WO1994005279A1 - Compositions therapeutiques dermatologiques, contenant du dimethylsulfone et un aminoacide contenant du soufre - Google Patents

Compositions therapeutiques dermatologiques, contenant du dimethylsulfone et un aminoacide contenant du soufre Download PDF

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Publication number
WO1994005279A1
WO1994005279A1 PCT/GB1993/001875 GB9301875W WO9405279A1 WO 1994005279 A1 WO1994005279 A1 WO 1994005279A1 GB 9301875 W GB9301875 W GB 9301875W WO 9405279 A1 WO9405279 A1 WO 9405279A1
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WO
WIPO (PCT)
Prior art keywords
skin
amino acid
composition
treatment
methylsulphonylmethane
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/GB1993/001875
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English (en)
Inventor
Aws Shakir Mustafa Salim
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Individual
Original Assignee
Individual
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
Priority claimed from GB929218772A external-priority patent/GB9218772D0/en
Priority claimed from GB939310608A external-priority patent/GB9310608D0/en
Application filed by Individual filed Critical Individual
Priority to AU49746/93A priority Critical patent/AU4974693A/en
Publication of WO1994005279A1 publication Critical patent/WO1994005279A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/13—Amines
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids

Definitions

  • the present invention relates to a pharmaceutical synergistic composition suitable for use in the treatment of dermatological diseases and disorders and for improving the condition of the skin.
  • the skin Due to its susceptibility to environmental pollutants, irritants and noxious agents and due to its large surface area, the skin is a common site for a wide variety of diseases and disorders be they degenerative, inflammatory, endocrinal, metabolic or neoplastic. While there is a large number of dermatological agents on the market, these do little to combat the mediators of skin injury or diseases, or to enhance the repair of skin in the aftermath of injury or diseases, or to sustain the integrity of skin against recurrence of such disorders or protect against their development. Moreover, many of the therapeutic modalities currently available have limitations pertaining to patient selection or application.
  • An object of the present invention is, thus, to introduce a synergistic pharmaceutical composition which not only overcomes these limitations but also combats the forces directly involved in mediating disease or injury processes in the skin, enhances the repair of any injury or damage sustained and upholds the integrity of the skin by increasing its resistance against the recurrence of the diseases or disorders which had been treated.
  • the present invention provides a synergistic pharmaceutical composition
  • methyl sulphonylmethane and a sulphur containing amino acid such as cysteine, cystine, cysteamine, methionine carboxyl esterified and S-methyl methionine sulphonium derivatives.
  • the carboxyl group may have been esterified. preferably by lower alkyl having 1 to 6 carbon atoms e.g. methyl.
  • S-methyl substituted, ternary sulphonium, derivatives of methionine such as methionine-S- methylsulphoniu bromide, iodide and chloride.
  • the abovementioned compounds have one or more optically active centres, in particular in the case of the amino acids at the amino- and carboxyl-substituted carbon.
  • the present invention extends to both individual isomers such as D-and L- isomers and enantiomers, and, in the case where two or more optically active centres are present, diastereoisomers, as well as mixtures of isomers including racemic DL mixtures.
  • cytoprotection which refers to sustaining the physio-chemical properties of biological tissues, thus increasing their resistance to noxious stimuli.
  • application onto the skin improves its condition in a number of ways including: a. ameliorating the severity of degenerative changes that had already occurred. b. protection against the progression of such changes. c. increasing the resistance of the skin to damage by sustaining its physiochemical properties, thus affording protection against the adverse effects of environmental irritants, pollutants and noxious agents. d. affording a potent sunscreening effect thereby protecting against ultraviolet sunrays which precipitate skin degeneration and premature ageing besides increasing the susceptibility to malignant transformation. e. enhancing the healing of inflamatory, endocrinal and metabolic disorders. f. enhancing the healing of wounds, ulcers, fissures and sinuses in addition to increasing the take and healing of skin grafts.
  • the improvements in skin condition can also include maintenance of its vitality, smoothness, firmness and texture.
  • vasodilator substance such as menthol in order to further increase the effectiveness of the composition in the skin.
  • enhanced therapeutic gains have been noted with the incorporation of vitamins A and E in compositions of the present invention.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising methyl sulphonylmethane and a sulphur containing amino acid, in intimate admixture with a physiologically acceptable carrier therefor, for use in improving the condition of the skin.
  • this invention provides a topical formulation comprising methylsulphonylmethane and a suphur containing amino acid in intimate admixture with a pharmaceutically acceptable vehicle.
  • This vehicle should not be deleterious to biological tissues or incompatible with any of the ingredients of the formulation. Since some individuals have more sensitive skin than others, alternative vehicles to those used normally may have to be tried.
  • Suitable vehicles are well known in the art and are presented in all its standard publications such as the British National Formulary and British Pharmacopoeia. They include ointment and cream bases, lotions, pastes, jellies, sprays, aerosols and bath oils. Ointments and creams may contain oleaginous absorption colloidal clays, thickening agents such as gum tragacanth or sodium alginate and other pharmaceutically acceptable accessory ingredients such as hu ectants, preservatives, buffers and antioxidants which have utility in such formulations. In general cream formulations are preferred as being most acceptable to the majority of users.
  • a particularly convenient base is one utilizing cetomacrogol, comprising for example 30% w/v cetomacrogol emulsifying ointment (30% w/v cetomacrogol emulsifying wax, 20% w/v liquid paraffin wax, 50% white soft paraffin) in freshly boiled and cooled purified water with for example 0.1% w/v chlorocresol or 0.08% w/v propyl hydroxybenzoate, 0.15% w/v methyl hydroxybenzoate and 1.5% w/v benzyl alcohol.
  • the topical formulations of the invention contain at least 0.5% w/w of each of its active ingredients, preferably from 1 to 20% w/w and most preferably from 1 to 10%, e.g. 5% methyl sulphonylmethane and 2% cysteine or methionine. Where menthol is included, this is generally used in an amount from 1 to 20% w/w and most preferably from 1 to 5% w/w.
  • the invention being presented can be administered orally or parenterally in a suitable vehicle, in particular by intravenous injection.
  • ingredients of the invention and any accompanying material may be presented as a draught in water or in a syrup, in capsules, sachets, boluses or tablets, as an aqueous or oleaginous solution or suspension or in suspension in a syrup, such suspensions optionally including suspending agents or as an oil-in-water or water-in-oil emulsion.
  • compositions of the invention can be taken in an alcoholic drink be that a spirit, wine or beer.
  • the non-alcoholic forms of these drinks may also serve as vehicles for the oral consumption of the invention.
  • compositions of the present invention may be added to fruit juices, mineral waters be they carbonated or not, and to all forms of soft drinks.
  • compositions of the invention can be directly delivered to the lung via smoke and in this respect, they can be added as a powder or solution to tobacco leaves or to the tobacco of cigarettes, cigars and pipes.
  • the compositions of the invention may also be included as a solution or powder in cigarette filters or small delivery compartments incorported in the cigarette. This compartment may also contain the composition of the invention in granules which evaporate upon contact with the smoke thereby delivering their active ingredients to be carried by the smoke.
  • flavouring sweetening, preserving, thickening or emulsifying agents may be included in the formulation.
  • Tablets may contain the ingredients of the invention and any accompanying material as a powder or granules optionally mixed with binders, lubricants, inert diluents or surface-active or dispersing agents.
  • compositions of this invention and any accompanying material may be presented in sterile solutions or suspensions in aqueous or oleaginous vehicles, which may also contain preservatives, antioxidants and material for rendering the solution or suspension isotonic with the recipient's blood.
  • Such formulations may conveniently be presented in unit-dose or multi-dose sealed containers.
  • the compositions of this invention are preferably presented in solution, suspension, or emulsion at a concentration of from 0.5% to 20% w/v, more preferably 2 to 5% w/v in unit or multidose form.
  • each unit dose preferably contains from 100 to 500 mg of each of its ingredients.
  • This dosage may be given once or more daily preferably at intervals of from 2 to 8 hours, most ___ preferably every 6 hours.
  • the ingredients of the invention are administered in a slow release or a sustained release vehicle, various suitable vehicles of this type being known in the art.
  • composition For topical therapy the composition is applied onto the skin from 1 to 3 times a day whereby it is spread over the whole area to be treated and massaged in for about 3 to 5 minutes. It is advisable to leave the evening application overnight if repair of any skin damage is to be realised. It is not necessary to wash away the previous application so as to apply a fresh one, however this may be simply done using warm water alone.
  • Example 1 The creams described in Example 1 can be applied several times a day and the evening application may be left overnight and washed away the following morning using warm water with or without soap. Treatment may be for a few days or months depending on each case.
  • the formulation is applied once daily onto the parts of the skin to be protected, e.g. face and limbs, prior to exposure to environmental irritants or sunlight.
  • application is governed by the nature of the disorder to be treated, e.g. dermatitis 5-10 days (unless caused by varicose veins when treatment is extended to 4 weeks) , wound healing 2-3 weeks, varicose ulceration 12-16 weeks. In these cases, the application is 2 to 3 times every day most preferably at 8 hourly intervals. Maintenance therapy after successful treatment or to sustain the condition of skin may require a once daily application to a particular part of the skin for months, years or even indefinitely.
  • Alcohol disrupts the gastric mucosal barrier causing hydrogen ion back diffusion and coagulative necrosis.
  • the alcohol-induced acute gastric mucosal injury has been shown to be mediated by oxygen-derived free radicals. Dose dependent protection against this injury was afforded by each of cysteine and methylsulphonylmethane. Moreover, administration of these agents together exhibited a synergistic influence in protection against tissue damage. No influences on the gastric acid secretion were associated with these actions.
  • cysteine and methylsulphonylmethane exhibit cytoprotective activities against tissue injury and interact with each other in this respect synergistically.
  • the mechanism of this action is believed to be scavenging the oxygen-derived free radicals which mediate tissue damage.
  • MMSC methylmethionine sulphonium chloride
  • Administration of methylsulphonylmethane and/or cysteine or methylmethionine sulphonium chloride did not influence gastric acid secretion in a significant manner, thus, the actions of these agents is independent of and not mediated via acid output.
  • the results show that each of cysteine, methylmethionine sulphonium chloride, and methylsulphonylmethane stimulates the healing of acute mucosal damage and that they interact synergistically with each other towards this objective.
  • Example l.A The sunscreening effect of the formulation described in Example l.A and its ability to protect patients against skin burns, erythema, itching and scaling following a few hours' exposure to the sun were examined.
  • Complete protection (100%) was afforded by active therapy against all the adverse effects produced by exposure to the sunlight. This protection extended to prevention of skin burn or irritation. Controls had no protection at all.
  • Example l.C. The therapeutic effect of the formulation described in Example l.C. in the treatment of contact dermatitis was examined. Treatment was applied twice every day for 5 days. There were 10 controls (5 men and 5 women, age range 18 to 34 years, mean 22) and 12 treatment cases (8 men and 4 women, age range 20 to 39 years, mean 26) . While complete healing of the dermatitis was noted at the end of the study in all the active treatment cases (100%) , only one control (10%) demonstrated this favourable response.
  • Hyperkeratosis is a proliferative skin disorder which represents hyperplasia of the epidermis and may have a malignant potential.
  • the condition affects the exposed parts of the skin of middle aged people, particularly the face and upper limbs.
  • Treatment of these lesions by the twice daily application of the formulation described in Example l.D. for four weeks 21 cases, 12 women and 11 men with an age range of 55 to 69 years, mean 63) caused complete shedding of the lesions and their replacement by normal skin in all cases. No response was noted in any of the control cases (20 patients, 13 women and 7 men with an age range of 54 to 67 years, mean 61) . It is, thus, construed that the formulation used stimulates repair of skin lesions.
  • Example D The therapeutic efficacy of the formulation described in Example l.B. in controlling the symptoms caused by skin burns resulting from exposure to the sun and in treating this condition was examined by its application onto the affected parts of skin every 8 hours for 10 days.
  • the burnt skin had been shed off and a return to normal skin was achieved by the 10th day of treatment in all cases.
  • Example l.D The efficacy of the formulation described in Example l.D in maintaining the skin smoothness and avoiding its roughening and/or fissuring was examined in a group of women who were already using some form of beauty cream to this end and who had no previous history of any skin diseases. All the cases entered into the study abstained from using their original cream and were then randomized to the control or active therapy group and instructed to use their cream whether for the hands and/or face once daily before retiring to bed and to leave it overnight for 2 months. There were 20 cases in the active therapy group (age range 18 to 26 years, mean 23) and 21 cases in the control group (age range 18 to 25 years, mean 21) .
  • Example IA a liberal amount of the formulation described in Example IA or the control cream was applied over the grafted area before dressing it up. Twelve patients were randomized to the active therapy group (8 women and 4 men, age range 18 to 38 years, mean 25) and 14 patients were randomized to the control group (7 women and 7 men, age range 18 to 43 years, mean 29) . When the dressing was removed five days after grafting, a completely successful take was observed in all members of the active therapy group. Two controls (14%) , however, showed failure of graft taking. This study reflects the ability of the active treatment used to enhance skin grafting.
  • the skin surrounding the ulcer was treated with propylene glycol onostearate then a below knee graduated compression bandage as described above was applied over the dressing. This procedure was repeated every day for 7 days then weekly until the ulceration had healed or until the end point of the study at 3 months. Patients were advised to sleep with the foot of the bed raised, to avoid long periods of standing without exercising the calf pump, to walk whenever possible and to elevate the leg when sitting.
  • MSM methylsulphonylmethane
  • CYS DL-cysteine hydrochloride
  • MMSC methylmethionine sulphonium chloride
  • Example 1 In groups of ten healthy male volunteers of ages ranging between 20 and 48 years, 5 grams of each of the formulations described in Example 1 was applied onto the face, neck and shoulders once in the morning, once again in the morning and then in the evening or once every eight hours. Treatment lasted for ten days and the applications were spread over the skin of the face, neck and shoulders, gently rubbed in for a few minutes then left for at least 3 hours before being washed away with warm water.
  • Example 1 All the therapeutic regimens were comfortably tolerated without any apparent allergic or adverse reactions. In addition, no toxicity was produced by the treatment used. It is, therefore, concluded that the formulations described in Example 1 are safe for use in main within the recommended doses.
  • methylsulphonylmethane and sulphur containing amino acid are advantageously used in generally equal amounts, by weight, in the synergistic compositions of the invention, other ratios may also be used. Generally there is used a ratio of from 10:1 to 1:10, preferably from 5:1 to 1:5, most preferably about 1:1, by weight. It will be understood though that preferred proportions may differ from one amino acid to another and as noted hereinbefore preferred proportions of methylsulphonylmethane to cysteine or methionine are approximately 5:2 or 5:1.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention se rapporte à des compositions synergiques comprenant du méthylsulfonylméthane et un aminoacide contenant du soufre, ainsi qu'à leur utilisation dans des formulations et des méthodes thérapeutiques permettant de protéger la peau et d'en améliorer l'état.
PCT/GB1993/001875 1992-09-04 1993-09-03 Compositions therapeutiques dermatologiques, contenant du dimethylsulfone et un aminoacide contenant du soufre Ceased WO1994005279A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU49746/93A AU4974693A (en) 1992-09-04 1993-09-03 Dermatological treatment compositions containing dimethylsulphone and a sulfur containing amino acid

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB9218772.3 1992-09-04
GB929218772A GB9218772D0 (en) 1992-09-04 1992-09-04 Biologically active dermatological treatment
GB939310608A GB9310608D0 (en) 1993-05-22 1993-05-22 Biologically active dermatological treatment
GB9310608.6 1993-05-22

Publications (1)

Publication Number Publication Date
WO1994005279A1 true WO1994005279A1 (fr) 1994-03-17

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PCT/GB1993/001875 Ceased WO1994005279A1 (fr) 1992-09-04 1993-09-03 Compositions therapeutiques dermatologiques, contenant du dimethylsulfone et un aminoacide contenant du soufre

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WO (1) WO1994005279A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5645825A (en) * 1995-06-07 1997-07-08 The Procter & Gamble Company Depilatory compositions comprising sulfhydryl compounds
US5681852A (en) * 1993-11-12 1997-10-28 The Procter & Gamble Company Desquamation compositions
US5821237A (en) * 1995-06-07 1998-10-13 The Procter & Gamble Company Compositions for visually improving skin
JP2006525951A (ja) * 2003-05-30 2006-11-16 デ・パオリ・アムブロスィ、ジアンフランコ 刺激、炎症および皮膚紅斑の治療および予防のための化粧品および／または薬学的組成物
JP2008291032A (ja) * 2008-06-04 2008-12-04 Paoli Ambrosi Gianfranco De ケミカルピーリングのための処方
EP2033689A1 (fr) * 2007-08-22 2009-03-11 Italfarmacia S.r.l. Composition dermatologique injectable pour le traitement des rides
WO2010082177A3 (fr) * 2009-01-16 2012-01-19 Sederma Nouveaux composés, notamment des peptides, compositions comprenant ces derniers et leurs utilisations dans les domaines cosmétique et dermopharmaceutique
US8293801B2 (en) * 2004-04-09 2012-10-23 Thienna Ho Skin lightening method

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2057263A (en) * 1979-08-30 1981-04-01 Herschler R J Compositions containing methylsulphonylmethane
GB2177917A (en) * 1985-07-09 1987-02-04 Aws Shakir Mustafa Salim Dermatologically active substances

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2057263A (en) * 1979-08-30 1981-04-01 Herschler R J Compositions containing methylsulphonylmethane
GB2177917A (en) * 1985-07-09 1987-02-04 Aws Shakir Mustafa Salim Dermatologically active substances

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5681852A (en) * 1993-11-12 1997-10-28 The Procter & Gamble Company Desquamation compositions
US5645825A (en) * 1995-06-07 1997-07-08 The Procter & Gamble Company Depilatory compositions comprising sulfhydryl compounds
US5821237A (en) * 1995-06-07 1998-10-13 The Procter & Gamble Company Compositions for visually improving skin
US5897857A (en) * 1995-06-07 1999-04-27 The Procter & Gamble Company Depilatory compositions comprising sulfhydryl compounds
JP2006525951A (ja) * 2003-05-30 2006-11-16 デ・パオリ・アムブロスィ、ジアンフランコ 刺激、炎症および皮膚紅斑の治療および予防のための化粧品および／または薬学的組成物
US8293801B2 (en) * 2004-04-09 2012-10-23 Thienna Ho Skin lightening method
EP2033689A1 (fr) * 2007-08-22 2009-03-11 Italfarmacia S.r.l. Composition dermatologique injectable pour le traitement des rides
WO2009024350A3 (fr) * 2007-08-22 2009-07-16 Italfarmacia S R L Composition dermatologique injectable pour le traitement des rides
EA021963B1 (ru) * 2007-08-22 2015-10-30 Италфармация С.Р.Л. Инъецируемая дерматологическая композиция для лечения морщин
JP2008291032A (ja) * 2008-06-04 2008-12-04 Paoli Ambrosi Gianfranco De ケミカルピーリングのための処方
WO2010082177A3 (fr) * 2009-01-16 2012-01-19 Sederma Nouveaux composés, notamment des peptides, compositions comprenant ces derniers et leurs utilisations dans les domaines cosmétique et dermopharmaceutique

Also Published As

Publication number Publication date
AU4974693A (en) 1994-03-29

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