WO2025114598A1

WO2025114598A1 - Composition comprising herbal extracts to alleviate snoring

Info

Publication number: WO2025114598A1
Application number: PCT/EP2024/084278
Authority: WO
Inventors: Anders PERMIN; Jacob Boes; Tom HORNSHØJ-MØLLER
Original assignee: Nyx Medico Aps
Current assignee: Nyx Medico Aps
Priority date: 2023-11-30
Filing date: 2024-12-02
Publication date: 2025-06-05
Anticipated expiration: 2026-05-30

Abstract

The present invention relates to a composition comprising the combination of extracts from Centella asiatica or other members of the family Apiaceae, extract from the family Zingiberaceae, extract from the family Valerianaceae, extract from the family Capsicum, xylitol, sodium hyaluronate, glycerine, vitamins and minerals for treating and/or alleviating snoring, chronic sinusitis, cold, and/or obstructive sleep apnea in humans and animals.

Description

Composition comprising herbal extracts to alleviate snoring

Technical field of the invention

The present invention relates to a composition comprising the combination of two or more of extracts selected from the list of Centella asiatica or other members of the family Apiaceae, extract from the family Zingiberaceae, extract from the family Capsicum, extract from the family Valerianaceae, xylitol, hyaluronate, glycerine, vitamins and minerals for treating and/or alleviating snoring, chronic sinusitis, cold, and/or obstructive sleep apnea in humans and animals.

The composition may be administered to the nose or oral cavity.

Background of the invention

Snoring is a worldwide problem, not only for the snorer who has a disturbed sleeping rhythm or an increased risk of developing a serious illness, but also for the partner sleeping next to them.

Snoring is not defined a disease per se, but it is a symptom of restricted air passage in the upper airways that millions of people suffer from during their sleep. Most importantly, it is a symptom that most people are familiar with, and it is also extremely important to seek help for treatment. This is important as the snoring can cause more physiological diseases. In addition, it is often the first symptom of sleep apnea, which is a serious disease if untreated.

Chronic sinusitis is a nasal condition with constant production of mucus and may lead to snoring.

Sleep apnea, also spelled sleep apnoea, is a sleeping disorder characterized by pauses in breathing or periods of shallow breathing during sleep. Each pause can last for a few seconds to a few minutes, and they happen many times a night. In the most common form, this follows loud snoring. There may be a choking or snorting sound as breathing resumes. As the disorder disrupts normal sleep, those affected may experience sleepiness or feel tired during the day. In children it may cause problems in school, or hyperactivity.

There are three forms of sleep apnea: obstructive (OSA), central (CSA), and a combination of the two called mixed sleep apnea. OSA is the most common form. Risk factors for OSA include being overweight, a family history of the condition, allergies, a small airway, and enlarged tonsils. In OSA, breathing is interrupted by a blockage of airflow, while in CSA breathing stops due to a lack of effort to breathe. People with sleep apnea may not be aware that they suffer from it. In many cases, it is first observed by a family member/bed partner. Sleep apnea is often diagnosed with an overnight sleep study. For a diagnosis of sleep apnea, more than five episodes an hour must occur.

Treatment may include lifestyle changes, mouthpieces, breathing devices, and surgery. Lifestyle changes may include avoiding alcohol, losing weight, stopping smoking, and sleeping on one's side. Breathing devices include the use of a CPAP machine (Continuous Positive Airway Pressure machine). Presently, no medical treatment is available for the treatment of snoring/sleeping apnea. Further, lack of free airway passage through the nose and throat may negatively influence the effect of e.g. sleeping with a CPAP machine.

Without treatment, sleep apnea may increase the risk of heart attack, stroke, diabetes, heart failure, irregular heartbeat, obesity, and traffic accidents.

Hence, there is a need for an improved and less invasive way to deal with snoring, and in particular an efficient and/or reliable way to deal with snoring where lifestyle changes, mouthpieces, breathing devices, and/or surgery may be avoided would be advantageous, or to improve the effect of existing treatments such as of CPAP or of lifestyle changes.

Summary of the invention

Thus, an object of the present invention relates to compositions for treating, and/or alleviating snoring, chronic sinusitis, cold, and/or sleep apnea in a subject. In some embodiments, the present compositions are for use in combination with existing treatment.

In particular, it is an object of the present invention to provide a composition comprising a mixture of plant extracts for treating, and/or alleviating snoring, cold, chronic sinusitis, and/or sleep apnea in humans and animals that solves the above-mentioned problems of the prior art with snoring where lifestyle changes, mouthpieces, breathing devices, and/or surgery are the presently offered treatments. The present invention provides compositions that may be used alone, or in combination with the existing treatments to provide a combined enhanced effect.

In some embodiments, the compositions are for reducing swelling and/ or stimulating contraction of tissues in the nasal and oral cavities. Thus, one aspect of the invention relates to a composition comprising the combination of:

(i) an extract obtained from plant material selected from the family Apiaceae

(ii) an extract obtained from plant material selected from the family Zingiberaceae

(iii) an extract from plant or fruit selected from the families Capsicum annuumannuum or Capsicum frutescens and

(iv) a lubricant

In some aspects of the present invention, the compositions are formulated as a spray such as a nasal or mouth spray, so that the invention provides a nasal or mouth spray comprising a composition according to the present invention. Such a composition is useful for treating or alleviating swelling of nose or oral cavity tissues such as mucosa, and for treating or alleviating snoring, chronic sinusitis, cold, and/or sleep apnea in humans and animals.

In some such embodiments the composition comprises the combination of:

(i) an extract obtained from plant material selected from the family Apiaceae, preferably of the species Centella asiatica,

(ii) an extract obtained from plant material selected from the family Zingiberaceae, preferably of the species Zingiber officinale,

(iii) an extract from plant or fruit from the family Capsicum selected from Capsicum annuum or Capsicum frutescens, and

(iv) sodium hyaluronate.

In some embodiments the composition comprises the combination of: (i) an extract obtained from plant material selected from the family Apiaceae , preferably of the species Centella asiatica,

(iv) one or more of a sodium salt of the acids: Sodium Hyaluronate - 40-60 kDa or Sodium Hyaluronate 1000-2500 kDa.

In some embodiments the composition comprises the combination of:

(i) an extract obtained from plant material selected from the family Apiaceae , preferably of the species Centella asiatica,

(iii) an extract from plant or fruit from the family Capsicum selected from Capsicum annuum or Capsicum frutescens,

(iv) A sodium salt of the acid : Sodium Hyaluronate - 40-60 kDa and a sodium salt of the acid : Sodium Hyaluronate 1000-2500 kDa. and

(v) A lubricant

In some embodiments the composition comprises the combination of:

(ii) an extract obtained from plant material selected from the family Zingiberaceae, preferably of the species Zingiber officinale, (Hi) an extract from plant or fruit from the family Capsicum selected from Capsicum annuum or Capsicum frutescens,

(v) glycerine

A further aspect of the present invention relates to a composition for treating or alleviating swelling of nose or oral cavity tissues such as mucosa, and for avoiding the development of snoring, chronic sinusitis, cold, and/or sleep apnea in humans and animals, characterised in that the composition comprises the combination of:

(i) an extract obtained from plant material selected from the family Apiaceae

(iii) an extract from plant or fruit selected from the families Capsicum annuum or Capsicum frutescens

(iv) an extract from plant material selected from the family Valerianaceae

(v) sodium hyaluronate, such as a sodium salt of the acid: Sodium Hyaluronate - 40-60 kDa and/or a sodium salt of the acid: Sodium Hyaluronate 1000- 2500 kDa and

(vi) glycerine

The compositions of the invention are also for use in combination with existing treatments of the conditions described in this application, including those of swelling of nose or oral cavity tissue such as mucosa, and for treating or alleviating snoring, chronic sinusitis, cold, and/or sleep apnea in humans and animals. In some embodiments of the invention, the compositions are in the form of an oral or nasal spray. Detailed description of the invention

Lack of tissue tonus, swelling and congestion of the airway passage is a widespread problem that affect the sleeping quality of many people. In example, millions of people suffer from snoring, caused or enhanced by such swelling or congestion of the airway passage. Consequently, most people are familiar with snoring. Snoring and other conditions such as sleep apnea may lead to serious conditions. The present invention provides compositions for alleviating or treating some of the underlying conditions causing snoring or sleep apnea. The compositions of the invention comprise a novel combination of extracts from various plants, shown in the present invention to be effective for preventing, and/or treating, and/or alleviating some of the fundamental causes of snoring, chronic sinusitis, cold, and/or sleep apnea in humans and animals.

In the present application, the term "sleep apnea" is related only to obstructive sleep apnea (OSA). Obstructive sleep apnea happens when the upper airway becomes blocked many times during sleep, reducing or completely stopping airflow. This is the most common type of sleep apnea. Anything that could narrow the airways such as obesity, large tonsils, or changes in hormone levels can increase the risk for obstructive sleep apnea.

In one embodiment, the present invention provides compositions comprising combinations of:

(v) an extract obtained from plant material selected from the family Apiaceae

(vi) an extract obtained from plant material selected from the family Zingiberaceae

(vii) an extract from plant or fruit selected from the families Capsicum annuum or Capsicum frutescens and

(viii) a lubricant

In some embodiments, the compositions comprise a lubricant.

In some embodiments, the composition comprises glycerine as a lubricant. In the context of the present invention the term "extract" relates to a substance made by subjecting plant material to a solvent resulting in concentrating one or more analytes from the plant material into the solvent.

In the present application, the terms "an extract obtained from a plant material selected from the family Zingiberaceae", or "an extract obtained from a plant material selected from the family Apiaceae" or "an extract obtained from a plant material selected from the family Valerianaceae" or "an extract obtained from a plant material selected from the family Capsicum" relates to the process of subjecting the plant materials (one selected from the family Zingiberaceae; one selected from the family Apiaceae; one selected from the family Valerianaceae, or herb or combination of herbs containing valerenic acid; and one selected from the family Capsicum containing capsaicin) to a solvent extracting the analytes of interest and providing the extracts.

In an embodiment of the present invention, the composition comprises plant extract from Apiaceae selected from the Centella family. Preferably, in such embodiments the plant extract is from the species Centella asiatica.

In some embodiments of the present invention, the composition comprises extract from plant material selected from the family Valerianaceae.

In some embodiments of the present invention, the composition further comprises valerian root extract from Valeriana officinalis. In some embodiments of the present invention, the plant material is selected from the family Apiaceae comprises a plant material extracted from the species Centella asiatica.

In some embodiments the composition according to the invention comprises plant material from the family Zingiberaceae such as from the species Zingiber officinale, such as root extracts from Zingiber officinale. In a preferred embodiment, the Zingiber extract is a root extract.

In some embodiments, the composition according to the invention comprises plant extract from Capsicum in the form of a fruit extract from the species Capsicum annuum or Capsicum frutescens.

In a preferred embodiment, the composition according to the present invention comprises the combination of:

(vi) an extract obtained from plant material selected from the family Apiaceae preferably of the species Centella asiatica,

(vii) an extract obtained from plant material selected from the family Zingiberaceae preferably of the species Zingiber officinale, (viii) an extract from plant or fruit from the family Capsicum selected from the species Capsicum annuum or Capsicum frutescens, and

(ix) sodium hyaluronate

In some embodiments, the composition according to invention, further comprises one or more of vitamins A, D, E, K, B and C and minerals Ca, Mg, Se and Zn and a lubricant such as glycerine.

Centella contains pentacyclic triterpenoids, including madecassic acid (brahmic acid), asiaticoside, and asiatic acid. In traditional medicine, Centella asiaticaCentella asiatica (C. asiatica) has been used to treat various disorders and minor wounds and to encourage lactation. There are no records of the synergistic effect of Centella, Centella asiatica, and herbs of the family Zingiberaceae, on wound-healing, collagen, edema and mucosal membranes.

In an embodiment of the present invention, the composition comprises madegassic acid, and/or asiatic acid; and/or asiaticoside.

In a further embodiment of the present invention the composition comprises zingiber extract and madegassic acid; and/or asiaticoside; and/or asiatic acid.

The content of the extract obtained from a plant material selected from the family Zingiberaceae; preferably Zingiberaceae present in the composition may be standardizing from the flavonoid content, preferably from the content of zingiber.

In a further embodiment of the present invention, the compositions according to the invention comprises valerian root extract (Valeriana Officinalis') containing valerenic acid. Valerian can be added to give a calming, sedative and anxiolytic effect. The root extract of Valeriana officinalis contains several active compounds, including valerenic acid, valerenal, and volatile oils, which contribute to its observed effects.

The primary scientific effect of Valeriana officinalis root extract is its ability to promote relaxation and alleviate symptoms of anxiety and sleep disorders. Several studies have investigated the effects of valerian extract on sleep quality and anxiety reduction. Valeriana officinalis root extract has also been investigated for its anticonvulsant, antioxidant, and anti-inflammatory properties. In a further embodiment of the present invention, the composition comprises xylitol. Xylitol is a prebiotic moisturizer that supports the microbiome profile of skin. Highly purified xylitol prebiotic provides moisturizing benefit and improves microbiome diversity. Xylitol is included in many oral hygiene products because it works against bacteria and other microorganisms that can cause challenges in the oral cavity.

Studies show that xylitol may possess anti-inflammatory properties. It has been found to reduce the production of inflammatory cytokines and inhibit the activation of certain inflammatory pathways. Xylitol has been investigated for its potential in preventing and treating ear and sinus infections. It has been found to inhibit the growth of bacteria responsible for these infections and can be used as a nasal spray or in chewing gum to help reduce the occurrence of these conditions.

In a preferred embodiment, the composition according to the invention comprises extracts of the herbs: Centella asiatica, Zingiber officinale, and from the family Capsicum selected from the species Capsicum annuum or Capsicum frutescens. In some preferred embodiments, the composition according to the invention comprises extracts of the herbs: Centella asiatica, Zingiber officinale, and from the family Capsicum selected from the species Capsicum annuum or Capsicum frutescens, as well as sodium hyaluronate. In some preferred embodiments, the composition according to the invention comprises extracts of the herbs: Centella asiatica, Zingiber officinale, and from the family Capsicum selected from the species Capsicum annuum or Capsicum frutescens, as well as Sodium Hyaluronate - 40-60 kDa and Sodium Hyaluronate 1000-2500 kDa. In some embodiments, the compositions according to the invention further comprise a lubricant. In some embodiments, the lubricant is glycerine. In a preferred embodiment, the composition according to the invention comprises extracts of the herbs: Centella asiatica, Zingiber officinale, and from the family Capsicum selected from the species Capsicum annuum or Capsicum frutescens, as well as Sodium Hyaluronate - 40-60 kDa and Sodium Hyaluronate 1000-2500 kDa, and glycerine.

In some embodiments of the invention, the composition has a pH value in the range of pH 4-7,5, such as in the range of pH 4, 5-6, 5, e.g., in the range of pH 5-6, such as in the range of pH 5, 5-5,8, such as about pH 5.

In some embodiments of the invention, the composition comprises less than 3% extraction liquid; such as less than 2%; such as less than 1,5%; e.g. less than 1%; such as less than 0,5%; e.g. less than 0,3%; such as less than 0,1%.

The content of the extract obtained from a plant material selected from the family Apiaceae present in the composition may be standardizing from the content of asiatic acid. In an embodiment of the present invention the composition comprises the range of 0, 1-0,4 w/w% asiatic acid.

In some embodiments, the composition according to the invention comprises within the range of 0, 1-0,4 w/w% asiatic acid, such as in the range of 0,1-0, 2 w/w% asiatic acid, e.g., in the range of 0,2-0, 4 w/w% asiatic acid, such as in the range of 0,2-0, 3 w/w% asiatic acid.

The composition may comprise flavonoids, preferably glycosidic bound flavonoids (such as zingiber, asiatic acid; asiaticoside; and/or madegassic acid).

In an embodiment of the present invention the composition comprises in the range of 0-

1.5 w/w% zingiber extract, such as in the range of 0,01 - 1,5 w/w%.

The capsaicin extract is based on chili, red pepper or other plants of the Capsicum family containing the capsaicin compound. In some embodiments, the composition according to the invention comprises in the range of 0-5,0 w/w% capsaicin, such as in the range of 0,5-

4.5 w/w% capsaicin, such as in the range of 0,01-5 w/w% capsaicin extract, e.g., in the range of 1,0-3, 5 w/w% capsaicin, such as in the range of 1,5-2, 5 w/w% capsaicin extract. In some embodiments, the composition according to the invention comprises in the range of 0-0,5 w/w% valerenic acid, such as in the range of 0,1-0, 5 w/w% valerenic acid, e.g., in the range of 0,2-0, 4 w/w% valerenic acid, such as in the range of 0,2-0, 3 w/w% valerenic acid.

In an embodiment of the present invention the composition comprises a higher content of madecassoside than asiatic acid and/or than asiaticoside.

Preferably, the composition comprises a content of madecassoside which between 1,5-10 times higher than the content of asiatic acid on a weight-by-weight basis, such as between

2-5 times higher, e.g., about 3 times higher.

Preferably, the composition comprises a content of madecassoside which between 2-10 times higher than the content of asiaticoside on a weight-by-weight basis, such as between

3-5 times higher, e.g., about 4,5 times higher.

In some embodiments, the composition according to the invention comprises a content of asiatic acid which is between 1,25-5 times higher than the content of asiaticoside on a weight-by-weight basis, such as between 1,5-2, 5 times higher, e.g. about 2 times higher. In some embodiments, the composition according to the invention comprises a preservation agent. Suitable preservation agents may routinely be chosen by the skilled person.

In some embodiments, the composition according to the invention comprises a sorbate compound, such as potassium sorbate as a preservation agent.

In some embodiments, the composition according to the invention comprises a sorbate compound as preservation agent, wherein the sorbate compound is added in a concentration in the range of 0,1-0, 5% (w/w) on a dry-matter basis, such as about 0,2% (w/w) on a dry-matter basis.

In an embodiment of the present invention, the composition comprises valerenic acid in the range of 0-0,5 w/w%.

In a further embodiment of the present invention the composition comprises xylitol in the range of 0-10 w/w%.

In a further embodiment of the present invention the composition comprises in the range of 0, 1-0,4 w/w% asiatic acid and 0-1,5 w/w% zingiber.

In a further embodiment of the present invention the composition comprises in the range of 0, 1-0,4 w/w% asiatic acid; 0-1,5 w/w% zingiber; and 0-5,0 w/w% capsaicin.

In a further embodiment of the present invention the composition comprises in the range of 0, 1-0,4 w/w% asiatic acid; 0-1,5 w/w% zingiber; 0-5,0 w/w% capsaicin; and 0-0,5 w/w% valerenic acid.

In a further embodiment of the present invention the composition comprises in the range of 0, 1-0,4 w/w% asiatic acid; 0-1,5 w/w% zingiber; 0-5,0 w/w% capsaicin; and 0-25 w/w% lubricant, such as glycerine.

In order to improve the taste and odour experience of the product, the composition may comprise a flavouring agent.

The solvents used for providing the extracts according to the present invention may be an aqueous solvent, such as water, or an alcoholic solvent. The alcoholic solvent may be selected from methanol, ethanol, isopropanol, or a mixture hereof.

In an embodiment of the present invention the composition comprises less than 2% alcoholic solvent; such as less than 1,5% alcoholic solvent; e.g., less than 1% alcoholic solvent; such as less than 0,5% alcoholic solvent; e.g., less than 0,3% alcoholic solvent; such as less than 0,1% alcoholic solvent, e.g., no alcoholic solvent.

In a further embodiment according to the present invention comprises an extract obtained from plant material selected from the family Apiaceae in an aqueous solvent.

Preferably, the extract obtained from a plant material selected from the family Apiaceae is a liquid, a juice, a syrup, or a powder. Preferably, the extract obtained from plant material selected from the family Apiaceae is a powder.

In the present context the term "powder" relates to a composition having a moisture content of 15% (w/w) or less, such as a moisture content of 10% (w/w) or less, e.g. a moisture content of 7,5% (w/w) or less, such as a moisture content of 5% or less.

In some embodiments, the composition according to the invention comprises sodium levulinate as a preservation agent in a concentration in the range of 0,1-0, 5% (w/w) on a dry-matter basis, such as about 0,2% (w/w) on a dry-matter basis.

In some embodiments, the composition according to the invention is for use as a medicament. The unique combination of extracts in the compositions of the invention are useful in a variety of treatments of medical conditions, in non-limiting example including those of for use in the prevention, treatment or alleviation of inflammation or swelling in the nose or oral cavity, or for use in the prevention, treatment or alleviation of snoring, obstructive sleep apnea, chronic sinusitis and/or cold in mammals such as in humans.

In some embodiments, the composition according to the invention is for administration to the nose or to the oral cavity or throat.

In some embodiments, the composition according to the invention is for administration to the oral cavity or throat, such as to the mucosa in the oral cavity or throat in the form of anyone of an oral solution, a suspension, an emulsion, a lozenge or troche, a spray, a gel, a mouthwash or gargle, or a tablet or capsule.

In some embodiments, the composition according to the invention is for administration to the nose, such as to the mucosa in the nose, in the form of anyone of a nasal spray, nasal drops, nasal gels, nasal powders, nasal aerosols, nasal patches or films, or nasal implants. In some embodiments, the composition according to the invention is an oral solution, a suspension, an emulsion, a lozenge or troche, a spray, a gel, a mouthwash or gargle, or a tablet or capsule.

In some embodiments, the composition according to the invention is a nasal spray, nasal drops, nasal gels, nasal powders, nasal aerosols, nasal patches or films, or nasal implants. In some embodiments, the composition according to the invention is a nasal and oral cavity composition or formulation for relief of congestion in the nose or oral cavity.

In some embodiments, the composition according to the invention is a nasal or oral cavity or throat composition or formulation in the form of a spray.

Thus, a preferred embodiment of the present invention relates to a nasal spray comprising a composition according to the present invention. The nasal spray may be a decongestant nasal spray.

In an embodiment of the present invention the nasal spray may comprise a capacity in the range of 5-100 ml, such as in the range of 10-75 ml, e.g., in the range of 20-50 ml, such as 30 ml.

In a further embodiment of the present invention the nasal spray may be adjusted to provide 25-300 pl/unit dose; such as 50-200 pl/unit dose; e.g., 75-150 pl/unit dose, such as 100 pl/unit dose.

The composition according to the present invention has shown a contractive effect on the structure of the connective tissue in the soft part of the palate and throat, creating a more open passage in the upper respiratory tract.

In some embodiments, the composition according to the invention is for use in the treatment or alleviation of snoring, obstructive sleep apnea, chronic sinusitis and/or cold in a mammal such as a human, characterised in that the composition comprises the combination of: (i) an extract obtained from plant material from the family Apiaceae

(ii) an extract obtained from plant material from the family Zingiberaceae

(iii) an extract from plant or fruit selected from the families Capsicum annuum or Capsicum frutescens and

(iv) sodium hyaluronate

In some embodiments, the composition according to the invention further comprises an extract from plant material selected from the family Valerianaceae. In some embodiments, the composition according to the invention further comprises xylitol.

In some embodiments according to the previous embodiment, the composition according to the invention is for oral and/or nasal administration.

Furthermore, in some embodiments the composition is for use as a medicament, such as in non-limiting example for preventing, treating, or alleviating swelling of tissues in the nose or oral cavity, or for treating or alleviating snoring, chronic sinusitis, cold, and/or sleep apnea in mammals such as in humans. In some such embodiments, the compositions are for administration in two-unit doses, each in the range of 25-300 pl of the composition. In some embodiments, the composition is for administration in an effective dosage to the nose or oral cavity. In some embodiments, the composition according to the invention is for administration to a mammal such as a human, with a frequency at least 1-2 times a day. In some embodiments, the composition is administered as two-unit doses, each in the range of 50-200 pl such as two unit doses, each in the range of 75-150 pl, such as two unit doses, each of 100 pl.

In some embodiments, the composition is for use in treating or alleviating swelling of tissue in the nose or oral cavity, or for treating or alleviating snoring, cold, chronic sinusitis and/or sleep apnea in mammals such as in humans. In such embodiments the composition may be administered as two-unit doses nasally such as to each nostril and two-unit doses may be orally administered to humans and animals, preferably by administration at least 1-2 times a day.

In some embodiments, the compositions are for use in treating or alleviating swelling of tissues in the nose or oral cavity of subjects using a CPAP machine when sleeping. In such embodiments, the compositions of the invention is for administration in an effective dosage before sleeping, such as once or twice a day, or with such time interval before sleeping to allow the composition to be effective. Subjects suffering from snoring, chronic sinusitis, cold, and/or sleep apnea may use an increased dosage such as an effective dosage of the composition according to the present invention, to treat and/or alleviate the snoring, chronic sinusitis, cold, and/or sleep apnea as described above.

The composition according to the present invention is preferably an aqueous solution such as an aqueous buffer solution. In some such embodiments, the aqueous solution comprises extract obtained from a plant material selected from the family Zingiberaceae. In some embodiments, the composition of the invention further comprises extract obtained from a plant material selected from the family Apiaceae. In some embodiments, the compositions of the invention further comprises extract obtained from a plant from the family Capsicum, and in some embodiments additionally extract obtained from a plant from the family Valerianaceae.

The dry matter content provided in step (i) and/or (ii) during the extraction process may be in the range of 40-70% (w/w); such as in the range of 50-65% (w/w); e.g. about 60% (w/w).

Preferably, the extract obtained from plant material selected from the family Zingiberaceae, comprises the flavonoids, kaempferol and quercetin.

Preferably, the extract obtained from plant material selected from the family Apiaceae comprises madegassic acid, asiaticoside, and/or asiatic acid.

Preferably, the extract obtained from plant or fruit material selected from the family Capsicum, preferably Capsicum annuum or Capsicum frutescens, comprises capsaicin.

Preferably, the extract obtained from plant material selected from the family Valerianaceae comprises valerenic acid.

The method according to the present invention further comprises the step of adding a preservation agent to the mixed composition. Preferably, the preservation agent is a sorbate compound, such as potassium sorbate. In preferred embodiment, the sorbate compound is in the composition to reach a content within the range of 0,1-0, 5% (w/w) on a dry-matter basis, such as about 0,2% (w/w) on a dry-matter basis.

In some embodiments, the extract obtained from a plant material from the family Zingiberaceae is obtained from rhizoma. In some embodiments, the extract of Zingiberaceae is in the form of a liquid, a juice, a paste or in the form of a syrup, preferably in the form of a syrup.

The extract obtained from a plant material selected from the family Apiaceae may be in the form of a dry powder. Such dry powder comprising the Apiaceae extract may subsequently be dissolved in water or in the liquid extract of plant material selected the family Zingiberaceae. In preferred embodiment, the Apiaceae powder is dissolved in Zingiberaceae extract provided in the form of a liquid, a juice, a paste or a syrup.

The extract obtained from plant material selected from the family Capsicum may in some embodiments be in the form of a liquid, a juice or a syrup.

The extract obtained from a plant material selected from the family Valerianaceae may in some embodiments be in the form of a liquid, a juice or a syrup.

In an embodiment of the present invention, water may be added to the extract obtained from plant material selected from the family Zingiberaceae. Preferably Zingiberaceae (step

(a)) to the extract obtained from a plant material selected from the family Apiaceae (step

(b)) or to the mixture provided in step (c), where the extract obtained from a plant material selected from the family Zingiberaceae. Preferably, Zingiberaceae obtained in step (a) are mixed with the extract obtained from plant material from one or more of the plant materials selected from the family Apiaceae, Valerianaceae and/or Capsicum as obtained in step (b), to provide the desired concentration of ingredients.

Results from fibroblast cell culture experiments described in the examples section of this application indicate that the compositions of the invention affect cell morphology leading to less swelling of the fibroblast cells in the cultures. This indicate that the compositions may cause less swelling of fibroblastic tissues in conditions of the nose or oral cavity where such swelling is part of the pathology. Further, experiments wherein the compositions are administered to patients showed improved breathing during sleep due to less swelling of nasal and oral cavity tissues, and further much improvement in sleep quality. Snoring was reduced significantly in the patients receiving daily doses of the composition of the invention.

It should be noted that embodiments and features described in the context of one of the aspects of the present invention also apply to the other aspects of the invention.

The invention will now be described in further details in the following non-limiting examples.

Examples

Example 1 - Preparation of the composition according to the present invention. Reversed osmosis cleaned water was heated to 20 degrees Celsius and pH adjusted with citric acid to 5 +/-0,2.

Add NaCI to reach isotonic solution.

Add sodium hyaluronate, and stir until a homogenous solution appear.

Add Centella asiatica powder, and dissolve under stirring. Add the two extracts of Zingiber officinale Rhizome and Capsicum Annuum fruit extract and stir briefly. Add Glycerine and preservative (Versatil SL). Adjust pH to 5,0 using citric acid (again).

Stir for 10 min and the solution is ready.

The composition was packed in 30 ml nasal spray bottles and ready for use.

Example 2 - Demonstrating the effect of the spray developed in Example 1

25 volunteers 11 males and 14 females suffering from snoring tested the spray.

Each volunteer received a nasal spray bottle as provided in example 1 above. Two unitdosages were administered to each volunteer in each nostril at the beginning of the experimental period before bedtime. The administration was repeated daily for 15 days.

The results showed that all 25 volunteers experienced an improved condition with less snoring and better breathing during sleep during the 15-day test period, and also experienced a better condition and wellbeing after the 15-day test period, relative to the condition before receiving the nasal spray bottle as provided in example 1. The improved breathing was explained as due to less swelling of nasal and oral cavity tissues leading to better airway passage and consequently better breathing during sleep.

Example 3

Tests of plant extract inferred morphology changes

The effect of the composition of example 1 on morphology of fibroblast cell lines

Compound : Plant extract at three concentrations: 0,5x, 0,2x and 0,lx

Cell lines: MRC5 (lung fibroblast) grown in EMEM and 1BR.3.G (skin fibroblast) grown in DMEM

MRC5 were seeded at 2000 cells/well and 1BR.3.G were seeded at 5000 cells/well in 96- well plates

Cells were incubated for 24 hrs before the exposure experiment was performed.

Vehicle: Citric acid at 0,05 g/100 ml water (pH 4,6) Before exposure of cells to the plant extract they were imaged in bright field microscopy (t=0). Subsequently, after 5 and 24 hrs the same wells were imaged again with bright field microscopy.

Using ImageJ-tools (Find Edges+Sharpen+Enhance Contrast), morphology features of the cells in the images were clarified.

Observations during the experiment:

As is evident in the images of the MRC5 cells with 0,5x and 0,2x plant extract, the addition of the extract to the EMEM medium results in precipitation of presumably plant extract components. This is, however, not the case in the 1BR.3.G cultures where another medium (DMEM) has been used. The precipitation in 0,5x MRC5 cultures made it difficult to evaluate the morphology of the cells.

When the plant extract was added to the cell cultures in general, a change in colour of the medium going from red to yellow could be observed, indicating a change in pH. Indeed, when pH was measured in the EMEM+plant extract the pH dropped from 7,5 to 5, and in the DMEM+plant extract the pH dropped from 7 to 6. The plant extract alone had a pH of 4,5, as did the vehicle solution.

Conclusions on tests on plant extract inferred morphology changes:

MRC5 cultures

• This cell line establishes a classical elongated fibrillar cellular morphology that adheres firmly to the surface of the well. This is confirmed in the t=0 images and in the vehicle and medium controls.

• After 5 hrs of the plant extract incubation, a clear reduction in cells with a fibrillar structure and an increase in number of cells with a round structure were observed in the 0,2x treatment compared to the vehicle control. In the 0,lx this effect was not clear.

• After 24 hrs of incubation with the plant extracts, when compared with the effects observed at 5 hrs, were more pronounced, and a slight effect was also seen in the 0,lx samples compared to vehicle. Contraction of the cells could be the cause of the change in morphology in this experiment.

• Vehicle and medium controls appeared identical throughout the experiment indicating that the pH change induced by the plant extract and the citric acid dilution-buffer did not affect the cell morphology.

1BR.3.G cultures

This cell line established a less classical fibroblast cellular morphology compared to MRC5. A higher fraction of cells had a rounded structure in the early phase and when they adhered to the surface of the well, the cellular shape was less well defined, but a clear irregular cytoplasmic shape observed. This was confirmed in the t=0 images and in the vehicle and medium controls. The less well-defined cellular morphology complicates the interpretation of the effect of the plant extract.

• After 5 hrs incubation with the plant extract, no significant difference was observed between treatments and controls.

• After 24 hrs of incubation with the plant extracts, the 0,5x and 0,2x treatments resulted in cells with less expanded cytoplasmic area compared to the vehicle.

• Vehicle and medium controls were identical throughout the experiment indicating that the pH change induced by the plant extract and the citric acid dilution-buffer did not affect cell morphology.

The cell culture experiments indicate that the compositions of the invention affect cell morphology leading to less swelling of the fibroblast cells in the cultures. This indicate that the compositions may cause less swelling of fibroblastic tissues in conditions of the nose or oral cavity where such swelling is part of the pathology.

Example 4

To assess clinical efficiency of the composition according to the present invention, wherein Test batch 000 was delivered as a Nasal Spray, an open acceptance study was performed using Test-Batch 000, produced by Persano.

Test batch 000 comprised extracts of Centella asiatica, Zingiber officinale, Capsicum and sodium hyaluronate, as well as glycerine as lubricant.

The study was conducted as an open acceptance study involving 20 randomly selected every night snores meeting the following inclusion criteria: a BMI of less than 30, age range of 35-55 years (average 45 years), no documented history of sleep apnea or allergies, and a self-reported history of snoring. Participants were provided with instructions on the proper application of the nasal spray and were directed to administer two squirts into each nostril every evening before bedtime. Following a two-week intervention period, all participants and their bedpartners completed a standardized questionnaire to assess outcomes.

In total 20 individuals participated in the study. Of these 60% reported less snoring and 65% reported an improved sleep (table 1). Snoring did not disappear completely but was reduced.

Table 1 : Results from the two-week intervention period based on self-assessment.

Example 5

Separate from the clinical experiment in example x, collection of user reported outcomes showed promising results, from a group of individuals that had not undergone any selection with regard to BMI, sleep apnea or other possible selection criteria.

In total 11 individuals reported outcomes, all reported one or more of better sleep, or feeling of being refreshed, or improvements in perceived mucus surface dryness.

These reports were not via a questionnaire with leading questions, but rather by individual stories.

Table 2: User reported outcomes from users mentioning specifically

Example 6

Based upon the encouraging results of the experiments of examples 3, 4 and 5, an experiment for testing potential effects of various compositions in enhancing tissue tonus in the nasal and oral cavities was designed. Endpoints included detecting reduction of tissue inflammation associated swelling and enhancing mucosal membrane health.

The following compounds were selected for further examination

Two versions of sodium hyaluronate was tested : Sodium Hyaluronate - 40-60 kDA and Sodium Hyaluronate >2000 kDa.

Test versions of sprays with variable amounts of each compound and combinations of compounds were created. Sodium was added to create an isotonic solution, and an appropriate compound to adjust pH to a range of 4-7,5 included, as was a preservative to ensure an appropriate shelf-life for the spray.

Test subjects were recruited, results are not yet available, but will later be available by way of user reported outcomes and structured questionnaires. Embodiments

1. A composition comprising the combination of:

(i) an extract obtained from plant material selected from the family Apiaceae

(iv) a lubricant

2. The composition according to embodiment 1, wherein the lubricant is glycerine.

3. The composition according to embodiment 1 or 2, wherein the composition further comprises sodium hyaluronate.

4. The composition according to any of embodiments 1 - 3, wherein the sodium hyaluronate comprise Sodium Hyaluronate - 40-60 kDa and/or Sodium Hyaluronate 1000- 2500 kDa.

5. The composition according to anyone of the preceding embodiments, wherein the plant material selected from the family Apiaceae comprises a plant material extracted from the species Centella asiatica.

6. The composition according to anyone of the preceding embodiments, wherein the plant material selected from the family Zingiberaceae comprises a plant material extracted from the species Zingiber officinale.

7. The composition according to anyone of the preceding embodiments, wherein the plant material selected from Capsicum is a fruit extract from the species Capsicum annuum or Capsicum frutescens. 8. The composition according to anyone of the preceding embodiments, wherein the composition comprises the combination of:

(i) an extract obtained from plant material selected from the family Apiaceae of the species Centella asiatica,

(ii) an extract obtained from plant material selected from the family Zingiberaceae of the species Zingiber officinale,

(iii) an extract from plant or fruit from the family Capsicum selected from the species Capsicum annuum or Capsicum frutescens, and

(iv) sodium hyaluronate

9. The composition according to anyone of the preceding embodiments, wherein the composition comprises the combination of:

(iv) sodium hyaluronate wherein the sodium hyaluronate comprise Sodium Hyaluronate - 40-60 kDa and/or Sodium Hyaluronate 1000-2500 kDa

10. The composition according to anyone of the preceding embodiments, wherein the composition comprises the combination of:

(ii) an extract obtained from plant material selected from the family Zingiberaceae of the species Zingiber officinale, (Hi) an extract from plant or fruit from the family Capsicum selected from the species Capsicum annuum or Capsicum frutescens.

(iv) sodium hyaluronate, wherein the sodium hyaluronate comprise Sodium Hyaluronate - 40-60 kDa and/or Sodium Hyaluronate 1000-2500 kDa and

(v) a lubricant

11. The composition according to anyone of the preceding embodiments, wherein the composition comprises the combination of:

(iii) an extract from plant or fruit from the family Capsicum selected from the species Capsicum annuum or Capsicum frutescens.

(v) a lubricant which is glycerine

14. The composition according to any one of the previous embodiments, for use as a medicament.

15. The composition according to any one of the previous embodiments, wherein the composition is for use in the prevention, treatment or alleviation of inflammation or swelling in the nose or oral cavity.

16. The composition or formulation according to anyone of the preceding embodiments, wherein the composition is for prevention or relief of congestion in the nose or oral cavity.

17. The composition according to any one of the previous embodiments, wherein the composition is for use in the prevention, treatment or alleviation of snoring, obstructive sleep apnea, chronic sinusitis and/or cold in mammals such as in humans. 18. The composition according to any one of the previous embodiments, wherein the composition is for administration to the nose or to the oral cavity or throat.

19. The composition according to embodiment 18, wherein the composition is for administration to the oral cavity or throat, such as to the mucosa in the oral cavity or throat in the form of anyone of an oral solution, a suspension, an emulsion, a lozenge or troche, a spray, a gel, a mouthwash or gargle, or a tablet or capsule.

20. The composition according to embodiment 18, wherein the composition is for administration to the nose, such as to the mucosa in the nose, in the form of anyone of a nasal spray, nasal drops, nasal gels, nasal powders, nasal aerosols, nasal patches or films, or nasal implants comprising the composition according to anyone of embodiments 1-18.

21. An oral solution, a suspension, an emulsion, a lozenge or troche, a spray, a gel, a mouthwash or gargle, or a tablet or capsule comprising a composition according to anyone of embodiments 1-18.

21. A nasal spray, nasal drops, nasal gels, nasal powders, nasal aerosols, nasal patches or films, or nasal implants comprising the composition according to anyone of embodiments 1-18.

22. The nasal or oral cavity or throat composition or formulation according to anyone of embodiments 18-21, wherein the composition or formulation is a spray.

23. A composition formulated as a nasal spray comprising the combination of:

(v) a lubricant which is glycerine wherein the composition is for use in the prevention, treatment or alleviation of inflammation or swelling in the nose or oral cavity.

24. A composition formulated as a nasal spray comprising the combination of:

(v) a lubricant which is glycerine wherein the composition is for use in prevention or relief of congestion in the nose or oral cavity.

25. A composition formulated as a nasal spray comprising the combination of:

(v) a lubricant which is glycerine wherein the composition is for use in the prevention, treatment or alleviation of snoring, obstructive sleep apnea, chronic sinusitis and/or cold in mammals such as in humans. 26. The composition according to anyone of the preceding embodiments, wherein the composition further comprises vitamins A, D, E, K, B and C and minerals Ca, Mg, Se and Zn and glycerine.

27. The composition according to anyone of the preceding embodiments, wherein the composition has a pH value in the range of pH 4-7,5, such as in the range of pH 4, 5-6, 5, e.g., in the range of pH 5-6, such as in the range of pH 5, 5-5,8.

28. The composition according to anyone of the preceding embodiments, wherein the composition comprises less than 3% extraction liquid; such as less than 2%; such as less than 1,5%; e.g. less than 1%; such as less than 0,5%; e.g. less than 0,3%; such as less than 0,1%.

29. The composition according to anyone of the preceding embodiments, wherein the composition comprises within the range of 0, 1-0,4 w/w% asiatic acid, such as in the range of 0, 1-0,2 w/w% asiatic acid, e.g., in the range of 0,2-0, 4 w/w% asiatic acid, such as in the range of 0.2-0, 3 w/w% asiatic acid.

30. The composition according to anyone of the preceding embodiments, wherein the composition comprises within the range of 0-1,5 w/w% zingiber extract, such as in the range of 0,01-1,5 w/w% zingiber extract or powder.

31. The composition according to anyone of the preceding embodiments, wherein the composition comprises in the range of 0-5,0 w/w% capsaicin, such as in the range of 0,01- 5 w/w%, such as in the range of 0,5-4, 5 w/w% capsaicin, e.g., in the range of 1,0-3, 5 w/w% capsaicin, such as in the range of 1,5-2, 5 w/w% capsaicin.

32. The composition according to anyone of the preceding embodiments, wherein the composition comprises in the range of 0-0,5 w/w% valerenic acid, such as in the range of 0,1-0, 5 w/w% valerenic acid, e.g., in the range of 0,2-0, 4 w/w% valerenic acid, such as in the range of 0,2-0, 3 w/w% valerenic acid.

33. The composition according to anyone of the preceding embodiments, wherein the composition comprises a content of asiatic acid which is between 1,25-5 times higher than the content of asiaticoside on a weight-by-weight basis, such as between 1,5-2, 5 times higher, e.g. 2 times higher.

34. The composition according to anyone of the preceding embodiments wherein the composition comprises a preservation agent. 35. The composition according to embodiment 34, wherein the preservation agent is a sorbate compound, such as potassium sorbate.

36. The composition according to embodiment 35, wherein the sorbate compound is added in a concentration in the range of 0,1-0, 5% (w/w) on a dry-matter basis, such as about 0,2% (w/w) on a dry-matter basis.

37. The composition according to embodiment 34, wherein the preservation agent is sodium levulinate in a concentration in the range of 0,1-0, 5% (w/w) on a dry-matter basis, such as about 0,2% (w/w) on a dry-matter basis.

38. The composition according to any one of the preceding embodiments, wherein the composition is for use in the treatment or alleviation of inflammation or swelling in the nose or oral cavity.

39. The composition according to any one of the preceding embodiments, wherein the composition is for use in the treatment or alleviation of snoring, obstructive sleep apnea, chronic sinusitis and/or cold in mammals such as in humans.

40. The composition according to anyone of the preceding embodiments, wherein the composition is for administration to the nose or to the oral cavity or throat.

41. The composition according to the preceding embodiment, wherein the composition is for administration to the oral cavity or throat, such as to the mucosa in the oral cavity or throat in the form of anyone of an oral solution, a suspension, an emulsion, a lozenge or troche, a spray, a gel, a mouthwash or gargle, or a tablet or capsule.

42. The composition according to embodiment 40, wherein the composition is for administration to the nose, such as to the mucosa in the nose, in the form of anyone of a nasal spray, nasal drops, nasal gels, nasal powders, nasal aerosols, nasal patches or films, or nasal implants comprising the composition according to anyone of embodiments 1-23.

43. An oral solution, a suspension, an emulsion, a lozenge or troche, a spray, a gel, a mouthwash or gargle, or a tablet or capsule comprising a composition according to anyone of the preceding embodiments. 44. A nasal spray, nasal drops, nasal gels, nasal powders, nasal aerosols, nasal patches or films, or nasal implants comprising the composition according to anyone of the preceding embodiments. 45. The nasal and oral cavity composition or formulation according to anyone of embodiments 40-44, wherein the composition is for relief of congestion in the nose or oral cavity.

46. The nasal or oral cavity or throat composition or formulation according to anyone of embodiments 40-45, wherein the composition or formulation is a spray.

Claims

1. A composition comprising the combination of:

(v) an extract obtained from plant material selected from the family Apiaceae

(vii) an extract from plant or fruit selected from the family Capsicum and

(viii) a lubricant

2. The composition according to claim 1, wherein the lubricant is glycerine.

3. The composition according to claim 1 or 2, wherein the composition further comprises sodium hyaluronate.

4. The composition according to any of claims 1 - 3, wherein the sodium hyaluronate comprise Sodium Hyaluronate - 40-60 kDa and/or Sodium Hyaluronate 1000-2500 kDa.

5. The composition according to anyone of the preceding claims, wherein the plant material selected from the family Apiaceae comprises a plant material extracted from the species Centella asiatica.

6. The composition according to anyone of the preceding claims, wherein the plant material selected from the family Zingiberaceae comprises a plant material extracted from the species Zingiber officinale.

7. The composition according to anyone of the preceding claims, wherein the plant material selected from Capsicum is a fruit extract from the species Capsicum annuum or Capsicum frutescens.

8. The composition according to anyone of the preceding claims, wherein the composition comprises the combination of: (v) an extract obtained from plant material selected from the family Apiaceae of the species Centella asiatica,

(vi) an extract obtained from plant material selected from the family Zingiberaceae of the species Zingiber officinale,

(vii) an extract from plant or fruit from the family Capsicum selected from the species Capsicum annuum or Capsicum frutescens, and

(viii) sodium hyaluronate

9. The composition according to anyone of the preceding claims, wherein the composition comprises the combination of:

(v) an extract obtained from plant material selected from the family Apiaceae of the species Centella asiatica,

(viii) sodium hyaluronate wherein the sodium hyaluronate comprise Sodium Hyaluronate - 40-60 kDa and/or

Sodium Hyaluronate 1000-2500 kDa

10. The composition according to anyone of the preceding claims, wherein the composition comprises the combination of:

(vi) an extract obtained from plant material selected from the family Apiaceae of the species Centella asiatica,

(vii) an extract obtained from plant material selected from the family Zingiberaceae of the species Zingiber officinale,

(viii) an extract from plant or fruit from the family Capsicum selected from the species Capsicum annuum or Capsicum frutescens. (ix) sodium hyaluronate, wherein the sodium hyaluronate comprise Sodium Hyaluronate - 40-60 kDa and/or Sodium Hyaluronate 1000-2500 kDa and

(x) a lubricant

11. The composition according to anyone of the preceding claims, wherein the composition comprises the combination of:

(viii) an extract from plant or fruit from the family Capsicum selected from the species Capsicum annuum or Capsicum frutescens.

(ix) sodium hyaluronate, wherein the sodium hyaluronate comprise Sodium Hyaluronate - 40-60 kDa and/or Sodium Hyaluronate 1000-2500 kDa and

(x) a lubricant which is glycerine

12. The composition according to any one of the previous claims, for use as a medicament.

13. The composition according to any one of the previous claims, wherein the composition is for use in the prevention, treatment or alleviation of inflammation or swelling in the nose or oral cavity.

14. The composition or formulation according to anyone of the preceding claims, wherein the composition is for prevention or relief of congestion in the nose or oral cavity.

15. The composition according to any one of the previous claims, wherein the composition is for use in the prevention, treatment or alleviation of snoring, obstructive sleep apnea, chronic sinusitis and/or cold in mammals such as in humans.

16. The composition according to any one of the previous claims, wherein the composition is for administration to the nose or to the oral cavity or throat.

17. The composition according to claim 15, wherein the composition is for administration to the oral cavity or throat, such as to the mucosa in the oral cavity or throat in the form of anyone of an oral solution, a suspension, an emulsion, a lozenge or troche, a spray, a gel, a mouthwash or gargle, or a tablet or capsule.

18. The composition according to claim 15, wherein the composition is for administration to the nose, such as to the mucosa in the nose, in the form of anyone of a nasal spray, nasal drops, nasal gels, nasal powders, nasal aerosols, nasal patches or films, or nasal implants comprising the composition according to anyone of claims 1-15.

19. An oral solution, a suspension, an emulsion, a lozenge or troche, a spray, a gel, a mouthwash or gargle, or a tablet or capsule comprising a composition according to anyone of claims 1-15.

20. A nasal spray, nasal drops, nasal gels, nasal powders, nasal aerosols, nasal patches or films, nasal wash or nasal implants comprising the composition according to anyone of claims 1-15.

21. The nasal or oral cavity or throat composition or formulation according to anyone of claims 16-20, wherein the composition or formulation is a spray.

22. A composition formulated as a nasal spray comprising the combination of:

(x) a lubricant which is glycerine wherein the composition is for use in the prevention, treatment or alleviation of inflammation or swelling in the nose or oral cavity.

23. A composition formulated as a nasal spray comprising the combination of:

(x) a lubricant which is glycerine wherein the composition is for use in prevention or relief of congestion in the nose or oral cavity.

24. A composition formulated as a nasal spray comprising the combination of:

(x) a lubricant which is glycerine wherein the composition is for use in the prevention, treatment or alleviation of snoring, obstructive sleep apnea, chronic sinusitis and/or cold in mammals such as in humans.