CA2242636A1 - Skin treatment formulation and uses thereof - Google Patents
Skin treatment formulation and uses thereof Download PDFInfo
- Publication number
- CA2242636A1 CA2242636A1 CA002242636A CA2242636A CA2242636A1 CA 2242636 A1 CA2242636 A1 CA 2242636A1 CA 002242636 A CA002242636 A CA 002242636A CA 2242636 A CA2242636 A CA 2242636A CA 2242636 A1 CA2242636 A1 CA 2242636A1
- Authority
- CA
- Canada
- Prior art keywords
- parts
- preparation according
- hydrolysed
- equivalent
- elastin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title description 20
- 238000009472 formulation Methods 0.000 title description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 37
- 229920001436 collagen Polymers 0.000 claims abstract description 31
- 229920002549 elastin Polymers 0.000 claims abstract description 31
- 102000016942 Elastin Human genes 0.000 claims abstract description 30
- 108010014258 Elastin Proteins 0.000 claims abstract description 30
- 102000008186 Collagen Human genes 0.000 claims abstract description 29
- 108010035532 Collagen Proteins 0.000 claims abstract description 29
- 229920002477 rna polymer Polymers 0.000 claims abstract description 18
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 14
- 102000053602 DNA Human genes 0.000 claims abstract description 10
- 108020004414 DNA Proteins 0.000 claims abstract description 10
- 239000002253 acid Substances 0.000 claims abstract description 9
- 239000000126 substance Substances 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 230000000304 vasodilatating effect Effects 0.000 claims abstract description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 25
- 229910052708 sodium Inorganic materials 0.000 claims description 25
- 239000011734 sodium Substances 0.000 claims description 25
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 23
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 20
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 19
- 239000003981 vehicle Substances 0.000 claims description 17
- 230000008595 infiltration Effects 0.000 claims description 13
- 238000001764 infiltration Methods 0.000 claims description 13
- 229960002685 biotin Drugs 0.000 claims description 11
- 235000020958 biotin Nutrition 0.000 claims description 11
- 239000011616 biotin Substances 0.000 claims description 11
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 10
- 239000004471 Glycine Substances 0.000 claims description 10
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims description 10
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 10
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 10
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 10
- 239000004472 Lysine Substances 0.000 claims description 10
- 102000057297 Pepsin A Human genes 0.000 claims description 10
- 108090000284 Pepsin A Proteins 0.000 claims description 10
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical group Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 claims description 10
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 10
- 229930003268 Vitamin C Natural products 0.000 claims description 10
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims description 10
- 229960002591 hydroxyproline Drugs 0.000 claims description 10
- 229940111202 pepsin Drugs 0.000 claims description 10
- 229960001309 procaine hydrochloride Drugs 0.000 claims description 10
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 10
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims description 10
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 10
- 235000019154 vitamin C Nutrition 0.000 claims description 10
- 239000011718 vitamin C Substances 0.000 claims description 10
- 102000011782 Keratins Human genes 0.000 claims description 9
- 108010076876 Keratins Proteins 0.000 claims description 9
- 150000001413 amino acids Chemical class 0.000 claims description 9
- RGXCTRIQQODGIZ-UHFFFAOYSA-O isodesmosine Chemical compound OC(=O)C(N)CCCC[N+]1=CC(CCC(N)C(O)=O)=CC(CCC(N)C(O)=O)=C1CCCC(N)C(O)=O RGXCTRIQQODGIZ-UHFFFAOYSA-O 0.000 claims description 9
- 230000000699 topical effect Effects 0.000 claims description 8
- 230000007170 pathology Effects 0.000 claims description 7
- AEDORKVKMIVLBW-BLDDREHASA-N 3-oxo-3-[[(2r,3s,4s,5r,6r)-3,4,5-trihydroxy-6-[[5-hydroxy-4-(hydroxymethyl)-6-methylpyridin-3-yl]methoxy]oxan-2-yl]methoxy]propanoic acid Chemical compound OCC1=C(O)C(C)=NC=C1CO[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](COC(=O)CC(O)=O)O1 AEDORKVKMIVLBW-BLDDREHASA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 238000007920 subcutaneous administration Methods 0.000 claims description 6
- 229940124549 vasodilator Drugs 0.000 claims description 6
- 239000003071 vasodilator agent Substances 0.000 claims description 6
- 102000004190 Enzymes Human genes 0.000 claims description 5
- 108090000790 Enzymes Proteins 0.000 claims description 5
- 229940088598 enzyme Drugs 0.000 claims description 5
- 229940011671 vitamin b6 Drugs 0.000 claims description 5
- 239000006071 cream Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000004359 castor oil Substances 0.000 claims description 3
- 235000019438 castor oil Nutrition 0.000 claims description 3
- 239000002537 cosmetic Substances 0.000 claims description 3
- 239000008367 deionised water Substances 0.000 claims description 3
- 229910021641 deionized water Inorganic materials 0.000 claims description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 3
- 235000008160 pyridoxine Nutrition 0.000 claims description 3
- 239000011677 pyridoxine Substances 0.000 claims description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims 1
- 239000007900 aqueous suspension Substances 0.000 claims 1
- 229940127554 medical product Drugs 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 21
- 102000004169 proteins and genes Human genes 0.000 description 21
- 108090000623 proteins and genes Proteins 0.000 description 21
- 210000003491 skin Anatomy 0.000 description 21
- 239000000047 product Substances 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 235000001014 amino acid Nutrition 0.000 description 9
- 210000004761 scalp Anatomy 0.000 description 9
- 238000000034 method Methods 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 6
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 6
- 229960004919 procaine Drugs 0.000 description 6
- 206010003694 Atrophy Diseases 0.000 description 5
- 206010040799 Skin atrophy Diseases 0.000 description 5
- 239000003708 ampul Substances 0.000 description 5
- 230000037444 atrophy Effects 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000005515 coenzyme Substances 0.000 description 4
- 201000004384 Alopecia Diseases 0.000 description 3
- 206010040925 Skin striae Diseases 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000037303 wrinkles Effects 0.000 description 3
- 239000001828 Gelatine Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 231100000360 alopecia Toxicity 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 2
- 230000008591 skin barrier function Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- 235000019158 vitamin B6 Nutrition 0.000 description 2
- 239000011726 vitamin B6 Substances 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 206010006784 Burning sensation Diseases 0.000 description 1
- 241000237074 Centris Species 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 241000283715 Damaliscus lunatus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229930003756 Vitamin B7 Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 235000011912 vitamin B7 Nutrition 0.000 description 1
- 239000011735 vitamin B7 Substances 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K8/41—Amines
-
- 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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered 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
- A61K8/60—Sugars; Derivatives thereof
- A61K8/606—Nucleosides; Nucleotides; Nucleic 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
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products 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
- A61K8/64—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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- 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
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8164—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical, and containing at least one other carboxyl radical in the molecule, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers, e.g. poly (methyl vinyl ether-co-maleic anhydride)
-
- 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
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
Abstract
The skin treatment preparation comprises, in combination: collagen; elastin;
an optional vasodilatory substance; at least one acid chosen from deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), or a salt thereof; a vehicle and/or an excipient.
an optional vasodilatory substance; at least one acid chosen from deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), or a salt thereof; a vehicle and/or an excipient.
Description
PCT~T97/00002 "Skin treatment formulation and uses thereof"
DESCRIPTION
Technical field The present invention relates to a compound for the treatment of skin pathologies and unaesthetic conditions and optionally of pathologies of the skin and related tissues. More particularly, the invention relates to a product for the treatment of:
1. skin atrophy striae, 2 skin wrinkles, 3. ageing of the skin, 4. hair loss and alopecia, 5. chapping of the skin, 6. slow cicatrization, 7. skin atrophy pathologies of various types, 8. scars.
The invention also relates to the uses of the said compound.
Backqround art Skin atrophy and the phenomena associated therewith are mainly due to a deficiency in the two proteins of the skin, collagen and elastin, the first being responsible for nourishing and revitalizing the skin tissues while the second has the functiDn of making the skin tissues elastic.
More generally, three main aspects which characterize skin atrophy may be identified:
a) deficiency or lack of collagen in the skin;
b) deficiency of lack of elastin in the skin;
c) lack of or reduction in vascularization.
There are two approaches to treating skin atrophy, involving the integration of the two proteins into the skin: supplying the two proteins directly and supplying the corresponding amino acids, which allow the body to reproduce these proteins by itself, that is to say to metabolize them. Treatment of sk n pathologies by integration of collagen and elastin proteins has already been attempted, in particular by topi~al application of W097/25023 PCT~T97/00002 ointments containing-the said prcteins.
Direct a~m;~tration of the proteins is theoretically the fastest route, since the body is supplied directly with the proteins it lacks rather than the components (amino acids) via which it me.tabolizes these proteins.
However, the treatment methods and the relevant compounds used hitherto have not given satisfactory results. The reason for this is that the mainly topical administration of the two proteins affords a transient and therefore unsatisfactory result, or even shows no results at all owing to the fact that the protein is not absorbed on account of the skin barrier.
Disclosure of the invention 1~ The subject of the present invention is a product for the treatment of skin pathologies and unaesthetic conditions and optionally of pathologies of the skin, based on elastin and collagen, which product makes it possible to obtain better and especially longer lasting results.
Basically, the product of the invention contains a combination of at least the following components:
1) collagen, 2) elastin, 3) preferably at least one local vasodilatory substance 4) at least one acid chosen from deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), or a salt thereof, in combination with a suitable vehicle which may also consist of a physiologically acceptable solution, depending on the type of a~m; ni ~tration for ~hich the formulation is intended.
The combination of these four components makes it possible to obtain results which are markedly superior 3~ to those which can be obtained with the products currently available, by virtue of the simultaneous presence not only of the two fundamental prot:eins but also of an optional vasodilator and at least one of the . .
W097/25023 PCT~T97/00002 RNA or DNA acids, which play a fundamental role in the treatment, as will ~e clarified later.
In certain cases, a reduction in vascularization accompanies the unaesthetic skin conditions mentioned. In these cases, administration of the optional local vasodilator together with the collagen and elastin, makes it possible to re-establish peripheral blood circulation in the zone treated, thereby giving rise to localized vasodilation and thus allowing the two proteins to reach the treated zones. Moreover, the temporary vasodilation produced by the vasodilatory substance helps vascularization in the tissues and facilitates the provision of nutrients by the blood.
If th~re is poor vascularization of the tissues 1~ treated, despite the administration of a vasodilator together with the proteins, some of the proteins administered may not be bound to the tissues concerned but will be absorbed by the body. The simultaneous provision of at least one of the ribonucleic and deoxyribonucleic acids, or of a salt thereof, allows the tissues treated autonomously to reproduce the two types of protein administered. The reason for this is that DNA
helps the tissues receiving it to manufacture proteins with characteristics similar to the proteins 2~ administered, while RNA serves to create a memory, in the tissues receiving it, for the two proteins supplied in order to allow the tissues themselves to reproduce these proteins.
The use of one of the two acids RNA or DNA
therefore makes it possible to accelerate the healing process by stimulating the autonomous production of collagen and elastin by the skin tissues being treated.
The two acids (or their salts) are preferably used in combination, but appreciable results may also be 3~ obtained with only one of the two acids or the respective salt.
According to an improved feature of the invention, the compound may comprise, besides the four main components referred to above, one or mor-e secondary components chosen from one or more of the following groups:
- - amino acids;
S - enzymes and coenzymes;
- Vitamin C
- keratin (restricted to treatment of the scalp).
Among the amino acids which may be used in the product according to the invention, mention may be made of the following: glycine, proline, hydroxyproline, lysine, tyrosine, isodesmosine. Among the useful enzymes for the use according to the invention are the following:
pepsin, pyridoxine (Vitamin B6 coenzyme), biotin or Vitamin H (Vitamin B6 coenzyme).
1~ The amino acids added to the formulation metabolize the proteins, that is to say they are involved in the formation of collagen and elastin. The enzymes and coenzymes are catalysts of the process of protein metabolism, that is to say they increase the rate of biochemical reaction of the amino acids to proteins.
Their presence in combination with amino acids therefore accelerates the metabolization of protein.
The presence of antioxidant, represented by Vitamin C, makes it possible to reduce the oxygen requirement of the cells.
Keratin, the use of which is limited to formulations for treating the scalp, constitutes specific nourishment for promoting the regrowth and strengthening of the hair.
Detailed descriPtion of preferred embodiments The composition of the product varies depending on the mode of administration, in particular as regards the vehicles and the excipients. As regards the four fundamental components (or five in the case of the use of both DNA and RNA), they may be used in the following amounts, expressed in parts by weight, including in the absence of other components:
Hydrolysed collagen: 3-10 parts WO 97/25023 PCT/lT97/00002 Hydrolysed elastin: -1-4 parts Procaine hyrochloride (vasodilator) 1-3 parts Sodium deoxyribonucleate (DNA) 3-10 parts Sodium ribonucleate (RNA)3-10 parts 5 Excipients and vehicles qs The sodium deoxyribonucleate and ribonucleate can be used independently of or in combination with each other.
Particularly good results are obtained with compositions varying within the following ranges, again expressed in parts by weight:
Hydrolysed collagen: 5-9 parts Hydrolysed elastin: 2-4 parts Procaine hyrDchloride (vasodilator) 1.5-2. 5 parts 15 Sodium deoxyribonucleate (DNA) 4-8 parts Sodium ribonucleate (RNA)4-8 parts in the presence of appropriate vehicles and/or excipients. The latter may vary depending on the applications and the form of administration. For administration by subcutaneous or intradermal injection or infiltration, the components mentioned above are prepared in a physiological solution, which in this case represents the vehicle. Typically, the parts by weight shown above are combined with 1000 parts by weight of physiological solution. Appropriate excipients and vehicles are used for topical administration, and a few examples of these will be given in the following text together with respective amounts, with respect to a few particularly effective formulations.
As mentioned above, faster results may be obtained with the addition of secondary components, such as certain enzymes and amino acids. A formulation to which all the secondary components mentioned above have been added is given below. The composition relates to an amount of 10 ml, equivalent to 10 g in physiological solution:
Hydrolysed collagen: 30-100 mg Hydrolysed elastin: 10-40 mg CA 02242636 l998-07-09 PCT,~T97/00002 W097~5023 Procaine hyrochloride: 10-30 mg Sodium deoxyribonucleate 30-90 mg Sodium ribonucleate 30-90 mg Glycine 25-75 mg Proline 100-300 mg Hydroxyproline 25-75 mg Lysine 75-225 mg Tyrosine 5-15 mg Isodesmosine 20-60 mg 10 Pepsin 375-1125 mg Pyridoxine 250 750 mg Biotin 25-75 mg Vitamin C 250-750 mg Hydrolysed keratin (*) 15-45 mg 1~ (*) only for treatment of the scalp Physiological solution qs The best results were obtained with formulations having compositions encompassed within the following ranges, again relative to 10 g of product:
20 Hydrolysed collagen: 45-85 mg Hydrolysed elastin: 15-35 mg Procaine hyrochloride: 15-25 mg Sodium deoxyribonucleate 40-80 mg Sodium ribonucleate 40-80 mg 2~ Glycine 35-65 mg Proline 140 260 mg Hydroxyproline 35-65 mg Lysine 100 200 mg Tyrosine 7-13 mg 30 Isodesmosine 30-50 mg Pepsin 525~975 mg Pyridoxine 350-650 mg Biotin 35-65 mg Vitamin C 350-650 mg - 3~ Hydrolysed keratin (*) 20-40 mg (*) only for treatment of the scalp Physiological solution qs The compositions given above remain valid for CA 02242636 l998-07-09 W097/25023 PCT~T97/00002 topical application as regards the first fifteen components, except that they would be in a different and~
higher concentration, in view of the increased difficulty of absorption and the increased dispersion. Moreover, the physiological solution would be replaced by a combination of various vehicles and excipients.
Typically, in a cream for the local treatment of atrophy, the following compositions may be used, relative to 10 g of product (where the preferred amounts, again in mg, are shown in parentheses):
Hydrolysed collagen:65-200 mg (90-170) Hydrolysed elastin:25-75 mg (30-70) Procaine hydrochloride:20-60 mg (30-50) Sodium deoxyribonucleate60-180 mg (80-160) 15 Sodium ribonucleate60-180 mg (80-160) Glycine 50-150 mg (70-130) Proline 200-600 mg (280-520) Hydroxyproline 50-150 mg (70-130) Lysine 150-450 mg (200-400) 2~ Tyrosine 10-30 mg (15-25) Isodesmosine 40-120 mg (60-150) Pepsin 750-2250 mg (1050-1950) Pyridoxine 500-1500 mg (700-1300) Biotin 50-150 mg ~70-130) 25 Vitamin C 500-1500 mg (700-1300) Sodium hydroxide 0-15 mg (2-10) Vehicle (hydrogenated polyoxyethylenated castor oil) 100-300 mg (150-230) Excipient (acrylic acid 3~ polymer) 50-200 mg (80-140) Deionized water qs 10 grams The same composition may be employed for a product in ampules for topical use in the treatment of atrophy, in which case the excipient is replaced by water, with the addition of preserving agents. Ampules for the treatment of the scalp may have the same composition as ampules ~or the treatment of atrophy, with the addition of keratin in an amount of from 60 to 120 mg W097/25023 PCT~T97/00002 per lO g of product.
In all the compQ~itions, the DNA and the RNA-may also be used in the form of potassium deoxyribonucleate and potassium ribonucleate or in another compatible form.
In the case of a product for topical use, vehicles other than the ones mentioned may also be used.
However, hydrogenated polyoxyethylenated castor oil has given particularly advantageous results since it allows the skin barrier to be crossed efficiently.
In the case of preparations for application by subcutaneous or intradermal injection or infiltration, it is advantageous to provide for the addition of sodium bicarbonate in order to eliminate the burning sensation caused by the acidity and the presence of the physiological solution.
The application methods vary depending on the type of treatment and on the route of administration. The latter may be carried out topically or by infiltration via subcutaneous, intra- or mesodermal injection of the compound into the site of the atrophies. The number of applications and the amount of product applied vary according to the area of tissue to be treated and its condition. A few general indications are given below, 2~ which a person skilled in the art will use as a guideline for selecting the most suitable mode of application in each individual case. In the case of treatment by infiltration:
l. Treatment of cutaneous striae: subcutaneous infiltrations are performed, using a syringe with a microneedle, by inserting the needle parallel to the surface of the stria along its entire length. On inserting the needle, a tunnel is formed which is filled with the solution as the needle is withdrawn.
3~ 2. Txeatment of skin wrinkles: intradermal infiltrations are performed, using a syringe with a microneedle, by inserting the needle parallel to the surface of the wrinkle along its entire length. On inserting the needle, g a tunnel is formed which is filled with the solution as the needle is withdrawn. ~
3. Treatment of skin aqeinq: mesodermal infiltrations (that is to say infiltrations into the dermis but to a S deeper level than intradermal infiltrations) are performed, with a syringe with a microneedle, in order to provide deep and diffuse nourishment for the tissues concerned.
4. Treatment of the scalP and of aloPecia: intradermal 10 infiltrations into the scalp (trichomesotherapy) are performed using a syringe with a microneedle.
5. Treatment of skin chapPinq: intradermal infiltrations are performed into the area concerned using a syringe with a microneedle.
1~ 6. Treatment of slow cicatrization: intradermal infiltrations are performed into the area concerned using a syringe with a microneedle.
For all the applications listed above, the number of applications depends on the seriousness of the 20 condition of the tissue treated. In general, the number of applications may range from 5 to 50. The amount of solution administered varies according to the size of the area under treatment. Generally speaking, about 0.1 ml of product per cm2 of tissue treated may be applied in the 2~ treatment of cutaneous striae.
Cosmetic treatment by means of topical application of the compound is carried out by rubbing the ampule preparation onto the area to be treated or by massaging into the area concerned in the case of cream 30 preparations. Topical use involves application twice daily over a period varying between one and six months, depending on the seriousness of the condition of the skin tissue.
With regard to treatment of the scalp, the 3~ administration of 2 ml of preparation per application may be envisaged for treating the entire scalp, while for atrophy and ageing of the skin, 1 cm3 of cream or ampule containing 1 ml of solution is used per 500 cm2 of surface area.
_Preparation of the composition:
An example for the preparation of the following formulation is given hereinafter:
5 NaCl ~ueous solution (0.9%):
stabilized pig-collagen 30 g/l sterilized pig-elastin 10/15 g/l glycine 2/4 g/l proline 6/10 g/l 10 hydroxyproline 2/4 g/l Lysine 5/15 g/l Tyrosine 1/3 g/l Pepsin 10/30 g/l pyroxidine 10/30 g/l 1~ DNA 60 g/l RNA 60 g/l Biotin 3/6 g/l Procaine 1/3 g/l Collagen and elastin may be of a~limal or vegetal origin. A process for obtaining hydrolysed cross-linked collagen and hydrolysed cross-linked elastin is described hereinbelow:
A.stabilised pig-collagen is mixed in a vacutainer under nitrogen atmosphere at 35/38~ for 9C min.;
2~ B.the product is filtered on a 1-micrometre filter;
C.the filtered product is subject to centrifugation at 3500 rpm for 10 min.;
D.the supernatant is eliminated in order to obtain a perfectly clear product;
E.after centrifugation the corpuscular part is brought to its starting volume again, by replacing the removed supernatant with a 3% glutoraldehyde or cross-linked polyvinylpolyppyrrolidone solution;
F.the solution thus obtained is mixed for 30 min at 35/38~C;
G.steps C, D and E are repeated;
H.the solution is made to rest for 12 hours;
I.thereafter the solution si subject to centri~ugation at PCT~T97/00002 3500 rpm for 2 hours;
J.the supernatant is removed.
on the bottom of the container a translucent homogeneous gelatine is collected. The gelatine may be brought at the desired viscosity by addition of a sterilized 0.9% acqueous solution of NaCl.
The same process can be used to produce cross-linked elastin starting from sterilized pig-elastin.
Hydrolized aminoacids, hydrolized DNA and RNA
and hydrolized biotin as well as procaine hydrocloride are added to the proteins treated as above described in order to obtain the above preparation.
The same process can be used with twice the amount of elastin and collagen (i.e. 60 g/l collagen and 20/30 g/l elastin.
The product thus obtained is sucked in a syringe or other suitable container and the final package sterilized with gamma-irradiation. The whole process is performed in a white chamber (class "lO0") under laminar flux hood.
It should be understood that the formulations mentioned constitute an example given solely by way of practical demonstration of the invention, it being possible for the composition to vary within the limits defined in the attached claims without thereby departing 2~ from the scope of the underlying concept of this invention.
DESCRIPTION
Technical field The present invention relates to a compound for the treatment of skin pathologies and unaesthetic conditions and optionally of pathologies of the skin and related tissues. More particularly, the invention relates to a product for the treatment of:
1. skin atrophy striae, 2 skin wrinkles, 3. ageing of the skin, 4. hair loss and alopecia, 5. chapping of the skin, 6. slow cicatrization, 7. skin atrophy pathologies of various types, 8. scars.
The invention also relates to the uses of the said compound.
Backqround art Skin atrophy and the phenomena associated therewith are mainly due to a deficiency in the two proteins of the skin, collagen and elastin, the first being responsible for nourishing and revitalizing the skin tissues while the second has the functiDn of making the skin tissues elastic.
More generally, three main aspects which characterize skin atrophy may be identified:
a) deficiency or lack of collagen in the skin;
b) deficiency of lack of elastin in the skin;
c) lack of or reduction in vascularization.
There are two approaches to treating skin atrophy, involving the integration of the two proteins into the skin: supplying the two proteins directly and supplying the corresponding amino acids, which allow the body to reproduce these proteins by itself, that is to say to metabolize them. Treatment of sk n pathologies by integration of collagen and elastin proteins has already been attempted, in particular by topi~al application of W097/25023 PCT~T97/00002 ointments containing-the said prcteins.
Direct a~m;~tration of the proteins is theoretically the fastest route, since the body is supplied directly with the proteins it lacks rather than the components (amino acids) via which it me.tabolizes these proteins.
However, the treatment methods and the relevant compounds used hitherto have not given satisfactory results. The reason for this is that the mainly topical administration of the two proteins affords a transient and therefore unsatisfactory result, or even shows no results at all owing to the fact that the protein is not absorbed on account of the skin barrier.
Disclosure of the invention 1~ The subject of the present invention is a product for the treatment of skin pathologies and unaesthetic conditions and optionally of pathologies of the skin, based on elastin and collagen, which product makes it possible to obtain better and especially longer lasting results.
Basically, the product of the invention contains a combination of at least the following components:
1) collagen, 2) elastin, 3) preferably at least one local vasodilatory substance 4) at least one acid chosen from deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), or a salt thereof, in combination with a suitable vehicle which may also consist of a physiologically acceptable solution, depending on the type of a~m; ni ~tration for ~hich the formulation is intended.
The combination of these four components makes it possible to obtain results which are markedly superior 3~ to those which can be obtained with the products currently available, by virtue of the simultaneous presence not only of the two fundamental prot:eins but also of an optional vasodilator and at least one of the . .
W097/25023 PCT~T97/00002 RNA or DNA acids, which play a fundamental role in the treatment, as will ~e clarified later.
In certain cases, a reduction in vascularization accompanies the unaesthetic skin conditions mentioned. In these cases, administration of the optional local vasodilator together with the collagen and elastin, makes it possible to re-establish peripheral blood circulation in the zone treated, thereby giving rise to localized vasodilation and thus allowing the two proteins to reach the treated zones. Moreover, the temporary vasodilation produced by the vasodilatory substance helps vascularization in the tissues and facilitates the provision of nutrients by the blood.
If th~re is poor vascularization of the tissues 1~ treated, despite the administration of a vasodilator together with the proteins, some of the proteins administered may not be bound to the tissues concerned but will be absorbed by the body. The simultaneous provision of at least one of the ribonucleic and deoxyribonucleic acids, or of a salt thereof, allows the tissues treated autonomously to reproduce the two types of protein administered. The reason for this is that DNA
helps the tissues receiving it to manufacture proteins with characteristics similar to the proteins 2~ administered, while RNA serves to create a memory, in the tissues receiving it, for the two proteins supplied in order to allow the tissues themselves to reproduce these proteins.
The use of one of the two acids RNA or DNA
therefore makes it possible to accelerate the healing process by stimulating the autonomous production of collagen and elastin by the skin tissues being treated.
The two acids (or their salts) are preferably used in combination, but appreciable results may also be 3~ obtained with only one of the two acids or the respective salt.
According to an improved feature of the invention, the compound may comprise, besides the four main components referred to above, one or mor-e secondary components chosen from one or more of the following groups:
- - amino acids;
S - enzymes and coenzymes;
- Vitamin C
- keratin (restricted to treatment of the scalp).
Among the amino acids which may be used in the product according to the invention, mention may be made of the following: glycine, proline, hydroxyproline, lysine, tyrosine, isodesmosine. Among the useful enzymes for the use according to the invention are the following:
pepsin, pyridoxine (Vitamin B6 coenzyme), biotin or Vitamin H (Vitamin B6 coenzyme).
1~ The amino acids added to the formulation metabolize the proteins, that is to say they are involved in the formation of collagen and elastin. The enzymes and coenzymes are catalysts of the process of protein metabolism, that is to say they increase the rate of biochemical reaction of the amino acids to proteins.
Their presence in combination with amino acids therefore accelerates the metabolization of protein.
The presence of antioxidant, represented by Vitamin C, makes it possible to reduce the oxygen requirement of the cells.
Keratin, the use of which is limited to formulations for treating the scalp, constitutes specific nourishment for promoting the regrowth and strengthening of the hair.
Detailed descriPtion of preferred embodiments The composition of the product varies depending on the mode of administration, in particular as regards the vehicles and the excipients. As regards the four fundamental components (or five in the case of the use of both DNA and RNA), they may be used in the following amounts, expressed in parts by weight, including in the absence of other components:
Hydrolysed collagen: 3-10 parts WO 97/25023 PCT/lT97/00002 Hydrolysed elastin: -1-4 parts Procaine hyrochloride (vasodilator) 1-3 parts Sodium deoxyribonucleate (DNA) 3-10 parts Sodium ribonucleate (RNA)3-10 parts 5 Excipients and vehicles qs The sodium deoxyribonucleate and ribonucleate can be used independently of or in combination with each other.
Particularly good results are obtained with compositions varying within the following ranges, again expressed in parts by weight:
Hydrolysed collagen: 5-9 parts Hydrolysed elastin: 2-4 parts Procaine hyrDchloride (vasodilator) 1.5-2. 5 parts 15 Sodium deoxyribonucleate (DNA) 4-8 parts Sodium ribonucleate (RNA)4-8 parts in the presence of appropriate vehicles and/or excipients. The latter may vary depending on the applications and the form of administration. For administration by subcutaneous or intradermal injection or infiltration, the components mentioned above are prepared in a physiological solution, which in this case represents the vehicle. Typically, the parts by weight shown above are combined with 1000 parts by weight of physiological solution. Appropriate excipients and vehicles are used for topical administration, and a few examples of these will be given in the following text together with respective amounts, with respect to a few particularly effective formulations.
As mentioned above, faster results may be obtained with the addition of secondary components, such as certain enzymes and amino acids. A formulation to which all the secondary components mentioned above have been added is given below. The composition relates to an amount of 10 ml, equivalent to 10 g in physiological solution:
Hydrolysed collagen: 30-100 mg Hydrolysed elastin: 10-40 mg CA 02242636 l998-07-09 PCT,~T97/00002 W097~5023 Procaine hyrochloride: 10-30 mg Sodium deoxyribonucleate 30-90 mg Sodium ribonucleate 30-90 mg Glycine 25-75 mg Proline 100-300 mg Hydroxyproline 25-75 mg Lysine 75-225 mg Tyrosine 5-15 mg Isodesmosine 20-60 mg 10 Pepsin 375-1125 mg Pyridoxine 250 750 mg Biotin 25-75 mg Vitamin C 250-750 mg Hydrolysed keratin (*) 15-45 mg 1~ (*) only for treatment of the scalp Physiological solution qs The best results were obtained with formulations having compositions encompassed within the following ranges, again relative to 10 g of product:
20 Hydrolysed collagen: 45-85 mg Hydrolysed elastin: 15-35 mg Procaine hyrochloride: 15-25 mg Sodium deoxyribonucleate 40-80 mg Sodium ribonucleate 40-80 mg 2~ Glycine 35-65 mg Proline 140 260 mg Hydroxyproline 35-65 mg Lysine 100 200 mg Tyrosine 7-13 mg 30 Isodesmosine 30-50 mg Pepsin 525~975 mg Pyridoxine 350-650 mg Biotin 35-65 mg Vitamin C 350-650 mg - 3~ Hydrolysed keratin (*) 20-40 mg (*) only for treatment of the scalp Physiological solution qs The compositions given above remain valid for CA 02242636 l998-07-09 W097/25023 PCT~T97/00002 topical application as regards the first fifteen components, except that they would be in a different and~
higher concentration, in view of the increased difficulty of absorption and the increased dispersion. Moreover, the physiological solution would be replaced by a combination of various vehicles and excipients.
Typically, in a cream for the local treatment of atrophy, the following compositions may be used, relative to 10 g of product (where the preferred amounts, again in mg, are shown in parentheses):
Hydrolysed collagen:65-200 mg (90-170) Hydrolysed elastin:25-75 mg (30-70) Procaine hydrochloride:20-60 mg (30-50) Sodium deoxyribonucleate60-180 mg (80-160) 15 Sodium ribonucleate60-180 mg (80-160) Glycine 50-150 mg (70-130) Proline 200-600 mg (280-520) Hydroxyproline 50-150 mg (70-130) Lysine 150-450 mg (200-400) 2~ Tyrosine 10-30 mg (15-25) Isodesmosine 40-120 mg (60-150) Pepsin 750-2250 mg (1050-1950) Pyridoxine 500-1500 mg (700-1300) Biotin 50-150 mg ~70-130) 25 Vitamin C 500-1500 mg (700-1300) Sodium hydroxide 0-15 mg (2-10) Vehicle (hydrogenated polyoxyethylenated castor oil) 100-300 mg (150-230) Excipient (acrylic acid 3~ polymer) 50-200 mg (80-140) Deionized water qs 10 grams The same composition may be employed for a product in ampules for topical use in the treatment of atrophy, in which case the excipient is replaced by water, with the addition of preserving agents. Ampules for the treatment of the scalp may have the same composition as ampules ~or the treatment of atrophy, with the addition of keratin in an amount of from 60 to 120 mg W097/25023 PCT~T97/00002 per lO g of product.
In all the compQ~itions, the DNA and the RNA-may also be used in the form of potassium deoxyribonucleate and potassium ribonucleate or in another compatible form.
In the case of a product for topical use, vehicles other than the ones mentioned may also be used.
However, hydrogenated polyoxyethylenated castor oil has given particularly advantageous results since it allows the skin barrier to be crossed efficiently.
In the case of preparations for application by subcutaneous or intradermal injection or infiltration, it is advantageous to provide for the addition of sodium bicarbonate in order to eliminate the burning sensation caused by the acidity and the presence of the physiological solution.
The application methods vary depending on the type of treatment and on the route of administration. The latter may be carried out topically or by infiltration via subcutaneous, intra- or mesodermal injection of the compound into the site of the atrophies. The number of applications and the amount of product applied vary according to the area of tissue to be treated and its condition. A few general indications are given below, 2~ which a person skilled in the art will use as a guideline for selecting the most suitable mode of application in each individual case. In the case of treatment by infiltration:
l. Treatment of cutaneous striae: subcutaneous infiltrations are performed, using a syringe with a microneedle, by inserting the needle parallel to the surface of the stria along its entire length. On inserting the needle, a tunnel is formed which is filled with the solution as the needle is withdrawn.
3~ 2. Txeatment of skin wrinkles: intradermal infiltrations are performed, using a syringe with a microneedle, by inserting the needle parallel to the surface of the wrinkle along its entire length. On inserting the needle, g a tunnel is formed which is filled with the solution as the needle is withdrawn. ~
3. Treatment of skin aqeinq: mesodermal infiltrations (that is to say infiltrations into the dermis but to a S deeper level than intradermal infiltrations) are performed, with a syringe with a microneedle, in order to provide deep and diffuse nourishment for the tissues concerned.
4. Treatment of the scalP and of aloPecia: intradermal 10 infiltrations into the scalp (trichomesotherapy) are performed using a syringe with a microneedle.
5. Treatment of skin chapPinq: intradermal infiltrations are performed into the area concerned using a syringe with a microneedle.
1~ 6. Treatment of slow cicatrization: intradermal infiltrations are performed into the area concerned using a syringe with a microneedle.
For all the applications listed above, the number of applications depends on the seriousness of the 20 condition of the tissue treated. In general, the number of applications may range from 5 to 50. The amount of solution administered varies according to the size of the area under treatment. Generally speaking, about 0.1 ml of product per cm2 of tissue treated may be applied in the 2~ treatment of cutaneous striae.
Cosmetic treatment by means of topical application of the compound is carried out by rubbing the ampule preparation onto the area to be treated or by massaging into the area concerned in the case of cream 30 preparations. Topical use involves application twice daily over a period varying between one and six months, depending on the seriousness of the condition of the skin tissue.
With regard to treatment of the scalp, the 3~ administration of 2 ml of preparation per application may be envisaged for treating the entire scalp, while for atrophy and ageing of the skin, 1 cm3 of cream or ampule containing 1 ml of solution is used per 500 cm2 of surface area.
_Preparation of the composition:
An example for the preparation of the following formulation is given hereinafter:
5 NaCl ~ueous solution (0.9%):
stabilized pig-collagen 30 g/l sterilized pig-elastin 10/15 g/l glycine 2/4 g/l proline 6/10 g/l 10 hydroxyproline 2/4 g/l Lysine 5/15 g/l Tyrosine 1/3 g/l Pepsin 10/30 g/l pyroxidine 10/30 g/l 1~ DNA 60 g/l RNA 60 g/l Biotin 3/6 g/l Procaine 1/3 g/l Collagen and elastin may be of a~limal or vegetal origin. A process for obtaining hydrolysed cross-linked collagen and hydrolysed cross-linked elastin is described hereinbelow:
A.stabilised pig-collagen is mixed in a vacutainer under nitrogen atmosphere at 35/38~ for 9C min.;
2~ B.the product is filtered on a 1-micrometre filter;
C.the filtered product is subject to centrifugation at 3500 rpm for 10 min.;
D.the supernatant is eliminated in order to obtain a perfectly clear product;
E.after centrifugation the corpuscular part is brought to its starting volume again, by replacing the removed supernatant with a 3% glutoraldehyde or cross-linked polyvinylpolyppyrrolidone solution;
F.the solution thus obtained is mixed for 30 min at 35/38~C;
G.steps C, D and E are repeated;
H.the solution is made to rest for 12 hours;
I.thereafter the solution si subject to centri~ugation at PCT~T97/00002 3500 rpm for 2 hours;
J.the supernatant is removed.
on the bottom of the container a translucent homogeneous gelatine is collected. The gelatine may be brought at the desired viscosity by addition of a sterilized 0.9% acqueous solution of NaCl.
The same process can be used to produce cross-linked elastin starting from sterilized pig-elastin.
Hydrolized aminoacids, hydrolized DNA and RNA
and hydrolized biotin as well as procaine hydrocloride are added to the proteins treated as above described in order to obtain the above preparation.
The same process can be used with twice the amount of elastin and collagen (i.e. 60 g/l collagen and 20/30 g/l elastin.
The product thus obtained is sucked in a syringe or other suitable container and the final package sterilized with gamma-irradiation. The whole process is performed in a white chamber (class "lO0") under laminar flux hood.
It should be understood that the formulations mentioned constitute an example given solely by way of practical demonstration of the invention, it being possible for the composition to vary within the limits defined in the attached claims without thereby departing 2~ from the scope of the underlying concept of this invention.
Claims (29)
1. Preparation for treating the skin, including, in combination:
- collagen;
- elastin;
- at least one acid chosen from deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) or a salt thereof;
- a local vasodilatory substance - a vehicle and/or an excipient.
- collagen;
- elastin;
- at least one acid chosen from deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) or a salt thereof;
- a local vasodilatory substance - a vehicle and/or an excipient.
2. Preparation according to Claim 1, additionally including at least one enzyme chosen from the group including: pepsin, pyridoxine, biotin.
3. Preparation according to Claim 1 or 2, additionally including at least one amino acid chosen from the group including: glycine, proline, hydroxyproline, lysine, tyrosine, isodesmosine.
4. Preparation according to one or more of the preceding claims, additionally including Vitamin C.
5. Preparation according to one or more of the preceding claims, additionally including keratin.
6. Preparation according to claim 1, in which the said vasodilatory substance is procaine hydrochloride.
7. Preparation according to Claim 1, including in combination, expressed in parts by weight:
Hydrolysed collagen: 3-10 parts Hydrolysed elastin: 1-4 parts Procaine hydrochloride (vasodilator) 1-3 parts Sodium deoxyribonucleate or equivalent 3-10 parts Sodium ribonucleate or equivalent 3-10 parts.
Hydrolysed collagen: 3-10 parts Hydrolysed elastin: 1-4 parts Procaine hydrochloride (vasodilator) 1-3 parts Sodium deoxyribonucleate or equivalent 3-10 parts Sodium ribonucleate or equivalent 3-10 parts.
8. Preparation according to Claim 7, including in combination, expressed in parts by weight:
Hydrolysed collagen: 4-9 parts Hydrolysed elastin: 2-4 parts Procaine hydrochloride 1.5-2.5 parts Sodium deoxyribonucleate or equivalent 4-8 parts Sodium ribonucleate or equivalent 4-8 parts.
Hydrolysed collagen: 4-9 parts Hydrolysed elastin: 2-4 parts Procaine hydrochloride 1.5-2.5 parts Sodium deoxyribonucleate or equivalent 4-8 parts Sodium ribonucleate or equivalent 4-8 parts.
9. Preparation according to Claim 1, including in combination, expressed in parts by weight:
Hydrolysed collagen: 3-10 parts Hydrolysed elastin: 1-4 parts Procaine hydrochloride 1-3 parts Sodium deoxyribonucleate or equivalent 5-20 parts.
Hydrolysed collagen: 3-10 parts Hydrolysed elastin: 1-4 parts Procaine hydrochloride 1-3 parts Sodium deoxyribonucleate or equivalent 5-20 parts.
10. Preparation according to Claim 1, including in combination, expressed in parts by weight:
Hydrolysed collagen: 3-10 parts Hydrolysed elastin: 1-4 parts Procaine hydrochloride 1-3 parts Sodium ribonucleate or equivalent 5-20 parts.
Hydrolysed collagen: 3-10 parts Hydrolysed elastin: 1-4 parts Procaine hydrochloride 1-3 parts Sodium ribonucleate or equivalent 5-20 parts.
11. Preparation according to one or more of the preceding claims, including an excipient and a vehicle for topical application.
12. Preparation according to one or more of Claims 1 to 10, including a physiological solution for intradermal or subcutaneous application as vehicle.
13. Preparation according to one or more of Claims 1 to 10, including, per 10 grams of product:
Hydrolysed collagen: 30-100 mg Hydrolysed elastin: 10-40 mg Procaine hydrochloride: 10-30 mg Sodium deoxyribonucleate or equivalent 30-90 mg Sodium ribonucleate or equivalent 30-90 mg Glycine 25-75 mg Proline 100-300 mg Hydroxyproline 25-75 mg Lysine 75-225 mg Tyrosine 5-15 mg Isodesmosine 20-60 mg Pepsin 375-1125 mg Pyridoxine 250-750 mg Biotin 25-75 mg Vitamin C 250-750 mg Physiological solution qs 10 grams
Hydrolysed collagen: 30-100 mg Hydrolysed elastin: 10-40 mg Procaine hydrochloride: 10-30 mg Sodium deoxyribonucleate or equivalent 30-90 mg Sodium ribonucleate or equivalent 30-90 mg Glycine 25-75 mg Proline 100-300 mg Hydroxyproline 25-75 mg Lysine 75-225 mg Tyrosine 5-15 mg Isodesmosine 20-60 mg Pepsin 375-1125 mg Pyridoxine 250-750 mg Biotin 25-75 mg Vitamin C 250-750 mg Physiological solution qs 10 grams
14. Preparation according to Claim 13, additionally including from 15 to 45 mg of hydrolysed keratin per 10 g of product.
15. Preparation according to Claim 14, including, per 10 grams of product:
Hydrolysed collagen: 45-85 mg Hydrolysed elastin: 15-35 mg Procaine hydrochloride: 15-25 mg Sodium deoxyribonucleate or equivalent 40-80 mg Sodium ribonucleate or equivalent 40-80 mg Glycine 35-65 mg Proline 140-260 mg Hydroxyproline 35-65 mg Lysine 100-200 mg Tyrosine 7-13 mg Isodesmosine 30-50 mg Pepsin 525-975 mg Pyridoxine 350-650 mg Biotin 35-65 mg Vitamin C 350-650 mg Hydrolysed keratin 20-40 mg Physiological solution qs 10 grams
Hydrolysed collagen: 45-85 mg Hydrolysed elastin: 15-35 mg Procaine hydrochloride: 15-25 mg Sodium deoxyribonucleate or equivalent 40-80 mg Sodium ribonucleate or equivalent 40-80 mg Glycine 35-65 mg Proline 140-260 mg Hydroxyproline 35-65 mg Lysine 100-200 mg Tyrosine 7-13 mg Isodesmosine 30-50 mg Pepsin 525-975 mg Pyridoxine 350-650 mg Biotin 35-65 mg Vitamin C 350-650 mg Hydrolysed keratin 20-40 mg Physiological solution qs 10 grams
16. Preparation according to one or more of Claims 1 to 10, for topical use, including, per 10 grams of product:
Hydrolysed collagen: 65-200 mg Hydrolysed elastin: 25-75 mg Procaine hydrochloride: 20-60 mg Sodium deoxyribonucleate or equivalent 60-180 mg Sodium ribonucleate or equivalent 60-180 mg Glycine 50-150 mg Proline 200-600 mg Hydroxyproline 50-150 mg Lysine 150-450 mg Tyrosine 10-30 mg Isodesmosine 40-120 mg Pepsin 750-2250 mg Pyridoxine 500-1500 mg Biotin 50-150 mg Vitamin C 500-1500 mg Vehicle 100-300 mg Deionized water qs 10 grams
Hydrolysed collagen: 65-200 mg Hydrolysed elastin: 25-75 mg Procaine hydrochloride: 20-60 mg Sodium deoxyribonucleate or equivalent 60-180 mg Sodium ribonucleate or equivalent 60-180 mg Glycine 50-150 mg Proline 200-600 mg Hydroxyproline 50-150 mg Lysine 150-450 mg Tyrosine 10-30 mg Isodesmosine 40-120 mg Pepsin 750-2250 mg Pyridoxine 500-1500 mg Biotin 50-150 mg Vitamin C 500-1500 mg Vehicle 100-300 mg Deionized water qs 10 grams
17. Preparation according to Claim 16, including, per 10 grams of product:
Hydrolysed collagen: 90-170 mg Hydrolysed elastin: 30-70 mg Procaine hydrochloride: 30-50 mg Sodium deoxyribonucleate or equivalent 80-160 mg Sodium ribonucleate or equivalent 80-160 mg Glycine 70-130 mg Proline 280-520 mg Hydroxyproline 70-130 mg Lysine 200-400 mg Tyrosine 15-25 mg Isodesmosine 60-150 mg Pepsin 1050-1950 mg Pyridoxine 700-1300 mg Biotin 70-130 mg Vitamin C 700-1300 mg Vehicle 150-230 mg Deionized water qs 10 grams
Hydrolysed collagen: 90-170 mg Hydrolysed elastin: 30-70 mg Procaine hydrochloride: 30-50 mg Sodium deoxyribonucleate or equivalent 80-160 mg Sodium ribonucleate or equivalent 80-160 mg Glycine 70-130 mg Proline 280-520 mg Hydroxyproline 70-130 mg Lysine 200-400 mg Tyrosine 15-25 mg Isodesmosine 60-150 mg Pepsin 1050-1950 mg Pyridoxine 700-1300 mg Biotin 70-130 mg Vitamin C 700-1300 mg Vehicle 150-230 mg Deionized water qs 10 grams
18. Preparation according to Claim 16 or 17, additionally including, per 10 grams of product, from 0 to 10 mg and preferably from 3 to 6 mg of sodium hydroxide.
19. Preparation according to one or more of Claims 16 to 18, in which the said vehicle includes hydrogenated polyoxyethylenated castor oil.
20. Preparation according to one or more of Claims 16 to 19, additionally including, per 10 grams of product, from 50 to 200 mg and preferably from 80 to 140 mg of an excipient which is physiologically compatible with topical application.
21. Preparation according to Claim 20, in which the said excipient is an acrylic acid polymer.
22. Preparation according to one or more of Claims to 17, additionally including, per ten grams of product, from 30 to 90 mg and preferably from 40 to 70 mg of hydrolysed keratin.
23. Cosmetic treatment of the skin, including the application of a preparation according to one or more of Claims 1 to 22.
24. Treatment according to Claim 23, in which the said preparation is applied by subcutaneous, intradermal or mesodermal infiltration into the area to be treated.
25. Treatment according to Claim 23, in which the said preparation is applied topically.
26. Treatment according to Claim 25, in which the said preparation is applied in the form of a cream or an ointment.
27. Treatment according to Claim 25, in which the said preparation is applied in the form of an aqueous suspension by rubbing it in.
28. Use of a combination of the following substances:
- collagen;
- elastin;
- at least one acid chosen from deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), or a salt thereof;
- a local vasodilatory substance;
- a vehicle and/or an excipient, for the preparation of a medical product for the therapeutic treatment of skin pathologies.
- collagen;
- elastin;
- at least one acid chosen from deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), or a salt thereof;
- a local vasodilatory substance;
- a vehicle and/or an excipient, for the preparation of a medical product for the therapeutic treatment of skin pathologies.
29. Use of a combination of the following substances:
- collagen;
- elastin;
- at least one acid chosen from deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), or a salt thereof;
- a local vasodilatory substance;
- a vehicle and/or an excipient, for the preparation of a product for cosmetic use in the treatment of unaesthetic skin conditions.
- collagen;
- elastin;
- at least one acid chosen from deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), or a salt thereof;
- a local vasodilatory substance;
- a vehicle and/or an excipient, for the preparation of a product for cosmetic use in the treatment of unaesthetic skin conditions.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITFI96A000002 | 1996-01-10 | ||
IT96FI000002A IT1289845B1 (en) | 1996-01-10 | 1996-01-10 | FORMULA FOR THE TREATMENT OF SKIN AND ITS USES |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2242636A1 true CA2242636A1 (en) | 1997-07-17 |
Family
ID=11351445
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002242636A Abandoned CA2242636A1 (en) | 1996-01-10 | 1997-01-08 | Skin treatment formulation and uses thereof |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0873113A1 (en) |
AU (1) | AU709842B2 (en) |
BR (1) | BR9706943A (en) |
CA (1) | CA2242636A1 (en) |
IT (1) | IT1289845B1 (en) |
WO (1) | WO1997025023A1 (en) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2758458B1 (en) | 1997-01-21 | 2000-01-07 | Jean Noel Thorel | COSMETIC OR DERMO-PHARMACEUTICAL PRODUCTS RESPECTING SKIN ECOLOGY |
BR0214259A (en) * | 2001-11-27 | 2004-09-21 | Unilever Nv | Aqueous hair treatment composition, hair use and hair treatment method |
US7235249B2 (en) * | 2002-03-28 | 2007-06-26 | The Procter & Gamble Company | Methods for regulating the condition of mammalian keratinous tissue via topical application of vitamin B6 compositions |
IT1393422B1 (en) * | 2009-03-23 | 2012-04-20 | Nicoletti | COSMETIC COMPOSITION CONTAINING COLLAGEN AND ELASTIN |
WO2012101473A1 (en) * | 2011-01-27 | 2012-08-02 | Abdula Kurkayev | Nanocomposite formulations and method of skin care treatment for rejuvanation and correction of skin defects |
JP5997485B2 (en) * | 2012-04-16 | 2016-09-28 | 山口 勝美 | Skin quality improving composition and method for producing the same |
CN108024914A (en) | 2015-09-17 | 2018-05-11 | Jrx生物技术有限公司 | Improve the method for the aquation or wetting action of skin |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1256235A (en) * | 1966-06-20 | 1971-12-08 | Rumanian Minister Of The Food | Cream for the care and regeneration of the skin |
FR2592790A1 (en) * | 1986-01-16 | 1987-07-17 | Villano Guy | Cosmetic preparation having a regenerative and anti-wrinkle action |
IT1215392B (en) * | 1987-03-23 | 1990-02-08 | Denis R P Spa | COSMETIC FORMULATIONS |
FR2609393A1 (en) * | 1988-02-23 | 1988-07-15 | Serobiologiques Lab Sa | Composition which is useful, in particular, as a base material for the preparation of pharmaceutical, in particular dermatological and/or cosmetic, compositions, comprising a nitrogenous substance, in particular amino acids, oligo- or polypeptides, proteins, and their derivatives, and pharmaceutical or cosmetic composition thus prepared |
ES2104597T3 (en) * | 1990-08-14 | 1997-10-16 | Kenneth M Hallam | COMPOSITION FOR THE PROMOTION OF HAIR GROWTH. |
JP3202810B2 (en) * | 1992-10-15 | 2001-08-27 | 協和醗酵工業株式会社 | Cosmetics |
-
1996
- 1996-01-10 IT IT96FI000002A patent/IT1289845B1/en active IP Right Grant
-
1997
- 1997-01-08 AU AU13185/97A patent/AU709842B2/en not_active Ceased
- 1997-01-08 BR BR9706943A patent/BR9706943A/en unknown
- 1997-01-08 CA CA002242636A patent/CA2242636A1/en not_active Abandoned
- 1997-01-08 EP EP97900732A patent/EP0873113A1/en not_active Withdrawn
- 1997-01-08 WO PCT/IT1997/000002 patent/WO1997025023A1/en not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
AU709842B2 (en) | 1999-09-09 |
AU1318597A (en) | 1997-08-01 |
BR9706943A (en) | 1999-04-06 |
ITFI960002A0 (en) | 1996-01-10 |
EP0873113A1 (en) | 1998-10-28 |
ITFI960002A1 (en) | 1997-07-10 |
IT1289845B1 (en) | 1998-10-16 |
WO1997025023A1 (en) | 1997-07-17 |
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Date | Code | Title | Description |
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FZDE | Discontinued |