WO2008044046A1 - Perfume compositions - Google Patents

Perfume compositions Download PDF

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Publication number
WO2008044046A1
WO2008044046A1 PCT/GB2007/003893 GB2007003893W WO2008044046A1 WO 2008044046 A1 WO2008044046 A1 WO 2008044046A1 GB 2007003893 W GB2007003893 W GB 2007003893W WO 2008044046 A1 WO2008044046 A1 WO 2008044046A1
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WO
WIPO (PCT)
Prior art keywords
perfume composition
essential oil
essential oils
component
user
Prior art date
Application number
PCT/GB2007/003893
Other languages
French (fr)
Inventor
Pam Asplund
Original Assignee
Reckit Benckiser (Uk) Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Reckit Benckiser (Uk) Limited filed Critical Reckit Benckiser (Uk) Limited
Publication of WO2008044046A1 publication Critical patent/WO2008044046A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/007Pulmonary tract; Aromatherapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • CCHEMISTRY; METALLURGY
    • C11ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11BPRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B9/00Essential oils; Perfumes

Definitions

  • This invention relates to compositions for use in air fresheners which impart a measurably improved physiological response to a subject, to methods of air- freshening using said compositions, and to air-freshening devices containing said compositions.
  • Air freshening compositions and devices are well known in ' the art as a means of delivering a pleasant and desirable fragrance to an environment, and/or masking or removing malodours in the ' process, thus imparting a sense of well- being to individuals in said environment.
  • aromatherapy oils have been widely used, typically in a simple receptacle where the evaporation of the active components occurs naturally or is aided by heat provided by a candle.
  • EP1424071 describes a perfume composition for mental control comprising one of a long list of chemical components having a psycho-sedative effect but does not disclose the use of essential oils as the primary source of these chemicals, and the compositions disclosed comprise at least 20 of these chemical components.
  • WO 2002/49600 describes a perfume composition comprising at least 25 wt% of at least 5 selected relaxing fragrance materials, again selected from an extensive list of pure chemical components. Qualitative measurements of the change in brain (alpha wave) activity are disclosed.
  • a perfume composition containing between 0.5 to 10 wt% of essential oils, wherein said essential oil component comprises a first component of at least 5 essential oils selected from: bergamot; bitter orange; carrot seed; chamomile; coriander; cypress; fennel; jasmine; lavender; marjoram; Melissa (lemon balm) ; neroli; patchouli; petitgrains; rose; sage clary; sandalwood; thyme; valerian; vetiver; yarrow; and characterised in that said essential oil component further comprises a second essential oil component of at least one additional essential oil selected from: basil; bay laurel; benzoin resin; cedarwood; celery; cinnamon leaf; cubeba; frankincense; galbanum; geranium; grapefruit; laurel; lavendin; litsea; myrrh; orange; rosemary; vanilla; ylang- ylang.
  • said essential oil component comprises a first component of at least 5 essential oils selected from:
  • the essential oil component of the perfume composition comprises a first component of at least 5 essential oils selected from: chamomile; coriander; lavender; neroli; patchouli; rose; sage clary; and further comprises a second essential oil component of at least one essential oil selected from: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; ylang-ylang.
  • the essential oil component of the perfume composition comprises a first essential oils component of: chamomile; coriander; lavender; neroli; patchouli; rose; and sage clary; and further comprises a second essential oil component of at least one essential oil selected from: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; ylang-ylang.
  • the essential oil component of the perfume composition comprises a first essential oils component of: chamomile; coriander; lavender; neroli; patchouli; rose; and sage clary; and further comprises a second essential oil component of at least 5 essential oils selected from: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; ylang-ylang.
  • the essential oil component of the perfume composition comprises a first essential oils component of: chamomile; coriander; lavender; neroli; patchouli; rose; and sage' clary; and further comprises a second essential oils component of: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; and ylang-ylang.
  • the ratio of the first essential oils component to the second essential oils component is in the range of
  • the wt% of the individual essential oils within the first essential oil component are provided in a range of 0.00001wt% to 1.0wt%, and preferably in a range of 0.0001wt% to 0.5wt%, and most preferably in a range of 0.0005wt% to 0.2wt%.
  • the wt% of the individual essential oils within the second essential oil component are provided in a range of 0.00001wt% to 5.0wt%, and preferably in a range of 0.0001wt% to 2.0wt%/ and most preferably in a range of 0.0005wt% to 1.0wt%.
  • the perfume composition of the present invention may be diluted to using standard excipients and/or solvents in order to produce the desired range of essential oils within said composition.
  • an inhaleable medicament wherein said medicament comprises the perfume composition according to the first aspect present invention, and wherein the perfume composition has been volatilised, in use, for inhalation by a user.
  • the medicament is adapted -for administration by the perfume composition being initially provided in liquid form before subsequently being volatilised so that it may be inhaled by a user.
  • a sedative composition wherein said sedative comprises the perfume composition according to the first aspect present invention, and wherein the perfume composition has been volatilised, in use, for inhalation by a user.
  • the perfume inhaleable medicament and/or sedative composition may utilise the perfume composition to impart detectable physiological responses to a user, in particular, such responses may have relaxant and/or anti- stress and/or anti-depressant properties.
  • a perfume composition according to the first aspect of the present invention wherein the composition has, upon inhalation by a user, a measurable beneficial physiological response on the user which improves the ability of the user to sleep.
  • a perfume composition according to the first aspect of the present invention wherein the composition has, upon inhalation by a user, a measurable beneficial physiological response on said user wherein said response is at least one of: a reduction in brain alpha waves: a reduction in systolic blood pressure: a reduction in respiration rate; and/or a decrease in skin conductance.
  • a method of making the perfume composition of the first aspect of the present invention available for inhalation by a user comprising the steps of: loading said composition into an aerosol; charging the aerosol with propellant; and activating the aerosol to emanate said composition.
  • the method comprises the step of loading the aerosol into a device and the device is configured to activate the aerosol to emanate said composition.
  • a seventh aspect of the present invention there is provided an alternative method of making the perfume composition of the first aspect available for inhalation by a user, comprising the steps of: loading liquid perfume composition into a reservoir container; using a wick immersed in said reservoir to uptake the composition from the reservoir to a distal portion of the wick beyond outside of said reservoir; and emanating the composition from the distal portion of the wick.
  • the method of the seventh aspect uses an emanation device wherein the device comprises a support structure adapted to hold the reservoir container and, optionally, support a heating means and/or a fan means substantially adjacent the distal portion of the wick to increase the rate of emanation of the perfume composition from said wick portion.
  • the emanation device may be provided with boost functionality wherein upon activation of the boost mechanism the heating means and/or the fan means are activated to impart heat and/or the passage of air respectively over at least a part of the distal portion of the wick.
  • said boost mechanism may, upon activation, increase the heat and/or the rate of the passage of air respectively from said heating means and/or fan means.
  • a method of improving the sleep of a user which comprises the inhalation of a perfume composition according to a first aspect of the present invention.
  • a method of improving the sleep of a user which comprises the volatilisation of a perfume composition as hereinbefore described into the ambient atmosphere of the subject.
  • a patch for emanating a perfume composition according to a first aspect of the present invention, wherein the patch is configured to retain a quantity of the composition and the patch is adapted, in use, to be located adjacent to a user.
  • the patch is adapted to be releasably attached to the skin of a user.
  • the patch may comprise an adhesive side which is configured, in use, to adhere to a user and further comprise an emanation side which is configured, in use, to permit the emanation of the composition therefrom.
  • the patch comprises heating means.
  • the heating means may be configured to impart an amount of heat which may be suitable to increase the rate of emanation of the composition from the patch and/or may impart a heating effect on a user.
  • the patch may be provided with a reservoir section that is capable of retaining a quantity of the perfume composition for subsequent emanation.
  • the patch may be impregnated with and/or permitted to superficially absorb a quantity of perfume composition for subsequent emanation. Such impregnation/absorption may be achieved by direct addition or microencapsulation with subsequent addition.
  • This overall mixture was then diluted to a level of 4.2 wt% with standard excipients and introduced into the refill bottle of an electrical plug-in air freshener unit, which served as a fragrance warmer.
  • composition 1 On sleep, sleep data were collected from subjects over a six week period, before and during a conditioning phase. During the conditioning phase the subjects were exposed to the fragrance at night.
  • fragrance induced relaxation was tested by measuring a range of key physiological parameters in response to a controlled exposure protocol. These parameters were measured before, during and after a conditioning phase.
  • Fragrance Fragrance composition 1 as described above was used for these tests.
  • Standard electrical plug-in fragrance warmer units supplied by Reckitt Benckiser under the Airwick trademark
  • fragrance warmers were supplied with 20.5g of fragrance composition 1 each.
  • the fragrance warmers remained plugged into the subjects bedrooms and were left on continuously at the lowest setting (1 on a 1- 5 scale) .
  • the fragrance composition described above was used at a dilution of 1:100 (diluted in dipropylene glycol (DPG)) of which lOO ⁇ l was applied to a face mask.
  • DPG dipropylene glycol
  • Pre-trial sleep study Subjects filled in a sleep log for two weeks recording the time they went to bed, approximate time they fell asleep and the time they woke up. In addition they scored the ease with which the fell asleep and the quality of their sleep on a +5/-5 scale where zero was the normal level for them.
  • Heart rate was measured with a 1 SIMS Oximeter. The output . was averaged over either 8 or 16 heart beats and presented as a continuous output to the data handling programme. b) Respiration rate
  • the rate of respiration was monitored continuously using a nasal thermistor connected to a preamplifier/amplifier (CED1902, Cambridge Electronic Design, Cambridge, UK) , from where the signal was digitized (CED1401 laboratory interface) and sent to a computer for storage and subsequent analysis, c) Skin resistance
  • Systolic/diastolic blood pressure was taken before (x 2) and immediately after exposure to the fragrance using a upper arm cuff monitor (Boots, UK) .
  • the first blood pressure reading was not used. It is often the case that subjects are nervous at first when they enter the laboratory. This renders the first reading of blood pressure artificially high in some cases.
  • the number of subjects was determined by the required statistical power required for the experiment.
  • 40 subjects were needed. Additional subjects were recruited to allow for drop-out. Sleep Trial (conditioning phase)
  • Subjects were required to keep a sleep log (as above "Pre- Trial Sleep ' Log", see Appendix 1) for the 28 days of the trial during which they were exposed to the fragrance in their bedrooms. This period is referred to as the "conditioning phase”.
  • the analysis of the digitised data was performed by the programme Spike2 (CED, Cambridge, UK) .
  • the first two minutes of the lOmin test period was sampled for EEG and the last two minutes of the lOmin test period was sampled for the remaining physiological parameters (skin resistance, heart rate, SpO2, respiration).
  • the change in each parameter following a brief (lOmin) exposure to the fragrance was measured as the difference between the test period and the first control period. This change was then compared between the control (no odour) and each of the 4 tests during the conditioning phase.
  • This study has a within subjects single factor design with duration of conditioning phase as the main factor.
  • the data are presented as mean ⁇ standard error.
  • One-way analysis of variance (ANOVA) was performed on the data using a repeated measures general linear model with duration of the study.
  • Post hoc analysis was performed using the LSD (least significant difference) test to determine pair-wise differences.
  • Quality of sleep • The values for quality of sleep, measured on a +5/-5 scale, for the pre-trial period were; females 0.39 + 0.24 and males 1.07 ⁇ 0.25. This increased significantly over the conditioning phase to 1.48 ⁇ 0.33 (P ⁇ 0.01; post hoc , analysis, LSD) for females - a 287% increase, and 1.60 + 0.29 (P ⁇ 0.05) for males - a 50% increase. Analysis of variance showed a main effect for duration of exposure to the fragrance for females (P ⁇ 0.001) and for males (P ⁇ 0.05) .
  • the heart rate (HR) was measured before, during and after lOmin exposure to the fragrance on days 0, 7, 14 and 28 of the conditioning phase of the study and compared to a separate control measurement during which the subjects were exposed to the solvent (DPG) alone without fragrance.
  • the protocol was otherwise identical.
  • the data are presented as the change, in percent, in HR during the 10 min fragrance exposure compared to the value before exposure.
  • respiration rate was measured before, during and after lOmin exposure to the fragrance on days 0, 7, 14 and 28 of the study and compared to a separate control measurement during Which the subjects were exposed to the solvent (DPG) alone.
  • the data are presented as the change, in percent, in respiration rate during the 10 min fragrance exposure compared to the value before exposure.
  • the skin resistance (GSR) was measured before, during and after lOmin exposure to the fragrance on days 0, 7, 14 and 28 of the conditioning phase of the study and compared to a separate control measurement during which the subjects were exposed to the solvent (DPG) alone.
  • the data are presented as the change, in percent, in GSR during the 10 min fragrance exposure compared to the value before exposure.
  • the power in the alphawave frequency band (8-13Hz) was measured in the left and right frontal hemispheres (F7 and F8 electrode positions, International System) before, during and after lOnain exposure to the fragrance on days 0, 7, 14 and 28 of the conditioning phase of the study and compared to a separate control measurement during which the subjects were exposed to the solvent (DPG) alone.
  • the data are presented as the change, in percent, in alpha power during the 10 minute fragrance exposure compared to the value before exposure.
  • Blood pressure was taken in the lab before, during and after the 10 minute fragrance exposure. The data are presented as the change in blood pressure (BP dur ⁇ n g ⁇ ⁇ BPbefore) in percent for the control test and the different test days during the 28-day trial.
  • the blood pressure (BP) in response to the lOmin fragrance exposure was measured on days 0, 7, 14 and 28 of the study and compared to a separate control measurement during which the subjects were exposed to the solvent (DPG) alone.
  • ⁇ - Alphawaves changed significantly in women - this was a result of the difference in brain activity between the odour and no odour control. There was no evidence for a conditioned association effect. ⁇ Blood pressure changed significantly in women. A 3% and 4.6% drop in systolic and diastolic BP respectively.

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Abstract

The present invention describes a perfume composition containing between 0.5 to 10 wt% of essential oils, wherein said essential oil component comprises a first component of at least 5 essential oils selected from: bergamot; bitter orange; carrot seed; chamomile; coriander; cypress; fennel; jasmine; lavender; marjoram; Melissa (lemon balm); neroli; patchouli; petitgrains; rose; sage clary; sandalwood; thyme; valerian; vetiver; yarrow; and characterised in that said essential oil component further comprises a second essential oil component of at least one additional essential oil selected from: basil; bay laurel; benzoin resin; cedarwood; celery; cinnamon leaf; cubeba; frankincense; galbanum; geranium; grapefruit; laurel; lavendin; litsea; myrrh; orange; rosemary; vanilla; ylang- ylang. The present invention further describes the use of such a composition to impart a measurable beneficial physiological response on a user which improves the ability of the, user to sleep.

Description

PERFUME COMPOSITIONS
This invention relates to compositions for use in air fresheners which impart a measurably improved physiological response to a subject, to methods of air- freshening using said compositions, and to air-freshening devices containing said compositions.
Air freshening compositions and devices are well known in ' the art as a means of delivering a pleasant and desirable fragrance to an environment, and/or masking or removing malodours in the' process, thus imparting a sense of well- being to individuals in said environment.
Such effects have hitherto only been temporary and perceptually subjective, and much focus has been on the achievement of a longer lasting benefit by delivery mechanisms which overcome the so-called "habituation' or Λfragrance-fatigue' phenomenon.
As an alternative means of improving the environment of an individual, aromatherapy oils have been widely used, typically in a simple receptacle where the evaporation of the active components occurs naturally or is aided by heat provided by a candle.
EP1424071 describes a perfume composition for mental control comprising one of a long list of chemical components having a psycho-sedative effect but does not disclose the use of essential oils as the primary source of these chemicals, and the compositions disclosed comprise at least 20 of these chemical components.
WO 2002/49600 describes a perfume composition comprising at least 25 wt% of at least 5 selected relaxing fragrance materials, again selected from an extensive list of pure chemical components. Qualitative measurements of the change in brain (alpha wave) activity are disclosed.
It is an object of the present invention therefore to provide a solution to the objective technical problem of providing a perfume composition which imparts a measurably improved physiological response on humans the active part of which is based solely on essential oils.
According to a first embodiment of the present invention there is provided therefore a perfume composition containing between 0.5 to 10 wt% of essential oils, wherein said essential oil component comprises a first component of at least 5 essential oils selected from: bergamot; bitter orange; carrot seed; chamomile; coriander; cypress; fennel; jasmine; lavender; marjoram; Melissa (lemon balm) ; neroli; patchouli; petitgrains; rose; sage clary; sandalwood; thyme; valerian; vetiver; yarrow; and characterised in that said essential oil component further comprises a second essential oil component of at least one additional essential oil selected from: basil; bay laurel; benzoin resin; cedarwood; celery; cinnamon leaf; cubeba; frankincense; galbanum; geranium; grapefruit; laurel; lavendin; litsea; myrrh; orange; rosemary; vanilla; ylang- ylang.
Preferably the essential oil component of the perfume composition comprises a first component of at least 5 essential oils selected from: chamomile; coriander; lavender; neroli; patchouli; rose; sage clary; and further comprises a second essential oil component of at least one essential oil selected from: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; ylang-ylang.
Even more preferably the essential oil component of the perfume composition comprises a first essential oils component of: chamomile; coriander; lavender; neroli; patchouli; rose; and sage clary; and further comprises a second essential oil component of at least one essential oil selected from: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; ylang-ylang.
Even more preferably still, the essential oil component of the perfume composition comprises a first essential oils component of: chamomile; coriander; lavender; neroli; patchouli; rose; and sage clary; and further comprises a second essential oil component of at least 5 essential oils selected from: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; ylang-ylang.
Most preferably, the essential oil component of the perfume composition comprises a first essential oils component of: chamomile; coriander; lavender; neroli; patchouli; rose; and sage' clary; and further comprises a second essential oils component of: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; and ylang-ylang.
Preferably the ratio of the first essential oils component to the second essential oils component is in the range of
2:3 to 1:25, and more preferably in the range of 1:2 to
1:10, and most preferably in the range of 1:4 to 1:7. .
The wt% of the individual essential oils within the first essential oil component are provided in a range of 0.00001wt% to 1.0wt%, and preferably in a range of 0.0001wt% to 0.5wt%, and most preferably in a range of 0.0005wt% to 0.2wt%.
The wt% of the individual essential oils within the second essential oil component are provided in a range of 0.00001wt% to 5.0wt%, and preferably in a range of 0.0001wt% to 2.0wt%/ and most preferably in a range of 0.0005wt% to 1.0wt%.
The perfume composition of the present invention may be diluted to using standard excipients and/or solvents in order to produce the desired range of essential oils within said composition.
According to a second aspect of the present invention there is provided an inhaleable medicament, wherein said medicament comprises the perfume composition according to the first aspect present invention, and wherein the perfume composition has been volatilised, in use, for inhalation by a user.
Preferably the medicament is adapted -for administration by the perfume composition being initially provided in liquid form before subsequently being volatilised so that it may be inhaled by a user.
According to a third aspect of the present invention there is provided a sedative composition, wherein said sedative comprises the perfume composition according to the first aspect present invention, and wherein the perfume composition has been volatilised, in use, for inhalation by a user. The perfume inhaleable medicament and/or sedative composition may utilise the perfume composition to impart detectable physiological responses to a user, in particular, such responses may have relaxant and/or anti- stress and/or anti-depressant properties.
According to a fourth aspect of the present invention there is provided a perfume composition according to the first aspect of the present invention wherein the composition has, upon inhalation by a user, a measurable beneficial physiological response on the user which improves the ability of the user to sleep.
According to a fifth aspect of the present invention there is provided a perfume composition according to the first aspect of the present invention wherein the composition has, upon inhalation by a user, a measurable beneficial physiological response on said user wherein said response is at least one of: a reduction in brain alpha waves: a reduction in systolic blood pressure: a reduction in respiration rate; and/or a decrease in skin conductance.
According to a sixth aspect of the present invention there is provided a method of making the perfume composition of the first aspect of the present invention available for inhalation by a user, comprising the steps of: loading said composition into an aerosol; charging the aerosol with propellant; and activating the aerosol to emanate said composition.
Preferably the method comprises the step of loading the aerosol into a device and the device is configured to activate the aerosol to emanate said composition. According to a seventh aspect of the present invention there is provided an alternative method of making the perfume composition of the first aspect available for inhalation by a user, comprising the steps of: loading liquid perfume composition into a reservoir container; using a wick immersed in said reservoir to uptake the composition from the reservoir to a distal portion of the wick beyond outside of said reservoir; and emanating the composition from the distal portion of the wick.
Preferably the method of the seventh aspect uses an emanation device wherein the device comprises a support structure adapted to hold the reservoir container and, optionally, support a heating means and/or a fan means substantially adjacent the distal portion of the wick to increase the rate of emanation of the perfume composition from said wick portion.
The emanation device may be provided with boost functionality wherein upon activation of the boost mechanism the heating means and/or the fan means are activated to impart heat and/or the passage of air respectively over at least a part of the distal portion of the wick. Alternatively or additionally, said boost mechanism may, upon activation, increase the heat and/or the rate of the passage of air respectively from said heating means and/or fan means.
According to an eighth aspect of the present invention, there is provided a method of improving the sleep of a user which comprises the inhalation of a perfume composition according to a first aspect of the present invention. According to a ninth aspect of the present invention, there is provided a method of improving the sleep of a user which comprises the volatilisation of a perfume composition as hereinbefore described into the ambient atmosphere of the subject.
According to a tenth aspect of the present invention there is provided a patch for emanating a perfume composition according to a first aspect of the present invention, wherein the patch is configured to retain a quantity of the composition and the patch is adapted, in use, to be located adjacent to a user.
Preferably the patch is adapted to be releasably attached to the skin of a user. The patch may comprise an adhesive side which is configured, in use, to adhere to a user and further comprise an emanation side which is configured, in use, to permit the emanation of the composition therefrom.
Preferably the patch comprises heating means. The heating means may be configured to impart an amount of heat which may be suitable to increase the rate of emanation of the composition from the patch and/or may impart a heating effect on a user.
The patch may be provided with a reservoir section that is capable of retaining a quantity of the perfume composition for subsequent emanation. Alternatively or additionally, the patch may be impregnated with and/or permitted to superficially absorb a quantity of perfume composition for subsequent emanation. Such impregnation/absorption may be achieved by direct addition or microencapsulation with subsequent addition. The invention will now be described with reference to the following examples, without limitation in any way.
Example
Composition 1
A blend of the following essential oil components was prepared (amounts in wt%) :
Benzoin Resin Siam (LMR) 0.15 Cedarwood Oil Texas 0.99
Chamomile Oil English 0.05
Cinnamon Leaf Ceylon Oil 0.15
Coriander Oil 0.20
Galbanum Oil 0.10 Geranium African Oil ' 0.20
Grapefruit Phase Oil (low allergens) 0.30
Lavandin Oil Pure 1.00
Lavender Oil (LMR) 0.20
Neroli Bigarade Petale Oil 0.002 Orange Tarocco Oil 0.60
Patchouli Oil Indonesia MD (LMR) 0.10
Rose Otto Pure Oil 0.0005
Sage Clary Oil French (LMR) 0.006
Vanilla Surabsolute Oil 0.0006 Ylang Oil 0.30
This overall mixture was then diluted to a level of 4.2 wt% with standard excipients and introduced into the refill bottle of an electrical plug-in air freshener unit, which served as a fragrance warmer.
Test
To test the effect of Composition 1 on sleep, sleep data were collected from subjects over a six week period, before and during a conditioning phase. During the conditioning phase the subjects were exposed to the fragrance at night.
To test whether the fragrance induced relaxation was tested by measuring a range of key physiological parameters in response to a controlled exposure protocol. These parameters were measured before, during and after a conditioning phase.
This approach was designed to reveal any intrinsic relaxing properties of the fragrance as well as to demonstrate conditioned associations.
Subjects
Male (n=23) and female (n=24) were recruited of average age; men = 31.7 ± 2.1 years (mean ± standard error, range 23-55), women = 32.5 + 1.6 (range 23 - 49) years. The following were excluded from the study: pregnant or nursing mothers, allergy sufferers (e.g. hay fever), those with nasal/respiratory disorders, subjects taking prescription medications, subjects working in chemistry laboratories, or those exposed to chemicals during the workday.
Fragrance Fragrance composition 1 as described above was used for these tests. Standard electrical plug-in fragrance warmer units (supplied by Reckitt Benckiser under the Airwick trademark) were supplied with 20.5g of fragrance composition 1 each. For the duration of the 4 week sleep trial the fragrance warmers remained plugged into the subjects bedrooms and were left on continuously at the lowest setting (1 on a 1- 5 scale) . For the laboratory tests the fragrance composition described above was used at a dilution of 1:100 (diluted in dipropylene glycol (DPG)) of which lOOμl was applied to a face mask.
Pre-trial sleep study Subjects filled in a sleep log for two weeks recording the time they went to bed, approximate time they fell asleep and the time they woke up. In addition they scored the ease with which the fell asleep and the quality of their sleep on a +5/-5 scale where zero was the normal level for them.
Physiological response
During the four week conditioning phase the following physiological parameters were measured: a) Heart rate b) Respiration rate c) Skin resistance d) Alpha-waves (left-right frontal brainwave activity) e) Blood pressure
a) Heart rate
Heart rate was measured with a1 SIMS Oximeter. The output . was averaged over either 8 or 16 heart beats and presented as a continuous output to the data handling programme. b) Respiration rate
The rate of respiration (breathing) was monitored continuously using a nasal thermistor connected to a preamplifier/amplifier (CED1902, Cambridge Electronic Design, Cambridge, UK) , from where the signal was digitized (CED1401 laboratory interface) and sent to a computer for storage and subsequent analysis, c) Skin resistance
Skin resistance was monitored using a conductance meter (Cambridge Electronic Design CED2502SA) designed to make direct measurements of the conductivity between two electrodes attached to the body (usually the first and third fingers of one hand) . The unit generates a continuous output of skin conductance (I/resistance) . d) Electroencephalography Alpha brain wave production was measured using EEG Ag/AgCl scalp electrodes and conventional electroencephalography. Electrodes were placed according the International 10/20 system such that the frontal asymmetry can be monitored (i.e. at F7 and F8) and connected to a series of amplifiers (CED1902) . Alpha waves are a sign of cortical inactivity and relaxation and there are well established hemispheric differences between positive and negative hedonic affect. The signal was digitised using a laboratory interface (CED 1401) and analyzed by power spectrum (Spike 2, CED) . e) Blood pressure
Systolic/diastolic blood pressure was taken before (x 2) and immediately after exposure to the fragrance using a upper arm cuff monitor (Boots, UK) . The first blood pressure reading was not used. It is often the case that subjects are nervous at first when they enter the laboratory. This renders the first reading of blood pressure artificially high in some cases.
Statistical Power
The number of subjects was determined by the required statistical power required for the experiment. The power in this within-subjects design study was determined by the physiological measure with the greatest variance, in this case the EEG signal (variance = 37.7% of signal mean). In order to detect a 20% change in the spectral power of the alpha band with an 80% likelihood at the 0.05 probability level, 40 subjects were needed. Additional subjects were recruited to allow for drop-out. Sleep Trial (conditioning phase)
Subjects were required to keep a sleep log (as above "Pre- Trial Sleep 'Log", see Appendix 1) for the 28 days of the trial during which they were exposed to the fragrance in their bedrooms. This period is referred to as the "conditioning phase".
Physiological testing
Subjects were given the physiological tests on days 0, 7, 14 and 28 of the conditioning phase. As far as possible these tests were given at the same time of the day on each occasion to minimise the effect of olfactory threshold changes occurring throughout the day.
Protocol for physiological recording:
1. Take blood pressure (sham)
2. Electrodes and sensors attached
3. Pre-acclimatise subject (lOmins, sitting)
4. Take blood pressure 5. Apply face mask
6. Eyes closed, record physiological parameters (as above) , 2 mins
7. Apply aliquot (lOOμl, 1:100 diluted in DPG) of fragrance to face mask. This system delivers the fragrance to the nose and mouth.
8. Eyes closed, record 10 mins.
9. Remove face mask and fragrance, eyes open, rest, 5 mins
10. Take blood pressure 11. Eyes closed, record 2 mins
12. Eyes open, take blood pressure.
Control test
As a control to the fragrance exposure tests above subjects were given the same protocol as described above but instead of the fragrance, the solvent alone (DPG) was applied to the face mask. The subjects were told that as usual a fragrance would be applied that they might, or might not, be able to smell. Analysis
The analysis of the digitised data was performed by the programme Spike2 (CED, Cambridge, UK) . The first two minutes of the lOmin test period was sampled for EEG and the last two minutes of the lOmin test period was sampled for the remaining physiological parameters (skin resistance, heart rate, SpO2, respiration). The change in each parameter following a brief (lOmin) exposure to the fragrance was measured as the difference between the test period and the first control period. This change was then compared between the control (no odour) and each of the 4 tests during the conditioning phase.
Statistics
This study has a within subjects single factor design with duration of conditioning phase as the main factor. The data are presented as mean ± standard error. One-way analysis of variance (ANOVA) was performed on the data using a repeated measures general linear model with duration of the study. Post hoc analysis was performed using the LSD (least significant difference) test to determine pair-wise differences.
Results
Because of gender differences the results for males and females are presented separately.
Sleep
Ease of getting to sleep
The values for ease of getting to sleep, measured on a +5/-5 scale, for the pre-trial period were; females 0.71 ± 0.30 (mean ± standard error) and males 1.17 ± 0.30. This increased significantly over the conditioning phase to 1.59 ± 0.31 (P<0.01; post hoc analysis, LSD) for females - a 124% increase and 1.79 ± 0.32 (P<0.01) for males a 53%. Analysis of variance (repeated measures general linear model) showed a main effect for duration of exposure to the fragrance for females (P<0.01) and for males (P<0.01).
Quality of sleep • The values for quality of sleep, measured on a +5/-5 scale, for the pre-trial period were; females 0.39 + 0.24 and males 1.07 ± 0.25. This increased significantly over the conditioning phase to 1.48 ± 0.33 (P<0.01; post hoc , analysis, LSD) for females - a 287% increase, and 1.60 + 0.29 (P<0.05) for males - a 50% increase. Analysis of variance showed a main effect for duration of exposure to the fragrance for females (P<0.001) and for males (P<0.05) .
Physiological tests
Heart rate
The heart rate (HR) was measured before, during and after lOmin exposure to the fragrance on days 0, 7, 14 and 28 of the conditioning phase of the study and compared to a separate control measurement during which the subjects were exposed to the solvent (DPG) alone without fragrance. The protocol was otherwise identical.
The data are presented as the change, in percent, in HR during the 10 min fragrance exposure compared to the value before exposure.
Females While there was a decrease in the HR during the brief 10 min exposure to the fragrance, analysis of variance revealed that there was no significant main effect for duration of the study. There was no significance in heart rate changes during the different stages of the study.
Males Analysis of variance also revealed that there was no significant main effect for duration of the study. There was no significance in heart rate changes during the different stages of the study.
Respiration rate
The respiration rate (breathing) was measured before, during and after lOmin exposure to the fragrance on days 0, 7, 14 and 28 of the study and compared to a separate control measurement during Which the subjects were exposed to the solvent (DPG) alone.
The data are presented as the change, in percent, in respiration rate during the 10 min fragrance exposure compared to the value before exposure.
Females Analysis of variance revealed that there was a significant main effect for duration of the study (P<0.05) for females. The change in the control was 1.64 ± .1.44% compared to -2.72 ± 1.29% by day 28 of the study - a total change of 4.36% compared to control. There was a progressive increase in the percent fall of respiration during the conditioning phase of the study. This was found to be significant at the 0.01 level for days 14 and 28 compared to control.
Males Analysis of variance revealed that there was a significant main effect for duration of the study (P<0.05) for males. The change in the control was -2.14 ± 1.09% compared to -6.61 ± 1.78% by day 28 of the study - a total change of 4.47% compared to control. There was a progressive increase in the percent fall of respiration during the conditioning phase of the study from day 0 to day 28. This was found to be significant at the 0.05 level for day 28 compared to control.
Skin resistance
The skin resistance (GSR) was measured before, during and after lOmin exposure to the fragrance on days 0, 7, 14 and 28 of the conditioning phase of the study and compared to a separate control measurement during which the subjects were exposed to the solvent (DPG) alone.
The data are presented as the change, in percent, in GSR during the 10 min fragrance exposure compared to the value before exposure.
Females Analysis of variance revealed that there was a significant main effect for duration of the study (P<0.01) for females. The change in the control was -15.6 ± 2.53% compared to -29.46 ± 4.32% by day 28 of the study. There was a progressive increase in the percent fall of GSR during each stage of the study. This was found to be significant at the 0.01 level for days 7, 14 and 28 compared to control.
Males Analysis of variance revealed that there was a significant main effect for duration of the study (P<0.01) for males. The change in the control was -12.25 ± 1.53% compared to -23.17 ± 2.10% by day 28 of the study. There was a progressive increase in the percent fall of GSR during the study. This was found to be significant at the 0.05 level for day 7 and at the 0.01 level for days 0, 14 and 28 compared to control. EEG alpha waves
The power in the alphawave frequency band (8-13Hz) was measured in the left and right frontal hemispheres (F7 and F8 electrode positions, International System) before, during and after lOnain exposure to the fragrance on days 0, 7, 14 and 28 of the conditioning phase of the study and compared to a separate control measurement during which the subjects were exposed to the solvent (DPG) alone.
The data are presented as the change, in percent, in alpha power during the 10 minute fragrance exposure compared to the value before exposure.
Females Analysis of variance revealed that there was a significant main effect (P<0.05) for females in both hemispheres. The change in the control was -22.80 ± 4.67% (Left), -25.99 ± 5.34% (Right) compared to -5.93 ± 5.10% (Left), -10.78 ± 5.53% (Right) by day 28 of the study. There was a reduction in the percent fall of alpha power for each stage of the study compared to control. For the left hemisphere this was found to be significant at the 0.01 level for day 0 and at the 0.05 level for days 7, 14 and 28 compared to control; for the right hemisphere this was significant at level 0.05 for days 0, 7, 28 and at level 0.01 for day 14.
Males Analysis of variance revealed that there was no significant main effect. Although there was an apparent reduction in the % decrease in alpha power at day 28 compared to control in both hemispheres, this did not reach significance.
Blood pressure
Blood pressure was taken in the lab before, during and after the 10 minute fragrance exposure. The data are presented as the change in blood pressure (BPdurαng ~~ BPbefore) in percent for the control test and the different test days during the 28-day trial. The blood pressure (BP) in response to the lOmin fragrance exposure was measured on days 0, 7, 14 and 28 of the study and compared to a separate control measurement during which the subjects were exposed to the solvent (DPG) alone.
Females In the control test (subjects exposed to the solvent DPG alone) the blood pressure (BP) for females changed by 0.58 ± 1.2% (systolic) and -0.71 ± 1.05% (diastolic) . There was a significant main effect for duration of the study (ANOVA, P<0.05) for systolic 1BP and the decreases in BP in response to the fragrance at day 28 of the study were -2.92 ± 0.90% (systolic; P<0.05) and - 4.65 ± 1.41% (diastolic; P<0.0.5).
Males For males the changes during the control test were -2.19 ± 0.69% (systolic), -3.49 ± 1.19% (diastolic). There were no significant changes in either systolic or diastolic BP for males between the control and any of the test days during the study.
Following the 28-day exposure period: > Ease of getting to sleep improved significantly for men (53%) and women (124%) .
> Quality of sleep improved significantly for men (50%) and women (287%) .
Following the 28-day exposure period (conditioning phase) , a short exposure (10 min) to the fragrance was found to have a significantly relaxing effect: y Respiration rate decreased significantly in both men and women. A 10 minute exposure to the fragrance caused a 4.4% reduction in women and a 4.5% reduction in men.
> Skin conductance decreased significantly in both men and women. A 10 minute exposure to the fragrance caused a 15% decrease in women and 11% decrease in men.
> The significant difference in skin conductance between control and day 0 in men suggests an intrinsic effect of the fragrance on relaxation as measured by skin conductance. The change between control and day 0 in women, although in the same direction, did not reach significance.
This conditioning trial found evidence that women were better at forming the conditioned association between the fragrance and sleep than men.
Effects on women alone:
^- Alphawaves changed significantly in women - this was a result of the difference in brain activity between the odour and no odour control. There was no evidence for a conditioned association effect. ^ Blood pressure changed significantly in women. A 3% and 4.6% drop in systolic and diastolic BP respectively.

Claims

1. A perfume composition containing between 0.5 to 10 wt% of essential oils, wherein said essential oil component comprises a first component of at least 5 essential oils selected from: bergamot; bitter orange; carrot seed; chamomile; coriander; cypress; fennel; jasmine; lavender; marjoram; Melissa (lemon balm); neroli; patchouli; 'petitgrains; rose; sage clary; sandalwood; thyme; valerian; vetiver; yarrow; and characterised in that said essential oil component further comprises a second essential oil component of at least one additional essential oil selected from: basil; bay laurel; benzoin resin; cedarwood; celery; cinnamon leaf; cubeba; frankincense; galbanum; geranium; grapefruit; laurel; lavendin; litsea; myrrh; orange; rosemary; vanilla; ylang- ylang.
2. The perfume composition according to claim 1, wherein the essential oil component of the perfume composition comprises a first component of at least 5 essential oils selected from: chamomile; coriander; lavender; neroli; patchouli; rose; sage clary; and further comprises a second essential oil component of at least one essential oil selected from: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; ylang-ylang.
3. The perfume composition according to claim 1 or claim 2, wherein the essential oil component of the perfume composition comprises a first essential oils component of: chamomile; coriander; lavender; neroli; patchouli; rose; and sage clary; and further comprises a second essential oil component of at least one essential oil selected from: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; ylang- ylang.
4. The perfume composition according to any preceding claim, wherein the essential oil component of the perfume composition comprises a first essential oils component of: chamomile; coriander; lavender; neroli; patchouli; rose; and sage clary; and further comprises a second essential oil component of at least 5 essential oils selected from: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; ylang- ylang.
5. The perfume composition according to any preceding claim, wherein the essential oil component of the perfume composition comprises a first essential oils component of: chamomile; coriander; lavender; neroli; patchouli; rose; and sage clary; and further comprises a second essential oils component of: benzoin resin; cedarwood; cinnamon leaf; galbanum; geranium; grapefruit; lavendin; orange; vanilla; and ylang-ylang.
6. The perfume composition according to any preceding claim, wherein the ratio of the first essential oils component to the second essential oils component is in the range of 2:3 to 1:25.
7. The perfume composition according to any of claims 1- 5, wherein the ratio of the first essential oils component to the second essential oils component is in the range of 1:2 to 1:10.
8. The perfume composition according to of claims 1-5, wherein the ratio of the first essential oils component to the second essential oils component is in the range of 1:4 to 1:7.
9. The perfume composition according to any preceding claim, wherein the wt% of the individual essential oils within the first essential oil component are provided in a range of 0.00001wt% to 1.0wt%.
10. The perfume composition according to any of claims 1- 8, wherein the wt% of the individual essential oils within the first essential oil component are provided in a range of 0.0001wt% to 0.5wt%.
11. The perfume composition according to any of claims 1- 8, wherein the wt% of the individual essential oils within the first essential oil component are provided in a range of 0.0005wt% to 0.2wt%.
12. The perfume composition according to any preceding claim, wherein the wt% of the individual essential oils within the second essential oil component are provided in a range of 0.00001wt% to 5.0wt%.
13. The perfume composition according to any of claims 1- 11, wherein the wt% of the individual essential oils within the second essential oil component are provided in a range of 0.0001wt% to 2.0wt%.
14. The perfume composition according to any of claims 1- 11, wherein the wt% of the individual essential oils within the second essential oil component are provided in a range of 0.0005wt% to 1.0wt%.
15. An inhaleable medicament, wherein said medicament comprises the perfume composition according to any preceding claim, and wherein the perfume composition has been volatilised, in use, for inhalation by a user.
16. The inhaleable medicament according to claim 15, wherein the medicament is adapted for administration by the perfume composition being initially provided in liquid form before subsequently being volatilised for inhalation by a user.
17. A sedative composition, wherein said sedative comprises the perfume composition according to any of claims 1-14, and wherein the perfume composition has been volatilised, in use, for inhalation by a user.
18. A perfume composition according to any of claims 1-14, wherein the composition has, upon inhalation by a user, a measurable beneficial physiological response on the user which improves the ability of the user to sleep.
19. A perfume composition according to any of claims 1-14, wherein the composition has, upon inhalation by a user, a measurable beneficial physiological response on said user wherein said response is at least one of: a reduction in brain alpha waves: a reduction in systolic blood pressure: a reduction in respiration rate; and/or a decrease in skin conductance .
20. A method of making the perfume composition as claimed in any of claims 1-14 available for inhalation by a user, wherein the method comprises the steps of: loading said perfume composition into an aerosol; charging the aerosol with propellant; and activating the aerosol to emanate said composition.
21. The method of claim 20, wherein the method comprises the step of loading the aerosol into a device and wherein the device is configured to activate the aerosol to emanate said composition.
22. A method of making the perfume composition as claimed in any of claims 1-14 available for inhalation by a user, wherein the method comprises the steps of: loading liquid perfume composition into a reservoir container; using a wick immersed in said reservoir to uptake the composition from the reservoir to a distal portion of the wick beyond outside of said reservoir; and emanating the composition from the distal portion of the wick.
23. The method according to claim 22, wherein the method uses an emanation device, and wherein said device comprises a support structure adapted to hold the reservoir container and, optionally, support a heating means and/or a fan means substantially adjacent the distal portion of the wick to increase the rate of emanation of the perfume composition from said wick portion.
24. The method according to claim 23, wherein said emanation device is provided with boost functionality wherein upon activation of the boost mechanism the heating means and/or the fan means are activated to impart heat and/or the passage of air respectively over at least a part of the distal portion of the wick.
25. A method of improving the sleep of a user comprising the inhalation of a perfume composition according to any of claims 1-14.
26. A method of improving the sleep of a user, wherein said method comprises the volatilisation of a perfume composition as claimed in any of claims 1-14 into the ambient atmosphere of the user.
27. A patch for emanating a perfume composition according to any of claims 1-14, wherein the patch is configured to retain a quantity of the composition and the patch is adapted, in use, to be located adjacent to a user.
28. A patch according to claim 27, wherein the patch comprises heating means.
PCT/GB2007/003893 2006-10-13 2007-10-15 Perfume compositions WO2008044046A1 (en)

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CN103025339A (en) * 2010-03-31 2013-04-03 株式会社资生堂 Expression modulator for clock gene Period
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CN102776071A (en) * 2012-08-15 2012-11-14 上海应用技术学院 Transparent microcapsule flavoring jasmine essence and preparation method thereof
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