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WO2004041231A1 - Procede de protection de la peau contre la deterioration induite par le soleil par l'administration orale d'un extrait de emblica officinalis (phyllantus emblica) - Google Patents

Procede de protection de la peau contre la deterioration induite par le soleil par l'administration orale d'un extrait de emblica officinalis (phyllantus emblica) Download PDF

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Publication number
WO2004041231A1
WO2004041231A1 PCT/EP2003/011847 EP0311847W WO2004041231A1 WO 2004041231 A1 WO2004041231 A1 WO 2004041231A1 EP 0311847 W EP0311847 W EP 0311847W WO 2004041231 A1 WO2004041231 A1 WO 2004041231A1
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WO
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Prior art keywords
extract
dosage form
skin
form according
emblica officinalis
Prior art date
Application number
PCT/EP2003/011847
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English (en)
Inventor
Ratan Chaudhuri
Original Assignee
Merck Patent Gmbh
Natreon Inc.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Merck Patent Gmbh, Natreon Inc. filed Critical Merck Patent Gmbh
Priority to EP03758062A priority Critical patent/EP1560561A1/fr
Priority to AU2003274079A priority patent/AU2003274079A1/en
Priority to JP2004548774A priority patent/JP2006512310A/ja
Publication of WO2004041231A1 publication Critical patent/WO2004041231A1/fr

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0216Solid or semisolid forms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/47Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics 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
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9789Magnoliopsida [dicotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics 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
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9794Liliopsida [monocotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/16Emollients or protectives, e.g. against radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/004Aftersun preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52Stabilizers
    • A61K2800/522Antioxidants; Radical scavengers

Definitions

  • This invention relates to sun protection, and, more particularly, to a method for sun protection of skin by oral administration of an extract of the Emblica officinalis (syn. Phyllanthus emblica) plant.
  • the predominant extracellular matrix component of the dermis and a variety of other human tissues is collagen, a super family of closely related, yet genetically distinct p roteins. E ach o f t he g enetically d istinct c ollagen types has an important functional role within its compartmentalized distribution in the skin.
  • Extrinsic aging of the skin comprises changes that represent the accumulation of the many environmental insults to the skin. The most important of these insults is obviously long-term sun exposure. The changes in collagen quantity and its structure, skin elasticity and extensibility are exaggerated in photo damaged skin. A recent study suggests that the decline in dermal collagen is greater in extrinsically photo damaged skin than in intrinsically aged skin.
  • UV-inducible genes involved in this pathological degradation comprise several proteases, among them matrix-degrading metalloprotease (MMPs), which contribute to degradation of connective tissue compounds such as collagen and thus cause wrinkle formation, loss of elasticity and promote invasion and metastasis of skin cancer.
  • MMPs matrix-degrading metalloprotease
  • UVR-induced inflammatory response is one of the prevailing m echanisms p roposed to account for the majority of the UVR- dependent increases in ROS as well as UVR-dependent oxidative damage to the skin.
  • the proinflammatory and redox-regulated transcription factor ⁇ F- k B has been identified as among the primary molecules targeted during the signal transduction initiated by UVR in human skin.
  • UVR stimulates the expression of a wide variety of proinflammatory genes such as tumor necrosis factor- ⁇ (T ⁇ F- ⁇ ), interleukin-1 ⁇ (IL-1 ⁇ ), interleukin-6 (lL-6), and interleukin-8 (IL-8), which contain nuclear factor- k B ( ⁇ F- k B)-binding sites in their 5' flanking region.
  • T ⁇ F- ⁇ tumor necrosis factor- ⁇
  • IL-1 ⁇ interleukin-1 ⁇
  • L-6 interleukin-6
  • IL-8 interleukin-8
  • Ghosal, S. in U.S. Pat. 6,124,268, described a natural antioxidant blend obtained by extraction from the Emblica officinalis plant, which could be used as a sunscreen when applied as a spray lotion, aqueous gel, or cream, to the skin of the user.
  • This patent also describes orally administrable compositions, for example with vitamins to take advantage of the antioxidant property of the extract described therein, but with no suggestion that such composition can protect skin from sun- induced damage.
  • Lorenz, R. in U.S. Pat. 6,433,025 disclosed a method of retarding or preventing sunburns by oral administration of astaxanthin.
  • an antioxidant composition based o n an extract of the Emblica officinalis plant can provide effective sun protection of skin when taken orally by the user.
  • the antioxidant composition in the present invention comprises an extract of Emblica officinalis, e.g. that of U.S. 6,124,218 and preferably a standardized extract of low molecular weight ( ⁇ 1000) hydrolysable tannins, suitably over 40%, preferably 50-80%, w/w, of Emblicanin A, Emblicanin B, Pedunculagin and Punigluconin, with low levels, ⁇ 1 %, w/w, preferably ⁇ 0.6%, of total flavonoids, which standardized extract differs from the extract described by Ghosal.
  • the total flavonoids levels in the standardized extract does not impair the desired elegant off white-to-yellow color of the composition.
  • the desired concentrations of the rutin species of flavonoids (3',4',5',7-tetrahydroxy-flavone-3-0-rhamnoglucoside) in the standardized extract of the invention are less than 1.0%, preferably less than 0.01 %, with a value of 0.001 to 0.01 % being particularly preferred.
  • the most preferred concentrations of the components are on a percent by weight basis of the total dried extract:
  • the standardized composition may exhibit average percentage deviations from these preferred values of:
  • the preferred antioxidant compositions of the invention can be obtained by removal of the total flavonoids by reverse-phase column chromatography, or HPLC, using a solvent system of acetonitrile, water/phosphoric acid (20/80/1), or other solvent combinations, as they elute faster than the low molecular-weight tannins.
  • a lso by selection of geographical l ocation, the P hyllanthus emblica fruit extract can provide a substantially lower level of the total flavonoids ( ⁇ 1.0%). More particularly, it has been observed that medium-sized fruits collected from some parts of eastern India, during November-February, after water extraction and drying, yield the preferred antioxidant composition as a p owder with the d esired low content of total flavonoids. Accordingly, by analyzing the total flavonoids content of extracts and selecting extracts that contain the desired low content of total flavonoids, it is possible to prepare the desired standardized extract in a reproducible manner.
  • flavonoids include a family of compounds, which exhibit a peak at 350 nm when analyzed by UV spectral data.
  • flavonoids include but are not limited to flavonols and flavones, a species thereof being rutin as discussed above.
  • a substantially water- soluble (over 95% by weight) extract of Phyllanthus Emblica comprising less than 5% by weight of polymeric tannins, with substantially no black specks and at high levels, e.g. over 75% by weight of bio-active, low molecular-weight hydrolysable tannins having molecular weights below 1 ,000 is used.
  • This extract can be obtained by an process which removes ologomeric and polymeric tannins.
  • a suitable process comprises the following steps: 1 ) providing an extract of Phyllanthus Emblica either resulting from the original extract from the plant, or from a suspension of a powdered composition obtained after the extract is processed, e.g. after a drying step; 2) If necessary, physically separating the black specks and/or precursors thereof and/or polymeric tannins from the water-soluble components, for example by filtration with the use of a filter aid; 3) If desired, concentrating the resultant aqueous solution of the enriched composition of Emblica officinalis, for example to a dry powder.
  • the antioxidant composition of present invention is truly innovative as it uniquely provides the four features of Dermal Defense
  • No Pro-Oxidation Activity To control oxidative processes, i.e. to reduce, if not prevent their harmful effects to skin, diverse antioxidants can be used to protect skin from photo-damage. When a general use of antioxidants is advocated, it is often disregarded that these compounds not only function ' 5 as antioxidants, but (intrinsically) have pro-oxidant action as well, especially in the presence of transition metals like iron and copper. Release of iron from the iron-storage protein ferritin under UV-light has been ascribed to be the main source of oxidative stress. The consequent release of potentially harmful free iron within the cells will clearly exacerbate the damaging on
  • the antioxidant of the present invention is c ompletely f ree o f p ro-oxidation a ctivity i nduced b y t ransition metals whereas well-known antioxidants like Vitamin C, Vitamin E, proanthocyanidins (from pine and grape), Superoxide Dismutase and
  • the antioxidant of the present invention is unique in that it inhibits collagenase activity (collagenase is one of the MMP's) which digests collagen and therefore degrades collagen. Exposure to UV tends to increase the expression of the collagenase enzyme which contributes to the visible signs of aging. The antioxidant of the present invention is able to block this enzyme activity and thereby reduces the destruction of collagen. Literature data shows that the protection of existing collagen is more important than stimulating collagen production (EF Bernstein and J Uitta, Clinics in Dermatology, 14, 143- 151 ,1996).
  • Stromelysin-1 has a much broader substrate specificity than collagnease as it degrades various proteogylcan components of the extracellualr matrix as well as fibronectin and laminin. Exposure to UV tends to increase the expression of the stromelysin-1 enzyme which contributes to the visible signs of aging.
  • the antioxidant of the present invention is able to block this enzyme activity and thereby reduces the destruction of extracelluar matrix proteins.
  • Iron is the primary growth factor for all living cells. Most of the iron in the body resides in the blodd stream. However, not all iron that enters the circulation can be carried by hemoglobin. If iron circulate through the blood stream unattached to a protein, what is called “free iron” they can wreak havoc, promoting oxidative stress. Iron-induced oxidation occuring within fatty tissues is called lipid peroxidation. For example, neurons (nerve cells) in the brain and nervous system are lined with fat called myelin and are very vulnerable to destruction by excessive levels of unbound iron.
  • the antioxidant of the present invention is a very efficient iron and copper chelator.
  • Iron and copper are the principal players involved in the degredation of collagen and free radical damage which causes premature aging and photodamage to the skin. Altering the reduction potential of iron to disfavor reaction with H 2 O 2 or blocking available sites on the iron to which H 2 O 2 m ight attach m ay p rovide a solution to stop transition metal- induced oxidation. These two principles are important in the design of chelators having antioxidant functionality for skin care use.
  • the antioxidant of the present invention has all the attributes of an ideal antioxidant but no pro-oxidant activity induced by transition metals because of its excellent chelating property for Fe 3+ and Cu 2+ thereby eliminating the generation of the h ydroxyl radical a nd its detrimental effects on skin, most significantly when skin is exposed to ultraviolet light.
  • the antioxidant of the present invention is one of a very small group of antioxidants providing a unique "cascading effect" which potentiates free radical scavenging activity by allowing the actives to continuously recycle to remain active for a longer period of time. While most antioxidants go from an active to an inactive role, the antioxidant of the present invention utilizes a multilevel cascade of antioxidant compounds resulting in a totally unique prolongation of its antioxidant capabilities.
  • a further embodiment of the current invention is a dosage form suitable for oral administration, characterized in that it comprises an extract of Emblica officinalis.
  • the dosage form preferably includes excipients suitable for such oral administration.
  • the dosage form can be a tablet or a capsule or an elixir or suspension or a drink.
  • the dosage form may contain other ingredients capable of retarding, preventing and reversing the sign of skin photo-damage.
  • Nutritional supplements take many forms, varying in some instances with the intended application. They have been used in the form of liquids, pills or tablets and confectionery bars to supply diets with additional vitamins, minerals or other food groups. Protein supplements are available commercially in several forms, such as powders, tablets and self- supporting solid structures. The powders are typically sprinkled on or mixed with other foods and most typically mixed with a liquid such as water or milk. Flavoring agents and other additives are typically used to make the supplement more palatable and more easily dispersed in a liquid medium.
  • the self-supporting solid structures are available commercially, typically as confectionery bars, e.g. "candy" bars. Like their powdered counterparts, they usually contain flavoring agents and other additives intended to provide better texture and palatability.
  • the dosage form is a nutritional supplement, preferably in the form of liquids, powders, pills or tablets and confectionery bars, especially preferred a baked, edible, high protein product.
  • One especially preferred dosage form comprises a) at least 0.1 % Emblica officinalis extract, b) a mixture of high protein components, c) flour, d) leavening agent, e) sweetener, and f) water.
  • Additional the dosage form may comprise a flavor component for imparting a characteristic taste to said nutritional composition selected from the group consisting of water soluble natural or artificial extracts that include apple, banana, cherry, cinnamon, cranberry, grape, honeydew, honey, kiwi, lemon, l ime, o range, peach, peppermint, p ineapple, raspberry, tangerine, watermelon, wild cherry and equivalents thereof; being in the overall range of 0.10% to 2.0% by weight of said dry composition and/or a colorant component for imparting a characteristic color to said nutritional composition selected from the group consisting of water soluble natural or artificial dyes of blue, green, orange, red, violet, and yellow; iron oxide dyes, ultramarine pigments of blue, pink, red, and violet; and equivalents thereof; being in the overall range of 0.10% to 2.0% by weight of said dry composition.
  • a flavor component for imparting a characteristic taste to said nutritional composition selected from the group consisting of water soluble natural or artificial extracts that include apple, banana
  • Fresh Emblica officinalis fruit (5 kg) was finely pulped and mixed with water (2-liter), containing sodium chloride (1% w/w). The mixture was left standing at room temperature for about 12 hours. Then the mixture was stored in the cold (10°C.) for 3 days. Thereafter it was filtered through a thin cloth and the filtrate was spray-dried.
  • the antioxidant fraction in the spray-dried b lend was a bout 0.1 g/100 g of pulp as determined by high- pressure thin layer chromatography (HPTLC). Some free gallic acid (1.8 g/100 g of pulp), and monosaccharides and starches (glucose, rhamnose, galactose, etc.) (12 g/100 g of pulp) also was present in the blend.
  • HPTLC high- pressure thin layer chromatography
  • Extract of Invention (EX. 1 ) 60.0 250.0
  • Extract is granulated with starch paste to make it a free-flowing powder. Blend all the ingredients, except 4, for 25 min. in a blender. Screen in 4 and blend for an additional 5 min. Compress into tablets using 7/16-in standard concave tooling. Alternately, the blended material can be filled into appropriate capsules.
  • Vitamins Vitamins
  • Vitamin B6 Pyridoxine Hcl
  • Vitamin B2 Roboflavin
  • Vitamin B1 Thiamin Mononitrate
  • Vitamin A Palmitate
  • Vitamin A B Folic acid
  • Vitamin B12 Vitamin D
  • Iron-catalyzed formation of hydroxyl radical from superoxide anion radical and hydrogen peroxide requires the availability of at least one iron coordination site that is either empty or occupied by a readily dissociable ligand, such as water. This coordination with water may be completely displaced by stronger ligands like azide (N 3 ⁇ ) anion. This principle was applied to determine if any coordination site is free in the Fe 3+ -antioxidant complex by UV spectrophotometric method (E. Graf et al. "Iron-catalyzed hydroxyl radical formation, stringent requirement for free iron coordination site" J. Biol Chern. 1984 259:3620-3624.; A. E.
  • the peak positions are obtained from differential spectroscopic scans of 1.0 mM Fe 3+ and 5 mM chelator, 1 M NaN 3 , 50 mM phosphate buffer, pH 7.4, vs. the same solution without sodium azide
  • this extract food supplement after oral administration for 8 weeks, in an amount of 1-500 mg/day should increase the UV radiation necessary to produce a minimal erythemal dose (MED). Erythema would then be evaluated by expert visual assessment. Minolta Chromameter readings would be performed on baseline skin before and after 4 and 8 weeks of usage to evaluate for skin lightening potential of the extract food supplement.
  • MED minimal erythemal dose
  • INCLUSION CRITERIA a. 36 healthy male and female subjects of skin types ll-lll (described below) would be selected for the study.
  • EXCLUSION CRITERIA a. Subjects with a history of abnormal response to sunlight or those taking medication, which might produce an abnormal response to sunlight, are excluded from the study. b. Subjects exhibiting current sunburn, suntan, uneven skin tone or visible skin disease, which might interfere with evaluation of test results, are excluded from the study. c. Pregnant or lactating females are excluded. d. Subjects who regularly use UVA sunbeds. e. Subjects with a history of lupus, erythematosis, or skin cancer. f. Subjects who are taking any vitamin supplements within 2 weeks prior to the start of the study. 3.
  • LIGHT SOURCE A Xenon Arc Solar Simulator (150 w) would be used as the source of ultraviolet light irradiation (Solar Light Company, Philadelphia, PA). T his instrument, described in detail in J. Invest. Dermatol. 53, 192 (1969), provides a spectral output in the ultraviolet range comparable to that of natural sunlight.
  • W G-320 a nd U G-11 filters a re u sed to p rovide a b asic
  • UV-A and UV-B wavelength spectrum with wavelength ranges of 290-400 nm.
  • the lamp output would be measured with a UV intensity meter (Model
  • the study would be performed by randomized, controlled trials with 36 volunteers randomly selected and divided into 2 groups consisting of 18 subjects each. 18 would be assigned to the orally administered group and 18 to the control group.
  • the MED is defined as the time interval or dosage of UV light irradition sufficient to produce a minimal, perceptible erythema on untreated skin.
  • the MED of each subject would be determined by a progressive sequence of timed UV light exposures, each of which would be graduated incrementally by 25% over that of the previous exposure. 16 to 24 hours after irradiation, the sites would be evaluated for erythema according to the following scoring system:
  • readings of Baseline skin would be taken using the Minolta Chroma Meter.
  • the L*a*b* color notation system would be used to evaluate if there is a change in color over the duration of the study. Measurements would be made in triplicate and the average would be used as the data point.
  • Subjects in the treated groups would be instructed to administer orally 2 tablets of the extract composition of invention twice daily for 8 weeks. Subjects would be instructed to remain out of the sun and to keep a daily diary to document compliance.
  • the subjects would then return to the laboratory for determination of MED values.
  • the subjects would be irradiated as described above adjacent to the Baseline MED.
  • the MED would be evaluated 16 to 24 hours after irradiation using the scoring system listed above.
  • the subjects would then return to the laboratory for determination of MED values.
  • the subjects would be irradiated as described above adjacent to the Baseline MED.
  • Minolta Chroma Meter readings would be taken on Baseline skin as described above.
  • the MED would be evaluated 16 to 24 hours after irradiation using the scoring system listed above. Week 8
  • the subjects would return to the laboratory for determination of MED values. The subjects then would be irradiated as described above adjacent to the Baseline MED. Minolta Chroma Meter readings would be taken on
  • the MED would be evaluated 16 to 24 hours after irradiation using the scoring system listed above.
  • the pre- and post-study MED's as well as the Chroma Meter readings would be compared to determine if any significant changes are observed.
  • Exposure to sunlight or UV irradiation produces marked and signifcatnt changes in LC in the human skin.
  • the LC count is reduced as a function of UV dose. They lose their dendritic morphology and ball up. The LC lose their antigen-presenting ability. These two variables can be detected and followed with the aid of ATPase staining technology ( K Wolff and G. Stibgl, J. Invest. Dermatol, 80, 17s-21s, 1983).
  • the pre- and post-study LC level would be compared to determine if any significant changes are observed.
  • lipid peroxide level Exposure to sunlight or UV irradiation produces oxidative stress and significant changes in lipid peroxide level in the human skin.
  • the level of lipid peroxide level can be detected and followed by the procedure described by P. Pugliese, Assessment of anti-aging products, In Clinical Safety and efficacy testing of Cosmetics, Vol 1 , Marcel Dekker, NY, 295- 309, 1990.
  • Level of lipid peroxides in skin of the human volunteers before sun exposure (placebo, negative control) 2.
  • Level of lipid peroxides in skin of the human volunteers orally administered with the antioxidant of the present invention (50 to 500 mg/day for one month to two months, once or twice daily) after sun exposure
  • the pre- and post-study lipid peroxide level would be compared to determine if any significant changes are observed.
  • one aspect of the invention is to provide a regimen wherein a person will administer a topical sunscreen to the person's skin and before and/or during exposure to sun, the person will ingest a composition containing an extract of Emblica officinalis, preferably a standardized extract.
  • Preferred regimens comprises orally administering the extract- containing composition before sun exposure, for example at least one week, or at least 2 or 3 days before sun exposure.
  • the contemplated dosage is a sufficient to ameliorate damage to skin from exposure to sun, e.g. 1-500, preferably 2-200 mg of the standardized extract per day.
  • hydrophobic antioxidants such as, Vitamin E, Lipoic Acid, Carotenoids, lutein, melatonin, with the antioxidant of the present invention generically or specifically described operating conditions of this invention for those used in the preceding examples.

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Abstract

La présente invention a trait à la protection solaire, et, plus particulièrement, à un procédé de protection solaire de la peau par l'administration orale d'un extrait de la plante Emblica officinalis (Phyllantus emblica). L'invention a également trait à des formes de dosage appropriées à cet effet.
PCT/EP2003/011847 2002-11-08 2003-10-24 Procede de protection de la peau contre la deterioration induite par le soleil par l'administration orale d'un extrait de emblica officinalis (phyllantus emblica) WO2004041231A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP03758062A EP1560561A1 (fr) 2002-11-08 2003-10-24 Procede de protection de la peau contre la deterioration induite par le soleil par l'administration orale d'un extrait de i emblica officinalis /i ( i phyllantus emblica /i )
AU2003274079A AU2003274079A1 (en) 2002-11-08 2003-10-24 METHOD FOR PROTECTION OF SKIN AGAINST SUN-INDUCED DAMAGE BY ORAL ADMINISTRATION OF AN EXTRACT OF EMBLICA OFFICINALIS (syn. PHYLLANTHUS EMBLICA)
JP2004548774A JP2006512310A (ja) 2002-11-08 2003-10-24 アムラ(別名フィランタスエンブリカ)抽出物の経口投与による日光に誘発される(sun−induced)損傷からの皮膚の保護方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US42471202P 2002-11-08 2002-11-08
US60/424,712 2002-11-08

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WO2004041231A1 true WO2004041231A1 (fr) 2004-05-21

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Cited By (13)

* Cited by examiner, † Cited by third party
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WO2005070383A1 (fr) * 2004-01-24 2005-08-04 Unilever Plc Compositions eclaircissantes pour la peau
JP2006028090A (ja) * 2004-07-16 2006-02-02 Taiyo Kagaku Co Ltd 最終糖化産物生成阻害組成物
WO2006106996A1 (fr) * 2005-03-31 2006-10-12 Kobayashi Pharmaceutical Co., Ltd. Inhibiteur de la proliferation de cellules epitheliales gingivales
WO2011001441A1 (fr) * 2009-06-29 2011-01-06 Benny Antony Composition d’extrait d’emblica officinalis et son procédé de préparation
CN102590430A (zh) * 2012-01-17 2012-07-18 西藏奇正藏药股份有限公司 六味锦鸡儿制剂的检测方法
US8980340B1 (en) 2013-10-08 2015-03-17 Benny Antony Medicinal composition of extract of seed of emblica officinalis and method of preparing the same
US9066911B2 (en) 2013-10-08 2015-06-30 Benny Antony Medicinal composition of extract of seed of Emblica officinalis and method of preparing the same
US9757423B2 (en) 2003-03-03 2017-09-12 Arjuna Natural Extracts, Ltd. Composition to enhance HDL cholesterol and to decrease intima-media thickening in animals and humans and a method for its preparation
CN109580846A (zh) * 2019-01-22 2019-04-05 北京九龙制药有限公司 一种治疗高尿酸血症的中药复方制剂的质量检测方法
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US10434129B2 (en) 2003-03-03 2019-10-08 Arjuna Natural Ltd. Composition to enhance HDL cholesterol and to decrease intima-media thickening in animals and humans and a method for its preparation
US9757423B2 (en) 2003-03-03 2017-09-12 Arjuna Natural Extracts, Ltd. Composition to enhance HDL cholesterol and to decrease intima-media thickening in animals and humans and a method for its preparation
WO2005070383A1 (fr) * 2004-01-24 2005-08-04 Unilever Plc Compositions eclaircissantes pour la peau
JP2006028090A (ja) * 2004-07-16 2006-02-02 Taiyo Kagaku Co Ltd 最終糖化産物生成阻害組成物
WO2006106996A1 (fr) * 2005-03-31 2006-10-12 Kobayashi Pharmaceutical Co., Ltd. Inhibiteur de la proliferation de cellules epitheliales gingivales
WO2011001441A1 (fr) * 2009-06-29 2011-01-06 Benny Antony Composition d’extrait d’emblica officinalis et son procédé de préparation
CN102590430A (zh) * 2012-01-17 2012-07-18 西藏奇正藏药股份有限公司 六味锦鸡儿制剂的检测方法
CN102590430B (zh) * 2012-01-17 2014-08-13 西藏奇正藏药股份有限公司 六味锦鸡儿制剂的检测方法
EP2972324B1 (fr) * 2013-03-15 2020-04-22 The Procter and Gamble Company Procédé non invasif pour le diagnostic des pellicules
US10485831B2 (en) 2013-10-08 2019-11-26 Benny Antony Medicinal composition of extract of seed of emblica officinalis and method of preparing the same
US10286022B2 (en) 2013-10-08 2019-05-14 Benny Antony Medicinal composition of extract of seed of emblica officinalis and method of preparing the same
US9066911B2 (en) 2013-10-08 2015-06-30 Benny Antony Medicinal composition of extract of seed of Emblica officinalis and method of preparing the same
US8980340B1 (en) 2013-10-08 2015-03-17 Benny Antony Medicinal composition of extract of seed of emblica officinalis and method of preparing the same
US9775869B2 (en) 2013-10-08 2017-10-03 Benny Antony Medicinal composition of extract of seed of Emblica officinalis and method of preparing the same
US10953055B2 (en) 2013-10-08 2021-03-23 Benny Antony Medicinal composition of extract of seed of emblica officinalis and method of preparing the same
US11125130B2 (en) 2013-10-08 2021-09-21 Benny Antony Medicinal composition of extract of seed of Emblica officinalis and method of preparing the same
CN109580846A (zh) * 2019-01-22 2019-04-05 北京九龙制药有限公司 一种治疗高尿酸血症的中药复方制剂的质量检测方法
CN114699462A (zh) * 2022-02-24 2022-07-05 无限极(中国)有限公司 组合物及其在制备具有抗蓝光功效的产品中的应用
CN115252496A (zh) * 2022-08-18 2022-11-01 云南贝泰妮生物科技集团股份有限公司 一种余甘子提取物的制备方法及其在防治紫外线损伤中的应用

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