FR2959131A1 - Composition, useful for limiting a replication of heat-sensitive virus such as rhinovirus, treating common cold and to inhibit inflammatory response, comprises at least one rubefacient and a carrier - Google Patents
Composition, useful for limiting a replication of heat-sensitive virus such as rhinovirus, treating common cold and to inhibit inflammatory response, comprises at least one rubefacient and a carrier Download PDFInfo
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- FR2959131A1 FR2959131A1 FR1053146A FR1053146A FR2959131A1 FR 2959131 A1 FR2959131 A1 FR 2959131A1 FR 1053146 A FR1053146 A FR 1053146A FR 1053146 A FR1053146 A FR 1053146A FR 2959131 A1 FR2959131 A1 FR 2959131A1
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- nicotinate
- replication
- heat
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- 239000000203 mixture Substances 0.000 title claims abstract description 63
- 241000700605 Viruses Species 0.000 title claims description 20
- 241000709661 Enterovirus Species 0.000 title claims description 9
- 230000010076 replication Effects 0.000 title claims description 7
- 239000003542 rubefacient Substances 0.000 title abstract 2
- 230000028709 inflammatory response Effects 0.000 title description 2
- 201000009240 nasopharyngitis Diseases 0.000 title description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 0.000 claims description 14
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 230000001476 alcoholic effect Effects 0.000 claims description 8
- 229950004580 benzyl nicotinate Drugs 0.000 claims description 7
- 229960001238 methylnicotinate Drugs 0.000 claims description 7
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 5
- XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 241000709664 Picornaviridae Species 0.000 claims description 4
- 235000002566 Capsicum Nutrition 0.000 claims description 2
- 240000008574 Capsicum frutescens Species 0.000 claims description 2
- 229960003116 amyl nitrite Drugs 0.000 claims description 2
- 239000001390 capsicum minimum Substances 0.000 claims description 2
- 229940064982 ethylnicotinate Drugs 0.000 claims description 2
- 239000000284 extract Substances 0.000 claims description 2
- CSDTZUBPSYWZDX-UHFFFAOYSA-N n-pentyl nitrite Chemical compound CCCCCON=O CSDTZUBPSYWZDX-UHFFFAOYSA-N 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 229940123627 Viral replication inhibitor Drugs 0.000 abstract 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract 1
- 230000010534 mechanism of action Effects 0.000 abstract 1
- 239000012873 virucide Substances 0.000 abstract 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000006071 cream Substances 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000009472 formulation Methods 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000430519 Human rhinovirus sp. Species 0.000 description 2
- 206010020843 Hyperthermia Diseases 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 239000003240 coconut oil Substances 0.000 description 2
- 235000019864 coconut oil Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 230000036031 hyperthermia Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000003020 moisturizing effect Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- FGAPNSHKBZMPFL-UHFFFAOYSA-N 2-[bis(2-hydroxyethyl)amino]ethanol;pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1.OCCN(CCO)CCO FGAPNSHKBZMPFL-UHFFFAOYSA-N 0.000 description 1
- BSTITMHKRRGVPH-UHFFFAOYSA-N 2-phenylethyl pyridine-3-carboxylate Chemical compound C=1C=CN=CC=1C(=O)OCCC1=CC=CC=C1 BSTITMHKRRGVPH-UHFFFAOYSA-N 0.000 description 1
- 244000144927 Aloe barbadensis Species 0.000 description 1
- 235000002961 Aloe barbadensis Nutrition 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010061494 Rhinovirus infection Diseases 0.000 description 1
- MSCCTZZBYHQMQJ-AZAGJHQNSA-N Tocopheryl nicotinate Chemical compound C([C@@](OC1=C(C)C=2C)(C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)CC1=C(C)C=2OC(=O)C1=CC=CN=C1 MSCCTZZBYHQMQJ-AZAGJHQNSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000219094 Vitaceae Species 0.000 description 1
- 235000018936 Vitellaria paradoxa Nutrition 0.000 description 1
- 241001135917 Vitellaria paradoxa Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 235000021302 avocado oil Nutrition 0.000 description 1
- 239000008163 avocado oil Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- IZJRISIINLJVBU-UHFFFAOYSA-N beta-Butoxyethyl nicotinate Chemical compound CCCCOCCOC(=O)C1=CC=CN=C1 IZJRISIINLJVBU-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 235000021324 borage oil Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000215 ciliated epithelial cell Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 235000021021 grapes Nutrition 0.000 description 1
- RVYGVBZGSFLJKH-UHFFFAOYSA-N hexyl pyridine-3-carboxylate Chemical compound CCCCCCOC(=O)C1=CC=CN=C1 RVYGVBZGSFLJKH-UHFFFAOYSA-N 0.000 description 1
- 229940051295 hexylnicotinate Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 229940119170 jojoba wax Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000001989 nasopharynx Anatomy 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- QEJPOSAIULNDLU-UHFFFAOYSA-N phenyl pyridine-3-carboxylate Chemical compound C=1C=CN=CC=1C(=O)OC1=CC=CC=C1 QEJPOSAIULNDLU-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 229940057910 shea butter Drugs 0.000 description 1
- 206010041232 sneezing Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- RQAITHJHUFFEIV-UHFFFAOYSA-N thurfyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1CCCO1 RQAITHJHUFFEIV-UHFFFAOYSA-N 0.000 description 1
- 229950006036 thurfyl nicotinate Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229950009883 tocopheryl nicotinate Drugs 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000006200 vaporizer Substances 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229940045860 white wax Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- 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
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/14—Ectoparasiticides, e.g. scabicides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Emergency Medicine (AREA)
- Tropical Medicine & Parasitology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
L'invention concerne une composition à usage externe comprenant un agent rubéfiant pour la limitation de la réplication des virus thermosensibles (i.e. sensibles à la température), ainsi que l'utilisation de cette composition. Les virus sensibles à la température sont des virus dont la réplication dépend de la température à laquelle ils sont soumis. Cette température est très variable selon la nature du virus. Au sens de la présente invention, les virus thermosensibles dont des virus qui ne se répliquent dans les tissus qu'à une température corporelle inférieure à environ 33°C. Les rhinovirus sont des virus thermosensibles au sens de la présente invention. The invention relates to a composition for external use comprising a rubefiant agent for limiting the replication of heat-sensitive (i.e. temperature-sensitive) viruses, as well as the use of this composition. Temperature-sensitive viruses are viruses whose replication depends on the temperature to which they are subjected. This temperature is very variable depending on the nature of the virus. For the purposes of the present invention, temperature-sensitive viruses include viruses that replicate in tissues only at a body temperature below about 33 ° C. Rhinoviruses are heat-sensitive viruses within the meaning of the present invention.
Les agents rubéfiants sont utilisés essentiellement dans des formulations pour application externe (i.e. sur la peau) afin de dilater les vaisseaux sanguins et augmenter la circulation sanguine. Ainsi, on utilise des gels capillaires comprenant des rubéfiants pour faciliter l'irrigation du cuir chevelu. Root agents are used primarily in externally applied formulations (i.e., on the skin) to dilate blood vessels and increase blood circulation. Thus, hair gels comprising rubefiants are used to facilitate irrigation of the scalp.
La demande internationale WO 91/16103 décrit notamment une formulation et un système pour améliorer l'administration iontophorétique de principes actifs. Par iontophorétique, on entend généralement relatif à l'introduction dans un organisme d'ions médicamenteux à l'aide d'un courant électrique continu. Les formulations décrites sont destinées à une application locale externe. Elles peuvent contenir un agent rubéfiant qui agit comme vasodilatateur afin de favoriser l'administration d'une substance active. Les formulations décrites dans WO 91/16103 peuvent se présenter sous forme de compositions pulvérisables. Le rhume banal est le plus souvent la conséquence d'une infection virale à HRV (Human Rhinovirus). Ce dernier, qui appartient à la famille des Picornaviridae, présente une grande diversité antigénique avec environ 100 sérotypes connus aujourd'hui. Ce haut niveau de diversité antigénique rend très difficiles les projets de vaccin anti-rhinovirus. Les rhinovirus se déposent sur la muqueuse nasale ou conjonctive, et sont transportés au niveau du nasopharynx par les cellules épithéliales ciliées. Le mode de transmission des infections par rhinovirus peut ainsi se faire aussi bien par des aérosols (éternuements) que par inoculation directe. The international application WO 91/16103 describes in particular a formulation and a system for improving the iontophoretic administration of active principles. Iontophoretic is generally understood to mean the introduction into an organism of medicinal ions with the aid of a continuous electric current. The formulations described are intended for external local application. They may contain a rubefactor which acts as a vasodilator to promote the administration of an active substance. The formulations described in WO 91/16103 may be in the form of sprayable compositions. The common cold is most often the consequence of a viral infection with HRV (Human Rhinovirus). The latter, which belongs to the family Picornaviridae, has a large antigenic diversity with about 100 serotypes known today. This high level of antigenic diversity makes it very difficult for rhinovirus vaccine projects. Rhinoviruses are deposited on the nasal or conjunctive mucosa and are transported to the nasopharynx by ciliated epithelial cells. The mode of transmission of rhinovirus infections can be done by aerosols (sneezing) as well as direct inoculation.
Les infections par les rhinovirus sont extrêmement fréquentes comme l'illustrent les chiffres suivants fournis pour les USA et par an : - un milliard de cas, - 25 millions d'absences au travail, - 23 millions d'absences à l'école, et - 40 milliards de dollars en dépenses de santé et en perte de productivité. Les traitements connus des rhinovirus se réduisent généralement à alléger les symptômes viraux. Aucun traitement réellement efficace n'existe à 10 ce jour (Antiviral Research, Vol 71, 2006, 391 û 396, Patick). L'hyperthermie a été envisagée en tant que moyen d'atténuer les symptômes des rhinovirus. Ainsi, l'article BMJ Vol 298 13 Mai 1989, 1280 - 1283 Tyrrell et al. décrit un traitement par inhalation d'air totalement humidifié à 43°C. Ce traitement est jugé bénéfique, comparé à un traitement par inhalation 15 d'air totalement humidifié à 30°C. Il a été trouvé qu'une composition à usage externe comprenant au moins un agent rubéfiant et un support permet, de manière tout à fait surprenante, de limiter voire d'inhiber la réplication de virus thermosensibles. Par « usage externe » on entend selon l'invention un usage 20 d'application topique. Avantageusement, la composition selon l'invention permet ainsi d'éviter un développement desdits virus. Sans vouloir être limité par une quelconque théorie, il est probable que la composition selon l'invention ait aussi un effet inhibiteur sur la réponse inflammatoire, ce qui renforce l'efficacité de 25 cette composition. La composition selon l'invention peut être une composition de type pommade (comportant généralement une seule phase) ou crème (comportant généralement au moins deux phases), d'application topique. Cette composition peut aussi, et de préférence, être pulvérisable, 30 c'est-à-dire qu'elle est généralement conditionnée en pulvérisateur (ou spray). Le support est alors, de préférence, alcoolique. Cette composition pulvérisable est appliquée sur la peau, et n'est pas inhalée dans l'organisme. Infections with rhinoviruses are extremely frequent as illustrated by the following figures provided for the USA and per year: - one billion cases, - 25 million absences from work, - 23 million school absences, and - $ 40 billion in health spending and lost productivity. The known treatments of rhinoviruses are generally reduced to lighten the viral symptoms. No truly effective treatment exists to date (Antiviral Research, Vol 71, 2006, 391-396, Patick). Hyperthermia has been considered as a means of alleviating the symptoms of rhinoviruses. Thus, the article BMJ Vol 298 13 May 1989, 1280 - 1283 Tyrrell et al. describes an inhalation treatment of fully humidified air at 43 ° C. This treatment is considered beneficial, compared to inhalation treatment of fully humidified air at 30 ° C. It has been found that a composition for external use comprising at least one rubéfiant agent and a support makes it possible, quite surprisingly, to limit or even to inhibit the replication of heat-sensitive viruses. By "external use" is meant according to the invention a topical application. Advantageously, the composition according to the invention thus makes it possible to avoid a development of said viruses. Without wishing to be bound by any theory, it is likely that the composition according to the invention also has an inhibitory effect on the inflammatory response, which enhances the effectiveness of this composition. The composition according to the invention may be a composition of ointment type (generally comprising a single phase) or cream (generally comprising at least two phases), topical application. This composition may also, and preferably, be sprayable, i.e., it is generally packaged as a spray (or spray). The support is then, preferably, alcoholic. This sprayable composition is applied to the skin, and is not inhaled into the body.
La composition selon l'invention est le plus souvent une composition de type cosmétique ou pharmaceutique, d'usage externe, principalement pour application topique sur l'être humain. Par suite, tous les composants de la composition sont généralement acceptables d'un point de vue cosmétique ou pharmaceutique. La composition selon l'invention permet d'agir directement sur la réplication virale voire d'inhiber le processus inflammatoire, sans pour autant altérer la réponse immunitaire. La composition selon l'invention permet d'augmenter localement la température cutanée, le plus souvent de quelques dixièmes de degrés Celsius, généralement d'un dixième de degré Celsius à un degré Celsius, par exemple de trois ou quatre dixièmes de degrés Celsius. Ce résultat est d'autant plus surprenant que la littérature mentionne un traitement d'hyperthermie par inhalation d'air totalement humidifié à une température de 43°C, relativement élevée par rapport à la température corporelle. L'ampleur de cet effet dépend généralement de la personne sur laquelle est appliquée la composition. On a constaté en particulier que cette ampleur semble dépendre de nombreux paramètres liés à la peau (aspect, état, etc.) de la personne concernée. Cela conditionne la fréquence d'application de ladite composition sur la peau de ladite personne. La mesure de la température cutanée s'effectue de façon connue de l'homme du métier, le plus souvent par une sonde thermique d'application topique. L'augmentation locale de la température cutanée est effective 25 généralement sur une durée de quelques dizaines de minutes, par exemple 45 minutes. La composition selon l'invention est de préférence utilisée directement sur la peau, généralement au niveau de la gorge. Ainsi, si cette température augmente de quelques dixièmes de 30 degrés, le virus ne se réplique pas. The composition according to the invention is most often a composition of the cosmetic or pharmaceutical type, for external use, mainly for topical application to humans. As a result, all the components of the composition are generally acceptable from a cosmetic or pharmaceutical point of view. The composition according to the invention makes it possible to act directly on viral replication or even to inhibit the inflammatory process, without impairing the immune response. The composition according to the invention makes it possible to locally increase the cutaneous temperature, most often a few tenths of a degree Celsius, generally from one tenth of a degree Celsius to one degree Celsius, for example three or four tenths of a degree Celsius. This result is all the more surprising since the literature mentions a treatment of hyperthermia by inhalation of air totally humidified at a temperature of 43 ° C, relatively high compared to the body temperature. The magnitude of this effect usually depends on the person on whom the composition is applied. In particular, it has been found that this magnitude seems to depend on many skin-related parameters (appearance, condition, etc.) of the person concerned. This conditions the frequency of application of said composition on the skin of said person. The skin temperature is measured in a manner known to those skilled in the art, most often by a topical thermal probe. The local increase in cutaneous temperature is generally effective over a period of a few tens of minutes, for example 45 minutes. The composition according to the invention is preferably used directly on the skin, generally at the level of the throat. Thus, if this temperature increases by a few tenths of 30 degrees, the virus does not replicate.
Les virus thermosensibles selon l'invention sont plus particulièrement, des virus de la famille des Picornaviridae (picornavirus) tels que les rhinovirus. Les virus thermosensibles sur lesquels agit la composition selon l'invention sont en général présents dans la voie rhinopharyngée de la personne sur laquelle est appliquée ladite composition. De façon préférée, l'agent rubéfiant selon l'invention est choisi parmi les extraits de capsicum, les sels de l'acide nicotinique tel que le nicotinate de triéthanolamine, les esters de l'acide nicotinique tels que le nicotinate de méthyle, le nicotinate d'éthyle, le nicotinate d'hexyle, le nicotinate de phényle, le nicotinate de butoxyéthyle, le nicotinate de phénéthyle, le nicotinate de thurfyle ou le nicotinate de benzyle ainsi que le nicotinate d' a-tocophérol, et le nitrite d'amyle. L'agent rubéfiant est de manière préférée choisi dans le groupe formé par le nicotinate de méthyle, le nicotinate d'éthyle, et le nicotinate de benzyle, et de manière encore plus préférée le nicotinate de méthyle et le nicotinate de benzyle. L'agent rubéfiant est généralement présent à une teneur de 0,1 à 5%, de préférence de 0,1 à 3%, de façon encore plus préférée de 0,1 à 1%, en poids par rapport au poids total de la composition. Les ingrédients des supports sont des composés acceptables pour application sur la peau humaine. Le support d'une composition de type pommade ou crème est généralement principalement composé d'un corps gras, par exemple du beurre 25 de cacao ou un ester. Le support alcoolique, aqueux ou non, est de préférence choisi dans le groupe formé par le butanol, l'éthanol, le méthanol et l'isopropanol, de façon encore plus préférée l'éthanol, le méthanol et l'isopropanol. Un support particulièrement préféré est l'éthanol dans l'eau, par exemple à proportion de 30 40%, 50%, 60% 70% ou 80% en volume. D'autres composés tel que le propylène glycol peuvent aussi être utilisés en tant que support alcoolique, typiquement pour accroître la durée d'action. The heat-sensitive viruses according to the invention are more particularly viruses of the family Picornaviridae (picornavirus) such as rhinoviruses. The heat-sensitive viruses on which the composition according to the invention acts are generally present in the nasopharyngeal route of the person to whom said composition is applied. Preferably, the rubefactor according to the invention is chosen from capsicum extracts, nicotinic acid salts such as triethanolamine nicotinate, nicotinic acid esters such as methyl nicotinate and nicotinate. of ethyl, hexyl nicotinate, phenyl nicotinate, butoxyethyl nicotinate, phenethyl nicotinate, thurfyl nicotinate or benzyl nicotinate as well as α-tocopherol nicotinate, and amyl nitrite . The rubefiant agent is preferably selected from the group consisting of methyl nicotinate, ethyl nicotinate, and benzyl nicotinate, and even more preferably methyl nicotinate and benzyl nicotinate. The rubéfiant agent is generally present at a content of 0.1 to 5%, preferably 0.1 to 3%, even more preferably 0.1 to 1%, by weight relative to the total weight of the composition. The ingredients of the carriers are acceptable compounds for application to human skin. The carrier of an ointment or cream composition is generally mainly composed of a fatty substance, for example cocoa butter or an ester. The alcoholic carrier, aqueous or otherwise, is preferably chosen from the group formed by butanol, ethanol, methanol and isopropanol, even more preferably ethanol, methanol and isopropanol. A particularly preferred carrier is ethanol in water, for example in the proportion of 40%, 50%, 60% 70% or 80% by volume. Other compounds such as propylene glycol can also be used as an alcoholic carrier, typically to increase the duration of action.
Selon un mode de réalisation préféré, le support est hydroalcoolique, et comporte de préférence une proportion de 20 à 50 % en volume d'alcool dans l'eau. Selon un mode de réalisation préféré, le support alcoolique est 5 présent à une teneur de 10% à 99% en poids, de préférence de 20 à 99% en poids, par rapport au poids total de la composition. La composition selon l'invention peut en particulier comprendre : - de 0,1 % à 5 %, de préférence de 0,1 % à 1 %, d'agent rubéfiant, et 10 - de 95% à 99,9 %, de préférence de 99% à 99,9%, de support alcoolique ou hydroalcoolique, en poids par rapport au poids total de la composition. La composition selon l'invention peut aussi comprendre d'autres composants tels que de l'eau, une ou des huiles minérales, et d'autres 15 composés acceptables d'un point de vue pharmaceutique pour application sur la peau, tels que des solvants ou autres ingrédients. Par exemple, l'eau, le propylène glycol, ainsi que l'alcool méthylique ou éthylique, peuvent être utilisés dans la composition selon l'invention. Ainsi la composition peut avantageusement comprendre de 1 à 2 % en poids de 20 propylène glycol, par rapport au poids total de la composition. Une huile minérale peut être présente dans la composition, généralement à teneur de 10 à 50% en poids, par rapport au poids total de la composition, par exemple à teneur d'environ 30% en poids. L'invention concerne enfin l'utilisation d'une composition selon 25 l'invention pour limiter la réplication des virus thermosensibles. Ces utilisations consistent en au moins une application externe, généralement locale. Une telle utilisation est généralement envisagée quand l'utilisateur estime être soumis et/ou avoir été soumis à des circonstances susceptibles d'entraîner le développement d'une infection liée à un virus 30 thermosensible. Une telle circonstance est par exemple un refroidissement. La fréquence de l'utilisation dépend de l'utilisateur et des circonstances. According to a preferred embodiment, the support is hydroalcoholic, and preferably comprises a proportion of 20 to 50% by volume of alcohol in water. According to a preferred embodiment, the alcoholic carrier is present in a content of 10% to 99% by weight, preferably 20 to 99% by weight, relative to the total weight of the composition. The composition according to the invention may in particular comprise: from 0.1% to 5%, preferably from 0.1% to 1%, of rubéfiant agent, and from 95% to 99.9%, of preferably from 99% to 99.9%, of alcoholic or hydroalcoholic support, by weight relative to the total weight of the composition. The composition according to the invention may also comprise other components such as water, mineral oil (s), and other pharmaceutically acceptable compounds for application to the skin, such as solvents. or other ingredients. For example, water, propylene glycol, as well as methyl or ethyl alcohol can be used in the composition according to the invention. Thus the composition may advantageously comprise from 1 to 2% by weight of propylene glycol, relative to the total weight of the composition. A mineral oil may be present in the composition, generally at a content of 10 to 50% by weight, relative to the total weight of the composition, for example at a content of approximately 30% by weight. The invention finally relates to the use of a composition according to the invention for limiting the replication of heat-sensitive viruses. These uses consist of at least one external application, usually local. Such use is generally contemplated when the user feels that he is subjected to and / or has been subjected to circumstances which may lead to the development of a heat-sensitive virus-related infection. Such a circumstance is for example a cooling. The frequency of use depends on the user and the circumstances.
Exemples L'invention a été mise en oeuvre selon deux exemples illustratifs, et non limitatifs. Examples The invention was implemented according to two illustrative and nonlimiting examples.
Exemple 1 : crème selon l'invention Example 1 Cream According to the Invention
Une crème a été réalisée comportant 1% de nicotinate de méthyle et 99% d'une composition réalisée de la façon suivante : - on a chauffé en bain-marie 3 cl d'huile hydratante, qui est de l'huile d'amande douce. Selon l'invention, il aurait été aussi possible d'utiliser en tant qu'huile hydratante de l'huile d'avocat, de l'huile de bourrache, de l'huile de noix de coco, de l'huile de pépins de raisins, de l'huile de jojoba, de l'aloe vera, du beurre de karité ou du beurre de cacao. On a ajouté lentement à l'huile chauffée 4cl de glycérine et 2cl de cire blanche. On a retiré le mélange du feu, laissé refroidir puis on a ajouté le nicotinate de méthyle en fin de refroidissement. Enfin, on a remué la composition jusqu'à obtenir une texture de crème. A cream was made comprising 1% methyl nicotinate and 99% of a composition made as follows: - was heated in a bain-marie 3 cl moisturizing oil, which is sweet almond oil . According to the invention, it would have also been possible to use as a moisturizing oil avocado oil, borage oil, coconut oil, coconut oil, grapes, jojoba oil, aloe vera, shea butter or cocoa butter. 4cl of glycerin and 2cl of white wax were slowly added to the heated oil. The mixture was removed from the heat, allowed to cool and the methyl nicotinate was added at the end of cooling. Finally, the composition was stirred until a cream texture.
20 Cette crème était prête à être utilisée. En application externe sur le cou, cette crème a permis une élévation de température de quatre dixièmes de degrés Celsius. This cream was ready to use. In external application on the neck, this cream allowed a rise of temperature of four tenths of degrees Celsius.
Exemple 2 : composition pulvérisable selon l'invention 25 Une composition pulvérisable a été réalisée, qui comportait 1% de nicotinate de benzyle dans une solution d'éthanol à 50% (vol) dans de l'eau, par mélange du nicotinate de benzyle dans le mélange hydroalcoolique puis incorporation du mélange dans un vaporisateur du type à usage 30 pharmaceutique. Le mélange pulvérisable était prêt à être utilisé. En application externe sur le cou, cette composition pulvérisable a permis une élévation de température de trois dixièmes de degrés Celsius. Example 2 Sprayable Composition of the Invention A sprayable composition was made which contained 1% benzyl nicotinate in a 50% ethanol (vol) solution in water by mixing the benzyl nicotinate in the hydroalcoholic mixture and incorporation of the mixture into a vaporizer of the pharmaceutical type. The sprayable mixture was ready for use. In external application on the neck, this sprayable composition allowed a rise in temperature of three tenths of degrees Celsius.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3276960A (en) * | 1961-08-21 | 1966-10-04 | Kendall & Co | Analgesic methods and compositions |
| WO1991016103A1 (en) * | 1990-04-12 | 1991-10-31 | Gensia Pharmaceuticals, Inc. | Improved iontophoretic administration of drugs |
| WO2002064088A2 (en) * | 2001-02-14 | 2002-08-22 | Niazi Sarfaraz K | Pharmaceutical composition for the treatment of alopecia |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3276960A (en) * | 1961-08-21 | 1966-10-04 | Kendall & Co | Analgesic methods and compositions |
| WO1991016103A1 (en) * | 1990-04-12 | 1991-10-31 | Gensia Pharmaceuticals, Inc. | Improved iontophoretic administration of drugs |
| WO2002064088A2 (en) * | 2001-02-14 | 2002-08-22 | Niazi Sarfaraz K | Pharmaceutical composition for the treatment of alopecia |
Non-Patent Citations (3)
| Title |
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| BODE CHEMIE GMBH: "Sterillium classic pure", November 2009 (2009-11-01), pages 1 - 16, XP002593721, Retrieved from the Internet <URL:http://www.bode-chemie.de/produkte/haende/produktblaetter/sterillium_classic_pure.pdf> [retrieved on 20100726] * |
| BODE CHEMIE GMBH: "Sterillium Virugard", March 2010 (2010-03-01), pages 1 - 3, XP002593720, Retrieved from the Internet <URL:http://www.bode-chemie.com/products/hands/product_information/sterillium_virugard_int.pdf> [retrieved on 20100726] * |
| PROCTER & GAMBLE: "Vicks Vaporub ointment", 15 February 1994 (1994-02-15), pages 1 - 2, XP002593722, Retrieved from the Internet <URL:http://home.intekom.com/pharm/procter/vaporub.html> [retrieved on 20100723] * |
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