2. A ventilator, a translator, an atomizer, a nebulizer, an air mask, a means for direct physical or mechanical application, or an inhaler, administered to the respiratory system of the subject. Method. The method of claim 1, wherein the calcium glycerophosphate is administered to the subject's respiratory system using a metered dose inhaler (MDI), a dry powder inhaler (DPI), a nebulizer, or a swab. The method of claim 1, further comprising administering one or more pharmaceutical agents to the subject's respiratory system for the respiratory disease, disorder, and / or condition. The one or more pharmaceuticals are β-2 agonist, α agonist, bronchodilator, glucocorticoid, leukotriene modifier, mast cell stabilizer, antimuscarinic / anticholinergic agent, methylxanthine, antihistamine, omalizumab, methotoxa 13. The method of claim 12, wherein the method is selected from the group consisting of a rate, tianipetin, albuterol, and cromolyn. The method of claim 1, further comprising administering the analgesic to the respiratory system of the subject. 15. The method of claim 14, wherein the disease, disorder and / or symptom of the respiratory system is a respiratory disease, disorder and / or symptom caused by a cold, pollen, or airborne or seasonal allergen or irritant. 15. The method of claim 14, wherein the pharmaceutical composition is formulated for nasal administration and administered nasally to the subject. 15. The method of claim 14, wherein the analgesic is selected from the group consisting of ibuprofen, acetaminophen, aspirin, naproxen, and capsaicin. The test subject is selected from the group consisting of pediatric patients, elderly patients, pregnant women, and patients who frequently require palliative and / or prophylactic drugs for respiratory diseases, disorders and / or symptoms The method according to claim 1, which is a test subject. A composition comprising an effective amount of calcium glycerophosphate for treating or preventing a respiratory disease, disorder and / or symptom in a test subject, wherein the composition comprises a nasal spray, a nasal spray, a nasal wash, Instantly dissolving tablets, powders for inhalation, solutions or suspensions for oral inhalation, syrups, mechanical intermittent liquid pulsars, inhalers, ventilators, translators, atomizers, nebulizers, air masks, inhalers, nebulizers Or formulated for oral or nasal administration to the respiratory system of a subject by means of direct physical or mechanical application. 20. The composition of claim 19, comprising a formulation selected from the group consisting of:
(a) a powder, gel, microsphere, or suspension formulation;
(b) a formulation comprising an adhesion molecule or substance capable of adhering the composition to airway tissue for an extended period of time; and
(c) A powder, gel, microsphere or suspension formulation containing an adhesion molecule or substance. 20. The composition of claim 19, wherein the composition comprises an absorption enhancer that improves the absorption of calcium glycerophosphate into airway tissue. 20. The composition of claim 19, wherein the effective amount of calcium glycerophosphate is from about 0.05% to 10% (w / w) in the composition. 20. A composition according to claim 19, formulated for administration by metered dose inhaler (MDI), dry powder inhaler (DPI) or swab. 20. The composition of claim 19, wherein the pH has a pH of about 4.5 to about 10.0. The composition of claim 19, wherein the composition has a pH of about 4.5 to about 6.0. β-2 agonists, α agonists, bronchodilators, glucocorticoids, leukotriene modifiers, mast cell stabilizers, antimuscarinic / anticholinergic agents, methylxanthine, antihistamines, omalizumab, methotoxalate, tianepitine, albuterol, cromolyn 21. The composition of claim 19, further comprising one or more pharmaceuticals selected from the group consisting of ibuprofen, acetaminophen, aspirin and naproxen. Apparatus for treating or preventing respiratory diseases, disorders and / or symptoms in a subject, wherein the apparatus comprises an effective amount of calcium glycerophosphate and an effective amount of calcium glycerophosphate to the subject's respiratory system Means for administering. The means for administering to the respiratory system is selected from the group consisting of means for administering to the lungs, means for administering the respiratory tract, means for absorbing the respiratory tract, and means for nasal absorption 28. The apparatus of claim 27, comprising: The means for administration to the respiratory tract is from the group consisting of inhalers, ventilators, translators, atomizers, nebulizers, air masks and inhalers, and means for direct physical or mechanical application. 28. The apparatus of claim 27, comprising means for selection. Means for administration to the respiratory tract are selected from the group consisting of a metered dose inhaler (MDI), a dry powder inhaler (DPI), a nebulizer, a means for nasal wash applications, and a swab. 28. The apparatus of claim 27, comprising: