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    • 专利摘要:
    The object of the invention is a composition containing as active ingredient monochloroacetic acid (mca), in solution with ethanol (50% by volume), prepared according to a method described, used for the systematic chemical treatment of plantar wart (papillomavirus) plantar human), without surgery, producing its chemical cauterization. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2614779A1
    申请号:ES201500881
    申请日:2015-12-01
    公开日:2017-06-01
    发明作者:Jose Maria JUAREZ JIMÉNEZ；Mario ROMERO PRIETO；Antonio CORDOBA FERNÁNDEZ；Rafael RAYO ROSADO；Pedro MONTAÑO JIMENEZ；Miguel Angel AVILÉS ESCAÑO；Pedro José SÁNCHEZ SOTO
    申请人:Consejo Superior de Investigaciones Cientificas CSIC；Universidad de Sevilla；
    IPC主号:
    专利说明:

    image 1
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    image3 DESCRIPTION
    Composition for the systematic chemical treatment of the plantar wart. Sector and object of the invention
    Sectors of health and biomedicine.
    The object of the invention is a composition containing as active ingredient monochloroacetic acid (MCA), in 50% volume solution with 96% volume ethanol, prepared according to a procedure described, and which is used for chemical treatment. Systematic plantar wart (plantar human papillomavirus), without surgery, producing its chemical cauterization. State of the art
    Warts are very common, benign and, normally, self-limited to skin lesions, being more common in hands and feet. It is a circumscribed benign epithelial neoplasm, highly vascularized caused by a "papovavirus", capable of producing frequent infections in humans and whose viral particles have been found only in the nucleus of the granular stratum and keratinized cells of the epidermis. When they develop, they form a fibrous and connective tissue that contains numerous hypertrophied papillae and capillaries inside. It is surrounded by epithelial tissue, which forms a capsule.
    The term "papilloma" comes from the conceptual deficiency of "benign epithelial tumor", thus calling all the circumscribed epidermal hyperplasia and the macro-microscopic classification of these lesions. The fact of the previous belief that lesions caused by human papillomavirus (HPV) were only with the papillomatous pattern has caused these lesions to be called, not very correctly, as papillomas.
    Plantar warts are invaded by the pressures that the foot undergoes in standing or walking. This forms a wand surrounded by corneal tissue that sinks like a nail into the plantar tissues, compressing the nerve endings and causing pain. Papillomas have perilesional inflammation symptoms, especially when they are under pressure. Dorsal warts occur anywhere on the foot, except on the floor, and grow "above" with a cauliflower-like appearance. According to its location, HPV foot infection is located in 72% in pressure zones, 19% in medium load zone and only 9% in discharge zone. The plantar wart is considered a painful wart lesion that is usually located on the sole of the foot, especially at the points of maximum pressure, such as the heads of the metatarsals and the heel itself.
    Warts can be classified into periungual, subungual, interdigital, dorsal and plantar, the latter the most common and grow in depth due to pressure and are painful. It is important to differentiate, with a previous diagnosis, the neurovascular heloma from the plantar wart. The first presents vascularization parallel to the cutaneous surface, being very different from plantar warts, which have a vertical and radiated vascularization towards the periphery.
    The importance that can be assigned to the human papillomavirus (HPV) can be measured with respect to the amount of resources available for the treatment of this infection, resources that increase in number and form as new research techniques are developed and they carry out new studies that increase knowledge about possible therapeutic alternatives for this type of infection.
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    The first publications that were completed and documented scientifically are from the 19th century, in which various treatments for this virus have already begun to be studied. Currently, there are many publications on clinical treatment of these infections through a wide range of different methodologies.
    After carrying out an exhaustive study of the existing literature and the examination of the state of the art, a common characteristic has been found in all of them and that there is no definitive clinical procedure or technique or a perfect treatment that has been published, totally valid, to achieve results that can approach 100% efficacy against HPV infection.
    Also the number of verified and validated publications on HPV is an index of the importance of this condition, which in itself can justify the development of new techniques that allow lower rates of failure or recurrence of HPV lesions, such as that appear in these previous studies, all of which are still very high so that these treatments can be taken as definitive or of first choice. Thus, for treatments that are not very aggressive, such as the one that uses salicylic acid, different studies estimate their effectiveness in resolving HPV lesions by 60%; others, in 59%, practically coincide. However, very different results are also found because they can approximate values of effectiveness close to 68% or even higher, of 82 and 85%, being the maximum recorded in a 87% study. In other publications on treatments frequently used in the therapy of plantar warts, such as Cryotherapy, the results are also very diverse: from a value of 9% success to 58 or even 92.5% success.
    A widely used and widely studied method in the literature for the treatment of plantar warts, such as intralesional Bleomycin, also shows disparity of successful results; in that case, from 18% to 92% success after four months of treatment. With this type of treatment, it is found that the results of different studies range between 16% and 94% and this variation is explained by the difficulty of comparing different trials or conducting studies on infection or treatment of plantar warts due to the complexity of this infection, as well as the existence of multiple variables that are difficult to control that can influence the results obtained. There is no similarity of results, but rather notable differences in the success figures according to the different studies based on statistical data. To all this is added the complexity of HPV infection, the different study criteria and the difference in the methodological quality of published clinical trials on plantar warts.
    The choice of the type of treatment can be even more complicated in the case of the appearance of multiple plantar warts because, according to various studies, this multiple appearance is linked to an increase in the resistance of the virus and, consequently, to the search for much more aggressive treatments.
    The majority of existing treatments and possible therapeutic alternatives for HPV infection are interventional therapeutic actions, which entails therapies of some aggressiveness for the patient and all of them with side effects or undesirable effects of different severity, but clinically important. These effects can range from a mildness to a significant risk to the patient's health. Therefore, the need to choose the best treatment proves to be a professional and methodological challenge. That is, treatment that is aggressive enough to eliminate the infection, but that does not pose a danger to the patient or, at least, that has a reduced degree of discomfort, since it usually exists and is suffered by all patients treated for this infection. .
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    In short, any procedure proposal in which an interventionist therapeutic action is carried out to treat plantar warts should have the following purposes:
    a) achieve the highest success rate and
    b) decrease the development of unwanted effects or complications for the patient.
    There are several treatments for plantar warts, considered depending on the patient's characteristics, personal history and type of injury. The treatment of warts has been and continues to be a real headache for all health professionals.
    Such treatments are associated with high recurrence rates after removing the wart, since latent HPV remains in clinically normal skin and / or in the membranes and mucous membranes that surround the site of the wart. Among the various classifications, one of the most used is related to the properties of the therapeutic methods used. Physical, medicated, chemical and other treatments are available.
    (1) Physical treatments. Among the physical treatments, cold treatment or Cryotherapy stand out, although the most correct name would be Cryosurgery. It is a cytodestructive treatment that uses liquid nitrogen, at a temperature of -196ºC, with the precautions involved in its handling. It requires 2 to 3 sessions, with intervals of 1 and 2 weeks, removing warts between 70 and 75% of patients with HPV.
    It can be used safely in pregnant women, but it is contraindicated in cases of malignant or suspicious lesions of malignancy.
    In addition to liquid nitrogen, carbonic anhydride and nitrogen protoxide can also be used prior to delamination of hyperkeratotic tissue, but like other cold treatments, it is not recommended in mosaic warts, vascular and innervated areas, in diabetics or on tendons. A commercial product (brands: Askina ©, Skin Freeze © or Histofreezer ©) can also be used as a mixture of two chemical compounds that have the advantages of being easier to use and store than previous cryogens, under the name "Dimethyl ether-propane", with a temperature of -57ºC, as an alternative to liquid nitrogen and used in Primary Care consultations.
    On the other hand, as physical heat treatments, electrocoagulation stands out, using a high frequency alternating current, as well as radiotherapy, painless but highly dangerous if the dose is exceeded since it can produce trophic trophic ulcers and radiodermitis.
    (2) Medi camentoous treatments. Among the medication-sos treatments, orally, a series of drugs are administered when there is a large number of warts
    or antirecidivante. The main ones are: "Verrulyse", "lnmunoferon", Lysozyme, Vitamin A, "Rasave" and others. Intralesionally, there is a cytostatic or cytotoxic glucopeptide antibiotic product derived from Streptomices verticillus called Bleomycin.
    It is applied intralesionally, called intralesional Bleomycin, its administration being very painful, but it is rapidly inactivated in all organs except the lungs and skin. Doses greater than 150 mg can lead to skin lesions and above 300 mg to lung reactions. This treatment presents a disparity of success, as already mentioned in a previous section.
    (3) Surgical treatments. A surgical treatment can also be performed, although in plantar warts it is only used when other treatments have failed. Surgical excision has the advantage of rapid removal of the wart, with success rates of up to 90% and recurrence rates of approximately 20%. However, with this type of treatment, extensive preparation and good qualification of the professional who performs it is necessary. Other treatment alternatives are acupuncture, painless and dry wart technique, homeopathy (with administration of certain medications that activate mechanisms for self-recovery and rebalancing), psychotherapy, ultrasound (recommended under water) and CO2 laser treatment and all them with their advantages and disadvantages.
    (4) Chemical treatments. For the systematic chemical treatment of the plantar wart (plantar human papillomavirus) chemical agents are used which, when applied, produce caustic burn necrosis. The use of these requires special precautions and are characterized by the dose and the format in which the product is applied, as well as the possible sensitization of the plantar wart that can lead to a resistance and an encapsulation process, being subsequently Its treatment is very difficult, which is usually very common in recurrent plantar warts. The main chemical treatments are described below.
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    There are two large groups of chemical treatments using alkaline agents or acid agents. Among the most commonly used alkaline chemical agents are sodium hydroxide (NaOH) and potassium hydroxide (KOH), being used as a solution at a certain concentration. These are hygroscopic and caustic products: both hydroxides have a great energetic power, cause considerable burns and have a great penetration power. Their main drawback is that it is a painful, highly irritating technique and for which a lot of product is needed .
    The acidic chemical agents used in the treatment of plantar warts can be soft and strong. They are presented in liquid form and in crystals, also being used as ointments. The crystals are the ones with the greatest energy power, since they are usually used as pure chemicals. The form of presentation is important at the time of the application technique, since the liquid forms are applied with cotton swab; in ointment or in crystalline form they are applied directly on the lesion with dressing coating The amount of substance applied and its effect varies according to the application format. In this way, the liquid forms are applied in less quantity than the ointment forms and these are less than the pure forms in crystals. In all cases it is essential to use felt or protective material of the tissues adjacent to the lesions to avoid cauterization of healthy tissues.
    Among the mild acidic chemical agents, salicylic acid is used both in liquid form with a concentration of 30% by weight or in ointment (pharmaceutical preparation of salicylic petrolatum) in a concentration of 30 to 80%. It does not produce large burns, varying its effectiveness rate according to various studies, as already mentioned in a previous section. Treatment is contraindicated in children because of the risk of systemic toxicity (salicemia). Lactic acid is also used, already used by the Egyptians to perform skin exfoliations, being painless but very prolonged treatment. It is indicated in areas of pressure and for children. Silver nitrate is widely used, widely used in risk areas, such as the periungual zone. It usually comes in the form of white crystals arranged in a bar. Once wet, it is applied to the wart that will present, within two days, a black color of reduced metallic silver. The treatment is usually combined with others using stronger acids.
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    As for strong acids, nitric acid is widely used at usual concentrations of 60 and 70% by weight and is applied by touches of the liquid to the wart. It has a great penetration power and the skin acquires a yellow color (reaction of xanthoproteic acid), repeating the process every three days until the skin acquires a pink hue without the presence of capillaries or papillae.
    Monochloroacetic acid or monochloroethanoic acid, an intermediate product in the manufacture of dyes, is an important raw material for the synthesis of carboxymethylcellulose, as well as for pesticides, drugs and dyes and organic synthesis in general as an alkylating agent. It is a very toxic substance. It is presented in the form of colorless, hygroscopic crystals, being very soluble in water (421 g per 100 mL of water at 25 ° C), as well as in other solvents. The pH of a 0.1 M aqueous solution at 20 ° C drops to 1.9. This acid, in its pure state, produces a great burn due to the hydrolysis of proteins, being an effective alternative for the treatment of warts but aggressive and painful, the combination with analgesics being very common in the treatment. It has the advantage that it applies to any patient with HPV infection, especially in young people without sex difference and in recurrent lesions. In patients with diabetic or peripheral vascular disease, scarring of any complication can be difficult and another substance with less aggressive power is needed. Also in multiple or very large lesions it is not recommended and the application of another method is necessary.
    In addition to its effect in diabetic patients, it is important to mention that the direct application of this chemical agent can cause an exaggerated reaction in some patients, leading to significant erythema and inflammation. The presence of hyperhidrosis decreases its effect because it facilitates self-contagion due to the opening of the pores of the skin and penetration of the virus into the epidermis. There are also other possible alternatives in the state of the art that combine this substance with salicylic acid to resolve papillomatous lesions more quickly, in addition to master formulas in which it serves as a basis for dermatological applications.
    Some documents that refer to the use of monochloroacetic acid (MCA) are:
    - "Current Contents in Wart Treatments" published in
    http://www.podiatrytoday.com/article/2606#sthash.XbMj39IG.douf
    Describes the use of MCA for the treatment of all types of warts. The treatment is applied by adding 100 gr of MCA crystals to 100 ml of water and acts as a chemo-surgical agent.
    - "Monochloroacetic acid application is an effective alternative to cryotherapy for common and plantar warts in primary care: a randomized controlled trial" S.C. Bruggink et al. J lnvest Dermatol. 2015 May; 135 (5): 1261-7
    It describes a comparison between treatment with ACM and treatment with cryotherapy in common and plantar warts. In this case the alternative treatment is cryotherapy with salicylic. The topical application of the MCA is done in a 76% saturated solution, in water.
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    In another article by this same author, S.C. Bruggink, obtained from the repository of the Universiteit Leiden, "Transmission and treatment of cutaneous warts in general practice", indicates that the MCA can be used as a keratolytic agent, but without reference to the form of application.
    - In CA2039643 "Anti - Wart Composition", the use of keratolytic agents, including MCA, is described for the treatment of warts in combination with a local anesthetic agent, a film forming fluid ("film forming fluid") and a adjuvant that can be ethanol.
    In GB2496656 "Film-forming formulation", a formulation is described which can be effective for the treatment of warts and which can comprise a keratolytic agent, a solvent that can be ethanol, a film-forming agent and a propellant.
    Other more aggressive chemical agents with properties similar to MCA are dichloroacetic acid (DCA) and, in particular, trichloroacetic acid (TCA). Either can be used to treat small warts. Both acids cause chemical coagulation of genital warts. The TCA was already used in the nineteenth century as an exfoliating agent.
    These two acids are presented in the form of crystals or in liquid form in solution, being applied identically to the MCA. It is always necessary to take precautions about the depth of the treatment in order to minimize the ulcerations and scars that these three golden organic acids can cause on the skin. All these treatments have great efficacy, but are associated with various degrees of irritation. Various pharmaceutical preparations with various chemical agents and active ingredients can also be used in the treatment of plantar warts. Among them, the use of cantaridine in solution, also associated with podophyllin and salicylic acid, can be highlighted. Podophyllotoxin (Podofilox) is the active substance in podophyllin, a resin composed of podophyllotoxin, 4-dimethylpodophyllotoxin, peltatin and b-peltatin and does not contain mutagens. It is used in a concentration of 1025% by weight diluted in alcohol or benzoin. It produces tissue necrosis. The use of a 0.5% podophyllin solution or gel by weight has also been proposed, the most common adverse effects of which are the signs and symptoms of local skin irritation. Even cantharidin and podophyllin have been combined in a pharmaceutical preparation with good results, close to 96% success after six months of treatment.
    An extended use in podiatric treatments is the application of "officinal formalin", formaldehyde (H-CHO) in solution at 40% by volume, which produces coagulation of proteins and, therefore, is used for conservation and embalming. It is used for the treatment of mosaic warts.
    Other acidic substances in less use and that constitute a true arsenal of chemical agents used for the treatment of plantar warts are citric acid, chromic acid, bichromate or potassium chromate, acetic acid, glacial acetic acid, pyrogallic acid, chlorabine, hydrochloric acid , naftol and others. Each has a different caustic power and effectiveness with different aggressiveness and irritability.
    With the composition object of the present invention a valid therapeutic alternative is offered without surgical treatment in the case of recurrent, resistant and multiple warts that allows to offer, to health professionals, an immediate solution for these cases, obtaining a high index of success, a high degree of safety and less suffering on the part of the patients, in addition to serving as the basis for a definitive treatment or of choice for such infections.
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    image19 Explanation of the invention.
    A first aspect of the present invention constitutes a composition for the systematic chemical treatment of the plantar wart consisting of a solution of monochloroacetic acid in ethanol.
    In a particularly preferred embodiment, the concentration of the monochloroacetic acid solution in ethanol is 50% by volume and 96% by volume ethanol (96 ° in alcoholic grade) is used to prepare the monochloroacetic acid solution.
    A second aspect of the present invention is a process for the preparation of the composition for the systematic chemical treatment of the plantar wart comprising the following steps:
    -  heating the monochloroacetic acid crystals to a temperature between 61 and 63 ° C to cause them to melt.
    -  mixing the liquid monochloroacetic acid resulting from the previous stage with 96% by volume ethanol (96 ° in alcoholic strength) in a 1: 1 volume ratio and the order of addition of 96% ethanol on the liquefied monochloroacetic acid.
    -  gentle agitation to favor mixing.
    The solution thus obtained is kept in a liquid state for a minimum of 15 days in a tightly sealed container. Detailed description of the invention
    The technical problem to be solved by the present invention would be to achieve a composition for the treatment of plantar warts that improves the results of other treatments already established with or without MCA, especially in relation to:
    -  less pain in removing the wart
    -  greater ambulatory capacity of patients
    -  Improvement of unwanted effects, such as the formation of vesicles or flictenas, or the reduction of inflammation.
    For this, it is proposed to use diluted MCA especially in cases of multiple warts or very large warts on the foot. In its purest form, the MCA is an aggressive chemical agent, so for its use it is recommended to take protective measures both for the patient (protection of the adjacent area) and for the professional who performs the application (handling care).
    It is known to perform a previous dilution of the MCA. Thus, for example, in the document
    '' Monochloroacetic acid application is an effective alternative to cryotherapy for common and plantar warts in primary care: a randomized controlled trial "by S.C. Bruggink et al. J
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    lnvest Dermatol. 2015 May; 135 (5): 1261-7 it is indicated that 76% saturated concentrations are used for topical application of MCA in plantar warts.
    Given the available data of solubility of the MCA (Solubility in water, 85 g / 100 ml at 20 ° C) it follows that the data refers to an aqueous solution. The solubility of MCA in other solvents is known: methanol, ethanol, isopropanol, diethyl ether and acetone. It is poorly soluble in hydrocarbons and chlorinated hydrocarbons. Of all of them, the most affordable for purity and low cost is ethanol.
    In view of the state of the art available, it could be considered that the professional who wishes to seek an alternative to the treatment of plantar warts using ACM and looking for a reduction of pain and unwanted effects and better ambulatory capacity, decided to use a solution of MCA instead of the pure product.
    It is intended that the undesirable negative effects with the application of MCA, according to the method of the invention, in the treatment of plantar warts be completely reduced, since it is an aggressive chemical agent. It is also about achieving an increase in internal validity in the treatment of plantar warts as it is a very varied and complex pathology, in general, that observed in patients. The reduction of negative or unwanted effects for its use is carried out through its use in liquid form after dilution, which implies a reduction of the aggressiveness of the substance, so that its use could be generalized for the treatment of all HPV conditions in the foot. As the solvent for this acid, organic compounds with hydroxylated derivatives, preferably alcohols and more preferably ethanol can be used for their purity and low cost.
    In general, due to the existence of multiple and different influence variables that imply a statistical study to verify the success or failure as well as the effectiveness of a therapeutic treatment, it can be noted that the unwanted effects and pain decrease with the application of acid in a certain concentration, but with an increase in the number of treatment sessions and could even lead to a decrease in the effectiveness of the treatment. On the contrary, the use of pure or more concentrated acid would lead to greater effectiveness, but at the expense of greater discomfort, discomfort and pain for the patient.
    With respect to other treatments, the method of the invention has as an advantage a specific treatment of the plantar wart as a valid alternative to improve the results of other treatments already established, with the proposal of a more valid and unique method of choice for most of the cases.
    In the usual forms of treatment with MCA, commercially crystallized monochloroacetic acid of 98.5% by weight is used, although the purest can reach 99.0% of wealth. It can be used by directly applying the crystals to treat HPV infection following a protocol of use. After this application on the tissue, normal heating occurs due to body temperature, liquefying by phase change to the liquid state. As an important advantage, the MCA burn is usually more progressive and late than other acids that perform a chemical cauterization at the first contact, such as nitric acid that is presented as a concentrated liquid. However, it is impossible to calculate the amount of MCA that is applied in crystalline form, even with a very specific control of the weight of applied crystals, previously crushed, when compared with a liquid state application of the same acid. Likewise, the different form of application produces a different amount of product as an active principle that can act and also implies a very different duration of the caustic effect.
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    Consequently, the problems of applying MCA are easily solved if the use and use of this monochlorinated organic acid is carried out in a liquid state. To do this, the pure acid can be liquefied or used in diluted form from the liquid, but still effective. In the process of the invention, a small amount of pure MCA crystals are taken and subjected to the action of heat taking advantage of the fact that their melting range is relatively low (61-63 ° C). Therefore, a high temperature is not necessary to get the crystals from the solid state to the liquid.
    Of all the existing dissolution possibilities, it has been found that the choice of a composition consisting of a solution of MCA crystals, previously molten, in ethanol from 96% by volume (96º in alcoholic degree) to 50% is the one with the lowest unwanted symptoms or effects, in particular flictena and inflammation compared to the application of pure acid. Embodiment of the invention
    Preparation of the MCA solution
    In a non-limiting example of the invention, 3,000 grams of 98.5% pure MCA are weighed and treated in a sterile glass vessel arranged in a water bath. In a few minutes (5-10 minutes), the crystals enter the liquid state due to the melting range of this substance, which is 61 to 63 ° C. The temperature can be controlled with a thermometer so that it is not higher. The 3,000 grams of MCA crystals produce 2 mL of liquid, which almost coincides with the theoretical value calculated if the density of pure MCA at 25 ° C is considered to be 1.40 g / mL.
    The temperature in this preparation should not be exceeded because the heating of the acid can cause its decomposition with the emission of toxic gases that must not be inhaled by the operator or the patient.
    Once the molten or liquefied form of the pure acid is obtained, an exact amount thereof is collected using, for example, a sterile, heat-resistant syringe of 5 ml of maximum capacity. The amount of acid in its liquefied form is introduced into a sterile glass container. Then another sterile syringe is filled with the exact same amount of a short chain alcohol, preferably ethyl alcohol (ethanol) for its purity and low cost, and more preferably with a concentration of 96% by volume, 96 ° expressed as alcoholic strength .
    The alcohol is carefully mixed with the acid in the container where the liquid MCA was introduced before. Mixing is favored by very gentle agitation.
    The order of addition is alcohol over liquefied acid. In this way, an exact dilution of 50% by volume is easily achieved. With the process of the invention it is found that this 1: 1 volume solution thus obtained is stable for a long time and does not quickly return to its solid state at room temperature, keeping it in a liquid state for many applications. It can be kept in a liquid state for more than 15 days in a tightly closed container.
    It is important to mention in this example that in the tests carried out to determine the effectiveness of the treatment, this dilution of the MCA with 96º ethanol has been carried out just before its application and has been used only for a single session. In this way, attempts have been made to eliminate any external factor that may intervene in an undesirable way in the results obtained.
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    To compare the validity of the undiluted MCA treatment or mixed with solvent for control purposes, the pure MCA crystals are heated and liquefied in a water bath as described above, pouring into a sterile container or treatment vessel. In this case, the speed of action is important because the pure acid in liquefied form is not as stable as that diluted with 50% volume ethanol, precipitating upon cooling below its melting point and returning to the solid state in form crystalline Therefore, the application must be consecutive to the liquefying of the crystals.
    In the development of the treatment tests and their effectiveness, the two products, MCA diluted with 96% by volume ethanol and pure liquefied acid, are properly discarded after use, the process being re-carried out in each application session. Therapeutic use method
    For the therapeutic application method, the review of the state of the art is taken into account to achieve a thorough and careful method of applying the treatment in order to achieve validity results.
    According to the study carried out, the method or the correct use of monochloroacetic acid (MCA) in treatments is not clearly described from the previous background. Thus, if solid MCA is directly applied as a crystalline substance, it can happen that a given crystal has a larger section, size or weight in one application than in another, with the consequent increase in its caustic effect and the impossibility of a correct measurement for the Follow-up of therapeutic treatment. This could be resolved after crushing, but the crystals are hygroscopic and the reduction in particle size accelerates this process in the air. The crystalline form of the acid produces a more lasting burn on contact with the skin than under liquid form (liquefied) and there would be some inability to perform an estimate of the amount of MCA used. Accordingly, a form of application should also be chosen using a sterile cotton swab or stick that has previously been introduced and impregnated in the acid and better in liquid form. It is an easy way to use, perhaps the easiest, being homogeneous and so it can be applied in all sessions and in a more exact way during the same application time.
    According to several previous studies of the state of the art, an application of MCA is usually accompanied by other substances. The application of salicylic acid or neutral petrolatum is very frequent as well as both (salicylic petrolatum) to increase the effect of the ACM or decrease its negative effects, such as irritation of the surrounding tissues. With the process of the invention only MCA is applied and thus its results are evaluated without variation of techniques or other chemical substances during the entire treatment time.
    The design of the method of use and therapeutic application of MCA involves the following stages:
    1) Delamination. The wart lesion must first be delaminated from its external hyperkeratotic tissue, for which a scalpel blade is used, it is important not to bleed the warty papillae, since bleeding could also alter
    or modify the action of the MCA.
    2) Protection. Once the plantar wart is delaminated and exposed, it is delimited around with a felt or "moleskin", thus protecting the healthy peripheral tissue.
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    3) Impregnation. The preparation for the application of the MCA according to the process of the invention is carried out by completely impregnating a swab or a sterile cotton swab and without draining, preventing only its dripping or exit out of the application area.
    4) Normal use and application in warts. The application of the stick on the wart is carried out for a time between 20 and 40 seconds, preferably 30 seconds, after which a reasonable time is allowed to dry, not exceeding 5 minutes, then covered with sterile gauze and a bandage of crepe. Experience indicates that it is not advisable to use felt or adhesive tape on the wart and should be discarded to avoid possible irritation and maceration that they produce in some cases.
    5) Use and application in warts located in loading areas. It is important to keep in mind that if the warty lesions occur in loading areas, as is usually more frequent in this type of isolated lesions, the burn due to the application of pure MCA in crystals or liquefied can be greater. Therefore, the use of MCA in a liquid state following the procedure of the invention of dilution 1: 1 by volume with 96 ° alcohol, has the advantage that limits this possible confounding factor.
    6) Use and application sessions. After each session, you can give regular guidelines or normal recommendations for this type of treatment, as follows:
    a) The patient cannot wet the treated area for four days since the MCA is a very soluble product, being able to move to other areas and producing burns in healthy parts of the skin or also decreasing its effectiveness. The initial bandage placed after the application of the MCA should not be removed or changed.
    b) Antiseptics, creams or other substances should not be applied until indicated in case the bandage is moved.
    c) Use pain relievers only if necessary when pain has been experienced.
    d) Consult the practitioner any doubt or unforeseen situation before the review or next application.
    7) Evaluation of the treatment. After an estimated time between 90 and 100 hours, preferably 96 hours, after the application of the treatment, its effect is assessed. An estimated time is established for a new session and application that can last from days to weeks.
    In the process of the invention and its method of application, the time is set to 2 weeks. This time is assumed to be sufficient for the healing of the burn produced and the possible flictena or vesicle.
    After this period of 2 weeks after the treatment, it is reexamined, proceeding with a delamination and cleaning of the area treated with a scalpel, verifying that there are no papillae or tissue suspected of persistence of the wart from which a new application is decided. If this is the case, the patient is monitored for a period of 6 months with successive revisions, verifying the total removal of the wart and not recurrence.
    8) Number of sessions. If necessary due to the clear existence of warty tissue, the treatment is reapplied as described in the method of application of the invention, establishing a maximum of five (5) sessions for infection reduction.
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    It is very important to take into account the case of patients who are diabetic or with peripheral vascular disease. In these cases, the healing of any complication can be difficult and, therefore, the use of another substance with less aggressive power is necessary. Also, in multiple or very large lesions, the application of another method is recommended. Determination of the result of u so and application of the procedure of the invention (following a treatment protocol)
    In determining the result of the use and application of the therapeutic method and method of the invention it is necessary to resort to statistical analysis of the data obtained in patients.
    As a multitude of variables influence, this statistical analysis is carried out taking into account a randomized, parallel and simple blind clinical trial from two groups (53 subjects in the study group and 49 subjects in the control group) and the tables of contingency and categorical variables in terms of frequency, expressed in certain cases in percentages; the quantitative variables, by means of measures of central tendency (average), standard deviation (dispersion of data) and, in certain cases, minimum and maximum values. A study of the form is carried out, thus checking whether certain variables follow or not the normal distribution model through different methods, such as inferential tests or asymmetry indices, to which descriptive descriptions of centrality and variability are added.
    In some cases it is usually checked whether there are variables with strange values outside the usual range in the study population or "outliers" data, for which different "box-plof" graphics can be used. The study of the form determines the parametric techniques used for hypothesis contrast. For inferential analysis using contrast tests, various tests (such as those of Kolmogorov-Srminov and Shapiro-Wilk) are used to determine the normality of certain variables.
    The "t" test (Student-Fisher) is also used to compare means, Pearson's Chicuadrado for the comparison of qualitative variables and, where appropriate, continuity correction (Yates correction). As a non-parametric test, the U (Mann-Whitney) test and the Pearson correlation test have been used for some quantitative variables.
    To carry out a comparative statistical study of the validity and effectiveness of treatment with undiluted MCA or mixed with solvent for control purposes, the two products, MCA diluted with alcohol and liquefied pure acid, are properly discarded after use, being re-performed the process in each application session.
    In the clinical trial, the patient sample is selected by statistical criteria: 102 patients in total, 49 patients being for the control group and 53 patients for the study. Pure MCA is applied to the control group and MCA diluted in alcohol of 96º to 50% by volume is applied to the study group and, in both cases, with the application method described. For the evaluation of the results obtained, a randomized, parallel and simple blind clinical trial is designed and the statistical treatment is carried out. With these tests to verify and quantify the success of the treatment, the patients who are the object of the statistical study do not know at any time what treatment they are being applied, since the color, method of administration and packaging must always be identical. The results obtained are highlighted below:
    image35
    image36
    image37
    (to)  The use and application of MCA diluted in alcohol of 96º to 50% by volume, according to the method of the invention, produces the same result in terms of the elimination of the plantar wart when compared with the application of pure MCA following in both cases the method described in the process of the invention with a Significance Level (NS) of 0.203 for an established type I error (α) of 0.05 and no significant differences in relapses, with NS being = 1,000 for α = 0.05.
    (b)  The use and application of MCA diluted in alcohol of 96º to 50% by volume according to the method of the invention also produces less pain in the elimination of the plantar wart, since N.S. = 0.000 but not only in the total treatment, but in each of the 5 treatment sessions performed, N.S. = 0.000 in first, second and third session, and N.S. = 0.006 and N.S. = 0.008 in the fourth and fifth sessions, respectively.
    (C)  The use and application of MCA diluted in alcohol of 96º to 50% by volume in the treatment of plantar wart also produces an improvement in the ability of patients to wander normally after each treatment (N.S. <0.001). The number of sessions necessary for the elimination of the infection is increased substantially (N.S. = 0.0000).
    (d)  With the use and application of the MCA diluted by the composition object of the invention, a substantial improvement of the undesirable effects is also achieved, such as the formation of vesicles (NS <0.0001) although it is not so with other effects, such as inflammation, obtaining NS = 0.969 with α = 0.05 as well as other unpredictable effects (N.S. = 0.297), the latter occurring very infrequently.
    (and)  Through the use and application of diluted MCA, through the composition object of the invention and the method described, it is deduced from the statistical test results of the clinical trial that there is a greater ambulatory capacity and less flictena since the patients examined do not they suffer from it or suffer in a significantly lower percentage compared to the application of pure MCA.
    In short, the use of MCA diluted in alcohol from 96% by volume (96º in alcoholic strength) to 50% by volume by means of the composition object of the invention and the method described, produces an improvement in the pain manifested by patients without decrease its effectiveness in the treatment of plantar warts, also improving pain and ambulatory disability caused during treatment, although the number of sessions necessary for the elimination of this infection increases.
    权利要求:
    Claims (5)
    [1]
    image 1
    one.  Composition for the systematic chemical treatment of the plantar wart consisting of a solution of monochloroacetic acid in ethanol.
    [2]
    2.  Composition for the systematic chemical treatment of the plantar wart according to claim 1, characterized in that the concentration of the monochloroacetic acid solution in ethanol is 50% by volume.
    [3]
    3.  Composition for the systematic chemical treatment of the plantar wart according to claims 1 or 2, characterized in that 96% by volume ethanol is used in the preparation of the monochloroacetic acid solution.
    [4]
    Four.  Method for the preparation of a composition for the systematic chemical treatment of the plantar wart as defined in claims 1 to 3, characterized in that it comprises the following steps:
    -  heating the monochloroacetic acid crystals to a temperature between 61 and 63 ° C to cause them to melt.
    -  mixing of the liquid monochloroacetic acid resulting from the previous stage with 96% by volume ethanol in 1: 1 volume ratio and the order of addition of 96% ethanol on the liquefied monochloroacetic acid.
    -  gentle agitation to favor mixing.
    [5]
    5. Procedure for the preparation of a composition for the systematic chemical treatment of the plantar wart according to claims 1 to 4, characterized in that the solution obtained is kept in a liquid state for a minimum of 15 days in a tightly sealed container.
    fifteen
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    同族专利:
    公开号 | 公开日
    ES2614779B1|2018-05-04|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    CA2039643A1|1990-05-07|1991-11-08|Karl F. Popp|Anti-wart composition|
    US20020044816A1|2000-10-13|2002-04-18|Pedinol Pharmacal, Inc.|Method for applying a medicament and swab applicator for use therewith|
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