Patent Application
20210069277
The present invention generally relates to phytosanitary and/or pharmaceutical compositions and methods for the prevention and/or treatment of nail infections. In particular, the phytosanitary and/or pharmaceutical compositions are herbal compositions and the nail infections are fungal and bacterial infections.
The plant cuticle is composed of three distinct substances (i.e., waxes, cutin, and pectin) that typically act as barriers against the entry of many compounds into plant tissues. Certain chemical adjuvants (such as penetration enhancing components) can directly modify leaf waxes and increase film tension of the leaf surface in order to enhance cuticular permeability. Foliar spray of adjuvants onto plants has been associated with effective fungicidal activity.
Aqueous type pesticides have a short history. The pesticide water solubility was overcome by the 1970s and water is now used as a carrier. Previous pesticide formulations were not formulated to use water as their carrier. The waxy surfaces of many insects, fungi, and plants make it difficult for most water-based spray solutions to penetrate their target. To overcome this barrier, adjuvants were developed. Adjuvants are ingredients added to a spray tank to enhance the pesticide's activity, such as surfactants, spreader stickers, crop oils, antifoaming materials, buffering agents, and compatibility agents.
Surfactants are adjuvants that facilitate and accentuate the emulsifying, dispersing, spreading, wetting, or other surface modifying properties of liquids. It is recognized that without an adjuvant, 30-50% reduction in efficacy occurs.
Several types of formulations exist to try to deliver the active agents across the cuticle:
There is a need for a new phytosanitary compositions for treating plant infections allowing a better penetration in the plant to treat the infection while minimizing or avoiding the use of chemical pesticides that can be damageable for the environment.
The conventional approach used is to design formulations that will penetrate through the nail plate to deliver the antifungal or antibacterial agent to the site of infection. Conventional treatments are administered for 6 to 12 months to patients but fail because the fungus or its spores remain ‘hidden’ within the nail tissue including the nail root.
Alternative medicine practitioners may treat fungal or bacterial infections of the nails using thymol dissolved in alcohol. This formulation is applied once or twice daily to the affected area. Other plant-based formulations includes the use of creams or ointments or tinctures (alcoholic) containing Tea tree oil and or thymol.
For the treatment of onychomycosis, penetration of the topical antifungal agent through the nail plate from the surface of the nail and diffusion of the antifungal drug through the nail bed is the basis of the past and current medical treatment. Oral administration of antifungal agents is rarely used because of the systemic toxicity of the antifungal drugs and the dose levels required to achieve effective dosages at the site of infection. The medical practice may include the combination of an antifungal with topical urea; where the urea is used to degrade protein (keratin protein is part of the composition/structure of the nail) and enhance the penetration of the antifungal agent.
The medical literature defines onychomycosis as a progressive fungal infection of the nails and if left untreated may cause destruction and deformity of the nail. It is primarily caused by dermatophytes, particularly Trichophyton rubrum and Trichophyton mentagrophytes (Ghannoum M. A. et al., J Am Acad Dermatol 2000; Vol. 43, Number 3: 641-648). Today, both oral drugs (e.g. terbinafine and itraconazole) and topical drugs (e.g. ciclopirox, amorolfine, efinaconazole, and tavaborole) are available for the treatment of fungal nail infection. Unfortunately, these agents can cause systemic toxicity, such as liver toxicity, as well as cause drug-drug interactions. The efficacy of topical formulations has been demonstrated in clinical trials to be relatively low and this poor efficacy is associated to poor nail penetration/permeability and high binding to keratin protein. Additionally, the recently approved topical drugs efinaconazole and tavaborole have low efficacy and local side effects issues. According to current scientific state of the art (see Tabata Y. et al., Antimicrob Agents Chemother. 2015 Dec. 7; 60(2):1035-9), in order to be effective against onychomycosis, a topical antifungal should have low molecular weight and low affinity to keratin protein. The low molecular weight is considered an important factor for penetration of the nail.
Traditional and modern scientific art has only resulted in very low efficacy against what is clinical defined as mild-to-moderate onychomycosis despite the use of relatively small molecules to attempt to penetrate through the nail plate. Scientists have used methods such as applying urea (as part of the formulation) to limit binding to the keratin in the nail and hence increase penetration. Other formulations, such as PenlacTM, use a lacquer formulation to help increase penetration. Other methods include grinding the nail surface to increase penetration. Unfortunately, both old and modern pharmaceutical and natural agents (such as thymol and tea tree oil) have failed to significantly treat mild-to-moderate nail infections and completely failed to treat severe nail infections. For instance, recently approved drug JubliaTM boasts a 17% efficacy (versus 3% for placebo) in mild-to-moderate onychomycosis and there is no approved drug or natural agent for the treatment of severe infections.
There is a need for a new pharmaceutical compositions for treating nail or skin infections allowing a better nail or skin penetration while minimizing or avoiding side effects.
It has been discovered that the same herbal composition can be useful for treating either plant infections or for treating nail infections.
The shortcomings of the prior art are generally mitigated by highly effective compositions for the prevention or treatment of foliar or root fungal and bacterial infections; or for the treatment of nail infections as disclosed herein.
The invention is first directed to a pharmaceutical and/or phytosanitary composition comprising an aqueous extract of Chelidonium majus root and an acceptable pharmaceutical or phytosanitary excipient, for the prevention or treatment of plant infections and/or for the prevention or treatment of nail infections.
According to a preferred embodiment, the composition may further comprise from about 1 to 5% of at least one natural phenolic compound. Preferably, the at least one natural phenolic compound may comprise phenolic acids, thymol, carvacrol, eugenol, crassinervic acid, aduncumene, hostmaniane, gaudichaudanic acid, flavonoids, tannins, stilbenes, curcuminois, coumarins, ligans, quinines, or mixture thereof.
According to a preferred embodiment, the composition may further comprise an aqueous extract of Thuja occidentalis leaf.
According to a preferred embodiment, the composition may further comprise a film-forming surfactant, such as but not limited to film-forming surfactant comprising a polysorbate-type nonioninc surfactant.
According to a preferred embodiment, the composition may further comprise additives selected form the group consisting of penetrants, thickeners, emulsifiers, spreader, stickers, crop oils, inorganic oils, alkyl polyglucosides, and organosilicate surfactants.
According to a preferred embodiment, the composition may further comprise an antifungal compound. Preferably, the antifungal compound is selected from the group consisting of amphotericin B, terbinafine, tavaborole, ciclopirox, griseofulvin, an azole antifungal, an echinocandins, and flucytosine. More preferably, the azole antifungal is ketoconazole, fluconazole, itraconazole, posaconazole, voriconazole, or efinaconazole; and the echinocandin is anidulafungin, caspofungin, or micafungin.
According to a preferred embodiment, the composition may further comprise an antibacterial compound. Preferably, the antibacterial compound comprises beta-lactam antibiotics, macrolide antibiotics, lincosamides, streptogramins, aminoglycosides, quinolones, sulfonamides, tetracyclines, chloramphenicol, metronidazole, tinidazole, nitrofurantoin, glycopeptides, lipoglycopeptides, oxazolidinones, rifamycins, polypetides and tuberactinomycins or mixtures thereof.
According to a preferred embodiment, the aqueous extract of Chelidonium majus root is a 10:1 ethanol-water extract of the Chelidonium majus root, with 10 being the amount of Chelidonium majus root and 1 being the amount of ethanol-water.
The invention is also directed to a phytosanitary composition for treating plant infection, comprising:
The invention is also directed to a pharmaceutical composition for treating nail infection, comprising:
According to a preferred embodiment, the pharmaceutical composition may comprise:
The invention is also directed to the use se of a pharmaceutical or phytosanitary composition as defined herein, for the prevention or treatment of plant infection or for the prevention or treatment of nail infection.
The invention is also directed to a method for the prevention and treatment of plant bacterial and fungus infections, comprising the step of applying at least once, a composition as defined herein on the plant.
The invention is also directed a method for the prevention and treatment of nail infections, comprising the steps of:
The present invention is a highly effective phytosanitary or pharmaceutical composition for the prevention or treatment of fungal and bacterial infections on plants or nails.
Preferably, the phytosanitary composition is used for foliar applications such as on leaves, stems, branches, twigs, buds and/or flowers of the plant to be treated.
In accordance with a preferred embodiment, the composition may comprise an aqueous extract of Chelidonium majus root.
In accordance with a preferred embodiment, the composition may comprise an aqueous extract of Chelidonium majus root combined with Thuja occidentalis leaf.
In accordance with a preferred embodiment, the composition may comprise an aqueous extract of Chelidonium majus root:
It is also disclosed a method for phytosanitary treatment of plants, the method comprising at least the steps of applying once or several times the composition as defined herein on the plants. Preferably, the composition is applied on leaves, stems, branches, twigs, buds and/or flowers of the plant to be treated.
It is also disclosed the use of the composition as defined herein for phytosanitary treatment of plants. For instance, the composition is particularly useful for treating mildew. Other infections can also be treated.
Natural phenolic compounds found in essential oils may be used to avoid the oil-base to damage the plant.
Natural phenolic compounds are defined as low molecular weight naturally occurring organic compounds which contains one or more phenolic group. They are naturally produced by plants. These include: phenolic acids, thymol, carvacrol, eugenol, crassinervic acid, aduncumene, hostmaniane, gaudichaudanic acid, flavonoids, tannins, stilbenes, curcuminois, coumarins, ligans, quinines, etc.
The composition is particularly efficient in the treatment of plant infection (mildew fungus, blight fungus, etc); the treatment of intumescence of a plant; the treatment of potatoes (powdery or common scab, Rhizoctonia, etc), and also allows a higher crop yield: without the use of a chemical fungicide.
The composition is also particularly efficient in the treatment of fungus infection of nails.
In an aspect of the invention, a pharmaceutical composition is provided, the composition comprising between 40 to 50 wt. % of Chelidonium majus root aqueous extract and between 0.1 to 5 wt % of at least one natural phenolic compound, wherein the composition is usable for the prevention or treatment of nail fungal and bacterial infections. The at least one natural phenolic compound may further comprise thymol, carvacrol, eugenol, crassinervic acid, aduncumene, hostmaniane, gaudichaudanic acid, or mixture thereof. The at least one natural phenolic compound may comprise between 0.1 to 0.5 wt. % of thymol. The at least one natural phenolic compound may further comprise from 40 to 50 wt. % of an aqueous extract of Thuja occidentalis leaf. The pharmaceutical composition may further comprise between 0.1 to 0.5 wt. % of Carvacrol.
The phytosanitary composition may further comprise between 0.1 and 10 wt. % of film-forming surfactant. In another embodiment, the film-forming surfactant may comprise a polysorbate-type nonionic surfactant. In yet another embodiment, the polysorbate-type non-ionic surfactant is Polysorbate 20.
The pharmaceutical composition may further comprise essential oil. The pharmaceutical composition may comprise between 0.1 to 5 wt. % of Eucalyptus citriodora essential oil, between 0.1 to 4 wt. % of Tea tree essential oil or between 0.1 to 1 wt. % of Thymus vulgaris flower-leaf essential oil.
The pharmaceutical composition may be a topical solution for application to the nail or to the skin. The topical solution may further be configured to be applied with a brush, in a metered dose device, with a patch or with a bandage.
The pharmaceutical composition may be a sprayable solution for application to the nail or to the skin. The sprayable solution may further be configured to be applied with a brush, in a metered dose device, with a patch or with a bandage.
The pharmaceutical composition may form a film on the nail where the pharmaceutical composition is applied. The pharmaceutical composition may be used in the treatment of fungal nail, mucosal and cutaneous infections.
In an aspect of the invention, a pharmaceutical composition for the treatment of nail fungus and bacterial infections is provided, the pharmaceutical composition comprising between 40 and 50 wt. % of Chelidonium majus root aqueous extract; between 40 and 50 wt. % of Thuja occidentalis leaf extract, between 0.1 and 5 wt. % of Eucalyptus citriodora, essential oil, between 0.1 and 4 wt. % of Tea tree oil, between 0.1 and 1 wt. % of Thymus vulgaris flower-leaf and between 0.1 and 10 wt. % of film-forming surfactant. The pharmaceutical composition may comprise about 44.6 wt. % of Chelidonium majus root extract, about 44.6 wt. % of Thuja occidentalis leaf extract, about 1.8 wt. % of Eucalyptus citriodora, essential oil, about 2.7 wt. % of Tea tree oil, about 0.9 wt. % of Thymus vulgaris flower-leaf and about 5.36 wt. % of Polysorbate 20. The pharmaceutical composition may be used for the prevention of nail fungus and bacterial infections.
In an aspect of the invention, a method for the treatment of nail fungus and bacterial infections is provided, the method comprising the steps of applying at least one time, the pharmaceutical composition comprising between 40 to 50 wt. % of Chelidonium majus root aqueous extract and between 0.1 to 5 wt % of at least one natural phenolic compound on a nail to be treated and letting the composition to dry such as to form a film on the nail. The method may be used for the prevention of nail fungus and bacterial infections.
The method may be used for the prevention of nail fungus and bacterial infections.
Other and further aspects and advantages of the present invention will be obvious upon an understanding of the illustrative embodiments about to be described or will be indicated in the appended claims, and various advantages not referred to herein will occur to one skilled in the art upon employment of the invention in practice.
The above and other aspects, features and advantages of the invention will become more readily apparent from the following description, reference being made to the accompanying drawings in which:
A novel pharmaceutical and/or phytosanitary composition will be described hereinafter. Although the invention is described in terms of specific illustrative embodiments, it is to be understood that the embodiments described herein are by way of example only and that the scope of the invention is not intended to be limited thereby.
As used herein % or wt. % means weight % unless otherwise indicated. When used herein % refers to weight % as compared to the total weight percent of the phase or composition that is being discussed.
By “about”, it is meant that the value of weight %, time, or temperature can vary within a certain range depending on the margin of error of the method or device used to evaluate such weight %, time, or temperature. A margin of error of 10% is generally accepted.
The pharmaceutical and/or phytosanitary composition (hereafter named “the composition”) as disclosed herein comprises an aqueous extract of Chelidonium majus root and an acceptable pharmaceutical and/or phytosanitary excipient or base. According to a preferred embodiment, the aqueous extract of Chelidonium majus root is a 10:1 ethanol-water extract of the Chelidonium majus root, with 10 being the amount of Chelidonium majus root and 1 being the amount of ethanol-water.
The composition as disclosed herein may further comprise Thuja occidentalis leaf.
The composition as disclosed herein may further comprise from about 1 to 5% of natural phenolic compounds. Natural phenolic compounds found in essential oils may be used to obtain a synergistic response while avoiding the oil-base that will damage the plant. Natural phenolic compounds are defined as low molecular weight naturally occurring organic compounds which contains one or more phenolic group. They are naturally produced by plants. These include, but are not limited to: phenolic acids, thymol, carvacrol, eugenol, crassinervic acid, aduncumene, hostmaniane, gaudichaudanic acid, flavonoids, tannins, stilbenes, curcuminois, coumarins, ligans, quinines, etc.
The composition as disclosed herein may further comprise a film-forming surfactant.
The composition as disclosed herein may further comprise several additives such as, but not limited to penetrants, thickeners, emulsifiers, spreader and stickers, crop oils and inorganic oils, alkyl polyglucosides, and/or organosilicate surfactants.
Treatment of Plant Infections
Dormant Bud Foliar Application:
Depending on the agricultural/horticultural use, the composition or formulation may contain essential oils instead of the natural phenolic compounds. In these cases, the standardized (standardized to the natural phenolic compound) essential oils replace the natural phenolic compounds normally found within the oil; for example, Thymus vulgaris flower-leaf essential oil replaces the thymol compound. The switch to the standardized essential oil is to provide a better coating (film-formation) of the dormant bud. The standardized essential oil may contain an equivalent amount of the phenolic compound.
Soil (With or Without Fertilizer) Application Formulations:
It is also disclosed a highly effective root (soil application) composition for the prevention or treatment of fungal and bacterial infections, comprising an aqueous extract of Chelidonium majus root with or without Thuja occidentalis leaf with or without from about 1 to 5% natural phenolic compounds with or without fertilizer ingredients with or without film-forming surfactant, penetrants, thickeners, emulsifiers, spreader and stickers, crop oils and inorganic oils, alkyl polyglucosides, and/or organosilicate surfactants.
This invention is based on the synergistic activity between aqueous herb extracts and the natural phenolic compounds obtained from plants. Natural phenolic compounds found in essential oils are used to obtain the synergistic response while avoiding the oil-base that will damage the plant.
Natural phenolic compounds are defined as low molecular weight naturally occurring organic compounds which contains one or more phenolic group. They are naturally produced by plants. These include: phenolic acids, thymol, carvacrol, eugenol, crassinervic acid, aduncumene, hostmaniane, gaudichaudanic acid, flavonoids, tannins, stilbenes, curcuminois, coumarins, ligans, quinines, etc.
It is also disclosed a method for the phytosanitary treatment of plants, comprising the step of applying a phytosanitary composition as defined herein on the plants, such as on the roots of the plants, or on the leaf, the stem, the branch, the twig, the bud and/or the flower.
As demonstrating with the following examples, efficacy of the treatment can be seen after one day and only one single application of the formulation.
The following composition in accordance with a preferred embodiment of the invention has been tested on plants.
Formulation Used for Infected Plants:
Chelidonium majus root extract
Thuja occidentalis leaf extract
Chelidonium majus
Thuja occidentalis
0.5-1%
Method of Making: 1000 mL Preparation of Agricultural Formula
Step 1:
Thuya extract: 260 gram foliage dried macerated in 3 times its volume in water for 72 hours; filtered and solution retained.
Step 2:
Add Chelidonium majus extract (CELEXT07) according to table xx to 900 mL water in the spray tank or drench container and mix to dissolve the extract powder.
Step 3: Add Thuya extract, thymol, carvacrol and or surfactant to container of Step 2 according to table XX. QS to 1000 mL.
Passalora fulva (Cladosporium fulvum) causes tomato leaf mould. Foliage is often the only part of the plant infected and causes infected leaves to wither and die, indirectly affecting yield. In severe cases, blossoms and fruit can also be infected directly reducing yield.
Treatment of infected tomato plants has been done on Day 1, 3 and 5 with foliar spray comprising an aqueous 1:10 (1 part root to 10 parts water) extract of Chelidonium majus root with 0.25% of a surfactant such as polysorbate 20.
As shown by comparing the pictures presented in
Powdery mildew is a disease of leaf tissue (see
Treatment of infected tomato plants has been done on Day 1 and 3 with foliar spray comprising 1% of an aqueous 10:1 (10 part root to 1 parts water-ethanol) extract of Chelidonium majus root, 1% thymol with 0.25% of a surfactant such as polysorbate 20. Two sprays to end-of-season hydroponic tomato plants, heavily infected with powdery mildew, resulted in significant improvement in comparison to unsprayed plants (See
As a result of this test, is noted plant's vigor and health are regained; plants flower and produced crop again. Fungi has first browned and then died. 14 days post last treatment one of the infected leaves is still alive with green zones. If the fungus infection had survived the leaf would have died and browned completely.
As a result of this test, is noted plant's vigor and health are regained; plants flower and produced crop again with a nice shining green color of the leaves. Fungi has first browned and then died.
A test using aqueous 1:10 (1 part root to 10 parts water) extract of Chelidonium majus root with 0.25% surfactant (polysorbate 20). in the treatment of Mildew infection of cucurbits. A single daily application has been performed over 3 days.
The pictures of
CELEXT07 is a proprietary botanical extract that can be used alone or in combination with algae fertilizers to help increase crop yield and stimulate plant growth.
The botanical agent can also be used to help prevent and treat fungal infections.
Field studies have shown that the botanical agent does not cause damage to plants during growth, flowering and fruit growth.
CELEXT07 is readily soluble in water at room temperature at 0.2%, 0.5% and 1% with or without the algae fertilizer at 6 ml per litre.
CELEXT07 increased crop growth in greenhouse grown English cucumber plants.
Plants were treated every 14 days with a solution containing Stimulagro™ with or without 0.5% of CELEXT07.
Results are presented on
CELEXT07 was applied every two weeks in combination with an algae fertilizer on Ground Cherry.
As shown on
CELEXT07 was sprayed every two weeks onto the foliage of two year old marshmallow plants grown on a soil plot with a black colored plastic membrane.
The comparator groups consisted of two year old plants: control with no method to enhance growth; and a comparator group that used a black color plastic membrane over the soil surrounding the plants.
As shown on
Several studies were performed to assess the safety and tolerability of the compositions according to the present invention.
One study involved the application of CELEXT07 in combination with an algae fertilizer every two weeks. The formulation was applied as a soil drench and sprayed onto the foliage, flowers and fruit of a variety of crops grown in a greenhouse environment in full sun.
The study began on May 24th and there are no signs of injury or suggestion of a negative effect on growth after 7 applications.
A second study was performed on crops, ornamentals and herbs growing outdoors. Plants were sprayed weekly with escalating doses of CELEXT07 and subsequently with CELEXT07 in combination with other antimicrobial herbal agents. The study also began on May 24th and to date there have been no signs of injury or toxicity.CELEXT07 was applied using a pressurized spray tank and tested at 0.5%, 1% and 2% CELEXT07. For each concentration, CELEXT07 was applied weekly for 3 or 5 consecutive weeks.
The combination study is still ongoing and the other agents are tested in combination with 1% CELEXT07. To date there are also no signs of toxicity or injury.
Intumescences is a physiological disease that affects plant growth in greenhouses. Intumescences are small, bump-like protrusions on the surface of leaves, petioles and stems of affected plants. Prevention of intumescences is important for crops or ornamental plants with an aesthetic value. Any reduction in aesthetic value can reduce salability as consumers may be hesitant to buy a plant that looks diseased or injured.
Aesthetics aside, intumescences can also dramatically alter physiological processes in the plant. As intumescences form across the leaf surface, photosynthetic activity may decrease as plants slowly lose leaf area available for this process.
Additionally, as intumescences form on the leaf veins and stems, water and nutrient transport may also be affected in the plant. In cases of severe intumescence development, gradual senescence of leaf tissue can occur.
Use of 0.5% CELEXT07 has prevented the development of Intumescences in greenhouse grown Ground Cherry fruit plants. Plants were treated every 14-days with a solution containing Stimulagro™ with or without 0.5% CELEXT07.
Primary objective: The primary objective of this study is to demonstrate that a bimonthly application of the product prevent the development of fungal infections.
Secondary objective: The primary objective of this study is to demonstrate that the bimonthly application of the product does not damage the foliage or hinder growth, and also that the bimonthly application improve crop yield.
Description of Study Design: This study is a parallel group design comparing various antifungal formulations containing the algae-fertilizer with CELEXT07 with and without polyphenols (thymol and carvacrol). The products are applied bimonthly by soil application to drench the roots. Photos of plants treated in all groups were taken bimonthly. The weight and length of the daughter potatoes were taken at the end of the growth season as well as a count of the number of scab-like markings, and that from other microorganisms, on the potato.
Groups:
There are over 2400 potatoes that have been processed. The method used for scoring is given in “Potato Field Guide, Insects, Diseases and Defects, Publication 823, Eugenia Banks, 2004, Ministry of Agriculture and Food, Queens Printer for Ontario, Toronto, Ontario”.
Dilute 60 ml of the algae preparation in 10 litres of water (6 ml per litre). Products tested for groups A to G contain the 6 mL per litre of algae fertilizer. Group H has is a sham control and does not receive any antifungal products and no algae fertilizer. The other groups contain ingredients as described in the table below.
Groups:
Study Procedures—Bimonthly treatment
Every 14 days, the solution is applied to the soil surrounding each plant. The plants in all groups were examined daily for signs of injury and photos were taken bimonthly. The weight and length of the daughter potatoes were taken at the end of the growth season.
The number of potatoes will be recorded for each of the following observations:
Compounds:
CELEXT07 is a 10:1 ethanol-water extract of the Chelidonium majus root. 10=amount of root; 1=amount of ethanol-water.
Results:
Powdery and Common Scab
Rhizoctonia:
We are seeing a clear antifungal preventive and treatment effect of the formulation. The treatment shows that it can penetrate a wax cuticle just like in the case of a finger or toe nail.
With these examples of treatment of tomatoes, cucurbits and potatoes, antifungal properties of the composition according to the present invention has been demonstrated.
Nail Infection
According to a preferred embodiment, the pharmaceutical composition disclosed herein comprises a suspension of botanical essential oils in ethanol-water fluid extracts as a treatment of fungal and bacterial infections of nails. The pharmaceutical composition is preferably a topical formulation
The pharmaceutical composition for the treatment of nail or skin fungal and bacterial infections, may comprise an alcoholic extract (30-70% H2O ethanol or methanol) of Chelidonium majus root. It is preferably combined with an alcoholic extract (30-70% H2O ethanol or methanol) of Thuja occidentalis leaf, and more preferably combined with from about 1 to 5% of each of the following essential oils Eucalyptus citriodora, Tea tree oil and Thymus vulgaris flower-leaf and optionally a film-forming surfactant.
The pharmaceutical composition ay comprise herbal natural phenolic compounds such as, but not limited to, natural phenolic compounds are thymol, carvacrol, eugenol, crassinervic acid, aduncumene, hostmaniane, gaudichaudanic acid, or the like.
The following composition in accordance with a preferred embodiment of the invention has been tested on plants or on patients suffering of nail infection:
Chelidonium majus root extract
Thuja occidentalis leaf extract
Eucalyptus citriodora, essential oil
Thymus vulgaris flower-leaf
Method of Making: 500 mL Preparation of Human Nail Formula
Step 1:
Thuya extract: 260 gram foliage dried macerated in 3 times its volume in 50% ethanol-water for 72 hours; filtered and solution retained.
Step 2:
Chelidonium majus extract (CELEXT07): 50 grams of 10:1 extract dissolved in 500 mL
Step 3: Ccombine
It is also disclosed a method for the making of the formulation as defined herein. The method comprises the step of macerating the plants in solvent for 24 to 72 hours.
The invention can be used as a topical solution or spray for application to the nail or skin: brush, metered dose device, patch, bandage or spray, thereby forming a film on the treated surface.
The lipophilic nature of the oil-film coating remains on the nail or skin surface enabling the active molecules to penetrate the nail or skin for topical therapeutic use in the treatment of fungal nail, mucosal and cutaneous infections.
It is also disclosed a method for treating nail and/or skin infections, comprising the step of applying at least once a day the formulation as defined herein to a site of the body to be treated (nail or skin).
The method of application includes injecting locally above or adjacent to the nail's root a small volume of about 10 to 500 microliters of a drug depot formulation. The formulation may preferably contain between about 0.1 and 10 μg per μL of active ingredients.
The term “Drug depot” is hereby defined as injection of a liquid that remains at the site of injection (adjacent or above the nail root where injected) and slowly diffuses from the site over a period of several weeks. The liquid may remain a liquid at the site.
The drug depot formulation may consist of the natural phenolic compound alone as monotherapies, or in combination with other natural phenolic compounds, or in combination with synthetic antifungal or antibacterial drugs dissolved in a vehicle base that is biocompatible with tissues.
The vehicle that is biocompatible with tissues can be:
Vehicle-Base Formulations for Local Injection:
Oil-based injectable solutions, injectable-drug suspensions, polymer-based microspheres (PLGA microspheres, PCL microspheres, polyanhydride microspheres, polyorthoesters microspheres, and polyalkylcyanoacrylate microspheres) and polymer-based in-situ forming. Formation of microspheres includes use of homopolymers and copolymers of lactic acid and glycolic acid (PLGA). Microparticles prepared using lipids to encapsulate the antifungal/antibacterial composition include Liposomes composed of a single or multiple phospholipids and cholesterol bilayers.
Alternatively, a conventional long-acting injection formulation that consists either of lipophilic compounds in aqueous solvents as suspensions or of lipophilic compounds dissolved in vegetable oils.
Conventional biodegradable polymers used for controlled drug delivery can be used: includes polylactides (PLA), polyglycolides (PGA), poly(lactide-co-glycolide) (PLGA), poly(ϵ-caprolactone) (PCL), polyglyconate, polyanhydrides, polyorthoesters, poly(Dioxanone), and polyalkylcyanoacrylates.
The patients used the product to treat an active infection of the toe nail. The product was applied once in the morning. After several 12 weeks of treatment, the infected zone of the nail began to darken and eventually became dark brown and the patients began to observe new growth that was not infected. As the new nail grew, the dark zone was removed by frequent cutting.
While illustrative and presently preferred embodiments of the invention have been described in detail hereinabove, it is to be understood that the inventive concepts may be otherwise variously embodied and employed and that the appended claims are intended to be construed to include such variations except insofar as limited by the prior art.
The present patent application is a divisional application of the U.S. patent application Ser. No. 16/076,352 entitled “HERBAL COMPOSITIONS AND METHODS FOR THE PREVENTION AND TREATMENT OF PLANT OF NAIL INFECTIONS” having a filing date of Aug. 2, 2017 and having a 371 date of Aug. 8, 2018 at the United States Patent and Trademark Office (USPTO). The present patent application further claims the benefits of priority of the following U.S. Provisional Patent Applications: U.S. Provisional Patent Application No. 62/292,608 entitled “Compositions And Methods For Treatment Of Nail Fungal Or Bacterial Infections” and filed at the USPTO on Feb. 8, 2016; U.S. Provisional Patent Application No. 62/293,479 entitled “Herbal Phytosanitary Compositions And Methods For The Prevention And Treatment Of Plant Infections” and filed at the USPTO on Feb. 10, 2016; and U.S. Provisional Patent Application No. 62/293,519 entitled “Herbal compositions for treatment of nail and skin infections” and filed at the USPTO on Feb. 10, 2016; the content of which is incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 62292608 | Feb 2016 | US | |
| 62293479 | Feb 2016 | US | |
| 62293519 | Feb 2016 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16076352 | Aug 2018 | US |
| Child | 17031137 | US |
