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
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
  • A61Q19/08—Anti-ageing preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • 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
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
  • A61K8/9783—Angiosperms [Magnoliophyta]
  • A61K8/9789—Magnoliopsida [dicotyledons]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders

Definitions

• the present invention relates to the field of cosmetic and dermatological products or preparations, in particular those which are effective for the treatment of signs of aging of the tissue and the object of which is to use a bold extract for the treatment of signs of aging of the tissue and a cosmetic or dermatological product which contains such an extract.
• the boldo tree (Peumus boldus Mol.) Is a small bush tree belonging to the Monimiaceae family that grows spontaneously on the sunny Chilean hills.
• the boldo tree is used as a medicinal plant in conventional medicine.
• the Boldo leaves are used as herbal tea against hepatic diseases and intestinal poisoning, as cataplasma on the temples for headaches and migraines, as a bath against rheumatism and as decoction (decoction) as an emetic.
• the Boldo leaves are used as a diuretic, gastric tonic (stomach agent) and as a sedative (sedative).
• the leaves are used as a worming agent (anthelmintic) and the juice obtained from the leaves is used as a instillation in the ear (instillation) to treat ear infections (otitis).
• boldo leaves contain 1.2% tannins, 2-3% essential oils (45% askaridol and 30% cineol and a mixture of numerous terpenes), flavonoids or flavonic glycosides (pneumoside, boldoside, fragoside were separated / isolated). ..) and 0.25-0.50% aporphine alkaloids, with boldine being the main alkaloid (25% of the total alkaloid content).
• Boldine has a choleretic and cholagogical effect (DE-2 547 243) and a relaxing effect on smooth muscle (Speisky and Cassels, Pharmalogical Research -Pharmacological Research, Volume 29, N ° 1, 1 -12 , 1994).
• Boldine has also been assigned an anti-oxidizing property, a neutralizing effect of free radicals and a peroxidizing inhibiting effect (inhibit) (P-450 cytochrome system, microsomal membrane).
• document US-5 348 755 discloses the use of boldine as an anti-oxidant in edible oils
• documents US-4 1 85 1 19 and US-5 594 033 each mention an anti-allergic and an anti-rhythmic property by Boldine.
• the main object of the present invention is the use of a bold extract as an active agent, added alone or at least one other active agent, for the preparation of a cosmetic or dermatological product for the preventive or curative treatment of aging symptoms of the tissue, with topical external application for skin, nails and / or hair.
• the bold extract used consists of boldine or an extract enriched with boldine, in particular the extract obtained from boldo leaves.
• DMEM defined culture medium
• Boldine for example, but not limited to, Boldine commercialized by SIGMA, reference B391 6, pack # 94H10481 was added to two different concentrations.
• the improvement in survival was evaluated on a culture saturated with fibroblasts. During saturation, the proliferation of the fibroblasts is subjected to a so-called "contact" block. The test enables a certain number of parameters to be quantified on the resting (quiesced) cells:
• the fibroblasts were inoculated into the defined culture medium (DMEM). Boldine was added to the culture 72 hours after inoculation. The stated parameters were evaluated after a 72-hour incubation at 37 ° C. in a 5% CO 2 atmosphere.
• DMEM defined culture medium
• ATP was dosed by an enzymatic, chemiluminescent system (Kemp, 1 986), the proteins were dosed by the Bradford colorimetric reaction (Bradford, 1986) and the reduced glutathione (GSH) was measured with a fluorescent probe, the orthophthalaldehyde (Hissin and Hilf , 1976).
• Boldine has stimulated the synthesis of ATP, proteins and GSH. With regard to ATP and GSH, Boldine, although tested in doses 50 times smaller than that of the SVF, has shown effects comparable to those of the SVF. With regard to proteins, Boldine's stimulation was also greater than that achieved for SVF.
• Sections I and II prove that it is interesting to use Boldine in care cosmetology (skin care, hair care, nail care) and its predictable effect in cosmetic preparations with topical application for combating skin and hair aging or in the treatment of skin, hair, tired phaners, the metabolism and protein synthesis of which require stimulation.
• PMN neutrophil polymorphonuclear
• the tests were carried out with a Clostridium histolyticum collagenase and a synthetic chromogenic substrate: the FALGPA.
• the incubation time is 30 minutes at room temperature and the optical density is measured at 324 nm.
• the inhibitor test measure tested as a comparison is cysteine.
• Substance P is a neuropeptide released by certain sensory nerve fibers of the skin after irritation. This peptide acts on specific recipients that are present on the cells of the skin (fibroblasts, keratinocytes, Langerhans cells) in order to induce either a strong increase (proliferation) (fibroblasts and keratinocytes) or an immunomodulation (Langerhans cells). Substance P initiates the release of histamine on the mastocytes, which is responsible for the erythema observed in vivo. This phenomenon was evaluated on biopsies of the skin incubated at 37 ° C in the presence of substance P. The released histamine is dosed by an ELISA technique.
• the non-enzymatic glycation of the proteins is a crucial process in the aging of human tissue and explains the reticulation of the extra-cellular matrix and the basement membrane, which are largely responsible for the pathologies observed in diabetics.
• the Schiff bases also catalyze the production of reactive forms of oxygen that exacerbate the effects of non-enzymatic glycation.
• the tubo tests were performed on type I collagen, which had been incubated for 21 days at 45 ° C in the presence of 1% glucose. The content of the Schiff bases was evaluated by fluorimetry at 430 nm (excitation at 350 nm). The glucose content determined by the collagen was evaluated by thiobarbiturate acid (densitometry at 443 nm).
• Aminoguanidine was also tested as a positive test measure in this glycation model in tubo. Aminoguanidine results in% relative to the control agent
• Apoptosis is an active, biological process that is used by living organisms to remove tissue from certain cells through autolysis, and particularly by destroying proteins and nuclear ADN into small fragments that are salted out in the cytoplasm.
• Apoptosis can be induced by an oxidative stress (UV-R, inflammation), by a deprivation of the growth factors or by toxic substances (pollutants, genotoxic substances etc. ).
• UV-R oxidative stress
• toxic substances polypeptides, genotoxic substances etc.
• the apoptosis inducer used for this study was the deprivation of growth factors: this mechanism would be at least partially responsible for the aging of the tissue due to the disappearance of the living cells.
• the cells were given a culture medium without serum, which contained the various substance concentrations to be tested, and were incubated at 37 ° C. for 4 days. A portion of cells that received calf serum media (containing growth factors) were used as a negative control agent. Thereafter, the cells were recovered by trypsination to be stained and analyzed in flow cytometry.
• the cells are stained simultaneously with an ethidium bromide (5 micrograms / ml) and acridine orange solution (1.5 micrograms / ml).
• necrosis cells are stained by ethidium bromide, while the living cells are stained only by acridine orange.
• the living cells are separated into two populations according to the fluorescence intensity of acridine orange in relation to the quantity of ADN: the apoptotic cells with weak fluorescence and the non-apoptotic cells with strong fluorescence.
• part of the cells are treated with trypan blue under a conventional microscope to stain and count the number of necrosis cells.
• the other part of the cells is made permeable and then stained with an ethidium bromide solution (5 micrograms / ml) and quantified in flow cytometry.
• the apoptotic cells appear in the form of a maximum (peak), which is called “Sub-Gl", because they have an ADN content which is smaller in relation to the non-apoptotic cells.
• the maximum (peak) is called “Sub-G1” because it occurs just before the Gl peak in the frequency chart (histogram) of the studies of the cell cycle.
• the GO / GI peak corresponds to the cells at rest or at the beginning of the cycle that contain only one copy of their genetic material.
• the G2 / M peak corresponds to the cells that have their genetic material in duplicate or already during mitosis (separation of the two daughter cells).
• the G0 / G1 and G2 / M peaks are separated by a tray containing the cells in the intermediate phase S of the synthesis of their second copy of the genetic material (after F. Lacombe, 1992). 3) results
• FIGS. 1 and 2 must be interpreted in relation to the control agent proportions given in the tables below.
• tho-living apoptode 2 table cells 16 +/- 4 2 +/- 0 necrosis cells 26 +/- 7 21 +/- 5
• method 1 the deprivation of cells of growth factors caused the apoptosis rate to increase from 2 to 15%.
• the apoptosis rate for the 5 mg / l dose dropped to 4%.
• this effect of the boldine is not due to a transfer of apoptosis to necrosis, since the rate of cells in the necrosis changes little after the dose of boldine.
• the effects and positive activities of the boldine or an extract enriched with boldine which have recently been found by the inventors and are mentioned below, consequently contain a very strong, stimulating (stimulating) activity of the metabolism (metabolism) (especially the stimulation of the ATP- Synthesis, the GSH-reduced glutathione and the proteins), an anti-glycation activity of the collagen and the cutaneous proteins and a pronounced stimulating effect of cell growth.
• the additional activities confer the boldine or an extract enriched with boldine which is also mentioned above and have recently been discovered or verified by the inventors, such as anti-protease activity (especially anti-collagenase), anti-P substance activity and inhibition of induction of apoptosis, give the boldine additional biological Properties, especially anti-stress, soothing, protective and regenerating effects on the skin, especially after sun exposure.
• the invention consequently also relates to the particularly advantageous use of the boldins in a product which preferably treats the real or photo-induced aging of the tissue, particularly in the area of the skin.
• the aim of the invention is also a cosmetic or dermatological product for the treatment of signs of aging of the tissue, particularly photo-induced, characterized in that it is added as an active agent, alone or at least to another active agent, a cosmetically or dermatologically contains an effective amount of a boldo extract, preferably boldine or an extract enriched with boldine.
• the cosmetic or dermatological product advantageously contains between 0.0001% and 10% in weight of boldine, preferably between 0.001% and 2% in weight.
• boldine is present in the form of a hydropolyolic solution or in vectorized form (liposomes, nanospheres, nanocapsules, microspheres, microcapsules, micelles and the like).
• boldine is present in a form substituted for example by amino acids, sugars, lipids or peptides.
• various products or cosmetic compositions containing boldine as the only active agent or added to at least one other agent are described below.
• a cosmetic product according to the invention in the form of hair tonic for protection or stimulation can have, for example, a weight composition as indicated below:
• the process for the preparation and manufacture of the above-mentioned water consists mainly in heating all fat bodies (ketostearyl alcohol (and) ceteareth-20, lipodermol and glycol stearate) to 75 ° C., the mixture of water and propylene glycol Heat 70 ° C, dissolve the hydroxyethyl cellulose, the cetrimonium chloride, the preservative, boldine and the hydrolyzed wheat protein in this mixture and at this temperature, pour the fat phase into the aqueous phase with stirring and continue stirring until the the resulting lotion has cooled completely.
• Example 2 Example 2:
• a cosmetic product according to the invention in the form of a stimulating, regenerating night cream for wrinkles may have a weight composition as set forth below.
• HGP soy protein (soy glycine) 5.00
• the process for the preparation and manufacture of the above-mentioned cream consists mainly of heating the components of the fatty phase to 80 ° C, heating the mixture of water + glycerin + preservative to 80 ° C and dissolving the fat phase therein by stirring Pour into the aqueous phase under turbine stirring, allow the resulting mixture to cool, add Vegeseryl (£) HGP at 60 ° C, add the perfume at 45 ° C and finally continue cooling to room temperature.
• Example 3 Example 3:
• a cosmetic product according to the invention in the form of a protective, anti-irritating day cream for sensitive skin may contain a weight composition as set forth below.
• the process for the preparation and manufacture of the cream mentioned above can consist of heating the components of the fatty phase to 80 ° C, heating the water and glycerol to 75 ° C and in this mixture at this temperature the methyl paraben and the propyl paraben and then dissolve the imidazolidinyl urea, then dissolve the boldine in this mixture, just before it is brought into the form of an emulsion, pour the fat phase into the aqueous phase with turbine stirring, then gradually cool the mixture obtained by stirring the turbines and planets, add the perfume at 45 ° C and then let it cool at room temperature.
• Example 4 Example 4:
• a cosmetic product according to the invention in the form of a protective, anti-glycation and anti-protease cream against signs of aging can, for example, have a weight composition as stated below.
• the process for the preparation and manufacture of the above-mentioned cream can consist of heating the components of the fatty phase to 80 ° C with stirring, heating the mixture of water + butylene glycol + preservative to 80 ° C and dissolving the allantoin and boldine therein , the fat phase into the aqueous phase Pour turbine stirring and finally cool the resulting mixture gradually to room temperature while stirring.
• a cosmetic product according to the invention in the form of a tonic can have a weight composition as set out below.
• the process for the preparation and manufacture of the above-mentioned lotion consists mainly of heating the distilled water and the glycol propylene to 50 ° C and dissolving the preservative and the boldins therein, and then dissolving the perfume and the dissolver (castor oil) while stirring Add witch hazel water and stir until cool and then filter.
• a cosmetic product according to the invention in the form of an anti-apoptosis emulsion may have a weight composition as set forth below.
• the process for the preparation and preparation of the above-mentioned emulsion can consist of heating the components of the fatty phase to 80 ° C. with stirring, heating the water to 80 ° C. and stirring the butylene glycol, the preservative, the allantoin and the Add Boldine, pour the fatty phase into the aqueous phase with turbine stirring, gradually cool the resulting mixture, add the perfume at about 45 ° C and finally continue stirring until completely cooled.

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• 1998
  • 1998-10-05 FR FR9812532A patent/FR2784027B1/fr not_active Expired - Fee Related
• 1999
  • 1999-10-01 WO PCT/EP1999/007261 patent/WO2000019973A1/de not_active Application Discontinuation
  • 1999-10-01 KR KR1020017003877A patent/KR20010079933A/ko not_active Application Discontinuation
  • 1999-10-01 JP JP2000573335A patent/JP2002526395A/ja not_active Withdrawn
  • 1999-10-01 EP EP99950583A patent/EP1117376A1/de not_active Withdrawn
  • 1999-10-01 ID IDW20010758A patent/ID28486A/id unknown
  • 1999-10-01 AU AU63314/99A patent/AU6331499A/en not_active Abandoned
  • 1999-10-01 CN CN99811788A patent/CN1329482A/zh active Pending

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