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    • 专利摘要:
    Pharmaceutical composition for topical use of salicylic acid for treatment of hyperkeratosis and corresponding method. Pharmaceutical composition for topical use of salicylic acid, having a salicylic acid content higher than 20%, and comprising a copolymer of the monoalkyl ester type of poly (methyl vinyl ether/maleic acid) of the general formula: {image-01} As filmogenic agent and stabilizer of the formulation, forming a stable solution in a hydroalcoholic medium, being suitable for the treatment of cutaneous hyperkeratosis. The hydroalcoholic solution contains one or more c1-c6 alcohols. The copolymer has a molecular weight between 70,000 and 170,000 and the r group is an ethyl group, an iso-propyl group or a butyl group. The pharmaceutical composition is obtained by adding the salicylic acid to a hydroalcoholic base and subsequently adding the copolymer. The pharmaceutical composition is used as a pharmaceutical preparation for the treatment of localized cutaneous hyperkeratosis. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2620319A1
    申请号:ES201531915
    申请日:2015-12-28
    公开日:2017-06-28
    发明作者:Antonio BUXADÉ VIÑAS；Montserrat Albreda Plaza；Miguel CÁNOVAS UBERA；Antonio Conchillo Teruel
    申请人:Laboratorios Vinas SA；
    IPC主号:
    专利说明:

    image 1
    PHARMACEUTICAL COMPOSITION FOR TYPICAL USE OF SALYCYLIC ACID FOR TREATMENT OF HYPERKERATOSIS AND CORRESPONDING METHOD 5 DESCRIPTION
    Field of the Invention
    The present invention describes a pharmaceutical composition in the form of a stable solution of salicylic acid at a high concentration, in a hydroalcoholic medium containing as a film forming agent a monoalkyl ester copolymer of poly (methyl vinyl ether / maleic acid), useful for the treatment of hyperkeratotic states
    15 cutaneous localities such as calluses or tylosis, helomas or nails, seborrheic keratoses, hyperkeratotic warts and the like.
    The invention also relates to a method of preparing a composition according to the invention and a use thereof. twenty State of the art
    Hyperkeratosis consists in an increase in the thickness of the stratum corneum due to excessive cohesion of the corneal or corneocyte cells. It can occur in different locations and varying degrees of intensity.
    A large number of chemical substances and physical materials have been used in cosmetic and therapeutic skin treatments. It is known, among others, the use of organic acids for their exfoliating chemical activity, among which is salicylic acid, as well as the use of solid materials for their physical action as
    image2
    abrasives (peeling effect) in powder form or suspended in different formulations, depending on the area to be treated.
    To increase the keratolytic efficacy of salicylic acid, it is common to use
    5 cosmetic and pharmaceutical formulations with a high content thereof or combine it with other keratolytic substances that enhance the keratolytic effect, and even with excipients that facilitate the peeling effect.
    For example, in documents ES 2322836 and ES 2539520, salicylic acid has
    10 it has been used dispersed as a micronized solid, both for a general keratolytic action on the skin (up to 20%) or for hyperkeratosis of the scalp (up to 30%), together with other additives, but especially in combination with inorganic particulate agents and organic, in order to combine a keratolytic action by a chemical and physical peeling effect.
    In US 5728390, compositions are used in the form of solutions, suspensions, gels, etc. with mixtures of beta-hydroxy acids at concentrations between 1% and 10% and alpha-hydroxy acids at concentrations between 1% and 20% and a low irritability complexing agent such as polyvinylpyrrolidone at a
    20 concentration between 1% and 10% in an appropriate solvent to solve skin problems and develop a smooth and smooth skin.
    In US 2004/0067243, gel-type compositions are described using cellulose-derived gelling agents, in which solubility is increased in
    Alcoholic medium of beta-hydroxy acids, including salicylic acid at concentrations of 1% to 50%, adding at least one alpha-hydroxy acid at concentrations of 1% to 20% in an alcoholic solvent, preferably a glycolic solvent.
    image3
    In WO 94/12194 compositions, gel type or solutions are prepared for the treatment of calluses and warts with a combination of halides or lanthanide oxides between 1% and 20% and salicylic acid between 5% and 64% in a base of organic solvents such as propylene glycol, acetone, ethanol, dimethyl sulfoxide
    5 or petrolatum.
    WO 2015/14069 also uses the combination of the mixture of salicylic acid and lactic acid, at concentrations between 10% and 20%, respectively, with formic acid between 5% and 20% to enhance activity
    10 keratolytic
    In US 2002/0187171 it is revealed, the need to increase the amount of salicylic acid dissolved in a dermatological composition in order to increase bioavailability and thereby the therapeutic efficacy. However, the 15 stability problems of the solution are manifested at high concentrations, since salicylic acid crystallization can occur, especially if the composition is exposed to different temperatures, with the consequent decrease in bioavailability and with additional problems of appearance and texture . To avoid these problems, a mixture of butylene glycol and glycereth-26 is used to prepare
    A solution of salicylic acid between 1% and 40% as a precursor of the final preparation resulting from absorbing said solution in a polymeric substrate type nylon, acrylic, polyester, cellulosic and others, with a final concentration of up to 15% acid salicylic.
    In US 5433950 a "gel-forming" fluid gel composition is prepared from a flexible collodion (between 20% and 60%), which contains nitrocellulose as "film-forming", and other additives, such as copolymers and Crystallization inhibitors of salicylic acid (ethyl lactate between 15% and 45%) in order to achieve concentrations in salicylic acid between 5% and 40%, although finally the
    30 preferred concentration is 17%. However, this composition has the important drawback of the high content of ethyl ether, a very volatile and highly flammable solvent.
    image4
    In a similar line, US patent 2011/0086109, aims to solve the problem of
    5 high content of ethyl ether, - maintaining the concentration of 17% salicylic acid, which in addition to being very flammable, due to its high volatility easily causes losses in the devices using the composition, leading in some cases where the concentration of the asset is regulated, to create problem of specifications in use, when the asset is concentrated, so they propose the
    Preparation of the gel composition from a collodion at a lower concentration (5% to 20%) and, in turn, with a much lower content of ethyl ether (3% to 14%) but compensating for this in the composition with a higher concentration in ethyl alcohol (up to 55%). Nitrocellulose with between 0.2% and 1% is still "film-forming", as in US 5433950, and lactate is still used
    Ethyl 15 as a plasticizer and crystallization inhibitor. In addition, it is possible to use other polymers, provided they are compatible with nitrocellulose, to improve the characteristics of the final "film".
    A solution of salicylic acid is described in US 2005/6869611,
    20 preferably in ethyl alcohol, in amounts up to more than 30% and based its benefit and efficacy on the residence time on the affected skin of the solution and not as a dry residue after evaporation of the solvent, so it is considered that the Therapeutic treatment time of this composition is the time that the skin is subjected to the concentrated salicylic acid solution, ending
    Once the solvent has evaporated, so that it is still wet, the deposited film must be washed or removed. Thus, the volatile solvent is considered important for controlling the treatment time, since it depends on the evaporation time and because, in addition, once the solvent has evaporated, the salicylic acid tank is removed, thereby avoiding excessive exposure to the solution of
    30 concentrated salicylic acid.
    image5
    Therefore, in general, the interest in the pharmaceutical field is evident in the formulation of compositions with keratolytic agents and, in particular, in stable formulations of high salicylic acid content, with the drawback that the high concentration presents problems of stability due to the tendency to crystallize salicylic acid, thus reducing the bioavailability of the acid in its application, as well as not being tolerable to patients due to an irregular and unpleasant texture in the application that can lead to low acceptability of the prepared, which also justifies the
    The need for formulations of easy application, high bioavailability and tolerance and with it the interest of developing topical formulas with components capable of providing such therapeutic and pharmacotherapeutic qualities. 15 Exhibition of the Invention
    A subject of the present invention is a pharmaceutical composition in the form of a stable solution, of salicylic acid at a high concentration, in a hydroalcoholic medium containing as a film-forming agent a copolymer of the monoalkyl ester type of poly (methyl vinyl ether / maleic acid). The composition is suitable for the treatment of cutaneous localized hyperkeratotic states such as calluses or tylosis, helomas or nails, seborrheic keratoses, hyperkeratotic warts and the like. The dependent claims are aimed at advantageous alternatives and / or optional improvements of the composition according to the
    Invention
    In relation to the issues and complexities set forth above, the inventors of this patent application have discovered that it is possible to obtain pharmaceutical formulations of salicylic acid at high concentration, in solution, 30 stable and with high keratolytic action, simpler: free of other keratolytic agents such as other beta-hydroxylic or alpha-hydroxylic acids, or other acids that in turn favor the solubilization of salicylic acid, or of crystallization inhibitors such as ethyl lactate or others, or of solid materials by their action physical as abrasives (peeling effect) in the form of powder or suspended in 5 different formulations, or of dangerous solvents such as ethyl ether, or of other additives that decrease irritability, or that increase the film-forming capacity, or of complementary thickening substances or of fats and paraffins, but that maintain good qualities of formulation galén ico-pharmaceutical and therapeutic, such as the high concentration of solubilized acid, the high capacity and quality
    image6
    10 film-forming, and the high keratolytic action, when formulating salicylic acid at a high concentration in a hydroalcoholic base and a monoalkyl ester copolymer of poly (methyl vinyl ether / maleic acid).
    High concentration salicylic acid formulations usually have
    15 stability problems, as a consequence of its tendency to crystallize salicylic acid. However, surprisingly, the stability of the formulation as a solution of high salicylic acid content (greater than 20%) and its therapeutic capacity, in the absence of other keratolytic chemical agents or abrasive solid matter, is achieved by the solubilization of salicylic acid on a base
    20 hydroalcoholic containing a copolymer, also dissolved, of the monoalkyl ester type of poly (methyl vinyl ether / maleic acid), which also leads, in its application, to the formation of a film, also very stable, on the hyperkeratotic skin, producing , advantageously, an occlusive keratolytic effect that makes it possible to dispense with other types of keratolytic agents or abrasive particulate material
    25 as enhancers. The high concentration of salicylic acid when dissolved dissolved facilitates penetration into hyperkeratolytic plates to carry out a chemical action, which is subsequently maintained by the occlusive action that occurs when the hydroalcoholic solution medium evaporates and a film that acts as permanent reservoir of salicylic acid. So that,
    30 advantageously, unlike other compositions formulated so that time and
    image7
    the keratolytic therapeutic action ends once the solution is deposited and the salicylic acid precipitates, by evaporation of the solvent, and the skin is cleaned (and therefore the keratolytic agent is removed), in the composition and the method of treatment object It is intended, on the contrary, that once the high concentration of salicylic acid in solution is deposited and the solvent evaporates, a layer ("film") is formed by the presence of the film-forming copolymer that will also be saturated with acid salicylic and with it the therapeutic keratolytic action will be maintained for a prolonged time of at least several hours, preferably for eight hours. In addition, due to the characteristics of the final composition, in particular due to the presence of the monoalkyl ester poly (methyl vinyl ether / maleic acid) film-forming copolymer, no prior treatment or cleaning prior to disposal of the composition on keratinized skin; remaining, in turn, a flexible occlusive film of homogeneous texture, with good adhesion, soft and very resistant to rubbing and moisture.
    15 which makes it easily accepted by the patient.
    In addition, given the fluidity of the formulation object of the invention, it can be applied, if deemed necessary, convenient or advantageous, on the skin by means of a brush in order to limit the keratolytic and occlusive therapeutic activity of the film.
    20 that is formed, strictly to the keratinized zone.
    Also, if deemed necessary, convenient or advantageous, a greater occlusive effect can be achieved by covering the application area with an adhesive patch.
    The present invention also relates to the process of obtaining the formulation object of the patent, as defined in the corresponding independent claim. The combination and proportion of the keratolytic asset: salicylic acid at high concentration, in a hydroalcoholic and film-forming base in which the type and concentration of the film-forming agent is selected
    Among the monoalkyl esters of poly (methyl vinyl ether / maleic acid) to allow a
    image8
    formulation in the form of a stable keratolytic and film-forming solution that does not require any previous or subsequent treatment of dissolution or suspension of the different elements in any other vehicle or solvent, neither aqueous nor of fatty or paraffinic type. After the formulation of the salicylic acid solution with the hydroalcoholic solvent and the incorporation of the film-forming copolymer, the stability of the formulation is maintained, without crystallization and with the film-forming properties at different temperatures: from elevated temperatures of 40 ° C to refrigerator conditions at 5 ° C ± 3 ° C. The corresponding dependent claims are aimed at advantageous alternatives and / or optional improvements of the method according to the
    10 invention.
    The use of a pharmaceutical composition according to the invention for the treatment of localized cutaneous hyperkeratotic states such as calluses or tylosis, helomas or nails, is also an object of the invention.
    15 seborrheic keratoses, hyperkeratotic warts and the like. Detailed description of embodiments of the invention
    The invention describes a composition in the form of a stable solution, for topical use, of salicylic acid at a high concentration, containing a hydroalcoholic solution containing a monoalkyl ester copolymer of poly (methyl vinyl ether / maleic acid) as a solubilizing and film-forming base. . The composition is for the treatment of cutaneous localized hyperkeratotic states such as
    25 calluses or tylosis, helomas or nails, seborrheic keratoses, hyperkeratotic warts and the like.
    The active agent of the formulation is salicylic acid and the concentration at which it may be present is advantageously between 20% and 35%, preferably
    30 between 23% and 30%.
    image9
    The hydroalcoholic solution can be prepared from one or more low molecular weight alcohols, such as ethyl alcohol, iso-propyl alcohol, n-propyl alcohol
    or iso-butyl alcohol, preferably ethyl alcohol or iso-propyl alcohol and, more
    5 preferably ethyl alcohol, containing water between 2% and 5% by weight of the final pharmaceutical composition. The required concentration of water can be added directly or contained in the alcohols themselves.
    The concentration of the alcoholic component may be between 55% 10 and 75%, preferably between 60% and 70% by weight with respect to the final pharmaceutical composition.
    The film forming agent is a monoalkyl ester copolymer of poly (methyl vinyl ether / maleic acid) with a molecular weight between 70,000 and 170,000, preferably between 90,000 and 150,000, which responds to the formula:
    image10
    OCH3 CH2CH CH CH OC CO OH O R
    n
    image11
    The R group may be an ethyl group, an isopropyl group or a butyl group, preferably an ethyl group.
    The concentration of film-forming copolymer will preferably be between 6% and 15%, depending on the final required viscosity of the composition, and preferably between 8% and 13% by weight, based on weight.
    25 total composition.
    image12
    The poly (methyl vinyl ether / maleic acid) monoalkyl ester film-forming copolymer can be added from the individual commercial components, or using commercial mixtures that can be compensated, up to the total amount
    5, by adding the necessary amounts of the individual components.
    The monoalkyl ester film-type copolymer of poly (methyl vinyl ether / maleic acid) can also be added in an alcohol solution previously prepared by dissolving the copolymer in the alcohol relevant to the formulation.
    The film forming copolymer can also be incorporated from commercial alcoholic solutions with the alcoholic component relevant to the formulation.
    If the incorporation of the film-forming copolymer is carried out in the form of a solution, prepared or commercial, it is preferred at a concentration of 40% to 60%.
    The stability of the high salicylic acid formulation (greater than 20%) and its therapeutic capacity, in the absence of other keratolytic components or abrasive solid matter, is achieved by the solubilization of salicylic acid in
    20 a hydroalcoholic base and by the presence, at the indicated concentration, of the film-forming copolymer, also dissolved in the hydroalcoholic solution, to allow the rapid formation of an occlusive film that itself contains salicylic acid and acts as a saturated salicylic acid reservoir.
    The invention also refers to the manufacturing process of the pharmaceutical composition described in the form of a hydroalcoholic solution, characterized in that the salicylic acid is previously dissolved in the hydroalcoholic solution and subsequently the monoalkyl ester copolymer of poly (methyl vinyl ether / maleic acid) to the salicylic acid hydroalcoholic solution when
    30 has the copolymer as a single substance or alternatively by incorporating the copolymer also dissolved in a previously prepared hydroalcoholic solution or when the copolymer is a commercial grade solution in which it is also dissolved in the alcoholic solvent relevant to the formulation.
    image13
    The manufacturing process is characterized in that the preparation of the salicylic acid solution in the hydroalcoholic solvent, as well as the incorporation of the monoalkyl ester copolymer of poly (methyl vinyl ether / maleic acid) is preferably carried out at a temperature between 20 ºC and 40 ºC and with agitation between 2,500 rpm and 3,500 rpm
    The formulation obtained under the conditions described and with the selected components is a hydroalcoholic composition with a water content of less than 5% and greater than 2%.
    fifteen Examples
    Example 1 190 g of butanol, 10 g of deionized water are added in a reactor and heated to 20 ° C. When the temperature has been reached, they are slowly added to
    3,000 rpm, 75 g of Salicylic Acid, stirring and temperature are maintained until the total solution of Salicylic Acid is achieved.
    Once the acid has dissolved, 25 g of poly (methyl vinyl ether / maleic acid) 25 butyl ester copolymer are added slowly, stirring and temperature are maintained until complete homogenization and dissolution is achieved.
    Example 2 In a reactor, 160 g of 96 ° ethyl alcohol are added and heated to 25 ° C. 30 When the temperature has been reached, slowly, at 3,000 rpm, 75 g are added
    image14
    of Salicylic Acid, stirring and temperature are maintained until the total dissolution of Salicylic Acid is achieved.
    In parallel, a solution of 27 g of poly ethyl ester copolymer is prepared
    5 (methyl vinyl ether / maleic acid) in 38 grams of ethyl alcohol and once the salicylic acid has dissolved, it is added to the hydroalcoholic solution containing the dissolved salicylic acid.
    After the addition of the copolymer solution, stirring and temperature are maintained until homogenization and total dissolution is achieved.
    Example 3 In a reactor 165 g of iso-propyl alcohol, 10 g of deionized water are added and heated to 30 ° C. When the temperature has been reached they are added,
    Slowly, at 3,000 rpm, 75 g of Salicylic Acid, stirring and temperature are maintained until total dissolution of Salicylic Acid is achieved.
    In parallel, a solution of 35 g of poly (methyl vinyl ether / maleic acid) iso-propyl ester copolymer in 35 grams of iso-propyl alcohol is prepared and once the salicylic acid is dissolved, it is added to the hydroalcoholic solution containing the dissolved salicylic acid.
    After the addition of the copolymer solution, stirring and temperature are maintained until homogenization and total dissolution is achieved. 25
    image15
    Table 1:
    Formulation 1 Formulation 2Formulation 3
    Salicylic acid 75 g75 g75 g
    96º ethyl alcohol 160 g
    Isopropyl alcohol 165 g
    Butyl alcohol 190 g
    Deionized water 10 g10 g
    Mono ethyl ester copolymer 96 ° ethyl alcohol 27 g 38 g
    Iso-propyl ester mono copolymer Iso-propyl alcohol 35 g 35 g
    Mono Butyl Ester Copolymer 25 g
    Total weight 300 g300 g320 g
    5 Stability
    In tables 2 and 3, the results of the stability tests of the 10 previous formulations carried out at a refrigerator temperature (5 ° C ± 3 ° C) and at 25 ° C at 6 months after formulation are attached.
    image16
    Table 2: Time: 6 months in a refrigerator (5 ºC ± 3 ºC)
    Galenic Characteristics
    Formulation Salicylic acid (% content)OrganolepticPhysical-chemical
    one 25.4Colorless solution No strange odors.Crystallization is not observed
    2 25.7Colorless solution No strange odorsCrystallization is not observed
    3 24.0Colorless solution No strange odorsCrystallization is not observed
    Table 3: Time: 6 months at 25 ° C
    Galenic Characteristics
    Formulation Salicylic acid (% content)OrganolepticPhysical-chemical
    one 25.2Colorless solution No strange odors.Crystallization is not observed
    2 25.1Colorless solution No strange odorsCrystallization is not observed
    3 23.8Colorless solution No strange odorsCrystallization is not observed
    The stability results show how the described formulations are stable for a prolonged period of time (at least 6 months) at a temperature of 10 refrigerator (5 ° C ± 3 ° C) and ambient (25 ° C); both in relation to the active substance and to the galenic characteristics of the formulation.
    image17 Film Formation Time
    Table 4 shows the results of the evaluation tests for the formation of the film applied to skin.
    Table 4:
    Formulation Film formation time
    one 5 -10 min
    2 <2 min
    3 <2 min
    10 In all cases the film formation is fast, being almost immediate with formulations 2 and 3. Efficacy and acceptability study
    The keratolytic efficacy and pharmacogenic acceptability of the pharmaceutical composition object of the invention have been clinically evaluated, accompanied by a brush for precise application and occlusive adhesive patches in the treatment of vulgar, plantar or mosaic warts.
    20 65 patients who presented warts (54% vulgar type, 38% plantar, 5% mosaic and a flat wart case) with an age between 3 and 69 years (mean 31 years) have been studied. The treatment consisted of 1 daily topical application before going to bed with the brush, avoiding touching the area of surrounding healthy skin. Let dry a few moments and then cover with a patch until the next night. Before applying the product again, the keratotic material exfoliated with a file should be removed and the product and the patch reapplied.
    image18
    5 In total, 175 warts were treated whose location was mostly in the extremities (50% lower, 48% higher and 2% in the trunk). 95% of patients followed the nocturnal application pattern. At the end of the treatment, at 6 weeks, 96% of the warts had remitted or improved (62% of total remissions and 34% improvements), while 7 lesions remained unchanged. 81%
    10 (n = 22) of the patients who had received prior treatment for their injuries considered that the preparation under study was better than this and 5 patients (19%) rated it as equal. Medical trials were good for efficacy in 77%, for tolerability in 95% and for applicability in 100%. According to the patients, the overall efficacy was good in 72%, the tolerability in 94% and the
    15 applicability in 98%.
    权利要求:
    Claims (2)
    [1]
    image 1
    1-Pharmaceutical composition for topical use of salicylic acid, characterized in that it has a salicylic acid content greater than 20% by weight with respect to the total weight of the composition, and comprises a monoalkyl ester copolymer of poly (methyl vinyl ether / acid maleic) of general formula:
    image2
    OCH3 CH2CH CH CH OC CO OH O R
    n
    image3
    10 as a film forming agent and stabilizer of the formulation,
    forming a stable solution in a hydroalcoholic medium, being suitable for the treatment of cutaneous hyperkeratosis.
    Composition according to claim 1, characterized in that it comprises between 20% and 35% salicylic acid, preferably between 23% and 30% by weight, with respect to the total composition.
    Composition according to one of claims 1 or 2, characterized in that the hydroalcoholic solution contains one or more C1-C6 alcohols, preferably ethyl alcohol, iso-propyl alcohol, n-propyl alcohol or iso-butyl alcohol and more preferably alcohol ethyl or iso-propyl alcohol.
    image4
    4 - Composition according to claim 3, characterized in that the concentration of the alcoholic component can be comprised between 55% and 75%, preferably between 60% and 70% by weight with respect to the final composition.
    5. Composition according to one of claims 3 or 4, characterized in that the hydroalcoholic solution has a water content between 2% and 5% by weight of the final composition.
    6 - Composition according to any of claims 1 to 5, characterized by
    10 that the monoalkyl ester copolymer of poly (methyl vinyl ether / maleic acid) has a molecular weight between 70,000 and 170,000, preferably between 90,000 and
    [150]
    150,000
    7 - Composition according to any one of claims 1 to 6, characterized by
    The group R is an ethyl group, an iso-propyl group or a butyl group, preferably an ethyl group or an iso-propyl group.
    8 - Composition according to one of claims 6 or 7, characterized in that the concentration of film-forming copolymer is between 6% and 15%,
    20 preferably between 8% and 13% by weight, based on the total weight of the composition.
    9 - Composition according to any of claims 1 to 8, characterized in that it is free of other keratolytic agents, preferably free of acids
    25 beta-hydroxylic or alpha-hydroxylic acids.
    10 - Composition according to any one of claims 1 to 9, characterized in that it is free of acids that favor the solubilization of salicylic acid.
    image5
    11 - Composition according to any of claims 1 to 10, characterized in that it is free from inhibitors of crystallization of salicylic acid, preferably free of ethyl lactate.
    Composition according to any one of claims 1 to 11, characterized in that it is free of abrasive solid materials.
    13 - Composition according to any of claims 1 to 12, characterized in that it is free of ethyl ether.
    A method for preparing a pharmaceutical composition according to any one of claims 1 to 13, characterized in that the salicylic acid is added to a hydroalcoholic base and subsequently the monoalkyl ester film copolymer of poly (methyl vinyl ether) is added / maleic acid).
    The method according to claim 14, characterized in that the preparation of the stable solution of salicylic acid in the hydroalcoholic base containing the film-forming copolymer is carried out at a temperature between 20 ° C and 40 ° C and with stirring between 2,500 rpm and 3,500 rpm
    Method according to one of claims 14 or 15, characterized in that the salicylic acid dissolves at a concentration of between 20% and 35% by weight, based on the total weight of the composition, preferably at a concentration between 23% and 30% by weight, based on total weight
    25 of the composition.
    17 - Method according to any of claims 14 to 16, characterized in that the film-forming copolymer is at a concentration between 6% and 15% by weight, based on the total weight of the composition, preferably with a concentration of 8% at 13% by weight, based on the total weight of the composition.
    image6
    18 - Method according to any of claims 14 to 17 characterized in that
    5 the monoalkyl ester copolymer of poly (methyl vinyl ether / maleic acid) copolymer is added from the commercial individual components, or added using commercial mixtures that can be compensated, up to the desired total amount, by adding the amounts necessary of the individual components, or is added in alcoholic solution prepared previously by
    The solution of the copolymer in the alcohol relevant to the formulation, or is added in solution from commercial alcoholic solutions with the alcohol component relevant to the formulation.
    19 - Method according to claim 18, characterized in that when the
    The incorporation of the film-forming copolymer is carried out in solution, prepared or commercial, said solution has a concentration of 40% to 60% of the film-forming copolymer.
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    同族专利:
    公开号 | 公开日
    ES2620319B1|2018-05-04|
    引用文献:
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    US6428772B1|2001-06-25|2002-08-06|Blistex Inc.|Acne treatment composition with cooling effect|
    US20030175333A1|2002-03-06|2003-09-18|Adi Shefer|Invisible patch for the controlled delivery of cosmetic, dermatological, and pharmaceutical active ingredients onto the skin|
    US20110086109A1|2009-10-08|2011-04-14|Schering-Plough Healthcare Products, Inc.|Low ether compositions and delivery apparatus|
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    ES201531915A|ES2620319B1|2015-12-28|2015-12-28|PHARMACEUTICAL COMPOSITION FOR TYPICAL USE OF SALYCYLIC ACID FOR TREATMENT OF HYPERKERATOSIS AND CORRESPONDING METHOD|ES201531915A| ES2620319B1|2015-12-28|2015-12-28|PHARMACEUTICAL COMPOSITION FOR TYPICAL USE OF SALYCYLIC ACID FOR TREATMENT OF HYPERKERATOSIS AND CORRESPONDING METHOD|
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