a trigger substance according to this invention is defined as any substance that , when exposed in the form of a vapor to a susceptible human subject , reproducibly gives rise to a running nose condition in such subject in a time period of thirty minutes or less . preferred trigger substances are those whose vapors are known to be safe to expose to a human subject in the amounts needed , particularly substances known to be present in products sold in retail establishments for household use or authoritatively regulated for such use under observance of appropriate limitations . included among such trigger substances are basic nitrogen compounds such as alkanolamines and especially ammonia as found in aqueous ammonia solutions , formulated liquid household cleaning products , hair waving preparations , and the like . an immediate effect of such basic nitrogen compounds in triggering symptoms of the common cold such as running nose within thirty minutes or less has not previously been reported . the quantity of trigger substance to be exposed to a susceptible person for appearance of cold symptoms to be reproducible is readily determined empirically . for example , a reproducible appearance of a running nose condition within thirty minutes or less has been noted by a susceptible individual upon exposure within 4 feet of a 40 milliliter sample of household ammonia for less than five minutes . in accordance with this invention , any desired agent can be tested for its effectiveness in preventing the appearance of cold symptoms otherwise produced in a susceptible individual by exposure to a trigger substance . the only limitation is the practical requirement of not doing harm to such individual . for that reason , i have sought effective agents principally among substances known to be safe to administer to a human subject , particularly substances known to be nutrients ingested and metabolized by human beings on a daily or at least frequent basis . i have tested many nutrient substances and found effective among these a restricted group of water soluble aminocarboxylic acid compounds at dose levels in the range from 200 to 20000 milligrams . i use the term water soluble to refer to a solubility of at least three grams in 100 ml of water at 25 ° c . a preferred group of water soluble aminocarboxylic acid compounds effective according to this invention in preventing appearance of cold symptoms can be represented by formula ( i ): ## str1 ## in which x is selected from the group consisting of -- sh , -- conh 2 , ## str2 ## n is zero , one , or two , and p and q are each zero or one , provided that p and q are not both zero and p is zero and q is one only when x is -- n ( ch 3 ) 3 +. table 1 which follows includes particularly preferred water soluble aminocarboxylic acid compounds represented by formula ( i ) which i have found effective in preventing appearance of cold symptoms when administered before exposure to a trigger substance . table 1__________________________________________________________________________ # name x n p q__________________________________________________________________________1 2 - amino - 3 - mercapto - sh 0 1 0 propanoic acid2 2 - amino - 4 - carbamoyl - conh . sub . 2 1 1 0 butanoic acid3 2 - amino - 4 - methylthio - sch . sub . 3 1 1 0 butanoic acid4 2 , 5 - diaminopentanoic acid nh . sub . 2 2 1 0 ## str3 ## ## str4 ## 2 1 06 ## str5 ## ## str6 ## 1 1 07 3 - hydroxy - 4 - trimethyl - n ( ch . sub . 3 ). sub . 3 + 1 0 1 ammoniobutanoate__________________________________________________________________________ formula ( i ) and all the effective compounds listed in table 1 contain an assymetric carbon atom and hence exist in non - superimposable optically active forms ( so - called d and l forms ) and in racemic mixtures or dl forms . both d and l forms of the effective compounds and racemic mixtures thereof are contemplated in accordance with this invention . there is nothing about the structures of the effective compounds of this invention or their known nutrient properties that would have enabled one to predict their effectiveness in preventing appearance of cold symptoms in accordance with this invention . this unpredictability is further underscored by the finding that a number of aminocarboxylic acid compounds structurally similar to those effective according to this invention but not structured according to formula ( i ) are ineffective . in table 2 following , there are listed a number of aminocarboxylic acid compounds found ineffective in preventing appearance of cold symptoms when administered before exposure to a trigger substance . some of these compounds can be represented by formula ( ii ) ## str7 ## in which the assignments of x and / or n differ from those in formula ( i ) table 2______________________________________ # name x n p q______________________________________a 2 - aminopropanoic acid hydrogen 0 1 0b 2 - amino - 3 - phenylpropanoic phenyl 0 1 0acidc 2 - amino - 3 - imidazolyl - imidazolyl 0 1 0propanoic acidd 2 - aminoacetic acid not applicable not applicablee 2 - aminopentanedioic acid -- cooh 2 1 0______________________________________ while these substances are ineffective in preventing appearance of cold symptoms , they do not act as trigger substances and thus can be present in modest amounts as companion substances to effective agents according to this invention . in this way such substances can contribute to the useful properties of the effective agents by enhancing their speed of action , palatability and / or taste characteristics . when present as companion substances to effective agents their concentration will typically range from 1 to 10 weight percent of the effective agent . also in accordance with this invention , a pharmaceutically acceptable carrier can be combined with effective amounts of an effective agent according to this invention to provide a palatable oral dosage form for administering to a person in need of preventing appearance of cold symptoms . accordingly , palatable oral dosage forms according to this invention comprise at least one pharmaceutically acceptable carrier and an effective amount of an effective agent according to this invention . preferably the effective agent is an aminocarboxylic acid nutrient compound having formula ( i ). particularly preferred effective agents are those listed in table 1 . one preferred palatable oral dosage form according to this invention is a tablet . a particularly preferred tablet according to this invention comprises a high percentage of at least one aminocarboxylic acid nutrient compound having formula ( i ) and minor amounts of carrier material acting as binder for the tablet . suitable binder materials include naturally occurring carbohydrates such as cellulose , starch , galactomannan , fructose , lactose , and sucrose ; finely divided ingestible mineral substances such as calcium and magnesium carbonates , calcium and magnesium silicates , calcium and magnesium phosphates , alumina hydrates and hydrotalcite ; waxy materials such as beeswax , stearin , stearates of calcium , magnesium , and aluminum , microcrystalline wax and paraffin , and mixtures thereof . another preferred palatable oral dosage form according to this invention is a capsule . capsules have the advantage of delivering the effective agent directly to the alimentary canal without being tasted in the mouth . suitable capsules are commercially available and are typically made of gelatin , but any sufficiently pure water soluble polymer can be used . preferably the capsule is filled with the pure aminocarboxylic acid nutrient compound having formula ( i ); alternatively , suspensions of aminocarboxylic acid nutrient compound having formula ( i ) in a liquid carbohydrate such as corn syrup or honey , or in a lipid such as lecithin or canola oil can be encapsulated . a further palatable oral dosage form according to this invention comprises an effective amount of an effective agent according to this invention in a liquid carrier such as a prepared soup or a fruit flavored drink , or in a solid concentrate ready to be converted to such liquid carrier by addition of water at the point of use . preferably the effective agent is an aminocarboxylic acid nutrient compound having formula ( i ). particularly preferred effective agents are those listed in table 1 . suitable prepared soups include all flavors of canned and dehydrated soups , preferably in containers sized so as to deliver a single serving of soup containing an appropriate dose of the effective agent . suitable fruit flavored drinks include natural fruit juices such as pineapple juice , apple juice , grape juice , orange juice , grapefruit juice , cranberry juice , and mixtures thereof ; reconstituted juices prepared from water and fruit juice concentrates , and fruit juice drinks containing water and at least 10 % of natural fruit juice . in oral dosage forms according to this invention , the proportions of carrier to effective agent can vary over a broad range in accordance with the kind of carrier selected and the strength desired . thus the proportion of carrier can be as little as 0 . 1 % by weight , as in a tablet , and as high as 85 % or even more , as in a fruit flavored drink . tablets in accordance with this invention can be prepared , for example , from 750 milligrams of each of compounds # 1 , 3 , 5 , 6 , or 7 of table 1 and 5 milligrams each of stearin , magnesium stearate , and magnesium silicate . capsules in accordance with this invention can be prepared , for example , by filling elliptical capsules of 1 . 5 ml capacity with 500 milligrams of each of compounds # 1 , 2 , 3 , 4 , 5 , 6 , or 7 of table 1 . fruit flavored drinks in accordance with this invention can be prepared , for example , from 3750 milligrams of each of compounds # 1 , 2 , 3 , 4 , 5 , 6 , or 7 of table 1 and 75 milliliters of commercially available apple - cranberry drink . also in accordance with this invention , a pharmaceutically acceptable carrier can be combined with effective amounts of an effective agent according to this invention and a flavorant to provide a pleasant tasting oral dosage form for administering to a person in need of preventing appearance of face pimples . accordingly , pleasant tasting oral dosage forms according to this invention comprise at least one pharmaceutically acceptable carrier , an effective amount of an effective agent according to this invention , and a flavorant . preferably the effective agent is an aminocarboxylic acid nutrient compound having formula ( i ). particularly preferred effective agents are those listed in table 1 . preferred flavorants that can be used in a pleasant tasting oral dosage form according to this invention include herbs such as basil , cilantro , dill , oregano , tarragon , and thyme ; spices such as cinnamon , clove , ginger , mace , and nutmeg , and essential oils such as oil of lemon , oil of orange , oil of peppermint , and oil of sassafras . in a particularly preferred pleasant tasting oral dosage form according to this invention , there are present in amounts selected to complement the taste characteristics of each at least one first nutrient compound having the formula ## str8 ## in which x is selected from the group consisting of ## str9 ## , n is two , p is one and q is zero , and at least one second nutrient compound having the formula ## str10 ## in which x is selected from the group consisting of -- sh , -- conh 2 , ## str11 ## n is zero or one , and p and q are each zero or one , provided that p and q are not both zero and p is zero and q is one only when x is -- n ( ch 3 ) 3 +. in such compositions , the taste characteristics of the first nutrient compound and the second nutrient compound interact in such a way as to produce an overall pleasant tasting composition . pleasant tasting tablets in accordance with this invention can be prepared , for example , from 750 milligrams of each of compounds # 1 , 3 , 5 , 6 , or 7 of table 1 , 5 milligrams each of stearin , magnesium stearate , and magnesium silicate , and 10 milligrams of finely powdered cinnamon . a pleasant tasting fruit flavored drink in accordance with this invention can be prepared , for example , by blending 4500 milligrams of each of compounds # 1 , 3 , 5 , 6 , or 7 of table 1 , 110 milliliters of commercially available chilled grapefruit juice , and 5 drops oil of orange . pleasant tasting tablets containing a first nutrient compound and a second nutrient compound in accordance with this invention can be prepared , for example , from 500 milligrams of each of compounds # 1 , 2 , 3 , 5 , 6 , or 7 of table 1 , 250 milligrams of each of compounds # 4 or 6 of table 1 , and 5 milligrams each of stearin , magnesium stearate , and magnesium silicate . the following examples are provided to illustrate the invention without intending to limit its scope , which is defined by the appended claims . conditions required to reproducibly trigger a running nose in a susceptible person were determined as follows : a male volunteer subject known to be susceptible to attacks of running nose upon exposure to vapors of ammonia was seated in an enclosed room at varying distances from a 51 / 2 inch diameter dish placed 3 feet above the floor and containing 40 milliliters of household ammonia ( approximately 9 % ammonia by weight in water ). trials were carried out on alternate days only to allow full recovery between trials . the time was noted from the start of exposure to the occurrence of a pronounced running nose , defined as having to blow clear 3 or more times in a 10 minute period and continuing for at least a six hour period . for each exposure distance , three trials were carried out , arranged in a random order . ______________________________________ distance of time to onsettrials subject from source of running nose______________________________________a - 1 , a - 2 , a - 3 12 feet no reaction in one hourb - 1 , b - 2 , b - 3 8 feet 15 , 16 , and 19 minutesc - 1 , c - 2 , c - 3 4 feet 4 , 4 , and 3 minutesd - 1 , d - 2 , d - 3 2 feet 2 , 2 , and 3 minutes______________________________________ the results show that exposure to ammonia vapors at a distance of 8 feet or less is clearly sufficient to reproducibly trigger a running nose in this individual . in each of the following trials , the same subject as in example 1 was exposed to a dish of household ammonia at a distance of 4 feet . after the onset of running nose was noted , approximately eight minutes after exposure , there was administered a dose of a substance as noted below . ______________________________________ time from admin - example istration to abate - no . substance dose ment of sneezing______________________________________2 blend of substances 2000 mg 30 minutes from table 14 blend of substances 4000 mg 20 minutes from table 1comparison 1 none no effect in six hourscomparison 2 blend of substances 4000 mg no effect in from table 2 six hours______________________________________ the results show the blend of substances shown in examples 2 and 3 was an effective agent according to this invention in relieving cold symptom such as running nose triggered by ammonia in accordance with a method of this invention . the results also show that compounds of table 2 with structural similarity to those effective according to this invention but differing in the assignments of x and / or n in the formula were ineffective . in each of the following trials , there was administered a dose of a substance as noted below to the same subject as in example 1 , and after a waiting period of 30 minutes he was exposed to a dish of household ammonia at a distance of four feet . the following results were noted . ______________________________________example no . substance dose results______________________________________4 blend of substances 2000 mg no running nose from table 1 within 6 hr5 blend of substances 4000 mg no running nose from table 1 within 6 hrcomparison 3 none running nose after 4 mincomparison 4 blend of substances 4000 mg running nose from table 2 after 4 min______________________________________ the results show the blend of substances shown in examples 5 and 6 was an effective agent according to this invention in preventing cold symptom such as running nose triggered by ammonia in accordance with a method of this invention . the results also show that compounds of table 2 with structural similarity to those effective according to this invention but differing in the assignments of x and / or n in the formula were ineffective .
disclosed is the method of determining the effectiveness of an agent for relieving symptoms of the common cold , comprising the steps of a ) exposing a susceptible subject to vapors of a trigger substance reproducibly effective in producing within a period of 30 minutes a running nose lasting for at least 6 hours in the absence of treatment , b ) administering to said subject having been exposed to a trigger substance a predetermined quantity of the agent whose effectiveness is to be determined , c ) measuring the time required for the running nose to be abated , and d ) comparing the time required for the running nose to be abated with and without the administration of said agent . also disclosed are effective quantities of certain nutrient substances which can reproducibly relieve symptoms of the common cold produced in a susceptible subject by the administration of a trigger substance .