WO1994005291A1 - Compositions therapeutiques destinees au cancer de la peau, contenant du dimethylsulfone et de l'oxypurinol ou de l'allopurinol - Google Patents

Compositions therapeutiques destinees au cancer de la peau, contenant du dimethylsulfone et de l'oxypurinol ou de l'allopurinol Download PDF

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Publication number
WO1994005291A1
WO1994005291A1 PCT/GB1993/001868 GB9301868W WO9405291A1 WO 1994005291 A1 WO1994005291 A1 WO 1994005291A1 GB 9301868 W GB9301868 W GB 9301868W WO 9405291 A1 WO9405291 A1 WO 9405291A1
Authority
WO
WIPO (PCT)
Prior art keywords
oxypurinol
allopurinol
msm
skin
composition
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/GB1993/001868
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English (en)
Inventor
Aws Shakir Mustafa Salim
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.)
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
Application filed by Individual filed Critical Individual
Priority to AU49739/93A priority Critical patent/AU4973993A/en
Publication of WO1994005291A1 publication Critical patent/WO1994005291A1/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
    • 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
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations

Definitions

  • the present invention relates to the treatment of and prophylaxis against skin and/or mucosal cancer and to novel synergistic compositions for use therein.
  • the skin Owing to its susceptibility to occupational trauma and to carcinogenic agents, the skin is the commonest site for carcinoma, including basal-cell and squamous-cell carcinoma. Although some of the tumours resulting from occupational hazards are now of historic interest, there remains one carcinogenic agent which is subject to no statutory protective legislation and to which the human skin is being increasingly exposed, namely the ultraviolet (UV) rays of sunlight. It has long been recognized that skin cancer occurs most often on the exposed parts and that it is seen in those exposed to sunlight for long periods.
  • the therapeutic modalities employed in the management of skin cancer have limitations pertaining to patient selection or therapy application and none can be used purely for prophylaxis.
  • the present invention aims at minimizing one or more of these disadvantages by providing a synergistic pharmaceutical composition for the protection against and treatment of skin and/or mucosal cancer.
  • This composition comprises at least one of allopurinol and oxypurinol together with methyl sulphonyl ethane.
  • compositions of this invention have been found in a very surprising and unexpected manner to protect skin and mucosa when applied thereto against malignant transformation and cancer development in addition to cancer treatment and prevention of recurrence. It was also noted that the compositions have the advantageous property of adhesion to the skin and/or mucosal lesions and binding to mucosal surfaces, thereby affording prolonged contact and enhanced therapeutic delivery to the intended target. Moreover, the active ingredients of the compositions exhibit a greater or lesser degree of synergism whereby the sum of the individual activities of these ingredients is less than that of their combination together.
  • compositions afford the benefit of sunscreening thereby exhibiting protection against skin irritation and burns caused by the ultraviolet rays of sunlight. Consequently, it can be construed that this action prevents the DNA damage caused by the above mentioned rays which in turn leads to oncogene expression and tumour development.
  • this invention has been found to exert therapeutic activities against hyperkeratosis, a condition which in itself enhances skin cancer development.
  • vasodilator such as for example menthol in order to further increase the effectiveness of the compositions in the skin and/or mucosa.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a combination of the present invention in intimate admixture with a physiologically acceptable carrier for use in improving the condition of the skin and/or mucosa.
  • this invention provides a topical formulation comprising a composition of the invention in intimate admixture with a pharmaceutically acceptable vehicle.
  • a pharmaceutically acceptable vehicle should not be deleterious to the skin or mucosa 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 employed.
  • 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 ointments and creams bases, lotions, pastes, jellies, sprays, aerosols and bath oils. Ointments and creams may contain oleaginoius absorption colloidal clays, thickening agents such as gum tragacanth or sodium alginate and other pharmaceutically acceptable accessory ingredients such as humectants, 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% w/v 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 ingredients, preferably from 1 to 30% w/w and most preferably from 1 to 10% w/w, e.g. 5% methyl sulphonylmethane and 1% allopurinol or oxypurinol. Where menthol is included, this is generally used in an amount of from 1 to 30% w/w and most preferably from 1 to 5% w/w.
  • the compositions of the present invention may also be administered orally or parenterally, in particular by intravenous injection.
  • the active 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.
  • the compositions of the invention can be taken orally 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.
  • the compositions of the invention can be added for oral administration to fruit juices, mineral waters be they carbonated or not, and to all forms of soft drinks.
  • flavouring sweetening, preserving, thickening or emulsifying agents
  • Tablets may contain the active ingredients of the combinations 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.
  • the active ingredients of the compositions of the invention and any accompanying material may be presented in sterile solutions or suspensions in aqueous or oleaginous vehicles, which may also contain preservatives and material for rendering the solution or suspension isotonic with the blood of the recipient.
  • Such formulations may conveniently be presented in unit-dose or multi-dose sealed containers.
  • the ingredients of the invention are preferably presented in solution or suspension or emulsion at a concentration of from 0.5 to 15% w/v, more preferably from 1 to 5% w/v, advantageously in unit multi-dose form.
  • each of these doses contains 500mg methyl sulphonyl ethane and 50mg allopurinol or oxypurinol.
  • the dosage may be given one or more times a day, preferably at intervals of from 2 to 6 hours, most preferably every 4 hours.
  • the active ingredients of the compositions 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.
  • 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 incorporated in the cigarette. These compartments may also contain the compositions of the invention in granules which evaporate upon contact with the smoke thereby delivering their subtances to be carried by the smoke.
  • the fomulation is applied onto the skin and/or mucosa from 2 to 6 times a day. It is generally spread over the area to be treated and gently rubbed in.
  • the formulae were prepared at a temperature of 25°C. Five grams of methyl sulphonylmethane are mixed with one gram of allopurinol or oxypurinol in a glass or stainless steel container then 94 grams of cetomacrogol 'A' (or 93 grams if menthol is to be used) are added and mixed for 10 minutes. After standing for 30 minutes, one gram of finely ground menthol crystals can be added and mixed for 10 minutes. The product is then placed in a dark-coloured airtight glass container and stored at an optimal temperature of 26°c, and most preferably no higher, away from direct sunlight. After preparation, none of these formulae should be used for at least 24 hours, should not be left exposed to the air for long periods of time and should not be directly exposed to the sun.
  • the creams described in Example 1 can be applied several times a day.
  • 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 daily application is limited to the period of exposure and is preferably twice a day, where one of the applications is used prior to the exposure to afford protection, and the other is used before retiring to bed and left overnight to induce therapy for any ultraviolet damage to the skin that may have occurred.
  • Treatment of hyperkeratosis may require therapy for up to 8 weeks.
  • treatment of skin cancer and protection against its recurrence may require several months of treatment.
  • the cream should be applied to all the exposed parts of the skin throughout the period of exposure, indefinitely.
  • MSM + coal tar 12 60% 1% MSM + coal tar 11 55% 5% MSM + coal tar 9 45% 10% MSM + coal tar 9 45% 20% MSM + coal tar 9 45% 30% MSM + coal tar 9 45%
  • squamous-cell carcinoma was defined as extension from the epidermis into the dermis of coherent masses or columns of cells. Prickle cells are evident and there is keratinisation with cell nests or epithelial pearls. For the purposes of this experiment extension into the subcutaneous tissues was defined as tumour spread. The following observations were made:
  • Example l.A as a sunscreen protection against various degrees of sunlight-induced skin burn (itching, erythema, blistering and scaling) was examined in volunteers exposed to the sun for no more than three hours every day, who had a clear history of skin damage following such exposure. Treatment was applied twice every day during the period of exposure to the sun (once in the evening left overnight and then again prior to the actual exposure) .
  • Example D The effect of the composition of Example i.e. on hyperkeratosis, a condition characterised by prickle cell hyperplasia and usually preceding the development of squamous cell carcinoma of the face and limbs, was examined. Twice daily application for four weeks induced shedding of the lesions coupled with the appearance of normal looking skin in all cases, thus demonstrating a reversal of the state of hyperplasia with stimulation of normal skin growth and renewal
  • Allopurinol or oxypurinol powder was dissolved in a few drops of 0.1M aqueous NaOH and then added to a solution of methyl sulphonylmethane (MSM) in double distilled water to prepare the following formulations:

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Birds (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte à des compositions synergiques comprenant du méthylsulfonylméthane et de l'oxypurinol et/ou de l'allopurinol, ainsi qu'à leur utilisation dans des formulations et des méthodes thérapeutiques et prophylactiques destinées au cancer de la peau et de la muqueuse.
PCT/GB1993/001868 1992-09-04 1993-09-03 Compositions therapeutiques destinees au cancer de la peau, contenant du dimethylsulfone et de l'oxypurinol ou de l'allopurinol Ceased WO1994005291A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU49739/93A AU4973993A (en) 1992-09-04 1993-09-03 Skin cancer treatment compositions containing dimethyl sulphone and oxypurinol or allopurinol

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB929218711A GB9218711D0 (en) 1992-09-04 1992-09-04 Skin cancer treatment
GB9218711.1 1992-09-04
CN94104812.8A CN1108532A (zh) 1992-09-04 1994-03-16 皮肤癌治疗

Publications (1)

Publication Number Publication Date
WO1994005291A1 true WO1994005291A1 (fr) 1994-03-17

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1993/001868 Ceased WO1994005291A1 (fr) 1992-09-04 1993-09-03 Compositions therapeutiques destinees au cancer de la peau, contenant du dimethylsulfone et de l'oxypurinol ou de l'allopurinol

Country Status (4)

Country Link
CN (1) CN1108532A (fr)
AU (1) AU4973993A (fr)
GB (1) GB9218711D0 (fr)
WO (1) WO1994005291A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005002582A3 (fr) * 2003-07-02 2005-05-26 Genentech Inc Composes actifs de trp-p8 et methodes de traitement therapeutique
EP2246057A1 (fr) 2009-04-29 2010-11-03 Nobera Pharma, S.L. Utilisation d'allopurinol pour le traitement d'une cutiréaction sur les mains et sur les pieds
US7973046B2 (en) 2006-06-01 2011-07-05 Nobera Pharma, S.L. Use of allopurinol for the treatment of palmar plantar erythrodysesthesia
WO2023133199A1 (fr) 2022-01-05 2023-07-13 Asymmetric Therapeutics, Llc Méthodes et compositions pour le traitement de troubles cutanés prolifératifs et d'autres affections cutanées

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5245374B2 (ja) 2007-11-28 2013-07-24 ソニー株式会社 投射型画像表示装置及び偏光変換素子
US20210267984A1 (en) * 2018-09-03 2021-09-02 Wei Zhu Application of allopurinol in preparation of drug for treating cancer with high expression of paics gene

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
EP0103836A2 (fr) * 1982-09-14 1984-03-28 Robert J. Herschler Compositions diététiques et pharmaceutiques à base de méthylsulfonylméthane

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
EP0103836A2 (fr) * 1982-09-14 1984-03-28 Robert J. Herschler Compositions diététiques et pharmaceutiques à base de méthylsulfonylméthane

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SALIM A.S.: "Role of Oxygen derived free radicals in the mechanism of chronic gastric ulceration in the rat: Implications for Cytoprotection", DIGESTION, vol. 43, no. 1-2, 1989, pages 113 - 119 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005002582A3 (fr) * 2003-07-02 2005-05-26 Genentech Inc Composes actifs de trp-p8 et methodes de traitement therapeutique
AU2004253582B2 (en) * 2003-07-02 2011-02-10 Genentech, Inc. TRP-P8 active compounds and therapeutic treatment methods
US7893072B2 (en) 2003-07-02 2011-02-22 Genentech, Inc. Trp-p8 active compounds and therapeutic treatment methods
CN102389409B (zh) * 2003-07-02 2014-01-22 健泰科生物技术公司 Trp-p8活性化合物和治病性治疗方法
US7973046B2 (en) 2006-06-01 2011-07-05 Nobera Pharma, S.L. Use of allopurinol for the treatment of palmar plantar erythrodysesthesia
RU2438673C2 (ru) * 2006-06-01 2012-01-10 Нобера Фарма, С.Л. Применение аллопуринола для лечения ладонно-подошвенной эритродизестезии
US8557829B2 (en) 2006-06-01 2013-10-15 Nobera Pharma, S.L. Use of allopurinol for the treatment of palmar plantar erythrodysesthesia
EP2246057A1 (fr) 2009-04-29 2010-11-03 Nobera Pharma, S.L. Utilisation d'allopurinol pour le traitement d'une cutiréaction sur les mains et sur les pieds
US8623878B2 (en) 2009-04-29 2014-01-07 Nobera Pharma, S.L. Use of allopurinol for the treatment of hand foot skin reaction
WO2023133199A1 (fr) 2022-01-05 2023-07-13 Asymmetric Therapeutics, Llc Méthodes et compositions pour le traitement de troubles cutanés prolifératifs et d'autres affections cutanées

Also Published As

Publication number Publication date
GB9218711D0 (en) 1992-10-21
AU4973993A (en) 1994-03-29
CN1108532A (zh) 1995-09-20

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