WO2017034384A1 - Epidermal lipid barrier restoring cream for facial skin, neck and decollete area for metabolic syndrome patients - Google Patents

Epidermal lipid barrier restoring cream for facial skin, neck and decollete area for metabolic syndrome patients Download PDF

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WO2017034384A1
WO2017034384A1 PCT/LV2015/000006 LV2015000006W WO2017034384A1 WO 2017034384 A1 WO2017034384 A1 WO 2017034384A1 LV 2015000006 W LV2015000006 W LV 2015000006W WO 2017034384 A1 WO2017034384 A1 WO 2017034384A1
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cream
skin
metabolic syndrome
patients
neck
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PCT/LV2015/000006
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English (en)
French (fr)
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Jūlija VOICEHOVSKA
Jana JANOVSKA
Irēna DABERTE
Vladimirs VOICEHOVSKIS
Andrejs ŠĶESTERS
Alise SILOVA
Sergejs BABIKOVS
Olga ZUBOVA
Dagmāra SPRUDŽA
Jānis ĶĪSIS
Ludmila Ivanova
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Rīgas Stradiņa Universitāte
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Priority to EP15902371.2A priority Critical patent/EP3439616A4/en
Publication of WO2017034384A1 publication Critical patent/WO2017034384A1/en

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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/01—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61K8/31—Hydrocarbons
    • 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
    • A61K8/342—Alcohols having more than seven atoms in an unbroken chain
    • 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
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • 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
    • A61K8/37—Esters of carboxylic acids
    • 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
    • A61K8/37—Esters of carboxylic acids
    • A61K8/375—Esters of carboxylic acids the alcohol moiety 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
    • A61K8/39—Derivatives containing from 2 to 10 oxyalkylene groups
    • 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/58—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
    • 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
    • A61K8/67—Vitamins
    • A61K8/678—Tocopherol, i.e. vitamin E
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/86—Polyethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions

Definitions

  • the invention relates to the field of medicine, namely family medicine (general practitioners), therapy, endocrinology, gerontology, dermatology and cosmetology and solves the problem of restoration of epidermal lipid barrier in facial skin, decollete and the neck in metabolic syndrome patients.
  • Metabolic syndrome is a combination of changes linked to disruption of metabolism, in which the lack of sensitivity to insulin develops and cell glucose uptake is diminished. Metabolic syndrome features hypertony, obesity, ischaemic heart disease, diabetes mellitus type 2. Development of metabolic syndrome includes, but not limited to increase in waist circumference (more than 102 cm in men, more than 88 cm in women); arterial blood pressure of at least 135/85 raraHg. These patiens' blood features increased lipid peroxidation markers. Oxidants activate cell responses with protein, lipid and DNA destruction.
  • Human skin represents an intricate tissue system that is based on epidermis, derma and subcutaneous fat outline. Inside basal epidermal layer melanocytes and Langerhans cells reside. Principal epidermal layer consists of fibers of protoplasm and granulous layer is comprised of cells rich in keratohyalin complexes. Derma is the connective part of the skin and makes up for the majority of volume. Derma is separated from epidermis with the basal membrane [2].
  • Water-lipid mantle forms and epidermal barrier that is made up of corneal scale-like cells which are called corncocytcs. Among them lie intercellular lipids - ceramides. Ceramides glue corneocytes together and form an impenetrable, uniform epidermal barrier.
  • Ceramid molecules posess polar structure - they feature hydrophilic heads (attract water) and lipophilic tails (attract fats).
  • Epidermal lipid barrier blocks harmful substances from entering the skin and takes part in humoral homeostasis in derma.
  • Lipid barrier consists of cholesterol, ceramides and unsaturated fatty acids (Omega-3, Omega-6). These fatty acids posess antiinflammatory properties, stimulate Langerhans cells and strengthen epidermal lipid layer [4]. Free fatty acids are located around ceramides inside the lipid layer and provide water repellency, form water-in-oil emulsion. Under the disruptive conditions, microorganisms chemicals and other exogenous, aggressive factors enter the skin through a damaged lipid layer.
  • Skin features its own system of immune cells, starring Langerhans cells (2-5% of cellular epidermis). Langerhans cells take part in destruction of bacteria and initiate immune response, under which dermal dendritic cells, epidermal macrophages and other cells take part.
  • Skin ageing is related to the state of immune system [5].
  • skin macrophage amount reduces, oxidants activate cell reactions that disrupt protein, lipid and DNA structures.
  • oxidants activate cell reactions that disrupt protein, lipid and DNA structures.
  • Such processes are most active and prominent in patients eith metabolic syndrome (MS).
  • MS eith metabolic syndrome
  • metabolic syndrome also features a latent inframmation that activates peroxidation. Accumulation of lipid peroxidation and oxidative lipoprotein and lipid layer damage lead to morphologic changes of skin structural components [6].
  • Antioxidative defense system is weakened and/or ineffective in patients with metabolic syndrome due to oxidative stress. Under such stress, keratinocyte synthesis is reduced, transepidermal water evaporation intensifies, skin becomes markedly dry with cracks and erosions present. These changes lead to microbiota imbalance, fungal skin infections and papilloma development. Restoration of epidermal lipid layer of the skin is a particularly urgent task in patients with metabolic syndrome [7].
  • Table 1 we provide the spectrum of epidermal lipid layer disorders and respective clinical features.
  • Detection of epidermal lipid barrier damage is performed via dermatoscopy (dampness/dryness, oiliness, pH) and sciasopy (dispigmentation ratio and microrelief studies). Transepidermal water loss is measured with Tewameter® TM 300 probe, Courage + Khazaka electronic GmbH, Germany. Sciascopy is performed with MoleView SIAscope V Handset, Astron, United Kingdom, and for dermatoscopy is done with HEINE alpha+, Heine Optotechnic, Germany. In testing, data on multiple characteristics is analysed and reflect the state of epidermal lipid layer [8-1 1]:
  • coriicometry skin dampness, stratum corneum water content
  • Corneometry is based on capacitance measurement in a dialectric medium. Any change of dielectric constant under water amount fluctuations in superficial skin layers leads to capacitance change. Dampness is measured on a scale, a base for which is dielectric capacitance of water - 81. Usually, skin dampness is classified in 4-6 grades (very high 45-99.0, high-normal 35.1-40.0, reduced-low 20.1-29.9, dehydrated - lower than 20.0);
  • transepidermal fluid loss - water evaporation measurement at the skin surface based on open-chamber diffusion.
  • Method is based measurement of partial water pressure in a closed chamber with a single humidity probe. An increase in partial water pressure in the chamber in a certain amount of time;
  • pH meter - pH meter is equipped with high precision glass electrode
  • mexametry evaluation of various pigments in the skin
  • Method is based on different waavelength absorption of light spectrum by the skin.
  • Mexametry is especially useful in quantitative allergy and inflammation evaluation under UV-induced damage.
  • microrelicf studies via microphotography - equipping digital tools for relief and microstructure evaluation allows for further data reevaluation and comparison through treatment.
  • compositions for treatment and prophylaxis of UV-induced skin dryness are mixtures of plants and various oils [12-14]. UV-related prooxidative influence may be corrected with vitamins- antioxidants [15-21]. Retinoids are widely used in UV-induced damage prophylaxis [22]. Local use of selenomethionine cream under sun exposure is known for skin cancer prevention [23]. Ceramides-rich moistening cream is frequently used in children with atopic dermatitis [24].
  • petroleum jelly may be used [28].
  • Petrolatum and derivatives are used after medical or cosmetic procedures that feature removal of corneal stratum (laser grinding, dermabrasion, mechanical epidermis removal, peeling).
  • a disadvantage of petrolatum is a very low absorbability, due to which it covers the skin with a greasy layer that reduces its usage, and strong occlusive effect (blocks evaporation), which leads to reduction of skin permeability and other complications.
  • Use of petrolatum is recommended only in severe damage to epidermal layer, when an overwhelming skin cell reaction is expected due to loss of external protection, and in cases when the skin itself is not able to sustain full barrier. In other cases blocking evaporation through horny layer is strongly discouraged.
  • Fatty emulsion that provides simultaneous moistening and nutrition to the skin is well researched [29]. Said emulsion does not protect from ageing that is related to free radicals induced damage of the skin in patients with metabolic syndrome.
  • the cream contains seleno-L-methionine, Vitamin E alpha- tocopherol, squalane, methyl hydroxybenzoate, glycerol monostearate 60, cetyl alcohol, middle chain triglyceride, white petrolatum, macrogol-20-glycerol monostearate, 1,2-propanediol and distilled water in the ratio of components, mass g (%):
  • cetyl alcohol 3,78 - 6,29 middle chain triglyceride 4,72 - 7,87;
  • Cream is composed as a white or yellow tinted homogenous mass with pleasant odor, according to its fatts used in composition. All cream components are permitted for use as pharmaceuticals.
  • Cream is designed for restoration of epidermal lipid barrier of facial skin, neck and decollete area in patients with metabolic syndrome.
  • Seleno-L methionine (Selenomethionine, Se-Met (SEM)— selenomethionine L-enantiomere, naturally-occurring selenium containing amino acid, notable source of selenium.
  • Selenomethionine functions as a bioantioxidant, interacts with vitamins, enzymes, biological membranes in biosystems and an organism as a whole. Interacting with glutationperoxidase, it neutralises oxides and peroxides, protects cell membranes from destruction, works as an antihistamine, stimulates collagen and keratin biosynthesis. Not only it makes skin more elastic and resilient, it also lowers seborrheic events, activates skin regeneration and restores epidermal structure.
  • Inorganic selenium selenium disulfide
  • scalp seborrhea As accepted in the US, selenium recommended daily allowance for an adult is 50-220 mkg, and in China no toxicity was noted when intake reached 750 mkg, with intoxication symptoms apearing when daily selenium intake was around 5000 mkg [38].
  • Selenomethionine is a hydrophilic substance, and its optimal amount in the cream is 0,0005-0,0015 g. With its amount lower than 0,0005 g, antioxidant action was also lowered and with amount higher than 0,0015 g it was difficult to produce the cream due to change in consistency and excessive lamination, with cream becoming less homogenous.
  • Squalane - naturally-occurring hydrocarbon of carotinoid group that resembles transparent oil with no colour or odor.
  • Squalane does not have double bonds, thus being chemically stable and may be stored for over 2 years, does not oxidize and rancidify.
  • Squalane is synthesized in sebaceous glands, is a major component of sebum and water-lipid mantle of the skin. According to demiatocosmetology, squalane is a high-grade emollient. In contrast to triglicerydes and sebum fatty acids, squalane is non-comedogenic [39-40]. On application, squalane spreads easily, forms a protective film that prevents moisture loss and enhances skin breathing.
  • Squalane Bearing natural similarity to the skin itself, squalane easily transfers through epidermis, does not leave trace of oiliness, all while giving the skin a softer and silky feel. Squalane is hydrophobic, takes active role in metabolism and bological steroid synthesis, possesses antibacterial properties and helps prevent ageing spots.
  • Optimal squalane content in the cream is 11,25 - 18,75 g. If squalane is less than 1 1 ,25 g, its smoothing and skin restoring properties were markedly reduced, and more than 18,75 g of squalane introduced difficulties in cream synthesis as decrease in compositional stability and lamination.
  • Optimal alpha-tocopherol (Vitamin E) content in the composition is 0,50 - 1,50 g.
  • Vitamin E is less than 0,5 g, its effects were markedly reduced and when it was more than 1,5 g, consistency of the cream changed, it becoming less viscous.
  • Methyl hydroxybenzoate (methyl paraben) CH3(C 6 H 4 (OH)COO - white or cream-coloured crystalline powder, poorly soluble in cold water, soluble in wark water, ethanol and propylenglycole. Possesses wide spectrum of antibacterial and antifungal properties, naturally occurs in several plants, i.e in blueberries. It is used to counter Gram-positive bacterias, molds and Gram-negative bacterias [42]. In human body, methyl parabens is absorbed easily and fully through skin or gastrointestinal tract and breaks down into simple substances and is rapidly excreted with urine without accumulation in the organism.
  • methyl paraben is used as a stabilizer and/or prolonger and effective in very low concentrations, pure form and as a 0,25%-5% alcohol solution.
  • Optimal amount of methyl paraben is noted at 0,05 - 0,15 g. When its amount was lower than 0,05 g, stabilizing effect was reduced dramatically and when it was more than 0,15 g, consistency of the cream changed with insoluble inclusions being present and visible.
  • Glycery monostearate 60 - white powder obtained from naturally occurring stearic acid and glycerol. It is a pearlescent (light reflecting), waxlike emollient, emulsifier and thickener, which was added during stabilization phase to form a homogenous emulsion.
  • Glyceryl monostearate 60 is used as a stabilizer and structuring component to prevent separation of hydrophobic and hydrophilic phases of the composition [43]. With it being less than 2,52 g, thickening effect was markedly reduces and if there was more than - 4,20 g, the composition turned excessively thick, which introduced difficulties in application.
  • Recommended amounts are 3,78 - 6,29 g. When the amount of cetyl alcohol is less than 3,78 g, emulsifying properties were reduced and cream laminated. When its amount was more than 6,29 g, composition became fluent.
  • Medium chain triglycerydes - oily fluid obtained from coconut oil, water- insoluble, can be mixed with other oils [45]. It enhances cream spreadability, dissolves lipophilic components. Recommended amounts to use are 4,72 - 7,87 g. If the composition had less than 4,72 g of medium chain triglycerides, the cream laminated markedly and in there was more than 7,87 g of said triglycerides, the cream became more fluent.
  • White petrolatum - a semi-solid hydrocarbon mixture obtained through mixing white ceresine and paraffin with fragrance oils [46].
  • Soft paraffin is used as a thickener in skin cream and ointment design. External use of petrolatum restores water-lipid protective mantle of the skin, prevents loss of fluid by the cells, reduces scaling and cracking of the skin.
  • Petrolatum is used to soften facial and hand skin, especially in environment-induced damage (sun, wind, temperature fluctuations). With its amount in the composition less than 16,05 g, its thickening effects were less pronounced and over 26,74 g cream consistency changed for markedly thicker.
  • Macrogol-20-glycerol monostearate (HO-(CH2 ⁇ CH2 ⁇ 0) perennial-H) - white powder that forms hydrogen bonds with water molecules. It is used in medicine and cosmetics as a bonding, structuring and stabilizing component that introduces smoothness to the composition [47].
  • High degree of hydrophyly allows for an effective homogenization of the composition in amount 4,40 - 7,34 g when emulsifying cream hydrophobic components. With it being less than 4,40 g, thickening effect was markedly diminished and when macrogol was more than 7,34 g, cream consistency turned excessively thick, which made the cream difficult to apply.
  • 1,2-propanediol fCH3CH(OH)CH20H) - organic substance colorless hygroscopic, odorless fluid that keeps moist, softens and disperses, and is a good solvent [48].
  • Most of low-molecular organic compounds mix with 1,2 propanedion easily, especially those containing oxygen and nitrogen. With its amounts less than 6,29 g, thickening effect was markedly reduced and when its amount was over 10,49 g cream became excessively thick.
  • Aqua - basic component of water-in-oil emulsion Recommended use is 33,0- 34,6 g. When it was less than 33,0 g, thickening effect was markedly reduced. When the amount of aqua was more than 34,6 g, cream became excessively thick, which made it difficult to use and apply.
  • Novelty cream composition was successfully used to obtain dosage forms into the tin tubes of 65,0 g and/or 30,0 g.
  • Composition of the novelty cream and production technology corresponds to standards of REGULATION (EC) No 1223/2009 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 30 November 2009 on cosmetic products, Article 11.
  • Composition includes:
  • Difficulty in manufacturing a novelty composition was in squalane, glycerol, triglycerides, petrolatum and alpha-tocopherol being hydrophobic agents and selenomethionine, macrogol and propanediol being hydrophilic agents.
  • Cream hydrophobic part manufacturing hydrophobic part of the cream was produced by melting 2,52 g of glycerol monostearate 60 and 3,78 cetyl alcohol under 65-70°C, then adding melting 16,05 g of petrolatum, then adding 11,25 g of squalane and 4,72 g of medium-chain triglycerides, then stirring until homogenous. Composition must be 60°C.
  • hydrophilic part of the cream is the following: dissolve 6,29- 10,49 g of 1,2 propanediol and 0,05-0,15 g of methyl paraben at 45-50°C in heat-resistant glassware, add remaining distilled water (aqua), stir, add 4,40-7,34 g of macrogol-20-glycerol monostearate, dissolve through heating to 60°C.
  • Cream is composed as a white or yellow tinted homogenous mass with pleasant odor, according to its fatts used in composition. Obtained cream is packed in opaque containers (tin tubes) in 65,0 and 30,0. Cream is intended for use in patients with metabolic syndrome with the aim of restoring epidermal lipid layer of facial skin, neck and decollete area. Cream possesses good component biocompatibility, is easily absorbed by the skin, cover the skin in thin elastic layer, has pH of 4,0-5,0. It also exhibits soothing effects, reduces irrtation and in prolonged use does not cause adverse reactions.
  • Clinical trial included anthropometric data (BMI, waist circumference, arterial blood pressure), blood sample tests (glucose, lipoproteins).
  • BMI waist circumference
  • blood sample tests glucose, lipoproteins.
  • MoleView SIAscope V Handset Astron, United Kingdom
  • HEINE alphas Heine Optotechnic, Germany, respectively.
  • Immunohistochemistry included CD la, CD31, CD34, CD3, CD8.
  • the cream of the new formulation has a cosmetic and medical - preventive properties, restores epidermal lipid barrier of the skin and skin barrier function in patients with the metabolic syndrome: improves turgor and hydration of the skin, restores elasticity and smooth skin relief, reduces the phenomenon of pigmentation, inflammatory papilloma.
  • Novelty cream composition represents a mixture of water and fats, fat-like and other compounds. High percentual fat and fat-like substance content is crucial in achieving epidermal bilipid layer restoration and its water-lipid mantle. Technologically it is difficult to combine such amounts of fats without the risk of lamination of end-product. For creams of this type, it is important to use specialized emulsifiers, which, when introduced in stated amounts, provide smoothness and cream-like consistency of the novelty composition. Stability under storage and good extrusion of a finished medicinal form from a container (tin tube) is crucial for patient use.
  • the stand-out feature of our composition is the use of several structure defining emulsifiers. Simultaneous use of these emulsifiers and their strictly sequential introduction in a technique described in the disclosure, provide a prominent and stable effect of complex cream composition preservation. Presence of specific hydrophilic components (aqua, selenomethionine, glycerol) and specific ratios of solvents (cetyl alcohol, glycerol), allows to retain the activity of hydrophilic (selenomethionine) and hydrophobic (tocopherol, squalane, triglicerides) active substances that form the cream.
  • hydrophilic components aqua, selenomethionine, glycerol
  • solvents cetyl alcohol, glycerol
  • Bissett DL Chatterjee R, Hannon DP. Photoprotective effect of superoxide- scavenging antioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse. Photodermatol Photoimmunol Photomed.

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  • Engineering & Computer Science (AREA)
  • Dispersion Chemistry (AREA)
  • Cosmetics (AREA)
PCT/LV2015/000006 2015-08-24 2015-08-25 Epidermal lipid barrier restoring cream for facial skin, neck and decollete area for metabolic syndrome patients WO2017034384A1 (en)

Priority Applications (1)

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EP15902371.2A EP3439616A4 (en) 2015-08-24 2015-08-25 EPIDERMAL LIPID BARRIER FOR BUILDING CREAM FOR THE FACIAL SKIN, NECK AND DECOLLETE AREA FOR METABOLISM SYNDROMPATIENTS

Applications Claiming Priority (2)

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LVP-15-90A LV15082B (lv) 2015-08-24 2015-08-24 Krēms sejas ādas, kakla un dekoltē zonas epidermālās lipīdu barjeras atjaunošanai pacientiem ar metabolisko sindromu
LVP-15-90 2015-08-24

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US9949915B2 (en) 2016-06-10 2018-04-24 Clarity Cosmetics Inc. Non-comedogenic and non-acnegenic hair and scalp care formulations and method for use

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US5143940A (en) * 1988-04-08 1992-09-01 Stada Arzneimittel Ag Ambiphile cream
WO2001017484A2 (en) * 1999-09-07 2001-03-15 D.T.R. Dermal Therapy Research Inc. Topical urea composition

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US5143940A (en) * 1988-04-08 1992-09-01 Stada Arzneimittel Ag Ambiphile cream
WO2001017484A2 (en) * 1999-09-07 2001-03-15 D.T.R. Dermal Therapy Research Inc. Topical urea composition

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BB SOKMEN ET AL.: "Combined effects of treatment with vitamin C, vitamin E and selenium on the skin of diabetic rats.", HUMAN AND EXPERIMENTAL TOXICOLOGY, vol. 32, no. 4, 2013, pages 379 - 384, XP009510359, ISBN: 0144-5952, DOI: 10.1177/0960327112454897 *
K E BURKE.: "Photodamage of the skin: protection and reversal with topical antioxidants.", JOURNAL OF COSMETIC DERMATOLOGY, vol. 3, no. 3, 2004, pages 149 - 155, XP 002586516 *
See also references of EP3439616A4 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9949915B2 (en) 2016-06-10 2018-04-24 Clarity Cosmetics Inc. Non-comedogenic and non-acnegenic hair and scalp care formulations and method for use
US10159637B2 (en) 2016-06-10 2018-12-25 Clarity Cosmetics Inc. Non-comedogenic and non-acnegenic hair and scalp care formulations and method for use
US10813872B2 (en) 2016-06-10 2020-10-27 Clarity Cosmetics Inc. Hair and scalp formulations
US11160746B2 (en) 2016-06-10 2021-11-02 Clarity Cosmetics Inc. Non-comedogenic and non-acnegenic hair and scalp care formulations and method for use

Also Published As

Publication number Publication date
EP3439616A4 (en) 2020-03-04
EP3439616A1 (en) 2019-02-13
LV15082B (lv) 2016-04-20
LV15082A (lv) 2015-12-20

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