US20230137840A1 - Mint mask and methods of use thereof - Google Patents
Mint mask and methods of use thereof Download PDFInfo
- Publication number
- US20230137840A1 US20230137840A1 US17/957,524 US202217957524A US2023137840A1 US 20230137840 A1 US20230137840 A1 US 20230137840A1 US 202217957524 A US202217957524 A US 202217957524A US 2023137840 A1 US2023137840 A1 US 2023137840A1
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- US
- United States
- Prior art keywords
- api
- certain embodiments
- subject
- effective amount
- menthol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
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Images
Classifications
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/534—Mentha (mint)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/06—Respiratory or anaesthetic masks
Definitions
- Peppermint oil oil of peppermint is readily available a number of commercial suppliers. It is volatile at room temperature.
- a “therapeutically effective amount” as used herein refers to an amount that is sufficient to achieve a desired therapeutic effect.
- the therapeutically effective amount can vary depending on such factors as the particular API, the particular condition to be treated, and the age, size, and condition of the subject to be treated.
- the therapeutically effective amount can also vary depending on the particular arrangement of the rebreathing device and the duration of treatment. A person of ordinary skill will be able to determine what is a therapeutically effective amount based on in vitro data, small animal data, and routine optimization.
- the therapeutically effective amount of the API is about 2.5 ⁇ g to about 1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 25 ⁇ g to about 1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 250 ⁇ g to about 1 mg per kilogram of body weight.
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Abstract
Provided are methods and devices useful for treating a respiratory disease or disorder involving the central or upper airways. The methods and devices deliver to central or upper airways of a subject a vapor or aerosol comprising an effective amount of an active ingredient selected from the group consisting of menthol, menthone, neomenthol, isomenthol, and menthofuran. The methods are useful for treating conditions including cough, asthma, bronchitis, and allergic rhinitis.
Description
- This application is a continuation of U.S. patent application Ser. No. 16/824,177, filed Mar. 19, 2020, which is a division of U.S. patent application Ser. No. 15/689,332, filed Aug. 29, 2017, now U.S. Pat. No. 10,610,494, which claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 62/381,270, filed Aug. 30, 2016, the entire contents of which are incorporated herein by reference.
- Along with vanilla and chocolate, peppermint is one of the most common flavorings in the world, and it is widely used to flavor confectionary, chewing gum, desserts, oral hygiene products, and many other products. In addition to being a benign and ubiquitous flavoring, peppermint is also a potent antispasmodic phytomedicine that relaxes smooth muscles in many instances. The main constituents of volatile oil of peppermint are the cyclic terpene alcohol (−)-menthol (C10H20O, MW 156.27) (35-55%) and its stereoisomers menthane (10-40%), (+)-neomenthol (about 3%), and (+) isomenthol (3%). Menthol is the most prevalent and most studied constituent, but other components may contribute to the effect of peppermint oil.
- Asthma is a common chronic lung disorder in which inflammation causes the bronchi to swell and narrow the airways, creating breathing difficulties that may range from mild to life-threatening. Symptoms include acute episodes of shortness of breath, cough, wheezing, and chest tightness lasting minutes to hours, even to days. Approximately 5 percent of the population of the United States is affected. Current treatments typically include beta-adrenergic agonists, methylxanthines, anticholinergics, and anti-inflammatory agents such as glucocorticoids. Beta-adrenergic agonists and anticholinergics typically are administered as aerosols, whereas methylxanthines and glucocorticoids are typically administered orally or intravenously; glucocorticoids are sometimes administered as aerosols.
- Bronchitis is a common lung disorder associated with excessive tracheobronchial mucus production with cough with expectoration. Chronic bronchitis is a common chronic lung disorder associated with excessive tracheobronchial mucus production sufficient to cause cough with expectoration for at least three months of the year for more than two consecutive years, A subset of patients with chronic bronchitis have clinically significant airway obstruction accompanied by severe dyspnea (air hunger) and wheezing in association with inhaled irritants or during acute respiratory infections. Current treatments typically include beta-adrenergic agonists, methylxanthines, anticholinergics, and antibiotics. Beta-adrenergic agonists and anticholinergics typically are administered as aerosols, whereas methylxanthines and glucocorticoids are typically administered orally or intravenously; glucocorticoids are sometimes administered as aerosols.
- A need still exists for effective, accessible treatments for these and other respiratory diseases and disorders.
- The invention provides a phytomedicine delivery device and related methods useful to treat asthma, allergic rhinitis, bronchitis, respiratory infections, cough, and wheezing. The delivery device, which can be made of simple, easily obtainable, inexpensive materials, is designed to be portable, disposable, inexpensive, biodegradable, and suitable to be sold over-the-counter. In certain embodiments, the delivery device and methods of the invention comprise a simple mechanical rebreathing device and a pharmacologically active phytomedicine, volatile oil of peppermint. In certain embodiments, the device can be breath-activated. In certain embodiments, the device delivers therapeutic levels of two bronchodilating agents: menthol and related compounds from the peppermint oil, and carbon dioxide from trapped exhalations.
- An aspect of the invention is a method of treating a respiratory disease or disorder involving the central airways, comprising administering to the central airways of a subject in need thereof a vapor or aerosol comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) selected from the group consisting of menthol, menthone, neomenthol, isomenthol, menthofuran, and any combination thereof.
- In certain embodiments, the API comprises menthol.
- In certain embodiments, the API is provided as volatile oil of peppermint.
- In certain embodiments, the vapor or aerosol is a vapor.
- In certain embodiments, the vapor or aerosol is an aerosol.
- In certain embodiments, the API is administered in conjunction with a rebreathing device.
- In certain embodiments, the rebreathing device comprises a semi-porous substrate impregnated with the API.
- In certain embodiments, the rebreathing device is a mask comprising a semi-porous substrate impregnated with the API, and the mask is constructed and arranged to fit over nose, mouth, or both nose and mouth of the subject.
- In certain embodiments, the rebreathing device is breath-activated.
- In certain embodiments, the vapor or aerosol is delivered to the central airways by inhalation by the subject.
- In certain embodiments, the respiratory disease or disorder involving the central airways is bronchitis.
- In certain embodiments, the respiratory disease or disorder involving the central airways is respiratory infection involving the central airways.
- In certain embodiments, the method treats cough.
- In certain embodiments, the method treats wheezing.
- In certain embodiments, the subject is a human.
- An aspect of the invention is a method of treating allergic rhinitis, comprising administering to the upper airways of a subject in need thereof a vapor or aerosol comprising a therapeutically effective amount of an API selected from the group consisting of menthol, menthone, neomenthol, isomenthol, menthofuran, and any combination thereof, wherein the API is administered in conjunction with a rebreathing device.
- An aspect of the invention is a method of treating cough, comprising administering to the airways of a subject in need thereof a vapor or aerosol comprising a therapeutically effective amount of an API selected from the group consisting of menthol, menthone, neomenthol, isomenthol, menthofuran, and any combination thereof, wherein the API is administered in conjunction with a rebreathing device.
-
FIG. 1 depicts an embodiment of the rebreathing device. -
FIG. 2 depicts a subject using a rebreathing device covering the nose. -
FIG. 3 depicts a subject using a rebreathing device covering both the nose and mouth. - Active Pharmaceutical Ingredient (API)
- Oil of peppermint has proven medical applications, primarily because of its antispasmodic effects on smooth muscle. Therapeutically, an oral preparation of volatile oil of peppermint oil has proven beneficial for irritable bowel syndrome in many randomized controlled trials. Khanna et al., J. Clin. Gastroenterol. 48: 505-12 (2014). Instilled preparations reduce spasm after colonoscopy (Shavakhi et al., Nihon Rinsho 68: 2126-34 (2010)), endoscopic retrograde cholangiopancreatography (ERCP; Yamamoto et al., J. Gastroenterol Hepatol 21: 1394-8 (2006)), and during upper gastrointestinal endoscopy (Fujishiro et al., J. Gastroentrol. 49: 446-54 (2014); Hiki et al., Dig. Enclose. 24: 79-86 (2012)).
- Few studies have been conducted on the effects of peppermint or menthol on the respiratory tract; most of these studies have focused on the nasal airway, for which results are not impressive. A recent randomized crossover trial in ten normal subjects found no effect of inhaled menthol on upper airway resistance. Pereira et al., Can. Respir. J. 20: el-4 (2013).
- Nevertheless, menthol is a common ingredient in cough and cold products, usually in decongestant preparations, although several studies have shown that menthol has no effect on nasal resistance. For example, menthol is an ingredient in Vicks VapoRub, an over-the-counter ointment indicated for topical use on the chest, back, and throat for cough suppression due to the common cold or on muscles and joints for minor aches and pains. Vicks VapoRub also contains camphor and eucalyptus oil, which also act as cough suppressants.
- Menthol is also a common additive in cigarettes; 90% of marketed cigarettes contain menthol, including many that are not marketed as menthol cigarettes.
- In guinea pigs, menthol has antitussive (cough suppressant) effects (Laude et al., Pulm. Pharmacol. 7: 179-84 (1994) and attenuates capsaicin- and neurokinin A-induced bronchoconstriction (Wright et al., Br. J. Pharmacol. 121: 1645-50 (1997)). Menthol inhibits bronchial contraction due to methacholine and high extracellular potassium; inhibition of calcium influx is important in menthol-mediated inhibition of smooth muscle contraction in airways. Ito et al., Pulm. Pharmacol. Ther. 21: 812-7 (2008). Other experiments have shown that menthol relaxes bronchi preconstricted with acetylcholine or potassium chloride, and has surfactant effects, lowering surface tension on bronchial surfaces. Additionally, menthol may prolong breath holding. Menthol vapor reduces reactivity to chemical irritants (Wise et al., Nicotine Tob. Res. 13: 989-97 (2011)) including acrolein, acetic acid, and cyclohexanone (Willis et al., FASEB J. 25: 4434-44 (2011)).
- The mammalian transient receptor potential (TRP) cation channels are divided based on sequence homology into six categories: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPP (polycystin), and TRPML (mucolipin). These channels are activated by many chemical and physical stimuli and appear to be important in various respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD). Banner et al., Pharmacol. Ther. 130: 371-84 (2011). Menthol interacts with transient receptor potential melastatin 8 (TRPM8), present in cold-sensitive sensory neurons, and transient receptor potential ankyrin 1 (TRPA1), an irritant-sensing channel.
- Menthol, which is thought to have decongestant properties although it does not, is not used or marketed for bronchitis or asthma. Two of three studies have found a benefit of menthol and cough. Menthol inhalation in patients with chronic cough reduced cough sensitivity to inhaled capsaicin and had an effect on inspiratory flows. Millqvist et al., Respir. Med. 107: 43-8 (2013). Menthol vapor and the taste of sucrose also reduced cough reflex to capsaicin challenge in another study. Wise et al., Pulm. Pharmacol. Ther. 25: 236-41 (2012). Another clinical study found no effect of premedication with 1% menthol inhalation on cough after fiberoptic bronchoscopy. Haidl et al., Pneumologie 55: 115-9 (2001).
- There is only one published study on the use of menthol to treat asthma. In a study of 23 asthmatics, 4 weeks of nebulized menthol (10 mg twice daily for four weeks) decreased diurnal variation in peak expiratory flow rate (PEER), a measure of airway excitability, reduced wheezing episodes, and reduced use of metered dose inhalers. The treatment had no effect on VC (vital capacity) or FEV1 (forced expiratory volume at 1 second). Menthol may reduce airway hyperresponsiveness without changing the magnitude of airflow limitation. Tamaoki et al., Resp. Med. 89: 503-4 (1995).
- Peppermint oil (oil of peppermint) is readily available a number of commercial suppliers. It is volatile at room temperature.
- Menthol ((1R,2S,5R)-2-Isopropyl-5-methylcyclohexanol) is readily available from a number of commercial suppliers; it is typically presented either as waxy crystals or as an oil. The main form of menthol occurring in nature is (—)-menthol, which is assigned the (1R,2S,4R) configuration. Menthol is manufactured as a single enantiomer (1R,2S,5R-menthol; 94% ee) on the scale of 3,000 tons per year by Takasago International Corporation. The process involves an asymmetric synthesis developed by a team led by Ryōji Noyori, who won the 2001 Nobel Prize for Chemistry in recognition of his work on this process. The process begins by forming an allylic amine from myrcene, which undergoes asymmetric isomerization in the presence of a BINAP rhodium complex to give (after hydrolysis) enantiomerically pure R-citronellal. This is cyclized by a carbonyl-ene-reaction initiated by zinc bromide to isopulegol, which is then hydrogenated to give pure (1R,2S,5R)-menthol.
- Rebreathing Device
- Asthmatics often breathe faster as a way of compensating for airway constriction, but hyperventilation decreases carbon dioxide, thereby worsening the condition by causing lightheadedness, anxiety, and bronchoconstriction. Slow breathing not only relieves symptoms of hyperventilation, but also has a beneficial effect on asthma. Asthmatic patients can be trained in Buteyko breathing techniques, which intersperse breath holding with periods of shallow, slow breathing. Buteyko breathing has been shown to be an effective treatment for asthmatics, but it requires effort and training on the part of the subject.
- Controlled breathing builds up carbon dioxide in the airways, dilating smooth muscles in the bronchi while maintaining a eucapnic state (i.e., without increasing carbon dioxide in the blood). Prem et al., Clin. Rehabil. 27: 133-41 (2013). A number of studies have found that Buteyko breathing techniques reduce symptoms and medication use in asthmatic patients.
- Compared to control and pranayama breathing, Buteyko breathing improved Asthma Control Questionnaire scores at 3 months, improved FEV1, and improved FEV1/FVC (forced vital capacity). Prem et al., Clin. Rehabil. 27: 133-41 (2013).
- A systematic review of 13 studies of asthmatic patients involving 906 participants (11 compared breathing exercise with inactive control, and two with asthma education) found improvement in quality of life in all eight studies that assessed this and an improvement (reduction) in the number of acute exacerbations in the one study that assessed this. Six of seven studies showed significant differences favoring breathing exercises for asthma symptoms. Effects on lung function were variable. A meta-analysis of the two studies assessing changes in the Asthma Quality of Life Questionnaire favored breathing exercises.
- By having the user breathe into a semi-porous enclosed space, the device portion of the invention reproduces the beneficial effect of controlled breathing without requiring any effort or training on the part of the user. A semi-porous enclosed space provides plenty of oxygen and will not make a person feel air hunger; the effect is similar to breathing into a paper bag. Rebreathing also warms and humidifies air, which is helpful in preventing cold-induced asthma.
- In certain embodiments, the rebreathing device is a generally cup-, cone-, or beak-shaped mask comprising a semi-porous substrate material (paper, woven or non-woven cloth, cellulose, sponge, foam, other natural fiber, or other synthetic material); for use, the semi-porous substrate material is at least partially impregnated with volatile oil of peppermint (Mentha x piperita) or of other Mentha species, or one or more of the major constituents of peppermint oil (e.g., menthol, menthone, or menthofuran). The mask will conformably cover the nose, or the nose and mouth, with an adjustable band, strap or tie that encircles the head or hooks over the ears to hold the mask in place. In certain embodiments, the mask will also have a flexible band or other device made of plastic, metal, or another material to improve fit over the nose. In certain embodiments, the rebreathing device is similar to or essentially the same as a commercially available dust mask. In certain embodiments, the rebreathing device is similar to or essentially the same as a commercially available surgical or medical mask.
- For use, the volatile oil or constituent (API) is contacted with the device, or at least the semi-porous substrate material portion of the device, using any suitable method. In certain embodiments, the API is supplied with the mask in a container such as a small foil or plastic film or pouch with a tear-off strip that, when opened, exposes the compound. In certain embodiments, the API is provided attached to the mask in a small foil or plastic film or pouch with a tear-off strip that, when opened, exposes the compound.
- The rebreathing device is constructed and arranged so that the user can breathe while wearing the device. That is, in certain embodiments, the rebreathing device is constructed and arranged so that the user can breathe through the mask.
- In certain embodiments, the rebreathing device is generally a bag, inside of which is a semi-porous substrate material (paper, woven or non-woven cloth, cellulose, sponge, foam, other natural fiber, or other synthetic material); for use, the semi-porous substrate material is at least partially impregnated with volatile oil of peppermint (Mentha x piperita) or of other Mentha species, or one or more of the major constituents of peppermint oil (e.g., menthol, menthone, or menthofuran). For use, the volatile oil or constituent (API) is applied to the device or at least the semi-porous substrate material portion of the device using any suitable method. In certain embodiments, the API is supplied with the bag in a container such as a small foil or plastic film or pouch with a tear-off strip that, when opened, exposes the compound. The user can breathe into the bag.
- Other embodiments are also contemplated by the invention. For example, in certain embodiments, the rebreathing device is generally a rigid or semi-rigid cylinder, comprising or inside of which is a semi-porous substrate material (paper, woven or non-woven cloth, cellulose, sponge, foam, other natural fiber, or other synthetic material); an open end of the cylinder is suitably sized to accommodate a user's nose or nose and mouth. For use, the semi-porous substrate material is at least partially impregnated with volatile oil of peppermint (Mentha x piperita) or of other Mentha species, or one or more of the major constituents of peppermint oil (e.g., menthol, menthone, or menthofuran). For use, the volatile oil or constituent (API) is contacted with the device, or at least the semi-porous substrate material portion of the device, using any suitable method.
- Methods
- An aspect of the invention is a method of treating a respiratory disease or disorder involving the central airways, comprising administering to the central airways of a subject in need thereof a vapor or aerosol comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) selected from the group consisting of menthol, menthone, neomenthol, isomenthol, menthofuran, and any combination thereof.
- As used herein, “treat” or “treating” refers to ameliorating at least one sign or symptom of a disease or disorder in a subject. In certain embodiments, the improvement can be objectively measured. For example, in treating asthma, improvement may include improvement in forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR), or both. In certain embodiments, the improvement can be subjective. In certain embodiments, “treat” or “treating” refers to fully resolving at least one sign or symptom of a disease or disorder in a subject. In certain embodiments, “treat” or “treating” refers to fully resolving a disease or disorder in a subject.
- As used herein, “central airways” refers generally to the lower respiratory system, comprising larynx, trachea, bronchi, bronchioles, and alveoli. In certain embodiments, “central airways” refers to conducting airways of the lungs, i.e., trachea, bronchi, and bronchioles.
- In certain embodiments, the vapor or aerosol is a vapor.
- In certain embodiments, the vapor or aerosol is an aerosol.
- A “respiratory disease or disorder involving central airways” refers generally to any inflammatory, allergic, irritant, or infectious disease or disorder involving central airways, or any combination thereof.
- In certain embodiments, the respiratory disease or disorder involving central airways is asthma. The asthma can be allergic, cold-induced, exercise-induced, irritant-induced, or idiopathic.
- In certain embodiments, the respiratory disease or disorder involving central airways is bronchitis. In certain embodiments, the bronchitis is chronic bronchitis.
- In certain embodiments, the respiratory disease or disorder involving central airways is a respiratory infection involving the central airways, e.g., pneumonia or pneumonitis.
- In certain embodiments, the method treats cough.
- In certain embodiments, the method treats wheezing.
- A “subject”, as used herein, refers to a mammal. In certain embodiments, the subject is a mouse, rat, guinea pig, rabbit, cat, dog, pig, sheep, goat, cow, horse, non-human primate, or a human.
- In certain embodiments, the subject is a human.
- In certain embodiments, the API comprises menthol. In certain embodiments, the API consists of menthol.
- In certain embodiments, the API is provided as volatile oil of peppermint.
- In accordance with each of the foregoing embodiments, in certain embodiments, the API is administered in conjunction with a rebreathing device. In certain embodiments, the rebreathing device comprises a semi-porous substrate that is at least partially impregnated with the API. In certain embodiments, the rebreathing device is a mask comprising a semi-porous substrate that is at least partially impregnated with the API, and the mask is constructed and arranged to fit over the nose, mouth, or both the nose and mouth of the subject.
- In certain embodiments, the rebreathing device is breath-activated. That is, the rebreathing device is activated by the subject breathing spontaneously through or into the rebreathing device, without assistance of a mechanical ventilator. The simple act of inhalation entrains the vaporized or aerosolized API and delivers the vapor or aerosol, including in particular the API, to the central airways of the subject.
- Additional details and embodiments in connection with the rebreathing device are provided above.
- To operate the rebreathing device, a user or subject applies the volatile oil or API to the semi-porous substrate, thereby activating the rebreathing device. In certain embodiments, for this purpose the volatile oil or API can be dissolved in alcohol or other suitable solvent. The subject dons the activated rebreathing device (e.g., mask), adjusts the fit to his or her face, and breathes using the device for a period of time sufficient to achieve a desired effect. Typically, this period of time will be about 1-30 minutes. In some embodiments, this period of time will be about 1-20 minutes. In some embodiments, this period of time will be about 1-15 minutes. In some embodiments, this period of time will be about 1-10 minutes. In some embodiments, this period of time will be about 1-5 minutes. In some embodiments, this period of time will be about 1-2 minutes. In some embodiments, this period of time will about 2-30 minutes. In some embodiments, this period of time will be about 2-20 minutes. In some embodiments, this period of time will be about 2-15 minutes. In some embodiments, this period of time will be about 2-10 minutes. In some embodiments, this period of time will be about 2-5 minutes. In some embodiments, this period of time will be about 5-30 minutes. In some embodiments, this period of time will be about 5-20 minutes. In some embodiments, this period of time will be about 5-15 minutes. In some embodiments, this period of time will be about 5-10 minutes. In some embodiments, this period of time will be about 10-30 minutes. In some embodiments, this period of time will be about 10-20 minutes. The treatment can be repeated as needed.
- In certain embodiments, the vapor or aerosol is delivered to the central airways by inhalation by the subject. For example, the subject breathes spontaneously through or into the rebreathing device, without assistance of a mechanical ventilator. The simple act of inhalation entrains the vaporized or aerosolized API and delivers the vapor or aerosol, including in particular the API, to the central airways of the subject.
- An aspect of the invention is a method of treating allergic rhinitis, comprising administering to the upper airways of a subject in need thereof a vapor or aerosol comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) selected from the group consisting of menthol, menthone, neomenthol, isomenthol, menthofuran, and any combination thereof, wherein the API is administered in conjunction with a rebreathing device.
- Allergic rhinitis, also known as hayfever, is a common type of inflammation in the nose which occurs when the immune system reacts to allergens in the air. Symptoms typically include sneezing, rhinorrhea, post-nasal drip, nasal obstruction, and nasal, conjunctival, and pharyngeal itching.
- As used herein, “upper airways” refers to the nasal cavities and pharynx.
- In certain embodiments, the API comprises menthol. In certain embodiments, the API consists of menthol.
- In certain embodiments, the API is provided as volatile oil of peppermint.
- In certain embodiments, the vapor or aerosol is a vapor.
- In certain embodiments, the vapor or aerosol is an aerosol.
- In certain embodiments, the rebreathing device and its operation are as described above.
- In certain embodiments, the rebreathing device is a mask comprising a semi-porous substrate impregnated with the API, and the mask is constructed and arranged to fit over nose, mouth, or both nose and mouth of the subject.
- In certain embodiments, the mask is constructed and arranged to fit over the nose of the subject.
- In certain embodiments, the rebreathing device is breath-activated.
- In certain embodiments, the vapor or aerosol is delivered to the upper airways by inhalation by the subject.
- In certain embodiments, the method treats cough.
- In certain embodiments, the subject is a human.
- An aspect of the invention is a method of treating cough, comprising administering to the airways of a subject in need thereof a vapor or aerosol comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) selected from the group consisting of menthol, menthone, neomenthol, isomenthol, menthofuran, and any combination thereof, wherein the API is administered in conjunction with a rebreathing device.
- As used herein, “airways” refers to upper, central, and/or both upper and central airways as used herein.
- In certain embodiments, the API comprises menthol. In certain embodiments, the API consists of menthol.
- In certain embodiments, the API is provided as volatile oil of peppermint.
- In certain embodiments, the vapor or aerosol is a vapor.
- In certain embodiments, the vapor or aerosol is an aerosol.
- In certain embodiments, the rebreathing device and its operation are as described above.
- In certain embodiments, the rebreathing device is a mask comprising a semi-porous substrate impregnated with the API, and the mask is constructed and arranged to fit over nose, mouth, or both nose and mouth of the subject.
- In certain embodiments, the mask is constructed and arranged to fit over the nose of the subject.
- In certain embodiments, the rebreathing device is breath-activated.
- In certain embodiments, the vapor or aerosol is delivered to the airways by inhalation by the subject.
- In certain embodiments, the subject is a human.
- In accordance with each of the foregoing methods, a “therapeutically effective amount” as used herein refers to an amount that is sufficient to achieve a desired therapeutic effect. The therapeutically effective amount can vary depending on such factors as the particular API, the particular condition to be treated, and the age, size, and condition of the subject to be treated. The therapeutically effective amount can also vary depending on the particular arrangement of the rebreathing device and the duration of treatment. A person of ordinary skill will be able to determine what is a therapeutically effective amount based on in vitro data, small animal data, and routine optimization.
- In general, a therapeutically effective amount of the API is about 1 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 10 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 100 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 1 mg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 10 mg to about 100 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 1 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 10 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 100 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 1 mg to about 10 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 1 μg to about 1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 10 μg to about 1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 100 μg to about 1 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 1 μg to about 0.1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 10 μg to about 0.1 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 2.5 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 25 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 250 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 2.5 mg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 25 mg to about 100 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 2.5 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 25 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 250 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 2.5 mg to about 10 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 2.5 μg to about 1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 25 μg to about 1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 250 μg to about 1 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 2.5 μg to about 0.1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 25 μg to about 0.1 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 5 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 50 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 500 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 5 mg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 50 mg to about 100 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 5 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 50 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 500 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 5 mg to about 10 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 5 μg to about 1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 50 μg to about 1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 500 μg to about 1 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 5 μg to about 0.1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 50 μg to about 0.1 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 7.5 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 75 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 750 μg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 7.5 mg to about 100 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 75 mg to about 100 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 7.5 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 75 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 750 μg to about 10 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 7.5 mg to about 10 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 7.5 μg to about 1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 75 μg to about 1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 750 μg to about 1 mg per kilogram of body weight.
- In certain embodiments, the therapeutically effective amount of the API is about 7.5 μg to about 0.1 mg per kilogram of body weight. In certain embodiments, the therapeutically effective amount of the API is about 75 μg to about 0.1 mg per kilogram of body weight.
- The administering can be accomplished in a single dose or in a plurality of doses. In certain embodiments, the administering is accomplished in a single dose. In certain embodiments, the administering is accomplished in two doses. In certain embodiments, the administering is accomplished in three doses. In certain embodiments, the administering is accomplished in four or more doses.
- The administering can be one or more times a day. In certain embodiments, the administering is once a day. In certain embodiments, the administering is twice a day. In certain embodiments, the administering is three times a day. In certain embodiments, the administering is four times a day. In various additional embodiments, the administering is 5, 6, 7, 8, 9, 10, 11, or 12 times a day. In general, the frequency and spacing of dosing can be adapted to the subject's symptoms and needs.
- Kits
- Also provided are kits useful in practicing the methods of the invention. In an embodiment, a kit comprises an API as disclosed herein, and a semi-porous substrate. The semi-porous substrate is suitably constructed and arranged for application of the API to the semi-porous substrate.
- In an embodiment, a kit comprises an API as disclosed herein, and a rebreathing device. The rebreathing device is suitably constructed and arranged to receive the API and then deliver the API to the airways of a subject. In certain embodiments, the rebreathing device comprises a semi-porous substrate. In such embodiments, the rebreathing device is suitably constructed and arranged for application of the API to the substrate.
- In certain embodiments, a kit comprises an API as disclosed herein, and a rebreathing device, wherein the rebreathing device is a mask comprising a semi-porous substrate. The rebreathing device is suitably constructed and arranged to receive the API and then deliver the API to the airways of a subject when placed over the nose or both the nose and mouth of the subject.
- In each of the foregoing embodiments, the kit can further include instructions, written or otherwise, for how to use the components of the kit. For example, the instructions can direct a user how to assemble the components, e.g., how to contact the API with the rebreathing device. The instructions can also direct a user how to use the assembled, activated rebreathing device to treat the condition to be treated, e.g., how to use the assembled device to treat asthma.
- The various components of the kit are typically provided in a tray or box assembly, each component optionally provided in its own compartment or packaging material. Each component optionally is provided in a sealed package, e.g., the API may be provided in a vial, pouch, or tube. A kit can include components sufficient for a single use, or it can include components sufficient for two or more uses.
Claims (20)
1. A method of treating a respiratory disease or disorder involving the central airways, comprising administering to the central airways of a subject in need thereof a vapor or aerosol comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) selected from the group consisting of menthol, menthone, neomenthol, isomenthol, menthofuran, and any combination thereof, wherein the respiratory disease or disorder involving the central airways is selected from the group consisting of bronchitis and a respiratory infection involving the central airways.
2. The method of claim 1 , wherein the API comprises menthol.
3. The method of claim 1 , wherein the API is provided as volatile oil of peppermint.
4. The method of claim 1 , wherein the API is administered in conjunction with a rebreathing device.
5. The method of claim 4 , wherein the rebreathing device comprises a semi-porous substrate impregnated with the API.
6. The method of claim 4 , wherein the rebreathing device is a mask comprising a semi-porous substrate impregnated with the API, and the mask is constructed and arranged to fit over nose, mouth, or both nose and mouth of the subject.
7. The method of claim 1 , wherein the vapor or aerosol is delivered to the central airways by inhalation by the subject.
8. The method of claim 1 , wherein the subject is a human.
9. A method of treating allergic rhinitis, comprising administering to the upper airways of a subject in need thereof a vapor or aerosol comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) selected from the group consisting of menthol, menthone, neomenthol, isomenthol, menthofuran, and any combination thereof, wherein the API is administered in conjunction with a rebreathing device.
10. The method of claim 9 , wherein the API comprises menthol.
11. The method of claim 9 , wherein the API is provided as volatile oil of peppermint.
12. The method of claim 9 , wherein the rebreathing device comprises a semi-porous substrate impregnated with the API.
13. The method of claim 12 , wherein the rebreathing device is a mask comprising a semi-porous substrate impregnated with the API, and the mask is constructed and arranged to fit over nose, mouth, or both nose and mouth of the subject.
14. The method of claim 9 , wherein the vapor or aerosol is delivered to the upper airways by inhalation by the subject.
15. A method of treating cough, comprising administering to the airways of a subject in need thereof a vapor or aerosol comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) selected from the group consisting of menthol, menthone, neomenthol, isomenthol, menthofuran, and any combination thereof, wherein the API is administered in conjunction with a rebreathing device.
16. The method of claim 15 , wherein the API comprises menthol.
17. The method of claim 15 , wherein the API is provided as volatile oil of peppermint.
18. The method of claim 15 , wherein the rebreathing device comprises a semi-porous substrate impregnated with the API.
19. The method of claim 18 , wherein the rebreathing device is a mask comprising a semi-porous substrate impregnated with the API, and the mask is constructed and arranged to fit over nose, mouth, or both nose and mouth of the subject.
20. The method of claim 15 , wherein the vapor or aerosol is delivered to the airways by inhalation by the subject.
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US17/957,524 US20230137840A1 (en) | 2016-08-30 | 2022-09-30 | Mint mask and methods of use thereof |
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US16/824,177 US11484509B2 (en) | 2016-08-30 | 2020-03-19 | Mint mask and methods of use thereof |
US17/957,524 US20230137840A1 (en) | 2016-08-30 | 2022-09-30 | Mint mask and methods of use thereof |
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US17/957,524 Abandoned US20230137840A1 (en) | 2016-08-30 | 2022-09-30 | Mint mask and methods of use thereof |
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US16/824,177 Active 2038-02-03 US11484509B2 (en) | 2016-08-30 | 2020-03-19 | Mint mask and methods of use thereof |
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USD1001998S1 (en) * | 2019-06-21 | 2023-10-17 | Benjamin Emery | Mask |
US20220030967A1 (en) * | 2020-07-29 | 2022-02-03 | Jennifer Bowie | Mask Scenting Systems and Methods |
US20220370834A1 (en) * | 2021-05-21 | 2022-11-24 | Zverse, Inc. | Retaining ring for respiratory face masks |
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US8061357B2 (en) * | 2004-12-08 | 2011-11-22 | Ventus Medical, Inc. | Adhesive nasal respiratory devices |
US7651270B2 (en) | 2007-08-31 | 2010-01-26 | Rigaku Innovative Technologies, Inc. | Automated x-ray optic alignment with four-sector sensor |
US20160375205A1 (en) | 2015-06-24 | 2016-12-29 | Philip Wayne Cressman | Nasal Inhaler Band |
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