WO2020121017A1 - Synthèse de crème à partir de médiateurs de plaquettes avec des activateurs de pénétration à base d'herbes permettant d'augmenter la teneur en collagène de la peau - Google Patents

Synthèse de crème à partir de médiateurs de plaquettes avec des activateurs de pénétration à base d'herbes permettant d'augmenter la teneur en collagène de la peau Download PDF

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Publication number
WO2020121017A1
WO2020121017A1 PCT/IB2018/059802 IB2018059802W WO2020121017A1 WO 2020121017 A1 WO2020121017 A1 WO 2020121017A1 IB 2018059802 W IB2018059802 W IB 2018059802W WO 2020121017 A1 WO2020121017 A1 WO 2020121017A1
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WIPO (PCT)
Prior art keywords
skin
collagen
cream
platelet
mediators
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PCT/IB2018/059802
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English (en)
Inventor
Hamidollah AFRASIABIAN
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Afrasiabian Hamidollah
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Priority to PCT/IB2018/059802 priority Critical patent/WO2020121017A1/fr
Publication of WO2020121017A1 publication Critical patent/WO2020121017A1/fr

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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)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484—Glycyrrhiza (licorice)
    • 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)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/734—Crataegus (hawthorn)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • 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
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/925—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of animal 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
    • 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]
    • A61K8/9794—Liliopsida [monocotyledons]
    • 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
    • A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • A61K8/983—Blood, e.g. plasma

Definitions

  • the technical field of this invention is related to skin’s collagen Cream.
  • Skin is a natural barrier, so it is necessary to employ enhancement strategies to improve topical bioavailability. Therefore, many different approaches have been developed to overcome the impervious nature of the skin’s outer layer (stratum corneum) by various physical, chemical, biochemical enhancement strategies. But, we should note that the physical and chemical permeation enhancers have different side effects. While the natural products have got the potential to enhance the permeation of drug through the skin by reversibly reducing the skin barrier resistance. They are safe, non-toxic, pharmacologically inert, non-irritating and non- allergenic to use.
  • non-invasive laser is one of new methods that increase skin collagen, which is named as "non-invasive laser procedure”.
  • the invention provides a ginseng compounded cream for improving the collagen structure of human skins.
  • the ginseng compounded cream comprises, by weight, 3-10 parts of ginseng extract, 1-5 parts of collagen tripeptides, 3-10 parts of Folium Phyllostachys extract, 0.1-0.5 part of capsaicin, 3-10 parts of glycerin monostearate, 1-5 parts of tretinoin, 20-30 parts of glycerin and 10-20 parts of water. All above components have synergistic effects, so the collagen structure of human skins is remarkably improved, and the diameters and the spacing of fibrils are structure, thereby collagen fibers have good cohesiveness and stability, skin pores are shrunk, and ultraviolet radiation, blue light radiation and other damages are resisted.
  • Licorice extract have effectively treated skin disorders such as rosacea, eczema, psoriasis and dermatitis. Also, it has been known to fade dark spots and lighten skin.
  • One of the ingredients is glabridin which acts to depigment. Pigmentation is caused by exposure to the sun's ultra violet rays on the other hand, potent antioxidants in licorice extract fight skin-damaging free radicals.
  • Glycyrrhiza glabra was reported to show improvement in the viscoelastic and hydration properties of the skin. 8
  • Wheat germ is widely recognized as a nutritious raw material for incorporation into food and cosmetic products. Wheat germ was found to be a rich source of carbohydrate (46.07 gr/lOOgr), protein (31.69 gr/lOOgr), and fatty acid (10.29 gr/lOOgr) especially linoleic, palmitic, oleic, linolenic acids. Also, it has antioxidant and antibacterial activity. 9,10 But it is a great source of vitamins such as E, Be, zinc, copper, phosphorus, manganese, and folic acid. So, it can act as an anti-aging agent for the skin. In addition, we used it as a humidifier.
  • Cholesterol is a vital component of human epidermal keratinocyte membranes and lipid micro environments on the cell surface known as lipid rafts. 15 It was demonstrated that UVA radiation (320- 400 nm) reduces the content of cholesterol in plasma membranes and lipid rafts as a consequence of sphingomyelin hydrolysis and conversion to ceramide. Cholesterol plays a crucial role for stabilization of rafts which ideally need a cholesterol to ceramide ratio of > 1. Cholesterol depletion increased the susceptibility of keratinocytes for UVA-induced gene expression, whereas pre treatment with cholesterol completely abrogated the UVA stress response.
  • phytosterols was reported to be used in 177 cosmetic products such as lipsticks, non-spray deodorant, eye make-up, face powders and... .
  • the phytosterols are used in all of the FDA's cosmetic category groups except baby product. They are used at maximum concentration ranging from 0.000001%-8%. Most of them have been used as skin-conditioning agents or skin protectant or antioxidant. 17 19
  • This study is a randomized clinical trial; 106 patients referred to the clinic with positive cases from skin wrinkles along with 20 MHz frequency ultrasound images of their skin faces. All individual enrolled in the study were randomly divided into two groups. 1
  • group A the platelet cream was prepared including emulsion of Lecithin and Eucerin as basic cream (this cream purchased from Farabi Pharmaceutical Company of Iran). 10 cc of blood was taken from each patient, then placed in a centrifuge machine at a speed of 1200 rpm for 15 minutes (the centrifuge tube contains an anticoagulant). Finally, after completion of the plasma centrifuge, plasma plate was added to the cream base. At first, the amount of plasma solution is 5 cc.
  • group B 60cc of basic cream group A along with lOcc glycerin was added as placebo. Consequently, 70 cc cream including placebo submitted to group B people.
  • the cream was delivered to everyone in the two groups for one month's use. All people were advised to wash their face 2 hours before bed, rub it with a relatively rough texture, then dry the face. Then rub 2.3 g of the cream into the face skin slowly, also for each person, certain dishes with a capacity of 2.3 g of cream were prepared.
  • the numerical comparison of the difference in skin tissue collagenization in two groups was very important. For the measurement of collagen before and after using the cream, ultrasound images of 20 MHz frequency were used.
  • the B-mode scanner and the DUB- USB-Luneburg Germany devices were used in current project. Sonographic images of both groups were obtained before and after the use of platelet and placebo creams. The reflection of the frequency transmitted to the skin tissue appears as an increase in the amount of brightness in the skin. Whatever collagen content per unit volume, collagen fibers are seen in bright or gray stripes. But the basis for comparing the tissue repair of the skin should be expressed in numerical units. In this image, the reflection energy of ultrasound radiation was evaluated based on the base ROI, to transform into a meaningful and numerical physical quantity; the radius energy square was expressed as the numerical quantity as shown in equation. Finally, a comparison was made by converting the numerical values of these values.
  • the results in the various aspects include; there is no significant correlation between demographic conditions of the participants and the amount of collagen in the skin through numerical evaluation of RE .
  • the demographic conditions in this research include sex, occupation, economic status and literacy level had no effect on the response to treatment but the age demographic index had a significant effect on response to treatment.
  • the effective factor in responding to treatment is the amount of skin collagen compression; the better collagen production is in the skin with a higher collagen density.
  • the minimum and maximum of the RE value or the reflectance energy square was 10 and 25 respectively. But the amount of change in either the production or increase of collagen in the worst and best case was obtained 1 and 7 respectively. Noticeably, only one person in group A had the highest increase in collagen content. In group A, 2 patients left the study due to an allergic reaction, and 3 individuals did not continue the study. As in group B, 5 patients did not go on the study.
  • Structure of the skin can be divided into epidermis, dermis and hypodermis (figure 3).
  • the epidermis can be subdivided into different layer.
  • the outer layer is stratum corneum. It is typically 10-20 pm thick and compose of corneocytes which are non-living cells without nuclei and cytoplasmic organelles but are filled with keratin and are interspersed in a lipid-enriched extracellular matrix. Since diffusion across the stratum corneum is considered as the major pathway of skin permeation, the structural properties of this layer have been extensively studied to elucidate it’s barrier function. 20,21
  • Ceramides, cholesterol and saturated free fatty acids are the main constituents of the extracellular matrix in approximately equimolar proportions. 22
  • Each ceramide molecule consists of a sphingoid moiety, containing a polar head group and a hydrocarbon chain which -NH2 functional group of it can reacted with a fatty acid as shown in figure 4. 23
  • ceramides are fully extended in the stratum corneum with the two hydrocarbon tails in opposite directions.
  • the rest of epidermis is composed of keratinocytes (95%).
  • Keratin is a fibrous structural protein from alanine, leucine, arginine and cysteine. It is two polypeptide chain with disulfide cross-linked ( Figure 5). Consequently, we found the first barrier for penetration of a drug has both lipophilic and hydrophilic structures.
  • the dermis is composed mainly of collagen and elastin.
  • the hypodermis is composed mainly of subcutaneous fat.
  • Permeation enhancers are defined as substances that are capable of promoting penetration of drugs into skin. There are two pathways for permeation (Figure 6). The first is trans epidermal (diffusing across the skin layers containing Intracellular or Intercellular routes), and the second is appendageal pathway (through hair follicles or sweat ducts).
  • the trans epidermal pathway is usually the predominant route and it is comfortable, convenient and non-invasive way to administer drugs. 25 But, the greatest obstacle in the transdermal drug delivery is stratum comeum because it provides a rate-limiting step for the delivery of drugs. So, many different approaches have been developed to overcome the impervious nature of stratum corneum by various physical, chemical, biochemical enhancement strategies. The physical strategies involve phonophoresis, electrophoration, iontophoresis, magnetophoresis, micro fabricated needle and laser technologies.
  • LPP lipid-protein-partition
  • SAR structure- activity relationship
  • the water content of human stratum corneum is typically around 15-20% of tissue dry weight and it can approach 400%. In general, increased tissue hydration appears to increase transdermal delivery of permeant.
  • the water within this membrane is found in two states: The water present in stratum comeum can be assessed as bound i.e. is associated with some structural functional groups within the tissue (hydrogen bonding or covalent bond), and the free water which is available to act as a solvent within the membrane for polar parts of permeants. 35
  • saturated alky chain lengths of around C10-C12 attached to a polar head group yields a potent enhancer and unsaturated alky chains up to Cis (e.g. oleic, linoleic, linolenic arachidonic acids) can optimum the penetration especially cis configuration (figure 7) is expected to disturb intercellular lipid packing as pools more than the trans arrangemet. 36 38 The formation of such pools would provide permeability defects within the bilayer lipids to facilitate permeation. Also, the fatty acids in transdermal formulations appear to reduce the skin irritation and sensitization which is most common problem associated with some drugs.
  • Cis e.g. oleic, linoleic, linolenic arachidonic acids
  • Surfactants are added to formulations in order to solubilize lipophilic ingredients within the stratum comeum. They are divided to four groups non-ionic, anionic, cationic and zwitter ionic. Anionic and cationic surfactant have potential to damage human skin 39 and non-ionic surfactants tend to be widely regarded as safe. 40 But natural surfactants such as saponins have great potential for use as permeation enhancers. 41,42
  • the natural products containing essential oils, terpenes, and herbal extract (e.g. flavonoids, alkaloids) permeation enhancers exhibit low toxicity while maintaining their enhancing activity. 43
  • terpenes could form hydrogen bonds with intercellular lipids and the polar extracts of plant can be more effective for hydrophilic drugs penetration. 44 So, we should consider all of the points mentioned above to provide a targeted formulation.
  • Collagen is protein molecules made up of amino acids. There are various types of collagen (30) that have been discovered but, the most common are type 1 through IV and specially type 1. The differences lie in the make-up of the alpha peptides.
  • the primary amino acid sequence of collagen is glycine -proline-X or glycine-X-hydroxyproline ( Figure 8).
  • X can be any of the other 17 amino acids.
  • Collagen is composed of 3 chains which are wound together to form a triple helix.
  • a-chain The interaction of a-chains is stabilized via interchain hydrogen bonding making the molecule fairy resistant to attack by other molecules.
  • Each a-chain is surrounded by a hydration sphere (hyaluronic acid) which allows a hydrogen bonding network to be present between the water molecules and the peptide acceptor groups. 45
  • the synthesis of fibrillary collagen is discussed in the following. 1. Transcription of mRNA.
  • prolyl hydroxylase and lysyl hydroxylase to produce hydroxyproline and hydroxylysine
  • the enzymatic step requires vitamin C as a cofactor.
  • oligosaccharides are added.
  • the enzymes known as collagen peptidases remove the loose ends of the procollagen.
  • Fysyl oxidase an extracellular copper-dependent enzyme, produces the collagen according the following process (figure 9).
  • Hyaluronic acid has water-binding properties which allows the skin to maintain a water-electrolyte imbalance. As a result of aging, the amount of hyaluronic acid in the skin is almost completely reduced. As it is known, we should notice to the existence of vitamin C and Cu element as cofactors in reconstruction of collagen.
  • thrombin adenine, nucleotides, serotonin, Ca 2+ ions.
  • thrombocytes The most important growth factors stored in thrombocytes are:
  • PDGF Plate Derived Growth Factor
  • TGF-b Transforming Growth Factor b
  • EGF Epidermal Growth Factor
  • FGF Fibroblast Growth Factor
  • VEGF Vascular Endothelial Growth Factor
  • This cytokine acts via receptors mainly on the surface of endothelial cells triggering the signal that stimulates angiogenesis. This results in the construction of new vessels on the scaffold composed of collagen and other proteins of the extracellular matrix. VEGF was also shown to participate in the production of collagen fibers and stimulation of thrombocyte agglomeration and clot formation.
  • IGF Insulin-like Growth Factor
  • HGF Hepatocyte Growth Factor
  • the platelet can be divided into four zones ( Figure 10).
  • glycoproteins for adhesion, aggregation and so on.
  • the platelet plasma membrane is a standard bilayer composed of proteins and lipids.
  • platelet granules such as Alpha or Delta granules contain ADP, Ca and serotonin which are platelet-activating mediators
  • the platelet possesses a standard biological membrane composed of a phospholipid bilayer with polar head groups oriented toward the aqueous plasma and cytoplasm and nonpolar fatty acid tails the orient toward the center.
  • the phospholipid layers contain the neutral and anionic ones. The most important one of them is phosphatidylinositol which support platelet activation by supplying arachidonic acid that becomes converted to the eicosanoids prostaglandin and thromboxane A2 during platelet activation.
  • cholesterol stabilizes the membrane, maintains fluidity and helps control the trans membranous passage of materials. So, the platelet mediators are the best biological tool to promote the collagen production.
  • This method isn’t painful and the skin of patients hasn’t been suffered as a result of swelling, blood disorder, or treatment of tissue damage such as infection. 3. This method is non-thermal, so it doesn’t cause burns in the skin such as laser techniques.
  • This cream uses from platelet of the own patient, so it is a natural and biological cream for the skin rejuvenation.
  • the herbal extracts with useful properties has been used as penetration enhancers which don’t have any side effects
  • FGF fibroblastic growing factor

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Abstract

La présente invention utilise des médicaments complémentaires pour la synthèse d'une crème anti-âge efficace et non-invasive reposant sur des principes scientifiques. Ainsi, nous avons utilisé des médiateurs plaquettaires approuvés par la FDA et des pénétrateurs à base d'herbes sans danger ayant de nombreuses propriétés utiles. Pour la première fois, le musc a été utilisé comme activateur de pénétration efficace dans la formule avec des effets positifs inattendus. L'essai clinique randomisé a montré que le produit final aidera au rajeunissement de la peau.
PCT/IB2018/059802 2018-12-09 2018-12-09 Synthèse de crème à partir de médiateurs de plaquettes avec des activateurs de pénétration à base d'herbes permettant d'augmenter la teneur en collagène de la peau WO2020121017A1 (fr)

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PCT/IB2018/059802 WO2020121017A1 (fr) 2018-12-09 2018-12-09 Synthèse de crème à partir de médiateurs de plaquettes avec des activateurs de pénétration à base d'herbes permettant d'augmenter la teneur en collagène de la peau

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PCT/IB2018/059802 WO2020121017A1 (fr) 2018-12-09 2018-12-09 Synthèse de crème à partir de médiateurs de plaquettes avec des activateurs de pénétration à base d'herbes permettant d'augmenter la teneur en collagène de la peau

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112535691A (zh) * 2020-12-30 2021-03-23 广州瑞铂茵健康科技有限公司 一种用于创口愈合的复合细胞制剂

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008070368A2 (fr) * 2006-11-01 2008-06-12 Living Proof, Inc. Procédés et compositions pour le soin de la peau
WO2014103475A1 (fr) * 2012-12-27 2014-07-03 株式会社林原 Composition antivieillissement pour l'extérieur de la peau et son procédé de production
WO2014126931A1 (fr) * 2013-02-15 2014-08-21 Victor Steven Compositions stables de plasma riche en plaquettes et leurs procédés d'utilisation

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008070368A2 (fr) * 2006-11-01 2008-06-12 Living Proof, Inc. Procédés et compositions pour le soin de la peau
WO2014103475A1 (fr) * 2012-12-27 2014-07-03 株式会社林原 Composition antivieillissement pour l'extérieur de la peau et son procédé de production
WO2014126931A1 (fr) * 2013-02-15 2014-08-21 Victor Steven Compositions stables de plasma riche en plaquettes et leurs procédés d'utilisation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
AJAZUDDIN, S. SARAF: "Applications of novel drug delivery system for herbal formulations", FITOTERAPIA, vol. 81, 2010, pages 680 - 689, XP027275806 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112535691A (zh) * 2020-12-30 2021-03-23 广州瑞铂茵健康科技有限公司 一种用于创口愈合的复合细胞制剂

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