MXPA96006055A - Formulation of topical use of acetic acid and blue methylene, for treatment of local skin and mucous infections caused by vi - Google Patents

Abstract

The present invention relates to the formulation of 99.8% acetic acid plus 1% methylene blue, useful and effective for topical application in viral infections located on skin and mucous membranes. This utility derives from the ability of the formulation to inactivate viruses locally and denaturalize proteins on contact with surfaces and epithelia, causing surface destruction of infected cells. The proper and prudent use of the formulation can be applied in vivo in affected patients and benefit thousands of people.

Description

DESCRIPTION TITLE Formulation of topical use with acetic acid plus methylene blue, for the treatment of local skin infections and many things caused by viruses. TECHNICAL FIELD Pharmaceutical, topical medication BACKGROUND MUCOCUTANEOUS INFECTIONS CAUSED BY VIRUSES The most common infections caused by viruses at the skin and mucous membranes are due to human papillomaviruses. The infectious nature of vulgar warts was demonstrated in 1907 by Ciuffo, obtaining the induction of warts-by autoinoculation (1). Viral DNA sequences can be demonstrated in infected tissues (2,3,4). The location of the papillomavirus is very varied, it can be found in benign lesions such as vulgar warts on the skin, laryngeal papillomas and genital warts, they have also been associated with premalignant lesions such as cervical, vaginal and vulvar dysplasia. The association of human papillomavirus and cancer-is demonstrated, being the most frequent association in genital cancer, respiratory and digestive tract (5,6,7). The diseases that produce these viruses are diverse, requiring clinical experience and several diagnostic methods to determine the association of human papillomavirus and disease. Clinical experience serves to diagnose macroscopic lesions such as warts on the skin, papillomas on many things and condylomas on the genitals. For less obvious lesions, colposcopy, cytology and histopathological study are required. Human papillomaviruses cause cell-cell changes called atypia coilocitica with or without dysplasia, due to pathology criteria. Colposcopy is a subjective method, for relate changes in the epithelium, which are observed with optical magnification and applying liquids to react the e-pitelio and offer a change of color. The frequently used liquids are saline solution, lugol and acetic acid in this diagnostic method the acetic acid is used very diluted at 3 _ 5% and without dye and without therapeutic intention. The saline solution and the diluted acetic aido add a color change of the epithelium to white color, which is called a white or acto-reactive active area. Lugol causes a brown color in the normal cervical epithelium and does not stain areas with dysplasia, with iodonegative areas being called. It is important to point out that since the colposcope was invented in 1925 by Hinselmann, 99.8% acetic acid and -1% methylene blue were not used as therapeutic in viral lesions. Molecular biology techniques confirm the presence of -viruses in infected tissues. At present, 70 types of human papillomavirus are known and some of them, such as el-16-18, have oncogenic power, being able to transform human keratinocytes in vitro (8,9,10). The management of human papillomavirus infections has been difficult and - it continues to be so. Invasive methods are used to destroy infected tissues, in this group surgical excision, cauterization, cryotherapy and laser are found. All these methods - they are expensive, they are not free of percentage of failure or relapse - it is not possible to apply them in 100% of the genitals. Another alternative or complement to the previous ones are the non-invasive methods which pursue some effect to limit or diminish the infection and favor the eradication of the virus, the routes of administration are generally intralesional or intramuscular topical. As a historical antecedent, reports of local application of bleomycin, meto trexate, thiotepa and podophyllin are considered obsolete (10). The useful medicines are the following: P0D0FIL0T0XINA: Topical use, once a week. It has local toxicity characterized by burning and pain. It can be applied -in penis and vulva (11). FLUOROURACIL: Topical use, cream at 5%, once a day 5 - days, has local and systemic toxicity, it is applied to the anus, vagina and urethra (10). ACID TRICL0R0-: Topical use, local toxicity.is used in injuries 90% ACETIC, isolated as a single touch, can be applied to the vulva, penis and perineum (12). INTERFERON: Topical, local and sitemic toxicity, different is-ALFA burn and dose, variable results, it is applied on infected skin and mucous membranes, it is expensive (13). INTERFERON: Topical or intralesional, local and systemic toxicity BETA different schemes and doses, variable results- is applied on infected skin and mucous membranes.is expensive (14) INTERFERON: Intramuscular, systemic toxicity, is used in lesio-extensive gamma, different doses and schemes, variable results, it is expensive (15). FILIPÉNDULA: Topical preparation of the flowers, experimental (16) ULMARIA RETINOIDES Y: Variable results in topical use (17) VITAMIN A FOLINIC ACID: Variable results, orally (18). None of these methods is free from failure, they can not be applied to the general population. There are no previous reports with the use of 99.8% acetic acid plus A1.6 methylene blue for topical treatment of human papillomavirus infections. VIRUS OF HERPES The existence of herpes has been known for 2000 years; the term derives from the Greek (herpein = drag), in 1700 it is considered venereal infection and in 1940 the viral character of the infection was postulated, in 1960 two types of herpes virus were identified, the type 1 that causes more commonly the labial lesions and the type 2 most frequently causing genital lesions. Herpes viruses are a group of about 80 -types are DNA, considered epi teliomuconeurotropes. Of this group only 5 can affect man and are HSV 1, HSV 2, VZV-varicella-zoster, EBV Epstein-Barr virus and CMV cytomegalo-virus. These viruses cause primary, latent and recurrent infection. The diagnosis requires experience and auxiliary methods such as cytology, colposcopy, molecular biology techniques. The treatment includes drugs that improve the response in the wrist, such as interferon, levamisole, cimetidine, metisoprinol and topically to fight bacterial infection added local antiseptics and creams with antibiotics. The direct anti viral therapy with acyclovir, whose chemical name is 9- (2-hi-d-oxethoxymethyl) guanine, causes a selective blockade of viral replication, is administered intravenously and orally. The HIV human acquired immunodeficiency virus also affects skin and mucous membranes, one of its transmission routes is sexual. They are retroviruses that depend on a reverse transcriptase enzyme (RNA-directed DNA polymerase) to replicate -in the cell. It mainly affects CD4 lymphocytes because they have a receptor for the virus, they cause latent infection remaining integrated into the genome or active infection by viral replication. The treatment is aimed at limiting or eradicating the infection if you fear, but topical genital treatment is neglected. The treatment includes antibiotics against opportunistic infections and against the virus, the best medication until now is zidovudine (AZT) (10) All mentioned viruses can be inactivated locally in-vivo using 99.8% acetic acid and blue 1% methylene - this offers a valuable alternative to add to local control of viral infections. This novelty has not been applied so far in medicine. The proper use of the formulation of this description can be very beneficial for thousands of people. BACKGROUND TO ACETIC ACID Pure acetic acid is a colorless liquid (d = 1.05) of spicy color, it crystallizes easily (mp = 16.6 ° C), which is why it is known as glacial or crystallizable, it boils at 118 ° C under pressure atmospheric. It is miscible with water in all proportions - with heat release and volume contraction. It is dissolvent of a large number of organic substances, it is hardly combustible and its vapor burns badly. It is considered a weak acid (Pk = 4.76). The name comes from acetum or vinegar because it is found in this product. Its formula is CH -C0.0H. * 15 INDUSTRIAL MANUFACTURE The oxidation of acetaldehyde at 80 ° C in the presence of manganese acetate Mn (CH-C0.0). Currently satisfies most of the industrial needs. CH-CHO + 0 - * CH -C0.0H 80 ° CMn (CH -CO.O) BACKGROUND OF THE METHYLENE BLUE It is a derivative of phenothiazine.es synthetic dye, basic-antiseptic properties. The use in medicine is like coloring of cells and treatment of methemoglobinemia. Its formula is the following.

DETAILED DESCRIPTION OF THE INVENTION The formulation is considered to be acetic acid -99.8% plus 1% methylene blue, for topical use in skin and -mucosa infected by viruses. Because there is no history with the same formulation and use. Acetic acid at concentrations of 80-100% has the ability to locally inactivate viruses on living surfaces - and objects. This inactivation is due to the denaturation of viral proteins upon contact with the acid pH. Acetic acid at concentrations of 80 to 100% has the ability to denature cell proteins of superficial skin cells and mucous membranes, causing superficial destruction limited to contact with acid PH. These two properties of acetic acid at said concentration can be applied in vivo in patients with viral skin and mucous infections. The capacity of acetic acid at a concentration of 80 to 100% of the virus to locally inactivate and denature proteins, is not lost by mixing the acid with dyes, local anesthetics and their miscible substances with it. Methylene blue is miscible with 80-100% acetic acid, gives blue to the formulation-which allows to observe the penetration of the formulation to the cells. The formulation of acetic acid and methylene blue at the mentioned concentrations is a universal inactivator of vi-rus, among which are those transmitted by sexual contact such as human papilloma virus, herpes sim virus type foot 1 and 2, virus of Epstein-Barr, cytomegalovirus and human immunodeficiency virus. The formulation is preferably prepared with 100 ml of 99.8% acetic acid by adding 50 mg of methylene blue at 1% - for every 10 ml of 99.8% acetic acid, 5 mg of 1% methylene azole is added. In the following examples, I mean ^ :; to the use of this formulation. EXAMPLES The formulation of acetic acid and methylene blue results in an effective local inactivating of viruses at the skin and mucous levels. The infection with human papillomavirus is the most common so I start with a clinical trial on them. The Maternal and Child Hospital (HMI) of the Social Security Institute for workers of the State of Mexico and Munici pios (ISSEMY (has a clinical trial in charge of the oncology service, where it has been possible to demonstrate the efficacy of the formulation of acetic acid and methylene blue for the treatment of genital infections caused by papilloma papiloma virus The trial is prospective, controlled, non-randomized INCLUSION CRITERIA: Female patients, over 16 years of age, without serious chronic diseases, with clinical evidence of warts, papillomas or condylomas in genitalia Patients with colposcopic, cytological or histological evidence of infection of human papillomavirus EXCLUSION CRITERIA: Patients who did not meet the requirements, patients with vasculitis and collagen diseases with geniinfection such, patients with chronic diseases of non-infectious skin and genital involvement.

CHARACTERISTICS OF THE EXPERIMENTAL AND CONTROL GROUPS EXPERIMENTAL GROUP CONTROL GROUP No of patients 15 No of patients 10 Age range 17-50 years Age range 23-50 years Average age 34.4 years Average age 34.1 years Background of. . ,. , Antecedent of cancer 13. .3% cancer 50.0% Residence ur- Residency ur bathes 53., 3% bathes 60.0% Smoking + 6., 6% Smoking + 20.0% 0 Occupation remu¬ Remunerated occupation 46.6% nerada 70.0 Start of life- Starts of sexual life, range 15-32 years sexual, range 17-25 years Average 21 years Average 21.6 years 5Promiscuity + 26.6% Promiscuity + 10.0% Parity, average 2.4 deliveries Parity, average 2.6 deliveries Time of sickness Decrease me to less than two years 90% to 2 years 80% Injuries in vul Injuries in vul- »va" va Injuries in va- "Injuries in va-"? _ ".? .D *. 30.0% gina gina Le si ón es en cer - 0. - 13.3% Lesions in cer, _ "". Vix - 10.0% vix 5TRATAMIENTO IN THE EXPERIMENTAL GROUP Partial resection of the affected area or application of cryotherapy was carried out in the affected area not resectable, then the formulation of acetic acid and methylene blue form topical form was applied to the external genitalia CONTROL GROUP TREATMENT Partial resection of the affected area or application of cryotherapy was performed in the unresectable affected area. applied bidistilled water on the external genitalia.

DURATION OF THE TREATMENT 6 months, applying topical treatment once a month with or without repeated application of cryotherapy or surgery, depending on the number of lesions and area affected. The same was done in the control group, but bidistilled water was applied in each treatment. POSOLOGY The maximum benefit of the formulation of acetic acid and methylene blue is achieved by carefully and prudently using the solution in strict accordance with the following steps. 1. All the patients are explained the effect of burning and tolerable pain that they will feel and that will be reduced to the minimum use of local anesthetic prior to the application. 2. Before applying the formulation, the application of local anesthetic at 10% Spray on the skin and mucosa to be treated is required. This is very important to be able to apply the genital, perineal and anus solution. Without the local anesthetic the formulation is not applied because it causes intense pain and burning. 3. After waiting 2 minutes. 4. Wet a swab with the formulation, removing the excess in the same container so that it does not drip. With a quick maneuver, the gents are contacted with the area to be treated. 5. At the moment in which the patient reports burning and pain, more local anesthetic is applied and washed with water until the discomfort is controlled (fast maneuvers). 6. Finally, the treated area is dried. 7. The effect of inactivating viruses locally is - at the moment of contact of the formulation with the epithelia - no more applications are required at the same site in a treatment, nor to prolong the patient's burning and pain, because what can be washed with water to mitigate the discomfort. 8. The first time someone uses the formulation, it should be done in small areas, as experience is gained, the discomfort is minimal for the patient.

SIDE EFFECTS OF SYSTEMIC FORMULATION: not detectable with the topical dose used. LOCAL: Ardor_y__dolor_al_momento of the application, which - was tolerable when previously using a local anesthetic in 10% Spray. It was quickly mitigated when washed with water. Erythema after the application which lasts 2 to 3 days. 5 - £ -? - í £ í2Il_ £ iliS "was observed at 8 days] _l ££ __-__ i £ __- £ Ii ^ e ampoules, a case of the trial at 2 - hours of the application, was limited and did not require more care than local cleaning. MECHANISM OF ACTION The formulation of 99.8% acetic acid and 1% methylene blue has the capacity to inactivate viruses locally due to its acid pH, secondary to the denaturation of viral and cellular proteins. This causes superficial destruction of infected cells without penetrating the entire thickness of the epithelium. This effect is achieved at the moment of the contact of the formulation. MEASUREMENT OF THE EFFICACY OF THE FORMULATION It was assessed by percentage of response considering: COMPLETE ANSWER: Disappearance of 100% of injuries and all the symptoms. PARTIAL RESPONSE: Disappearance of more than 50% of the lesions and incomplete disappearance of symptoms NO RESPONSE: Disappearance of less than 50% of the lesions and persistence of the symptoms RESULTS IN THE EXPERIMENTAL AND CONTROL GROUPS EXPERIMENTAL GROUP CONTROL GROUP Effect of the treatment- Effect of the treatment with-with the formulation of acrycotherapy or surgery, followed acetic and blue of double-distilled water. In -leno, after criotera- patients with infection with pia or surgery in papilloma humanot-genital infection patients with genital infection. human papilloma virus. No of patients 15 No of patients 10 Complete answer 12 Complete answer 5 Partial answer 3 Partial answer 5 No answer 0 No answer 0 Proportion 0.8 Proportion 0.5 Confidence interval Confidence 95% za 95% 0.69 69% 0.27 27% 1.0 100% 0.88 88% CONCLUSION The formulation of 99.8% acetic acid and -1% methylene blue is effective in the treatment of local infections by human papilloma virus, increasing the control of viral infection using invasive methods of surgery and cryotherapy. THE EFFECT OF THE VIRAL INACTIVATION OF THE FORMULATION HAS ALSO OBSERVED WITH THE VIRUSES OF THE SIMPLE HERPES TYPE 1 AND 2 AND VIRUSES - OF THE HUMAN IMMUNODEFICIENCY, I POINT THREE CASES AS EXAMPLES.

CASE No 1 A 24-year-old female patient, married, a secretary- with an active sex life and a promiscuous husband. He went for - presenting Papanicolaou with coilocitic atypia and lesions of genital herpes. The formulation of acetic acid was applied to the genitals and oral acyclovir was indicated. - In this patient faster recovery was observed and - less relapse than in other patients with genital herpes, CASE No 2 Female patient of 32 years of age, Married, dedicated to the home who came to present aphthae in mucosa of oral cavity, had already received treatment with acyclovir, but relapses were presented with fever or heat. The oral mucosal formulation was applied, controlling infection and relapses. It was observed that local control is added to the systemic control in the case of herpes simplex. In the two cases of herpes simplex, greater control of the symptoms was observed using the acetic acid formulation, than in that observed in other patients treated only with acyclovir. CASE No 3 Female patient of 35 years of age, married, dedicated to the home, with a promiscuous husband, with a history of being seropositive patient for HIV, attended because of genital infection due to human papillomavirus. The control of the patient with respect to human papilloma virus infection with conventional methods had not been complete. That is to say, with cryotherapy, persisting the infection and the symptoms of vaginal discharge and pruritus. Until the formulation of acetic acid and methylene blue was added topically in the genitals, control of the human papilloma virus was achieved. It is possible that the human immunodeficiency virus also requires local inactivation to improve the systematic control of the infection

Claims (2)

1. CLAIMS Having sufficiently described my invention, I consider it a novelty and therefore I claim as my exclusive-property, contained in the following clauses 1 The use of the formulation of 99.8% acetic acid plus 1% methylene blue as a topical treatment for skin and mucous infections caused by human papillomavirus herpes simplex type 1 and 2 and human immunodeficiency virus. 2. The use of the acetic acid formulation as a universal virus inactivator in vivo and in vitro. On live surfaces and contaminated eyes. 3. The use of the formulation of acetic acid to 99.8% plus the mixture of dyes, local anesthetics or miscible substances with it, for the same use. SUMMARY The formulation of 99.8% acetic acid plus 1% methylene blue is useful and effective for topical application in viral infections located in skin and mucous membranes. This utility derives from the ability of the formulation to inactivate viruses locally and denaturalize proteins on contact with epithelia, causing surface destruction of infected cells. The proper and prudent use of the formulation can be applied in vivo in affected patients and benefit thousands of people. lf3.7 BIBLIOGRAPHY 1 Ciuffo G. 1907 Inesto positiv with filtered di verrucae vol gare Giorn Ital Mal Venereol 48:12.
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