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Home , Antazoline, Bamipine, Benactyzine, Chlorphenoxamine, Clocinizine, Dexbrompheniramine

US 20170020873A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0020873 A1 Mitchell (43) Pub. Date: Jan. 26, 2017

(54) PHARMACEUTICAL COMPOSITIONS Publication Classification (71) Applicant:- - - sy earmaceutical, Inc., Arlington, (51) AInt. 6LX Cl. 3L/505 (2006.01) A63/37 (2006.01) (72) Inventor: Odes W. Mitchell, Arlington, TX (US) A6II 3/167 (2006.01) A6II 3/09 (2006.01) A63/495 (2006.01) (21)21) Appl. No.:No 15/287,0479 A63L/485 (2006.01) 1-1. A63L/35 (2006.01) (22) Filed: Oct. 6, 2016 A6II 3/4402 (2006.01) Related U.S. ApplicationO O Dat ( 52) U.S. Cl. e pplication Uata CPC ...... A61 K3I/505 (2013.01); A61K 3 1/135 (63) Continuation of application No. 14/733.731, filed on (2013.01); A61 K3I/137 (2013.01); A61 K Jun. 8, 2015, now Pat. No. 9,463,191, which is a 3 I/4402 (2013.01); A61 K3I/09 (2013.01); continuation of application No. 13/703.584, filed on A61K 31/495 (2013.01); A61K 31/485 Feb. 2, 2013, now Pat. No. 9,050,289, filed as appli- (2013.01); A61K 31/167 (2013.01) cation No. PCT/US2011/040231 on Jun. 13, 2011. (60) Provisional application No. 61/354,053, filed on Jun. (57) ABSTRACT 11, 2010, provisional application No. 61/354,057, A composition of an antitussive, a , or an filed on Jun. 11, 2010, provisional application No. to treat upper respiratory and oral pharyngeal 61/354,061, filed on Jun. 11, 2010. congestion and related symptoms in a patient. US 2017/0020873 A1 Jan. 26, 2017

PHARMACEUTICAL COMPOSITIONS hydrocodone bitartrate, has generally been administered to relieve pain consistent with the congestion while Suppress CROSS-REFERENCES TO RELATED ing a cough. Also , such as and APPLICATIONS , have been administered to both children and adults in flavored formulations for reducing mucosal 0001. This Application is a continuation of application Swelling and draining the mucus build-up to clear conges Ser. No. 14/733,731, filed Jun. 8, 2015, which is a continu tion in the air passages. Symptoms due to or ation of application Ser. No. 13/703.584, filed Dec. 11, 2012, are often treated with an antihistamine. Antihista which is a US national stage application of PCT/US2011/ mines, often referred to as -class receptor blockers, 040231 under 35 U.S.C. S371 filed Jun. 13, 2011, which are compounds that may antagonistically block the hista claims priority from U.S. Provisional Patent Application No. mine receptor from binding histamine thereby preventing 61/354,053 filed Jun. 11, 2010, U.S. Provisional Patent the symptoms of an . Application No. 61/354,057 filed Jun. 11, 2010, and U.S. 0006. There are many different treatment 61/354,061 filed Jun. 11, 2010, all of which are hereby utilizing a combination of agents in therapeutic doses for incorporated by reference as if fully set forth herein. treating multiple symptoms of upper respiratory tract and oral pharyngeal congestion. As one example, a single medi FIELD OF THE INVENTION cation may include an expectorant, in combination with an 0002 The present invention relates to the treatment and antitussive agent, for removing phlegm or mucus that may relief of various symptoms of upper respiratory and oral have accumulated in the lungs and other air passages in pharyngeal congestion, and in particular, to a combination addition to suppressing a cough. The expectorant is helpful for treatment and relief thereof. in preventing the progression of a mild case of bronchitis to a more severe case of pneumonia. BACKGROUND OF THE INVENTION 0007 Combination therapy provides many benefits. For 0003. People around the world frequently suffer from example, it allows patients suffering from congestion and upper respiratory tract and oral pharyngeal congestion. This related symptoms to take only a single dosage medication, congestion may be caused by allergies, infections in the as opposed to multiple medications, for relief therefrom. respiratory tract and/or oral and pharyngeal cavities, Further, it enhances compliance in accordance with a regi changes in weather conditions, as well as from the overall men by eliminating the need for the patient to take different health and genetic disposition of the person. This congestion medications. To this end, combination therapy provides is generally diagnosed from partially or fully blocked air convenience, ensures compliance, and saves cost. passages including airways in the lungs, mouth, nose, and 0008 Combined treatment medications may be formu throat. Other symptoms related to the cause typically accom lated as syrups, pills, tablets, and capsules. Formulations pany the congestion. Cough, tickles in the throat, cold may include flavoring agents to mask undesirable flavors or symptoms Such as fever, flu, sinus infections, and throat or tastes from desired medicinal agents and colorants to render gland pain are some of the more common symptoms found the medication more attractive and appealing to the eye. For with upper respiratory and oral pharyngeal congestion. example, many formulations have a raspberry, cherry, 0004 Congestion of the upper respiratory tract and oral orange, or grape flavor well liked by both children and pharyngeal cavity and related symptoms generally have adults. Moreover, these flavors are easily identified by their undesirable effects for the afflicted person. For example, the color. In combination formulations, the individual ingredi congestion may affect performance in the workplace, School, ents are included in amounts proven to be effective to treat and at home up to and including loss of work and loss of targeted symptoms. Effective amounts have varied depend School attendance. Further, congestion may reduce the abil ing on the particular formulation, type and degree of the ity to perform routine activities, such as housework, driving, symptoms, and desired user or consumer. For example, a running errands, and may even totally incapacitate the child's dose of an elixir or syrup for the relief of cough and person. Severe and intolerable congestion often requires pain related to congestion may have the antitussive and visits to the hospital and treatment. In addition, viral or analgesic in reduced quantities based on size, weight, and bacterial infections of the sinus passage or other airway may age of the child targeted, comparable to a composition or be passed to healthy persons through symptoms of the formulation for an adult which may have double the dosage congestion. For example, a cough or Sneeze may convey a of the antitussive and analgesic. bacterium or virus to another person. Thus, upper respira 0009. Accordingly, it is desirable to have an adminis tory tract and oral pharyngeal congestion and its symptoms trable composition to reduce symptoms of upper respiratory need to be treated. tract and oral pharyngeal congestion. It is further desirable 0005 Generally, there are two typical approaches to that the composition be effective in reducing cough, con treating symptoms of the congestion. One approach involves gestion, histamine-stimulated allergy symptoms and related initially treating the underlying cause of the symptom. For pain. Still further, it is desirable for the composition to example, a bacterial infection is generally treated by admin contain dosages Suitable for administration to a child as well istering an antibiotic to kill the bacteria causing the infec as an adult. In addition, it is desirable to have the compo tion. The second approach involves treating the symptoms sition in a convenient and pharmaceutically acceptable dos themselves, typically in addition to treating the underlying age form. cause, by independently administering one or more medi cations for relief of specific symptoms. For example, an SUMMARY OF THE INVENTION antitussive agent, commonly referred to as a cough Suppres 0010. The present invention provides compositions and sant, has been typically administered for the treatment or methods for treating upper respiratory and oral pharyngeal relief of cough. An medication, such as codeine and congestion and related symptoms in a person Suffering US 2017/0020873 A1 Jan. 26, 2017

therefrom. To this end, and in accordance with the principles infections, and common cold and flu, the symptoms of the present invention, there is provided a composition of described herein may also be due to poor health or a a decongestant, and an antihistamine. Optionally, a compo predisposition for the symptom through genetic make-up. sition may include an antitussive, an expectorant and an The terms “treating and “alleviating, as used herein with analgesic. The combination of an antitussive, a deconges respect to upper respiratory and oral pharyngeal congestion tant, and an antihistamine in a single composition provides and related symptoms, include any reduction in severity or relief of cough, congestion in the air passageways, and duration, of any degree, of the congestion and/or one or common allergy-type symptoms resulting from exposure to more of the related symptoms. The terms also include any various allergens, in a convenient and effective dosage delays in onset of and any general relief from the congestion formulation. and/or one or more of the related symptoms. Thus, the 0011. The composition is formulated in pharmaceutically present invention encompasses palliative compositions and acceptable forms such as liquids, pills, capsules, tablets, and methods. the like. Suitable capsule forms include, without limitation, 0014) To this end, and in accordance with the principles liquid gelatin capsules and enteric-coated capsules. The of the present invention, the compositions include an anti tablet form may be chewable, may melt or disintegrate in the tussive, a decongestant, and an antihistamine. Inclusion of mouth, or may be enteric-coated to provide delayed-release an antihistamine, in combination with an antitussive and a and Sustained-release characteristics for the composition. In decongestant provides relief of histamine-stimulated allergy one embodiment, the composition is formulated into a symptoms in addition to relieving other symptoms, such as liquid. The composition may further include other compo cough, congestion, Swelling, and pain. These added benefits nents, such as conventional excipients including binders, provide increased efficacy and translate into convenience colorants, fragrances, and the like, to render the composition and cost savings for the patient. more attractive and suitable for use. 0015 The present invention provides pharmaceutical 0012. By virtue of the foregoing, there is thus provided compositions containing an antihistamine along with a compositions and methods for treating upper respiratory and decongestant and optionally an analgesic or an antitussive. oral pharyngeal congestion and related symptoms in effec The compositions of the invention may be administered in tive formulations. These and other benefits and advantages effective dosages for treating symptoms. To of the present invention shall be made apparent from the this end, the pharmaceutical compositions include at least accompanying detailed description thereof. one antihistamine and at least one stimulant. The most potent are generally sedating in nature and DETAILED DESCRIPTION OF EXEMPLARY the sedation is reduced or alleviated with the stimulant. The EMBODIMENTS compositions are useful for treating allergic reactions and 0013 The present invention provides compositions and other histamine-mediated symptoms, as well as for provid methods for treating upper respiratory and oral pharyngeal ing other physiological effects including, for example, anti congestion and related symptoms in a patient in need effects, analgesic effects, analgesic adjuvant thereof. The term “upper respiratory and oral pharyngeal effects, soporific effects, anti-secretory effects, and combi congestion” as used herein includes congestion in the oral, nation effects thereof. By combining a potent, effective pharyngeal, nasal, and bronchial passages of the upper antihistamine with an effective, anti-sedating stimulant, the respiratory tract. It also is intended to include other symp compositions of the present invention may be administered toms, such as cough and pain related to allergies, infections, more safely than prior art antihistamine-containing medica colds, coughs, flu, viral and bacterial infections, and other tions utilized for the same purpose. The present invention common causes for the congestion. Thus, multiple symp also provides methods of use for the pharmaceutical com toms including congestion may be treated with the compo positions. sitions of the present invention. Treatment includes a reduc 0016. Antihistamines suitable for the compositions tion in severity or duration, delay in onset, and/or general include, without limitation, , cyprohepta relief of one or more of these symptoms. The term is dine hydrochloride, brompheneramine, hydroxy Zine, chlo intended to refer to congestion as described herein, as well ropheniramine, pyrilamine maleate, pyrilamine tannate, as to a wide range of symptoms related to the congestion or acepromazine, aceprometazine, , alimemazine its cause and treatable with the present compositions. For tartrate, amoxydramine camsilate, chlorhydrate, example, symptoms related to a common cold or flu Such as antazoline mesilate, antazoline phosphate, , aza cough, fever, and the like, and allergy symptoms such as tadine dimaleate, hydrochloride, hydro , breakouts, Swelling, and runny nose due to external chloride, hydrochloride, bretylium tosilate, bro stimulants are treated with the present compositions. In mazine hydrochloride, maleate, addition, symptoms, such as congestion, cough, pain and dihydrochloride, bufeXamac, maleate acid, discomfort associated with the congestion, resulting from a cetiedil citrate, dihydrochloride, bacterial or viral infection, particularly an infection in the hydrochloride, maleate, respiratory tract, are also treated with the present composi hydrochloride, hydrochloride, , tions. The term “congestion', as use herein, is intended to fumarate, hexachlorophenate, clem refer to the narrowing of an airway including the oral, izole penicilline, clemizole undecylenate, dihy pharyngeal, nasal and bronchial passages due to fluid or a drochloride, clo?edanol, clofenetamine hydrochloride, cycl Solid Substance, Such as mucus or phlegm. Narrowing of the izine hydrochloride, maleate, di airway is often due to Swelling or inflammation of the (acefylline) diphenhydramine, difencloxazine, dimelazine mucous membrane lining the passage to result in a partially hydrochloride, , dimethoxanate hydrochlo or fully blocked passage. Severe cases of congestion often ride, cimetotiazine mesilate, diphenhydramine hydrochlo cause difficulties in breathing. Besides allergic reactions, ride, diphenhydramine mesilate, hydro US 2017/0020873 A1 Jan. 26, 2017 chloride, diprocqualone camsilate, , metaraminol, phenylephrine, tyraine, hydroxyamphetamine, Succinate, eproZinol dihydrochloride, ritodrine, prenalterol, methoxyamine, albuterol, amphet dimaleate, bromhydrate, etybenzatropine amine, , benzphetamine, , phe hydrochloride, hydrochloride, nylpropanolamine, mephentermine, phentermine, fenflu hydrochloride, hydrochloride, fenpentadiol, ramine, , diethylpropion, phenmetrazine, hydrochloride, decanoate, flupentixol phendimetrazine, , , and pseu dihydrochloride, hydrochloride, doephedrine. dihydrochloride, hydroxyzine embonate, indoramine hydro 0020. It should be understood that an effective amount of chloride, hydrochloride, ketotifene fumarate, the antitussive and the decongestant generally vary with the hydrochloride, , levomepro particular antitussive and decongestant chosen. In addition, mazine hydrochloride, levomepromazine embonate, an effective amount depends upon many other factors. Such levomepromazine maleate, , hydro as known differences in pharmacokinetic parameters (ab chloride, maprotiline mesilate, maprotiline resinate, Sorption, distribution and clearance) regardless of the cause. meclozine hydrochloride, mecysteine hydrochloride, medi For example, in a patient with a renal dysfunction or foxamine fumarate, mefenidramium metilsulfate, mepyra disorder, the effective dose of the antihistamine, the antitus mine maleate, meduitazine, methaqualone, sive, and the decongestant is generally half of an effective hydrochloride, hydrochloride, , moxi dose for a patient without renal dysfunction. Sylyte hydrochloride, , hydrochlo 0021 While the present composition includes an antitus ride, oxaflumazine disuccinate, , oxolamine ben sive, a decongestant, and an antihistamine, the present Zilate, oxolamine citrate, , oXomemazine composition is not so limited and may include other com hydrochloride, parathiazine teoclate, perimetazine, pheni ponents. These components include conventional excipients, ramine maleate, phenoxybenzamine hydrochloride, phenyl useful and/or desirable to render the composition suitable or toloxamine, citrate, , pipoti attractive for consumption and use. Excipients providing azine, pipretecol dihydrochloride, pizotifene malate, physical and aesthetic properties for formulation or delivery prednazoline, hydrochloride, , of the composition are desirable. For example, with respect promethazine hydrochloride, promethazine embonate, pro to physical properties, ingredients imparting desirable and methazine polyvinylbenzene-metacrylate, , acceptable hardness, disintegration properties, dissolution , tartrate, hydrochlo rate for release of therapeutic components, stability, and size ride, thiazinamium metilsulfate, hydrochlo to effectively deliver the composition may be included. ride, hydrochloride, hydrochlo Disintegrants may be included for the purposes of facilitat ride, and hydrochloride, and combinations ing the breakup of a tablet after the tablet is administered to thereof. the patient. Examples of disintegrants include, but are not 0017. The antihistamine is included in an amount, per limited to, modified or unmodified Starches Such as corn dosage of the composition, Sufficient to alleviate one or more starch, potato starch, wheat starch, or sodium cross-carmel histamine-mediated responses in a patient. Effective doses los. With respect to aesthetics, it may be desirable for the of the antihistamine will generally vary depending upon the composition to contain additives that appeal to the human antihistamine (S) administered. senses such as colorants, fragrances, texture modifiers, and/ 0018. The present composition also includes an antitus or flavorants. Additionally, many flavoring agents such as, sive. The term “antitussive’, as used herein, is intended to for example, fruit flavors, or Sweeteners, such as sodium include any agent or active ingredient effective for cough saccharin, confectionery Sugar, Sucrose, Xylitol, or combi Suppression Such as chlophedianol hydrochloride. These nations thereof, may be included. Additionally, suitable also include, but are not limited to, common opioid analge colorants including, for example, red beet powder, ferric sics such as hydrocodone, codeine, , morphine oxide, FD&C dyes, or combinations thereof, may be related compounds including diacetylmorphine, oxymor included in the present compositions. Desirable excipients phone, hydromorphone, , , may also include buffering agents, Surfactants, electrolytes, oxycodone, , , meperidine, pentazo and thixotropic agents. It should be understood that these cine, buprenorphine, , , Sufentanyl. other components should not affect the action or mechanism alfentanyl and propoxyphene, and opioid antagonists not of action of the antitussive, decongestant, and/or the anti structurally-related to morphine, such as , nalox histamine in the composition. one, naltrexone and fentanyl. In one embodiment, the anti 0022 Excipients or formulations affecting the release tussive agent is hydrocodone or a pharmaceutically accept properties, mechanisms, and/or rates of the antitussive, the able salt form thereof, such as hydrocodone bitartrate. decongestant, and the antihistamine, from the composition 0019. The present composition also includes a deconges upon oral ingestion may be provided. For example, the tant. The term “decongestant as used herein, is intended to composition may be formulated such that the release of the refer to any agent or ingredient, active for reducing or antitussive, the decongestant, and/or the antihistamine or eliminating congestion of the air passages by widening the other active ingredients from the composition is delayed for airway, and/or by stimulating the release of phlegm and a period of time or to Survive a particular environment. mucus from these passages. Airpassages may be widened by 0023 Advantageously, the composition may be formu reducing the Swelling of the mucous membranes in the lated so as to prevent the release of the antitussive, the passage. Generally, sympathomimetic have deconges decongestant, and/or the antihistamine in the stomach where tant properties. Examples of Suitable decongestants include, they may likely be acidified, salted out and excreted from the without limitation, phenylethylamine, epinephrine, norepi body rather than absorbed into the circulation. For example, nephrine, , dobutamine, colterol, ethylnorepineph the composition may be coated with a coating to improve rine, isoproterenol, isoetharine, metaproterenol, terbutaline, absorption and render the composition more bioavailable US 2017/0020873 A1 Jan. 26, 2017

than it would otherwise be without the coating. Enteric and other blockage of air passages, the composition of the coatings or encapsulation-type coatings as known to one present invention includes the antitussive, the decongestant, skilled in the art are suitable for this purpose. In one and the antihistamine in amounts suitable for treating chil embodiment, a table or a capsule form of the composition is dren and adults alike. enterically coated so as to provide delayed-release and 0028. In yet another embodiment of the present inven Sustained-release properties to the composition. Sustaining tion, there is provided methods of alleviating symptoms of upper respiratory and oral pharyngeal congestion by orally the release of individual active ingredients to the body over administering to a patient in need thereof a single dose of a a period of time prolongs the effective time period of relief composition or formulation including an antitussive, a from the congestion and related symptoms, provided, how decongestant, and an antihistamine. The patient in need may ever, the amount of the ingredient in the blood stream is be a child or an adult Suffering from the congestion. Admin within the effective therapeutic window for that particular istration of the composition will depend upon the form of the ingredient. Further, preservatives may be provided to pre composition. For example, a liquid formulation may be vent degradation of components in the composition or administered to a child in amounts Smaller than that admin degradation of the composition as a whole, thereby improv istered to an adult. Administration will also depend upon ing the stability and prolonging the shelf life of the com various other factors related to the patient. For example, age, position. health, weight, prior medical history, extent and degree of 0024. The composition of the present invention may be symptoms, and overall medical diagnosis will generally formulated in a single form. In one embodiment, the form is influence the amounts administered. The composition is convenient to Swallow, and has a generally accepted appear generally administered for alleviating cough, pain, cold and ance and taste to promote consumption and compliance with allergy symptoms and also provides a sedative effect, an a dosing regimen. In accordance with one aspect of the analgesic adjuvant effect, an anti-cholinergic affect, and a present invention, the composition is formulated into a mild analgesic effect. dosage form that may be an ingestible liquid, a pill, a tablet, 0029. Formulations of the invention may contain any or all of the following in any combination: Purified Water; Any a capsule, a Suppository, etc. In accordance with another combination of permitted API's added as powders or as aspect of the invention, the composition may be formulated Solutions, emulsions, Suspensions: Chlophedianol Hydro into a parenterally administrable form. It should be under chloride, Pseudoephedrine Hydrochloride, Phenylephrine, stood by one skilled in the art that certain active agents, such or any approved oral nasal decongestant: Dexchlorpheni as hydrocodone, are typically not parenterally administered, ramine Maleate, Maleate, Bromphe such as by intra-venous administration. However, other niramine Maleate, Chlorcyclizine Hydrochloride, such as codeine, morphine, methadone, and fentanyl Thonzylamine Hydrochloride, Pyrilamine Maleate, Phenin may be administered with antihistamine in a non-orally damine Tartrate, or any approved oral antihistamine; Guaife administrated formulation. In accordance with a further nesin or any approved oral expectorant, Acetaminophen or aspect of the invention, the present composition may include any approved analgesic, antipyretic or anti-inflammatory; active ingredients Suitable for Sub-lingual administration. In Citric Acid, Sodium Citrate; Propylene Glycol; Flavor; accordance with yet another aspect of the invention, the Sodium Saccharin Solution (Sodium Saccharin dissolved in present composition may be administered via mucous mem water or any other solvent); Sorbitol; Glycerin; and Purified branes of the buccal, nasal, rectal cavities, etc. The desired Water formulation may be prepared by a process known in the art 0030 The formulations of the invention may be com of pharmaceutical manufacture. For example, liquid formu bined with any of the following pharmaceutical aids or lations may be prepared in the form of a syrup or a excipients or preservatives, added as solutions, Suspension, Suspension. In one embodiment, the composition is formu emulsions, or directly added as liquids or powders: Preser lated into an elixir or a syrup having a desirable flavor for vatives—including but not limited to the following: Para bens, Benzoates, Sorbates: Artificial Sweeteners including easy, trouble-free administration to a child. but not limited to the following: Sucralose, Saccharin, 0025 Solid formulations, such as capsules may be pre Acesulfame: Sweeteners including but not limited to the pared by first blending the antitussive, the decongestant, and following: Sucrose, Corn Syrup, High Fructose Corn Syrup, the antihistamine with other desirable additives and then Maltitol, Mannitol, Dextrose, Glucose: Thickeners—includ filling capsular materials with the blended mixture using ing but not limited to the following: Gums, Mucilages, conventional filling equipment. In one embodiment, the Xanthan Gum, Guar Gum, Veegum, Methylcellulose capsular material is a gelatin. The capsule formed may be a Derivatives; Buffering Agents—including but not limited to liquid gelatin capsule. Further, where desired, the capsule the following: Phosphates, Citrates, Sulfates, Carbonates, may be coated for added benefits. In general, tablets may be etc.; and Alcohol Derivatives as Solvents, Preser formed by first blending the components and then either vatives, Flavors: Emulsifiers; Coloring Agents, Dyes, Cer directly compressing the blended components, or granulat tified Colors: Any and all pharmaceutical excipients ing the components followed by compressing them into a 0031 While the present invention has been illustrated by tablet form. Additional ingredients may be included during the description of embodiments thereof, and while the compression where desired. For example, the granular mix embodiments have been described in considerable detail, it ture may contain one or more lubricants to inhibit sticking is not intended to restrict or in any way limit the scope of the during compression. Examples of Suitable lubricants appended claims to such detail. Additional advantages and include, but are not limited to, Stearic acid, palmetic acid, modifications will be readily apparent to those skilled in the Stearates, talc, and oils. art. The invention in its broader aspects is, therefore, not 0026. The compositions of the invention may also be limited to the specific details, representative method, and formulated as a powder or sprinkles. illustrated examples described. Accordingly, departures may 0027. To effectively suppress cough, relieve pain, and be made from Such details without departing from the scope reduce mucus membrane Swelling for reducing congestion or spirit of Applicant’s general inventive concept. US 2017/0020873 A1 Jan. 26, 2017

0032 Examples of the compositions of the invention are set forth below:

ACTIVE 1 ACTIVE 2 ACTIVE 3

C l O hedianol H 12.5 mg Pseudoephedrine HCl 30 mg Dexchlorpheniramine Maleate 1 mg Ole ianol H 12.5 mg Pseudoephedrine HCl 30 mg Guaifenesin 100 mg ophedianol H 12.5 mg Pseudoephedrine HCl 30 mg Guaifenesin 200 mg ophedianol H 12.5 mg Pseudoephedrine HCl 30 mg Chlorcyclizine 9.375 mg orcyclizine H 9.375 mg Pseudoephedrine HCl 30 mg ophendianol H C 2 5 l 9. Guaifenesin 200 mg orcyclizine H 9.375 mg Pseudoephedrine HCl 30 mg orcyclizine H 9.375 mg Pseudoephedrine HCl 30 mg Codeine Phosphate 10 mg orcyclizine H 9.375 mg Codeine Phosphate 10 mg ophedi 12.5 mg Dexbrompheniramine 1 mg henylephrine HCl 5 mg Ole ianol H 25 mg Pseudoephedrine HCl 60 mg hlorpheniramine Maleate ng orcyclizine H 9.375 mg Pseudoephedrine HCl 30 mg hilophedianol HCl 12.5 mg orcyclizine H 9.375 mg Pseudoephedrine HCl 30 mg extromethorphan HBr 15 mg 12.5 mg Guaifenesin 100 mg henylephrine HCl 5 mg O l Zylamine H 50 mg O l Zylamine H 50 mg Pseudoephedrine HCl 30 mg hedianol H 12.5 mg hedianol H 12.5 mg henylephrine HCl 5 mg hedianol H 12.5 mg f rompheniramine Maleate 2 9. hedianol H 12.5 mg hlorcyclizine 9.375 mg hedianol H 25 mg hlorcyclizine 18.75 mg hedianol H 12.5 mg hlorcyclizine 9.375 mg hedianol H 25 mg hlorcyclizine 18.75 mg hendiano HCI 25 mg Pyrilamine maleate 50 mg hendiano HCI 25 mg Guaifenesin 200 mg hendiano HCI 25 mg Guaifenesin 400 mg hendiano HCl 12.5 mg hendiano HCl 12.5 mg Thonzylamine HCl 50 mg hendiano HCI 25 mg Thonzylamine HCl 100 mg hendiano HCI Thonzylamine HCl 50 mg 2 9. l hendiano HCI 25 mg Thonzylamine HCl 100 mg l hendiano HCI 25 mg l hendiano HCI 25 mg Guaifenesin 400 mg l orcyclizine HC19.375 l orcyclizine HCl 18.75 mg HCl 10 mg l orcyclizine HCl 18.75 mg Pseudoephedrine HCl 60 mg honzylemine HCl 50 mg Pseudoephedrine HCl 30 mg honzylemine HCl 100 mg Pseudoephedrine HCl 60 mg honzylemine HCl 50 mg Phenylephrine HCl 5 mg honzylemine HCl 100 mg Phenylephrine HCl 10 mg hlorcyclizine HCl 9.375 mg hedrine HCl 30 mg Acetaminophen 325 mg honzylamine HCl 50 mg hedrine HCl 30 mg Acetaminophen 325 mg hlorcyclizine HCl 18.75 mg hedrine HCl 60 mg Acetaminophen 500 mg honzylamine HCl 100 mg hedrine HCl 60 mg Acetaminophen 500 mg hlophendianol HCl 12.5 mg hedrine HCl 30 mg Thonzylamine HCl 50 mg hlophendianol HCI 25 mg hedrine HCl 60 mg Thonzylamine HCl 100 mg hlophendianol HC Phenylephrine HCl 5 mg Thonzylamine HCl 50 mg 2 .5 mg l ophendiano 25 mg Phenylephrine HC 10 mg Thonzylamine HC 100 mg l ophendiano 12.5 mg Phenylephrine HCl 5 mg Chlorcyclizine HC 9.375 mg l ophendiano 25 mg Phenylephrine HCl 10 mg Chlorcyclizine HC 18.75 mg hlophendiano HCI 25 mg Pseudoephedrine HCl 60 mg Guaifenesin 200 mg l ophendiano HCI 25 mg Phenylephrine HCl 10 mg Brompheniramine 4 mg l orcyclizine HCl 9.375 mg Codeine Phosphate 10 mg Pseudoephedrine HCl 30 mg l orcyclizine HCl 9.375 mg Codeine Phosphate 10 mg Acetaminophen 325 mg onzylamine HCl 50 mg Codeine Phosphate 10 mg Pseudoephedrine HCl 30 mg onzylamine HCl 50 mg Codeine Phosphate 10 mg Acetaminophen 325 mg honzylamine HCl 50 mg Codeine Phosphate 10 mg Phenylephrine HCl 5 mg hlorcyclizine HCl 9.375 mg Codeine Phosphate 10 mg Phenylephrine HCl 5 mg hlorcyclizine HCl 9.375 mg Codeine Phosphate 10 mg Phenylephrine HCl 5 mg honzylamine HCl 50 mg Codeine Phosphate 10 mg Phenylephrine HCl 5 mg hlophendiano HCl 12.5 mg Pseudoephedrine HCl 30 mg Chlorpheniramine Maleate 2 ng C hlophendianol HCl 12.5 mg Pseudoephedrine HCl 30 mg Dexbrompheniramine Maleate ng honzylamine HCl 50 mg Pseudoephedrine HCl 30 mg Dextromethorphan HBr 15 mg honzylamine HCl 50 mg Phenylephrine HCl 5 mg Dextromethorphan HBr 15 mg hlorcyclizine HCl 9.375 mg Pseudoephedrine HCl 30 mg Dextromethorphan HBr 15 mg US 2017/0020873 A1 Jan. 26, 2017 6

-continued

ACTIVE 1 ACTIVE 2 ACTIVE 3 Chlorcyclizine HCl 9.375 mg Phenylephrine HCl 5 mg Dextromethorphan HBr 15 mg Chlophedinol HCl 12.5 mg Pseudoephedrine HC Guaifenesin 75 mg 30 mg Chlorcyclizine HCl 9.375 mg Pseudoephedrine HCl 30 mg Dextromethorphan HBr 15 mg Thonzylamine HCl 50 mg Phenylephrine HCl 5 mg Dextromethorphan HBr 15 mg Chlophendianol HCl 12.5 mg Phenylephrine HCl 5 mg Guaifenesin 200 mg Chlophendianol HCl 12.5 mg Pseudoephedrine HCl 30 mg Pyrilamine Maleate 25 mg Chlophendianol HCl 12.5 mg Phenylephrine HCl 5 mg Pyrilamine Maleate 25 mg Chlophendianol HC Pseudoephedrine HCl 30 mg Guaifenesin 100 mg 12.5 mg Chlophendianol HCI 25 mg Pseudoephedrine HCl 60 mg Guaifenesin 200 mg Chlophendianol HCl 12.5 mg Phenylephrine HCl 5 mg Guaifenesin 100 mg Chlophendianol HCI 25 mg Phenylephrine HCl 10 mg Guaifenesin 200 mg Chlophendianol HCI 25 mg Pseudoephedrine HCl 60 mg Guaifenesin 400 mg Chlophendianol HCI 25 mg Phenylephrine HCl 10 mg Guaifenesin 400 mg Chlophendianol HCl 12.5 mg Pseudoephedrine HCl 30 mg Guaifenesin 200 mg Chlophendianol HCl 12.5 mg Phenylephrine HCl 5 mg Guaifenesin 200 mg Chlophendianol HCl 12.5 mg Pseudoephedrine HCl 30 mg Doxylamine Succinate 6.25 ng Chlophendianol HCl 12.5 mg Pseudoephedrine HCl 30 mg Doxylamine Succinate 6.25 ng Chlophendianol HCl 12.5 mg Phenylephrine HCl 5 mg Doxylamine Succinate 6.25 ng Chlophendianol HCl 12.5 mg Phenylephrine HCl 5 mg Doxylamine Succinate 6.25 ng Chlophendianol HCl 12.5 mg Pseudoephedrine HCl 30 mg Diphenhydramine HCI 25 mg Chlophendianol HCl 12.5 mg Phenylephrine HCl 5 mg Diphenhydramine HCI 25 mg Chlophendianol HCl 12.5 mg Pseudoephedrine HCl 30 mg Diphenhydramine HCI 25 mg Chlophendianol HCl 12.5 mg Phenylephrine HCl 5 mg Diphenhydramine HCI 25 mg Chlophendianol HCl 12.5 mg Guaifenesin 200 mg Chlophendianol HCl 8.33 mg Brompheniramine 1.33 mg Phenylephrine 33.33 mg Chlorcyclizine HCI 25 mg Pseudoephedrine HCl 60 mg Codeine Phosphate 10 mg Thonzylamine HCl 100 mg Pseudoephedrine HCl 60 mg Codeine Phosphate 10 mg Chlorcyclizine HCI 25 mg Pseudoephedrine HCl 60 mg Chlorcyclizine HCI 25 mg Chlophedianol HCI 25 mg Chlorcyclizine HCI 25 mg Chlophedinol HCI 25 mg Pseudoephedrine HCl 60 mg Chlorcyclizine HCI 25 mg Chlophedianol HCl 12.5 mg Chlophedianol HCI 25 mg Thonzylamine HCl 100 mg Codeine Phosphate 10 mg Thonzylamine HCl 100 mg Pseudoephedrine HCl 60 mg Dextromethorphan HBr 30 mg Thonzylamine HCl 100 mg Pseudoephedrine HCl 60 mg Dextromethorphan HBr 15 mg Thonzylamine HCl 100 mg Pseudoephedrine HCl 60 mg Dextromethorphan HBr 20 mg Chlorcyclizine HCI 25 mg Pseudoephedrine HCl 60 mg Dextromethorphan HBr 30 mg Dextromethorphan HBr 15 mg Chlorcyclizine HCl 9.373 Dextromethorphan HBr 30 mg Chlorcyclizine HCl HBr 18.75 ng Dextromethorphan HBr 15 mg Thonzylamine HCl 50 mg Dextromethorphan HBr 30 mg Thonzylamine HCl 100 mg Chlophedianol HCl 12.5 mg Thonzylamine HCl 50 mg Chlophedianol HCl 12.5 mg Chlorcyclizine HCl 9.375 mg

What is claimed is: bromide, bromopheniramine maleate, Guaifenesin, Codeine phosphate, and thonzylamine hydrochloride. 1. A pharmaceutical composition for alleviating Symp 2. The pharmaceutical composition of claim 1, further toms of upper respiratory and oral-pharyngeal congestion in comprising a third active ingredient selected from the group a Subject, the composition comprising: consisting of pyrilamine maleate, Pseudoephedrine Hydro a first active ingredient selected from the group consisting chloride, chlorcyclizine hydrochloride, dexbrompheni of chlophedianol hydrochloride, chlorcyclizine hydro ramine maleate, diphenhydramine hydrochloride, diphenhy dramine citrate, chlorpheniramine maleate, chloride, phenylephrine hydrochloride, dextrometho dexchlorpheniramine maleate, doxylamine Succinate, tripro rphan hydrobromide and thonzylamine hydrochloride; lidine hydrochloride, dextromethorphan hydrobromide, bro and mopheniramine maleate, Guaifenesin, Codeine phosphate, a second active ingredient selected from the group con and thonzylamine hydrochloride. sisting of pyrilamine maleate, Pseudoephedrine Hydro 3. The pharmaceutical composition of claim 1, wherein chloride, chlorcyclizine hydrochloride, dexbrompheni the first active ingredient is present at a range of 9.375 mg ramine maleate, diphenhydramine hydrochloride, to 100 mg. diphenhydramine citrate, chlorpheniramine maleate, 4. The pharmaceutical composition of claim 1, wherein dexchlorpheniramine maleate, doxylamine Succinate, the second active ingredient is present at a range of 1 mg to triprolidine hydrochloride, dextromethorphan hydro 100 mg. US 2017/0020873 A1 Jan. 26, 2017

5. The pharmaceutical composition of claim 2, wherein third active ingredient is present at a range of 1 mg to 500 ng.