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WO2010004367A1 - Utilisation d'un mélange de superoxyde dismutase et de catalase pour traiter le prurit et soulager ses symptômes - Google Patents

Utilisation d'un mélange de superoxyde dismutase et de catalase pour traiter le prurit et soulager ses symptômes Download PDF

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Publication number
WO2010004367A1
WO2010004367A1 PCT/IB2008/052791 IB2008052791W WO2010004367A1 WO 2010004367 A1 WO2010004367 A1 WO 2010004367A1 IB 2008052791 W IB2008052791 W IB 2008052791W WO 2010004367 A1 WO2010004367 A1 WO 2010004367A1
Authority
WO
WIPO (PCT)
Prior art keywords
catalase
use according
mixture
superoxide dismutase
extracts
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/IB2008/052791
Other languages
English (en)
Inventor
Silvia Cristina Chami De Diehl
Christian Diehl
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.)
Life Science Investments Ltd
Original Assignee
Life Science Investments Ltd
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 Life Science Investments Ltd filed Critical Life Science Investments Ltd
Priority to EP08789269A priority Critical patent/EP2318521A1/fr
Priority to PCT/IB2008/052791 priority patent/WO2010004367A1/fr
Publication of WO2010004367A1 publication Critical patent/WO2010004367A1/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
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A61K38/446—Superoxide dismutase (1.15)
    • 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
    • A61P17/04—Antipruritics
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0065—Oxidoreductases (1.) acting on hydrogen peroxide as acceptor (1.11)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0089—Oxidoreductases (1.) acting on superoxide as acceptor (1.15)

Definitions

  • Pruritus is one of the most common symptoms of skin diseases, but can also be a major symptom of systemic diseases (e.g. malignancy, infection or metabolic disorders). However, despite a century of research and investigations on pruritus, there is no generally accepted therapy for the treatment of itch.
  • pruritus is not easy to define.
  • a simple description is that pruritus is an unpleasant cutaneous sensation that provokes a desire to scratch, but this simple attempt to define pruritus is certainly not perfect.
  • Pruritus can be a physiological sensation if the consecutive scratching removes a potentially agent, or pathological, if associated with skin and/or intestinal diseases, and psychic disorders, or caused by some food and drugs.
  • Pruritus can be experienced only in the skin, because of the unique neural mechanisms it involves. Its intensity can be mild, moderate, severe and even distressing with sleep disturbances, loss of weight, discomfort, increased irritability, problems in daily activities and even stress. It can be acute or chronic, sometimes long lasting, and may affect any part of the body. It is always a diagnostic challenge to the clinician.
  • Pruritus may be provoked both by exogenous agents or by endogenous causes or stimuli.
  • the major pruritogens are the following: acetylcholin (nicotinergic and muscarinergic [mAChR] receptors), CGRP (CGRP receptors), CRM and POMC (CRH-Rl and CRH-R2), cytokines (Cytokine receptors), endocannabinoids (CBs - CBl and CB2), ETs (ET receptors), Endovanilloids (activation of TRPVl and sensatization of TRPVl via activation of specific receptors), histamine (histamine receptors HlR and H4R), kallikreins and proteases (PARs), kinins (bradykinin receptors BlR or B2R), leukotriene B4 (leukotriene receptors), NKA and Substance P (tachykinin receptors), NKA, BDNF, NT (specific receptors TrkA [mAChR] receptors), CGRP (CGRP receptors), CRM and
  • the neuroanatomical basis of pruritus is relatively well known. Itch originates in free nerve endings, near the dermo-epidermal junction and is conducted centripetally by afferent nerves entering the spinal cord via the dorsal roots.
  • the sensitive nerves for pruritus are small, non-myelinated C fibers with a slow conduction rate.
  • the cell bodies of these nociceptive primary neurons are located in the dorsal root ganglion. After entering into the spinal cord the primary neurons synapse secondary neurons whose axons cross to the opposite side, and then by the tractus spinothalamicus reach the laminar nuclei of the thalamus. Finally, these nuclei relay to the cerebral cortex, i.e. the sensory area in post central gyrus.
  • the cerebral cortex i.e. the sensory area in post central gyrus.
  • the epidermis itself especially the ker- atinocytes which form the bulk of the epidermis, constitute the itch receptor.
  • Keratinocytes express a range of neuropeptide mediators and receptors which appear to be involved in pruritus, including opioids, nerve growth factor (NGF), substance P and receptors including vanilloid receptors, and protease activated receptors type-2 (PAR-2).
  • NNF nerve growth factor
  • substance P and receptors including vanilloid receptors
  • PAR-2 protease activated receptors type-2
  • Pruritus is caused by the release of mediators acting peripherally on receptors, cells or nerves. Some of these substances can act directly on the free nerve endings, others act indirectly through mastocytes or other cells, in particular keratinocytes.
  • Histamine an imidazolethylamine, was the first and most important recognized pru- ritogenic substance, but does not account for all the types of pruritus.
  • Serotonin (5-hydroxytryptamine, 5-HT) can also cause pruritus in some circumstances.
  • Substance P is a pro-inflammatory neuropeptide, produced in the dorsal ganglia and the transported to the periphery by nociceptive nerves A and C.
  • SP-reactive fibers are localized close to mast cells, and hence release of SP from sensory afferents can stimulate mast cell secretion in vivo. SP degranulates mast cells, and therefore can release histamine from them, provoking itch.
  • CGRP Calcitonin gene-related peptide
  • NGF Nerve Growth Factor
  • Cytokines are also key molecular players in the occurrence and maintenance of pruritus.
  • Interleukins constitute another interesting family, some members of which seem to be deeply involved in the mechanism of pruritus, namely Interleukin-1 (IL-I), In- terleukin-2 (IL-2) and Interleukin-6 (IL-6).
  • IL-1 Interleukin-1
  • IL-2 In- terleukin-2
  • IL-6 Interleukin-6
  • Vessels and adhesion molecules like E-selectin appear to play a role in the occurrence and development of pruritus, at least in certain dermatological diseases.
  • Pruritus may be elucidated by the opioid system as well: it is believed that activation of m ⁇ -opioid receptor induces while activation of ⁇ -opioid receptors alleviates pruritus.
  • compositions for treating and alleviating pruritus do exist. They are essentially antihistaminic Hl and H2, which are histamine antagonists, inhibiting the release of histamine or blocking Hl or H2 receptors.
  • Pruritus is one of the most common symptoms of skin diseases, but laso of major systemic diseases.
  • Pruritus is always a diagnostic and a therapeutic challenge to the clinician, and despite a great amountr of research and investigation, there is still no generally accepted therapy for the treatment of itch and pruritus.
  • the present invention accordingly relates to the use of a mixture of superoxide dismutase and catalase for preparing a topical composition intended for the treatment of pruritus and to alleviate it.
  • Superoxide dismutase is a stable enzyme of natural origin: it gives out superoxide radicals without being consumed, and it is generally soluble in water. Superoxide dismutase is either of animal or plant origin or obtained by biotechnology.
  • Catalase is a ferriporphyrin enzyme that catalyzes the liberation of molecular oxygen from hydrogen peroxide.
  • Cu/zn SOD protects the cytoplasm, where the free radicals are produced by metabolic reactions
  • Mn SOD protects the mitochondria of the cell, that contains the genetic information and acts as the site for the production of cell energy.
  • the SOD may be of any origin.
  • SOD is naturally present in the majority of plants: it is found in extracts, apples, certain varieties of cabbage, broccolis, Brussels sprouts, tomatoes, or even cabbage or melon, which are optionnally transgenic, and also horseradish, or it may be extracted from seeds or shoots of enzyme-rich cereals, such as wheat, corn, soybean or barley.
  • the invention accordingly relates in one embodiment to a composition characterized in that the superoxide dismutase is obtained by biotechnology, originating for example from a natural strain of Saccharomyces cerevisiae.
  • the SOD may be complexed or bonded to polymers without prejudice to its enzymatic activity, for example polysaccharides.
  • the catalase (CAT) which converts hydrogen peroxide to water and oxygen may be of any origin.
  • the catalase may, for example, be obtained from mammalian liver extract or from microorganisms such as Aspergillus niger. [44] It may also be obtained from plant extracts or obtained by recombinant synthesis.
  • the two enzymes may be encapsulated or incorporated in polymeric microparticles, composed for example of crosslinked ionic polysaccharides and/or hydrophilic polymers.
  • These formulations of these two enzymes, alone or as a mixture, allow the enzymatic activity to be protected, for example, from the interactions with the outside environment, while promoting targeting, spreading and also pharmaceutical formulation.
  • These two enzymes may be present in a lyophilized form, powder for example, in crystalline suspension form, in ammonium sulfate suspension form or in a solution in any solvent.
  • SOD/CAT mixture whether original, meaning that the extract contains the mixture of the two enzymes on extraction, or whether prepared, must allow an enzymatic activity ratio of between 14/2 and 15/5, with an enzymatic
  • the activity of the catalase will be between approximately 30 and 80 IU per gram.
  • the invention accordingly relates to the use of a mixture of superoxide dismutase and catalase for preparing a topical composition intended for the treatment of pruritus and to alleviate it.
  • the pruritus can be caused by external agents, or consecutive to dermatological diseases such as atopic dermatitis, psoriasis, eczema, scarring, internal diseases or psychic disorders.
  • the superoxide dismutase is extracted from apples, broccolis, Brussels sprouts, cabbage, melon, horseradish or tomato, which are optionnally transgenic.
  • catalase is obtained from mammalian liver extracts or extracts of microorganisms such as Aspergillus niger.
  • catalase is obtained from plant extracts, for instance apples, broccolis, Brussels sprouts, cabbage, melon, horseradish or tomato, which are optionally transgenic.
  • polymers are preferably selected from polysaccharides.
  • polymeric microparticles are composed of crosslinked ionic polysaccharides and/or of hydrophilic polymers.
  • catalase and the superoxide dismutase are in a lyophilized powder form, in crystalline suspension form, in ammonium sulfate suspension form or in solution in any solvent.
  • the catalase and the superoxide dismutase are present as a mixture in a natural extract.
  • the natural extract is selected from melon extracts, tomato extracts, cabbage extracts or mammalian liver extracts.
  • the SOD/CAT mixture exhibits an enzymatic activity ratio of between 14/2 and 15/5 with a SOD enzymatic activity of between 150 and 300 IU per gram.
  • the catalase activity is between approximately 30 and 80 IU per gram.
  • the SOD/CAT mixture used is a mixture extracted from a variety of Brassica napus.
  • the enzymatic activity of the SOD is evaluated by the method described above as being approximately 280 IU per gram.
  • the enzymatic activity of the catalase by the method described above is evaluated as being 60 IU per gram.
  • the SOD/CAT mixture is provided by a melon extract: the stabilized extract sold under the brand name Extramel by the company Bionov.
  • the enzymatic activity of the SOD is evaluated by the method described above as being approximately 270 IU per gram.
  • the enzymatic activity of the catalase by the method described above is evaluated as being 40 iu per gram.
  • the SOD/CAT mixture is provided by a mixture comprising SOD and catalase which are obtained fromn tomato extracts sold by the company Dirsey Corporation.
  • the enzymatic activity of the SOD is evaluated by the method described above as being approximately 320 IU per gram.
  • the enzymatic activity of the catalase by the method described above is being approximately 85 IU per gram.
  • the SOD/CAT mixture is provided by a mixture prepared in accordance with the final enzymatic activity required, namely 280 IU per gram for SOD and 60 iu per gram for catalase, of SOD extracted from Escherichia coli in the form of lyophilized powder (2,500 IU/mg) and from catalase extracted from Aspergillus niger in lyophilized form (170 IU/mg).
  • compositions according to the invention are formulated to give all of the pharmaceutical forma that are conventionnally used for the topical apllication of a composition to the skin.
  • compositions according to the invention may optionally contain various additives, such as suspension agents, emulsifiers, anionic, cationic, nonionic or amphoteric polmers, proteins, vitamins, surfactants, mineral oils, vegetal oils, waxes, silicone resins and/or rubbers, thickeners, acidifying or alkalifying agents, solvents, pH stablizers, UV protectors, preservatives, antibacterial agents, antifungal agents, fragrances or other adjuvants which are commonly used in cosmetology or dermatology.
  • additives such as suspension agents, emulsifiers, anionic, cationic, nonionic or amphoteric polmers, proteins, vitamins, surfactants, mineral oils, vegetal oils, waxes, silicone resins and/or rubbers, thickeners, acidifying or alkalifying agents, solvents, pH stablizers, UV protectors, preservatives, antibacterial agents, antifungal agents, fragrances or other adjuvants which are commonly used in cosmetology or dermatolog

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dermatology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne l'utilisation d'un mélange de superoxyde dismutase et de catalase pour préparer une composition topique pour traiter et soulager le prurit provoqué par des agents externes, ou consécutif à des maladies dermatologiques telles que la dermatite atopique, le psoriasis, l'eczéma, le processus de cicatrisation, les maladies internes ou les troubles psychiques. Les compositions de l'invention sont formulées pour obtenir toutes les formes galéniques utilisées de façon classique pour appliquer une composition topique sur la peau, telles que, par exemple, gel, lait, crème, lotion, plâtre ou timbre, de même que poudre à solubiliser dans l'eau ou le sérum physiologique avant utilisation.
PCT/IB2008/052791 2008-07-10 2008-07-10 Utilisation d'un mélange de superoxyde dismutase et de catalase pour traiter le prurit et soulager ses symptômes Ceased WO2010004367A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP08789269A EP2318521A1 (fr) 2008-07-10 2008-07-10 Utilisation d'un mélange de superoxyde dismutase et de catalase pour traiter le prurit et soulager ses symptômes
PCT/IB2008/052791 WO2010004367A1 (fr) 2008-07-10 2008-07-10 Utilisation d'un mélange de superoxyde dismutase et de catalase pour traiter le prurit et soulager ses symptômes

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2008/052791 WO2010004367A1 (fr) 2008-07-10 2008-07-10 Utilisation d'un mélange de superoxyde dismutase et de catalase pour traiter le prurit et soulager ses symptômes

Publications (1)

Publication Number Publication Date
WO2010004367A1 true WO2010004367A1 (fr) 2010-01-14

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9592280B2 (en) 2014-10-10 2017-03-14 Rochal Industries Llc Compositions and kits for enzymatic debridement and methods of using the same
US10238719B2 (en) 2014-10-10 2019-03-26 Rochal Industries, Llc Compositions and kits for enzymatic debridement and methods of using the same
US10688159B2 (en) 2014-10-10 2020-06-23 Rochal Industries, Llc Compositions and kits for treating pruritus and methods of using the same
CN113318222A (zh) * 2021-07-15 2021-08-31 济宁医学院 超氧化物歧化酶在制备治疗银屑病药物中的应用及方法
CN116600651A (zh) * 2020-10-07 2023-08-15 诺维信公司 动物饲料中益生菌的酶保存
CN117982405A (zh) * 2023-12-06 2024-05-07 中国医学科学院北京协和医院 抑制瘢痕的过氧化氢酶脂质体乳膏及其制备方法
US12421504B2 (en) 2020-10-07 2025-09-23 Novozymes A/S Bacterial superoxide dismutases

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007000619A1 (fr) * 2005-06-28 2007-01-04 Life Science Investments Ltd Utilisation d’un melange de superoxyde dismutase et de catalase pour le traitement des lesions d’origine inflammatoire de la peau

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007000619A1 (fr) * 2005-06-28 2007-01-04 Life Science Investments Ltd Utilisation d’un melange de superoxyde dismutase et de catalase pour le traitement des lesions d’origine inflammatoire de la peau

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9592280B2 (en) 2014-10-10 2017-03-14 Rochal Industries Llc Compositions and kits for enzymatic debridement and methods of using the same
US10238719B2 (en) 2014-10-10 2019-03-26 Rochal Industries, Llc Compositions and kits for enzymatic debridement and methods of using the same
US10688159B2 (en) 2014-10-10 2020-06-23 Rochal Industries, Llc Compositions and kits for treating pruritus and methods of using the same
CN116600651A (zh) * 2020-10-07 2023-08-15 诺维信公司 动物饲料中益生菌的酶保存
US12421504B2 (en) 2020-10-07 2025-09-23 Novozymes A/S Bacterial superoxide dismutases
CN113318222A (zh) * 2021-07-15 2021-08-31 济宁医学院 超氧化物歧化酶在制备治疗银屑病药物中的应用及方法
CN113318222B (zh) * 2021-07-15 2022-05-06 济宁医学院 超氧化物歧化酶在制备治疗银屑病药物中的应用及方法
CN117982405A (zh) * 2023-12-06 2024-05-07 中国医学科学院北京协和医院 抑制瘢痕的过氧化氢酶脂质体乳膏及其制备方法

Also Published As

Publication number Publication date
EP2318521A1 (fr) 2011-05-11

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