US 2013 0309296A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0309296A1 Moreno González et al. (43) Pub. Date: Nov. 21, 2013

(54) PHARMACEUTICAL COMPOSITION AND Publication Classification DEVICE FOR PREVENTING, TREATING AND CURING ULCERS ON ADABETC FOOT (51) Int. Cl. AND OTHERWOUNDS, WHICH INCLUDES A6IL 5/44 (2006.01) SNAL SLIME FROM THE SPECIES A6IF I3/06 (2006.01) CRYPTOPHALUS ASPERSUS OR HELIX (52) U.S. Cl. ASPERSA MULLER AND CPC ...... A61L 15/44 (2013.01); A61F 13/064 PHARMACEUTICALLY ACCEPTABLE (2013.01) CARRIERS AND/OR ADDITIVES USPC ...... 424/446; 424/547: 602/48 (57) ABSTRACT (76) Inventors: Elmo Ernesto Moreno González, Santiago (CL); Nieves Galdames Flores, The present invention is related to a pharmaceutical compo Santiago (CL) sition comprising Snail slime of Helix aspersa miller (Cryp tophalus aspersus) (5% to 50%) and marigold extract, pro (21) Appl. No.: 13/980,735 polis and/or almond oil and pharmacologically accepted additives for the prevention additives and/or pharmaceuti (22) PCT Fled: May 20, 2011 cally acceptable excipients to form a formulation of interme diate to high viscosity (200 to 1000 Pa-s). This invention also (86) PCT NO.: PCT/CL11AOOO31 relates to the use of a composition which can be formed as a S371 (c)(1), cream or a gel, is preferably soaked in gauze, and shaped as a (2), (4) Date: Jul.19, 2013 bandage or sock for the treatment and cure of diabetic foot ulcers and other severe wounds, particularly those associated (30) Foreign Application Priority Data with diabetes, gout, Lesch Nyhan syndrome or other condi tions to the skin, including, keratosis, onychomycosis, ring Jan. 21, 2011 (CL) ...... 143-2011 worm, among others.

Patent Application Publication Nov. 21, 2013 Sheet 1 of 3 US 2013/030929.6 A1

Figura 1 Patent Application Publication Nov. 21, 2013 Sheet 2 of 3 US 2013/030929.6 A1

S(36) M.39) LA2) XL(45) ///

Figura 2 Patent Application Publication Nov. 21, 2013 Sheet 3 of 3 US 2013/030929.6 A1

US 2013/030929.6 A1 Nov. 21, 2013

PHARMACEUTICAL COMPOSITION AND DM type 1 estimated prevalence of 0.5% of the diabetic DEVICE FOR PREVENTING, TREATING AND population, is significantly lower than global estimates (4 and CURING ULCERS ON ADABETC FOOT 6%)(Ministry of Health, MINSAL, Chile 2005). AND OTHER WOUNDS, WHICH INCLUDES 0005 According to the results of the Multinational Project SNAL SLIME FROM THE SPECIES of Diabetes in Children (DiaMOND), Santiago of Chile have CRYPTOPHALUS ASPERSUS OR HELIX one of the lowest incidence of type 1 DM in the world, 1.6 per ASPERSA MULLER AND 100,000 in children under 14 years old, between 1990-1992. PHARMACEUTICALLY ACCEPTABLE (Karvonen M, et al., 2000). CARRIERS AND/OR ADDITIVES 0006 Based on the National Register of incidence of DM1 in children under 15 years old, conducted by the MINSAL FIELD OF THE INVENTION between 1995 and 2000, there was an average of 150 cases per 0001. This invention relates to the use of a composition year. To determine the incidence in the entire population, one and device containing Snail slime, marigold extract, propolis should add in the incident cases of patients over age 15 and/or almond oil and pharmacologically accepted additives (estimated at 30 additional cases), which would give a total of for the prevention, treatment and cure of diabetic foot ulcers 180 cases per year in the country. It is estimated that approxi and other severe wounds, especially those associated with mately 75% of these would be beneficiaries of System of diabetes. National Services of Health (SNSS), bringing 135 new cases of DM1 each year (Ministry of Health, Chile 2005.) BRIEF DESCRIPTION OF THE INVENTION 0007 Diabetes mellitus Type 2 is characterized by insulin resistance, which is usually accompanied by a relative defi 0002 The present invention is related to a pharmaceutical ciency of insulin (Ministry of Health, Chile 2005). composition comprising Snail slime of Helix aspersa miller 0008 Diabetes Mellitus Type 2 (DM 2) is frequently (Cryptophalus aspersus) (5% to 50%) and additives and/or asymptomatic, so the diagnosis is made in about 50% of cases pharmaceutically acceptable excipients to form a formulation for laboratory tests ordered for another reason and not by of intermediate to high viscosity (200 to 1000 Pa-s). This clinical Suspicion. The scant classic symptoms determine, composition, which can be formed as a cream or a gel, is with high frequency, a late diagnosis and the presence of preferably soaked in gauze, and shaped as a bandage or sock chronic complications. This type of diabetes increases with to be applied over ulcerous wounds or other skin-like condi age, obesity and physical inactivity and usually is associated tions. The composition contains natural extracts such as mari with other high-risk cardiovascular diseases such as hyper gold extract, propolis and vegetable oils. Further claimed is tension and dyslipidemia, so inquest to DM is indicated in the preparation process of the composition and its use for these individuals (Ministry of Health, MINSAL, Chile 2005). preparing a medicament or device for preventing or treating 0009. By 2000, it was estimated that over 35 million illnesses of ulcers or poor prognosis wounds generated by people would suffer from DM in the South American conti metabolic diseases such as diabetes, gout, Lesch Nyhan Syn nent, with 54% in Latin America and the Caribbean (LAC), drome or other conditions to the skin, including, keratosis, with a projected 64 million people in 2025, rising to 62% in onychomycosis, ringworm, among others. the Latin American region (Barceló A & Rajpathak Set al., 2001). DISCUSSION OF PRIOR ART 0010. The global demonstrated prevalence by the National 0003 Diabetes is a chronic non-communicable disease Health Survey was 4.2% (4.8% in men and 3.8% in women), with high prevalence worldwide (6.1 to 8.1/100,000). It is which is higher in people older than years old and in poorer estimated that 150 million people suffer from some form of women (http://epiminsal.cl/epi/html/invet/ENS/Informe diabetes. It is estimated that by 2025there will be 300 million Final ENS.pdf). To curb the rise in mortality from diabetes cases, most occurring in developing countries, preferably was one of the goals that Chile address as part of the Health affecting individuals in the middle of productive age (45-64 Objectives for the decade 2000-2010, and the main goal was years) (ALAD Guides et al., 2007). Chronic hyperglycemia, to keep the age-standardized rate in 14 per 100,000 inhabit characteristic of diabetes, affects the long term, the develop ants (Ministry of Health, MINSAL, Chile 2002). ment of nephropathy, retinopathy, neuropathy and cardiovas 0011 Diabetes has a number of complications that can be cular complications, which results in high morbidity and initiated individually or combined, especially the acute com mortality of diabetic patients compared to the general popu plications (hyperglycemia and hypoglycemia), ophthalmo lation (Ministry of Health, MINSAL, Chile 2005). logic, renal, neurologic, diabetic foot, hypertension and dys 0004 Diabetes mellitus type 1 (DM1) is characterized by lipidemia (ALAD Guides et al., 2007). destruction of pancreatic B cells, which results in absolute 0012. The Diabetic Foot, as sequel of two most common insulin deficiency and vital dependence on exogenous insu chronic complications of this disease, peripheral neuropathy lin. It occurs at any age, but the highest incidence is observed and vascular insufficiency, is a condition with high morbidity in youngsters under the age of 15 years, most commonly in and therefore it impacts negatively on the quality of life of preschoolers, especially pre-pubertal. Its etiology is 90% patients as a result of the frequent admissions, longer hospital autoimmune, which is determined by the presence of anti stays and amputations. It is estimated that one in ten people in islet (ICA), anti-GAD and anti-insulin antibodies. About 10% the time of diagnosis of diabetes type 2 (mellitus) have risk of cases are idiopathic (Ministry of Health, Chile 2005). The factors for foot lesions (Boulton, 2005). prevalence estimated by the World Health Organization 0013 The magnitude of the problem is evident consider (WHO) for 2000 was 6.5%. (King H. etal, 1998.). Taking into ing that over 25% of hospital admissions of diabetics in the account the number of people with DM1 under control in the U.S., U.K., Spain and Mexico are related to foot problems National Health Services of the Ministry of Health in Chile (Irkovska, 2001; Got, 2001). About 15% to 25% of all dia (MINSAL) of approximately 3,000 (children and adults), the betic patients will develop a foot or leg ulcer during the course US 2013/030929.6 A1 Nov. 21, 2013

of their disease (Boulton 2005, Pinzur Metal., 2005). Among acteristic wounds of diabetic foot, that in a high percentage of the associated risk factors are described, patients with long cases will result in amputation, thereby leading to large Social term Diabetes mellitus (>10 years), age (>50 years), history and economic costs for the patient, his family and the state. of ulcer or amputation, presence of neuropathy, arthropathy Helix aspersa Miller or vascular disease, presence of other diabetes complications, 0020. The common garden snail, Helix aspersa Miller, low Socioeconomic status of the patient and social isolation, also known as Cryptophalus aspersusa, is a gastropod mol poor diet, poor education on foot care and other risk factors lusk of the Pulmonata order, of terrestrial life. It is one of associated with vascular disease (Gallardo et al 2004, Minis various species of Helix, Very similar among them, also called try of Health, Chile 2005). There are few studies on the Snails. It requires secretion of mucus or slime for its move prognosis and outcome of diabetic foot; however, Chilean ment, which upon solidification serves as a Support that iso Surgeons have the perception that the prevalence is increasing lates it from an otherwise unfavorable environment. Other (Iribarren O. et al., 2007: Olmos P. et al., 1994). names used are Cryptomphalus aspersus, Cornu aspersum 0014 Diabetic foot is called to that foot of patients that due and Cantareus aspersus, I Shermaphrodite, oviparous and to alterations characteristic of diabetes, present risk of inju has a spiral wound calcareous shell. The slime Snail Suitable ries and/or amputations. These lesions occur especially in for cosmetic application is obtained from fasting caused by high-risk patient, Smokers and those with previous vascular innocuous stimulation (radiation or mechanical stress). This complications of lower extremities (Ministry of Health, Chile stimulation does not alter the survival of the animal and can be 2005). As an example, only in the south area of Santiago there repeated several times during its life cycle. The slime secreted are 4,000 diabetic foot patients receiving attention in the 6 because of this external stimulus has the ability to repair the medical centers of the Municipal Health Corporation of San Snail skin and protect it from external aggressions. These Bernardo (Source: Municipal Health Corporation of San Ber properties can be extrapolated to the formulation and imple nardo, Santiago, Chile). mentation of preparations for cosmetic use (Abbot R, 1996). 0015 Early detection of diabetic foot is performed 0021 Snail slime, particularly of the species Cryp through a foot exam, including the use of monofilament, tophalus aspersus or Helix aspersa Miller, is mainly com palpation, visual and sensitivity examination. If preventive posed of the following active principles, considered the most measures fail and injury occurs or a high-risk foot is con relevant: firmed, a multidisciplinary management should be per Allantoin (glioxil diurea): Stimulating agent of the skin cell formed, especially in those cases with a history of ulcer or proliferation. It helps to remove necrotic tissue, replacing amputation of the other extremity. them with new tissues. It is an anti-irritant, and promotes and 0016 For injuries management in the neuropathic diabetic accelerates the natural healing processes in the body. There foot, it is used the Wagner classification, where the lesions of fore, it is a stimulant of epithelialization and helps to cleaning 0, I and II grades should be handled at the primary level and removing necrotic tissue, accelerating the growth of mainly with resting, non-traditional cures according to stan healthy new tissue (SZnitowska Janicki M & S, 1988). The dards and oral antibiotic therapy, if required. If no response is FDA has not recognized allantoin as a wound healing agent, observed to these measures, patient should be referred to but has recognized it as a skin protector, and has classified it secondary and tertiary levels, as well as those who have into category I, which means it is safe and effective (www. lesions of III, IV or V grades for eventual surgical solution fila.com). and intravenous antibiotic therapy (Brodsky J.W. 2001). Glycolic acid (hydroxy acetic acid): It is a natural organic 0017. If there is indication of utility of antibiotic therapy, it compound of Small molecular chain, which allows it to will typically be an oral monotherapy (1st generation cepha quickly penetrate the skin up to deeper layers. This acid is losporins, clindamycin, lincomycin, amplicillin-Sulbactam, primarily widely used in skin treatments to fade, in any sec amoxicillin-clavulanate, ciprofloxacin and other quinolones) tion of the skin, wrinkles, stretch marks, Scars and to reduce for 10-14 days for a mild acquired infection, expanding the acne. As an irritant, it is recommended for use with plant spectrum (clindamycin and third generation cephalosporins extracts, collagen and vitamins to Support cellular reconstruc or quinolones, amplicillin-Sulbactam and metronidazole, van tion (Denda S, 2010). The action of this treatment is to comycin) with a treatment duration of 14-21 days for severe decrease the thickness of the Stratum corneum of the skin and infections (B. Beltran et al., 2001). increase the thickness of stratum malpigio. It is also an excel 0018. In the case of ischemic diabetic foot, all patients lent exfoliating and helps other components to penetrate the should have an initial assessment at the primary level of the skin easier (M L Elson, 1993 Trib6 et al., 2004). health system hierarchy for early detection of risk and another Elastin: It is a 70 KDa protein, present in all vertebrates, with assessment quarterly to prevent episodes. At this level the structural features that provide strength and elasticity to the assessment should include and emphasize education and pre tissues, greatly expanded capacity, allowing the healing by ventive management and early detection of pediatric cases regenerating tissue expansion in the treatment of wounds requiring referral to emergency services. Symptomatic (Sage & Gray, 1977; Young GL, Jewell D, 2000). patients are derived to the upper level of health care and those Collagen: This molecule allows replacement of denatured or with absence of pulses in one extremity, determining at the oxidized collagen and production of metalloproteinase tertiary level the procedure to follow (revascularization, inhibitors (TIMP) which facilitates regulation between syn amputation or conservative management) (Ministry of thesis and degradation of the components of the dermis. It Health, MINSAL, 2005.) also improves cell cytoskeleton structure, since it induces 0019 Diabetic foot problems are known in medicine, proliferation and activation of fibroblasts by beta-EGF activ there are many research publications, programs established ity. Accordingly, it increases hyaluronic acid, collagen fibers and investigations described, some of them mentioned in the production and elastin deposition in the extracellular matrix item “Discussion of prior art of this application, indicating fibronectin, so it promotes dermal support (Young GL, Jewell that diabetic patients without strict treatment will suffer char D, 2000). US 2013/030929.6 A1 Nov. 21, 2013

0022 Finally, natural antibiotics content in the slime snail 0035. Therefore, the formulation disclosed in this appli are substances capable of acting against bacteria usually cation, is aimed at a problem (disease) of patients who are present on the skin, especially Escherichia coli, Staphylococ initially diagnosed with Diabetes. These patients may suffer cus aureus, Pseudomonas aeruginosa and Acne vulgaris, from disorders that can be classified as non-ulcerating or protecting from its infection. Besides these most relevant ulcerating wounds in the lower extremities (feet). This is the components, the presence of vitamins and antibiotics are main source of the problem, and the product we develop estimated allowing faster skin regeneration, reduced inflam becomes our opportunity to be a complementary alternative mation and inhibition of infectious processes characteristic of to the treatments currently applied to diabetic footpatients in diabetic foot. Chile, hoping to generate savings to 3.75% of the country 0023. In this regard it is particularly noteworthy that the spending per year in this disease which it is estimated is about empirical evidence Suggests that all components of the Snail USS200 million. Therefore, we believe, the health centers slime together, particularly the Chilean species (Helix will decrease their costs by using the product. aspersa miller), act synergistically, an important aspect to be 0036. The inventors of the present application initially analyzed within the proposed application. assessed the product as dermo-cosmetic, as part of popular use being given to the Snail slime, clearly taking advantage of DESCRIPTION OF THE FIGURES its extraordinary qualities that have been displayed on a large number of people with different conditions to skin, especially 0024 FIG. 1 is a photograph of the strain snail Helix in patients with some type of disorder in the lower extremities aspersa miller (feet). The product has been used as a complement to healing 0025 FIG. 2 depicts the shape and size of agauze sock diabetic foot treatments in over 100 patients with this condi soaked in gel formulation of the invention for therapeutic tion. Surprisingly it has been observed that the formulation in purposes. study performs functions not only palliative but curative of diabetic foot, especially in more complex cases for its DETAILED DESCRIPTION OF THE INVENTION advanced state of ulceration. Therefore, it is clear that the 0026. From a few years, the applicants of the present slime Snail has an activity that stands out to conventional invention have been dedicated to the development of products treatment. based on Snail slime national species. Its development has 0037. The prophylactic and therapeutic continuous use of been eminently cosmetic, generating various products this specific formulation of snail slime (Helix aspersa Müller including face cream, hand and body, shampoo, conditioner, species) significantly decreases the incidence and prevalence bath Soaps, all currently registered and marketed. rate of wounds, allows prevention, treatment and wound heal 0027 Considering that the components of the snail slime ing in an advanced stage, particularly those related with have healing properties, regenerative and antiseptic, among ulcers of diabetic foot. This can increase the chances of heal others, the applicants began to develop a product specifically ing of patients, decrease the percentage of amputations and formulated for healing and regeneration of ulcerated wounds, ultimately improve the quality of life of people in that condi and particularly, for one of the most complicated cases of this tion. type of wounds, the diabetic foot. 0038. The present invention is further directed to the 0028. In this regard, it should be noted that 15% of diabetic development of an application/device of a finished product, patients develop a foot ulcer during their lifetime (Pinzur Met which will be more efficient and effective than current treat al., 2005). As we mention above, diabetic foot is called the ment, which is essentially palliative and generic, with con foot of those patients that due to alterations characteristic of ventional nursing cares. This treatment may, in the best case, diabetes, present risk for injuries and/or amputations. These arrest the development of the wound. The use of our product lesions occur especially in high-risk patient, Smokers and may allow further peeling of dead skin and regeneration new those with previous vascular complications of lower extremi skin due to the properties of its components. ties (Ministry of Health, Chile 2005). 0039. The product can be run or installed by the same 0029. The main problem of this disease for any country is patient, ie, the patient does not need to move and requires no the high cost. The effects of the topical product that involves other human resources associated with the treatment of dis this project aims eventually to provide an effective and easily eases that are used in a medical center (nurse, administrative administrable treatment to diabetic foot wounds, which staff, physician on duty). This is where the product generates allows in the short and medium term: savings. For maximum effectiveness, our device incorporates 0030 Reducing the number of amputations and disability a monograph of use with appropriate indications. days, 0040. The product/composition may be used as an appli 0031 Reduction of medical hours used in the follow-up, cation to a sock or as a device including a diabetic Sock (FIG. 0032 Reduction of overhead costs (personal and public 1), is easy to use by both qualified personnel and the patient, service) by attention to diabetic footpatients in the country, and can be applied to variously sized individuals. Its use is and complementary to any other treatment. 0033 Improving of quality of life for patients and their 0041 Discussion of prior art has concluded that there is families. not a national or worldwide similar alternative to this product, 0034. In summary, the problem being addressed is a major so this would be novel, inventive and with a certain industrial cause of morbidity and is also a chronic complication of application, the three fundamental aspects for acceptance of a Diabetes mellitus that affects the quality of life of patients, patent application. Both the design and the application forms which generates disabling as a result of Surgical treatment that are not obvious because in previous analyses we have Sometimes is necessary So as not to compromise the patients observed greater effectiveness of the sock versus the cream or life. gel applied to the ulcerative skin, which exposed to the envi US 2013/030929.6 A1 Nov. 21, 2013

ronment undergoes chemical, photochemical or microbio -continued logical transformation, decreasing the effectiveness and time of therapeutic utility. INGREDIENTNAME PERCENTAGE (%) 0042. The ultimate beneficiaries of the solution presented Marigold extract 3.00 by this application will be the primary care centers, dependent Almond oil 3.00 on the municipalities, private clinics, hospitals and all patients mainly with diabetic foot. This invention will also benefit patients who exhibit other disorders such as wound infections, onychomycosis (usually painless fungal infection, b) Gel Formulation characterized by affecting potentially all toenails and produce 0047 1.50 g Laboratory cream Bellcos deformities and color change), ringworm (fungus on skin 2.30 g of sterile snail slime where there is itching, redness, blisters, cracks and Sores in 3.10 g of vaseline Some cases changes color with exposure to heat and humid 4. 10 mL of bi-distilled water or normal saline ity), hyperkeratosis (thickening of the stratum corneum, with varying degrees of acanthosis, leading to what is popularly Example 2 known as “callus’), ulcers by friction or pressure. 0043. It is important to highlight that the suitable formu Example of Formulation lation also comprises marigold extract, propolis and/or almond oil, excipients and/or pharmaceutically acceptable Manufacture of a Gel for 15 to 20 Gauze Sock-Shaped additives, which are the basis of a synergistic effect observed 0048 50 grams of body cream are sterilized by autoclav which gives higher efficacy of the formulation due to its ing at 150°C. with a temperature rise time, exposure time and cosmetic properties. cooling time (30 minutes each), and then 30 grams of steril 0044) The contribution of the product is relevant to public ized Helix aspersa Muller slime is added, afterwards it is health, since this product is able to stop and reverse the regular homogenized with stirring, next 10 grams of petrolatum and process of advancing a patient’s wounds (ulcers) of diabetic 10 mL of bi-distilled water are added to maintain humidity. foot, it will improve quality of life, reduce treatment costs and Finally, the cream is homogenized with marigold extract, use of biomedical staff time in treatment, avoid amputations propolis and/or almond oil and then the gauzes are Subjected in a significant percentage, preventing the increase of dis to soaking into gel formulation. abled people in our country and avoiding disruption of family and social environment. It is estimated that the use of the Example 3 product could allow at least 3.75% savings in annual spending in this disease, which as stated above is estimated at approxi Administration and Dosage mately $200 million annually just in Chile (Source: Funds capital angels, Faculty of Economics and Business, Univer 0049. The product is applied as a gauze band or sock sity of Chile). directly on the wound in the following manner: Case 1: Wound Surface: wash the wound with normal saline EXAMPLES serum and then placed the plaster (gauze band) containing our formula and every three days should be monitoring the evo 0045. The following examples are preferred but not exclu lution. sive of our invention: Case 2: Deep wounds (ulcers): wound is washed with normal saline serum, applied the gel, in areas of the wound that has no Example 1 contact with the gauze band and depending on the location of the wound is placed a sock. If the deep wound (ulcer) is Example of Formulation located in the heel of the foot, it is recommended to use the 0046) a) Formulation of the basal cream sock. Evolution is observed every 3 days. Example 4

NGREDIENTNAME PERCENTAGE (%) Application Example Water 73.50 0050 We conducted a case study in podiatric clinics and Filtered snail slime S.OO centers in the municipality of San Bernardo, Santiago, Chile, Liquid Paraffin 6.OO according to the procedure described in Example 3. This Glycerib (R) S.OO Cetearth-20 (R) 3.00 study yielded the following results: of 104 documented cases Hydrogenated Polyisobutene 3.00 (33 cases with clean wounds, 31 cases with infected wounds, Dimethicone 1.00 10 cases with onychomycosis, 10 cases with ringworm, 10 Glyceril/PEG-100 stearate 1.00 Propylene glycol O.S6 cases with hyperkeratosis and 10 cases with rubbing or pres Tocopherol Acetate O.SO sure ulcers), 100% of patients showed a clear recovery/heal Diazotidinil urea O.30 ing their wounds with the use of a formulation with snail Methylparaben O.26 slime, it is statistically better than the results obtained with Crosslinked alkyl acrylate polymer O.20 DMDM Hydantoin O.14 conventional treatmentalone. It was also possible to infer that Propylparaben O.O3 the application modesignificantly influence the effectiveness odo propynylbutyl carbamate O.O1 of treatment, because when a Sub-group of patients were Triethanolamine O.30 given the formulation by the foot bandaged the results were better in over 50% of cases in terms of curation. US 2013/030929.6 A1 Nov. 21, 2013

REFERENCES 0069 Trib6 MJ, Parrado C, Rais B et al. Resultados pre 0051 Boulton Andrew. El pie diabético: epidemiologia, liminares de la eficacia del tratamiento intensivo con la factores deriesgo y atención. Diabetes Voice, Noviembre secreción de Cryptomphalusaspersa (SCA) en laterapéu 2005 Vol. 50 Nüm, especial, US Pharmacopea, XXIII tica del foto envejecimiento cutáneo. Med CutanlberLat 0052 Brodsky J. W. An improved method for staging and Am. 2004; 32:265-270. clasification of foot lesions on diabetic patients en “The 0070 Young GL, Jewell D. Creams for preventing stretch diabetic foot, Cap. 11. Bowker J. H. Pfeifer M.A., 6th ed. marks in pregnancy. Cochrane Database Syst Rev. 2000; Mosby 2001:273-282). (2): CD000066. 0053 Denda S. Denda M, Inoue K, Hibino T. Glycolic 1. A pharmaceutical composition for use in serious injury acid induces keratinocyte proliferation in a skin equivalent that consists of about 15% to 30% of snail Helix aspersa model via TRPV1 activation. J DermatolSci. 2010 Febru Miller (Cryptophalus aspersus) dissolved in a body cream ary: 57(2):108-13. Epub 2010 Jan. 8. base containing additives and/or pharmaceutically acceptable 0054 Iribarren O., Ais. Gabriela Passim. Natalia Aybar excipients together with natural products Such as marigold M., Drs. Paulo Ríos M. Lain González, A., Marco A Rojas extract, propolis and/or almond oil, generating a viscosity G. Fernando Saavedra P. Pie diabético: EvoluciOn enuna formulation of 200 to 1000 Pa-S. serie de 121 pacientes Rev. Chilena de Cirugia. Vol 2. A pharmaceutical composition according to claim 1 that 59-N'5, Octubre 2007: pags. 337-341. consists of Snail slime Helix aspersa Miller (Cryptophalus 0055) Elson ML. The molecular structure of glycolic acid aspersus), marigold extract, propolis and/or almond oil and and its importance in dermatology. Cosmetic Dermatol additives and/or pharmaceutically acceptable excipients that ogy: 6(7): 35-40, 1993. generate a viscosity formulation between 50-100 Pa-s. 0056 Got I. Necessary multidisciplinary management of 3. A pharmaceutical composition according to claim 1, that diabetic foot. J. Mal Vasc 2001; 26(2): 130-4. is soaked in gauze type bandage shaped fabric to be applied to 0057 Guías ALAD de diagnostico, controlytratamiento advanced ulcerous wounds or other serious skin conditions de la diabetes Mellitus tipo 2. ALAD Asociación lati similar or sock to be applied to advanced diabetic foot ulcers. noamericana de diabetes, 2007.pág.: 50-52. 4. The composition of claim 1 that is in a state of cream or 0058 Irkovska A. Care of patients with the diabetic foot gel of medium to high Viscosity. syndrome based on an international consensus. CasLe 5. Procedure for obtaining a composition according to kCesk 2001: 140(8):230-3. claim 1 which comprises a) formulation on the basis of ster 0059) Karvonen M, Viik-Kajander M, Molichanova E et ilized body cream and chilled with low content of snail slime al, for The Diabetes Mondiale (DiaMOND) Project Group: formulation, b) addition of snail slime sterilized Helix Incidence of Childhood Type 1 Diabetes Worldwide. Dia aspersa Muller, c) homogenization by stirring, d) addition of betes Care 21:10, 2000. 1516-26). marigold extract, propolis and/or almond oil, e) addition of 0060 Ministry of Health, MINSAL, Clinical Guidelines, liquid vaseline and bidistilled water, and finally f) homogeni Advanced Healing of diabetic foot ulcers, Chile, Septem Zation until a creamy or gel formulation is formed. ber 2005. 6. Use of the composition of claim 1 which comprises to 0061 Ministry of Health, MINSAL, Clinical Guidelines prepare a formulation in a gauze bandage or sock useful for Diabetes Mellitus II. 1st Ed. Santiago: Minsal, Chile 2005. preventing or treating illnesses of Sores or wounds of poor 0062 Ministry of Health, MINSAL, Clinical Guidelines prognosis (severe). Diabetes Mellitus I. 1st Ed. Santiago: Minsal, Chile 2005. 7. Use of the composition according to claim 6 because is 0063 Ministry of Health. MINSAL, Health Objectives for used to prepare a formulation or device useful for preventing the Decade 2000-2010. Division of steering role and health or treating ulcers or wounds generated by serious metabolic regulations, department of epidemiology. First Edition, diseases such as diabetes, gout, Lesch Nyhan syndrome or Chile, October 2002. another skin conditions, including, keratosis, onychomycosis 0064 Olmos P. Catalán S. Roberts C, O’Dorisio T. Aburto or ringworm in advanced, among others. M. Buscando indicadores deriesgo de pie diabético. Parte 8. Use of the composition according to claim 7 to prepare II. RevChilCir 1994; 46:552-582. a pharmaceutical composition useful for preventing or treat 0065 PérezY, Menéndez R, GameZR Mas R, González, R ing ulcers or wounds of diabetic foot or others wounds in My Mas REfectos dela administración oral de D-004 (400 advanced stage. mg/kg) sobre la peroxidación lipidica en ratas ovariecto 9. Use of the composition of claim 1 characterized because mizadas. Rev GENIC Cien Biol. 36(No. Especial), 2005. it serves to prepare a drug useful to prevent or treat conditions 0.066 Pinzur M. Freeland R, Juknelis D. The association of ulcers or injuries of poor prognosis. between body mass index and foot disorders in diabetic 10. Use of the composition according to claim 9 character patients. ized because it is used to prepare a medicine useful to prevent 0067 Sage E H & Gray W R 1977 Evolution of elastin and or treat ulcers or general metabolic diseases such as Diabetes elastin structure, p 291. in; Advances in Experimental Mellitus, Gout, Lesch Nyhan and other afflictions of the skin Medicine and Biology, Vol. 79 LB Sandberg & C Franz including, such as Soriasis, keratosis, onychomycosis, ring blaw, eds) Plenum Press, NY & London). worm, among others. 0068 SZnitowska M, JanickiS. The effect of vehicle on 11. Use of the composition according to claim 8 character allantoin penetration into human skin from an ointment for ized because it is used to prepare a useful drug to prevent improving scar elasticity. Pharmazie. 1988 March; 43(3): ulcers or treat diabetic foot. 218. k k k k k