EP4405045A1 - Compositions cosmétiques comprenant du cannabidiol et un extrait de zingiber - Google Patents

Compositions cosmétiques comprenant du cannabidiol et un extrait de zingiber

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Publication number
EP4405045A1
EP4405045A1 EP22793528.5A EP22793528A EP4405045A1 EP 4405045 A1 EP4405045 A1 EP 4405045A1 EP 22793528 A EP22793528 A EP 22793528A EP 4405045 A1 EP4405045 A1 EP 4405045A1
Authority
EP
European Patent Office
Prior art keywords
extract
cbd
weight
skin
zingiber
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP22793528.5A
Other languages
German (de)
English (en)
Inventor
Christoph Abels
Michael Soeberdt
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bionorica SE
Original Assignee
Bionorica SE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bionorica SE filed Critical Bionorica SE
Publication of EP4405045A1 publication Critical patent/EP4405045A1/fr
Pending legal-status Critical Current

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Classifications

    • 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
    • A61P17/06—Antipsoriatics
    • 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/345—Alcohols containing more than one hydroxy group
    • 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • 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
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • 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
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • 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
    • A61P17/04—Antipruritics
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • 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
    • A61Q19/005—Preparations for sensitive skin
    • 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
    • A61Q19/007—Preparations for dry skin
    • 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
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the present invention relates to cosmetic compositions of cannabidiol (CBD) and an extract of Zingiber, preferably Zingiber officinale Roscoe rhizoma.
  • CBD cannabidiol
  • Zingiber preferably Zingiber officinale Roscoe rhizoma.
  • CBD cannabidiol
  • cannabidiol a cannabinoid derived from female hemp (cannabis)
  • CBD cannabidiol
  • Cannabisbis cannabinoid derived from female hemp
  • Cannabisbis has attracted interest for topical use on the skin due to its anti-inflammatory properties.
  • cannabis is classified as a narcotic and its use is heavily regulated or prohibited.
  • the production of synthetic cannabidiol is also expensive.
  • cannabidiol in the medical and cosmetic field have already been described, including analgesic, anti-inflammatory, antimicrobial and sebostatic effects.
  • Atopic eczema is a chronic, inflammatory skin disease that cannot be cured.
  • the characteristic symptoms are severe skin dryness combined with scaling and itching and, if the condition worsens, eczema, especially in the bends, with reddening and weeping.
  • Zingiber (ginger) is traditionally used in the treatment of arthrosis and rheumatism and to relieve pain, inflammation and colds.
  • the endocannabinoid system comprises cannabinoid receptors (CB1 and CB2, TRPV1 and possibly also GPR55), arachidonic acid-derived ligands and their regulatory enzymes.
  • CB1 and CB2, TRPV1 and possibly also GPR55 cannabinoid receptors
  • arachidonic acid-derived ligands arachidonic acid-derived ligands
  • GPR55 cannabinoid receptors
  • arachidonic acid-derived ligands and their regulatory enzymes.
  • the importance of the endocannabinoid system in peripheral tissues has been demonstrated in numerous recent studies (Di Marzo V. Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov. 2008 May; 7(5):438-55). While activation of the peripheral endocannabinoid system is commonly associated with anti-inflammatory and immunosuppressive effects, the role of the ECS in the skin is more complex.
  • CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids Proc Natl Acad Sci USA 2005 Feb 22;102(8):3093-8).
  • Falcarinol is a covalent cannabinoid CB1 receptor antagonist and induces pro-allergic effects in skin. Biochem. Pharmacol 2010, 79: 1815-1826). Raising the tone of the endogenous cannabinoid system leads to antipruritic effects.
  • Increasing the local concentration of AEA by blocking FAAH or by Palmitoylethanolamide (PEA) by inhibiting N-acylethanolamine-hydrolyzing acid amidase (NAAA) leads to antipruritic effects in various animal models (Toth KF, Adam D, Biro T, Olah A. Cannabinoid Signaling in the Skin: Therapeutic Potential of the "C(ut )annabinoid" System. Molecules. 2019, 24: 918.
  • the object of the present invention was to provide a composition or combination or mixture that combines the positive effects of CBD and a Zzz / gz / v extract on the skin with the lowest possible proportion of CBD in order to keep costs low and narcotics law to avoid problems. Since CBD hardly penetrates the skin and consequently cannot produce any effect in the skin, the present invention provides a composition which surprisingly penetrates the skin with low concentrations of CBD and Zzz/gz/v extract and thus produce an effect can, although a clinical study detailed below showed no effect in much higher concentrations of CBD.
  • a cosmetic composition will be made available that has an anti-inflammatory and antipruritic effect with a very low proportion of CBD.
  • the composition of the invention with CBD and a Z / z / / Ac / 'extract both an anti-inflammatory and an antipruritic (itch-relieving) effect, for example in people - without being limited to - with neurodermatitis-prone skin or with atopic eczema, although this in the low concentration of CBD was not to be expected due to the disclosed study results on CBD by Botanix, among others, and the unknown mechanism of action.
  • the "Zzzz z/zcz'extract" may be synonymously referred to with the word ..zingibe or "ginger”; Zingiber extract is used in the present invention.
  • CBD chemical structure of the CBD, which (even at high concentrations, 4 and 5% respectively) did not produce the desired effect.
  • the structures of Zingiber's pungent substances preferably those of gingerol and shogaol derivatives as well as zingiberene and ar-curcumene, show a high structural similarity to CBD.
  • the aliphatic side chains (C5-C10) and the structural unit connected by the isopropyl/isopropylene function and connected via seven carbons suggest a similar activity and the synergistic effects observed according to the invention were therefore not to be expected, since the above-mentioned study with CBD had no effect had shown.
  • an anti-inflammatory effect is achieved by a surprisingly clear synergistic inhibition of the activation of the nuclear factor 'kappa light chain enhancer' of activated B cells (NF-KB) when the combination of CBD and Zzzz z/ v extract.
  • NF-KB nuclear factor 'kappa light chain enhancer' of activated B cells
  • the combination of Zzzz z/zcz' extract and CBD would have synergistic anti-inflammatory effects.
  • the combination of the two active ingredients did not lead to increased cytotoxicity.
  • NF- ⁇ B is a transcription factor that plays an important role in inflammatory processes in the skin. NF- ⁇ B influences the transcription of genes by binding to regulatory sections of DNA.
  • NF- ⁇ B Activation of NF- ⁇ B results in increased transcription of pro-inflammatory genes and genes that induce or exacerbate pruritus.
  • the transcribed proinflammatory cytokines include IL-lß, IL-6, IL-8 and TNF- ⁇ .
  • Inhibition of activation of NF- ⁇ B and the resultant reduced release of pruritogenic cytokines such as TSLP and IL-31 by the combination of CBD and Zzzz z/v extract according to the invention therefore also leads to antipruritic, ie itching-relieving effects, in addition to anti-inflammatory effects.
  • Pruritus (from the Latin prurire, "to itch") is an uncomfortable sensation on the skin that causes an urge to scratch or rub the itchy area called itchiness. Itching agents can both directly stimulate the endings of itch-sensitive nerves in the epidermis (upper skin) and act indirectly on these nerves by triggering an inflammatory response in keratinocytes, the main component of the epidermis. Recent work in cell and molecular biology has also shown that scratching or rubbing also activates the complex network of nervous and immune systems in the skin, which can strengthen the defense against potentially harmful substances. In particular, skin diseases of the epidermis are associated with itching.
  • a high concentration of externally supplied CBD could thus lead to a local lipid shift, including components of the endocannabinoid system such as anandamide, on or in the cell and disrupt the homeostasis of the various endocannabinoids that are important for the anti-inflammatory tone of the system , so that if necessary negative effects outweigh the positive effects.
  • the company Botanix more patients in the placebo group (without CBD) reached the primary endpoint than in the verum group with CBD (18.9% versus 12.1%).
  • the active ingredients contained in the formulation of a drug or cosmetic must first be applied to the skin from the container in the formulation. Thereafter, the active ingredients must be released from the formulation and penetrate through the horny layer, which consists of comeocytes and a lamellar lipid layer, into the epidermis with the keratinocytes and the sensory nerve fibers. As already described, it is only there that an effect can be achieved that reduces itching in inflammatory skin diseases such as e.g. B. atopic eczema, lindem. In the case of lipophilic active substances such as CBD or the substances contained in the Zzzz z/zcz extract, e.g. B.
  • ginger, shogaole this is a challenge, both in terms of the stability of the formulation, the stability of the active ingredients and in terms of a possible interaction of the active ingredients with each other, which then leads to reduced effectiveness in the epidermis on the keratinocytes or sensory nerve fibers, so that no anti-inflammatory or antipruritic effect occurs.
  • it is a challenge to transfer the effects observed in vitro, ie in particular the synergistic effects in certain ratios, to the clinical (in vivo) situation.
  • the Zingiber extracts used according to the invention so-called multi-substance mixtures, and the other substances contained therein are also of particular importance.
  • the present invention was also able to achieve improved penetration and thus a reduction in the active substance concentrations used by using suitable Zingiber extracts or combinations thereof, without the effectiveness being impaired.
  • the present invention thus relates to a cosmetic composition
  • a cosmetic composition comprising a) cannabidiol and b) an extract from zingiber, characterized in that the extract from zingiber is a lipophilic extract, an alcoholic extract, a CCE extract or the zingiber from the rhizome of zingiber, preferably originates from Zingiber officinale Roscoe rhizoma.
  • CBD is synthetically produced or of plant origin. In a preferred embodiment, synthetic CBD is used.
  • CBD is a cannabinoid (CAS 13956-29-1) with the following formula:
  • CBD can be obtained by methods that are well known, either by extraction from Cannabis sativa (e.g. as described in EP3799877 or US9,950,976), by fermentation (e.g. as described in WO2016/010827) or produced synthetically (e.g. as described in WO2020/229891, WO2020/169135 or WO2020/099283).
  • CBD can also be obtained as a commercially available active ingredient from manufacturers such as CBDepot, Teplice, Czech Republic or Purisys, Athens, GA, USA.
  • the composition according to the invention comprises 0.001-3% by weight (wt.%) CBD, more preferably 0.001-0.5 wt.% CBD, more preferably about 0.01-0.5 wt.% CBD, even more preferably 0.05 -0.1% by weight CBD, based on the weight of the total composition.
  • “Ca” means that the value includes a deviation of up to +/-20%.
  • the Zzrfgz'Zer extract used according to the invention can be a commercially available extract (produced as, for example, in US 2011/280976 or Mesomo MC et al., The Journal of Supercritical Fluids 2013, 80, 44-49). Suitable sources are Zingiber officinale Roscoe, where the extract can be obtained from the underground part of the plant (rootstock/rhizome). Zingiber officinale Roscoe is preferred.
  • the extraction methods are well known and can be used, for example, with organic solvents such as alcohols (alcoholic extracts, e.g. methanol, ethanol, isopropanol), aqueous solutions of alcohols (e.g.
  • methanol, ethanol, isopropanol alkanes (e.g. pentane, hexane, heptane), chlorinated hydrocarbons (e.g. chloroform, methylene chloride), ketones (e.g. methyl ethyl ketone, acetone), esters (e.g. ethyl acetate), mixtures of alcohols and esters (e.g. methanol and ethyl acetate) or by extraction with supercritical carbon dioxide (CO2).
  • Lipophilic extracts are preferred.
  • a lipophilic extract is preferably prepared using ethanol, acetone, ethyl acetate, heptane or supercritical CO2.
  • extraction with supercritical carbon dioxide is particularly preferred, since natural source carbonic acid can be used and the extract can be obtained gently and in a particularly pure manner.
  • the solvent CO2 can be easily removed without leaving any residue and recycled in a closed loop system.
  • the Zingiber CO2 extract can be obtained as a commercially available extract from manufacturers such as Mane Kancor Ingredients Private Limited, Kochi, Huawei, India or FLAVEX Naturextracts GmbH, Rehlingen, Germany.
  • the extract from Zingiber is preferably a lipophilic extract.
  • the extract from zingiber is particularly preferably an extract which is obtained using supercritical CO2.
  • a pungent content of the extract between 1-50%, preferably between 20-50% and particularly preferably between 40-50% (by weight) is also preferred.
  • Peptt substances within the meaning of the invention are ginger oil, shogaol, zingerone, ginger diols, dehydrogingerdiones and paradol.
  • the pungent ingredients include [6] gingerol, [8] gingerol, [10] gingerol, [6] shogaol, [8] shogaol, [10] shogaol and zingerone:
  • the composition of the lipophilic Zzzz z/zcz extract used differs significantly from pure essential oil extracts or distillates of this plant (Mahboubi M, Clinical Phytoscience 2019, 5, Article number: 6).
  • a lipophilic extract preferably obtained by extraction with supercritical CO2, contains above all the so-called spicy substance fraction (HagerROM Hagers Handbuch der Drugs und Arznei für - Zingiber HN: 2033300, page 7) of ginger, which is not volatile in water vapor and is absent in pure essential oil fractions .
  • the characteristic ingredients of the lipophilic extract are primarily the homologous series of gingerol and shogaol, in particular [6]-gingerol, [8]-gingerol, [10]-gingerol, [6]-shogaol, [8]-shogaol, [10 ]-Shogaol as well as Zingeron and Zingiberen.
  • the proportion of pungent substances outweighs that of the essential oil many times over. For example, for Zingiber CO2 extracts, a ratio of essential oil to [6]-gingerol from 1:7-10 (Mahboubi M, Clinical Phytoscience 2019, 5, Article number: 6).
  • the cosmetic composition comprises the components CBD and zzz/z/zcz extract in the weight ratios 1:100 to 1:1; preferably 1:10 to 1:2; particularly preferably 1:5 to 1:2.
  • the composition of the invention preferably comprises 0.001-3% by weight CBD, more preferably 0.001-0.5% by weight CBD, more preferably about 0.01-0.5% by weight CBD, even more preferably 0.05- 0.1% by weight CBD, based on the weight of the total composition, and 0.001 - 5% by weight Zzz/ z/zcz extract, preferably 0.01 - 2% by weight Zzz/ z/zcz extract, particularly preferably 0 0.05-0.5% by weight of Zingi/icv extract, each based on the weight of the total composition, and in the weight ratios CBD:Zzz/z/zcz extract described above.
  • Zzzzgz7>er CO2 extracts are particularly preferred, which include the following substances: 15-30% by weight [6]-gingerol, 3-10% by weight [8]-gingerol, 3-10% by weight [10 ]-gingerol, 0.5-4% wt. [6]-shogaol, 0.03-1.3% wt. [8]-shogaol, 0.03-1% wt. [10]-shogaol , 0.01-1% by weight Zingeron, with the ginger oil content being 24-50% by weight and the shogaol content being 0.5-6% by weight.
  • a Zingiber CO2 extract comprises: 25-30% by weight [6] gingerol, 5-10% by weight [8] gingerol, 5-10% by weight [10] gingerol, 1, 5-4 wt% [6] shogaol, 0.3-1.3 wt% [8] shogaol, 0.03-1 wt% [10] shogaol, 0.01-1 wt% Zingeron, , where the proportion of ginger oil is 35-50% by weight and the proportion of shogaole is 1.5-6% by weight. Extracts of this type and their preparation are described in EP 2772245 A1.
  • Another preferred Zzzz z/zcz-CCh extract contains 15-25% by weight [6]-gingerol, 3-5% by weight [8]-gingerol, 3-8% by weight [10]-gingerol, 0, 5-3 wt% [6] shogaol, 0.03-1 wt% [8] shogaol, 0.03-1 wt% [10] shogaol, 0.01-1 wt% zingerone,
  • the proportion of ginger oil is 24-35% by weight and the proportion of shogaole is 0.5-5% by weight.
  • the pungent content can be determined using known analysis methods.
  • An example is the mass spectrometric determination of the pungent content.
  • the pungent content can be determined chromatographically, e.g. by means of HPLC chromatography, using reference substances.
  • the composition according to the invention also preferably comprises one or more adjuvants.
  • the excipients are commercially available excipients, particularly those materials known to be employed in topical formulations for application to the skin. Suitable auxiliaries are described, for example, in WO2001/066076 A and DE 10 2005 029 387 A1, preferably solvents such as organic solvents, carriers, gelling agents, detergents, emulsifiers, solubilizers, humectants, fillers, bioadhesives, emollients, preservatives, bactericides, surfactants, perfumes , pearlescent waxes, consistency enhancers, thickeners, superfatting agents, softeners, humectants, oils, fats, waxes, lecithins, phospholipids, biogenic active ingredients, antioxidants, film formers, swelling agents, hydrotropes, water, alcohols, polyols, polymers, foam stabilizers, foaming agents, antifoaming
  • composition according to the invention can contain preservatives.
  • preservatives are organic acids such as formic acid, sorbic acid, p-anisic acid and benzoic acid.
  • esters of p-hydroxybenzoic acid formaldehyde-releasing agents such as DMDM hydantoin, imidazolidinylurea or methylchloroisothiazolinone, methylisothiazolinone, dibromodicyanobutane, iodopropynylbutylcarbamate, phenoxyethanol or benzyl alcohol can be used as bactericides.
  • compositions for the purposes of the present invention can be inorganic or organic substances for topical application to the skin.
  • the pH of the formulation can be stabilized with buffer systems consisting of polyacids and their salts. Examples of such polyacids are citric acid, tartaric acid or malic acid.
  • compositions according to the present invention may comprise carriers or solvents, preferably water, alcohols, esters, butylene glycol, dipropylene glycol, pentylene glycol, 1,2-hexanediol, caprylyl glycol, decylene glycol, ethanol, ethoxy di glycol, ethyl acetate, glycerol, propanol, isopropanol, macrogols ,
  • the composition is preferably a dermatological or cosmetic composition suitable for topical application to the skin of a mammal, preferably a human.
  • the cosmetic composition is preferably in the form of an emulsion or microemulsion.
  • Another preferred form is, for example, a cream (oil-in-water (O/W) or water-in-oil (W/O)), a lotion, a spray, shampoo, foam, serums, a face mask, ointment, Tincture or an oil, eye care products, cleansing products or soaked pads, and face or hand creams with sunscreen (such as SPF) and cooling eye care products.
  • sunscreen such as SPF
  • an acute cream, a face cream, a hand cream and a body lotion or skin lotion are preferred.
  • the cosmetic composition according to the invention is suitable for rinse-off or leave-on products (cosmetic products that are rinsed off, e.g. shampoo). Leave-on products (products that remain on the skin, e.g. body lotion) are preferred.
  • the composition is used as a cosmetic.
  • Cosmetic preferably refers to compositions intended to care for the skin, to improve skin conditions, to prevent, prevent or alleviate adverse skin conditions.
  • composition according to the invention is preferably used for the application or treatment of sensitive or sensitive skin, rough skin, dry skin and/or irritated skin (e.g. reddened skin after sunburn, abrasions or otherwise irritated skin etc.) with or without itching, but also of aged skin , xerosis cutis, inflammatory conditions of the skin, such as in particular atopic dermatitis (neurodermatitis, atopic eczema), acne, rosacea, psoriasis and the prevention of skin infections or to reduce susceptibility to contact allergies or to prevent the skin conditions mentioned.
  • atopic dermatitis neurodermatitis, atopic eczema
  • acne rosacea
  • psoriasis psoriasis
  • the composition of the present invention is preferably applied topically to the skin of mammals, preferably humans. Typical application sites are in addition to the entire body, face/head (e.g. forehead, chin, neck and scalp), armpit, armpits, palms, soles of feet, back of knees, torso and groin.
  • the composition of the present invention is applied to the skin of a mammal, preferably a human, preferably 1 to 4 times a day, preferably 1 to 2 times a day and more preferably 1 time a day before bedtime (for non-sunscreen products) and is applied in a cosmetic manner acceptable dosage used.
  • Figure 1 shows the multivariate evaluation (principal component analysis, PCA) of a cosmetic screen with 23 plant extracts and CBD. PCI and PC2 are plotted.
  • Figure 2 shows the anti-inflammatory effect of CBD and Zingiber (CO2 extract with 47.7% pungent substances) with increasing concentrations in percent of the control (TNFa DMSO) after stimulation of HaCaT cells by TNF- ⁇ . Mean values and the standard deviation are shown. *p ⁇ 0.05 vs. TNFa DMSO.
  • Figure 3 shows the anti-inflammatory effect of CBD and Zingiber (CO2 extract with 47.7% pungent substances) and combinations of CBD and Zingiber with increasing concentrations as a percentage of the control (UVB DMSO) after UVB irradiation of HaCaT cells. Mean values and the standard deviation are shown. *p ⁇ 0.05 versus UVB DMSO.
  • Figure 4 shows the anti-inflammatory effect of CBD and Zingiber (CO2 extract with 47.7% pungent substances) and combinations of CBD and Zingiber with increasing concentrations as a percentage of the control (TNFa DMSO) after stimulation of HaCaT cells by TNF- ⁇ . Mean values and the standard deviation are shown. *p ⁇ 0.05 vs. TNFa DMSO.
  • Figure 5 shows the anti-inflammatory effect of CBD and Zingiber (CO2 extract with 47.7% pungent substances) with increasing concentrations in percent of the control (UVB DMSO) after UVB irradiation of HaCaT cells. Mean values and the standard deviation are shown. *p ⁇ 0.05 *p ⁇ 0.05 versus UVB DMSO.
  • Figure 6 shows the anti-inflammatory effect of CBD (1 pg/ml) and Zingiber (CO2 extract with 47.7% pungent substances) (5 pg/ml) and a 1:5 combination of CBD and Zingiber (1 pg/ml and 5 pg /ml) in percent reduction compared to the control (TNFa DMSO) after stimulation of HaCaT cells by TNF- ⁇ . Mean values and the standard deviation are shown. *p ⁇ 0.05 vs. TNFa DMSO.
  • Figure 7 shows the anti-inflammatory effect of CBD (5 pg/ml) and Zingiber (CO2 extract with 47.7% pungent substances) (10 pg/ml) and a 1:2 combination of CBD and Zingiber (5 pg/ml and 10 pg/ml) in percent reduction compared to the control (TNFa DMSO). Stimulation of HaCaT cells by TNF- ⁇ . Mean values and the standard deviation are shown. *p ⁇ 0.05 vs. TNFa DMSO.
  • Figure 8 shows the anti-inflammatory effect of CBD (5 pg/ml) and Zingiber (CO2 extract with 47.7% pungent substances) (5 pg/ml) and a 1:1 combination of CBD and Zingiber (5 pg/ml and 5 pg /ml) in percent reduction compared to the control (TNFa DMSO) after stimulation of HaCaT cells by TNF- ⁇ . Mean values and the standard deviation are shown. *p ⁇ 0.05 vs. TNFa DMSO.
  • Figure 9 shows the amount of 1-arachidonylglycerol (1-AG) in cell pellets from HaCaT keratinocytes and the concentration of 1-AG in the cell supernatant. Values are shown for CBD (5 pg/ml) and Zingiber (CO2 extract with 47.7% pungent substances) (20 pg/ml) and for a 1:4 combination of CBD and Z/z/g/Ac/' extract (5 pg/ml and 20 pg/ml) compared to the control (TNFa DMSO) after stimulation of HaCaT cells by TNF- ⁇ . Non-stimulated cells and their supernatant were examined as a negative control (Crtl DMSO).
  • Figure 10 shows the amount of 2-arachidonylglycerol (2-AG) in cell pellets from HaCaT keratinocytes and the concentration of 2-AG in the cell supernatant. Values are shown for CBD (5 pg/ml) and Zingiber (CO2 extract with 47.7% pungent substances) (20 pg/ml) and for a 1:4 combination of CBD and Z/'/zg/Ac/' extract (5 pg/ml and 20 pg/ml) compared to the control (TNFa DMSO) after stimulation of HaCaT cells by TNF- ⁇ . Non-stimulated cells and their supernatant were examined as a negative control (Crtl DMSO).
  • Figure 11 shows the amount of anandamide (AEA) in cell pellets from HaCaT keratinocytes and the concentration of AEA in the cell supernatant. Values are shown for CBD (5 pg/ml) and Zingiber (CO2 extract with 47.7% pungent substances) (20 pg/ml) and for a 1:4 combination of CBD and Zzzzgz/zcz extract (5 pg/ml and 20 pg/ml) compared to the control (TNFa DMSO) after stimulation of HaCaT cells by TNF- ⁇ . Non-stimulated cells and their supernatant were examined as a negative control (Crtl DMSO).
  • CBD pg/ml
  • Zingiber CO2 extract with 47.7% pungent substances
  • Figure 12 shows the amount of oleoylethanolamide (OEA) in cell pellets from HaCaT keratinocytes and the concentration of OEA in the cell supernatant. Values are shown for CBD (5 pg/ml) and Zingiber (CO2 extract with 47.7% pungent substances) (20 pg/ml) and for a 1:4 combination of CBD and Zzzzgz/zcz extract (5 pg/ml and 20 pg/ml) compared to the control (TNFa DMSO) after stimulation of HaCaT cells by TNF- ⁇ . Non-stimulated cells and their supernatant were examined as a negative control (Crtl DMSO).
  • Figure 13 shows the amount of palmitoylethanolamide (PEA) in cell pellets from HaCaT keratinocytes and the concentration of PEA in the cell supernatant. Values are shown for CBD (5 pg/ml) and Zingiber (CO2 extract with 47.7% pungent substances) (20 pg/ml) and for a 1:4 combination of CBD and zzz/ z/zcz extract (5 pg/ ml and 20 pg/ml) compared to the control (TNFa DMSO) after stimulation of HaCaT cells by TNF- ⁇ . Non-stimulated cells and their supernatant were examined as a negative control (Crtl DMSO).
  • CBD pg/ml
  • Zingiber CO2 extract with 47.7% pungent substances
  • Figure 14 shows the anti-inflammatory effect (release of CCL20, IL-6, IL-8 and TNF-a) of Zingiber (CO2 extract with 47.7% pungent substances) with increasing concentrations in percent of the control (poly(EC)) after stimulation of normal human epidermal keratinocytes (NHEK) using poly(EC). Mean values and the standard deviation are shown. *p ⁇ 0.05 vs. Poly(EC).
  • Figure 15 shows the anti-inflammatory effect (CCL20, IL-6, IL-8 and TNF- ⁇ release) of CBD with increasing concentrations in percent of control (Poly(LC)) after stimulation of normal human epidermal keratinocytes (NHEK) with Poly (LC). Mean values and the standard deviation are shown. *p ⁇ 0.05 vs. Poly(LC).
  • Figure 16 shows the anti-inflammatory effect (release of CCL20, IL-6, IL-8 and TNF-a) for a combination of Zingiber (CO2 extract with 47.7% pungent substances) and CBD in a 4:1 ratio with increasing percentage concentrations the control (Poly(LC)) after stimulation of normal human epidermal keratinocytes (NHEK) with Poly(LC). Mean values and the standard deviation are shown. *p ⁇ 0.05 vs. Poly(LC).
  • Figure 17 shows the anti-inflammatory effect (release of CCL20, IL-6, IL-8 and TNF-a) for a combination of Zingiber (CO2 extract with 47.7% pungent substances) and CBD in a ratio of 4: 1 (4 pg/ml and 1 pg/ml) compared to the effects of Zingiber (CO2 extract with 47.7% pungent substances, 4 pg/ml) and CBD (1 pg/ml) in percent reduction compared to the control (poly(LC)) after Stimulation of normal human epidermal keratinocytes (NHEK) using poly(I:C). Mean values and the standard deviation are shown. *p ⁇ 0.05 vs. Poly(LC).
  • FIG. 18 shows the results of the subjective assessment of the itching by the subjects in a clinical cosmetics study of adults who were treated with a cream according to the invention containing 0.5% by weight of Zingiber CO2 extract and 0.1% by weight of CBD.
  • Example 1 Cosmetic screen with CBD and 23 plant extracts
  • epidermal proliferation, differentiation pathways and moisturizing activity were determined by studies of cellular toxicity, proliferation in fibroblasts and keratinocytes, and glucose uptake in keratinocytes.
  • Antioxidant tests were performed with isoprostane in fibroblasts, ROS in keratinocytes and NO in RAW macrophages.
  • the biology of coveris, skin tightening and anti-wrinkle activity was studied with MMP1, MMP9 and TIMP1 in keratinocytes.
  • Inflammatory characteristics of the skin were examined by measuring PGE2, IL-6, IL-8 in fibroblasts and NF- ⁇ B in HEK293t cells, skin lightening via melanin synthesis in melanocytes.
  • Example 2 Anti-inflammatory effects of CBD and Zzzzgz/zcz extract in HaCaT cells
  • Resazurin assay The resazurin assay, which was performed in parallel plates to the NF- ⁇ B test, was used to investigate the toxic potential in UVB-based inflammatory response screening. Resazurin is reduced by vital cells to resorufin, which can be detected by fluorescence measurements (extinction 560 nm, emission 590 nm) can be quantified. Cytotoxic substances reduce the metabolic activity of the cells, which leads to a slowdown in resazurin turnover and thus a reduction in the fluorescence signal, which is proportional to the metabolic activity of the culture.
  • DPBS Dynamic phosphate-buffered saline
  • 100 ⁇ l medium with 2% FBS (fetal bovine serum) and 10% resazurin solution working stock concentration 0.15 mg/ml in DPBS
  • the fluorescence signal was measured with a plate reader at an excitation-excitation wavelength of 540 nm/590 nm. All experiments were performed in the form of technical and biological triplicates.
  • the metabolic activity of the HaCaT NF- ⁇ B cells was determined 24 h after the induction of inflammation.
  • Lactate dehydrogenase (LDH) release test :
  • LDH test was used to monitor cell toxicity in TNF- ⁇ -based inflammatory response screening.
  • the lactate dehydrogenase release assay quantitatively measures lactate dehydrogenase (LDH) in the medium, a stable cytosolic enzyme that is released during cell lysis (the LDH half-life is approximately 9 hours).
  • the LDH test was carried out using the non-radioactive cytotoxicity test CytoTox 96® from Promega (Gl 780) according to the manufacturer's instructions. 50 ⁇ l of supernatant from each sample was transferred to a Sarstedt 96-well plate. Then 50 ⁇ l of reconstituted substrate mixture were added and incubated for 30 minutes at room temperature with the exclusion of light.
  • a HaCaT NF-KB reporter cell line was used for the inflammation assay. Treatment with extracts was carried out after exposure to UVB. The cells were irradiated with 0.15 J/cm 2 UVB light and then treated with the extract for 24 hours.
  • the reporter cell line HaCaT was also used for cytokine induction screening of NF- ⁇ B. In this screening setup, NF- ⁇ B activation was induced using 0.75 ng/ml TNF- ⁇ . The cytotoxicity was examined with the LDH assay. DMSO concentrations up to 0.5% on the HaCaT cells had no effect on the inflammation assay. Consequently, concentration differences below the threshold of 0.5% DMSO were not separately corrected and balanced.
  • the assays were performed as follows:
  • the luminescence signal was measured with a plate reader with injector function (Mithras LB940, Berthold Technologies LLC).
  • RLU relative light units
  • the cytotoxic effect of CBD and Zzzzgz/zcz extract was evaluated 24 hours after the start of treatment.
  • the HaCaT cells were treated with the test substances for 24 hours, then the cells were washed and their viability assessed.
  • CBD was used in non-toxic concentrations of 1, 2, 3, 4, 5 and 6 pg/ml and Zingiber (CO2 extract with 47.7% pungent substances) in non-toxic concentrations of 2.5, 5, 10 , 15, 20 and 25 pg/ml and 20, 40 and 60 pg/ml are used.
  • the Zzzzgz/zcz extract prepared with 70% ethanol was used in further investigations in non-toxic concentrations of 50, 100 and 150 pg/ml.
  • the non-toxic concentrations of the Zzzzgz/w extracts prepared with methanol, acetone, ethyl acetate and heptane selected for further investigations were 20, 40 and 60 pg/ml.
  • Anti-inflammatory effect after inflammation induction by TNF- ⁇ was evaluated 6 hours after treatment of the HaCaT cells with CBD.
  • the inflammatory induction was carried out by adding TNF- ⁇ , after which the cells were incubated with CBD for a period of 6 h.
  • Control cells were treated with the same amount of DMSO that served as the solvent for CBD.
  • a significant anti-inflammatory effect could already be demonstrated from a concentration of 4 pg/ml. Even at a CBD concentration of 20 pg/ml, there was a 49% reduction in reporter activity (Figure 1). This effect showed classic dose dependence. The maximum effect was 54%.
  • the simultaneous determination of the viability of the cells showed no reduction in viability in the control group after treatment with TNF- ⁇ .
  • the addition of CBD only led to a slight reduction in cell viability at concentrations of 5 and 6 pg/ml, but this was still over 80%.
  • the anti-inflammatory effect was evaluated 6 hours after treatment of the HaCaT cells with Zingiber (CO2 extract with 47.7% pungent substances).
  • the inflammatory induction was carried out by adding TNF- ⁇ , after which the cells were incubated with the extract for a period of 6 h.
  • the control cells were treated with the same amount of DMSO that served as the solvent for the Zingiber extract.
  • a significant anti-inflammatory effect could already be demonstrated from a concentration of 10 pg/ml.
  • Even a Zingiber extract concentration of 20 pg/ml reduced the reporter activity by 42% (Figure 1). This effect showed classic dose dependence.
  • the maximum effect was 56%.
  • the simultaneous determination of the viability of the cells showed no reduction in viability in the control group after treatment with TNF- ⁇ .
  • the addition of the Zingiber extract had no additional impact on cell viability.
  • the anti-inflammatory effect of CBD was evaluated by a 24-hour treatment with CBD following inflammation induction by UVB irradiation.
  • the Control cells were treated with the same amount of DMSO that served as the solvent for CBD.
  • a dose-dependent anti-inflammatory effect could be demonstrated.
  • a significant reduction in reporter activity by 23% was detected even at a concentration of 3 pg/ml ( Figure 2).
  • This effect increased with increasing concentration of CBD.
  • a 40% reduction in reporter activity was achieved for 6 pg/ml CBD.
  • the simultaneous determination of the viability of the cells showed a reduction to approx. 70% in the control group after irradiation with UVB (UVB DMSO).
  • the addition of CBD had no additional impact on cell viability.
  • the anti-inflammatory effect of Zingiber was evaluated by treatment with extract for 24 hours, following inflammation induction by UVB irradiation.
  • the control cells were treated with the same amount of DMSO that served as the solvent for the extract from Zingiber.
  • a dose-dependent anti-inflammatory effect could be demonstrated.
  • a significant reduction in reporter activity by 32% was detected even at a concentration of 15 pg/ml ( Figure 2).
  • This effect increased with increasing concentration of zingiber extract.
  • a 55% reduction in reporter activity was achieved for 25 pg/ml extract from Zingiber.
  • the simultaneous determination of the viability of the cells showed a reduction to approx. 70% in the control group after irradiation with UVB (UVB DMSO).
  • the addition of Zingiber extract had no additional impact on cell viability.
  • Example 3 Synergistic and additive anti-inflammatory effects of CBD and Zingiber extract in HaCaT cells
  • the anti-inflammatory effect was evaluated 6 hours after treatment of the HaCaT cells with CBD and/or Zingiber (CO2 extract with 47.7% pungent substances).
  • the inflammatory induction was carried out by adding TNF- ⁇ , after which the cells were incubated with CBD and/or extract for a period of 6 h.
  • Control cells were treated with the same amount of DMSO that served as the solvent for CBD and the Zingiber extract.
  • a significant anti-inflammatory effect was found for the individually tested test substances CBD (5 pg/ml) and Zingiber extract (5, 10 and 20 pg/ml), which confirms the results from example 1. All combinations of CBD and Zingiber extract also showed a significant reduction in NF- ⁇ B activation.
  • Dose-dependent effects are shown for each combination of a concentration of CBD with the extract from Zingiber.
  • the effect size for the combination is larger than the effect size for CBD alone ( Figure 3).
  • the difference between the groups 1 pg/ml CBD/1 pg/ml CBD + 20 pg/ml extract from Zingiber is statistically significant (p ⁇ 0.05).
  • Table 2 Anti-inflammatory effects of the combination of CBD and Zingiber officinale Roscoe Rhizome CCE extract and analysis of synergy after stimulation with TNF- ⁇
  • the anti-inflammatory effect of CBD and/or Zingiber was evaluated by a 24-hour treatment with the test substances or combinations thereof, following inflammation induction by UVB irradiation.
  • the control cells were treated with the same amount of DMSO that served as the solvent for the test substances.
  • a significant anti-inflammatory effect was found for the individually tested test substances CBD (1, 3 and 5 pg/ml) and Z/z/ /Ac/' extract (10 and 20 pg/ml), which confirms the results from Example 1. All combinations of CBD and Zingiber extract also showed a significant reduction in NF- ⁇ B activation. Dose-dependent effects are shown for each combination of a concentration of CBD with the extract from Zingiber.
  • the effect size for the combination of 1 pg/mL CBD with 10 or 20 pg/mL extract from Zingiber (39 or 57% reduction, respectively) is larger than the effect size for CBD alone (34% reduction).
  • For all combinations with 5 pg/ml CBD and extract from Zingiber will observe larger effects than for CBD alone (78, 80 and 87% reduction vs. 71% reduction for CBD alone) ( Figure 4).
  • the difference between the groups 1 pg/ml CBD, 3 pg/ml CBD and 5 pg/ml CBD and the respective combination with Zingiber extract is statistically significant (p ⁇ 0.05).
  • Example 4 Influencing the concentration of endocannabinoids by CBD and Zzz?gzZ>er extract (COg extract with 47.7% pungent substances) and a combination of CBD and Zzzzgz/zcz' extract in HaCaT cells after stimulation with TNF-q
  • the inflammation assay was performed as described in Example 2. After the incubation, the cells were centrifuged off and separated from the cell supernatant. The concentration of the endocannabinoids 1-arachidonylglycerol (1-AG), 2-arachidonylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) was measured by LC-MS in the cell pellet and in the cell supernatant.
  • the effect on the concentration of endocannabinoids was evaluated 4, 8 and 24 hours after stimulation of HaCaT cells with TNF- ⁇ .
  • the stimulation with TNF-a led to an increase in the concentration of 1-AG in the cell pellet after 8 and 24 hours compared to the unstimulated control (Crtl DMSO).
  • the concentration of 1-AG in the supernatant was lower than in the unstimulated control ( Figure 8).
  • the stimulation with TNF-a (TNF-a DMSO) led to an increase in the concentration of 2-AG in the cell pellet after 8 hours compared to the unstimulated control (Crtl DMSO) ( Figure 9).
  • CBD showed a reduction in 1-AG (8 hours and 24 hours) and 2-AG (8 hours) in the cell pellet compared to the stimulated control (TNF-DMSO) ( Figures 8 and 9). No effects were observed on the concentrations in the supernatants for 1-AG and 2-AG and the supernatants and cell pellets for AEA and OEA ( Figures 8-11).
  • the concentration of PEA in the cell pellet was reduced after 4, 8 and 24 h compared to the stimulated control. More PEA was found in the supernatant after 4 hours and less after 8 hours than in the stimulated control ( Figure 12).
  • Zzz/gz/zcz extract The effect of Zzz/gz/zcz extract on the concentration of endocannabinoids was evaluated 4, 8 and 24 hours after treatment of HaCaT cells with Zzzzgz/zcz extract (20 pg/ml).
  • Zzzzgz/zcz extract showed a reduction in 1-AG (8 hours and 24 hours) and 2-AG (8 hours) in the cell pellet and for 1-AG and 2-AG im compared to the stimulated control (TNF-a DMSO).
  • Supernatant 4 hours, Figures 8 and 9).
  • the concentrations of AEA and OEA were increased at all time points in the cell pellet and in the supernatant compared to the stimulated control (TNF-a DMSO) ( Figures 10 and 11).
  • the concentration of PEA in the cell pellet was reduced after 4, 8 and 24 hours compared to the stimulated control. More PEA was found in the supernatant after 4 and 24 hours and less after 8 hours than in the stimulated control ( Figure 12).
  • the effect of the mixture of CBD and Zzz/gz/zcz extract on the concentration of endocannabinoids was measured 4, 8 and 24 hours after treatment of HaCaT cells with CBD (5 pg/ml) and Zzz/gz/zcz extract (20 pg /ml) evaluated.
  • the mixture of CBD and Zingiber extract showed a reduction in 1-AG (8 hours and 24 hours) and 2-AG (8 hours) in the cell pellet as well as for 1-AG and 2 compared to the stimulated control (TNF-a DMSO). - AG in the supernatant (4 hours, Figures 8 and 9).
  • the concentrations of AEA and OEA were increased at all time points in the cell pellet and in the supernatant compared to the stimulated control (TNF-a DMSO) ( Figures 10 and 11).
  • the concentration of PEA in the cell pellet was reduced after 4 hours compared to the stimulated control. More PEA was found in the supernatant after 4 and 24 hours than in the stimulated control ( Figure 12).
  • CBD showed no effects on AEA, OEA and PEA (supernatant).
  • a significant increase in the effect of the zzz/gz/zcz extract by adding CBD was therefore not obvious.
  • An increase in the concentration of the endocannabinoids AEA, PEA and OEA leads to anti-inflammatory and anti-purity effects. These are mediated via the cannabinoid receptors CB1 and CB2 and the transient receptor potential cation channel of subfamily V 1 (TRPV1) for AEA and via activation of the peroxisome proliferator-activated receptor alpha (PPAR-a) for PEA and OEA.
  • TRPV1 transient receptor potential cation channel of subfamily V 1
  • PPAR-a peroxisome proliferator-activated receptor alpha
  • Example 5 Anti-inflammatory effects of CBD and Zzz?gzZ>er extract extract with 47.7% pungent substances) and a combination of CBD and Zzz?gzZ>er extract in normal human epidermal keratinocytes (NHEK)
  • the keratinocytes were seeded in 24-well plates and cultured in culture medium for 24 hours. The medium was then replaced with culture medium containing or not (control) the extracts, the combination or the reference (bafilomycin tested at 100 nM) and the cells were pre-incubated for 24 hours. After the pre-incubation, the medium was replaced, the treatments were renewed and the TLR3 agonist (poly(I:C) tested at 1 pg/ml) was added to all conditions except the unstimulated control. The cells were then incubated for 24 hours.
  • the anti-inflammatory effect was evaluated 24 hours after treatment of the NHEK cells with Zingiber (CO2 extract with 47.7% pungent substances).
  • the inflammatory induction was carried out by adding poly(LC) and the cells were incubated with Zingiber (CO2 extract with 47.7% pungent substances) for a period of 24 h.
  • Treatment with Zzzzgz/v' extract showed a dose-dependent reduction in poly(I:C)-stimulated release of the cytokines CCL20, IL-6, IL-8 and TNF- ⁇ .
  • CCL20 the results of all concentrations used differed significantly from those of the control (poly(EC).
  • the anti-inflammatory effect was evaluated 24 hours after treatment of the NHEK cells with CBD.
  • the inflammatory induction was carried out by adding poly(LC) and the cells were incubated with CBD for a period of 24 h.
  • the anti-inflammatory effect was evaluated 24 hours after treatment of the NHEK cells with a combination of CBD and Zingiber (CO2 extract with 47.7% pungent substances) 1:4.
  • the inflammatory induction was carried out by adding poly(LC) and the cells were incubated for a period of 24 h with a combination of CBD and Zingiber (CO2 extract with 47.7% pungent substances) 1:4.
  • Table 6 Effects of CBD and effects of the combination of CBD and Zingiber officinale Roscoe Rhizome CCL extract on the release of cytokines from NHEK in % of the control (poly(LC))
  • Example 6 Clinical cosmetic study to evaluate the skin tolerance and effectiveness of a cosmetic agent after five days of use in people with atopic dermatitis
  • the aim of this exploratory study was to determine the tolerability and effectiveness of the composition according to the invention in the form of a cream containing 0.1% by weight CBD and 0.5% by weight Zingiber officinale Roscoe Rhizome CCE extract in subjects with atopic dermatitis after 5 days of application to investigate.
  • children aged 6 months to 14 years and adults 18 years and older with a history of atopic dermatitis and pruritic skin were included.
  • At least 44 subjects 22 children and 22 adults were recruited for this test, so that a total of about 40 subjects should participate in the study. Subjects who withdrew from the study after randomization were not replaced.
  • Example 7 Clinical cosmetic study to evaluate the skin tolerance and effectiveness of a cosmetic agent after four weeks of use in people with atopic dermatitis
  • the aim of this exploratory study was to determine the tolerability and effectiveness of the cosmetic composition according to the invention in the form of a body lotion with 0.05% by weight CBD and 0.2% by weight Zingiber officinale Roscoe Rhizome CCE extract in volunteers with atopic dermatitis after four weeks of use. Children aged 6 months to 14 years with acute lesions in atopic dermatitis and adults 18 years and older with a history of atopic dermatitis were included for this study.
  • the SCORAD score was also used to assess the children's tolerance of the test product. Objective and subjective dermatological assessments were carried out to assess tolerability in adults.
  • the aim of this exploratory study was to assess the skin tolerance and product acceptance of two cosmetic compositions according to the invention, which were used by the subjects at home over a period of 2 weeks.
  • the subjects were divided into two equal groups, each group receiving a composition according to the invention either in the form of a face cream with 0.05% by weight CBD and 0.1% by weight Zingiber officinale Roscoe Rhizome CCE extract or in the form of a hand cream with 0 .05% wt CBD and 0.2% wt Zingiber officinale Roscoe Rhizome CO2 extract was used.
  • the products were tested on female and male test subjects with very dry skin on the face and hands. About half of the subjects in each group had skin prone to atopic dermatitis. An objective and subjective dermatological assessment was carried out at the beginning and end of the study.
  • compositions according to the invention with different formulations and different ratios of CBD and Zzz?gzZ> he extract, based on the preclinical studies, show on the one hand an excellent compatibility of the cosmetic composition according to the invention with these active ingredients, which is due to the ingredients of the extracts, in particular the Zingiber extract, was not to be expected.
  • the reduction in itching occurs after just a few days and does not lose its effectiveness over a period of up to 4 weeks, i.e. the effects of the compositions according to the invention with the combination of CBD and Zzz/zAcz extract do not weaken.
  • the compositions used show a significant improvement in the itching, which was not to be expected, despite a significantly lower concentration of CBD and Zzz/zAcz extract used compared to the prior art.
  • compositions/formulations according to the present invention are examples of compositions/formulations according to the present invention.
  • compositions/formulations according to the invention batch size: 300 g
  • water, glycerol and pentylene glycol are initially introduced and allantoin is stirred in for at least 30 minutes (phase 1).
  • Xanthan is sprinkled in with homogenization and the mixture is stirred until smooth with homogenization (16,000, 1 min).
  • Ceramide NP is pre-dissolved in the triglycerides at 80°C (phase 2).
  • the ingredients in the fat phase container are weighed out, heated to 75°C and the ceramide mixture is added.
  • Phase 2 is added to phase 1 with stirring and the mixture is homogenized (18,000, 3 min).
  • Phase 3 is added and stirred in at 35-40°C.
  • Phase 4 is added at 30° C. and homogenized (19,000, 2 min).
  • Zingiber officinale Roscoe Rhizome CCE extract and cannbidiol are added separately and briefly homogenized (19,000, 1 min; 19,000, 1.5 min). The pH is measured.
  • Body Lotion with CBD and Zingiber officinale Roscoe Rhizome CCE Extract INCI overview ingredients Cream with CBD and Zingiber officinale Roscoe Rhizome CCh extract:

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Abstract

La présente invention concerne des compositions cosmétiques contenant du cannabidiol et un extrait de Zingiber, ainsi que l'utilisation de ces compositions comme produit cosmétique.
EP22793528.5A 2021-09-22 2022-09-21 Compositions cosmétiques comprenant du cannabidiol et un extrait de zingiber Pending EP4405045A1 (fr)

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Family Cites Families (18)

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CA2397198C (fr) 2000-03-06 2011-06-21 Unilever Plc Extrait d'echinacea utilise comme stimulant anti-irritant et anti-age dans des compositions cosmetiques
DE102005029387B4 (de) 2005-06-23 2018-12-27 Beiersdorf Ag Wirkstoffkombinationen aus Glycopyrroniumbromid und Polyglyceryl(3)-Methylglucosedistearat
US8435575B2 (en) 2010-05-13 2013-05-07 Aphios Corporation Use of gingerols for cancer patients suffering from nausea and emesis induced by chemotherapy
ES2701758T3 (es) 2013-02-27 2019-02-25 Symrise Ag Extracto de jengibre para la protección de citoblastos
US9822384B2 (en) 2014-07-14 2017-11-21 Librede Inc. Production of cannabinoids in yeast
US20180280464A1 (en) * 2015-10-15 2018-10-04 Preleve Therapeutics, Llc Compositions and Methods for Pain Relief
US9950976B1 (en) 2015-10-27 2018-04-24 CLS Labs, Inc. Cannabidiol extraction and conversion process
US20190374552A1 (en) * 2016-11-02 2019-12-12 George Edward Hoag Multifunctional formulations and methods to control dermatitis and pruritus
EP3653596A1 (fr) 2018-11-14 2020-05-20 Indena S.p.A. Synthèse de cannabidiol en écoulement continu
DE102019104563A1 (de) 2019-02-22 2020-08-27 Chiracon Gmbh Verfahren zur Herstellung von Cannabidiol
KR20220007078A (ko) 2019-05-10 2022-01-18 베누비아 매뉴팩처링, 엘엘씨 칸나비디올 또는 칸나비디바린의 제조 방법 및 칸나비디올 또는 칸나비디바린 제조의 중간체
WO2021033149A1 (fr) * 2019-08-19 2021-02-25 Buzzelet Development And Technologies Ltd. Compositions pour le traitement d'un état caractérisé par une déficience en anandamide et leurs utilisations
US11951079B2 (en) * 2019-10-03 2024-04-09 Kongkrit Chaiyasate Topical cannabidiol composition
KR102277523B1 (ko) 2019-10-04 2021-07-14 한국과학기술연구원 칸나비스 식물로부터 칸나비디올을 연속으로 제조하는 방법 및 그 용도
CN111249215A (zh) * 2020-02-28 2020-06-09 广东肽世家生物科技有限公司 一种多效美白祛斑霜及其制备方法
WO2022098366A1 (fr) * 2020-11-09 2022-05-12 Redwood Ip Holding, Llc Compositions de soins de la peau destinées à prévenir la perte d'eau transépidermique
EP4284351A1 (fr) * 2021-01-28 2023-12-06 Specchiasol S.r.l. Composition pour le traitement d'états douloureux et/ou inflammatoires
CN112957301A (zh) * 2021-02-03 2021-06-15 广西民族师范学院 多种化学药物的通用制备方法

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