WO2012129683A1 - Extraits de plantes du genre tsuga et leurs utilisations dans le traitement de troubles cutanés - Google Patents

Extraits de plantes du genre tsuga et leurs utilisations dans le traitement de troubles cutanés Download PDF

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Publication number
WO2012129683A1
WO2012129683A1 PCT/CA2012/050161 CA2012050161W WO2012129683A1 WO 2012129683 A1 WO2012129683 A1 WO 2012129683A1 CA 2012050161 W CA2012050161 W CA 2012050161W WO 2012129683 A1 WO2012129683 A1 WO 2012129683A1
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Prior art keywords
extract
tsuga
prepared
dermatological formulation
weight
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Johane Guay
Nathalie Gendron
Brigitte PAGÉ
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Biopharmacopae Design International Inc
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Biopharmacopae Design International Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9755—Gymnosperms [Coniferophyta]
    • A61K8/9767—Pinaceae [Pine family], e.g. pine or cedar
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/13—Coniferophyta (gymnosperms)
    • A61K36/15—Pinaceae (Pine family), e.g. pine or cedar
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • G—PHYSICS
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06F—ELECTRIC DIGITAL DATA PROCESSING
    • G06F18/00—Pattern recognition
    • G06F18/20—Analysing
    • G06F18/24—Classification techniques
    • G—PHYSICS
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06F—ELECTRIC DIGITAL DATA PROCESSING
    • G06F3/00—Input arrangements for transferring data to be processed into a form capable of being handled by the computer; Output arrangements for transferring data from processing unit to output unit, e.g. interface arrangements
    • G06F3/01—Input arrangements or combined input and output arrangements for interaction between user and computer
    • G06F3/017—Gesture based interaction, e.g. based on a set of recognized hand gestures
    • G—PHYSICS
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06N—COMPUTING ARRANGEMENTS BASED ON SPECIFIC COMPUTATIONAL MODELS
    • G06N3/00—Computing arrangements based on biological models
    • G06N3/02—Neural networks
    • G06N3/04—Architecture, e.g. interconnection topology
    • G06N3/044—Recurrent networks, e.g. Hopfield networks

Definitions

  • the present invention relates to fields of pharmaceuticals and cosmetics and, in particular, to extracts from plants of the Tsuga genus for use to treat acne and other skin disorders associated with the formation of comedones.
  • Acne is a common multifactor pathology which affects skin rich in sebaceous glands (such as the face, scapula region, arms and inter-triginous regions).
  • Various pathogenic factors play a determining role in the formation of acne including genetic predisposition, overproduction of sebum (seborrhea), androgens, follicular keratinization disorders (comedogenesis) and bacterial colonization and inflammatory factors.
  • the clinical manifestations of acne include non-inflammatory closed (blackhead) or open (whitehead) comedones, as well as inflammatory lesions, including papules, pustules, cysts and nodules.
  • Acne can be divided into mild, moderate and severe based on the number of lesions and the surface of skin involved. Mild acne is characterized by open and closed comedones sometimes accompanied by few superficial inflammatory lesions, moderate acne is characterized by increasing largely superficial inflammatory lesions with pustules that have the tendency to scar with time. Nodules and cysts with marked scarring characterize severe acne.
  • the comedo is the primary lesion of acne vulgaris and results from the obstruction by cells of the wall of the follicle of the canal, preventing the sebum produced by sebocytes (cells of the sebaceous glands) from reaching the surface of the skin.
  • the mixture of sebum and cells forms a plug, referred to as a comedo.
  • Proliferation of bacteria which normally live on the skin, such as P. acnes and P. granulosum, in the plugged pore can bring about the inflammation of the surrounding tissue.
  • the treatment and prevention of acne includes various topical and systemic therapies and is guided by the type of clinical lesions present. Topical therapy is often preferred because of its safety compared with others forms of treatment.
  • Current topical therapies include comedolytic agents such as tretinoin, adapalene, azelaic acid, tazarotene and salicylic acid; antimicrobial agents such as benzoyl peroxide; antibiotics such as clindamycin, erythromycin and tetracycline; and anti-inflammatory agents such as sodium sulfacetamide.
  • comedolytic agents such as tretinoin, adapalene, azelaic acid, tazarotene and salicylic acid
  • antimicrobial agents such as benzoyl peroxide
  • antibiotics such as clindamycin, erythromycin and tetracycline
  • anti-inflammatory agents such as sodium sulfacetamide.
  • Oral antibiotics are often added to the treatment regimen when acne does not respond satisfactorily to topical therapy.
  • Other systemic treatments for more severe, recalcitrant acne include estrogens, antiandrogens, and isotretinoin.
  • PCT/CA04/02007 (WO 2006/053415) describes a large number of plant extracts that are useful for the preparation of dermatological formulations and uses of these formulations for ameliorating the effects of ageing and for the routine care of skin, hair and/or nails.
  • the Tsuga genus is a genus of conifers in the family Pinaceae. Plants in this genus are known under the common name of "hemlock.” Catechol tannins extracted from Tsuga or hemlock have been described for the treatment of burns (U.S. Patent No. 2,276,241; GB Patent No. 544,615 and Canadian Patent No. 406,408) due to their tanning action. As further described in these patents, tannins are not germicidal and as such the burn treatment compositions further comprise an effective germicide, specifically a phenolic compound, which is compatible with the tannin.
  • Tsuga extracts have been described for their deodorant properties.
  • Japanese Patent Application Publication No. 2002087973 describes extracts from Tsuga as part of cosmetic compositions for suppressing human body odour
  • Japanese Patent Application Publication No. 4030855 describes a mousse-like deodorant containing several plant extracts including a Tsuga extract
  • U.S. Patent No. 4,898,727 describes a deodorant containing several plant extracts including a Tsuga extract, a filter using same and a method of producing the deodorant.
  • European Patent Application Publication No. 0 870 507 describes a synergistic anti-bacterial composition that includes an extract of botanical materials and an essential oil.
  • the essential oil is described as having anti-microbial activity, whereas the extract of botanical materials has significantly lower activity, or no anti-microbial activity, when used alone.
  • a variety of potential botantical materials are described in the application including Tsuga, with the preferred material being a combination of Plantago, Hypericum, Echinacea and Propolis.
  • a method of reducing the number of acneic lesions, such as comedones, on the skin such of a subject comprising applying to the skin of the subject an effective amount of an extract from a plant of the Tsuga genus.
  • a method of treating acne comprising administering to the skin of a subject in need thereof an effective amount of an extract from a plant of the Tsuga genus.
  • a dermatological formulation comprising an extract from a plant of the Tsuga genus and optionally one or more anti-acne compounds.
  • the dermatological formulation is optionally formulated for sensitive skins and/or is optionally formulated as a cosmetic
  • the one or more anti-acne compounds are selected from antibiotics, antimicrobials, comedolytic agents and anti-inflammatory agents.
  • the antibiotics may optionally be selected from: erythromycin, clindamycin and tetracyclines.
  • the antimicrobials may optionally be selected from: chlorexidine, benzoylperoxide, 1- pentadecanol, derivatives of 1-pentadecanol, cedrene, caryophyllene, longifolene and thujopsene.
  • the comedolytic agents may optionally be selected from: tretinoin, isotretinoin, adapalene, azelaic acid, tazarotene, salicylic acid and salicylic acid derivatives.
  • the antiinflammatory agents may optionally be selected from NSAIDs, steroidal anti-inflammatory agents, cetylsalicylic acid, ibuprofen, naproxen, sulfacetamide and hydrocortisone.
  • the dermatological formulation may be for sensitive skins or a cosmetic.
  • the plant of the Tsuga genus is a Tsuga canadensis, Tsuga diversifolia or Tsuga heterophylla plant.
  • the extract is prepared by solvent extraction of needles, twigs, small branches, bark, or a combination thereof, from the plant of the Tsuga genus.
  • the Tsuga extract is an aqueous-alcoholic extract, aqueous-glycolic extract or aqueous-glycerine extract.
  • the extract is prepared using a glycol, an alcohol or a glycerine as the solvent.
  • the extract is a supercritical C0 2 extract.
  • the extract is prepared using a ratio of solven plant material between about 5: 1 and about 50: 1 ; about 15: 1 and about 25: 1; is about 70:30 by weight; is about 80:20 by weight; is about 30:70 by weight; is about 20:80 by weight.
  • the extract is prepared using a combination of a glycol and water as the solvent, wherein the range of glycol: water is between about 60:40 and about 40:60; is about 70:30 by weight; is about 30:70 by weight; is about 80:20 by weight or is is about 20:80 by weight.
  • Figure 1 presents the results demonstrating the anti-inflammatory effect of a Tsuga canadensis extract in human skin keratinocytes after UV irradiation % inhibition of interleukin (IL)-6 release.
  • Figure 2 presents the results of an evaluation of the antimicrobial effect of Tsuga canadensis extract 207-20156 at 2% and 5% against (A) Staphyloccocus epidermidis and (B) Propionibacterium acnes (results in CFU).
  • Figure 3 presents the results of an in vitro a wound healing assay demonstrating the effects of a Tsuga canadensis extract on wound healing.
  • Figure 4 presents results from a cosmetologist clinical evaluation of the effect of a cream containing a Tsuga canadensis extract (“Product B") on acneic lesions in human volunteers; (A) evolution of the number of lesions after 28 days of application of Product B; (B) evolution of the number of lesions after 42 days of application of Product B; (C) comparison of the number of lesions after 28 days of application of Product B and a placebo ("Product A"), and (D) comparison of the number of lesions after 42 days of application of Product B and a placebo.
  • Product B Tsuga canadensis extract
  • the present invention relates to the newly identified activity of extracts derived from plants of the Tsuga genus ("Tsuga extracts") in the treatment of comedones and/or acne.
  • Tsuga extracts extracts derived from plants of the Tsuga genus
  • the present invention provides for the use of the Tsuga extracts to treat skin disorders associated with the formation of comedones, such as acne.
  • the present invention provides for the use of Tsuga extracts to decrease comedones in a subject.
  • the present invention provides for the use of Tsuga extracts to treat acne.
  • the extracts may decrease comedones and/or other skin lesions in the subject under treatment.
  • the present invention also provides for the use of the Tsuga extracts in the prevention of acne and/or comedones.
  • the Tsuga extracts may be used in the treatment of skin having a tendency toward acne in order to combat the appearance of skin lesions, such as comedones, papules or pustules.
  • the Tsuga extracts also possess anti-inflammatory properties which allow the extracts to additionally combat the irritant or inflammatory effects of other acne treatment compounds (such as retinoids) and/or be incorporated into dermatological formulations for sensitive skins.
  • the ability of the Tsuga extracts to combat the irritant effects of retinoids and other anti-acne compounds allows for formulations that comprise the extract and higher than standard amounts of these agents.
  • the present invention provides for dermatological formulations that comprise a Tsuga extract and one or more of a retinoid or other anti-acne compound with irritant effects, wherein the retinoid or other anti-acne compound is present in a higher than standard amount.
  • the Tsuga extracts also possess healing properties as shown herein, which allow the extracts to additionally facilitate the healing of, and/or reduce the formation of scars that may result from, acneic lesions, such as comedones, papules or pustules. Definitions
  • plant material refers to any part or parts of a specified plant taken either individually or in a group. Examples include, but are not limited to, leaves, needles, roots, bark, stems, buds, twigs, cones, branches and the like.
  • extract refers to a composition prepared by mixing plant material with a solvent following the procedures described herein.
  • the extract can optionally be subjected to one or more separation and/or purification steps.
  • attenuate means to reduce or inhibit, wherein the inhibition may be complete or partial inhibition.
  • a “dermatological formulation,” as used herein, refers to a pharmaceutical composition, a cosmeceutical composition or a cosmetic formulated for topical administration to the skin.
  • ameliorate means to make more tolerable (for example by reducing the incidence or severity), to heal or to cure.
  • treatment refers to an intervention performed with the intention of improving a recipient's status.
  • the improvement can be subjective or objective and is related to the amelioration, either temporary or long-term, of one or more of the symptoms associated with a condition being treated.
  • treatment includes the prevention of the development of the condition.
  • the term treatment includes the prevention (prophylaxis), moderation, reduction, and/or curing of a condition at various stages.
  • prevention of deterioration of a recipient's status is also encompassed by the term.
  • Those in need of treatment thus may include those already having the condition as well as those prone to, or at risk of developing, the condition and those in whom the condition is to be prevented.
  • subject refers to an individual in need of treatment or who would otherwise benefit from the use of a dermatological formulation in accordance with the invention.
  • term “about” refers to approximately a +/-10% variation from a given value. It is to be understood that such a variation is always included in any given value provided herein, whether or not it is specifically referred to.
  • the present invention provides for extracts from plants of the Tsuga genus ("Tsuga extracts") suitable for dermatological use.
  • Tsuga extracts suitable for dermatological use.
  • the Tsuga extracts have comedolytic and/or anti-acne activity.
  • the Tsuga extracts are solvent-based extracts obtained by solvent extraction of plant material from a selected Tsuga plant.
  • the selected Tsuga plant can be, for example, Tsuga canadensis; Tsuga caroliniana; Tsuga chinensis; Tsuga diversifolia; Tsuga dumosa; Tsuga forrestii; Tsuga heterophylla; Tsuga mertensiana or Tsuga sieboldii.
  • the Tsuga plant is a plant native to North America, i.e. Tsuga canadensis; Tsuga caroliniana; Tsuga heterophylla or Tsuga mertensiana.
  • the Tsuga plant is a plant native to Asia, i.e. Tsuga chinensis; Tsuga diversifolia; Tsuga dumosa; Tsuga forrestii or Tsuga sieboldii.
  • the Tsuga plant is Tsuga canadensis; Tsuga heterophylla or Tsuga diversifolia.
  • the Tsuga plant is Tsuga canadensis.
  • the solvent used for the preparation of the extract can be an aqueous solvent (such as water or a buffer), or it can be a liquid organic compound, or a combination of an aqueous solvent and a liquid organic compound. Examples of solvents that may be used in the preparation of the Tsuga extracts are described in detail below. In some embodiments, the solvent may be a supercritical or sub-critical fluid.
  • the Tsuga extract is an aqueous, alcoholic or aqueous-alcoholic extract. In another embodiment, the Tsuga extract is an aqueous, glycolic or aqueous-glycolic extract.
  • Tsuga extracts in accordance with the invention are obtained by solvent extraction of plant material from a selected Tsuga plant.
  • the plant material is derived from one or a combination of the species of Tsuga noted above, i.e. Tsuga canadensis; Tsuga caroliniana; Tsuga chinensis; Tsuga diversifolia; Tsuga dumosa; Tsuga forrestii; Tsuga heterophylla; Tsuga mertensiana and/or Tsuga sieboldii.
  • the plant material employed in the extraction process can be the entire plant (tree), or it can be one or more distinct tissues from the plant or plants, for example, leaves (needles), cones, roots, branches, bark, stems, twigs, buds or various combinations thereof.
  • the Tsuga extract is prepared from needles, twigs, small branches, bark, or any combination thereof.
  • the Tsuga extract is prepared from needles and optionally other parts of the plant.
  • the plant material can be fresh, dried or frozen.
  • the plant material used in the preparation of the Tsuga extracts is dried.
  • the plant material may be used immediately after harvesting or it can be stored for a period of time prior to being subjected to the extraction process. If the plant material is stored, it can be treated prior to storage, for example, by drying, freezing, lyophilizing, or some combination thereof, as is known in the art.
  • the storage time may be of various durations, for example, the storage period may be between a few days and a few years. Typically storage times range between less than one week and about one year in duration.
  • the plant material can be treated prior to the extraction process in order to facilitate the extraction process.
  • treatment results in the plant material being fragmented by some means such that a greater surface area is presented to the solvent.
  • the plant material can be crushed or sliced mechanically, using a grinder or other device to fragment the plant parts into small pieces or particles, or the plant material can be frozen in liquid nitrogen and then crushed or otherwise fragmented into smaller pieces.
  • the plant material can be derived from a Tsuga plant that was subjected to a stress treatment.
  • a stress treatment comprises contacting or treating the plant, or material from the plant, with one or more stressor with the aim of inducing or eliciting increased production of one or more chemicals.
  • the stressor can be a chemical compound or a physical treatment.
  • chemical stressors include, but are not limited to, organic and inorganic acids including fatty acids; glycerides; phospholipids; glycolipids; organic solvents; amino acids; peptides; monosaccharides; oligosaccharides; polysaccharides; lipopolysaccharides; phenolics; alkaloids; terpenes; terpenoids; antibiotics; detergents; polyamines; peroxides; ionophores, and the like.
  • physical stress treatments include, but are not limited to, ultraviolet radiation, sandblasting, low and high temperature stress, and osmotic stress induced by salt or sugars.
  • Nutritional stress is another example of a physical stress and is defined as depriving the plant of essential nutrients (e.g. nitrogen, phosphorus or potassium) in order to induce or elicit increased production of one or more chemicals.
  • the one or more stressor i.e. chemical compound(s), physical treatment(s), or combination thereof
  • the one or more stressor may be applied continuously or intermittently to the plant material.
  • Various stressors and procedures for stressing plants prior to extract preparation have been described previously (see International Patent Application WO 02/06992) and are suitable for use in accordance with the present invention.
  • the solvent extraction process employed in the preparation of the Tsuga extracts typically employs as solvent an aqueous solvent (such as water or a buffer), a liquid organic compound, or a combination thereof.
  • Exemplary liquid organic compounds that can be used as solvents in the extraction process to prepare the Tsuga extracts include, but are not limited to, alcoholic solvents, which include primary alcohols such as methyl alcohol (methanol), ethyl alcohol (ethanol), 1-propanol and 1-butanol; secondary alcohols such as 2-propanol and 2-butanol; tertiary alcohols such as 2-methyl-2-propanol, and liquid polyhydric alcohols such as glycerine (glycerol) and glycols.
  • alcoholic solvents which include primary alcohols such as methyl alcohol (methanol), ethyl alcohol (ethanol), 1-propanol and 1-butanol; secondary alcohols such as 2-propanol and 2-butanol; tertiary alcohols such as 2-methyl-2-propanol, and liquid polyhydric alcohols such as glycerine (glycerol) and glycols.
  • Suitable glycols include, for example, ethylene glycol (1,2-ethandiol), propylene glycol (1,2-propanediol), trimethylene glycol (1,3-propanediol), 1,3-butylene glycol, pentylene glycol (1,2-pentanediol), hexylene glycol (2-methyl-2,4- pentanediol), diethylene glycol, dipropylene glycol and lower molecular weight polyethylene glycols.
  • organic solvents for plant extraction include acetone, tetrahydrofuran, acetonitrile, 1,4-dioxane, pyridine, dimethylsulfoxide, N,N-dimethyl formamide, acetic acid, diethyl ether, hexane, heptane, dichloromethane and ethyl acetate.
  • supercritical or sub-critical fluids such as water or carbon dioxide, are also suitable solvents for the preparation of the Tsuga extracts.
  • the solvent employed to prepare the Tsuga extracts comprises an alcohol.
  • the solvent employed to prepare the Tsuga extracts comprises a primary alcohol or a liquid polyhydric alcohol.
  • the solvent employed to prepare the Tsuga extracts comprises a supercritical or sub-critical fluid.
  • the content of the liquid organic compound ranges from about 5% to about 95% by volume.
  • the extraction process is carried out using a solvent that comprises a mixture of an aqueous solvent and a liquid organic compound in which the content of the liquid organic compound ranges from about 10% to about 95% by volume, from about 15% to about 95% by volume, from about 10% to about 90% by volume, from 20% to about 95% by volume, from about 20% to about 90% by volume, from about 10% to about 85% by volume and from about 20% to about 85% by volume.
  • a solvent that is compatible with mammalian skin is used in the extraction. This can, for example, allow for the extract to be incorporated directly into a dermatological formulation with little, or no, further processing.
  • solvents include, but are not limited to, water, an aqueous buffer, a combination of water/buffer with a lower alcohol or an anhydrous lower alcohol.
  • a lower alcohol refers to an alcohol having 1 to 6 carbon atoms, such as a primary, secondary, tertiary or liquid polyhydric alcohol.
  • the solvent for the preparation of the Tsuga extract is selected from water, a lower alcohol or a combination thereof.
  • the solvent for the preparation of the Tsuga extract comprises a lower alcohol selected from the group of: methyl alcohol (methanol), ethyl alcohol (ethanol), 1-propanol, 1-butanol, 2-propanol, 2-butanol, 2-methyl-l-propanol, 2- methyl-2-propanol, glycerine, ethylene glycol, propylene glycol, diethylene glycol, dipropylene glycol, 1,3 -propanediol and 1,3-butylene glycol.
  • the solvent for the preparation of the Tsuga extract is a glycol or a glycol-water mixture.
  • the lower alcohol content of the solvent typically ranges from about 5% to about 95% by volume, for example from about 10% to about 95% by volume.
  • the extraction process is carried out using a solvent that comprises a mixture of an aqueous solvent and a lower alcohol in which the content of the lower alcohol ranges from about 15% to about 95% by volume.
  • the extraction process is carried out using a solvent that comprises a mixture of an aqueous solvent and a lower alcohol in which the content of the lower alcohol ranges from about 20% to about 95% by volume.
  • the extraction process is carried out using a solvent that comprises a mixture of an aqueous solvent and a lower alcohol in which the content of the lower alcohol ranges from about 20% to about 90% by volume, and from about 20% to about 85% by volume.
  • the primary alcohol when the extraction process employs a solvent that is an aqueous solvent/primary alcohol mixture, the primary alcohol can be present in an amount between about 20% to about 90% by volume, for example from about 30% to about 90% by volume, whereas when the extraction process employs a solvent that is an aqueous solvent/glycol mixture, the glycol can be present in an amount between about 10% to about 80% by volume, for example from about 10% to about 60% by volume.
  • the glycerine when the extraction process employs a solvent that is an aqueous solvent/glycerine mixture, the glycerine can be present in an amount between about 10% to about 80% by volume, for example from about 10% to about 60% by volume.
  • the extraction process employs a solvent that is an aqueous solvent/primary alcohol mixture in which the primary alcohol is present in an amount between about 35% to about 90% by volume, between about 40% to about 90% by volume, between about 45% to about 90%, between about 45% to about 85%, and between about 50% to about 85% by volume.
  • the extraction process employs a solvent that is an aqueous solvent/glycol mixture in which the glycol is present in an amount between about 15% to about 80% by volume, for example, between about 15% to about 70% by volume, between about 15% to about 60% by volume, between about 15% to about 55% by volume, between about 20% to about 55% by volume, and between about 20% to about 50% by volume.
  • the extraction process entails contacting solid plant material with a solvent with adequate mixing and for a period of time sufficient to ensure adequate exposure of the solid plant material to the solvent such that activity present in the plant material can be taken up by the solvent.
  • the w/v (g/lOOmL) of plant material to solvent used in the extraction process is between about 1/2 and about 1/50. In another embodiment, the w/v (g/lOOmL) of plant material to solvent used in the extraction process is between about 1/5 and about 1/50. In another embodiment, the w/v (g/lOOmL) of plant material to solvent used in the extraction process is between about 1/10 and about 1/50. In other embodiments, the w/v (g/lOOmL) of plant material to solvent used in the extraction process is between about 1/10 and about 1/40; between about 1/10 and about 1/30; and between about 1/10 and about 1/25.
  • the extraction procedures are conducted over a period of time between about 10 minutes and about 72 hours at a temperature between about 4°C and about 50°C.
  • temperatures between about 4°C and about 90°C, for example between about 4°C and about 70°C can be employed.
  • Higher temperatures are also contemplated, with or without increased pressure, when certain extraction techniques are employed, for example, pressurized liquid extraction, sub-critical fluid extraction (for example, sub-critical water extraction (SWE)) or supercritical fluid extraction.
  • the extraction time may be varied depending on other extraction conditions, such as the solvent and temperature employed, for example, the extraction time can range from several minutes to several days. For example, in one embodiment, the extraction time is at least one hour. In another embodiment, the extraction time is between about one hour and about 72 hours. Determination of appropriate extraction temperatures and times is within the ordinary skills of a worker in the art.
  • Adequate contact between the solvent and the plant material can be encouraged by shaking, stirring, percolating and/or macerating the suspension.
  • an extraction device equipped with, for instance, a stirring machine, or a Soxhlet or other device known in the art can be employed which may improve the extraction efficiency.
  • the extraction can be carried out at ordinary pressure, under pressure or at reduced pressure established by, for example, aspiration.
  • Appropriate extraction conditions can readily be determined or selected by one skilled in the art taking into consideration the production conditions such as production facilities and yields.
  • the present invention also provides for the use of supercritical fluid extraction for the preparation of the Tsuga extracts.
  • Supercritical fluid extraction involves the use of a supercritical fluid (SCF) as a solvent.
  • SCF supercritical fluid
  • a SCF is a liquid or a gas at atmospheric conditions, but becomes supercritical when it is compressed above its critical pressure and heated above its critical temperature.
  • Supercritical fluids have increased dissolving power in their supercritical regions.
  • a supercritical fluid exhibits properties between those of a gas and a liquid, and has the capacity to dissolve compounds that may only dissolve poorly or not at all in the gas or liquid state.
  • Most components extracted from the plant material, once dissolved, can quickly and cleanly be precipitated or removed from the supercritical fluids by lowering the pressure and/or temperature to achieve separation.
  • Using the method of post- extraction fractionation with a column designed to allow for temperature and pressure drops at different levels to gain the desired results may effect further concentration and purification when desirable.
  • the starting plant material is placed in an extractor device together with the supercritical fluid, with or without a chemical modifier, at specified pressure and temperature conditions to extract the desired components from the plant material.
  • the fluid and the compound are passed through a separator which changes the pressure and temperature, thereby reducing the dissolving power of the supercritical fluid and causing the separation or fractionation of the dissolved components.
  • suitable supercritical fluids for the preparation of the Tsuga extracts include water and carbon dioxide.
  • Carbon dioxide has a critical temperature of 31.06°C, a critical pressure of 73.83 bar, and a critical density of 0.460 g/cm 3 , which allows the use of relatively low temperatures for the extraction process.
  • An exemplary SCF extraction process utilizing carbon dioxide as the SCF is as follows. Comminuted plant material is combined with the carbon dioxide with one or more modifiers in an extractor device. The extraction is conducted at a pressure between about 270 to about 320 bar, and a temperature of about 40°C to about 60°C.
  • the ratio of supercritical fluid solvent to starting plant material is typically between about 5: 1 and about 80: 1 by weight, for example between about 5: 1 and about 60: 1 by weight, between about 5: 1 and about 50: 1 by weight or between about 10: 1 and about 40: 1 by weight.
  • Tsuga extracts using subcritical fluids, with or without a co-solvent, is also contemplated.
  • suitable subcritical fluids for preparation of the Tsuga extracts include water and carbon dioxide.
  • one or more co-solvents are included in the supercritical fluid or subcritical fluid.
  • Modifiers generally possess volatility between that of the supercritical or subcritical fluid and of the components being extracted, and must be miscible with the supercritical/subcritical fluid.
  • Suitable modifiers include, for example, ethanol, methanol, propanol, acetone, ethyl acetate, methylene chloride, and the like.
  • Water is also a suitable modifier when the supercritical/subcritical fluid is carbon dioxide. Ethanol, for example, can be used as a modifier in a ratio of 35 to 75 kg ethanol solvent per kg of plant material.
  • the liquid fraction (the Tsuga extract) can be separated from the solid (insoluble) matter. Separation of the liquid and solid fractions can be achieved by one or more standard separation processes known to those skilled in the art, such as various centrifugation or filtration processes. In one embodiment of the invention, the Tsuga extract is separated from solid matter after the extraction by one or more filtration steps. In another embodiment, the Tsuga extract is separated from solid matter after the extraction by a series of filtration steps.
  • the Tsuga extract Once the Tsuga extract has been isolated, its activity can be tested directly or after being diluted in a suitable solvent, or it may be subjected to further procedures. For example, the Tsuga extract can be subjected to one or more additional steps to further purify or concentrate the extract.
  • the extract may be subjected to solid-liquid extraction, liquid-liquid extraction, solid-phase extraction (SPE), membrane filtration, ultrafiltration, dialysis, electrophoresis, solvent concentration, centrifugation, ultracentrifugation, liquid or gas phase chromatography (including size exclusion, affinity, and the like) with or without high pressure, lyophilization, evaporation, precipitation with various "carriers" (including PVPP, carbon, antibodies, and the like), the use of supercritical fluids (such as C0 2 ), or various combinations thereof.
  • the Tsuga extract is subjected to procedures to remove fatty acids or chlorophyll components that may interfere with its activity. Various procedures known in the art may be employed.
  • one or more additional partitioning steps using an organic solvent such as hexane, heptane or ethyl acetate, are included.
  • the liquid Tsuga extract can be concentrated and solubilised in an appropriate solvent prior to the one or more partitioning steps, if desired.
  • the Tsuga material is subjected to an extraction process that entails contacting the solid plant material with a solvent with adequate mixing over a period of time between about 10 minutes and about 72 hours at a temperature between about 4°C and about 50°C.
  • the liquid fraction (the Tsuga extract) is then separated from the solid (insoluble) matter by one or more standard processes known to those skilled in the art.
  • the Tsuga extract is prepared by extracting plant material with an alcoholic solvent alone or in combination with an aqueous co-solvent for a time period between about 4 hours and about 48 hours, for example between about 4 hours and about 24 hours, at a temperature between about 4°C to about 32°C, for example between about 4 °C to about 25°C.
  • the Tsuga extract is prepared by extracting plant material using a combination of ethanol and water as the solvent, wherein the range of ethanokwater is between about 50:50 and about 85: 15, and wherein the extraction is conducted for a time period between about 4 hours and about 48 hours, for example between about 4 hours and about 24 hours, at a temperature between about 4°C to about 32°C, for example between about 4°C to about 25 °C.
  • the Tsuga extract is prepared by extracting plant material using a combination of a glycol and water as the solvent, wherein the range of glycokwater is between about 100:0 and about 20:80, for example between about 80:20 and about 40:60 or between about 60:40 and about 40:60, and wherein the extraction is conducted for a time period between about 4 hours and about 48 hours, for example between about 4 hours and about 24 hours, at a temperature between about 4°C to about 32°C, for example between about 4°C to about 25°C.
  • the ratio of solvent to starting plant material for the extraction is between about 5: 1 and about 50: 1 by weight, for example, between about 10: 1 and about 50: 1 by weight, between about 5: 1 and about 40: 1 by weight, between about 10: 1 and about 40: 1 by weight, between about 5: 1 and about 30: 1 by weight, between about 10: 1 and about 30: 1 by weight, between about 5: 1 and about 25: 1 by weight, between about 10: 1 and about 25: 1 by weight, between about 15: 1 and about 25: 1 by weight, and about 20: 1 by weight.
  • the present invention contemplates that the extraction process and any subsequent purification steps may be carried out on various scales including known large, medium and small-scale methods of preparing extracts.
  • the Tsuga extract is prepared on a large-scale.
  • the Tsuga extract can be prepared on a commercial scale by using the extraction process employed in the initial analytical scale preparation of the extract.
  • the small-scale extraction procedure is simply scaled-up and additional steps of quality control can be included to ensure reproducible results.
  • modifications to the small-scale procedure as may be required during scale-up for industrial level production of the Tsuga extract.
  • modifications include, for example, alterations to the solvent being used or to the extraction procedure employed in order to compensate for variations that occur during scale-up and render the overall procedure more amenable to industrial scale production, or more cost effective. Modifications of this type are standard in the industry and would be readily apparent to those skilled in the art.
  • Tsuga extracts in accordance with the present invention have comedolytic and/or antiacne activity. These properties can be assessed using standard techniques known in the art. Exemplary techniques are provided below and in the Examples section.
  • Tsuga extracts to inhibit the growth of microbial cells can be assessed using standard in vitro methods known in the art. In general, these methods involve contacting a culture of the microbial cells with various concentrations of the extract and monitoring the growth of the cell culture relative to an untreated control culture. A second control culture comprising cells contacted with a known anti-microbial agent may also be included in such tests, if desired.
  • An exemplary test for determining the ability of the Tsuga extract to inhibit a variety of bacterial species is provided in the Examples (see Example IX).
  • the ability of the Tsuga extracts to inhibit the growth of bacterial cells can also be determined by measurement of the minimum inhibitory concentration (MIC).
  • the MIC is defined as the lowest concentration that inhibits growth of the organism to a pre-determined extent.
  • a MICioo value is defined as the lowest concentration that completely inhibits growth of the organism
  • a MIC 90 value is defined as the lowest concentration that inhibits growth by 90%
  • a MIC 50 value is defined as the lowest concentration that inhibits growth by 50%.
  • MIC values are sometimes expressed as ranges, for example, the MICioo for a compound may be expressed as the concentration at which no growth is observed or as a range between the concentration at which no growth is observed and the concentration of the dilution which immediately follows.
  • anti-bacterial MICs are measured using a broth macro- or microdilution assay (see Amsterdam, D. (1996) "Susceptibility testing of antimicrobials in liquid media," pp.52-111. In Loman, V., ed. Antibiotics in Laboratory Medicine, 4th ed. Williams and Wilkins, Baltimore, MD).
  • a standardised anti-bacterial susceptibility test is provided by the National Committee for Clinical Laboratory Standards (NCCLS) as NCCLS, 2000; document M7- A58.
  • the Tsuga extract would be diluted in culture medium in a sterile, covered 96-well microtiter plate.
  • An overnight culture of a single bacterial colony is diluted in sterile medium such that, after inoculation, each well in the microtiter plate contains an appropriate number of colony forming units (CFU)/ml (typically, approximately 5 x 10 5 CFU/ml).
  • Culture medium only (containing no bacteria) is also included as a negative control for each plate and known antibiotics are often included as positive controls.
  • the inoculated microtiter plate is subsequently incubated at an appropriate temperature (for example, 35°C - 37°C for 16-48 hours).
  • the turbidity of each well is then determined by visual inspection and/or by measuring the absorbance, or optical density (OD), at 595nm or 600nm using a microplate reader and is used as an indication of the extent of bacterial growth.
  • OD optical density
  • the Tsuga extracts may undergo additional testing on human volunteers to assess their ability to exert the desired dermatological effect(s).
  • the effect of the extracts on skin lesions can be assessed by visual examination.
  • the effect of the Tsuga extract on the skin can be evaluated by formulating the extract such that it is suitable for external application to the skin and subsequently sensory tests can be conducted on the formulation using a panel of human volunteers.
  • a sensory test typically involves application of the formulation to the skin of the panelists on a regular basis, such as once or twice a day, over a period of several weeks.
  • the effect of the formulation on the skin lesions can be evaluated by inspecting the skin of the panelists and assessing visually the effect on the number and/or size of the lesions.
  • the plant extracts may also undergo one or more safety, stability and/or bioavailability test prior to testing on human volunteers, for example, the Human Repeat Insult Patch Test (HRIPT).
  • HRIPT Human Repeat Insult Patch Test
  • the Tsuga extracts may be submitted to other standard tests to evaluate safety, cytotoxicity, stability, bioavailability and the like, as necessary.
  • the ability of the Tsuga extract to penetrate the skin may also be assessed, of desired, for example, by in vitro release tests (see, for example, the U.S. Center for Drug Evaluation and Research guidance document entitled "Guidance for Industry. Nonsterile Semisolid Dosage Forms. Scale-up and post-approval changes: in vitro release testing and in vivo bioequivalence documentation").
  • in vitro release tests see, for example, the U.S. Center for Drug Evaluation and Research guidance document entitled "Guidance for Industry. Nonsterile Semisolid Dosage Forms. Scale-up and post-approval changes: in vitro release testing and in vivo bioequivalence documentation").
  • in vitro release tests is conducted using an open chamber diffusion cell, such as a Franz cell, fitted with an appropriate membrane.
  • the test extract is placed on the upper side of the membrane and kept occluded to prevent solvent evaporation and compositional changes.
  • a receptor fluid such as aqueous buffer or hydro-alcoholic medium, is placed on the
  • the assay could comprise, for example, testing the ability of the collected sample to inhibit MMP- 9 activity, as the Tsuga extracts have been shown to have this activity.
  • the membrane can be a synthetic membrane, for example polysulphone, cellulose acetate or nitrate, or polytetrafluoroethylene, or it can be a skin sample, such as a sample taken from a cadaver.
  • a selected extract may need to meet certain criteria in order to meet regulatory requirements for human use. Conducting tests such as those described above, therefore, allows the suitability of an extract for human use to be assessed.
  • the present invention further provides for formulations comprising a Tsuga extract suitable for dermatological, including cosmetic, applications.
  • the formulations can optionally comprise other active agents, such as therapeutic or cosmetic agents and/or other plant extracts.
  • the formulations are prepared by standard techniques such that they have acceptable toxicity and stability.
  • the formulations are prepared by mixing a suitable amount of the Tsuga extract with a physiologically acceptable carrier or diluent.
  • the formulation comprises only the Tsuga extract and a diluent or carrier.
  • the formulation comprises the Tsuga extract and one or more thickener, excipient, binder or the like, and optionally one or more other active agent.
  • Suitable amounts of the Tsuga extract for incorporation into the dermatological formulation are generally in the range of between about 0.01% (v/v) and about 20% (v/v).
  • the dermatological formulation comprises between about 0.01% (v/v) and about 18% (v/v) of the Tsuga extract, between about 0.01% (v/v) and about 16% (v/v), between about 0.01% (v/v) and about 15% (v/v), between about 0.01% (v/v) and about 14% (v/v), between about 0.01% (v/v) and about 12% (v/v), between about 0.01% (v/v) and about 10% (v/v), between about 0.01% (v/v) and about 8% (v/v), and between about 0.01% (v/v) and about 6% (v/v) of the Tsuga extract.
  • the dermatological formulation comprises between about 0.1% (v/v) and about 20% (v/v), between about 0.1% (v/v) and about 10% (v/v), between about 0.2% (v/v) and about 20% (v/v), between about 0.4% (v/v) and about 20% (v/v), between about 0.5% (v/v) and about 20% (v/v), between about 0.5% (v/v) and about 18% (v/v), between about 0.6% (v/v) and about 15% (v/v), between about 0.8% (v/v) and about 12% (v/v), and between about 1.0% (v/v) and about 10% (v/v) of the Tsuga extract.
  • the amount of Tsuga extract for incorporation into the dermatological formulation can also be defined as % by weight.
  • suitable amounts of the Tsuga extract for incorporation into the dermatological formulation are generally in the range of between about 0.01% and about 20% by weight, for example, between about 0.01% and about 15% by weight, or between about 0.01% and about 10% by weight.
  • the dermatological formulation comprises between about 0.1% and about 18% by weight, between about 0.1% and about 16% by weight, between about 0.1% and about 15% by weight, between about 0.1% and about 14% by weight, between about 0.1% and about 12% by weight, between about 0.1% and about 10% by weight, between about 0.1% and about 8% by weight, between about 0.1% and about 6% by weight, between about 0.2% and about 20% by weight, between about 0.4% and about 20% by weight, between about 0.5% and about 20% by weight, between about 0.5% and about 18% by weight, between about 0.6% and about 15% by weight, between about 0.8% and about 12% by weight, and between about 1.0% and about 10% by weight of the Tsuga extract.
  • the dermatological formulations comprising the Tsuga extract are formulated for topical administration.
  • Such formulations may be presented as, for example, aerosol sprays, powders, sticks, granules, creams, liquid creams, mousses, pastes, gels, lotions, ointments, on sponges or cotton applicators, or as a solution or a suspension in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion, or a water- in-oil liquid emulsion.
  • hydroxypropyl cellulose starch (corn, potato, rice, wheat, quinoa), pregelatinized starch, gelatine, sucrose, acacia, alginic acid, sodium alginate, guar gum, ethyl cellulose, carboxymethylcellulose sodium, carboxymethylcellulose calcium, polyvinylpyrrolidone, methylcellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, polyethylene glycol, powdered cellulose, glucose, croscarmellose sodium, crospovidone, polacrilin potassium, sodium starch glycolate, tragacanth, calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, kaolin, mannitol, talc, cellulose acetate phthalate, polyethylene phthalate, shellac, titanium dioxide, carnauba wax, microcrystalline wax, calcium stearate, magnesium stearate,
  • Exemplary thickeners are cross-linked polyacrylate materials available under the trademark CarbopolTM (B. F. Goodrich Company), xanthan gum, carrageenan, gelatine, karaya, pectin and locust bean gum. Under certain circumstances the thickening function may be accomplished by a moisturiser component of the formulation. For instance, silicone gums and esters such as glycerol stearate have dual functionality. A thickener will usually be present in amounts from 0.1 to 20% by weight of the formulation.
  • the formulations can optionally include one or more moisturising agents, i.e. an agent that facilitates hydration of the skin by inhibiting or preventing loss of water from the skin, that absorbs water from the atmosphere and hydrates the skin, and/or that enhances the skin's ability to absorb water directly from the atmosphere.
  • moisturising agents generally minimise or prevent the skin from drying and cracking.
  • Moisturisers, when used, are typically present in an amount from about 0.01 to 20% by weight of the formulation.
  • moisturising agents include, but are not limited to, 2-hydroxyacetic acid (glycolic acid); 2-hydroxypropanoic acid (lactic acid); 2-methyl 2-hydroxypropanoic acid; 2- hydroxybutanoic acid; phenyl 2-hydroxyacetic acid; phenyl 2-methyl 2-hydroxyacetic acid; 3-phenyl 2-hydroxyacetic acid; 2,3-dihydroxypropanoic acid; 2,3,4-trihydroxybutanoic acid; 2,3,4,5,6-pentahydroxyhexanoic acid; 2-hydroxydodecanoic acid; 2,3,4,5- tetrahydroxypentanoic acid; 2,3,4,5,6,7-hexahydroxyheptanoic acid; diphenyl 2- hydroxyacetic acid; 4-hydroxymandelic acid; 4-chloromandelic acid; 3 -hydroxybutanoic acid; 4-hydroxybutanoic acid; 2-bydroxyhexanoic acid; 5-hydroxydodecanoic acid; 12- hydroxydodecanoic acid; 10-hydroxyde
  • moisturising agents include, but are not limited to, beeswax, shea butter, ceramide, borage oil (linoleic acid), tocopherol linoleate, dimethicone, glycerine, hyaluronic acid, sodium peroxylinecarbolic acid (sodium PCA), wheat protein (such as laurdimonium hydroxypropyl hydrolyzed wheat protein), primrose oil, flax seed oil and mixtures thereof.
  • the formulations may also comprise one or more preservatives.
  • Exemplary preservatives include, but are not limited to, benzoic acid and its derivatives with benzyl alcohol, benzalkonium chloride, sodium benzoate, bronopol, chlorhexidine, chlorocresol and its derivatives, ethyl alcohol, phenethyl alcohol, phenoxyethanol, potassium sorbate, diazolidinylurea, parabens such as propylparaben or methylparaben.
  • the formulations may additionally comprise one or more additives normally used in the cosmetics or pharmaceutical field, such as neutralizing agents, sunscreens, antioxidants, fillers, electrolytes, colorants, normal inorganic or organic bases or acids, fragrances, essential oils, cosmetic active principles, moisturizing agents, vitamins, essential fatty acids, sphingolipids, self-tanning compounds, such as DHA (with or without erythrulose), whitening agents such as kojic acid and arbutin, soothing and skin-protecting agents, propenetrating agents or a mixture of these.
  • additives normally used in the cosmetics or pharmaceutical field such as neutralizing agents, sunscreens, antioxidants, fillers, electrolytes, colorants, normal inorganic or organic bases or acids, fragrances, essential oils, cosmetic active principles, moisturizing agents, vitamins, essential fatty acids, sphingolipids, self-tanning compounds, such as DHA (with or without erythrulose), whitening agents such as kojic acid and arbutin, soothing and skin
  • the dermatological compositions may optionally include one or more other active agents and/or plant extracts that are intended to impart additional beneficial properties to the formulation, for example components that have auxiliary action in the treatment of acne or that provide skin benefits.
  • the dermatological formulation includes one or more additional anti-acne components, such as anti-seborrheics and anti- infectives.
  • anti-acne components include, but are not limited to, antibiotics (such as erythromycin, clindamycin and tetracyclines), antimicrobials (such as chlorexidine and benzoylperoxide), synthetic or natural substances which have been described as possessing antimicrobial activity (such as 1-pentadecanol and derivatives thereof, cedrene, caryophyllene, longifolene and thujopsene), comedolytic agents (such as tretinoin, isotretinoin, adapalene, azelaic acid, tazarotene, salicylic acid and derivatives thereof), antiinflammatory agents (such as NSAIDs (for example, acetylsalicylic acid, ibuprofen, naproxen and sulfacetamide) and steroidal anti-inflammatory agents (for example, hydrocortisone)), vitamins (such as retinoic acid and derivatives thereof), and oil or sebum control agents (such as clay silicones
  • the anti-acne components when used, can each be incorporated into the formulations of the present invention in an amount between about 0.001% and about 10 % by weight, for example, between about 0.001% and about 8 % by weight or between about 0.001% and about 5 % by weight.
  • the Tsuga extracts can be used to combat the irritant effects of retinoids and other anti-acne compounds and thus allow formulations to be prepared that comprise the extract in combination with a higher than standard amount of one or more of these compounds.
  • Retinoids are generally included in anti-acne formulations in an amount between about 0.1% and about 0.5% by weight, with the upper limit of this range being considered “high.” Accordingly, in the context of the present invention a "higher than standard amount" of a retinoid is considered to be 0.3% by weight or greater. In certain embodiments, a "higher than standard amount" of the retinoid can be considered to be 0.4% by weight or greater; 0.5 % by weight or greater, or 0.6% by weight or greater.
  • the dermatological formulation comprises one or more other plant extracts that can provide a benefit to the skin.
  • suitable plant extracts include those described in International Patent Application No. PCT/CA02/00285 (Publication No.
  • WO02/069992 and include, for example, extracts from Abelmoschus esculentus, Abies balsamea, Abies cephalonica, Abies firma, Abies lasiocarpa, Acer campestre, Acer mandshurica, Acer palmaturn "burgundy, " Acer tataricum, Acer truncatum, Achillea millefolium, Achillea ptarmica, Achillea tomentosa, Acolypha hispida, Aconitum napellus, Aconitum spp., Acorus calamus, Actaea racemosa, Actinidi colonicta, Actinidia arguta, Actinidia chinensis, Actinidia colomicta, Adansonia digitata, Adianthum radiatum, Adianthum trapezieformis, Adiantum pedatum, Adiantum tenerum, Aechmea luddemoniana
  • Cichorium intybus Cinnamomum verum, Cirsium arvense, Cissus discolor, Cistus incanus, Citinis coggriaria, Citrullus colocynthis, Citrullus lanatus, Citrus limettoides, Citrus Union, Citrus reticulata, Citrus sinensis, Citrus x paradisi, Clematis alpina, Clematis armandii, Clematis chiisanensis, Clematis rectae, Clerodendrurn speciossicum, Cobiaeum varilarturn, Coccoloba caracasana, Cocculus laurifolius, Cocos nucifera, Coix lacryma-jobi, Colocasia spp., Comus mass, Convalaria majalis, Conyza canadensis, Corchorus olitorius, Coreopsis verticillata, Coriandrum sativum, Cornus alba, Corn
  • balsamita Tanacetum cinerariifolium, Tanacetum parthenium, Tanacetum vulgare, Tapeinochilos spectabilis, Taraxacum officinale, Taraxacum officinalis, Taxodium dixticum, Taxus cuspidata, Taxus hiksii, Taxus media, Taxus x media, Tetraclinis articulata hinensis, Tetradenia riparia, Teucrium chamaedrys, Thalictrum aquilegiifolium, Thalictum flavum, Thlaspi arvense, Thuja occidentalis, Thymus camosus, Thymus cretaceus, Thymus cytridorus "aureus, Thymus fragantissimus, Thymus herba-barona, Thymus lemabarona, Thymus portugalense, Thymus praecox, Thymus praecox subsp.
  • Thymus pseudolamginosus Thymus pseudolanuginosus
  • Thymus puleglodes "lemons” Thymus puliglodes, Thymus serphylum, Thymus speciosa, Thymus thrasicus, Thymus vulgaris, Thymus vulgaris “argenteus, " Thymus vulgaris “oregano, " Thymus wooly, Thymus x citriodorus, Tiarella cordifolia, Tiarella spp., Tragopogon porrifolius, Tragopogon spp., Trambe pontica, Trevesia sungaica, Trichosanthes kirilowii, Trifolium hybridum, Trifolium incarnatum, Trifolium pannonicum, Trifolium pratense, Trifolium repens, Trigonella foenum-graecum, Triticum aestivum, Triticum aestivum subsp.
  • the dermatological compositions comprise one or more other plant extracts selected from the group of: Aconitum napellus, Acorus calamus, Alchemilla mollis, Allium cepa, Allium sativum, Allium tuberosum, Ambrosia artemisiifolia, Anethum graveolens, Anthemis tinctoria, Aronia melanocarpa (Michx.) Ell., Arctostaphylos uva-ursi, Aronia x prunifolia, Artemisia dracunculus, Avena sativa, Beta vulgaris, Beta vulgaris L. subsp.
  • Vulgare Hypomyces lactifluorum, Juniperus communis L., Lentinus edodes, Lotus corniculatus, Manihot esculenta, Matricaria recutita, Melilotus albus, Melilotus alba Medik., Melissa officinalis, Mentha x piperita, Oenothera biennis, Pastinaca sativa L., Petroselinum crispum, Phaseolus vulgaris, Physalis philadelphica, Phytolacca decandra, Phytolacca decandra syn. P.
  • the dermatological compositions comprise one or more other plant extracts selected from the group of: Caspicum annuum, Chenopodium quinoa, Geranium cantabrigiens, Glycyrrhiza glabra, Juniperus communis, Lotus corniculatus, Melilotus albus, Melissa officinalis, Pastinaca sativa L, Potentilla anserina, Rhus thyphina, Triticosecale sp., Vaccinium sp, Zea mays and Zingiber officinale.
  • plant extracts selected from the group of: Caspicum annuum, Chenopodium quinoa, Geranium cantabrigiens, Glycyrrhiza glabra, Juniperus communis, Lotus corniculatus, Melilotus albus, Melissa officinalis, Pastinaca sativa L, Potentilla anserina, Rhus thyphina, Triticosecale sp., Vaccinium s
  • plant derived components or extracts that may be added to the dermatological formulations in certain embodiments of the invention include jojoba oil, tea tree oil or extract, aloe, Spirea spp and Salix spp.
  • the dermatological formulations intended for topical application can be packaged in a suitable container to suit the viscosity and intended use.
  • a lotion, fluid cream, foam or mousse can be packaged in a bottle or a roll-ball applicator, a capsule, a propellant- driven aerosol device, a spray or a container fitted with a pump suitable for finger operation.
  • the composition is a cream or paste, it can simply be stored in a non-deformable bottle or squeeze container, such as a tube or a lidded jar.
  • the present invention provides for the use of the Tsuga extracts and formulations comprising same to treat comedones and/or acne present on the skin of a subject.
  • the skin can be facial skin or non-facial skin (for example, arms, legs, hands, chest, back, buttocks and other areas prone to lesions).
  • the present invention provides for the use of Tsuga extracts to decrease comedones in a subject.
  • the present invention provides for the use of Tsuga extracts to treat acne.
  • the extracts may decrease comedones and/or other skin lesions in the subject under treatment.
  • Examples of acne that may be treated in accordance with certain embodiments of the present invention include acne vulgaris, comedonal acne, papulopustular acne, papulocomedonal acne, nodulocystic acne, acne conglobata, acne keloid of the back of the neck, recurrent acne miliaria, acne necrotica, acne neonatorum, occupational acne, acne rosacea, senile acne, solar acne and acne medicamentosa.
  • the present invention provides for the use of the Tsuga extracts to treat acne vulgaris.
  • the present invention also provides for the use of the Tsuga extracts in the prevention of acne and/or comedones.
  • the Tsuga extracts may be used in the treatment of skin having a tendency toward acne in order to combat the appearance of skin lesions, such as comedones, papules or pustules.
  • the invention provides for the use of the Tsuga extracts in formulations comprising anti-acne compounds that can exert irritant or inflammatory effects on the skin of the user, for example, retinoids, in order to ameliorate the irritant/inflammatory effects of these compounds.
  • the invention provides for the use of the Tsuga extracts in dermatological formulations for sensitive skins.
  • the Tsuga extracts also possess healing properties as shown herein, which allow the extracts to additionally facilitate the healing of, and/or reduce the formation of scars that may result from, acneic lesions, such as comedones, papules or pustules.
  • the present invention additionally provides for pharmaceutical or cosmetic packs or kits comprising the Tsuga extracts.
  • the kit comprises the Tsuga extract or a formulation comprising the Tsuga extract, as described above, in a suitable container or containers.
  • the Tsuga extract or formulation thereof can be provided in a format or container that facilitates its application to the affected area of a subject.
  • the Tsuga extract or formulation can be provided as lotion or fluid cream packaged in a squeezable container, a container equipped with a nozzle or roll-ball applicator, a spray bottle or aerosol, or a container fitted with a pump suitable for finger operation.
  • the kit can optionally further comprise one or more suitable implements to facilitate application of the Tsuga extract or formulation.
  • the kit can comprise sufficient amounts of the Tsuga extract or formulation for application to the subject for a prescribed length of time, for example, for a length of time between one and twelve months.
  • the kit can further provide an appropriate usage regimen over a prescribed period of time for the Tsuga extract or formulation, for example in the form of a set of instructions, generally written instructions.
  • kits There may also be associated with the kit a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceutical or cosmetic products, which notice reflects approval by the agency of manufacture, use or sale for human or animal administration.
  • the solvents used in this Example were: butylene glycol (100%), butylene glycol/water (50/50, v/v), butylene glycol/water (20/80, v/v); ethanol (100%), ethanol/water (85/15, v/v), ethanol/water (50/50, v/v); water (100%); 1,3 -propanediol (100%); 1,3-propanediol/water (50/50, v/v) and 1,3-propanediol/water (20/80, v/v).
  • Glycol extracts such as butylenes glycol or 1,3 -propanediol extracts, for example, can be included directly into formulations intended for topical application.
  • Ethanol extracts may undergo one or more additional steps, such as C0 2 extraction, prior to incorporation into formulations intended for topical application.
  • Tsuga canadensis extract The following is an example of a specific protocol that was employed to prepare a Tsuga canadensis extract.
  • 100ml of a 50:50 butylene glycol: water was added.
  • the mixture was thoroughly stirred and macerated for 4 hours at room temperature.
  • the resulting mix was filtered through 40 ⁇ to 1.2 ⁇ filters to obtain a suitable extract for further analysis.
  • the Tsuga canadensis extracts 207-20252, 207-20156, 207-20376 and 207-20010 tested in the following examples are all extracts prepared from needles and small branches of Tsuga canadensis using 50:50 butylene glycohwater as the extraction solvent following the protocol outlined above.
  • the extracts differed in the individual Tsuga canadensis tree that the plant material came from and in the time that the plant material was harvested.
  • the Tsuga canadensis extract 207/2-20376 also tested in the following examples is an extract prepared from needles of Tsuga canadensis using 50:50 1.3-propanediol:water as the extraction solvent following the protocol outlined above.
  • Analysis of the results from the analytical scale preparation allows for the selection of appropriate plant materials for the large-scale extraction.
  • the selection includes a decision regarding part of the Tsuga tree and quantity of dried material needed to obtain a sufficient yield on a large scale.
  • the selection also involves a choice of solvent system for an active extract.
  • the extraction protocol is essentially the same as the procedure for the analytical preparation except for the filtration process.
  • the dried and pulverized material (2-3 Kg for large scale) is extracted repeatedly (maceration / percolation) with solvent (3 x 2 - 20 1) at room temperature for 24-72 h, based on the analytical scale yield of extraction results.
  • the resulting extract is then passed through a 60 mesh filter and then may be filtered through 10 to lOOkDa ultrafiltration column or on a 0.1 to 1 ⁇ ceramic column.
  • Non-limiting examples of large scale extraction preparations of extracts from Tsuga canadensis are provided below.
  • This example demonstrates the potential of Tsuga canadensis extracts to reduce a UV- induced inflammatory response in human skin keratinocytes after irradiation with a Solar Light Simulator.
  • the anti-inflammatory effect was evaluated by the inhibition of pro- inflammatory cytokines found in the media after the irradiation.
  • Keratinocytes were first grown in 175cm 2 to reach about 80% confluence then trypsinized and plated at 1X10 5 cells/well in a 24-well plate. After 24 to 48 hours (80% confluence), the extracts or controls were added to cells at a non-cytotoxic concentration. After 24 hours, media was removed, cells were washed with 1ml of HBSS and irradiated with 10 J/cm 2 of UVB. A corresponding non-irradiated plate was prepared at the same time and was submitted to all the same steps.
  • HBSS HBSS was removed and media added with the corresponding samples, (1 ml). Cells were incubated for another 24 hours at 37 °C, 5% C0 2 . Media from each well was recovered for ELISA testing, and Alamar Blue was added to the cells to evaluate viability. The protocol of each ELISA was performed according to the instructions provided in each kit.
  • Tsuga canadensis extract 207-20376 The results for Tsuga canadensis extract 207-20376 are presented in Figure 1 and are expressed as the % inhibition of IL-6 release after UV irradiation.
  • EXAMPLE III Non- Irritating Behaviour of Tsuga Extracts
  • This example provides results showing the non-irritating quality of the Tsuga extracts.
  • the amount of interleukin-8 (IL-8) released in the following assay is used to quantify a possible irritating reaction after exposure of keratinocytes to the Tsuga extract.
  • IL-8 Release of IL-8 was evaluated on human skin keratinocytes (Cascade Biologies, Portland, OR, catalog number C-005) and measured using the Quantikine hIL8 ELISA kit (R&D Systems, Minneapolis, MN, catalog number D8000C). Keratinocytes were first grown in a 96-well plate using complete medium M154 (M154 + HKGS cat S-001 from Cascade Biologies). This medium was used as a negative (non-irritating) control, while 2.5 ⁇ phorbol 12-myristate 13-acetate (PMA) (Sigma-Aldrich Canada, Oakville, Ontario) was used as a positive (irritating) control. All extracts and controls were diluted in complete medium M154.
  • M154 M154 + HKGS cat S-001 from Cascade Biologies
  • PMA phorbol 12-myristate 13-acetate
  • Cells were seeded into 96-well plates at a concentration of 8 X 10 3 cells/well in complete Ml 54 medium and plates were incubated for 48 hours at 37 °C in a humidified 5% C0 2 atmosphere. The medium was removed and 200 ⁇ 1 of Tsuga extract or control were added to the wells (all performed in duplicate) and then the plates were incubated for 48 hours at 37 °C in a humidified 5% C0 2 atmosphere. ELISA was performed using following the manufacturer's recommendations (R&D Systems). The absorbance was read at 450 nm on the Spectrafluor Plus plate reader (Tecan).
  • Tsuga canadensis extract 207-20252 stimulated 2.2pg/ml of IL-8 release at a concentration of 200 ⁇ g/ml, while PMA stimulated 282pg/ml of IL-8 release at a concentration of 5 ⁇ .
  • the basal level was evaluated at 18pg/ml.
  • EXAMPLE IV Wound Healing Effect of Tsuga Extracts in vitro This example demonstrates the increase in wound healing by Tsuga canadensis extract in the "scratch assay.” The increase in wound healing is evaluated by the increased migration rate of keratinocytes and/or reduced area of scratch evaluated each day for four days.
  • Keratinocytes were first grown in 175cm 2 to reach about 80% confluence, then trypsinized.
  • Tsuga canadensis extract 207-20376 are presented in Figure 3 and are expressed as the % migration of the keratinocytes for each day of the experiment.
  • creams were prepared using a 50:50 butylene glycokwater Tsuga canadensis extract prepared as described in Example I.
  • the creams were as follows (all % are w/w):
  • Cream #1 0.5% retinol
  • Cream #2 0.5% retinol and 5% Tsuga canadensis extract
  • Cream #3 1% retinol
  • Cream #4 1% retinol and 5% Tsuga canadensis extract
  • the patient was a healthy female volunteer age 39. She applied all four creams (#1 to #4, above) twice a day in a blinded manner to her forearms. She noted any sign of irritation. The study was stopped when the redness due to irritation was too strong and discomfort appeared.
  • EXAMPLE VI Determination of Irritation or Sensitization by Tsuga Extracts on Human Skin
  • HRIPT Human Repeat Insult Patch Test
  • Tsuga canadensis extract 207-20156 produced no signs of cutaneous irritation or skin sensitization in either the induction phase or the challenge phase of the test.
  • the extract is therefore considered non-irritant and potentially hypo- allergenic.
  • the test product may bear the claim "Tested under control of a dermatologist.”
  • EXAMPLE VII Determination of Irritation or Sensitization by Tsuga Extracts on Human Skin II 54 volunteers were selected for the study. The volunteers were men and women of ages 20 to 53. The agent, Tsuga canadensis extract 207/2-20376 10% (v/v) in a base cream, was applied to the skin of the volunteers repeatedly using 10 patches over a period of 3 weeks. The patches used in the study were TruMed® semi-occlusive, cotton "BBA149-129 Absorbent" with "3M1530 tape” adhesive backing. After a rest period (incubation phase) varying from 10 to 14 days, a challenge phase was conducted. The patch was applied for 48 hours and removed. The test sites were cleaned and examined for any signs of intolerance or irritation by a dermatologist.
  • Tsuga canadensis extract 207/2-20376 10% (v/v) produced no signs of cutaneous irritation or skin sensitization in either the induction phase or the challenge phase of the test.
  • the extract is therefore considered non-irritant and potentially hypo-allergenic.
  • the test product may bear the claim "Tested under control of a dermatologist.”
  • EXAMPLE VIII Exemplary Dermatological Formulations Comprising a Tsuga Extract
  • the following formulations comprising a Tsuga canadensis extract are non-limiting examples of suitable formulations for human efficacy studies (such as those described in Example X).
  • the formulations can be modified for commercial use as is known in the art. All % are w/w.
  • Triethanolamine (sol. 25%) 0.10%
  • formulations comprising Tsuga canadensis extracts include those in which the extract is added in an amount between 0.1 and 10% (w/w) into a pre-made skin formulation.
  • a cream base a lotion, an aftershave lotion, a soothing mask, or petrolatum jelly.
  • Staphyloccocus epidermidis ATCC 122278 and Propionibacterium acnes (ATCC 6919) were used to challenge different concentrations of Tsuga canadensis extract 207-20156 (diluted in water).
  • S. epidermidis was inoculated at 1.5 X 10 6 bacteria/ml in 10ml of diluted extract and P. acnes was inoculated at 1 X 10 6 bacteria/ml in 10ml of diluted extract. All samples of extract or vehicle (50:50 butylene glycokwater) were incubated at 37°C and evaluated at 0, 7, 14 and 28 days.
  • Experiments involving P. acnes were conducted under anaerobic conditions. The efficacy was analyzed by determining the colony forming units (CFU) per g on tryptic soy agar.
  • CFU colony forming units
  • EXAMPLE X Clinical Trials to Evaluate the Effect of the Tsuga Extracts on Skin Lesions The efficacy of a Tsuga canadensis extract in decreasing acneic lesions in volunteers was evaluated in a small clinical trial.
  • Tsuga canadensis extract 207-20376 was used in this trial and was prepared as described in Example I with respect to extract 207-20156.
  • the extract was formulated into a cream having the following composition:
  • the objective of this study was to evaluate the in vivo efficacy of a product for skins with acneic tendency in comparison with its placebo.
  • the products tested were coded Product A and Product B.
  • Product A cream formulation without any extract (control or placebo).
  • Product B cream formulation comprising the Tsuga canadensis extract.
  • the study was carried out as a "double blind test.” Neither the participating subjects nor the investigator were aware of the type of product being applied throughout the study.
  • the study was a comparative study in which the results obtained at one treated area by one of the products were compared with those obtained at another treated area with the other product. The subjects served as their own reference and results obtained at various assessment times were compared with those obtained at TO.
  • Skin at assessed area is healthy (free of psoriasis, eczema, erythema, oedema, scars, wounds).
  • Inclusion criteria Specific Having an oily skin with acneic tendency
  • a chronic medicinal treatment comprising any of the following products taken orally: aspirin-based products, anti-inflammatories, antihistamines, corticotherapy (the only medication permitted is paracetamol/tylenol). - Having applied a product and/or make up, including the usual cleanser (face cleaned with water only) to the studied area the day of the measurements.
  • Non-inclusion criteria Specific Having applied cosmetic products with anti-seborrheic aims or cosmetics for oily skin in the 2 weeks before the start of the study.
  • the selection of the half-face to be treated by one or the other product was determined at random for each subject. This randomization was carried out using software designed for this purpose.
  • the evaluation was carried out under a controlled temperature and relative humidity (temperature: 21 ⁇ 1°C, hygrometry: 45+5 %).
  • the lighting was provided by a ceiling lamp as well as a movable lamp to avoid shadows on the face.
  • Subject Each subject was evaluated sitting on a chair facing the cosmetologist. The subject was wearing a paper cap and a cloak. A 20-minute period of acclimatisation in the air- conditioned room was respected. Studied areas: each half-face
  • the cosmetologist evaluated in detail the number of retentional lesions (closed comedones and opened comedones) and/or inflammatory lesions (papules, pustules and excoriated lesions) and the number obtained for each type of lesion was noted. In cases where a large number of retentional lesions were observed, the evaluation of these lesions was made on a part of the face. This area was chosen at the discretion of the cosmetologist and specified in the observations record.
  • Verification of the normality of the distributions was evaluated using the Shapiro-Wilk test, threshold at 1%, for each product.
  • the statistical analysis of the evolution of the measured parameters during the study for each product was performed using the Student test (normality of distributions checked) or with the Wilcoxon test (normality of the distributions rejected).
  • the significance threshold is fixed at 5%.
  • Figure 3 A shows the evolution of lesions after 28 days of application of Product B
  • Figure 3B shows the evolution of lesions after 42 days of application of Product B.
  • the results show a statistically significant decrease in the amount of closed comedones after just 28 days of application of Product B.

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Abstract

L'invention concerne des extraits issus de plantes du genre Tsuga présentant une activité comédolytique et/ou anti-acné. Les extraits de Tsuga conviennent pour le traitement de troubles cutanés associés à la formation de comédons, tels que l'acné. L'invention concerne également l'utilisation des extraits de Tsuga dans la prévention de l'acné et/ou des comédons. Les extraits de Tsuga possèdent également des propriétés anti-inflammatoires qui permettent aux extraits de lutter additionnellement contre les effets irritants ou inflammatoires d'autres composés de traitement de l'acné (tels que les rétinoïdes) et/ou d'être incorporés dans des formulations dermatologiques pour peaux sensibles. De plus, les extraits de Tsuga possèdent des propriétés de cicatrisation qui peuvent faciliter la guérison de lésions acnéiques et/ou réduire les cicatrices provenant de lésions acnéiques.
PCT/CA2012/050161 2011-03-25 2012-03-15 Extraits de plantes du genre tsuga et leurs utilisations dans le traitement de troubles cutanés Ceased WO2012129683A1 (fr)

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* Cited by examiner, † Cited by third party
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KR20150112439A (ko) * 2014-03-28 2015-10-07 (주)보광코리아 여드름 예방 및 치료용 약학적 조성물, 피부 외용제 및 꽃범의 꼬리 추출물의 추출 방법
WO2016149424A1 (fr) * 2015-03-16 2016-09-22 Nature's Sunshine Products, Inc. Phytocomplexes présentant de multiples activités antioxydantes synergiques, utiles dans des aliments, des compléments alimentaires, des produits cosmétiques et des préparations pharmaceutiques
FR3042709A1 (fr) * 2015-10-21 2017-04-28 Laboratoires De Biologie Vegetale Yves Rocher Utilisation cosmetique d'un extrait de ledum groenlandicum
WO2018075086A1 (fr) * 2016-10-21 2018-04-26 Cosmetic Research Laboraties Llc Extrait pour le traitement d'affections cutanées
US9968703B1 (en) 2017-06-15 2018-05-15 Roland C. Schauer Burn wound composition and methods for treating burn wounds
CN109999175A (zh) * 2019-04-10 2019-07-12 孙和平 一种用于消除暗疮脓肿皮炎感染粉刺溃疡的复合制剂及其制备方法
US10806769B2 (en) 2016-03-31 2020-10-20 Gojo Industries, Inc. Antimicrobial peptide stimulating cleansing composition
US10874700B2 (en) 2016-03-31 2020-12-29 Gojo Industries, Inc. Sanitizer composition with probiotic/prebiotic active ingredient
CN112931747A (zh) * 2021-02-05 2021-06-11 西南科技大学 一种白芷的高能电子束辐照储藏工艺
FR3124084A1 (fr) * 2021-06-21 2022-12-23 Laboratoires De Biologie Vegetale Yves Rocher Utilisation cosmetique d’un extrait de phacelie, notamment pour le soin des phaneres
FR3124083A1 (fr) * 2021-06-21 2022-12-23 Laboratoires De Biologie Vegetale Yves Rocher Utilisation cosmetique d’un extrait de phacelie
US11564879B2 (en) 2016-11-23 2023-01-31 Gojo Industries, Inc. Sanitizer composition with probiotic/prebiotic active ingredient
US20230158093A1 (en) * 2020-05-24 2023-05-25 Phoenix Biotechnology, Inc. Extract containing oleandrin and method of production thereof
CN116236430A (zh) * 2023-03-29 2023-06-09 上海仁田生物科技有限公司 具有皮肤屏障修复功能的组合物及应用
JP2023527979A (ja) * 2020-05-24 2023-07-03 フェニックス・バイオテクノロジー・インコーポレイテッド オレアンドリンを含む抽出物及びそれを生成する方法
CN117064804A (zh) * 2023-06-27 2023-11-17 广州普吉丽生物科技有限公司 一种保湿嫩肤精华水及其制备方法
US12539324B2 (en) 2016-03-31 2026-02-03 Gojo Industries, Inc. Antimicrobial peptide stimulating sanitizing composition

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006039807A1 (fr) * 2004-10-15 2006-04-20 Biopharmacopae Design International Inc. Methodes et compositions therapeutiques comprenant des extraits de plantes pour le traitement du cancer
WO2009121168A1 (fr) * 2008-04-01 2009-10-08 Biopharmacopae Design International Inc. Extraits de plantes du genre tsuga et utilisations de ceux-ci dans le traitement de l’inflammation, de l’irritation et/ou de l’infection

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006039807A1 (fr) * 2004-10-15 2006-04-20 Biopharmacopae Design International Inc. Methodes et compositions therapeutiques comprenant des extraits de plantes pour le traitement du cancer
WO2009121168A1 (fr) * 2008-04-01 2009-10-08 Biopharmacopae Design International Inc. Extraits de plantes du genre tsuga et utilisations de ceux-ci dans le traitement de l’inflammation, de l’irritation et/ou de l’infection

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BLACK M.J.: "Algonquin Ethnobotany: an interpretation of Aboriginal Adaptation in South Western Quebec", MERCURY SERIES NUMBER 65, 1980, OTTAWA, pages 125 *
KERI J. ET AL.: "An update on the management of acne vulgaris", CLINICAL, COSMETIC AND INVESTIGATIONAL DERMATOLOGY, vol. 2, 2009, pages 105 - 110 *
TURNER N.J. ET AL.: "Ethnobotany of the Hesquiat Indians of Vancouver Island", 1982, VICTORIA., pages 44 - 45 *

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US10434131B2 (en) 2015-03-16 2019-10-08 Nature's Sunshine Products, Inc. Phytocomplexes exhibiting multiple, synergistic antioxidant activities useful in foods, dietary supplements, cosmetics and pharmaceutical preparations
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US12539324B2 (en) 2016-03-31 2026-02-03 Gojo Industries, Inc. Antimicrobial peptide stimulating sanitizing composition
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