Association of pyrimidine derivatives and urea and/or allantoin derivatives to induce and stimulate hair growth and to reduce hair loss.
Abstract
L'association comprend : a) un composant (A) contenant un dérivé de pyrimidine de formule : dans lequel R₃ et R₄, désignent hydrogène, alkyle, alcényle, alkylaryle, cycloalkyle, R₃ et R₄ peuvent également former un hétérocycle avec l'atome d'azote auquel ils sont liés, R₂ est hydrogène, alkyle, alcényle, alcoxyalkyl, cycloalkyle, aryle, alkylaryle, arylalkyle, alkylarylalkyle, alcoxyarylalkyle ou haloarylalkyle; etb) un composant (B), contenant un dérivé d'acide salicylique. Les composants (A) et (B) faisant partie d'une même composition ou étant destinés à être utilisés séparément, soit simultanément, soit de façon successive ou décalée dans le temps, sur les cheveux et le cuir chevelu.
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Projected expiry passed 23 March 2009, 17.5 years ago.
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15 claims: 3 independent, 12 dependent
- 1Association destinée à induire et à stimuler la croissance des cheveux et diminuer leur chute, caractérisée par le fait qu'elle comprend :a) un composant (A) contenant dans un milieu physiologiquement acceptable, au moins un dérivé de pyrimidine répondant à la formule : dans lequel R₃ et R₄, indépendamment l'un de l'autre, désignent hydrogène, un groupement alkyle, alcényle, alkylaryle, cycloalkyle, R₃ et R₄ peuvent également former un hétérocycle avec l'atome d'azote auquel ils sont liés, choisi parmi les groupements aziridinyle, azétidinyle, pyrrolidinyle, pipéridinyle, hexahydroazépinyle, heptaméthylèneimine, octaméthylèneimine, morpholine et alkyl(inférieur)-4 pipérazidinyle, les groupements hétérocycliques pouvant être substitués sur les atomes de carbone par un à trois groupements alkyle inférieur, hydroxy ou alcoxy;le groupement R₂ est choisi parmi un atome d'hydrogène, un groupement alkyle, alcényle, alcoxyalkyl, cycloalkyle, aryle, alkylaryle, arylalkyle, alkylarylalkyle, alcoxyarylalkyle ou haloarylalkyle, ainsi que les sels d'addition d'acides physiologiquement acceptables;et b) un composant (B), contenant dans un milieu physiologiquement acceptable, au moins un dérivé d'acide salicylique répondant à la formule (II) : dans laquelle R₆ représente un groupement de formule : - - R₇ dans laquelle R₇ représente une chaîne aliphatique, saturée, ayant de 1 à 11 atomes de carbone, linéaire, ramifiée ou cyclisée, une chaîne insaturée ayant de 3 à 17 atomes de carbone, portant une ou plusieurs doubles liaisons conjuguées ou non, ou bien un noyau aromatique lié au radical carbonyle, directement ou par l'intermédiaire d'une chaîne aliphatique, saturée ou insaturée, ayant de 2 à 7 atomes de carbone, ces différents substituants pouvant être eux-mêmes substitués par un ou plusieurs atomes d'halogène, par un ou plusieurs groupements trifluorométhyle, par un ou plusieurs groupements hydroxyle, sous forme libre ou estérifiée par un acide ayant de 1 à 6 atomes de carbone ou bien par une fonction carboxyle libre ou estérifiée par un alcool inférieur ayant de 1 à 6 atomes de carbone;R₆ désigne également un radical alkyle ayant 1 à 18 atomes de carbone, linéaire ou ramifié, ou bien un radical alcoxy ayant 1 à 18 atomes de carbone, linéaire ou ramifié;R₅ représente une fonction hydroxyle ou bien une fonction ester de formule : - O - - R₈ dans laquelle R₈ désigne un radical aliphatique, saturé ou insaturé, comportant de 1 à 15 atomes de carbone, les composants (A) et (B) faisant partie d'une même composition ou étant destinés à être utilisés séparément, soit simultanément, soit de façon successive ou décalée dans le temps, sur les cheveux et le cuir chevelu.
- 2Association selon la revendication 1, caractérisée par le fait que le composé de formule I est constitué par l'amino-6 dihydro-1,2 hydroxy-1 imino-2 diéthylamino-4 pyrimidine.
- 3Association selon la revendication 1, caractérisée par le fait que le composé de formule (I) est constitué par l'amino-6 dihydro-1,2 hydroxy-1 imino-2 pipéridino-4 pyrimidine ou "minoxidil".
- 4Association selon l'une quelconque des revendications 1 à 3, caractérisée par le fait que le dérivé d'acide salicylique est choisi parmi l'acide n-octanoyl-5 salicylique, l'acide n-décanoyl-5 salicylique, l'acide n-dodécanoyl-5 salicylique, l'acide n-octyl-5 salicylique, l'acide n-heptyloxy-5 salicylique, l'acide n-heptyloxy-4 salicylique ou leurs sels ou esters physiologiquement acceptables.
- 5Association selon l'une quelconque des revendications 1 à 4, caractérisée par le fait que le dérivé de pyrimidine de formule (I) est utilisé dans le composant (A) dans des proportions comprises entre 0,05 et 10% en poids et de préférence compris entre 0,05 et 5% en poids et que le dérivé d'acide salicylique de formule (II) est présent dans le composant (B) dans des proportions comprises entre 0,05 et 10% en poids et de préférence entre 0,05 et 5% en poids.
- 6Association selon l'une quelconque des revendications 1 à 5, caractérisée par le fait que le rapport en poids entre le dérivé de pyrimidine de formule (I) et le dérivé d'acide salicylique de formule (II) est compris entre 1 et 10.
- 7Association selon l'une quelconque des revendications 1 à 6, caractérisée par le fait que le milieu physiologiquement acceptable est constitué par un mélange d'eau et d'un ou plusieurs solvants organiques ou par un mélange de solvants organiques pharmaceutiquement ou cosmétiquement acceptables.
- 8Association selon la revendication 7, caractérisée par le fait que les solvents sont choisis parmi les alcools inférieurs en C₁-C₄, les alkylèneglycols, les alkyléthers de mono et de dialkylèneglycol.
- 9Association selon l'une quelconque des revendications 1 à 8, caractérisée par le fait que l'un au moins des milieux physiologiquement acceptables des composants (A) et (B) est épaissi au moyens d'agents épaississants et/ou gélifiants.
- 10Association selon l'une quelconque des revendications 1 à 9, caractérisée par le fait que l'un au moins des composants (A) et/ou (B) contient également au moins un adjuvant cosmétiquement ou pharmaceutiquement acceptable choisi parmi des agents conservateurs, des agents complexants, des colorants, des agents alcalinisants ou acidifiants, des agents tensio-actifs, anioniques, non ioniques ou amphotères ainsi que leurs mélanges, des polymères anioniques, cationiques, non ioniques ou amphotères ainsi que leurs mélanges.
- 11Association selon l'une quelconque des revendications 1 à 10, caractérisée par le fait qu'elle se présente sous forme d'une composition unique contenant les composants (A) et (B).
- 12Dispositif à plusieurs compartiments ou "kit" ou nécessaire, caractérisé par le fait qu'il comprend dans un premier compartiment le composant (A) contenant dans un milieu physiologiquement acceptable, au moins un dérivé de pyrimidine répondant à la formule (I) et dans un second compartiment, le composant (B) contenant dans un milieu physiologiquement acceptable, au moins un dérivé d'acide salicylique de formule (II).
- 13Association selon l'une quelconque des revendications 1 à 11 pour son application comme médicament dans le traitement de l'alopécie.
- 14Utilisation de l'association selon l'une quelconque des revendications 1 à 11 pour la préparation d'un médicament destiné à traiter l'alopécie.
- 15Procédé de traitement cosmétique des cheveux ou du cuir chevelu comprenant l'application de l'association définie dans l'une quelconque des revendications 1 à 11.
Independent claims15
60 paragraphs in 7 sections, as filed
The invention relates to the combination of pyrimidine derivatives and salicylic acid derivatives in order to induce and stimulate hair growth and reduce hair loss.
The activity of the hair follicles is cyclical. The active anagen phase, which lasts several years and during which the hair lengthens, is followed by a rest phase (telogen) of a few months. At the end of this rest period, the hair falls out and another cycle begins again.
The hair is therefore constantly renewed; out of the 100,000 to 150,000 hairs in hair, at any given moment around 10% are at rest and will therefore be replaced in a few months.
In almost all cases, hair loss occurs in genetically predisposed subjects and it affects men in particular. It is more particularly about androgenetic alopecia.
This alopecia is a disturbance of the capillary renewal which leads, initially, an acceleration of the frequency of the cycles at the expense of the quality of the hair, then of their quantity. There is a gradual depletion of the hair by regression of the so-called "terminal down hair". Areas are affected preferentially: the temporal glands, frontal, among others, in men and there is a diffuse alopecia of the vertex in women.
It has already been proposed to use compounds such as 6-amino-1,2-dihydro-1-hydroxy-2-imino-4 piperidino-pyrimidine or "Minoxidil" in compositions making it possible to reduce or eliminate the effect of alopecia and induce and stimulate hair growth and decrease their fall.
The Applicant has now discovered that by combining salicylic acid derivatives with certain pyrimidine derivatives, there is surprisingly an improved induction and stimulation of hair growth and an action on the braking of their fall, as well as '' a marked increase in skin bioavailability and / or transcutaneous penetration.
The more particularly preferred salicylic acid derivatives according to the invention are known in themselves and are described more particularly in French patent 2,581,542 for their keratolytic properties.
The association has been shown to have a higher activity compared to the pyrimidine derivatives used alone , the salicylic acid derivatives having in themselves no action on hair growth or the slowing down of hair loss.
The association also makes it possible to observe a more rapid action in the treatment of hair loss and allows the use of pyrimidine derivatives at lower concentrations for greater or equivalent effectiveness.
The Applicant has also discovered that, surprisingly, the association of the salicylic acid derivatives with the pyrimidine derivatives significantly modifies the solubility of the pyrimidine derivatives, and has in particular the advantage of allowing faster dissolution of the substances. active ingredients constituted by pyrimidine derivatives.
This consolidation phenomenon is particularly advantageous insofar as it is carried out with a derivative carrying a keratolytic activity and that it makes it possible, due to a greater solubility, to obtain better bioavailability and / or transcutaneous penetration.
In order to determine the effectiveness or the speed of action of the compositions for the treatment of alopecia, the trichogram or the phototrichogram is generally used which makes it possible to determine, among other things, the percentage of hair in the anagen phase relative to the hair in phase telogen.
An object of the invention therefore consists of the association of pyrimidine derivatives and salicylic acid derivatives with a view to inducing and stimulating hair growth and reducing their fall.
Another subject of the invention consists of cosmetic and / or pharmaceutical compositions containing these compounds.
The invention also relates to devices with several compartments allowing the implementation of the association according to the invention.
Other objects of the invention will appear on reading the description and the examples which follow.
The association in accordance with the invention is essentially characterized by the fact that it comprises:<ul id="ul0001" list-style="none"><li>a) a component (A) containing, in a physiologically acceptable medium, at least one pyrimidine derivative corresponding to the formula:<chemistry id="chem0001" num="0001"><img file="EP0336812A2_D0001.tif" /></chemistry> R₃ and R₄, independently of one another, denote hydrogen, an alkyl, alkenyl, alkylaryl, cycloalkyl group, R₃ and R₄ which can also form a heterocycle with the nitrogen atom to which they are linked, chosen from the groups aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, hexahydroazepinyl, heptamethyleneimine, octamethyleneimine, morpholine and lower alkyl - 4 piperazidinyl, the heterocyclic groups which may be substituted on the carbon atoms by one to three lower alkyl, hydroxy or alkoxy groups; the group R₂ is chosen from a hydrogen atom, an alkyl, alkenyl, alkylalkoxy, cycloalkyl, aryl, alkylaryl, arylalkyl, alkylarylalkyl, alkoxyarylalkyl or haloarylalkyl group, as well as the physiologically acceptable acid addition salts; and</li><li>b) a component (B) containing, in a physiologically acceptable medium, at least one salicylic acid derivative corresponding to the following formula (II):<chemistry id="chem0002" num="0002"><img file="EP0336812A2_D0002.tif" /></chemistry> in which : R₆ represents a group -<img file="EP0336812A2_D0003.tif" /> - R₇ in which R₇ denotes a saturated aliphatic chain, having from 1 to 11 carbon atoms, linear, branched or cyclized, an unsaturated chain having from 3 to 17 carbon atoms, carrying one or more double bonds conjugated or not, or else a ring aromatic linked to the carbonyl radical directly or via a saturated or unsaturated aliphatic chain, having 2 to 7 carbon atoms, these various substituents which can themselves be substituted by one or more halogen atoms, by one or more trifluoromethyl groups, by one or more hydroxyl groups, the hydroxyl group being present in free form or esterified by an acid having from 1 to 6 carbon atoms, or else by a carboxyl function, the carboxyl function possibly being free or esterified by a lower alcohol having from 1 to 6 carbon atoms; R₆ also represents a linear or branched alkyl group, having 1 to 18 carbon atoms or else alkoxy comprising 1 to 18 carbon atoms, linear or branched; R₅ represents a hydroxyl function or an ester function of formula: - O - <img file="EP0336812A2_D0004.tif" /> - R₈ R₈ representing an aliphatic group, saturated or unsaturated, having from 1 to 15 carbon atoms, components (A) and (B) forming part of the same composition or being intended to be used separately, either simultaneously, or successively or staggered over time, in order to induce and stimulate hair growth and decrease their fall.</li></ul>
For the compounds of formula (I), the alkyl or alkoxy groups preferably denote an alkyl or lower alkoxy group having from 1 to 4 carbon atoms; the alkenyl group preferably denotes a lower alkenyl group having 2 to 5 carbon atoms; the aryl group preferably denotes phenyl and the cycloalkyl group preferably denotes a group having 4 to 6 carbon atoms.
The preferred compounds of formula (I) are more particularly chosen from the compounds in which R₂ denotes hydrogen and R₁ represents a group:<chemistry id="chem0003" num="0003"><img file="EP0336812A2_D0005.tif" /></chemistry> in which R₃ and R₄ denote independently of one another hydrogen or a C₁ to C₄ alkyl group or R₃ and R₄ form a piperidinyl ring. Mention may more particularly be made of the compound consisting of 6-amino-1,2-dihydro-1 hydroxy-2-imino-4-diethylamino-pyrimidine and the compound consisting of 6-amino-1,2-dihydro-1-hydroxy-1-imino-2 piperidino-4 pyrimidine also called "Minoxidil". A preferred salt is more particularly constituted by sulfate.
For the compounds of formula (II), the group R₆ is preferably in position 5 of the ring and it is preferably chosen from alkanoyl groups having 2 to 12 carbon atoms and more particularly from n-octanoyl, 3-dimethyl groups , 3 butyroyl, 2-propyl pentanoyl, n-dodecanoyl, n-decanoyl, heptanoyl. The group R₆ can also be chosen from alkyl groups having 1 to 18 carbon atoms and in particular hexyl, octyl, decyl groups. The alkoxy groups are groups having between 1 and 18 carbon atoms and are more particularly chosen from n-hexyloxy, n-heptyloxy, n-decyloxy groups.
The particularly preferred compounds are chosen from n-octanoyl-5 salicylic acid, n-decanoyl-5 salicylic aid, n-dodecanoyl-5 salicylic acid, n-octyl-5 salicylic acid, acid n-heptyloxy-5 salicylic acid, n-heptyloxy-4 salicylic acid or their physiologically acceptable salts or esters.
The pyrimidine derivatives of formula (I) are used in component (A) in proportions of between 0.05 and 10% by weight and in particular between 0.05 and 5% by weight and preferably between 0.5 and 4 % in weight.
The salicylic acid derivatives corresponding to formula (II) are used in component B in proportions of between 0.05 and 10% by weight and in particular between 0.05 and 5% by weight.
The molar ratio between the pyrimidine derivatives of formula (I) and the salicylic acid derivatives of formula (II) is more particularly between 1 and 10.
The Applicant has found that thanks to this association, it is possible to dissolve a larger amount of the pyrimidine derivatives of formula (I) and more particularly of "Minoxidil", in the physiologically acceptable medium.
The physiologically acceptable medium for components (A) and (B) is a medium usable in pharmacy and in cosmetics and can be constituted by a mixture of water and one or more organic solvents or by a mixture of physiologically acceptable organic solvents .
These compositions can be pressurized in aerosol devices in the presence of a propellant.
The solvents which are more particularly usable are chosen from lower C₁-C₄ alcohols such as ethyl alcohol, isopropyl alcohol, tert-butyl alcohol, alkylene glycols such as propylene glycol, mono and dialkylene glycol alkyl ethers such that more particularly ethylene glycol monoethyl ether, propylene glycol monomethyl ether and diethylene glycol monoethyl ether.
Physiologically acceptable media can be thickened or not. To thicken them, thickening agents and / or gelling agents that are well known in the art can be used, such as more particularly heterobiopolysaccharides such as xanthan gum or scleroglucans, cellulose derivatives, crosslinked or non-crosslinked acrylic polymers. .
The solvents, when used in the aqueous medium, are preferably present in proportions of between 1 and 80% by weight relative to the total weight of the composition.
The thickeners, when used, are preferably present in proportions of between 0.1 and 5% by weight and in particular between 0.4 and 3% by weight relative to the total weight of each of the components (A) and (B) when these components are used separately or relative to the total weight of the composition containing the components (A) and (B).
The compositions consisting either of one and / or the other of components (A) and (B) or of the composition containing the two components (A) and (B), can also contain any other adjuvants usually used in compositions intended for topical application for cosmetic or pharmaceutical use, and more particularly preserving agents, complexing agents, dyes, basifying or acidifying agents, surfactants, anionic agents, cationic, nonionic, amphoteric or mixtures thereof, anionic, cationic, nonionic or amphoteric polymers as well as their mixtures. The pH of these compositions can vary between 4 and 9.
A preferred embodiment of the invention consists in using the combination in the form of a composition containing the components (A) and (B), such a composition constitutes another object of the invention.
This embodiment is particularly advantageous because of the co-solubilization properties of the compound of formula (II) on the compound of formula (I).
This composition contains the pyrimidine derivative of formula (I) in proportions of between 0.05 and 6% by weight relative to the total weight of the composition and preferably between 0.1 and 5% by weight and in particular between 0 , 5 and 2% by weight.
The salicylic acid derivatives of formula (II) are present in proportions of 0.05 to 10% by weight and preferably between 0.05 and 5% by weight.
Such a composition, due to the improved solubility characteristics, can also be prepared just before use, when the components (A) and (B) are stored separately.
Another embodiment may consist in applying the components (A) and (B) separately, either simultaneously, or successively or staggered in time.
When components (A) and (B) are used separately, component (A) contains the pyrimidine derivatives of formula (I), either in dissolved form in the physiologically acceptable medium or then, in whole or in part suspended in this medium, in particular in micronized form, that is to say in the form of particles having a particle size less than 80 microns and preferably less than 20 microns, and in particular less than 5 microns.
The combination according to the invention can be conditioned in this case in a device with several compartments also called a "kit" or necessary, a first compartment of which contains the component (A) containing the pyrimidine derivatives of formula (I) in a physiologically acceptable medium and the second compartment containing component (B) based on the salicylic acid derivative of formula (II).
The combination in accordance with the invention, as indicated above, makes it possible to treat hair loss therapeutically by acting more particularly on the dysfunction of the biological mechanisms at the origin of hair growth. The treatment may consist in carrying out a daily application of the composition containing the components (A) and (B) defined above, for a period of a few months, and this, at the rate of one application per day.
The Applicant has found that thanks to the combination in accordance with the invention, the cutaneous availability and the transcutaneous penetration are improved, which increases the effectiveness of the composition.
Furthermore, the composition also has the advantage of being bacteriostatic.
The compositions according to the invention also make it possible to cosmetically treat the hair, that is to say to give them greater vigor and a better appearance.
The invention also relates to the use of the combination as defined above for the preparation of a medicament intended for the treatment of alopecia acting in particular on the dysfunction of the hair cycle.
The following examples are intended to illustrate the invention without, however, being limiting in nature.
EXAMPLE 1
A gel of the following composition is prepared: <tables id="tabl0001" num="0001"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">- Minoxidil</entry><entry namest="col2" nameend="col2" align="char" char=",">3 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- 5-n-octanoyl salicylic acid</entry><entry namest="col2" nameend="col2" align="char" char=",">0.55 g</entry></row><row><entry namest="col1" nameend="col1" /></row><row><entry namest="col1" nameend="col1" align="left">- Xanthan gum sold under the name KELTROL T by the company KELCO</entry><entry namest="col2" nameend="col2" align="char" char=",">0.75 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- Ethyl alcohol</entry><entry namest="col2" nameend="col2" align="char" char=",">50 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">- Water qs</entry><entry namest="col2" nameend="col2" align="char" char=",">100 g</entry></row></tbody></tgroup></table></tables>
This composition is applied to the alopecic parts of the scalp.
EXAMPLE 2
A gel of the following composition is prepared: <tables id="tabl0002" num="0002"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">- Minoxidil</entry><entry namest="col2" nameend="col2" align="char" char=",">3.2g</entry></row><row><entry namest="col1" nameend="col1" align="left">- 5-n-octanoyl salicylic acid</entry><entry namest="col2" nameend="col2" align="char" char=",">2.25 g</entry></row><row><entry namest="col1" nameend="col1" /></row><row><entry namest="col1" nameend="col1" align="left">- Hydroxypropyl cellulose sold under the name KLUCEL G by the company HERCULES</entry><entry namest="col2" nameend="col2" align="char" char=",">2 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">- Ethyl alcohol / propylene glycol (95/5) qs</entry><entry namest="col2" nameend="col2" align="char" char=",">100 g</entry></row></tbody></tgroup></table></tables>
This composition is applied to the alopecic parts of the scalp.
EXAMPLE 3
Two compositions are prepared (A) and (B) packaged as a kit and containing respectively: <tables id="tabl0003" num="0003"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left"><u style="single">Composition (A):</u></entry><entry namest="col2" nameend="col2" /></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">- Minoxidil</entry><entry namest="col2" nameend="col2" align="char" char=",">1.5 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- Propylene glycol</entry><entry namest="col2" nameend="col2" align="char" char=",">20 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- Ethyl alcohol</entry><entry namest="col2" nameend="col2" align="char" char=",">50 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">- Water qs</entry><entry namest="col2" nameend="col2" align="char" char=",">100 g</entry></row></tbody></tgroup></table></tables><tables id="tabl0004" num="0004"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left"><u style="single">Composition (B):</u></entry><entry namest="col2" nameend="col2" /></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">- n-decanoyl-5 salicylic acid</entry><entry namest="col2" nameend="col2" align="char" char=",">0.4 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- Propylene glycol</entry><entry namest="col2" nameend="col2" align="char" char=",">20 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- Ethyl alcohol</entry><entry namest="col2" nameend="col2" align="char" char=",">50 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">- Water qs</entry><entry namest="col2" nameend="col2" align="char" char=",">100 g</entry></row></tbody></tgroup></table></tables>
Composition (A) is applied in a time-shifted manner in the morning and composition (B) in the evening or vice versa on the alopecic parts of the scalp.
It is also possible to apply the compositions (A) and (B) alternately every day (every other day: (A), every other day: (B)).
EXAMPLE 4
Two compositions are prepared (A) and (B) packaged as a kit and containing respectively: <tables id="tabl0005" num="0005"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left"><u style="single">Composition (A):</u></entry><entry namest="col2" nameend="col2" /></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">- Minoxidil</entry><entry namest="col2" nameend="col2" align="right">2 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- Propylene glycol</entry><entry namest="col2" nameend="col2" align="right">20 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- Ethyl alcohol</entry><entry namest="col2" nameend="col2" align="right">50 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">- Water qs</entry><entry namest="col2" nameend="col2" align="right">100 g</entry></row></tbody></tgroup></table></tables><tables id="tabl0006" num="0006"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left"><u style="single">Composition (B):</u></entry><entry namest="col2" nameend="col2" /></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">- n-dodecanoyl-5 salicylic acid</entry><entry namest="col2" nameend="col2" align="char" char=",">1.5 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">- Ethyl alcohol / propylene glycol (95/5) qs</entry><entry namest="col2" nameend="col2" align="char" char=",">100 g</entry></row></tbody></tgroup></table></tables>
The compositions (A) and (B) are applied in a time-shifted manner: (A) or (B) in the morning, (B) or (A) in the evening or successively one after the other on the alopecic parts scalp.
EXAMPLE 5
<tables id="tabl0007" num="0007"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">- Amino-6 dihydro-1,2 hydroxy-1 imino-2 diethylamino-4 pyrimidine</entry><entry namest="col2" nameend="col2" align="right">3 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- 5-n-octanoyl salicylic acid</entry><entry namest="col2" nameend="col2" align="right">2 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- Propylene glycol</entry><entry namest="col2" nameend="col2" align="right">20 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- Ethyl alcohol</entry><entry namest="col2" nameend="col2" align="right">50 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">- Water qs</entry><entry namest="col2" nameend="col2" align="right">100 g</entry></row></tbody></tgroup></table></tables>
This composition is applied to the alopecic parts of the scalp.
EXAMPLE 6
The following lotion is prepared: <tables id="tabl0008" num="0008"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">- Minoxidil</entry><entry namest="col2" nameend="col2" align="char" char=",">0.54 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- 5-n-octanoyl salicylic acid</entry><entry namest="col2" nameend="col2" align="char" char=",">2.2g</entry></row><row><entry namest="col1" nameend="col1" align="left">- Propylene glycol</entry><entry namest="col2" nameend="col2" align="char" char=",">22.8g</entry></row><row><entry namest="col1" nameend="col1" align="left">- Ethyl alcohol</entry><entry namest="col2" nameend="col2" align="char" char=",">55.1g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">- Water qs</entry><entry namest="col2" nameend="col2" align="char" char=",">100 g</entry></row></tbody></tgroup></table></tables> that is applied to the alopecic areas of the scalp to promote regrowth and reduce hair loss.
EXAMPLE 7
The following lotion is applied to the alopecic areas of the scalp: <tables id="tabl0009" num="0009"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">- Minoxidil</entry><entry namest="col2" nameend="col2" align="char" char=",">5.0 g</entry></row><row><entry namest="col1" nameend="col1" align="left">- 5-n-octanoyl salicylic acid</entry><entry namest="col2" nameend="col2" align="char" char=",">1.09 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">- Ethyl alcohol (50g) water (50g) qs</entry><entry namest="col2" nameend="col2" align="char" char=",">100.0 g</entry></row></tbody></tgroup></table></tables>
Contents7
10 sheets
Sheet 1 Sheet 2 Sheet 3 Sheet 4 Sheet 5 Sheet 6 Sheet 7 Sheet 8 Sheet 9 Sheet 10
Every citation, both ways
| Document | Relation | Office | Cited during |
|---|---|---|---|
| EP1269986A3 | Cited by | European Patent Office (EPO) | Search report |
| US9884017B2 | Cited by | United States of America | Applicant |
| US10322186B2 | Cited by | United States of America | Applicant |
| US12138311B2 | Cited by | United States of America | Applicant |
| US10363216B2 | Cited by | United States of America | Applicant |
| EP1269986A2 | Cited by | European Patent Office (EPO) | Search report |
| US9636405B2 | Cited by | United States of America | Applicant |
| US10029013B2 | Cited by | United States of America | Applicant |
| US10086080B2 | Cited by | United States of America | Applicant |
| US7485315B2 | Cited by | United States of America | Applicant |
| US10369102B2 | Cited by | United States of America | Applicant |
| US10967063B2 | Cited by | United States of America | Applicant |
| US11103454B2 | Cited by | United States of America | Applicant |
| US10821077B2 | Cited by | United States of America | Applicant |
| US10213512B2 | Cited by | United States of America | Applicant |
| US9795564B2 | Cited by | United States of America | Applicant |
| US10137200B2 | Cited by | United States of America | Applicant |
| US10835613B2 | Cited by | United States of America | Applicant |
| US9713643B2 | Cited by | United States of America | Applicant |
| US10322085B2 | Cited by | United States of America | Applicant |
| US10463742B2 | Cited by | United States of America | Applicant |
| US10092588B2 | Cited by | United States of America | Applicant |
| US11033491B2 | Cited by | United States of America | Applicant |
| US10117812B2 | Cited by | United States of America | Applicant |
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| US10610599B2 | Cited by | United States of America | Applicant |
| US9849142B2 | Cited by | United States of America | Applicant |
| FR2689008A1 | Cited by | France | Search report |
| US10588858B2 | Cited by | United States of America | Applicant |
| US10517882B2 | Cited by | United States of America | Applicant |
| US10213384B2 | Cited by | United States of America | Applicant |
| US11433025B2 | Cited by | United States of America | Applicant |
| US10350166B2 | Cited by | United States of America | Applicant |
| WO2011073281A1 | Cited by | World Intellectual Property Organization (WIPO) | Applicant |
| US9668972B2 | Cited by | United States of America | Applicant |
| US11324691B2 | Cited by | United States of America | Applicant |
| US9675700B2 | Cited by | United States of America | Applicant |
| US10398641B2 | Cited by | United States of America | Applicant |
| US9682021B2 | Cited by | United States of America | Applicant |
| US10821187B2 | Cited by | United States of America | Applicant |
| US11219631B2 | Cited by | United States of America | Applicant |
| US10849847B2 | Cited by | United States of America | Applicant |
| US10238746B2 | Cited by | United States of America | Applicant |
| US9622947B2 | Cited by | United States of America | Applicant |
| US9662298B2 | Cited by | United States of America | Applicant |
| FR2826271A1 | Cited by | France | Search report |
| WO2011073281A1 | Cited by | World Intellectual Property Organization (WIPO) | Applicant |
| US10946101B2 | Cited by | United States of America | Applicant |
| GB2175902A | Cites | United Kingdom | Search report |
| FR2581542A1 | Cites | France | Search report |
| WO8807361A1 | Cites | World Intellectual Property Organization (WIPO) | Search report |
12 members in 7 offices
Priority claims5
| Document | Office | Kind | Date |
|---|---|---|---|
| 87187 | Luxembourg | A | |
| 87187 | Luxembourg | A | |
| 87187 | Luxembourg | – | |
| 87187 | – | – | – |
| LU19880087187 | – | – | – |
Members12
| Document | Office | Kind | |
|---|---|---|---|
| EP0336812A2This record | European Patent Office (EPO) | A2 | |
| EP0336812A3 | European Patent Office (EPO) | A3 | |
| LU87187A1 | Luxembourg | A1 | |
| JPH01308216A | Japan | A | |
| EP0336812B1 | European Patent Office (EPO) | B1 | |
| AT79742T | Austria | T | |
| ATE79742T1 | Austria | T1 | |
| DE68902565D1 | Germany | D1 | |
| DE68902565T2 | Germany | T2 | |
| US5443823A | United States of America | A | |
| JP2744057B2 | Japan | B2 | |
| CA1341267C | Canada | C |
38 legal events, as 4 offices reported them to INPADOC
Over the term
Point at a mark for the eventEvents
| Event | Code | Office | |
|---|---|---|---|
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Notification of lapseLapsedST | ST | FR | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Gb: european patent ceased through non-payment of renewal feeCeasedGBPC | GBPC | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| European patent in force as of 2002-01-01IF02 | IF02 | GB | |
| Patent ceasedCeasedPL | PL | CH | |
| Be: lapsedLapsedBERE | BERE | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| Annual fee paid to national office [announced via postgrant information from national office to epo]GrantedPGFP | PGFP | EP | |
| No opposition filedOpposition26N | 26N | EP | |
| No opposition filed within time limitOppositionORIGINAL CODE: 0009261PLBE | PLBE | EP | |
| Information on the status of an ep patent application or granted ep patentGrantedSTATUS: NO OPPOSITION FILED WITHIN TIME LIMITSTAA | STAA | EP | |
| Nl: lapsed or annulled due to failure to fulfill the requirements of art. 29p and 29m of the patents actLapsedNLV1 | NLV1 | EP | |
| Corresponds to:REF | REF | EP | |
| Gb: translation of ep patent filed (gb section 77(6)(a)/1977)GBT | GBT | EP | |
| It: translation for a ep patent filedITF | ITF | EP | |
| It: translation for a ep patent filedITF | ITF | EP | |
| Designated contracting statesAK | AK | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Lapsed in a contracting state [announced via postgrant information from national office to epo]LapsedPG25 | PG25 | EP | |
| Corresponds to:REF | REF | EP | |
| (expected) grantORIGINAL CODE: 0009210GRAA | GRAA | EP | |
| Designated contracting states (corrected)RBV | RBV | EP | |
| First examination report despatched17Q | 17Q | EP | |
| Request for examination filed17P | 17P | EP | |
| Designated contracting statesAK | AK | EP | |
| Designated contracting statesAK | AK | EP | |
| Search report despatchedORIGINAL CODE: 0009013PUAL | PUAL | EP | |
| Public reference made under article 153(3) epc to a published international application that has entered the european phaseORIGINAL CODE: 0009012PUAI | PUAI | EP |
Numbers
- Publication
- 0336812
- Publication, DOCDB
- 0336812
- Publication, EPODOC
- EP0336812
- Application
- 89400821
- Application, DOCDB
- 89400821
- Application, EPODOC
- EP19890400821
Titles3
- German
- Assoziat, bestehend aus Pyrimidin-Derivaten und Harnstoff- und/oder Allantoin-Derivaten zum Induzieren und Stimulieren des Haarwuchses und zum Vermindern des Haarausfalles
- English
- Association of pyrimidine derivatives and urea and/or allantoin derivatives to induce and stimulate hair growth and to reduce hair loss
- French
- Association de dérivés de pyrimidine et de dérivés d'acide salicylique pour induire et stimuler la croissance des cheveux et diminuer leur chute
Classification
- CPC, 3
- A61K8/4953
- A61Q7/00
- A61K8/37
- IPC, 7
- A61K8 00
- A61K8 33
- A61K8 37
- A61K8 49
- A61K31 505
- A61Q5 00
- A61Q7 00
Designated states1
- Contracting states, 1
- Sweden