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WO2007105864A1 - Composition pharmaceutique contenant de la silymarine destinée à la prévention et au traitement de la dermatite de contact irritante - Google Patents

Composition pharmaceutique contenant de la silymarine destinée à la prévention et au traitement de la dermatite de contact irritante Download PDF

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Publication number
WO2007105864A1
WO2007105864A1 PCT/KR2007/000659 KR2007000659W WO2007105864A1 WO 2007105864 A1 WO2007105864 A1 WO 2007105864A1 KR 2007000659 W KR2007000659 W KR 2007000659W WO 2007105864 A1 WO2007105864 A1 WO 2007105864A1
Authority
WO
WIPO (PCT)
Prior art keywords
silymarin
contact dermatitis
irritant contact
lotions
silydianin
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.)
Ceased
Application number
PCT/KR2007/000659
Other languages
English (en)
Inventor
Hwan Mook Kim
Song-Kyu Park
Jong Soon Kang
Mi Hwa Han
Kiho Lee
Sang-Bae Han
Ki Hoon Lee
Chang Woo Lee
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Korea Research Institute of Bioscience and Biotechnology KRIBB
Original Assignee
Korea Research Institute of Bioscience and Biotechnology KRIBB
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 Korea Research Institute of Bioscience and Biotechnology KRIBB filed Critical Korea Research Institute of Bioscience and Biotechnology KRIBB
Publication of WO2007105864A1 publication Critical patent/WO2007105864A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A—HUMAN NECESSITIES
    • A41—WEARING APPAREL
    • A41D—OUTERWEAR; PROTECTIVE GARMENTS; ACCESSORIES
    • A41D3/00—Overgarments
    • A41D3/02—Overcoats
    • A41D3/04—Raincoats
    • A—HUMAN NECESSITIES
    • A41—WEARING APPAREL
    • A41D—OUTERWEAR; PROTECTIVE GARMENTS; ACCESSORIES
    • A41D13/00—Professional, industrial or sporting protective garments, e.g. surgeons' gowns or garments protecting against blows or punches
    • A41D13/015—Professional, industrial or sporting protective garments, e.g. surgeons' gowns or garments protecting against blows or punches with shock-absorbing means
    • A—HUMAN NECESSITIES
    • A41—WEARING APPAREL
    • A41D—OUTERWEAR; PROTECTIVE GARMENTS; ACCESSORIES
    • A41D13/00—Professional, industrial or sporting protective garments, e.g. surgeons' gowns or garments protecting against blows or punches
    • A41D13/05—Professional, industrial or sporting protective garments, e.g. surgeons' gowns or garments protecting against blows or punches protecting only a particular body part
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A41—WEARING APPAREL
    • A41D—OUTERWEAR; PROTECTIVE GARMENTS; ACCESSORIES
    • A41D2200/00—Components of garments
    • A41D2200/20—Hoods

Definitions

  • the present invention relates to a pharmacological composition comprising silymarin for prophylactic and therapeutic treatments for contact dermatitis.
  • Contact dermatitis is an acute or chronic inflammatory disease caused by skin contact with irritant substances. Contact dermatitis causes most trouble in workplaces in which a high risk of field exposure to dermatitis-inducing substances is present. According to a recent report (Saary, J. et al., J. Am. Acad. Dermatol. 53(5):845 ⁇ 855, 2005), between 24 to 170 out of 100,000 workers develop contact dermatitis and 29% to 72% of them leave their jobs, although results may vary according to survey methods and standards and many factors including the work environment. Contact dermatitis is classified into irritant contact dermatitis and allergic contact dermatitis.
  • TNF- ⁇ Tumor necrosis factor ⁇
  • Receptors for TNF- ⁇ are known to be expressed in virtually all cells of the human body and accordingly, most cells are affected by TNF- ⁇ .
  • TNF- ⁇ has been reported to play an important role in various inflammatory diseases such as rheumatoid arthritis and Crohn's disease.
  • TNF- ⁇ is also involved inflammatory skin diseases including allergic and irritant contact dermatitis and that suppressing TNF- ⁇ activity greatly helps in curing such diseases (LaDuca, J. R. et al., Dermatol. Clin. 19(4):617 ⁇ 635, [6]
  • Silymarin is a flavolignan complex belonging to the flavonoid family. It is a mixture of three major components of silybin, silydianin and silycristin as well as various flavonoids such as dehydrosilybin.
  • Silymarin is extracted from milk thistle ( Silybum marianurri), a plant that belongs to the family Compositae and native to southern Europe and north Africa, but has spread into the Americas and now grown as a garden plant or for medicinal purposes. The use of milk thistle as a herbal tea for promoting breast milk flow in nursing mothers has been well known since old times.
  • silymarin has been found to stabilize the membranes of liver cells as to block the inflow of harmful substances and upregulate protein synthesis in the liver to promote liver regeneration.
  • silymarin has been found to stabilize the membranes of liver cells as to block the inflow of harmful substances and upregulate protein synthesis in the liver to promote liver regeneration.
  • Silymarin was also reported to provide protection from inflammatory diseases such as sepses by suppressing the activity of macrophages and preventing inflammation (Kang, J. S. et al ., J. Pharmacol. Exp. Ther. 302:138-144, 2002). No studies have been reported, however, on the effects of silymarin against irritant contact dermatitis.
  • the objective of the present invention is to provide a novel use of silymarin as a prophylactic and therapeutic agent.
  • the present invention provides a pharmaceutical composition for the treatment and prevention of irritant contact dermatitis that includes silymarin or its major ingredients, i.e., silybin, silydianin and silychristin.
  • Another objective of the invention is to provide a cosmeceutical for treating and preventing the same disease containing said composition as the active ingredient.
  • Still another objective of the invention is to provide novel uses of silymarin or its main ingredients of silybin, silydianin and silychristin in the pharmaceutical manufacture of prophylactic and therapeutic agents for irritant contact dermatitis.
  • the present invention provides a pharmacological composition for treating and preventing irritant contact dermatitis, which contains silymarin or its main ingredients of silybin, silydianin and silychristin.
  • silymarin as used in this invention includes commercially available compositions of the flavolignan complex as well as extracts obtained from the seeds and fruits of plants belonging to the family Compositae, including dandelion (Taraxacum platycarpurri) and milk thistle (Silybum marianurri).
  • mice were either first given an application of the inventive composition and then after 30 minutes an application of l-chloro-2,4-dinitrochlorobenzene (DNCB)(subject group), or the DNCB alone (control group) in their ears to induce irritant contact dermatitis.
  • DNCB l-chloro-2,4-dinitrochlorobenzene
  • the subject group exhibited a gradual reduction in the swollen width of their ears (See FlG. 1), demonstrating a dose-dependent suppression of irritant contact dermatitis by silymarin.
  • the present inventors also examined whether this suppression of DNCB-induced dermatitis by silymarin requires pre-treatment with silymarin before DNCB.
  • B ALB/c mice were treated with silymarin either 30 minutes before or 15 minutes after the DNCB application and examined for swelling in their ears. It turned out that post-insult treatment of silymarin is capable of suppressing swelling in the ears on a level similar to pre-insult treatments (FlG. 3).
  • Corresponding weight increases in the lymph nodes were examined for B ALB/c mice after similarly receiving silymarin treatments either 30 minutes before or 15 minutes after the DNCB application. Again, a reduction in DNCB -induced weight increase was observed for those lymph nodes that received silymarin after DNCB, and their reduction was on a level similar to those received treatments before DNCB (FlG. 4)
  • silymarin characteristically keeps TNF- from being overproduced.
  • the present inventors applied the inventive pharmacological composition to B ALB/c mice 30 minutes before the application of DNCB to trigger dermatitis, and measured the TNF- ⁇ levels of the mice. The measured TNF- ⁇ levels confirmed silymarin s capability to repress DNCB-induced expression of TNF- ⁇ (FlG. 6).
  • the inventive pharmacological composition for the treatment and prevention of irritant contact dermatitis contains silymarin, or its major ingredients silybin, silydianin and silychristin in an amount of 0.02 to 90 weight parts per 100 weight parts of the composition.
  • the pharmacological composition of this invention may additionally comprise one or more active ingredients that exhibit equivalent or similar function to silymarin or its three main ingredients.
  • the pharmacological composition of this invention which contains silymarin or its main ingredients of silybin, silydianin and silychristin, may additionally comprise excipients conventionally used in the field of the invention.
  • the pharmacological composition containing silymarin, or its main ingredients, silybin, silydianin and silychristin, as described in this document may additionally comprise pharmaceutically allowable carriers, excipients and diluents that suit the purposes.
  • the inventive composition may be formulated into any pharmaceutically allowable form via methods well known in the field of pharmaceutics: for example, oral preparations including liquids, powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols; external preparations such as ointments; suppositories and sterile injections.
  • Examples of carriers, excipients and diluents for the inventive composition containing silymarin may include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginates, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, amorphous cellulose, polyvinyl pyrrolidone, water, methyl hydroxybezoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil.
  • Preparations may be formulated using routine diluents and excipients such as fillers, binders, humectants, disintegrants, and surfactants.
  • the appropriate dose for the inventive composition of silymarin or its main ingredients of silybin, silydianin can be determined by taking account of absorption and excretion rates for the active ingredients, patient s age, weight, gender, condition and severity of the symptoms.
  • an internal preparation containing 0.001-30% active ingredients can be applied to affected areas once or several times a day for adults. This dose can be adjusted according to sex, age and condition of the patient.
  • the administration dose for silymarin is subject to variation according to the route of administration, severity of the condition, sex and age. Thus, under no circumstances should the dose described above be understood as limiting the scope of the present invention.
  • the present inventors provide cosme- ceuticals containing silymarin or its main ingredients, silybin, silydianin and silychristin as the active ingredients.
  • the cosmeceutical of the present invention may additionally comprise one or more active ingredients equivalent or similar in activity.
  • the inventive cosmeceutical containing silymarin or its main ingredients may be formulated into conventional emulsions and solubilized formulations.
  • emulsions include moisturizers, nourishing creams, cosmetic essences and moisturizing essences.
  • solubilized formulations include skin softeners.
  • the silymarin-containing cosmeceutical of this invention may additionally comprise dermatologically-allowed vehicles and media to support formulation into topical or systemic cosmetic supplements routinely used in the cosmetics industry.
  • suitable cosmetic formulations include solutions, gels, anhydrous solids or pastes, oil-in-water emulsions, suspensions, microemulsions, microcapsules, microgranules, ionic (liposomes) or non-ionic vesicular dispersions, creams, lotions, moisturizing lotions, powders, ointments, sprays and concealing sticks.
  • foams and aerosols with compressed propellants are contemplated as possible formulations.
  • the cosmeceutical of the present invention may further comprise cosmetically or dermatologically-allowed conventional additives whose examples include: fats, organic solvents, solubilizer, thickeners, gellifiers, softeners, anti-oxidants, suspension agents, stabilizers, foaming agents, aromas, surfactants, water, ionic and non-ionic emulsifiers, extenders, metal ion se- questerers and chelators, preservatives, vitamins, screening agents, humectants, essential oils, dyes, pigments, hydrophilic or lipophilic activating agents and lipid vesicles.
  • additives may be introduced in amounts conventionally used in derma- tological applications.
  • the cosmeceutical of the present invention can be formulated into skin lotions, skin softeners, skin toners, astringents, lotions, milk lotions, moisturizing lotions, nourishing lotions, massaging creams, nourishing creams, hand creams, nourishing essences, packs, soaps, shampoos, cleansing foams, cleansing lotions, cleansing creams, body lotions, body cleansers, emulsions, pressed powders, loose powders and eye shadows.
  • the present inventors provide uses of silymarin or its main ingredients in the manufacture of therapeutic and prophylactic agents against irritant contact dermatitis.
  • the pharmacological composition of this invention can be administered to patients of irritant contact dermatitis to cure or improve the condition of the disease.
  • the daily dose for the administration of the inventive composition is 1-500 mg, or preferably 10-300 mg for adults. The actual dose, however, would be dependent on multiple factors such as age and sex of the patient, the exact nature of the illness, and its severity. Also the administration route can be varied according the condition of the patient and the severity of the symptoms.
  • FIG. 1 shows the effect of silymarin pre-treatment on the swelling of mouse ears induced by dichloronitrobenzene (DNCB).
  • FIG. 2 exhibits the effect of silymarin pre-treatment on the weight increase of mouse lymph nodes induced by DNCB.
  • FIG. 3 contrasts the effects of silymarin treatments before and after the DNCB treatment on the swelling of mouse ears induced by the latter.
  • FIG. 4 contrasts the effects of silymarin treatments before and after the DNCB treatment on the weight increase of mouse lymph nodes induced by the latter.
  • FIG. 5 contrasts the effects of silymarin treatments before and after the DNCB treatment on the DNCB-induced increases in the water content of mouse ears.
  • FIG. 6 exhibits the effect of silymarin pre-treatment on the DNCB-induced up- regulation of TNF- ⁇ expression in treated mice.
  • mice purchased from Orient Bio (Korea) were acclimatized until the 6th week. Silymarin was purchased from Sigma (USA).
  • the mouse model for irritant contact dermatitis was established by referring to the methods of Kuriyama (Kuriyama, K. et al., Inflamm. Res. 51(10):483 ⁇ 489, 2002) and Baolin (Baolin, L. et al., Planta Med. 71(5):424 ⁇ 428, 2005). Irritant contact dermatitis was induced in mice by applying 20 D of 1% dichloronitrobenzene (DNCB) in 4:1 mixture of acetone and olive oil (Sigma).
  • DNCB dichloronitrobenzene
  • TNF- ⁇ Tumor necrosis factor alpha
  • silymarin of the present invention or its main ingredients of silybin, silydianin and silychristin are active in suppressing symptoms arising from irritant contact dermatitis such as swelling of ears, weight increases in lymph nodes, increases in the water contents of ears and the upregulated expression of TNF- ⁇
  • inventive pharmacological compositions containing silymarin or its main ingredients are thus useful for preventing and curing irritant contact dermatitis

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Textile Engineering (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dermatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cosmetics (AREA)

Abstract

L'invention concerne une composition pharmaceutique contenant de la silymarine destinée à la prévention et au traitement de la dermatite de contact irritante. La composition selon l'invention contient de la silymarine ou ses ingrédients principaux, silybine, silydianine et silychristine, et élimine les symptômes de la dermatite de contact irritante, provoqués par une application de 1-chloro-2,4-dinitrobenzène sur des oreilles de souris, tels que le gonflement, une augmentation du contenu en eau des oreilles, une augmentation de poids des ganglions lymphatiques et une expression de TNF-α régulée vers le haut. Les compositions pharmaceutiques selon l'invention servent à la prévention et au traitement de la dermatite de contact irritante.
PCT/KR2007/000659 2006-03-14 2007-02-07 Composition pharmaceutique contenant de la silymarine destinée à la prévention et au traitement de la dermatite de contact irritante Ceased WO2007105864A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2006-0023580 2006-03-14
KR1020060023580A KR20070093574A (ko) 2006-03-14 2006-03-14 실리마린을 포함하는 자극성 접촉피부염 예방 및 치료용약학적 조성물

Publications (1)

Publication Number Publication Date
WO2007105864A1 true WO2007105864A1 (fr) 2007-09-20

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Application Number Title Priority Date Filing Date
PCT/KR2007/000659 Ceased WO2007105864A1 (fr) 2006-03-14 2007-02-07 Composition pharmaceutique contenant de la silymarine destinée à la prévention et au traitement de la dermatite de contact irritante

Country Status (2)

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KR (1) KR20070093574A (fr)
WO (1) WO2007105864A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130192624A1 (en) * 2012-01-27 2013-08-01 Mary Kay Inc. Cosmetic formulation
US20130209504A1 (en) * 2012-02-09 2013-08-15 Mary Kay Inc. Cosmetic formulation
US8815308B2 (en) 2010-12-30 2014-08-26 Mary Kay, Inc. Multi-purpose cosmetic compositions

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SINGH R.P. ET AL.: "Mechanisms and preclinical efficacy of silibini in preventing skin cancer", EUR. J. CANCER, vol. 13, 2005, pages 1969 - 1979, XP005014649 *

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10842733B2 (en) 2010-12-30 2020-11-24 Mary Kay Inc. Multi-purpose cosmetic compositions
US10188595B2 (en) 2010-12-30 2019-01-29 Mary Kay Inc. Multi-purpose cosmetic compositions
US8815308B2 (en) 2010-12-30 2014-08-26 Mary Kay, Inc. Multi-purpose cosmetic compositions
US11857667B2 (en) 2010-12-30 2024-01-02 Mary Kay Inc. Multi-purpose cosmetic compositions
US9320702B2 (en) 2010-12-30 2016-04-26 Mary Kay Inc. Multi-Purpose cosmetic compositions
US9358203B2 (en) 2010-12-30 2016-06-07 Mary Kay Inc. Multi-purpose cosmetic compositions
US20150099017A1 (en) * 2012-01-27 2015-04-09 Mary Kay Inc. Cosmetic formulation
US9278061B2 (en) * 2012-01-27 2016-03-08 Mary Kay Inc. Cosmetic formulation
US10588851B2 (en) 2012-01-27 2020-03-17 Mary Kay Inc. Cosmetic formulation
US20130192624A1 (en) * 2012-01-27 2013-08-01 Mary Kay Inc. Cosmetic formulation
US11376210B2 (en) 2012-01-27 2022-07-05 Mary Kay Inc. Cosmetic formulation
US8828455B2 (en) * 2012-01-27 2014-09-09 Mary Kay Inc. Cosmetic formulation
US12233153B2 (en) 2012-01-27 2025-02-25 Mary Kay Inc. Cosmetic formulation
US20130209504A1 (en) * 2012-02-09 2013-08-15 Mary Kay Inc. Cosmetic formulation
US8877259B2 (en) * 2012-02-09 2014-11-04 Mary Kay Inc. Cosmetic formulation
US9283171B2 (en) 2012-02-09 2016-03-15 Mary Kay Inc. Cosmetic formulation

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