EP-4736863-A1 - NOVEL MENTHOL-EUCALYPTUS OIL ANTITUSSIVE SPRAY AND USE THEREOF

EP4736863A1EP 4736863 A1EP4736863 A1EP 4736863A1EP-4736863-A1

Abstract

Provided is a novel menthol-eucalyptus oil antitussive spray and use thereof in preparation of a drug for treating coughs. The novel menthol-eucalyptus oil antitussive spray includes two natural botanicals, namely, menthol and eucalyptus oil, as active ingredients that work synergistically, and does not contain alcohol. The novel menthol-eucalyptus oil antitussive spray is directly administered to a respiratory tract in a form of spray, and has advantages of low dosage, rapid pharmaceutical action, and great safety.

Inventors

LI, Guanhan

Assignees

Sino-Shine Biopharmaceutical Co., Ltd

Dates

Publication Date: 20260506
Application Date: 20240626

Claims (16)

A novel menthol-eucalyptus oil antitussive spray, comprising active ingredients of menthol and a second active ingredient, the second active ingredient being eucalyptus oil or eucalyptol; in the novel menthol-eucalyptus oil antitussive spray, a concentration of menthol is in a range from 0.01% to 20% with a weight-to-volume ratio (w/v) and the second active ingredient is in a concentration from 0.01% to 20% with a volume ratio (v/v); and the novel menthol-eucalyptus oil antitussive spray is an oil-in-water emulsion, and further comprises: an oil phase, in which includes at least one selected from but not limited to at least one selected from olive oil, soybean oil, corn oil, avocado oil, tea seed oil, sunflower seed oil, peanut oil, sesame oil, and refined rapeseed oil; and an emulsifier, which includes at least one selected from but not limited to lecithin, phospholipid, gelatin, gum Arabic, tragacanth, sorbitan fatty acid ester, polysorbate, Pluronic F-68, polyoxyethylene fatty acid ester, polyoxyethylene fatty acid alcohol ether, and a polyoxyethylene-polyoxypropylene copolymer.
The novel menthol-eucalyptus oil antitussive spray as claimed in claim 1, wherein in the novel menthol-eucalyptus oil antitussive spray, the w/v concentration of the menthol is in a range of 0.25% to 1%, and the v/v concentration of the second active ingredient is in a range of 0.05% to 0.15%; alternatively, in the novel menthol-eucalyptus oil antitussive spray, the w/v concentration of the menthol is in a range of 1% to 3%, and the v/v concentration of the second active ingredient is in a range of 2.5% to 5%.
The novel menthol-eucalyptus oil antitussive spray as claimed in claim 1 or 2, further comprises but is not limited to at least one of: a co-emulsifier, wherein the co-emulsifier is at least one selected but not limited from the group consisting of Tween, methylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, sodium alginate, tragacanth, gum Arabic, cetyl alcohol, glyceryl monostearate, stearic acid, stearyl alcohol, cholic acid, cholate, oleic acid, and oleate; an antioxidant, wherein the antioxidant is at least one selected from but not limited to the group consisting of vitamin E, sulfite, pyrosulfite, sodium thiosulfate, methionine, glutathione, ascorbic acid, ascorbyl palmitate, thiourea, propyl gallate, tert-butyl-4-hydroxyanisole, and di-tert-butyl-p-cresol; a preservative, wherein the preservative is at least one selected from but not limited to the group consisting of sorbic acid and a salt thereof, and benzoic acid and a salt thereof; and a flavoring agent, wherein the flavoring agent is at least one selected from but not limited to the group consisting of sugar, maltitol, a non-sugar sweetener, and a fruit flavoring agent.
The novel menthol-eucalyptus oil antitussive spray as claimed in claim 3, wherein the sugar comprises at least one selected from but not limited to the group consisting of sucrose, glucose, fructose, and an isomerized sugar; or the non-sugar sweetener comprises but is not limited to at least one selected from but not limited to the group consisting of a natural sweetener and an artificial sweetener; the natural sweetener comprises at least one selected from but not limited to the group consisting of Glycyrrhiza uralensis, Stevia rebaudiana, and Siraitia grosvenorii; and the artificial sweetener comprises at least one selected from but not limited to the group consisting of saccharin sodium, sodium cyclamate, and acesulfame.
The novel menthol-eucalyptus oil antitussive spray as claimed in claim 3, wherein the sugar comprises one selected from but not limited to the group consisting of sucrose, glucose, fructose, and an isomerized sugar; the non-sugar sweetener comprises one selected from but not limited to the group consisting of a natural sweetener and an artificial sweetener; the natural sweetener comprises one selected from but not limited to the group consisting of Glycyrrhiza uralensis, Stevia rebaudiana, and Siraitia grosvenorii; and the artificial sweetener comprises one selected from but not limited to the group consisting of saccharin sodium, sodium cyclamate, and acesulfame.
The novel menthol-eucalyptus oil antitussive spray as claimed in claim 3, wherein the sugar is at least one selected from the group consisting of sucrose, glucose, fructose, and an isomerized sugar; the non-sugar sweetener is at least one selected from the group consisting of a natural sweetener and an artificial sweetener; the natural sweetener is at least one selected from the group consisting of Glycyrrhiza uralensis, Stevia rebaudiana, and Siraitia grosvenorii; and the artificial sweetener is at least one selected from the group consisting of saccharin sodium, sodium cyclamate, acesulfame, and aspartame.
The novel menthol-eucalyptus oil antitussive spray as claimed in claim 3, wherein the fruit flavoring agent comprises at least one selected from the group consisting of a natural fruit flavoring agent and an artificial fruit flavoring agent; the natural fruit flavoring agent comprises at least one selected from but not limited to the group consisting of strawberry, blueberry, blackberry, sweet orange, tangerine, grapefruit, lemon, grape, apple, ananas, passion fruit, mango, banana, lychee, longan, pear, plum, watermelon, chestnut, jujube, and hawthorn.
The novel menthol-eucalyptus oil antitussive spray as claimed in claim 3, further comprises but is not limited to other Chinese medicinal ingredients and Western medicinal ingredients with antitussive and/or expectorant activities, wherein the other Chinese medicinal ingredients and Western medicinal ingredients with antitussive and/or expectorant activities comprises and is not limited to at least one selected from the group consisting of: dextromethorphan, carbocisteine, ambroxol, bromhexine, loquat, Rhizoma Pinelliae, Fritillaria, Radix Platycodi, snow pear, Radix Ophiopogonis, Bulbus Lilii, almond, Fructus Trichosanthis, Cortex Mori, Rhizoma Anemarrhenae, and Radix Stemonae.
The use of the novel menthol-eucalyptus oil antitussive spray as claimed in any one of claims 1 to 8 in manufacture of a drug or a preparation for treating various types of coughs, asthma, upper respiratory tract infection, pharyngitis, or rhinitis.
The use of the novel menthol-eucalyptus oil antitussive spray as claimed in any one of claims 1 to 8 in manufacture of an oral hygiene preparation.
The use as claimed in claim 9, wherein the coughs comprise a cough related to inflammation caused by infections of a pathogen.
The use as claimed in claim 9, 10, or 11, wherein the novel menthol-eucalyptus oil antitussive spray is topically administered via respiratory tract.
The use of any one of menthol, eucalyptus oil, and eucalyptol as a principal active ingredient in manufacture of a drug or a preparation for treating various types of coughs, asthma, upper respiratory tract infection, pharyngitis, and rhinitis.
The euse of any one of menthol, eucalyptus oil, and eucalyptol as a principal active ingredient in manufacture of an oral hygiene preparation.
The use of eucalyptus oil or eucalyptol in combination with menthol in manufacture of a drug or a preparation for treating various types of coughs, asthma, upper respiratory tract infection, pharyngitis, and rhinitis, wherein the preparation contains or does not contain any other active ingredients than eucalyptol and menthol.
The use of eucalyptus oil or eucalyptol in combination with menthol in manufacture of an oral hygiene preparation, wherein the oral hygiene preparation contains or does not contain any other active ingredients than eucalyptol and menthol.

Description

The present application claims priority to Chinese Patent Application No. CN202310803538.5 filed to the China National Intellectual Property Administration (CNIPA) on June 30, 2023, and entitled "NOVEL MENTHOL-EUCALYPTUS OIL ANTITUSSIVE SPRAY AND USE THEREOF", which is incorporated herein by reference in its entirety. TECHNICAL FIELD The present disclosure pertains to the fields of pharmaceutics and therapeutics for respiratory diseases, specifically providing a novel menthol-eucalyptus oil antitussive spray and its use thereof. BACKGROUND Menthol, also known as L-1-methyl-4-isopropylcyclohexan-3-ol, is produced or extracted from the fresh stems and leaves of Lamiaceae plant Mentha haplocalyx Briq through distillation, lyophilization, and recrystallization. Menthol is widely used in pharmaceuticals, health, food, cosmetic and other fields. For example, menthol can be used as a flavoring agent in beverages, candies, toothpastes, perfumes, foods, etc. In medicine, menthol is usually used for cooling, relieving itches and pain on the skin or mucous membrane, treating headache, neuralgia, or inflammation from nose, pharynx, and throat. It can also be taken orally as a carminative in traditional Chinese medicine. In pharmacology, menthol has effects such as cooling, itch relief, analgesia, antisepsis, and anesthesia, and shows modest antibacterial and antiviral effects. The cooling effect of menthol is triggered through a cold sensing receptor, transient receptor potential melastatin (TRPM) 8[1], a member of the transient receptor potential (TRP) channels family. Activation of TRPM8 by cooling compounds, such as menthol, leads to membrane potential depolarization and Ca2+ ion influx, further opening the signaling channel. TRPM8 is expressed in the cold-responsive sensory neurons of dorsal root ganglia and trigeminal nerve. Menthol and cold stimulation can be conducted via the afferent vagus nerve of the lung, bronchi and trachea. Expression levels of TRPM8 vary in the mesenteric vagal ganglia, stomach, vascular smooth muscle, liver, and bladder epithelium[1, 2]. Another TRP family member, TRPV1, is a capsaicin receptor mainly expressed in sensory nerves. TRPV1-positive nerves innervate the entire respiratory tract, including the upper respiratory tract (nose, larynx, and trachea) and lung parenchyma (alveoli, smooth muscle, and blood vessels). TRPV1 agonists, such as capsaicin and citrate, can evoke coughs in humans and guinea pigs. The animal experiments of the present disclosure and other studies show that capsaicin or citric acid-evoked coughs can be significantly suppressed by menthol[3, 4]. Although the mechanism of antitussive effect by menthol is not exactly known, it is probably achieved by elevating the threshold of capsaicin or citric acid-inducing coughs. The antitussive effect of menthol has also been well verified in human clinical trials (including adults and children)[5-9]. Opposite to antitussive effect, menthol can stimulate swallowing, thereby eliminating the concerns regarding an anesthetic effect on the laryngopharynx. In addition, studies also shows that menthol has an expectorant effect. The antitussive effect of menthol is not recorded in the Chinese Pharmacopoeia, but it is used in a variety of antitussive preparations of traditional Chinese medicine as an assistant component or oral hygiene formulations. In United States, menthol is used in over-the-counter cough drops (e.g., Halls Cough Drops, Ricola Natural Herb Cough Drops, Honees Cough Drops, and CVS Cough Drops) and syrups (e.g., NatraBio Adult Cough Syrup). Eucalyptus oil, a volatile oil, is made by distillation from Eucalyptus globulus Labill in the Myrtaceae family, Cinnamomum camphora (L.) Sieb in the Lauraceae family, or other plants of these two families. According to the Chinese Pharmacopoeia, eucalyptus oil is required to contain not less than 70.0% (g/g) of eucalyptol or 1,8-cineol. In traditional Chinese medicine, eucalyptus oil is believed to possess the effect of dispelling chill and relieving pain, and is used to treat itches and neuralgia. In Western countries, eucalyptus oil is also used for treating upper respiratory tract infections, coughs, bronchitis and other conditions. Eucalyptol, a major component of the eucalyptus oil, has been proven to have anti-inflammatory and antitussive effects in clinical trials[10-12]. DETAILED DESCRIPTION OF THE INVENTION The present disclosure provides a novel antitussive spray based on menthol and eucalyptus oil, featuring an additive or synergistical antitussive effect by incorporating two drugs in one preparation. It exerts a rapid action to directly suppress coughs through a non-traditional, topical administration on the mucosa of respiratory tract. Currently, there are no actual cough suppressant sprays on the market. Some so-called "cough suppressant sprays" available online are essentially traditional Chinese medicine preparations exclusively for treating pharyngitis, without