WO2010013204A1 - Composition pour régénérer des tissus cutanés et sous-cutanés sénescents, et produits et utilisations associés - Google Patents

Composition pour régénérer des tissus cutanés et sous-cutanés sénescents, et produits et utilisations associés Download PDF

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Publication number
WO2010013204A1
WO2010013204A1 PCT/IB2009/053287 IB2009053287W WO2010013204A1 WO 2010013204 A1 WO2010013204 A1 WO 2010013204A1 IB 2009053287 W IB2009053287 W IB 2009053287W WO 2010013204 A1 WO2010013204 A1 WO 2010013204A1
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composition
cutaneous
composition according
propolis
asx
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PCT/IB2009/053287
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English (en)
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Luisa Gennero
Enrico De Vivo
Antonio Ponzetto
Chiara Cesano
Emanuella Morra
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Luisa Gennero
Enrico De Vivo
Antonio Ponzetto
Chiara Cesano
Emanuella Morra
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Publication of WO2010013204A1 publication Critical patent/WO2010013204A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/63—Arthropods
    • A61K35/64—Insects, e.g. bees, wasps or fleas
    • A61K35/644—Beeswax; Propolis; Royal jelly; Honey
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
    • 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
    • A61K8/42—Amides
    • 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
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/602—Glycosides, e.g. rutin
    • 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
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66—Enzymes
    • 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
    • A61K8/987—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of species other than mammals or birds
    • A61K8/988—Honey; Royal jelly, Propolis
    • 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
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • 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

  • composition for regenerating senescent cutaneous and subcutaneous tissue, products and use thereof
  • the present invention relates to a composition for regenerating senescent cutaneous and/or subcutaneous tissue.
  • the present invention has the object of providing a composition suitable for regenerating cutaneous and/or subcutaneous tissue with wrinkles and striae in the compromised areas.
  • BACKGROUND OF THE INVENTION Wrinkles are essentially linked to facial expressions- due to reflective action of the facial muscles - or to senescence - due to irreversible relaxation of the skin.
  • the cutaneous picture including wrinkles, crow's feet, sagging and relaxation of the skin, results from the normal organic decline occurring with the passing of the years. Climacteric and the endocrine collapse that characterises it play a major role in the development of these aesthetic imperfections. Furthermore, internal disturbances associated with aging can certainly enhance and impact the condition of the skin.
  • Aging of the epidermis results in a certain reduction in cellular reproduction, typical of the germinal layer of the skin and reduction in the cells of the malphighian layer that are extremely important to the epidermis.
  • the known skin products when well formulated, serve as preventives and coadjuvants in fighting the appearance of wrinkles, though they can not rejuvenate the skin, but only rehydrate it intensively.
  • the present invention has the objects of: blocking the unavoidable modification of the mucopolysaccharide component of the ground substance and the loosening of the elastic component and collagen of derma; - slowing the flattening of the papillary ridges, preventing the slowing of blood circulation, avoiding the accumulation of toxins;
  • antibiotics preferably aminoglycosides
  • ⁇ local amino amide anaesthetics, preferably lidocaine
  • proteolytic agents preferably papain
  • antiseptic and salt reconstituting agents preferably propolis.
  • Such activity is induced through the local- regional interaction of these compounds, inducing t recovery of the trophism of senescent or pathological cutaneous and/or subcutaneous tissue.
  • the above-identified compounds may be advantageous employed both in the cosmetic field, due to their efficacious anti-wrinkle action, and in the medical field for their efficacious action in re-equilibrating the cutaneous and subcutaneous microenvironments .
  • such compounds may be used advantageously for the cosmetic treatment of wrinkles in a mammal, preferably in a human being.
  • such compounds may be used advantageously for the regeneration of the cutaneous and subcutaneous tissue of a mammalian, animal or human being, subjected to the damaging of these tissues.
  • composition object of the present invention comprises at least two compounds selected among:
  • antibiotics preferably aminoglycosides, more preferably gentamicin
  • amino amide local anaesthetics preferably lidocaine
  • proteolytic agents preferably papain
  • antiseptic and salt reconstituting agents preferably propolis
  • the aminoglycoside antibiotics contained in the composition of the present invention may advantageously be selected from: gentamicin, micronomicin, spectinomycin, amikacin, kanamycin, tobramycin, neomycin, metilmycin, paromycin, streptomycin, or precursors or natural or synthetic derivative thereof.
  • gentamicin micronomicin
  • spectinomycin amikacin
  • kanamycin tobramycin
  • neomycin metilmycin
  • paromycin paromycin
  • streptomycin or precursors or natural or synthetic derivative thereof.
  • aminoglycoside antibiotic gentamicin is particularly preferred.
  • the amino amidic local anaesthetics contained in the composition object of the present invention may advantageously be selected from: lidocaine, lidocaine hydrochloride, mepivacaine, prilocaine, bupivacaine, etidocaine, ropivacaine, or precursors or natural or synthetic derivatives thereof.
  • lidocaine is particularly preferred.
  • the proteolytic agents contained in the composition object of the present invention can be advantageously selected from among: papain, papain FU, collagenase (preferably of type Ia, type II, type IV) , serratiopeptidases, bromelain, bradykinase, Clostridium peptidases, proteolytic enzymes expressed by Lactobacillus acidophilus, proteolytic enzymes expressed by the genus Aspergillus, proteases, alliinases and fibrinolysin, precursors or natural or synthetic derivatives thereof.
  • papain FU is particularly preferred.
  • the antiseptic and salt reconstituents contained in the composition object of the present invention can be advantageously selected from among: propolis, propolis concentrate, de-waxed propolis, concentrated de-waxed propolis, royal jelly and whole beeswax, precursors or natural or synthetic derivatives thereof.
  • propolis is particularly preferred.
  • the composition may be prepared in the form of a cosmetic composition (for an anti-wrinkle treatment ) , a pharmaceutical composition, a medical device, or in the form of a culture medium for the remodelling and regeneration of cutaneous and/or subcutaneous tissue or for the stimulation of normal trophism and/or pigmentation.
  • the composition object of the present invention in addition to containing at least two among compounds (i) to (iv) identified above, may optionally comprise one or more additional active ingredients that operate synergistically with those compounds, increasing the efficacy of the composition in restoring recovering the trophism of pathological or senescent cutaneous and/or subcutaneous tissue.
  • the additional active ingredients can be selected from amino acids, vitamins, glucosaminoglycans, sugars, peptides, supplements.
  • such preparations can optionally comprise a physiologically acceptable solvent and/or diluent, as well as common excipients and/or additives for pharmaceutical or cosmetic compositions.
  • the aminoglycoside antibiotic preferably gentamicin
  • the aminoglycoside antibiotic is used in a quantity comprised between 4 mg/Kg and 650 mg/Kg with respect to the total weight of the composition, preferably between 40 mg/Kg and 320 mg/Kg, more preferably between 40 mg/Kg and 160 mg/Kg for the substantially solid (creams) , gel or liquid compositions.
  • the amino amide local anaesthetic preferably lidocaine hydrochloride
  • the amino amide local anaesthetic is used in a quantity comprised between 1 mg/Kg and 400 mg/Kg with respect to the total weight of the composition, preferably between 1 mg/Kg and 100 mg/Kg, more preferably between 10 mg/Kg and 80 mg/Kg for the substantially solid , gel or liquid compositions.
  • the proteolytic agent preferably papain FU
  • the antiseptic and salt reconstituent preferably propolis
  • the antiseptic and salt reconstituent is used in a quantity comprised between 0.1% (w/v) and 50% (w/v) with respect to the total volume of the composition, preferably between 1% (w/v) and 30% (w/v) , more preferably between 10% (w/v) and 20% (w/v) for the substantially solid, gel or liquid compositions.
  • composition may be formulated as a solid or liquid, anhydrous or aqueous, for example in the form of a cream, unguent, ointment, powder, patch, impregnated membrane, solution, emulsion, suspension, vesicular dispersions, lotion, gel, spray.
  • a cream base is used as diluent or vehicle in the substantially solid preparations (such as creams, unguents, ointments); a physiological solution is used as diluent in the substantially liquid preparations .
  • amino acids such as methionine, cystine, N- acetylcysteine, cysteine, glycine, leucine, isoleucine, proline, glutamine, arginine, glutamic acid, histidine, histidine-HCl, lysine, lysine-HCl, phenylalanine, serine, threonine, tryptophan, tyrosine, tyrosine- disodium salt, valine, hydroxyproline .
  • amino acids are often used in mixtures comprising a large number of different amino acids.
  • vitamins and cofactors such as retinoic acid, retinaldehyde, retinol, alpha-tocopherol, beta-carotene, ascorbic acid, pantothenic acid, dexpanthenol, D-calcium pantothenate, cocarboxylase tetrahydrate, pyridoxine, pyridoxine-HCl, folic acid, niacinamide, riboflavin, cobalamin, para-aminobenzoic acid, biotin and as vitamin- related nutrients inositol and myoinositol; glucosaminoglycans, such as hyaluronic acid, chondroitin sulphates;
  • sugars such as rice starch, glucose, sucrose, glucans, mannan, glucomannan, fucose, fructose, heparan sulfates, pectin, starches, their alcohol derivatives; peptides, such as glutathione, collagen, elastin, wheat extract;
  • composition object of the present invention is represented by the composition denominated ASX described hereinafter in the form of a cream, gel and infusion.
  • compositions ASX- 1-GEL compositions ASX-I-CREMA and ASX-I-INFUS and ASX-2-GEL, ASX- 2-CREMA and ASX-2-INFUS and are illustrated by way of example only in tables 1 to 6.
  • Such composition may comprise, in addition to at least two of the above identified compounds (i) to (iv) and to the possible additional ingredients, a physiologically acceptable vehicle such as a cream base, a gel or a physiological solution.
  • a physiologically acceptable vehicle such as a cream base, a gel or a physiological solution.
  • Table 1 Composition ASX-I-GEL (medical device) for the treatment of senescent cutaneous and subcutaneous tissue.
  • composition ASX-I-CREMA for the treatment of senescent cutaneous and subcutaneous tissue.
  • Table 3 Composition ASX-I-INFUS for the treatment of senescent cutaneous and subcutaneous tissue.
  • Composition ASX-2-GEL (medical device) for the treatment of senescent cutaneous and subcutaneous tissue.
  • Table 5 Composition ASX-2-CREMA for the treatment of senescent cutaneous and subcutaneous tissue.
  • the cosmetic, pharmaceutical and medical device type compositions object of the present invention may also comprise further accessory elements such as excipients and vehicles whose choice and employment fall within the capacity of one skilled in the art with no need to exert inventive activity.
  • the animal biopsy samples under study are constituted by atrophic-senescent surgical specimens removed for the purpose of correcting major functional cutaneous or subcutaneous alterations.
  • Negative control the control 1 biopsy specimens were suspended in physiological solution in 10 cm plates
  • control 2 biopsy specimens were placed in 10 cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) in D-MEM medium supplemented with:
  • sample biopsy specimens 3 were placed in 10 cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) in Culture media ASX-I-INFUS.
  • Negative controls 1 treated with physiological solution: diffuse blue staining (score ++++) alternating with cytolytic and necrotic areas.
  • the present study was performed on a sample constituted by four dogs of different races and sizes presenting cutaneous lesions attributable to cutaneous laxity (genetically determined or acquired wrinkling) with consequent infective or fibrotic processes, ulceration or atrophy.
  • subjects were selected with the lesions indicated above.
  • the animals were brought to the clinical follow-up visits weekly until healing and subjected to cytological examination and evaluation of the extension and depth of the cutaneous lesions.
  • Diagnosis Clinical picture referable to chronic atrophy complicated by superficial secondary infections.
  • the cytological examination revealed a bacterial infection of the ulcerated lesion.
  • Diagnosis The cytological examination indicated bacterial superinfection of the burn wound with hypertrophic scars.
  • Marbofloxacin was administrated per os at 2.5 mg/Kg for 21 days.
  • the fur was shaved and wound cleaned with povidone-iodine followed by application of the preparation ASX-I-CREMA twice daily for 60 days.
  • the dog had cutaneous laceration areas (mainly of the adnexal structure type) of the posterior limbs for about one year that had progressively increased in diameter in the last 2 months . Surgical removal of the ulcer tissue and of the excess cutaneous mass was performed; antibiotic therapy with cefalexin for 15 days at 20 mg/kg bid was set up.
  • composition with anti-wrinkle action ASX-2- CREMA was administered with two daily applications for a period of no less than 30 days up to a maximum of ' 90 days. In no case was the onset of allergy or intolerance phenomena observed, instead in most cases a few days after starting therapy patients reported a feeling of local tension. Initially, in almost all subjects, elasticity was observed as an affect of the superficial vasodilation induced by the composition ASX-2-CREMA; definitely a positive effect considering the state of occlusion of many vessels observed both in expression grooves and in the atrophic senescent wrinkles. In the greater part of the subjects the significant regression of the wrinkles (90%) with respect to time zero was obtained. Highly significant results with respect to time zero were observed in the majority of subjects enrolled in group A (98%) . A significant reduction
  • EXAMPLE 3 COMPARATIVE STUDIES. ANTI-WRINKLE COMPOSITION ASX-I-CREMA AND ASX-2-CREMA.
  • the first group under study is formed by subjects with age comprised between 20-35 years presenting facial expression wrinkles and which were treated for thirty days exclusively with ASX-2 CREMA.
  • the second group under study is formed by subjects of age comprised between 60-75 years presenting deep facial wrinkles linked to senescence and which were treated for thirty days exclusively with ASX-I CREMA.
  • Each subject applies the product to the face twice per day (morning and evening) .
  • test is performed according to the principles of the Helsinki declaration, on 40 consenting subjects (all female), a group of 20 subjects with age comprised between 20 and 35 years (treatment ASX-2 CREMA) and a group of 20 subjects with age comprised between 60 and 75 years (treatment with ASX-I CREMA) .
  • treatment ASX-2 CREMA a group of 20 subjects with age comprised between 20 and 35 years
  • ASX-I CREMA a group of 20 subjects with age comprised between 60 and 75 years
  • Group 1 women between 20 and 35 years of age with mild cutaneous expression wrinkles (grade I on Larnier photographic scale) ;
  • Subjects have undergone filler treatments on the face (ex. collagen, hyaluronic acid, etc);
  • Subjects that had taken systemic retinoids during the year prior to the study - Subjects that had applied topical products based on alpha or beta hydroxyacids in the 45 days prior to the study;
  • Evaluation of tolerability appearance of possible undesirable effects such as erythema, desquamation, itching and swelling.
  • Instrumental measurements were performed inside a climate controlled room (24° + 2 C°; 50 +10% rh) after an acclimatisation period of 30 minutes.
  • Monaderm is based on the measurement principle described by Corcuff.
  • Biopsies treated with formulation ASX-I complete versus partial formulations .
  • Eight types of controls were prepared: (1) an untreated negative control-1 resuspended in physiological solution containing antibiotics as described below; (2) a positive control-2 treated with cell culture media commonly used for cutaneous biopsies; (3) a positive control-3 treated with incomplete ASX-I medium containing only gentamicin as active principle; (4) a positive control-4 treated with incomplete ASX-I medium containing only lidocaine as active principle; (5) a positive control-5 treated with incomplete ASX-I medium containing only papain as active principle; (6) a positive control-6 treated with incomplete ASX-I medium containing only gentamicin and lidocaine as active principles; (7) positive control-7 treated with incomplete ASX-I medium containing only papain and lidocaine as active principles; (8) a positive control-8 treated with incomplete ASX-I medium containing only papain and gentamicin as active principles.
  • a type (9) sample-9 was prepared, treated with COMPLETE ASX-I medium containing gentamicin, lidocaine and papain.
  • a type (10) sample-10 was prepared, treated with COMPLETE ASX-I + ASX-2 medium containing gentamicin, lidocaine, papain and propolis.
  • Negative Control-1 the control 1 biopsy specimens were suspended in physiological solution in 10- cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) .
  • Positive Control-2 the control 2 biopsy specimens were placed in 10-cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) in D-MEM medium supplemented with:
  • gentamicin Schering-Plough, Milan, Italy
  • L-glutamine Life Technologies; growth medium
  • EGF EGF
  • control 3 biopsy specimens were placed in 10-cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) in the solution whose composition is reported in table 11.
  • the above-said solution contains additional active ingredients as reported in table 12.
  • control 4 biopsy specimens were placed in 10-cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) in the solution whose composition is reported in table 13.
  • the above-said solution contains additional active ingredients as reported in table 12.
  • control 5 biopsy specimens were placed in 10-cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) in the solution whose composition is reported in table 14.
  • the above-said solution contains additional active ingredients as reported in table 12. Table 14.
  • control 6 biopsy specimens were placed in 10-cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) in the solution whose composition is reported in table 15.
  • the above-said solution contains additional active ingredients as reported in table 12.
  • control 7 biopsy specimens were placed in 10-cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) in the solution whose composition is reported in table 16.
  • the above-said solution contains additional active ingredients as reported in table 12. Table 16.
  • control 8 biopsy specimens were placed in 10-cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) in the solution whose composition is reported in table 17.
  • the above-said solution contains additional active ingredients as reported in table 12.
  • sample 9 biopsy specimens were placed m 10-cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) in Culture medium ASX-I-INFUS COMPLETE whose composition is reported in table 18.
  • ASX-I-INFUS COMPLETE whose composition is reported in table 18.
  • the above-said solution contains additional active ingredients as reported in table 12.
  • sample 10 biopsy specimens were placed in 10-cm plates (Lab-Tek chamber slides, Nunc, Kamstrup, Denmark) in Culture medium ASX-l-ASX-2-INFUS COMPLETE whose composition is reported in table 19.
  • ASX-l-ASX-2-INFUS COMPLETE whose composition is reported in table 19.
  • the above-said solution contains additional active ingredients as reported in table 12.
  • amino glycoside antibiotic for example gentamicin or a derivative thereof
  • amino-amidic anaesthetic, lidocaine or a derivative thereof for example gentamicin or a derivative thereof
  • proteolytic enzyme for example papain.
  • the solution ASX-l-ASX-2 COMPLETE (Sample-10) comprises in a single solution: - an aminoglycoside antibiotic, for example gentamicin or a derivative thereof; and an amino amide anaesthetic, lidocaine or a derivative thereof; and a proteolytic enzyme, for example papain; and an apitherapeutic product, for example propolis.
  • an aminoglycoside antibiotic for example gentamicin or a derivative thereof
  • an amino amide anaesthetic, lidocaine or a derivative thereof and a proteolytic enzyme, for example papain
  • an apitherapeutic product for example propolis.
  • the colorimetric method used to evaluate the entire cutaneous and subcutaneous matrix produced was described above ("Alcian blue"), the method of choice for evaluating the extracellular matrix in its entirety [2]. The results are reported in table 23.
  • WB Western Blot
  • Example- 9 of the solution Culture medium ASX-I-INFUS COMPLETE result in the deposition of normal cutaneous or subcutaneous matrix, but the use of all four synergistic active principles, such as gentamicin + lidocaine + papain + propolis (Sample-10) of the Culture medium ASX-l-ASX-2 INFUS COMPLETE, results in the deposition of an excellent corresponding to eutrophic cutaneous and subcutaneous tissue.

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Abstract

L'invention concerne une composition cosmétique, un dispositif médical et une composition pharmaceutique permettant le remodelage et la régénération des tissus cutanés et sous-cutanés relâchés, atrophiques ou sénescents qui caractérisent l'apparition des rides d'expression ou de vieillesse chez les mammifères, animaux ou humains, comprenant au moins deux composants parmi (i) des antibiotiques, (ii) des anesthésiques locaux amino-amidiques, (iii) des agents protéolytiques, et (iv) des reconstituants antiseptiques et salins.
PCT/IB2009/053287 2008-07-29 2009-07-29 Composition pour régénérer des tissus cutanés et sous-cutanés sénescents, et produits et utilisations associés WO2010013204A1 (fr)

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ITTO2008A000584 2008-07-29
IT000584A ITTO20080584A1 (it) 2008-07-29 2008-07-29 Composizione per la rigenerazione di tessuto cutaneo e sottocutaneo senescente, relativi prodotti ed usi

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WO2010013204A1 true WO2010013204A1 (fr) 2010-02-04

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITTO20090428A1 (it) * 2009-06-04 2010-12-05 Chiara Cesano Composizione cosmetica e farmaceutica e mezzo di coltura per la rigenerazione del tessuto mucoso orale, e relativi usi
WO2012095702A1 (fr) * 2011-01-13 2012-07-19 Medestea Internazionale S.P.A. Composition pour régénérer des tissus atrophiques
US11311582B2 (en) 2015-11-19 2022-04-26 Locus Biosciences, Inc. Bacteriophage compositions and methods of use thereof

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US4748022A (en) * 1985-03-25 1988-05-31 Busciglio John A Topical composition
DE19904801A1 (de) * 1999-02-05 2000-08-10 Klossner Axel Mittel zur topischen Behandlung von Hauterkrankungen
WO2001066066A1 (fr) * 2000-03-03 2001-09-13 Australian Importers, Ltd. Compositions cosmetiques comportant des enzymes exfoliantes et utilisations de telles compositions
WO2002076411A2 (fr) * 2001-03-27 2002-10-03 Dorian Owoc Agent dermatologique pour le traitement des lesions cutanees, particulierement des brulures
WO2004022034A1 (fr) * 2002-08-01 2004-03-18 Dermaphyt Ltd. Preparation dermatologique pour le traitement de lesions cutanees
US20040076671A1 (en) * 2002-10-21 2004-04-22 Aletha Tippett Methods and compositions for topical wound treatment
US20060233783A1 (en) * 2003-04-09 2006-10-19 Gomez Torres Harold A Topical composition in the form of a gel for treating skin burns
WO2007076446A1 (fr) * 2005-12-21 2007-07-05 Colgate-Palmolive Company Compositions orales comprenant de la propolis
US20080044459A1 (en) * 2006-05-12 2008-02-21 Livingston James A Enzymatic debridement therapy for abnormal cell proliferation

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4748022A (en) * 1985-03-25 1988-05-31 Busciglio John A Topical composition
DE19904801A1 (de) * 1999-02-05 2000-08-10 Klossner Axel Mittel zur topischen Behandlung von Hauterkrankungen
WO2001066066A1 (fr) * 2000-03-03 2001-09-13 Australian Importers, Ltd. Compositions cosmetiques comportant des enzymes exfoliantes et utilisations de telles compositions
WO2002076411A2 (fr) * 2001-03-27 2002-10-03 Dorian Owoc Agent dermatologique pour le traitement des lesions cutanees, particulierement des brulures
WO2004022034A1 (fr) * 2002-08-01 2004-03-18 Dermaphyt Ltd. Preparation dermatologique pour le traitement de lesions cutanees
US20040076671A1 (en) * 2002-10-21 2004-04-22 Aletha Tippett Methods and compositions for topical wound treatment
US20060233783A1 (en) * 2003-04-09 2006-10-19 Gomez Torres Harold A Topical composition in the form of a gel for treating skin burns
WO2007076446A1 (fr) * 2005-12-21 2007-07-05 Colgate-Palmolive Company Compositions orales comprenant de la propolis
US20080044459A1 (en) * 2006-05-12 2008-02-21 Livingston James A Enzymatic debridement therapy for abnormal cell proliferation

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITTO20090428A1 (it) * 2009-06-04 2010-12-05 Chiara Cesano Composizione cosmetica e farmaceutica e mezzo di coltura per la rigenerazione del tessuto mucoso orale, e relativi usi
WO2012095702A1 (fr) * 2011-01-13 2012-07-19 Medestea Internazionale S.P.A. Composition pour régénérer des tissus atrophiques
US11311582B2 (en) 2015-11-19 2022-04-26 Locus Biosciences, Inc. Bacteriophage compositions and methods of use thereof

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