A method for olfactory training, a kit of nose plugs for use in an olfactory training program, and a nose plug for use in an olfactory training program

Abstract

The disclosure relates a method for olfactory training and a computer program for use in the method for olfactory training, using a nose plug being adapted for insertion into a nostril of a human subject, wherein the nose plug comprises a structural molded material and a fragrance substance or mixture of fragrance substances experienced as an odor, said 5 fragrance substance or mixture of fragrance substances being evenly dispersed in the structural molded material. The disclosure further relates to a kit of nose plugs for use in an olfactory training program and a nose plug for use in an olfactory training program.

Description

[0001] A method for olfactory training, a kit of nose plugs for use in an olfactory training program, and a nose plug for use in an olfactory training program

[0002] Technical field

[0003] The present disclosure relates to a method for olfactory training and a computer program for use in an olfactory training program, a kit of nose plugs for use in an olfactory training program, and a nose plug for use in an olfactory training program, as defined in the introductory parts of the independent claims.

[0004] Background art

[0005] The loss of the sense of smell, either total (anosmia), partial (hyposmia), or dysfunctional smell detection (parosmia, being characterized by the inability of the brain to correctly identify an odor's natural smell) are relatively frequent states for many persons. The reasons for the loss of the sense of smell can be many, such as head injury, infection or medical or mechanical blockage of the nose. Psychological factors may also, at least partly, have a large impact on the experienced smell loss. Moreover, psychiatric disorders like depression are common in subjects experiencing loss of smell. Despite the reason for the loss of smell, and the severity of the loss, there are training programs for partly or completely improving the sense of smell, so called olfactory training programs.

[0006] Hummel et al. ("Effects of olfactory training in patients with olfactory loss", Laryngoscope 119: March 2009, p 496-499) discusses training programs for subjects having olfactory dysfunction, wherein the subjects are exposed to different odors in a training program over time (12 weeks). The study revealed that structured, short-term exposure to selected odors may increase olfactory sensitivity, whereas the olfactory sensitivity was unchanged for subjects not performing the training program.

[0007] Pieniak et al. ("Olfactory training. Thirteen years of research reviewed", Neuroscience and Biobehavorial Reviews 141 (2022) 104853) reviews the research area of olfactory training.

[0008] Thus, it appears vital to perform olfactory training to improve or regain loss of smell. Therefore, it is important to identify training programs and associated devices that facilitate such training, thereby improving the chances of successful development for the subject's olfactory sensitivity.

[0009] However, current training programs have been found to often not lead to expected or desired results. There is often a lack of scientific base for the training program used for the specific subject, and it is difficult to control and follow-up on the ability of the subject to perform the training program as planned. Sometimes this can be related to lack of motivation for the subject undergoing the training program, and / or practical difficulties and / or lack of time to enable a structured, daily training. Moreover, there are issues with regard to the efficiency and compatibility of presently used methods and devices.

[0010] Hence, there is a need for improved devices and training programs using such devices for improving the outcome of olfactory trainings for subjects in need thereof.

[0011] Summary

[0012] It is an object of the present disclosure to mitigate, alleviate or eliminate one or more of the above-identified deficiencies and disadvantages in the prior art and solve at least the above mentioned problem.

[0013] The present inventors have surprisingly found that a nose plug and / or a plurality of nose plugs structurally configured substantially as described in either WO2011 / 162677 or WO2018 / 206388 (both incorporated by reference herein), further comprising at least one fragrance substance or mixture of fragrance substances experienced as an odor, i.e. a substance or substance mixture capable of having a certain smell that can be used for training the sense of smell in a subject, facilitates the training of the olfactory sensitivity for subjects and patients in need thereof. In particular, using methods involving a nose plug for olfactory training leads to higher improvement of the sense of smell by increasing the compliance of the subject to the training program, compared to using traditional methods. This is largely due to the ease of use, and ability to wear the device while going about one's regular tasks.

[0014] Therefore, according to a first aspect there is provided a method for olfactory training, comprising the steps of a. providing a subject with at least two or more nose plugs adapted for insertion into a nostril of a human subject, the nose plugs comprising a structural molded material and a fragrance substance or mixture of fragrance substances collectively experienced as an odor, said fragrance substance or mixture of fragrance substances being evenly dispersed in the structural molded material, and said two or more nose plugs each comprising a different fragrance substance or mixture of fragrance substances collectively experienced as an odor, b. exposing at least one nostril of said subject to the two or more nose plugs one at a time and in a predetermined order and duration; c. repeating the exposure on a daily basis for a predetermined training period.

[0015] Hereby, a training program taking advantage of the nose plugs comprising fragrance substance(s) is provided, thereby facilitating training for subjects and patients having various needs of developing olfactory sensitivity. The primary purpose is to enhance the recognition and sensitivity to different odors in individuals, specifically in the context of smell training and olfactory rehabilitation. In particular, the methods and devices disclosed herein are intended to be performed and used by the subject themselves, i.e. by laypersons.

[0016] According to another aspect, the step of exposing the nostril to a nose plug comprises the action of the subject applying the nose plug to the nostrils by at least partial insertion of the nose plug into the nostrils. Preferably, the nose plug is inserted approximately 15-20 mm into the inferior portion of the nasal cavity using the hands.

[0017] In a further aspect, the step of exposing the nostril to a nose plug comprises allowing the nose plug to remain in the nostrils for at least approximately 5 minutes, more preferably approximately 10 minutes.

[0018] According to some aspects, the order of exposing the subject to the fragrance substances or mixtures of substances experienced as an odor is varied from day to day according to a predetermined scheme. Hereby, a structured and varied training program is provided in order to strengthen the olfactory sensitivity of the subject.

[0019] According to some aspects, at least two different nose plugs with different fragrance substances or mixtures of substances experienced as an odor are used in the predetermined order. In other aspects, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more different nose plugs with different fragrance substances or mixtures of substances experienced as an odor are used in the predetermined order.

[0020] Hereby, by varying the order of exposure to different fragrance substances or mixtures of substances experienced as an odor, an improved development can sometimes be observed.

[0021] According to some aspects, the predetermined order is that on day 1 the subject is exposed to at least four different fragrance substances or mixtures of substances experienced as an odor, and on day 2 the subject is exposed to at least one other fragrance substance or mixtures of substances experienced as an odor compared to day 1. Preferably, the predetermined order is that the subject is exposed to at least four different fragrance substances or mixtures of substances experienced as an odor each day.

[0022] According to some aspects, a nose plug used in a training program as described, when comprising two parts intended for a separate nostril, may comprise different fragrance substances on each side, such that each nostril is exposed to a different fragrance substance or mixture of substances experienced as an odor. In other aspects, a nose plug used in a training program as described, when comprising two parts intended for a separate nostril, may comprise different concentrations of the same fragrance substance or mixture of substances on each side, such that each nostril is exposed to a concentration of an odor.

[0023] Hereby, by varying the training program in a structured way on a daily basis, improved results can often be expected.

[0024] According to some aspects, the duration of the training program, i.e. the predetermined training period, is at least 1 month, and preferably at least 2-4 months, wherein the subject is exposed to fragrance substances 5 days per week, and the subject is pausing the training 2 days per week. Hereby, a structured program organized to help motivate and prolong training is provided, for the benefit of the subject in need thereof.

[0025] According to some aspects, exposing the nostril comprises inserting a large part of the nose plug, e.g. at least an entire flexible member fully into the nostril, such that only a support member remains outside the nostril.

[0026] Hereby, a strong and / or optimized effect of the fragrance substance is expected.

[0027] Another advantage of fully or almost fully inserting at least the flexible member or large part of a holder member, into the nostril, is that only a small part of the nose plug protrudes from the nostril, presenting a discrete visual experience such that the user may go about their daily tasks without a bulky device visible or in the way. Notably, all aspects of nose plugs described herein offer discrete use.

[0028] According to some aspects, the fragrance substances or mixtures of substances experienced as an odor are chosen from the group comprising strawberry, vanilla, lemon, melon, rosemary, menthol, cherry, orange, peach, cola, lavender, clove, cacao, coffee, citrus, carnation, rose, banana, apple clove and cinnamon.

[0029] According to some aspects, the training is for the treatment of hyposmia, anosmia and / or parosmia.

[0030] Hereby, the training program is intended for medical conditions as well as non-medical conditions, in order to improve olfactory sensitivity for subjects and patients with different needs.

[0031] According to some aspects, the hyposmia, anosmia and / or parosmia is a result of the subject having suffered from or is suffering from infection, covid, post-covid, injury to head and / or nervous system, Parkinson's disease, Alzheimer, stroke, or depression.

[0032] Thus, these are examples of conditions, for which the olfactory training program of this disclosure is useful in case of partial or complete loss of the sense of smell.

[0033] According to a yet another aspect, there is provided a computer program for use in olfactory training according to the aspects described above, comprising instructions which, when executed on at least one processor, cause the at least one processor to provide guidance to a subject undergoing olfactory training in accordance with methods disclosed herein, and / or following up activities performed by said subject as part of said olfactory training.

[0034] Hereby, a tool, e.g. in the form of an app (application) on a mobile device or computer or the like, that further facilitates the continuation and completion of an olfactory training program is provided.

[0035] According to another aspect there is provided a kit of nose plugs for use in the disclosed methods for olfactory training, the kit comprising:

[0036] - two or more nose plugs for two or more different odors, each nose plug comprising one fragrance substance or mixture of substances experienced as an odor, and

[0037] - instructions for use.

[0038] Hence, since an olfactory program advantageously comprises exposing the subject for a plurality of fragrance substances or mixtures of substances experienced as an odor over time, it will be convenient for the subject to be provided with a set of different nose plugs, each comprising different fragrance substances or mixture of substances experienced as an odor. Hereby, the likelihood of subject compliance and a successful olfactory training program is improved.

[0039] According to some aspects, the fragrance substance is chosen from the group comprising menthol, cherry, melon, rosemary, clove, cacao, cola, coffee, citrus, such as orange and lemon, carnation, rose, vanilla, strawberry, peach, banana, apple, clove, jasmine, cinnamon, honey, jam, juice, syrup, peanut butter, coconut oil, basil, oregano, parsley, coriander, lavender, cardamom, thyme, caraway, eucalyptus, ketchup, garlic, tuna, boiled egg, soya, coffee, tea, tooth paste and soap. In some aspects the fragrance substance is chosen from the group comprising strawberry, vanilla, lemon, melon, rosemary, menthol, cherry, orange, peach, cola, lavender, clove, cacao, coffee, citrus, carnation, rose, banana, apple, clove and cinnamon. Hereby, by combining a plurality of different fragrance substances chosen from different types of odors, successful training and ease of use is supported.

[0040] According to some aspects, the kit comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 different nose plugs with different fragrance substances or mixtures of substances experienced as an odor.

[0041] Thus, the content of the kit according to the present disclosure can be varied depending on the individual olfactory training program, and on the subject's need.

[0042] According to some aspects, the kit comprises nose plugs for about 10 fragrance substances or mixtures of substances experienced as an odor.

[0043] In some situations, it has proven beneficial to include about 10 different fragrance substances or mixtures of substances experienced as an odor in a kit.

[0044] According to some aspects, the kit comprises a plurality of nose plugs for each fragrance substance or mixture of substances experienced as an odor, such that a new nose plug can be used each time the nostrils of the subject is to be exposed to a particular odor.

[0045] In alternative aspects, a kit may comprise a limited number of nose plugs for each fragrance substance or mixture of substances experienced as an odor, such that each nose plug for a specific fragrance substance or mixture of substances experienced as an odor may be re-used two or more times during a specific time period.

[0046] Since the effect of the fragrance substance or mixture of substances experienced as an odor associated with the nose plug may decrease over time, and / or the nose plug itself may become broken or dirty, a kit comprising a plurality of nose plugs having the same fragrance substances or mixtures of substances experienced as an odor can be advantageous in some training programs. For example, the kit may comprise 2, 3, 4, 5, 6, 7, 8, 9 or 10 nose plugs for each fragrance or mixtures of substances experienced as an odor. However, the nose plugs as described herein are adapted to be used at least up to 8 hours a day, if needed.

[0047] In other aspects, nose plugs for use in an olfactory training program are disclosed. Such nose plugs are advantageously provided in the kits disclosed above, for use in a method as disclosed, and are preferably adapted for insertion into a nostril of a human subject, wherein the nose plug comprises a structural molded material and a fragrance substance or mixture of fragrance substances experienced as an odor, said fragrance substance or mixture of fragrance substances being evenly dispersed in the structural molded material.

[0048] The term "structural molded material" entails that the nose plug has a structural molded shape, e.g. a plug part, adapted for insertion into the nostril. In some aspects, the structural molded material forms essentially the entire nose plug, in other aspects the entire nose plug comprises the structural molded material.

[0049] In some aspects, the structural molded material is a plastic, polymer or cellulose-based material, preferably one of the following: silicone elastomers, thermoplastic elastomers (TPE), polyethylene (PE), polyethylene terephthalate (PET), polyvinylchloride (PVC), polyurethanes (PUR), fluoropolymers (PTFE, FEP, PFA, EFTE, ECTFE, PVDF), polyamide (PA), polypropylene (PP), polystyrene (PS), polylactic acid (PLA), polycarbonate (PC), polyetheretherketone (PEEK), polyactide (PLA) plastic, or polyhydroxyalkanoate (PHA) plastic, molded paper pulp, or molded cellulose fiber pulp.

[0050] As exemplified in further described aspects, the term "nose plug" is not meant to in any way describe a device that hinders airflow in and out of the nose. In fact, the nose plug is adapted to allow free airflow during breathing, and in some aspects, will lengthen the airflow path, to allow the air to come in contact with the fragrance substance or mixture of fragrance substances for a longer time before passing through the device. Various configurations of such a nose plug are conceivable.

[0051] In a preferred aspect, the nose plug comprises

[0052] - at least one flexible member and

[0053] - one rigid, elongated support member,

[0054] - wherein the flexible member is arranged to surround the support member, and

[0055] - the flexible member is adapted to be placed within a nostril to accurately fill the opening of the nostril, and is provided with means for guiding the flow of air entering the nostril in a serpentine or spiral like path by means of a plurality of plates or a band, wherein at least the flexible member comprises the at least one fragrance substance or mixture of substances experienced as an odor evenly dispersed in a structural molded material.

[0056] In this aspect, the flexible member comprises the plug part of the nose plug.

[0057] In some aspects, the entire nose plug comprises the at least one fragrance substance or mixture of substances experienced as an odor evenly dispersed in a structural molded material.

[0058] In other aspects, the nose plug comprises

[0059] - an elongated support member, and

[0060] - one or two rounded holder members, each arranged at a respective end of said elongated support member, wherein said holder members are adapted to be inserted into the nostril with a distal end directed into the nostril, and a proximal end adjacent the nostril openings,

[0061] - said holder members each comprise a bell-shaped cross-section in at least one plane in a distal-proximal extension,

[0062] - said holder members each comprising

[0063] - a rounded distal portion, and

[0064] - an open proximal portion comprising an outer rim disposed circumferentially around the outer perimeter of said proximal portion and extending radially outward from said holder member, and

[0065] - an intermediate waist portion arranged between said distal portion and said proximal portion, said intermediate portion having at least one outer circumference in a plane essentially transverse to a distal-proximal direction, said outer circumference being smaller than a respective largest outer circumference of at least said distal portion,

[0066] - wherein said outer rim disposed circumferentially around the outer perimeter of the proximal portion is adapted to engage with the nostril opening and protrude outward from the nostril when the nasal device is arranged in a nostril,

[0067] - wherein said rounded distal portion is provided with one or more through-going holes adapted to allow air to pass through said distal portion, - wherein at least the holder members comprise the at least one fragrance substance or mixture of substances experienced as an odor evenly dispersed in a structural molded material.

[0068] In this aspect, the holder members comprise the plug part of the nose plug.

[0069] Hereby, by using a nose plug that comprises a fragrance substance that is to be used in olfactory training, a convenient device for the subject is provided, making it easy to perform a structured training program.

[0070] In some aspects, the nose plug is molded in one piece, such that the entire nose plug comprises the at least one fragrance substance or mixture of substances experienced as an odor evenly dispersed in a structural molded material. This is advantageous as manufacturing is simplified, in having only one molding step. All-in-one molding may also decrease the risk of any structural integrity flaws in the device.

[0071] According to some aspects, the at least one fragrance substance or mixture of substances experienced as an odor is evenly dispersed throughout the entire structural molded material or on the surface of the structural molded material.

[0072] Hereby, the nose plug can be used for an extended time without loss of fragrance release, and also repeatedly, for the purpose of improving olfactory sensitivity.

[0073] In some aspects, the fragrance substance(s) are provided in an "oil-like" form or liquid form, or are suitable for being dissolved or dispersed in an oil-like solvent or other similar organic solvent. "Oil-like form" is herein defined to comprise substances that in themselves exhibit properties similar to that of an oil, such as biocompatibility, suitable viscosity, ability of diffusion of a smell, etc. In addition, "oil-like form" also comprises substances in any oil-based or organic solvent that has properties similar to that of an oil, such as biocompatibility, suitable viscosity, ability of diffusion of a smell, etc. An example of a substance with oil-like form is menthol oil.

[0074] According to some aspects, the fragrance substance is chosen from the group comprising menthol, cherry, melon, rosemary, clove, cacao, coffee, cola, citrus, such as orange and lemon, carnation, rose, vanilla, strawberry, peach, banana, apple, clove jasmine, cinnamon, honey, jam, juice, syrup, peanut butter, coconut oil, basil, oregano, parsley, coriander, lavender, cardamom, thyme, caraway, eucalyptus, ketchup, garlic, tuna, boiled egg, soya, coffee, tea, tooth paste and soap. In some aspects the fragrance substance is chosen from the group comprising strawberry, vanilla, lemon, melon, rosemary, menthol, cherry, orange, peach, cola, lavender, clove, cacao, coffee, citrus, carnation, rose, banana, apple, clove and cinnamon. Typically, any fragrance substance or mixture of substances experienced as an odor, that is experienced by the user as clear and pleasant, but not too strong or irritating, can be used.

[0075] A plurality of fragrance substances can be used, as long as the fragrance substance can be evenly dispersed in the structural molded material of the nose plug, or effectively coated on the surface of the structural molded material of the nose plug, and the fragrance substance is useful for the training program. Typically, a plurality of different types of fragrances are combined in a training program in order to achieve the desired results.

[0076] According to some aspects, a nose plug, when comprising two parts for inserting into separate nostrils, may comprise different fragrance substances on each side, such that each nostril is exposed to a different fragrance substance. In other aspects, a nose plug, when comprising two parts for inserting into separate nostrils, may comprise different concentrations of a particular fragrance substances on each side, such that each nostril is exposed to a different amounts of fragrance substance.

[0077] According to some aspects, the fragrance substance is added to the structural molded material at a dosing concentration in a range of fragrance-dependent or odor-dependent intervals, enough to produce a clear odor.

[0078] Thus, the amount and / or concentration of added fragrance substance is important to accomplish that the nose plug can be used over a longer time-period, and so that the fragrance is experienced by the subject at a suitable odor intensity level. The actual concentration of a substance may vary depending on the fragrance used, and / or the odor to be achieved. According to some aspects, the structural molded material is made of a thermoplastic elastomer and the fragrance substance or mixture of substances experienced as an odor is evenly dispersed therein.

[0079] Thus, the fragrance substance or mixture of substances experienced as an odor can alternatively be dispersed in the structural molded material.

[0080] According to some aspects, the structural molded material is coated with a coating that comprises the fragrance substance or mixture of substances experienced as an odor.

[0081] As yet an alternative, the structural molded material can be coated with the fragrance substance or mixture of substances experienced as an odor, or with a composition comprising the fragrance substance or mixture of substances experienced as an odor.

[0082] Effects and features of the nose plugs described herein are to a large extent analogous to those described above in connection with the methods, computer programs and kits. Aspects mentioned in relation to the disclosed nose plugs are largely compatible with the kits and methods described herein.

[0083] The present disclosure will become apparent from the detailed description given below. The detailed description and specific examples disclose preferred embodiments of the disclosure by way of illustration only. Those skilled in the art understand from guidance in the detailed description that changes and modifications may be made within the scope of the disclosure.

[0084] Hence, it is to be understood that the herein disclosed disclosure is not limited to the particular component parts of the device described or steps of the methods described since such device and method may vary. It is also to be understood that the terminology used herein is for purpose of describing particular embodiments only, and is not intended to be limiting. It should be noted that, as used in the specification and the appended claim, the articles "a", "an", "the", and "said" are intended to mean that there are one or more of the elements unless the context explicitly dictates otherwise. Thus, for example, reference to "a device" or "the device" may include several devices, and the like. Furthermore, the words "comprising", "including", "containing" and similar wordings does not exclude other elements or steps.

[0085] Brief descriptions of the drawings

[0086] The above objects, as well as additional objects, features and advantages of the present disclosure, will be more fully appreciated by reference to the following illustrative and non-limiting detailed description of example embodiments of the present disclosure, when taken in conjunction with the accompanying drawings.

[0087] Figure 1 shows an aspect of a nose plug in a perspective view,

[0088] Figure 2 illustrates the nose plug in figure 1 from above,

[0089] Figure 3 illustrates a cut along A-A in figure 2,

[0090] Figure 4 illustrates a cut along B-B in figure 2,

[0091] Figure 5 shows a nose plug moulded by using a 2K technique,

[0092] Figure 6 illustrates an aspect of a nose plug,

[0093] Figure 7 shows a helical aspect of a nose plug in a perspective view,

[0094] Figure 8 shows a helical aspect of a nose plug from above,

[0095] Figure 9a and 9b show two perspective views of another aspect of a nose plug, and

[0096] Figure 10 and 10b show two perspective views of yet another aspect of a nose plug.

[0097] Figure 11 illustrates a nose plug and how it may be intended to be placed in the nostrils of a user.

[0098] Figure 12 depicts a graph showing improvement of sense of smell using the method of the present disclosure, compared to standard care.

[0099] Figure 13 illustrates the compliance of users when using the method, kit and nose plugs disclosed herein, compared to standard care. Detailed description

[0100] The present disclosure will now be described with reference to the accompanying drawings, in which preferred example embodiments of the disclosure are shown. The disclosure may, however, be embodied in other forms and should not be construed as limited to the herein disclosed embodiments. The disclosed embodiments are provided to fully convey the scope of the disclosure to the skilled person.

[0101] The term "fragrance substance" as used herein is meant to encompass both individual fragrance substances and mixtures of fragrance substances collectively experienced as an odor. Furthermore, odor and fragrance may be used interchangeably, and are both intended to mean a specific smell.

[0102] The olfactory training method

[0103] One aspect of this disclosure provides a method for olfactory training, comprising the steps of: a. providing a subject with at least two or more nose plugs adapted for insertion into a nostril of a human subject, the nose plugs comprising a structural molded material and a fragrance substance or mixture of fragrance substances collectively experienced as an odor, said fragrance substance or mixture of fragrance substances being evenly dispersed in the structural molded material, and said two or more nose plugs each comprising a different fragrance substance or mixture of fragrance substances collectively experienced as an odor, b. exposing at least one nostril of said subject to the two or more nose plugs one at a time and in a predetermined order and duration; c. repeating the exposure on a daily basis for a predetermined training period.

[0104] For an olfactory training program to be successful it is typically essential that the program is planned and structured in a way that suits the needs of the individual subject, and the severity of the state of loss of smell of the subject. Hence, depending on whether the subject experiences a partial or complete loss of smell, and whether the reason for the loss of smell is a medical condition or not, the training program can be varied to suit the subject's need. Also, it is important that the subject is motivated to complete the training program, which is often a problem in training programs that extend over a longer period of time. In addition, training programs typically require frequent (such as daily) training on a regular basis, most often a specific period of time during the day that must be dedicated solely to the training, which may be difficult to align with the subject's other daily routines and life style. Hence, one of the main advantages of the solutions of the present disclosure is that the use of nose plugs and training-designed kits of nose plugs facilitate such training, by lowering the threshold for continuing and completing the training program over time. Also, the design of the nose plugs according to this disclosure is suitable for the training in that the exposure to fragrance substances is efficient and easy to use.

[0105] According to another aspect, the step of exposing the nostril to a nose plug comprises the action of the subject applying the nose plug to the nostrils by at least partial insertion of the nose plug into the nostrils. Figure 11 illustrates one example of a nose plug 1 and how it may be intended to be placed in the nostrils of a user. The left side of the figure shows a side cross-sectional view of a nose with a nose plug inserted, and the right side of the figure shows a front cross-sectional view of a nose with a nose plug inserted. Preferably, the nose plug is inserted approximately 15-20 mm into the inferior portion of the nasal cavity using the hands.

[0106] In a further aspect, the step of exposing the nostril to a nose plug comprises allowing the nose plug to remain in the nostrils for at least approximately 5 minutes, more preferably approximately 10 minutes.

[0107] In some aspects, exposing the nostril of the subject comprises allowing the nose plug to remain in the nostrils for around 10, 15, 20, 25 or 30 minutes. In most cases, the preferred time for exposure is 10 to 15 minutes per fragrance or mixtures of substances experienced as an odor.

[0108] In some aspects, the order of exposing the subject to the fragrance substances or mixtures of substances experienced as an odor is varied from day to day according to a predetermined scheme. Thus, by exposing the subject to a variation in the exposure to fragrance substances or mixtures of substances experienced as an odor, an improved olfactory training may be achieved. In some aspects, at least two different nose plugs with different fragrance substances or mixtures of substances experienced as an odor are included in the predetermined order.

[0109] In some aspects, the predetermined order is that on day 1 the subject is exposed to at least four different fragrance substances or mixtures of substances experienced as an odor, and on day 2 the subject is exposed to at least one other fragrance substance or mixtures of substances experienced as an odor compared to day 1. This principle may be extended over a longer period of time, such as over 10 consecutive training days, so that for example a training program including training of 10 different fragrance substances or mixtures of substances experienced as an odor may be varied so that the order of which the subject is exposed to fragrance substances or mixtures of substances experienced as an odor in the daily training, is repeated on a 10-day basis.

[0110] In some aspects, the duration of the training program is at least 1 or 2 weeks, 1 month, or at least 2-4 months, sometimes even over a longer period of time, such as 6-12 months.

[0111] In some aspects, the subject is exposed to fragrance substances or mixtures of substances experienced as an odor 5 days per week, and the subject is pausing the training 2 days per week.

[0112] In some aspects, the predetermined training period is approximately 8 weeks in total. In some aspects, the patient is exposed to four distinct odors daily for a cumulative duration of 40 minutes. This exposure is preferably split into four 10-minute sessions, two in the morning and two in the evening. Each session presents at least one different odor from the previous session, each session lasting for a period of 10 minutes.

[0113] In further aspects, the fragrance substances or mixtures of substances experienced as an odor are chosen from the group comprising strawberry, vanilla, lemon, melon, rosemary, menthol, cherry, orange, peach, cola, lavender, clove, cacao, coffee, citrus, carnation, rose, banana, apple, clove and cinnamon.

[0114] In some aspects, exposing the nostril of the subject comprises inserting at least an entire flexible member fully into the nostril, such that only a support member remains outside the nostril. Hereby, an efficient and optimized exposure to the fragrance substance is obtained, thereby supporting the olfactory training.

[0115] In some aspects, the training is for the treatment of hyposmia, anosmia and / or parosmia. Depending on whether the loss of smell is partial or complete, the training program may need to be adapted.

[0116] In some aspects, the hyposmia, anosmia and / or parosmia is a result of the subject having suffered from or is suffering from infection, covid, post-covid, injury to head and / or nervous system, Parkinson's disease, Alzheimer, stroke, or depression. Hence, the cause of the loss of smell may be different from subject to subject, which sometimes also may have an impact on the suggested olfactory training program.

[0117] The olfactory training app

[0118] According to yet another aspect, there is provided a computer program for use in olfactory training according to the present disclosure, comprising instructions which, when executed on at least one processor, cause the at least one processor to provide guidance to a subject undergoing olfactory training, and / or following up activities performed by said subject associated with said olfactory training.

[0119] Such computer program, which can be implemented in the form of a mobile "app" or on a computer or any other user-friendly digital device, will assist the subject in following the training program in a routinely and structured manner, and will assist in following up on the development of the training program. For example, the "app" could include reminders related to timing, duration, choice of fragrance and / or nose plug to the subject, to facilitate the continuation and completion of the training program. In addition, the "app" could display progress report to the user. The "app" could also include functionality related to following up on experienced development and results, i.e. so that the subject is requested to provide information on the experienced development of the olfactory training, and based on such feedback from the subject, the training program could be adjusted in terms of frequency, dosing, fragrances to be exposed to, duration etc. Furthermore, the "app" could also include functionality to share data with a medical practitioner or other party, with the intention to collect data and / or provide further feedback, and / or develop improved methods and kits.

[0120] The kit of nose plugs

[0121] Another aspect of this disclosure shows a kit of nose plugs for use in an olfactory training program according to the herein disclosed methods for olfactory training. The kit comprises

[0122] -at least two or more nose plugs for at least two or more different fragrance substances or mixtures of substances experienced as an odor, each nose plug comprising one fragrance substance or mixture of substances experienced as an odor, and

[0123] - instructions for use.

[0124] It is intended that the kit of nose plugs comprises at least two or a plurality of different nose plugs, wherein each type of nose plug comprises one fragrance substance or mixture of substances experienced as an odor, so that the kit comprises the necessary fragrance substances or mixture of substances experienced as an odor to perform a given olfactory training program. Such olfactory training program may differ between subjects, and according to the subject's needs. For example, a training program aiming at restoring olfactory sensitivity as a result of partial or complete loss of sense of smell, may differ in training design with regard to number and type of fragrances to include, and with regard to duration of the training program, and hence the content of a kit to be used for the training program may vary accordingly.

[0125] In some aspects, the kit comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or even more different nose plugs with different fragrance substances or mixtures of substances experienced as an odor.

[0126] Also, since it may be beneficial to provide nose plugs having different concentration and / or amount of fragrance substance depending on need of the subject, such as severity of the loss of smell, the kit could comprise nose plugs having different concentrations and / or amounts, such as low, medium and / or high concentration / amount. In some aspects, the kit comprises nose plugs for about 10 different fragrance substances or mixture of substances experienced as an odor, thereby providing a kit that can be used for an extensive training program including several fragrance substances of different type. For example, a kit suitable for the example training program of table 1 would comprise nose plugs for 10 different fragrance substances or mixture of substances experienced as an odor, wherein the nose plugs of the kit should be capable of being used with sufficient efficiency for a period of for example 4 months. In such case, the kit may need to comprise a plurality of nose plugs for each fragrance substance or mixture of substances experienced as an odor, so that any malfunction of the individual nose plug is accounted for. For example, the kit could comprise 2 nose plugs for each fragrance substance or mixture of substances experienced as an odor, thus including a total of 2 x 10 nose plugs for a training program in accordance with table 1. In other aspects, a kit could include only one of each nose plug for each fragrance substance or mixture of substances experienced as an odor, with the intention that the user reuses each nose plug for several sessions.

[0127] In some aspects, the kit comprises a plurality of nose plugs for each fragrance substance or mixture of substances experienced as an odor, so that a nose plug comprising a certain fragrance substance or mixture of substances experienced as an odor can be exchanged as result of loss of effect of the fragrance substance or loss of function of the nose plug, such as a mechanical failure. Hereby, a kit facilitating completion of the olfactory training program that typically extends over several months is provided, which improves the likelihood that the subject successfully regains complete or maximal sense of smell.

[0128] The nose plug

[0129] The nose plug disclosed herein for use an olfactory training program is adapted for insertion into a nostril of a human subject, wherein the nose plug comprises a structural molded material and a fragrance substance or mixture of fragrance substances experienced as an odor, said fragrance substance or mixture of fragrance substances being evenly dispersed in the structural molded material. The term "structural molded material" entails that the nose plug has a structural molded shape, or plug part, adapted for insertion into the nostril. The structural molded material is preferably made of one of or a combination of any moldable material suitable for use in a nostril. Examples include plastic materials, various polymers or a cellulose-based material, such as silicone elastomers, thermoplastic elastomers (TPE), polyethylene (PE), polyethylene terephthalate (PET), polyvinylchloride (PVC), polyurethanes (PUR), fluoropolymers (PTFE, FEP, PFA, EFTE, ECTFE, PVDF), polyamide (PA), polypropylene (PP), polystyrene (PS), polylactic acid (PLA), polycarbonate (PC), polyetheretherketone (PEEK), polyactide (PLA) plastic, or polyhydroxyalkanoate (PHA) plastic, molded paper pulp, or molded cellulose fiber pulp.

[0130] A preferred aspect of this disclosure, illustrated in Figures 1 to 8, shows a nose plug for use in an olfactory training program, comprising:

[0131] - at least one flexible member 2 and

[0132] - one rigid, elongated support member 3,

[0133] - wherein the flexible member is arranged to surround the support member, and

[0134] - the flexible member is adapted to be placed within a nostril to accurately fill the opening of the nostril, and is provided with means for guiding the flow of air entering the nostril in a serpentine or spiral like path by means of a plurality of plates or a band, characterized in that the flexible member comprises at least one fragrance substance.

[0135] The expression "nose plug" used in this application is not a stopper in the sense to close the nostrils completely. While a flexible member fills the nostril, thereby hindering air from flowing straight into the nose, it is not intended to hinder air from entering. In fact, the disclosed nose plug may for many users actually enhance ease of flow of air in and out of the nose, as the configuration of the flexible members may widen the nostril slightly and / or support a more open shape of the nostril when placed in the nostril. Through enabling air to flow in a tortuous structure, thus over a longer distance than without the nose plug, improved sensation of any fragrance substance comprised in the nose plug is experienced by the subject using the nose plug of this disclosure.

[0136] In another aspect, illustrated in Figures 10a, lb, 11a and lib, the nose plug comprises an elongated support member (2, 62), and one or two rounded holder members (3, 63), each arranged at a respective end of said elongated support member (2, 62), wherein said holder members (3, 63) are adapted to be inserted into the nostril with a distal end directed into the nostril, and a proximal end adjacent the nostril openings, said holder members (3, 63) each comprise a bell-shaped cross-section in at least one plane in a distal-proximal extension, said holder members (3, 63) each comprising a rounded distal portion (5), and an open proximal portion (7) comprising an outer rim (8, 68) disposed circumferentially around the outer perimeter of said proximal portion (7) and extending radially outward from said holder member (3, 63), and an intermediate waist portion (9) arranged between said distal portion (5) and said proximal portion (7), said intermediate portion (9) having at least one outer circumference in a plane essentially transverse to a distal-proximal direction, said outer circumference being smaller than a respective largest outer circumference of at least said distal portion (5), wherein said outer rim (8, 68) disposed circumferentially around the outer perimeter of the proximal portion (7) is adapted to engage with the nostril opening and protrude outward from the nostril when the nasal device is arranged in a nostril, wherein said rounded distal portion (5) is provided with one or more through-going holes (6, 66) adapted to allow air to pass through said distal portion (5), wherein at least holder members (3, 63) comprise the at least one fragrance substance or mixture of substances experienced as an odor evenly dispersed in a structural molded material.

[0137] The fragrance substance is preferably evenly dispersed throughout the entire structural molded material or coated on the entire surface thereof.

[0138] One material suitable for incorporation as a structural molded material and optionally as a support member in the nose plug according to the present disclosure may be prepared by mixing 3 parts of fragrance substance and 97 parts thermoelastic polymer to provide a thermoelastic polymer containing ~3% fragrance substance. Another suitable material may be prepared by mixing 7 parts of a fragrance substance and 93 parts thermoelastic polymer to provide a thermoelastic polymer containing ~7% fragrance substance. In some aspects, the structural molded material may be made of a thermoplastic elastomer and the fragrance substance, wherein the fragrance substance constitutes a percentage in the range of 2% and 20% of the total material in the structural molded material, or more preferably in the range of 3% to 10%. In some aspects, the fragrance substance constitutes approximately 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of the material in the structural molded material.

[0139] The fragrance substance may also be incorporated or added to the structural molded material of nose plug in such way that a slow release effect is achieved, i.e. so that the release of the fragrance substance is distributed over time for a prolonged life time of the nose plug, and / or for an increasing or decreasing release over time, to suit the training program of the subject. For instance, a fragrance substance may be evenly dispersed throughout a molded nose plug, and will then gradually diffuse out of the nose plug material over a period of time.

[0140] The concentration and / or amount of each fragrance substance to the structural molded material of the nose plug should be on a level so that the odour of the fragrance substance from the nose plug is clearly identifiable upon exposure in the nostril for a subject experiencing loss of smell. Also, the odour of the fragrance substance should not be on such a level that the odour is experienced as unpleasant and / or annoying by the subject. Hence, depending on the severity of the smell of loss for the subject, varying individual concentrations / amounts may be necessary for each subject. Therefore, in some aspects, nose plugs having for example low, medium and high concentration and / or amount of fragrance substance may be provided, so that a suitable level of concentration and / or amount may be chosen for the specific subject.

[0141] Figure 1 shows a nose plug 1 comprising a set of flexible members 2 comprising fragrance substance and one rigid, elongated support member 3 adapted to stabilize the flexible member. In this aspect of the nose plug the set of flexible members 2 comprise parallel plates 4 surrounding the support member. Between adjacent plates there are spaces 5. Furthermore, there is provided for communication between theses spaces through the plates. When the nose plug is placed in a nose and the flexible plates accurately fill the openings of the nostrils, air entering the nostrils will, when passing through the nose plug, first enter through a recess 7 in a first lowermost plate. The air flow then passes the nose plug in a tortuous manner and exits through a recess 6 in an uppermost final plate. Exhaled air will flow in the opposite direction. Thus, both when air is inhaled and when air is exhaled, the air will flow over a longer distance than without the nose plug arranged in the nostril, and will be exposed to the fragrance substance in both directions.

[0142] Throughout the passage through the nose plug, the air is in contact with the flexible member comprising a fragrance substance. This aspect illustrates a much extended path for the air to flow through, since every second recess is on a position at the periphery that is opposite on the transverse diameter in relation to the recess on an adjacent plate. The recess 7 of the first plate and the recess 6 of the final plate and all the recesses there between are clearly seen in figure 4, i.e. the recess 7 of the first lowermost plate and the recess of every second plate counted from the first plate has the same reference number and the recess 6 of the uppermost final plate and every second plate counted from the final plate has the same reference number. This is valid when the number of plates is an even number (as shown in the aspects in figure 1 to 6), otherwise in the case where the number of the plates is uneven the recess of the first and the final plate will have the same reference number.

[0143] In the aspects of a nose plug seen in figure 1 to 6 the set of flexible members 2 comprising a fragrance substance is adapted to guide the flow of air entering the nostril in a serpentine or meandering like path. This is achieved when the nose plug is placed in a nostril. The air flow enters the nose plug 1 through the recess 7 of the lowermost plate 4, the air flow is then passing in the space 5 between two adjacent plates, i.e. the first and second plate, arriving at the opposite transverse diametrical end of the first plate, where the air flow is further guided through the recess 6 of the second plate. Thereafter the air flow is passing between two further adjacent plates, i.e. the second and third plate, arriving at the opposite transverse diametrical end of the second plate, where the air flow is further guided through the recess 7 of the third plate. And so on, until the air flow passes between the two uppermost plates and exits into the nostril through the recess 6 of the final plate. In the aspect illustrated in figure 1 to 4 the number of the plates is 6 and in figure 5 and 6 the number of the plates is 8. The number of the plates may also be another number such as 7, 9 or 10. The number of the plates is preferably ranging from 4 to 12.

[0144] Figure 2 shows the nose plug of the aspect in figure 1 from above. As may be seen the plates 4 have an elliptical shape. The final uppermost plate is the smallest (transverse diameter and conjugate diameter) and the plates in the middle, i.e. plate number four and / or five is / are the largest plate(s). The first plate is somewhat larger than the final plate. Seen from the first plate each further adjacent plate has somewhat larger diameters, until the fourth or fifth plate, thereafter each further adjacent plate has somewhat smaller diameters, i.e. from the first to the fourth or fifth plate the transverse and conjugate diameter increases for each plate, from the fourth or fifth plate to the final plate the transverse and conjugate diameter diminishes for each plate. The increase or the diminution of each adjacent plate may be linear, but may also progress irregularly.

[0145] In figure 2, the lines A-A and B-B are shown. The line A-A coincides with the conjugate diameter of the plates and line B-B coincides with the transverse diameter of the plates.

[0146] The flexible members 2 comprise a fragrance substance. The fragrance substance can be incorporated within the material constituting the flexible member 2, such as evenly dispersed within the material. The fragrance substance can also be coated on the flexible member 2, as known in the art.

[0147] The flexible member 2 is preferably made of a thermoplastic elastomer, or other suitable polymer, with a fragrance substance dispersed evenly throughout the thermoplastic elastomer using any suitable manufacturing technique. In one aspect, the fragrance substance may be introduced into the thermoplastic elastomer or other suitable flexible material by using an additive master batch approach. In addition or as an alternative, a fragrance substance may be introduced by coating the flexible member and in some aspects, also the support member, with a fragrance substance in a suitable solution or dispersed into a thermoplastic elastomer or other suitable material. Thus, the flexible member 2 may be made of a thermoplastic elastomer with a fragrance substance coated on the surface. Other flexible materials may also be used in the flexible member and / or support member. The support member is preferably made of a thermoplastic polymer. Other firm or rigid materials are also possible to use. In some aspects, the support member and / or the flexible member may further comprise one or several reinforcing members, such as an internal core of a more rigid and / or shapeable material, such that parts of the nose plug may be more inflexible and / or the support member may be pressed into a shape to better fit an individual nose or nostril.

[0148] In figure 3 a cross-sectional view along A-A be seen. In this figure a set of flexible members 2 are integrally formed with the respective ends of support member 3, and the flexible members 2 surround the ends of support member 3. The support member 3 has a generally U-shaped form and has two sets of flexible members 2 attached thereto, one set on each end. The support member 3 extending between the two ends has a bent shape, in order to be easy to handle.

[0149] In figure 4 a cross-sectional view along B-B shown. This cut coincides with the transverse diameters of the plates 4. Therefore, the recesses 6 of every second plate are shown on the one side and the recesses 7 of every other second plate are shown on the other side.

[0150] As can be seen in figure 5 the two legs of the generally U-shaped support member 3 may be slightly inclined and / or angled in relation to each other. This facilitates adapting the nose plug to the extension and arrangement of the nostrils. The plug should be properly arranged within the nose, without widening the nostrils more than necessary.

[0151] The nose plug according to the present disclosure may be manufactured by moulding using a 2K technique, where two materials are moulded together. Thus, it is possible to first mould the support member in one material, and thereafter mould the flexible members directly onto the support member, using the same or different materials. This is illustrated in figures 5 to 7. The same applies to the nose plug described in connection with Figures 10a, 10b, 11a and lib below. The method of manufacturing the nose plug may also comprise other techniques, such as extrusion moulding, injection moulding, casting, compression moulding, transfer moulding or any other suitable technique for the material used. In some aspects, only one material may be used for manufacturing the entire nose plug, i.e. the same material for the flexible member or the holder member as for the support member. The fragrance substance will then be dispersed throughout the entire nose plug. Furthermore, the flexible member or holder member and the support member comprised in the nose plug according to the present disclosure may also be manufactured by moulding them separately, using the same material or two different materials, and thereafter assembling the two parts together. In such cases, the content of the fragrance substance can be adapted to different parts of the nose plug. For instance, one part may comprise the fragrance substance or mixture of fragrances, and the other part could be provided without fragrance. In another example, different parts of the nose plug could be provided with different concentrations of a fragrance, different types of fragrances or different mixtures of fragrances.

[0152] The disclosure supports the conclusion that the combination of the air being led through a longer path, without causing inhibition of air flow, and an incorporated fragrance substance in the material of the nose plug and thus along all surfaces of such a path, result in a very effective, comfortable and easy to use nose plug for improving the training of the olfactory sensitivity in a subject experiencing partial or complete loss of smell. More specifically, as mentioned previously, the arrangement of the flexible member of the nose plug allows air to be led through a longer path than in a nostril without a nose plug, while maintaining ease of breathing for a user. When the arrangement of the flexible members is combined with a fragrance substance being incorporated in the material, a significant effect of odor training in the subject is achieved.

[0153] The disclosure further points to a long-term effect, concluding that a nose plug as disclosed herein may be worn by a user for at least 8 hours and / or be used repeatedly for shorter sessions over a longer period of time (up to 2, 3, 4, 5, 6 months or even longer) and still maintain the high effectiveness of experiencing the odor of the fragrance substance.

[0154] Figure 6 illustrates an aspect, wherein each nose plug, comprises one flexible member arranged on a support member, is adapted to be arranged separately in one nostril each.

[0155] Figure 7 shows an aspect with a flexible member comprising a helically arranged band in a perspective view. This spiral like structure gives the air entering the nostrils an extended path. The distance of the path may be varied due to the pitch angle of the helical wings of the band. There may also be recesses provided on the helically arranged band. But since air is allowed to enter without recesses, this is not an essential feature.

[0156] In figure 8 the aspect in figure 7 is seen from above. The helically arranged band shown in figure 7 and 8 shows the flexible member being adapted to guide the flow of air entering the nostril in a spiral like path.

[0157] Figures 10a and 10b show different perspective views of another aspect of a nose plug, and figures 11a and lib show different perspective views of yet another aspect of a nose plug. Regarding the material, the at least one fragrance substance or mixture of substances experienced as an odor evenly dispersed in a structural molded material and the possible manufacturing techniques; these aspects have the same features as described for aspects described above.

[0158] The nose plugs of figures 10a, 10b, 11a and lib comprise a semi-rigid, elongated support member 2, 62. At both ends of the support member 2, 62, two rounded holder members 3, 63 are provided, wherein the distal end 4 of each of the rounded holder members are adapted to be inserted distally into a respective nostril. The shape of the holder members provides an intermediate waist portion 9, adapted to "hang" in the nostril opening, with the wider distal portion 5 and wider proximal portion 7 providing a secure fitting in the nostril opening. The outer rim 8, 68 is disposed circumferentially around the outer perimeter of the proximal portion 7 and is adapted to engage with the nostril opening and protrude outward from the nostril when the nasal device is arranged in a nostril.

[0159] The rounded distal portion 5 is provided with one or more through-going holes 6, 66 adapted to allow air to pass through the holder members 3, 63. In these aspects of nose plugs, at least the holder members 3, 63 comprise the at least one fragrance substance or mixture of substances experienced as an odor evenly dispersed in a structural molded material.

[0160] The above mentioned and described aspects and embodiments are only given as examples and should not be limited to the present invention. Other solutions, uses, objectives, and functions within the scope of the invention as claimed in the accompanying patent claims should be apparent for the person skilled in the art. The person skilled in the art realizes that the present disclosure is not limited to the preferred embodiments described above. The person skilled in the art further realizes that modifications and variations are possible within the scope of the appended claims. Additionally, variations to the disclosed embodiments can be understood and effected by the skilled person in practicing the claimed disclosure, from a study of the drawings, the disclosure, and the appended claims.

[0161] EXAMPLES

[0162] Example 1 - Olfactory training scheme

[0163] A suitable training program (see table 1) is for example that the subject is exposed to 4 different fragrance substances or mixtures of substances experienced as an odor, in about 10 min per fragrance substance, once or twice daily (such as in the morning and / or in the evening). Typically, such training program could last for about 4 months. Also, the fragrance substances to which the subject is exposed may be varied on a daily basis. For example, if the subject is exposed to fragrance substances 1, 2, 3 and 4 on day 1, exposure could be made to fragrance substances 2, 3, 4 and 5 on day 2 and so on. After 10 days, the training program cycle will be repeated.

[0164] Table 1. Example olfactory training scheme. Example 2 - Kit of nose plugs

[0165] A kit of nose plugs for use in the olfactory training scheme of example 1, could be designed as follows:

[0166] Table 2. Example olfactory training scheme. Another example is a kit of 10 different fragrances, with 16 nose plugs of each fragrance. For example, the ten different scents may be strawberry, vanilla, lemon, melon, rosemary, menthol, cherry, orange, cola, lavender. In other cases, one or more scents may be replaced, optionally removing one or more from the above list, and / or further incorporating one or more of peach, banana, apple, clove, and others as listed herein. Example 3 - Mobile device app for use in olfactory training

[0167] An app for olfactory training may be provided with one or more of the following:

[0168] • For purpose of scheduling and reminders: Provide users with a structured calendar to organize their smell training sessions and offer reminders, fostering a consistent routine.

[0169] • For visualization purposes: Utilize images to bolster the user's experience and engagement during the training sessions.

[0170] • For feedback purposes: Allow users to document subjective feedback on their sense of smell, quality of life, and progress over time for personal reflection and self-awareness.

[0171] Example 4 - study of use of a method for olfactory training using nose plugs

[0172] 116 hyposmic participants, 95 women and 21 men, 18 - 65 years old, participated in a randomized controlled trial and were randomized into two different treatment conditions (https: / / classic.clinicaltrials.gov / ct2 / show / NCT06142565). The study was approved by the Swedish Ethical Review Authority (Dnr: 2023-03779-01) and all participants provided written informed consent prior to participation. All procedures were in accordance with the Helsinki declaration. The two groups were similar in respect to age, sex, duration of olfactory dysfunction, and baseline olfactory measurements scores (Table 1). Inclusion criteria were functional hyposmia at baseline, defined as TDI (see below for definition) between 16.5 and 30.5, and an age between 18 and 65 years old. Exclusion criteria were psychiatric or non-viral or non-idiopathic cause of their olfactory dysfunction (such as head trauma, surgery etc.), as well as current enrollment in any other olfactory training studies.

[0173] Table 3 - Descriptive statistics of included research participants. At the initial visit, participants had experienced olfactory dysfunction for an average of 41 months. The second visit was held on average 2 months after the first visit. During their first visit, participants were randomized into one of the two olfactory training groups. Except in regard to the specific type of olfactory training, both groups received seemingly identical treatment and procedures throughout the study.

[0174] One group performed the other performed passive olfactory training with scented nose plugs according to the methods described herein and the other group performed standard care olfactory training using odors found in their own household. The training was conducted in the home of the individual during weekdays for two consecutive months, i.e. 8 weeks. Standard clinical practice recommended by the Swedish health care system is typically a 12-week long training regimen, but because the primary aim of the study was to address compliance, the training was limited to 8 weeks. Training was only done during weekdays, instead of daily training. These adjustments were done to avoid an excessive dropout given that informal observations at the clinic put patient training dropout to around 80%.

[0175] More specifically, the participants randomized to the nose plug olfactory training group (PT) were provided with scented nose plugs as described herein. The participants were instructed to wear the nose plugs for 20 minutes in the morning and 20 minutes in the evening, every Monday through Friday for 8 weeks. The nose plugs were inserted as illustrated in Figure 11, and each administered (released) a specific scent (vanilla, lemon, melon, rosemary, menthol, orange, peach, strawberry, cherry, or cola) when worn, while still allowing the individual to retain near normal air flow through the nostril. Participants were instructed to use one scented plug for 10 minutes and then replace it with another scented plug for the remaining 10 minutes of the session. They were further instructed to visualize and focus on the smell during training, aided by an image of the odor object printed on each individual nasal plug package. All participants were contacted twice during their 8 week at-home training period with information regarding where to reach out if they had any questions, comments, or concerns. A text message was sent out one week after the initial session, followed by a phone call approximately three weeks later. The participants allocated to the standard care olfactory training group (ST) were instructed to choose 4-6 household odors to smell for 20 minutes in the morning and 20 minutes in the evening, every Monday through Friday for 8 weeks. Participants were instructed to smell each item for 10 to 20 seconds and visualize and focus on the smell during training. Identical to the PT group, all participants were contacted twice during their 8-week at-home training period with information regarding where to reach out if they had any questions, comments, or concerns. A text message was sent out one week after the initial session, followed by a phone call approximately three weeks later. After completion of the study, participants in the ST group were offered to take home the same olfactory training kit that was provided to the PT group.

[0176] Subjective and objective measures of olfactory problems were assessed before and after treatment, as well as subjective measures related to quality of live and general wellbeing. The assessed measures included:

[0177] • Objective olfactory function using the standardized Sniffin' Sticks test extended test battery (Burghart Messtechnik, Holm, Germany). Objective olfactory function was assessed before and after 8 weeks of smell training. Pen-like tools are used to present odors and evaluate nasal chemosensory performance on odor detection threshold (T), odor quality discrimination (D), and cued odor identification (I). Added together, these generate a summarized TDI score, reflecting overall olfactory function with higher scores indicating better performance.

[0178] • Subjective olfactory function self-assessed using a 10-point visual analogue scale (VAS), ranging from 0 (no sense of smell) to 10 (excellent sense of smell).

[0179] • Compliance, including drop-out rate and adherence, using questions asking the participants about their experience during the olfactory training, specifically targeting their compliance, such as how often they actually completed the olfactory training and how often they forgot to. Dropout rate was defined as the percentage of individuals, in respective group, who did not complete the final testing session. This was obtained by counting the total number of participants who, at any point before their second visit, decided to discontinue their participation, either by informing the experiment leader or ending their communication without explanation. A six-item questionnaire of treatment adherence (Haas et al. 2024) individually assessed consistency, perceived tediousness, forgetfulness, and cause for potential discontinuation of the training. The questionnaire was presented to participants during their second visit.

[0180] Statistical analyses were performed using the statistical software R (v4.3.3; R Core Team 2024). The significance criterion for the statistical tests was set to a = 0.05. The study hypothesis, inclusion / exclusion criteria and analyses plan was preregistered on clinicaltrials.gov, ID NCT06142565.

[0181] Results of the study showed a nominal improvement in objective olfactory function, as shown in Figure 12. Individuals performing training, on average, improved their olfactory function with 3.5 scale steps whereas patients in the standard care group improved their olfactory function with 1.8 scale steps (measured on a relative scale of 16 to 42). Both values show statistical improvements and corresponded with subjective evaluation of treatment.

[0182] Furthermore, regarding compliance, as shown in Figure 13, considerably less participants (6,7%) dropped out of the training in the group using the nose plugs (depicted "NOSA Plug" in the Figure), than those using standard care training (23,2%) (depicted "Standard care" in Figure 13). Figure 13 illustrates the results of how many participants forgot (frequently, occasionally, seldom or never) to perform the daily training). Moreover, of the participants that completed the training, a significantly larger number performed the training on a regular basis, as seen by the large proportion of those who never forgot to perform the daily training (38,3% for the nose plug group and 10,7% for the standard care group).

[0183] In conclusion, using a nose plug and methods for olfactory training as disclosed herein show considerably improved results, in terms of both olfactory function and compliance, compared to standard care methods. Thus, the methods, kits and nose plugs disclosed herein provide improved outcome of olfactory trainings for subjects in need thereof. Furthermore, participants indicate, when asked about their experience, that using a nose plug as described herein is easier than standard care methods, and they are more compelled to follow the method of treatment as it is easier to incorporate in everyday life. Using a nose plug enables a user to go about their daily tasks while performing the olfactory training. This is positive for both the individual and for the society at large, with less cost for health care.

Claims

CLAIMS1. A method for olfactory training, comprising the steps of a. providing a subject with at least two or more nose plugs adapted for insertion into a nostril of a human subject, the nose plugs comprising a structural molded material and a fragrance substance or mixture of fragrance substances collectively experienced as an odor, said fragrance substance or mixture of fragrance substances being evenly dispersed in the structural molded material, and said two or more nose plugs each comprising a different fragrance substance or mixture of fragrance substances collectively experienced as an odor, b. exposing at least one nostril of said subject to the two or more nose plugs one at a time and in a predetermined order and duration; c. repeating the exposure on a daily basis for a predetermined training period.

2. The method for olfactory training according to claim 1, wherein exposing the nostrils to a nose plug comprises the action of said subject applying the nose plug to the nostrils by at least partial insertion of the nose plug into the nostrils.

3. The method for olfactory training according to any preceding claim, wherein exposing the nostrils to a nose plug comprises allowing the nose plug to remain in the nostrils for at least approximately 5 minutes, more preferably approximately 10 minutes.

4. The method for olfactory training according to any preceding claim, wherein the order of exposing the subject to the fragrance substances or mixtures of substances experienced as an odor is varied from day to day according to a predetermined scheme.

5. The method for olfactory training according to any preceding claim, wherein at least two different nose plugs with different fragrance substances or mixtures of substances experienced as an odor are used in the predetermined order.

6. The method for olfactory training according to any preceding claim, wherein the predetermined order is that on day 1 the subject is exposed to at least four differentfragrance substances or mixtures of substances experienced as an odor, and on day 2 the subject is exposed to at least one other fragrance substance or mixtures of substances experienced as an odor compared to day 1.

7. The method for olfactory training according to any preceding claim, wherein the duration of the training program is at least 1 to 2 weeks, preferably at least 1 month, and more preferably at least 2-4 months, wherein the subject is exposed to fragrance substances 5 days per week, and the subject is pausing the training 2 days per week.

8. The method for olfactory training according to any preceding claim, wherein exposing at least one nostril comprises inserting at least an entire flexible member fully into the nostril, such that only a support member remains outside the nostril.

9. The method for olfactory training according to any preceding claim, wherein the fragrance substances or mixtures of substances experienced as an odor are chosen from the group comprising strawberry, vanilla, lemon, melon, rosemary, menthol, cherry, orange, peach, cola, lavender, clove, cacao, coffee, citrus, carnation, rose, banana, apple, clove and cinnamon.

10. The method for olfactory training according to any preceding claim, wherein the training is for the treatment of hyposmia, anosmia and / or parosmia.

11. The method for olfactory training according to claim 10, wherein the hyposmia, anosmia and / or parosmia is a result of the subject having suffered from or is suffering from infection, covid, post-covid, injury to head and / or nervous system, Parkinson's disease, Alzheimer and stroke.

12. A computer program for use in olfactory training according to any preceding claim, comprising instructions which, when executed on at least one processor, cause the at least one processor to provide guidance to a subject undergoing olfactory training in accordance with any preceding claim, and / or following up activities performed by said subject as part of said olfactory training.

13. A kit of nose plugs for use in the method for olfactory training according to any of claims 1 to 11, comprising:-at least two or more nose plugs for at least two or more different odors, each nose plug comprising one fragrance substance or mixture of substances experienced as an odor, and- instructions for use.

14. The kit of nose plugs according to claim 13, wherein the fragrance substances or mixtures of substances experienced as an odor are chosen from the group comprising strawberry, vanilla, lemon, melon, rosemary, menthol, cherry, orange, peach, cola, lavender, clove, cacao, coffee, citrus, carnation, rose, , banana, apple, clove and cinnamon.

15. The kit of nose plugs according to claim 13 or 14, wherein the kit comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 different nose plugs with different fragrance substances or mixtures of substances experienced as an odor.

16. The kit of nose plugs according to any one of claims 13 to 15, wherein the nose plugs have different concentrations and / or amounts, such as low, medium and / or high concentration / amount of a fragrance substances or mixtures of substances experienced as an odor.

17. The kit of nose plugs according to any one of claims 13 to 16, wherein the kit comprises nose plugs for about 10 different fragrance substances or mixtures of substances experienced as an odor.

18. The kit of nose plugs according to any one of claims 13 to 17 wherein the kit comprises a plurality of nose plugs for each fragrance substance or mixtures of substances experienced as an odor.

19. A nose plug (1, 10) for use in an olfactory training program, the nose plug being adapted for insertion into a nostril of a human subject,characterized in that the nose plug comprises a structural molded material and a fragrance substance or mixture of fragrance substances collectively experienced as an odor, said fragrance substance or mixture of fragrance substances being evenly dispersed in the structural molded material.

20. The nose plug according to claim 19, wherein the structural molded material is a plastic, polymer or cellulose-based material.

21. The nose plug according to claim 19 or 20, further comprising: at least one flexible member (2) and one rigid, elongated support member (3), wherein the flexible member is arranged to surround the support member, and the flexible member is adapted to be placed within a nostril to accurately fill the opening of the nostril, and is provided with means for guiding the flow of air entering the nostril in a serpentine or spiral like path by means of a plurality of plates or a band, wherein at least the flexible member comprises the at least one fragrance substance or mixture of substances experienced as an odor evenly dispersed in a structural molded material.

22. The nose plug according to claim 19 or 20, further comprising an elongated support member (12, 62), and one or two rounded holder members (13, 63), each arranged at a respective end of said elongated support member (12, 62), wherein said holder members (13, 63) are adapted to be inserted into the nostril with a distal end directed into the nostril, and a proximal end adjacent the nostril openings, said holder members (13, 63) each comprise a bell-shaped cross-section in at least one plane in a distal-proximal extension, said holder members (13, 63) each comprising a rounded distal portion (15), and an open proximal portion (17) comprising an outer rim (18, 68) disposed circumferentially around the outer perimeter of said proximal portion (17) and extending radially outward from said holder member (13, 63), andan intermediate waist portion (19) arranged between said distal portion (15) and said proximal portion (17), said intermediate portion (19) having at least one outer circumference in a plane essentially transverse to a distal-proximal direction, said outer circumference being smaller than a respective largest outer circumference of at least said distal portion (15), wherein said outer rim (18, 68) disposed circumferentially around the outer perimeter of the proximal portion (17) is adapted to engage with the nostril opening and protrude outward from the nostril when the nasal device is arranged in a nostril, wherein said rounded distal portion (15) is provided with one or more through- going holes (16, 66) adapted to allow air to pass through said distal portion (15), wherein at least the holder members (13, 63) comprise the at least one fragrance substance or mixture of substances experienced as an odor evenly dispersed in a structural molded material.

23. The nose plug according to any one of claims 19 to 22, said nose plug being molded in one piece.

24. The nose plug according to any one of claims 19 to 23, wherein the at least one fragrance substance or mixture of substances experienced as an odor is evenly dispersed throughout the entire structural molded material.

25. The nose plug according to any one of claims 19 to 24, wherein the at least one fragrance substance or mixture of substances experienced as an odor is evenly dispersed on the surface of the structural molded material.

26. The nose plug according to any one of claims 19 to 25, wherein the fragrance substance(s) are provided in an "oil-like" or liquid form, or are suitable for being dissolved or dispersed in an oil-like solvent or other similar organic solvent.

27. The nose plug according to any one of claims 19 to 26, wherein the fragrance substance(s) is chosen from the group comprising strawberry, vanilla, lemon, melon, rosemary, menthol, cherry, orange, peach, cola, lavender, clove, cacao, coffee, citrus, carnation, rose, , banana, apple, clove and cinnamon.

28. The nose plug according to any one of claims 19 to 27, wherein the fragrance substance or mixture of substances experienced as an odor is added to the structural molded material at a dosing concentration in a range of fragrance-dependent or odor-dependent intervals.

29. The nose plug according to any one of claims 19 to 28, wherein the structural molded material is made of a thermoplastic elastomer and the fragrance substance or mixture of substances experienced as an odor is evenly dispersed therein.

30. The nose plug according to any one of claims 19 to 29, wherein structural molded material is coated with a coating comprising the fragrance substance or mixture of substances experienced as an odor.

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