in one form , a repetitive olfactory chemosensory stimulation ( rocs ) paradigm , and development of an otds device are provided herein . it has been unexpectedly discovered that by pulsing air and / or oxygen coupled with at least one active ingredient , such as an odorant , drug , medicament , or combination thereof , much of the desensitization that occurs from prolonged exposure to the materials can be minimized or otherwise avoided . in other words , overall treatment periods of the at least one odorant , drug , medicament , or combination can be shortened using a pulsed approach than if the same material were continuously delivered . it should be appreciated that when the term odorant is used , blends of odorants may also be used in a similar manner unless specifically stated otherwise . further , other materials such as drugs , medicaments , and the like , may be used in the place of the odorant and / or in combination with the odorant as described herein . for example , curcumin and / or curcumin analog may be used in place of and / or in combination with one or more odorants . similarly , other drugs , medicaments and other materials may be used . in one form , an active ingredient , such as at least one odorant , drug , medicament , or combination thereof , may be administered to a user in a pulsed manner whereby a plurality of active delivery periods and rest periods are used . for example , each active delivery period can include delivery of at least one active ingredient followed by a rest period whereby no active ingredient is delivered to the user . a plurality of the active delivery and rest periods can be combined for a treatment regimen . a variety of different active ingredients may be used . for example , a plurality of different odorants may be used . such odorants may include rosmarinus officinalis ( rosemary ), citrus sinensis ( orange ), citrus bergamia ( bergamot orange ), citrus limon ( lemon ), lavendular augustifolia ( lavender ), and cinnamon zeylanicum ( cinnamon ) which are classified as part 182 ( substances generally recognized as safe ) under fda cfr — code of federal regulations title 21 . the compounds are components of human food and have been detected in human blood following ingestion . by diluting each of these odorants in polyethylene glycol ( peg ) 400 ( sigma ) serially , it was determined the threshold concentration ( v / v ) perceivable by all 20 individuals ( age range 20 - 65 ) during 2 - seconds olfactory threshold tasks . the maximum threshold of detection by all subjects was 2 % ( for rosemary ). the minimum tolerable concentration by volunteers was 6 % ( for cinnamon ). in one aspect , the blend of odorants includes sweet orange also called citrus sinensis . bergamont orange also called citrus bergamia also can be used in lieu of sweet orange or blended with sweet orange . the blend further includes lemon oil also called citrus limon . as used herein , “ citrus ,” as opposed to “ citrus limon ” means sweet orange or bergamont orange . the odorant blend also includes cinnamon oil also known as cinnamomum zeylanicum and rosemary oil also called rosmarinus officinalis . odorants which are not from a botanical source such as cinnamonum zeylanicum , but are flavorings which mimic the botanical sourced odorant also may be used . other active ingredients may also be used such as drugs , medicaments , and the like . further , the active ingredients may be used individually , in combination with one another and in combination with other types of active ingredients . for example , blends of odorants , blends of drugs , blends of medicaments , blends of odorants with drugs , and the like may be used . in one form , curcumin may be used . additionally , the active ingredients may be further processed to increase the concentration of one or more components therein . for example , rosemary may be used , but may be processed such that the rosemary contains a higher concentration of carnosic acid than naturally occurs . for example , the concentration of carnosic acid may be increase to be at least about 3 wt . %. in other forms , the carnosic acid concentration is increased to at least about 10 wt . %. the increased carnosic acid may increase the efficacy of other active ingredients administered to the user . in one form , the duration of each active delivery period and / or rest period may be provided to achieve stimulation of different portions of a user . the active delivery period may be from about 1 to about 600 seconds per period before a rest period . for example , in one form , the active delivery period is about 1 to about 10 seconds to stimulate a first portion of the user . in one form , the active delivery period is about 30 to about 45 seconds to stimulate a second portion of the user . in one form , the active delivery period is about 60 to about 120 seconds to stimulate a third portion of the user . further , in addition to pulsing active delivery and rest periods , the active ingredients delivered may also change from one active delivery period to the next . in this regard , the user &# 39 ; s olfactory system may be “ confused ” as to what the next active ingredient may be . this may enhance the efficacy through the “ confusion .” in one form , a device is provided for olfactory activation . the device consists of a pump , filter , flow meter , check valve , odorant chambers , and cannula . the pump generates a current of filtered air directed into the odorant chamber through a tube with flow - directed valves . this flow is channeled through a user - controlled flow meter , on the outside of the device , for regulation of the rate of flow of odorant containing air / oxygen to the nose . the pump is operated with dc current supplied by a rechargeable battery . the apparatus has a housing to accommodate the battery and an outlet to effect recharging . for example , referring to fig1 , the apparatus includes cannula 2 having a conduit 4 into an odorant chamber 6 containing a blend of odorants 8 . pump 10 pumps air at a positive pressure through conduit 12 to filter 14 and flow meter 16 past check valve 18 into the odorant chamber 6 . the air under positive pressure sweeps the odorants from the blend of odorants into conduit 4 and pushes the odorants through cannula 2 into the nose of the user . in one aspect , the apparatus is portable to permit treatment over a day / evening . in this aspect , the pump is operated with dc current being supplied by a rechargeable battery . the apparatus has a housing to accommodate the battery and an outlet to effect recharging . in one form , a cpap type of machine and / or apap type of machine can be used to intranasally transmit odorants in a pulsed manner to the olfactory regions of the brain and therefore have a positive effect on the effectiveness of the treatment . in fact , such a use can cut treatment time compared to a cpap machine continuously intranasally delivering the odorants . to determine if exposure to a blend of multiple odorants will have greater positive impact on olfactory function compared to each odorant alone , 15 adults ( 40 - 65 years old ; 60 % males ) with stable moderate olfactory loss were exposed to daily 30 - minute long inhalation of limonene ( a simple molecule ), rosemary , lavender or a blend of rosemary and lavender . odor threshold ( i . e . minimum concentration of n - butanol detected ; higher scores indicate ability to detect higher number of dilutions ), odor identification ( i . e . the maximum number of odorants identified in a forced - choice test ), and odor memory were assessed . in table 1 below , daily exposure to lavender or rosemary significantly improved all 3 olfactory parameters , whereas limonene did not have any appreciable impact . those exposed to the blend of rosemary and lavender experienced the strongest improvement . to explore the impact of daily treatment with otds on olfaction , 14 volunteers ( 70 % females ; mean age 56 . 8 years ) with combined impairment of odor threshold and odor identification were subjected to one - hourly for 10 days and compared their odor identification and odor threshold pre - and post - treatment . the mean score for the 40 - point university of pennsylvania smell identification task ( 35 ), pre - and post - treatment were 30 . 4 and 36 . 5 , respectively , and this difference was statistically significant . although the odor threshold also improved with treatment , the change was not statistically significant with 10 days otds additionally , the immediate neural effect of 5 minutes of otds treatment on activation of the olfactory region of interest ( roi ) using functional magnetic resonance imaging ( fmri ). as shown in the representative result ( fig2 a ), orbitofrontal cortex ( ofc )— a high - order olfactory processing region — was activated . the temporal sequence of short duration ( 10 - sec and 30 - sec ) repeated olfactory stimulation with the same odorant in the otds was tested . as depicted in fig2 b , it was observed that activations of more primary olfactory roi with shorter duration of repeated chemosensory stimulation . in view of this , tests were focused on development of a pulse - based stimulation using the parameters for repeated stimulations and inter - stimulation intervals observed from the fmri studies . an otds device was reprogrammed for neuromodulation with rocs . in one form , the device includes user input / use specifications : 1 ) input duration of bursts 5 - 120 seconds with intermittent bursts of no odorant ; 10 second interval options ; 2 ) input frequency of bursts / min ; 3 ) input amount per burst 0 . 5 - 2 ml / min ; 3 ) should be able to deliver for up to a 1 hour therapy session ; 4 ) history of past uses ( 7 days ); 5 ) on / off / in use light ; and 6 ) indicator when low on charge / battery and low on fluids ( water / odorant ). in one form , the device can be portable and have a user - friendly lcd screen menu options ( fig3 , under aim 1 ), that enable configuration of treatment parameters . in one form , the otds is configured as a micro - controller regulated device to deliver repeated bursts or pulses of odorant stimulations with very flexible ranges of pulse parameters to enable targeting of olfactory brain regions impaired during aging . an example of such a device is shown in fig3 . any number of different settings can be configured by medical personnel and / or a user . examples of other configurable settings are shown in fig4 . for example , regulation of : durations of stimulation bursts and inter - burst intervals , burst frequency , input amount of odorants per bursts in liters / minute , and the total duration of treatment may be permitted . in one form , the device can deliver one or more odorants in discrete bursts where no odor reaches the nose during the rest period . in one form , the device includes a tdk ultrasonic nebulizer , arduino uno r3 — arduino mega 2560 , adafruit v2 motor shield , solenoid pinch valves , and blower motor . the ultrasonic nebulizer method ( fig5 ) works by periodic , high frequency vibrations of a piezo - transducer create small bubbles — negative pressure relating to bubble formation , positive pressure creating bubble collapse . the surface of the fluid experiences oscillations making standing capillary waves where water droplets are propelled when they deviate from the sine - like wave shape . efficiency and droplet size dependent on : ventilation ( air pump / fan ) psi and piezo vibration frequency . as discussed above , the active ingredients , active delivery periods , rest periods , treatment regimens , pressures , concentrations and the like may be modified to stimulate different portions of a user . for example , in one form , three primary olfactory ( poc ) regions of interest ( amygdala , piriform cortex and entorhinal cortex ) and the hippocampus may be stimulated in different manners . for example , different portions may react differently to the duration of the active delivery periods and rest periods . for example , very short active delivery periods may stimulate a first portion more than other portions while a longer duration active delivery period may stimulate other portions of a user more than the very short periods . further , the number of cycles ( the number of active delivery periods followed by rest periods ) may also impact different portions of a user in different manners . in one form , the hardware and / or software of the otds device for pulsatile delivery of our odorant formulations can be modified as needed for a particular user , odorant , drug , and the like . similarly , the pulse delivery parameters required to maximally engage the poc can be modified . further , single odorants , blends of odorants , rotations of single and blends of odorants can be used for engagement of poc and on enduring neuroplasticity . drugs and other materials may be uses in a similar manner . further , the device may be portable for home - use . according to one form , using pulsing , treatment times of 30 minutes are the equivalent of 12 hours with the same odorants where continuous delivery of the odorants is performed . pulsing also may be effective for using odorants in the treatment of post - traumatic stress disorder ( ptsd ), autism , depression and schizophrenia . for example , with ptsd , it is believed that the orbital cortex is not as active and this portion may be made more active by using pulsed treatments . symptoms of ptsd may be treated by using active delivery periods of about 60 seconds to help activate the orbital cortex . with autism , some symptoms may include lack of development at the amygdala . shorter active delivery periods , such as about less than 10 seconds , may be used to treat these symptoms . further , by pulsing , the olfactory bulb may increase in size , resulting from regeneration of neurons . in one form , a pulsatile approach may deliver odorants for 10 seconds , alternating with 30 seconds break . therefore , one cycle of treatment is 40 seconds . this gives 45 cycles of treatment over 30 minutes . a previous approach was a continuous treatment in which some of the key primary olfactory neural elements are inactivated ( i . e ., turned off ) ranging from 45 minutes to 3 hours . based on a very rough estimation , it requires 24 - 72 hours to deliver equivalent of 45 cycles of treatment , which is 30 minutes with the new pulsed approach . while the compositions , uses and forms of apparatus have been particularly described with specific reference to particular process and product embodiments , it will be appreciated that various alterations , modifications , and adaptations may be based on the present disclosure , and are intended to be within the spirit and scope of the application .
a method , apparatus and kit have been discovered which utilize pulsed odorants , drugs , medicaments , and combinations thereof to treat diseases , symptoms of diseases and the like . in one form , the pulsed odorants , drugs , medicaments , and combinations thereof can be used to regenerate the connections of the neurons of the brain and central nervous system in the treatment of symptoms of such person afflicted with neuro - disorders , such as caused by disease or trauma .