CA1276888C - Method of causing the reduction of physiological and/or subjective reactivity to stress in humans being subjected to stress conditions - Google Patents

Abstract

ABSTRACT

Described is a method for reducing physiological and/or subjective reactivity to stress in humans being subjected to stress conditions. The method consists of administering to such humans an effective amount of a physiological and/or subjective stress reactivity-reducing substance selected from the group consisting of:

(i) Nutmeg Oil;
(ii) Mace Extract;
(iii) Neroli Oil;
(iv) Valerian Oil;
(v) Myristicin;
(vi) Isoelemicin; and (vii) Elemicin.

Administration is through inhalation or transdermally using one or more of the above ingredients alone or in a suitable composition such as ethanol and/or a perfume composition, cologne or perfumed article (e.g., air freshener or deodorant stick).
Also described is a method for detecting the reduction of physiologi-cal and/or subjective reactivity to stress in a human.

Description

"r~ETHOD OF CAUSING THE REDUCTION OF PHYSIOLO~ICAL
AND/OR SUBJECTrVE REACTIVITY TO STRESS IN HUMANS
BEING SUB3ECTED TO STRESS CONDITIONS"

CRAIG B. WARREN, ~ARINA ALICE MUNTEANU, GARY E. SCHWARTZ, CARLOS BENAIM, HENRY G.
WALTER, JR., RONALD S. LEIGHT, DONALD ARTHUR
WITHYCOMBE, BRAJA DULAL MOORHERJEE A~D
ROBERT WALTER TRENKLE

BACKGROUND OF THE INVENTION
1. Field of the Invention .
(i) The results obtained through practice of this invention are comparable to results obtainable from meditation and biofeed-- back, including, notably, damping of the systolic blood pressure surges arising from stressful situations. However, unlike medita-tion or biofeedback, no trainin~ period is reouired in the use of the stress reactivity-reducing substances of our invention.
The effect of the stress reacti~ity-reducing substances of our invention occurs within four minute~ after inhalation of said substances.
P~ (ii) Unlike a~ti-anxiety drugs, the effect of the volatile compositions of matter employed in the practive of our invention, ~; (e.g., nutmeg oil, mace extract, neroli oil, valerian oil, myristicin, elemicin and/or isoelemicin) is prophylactic in nature~
reducing (the phy~iological and~or subjective) reactivity to ~-~ stress when stress conditions exist. Unstressed people do not respond to the method of this invention.
(iii) Practice of this invention may be distinquished from the prior art employment o active e~sential oils, e.~., from nutme~, in perfume compositions. Aside from generating ~resence of the actives in the surrounding atmosphere at a concentration less ; than is effective to re~uce reacti~ity to stress, perfume usa~e in modern day practice invol~es emplo~ment durin~ non-stress occurring situations.

2. The Prior Art The t~rm ~Aromatherapy~ is intended herein to mean the usP
of plant-derived ~ubstances; volatile ~ubstances derived from plants for the treatment of health problems. Generally, the volatile fraction---the essential oil fraction- -of the plant-!derived substance ls ~3ed. The use of the volatile fractions ofplants for treatme~t of various ailments is review~ed in the ~ following three monographs:
.~:
(1) J. Valnet, "The Practice of Aromatherapy", Destiny Books ~Division of Inner Traditions International, Ltd.
N~w York , N . Y ., 1 9 8 ~;

(2) R. Tisserand, ~The Art of Aromatherapy~, Destiny Books (Division of Inner ~raditions International, Ltd.~, New York, N.Y., l9B3; and ~3) ~. Leunq, "Encyclopedia of Common Natural Inqredients", J. Wiley 6 Sons Publishing Co., New York, N.Y~, 1980.

A detailed analysis of the aromatherapy folk medicine litera-ture suggested that a number of essential oils commonly used in perfumery might have a multiplicity of medical effects. Some of these oils are employed in the practice of this invention.

Neroli oil is the essential oil obtained from orange blossoms.
Neroli oil has a folk medicine history as being an anti-depressant, aphrodisiac, antiseptic, antispasmodic and of having digestive and sedative activity. The anecdotal literature suggests that neroli oil is an effective sedative and anti depressant and that it may be used or insomnia, hysteria, states of anxiety and depression tR. Tisserand, ~ Art of A~n~therapyn, cited, supra~. Tisserand further ~tates:

~ Neroli is ~ne of the most effective sedative-antidepressant oils: it may be used for insomnia, ¦ hysteria, states o~ anxiety and depression. It calms and slows down the mind. It also has a notable action on the heart, diminishing the amplitude of heart muscle contxaction, hence its use in palpitations or other types of cardiac spasm. Derived from this is its use in panicky, hysterial, fearful types of people - those who upset themselves unnecessarily, and become over wrought over nothing. One can also see that neroli is a valuable remedy for shock, or for disorders caused by sudden shock, or fear, causing a strain on the heart. It is valuable in chronic diarrhoea, when this is related to long-standing stress or fear. Its action is slow but sure.
Oil of neroli also has a pronouncecl action on the skln. Like lavender and geranium it can be used witn benefit on any type of skin. It is totally non-irritant and may be used where there is irritat:;on or redness.

It is saia ~o be useful for dry skin and broken veins.
It is one of the oils which acts on a cellular level stimu-lating the elimination of old cell~ and the growth of new ones. Neroli makes a luxurious, relaxing, and deodor-ant bath oil.
Orange-flower water is soothing, digestiv~, carminative. It makes a very useful, mild remedy for infants ' colic, ~nd its sedative action helps to send them to sleep. n Valerian oil is the essential oil obtained from the root of Valeriana Officinalis. The folk medicine literature lists the : valerian root (fresh or dried) as being useful as an antispasmodic, carminative, stomachic and sedative. It has been used to treat migraine, insomnia, hysteria, fatigue and stomach cramps that : : cause vomiting (A.Y. Leung, "Encyclopedia of Common Natural ~ Ingredients", John Wiley ~ Sons, New York, N.Y., 1980,pages 317-320).
:
Regardinq valerian oil' 5 US~ in ~ussia, Hutchens, et al, ~: ~ ~Indian Herbalogy of North America", ~published by Merco of :~ Windsor, Ontario, Canada), 5th edition, 1974, states: !
.~
.~ "Russian Experience: Valeriana is known to Folk Medicineas having a general calming and sedative effect on the ~- centra1 nexvous system, to induce sleep and rest, spasms of the stomach, intestines and blood vessels, nervous heart conditions. Further acknowledgement a~ appetizer, headache relief, hysteria, epilepsy, tape worm, diarrhoea, lose stomach, fever.
Externally: Vapour baths given to children will quieten and encourage restful sleep (Bello-Russ, Academy of ~ Science, Minsk, 19 65) . n : In "Sedative Principles of Valeriana Roots n ~ Hikino, et al,Shoyakugaku Zasshi, 34, (1), 1980, pages 19-24, it is indicated that compounds possessing sedative activity, isolated from : valerian roots, have failed to fully account for the sedative :~ activity exhibited by the roots per se. It is further statedtherein that, rece~tly, iridoids named valepotriates were isolated ¦las analgesic a edative principles from Inclian valerian roots.

1;~:76S~8 In this paper, a correlation between the contents of the valepotriates and the pharmacological activity of various valerian roots was examined. Napalese and Chinese valerian roots contain-ing an appreciable quantity of valepo~riates showed no sedative activity, while Japanese valerian root containing less valepotriates inhibited stress-induced ulcer formation and pro-longed hexobarbital-induced sleep in miGe. An extract of "Hokkai-kisso", i.e., roots of a Japanese valerian, was frac-tionated and the effect of each of the fractions on the enhance-ment of hexobarbital anesthesis was tested. Ressyl glycol diacetate, Kessyl glycol 8-acetate and Ressyl glycol 2-acetate were obtained as active principles therefrom. The enhancement of hexobarbital anesthesis by Kessyl glycol diacetate was assumed ~
~o be due to its inhibitory effect on the central nervous system. !
Kessyl glycol diacetate exhibited no inhibitory action on the stress-induced ulcer production.

The chemical constituents, pharmacology and known uses of valerlan are reviewed in: "Herbal Remedies Used in Sedative and Antirheumatic Preparations: Part I", Phillipson, et al, The Pharmaceutical Journal, July 21, 1984, pages 80-82.

Another potentially interestinq plant substance is nutmeg which was impcrtant in medicine as well as in cooking. It was used as a therapeutic by Arab physicians as early as the 7th Century A.D. for treatment for disorders of the digestive system, kidney disease, pain and lymphatic ailments. Nutmeg is a significant item in the Hindu Pharmacopeia wherein it has been prescribed for fever, consumption, asthma and heart disease.
Nutmeg is employed by folk practitioners in India as an analgesic and sedative. In large doses ttwo teaspoons or more of ground nutmeg~, nutmeg exhibits mild hallucinogenic activity, the description ~y Payne (R.B. Payne, New Ellgland Journal of Medicine, 269, pages 36-38 ~1963]) being illustrative of this activity.
Two college students, 19 and 2~ years old, each consumed two tablespoons (14 grams or the equivalent of two whole seeds) of powdered nutmeg in milk. About ~5 hours later, each had the onse~l of a leaden feeling in the extremities and a nonchalant detached I
mental state described as "unreal" or "dreamlike". Rapid heast 1, rates and palpitation were observed and both complained of dry mouth and thirst. See, also, Wiel tA.l'. Weil, Ethnoph~rmacol.
Search Psychoact. Drugs ~Proc. Symp.l, 19~7, lPub. 19~9J, 188-201).¦

~2768~

The fraction of nutmeg responsible for the mild hallucino-genic activity is suggested by the literature to be the aromatic fraction of the oil containing safrole, methyleugenol, eugenol, methylisoeugenol~ myristicin, elemicin, isoelemicin and methoxyeugenol as the major components. Of these, myristicin, elemicin and isoelemicin have been reported to be the active molecules (A.T. Shulgin, et al, Ethnopha.rmacol. Search Psychoact.
Drugs lProc. Symp~], l967, lPub. 1979], 202-214). The myristicin-~elemicin fraction of oil of nutmeg produ~es many of the activitiesof crude ground nutmeg but lacks adequate potency to explain the nutme~ intoxication syndrome on a quantitative basis. Nutmeg and synthetically-made myristicin show a mild degree of monoamine oxidase in~i~iting activity~ The monoamine oxidase activity is found in the volatile cQmponent of nutmeg (E.~. Truitt, Jr., EthnopharmaCol. Search Psychoact. Drugs [Proc. Symp.], 1967, [Pub. 197~, 215-2~2).

Nut~eg oil, ~nown as ~ , or myristicaceae, is the essential oil from the kernel of the fruit of t~e nut~eg tree. The stone of the fruit is enclosed within a husk which, when dri~d, is known as mace. "Mace Extract" is an aromatic essence extracted from mace. nNutmeg Butter~ is a fixed oil obtained by hot_pressing the nutmeg kernels, and contains myristine, butyrin, olein, palmitine and s~arine. The essence contains 80~ pinene and camphene, 8S dipentene, 6% terpenic alo~
(linalool, borneol, terpineo~.~nd ~eraniol), 44 myristicin and various substances such as eugenol and safrol. Valnet, "The Pr~ctice of Aromatherapy~, (supra) states that, for external use:

. ~
(a~ "nutmeg butter~ is used in liniments for the treat-ment of rheumatic pains and toothaches; and (b) "nutmeg butter" is used in the form ~f "nerve balm~
for treatment of rheumatic pains, the form being a mixture of the essences of rosemary and clove ~ogether with nutmeg butter.

~;Z 7~38 A form of nutmeg oil, 1~r~tica castaneifolia (Myristacaceae~
Fi ji is described as pos~essing biologica1 acti~,rity, specifica11 in the antitumor field, in t~.S. Letters Patent 4,352,797 issued on October 5 ~ 19 8 2 ., At page 4 of the Jarl~aary/February 19 8 4 (Vo1. 6 , No. 1) edition of FOCUS ~orld Wildlife Fund-U.S , ~, nutmeg is indicated as being an analsesic a~d a hal1~ir~gen. In ~e paper "Nutmeg a5 a Narcoticn by Ralbhen in Angew . Chem . 8 3, 379 ~19713, Kalbhen dis~loses that the hallucinogenic ingredients of nutmeg include, interalia,:

(i9 My~isticin having the structure E lemicin having the structure:

,~
P
~~

:' and (iii~ Isoe1emicin having the structure:
. ~
~ C~

~2~7688~

Fur~hermoxe, M _ is disclosed at Chem.
Abstracts, Vol. 101, No. 2831g (abstract of Japan Kokai ToXkyo Koho 59/55,827) as bein~ useful in the field of drug stabilization in conjunctiOn with the utilization of transdermal Dharmaceuticals.

Furthermore, isoelemicin having the structure.
..

O
~ ~o~f O~

.: ` .
i~ a known fla~or ingredient as set forth in U.S. ~etters Patent 3!686,004 issued on August 22, 1972~
__ . By th~ same to~en, myristicin having the structur~:
'' O~
:
~f, iY disclosed as a component of the aroma of blueberries in ; J. Sci. Food A~ric., 1983, ~4~9), 992-6 (abstracted at Chem. Ab~tracts, Vol. 99:174466rl.
~' Furthermore, re~arding myristicin, Arctander, nPerfume ~
Flavor Chemicals (Aroma Chemicals) n ~ published by the author in ' ' 76~

1969, state~ at l~no~raph 2291, that myxisticin is:

5'Pl~asant and waxm-balsamic, slightly wocsdy odor of good tenacity. ~e undiluted material Rhows ~ome ~p~pperines~ " .
This material, although co~nmonly fou~ld ir~ natural oils, has found only limited use in perfumery,, . "

T~l~ essential oils de~cribed above are al50 common perfumery ingredients ~3 de-~cribed in Arctan~er/ "~er~ume and Flavors ~ , Material5 o~ Natural r~ nn~ publi5hed by the ~uthor in 1960.
Mace extract at columns 391-393; neroli oil at columns 435-437;
nutmeg oil at coll~s 442-445; and valerian oil at columns ".

. `'~.

.

::, :
, ~ .
_, ." .

~'76~388 3. summary of the Invention our inYentiOn is concerned with a method for causing the reduction of physiological and/or subjective reactivi~y to stress in a human subject to stress conditions which comprises the step of administering transdermally or through inhalation to said human an effective physiological and/or subjective stress reacti-vity-reducing substance which may be one or a combination of any one of the following materials (sometimes referred to herein as "active(s) n);

(i~ Nutmeg oil;
lii) Mace extract;
(iii~ Neroli oil;
(iv) Valerian oil;
(v) Myristicin;
(vi) Elemicin; and ~-. (vii) Isoelemicin.

The active(s) can be administered alone or as part of a composition which may include ethyl alcohol and/or perfumes.
:~ Perfumed articles may be employed to apply the actives. Examplesof such perfumed articles are solid or liquid anionic, cationic, nonionic or zwitterionic detergents, fabric softener compositions fabric softener articles, cosmetic powders, hair preparations, deodora~t sticks, air fresheners and perfumed polymers.
. .
Specifically, with regard to dose levels, the "actives~ are to be divided into two groups:
.::
Gro_p "ALEPH"
. ~
Nutmeg oil;
Mace Extract;
Neroli oil; and Valerian oil : (taken alone or in combination~.
I
~ .

~L27~8~

;`- Group ~ETH~

.i , ..
;~ I M~ristlcin lemicin; and ~` Isoelemicin (taken alone or in c~mbinationi.

The Grou~ nALEPH" dose or amount administ~red, for the ~ur~ose : of our invention, is from about 13 micro~rams u~ to about ~`.. 1000 micrograms. The Gr~UP ~BETHn dose or amount administered,for th~ purpose of our invention, is from about 0.013 micrograms up to about 50 microgram.~. When Groups ~ALEPH" and nBET~"
are used in combination9 the dosage or amount administered is : from about 0.013 mierograms up to about 1~00 micrograms with an upper limit of the Grou~ "BETB~ ~a~tives~ within said ~h combination being at about 50 micrograms.
The term ~amount administered~ is intended herein to mean "amount ca}culated to have been br~athed in, retained and absorbed into the bloodstream or transdermally absorbed into the blood-streamn. The assumptions that underlie the calculations of the : . above levels are presented in Tables I and II and associated text, infra.

~;~, A preferred mode of this invention i~ administration throuqhinhalation, and to do so by incor~oratin~ the ~active(s)~ in an enclosed environment such as a room and, accordin~lv in the ~:~ atmosphere around the occu~ant(s) of the enclosed environment.
Such is accomplished, for exam~le, by in~luding an "active" in : an air freshening composition. Accordingly, another measure for practice of this invention is inclusion of from about 1 up to about 125 micrograms per liter in the air of a room o~ the stress reactivitv_reduction ~active~s~ n of our invention.
' ~
.

~ ' ,.

~L2~6888 Reduction of physiological and/or subjective reactivity to stress resulting from practice of this invention is demonstrable objectively by means of a decrease in the systolic blood pressure of the human and subjectively in self-report of a significant increase in calmness and happiness and a significant decrease in embarrassment and anqer under stress conditions.

The method by which ~he effect of the stress reactivity reducing substances of our invention has been ascertained is novel. This is the first method that uses a combination of psychological measurementS, physiological measurements and a stressor to measure the effect of postulated stress reactivity-reducing substances taken alone or taken further together with ethyl alcohol and/or perfume composi~
tions vr per~umed articles or colognes on physiological and/or subjective reactivity to stress~
~'., ~%7~ 38 DETAILED DESC~PTION OF THE INVENTION

,.'~
our invention n~cessarily also involves a method for detectin~
physiological and/or sub~ective reactivity to stress in a human comprising testing a human likely to exhibit physiological and/or ~:~ subjective reactivi~y by:
:
measuring the initi21 blood pressure and mood of said human; then ,~
ii) administering stress to said human by means : ~ i of application of a stressor:

(iii) simultaneously measuring blood pressure change and ~` ~ood change r~sulting from the application of said :~ stress to said human: thereafter - .
iv)~ administering a postulated stress reactivitV-reducing substance to said human; and ~ (v) simultaneously measuring the blood pressure change -~ and mood change in said human resulting from the ~ application of said postulated stress reactivity-:~ reducing substance during the aR?licatial of sa~d st~essor to said human.
.
: :~ As has already been pointed out, our invention is directed to a method for causing ~he reduction of physiologi ~ and/or sub-~: jective reactivity to stress in a human being subjected to stress . conditions whlch comprises administering to said human an effective i .
,;

~Z7~
amount of a substance which may be one or a mixture of:

Nutmeg oil;
Mace extract;
Neroli oil;
Valeria~ oil;
Myristici h~v ~ ~ e:

~lemicin h irg h~

; and/or Isoelemicin having the structure:
O~
/o~o~

:

-14-~27~
taken alone or taken fusther toqether with a carrier which may be a perf~med article or cologne and/or ethanol.

Inso~ar as the nutmeg oil, mace extract, neroli cil and valerian oil are concerned, the various varieties of such ma~erials are useful in the practice of our invention. Thus, for example, Nutmeg Oil East Indian or N~tmeg Oil West Indian are useful in the practice of our invention. Standard commercial mace extract is useful in our invention as is the more highly purified form thereof. Commercial valerian oil is useful in the practice of our invention as is the refined version, doubly : distilled Yalerian oil.

In addition, naturally occurring or synthetically produced myristicin, elemicin and isoelemicin are useful in the practice of our invention.

; Thus, myristicin haYing the structure:
. ~
`~ O~
0~"0 may be isolated as by distillation from Nutmeg Oil East Indian or West Indian or Nutmeg Oil Fiji or it may be synthesized according to the reaction sequence:
., j~
0~ O~

l I HO~[~ ~o~ H0~[~O~

~ ~27~8~13 ¦¦ o /0 ,~ 0~

1~ ~' ~'~
I ~ `.,Cl~

~
, ., ; Thus, our invention is directed to the use of one or a mixture f the following ingredients:

Nutmeg Oil;
Mace Extract;
Valerian Oil;
Neroli Oil;
Myristicin;
Elemicin; and/or Isoelemicin, : ::
`:~

. .

~,276~8 which lngr~dients~ i.e., the ~active(s)W~ mav be administered alone or further to~ether with a ~non-a~tive" cærrier comoosition (~uch ~s (~) ethanol or (ii) a carrier ~erfume com~osit~on or ~ ) a c~rrier perfumed article) for the reduct~on of phy5iologic chang~ and/or subjective ~anifestations of reactivity ~ a human bein~ ~ubjected to stress conditions.
Th~s reduction in reactivity decreases the ~ystolic blood pressure ~urge~ caused by 5tress and generates a ignificant increase in calmness and happiness and a si~nificant decrease in embarrassment and an~er in said human. The ~hysiological ch~nge and subjective manifestations of reactivity to stress and a reduction of reactivity to ~stress~ ar~ auantifiable, see Examples II, III, IV and ~, infra.
To repeat, the ~acti~e~ stress reactivity~reducing substances of our invent~o~, to wit:

Neroli C)il;
Mace Extract;
IJutmeg Oil;
Valer~L~n Oil;
~Syristicin;
Elemicin; and Isoelemicin are, in their ~wn right, perfumery sub5tances 1cnawn in the prior art. For example, myristi~in having the structure:

contributes an interesting spicy aroma to per~umes..

~%7G8~38 However, the terms ~carrier perfume~ and ~carrier perfume compo~ition" ar~ ~sed herein,within an inert carrier context to mean mixtures of organic compounds(other tha~ ~uch "a~tives") including. for exam~le, fra~rant alcohol~, fragrant aldehydes ~uch as~for examole,the aldehyde havinq the structure:
~ "

ketones, nitriles~ ethers such as,for example,the cyclic ether having the structure:

~ d and the cyclic ether having the structure:

~h (but excluding, of course, elemicin, isoelemicin and myristicin~, and ~uch materials as lactones, hydrocarbons, syn~hetic essential oils and natural essential oils (excluding, of course, the natural essentia~ oils: nutmeg o~l~ valerian oil, neroli oil and mace extract) in ~d~xture so t~at ~h~
combined ddors of the individual components produce a pleasant or desired fragrance.

.

~27~8!38 ~ lthough ~tate of th~ ært perfume and c~ologrl~ compo~ition~
are contemplated for ~arrier purposes in practice c: f this inventiO~, the '~active5n are fragrance3, ~nd therefore ~; i 30me comments here about perfumery practices are warran~ed.
.
Perf~ame compositions usually contain (a) the main note or the "bouquet" or foundation stone of the composition; tb) modifier~ which round off and accom~any the maln note; (c) fixatives which i~clude odorous substances which lend a particular note to the perfu~e ~hroughout all .8tag~s of ~aporation and ~ubstances which retard evaporation; and ~d) toDnotes which aEe usually low-boiling fresh smelling materials.

perfume com~ositions~ each indlvidual component will contrihute its particular olfactory charactexistics bl~t the overall effect of the perft~ne composit:Lon will be the sum of the ~f fe~ts of each in~lredient- Thus, individual perfumery compounds or mixtures thereof can be use~ to alter the aroma characteristics of a proposed perfume composition, for example, by highlighting or moderatin~ the olfactory rea~tion cor~tributed by anothex ingredient in the composition. The ~acti~e~" of this invention will alter ~he aroma characteristic3 of a carrier perfume composition in addition to causing stress reactivity redu~tion in a human who is subjected to stress conditions. ~herefore the aroma desired for the composit~on ~s a wh~le~Father than the ~roma Qf ~h~e~ ie.r pe~.~u~
formulation alone,should be made the basis upon which the carrier perfume composition is formulated.

It should be appreciated that a perfume or cologne composition containing "actives~ is b~ing administered by inhalation, and, to the extent the composition has been ap~lied to the skin, transdermally as well. Air freshener compositions are administered almost entirely throuqh inhala~ion.

-19- ~27~8~

The amount of the stress reactivity reduction perfume composition required for effective action (with r~gard to the user~
depends on many factors including the skin condition of the user;
the environmental conditions durinq the period of desired effec-tiveness (e.g., humidity, temperature and pressure)~ the emotional ~tate of ~he user at the point in time of a~plication; the physi-cal characteristiCs of the user including body weight and bas~
line systolic bl~od pressure at the point(s) in time of applica-tion(s). All of which is to say that individual reactivity and feelings of comfort by a user will determine the amount effective for that user.

The perfume composition may be used"a5 is~ (e.g., 10~%) or in a "cologne~. Directions for quantity to use and frequency of use, as w211 as variations in the formulation, e~g., summer and winter ormulations, may ~e employed to assure th~t effective levels ~: of the activesn may be administered. For the purpose of this invention, thé term ~colo~ne~, as exemplified hereinafter, means a perfume composition incorporated in an alcoholic or hydroalcoholic solution. ~he perfume.composition can vary between 1 to 99% and the balance of the formulation is comprised of alcohol or a mix-ture of water and alcoho~. The water:alcohol weight ratio can vary from 50:50 to 0:100. Examples of alcohols ty~ically used in these products are SDA 39-C and SDA-40, either 190 ~proof~
or anhydrous (See ~Ethyl Alcoho~ Handbookn, 5th Edition, Published by National Distillers and Chemical Co.). The cologne composition can also contain solubilizing agents, emollients, humectants, thickening agents, bacteriostats or other cosmetically-used ingredients.

Although perfume compositions and cologne~ would normally be considered to administer the "actives n by inhalation or smelling, pla~ement thereof on the e~idermal skin tissue generates, also, transdermal ~enetrative administration. -:' ;
: ~ Perfumery materials which are compatible with the stress reactivity reduction su~stances have been emDloyed in aromatizin~ carrier perfumed articles. Such ~erfumed articles in~lude fabric softener com~osit~ons, dryer-added fabric softener articles, ~.g., BOUNCE (a Registered Trademark of the Procter & Gamble Company of Cincinnati, Ohio~, cosmetic powders, t~lcs, solid or liquid anionic, cationic, nonionic or 2witterionic detergents ~nd perfumed polymers a~ well as deodorant sticks, hair preparations and bar soaps as exemplified, in~ra .
., .~.

-20~

Furthermore, ~erfume materials which are com~tible with the ~tre~s reactivity-reducing substances of our ~nvention h~e been employed in ~ir fres~ener~. Th~s, a gr~at number of state-of-the-art perfume composit~ons and perfumed articl~s are ~vailable for use 85 the non-active carrier (per~umed) sompositio~ and (perfumed) article5 within whlch the ~actives"
; may be incorporated for practice of this ~vention.

Thus, t~e stress reactivity-reducing substances can be used alone or taken toge~her with carrier perfume ~ompositions alone or through carrier perfumed article~. Many well known ;articles of commerce may be the carrier such as ~olid or ;liquid anionic, cationic, nonionic or zwitterionic detergents ' bar soaps, space odorants and deodorants; colognes, : toilet w~ters, hair pre~arations, such as lacquers, brilliantines, ~nd pomades; cosmetic pre~arations9 such as creams, deodorants, hand lotions and sun screens: and powders, such ~s ~talcs, dus~ing powders, face powders and th~ like. When erfume compositions are used as a~ olfactory com~onent of a perfumed article, such as a ~olid or liq~id anionic, cationic, nonionic or zwitterionic detergent or a cosmetic powder or a deodorant stick, as little as 0.1% by weight of the overall perfume and stress reactivity-reduci~g aactive(s)~
(in combination) in the perfumed article will suffice. In space odorant aPplications~ on ~he other ha~d, as much as 99% of the combin carrier perfume substance and stress reactivity-reducing substance can be present. Thus, perfumed articles may contain in the range of from about 0.1% up to about 99% of a composition of matter consisting essentially of the stress reactivity-reducing "active (S) n and "non-active" carrier perfume substance.

It is interesting to note that when a stress reactivity-reducing ~active~ is used in a deodorant stick or deodorant bar soaps to practice our invention, a twofold effect takes place:

li) the deodorant stick itself acts as a ~deodorant" in the axillary area o~ the human being and (ii) the stress reactivity-reducing "active(s)~ is administe:
hy inhalation or transdermally to cause reduction in physiological and/or subjective reactivlty to stress in tho5e individuals subjected to stress conditions ~2761~8 thereby g~ving rise to a double efflcaciou~ re~uction ~n "malodor"
evolved from the axillary r~gions of ~uch human to the surroundin~
environment.

The term ~perfumed article" also ~ncludes solid-form polymer-q, such as polyethylene, polypropylene and other oolymers which contain pores within which are occluded a carrier perfume composition combined with the ~tres~ reactivit~-reducing ~active(s)~. Such perfumed polymers can be produced as described herein or accordinq to an~ technique well know~ to one having ordinary s~ill in the art.

In addition, the stress reactivity-reducin~ substances of our invention, e.g., neroli oil, nutmeg oil, mace ~xtra~t, valerian oil, myristicin, elemicin and isoelemicin taken alone or taken in combinatio~ may, by themselves, be absorbed into the interstices of microporous or macroporous ~olymers~ Furthermore, like carrier-~ of materials other than synthetic polymers can be used to senerate a ~erfume article~ such as a gum (e. q., guar gum, xanthan gum, or gum arabic) or an enca~sulating compo~ition such as a gelatin (as by coacervation) or such as a urea~formaldehyde prepolymer to form a uxea/formaldehyde polymeric wall around a liquid center, which liquid center contains the stress re~ctivity-reducing "active(s) n alone in conjunction with ethanol and/or a ~ar~ier ~erfume composition.

Unli~e anti-anxiety drugs, as mentioned su~ra, the effect of the "actives" materials is to reduce the ~hysiological and/or subjective reactivity to stress in a oerson who is subjected to stress conditions. Individuals who are not being subjected to stres~ conditions do not react to the administration of any of the above-mentioned ~act~ve(s)~ according to the 'practice of this in~ention.

Unli~e meditation or biofeedback, no training ~eriod is required for the human who is to be treated in order to e~fect reduction of physiological and~or subjective reactivity to stress. The effect(sJ of an "active" material, e.g., nutmeg oil, mace extract, neroli oil, valerian oil, myristicin, elemicin and isoelemicin, o~curs within four ~inutes after initial inhalation or smelling of the substance by the individual under stress to whom the substance is aclministered.

~.27E;!3~

The wei~ht ratio of stress reactiv~ty-reducin~ ~active( )~
to the ingr~dient in the oarrier ~erfume com~osition, cologne or the perfumant applied to ~e~erate the carri~r ~erfumed article is in the ran~e of from about l~lao u~ to about 100:1.
Is is emphasized that the carrier perfume com~o~ition, colo~ne and perfumant ap~lied to generate the carrier perfumed article do not otherwise contain any other stress-reactivity reduoing substance~, or for that matter an~ stress-affecting or hypoten iv~ sub5tances ~mployed in the medical arts, for example, benzodiazepine dexivatives fo~ anxiety and methyldopa or propranolol for hypertension~

Our inv ntion expressly contemDlates the use of ethyl alcohol i~ conjunction with the "actives~. The ethyl alcohol may enhance he efficacy of the ~actives". As has already been ~ointed out ethyl alcohol is a major component in standard ~ologne compos itis~ns .

Whe~ the stress reactivity-reducin~ ~active(s)~ is used in conjunction with ethyl alcohol, the weight ratio of "aative (5) n to the ethyl alcohol (based upon pure ethanol) is in the range of from about 1:99 u~ to about ~9~ he ethanol used in conjunction with practice of our invention mav vary from 50~ aqueous ethanol up to 100~ (absolute ethanol~.

One great advanta~e of the practice of this invention f~r the reduetion of physiological and/or subjective reactivity to stress in humans is the fact that the dose level of ~active(s)~
is mlniscule: being of the order of micrograms.

' :
,,~

~9~7~

5pecifica11Y wit~ regard to dose level , the ~ctives n are to be divided into two groups:

Group "A~E _ Nutmeg oil~
~ace extract;
Neroli oil; and Valerian oil ~taken ~lone or in combination) Group n BETH ~1 Myristicin;
Elemicin; and Iso~lemicin (taken alone or in combination).

The groUD "ALEPH" dose for the purpose of our invention is from about 13 micrograms uo to about 1000 micrograms. The group ~BETHn dose ~or the ~ur~ose of our inventio~ is from about Q.~13 micrograms up to about 50 microgra~s.

When materials from the Groups ~LEPH" and "BETH~ are used in combination, the dosag~ of ~activesW is from about 00013 micrograms up to about 1000 micrograms with an upper llmit of the Group ~B~TH~ component within said combination being about 50 micrograms.

One of the preferred modes of this inventio~ is administration of the ~tress reactivitv-reducing composition by incorporatina the "active(s) n in the environment surrounding the user. Such is accomplished, for example, by including nactive (S) n in the air freshening composition. Accordingly, another measure for oractice Oe this in~ention is inclusion of from about 1 up to about }25 micrograms ~er liter of ~tress reactivity reducing ~active" in the air of a room.
Preferably, a qroup ~ALEPH" nactive" is used for this pur~ose.

~.
~i ~L~7~ 8 Reverting to "active~s)~ dosage ran~es in ~eneral,at the u~per bound of h~ ratio of weight of a carrier perfume compo~ition (containing no ~active5~):weight of na~tive" ~rou~
~ALEPH~ (that is, 100:1), the tot~l amount of ~erfume composition used requires a range of from about 13 micrograms up to about 1000 micro~rams nacti~ and thu~ requires a range of from about 1300 micrograms (1.3 mg) up to about 100,000 microgram~ (0.1 ~m) of non-active-containing ~arrier perfume compositionO Furthermor~, at the upper bound of the r~tio of weisht of perfum~ composition (containing no ~active~ weight of ~active~ Group "BETH~ (that i~ 0:1), the total amount of perfume composition used cont3ins a range of from about 0.013 micrograms up to about 50 micrograms "actives~ and thus oonstitutes a range of from abou 1.3 micrograms ~p to about 5000 micrograms ~5 mg) of non-active-containing carrier perfume composition.

By the same token, at the lower limit of the ratio of weight of a carxier perfume composition (containing no "actives n ):
weight of ~activc" Group "ALEPH" (that i9 ~ 00) ~ the total amount of perfume composition req~ires a range of fr~ about 13 mi~rograms up to about 1000 microgram~ nactives~ and thus require~ a range of from about ~.13 micrograms up to about 10 micrograms of non-acti~e-containing perfume composition. At the said lower limit, the ratio of weight of perfume composition (containing no ~activesn):weight of ~active" Group "BETH'I (that i8~ 1:100) ~ the total amount of perfume composition used nonetheless contains a range of from about 0.013 micrograms up to about S0 micrograms "actives" and thus constitutes a ran~e of from about 0.00013 micro~rams up to about 0.50 microqrams of non-active carrier perfume composition. Thus, the working ranges of perfume + "active~) compositions contemplated within the scope of the inve~tion vary as fol~ows:

(a) For Group WALEPHn ~activesn - from 13 micrograms up to 100,000 micrograms (0.1 grams); and (b) For Group ~BETH~ nactives~ - from 0.013 micrograms up to 5000 micrograms (5 mg~.

~76~

As previously ~ta'ced, perfumed article. contemolat~d w~in the scope of t~is in~nt~on m~y ~ontain ln the ranqe of from 0.1~ up to 99% by wei~ht of combined ~on-active c~rr~er perfume an~ ~active(~)n. Also, a5 pre~iouslv stated, the weight ratio of carrier per~ume: ~active~s)~ may vary from about 1:100 up tQ 1~0:1.

It thexefore follows th~t 100 grams of a perfumed article employed ~n pra~t~ce of our invention will co~tain rom about 0.1 gram~ up to about 99 .0 grams of a perfume composition that includes ~active(s)~.

It follows also that practical restraints exist u~on ~ractiee of this invention through perumed articles. ~r exam~le, when administration of nacti~es~ from Derfu~ed garments is desired, transfer of ~ac~iYes~ to the garments from perfumed ;detergent may not be ~ractical. ~owever, transfer from a perfumed fabric softener to th~ abric is more feasible. More oft~n than not practical restraints sim~ly challenge the skill of the formulator when administration is sou~ht from ~erfumed deodorant compositions, co metic ~owders, hand soa~s, and the l~ke, for example. Some perfumed articles offer less of a challenge to ~he formulator, or no challenge at all; air freshener ~ompositions, for example. The ran~e of 0.1 - 99.o gms o~ perfume co~position per 10~ grams of article shoul~ b~
considered guidelines rather than strict limits.

me uncertainty is acknowled~ed also for the~range of 13-1000 micrograms of "A~EPH~ group ~active(s)" and 0.013-5 micrograms of ~BE~H" group ~active(s) n, The experimental effort underlying this invention may not translate exactly to the dosage range suited to large scale practice of this inventio~ for 5necessarily) having been conducted under artificial conditions. For better understanding of this inventio~ and as aid to ~ranslation of the exemplary material ~herein into large scale practice of the invention,detail5 of the experimental conditions and dosage assumDtions made by the i~ventor hereof are now provided.

~27~ 38 - In ~pecific,the effective dose levels for Groups "AL~PH"
: and "BETH" s~t forth abov~ con~titute estimates of auantities breathed in and effectively taken u~ by the subjects from ~
per~E~'s blotter a~ described in Example I~, infra, or rom a wick-vial arrangement as described in xamDle~ and IV, infra.

The source of the stress reactivity reduction composition was about 1.5 inches from the subject t 8 nose. For the estimation of dosayes, the following assumptions were used:
:
~ 1. Breathing rate for an average subject at rest .~ is 10 liters per minute.

2. The ~otal amDunt of substance breathed in ~nd re~a~x~ is 25%
of the material that is eVaDOrating. We assumed ~:~ intake of 50% of the materi~l e~aDorating from the source. Of the material breathed in, 50% was subsequently exhaled.
~..
: 3. The total amount of the substance effectively taken ~~ up by the body is about 10% of the breathed in and ; retained substance.
. , 4. The average body weight of a human being is 6S ~g.

The assumptions used for estimation of dosages were based on measured plasma levels for ~9-tetrahydrocannabinol (~9THC) that had been administered by inhalation of marihuana smoke. For this situation S0~ of the ~9-THC breathed in was retained and approxi~
mately 10% of the retained material was found in the p}asma.
(Nahas, G. and Paton, D., eds., "Marihuana: Biological Effects,~, in Advances in the Biosciences, Vols. 22/23, Pergamon Press, ~.Y., f l979], page 289.) In addition to the abov~ assumptions, the lZ76888 followin~ parameters were measured:

1. The ~mount of substance evaporatinq from the source ¦ of post~lated stress reactivity-reduction composition was obtained by weight loss measuremen~s.

2. The concentration of Group "BETH" component~s), e.g., ¦ Myristicin, Elemicin and Isoelemicin in the head-space was measured by gas chromatography.

3. The total time that the subject breathed the stress reactivity-reduction substances was 20 min~tes.

The following Tables I and II present a summary of our results, ~` I
~ \ :
¦ \ 5SYACE Ll!:FT I~LANK INT13NTIONALLY

.,~. \, I

-28- ~,27~ 3a~3 Il I ~o 11 1 ~ I I ' C
1¦ r ~ X ~

~ S: O ~ h ~ .,~ 0:
~ ~ ) :~ ~ O ~: , ~ ~ ,o ~. .~ _ _ _ _ 11 ~o I ~c c ~ -c l ,,., ~D Uo~ lCI

11~u ~&~ I ~ c~
~ ~ I 1 , I ~ U o~
, `.' ~ ~ -- - - ~
:~ 11 v I v ~ , ~=~
~ o ~v ~ ~ : ~v v~
a~ ~ ~ ~ ~ ~ O
11 o ol g~
~) ~ N
F, r~ O ~ ~ _~ N
h ~ ~) ~5 0 o ô o o ~ _~
~ ~ r ~0 ~ -~0- I O

~ X ~ ~ ~
:

l ~o, I lZ76~

e t~

~ ~ I ~ O o O

~' I

9~

. L C i ll ~

ll~ ~ t~
::

~ -30- ~ 7G~

; i ~ O S

~ ~ ~ ~ ~ , 8 ¦ 8 h a 5~ v ~ E v ~ E

o ~ v ~e l s 0 ~ ~1 ~ p a tr~!~ .~ ~o ~ ~ ~ o ~ ul ~ ~r; ~ O O ~ dP
~ i9 . 2 cll .L i Q

u _ ~_ .~1 : h ~ V E S a~

- h 8 h C l ~ E :>h S ~c ~ ~ ~ ~ ~ O O O ,~, ~ a ~ a ~ I

~ : ~ ~ _ ~ ~ a~ o O E 3 ¦ C O x I h ~ I

~ ~,~ h ~

~276888 , : .

~ lthough the experlmental data i3 limited to ~dm~n~tr~tion through inh~lation which trea~ment mode involve~ tran~nort of ~actives~ acros~ inter~al body membrane~, the ~a~tive(s)~ are known to transport across external body membrane~, notably ~: acro~ epide~mal ti~QUe ~ee, for example, di~closure~ of external a~plication of ~a~tives~ in folk medic~n~ and aromatherpy art~. Practice of this invention in~ludes, then, both transdermal ~dmini~trat~on, and throuqh inhalation with, : it i~ believed, the 8ame dosage range for treatment by eithex treatment mode.
~.
`; Th~ followin~ Examples II, IIS, IV and V ~et forth ~rocesses : ~ for preparing and testing stre~s rea~tivity-reducing compositions of our inventio~. Examples foll~wing Example ~, e.g., xample VI, et seq, set forth incor~oration of the s~ress reactivity-reducing substances in perfumed articles.

The following Exam~le I sets forth methods f~r analyzing and producing certain of the stress reactivity-reducin~ substances :` e.g., myristicin and elemicin and the like.
: ., It is to be understood that the invention is not to be so limited to the embodiments herein exemplified, ' ' ~ ' .:
1' ~' ::.
, ~

~ `
: ;
' ' , ~

lZq68~ 1 ISOLATI~ C~F MYP~ISTICIN FROM EAST IND~
M~lTMEG C)IL AND HEAD SPACE ANALYSIS QF
. ~

East Indi~n Nutmeg Oil was carefully distilled on a 1 plate short path column yielding the following fractions:

WEIGHT
VAPOR LIQUID OF
F~CTIC>N ~EMP . TEMP. VACl~UM FRAC~ION
NO ._ ~ C~ ( ~C) ~s i~ t~ms 1 ;` 1 43/4~ 4~/4~ 2~/2~ 26.2 2 ~2 4~ 20.0 77.6 -~ 3 ~3 ~8 20.0 73.1 4 ~5 52 2~.0 67.~

- 5 45 52 20.0 ~4.0 6 ~ 5~ 2~.0 67.6 7 ~7 63 ~0.0 sa.4 ~- ~ ~9 76 2û.0 62.5 g 63 82 5. 0 38 . 4 7~ 1~0 1 . 2 45. 0 11 9~1 108 1 . 2 14 . 3 : ~ 12 98 ~11 1.2 2~.6 13 100 117 1.2 26.9 . 14 96 130 1 . ~ ~7 . 9 . ~ 15 100 1~0 1.0 10.5 . ~__ _ ~ ractions 13 and 14 werebulked and further purified by means o~ distillation on a 6pinning band distillation c~lumn (Nester ~aust Autl~ Annul~r Distillati~n Unit) yielding the following .
`' :

' ~

-33- ~LZq68813 f r~cti~ns:
WE~ G~T
VAPOR LI QU I D VACUUM O~
FRACTIONTEMP. ~EMP. mn~/Hg lFRACTION
tao ~-C3 ~C) PRESSURE (gms) _ _ , 1 68/72 ~56/lS~ ~ ~ 5/0 ~ 6 1 . 7 2 ~2 161 ~.~0 2.9 3 ~4 161 û.60 3.6 1~ 4 72 lSB 0.60 ~1.2 ~ 70 156 0.60 3.5 : 6 74 157 ~. 6~ 3. 2 7 71 159 0.50 ~8.2 8 71 160 0. 55 4 . 9 9 71 159 ~ . 55 3 . 6 71 161 ~. SS 2 . 5 1~ 71 ~6~ 0. 55 2 .
12 66 ~,R5 0.ss 1.7 :
:' ~
- Fractions 7-12 are bulked.

F~_~ is t~e GLC profile for bulked fractions 7-12 of the foregoing distillation (Conditions: ~00 ' X O . 032" ~used silica/
carbowax column programmed at 75-220C at 2C per minute).

The thus-produced substantially pure myristicin was used for . ~ further experimer ts ~s ~et forth in Examples II, et ~eq.
: ;

l _34- ~7~8 EXAMPLE ~(B~
: ~
HEAD SPACE ~ A~YSIS OF
NUTMEG OI~ AMD MACE OI~
'' ~:~ 2 Grams of Nutmeg Oil East Indi~n or 7Sace Oilwas placed in . a 25~ cc ~ingle neck receiver. ~he receiver was fitted with ~
rubber stopper into which was embedded a ~t3inless steel hook~ On the ~o~ was plaeed a 2 cm2 stainless steel 6creen impreg~ated ~ with di~ctylphthalate. The dioctylphthalate absor~ed the ingre-:: dients of the he~d space ab~ve the nutmeg oil for a period ~f~ 15 minutes. At the end ~f the 15 minute period, the ~topper with :~ the scre~n was removed from the flask and the ~ereen w~sremoved :~ from the hv~k. ~he ficreen WQS then placed in ~ ~mall clinical centerfuge and the dioctylphthalate containin~ the ingredients of ~he head ~pace wasseparated ~rom the ~creen by means o~
centrif~gation. The resulting product was then ~ubjected to GLC
' an~lysis (Conditions: OV-l fused silica column programmed at ~S^22DC at 2~C per minute).

~;~; Fi~ure 2 is ~he G~C profile for the head space above the ; nutmeg Oil.

The peak in~icated ~y reference numeral 10 is the peak for : ~ thujene.

The peak indicated by reference numera~ 11 is the peak f~r .` ~-pinene.

~ he pea~c indicated by reference numeral 12 is the peak for sabinene.
''"'..'.
''`' '''~' ,'.'''~', ::

,5 lZ76888 : ~he pe~k ~ndicated ~y reference numeral 13 is the peak for : ¦ B-pinen¢.
~ he pea~ ~ndic~ted by reference numer91 1~ ~6 the peak ~or myrcene.

The peak lndicated by reference numer~l 15 ~s the peak for G -phellandrene.

~ he peak indicated by reference numeral 16 is the peak for 6-3-carene.

. The peak indic~ted by reference numeral 17 is the peaX for c-terpinene.

~ The peak indi~ated by reference numeral 18 is the peak for .~ p-oyme~e.

The peak indicated ~y reference numeral 19 i5 the pe~k for ~-terpinene, The peak indicated by reference numer~l 20 is the peak for ;~ terpin~lene O

: ; The peak indicated by reference numeral 21 is the peak f~s ; linaloolO

~ ~he pea~sindicated by reference numerals 22A and 2~B are the : pea~s for l-hydsoxy-l-met~yl-4-isopropyl-2-cyclohexene, The peak indicated ~y reference numeral 23 is the peak for 2-methyl-5-ethyl furan.

The peak ~ndicated by refere~ce numeral 24 is the peak for 4-terpineol.

The peak indic2ted by reference numeral 25 lc the peak fo-~-terpineol.

~ ~ , :

~2~76~

¦ ~he peak ~ndie~t~ by reference ~umeral 26 is the peak fos l-met~yl-3-hydroxy~4~ propenyl benzene.

The pea~ ~n~cated by reference numeral 27 ~ the pe2k for ; isob~rnyl ~cet~te~

The peak indicated by reference numeral 2B ~ the peak for n-amyl methoxy benzenes.

The peak indicated by reference ~umeral 29 i5 the peak f~r eugenol.

~ he peak ~ndicated by reference numeral 3~ is the peaX for ~ ~ terpinyl ACetateO

~ he peak ~ndicated by reference numer~l 31 ~s t~e peak or . o-cubebene. ,, ¦ The peak $ndicated by reference n~meral 32 is the peak for ~ eugenyl me~hyl ether~

:~ The peak indicated by reference numeral 33 is the peak for ~-copene.

The peaX indicated by reference numeral 34 ls the peaX for trans-isoeugenol~

The peak indicated by reference numeral 35 is the peak for ~-bergamotene.

. The peak indic~ted by reference numeral 36 is the peak for ~;` -pr~penyl-1,2-dimethoxy benzene.

~:: The peak indicated by reference numeral 37 ls the peak for myrist~cin.

; ~he peak indicated by re~erence numeral 38 is the peak for ~-cadinene.

~ he peak ~ndicat~d by reference numer~l 39 is the peak fo~
¦elemicin~.

~27~88~3 ~ e pe~k l~icated by ref~r~nce numeral 40 1~ the pea~ for ~-14llyl-2 ,6-~limethoxyp~enol.
,;
S~ble IY zets fo~th t~-e he~d ~p~ce constituent5 ~f nutme~ oil ~fter the 15 m$~aut~ per~od usin~ the pr~edure ~et forth, supra ~ ter a one hour perioa, using the prc~ce~ure 8et fortll, ~upral, and ~fter ~ 2~ hour perio~, us~ng t~e pro~edure ~et forth, ~upra:

TAELE IV
' ~

5 A~t~r a ~bur~ A-t~r ~1 31ours hu~e~ ~.1~ 2.~10 2.3D
5~0Q 25o2~ SI~
C~ e O~Ct~ 2 S~b1rl~ 2S.20 2~ 0 . ~!1.00 21~ r~ 0 a~.~ 16.S0 a.~o ~ .oo adr~ e ~.00 1.1~ 1.10 :`
~.3 c~ IcOO ~1.00 I.00 rplr~ .00 ~.~0 ~.ao c~no a.30 . l.-o ll~onene ~.60 t.~10 17.00 ~-'ro-p1nen~ ~.50 li.10 6 ~0 Y~ nolelle 1.20 ~1.40 2.20 L1~1~1 ~to ~r~t~ 0.50 D7~ ~ 0 2.S0 ~.BI
~T~r~1n~D~ ~r~c~ 0.20 11.60 ~r~ .2~
' Pcr71~c1~l t~ac~ 0.30 0.~5 '~`
'-,:

, ~
For the purpose of the dose ~alculations, the head space concentr~tlor~s of myri~tl~in wa~ l~ssumed to be 0~ o~ e tota~
nu~meg oll that had evapora,t~d.
::

~7~

~ ble V ~NnaSiz~s tne per~ent myr~iti~n ~n t2~e vapor ~n ~quilibrilam witl~ nutmeg oil or ~n e~u~librium wit~ mace extract ~fter 15 ~ninutess ~ 1 hDur, 2 ~ours, 3 hour5, 41 hc~urs ~nd 24 hours.
The ~nalytic~l prQcedurc f~r the determin~t~on was ~gescribed previo~ly ~n th~ exampl~J

It Jlas been fc~und that nea~ ~autmeg Oil East ~n~ian contains 7.10- myri5tlcin and mace ext:~act contains 31.00~ myristicin.

~ABI.E: V

HEAD SPACE Sl~DY O~ N~'rMEG AND M~CE

15 ~ utes ~r~ce Tr~ce ~:our 0 .10 0 . ~0 2 Hou~s 0.40 2.00 : ~' 3 ~ours O.5o 5.00 4 l~ 0.~0 7.00 24 Hours 0. 75 ~ . Oo ' \

\S SFACE LEFT El~'X INTENTIC~NALLY

' \

~27~8~3 Table Vl ~ets forth overall ~omposition5 o~ Nutmeg Oil E~st Indian, Nutme~ Oil ~erpenless ~nd gwc~ other commerc~al nutmeg oils as well ~s Ma~e Extr~ct:
.~
TAI!ILE VI
..
;~
_ _ _ _ t~ O~L Nl,qME~ Ol t~:WC~ COS~ClRL Ps~
~sr ~DL~; ~ ~ OIL N.~X; OIL E~tr~
C~oun~ 5~ XS!~M?I ~ ' .
u~ ~.5b~- ~; i.5G~ ~.65:
t .. ~ i n2tl-t2 .20 ~ 0 ~. 7D ~.?6 l .10 t~ rl! O.~D 0~15 0.~3 ~rac~
S~b~n~ne ~.73 ~-.B0 ~6.SS 0.~0 l.lO
g-Pinen~ 15.~0 ~1.61a2.0~ l.~D 2.63 ~rc~n~ t.50: 7.70 ~.3D O.S0 0.~
~-Pt~21~ rer~ 0.~ l.lO ~.~0 0.1~ 0.25 uene 0.~ 0.~ ~.~15 ~.~D 0.6 n~n~ 3.~0 4.60 ~ 2.~0 1.3~
~Cgm~n~ 1 .0D ~ .~4~ .'J2 . I OSC
l1~neoæ 6.~0 ~.~0 l~ 2.9~ 3~0~
~ 3.S0 ~.92 a.-D a.~l~ a.2 Trar~-S~n~ne Ill~-et~ 0.~0 0.93 0~3~ 9.~3 ~.a5 tb,~t St~ ne 0.0~ 0.I2'Ir~lcttr~ce O.ID
~rpinolenlL~ 1.~ 3,.D0~.~S 0.'75 ~.20 tis-S~fn~n~ elr~tl~ 0.15 O.~D 0.20 0.~0 0.8B
l~ lool O.I9 ~.~100.~!0 ~.~0 O.. t~
U~ 71~01~ n) . , .. ~.~0 ~I.OD
2-p-~enthen-l.~l 0.14 0.25 0.16~race 'rr~cæ
a~ h~n-l-ol ~5~) Q.0~ ID~l~ 0.10 ~ ~r~;~
~-Eth,~)-5 i~t~l Fllr~nl~o~c~~rcte tt~c~ _ O
T~r~ineol.4 6.00 I0.-13 3.Stlli~90 1.6~
:-Ter~in~ol 11-~0 I-~B 0.470.~0 0.60 ~iper1t~1 ~r~ce ~r~ce tracæl'rae~ ~r-:e ~i~er~to1 tlscH~r) l~r~c~ Trae~ ~r~ce'Ir-ce ~rac~
p-~er.th-~-erl-4-yl-Etb~1 tst~r O - . 0.6D 9.SD
S-~ole ~.~0 ~.00 ~.la l.~ 4.115 ISD ~Orr~1 Acetst~ , , _ `Tr~ce ~race 80rn,r1 Jlc~t~te 'r~ee 0,.~3 lr~ceTr~c~ lracc t~lymol . . . ~r~c~
~ yl An1sole (~) 0.21 o.36 ~r~ceTr~ce E- genol 0.~1 0.36 0.l0O.SD i .0~
1 Acet~te 0.~0 0.20 0.050.10 ô~3G
-Cu~bene ID.OS 0.10 ~r~el~ 0.~10 7r~e V~n1111~n ., . _ tr~ct Ik~l At~t~tc 0.10 0.~ 0.0~0.10 Tr~ce ~us~n~l ~eth.~ r 11.30 O.SO 0.10 î .OD 1.80 ~-to~ne 11.23 0.4~ 0.16 0.93 O.SS
~rDr.i Iso E~ rol 0.31 0.60 tr~c~ 0.71 ~.30 ~B~rg~otl~nc '~r~ee 0.~2 ~-~e~ ~t~ce ~r~c~
le-h,~ S~ Ell~nol ~r~ce tr~cP ~r~t~ 0.35 0.~6 ~ t1t~n 1~ IGl 1 -C~d1nene lr~t~ lr3ce l~i ~r~ce o.lo ~ c~ll 0.1~ 0.-5 0.~7 l.~S 1.20 D~O~c~o1c ~cl~ . _ .. ~rDee -All~l 2,6~ ~ Pl~ l 0.0~ 0.19 tr~t~ 2.~0 ~.OD
ffr~stl~ ,. , . ~5 ~12 Y1 ~tr~fl~c~nat~ _ _ _ ~ 10 2.~0 ~1 ûtt~d~c~flDtçt _ _ _ ~.85 3.00 ~rrl ?al~1t~te . O _ 1 ~D ~.0~
tt~l Olellte .. l _ 1.5D
OCtS~?~nO~C ~C~ t~ E-t~l_ ~ . _~ _1.~0 . . ~g.~ 1~.g6100.00 11~.01 -I
-~o-~ E ~
: IS~LA~I~N OF E~EMICIN F~M Ol~ OF EL~MI
~:

Elemicin was separate~ ~rom Oil of Elemi us~ng the following procedure:

I! Elemi 9il (Contains 7~ ~lemol a~d 3~ Elemi~in) ~ I - 'I -! 1 Distillati~n ¦¦ Enriched Fra~tions (Elem~l 70~ ~nd Elemicin D h dra~on of Elemol ~; ¦ Ses~uiterpenes (70i and Elemicin 30 .1 ! ¦ Column Chromatography -~ I l_ ~
~: ' ~ ~ Dist.
ite~E5Do~ Elemic n~ 94~ Elernicin he 94~ Elemi~in is used ln ~hsequent Examples V, et seq.
~l i , , ~ 11 ::::

~3L2~

EXAMPLE ~(D~

MNRISSICIN SYNSH~SIS

Myristicin for use ~n subsequent Examples II, et ~e~, w~s ~ynthesized ~sing ~s a precursor~ 1,2 dihydroxy-3-methoxy benzene ~; according to the following reaction ~equence:

HD ` ~O

~; ~ ~Bl ~ j t)~ ~~ ~ 1 a~d ':

~ 76~

Oh ~ t ~`

~ o~O
o- I
:~

The is~lated myristicin was used in Examples V, et seq.

~1 lZ7fiE188 EX~MPLE I I

Four Dd ar~t cond~t;or,~i were tosted using l~ f~ctorial exper~- ¦
menta1 desiqn. ~nalysi~ of the resu1ts was ~ ~ two way ana1ys16 of variance. Factors were Fragr~nce ~A" ~nd ~NeutralW Fragrance and levels were ~/- the presence o~ ct;ves~O Ana1y~is of the results was wi~h ~he BMDP ~tatistica1 package ~nd a Digita1 Equipmen Co. (DEC) 11/780 VAX computer. ~n explanation of the analysis of variance (ANOVP.) technique is found in:

.B~ ~ScCa11, "Fundamenta1 Statistic:s ~or Psycho10gy,~ !
2nd Ed. ~ Harco~lrt ~race Jo~ans~vich, ~aew York, t~.Y.; 19750 paqes 236-64, ¦The term ~p~ i5 the ~ignificance 1eve} as s:btained from the ~F~
test ~pplie~ to the A~C~V~ ~esults. "p~ ~5 the proba~i1ity that the results obtained are due to random error.

The composition of the fragrances ~as as fc~ ws:

1. Fragrance ~A~ composit~c~n:

GAI.AXOLIDE ~) lRegistered Trademark of International Flavors ~ Fragran~es Inc.: a tricyclic ~sochroman having the structure:
ll ~ ~b , . 1 ..................... 0.. ~... 47.la : Verdox la ~emic~l manufactured by ~nternational Flavors & Fragrances Inc. ~avi~g the tructurc:

~ 2~76~

Die~hyl ~hthA1~te ........ 0.... ~..................... O 12.6 ~eac~ ~ldehyde C~eur ..... ~.................. ~....... ..10.5 ~renyl Acet~te ........... ~.... ~0.~.................. ...4.0 ~exyl Cin~amic ~lde~yde ....... .~.... 0............... ...2.6 ~o Amyl 8utyr~e ........ 0.... .O.................... ...103 ~lde~yde AA-Tr~plal l~ ~pecial~y ~an~actured by Internat~nal Flavor~
Fr~gran~es In~ h~ving the ~truc~ure:

~................................. ..Ø0~
: Veltol Plus ~ethyl maltol having the structure:
Ço~~ ool Ij 2. ctives~ compositisn-Nutmeg Oil East Indian ............................. ..97.10 Maee Extr~c~ r~ 0~14 Ner41i ~ O~ o.98 . D~et~y~ Phthalate .................................. ..Ø44~alerian Oil Inaia~ O~ o.~S~

. . 3. Fraqrance ~ Active:

Fragrance ~A~ ...... ~.......................... ...60.0 ~Actives~ .......... ~.............. ~........... ...40.0 .
~ ~: 4. Neutral~ Fraqran~e:
., ~ ~ Diethyl Phth~late .. ~.......................... ..100.0~
- ~
: 5. ~Neutral~ Fragrance ~ ~Actives~:

~ ~ ~iethyl Pht~alate .. ..~........................ ...50.9 - i Fraqrance ~A~ ....................... .......... ...10.
~ 'Actives".... ~...... ~.,.............. l......... ...~0.0 .' I
I

, ~ he ~ubjæcts use~ ~or the ~tu~y &7ere ~r~wn ~rom the New Haven, Coranectil:u~ l~re~. Or~ I~undre~ ~Lnd Swenty f~ ts were u ed for the 2xper~m~nt ox tl~rl:y ~l~bjeclts fo~ e~ch ~f th~ four ~el~s.
S~ Içtudy wl-~ run dlc~uble bl~n~. Sub~e~ts were xun ~t one ~t a tim~ ~nd tlle ~cript was presen~e~d ~y tape recorder. 81~od pres-sur~s ~nd heart rates wexe mehsured w~ th an lluto-~nflatable~ pr;nt~ng, dig~t~l sp~ygn~man~reter manufactur~d ~y the q~Sceda Medic~l Co., ~nc. vf ~o~cyc~, J~pzrl.

The prot9col allowed for ~nvestislation o th@ cardiovascular .

~: and mood responses tQ ~ t;tressor with and without Pfragrance1' ;~ or stress reactivity reducer (S2R) trea~mentsO Th~
ob~ective was to provi~le a ~tressor that would produce a ~tress type and level ~imilar tc~ that exper~nced ~n the work pla~e.
A further c~bjec~ive s~as tc~ n-easure both blood pressure and mood ` changes durin~ the ~tress period ~nce the litexature ~as ~h~swn t,hat reactiv~ty to ~tress corr~lat~s with disease. The protocol ~ wàs as follow~:

:~ 1. Attachment of the ~lood pressure cuf f, ~. Questionnaire.
..
3 . Stres~ ~:

~) baseline (b) mood ~elf report (c) 6 low ~tress questions ~LSl) (d) mood ~elf r~port ~e) 6 mild ~tress ques~cions (MS1) tf ) mc~od self report (g~ b2seline ~h) moo~ ~elf report ;, 4. ~reatmen~:

~) Fragrance ~A" c~r b) Fragran~e "A~ ~ ~A~t~ves a or (e) nNelJtr~l~ Fragrance or (d) ~Neutral~ Fra~rance ~ a'Ac;ive~

., , ~i ~2~6~

S O Stre~

~ asel ~ne Ib3 mood ~elf repc~xt ~c) 6 low stress quest~ons (LS2) ~d) moo~ ~elf repor~
~e) ~ mild ~tress questi~ns (MS2) ( f ) moo~ ~el f repor~
(g) base l~ne ~h) mc~od ~elf report .~ 6. Post-experimental questionnaire 7. ~emoval of recording devices and debriefing.

.i The initiaI questionnaire oontained 5~ true~false questions ~ i'taken from the Marlowe-Crowne repression test and the Bendig fo~m ::~ !'o~ the Taylor ~nxiety ~cale. It was used to classify subjects on !!~he basis of repression and anxie~y.
: ;
: Baseline periods in~lved the ~ubject sitting ~till, sesting.
Mood self reports were made by the ubject reporting by means of i'a ~even point ~cale (0-63 his or her degree of relaxation, anger, anxiety, happiness, tenseness, embarrassment, calmness, fear and ,sleepiness. Neutral and mi~d stress questions were taken from ~the Pha e Association ~ests ~. I
~ I Mandlex, et ~ Response t~ Threat: Relations Among : V~rbal and ~hysiological FindingsN ~sychological :~ Monographs, 1961, Vol. 7~, No. 9).

Subjects were ~sked to respond as quickly as possible with the : first phrase that came to mind followin~ presentation of a . ~ stimulus phrasel Neutral questions included ~My name is?U
:~ Stress~phrases ~ncluded: ~The thing 1 like least about myself ~ is.~ nd ~If my child were dating someone of a difference race : I would... ~O
:~

~7~
-~7-Dur~ng the trxatment period ~he ~ubject ~melled one of ~he fragran~es or po~tulated stress reactivity reducing agent~
from a RMeasuring I,lne- ~tyle perume ~lotter c~bta~ned frc~m Franlc Orlandi, Inc. 31-û2 N~rtllern 3c>ulev~rd, Long Island City, Queen, New Y~r~ 9Llltllo The bl~tter w~s ~bout 15 c!n lc>n~ by abou~ cm wide. It was dippe~ ~n~o a 20~ ~olut~on ~f fr~grance and/or postulatea stress reac~ivity redu~ing agent ~n ethyl alc~l to a level ~f a~out 2 cm (the second red line), ~llowed to dry fc~r five mi~utes and then pc~sitioned a~out C cm frt~m the subject's s~c~se .

The fir!al questionnaire asked for the subjectts reactions to tt~e exper;ment.

~ rhe analysis ~f variance of the resull:s ~howed significant changes in sys'co~ic blc>od pressure and ~el~ report:s for lthe subjects 6melli~g either fra~rance ~IAa plus ~actives~ or ~Ineutra fragrance plus ~actives~ versus the ~b~ects ~mell;nq the .fra~rance ~A~ or the ~neutr~fr~grance ~lone, The chan~es deemed to ~e relevant to the every day ~tress and stra~n of life were the blood pressure and mocd changes due t~ the stress ~uestions relative t~ the low stress questions ~UMs - LS); ~ee the protocol for definiti~ns ~f M5 and LS). Tc obtain ~ Change score for a part~ular c~ndition the changes before and after the c~ndition were c~mpared thusly:

Change due to the fragrance ~ or~neutrala fragrance ~ N;
and N ~ (~S2 - LS2) - (~Sl - LSl).
.
In the same way a change ~core can be calculated for the . fragrance ~A~ plus ~actives~ or the ~neutral~fragrance plus : ~actives~. This ~hange is referred t~ as ~Aa.
'.' ~,,2~6~88 - So o~t~in t~e ef fect of on~ eondition re~Lative to another t~e c~anye 3core ~or on~ cond~ t~os~ can ~e ~u~tracted from ltha~
~or anot~eE. Thus, the "a~t~ves~ effect ~5 ~ N) o For Table VI~ presented ~elow, th~ ~activesa eff~/:t was obt~ined by pooling: the r~5ults for the fragranca ~A" plus "actiYes~ and neutral~ pl~ls ~ tiYes~ to ~btain ~A" ~nd: poolin51 the resul~cs fo~ the f~agrans:e ~A~ and "neu~al~ fragranc~6 to obtain ~l~

n the as~lysi~ c~ varian~:e treatment o thc resul s, t~
~,: C:hange scc~re presented be~Low ~n Table Vl~ ~Ls numericallv ec~ual to the perio y tr~al ~y "actit~s~ three-way interactions. Is~
~his con~ext, ~period" is the aYera~e of the effects a~ter treatment relat~ve lto the effec~s before treatJnent:
: lLS~ ~ MS2~ - (LSl + HS13 averaged~ across all four trea~ments.
'Tr~ s t!h~ aver~g6~ of the effects due tc: mild st~ess relative 0 those due t~:> low st~ess: (~Sl + ~qS2~ ~ tI.Sl ~ ~S2) averaged ;~cross all treatments. ~ "Acti~esU ~s the average o~ e:ffects for the compositions containing "acti~re~ rel~tive to effects for the compositiol-s containing no "activesn: ~ISl + LS2 + ~ 52) avera~ed across fragrance "Aa ~ ~actives" and neutral fragrance ; ~act~ves" minus (~Sl ~ ~S2 ~ MSï + MS2~ ~veraged across fragraslce "A" an~ the ~leutral fragran~e, . ~ .
~ ' .

.~ i :
-' ;

,. , ~

~Z7~

TABLE VII
~ _ E~FECT 0~ UACTIVES" (:JN M~LD STRXSS

- r - ~ I
YARI~Bl.E CHANGE SlGNlFlC~NCE ~EV~I, ~ __ . _ _ Systo11c B1c:>od Pressur~ ~ 3g. O . 08 ____.____ __________~___ _____________ _________________ ___ Calmness O . 77 O . 01 ________________________ _____________ _____._ _____________ ~ Embarrasment -2. 31 O. 03 ________ _____~_~____~_ ___~________ ___;_________ _____~_ ~appiness O ~ 77 O . 0003 ___________ _~ _____ ___ ____ _____~__ _____________________ ~ O ~ 51 0 . 03 '., Thus, the presence of ~actives~ in either the fragrance ~A~
or the ~neutral~ fragrance decreases systo11c blood pressure:
increases ~almness; decxeases embarrassment; increases happiness;
-~ and decreases anger.

E~en th~ugh the subjective results in this case have been quantified, ~t ~s $mportant to point out that they ~lso corre1ated wit~ ~he ~ysto1ic b100d pressure ~hange.

~: .

~j _50_ EXAMPLE I I I (A ~

~ c~ odc~rant ~:~nait~ors were tested using 1~ r~al experimental desis~n. An~lysl5 of the result~ by ~ one way analys~s o~ v~ri~nce was done. The fActc>r wa!; ~fragrance~ or ~pos~ulated ~ress reactivity reduc~ng 2gent~; the levels were plus and min~s "ac~ivesn. ~he details of the ~tat~stical analy~$s techniques are presented ~n Example I~ v supra.

q~le s~ibstances tested ~re fragranoe aAn and a ~sitial of matter composed only of ~activesa. The compositi~ of the fragrance "A"
and of t~e "actives" are presented in ~Example ~I, supra.

The sub~ect~ used for the study were drawn fr~m tl~e Union : . Bea~h, New Jersey area (Monmouth County in the State c~f New Jersey~
Fourteerl ~ulbje~ts were used fc~r the ~tudy; ~eYen lrl each oP t~c two c:ells. The ~cript was presented ~y tape recDrder ~snd blood pressures were measured wi~ ~ recordin~ aute~matic sphygmomanometer as aescri1bed i~ Example II, supr~. The experimental session periods were the following:
~', 1. Attachmen'c of the blo~d pres~ure cuff.

2. Questi~nnaire.

3. Stress T:

~a) baseline (BL) . ~ lb) mood self repor~
(c) S lvw 6tress questions ~LSl ) , ~d) mood ~elf report (e) 6 mild &tress questions (MSl) t f ) mst~d xel f ~eport .

~76~

~, Srea~e~sen~

(IRl f ra~ranc~ ) 0 ~b~ ~octlves fragran~e S. ~tress II s ~1) mo~ self report [~ 6 low ~tress quesS~on~ ~1,52j ~3 mood ~1 report 6 mild ~tress questi3ns ~MS2) (e) moo~ ~elf repor'c (f3 baseline (BL2) .

6., ~stoexperimental ~u~t~onnaire.
~ i 7. Removal ~f recording aevice- ~nd debri~f ing .

. Det3ils o~ the parts of th~ protocol are set forth iJl Example II, ~upr~. During the treatmeJIt p~r~o~l th~ clts ~:~- smelled or~ of tl~e fragrance~ ~r postulatsd ~tr~ss reac~ivity :. : redu~ng agent~ fo~ ~ one~ ~!lra~n vial ~ontain~ng a wick ~turated ith ~ solution ~ad~ up ~f 6~- test substance a~d 40~ ~ood gr~de ethyl ~loohol.
, .
~, The experiment wa~ designed to 8~10w the ef fect o the stressor and ~i) r'ra~rance or ~i~) 6txess reactivity reducing age:~t on ~ystoli~ blood pressure. me stressor is designed to be mildy ~rus~rating ~d tension producing. m,e subj~ct d~es not have adequate tl~e to answer t}~e quest~ons which ~re controversial and have complex answsrs.
ure 3 ~hows the ~hange ~n ~ystoliG blood pressure during the peri~ds of the prot~cQ.l. ~or the ~before fragrance~ or "stress reacti~ity reducing agent~ p~riods, the moderate ~tress questions produ~e ~out ~ 5 n~n/Hg rise in blo~d pressure relative to the low stress questi~ns ~MSl - ISl~. In the after #fragrance~
:
or "s~ress reccti~ty redu~ing agent~ periods, ~he ~ub jects ~` ~ smelling th~ ~activesa experien~e ~ 1 mm/Rg de~sease in sy~tolic od pressure durin~ the moderate stress questions relative ~o `, ~

I ~76~

tJ~e low ~tres5 ~uest~ons ~hlle tlle ~ ects ~mell~n~ fragrance ~A-exper~ence ~n ~ Hg ~ncrease ~uring the s3me per~od 5Ms2 - ~LS2).
The chanye ~or the "~ctive~ qroup relat~ve to the fraqr~nce n~
grc~p a~ follow~ s .~Ac t iv~s a ~Oup .
A c (MS2 - ~LS2) o IMSl ~ S ~ -6 mm/Hg Norl-Act ives Grou P
N ~ ~MS2 - LS2) - (MSl - LSl) G fl - 5 -- 3 mm/~g .'; Chan~e o P. ~ 3 ~ -9 ~ g (p ~ 0.03~ .
~; The Change soore ~hows that the ~Actives" d~creases systolic blood pressure aurirl~ ~ mildly frustratinq eYent which has been own in the f irst part of the experiment to increase ~ystolic blood pressure. Th~ fragrance ~A'' does not exhibit this effect.

~

--s3 -EXAMPLE I I I ( B ) -prefer~e~ eRor~nt C~mp~S~t~Qn wa3 testea on ~ ~3 year ol~
male ~ ct. ~he c~mpo~it~on of th~ odor~nt ~5 61~ ~r~rance A~ ,lan~ ~10~ t~ve~ ~se~ ~xampl~ upr~ he mod~ of ~dmin~str~t~On w~l~ ~ means of tl~ v~al-w~ck ~y~tem a5 de~cr~bed : - ~; ln l:x~m~ III, supra . ~he test~ng proto~ol w~s the ~n~ descr~ed ln Ex~mp~ I, 6upra, ~nd tha pr~to~ol p~riodE ~L~, ~1, MSl, , LS2, 1452 ~nd ~L2a are ~130 descr~ n Exam~le III. ~igure ~
$hows the ~ ect'g ~ystol~c ~lood pressure ~n ~n~t~g for each of the periods tindicat~d Sy ref'erence numeral 813. The shap~ o~E the raph ~ ~m~l~r to that for ~h~ graoh for the ~actives~ ~roup nd~cated by refer~nce numberal 72) presented ln Figure 30 Of particular interest ~re systolic blood pressure changes between 51 ~nd MSl and ~52~nd MS2. T~e ~u~ect ex~erienced a 6~m~Hg increa~e ~n ~ystol~c blQod pressure ~HSl - LSl) for the ~before fr~gr~nc~ perio~s whereas he experienced an 8mm~Hg de~re~se : (MS~ 2) for the ~ame perioas after ~he odorant-conditioni~g p~r~od. Hen~e tb~ C~nge ~core t~ee Examp~e 11~, ~upra) is the followl~g:
.~
A ~ (MS2 - ~Sl~ - ~MSl - LSl) ~ B -6 ~ -14mm/Hg.

~ This example further shows that the aactives~ composition .~ ~ lowers a human'~ reaction ~o stre~Q.
' ;, ,-~' '~, :: ~

_54~ 888 EXAP~PLE IV (A) Two odosant conditions were te~ted u~ing a f~c:torial e~speri-~ental design. Analysis of the resulk~ by ~ one way analysis of variance wa~ done. The factor was ~ "~ragrance" or postulated ~tress reactivity reducing "agent"]: ~he levels were plus and ~oinu~ ~ctive~W. The details of th~ ~tatistical aslalysis technlques ~re presen ed in Exa~nple II, supra.

The ~ubstances tested were a caloposition of matter COII~pO5ed of Ethanol/~istilled Water ~nd a c~nposition of ~atter camposed of Ethanol,/"actiVi83~. Th~ ca~position of the "acti~7es" i~
presented in Ex~nple I~, supra.

The sub~ects used for the study were dras~n fr~n the Union Beach, New Jersey area (Monmouth Cc~u~lty in the State of New Jersey~.
Thirty sub~ects were used for the study: fifteen in each of the two cells~ The script wa~ presented by tape recorder and blood pressur~ were measured with a recs:~rding automatic sphygmomano-meter as described in Exam~le II 9 s~pra~, The experimental session periods were the following:

1. Attach~aent of the blood pres~ur~ cu~f.
2. Que~tlonnalre..
3. 5tres~ I:
~ a ) ~a~el ine ~ BLl ) 5b) mood self report ~c) 12 ~ld stres~ que~tions (VBl) ~d) ~ood self report (e) ~erial counting e~erci3e ~MBl) ~f~ mood aelf report 4. Tr~at~nt:
~a) Eth~nol/~ater ~E) or (b) Ethanol/~ctives SE~) 5. Stre~s II:
~) Basellne t~L2) ~ ~b~ ~ood self report :' 5c) 12 m$1d stre3~ que~tions ~VB2) ~d) ~ood Ye}f report (e) serial countlng e~erci~e (MB2 ~f) mood ielf report :~ 6. Po~t-esperi~ental q~e tionnalre.

7. ~e~oval of reco~ding devices and debrlefin~.

The initial ouestionnaires consist of practice mood evaluations and a number of!other ques~ionnaires unrelated to the main experiment, -~r . ~ .

~2~ 38 13a3eline period~ involved the sub~ect ~itt~ng still, re~tinq.
The ~ood 3elf reports w~re made by the 3ub~ect re~rtin~ by means of a nine poin'c ~cale (0-9) hi~ or her d~ree of relaxation; anger z~ruciety, happiness, terlseness, embarrassment, cal3nne~s, boredcnn, ~nd sxcitem~nt. The mild 8tre~s c~uestion3 are 8 set forth ln E:xa~ple II, ~upra. The ~erial counting ex~ro~8e CQJlsisted a~king sub~ects to write dowYI their respon~e~ to a ~eries of instn~ctiOnS such as "counlt ~orward frcnn zero by fives". The sub~ects were infonned that they would be given a bonus based on the nulober of correct operations they perfonned.

Starting at the beginning of the trea~nent peria~, the subjects sr6elled a fragrance or posulated stress reactivity reducing agents fr~m a one dr~n ~ial containing a wool wick saturated with a solution made up of 60% test substanee and 40%
food qrade ethyl alcohol. They colatinued ~Delling this fragrance through the end of Stress II.

This protocol was designed to b~ samewhat more stressf than that set forth in ~xam~le ~I, supra. The ~serial counting~
is designed to be a measured performance task.

The post-experi~ent ~uestionnaires consisted of the Marlowe-Crowrle/Taylor Anxiety Scale a~d a questlonnaIre regarding the subject ' s reaction to th0 experiment as ~t out in Ex~nple II, ~upra.

Two sets of "change scores- are calculated for this experiment in the same manner as set out in Examples II and III, ~upra. The fir5t ~ the difference between the baseline and verbal stress values and the second is the difference between the baseline and ma~hematical stress values as follows:

VB ch~nge ~ (VS2 - BS2) - (V51 - BSl) MB change = ~S2 - BS2~ - tMSl - BSl) The effect was then calculated as the difference between the change score for the "active~ and that of water. The significance is determined by three-way analysis of variance as set forth in Example II, supra.

~,-~%~6~

Table VI~I
Effect of "Actlve~" on Stre~
Signlf icance Slgnif lcance Varl~le VB change Level ~p) MB c~ange Level (p~

Systollc BP -6.2 o~mtHg 0.03 -1.5 ~/Hg 0~62 Dlastolic BP-6.7 mrd/Hg 0.05 -6.4 n~/ffg O.og Relaxed 1.1 0 .11 1. ~ 0. 04 Ar~xiou~ -1 . 1 ~. 12 -3. 1 0 . 002 Tense -1 . 6 0 . 0~ -2 . 3 0 . 06 Embarra~ed -0 . 7 0 . 45 1. 5 0 ~ 04 Bored 1.9 0.06 2.4 0.06 While the level of significance varies between the stressors, the presence of "active" reduces both systolic and diastolic blood pressure; increases relaxation; increases bored~m: decreases ~nxiety; decr ses tension and decreases embarrassment.

'::`
::`
. .

Il ~ Z76~188 EXAMPLE ~J ( B ) Two odorant conditions were tested as set forth in Example rv ~A), supra. The trea~ments tested were fragrance "A4 and fragrance (NA" + "activesa). The compositior o~ these is as se~
forth in Example II, supra.

The subjects used for the study were drawn fr~m the Union Beach, New Jersey area (monmouth County in the State of New Jersey). Thirty-five sub~ects were used for the study:
nineteen recei~ed fragrance ~Au and sixteen fragrance t"A
"actives").
~. . .
:~ ~ The change scores and statistical confidences levels were calculated as set forth in Example IV(A). The effect was then calculated as the difference bet~een the change score for :~ ("A" ~ ~activesn~ and that of "AN alone.
''..
~: Table IX
Effect of UA''+''Actlves'' on Stres Signif icance ~;ign~f icancc Vari~le VB changel,evel tp~ MB change Level (p) 5y~tolic BP -2 . 6 mmlHg0 . 39 -5 . 2 m~tH~ 0 . lB
.~ Dia3'colic BP -1.5 Dm/Hg 0.49 -7.2 mm/Hg 0-04 Anger -1. O O . 05 -1. O O . 05 Anxiety -1. 2 O . 04 -0 . 3 0 . 70 ffappy 0 . 8 0 . 27 1. 1 0 .13 Tense -2.Q 0.04 . -1.5 0.13 , '.' ~. ~hus, the presence of ~actives~ reduces blood ~ressure:
::` increases happiness; reduces anxiety; reduces tension and reduces anger. This ex~mple ~urther shows how the ~acti~es~

¦¦reduce human st 5s-::~
~'~

, ' ~27gi~

EXAMPLE rV(C~

Twc odorant conditions were tested a set forth in Example IY(A), supra. The treatments tested were ~ragrance "F" and fragrance ~"FN ~ "acti~es~). The composition of these is as follows:

. 1. Fragrance "F" Composition;
Isobornyl acetate... ,.....,.......... 19.42~
Cedarwood oil...................... .. 20.65%
Bornyl acetate..................... ... 6.75%
Pine oil.................. ~...... .. 6.50%
¦Hexalydro-4,7-methanoindan-5 1 j (or 6)-yl propionate 1..../ 3.50%
Ethyl acetoacetate............... .... . 2.50%
~-Terpeneol...................... .... . 2.38%
Methyl nonylacetaldehyde......... .... . 1.56%
Linalool....................,......... 1.62~
Coumarin............. O......O......... 1.25%
Dipropylene glycol................. .. 33.86%
'' _ .

~ :~
~:~ ~

lz~6~88 -s9-2. Yragrance "F~ + ~Acti~es":
Fragranre WF".................... ~ 60.00%
: Actives (Example II, supra)~........ 40.00 : ~, The sub~ects used for the study were drawn fr~m theUnion Beach, New Jersey area (Monmouth County in the State of New Jersey). 5ixty-fi~e subjects were used for the study:
: thirty three recei~ed fragrance "F" and thirty-two fragrance ("F" + ~Actives~).

: The change scores and statistical confidences levels were calculated as set forth in Example rV(A). The effect was then calculated as the difference between the change score for (llFn ~ aActive5n) and that of WF" alone.
~' ~:: Table IX
Effect of "F"~"Actives" on Stre3~

: Slgniicance Significance Varlable VB change Level ~p) ~B change Level ~p) Sy~tolic BP -3.1 ~/Hg 0.20 -3.2 am/Hg 0.16 Diastolic BP -4.0 ~m/Hg 0.03 -4.5 mm~Hg 0.04 Calm 1.4 0.04 1.? 0.04 Thus, the presence of "actives" reduces blood pressure and jincreases calmn s.

~ 11 .' ~X~ V

Exper$ments ~ov~ by Ex~mpl~s ~ re ~ried out us~ng 1~ pla~e ~ tl-e ~tive~ c~mp~siti~n tne ollowing cub~an-lly pur~ material~

~ii Nutmeq Oil E~st Indi~n5 erol~ O-~l 7 i i i ) Mace Ex'cr~t ~
v~ Yalerian O~l;
(v) MyristiC~nt V~L) Elemicin; ~J~d ~vi i 3 I soelemic~n .
`~`'~' . Results ~ubs~nti~lly e~e ~ame ~s t~-Pse ottained ~ Exa,~?les ~
and IV ~re obtained wh~n using th~ ~oregoing puxe material~ in-~tead of ~be ~act~ves~.

~ ~ *
.

In the followir~ Examples VI, ~t seq, the following materials are used in perfum~d ~rticles causiLng use of t~ese pe:rfumed ~r~icles lt~ cre~te mild ~tress reactivity reducinq effectson ~e user:

T~BLE X
.

; (~3 ~Activ~s" compos~t~on of ~x~mple II:
. ~ 6~i) Nutm~g Oil Eas Indian ~ubstan~ially puse;
(~ii) Mace ~xtract su~stantially pure;
(iv) Neroli O~l:
~V3 Vzll~xii!lA Oil;
v~) Myristicin:
~vii) Elemicin; ~and ~Yi~ soel~mi~in.

;~

7G~8 -. EXA~PLE VI

PREPAIU~TION OF A COSMETIC POWDER COMPOSITION
:'`

A cosmetic pow~r ~t~ prepar~ by a~ixin~ lh X ball ~111 100 grams o$ t~lcum powder with 0~25 gr~ms of each o~ th~ cc)mpos$-. ~: tion~ ~ ~le v~ ach o~ the cosmet~c ps:~wders prepared ~ith e~ch of t)~e ~ngredients of ~he compositi~r~s of ~atter set fort~a ~n Tabl~ VIII,supra, cr~tes ~n eff~ct which can ~e descr~bea . ~ as ~stress reactivity reducing~ in th~ user.

n each o~ 3 . (v~ii) taken g~lone is con~ined at ~
SO :50 ~weight:we~9ht) level ~ h ~r~granc:e "~ ~ pleas~nt apple arom~ mparted to t~e cosme ic pc~wder.

-:
AMPLE V I I
.
-~`. P~EPARATION ~ ~ COLO~NE AND HANDXERCHIEF P~RFUME
_ _ _ __ Sach ~f th~ compositions of matter of ~a~le V~ upra, are incorporated $nto colognes at concentr~tions o~ 2.0~, 2.5~, 3.0~, , 3.5~, 4.0%, ~.5~ ~nd 5.0~ ~n 95~ a~ueous ethanol toge her with ~:: 4.0~, 4.5~ and 5.0~ of fragrance ~A~ o~ Example II; and ~nto ~` handkerchief per~umes at concentrati~ns of 15~ 20~, 25~, 30~ and 40% in 95~ a~ueous ethanol together with 10~ by ~eight of fragr~
; ~A~ of Example lI. Distinctive apple aromas are imparted to each : of:th~ cologne a~d handkerchief perfumes and each of the colognes ~: and handkerchief ~erfumes gi~es rise to ~ ~stress reactivi~y-red~c~ng~ ef~ec~ on the us~r~
:, :~, ' ~

~2~ a EXAMPLE VI I I
D EODORA~T ST ~[CX
..
J~ ~eod~r~nt ~tick compos~t~n i~ prl~p~re~ ontaln~9 the following material~:
~' dGREDIE:~TS PAR'rS BY WEIG;H~

~ropylene Gly~ol ~ O " ~ O ~ r 4 68. 00 Sodium 5tearate .. ~............ ~... i.. , 7O00 .~ Distill~ Wat~r . ~ 0 .......... ,.. , .. ~, ... 23.75 IRGASAN ~ DP -300 12, 4, ~ trichloro-2 ' hydroxy diphenyl ether, manufactur~d by th~
Ciba-Geigy Chemic~I CoO
~nd A Tradem~rk ~f the:
Ciba-Geigy Chemic~l Co. ) . ~ , ..... 1..... 0.25 Composition containing fragrance ~AI' (50 parts ~y we~ght~ and one o~
items ~) (viii) of ~able VII~, ~xra;
~:50 parts by weight) ~ --6-~ 1.00 , _ ' The ingr~dients ~re ~cmbined without ~activ~" substance/
fragxanc~ composit~on ~ he~ted ~o 75~ ese ~ ts are ~x~d ~r~d cc~nti~ued to Ibe heated urtil the ~odium ~earate has diso solved. The resultin~ mixture ~s ~ooIed to 40-C ~nd the Pactive-su}: stance~fragrance ~omposition (containing one of the stress ~e~ctiYity reduction l;ubstances of Table V~ upra) is added and mixed at 40-t: un~ uspension is forared.
. .
l'he resultin~ suspension ~s formed into deodorant ~ti~}cs~
use there~ sers subje~ted to ~tress ~c>ndltions experien~e reductior~ ~n phy~ qi~al ~nd/or ~;ubjective react.i~,~ity t~ stress.

~63--E:SAMPLE IX
SO~ID ROO~ DEODORA~ COMPOSITION

'.
a ~olid room deodorant composition ls preparea ~ ~oll~ws:
:

~: IN~REDIENTS , ARTS BY W~IGHT
" :
PART A:
istil~ed Wa~r ~ OO~ O~ 88.4 -~ GELC~RIN A~ 15 ~1) Mari~e Colloid~3 ~--O~ o~ 3.00 ::~ Formalde~yde ... ~ .O....... ~.... O..... ~.... 0.05 :: PART ~:
Glyce~ine O~ O~ O~ 3.50 PART C:
_ Composition containing ~ragran~e ~
(50 parts by weight) and o~e of items (i)olviii) o~ Table VIII, ~upra (50 parts by weight) ~ O~ 1~00 P~RT D ~
Th'EEN 80 (ICI Americas) 3~O~ 4.00 ~%7~ 38 ~he composit$oll ~8 prepared by:

lo '8eat~ng t~e water to ~5"C and di~persing the GELCARIN
AF~; 15 thereln s 2. S1QW1Y ~d~ling t~ae glycerin wh~le ~ainta~ning tbe fnixture ~t 85-C5 3. Combining the TWE:EN 80 ana composition containing Uact iYes " and fragrarlce;

dding th~ EEN/(~ragrance plus "a~tives") ~omposition tc~ the resulting ~nixture, 5O Adding formaldehy~e to the resulting mixture and 6. ~ouring the result~ng mixture into ~ mold.
- - - .. ..

~he contents ~r~ allowed to cool, the mold ~s opened i~nd the fiolid "c~kes" ~re removea. Shz~ ~e~kes~ ~¢ placed ~ntc~ ~t~ndard air deodorizing ~ppar~ui~ .

0~ cperatiog~ of the ~ta3~dar~1 ~ir deodorizinq apparatus as il~ room dec~d;:~izer, ~fter ~our m~nu~es, the rc>om has an ,Destheti-$ally pleasing apple aroma ~nd further, ~ person placed $n said room who i~ ~ubject to ~tress ~onditions will have a Gignificant ~tress ~eactivity reduction.

Notes: 1. GELCAP~IN ~FG 15 is Carageerlan manufactured by . Marine C~lloids, Inc. Division of FMC Corporation vf Springfield, New Jersey 07081.

2 . ~WEEN 30 is Polyst~rbate 80 otherwise known as ~polyethylene qlycol 36 -Sorbitan Oleate, manufactured by IC~ Americas ~nc. of Wilming~on, Delaware 19897.

;

~%~388 EXA~SPI.~ ~

BODY OIL CO POSITION

A b~dy o~l c~mposlt~on 16 prep~red ~6 follow6 8 :.
I~GREDIENT5 PAR~S BY WEIGHT
- - ~
~ineral Oil lXLEARO~ ~ ~Witco)l .. ,...... ~ 45.0 :1 Is~propyl Myristate .............. ~...... ,....... 50.0 Composition containing fragrance "A~
:: l50 parts by weight) ~nd vne of i~ems lviii) of Table VIII, 8~pS~
~50 parts ~y weiqh~ O~O~ 5.0 The composition ~f th~s example ~s prepared by combinins the ingredients with mixing, geing an~ filterin~.

~ ach of the ~ody ~il preparations prepared with each of the ingredients of the compos~tions of matter ~et f~rth ln Table VIII, .
supra, creates an effect which can be described ~s Wstress reactivity-reducing~ in the user. In addition, a pleasant apple ~roma is i~p d tc ehe u5er in e~ch case.

' ~:276~

~X~MPLE XI

HOT OIL TRE~TMENT COMPOSITION (YOR HAIR) ~ hot ~11 treatment composlt~on for hair ~ prep~rgd a~
follow~:
, __ ~t!ao:l~L-LI~9~ ING~ED~EN~S

65.9 ~.. ~.~......... ....Ol.......... UCON Lubricant 50-HB-66011) ~Unio~ Carbi~e~
30.0 ......... ....... ,............... UCON ~ubricant 50~ 40~ ) : (Union Carb~de) 3.0 .... O........... ~ .............. LAN~ROL AWS IEmery(3) .
: O.l .... ~.... ~......... O... O.O...... Propyl Paraben l.Q .... ~ .O.... ..~............. Composition containinq fragrance ~Au (50 parts ~y weight) ~d one of ~tems (i)-(viii~ of Table V~IX, ~upra ~5~ ~arts by weight1 :
~e comp~sitio~ of t~s example ~s prepared by ~imply adding the in~redients in order while mixing.
i . .
; Each ~f the r2sulting hot oil treatment ~omposit~ons prepared witb ea~h of the ln~red~ents ~f the c~mp~ itio~s of ~attes set or~h in Table VII~,s~pra, c~eates an ~ffe~t ~hich can be descr~ as ~6tress react~vity-reducinga ~n the user. In addition~ a ple~sant apple ~roma i~ imp~rted to the user.

Nc~tes:
1. UC~N $ubricant 50-HB-660 is ~polypropylene slycol~ 12-bl~tyl ether manufactured ~y the t1nion Carbide .~ Corporation of E~anbury, t:onnecti~ut 06817.
2. UCON Lubricarlt 50-HB-400 ~s (polypropylene glycol) 9-t: utyl et~er manufactured by the Union ~arbide ; ~ Co~po~tion of Danbury, Connectict~t 06B17.
3. LAN~OL AWS ~s ~ water dlspersable alkoxylated Lanolin Qil mas~ceted by Emery Industries o~
. ~ cirJcinnatt, Oh$o 4S202.

~' , , ~ ~

~:7~8~3 EX~P~E x I I
AEROSOL Ro~M SPR~Y COMPOSITION
~ . .. __ aerosol rc~om ~pr~y compos~t~n ~ re~ared ~ ollows:

NG~EDI~NTS ~I~rs ~ G~I~

~PAN 80~ O~ O~ O~ Q
Composit~on ~ntaining fragrance ~
50 parts ~y weight) and one of ~tems viii~ of Table VIII, supra (50 parts ~y weight3 ~ . 0.25 Dist~lled Water ~ D~ O~O~O~O~ 68D75 Pr~el~an~ A-~6~ o~ 3~.00 ~, . . .

An aerosol room ~pray is prepared ~ follows-1. adding the wa~er to an ~erosol container;
, 2. m~x~ng the compos~tior~ containing fragrance "A~ ~nd ~actives" and the SPAN 8Q;

3~ ~dding the ~ragrance/nactiv~s~/SPAN 80 composi~ion ~o the container;

. crimping on ~n ~eros~l va~ve;

SO psessurizing th~ c~ntainer with Pr~pellant A-46; and ; 6. fittin~ ~n actuator ~o the valve~

When the resulti~g c~mposit~on is ~prayed from the ~erosol CDntainer int~ ~ 20' x 20' x 10' nonmally ventilated room i ,~

~L2~6~

,~
(~65F), ~ter four m~nute~ , the r~om t~as ~n ~e~h~$e~11y pleasing ~pple ~roma an~, further, ~ n placed ~n ~aid room who i~ s~jecte~ tt~ ~tres~ ct)n~it~n~ w~ll have ~ acignifican~
~tres- react~v~ty reduc~ n.
' :
~to~es:
PAN 1~0 1~ S~rbltan Ol~ate~ manufactur~ by ~CI ~mericas Tnc., o Wilmington, Delawar~ 19897, 2. PrQP~11ant A~q6 ~ mixtur~ 5 weight percent ~sob~ltane ~nd 15 weight percent propane.
. :~
, ~ .

~, . . ' .
~ .
~",'`', ' ' :: :
~ .:

: ~a 38~

DESCRIPTION OF THE DRAWINGS
_, _ Fi~ure 1 is ~he GLC profi~e of the head-space above nutmeg oil measured ac~ording to the procedure of Example I(B) (Condi-tions~ 1 fused sili~a col~mn pro~rammed at 75-220C at 2C per minut~. The nutmeg oil is East Indian Nutmeg Oil.

F ~ is the GLC profile for bulked fractions 7-12 of the second distillation of nutmeg oil East Indian according to the procedure of Example I~A) (Conditions; 400' x 0.032"
carbowax/fused silica column programmed at 75-220C at 2C per minute).

F ~ is a graph showing systolic blood pressure change (mm/~gj v~ protocol p~riod fora o~osition of "actives" containing nutmeg oil, mace extract~ neroli oil and valerian oil as well as for a composition containing a fragrance denGted as fragrance "A~
as described, infra~ which does not contain any "actives n . The actives" of our invention cause the reduct~on of physiological and/or subjective reactivity to stress in a human. The means for determininq the plot~ of data on the graph of Figure 3 is set forth in Example III.

F gure 4 is a graph showing systolic blood pressure (mm/Hg) vs.protocol period for a composition cont~ng both ~i) "actives"
~containing nutmeg oil, mace extract, neroli oil and valerian oil) and, in addition, (ii) a composition de~ote~ herein as fraqranoe ~AI' ~as aescribed, infra~. The "actives" of oux invention cause jthe reduction of physioloqical and/or subjective reactivity to stress in a human. The means for determining the plo~ o data on the graph of Figure 4 is set forth in Example IV.

Fiyure 5 is a cutaway side elevation view of apparatus used in preparing perfume-containinq and stress reactivity-reducing substance-containing polymers of oux invention.

Figure 6 is a cross sec~ional vi.ew taken along lines 6-6 of _ .
.~ Figure 5~
;

'' '~

~27~

EXPI~ATION OF THE D~AWINGS

Fi~ure 1 is a GLC profile for the head-space above nutmeg oil East Indian as determined according to the procedure of Example I (B) (GLC Conditions: OV-l fused silica colwnn progra~Ted at 75-220C at ;~C per minute), The peak indicated by reference nwneral 10 is the peak for ~-thujene.

' The peak indicated by reference numeral il is the peak for ~-pinene.

The peak indicated by reference numeral 12 is the peak for sabinene.
The peak indicated by reference numeral 13 is the peak for ~-pinene.

The peak indicated by reference numeral 14 is the peak for myrcene.

The peak indicated by reference numeral 15 is the peak for a-phellandrene.

The peak indicated by reference numeral 16 is the peak for ~-3-carene.
: ~
The peak indicated by re~erence numeral 17 is the peak for ~ ~-terpinene.

; ' The peak indicated by reference numeral 18 is the peak for 'I p-cymene.

', The peak indicated by reference numeral 19 is the peak for i~-terpinene.

~68~

The peak indicated by reference numer~l 20 i5 the peak fo~¦terpinolene.

, The peak ~ndicated by reference numeral 21 is the peak for linalool~

The pea~ indic~ted by reference numerals 22A and 22B are the peaks for l-hydroxy-l-methyl-4-isopropyl-2-cyclohexene.

~` The peak indicated by reference numeral 23 is the peak for 2-methyl-5-ethyl fuxan.
, The peak indicated by reference numeral 24 is the peak for 4-terpineol.

~ he peak i~dicated by referenoe numeral 25 is the peak for ~-terpineol.
:::
The peak indica~ed ~y reference numeral 26 is the peak for l-methyl~3-hydroxy-4-isopropenyl benzene.
': ~ 1.
The peak indicated by reference numeral 27 is the peak for ¦isobornyl acetate.
The peak indicated by reference numeral 28 is the peak for n-amyl methoxy benzenes.

I The peak indicated by reference numeral 29 is ~he peak for ¦'eugenol.
!, I ~he peak indicated by reference numeral 30 is the peak for terpinyl acetate.

The peak indicated by reference numeral 31 is the peak for cubebene.

The peak indicated by reference numeral 32 is the peak for eugenyl methyl ether.
~ ! ~

~ 7E;~

The pea~ indicated by reference numeral 33 is the peak for copene.

The pea~ indicated by reference numeral 34 is the peak for trans-isoeugenol.

The peak indicated by reference numeral 35 is the peak fvr ~-bergamotene.

The peak indicated by reference numeral 36 is the peak for 4-propenyl-1,2-dimethoxy benzene.

:: The peak inclicated by reference numeral 37 is the peak for ;~ myristicin.

::d I The peak indicated by reference numeral 38 is the peak forl ¦~-cadinene.
!
¦ The peak indicated by reference numeral 39 is the peak for elemicine.

~: The peak indicated by reference numeral 40 is the peak for : 4-allyl-2,6-dLmethoxy phenol.

Figure 3 sets forth the effect on ~lood pressure changes (of a human subject to stre~ cond~tions) of:

(i~ a composition of "actives" as set forth in Example Il ` according to the protocol of Example III; and ~ii) a fragrance composition entitled fragrance "A"
specifically described according to Example II

~; with the changes in blood pressure being in units of mm/Hg.

;1 The graph indicated by reference numeral 71 is the graph of systolic blood pressure (mm/Hg) versus protocol period (e.g., BLl, LS1, MSl, F, LS2, MS2 and BL2) defined in Example II
for fragrance "A-; that is,the fragrance that cloes not contain .~. l I

~z776~38~3 ~actives~, e.g., nutmeg oil, mace extract, neroli oil and valerian oil. The protocol periods are as foll~ws:

3Ll - baseline in ~Stress I";

LSl - 6 low stress questions in "Stress l";

MSl - 6 mild stress q~estions in "Stress I~;

F - two blood pressure points during applic~tion of fragrance "A" between "Stress 1" and "Stress II";

LS2 - 6 low stre s questions in "Stress II n;

MS2 - 6 mild stress questions in "Stress II";

BL2 - baseline at end of "Stress II~.

The graph indicated by reference numeral 72 is the graph ; of systolic blood pressure ~mm/Hg) versus pxotocol period when using the "actives" mixture, that is,the mixture of nutmeg oil, mace extract, neroli oil and valerian oil "actives compositionU
of Example II using the protocol of Example III. The meaning of each protocol period is as follows:

BLl - initial baseline for "Stress I n;

LSl - 6 low stress questions for "Stress I";

MSl - 6 mild stress questions for "Stress I"

F - two blood pressure points during a~plication of : stress reactivity-reduction composition (nactives") ~ after "Stress I n;

~LZ768s8 LS2 ~ low stre~ questions for ~tress II~;

MS2 - 6 mild stress questions for nStress XI~:
:
BL2 - end ~aseline for "Stress II~.
, Figure 4 sets forth the ef~ect on blood pressure (of a human subject to stress conditions) of a composition of ~actives" tas ~r ~: set forth in Example II3 according to the ~rotocol of Example III
~` and in combination with a fragrance composition denoted as ~ragrance ~A", ~;th the blood pressure being in units of mm/Hg and with the measurements ~eing made accQrding to the procedure of Example IV.
The graph indicated by reference numeral 81 is the graph ;! '~ of systolic blood pressure (mm~Hg) vs.protocol period (e.g., BLl, ~: LSl, MSl, F, LS2, MS2 and BL2~ defined in Example IV for the ~ combination: fragrance "A" and "activesn, e.gc, nu~ oil, mace extract, neroli oil and valerian oil. The protocol periods are as follows:
~ ' baseline in "Stress I";

. ~ LSl - 6 low stress questions in ~Stress I";
,~ . :
MSl - 6 mild stress questions in "Stress I a;

F two blood pressure points during application of the combination: fragrance "A" and "actives"
. between "Stress I" and "Stress IIn;
.`,~ `~,'i :; LS2 - 6 low stress questions in ~Stress II";
~ ~, ~ MS2 - 6 mild stress questions in "Stress II";
.,i~ .:
~ ~; BL2 - baseline at end of "Stress II n .

~' `: ~

~:' ~ ~6~8 ~ I~L~ nd 6 lllustrates 8 Dreferred m~thod for pr~oarinq composition8 for th~ pra~ice of our lnvention~ A thermo~la~tic polymer, e.g., polyethyle~e, is h~ated to about 220-250~ in a conta~ner 212 of the kind illustrated in Figures 5 and 6.. A
formulation containing fragran~e a5 well as stxess reactivity-reduction "active(s)~ (which includ~s o~e or a combination Oe the : following:

Nutmeg oil;
Macc extra~t, Neroli oil:
~ Valerian oil;
-.~ Myristicin;
Elemi~in; and/or Isoelemicin) ' ~ .
is then quickly added to the li~uified thermoplastic polymer.
The lid 228 i~ DUt in place and the asitatins means 273 is actuated. The temperature is main~ained at about 225F and the mixing is continued for about 5-15 minutes. The valve "V" is then opened to allow flow of the molten thermoplastic polymer enriched with fragrance and ~active" substance containing one or a combination of:

Nutmeg oil;
Neroli oil;
~ Valerian oil;
:; Mace extract:
Myristicin;
Elemicin; and/or ~:. Isoelemicin to exit through the orifices 234. The li~uid falling through the orifices 234 solidifies almost instantaneously upon impact with moving cooled conveyor 238. The thermoplastic polymer beads or pellets 224 having pronounced physiological and/or subjective reactivity reduction (to stress) effects are thus formed.

. ~D

~2768~

h~ conveyor 238 is moved using conveyor rollers 240 a~d 2~12.
The vessel 212 is heated using heating coil~ 212A powered using power input supplies indicated by reference n~nerals 214, 216, 224, 222, 220 and 226. The solidified beads containing stress reacti~vi~y reduction ~ are indicated by 244 traveling into container 245 where they are used for subse-quent processing. The conYeyor i~ cooled usin~ a ~oc31ing device indicated by reference numera}s 248, 256, 250 zl~nd 25~4.

. ~
'.
: ,~

, .
~:, . , ., ~ , .

Claims (81)

1. A composition for the reduction of reactivity to stress in a human being subjected to stress which comprises an effective amount of a stress reactivity-reducing substance which is one or more of:
Nutmeg Oil;
Mace Extract;
Neroli Oil; and/or Valerian Oil, wherein the amount of stress reactivity-reducing substance is in the range of from about 13 micrograms up to about 1000 micrograms.

2. The composition of Claim 1 wherein the stress reactivity-reducing substance is nutmeg oil.

3. A composition for the reduction of reactivity to stress in a human being subjected to stress which comprises an effective amount of a composition of matter consisting essentially of:
(a) a stress reactivity-reducing substance which is one or more of:
Nutmeg Oil;
Mace Extract;
Neroli Oil; and/or Valerian Oil;
and (b) a carrier perfume composition compatible with said stress reactivity-reducing substance, the amount of stress reactivity-reducing substance being in the range of from about 13 micrograms up to about 1000 micrograms and the weight ratio of said stress reactivity-reducing substance to said carrier perfume composition being in the range of from about 1:100 up to about 100:1.

4. The composition of Claim 3 wherein the stress reactivity-reducing substance is nutmeg oil.

5. A composition for the reduction of reactivity to stress in a human being subjected to stress which comprises an effective amount of a composition of matter consisting essentially of:
(a) a stress reactivity-reducing substance which is one or more of:
Nutmeg Oil;
Mace Extract;
Neroli Oil; and/or Valerian Oil;
and (b) ethyl alcohol, the amount of stress reactivity-reducing substance being in the range of from about 13 micrograms up to about 1000 micrograms and the weight ratio of said stress reactivity-reducing substance to said ethyl alcohol being in the range of from about 1:99 up to about 99:1.

6. The composition of Claim 5 wherein the stress reactivity-reducing substance is nutmeg oil.

7. A composition for the reduction of reactivity to stress in a human being subjected to stress which comprises an effective amount of a composition of matter consisting essentially of:
(a) a stress reactivity-reducing substance which is one or more of:
Nutmeg Oil;
Mace Extract;
Neroli Oil; and/or Valerian Oil;
(b) a carrier perfume composition compatible with said stress reactivity reducing substance;

and (c) ethanol, the amount of stress reactivity-reducing substance being in the range of from about 13 micrograms up to about 1000 micrograms and the weight ratio of said stress reactivity reducing substance to said carrier perfume composition being in the range of from about 1:100 up to about 100:1 and the weight ratio of said stress reactivity-reducing substance to said ethanol being in the range of from about 1:99 up to about 99:1.

8. The composition of Claim 7 wherein the stress reactivity reducing substance is nutmeg oil.

9. A composition for augmenting or enhancing the aroma of an enclosed environment and simultaneously causing the reduction of reactivity to stress in a human subjected to stress, said human being located in said environment, which composition comprises an effective stress reactivity-reducing concentration of a composition of matter which is one or more of:
Nutmeg Oil;
Mace Extract Neroli Oil; and/or Valerian Oil, wherein the concentration of effective stress reactivity-reducing substance in said environment is present in a concentration of from about 1 microgram per liter up to about 125 micrograms per liter.

10. A composition for augmenting or enhancing the aroma of an enclosed environment and simultaneously causing the reduction of reactivity to stress in a human subjected to stress, said human being located in said environment which composition comprises an effective stress reactivity reducing concentration of a composition of matter consisting essentially of:

(a) an effective stress reactivity-reducing substance which is one or more of:
Nutmeg Oil;
Mace Extract;
Neroli Oil; and/or Valerian Oil;

and (b) a carrier perfume composition compatible with said stress reactivity-reducing substance, the concentration of effective stress reactivity reducing substance in said environment being in the range of from about 1 microgram per liter up to about 125 micrograms per liter and the weight ratio of said stress reactivity-reducing substance to said carrier perfume composition being in the range of from about 1:100 up to about 100:1.

11. The composition of Claim 10 wherein the effective stress reactivity-reducing substance in said environment is nutmeg oil.

12. A composition for augmenting or enhancing the aroma of an enclosed environment and simultaneously causing the reduction of reactivity to stress in a human subjected to stress, said human being located in said environment, which composition comprises an effective stress reactivity-reducing concentration of a composition of matter consisting essentially of:
(a) an effective stress reactivity-reducing substance which is one or more of:
Nutmeg Oil;
Mace Extract;
Neroli Oil; and/or Valerian Oil;
and (b) ethyl alcohol, the concentration of effective stress reactivity-reducing substance in said environment being in the range of from about 1 microgram per litre up to about 125 micrograms per litre and the weight ratio of said stress reactivity-reducing substance to said ethyl alcohol being in the range of from about 1:99 up to about 99:1.

13. The composition of Claim 12 wherein the effective stress reactivity-reducing substance in said environment is nutmeg oil.

14. A composition for augmenting or enhancing the aroma of an enclosed environment and simultaneously causing the reduction of reactivity to stress in a human subjected to stress, said human being located in said environment which composition comprises an effective stress reactivity-reducing concentration of a composition of matter consisting essentially of:
(a) an effective stress reactivity-reducing substance which is one or more of:
Nutmeg Oil;
Mace Extract;
Neroli Oil; and/or Valerian Oil;

(b) a carrier perfume composition compatible with said stress reactivity-reducing substance;
and (c) ethyl alcohol, the concentration of effective stress reactivity-reducing substance in said environment being in the range of from about 1 microgram per litre up to about 125 micrograms per litre and the weight ratio of said stress reactivity-reducing substance to said carrier perfume composition being from about 1:100 up to about 100:1 and the weight ratio of said stress reactivity-reducing substance to said ethyl alcohol being in the range of from about 1:99 up to about 99:1.

15. The composition of Claim 14 wherein the stress reactivity-reducing substance in said environment is nutmeg oil.

16. A composition for the reduction of reactivity to stress in a human subjected to stress which composition comprises an effective amount of a stress reactivity-reducing substance which is one or more of:
Myristicin;
Elemicin; and/or Isoelemicin, wherein the amount of stress reactivity-reducing substance is from about 0.13 micrograms up to about 50 micrograms.

17. The composition of Claim 16 wherein the stress reactivity-reducing substance is myristicin.

18. A composition for the reduction of reactivity to stress in a human subjected to stress which comprises an effective amount of a composition of matter consisting essentially of:
(a) a stress reactivity-reducing substance which is one or more of:
Myristicin;
Elemicin; and/or Isoelemicin;
and (b) a carrier perfume composition compatible with said stress reactivity-reducing substance the amount of stress reactivity-reducing substance being in the range of from about 0.13 microgram up to about 50 micrograms and the weight ratio of said stress reactivity-reducing substance to said carrier perfume composition being in the range of from about 1:100 up to about 100:1.

19. The composition of Claim 18 wherein the stress reactivity-reducing substance is myristicin.

20. A composition for the reduction of reactivity to stress in a human subjected to stress which comprises an effective amount of a composition of matter consisting essentially of:
(a) a stress reactivity-reducing substance which is one or more of:
Myristicin;
Elemicin; and/or Isoelemicin;
and (b) ethyl alcohol;
the amount of stress reactivity-reducing substance being in the range of from about 0.13 micrograms up to 50 micrograms and the weight ratio of said stress reactivity-reducing substance to said ethyl alcohol being in the range of from 1:99 up to about 99:1.

21. The composition of Claim 20 wherein the stress reactivity-reducing substance is myristicin.

22. A composition for the reduction of reactivity to stress in a human subjected to stress which comprises an effective amount of a composition of matter consisting essentially of:
(a) a stress reactivity-reducing substance which is one or more of:
Myristicin;
Elemicin; and/or Isoelemicin;
(b) a carrier perfume composition compatible with said stress reactivity-reducing substance;
and (c) ethanol;
the amount of stress reactivity-reducing substance being in the range of from about 0.13 micrograms up to about 50 micrograms, the weight ratio of said stress reactivity reducing substance to said carrier perfume composition being in the range of from about 1:100 up to about 100:1 and the weight ratio of said stress reactivity-reducing substance to said ethanol being in the range of from about 1:99 up to about 99:1.

23. The composition of Claim 22 wherein the stress reactivity-reducing substance is myristicin.

24. A composition of augmenting or enhancing the aroma of an enclosed environment and simultaneously causing the reduction of reactivity to stress in a human subjected to stress, said human being located in said environment which composition comprises an effective concentration a composition of matter which is one or more of:

Myristicin;
Elemicin; and/or Isoelemincin, wherein the amount of stress reactivity-reducing substance is in the range of from about 0.13 microgram up to about 50 micrograms.

25. A composition for augmenting or enhancing the aroma of an enclosed environment and simultaneously causing the reduction of reactivity to stress in a human subjected to stress, said human being located in said environment which composition comprises an effective concentration of a composition of matter of one or more of:
(a) an effective stress-reactivity reducing substance which is one or more of:
Myristicin;
Elemicin; and/or Isoelemicin, and (b) a carrier perfume composition compatible with said stress reactivity-reducing substance;
the amount of stress reactivity-reducing substance being in the range of from about 0.13 microgram up to about 50 micrograms and the weight ratio of said stress reactivity-reducing substance to said carrier perfume composition being in the range of from about 1:100 up to about 100:1.

26. The composition of Claim 25 wherein the effective stress reactivity-reducing substance is myristicin.

27. A composition for augmenting or enhancing the aroma of an enclosed environment and simultaneously causing the reduction of physiological and/or subjective reactivity to stress in a human subjected to stress, said human being located in said environment which composition comprises an effective concentration a composition of matter consisting essentially of:
(a) an effective stress reactivity reducing substance which is one or more of:
Myristicin;
Elemicin; and/or Isoelemicin;
and (b) ethyl alcohol;
the amount of stress reactivity-reducing substance being in the range of from about 0.13 micrograms up to about 50 micrograms and the weight ratio of said stress reactivity-reducing substance to said ethyl alcohol being in the range of from about 1:99 up to about 99:1.

28. The composition of Claim 27 wherein the effective stress reactivity-reducing substance is myristicin.

29. A composition for augmenting or enhancing the aroma of an enclosed environment and simultaneously causing the reduction of reactivity to stress in a human subjected to stress, said human being located in said environment which composition comprises an effective concentration of a composition of matter consisting essentially of.
(a) an effective stress reactivity-reducing substance which is one or more of:
Myristicin;
Elemicin; and/or Isoelemicin;
(b) a carrier perfume composition compatible with said stress reactivity-reducing substance and (c) ethyl alcohol;

the amount of stress reactivity reducing substance being in the range of from about 0.13 micrograms up to about 50 micrograms, the weight ratio of said stress reactivity-reducing substance to said carrier perfume composition being from about 1:100 up to about 100:1 and the weight ratio of said stress reactivity-reducing substance to said ethyl alcohol being in the range of from about 1:99 up to about 99:1.

30. The composition of Claim 29 wherein the stress reactivity-reducing substance is myristicin, and the composition is a cologne.

31. A method for detecting reactivity to stress in a human comprising testing a human likely to exhibit physiological and/or subjective reactivity by:
(i) measuring the initial blood pressure and mood of said human; then (ii) applying stress to said human; then (iii) simultaneously therewith measuring blood pressure and mood changes resulting from the application of said stress to said human; thereafter (iv) administering to said human a substance which is to be tested as being effective to cause the reduction of reactivity to said stress; and (v) measuring blood pressure and mood changes resulting from the administering to said human of said substance which is to be tested as being effective in causing the reduction of reactivity to stress.

32. The method of Claim 31 wherein the stress reactivity-reducing substance to be tested which is one or more of:
Nutmeg Oil;
Mace Extract;
Neroli Oil;
Valerian Oil;
Myristicin;
Elemicin; and/or Isoelemicin.

33. A composition for the reduction of reactivity to stress in a human subjected to stress which comprises an effective stress reactivity-reducing amount of a composition of matter consisting essentially of an effective stress reactivity reducing substance which is one or more of:
Nutmeg Oil;
Mace Extract;
Neroli Oil; and/or Valerian Oil in intimate admixture with a carrier perfumed article compatible with said stress reactivity-reducing substance, wherein the stress reactivity-reducing substance present in the carrier perfumed article to cause said human to be treated with said stress reactivity-reducing substance is present in an amount of from about 13 micrograms up to about 1000 micrograms.

34. The composition of Claim 33 wherein the stress reactivity reducing substance is nutmeg oil.

35. A composition for the reduction of reactivity to stress in a human subjected to stress which comprises an effective stress reactivity-reducing amount of a composition of matter consisting essentially of an effective stress reactivity-reducing substance which is one or more of;
Nutmeg Oil;
Mace Extract;
Neroli Oil; and/or Valerian Oil, in intimate admixture with a carrier perfumed article compatible with said stress reactivity-reducing substance and ethanol, wherein the stress reactivity-reducing substance present in the carrier perfumed article to cause said human to be treated with said stress reactivity-reducing substance is present in an amount of from about 13 micrograms up to about 1000 micrograms.

36. The composition of Claim 35 wherein the stress reactivity-reducing substance is nutmeg oil.

37. A composition for the reduction of reactivity to stress in a human subjected to stress which comprises an effective stress reactivity-reducing amount of a composition of matter consisting essentially of an effective stress reactivity reducing substance which is one or more of:
Myristicin;
Elemicin; and/or Isoelemicin, in intimate contact with a carrier perfumed article compatible with said stress reactivity reducing substance, wherein the stress reactivity-reducing substance present in the carrier perfumed article to cause said human to be treated with said stress reactivity-reducing substance is present in an amount of from about 0.013 micrograms up to about 50 micrograms.

38. The composition of Claim 37 wherein the stress reactivity reducing substance is myristicin.

39. A composition for the reduction of reactivity to stress in a human subjected to stress which comprises a stress reactivity-reducing substance which is one or more of:
Myristicin;
Elemicin; and/or Isoelemicin, in intimate admixture with a carrier perfumed article compatible with said stress reactivity-reducing substance and ethanol, wherein the stress reactivity-reducing substance present in the carrier perfumed article to cause said human to be treated with said stress reactivity-reducing substance is present in an amount of from about 0.013 micrograms up to about 50 micrograms.

40. The composition of Claim 39 wherein the stress reactivity reducing substance is myristicin.

41. The composition of Claim 33 wherein the carrier perfumed article is a solid or liquid anionic, cationic, nonionic or zwitterionic detergent, or bar soap.

42. The composition of Claim 33 wherein the carrier perfumed article is a hair preparation.

43. The composition of Claim 33 wherein the carrier perfumed article is a deodorant stick.

44. The composition of Claim 33 wherein the carrier perfumed article is a fabric softener composition or a fabric softener article.

45. The composition of Claim 33 wherein the carrier perfumed article is a solid or liquid anionic, cationic, nonionic or zwitterionic detergent, or bar soap.

46. The composition of Claim 34 wherein the carrier perfumed article is a hair preparation.

47. The composition of Claim 34 wherein the carrier perfumed article is a deodorant stick.

48. The composition of Claim 34 wherein the carrier perfumed article is a fabric softener composition or a fabric softener article.

49. The composition of Claim 35 wherein the carrier perfumed article is a solid or liquid anionic, cationic, nonionic or zwitterionic detergent, or bar soap.

50. The composition of Claim 35 wherein the carrier perfumed article is a hair preparation.

51. The composition of Claim 35 wherein the carrier perfumed article is a deodorant stick.

52. The composition of Claim 35 wherein the carrier perfumed article is a fabric softener composition or a fabric softener article.

53. The composition of Claim 36 wherein the carrier perfumed article is a solid or liquid anionic, cationic, nonionic or zwitterionic detergent, or bar soap.

54. The composition of Claim 36 wherein the carrier perfumed article is a hair preparation.

55. The composition of Claim 36 wherein the carrier perfumed article is a deodorant stick.

56. The composition of Claim 36 wherein the carrier perfumed article is a fabric softener composition or a fabric softener article.

57. The composition of Claim 37 wherein the carrier perfumed article is a solid or liquid anionic, cationic, nonionic or zwitterionic detergent or bar soap.

58. The composition of Claim 37 wherein the carrier perfumed article is a hair preparation.

59. The composition of Claim 37 wherein the carrier perfumed article is a deodorant stick.

60. The composition of Claim 37 wherein the carrier perfumed article is a fabric softener composition or a fabric softener article.

61. The composition of Claim 38 wherein the carrier perfumed article is a solid or liquid anionic, cationic, nonionic or zwitterionic detergent, or bar soap.

62. The composition of Claim 38 wherein the carrier perfumed article is a hair preparation.

63. The composition of Claim 38 wherein the carrier perfumed article is a deodorant stick.

64. The composition of Claim 38 wherein the carrier perfumed article is a fabric softener composition or a fabric softener article.

65. The composition of Claim 39 wherein the carrier perfumed article is a solid or liquid anionic, cationic, nonionic or zwitterionic detergent, or bar soap.

66. The composition of Claim 39 wherein the carrier perfumed article is a deodorant stick.

67. The composition of Claim 39 wherein the carrier perfumed article is a deodorant stick.

68. The composition of Claim 39 wherein the carrier perfumed article is a fabric softener composition or a fabric softener article.

69. The composition of Claim 40 wherein the carrier perfumed article is a solid or liquid anionic, cationic, nonionic or zwitterionic detergent, or bar soap.

70. The composition of Claim 40 wherein the carrier perfumed article is a hair preparation.

71. The composition of Claim 40 wherein the carrier perfumed article is a deodorant stick.

72. The composition of Claim 40 wherein the carrier perfumed article is a fabric softener composition or a fabric softener article.

73. The composition of Claim 33 or 37 wherein the carrier perfumed article is an air freshener.

74. The composition of Claim 33 or 37 wherein the carrier perfumed article is an aerosol product.

75. The composition of Claim 33 or 37 wherein the carrier perfumed article is a cologne.

76. The composition of Claim 33 or 37 wherein the carrier perfumed article is a body oil.

77. The composition of Claim 33 or 37 wherein the carrier perfumed article is a candle.

78. A composition of material existing in the gaseous phase for reduction of reactivity to stress in a human being consisting essentially of, in intimate admixture;
(i) air (ii) ethanol; and (iii) a substance selected from the group consisting of myristicin and nutmeg oil.

79. The gaseous mixture of claim 78 comprising air, ethyl alcohol and from 13 micrograms to 1000 micrograms of nutmeg oil, the weight ratio of said nutmeg oil to said ethyl alcohol being in the range of from 1:99 to 99:1.

80. The gaseous mixture of claim 78 comprising air, ethyl alcohol and from 0.013 micrograms to 50 micrograms of myristicin, the weight ratio of said myristicin to said ethyl alcohol being in the range of from 1:99 to 99:1.

81. The gaseous mixture of claims 78, 79 or 80 additionally comprising a carrier perfume composition compatible with air, ethyl alcohol, nutmeg oil and myristicin.