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WO2021040645A1 - Produit cosmétique anti-âge - Google Patents

Produit cosmétique anti-âge Download PDF

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Publication number
WO2021040645A1
WO2021040645A1 PCT/TR2020/050721 TR2020050721W WO2021040645A1 WO 2021040645 A1 WO2021040645 A1 WO 2021040645A1 TR 2020050721 W TR2020050721 W TR 2020050721W WO 2021040645 A1 WO2021040645 A1 WO 2021040645A1
Authority
WO
WIPO (PCT)
Prior art keywords
extract
ethosome
radical
melissa officinalis
charged
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.)
Ceased
Application number
PCT/TR2020/050721
Other languages
English (en)
Inventor
Gokce KARATOPRAK
Cigdem YUCEL
Gamze BASKAL
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.)
Erciyes Universitesi
Original Assignee
Erciyes Universitesi
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 Erciyes Universitesi filed Critical Erciyes Universitesi
Publication of WO2021040645A1 publication Critical patent/WO2021040645A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • 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
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/11—Encapsulated compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • 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
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/24—Phosphorous; Compounds thereof
    • 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
    • A61K8/55—Phosphorus compounds
    • 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
    • A61K8/55—Phosphorus compounds
    • A61K8/553—Phospholipids, e.g. lecithin
    • 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
    • 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]
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin

Definitions

  • the present invention relates to obtaining an anti-aging dermocosmetic product which shows anti-radical and antioxidant effect.
  • the present invention essentially relates to obtaining anti-aging dermocosmetic active chemical substance, which shows high anti-radical and antioxidant effect, as ethosome formulation.
  • Carrier systems are the parts which comprise active substance or substances in cosmetic products. In preparation of cosmetic formulations, different carrier systems are used. Traditional cosmetic carrier systems are in the form of emulsions, creams, gels or aerosols. For providing development of technology and for bringing novelties to the related technical field, new carrier cosmetic carrier systems are begun to be formed. Some of these are micro emulsions, vesicular systems and particle systems.
  • dermocosmetic products The most important advantage of dermocosmetic products is that the active substance therein is protected from the first passage effect in liver and protected from being damaged in the gastrointestinal system. Another advantage thereof is that they are applicable to every patient.
  • the most important disadvantages of dermocosmetic products are that the active chemical substance therein can pass through the skin with difficulty and they lead to toxic effects or side effects (irritation, sensitivity) in the application region since the active substances are applied at high doses in transdermal application.
  • the effect expected from the cosmetic product remains in a superficial manner and the herbal extracts charged to the nano-carrier systems penetrate to the lower layers of the skin and exhibit a deeper effect by means of the structural advantages provided by nano-carrier.
  • the anti-aging cosmetic products have high antioxidant and anti radical activity and penetrate to the dermis layer of skin and show deep effect.
  • the present invention relates to obtaining an anti-aging dermocosmetic product which shows anti-radical and antioxidant effect, for eliminating the above mentioned disadvantages and for bringing new advantages to the related technical field.
  • the main object of the present invention is to provide an anti-aging dermocosmetic product.
  • Another object of the present invention is to provide a dermocosmetic product comprising nano-carrier ethosomes having high penetration activity.
  • Another object of the present invention is to provide a dermocosmetic product having high anti-radical and antioxidant effect.
  • Another object of the present invention is to provide a dermocosmetic product which can penetrate to the dermis layer of the skin layer.
  • Another object of the present invention is to provide a dermocosmetic product which is bio- compliant and natural.
  • the basic structure of the present invention is that Melissa officinalis L extract, which is the active substance of anti-aging dermocosmetic product with high anti-radical and antioxidant activity, is in ethosome nano-carrier formulation.
  • the value of Melissa officinalis L extract is at a value between 50% and 90%.
  • the dermocosmetic product shows high antioxidant values.
  • the extract in dermocosmetic product does not decrease cell viability under 50% at concentrations 500 pg/mL and below.
  • the viability in the cells, where the dermocosmetic product comprising ethyl acetate fraction is applied, is 100%.
  • the present invention relates to production of ethosome formulations charged with Melissa officinalis L extract with high anti-radical and antioxidant activity, the production of said dermocosmetic product is characterized by comprising application of the following process steps: i. Obtaining extract thanks to extraction of Melissa officinalis L herb by means of water- solvent chemical substance, ii. Fractioning the extract, obtained in step (i), by means of ethyl acetate chemical compound, iii. Charging the extract, where fractioning process is applied, to the ethosome formulation, iv. Determining the characterization of the prepared formulation.
  • the solvent chemical substance used in step (i) is ethyl alcohol.
  • the ethanol used in step (i) is at a value between 10% and 90% by volume in water.
  • step (i) said ethanol is at a value between 40% and 60% by volume in water.
  • step (ii) the amount of ethyl acetate used in the fraction process is 200 mL.
  • step (ii) said process is repeated 3 times.
  • step (iii) of the present invention the process of charging to the ethosome formulation is formulated in an encapsulated form into the ethosomes prepared beforehand.
  • Figure 1 is the view of drug penetration of ethosomes.
  • Figure 2 is the view of YBSK chromatogram of 60% ethanol extract.
  • Figure 3 is the view of YBSK chromatogram of 60% ethanol extract fractioned with ethyl acetate.
  • the subject matter relates to obtaining an anti-aging dermocosmetic product which shows high anti-radical and antioxidant effect and is explained with references to examples without forming any restrictive effect only in order to make the subject more understandable.
  • the basic subject of the present invention is to obtain the anti-aging dermocosmetic active chemical substance, which shows high anti-radical and antioxidant effect, as ethosome formulation.
  • Melissa officinalis L herb which is a member of Lamiaceae family
  • M. officinalis L herb there are volatile compounds (for instance, geranial, neral, citronellal and geraniol), triterpenes (for instance, ursolic acid and caryophyllin) and phenolic compounds (rosmarinic acid, caffeic acid derivatives, luteolin, naringin and hesperidin). Since the phenolic ingredient of Melissa officinalis L herb is very high, it has a very strong antioxidant activity.
  • the stratum corneum layer which exists at the epidermis which is the topmost layer of the skin, is functioning as an important barrier for the passage. While lipophilic drugs can pass through the skin, the passage of hydrophilic drugs is very difficult.
  • Penetration enhancers are used for providing penetration through the skin, and methods like phonophoresis, electroporation, iontophoresis, injection without needle and micro needles are utilized.
  • Melissa officinalis L herb which is the dermocosmetic product obtained by the present invention, is in the form of nano-carrier ethosome formulation.
  • Ethosomes which are a new lipid carrier formed by ethanol, phospholipid and water, are carriers which increase permeation.
  • Ethosomes are liposomes comprising high concentrations (20% - 45%) of ethanol. Ethosomes are formed by components proven to be safe and natural for pharmaceutical and dermocosmetic usage.
  • ethosomes which can carry various drug molecules which are in hydrophilic, lipophilic and amphiphilic structure, are drug carrier systems used in increasing penetration. Thanks to ethanol provided in the body of ethosomes formed by phospholipids, the fluidity of the lipid layer structure during passage through the skin is increased and the penetration of the active substance to the lower layers is facilitated and increased.
  • ethosomes The preparation of said ethosomes is realized as mentioned below by using mechanical dispersion method: i. Putting soy phosphatidyl to the choline pear-type glass balloon, ii. Adding chloroform: methanol (3:1 v/v) mixture to glass balloon and dissolving, iii. Evaporating the solvent existing in rotary vaporizer at 55 e C and obtaining dry lipid film, iv. Adding ethyl acetate fraction solution, which is in 30% ethanol, to the obtained dry lipid film and hydrating, v. Realizing vortex for 15 minutes and afterwards keeping in ultrasonic bath for 30 minutes and obtaining ethosome suspension, vi. By means of centrifuging the obtained suspension at 10000 rpm for 30 minutes and separating the clear part which exists at the top and obtaining ethosomes from the precipitate.
  • Melissa officinalis L extracts are charged to the obtained ethosome formulations as given in Figure 1 .
  • the present invention relates to production of ethosome formulations charged with Melissa officinalis L extract having high anti-radical and antioxidant activity, and the production of said dermocosmetic product is characterized by the application of the following process steps: i. Obtaining extract thanks to extraction of Melissa officinalis L herb by means of water- solvent chemical substance, ii. Fractioning the extract, obtained in step (i), by means of ethyl acetate chemical compound, iii. Charging the extract, where fractioning process is applied, to the ethosome formulation, iv. Determining the characterization of the prepared formulation.
  • step (i) of the present invention in the process of obtaining herb extract, the part of the herb which is above the soil is used.
  • the solvent chemical substance used in step (i) of the invention is ethyl alcohol.
  • the ethanol used in step (i) of the invention is at a value between 10% and 90% (v/v) in water.
  • the ethanol used in step (i) of the invention is preferably at a value between 40% and 60% (v/v) in water.
  • step (ii) of the invention The process of fractioning of the extract in step (ii) of the invention is realized by means of ethyl acetate chemical compound. After the extraction of Melissa officinalis L, the ethyl acetate fraction is added in the step of preparation of ethosomes at concentration of 1 mg/ml_ (dissolved in ethanol of 30%).
  • step (iii) of the invention the process of charging to the ethosome formulation is formulated in a form encapsulated into the ethosomes prepared beforehand.
  • step (iv) of the invention The characterization of the formulation prepared in step (iv) of the invention is determined by means of application of various tests as also mentioned under the titles given below.
  • the extracts In the rotary vaporizer, after the ethanol phase is condensed under low pressure at 37 e C, the extracts have been frozen at -20 e C, and afterwards, the extracts have been dried in the freeze drier.
  • Mwater extract is the reference extract where ethanol is not used.
  • the other extracts are the extracts formed by ethanol which is at different percents by volume.
  • M50 and M70 samples According to the obtained tests, the best results have been taken by means of M50 and M70 samples. Afterwards, M60 sample has been formed which comprises ethanol-water at 60% by volume and it has been observed that the optimum values are provided by means of this sample as a result of the experiments made afterwards.
  • M60 extract (60% ethanol extract): This is the sample considered to provide the best activity.
  • M60 extract is dispersed in water, it has been subjected to fractioning process by means of ethyl acetate.
  • M60F1 sample has been obtained by means of fraction with water and M60F2 sample has been fractioned by means of ethyl acetate.
  • M60F1 water fraction
  • M60F2 ethyl acetate fraction
  • 1 , 1 -diphenyl-2-picril-hydrazyl solution has been prepared in Tris-HCI buffer (50 mM, pH 7.4) and 1 mL 0.1 mM methanol, and it has been mixed.
  • As the reference sample reactive mixture which does not comprise extract has been used. After the samples are incubated at room temperature and for 30 minutes at dark, the absorbance has been read at 517 nm. The inhibition percent has been calculated by using the equation given below. IC50 values have been calculated by using non-linear regregation curves. The analyses have been repeated as three parallels, and the average values have been used.
  • Inhibition % [(Abs COntroi - Abs sampie ) / Abs COntroi ] x 100
  • the extracts have been studied at concentration between 0.1 mg/ml_ and 2 mg/mL.
  • the low IC 5 o value has been found as 0.1 ⁇ 0.004 mg/mL.
  • ABTS radical (7 mM) has been formed by keeping aqueous solution of ABTS and K2S2O8 (2.45 mM) in dark for 12-16 hours and the absorbance thereof has been adjusted so as to be 0.700 ( ⁇ 0.030) at 734 nm at room temperature.
  • the radical solution (990 gL) prepared in this manner has been mixed with extract solutions (10 gL) and the reaction kinetic has been measured for 30 minutes with intervals of 1 minute at 734 nm.
  • the inhibition percents measured against concentration have been calculated in an equivalent manner to Trolox (TEAC).
  • the experiments have been repeated as three parallels, and the average values have been calculated.
  • the extracts have been studied at concentrations of 0.2 mg/ml_ and 0.4 mg/mL.
  • M50 extract shows highest activity with value of 1 .90 ⁇ 0.09 mmol/L/Trolox at concentration of 0.4 mg/mL.
  • TEAC values are 1 .54 ⁇ 0.13 mmol/L/Trolox for M40, and 1.90 ⁇ 0.09 mmol/L/Trolox for M50, and 1.92 ⁇ 0.14 mmol/L/Trolox for M60 at concentration of 0.4 mg/mL.
  • TEAC value is 1.89 ⁇ 0.21 mmol/L/Trolox.
  • the ethyl acetate fraction (M60F2) which has been found active as a result of activity experiments and 60% Ethanol extract (M60), has been analyzed by means of High Pressure Liquid Chromatography.
  • the adherence times of the compounds, separated in YBSK, and UV spectrums thereof have been defined by comparing with the standards.
  • the rosmarinic acid used as standard has been worked in the interval between 6.25-400 pg/rnL, and caffeic acid and ferrulic acid have been worked in the concentration interval of 12-840 pg/rnL, and the calibration straight line has been formed. All standard and sample solutions have been analyzed three times and the average values have been given.
  • the cyto-toxicity of M60F2 sample on L929 cells has been determined by means of MTT colorimetric method.
  • the cells in the flask have been counted 24 hours before the study, and culturing has been realized to the micro-plaque with 96 wells such that there are 10x10 3 cells at 100 pL per well.
  • the extracts prepared at concentrations of 15.6 pg/mL, 31.25 pg/mL, 62.5 pg/mL, 125 pg/mL, 250 pg/mL, 500 pg/mL and 1000 pg/mL and diluted in the growth culture have been added to the wells at 100 pL. They have been kept for 24 hours in the stove with carbon-dioxide at 37 e C.
  • the toxic doses of empty ethosome formulation and extract charged ethosome of M60F2 fraction obtained from M. officinalis L have been determined by means of MTT experiment by using L929 (mouse fibroblast) cells. The results have been given in terms of cell viability %.
  • the extract has been tested at concentrations of 15.6 pg/mL, 31.25 pg/mL, 62.5 pg/mL, 125 pg/mL, 250 pg/mL, 500 pg/mL and 1000 pg/mL.
  • Ethyl acetate extract has not decreased viability below 50% at concentrations of 500 pg/mL and lower.
  • the best sample is M60F2 sample as a result of the tests and experiments made for determining the characterization of the prepared formulation. Accordingly, it is seen that the dermocosmetic product, formed by placement to ethosome formulation after being subjected to fractioning process with ethyl acetate and the extract of M. officinalis L herb extracted with ethanol at a value between 40% and 60%, can provide the desired characteristics with the best efficiency.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Mycology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Botany (AREA)
  • Microbiology (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Dermatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medical Informatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Inorganic Chemistry (AREA)
  • Cosmetics (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

La présente invention concerne un produit dermo-cosmétique anti-âge qui présente un effet antiradicalaire et antioxydant élevé. La présente invention concerne essentiellement un composé chimique anti-âge qui présente un effet antiradicalaire et antioxydant en tant qu'éthosome.
PCT/TR2020/050721 2019-08-28 2020-08-18 Produit cosmétique anti-âge Ceased WO2021040645A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2019/12996 2019-08-28
TR2019/12996A TR201912996A2 (tr) 2019-08-28 2019-08-28 Yaşlanma karşiti kozmeti̇k ürünü eldesi̇

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WO2021040645A1 true WO2021040645A1 (fr) 2021-03-04

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PCT/TR2020/050721 Ceased WO2021040645A1 (fr) 2019-08-28 2020-08-18 Produit cosmétique anti-âge

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR3159746A1 (fr) * 2024-03-01 2025-09-05 Patyka Cosmetics Utilisation cosmétique de Melissa officinalis pour diminuer les manifestations associées au stress

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009025532A2 (fr) * 2007-08-23 2009-02-26 Angiolab, Inc. Fraction d'extrait de feuille de mélisse présentant des activités inhibitrices d'angiogenèse et de mmp, et composition en comportant

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009025532A2 (fr) * 2007-08-23 2009-02-26 Angiolab, Inc. Fraction d'extrait de feuille de mélisse présentant des activités inhibitrices d'angiogenèse et de mmp, et composition en comportant

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
PEREIRA ROMAIANA PICADA, BOLIGON ALINE AUGUSTI, APPEL ANDRÉ STORTI, FACHINETTO ROSELEI, CERON CARLA SPERONI, TANUS-SANTOS JOSÉ EDU: "Chemical composition, antioxidant and anticholinesterase activity of Melissa officinalis", INDUSTRIAL CROPS AND PRODUCTS, vol. 53, February 2014 (2014-02-01), pages 34 - 45, XP055796499 *
YUCEL, ÇIGDEM ET AL.: "Anti-aging formulation of rosmarinic acid-loaded ethosomes and liposomes", JOURNAL OF MICROENCAPSULATION, vol. 36, no. 2, March 2019 (2019-03-01), pages 180 - 191 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR3159746A1 (fr) * 2024-03-01 2025-09-05 Patyka Cosmetics Utilisation cosmétique de Melissa officinalis pour diminuer les manifestations associées au stress

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