ITRM20090618A1 - "PHARMACEUTICAL COMPOSITION BASED ON METRONIDAZOLE AND ZINC OXIDE FOR THE TOPIC TREATMENT OF ACUTE AND CHRONIC DISTROPHIC AND POST-OPERATIVE PATHOLOGIES" - Google Patents
"PHARMACEUTICAL COMPOSITION BASED ON METRONIDAZOLE AND ZINC OXIDE FOR THE TOPIC TREATMENT OF ACUTE AND CHRONIC DISTROPHIC AND POST-OPERATIVE PATHOLOGIES" Download PDFInfo
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- ITRM20090618A1 ITRM20090618A1 IT000618A ITRM20090618A ITRM20090618A1 IT RM20090618 A1 ITRM20090618 A1 IT RM20090618A1 IT 000618 A IT000618 A IT 000618A IT RM20090618 A ITRM20090618 A IT RM20090618A IT RM20090618 A1 ITRM20090618 A1 IT RM20090618A1
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- metronidazole
- zinc oxide
- anal
- pathologies
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- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 title claims description 37
- 229960000282 metronidazole Drugs 0.000 title claims description 26
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 title claims description 25
- 238000011282 treatment Methods 0.000 title claims description 21
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- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
COMPOSIZIONE FARMACEUTICA A BASE DI METRONIDAZOLO ED OSSIDO DI ZINCO PER IL TRATTAMENTO TOPICO DI PATOLOGIE ANALI ACUTE E CRONICHE DISTROFICHE E POST-OPERATORIE; PHARMACEUTICAL COMPOSITION BASED ON METRONIDAZOLE AND ZINC OXIDE FOR THE TOPICAL TREATMENT OF ACUTE AND CHRONIC DYSTROPHIC AND POST-OPERATIVE ANAL DISORDERS;
DESCRIZIONE DESCRIPTION
Il presente trovato riguarda il settore proctologico e gastroenterologico, ed in particolare una composizione farmaceutica a base di ossido di zinco e metronidazolo per il trattamento topico acuto e cronico di lesioni distrofiche e chirurgiche di qualsiasi genere che interessano l’ano, generando dolore. The present invention relates to the proctological and gastroenterological sector, and in particular to a pharmaceutical composition based on zinc oxide and metronidazole for the acute and chronic topical treatment of dystrophic and surgical lesions of any kind affecting the anus, generating pain.
Il dolore anale, il bruciore, il prurito ed il tenesmo ano-rettale sono le cause più comuni per le quali il paziente si sottopone ad una visita Chirurgica Proctologica o Gastroenterologica . Anal pain, burning, itching and anorectal tenesmus are the most common causes for which the patient undergoes a Proctological or Gastroenterological Surgery.
Sono diverse le circostanze che determinano questa sintomatologia. Tra le più comuni possiamo indicare: le aniti, criptiti, proctiti, emorroiditi, che hanno un unico comune denominatore: lo stato infiammatorio, che tende a perdurare con frequente evoluzione flogistica alimentata dalla ricca flora batterica locale, presente nei diversi distretti anatomici descritti, funzionalmente connessi. There are several circumstances that determine this symptomatology. Among the most common we can indicate: anites, cryptites, proctites, hemorrhoids, which have a single common denominator: the inflammatory state, which tends to persist with frequent inflammatory evolution fed by the rich local bacterial flora, present in the various anatomical districts described, functionally connected.
Oltre a queste patologie, esiste la ragade anale che descriviamo specificatamente più avanti per la caratteristica di presentarsi come un danno morfologico di soluzione di continuo della mucosa anale. In addition to these pathologies, there is the anal fissure that we describe specifically later for the characteristic of presenting itself as a morphological damage of continuous solution of the anal mucosa.
La ragade anale, che può essere estremamente dolorosa, si presenta più frequentemente nella giovane età , rappresentando da sola il 50% dei dolori anali. Resistente alle comuni terapie mediche attualmente in commercio, costringe il paziente a sottoporsi a ripetuti e diversi trattamenti farmacologici, con un risultato clinico del 50%. Anal fissure, which can be extremely painful, occurs more frequently at a young age, alone accounting for 50% of anal pains. Resistant to common medical therapies currently on the market, it forces the patient to undergo repeated and different pharmacological treatments, with a clinical result of 50%.
I restanti pazienti sono costretti a sottoporsi a terapia chirurgica di sfinterotomia con riduzione della tensione sfinteriale e risoluzione della sintomatologia. The remaining patients are forced to undergo surgical sphincterotomy therapy with reduction of sphincter tension and resolution of symptoms.
Lo scarso risultato farmacologico stimola un grande interesse da parte degli specialisti colonproctologi e soprattutto gastroenterologi, alla ricerca di una terapia medica più efficace che possa evitare il trattamento chirurgico di tale patologia. The poor pharmacological result stimulates a great interest on the part of colorectal specialists and especially gastroenterologists, in search of a more effective medical therapy that can avoid the surgical treatment of this pathology.
FISIOPATOLOGIA DELLE RAGADI ANALI PHYSIOPATHOLOGY OF ANAL RADIUS
Si considera ragade anale una soluzione di continuo della mucosa ad insorgenza acuta o cronica, con caratteristica d’ulcera che tende a non guarire o recidivare frequentemente. Anal fissure is considered a continuous solution of the mucosa with acute or chronic onset, with an ulcer characteristic that tends not to heal or recur frequently.
Ancora oggi à ̈ molto dibattuta l’origine e la causa della ragade anale; alcuni autori sostengono l’ipotesi dell’ischemia, altri dell’alterazione dell’alvo (stipsi e /o diarrea); per altri si tratta d’infezioni di resti epiteliali o embrionali: per questi autori la ragade, la criptite e la fistola sono un’espressione clinica diversa, della stessa origine patologica disontogenica; ma la maggior parte degli autori sostiene che l’ipertono dello sfintere che mantiene lo spasmo anale, sia la causa iniziale della ragade, o la causa predominante al mantenimento della ragade stessa. The origin and cause of the anal fissure is still very much debated today; some authors support the hypothesis of ischemia, others of the alteration of the alvus (constipation and / or diarrhea); for others they are infections of epithelial or embryonic remains: for these authors the fissure, cryptitis and fistula are a different clinical expression, of the same disontogenic pathological origin; but most authors maintain that the hypertonicity of the sphincter that maintains the anal spasm is the initial cause of the fissure, or the predominant cause for the maintenance of the fissure itself.
Questa ipotesi viene rafforzata da numerosi studi manometrici, che confermano l’ipertono anale consensualmente alla presenza di una ragade. Questo dolore si risolve immediatamente praticando una sezione regolata dello sfintere interno che risolve l’ipertono. This hypothesis is reinforced by numerous manometric studies, which confirm anal hypertonus consensually to the presence of a fissure. This pain is resolved immediately by practicing a regulated section of the internal sphincter which resolves the hypertonus.
Un’altra caratteristica di questa lesione, à ̈ che la sintomatologia non à ̈ legata alla dimensione della ragade: si possono infatti trovare ampie soluzioni di continuo completamente asintomatiche, e piccolissime ragadi quasi non evidenziabili che presentano una fortissima sintomatologia dolorosa tanto da impedire lo svolgimento della stessa visita medica. Another characteristic of this lesion is that the symptomatology is not linked to the size of the fissure: in fact, it is possible to find large and continuously asymptomatic solutions, and very small, almost non-evident fissures that present a very strong painful symptomatology so as to prevent the carrying out the same medical examination.
QUADRO CLINICO CLINICAL FRAMEWORK
La clinica à ̈ abbastanza tipica da suggerire la diagnosi di primo impatto. The clinic is typical enough to suggest the first impact diagnosis.
La sintomatologia à ̈ caratteristica e di facile interpretazione già evidenziabile ad una anamnesi attenta. The symptomatology is characteristic and easy to interpret, which can already be highlighted with a careful medical history.
Si tratta di un dolore urente spesso definito atroce, che insorge da 5 a 15 minuti dopo la defecazione, che può essere più o meno faticosa. Tale dolore aumenta rapidamente e può durare 2-3 ore ma può persistere per tutta la giornata, per scomparire spontaneamente e ripresentarsi alla defecazione successiva. It is a burning pain often called excruciating, which occurs 5 to 15 minutes after defecation, which can be more or less tiring. This pain increases rapidly and can last 2-3 hours but can persist throughout the day, disappearing spontaneously and returning at the next defecation.
SCHEMA TERAPEUTICO ALLO STATO DELL’ARTE STATE OF THE ART THERAPEUTIC SCHEME
Gastroenterologi e chirurghi colon-proctologi, discutono a tutt’oggi sulla patogenesi della sintomatologia e sul trattamento più idoneo, che prevede sempre un primo tentativo farmacologico topico, associato a lassativi per rendere più facilitata la defecazione (quando coesiste alvo stitico con feci dure ed irregolari) e antidolorifici sistemici. Spesso si associano dilatazioni che il paziente esegue autonomamente e successivamente dilatazioni strumentali eseguite dallo specialista previa anestesia locale. I risultati non sono comunque soddisfacenti ( 50% circa della risoluzione) per questo si ricorre a trattamento chirurgico (sfinterotomia) che mostra risultati immediati sulla risoluzione del dolore. Gastroenterologists and colon-proctological surgeons are still discussing the pathogenesis of the symptoms and the most suitable treatment, which always involves a first topical pharmacological attempt, associated with laxatives to make defecation easier (when constipated alvo coexists with hard stools and irregular) and systemic pain relievers. Often there are associated dilations that the patient performs autonomously and subsequently instrumental dilations performed by the specialist after local anesthesia. However, the results are not satisfactory (about 50% of the resolution) for this reason surgical treatment (sphincterotomy) is used which shows immediate results on the resolution of the pain.
Per questo motivo, la ricerca di terapie mediche, ad azione topica locale, si à ̈ orientata su prodotti farmaceutici che mimassero l’atto chirurgico della sfinterotomia. For this reason, the search for medical therapies, with local topical action, has focused on pharmaceutical products that mimic the surgical action of sphincterotomy.
Nascono così le pomate alla nifedipina e nitroderivati con azione mio-rilasciante sullo sfintere liscio, e/o infiltrazioni con tossina di botulinum purificata e diluita, che agiscono paralizzando lo sfintere anale con un discreto risultato durante l’applicazione, associato a frequenti effetti collaterali locali: sanguinamento per vaso dilatazione del plesso emorroidario, incontinenza fecale,per over treatment con botulinum. Inoltre l’assorbimento sistemico per somministrazione protratta genera spesso cefalea ed ipotensione. La sospensione della terapia presenta ricomparsa della sintomatologia dolorosa nel 50% dei casi entro 30-60 giorni. This is how nifedipine and nitro-derivative ointments with myo-releasing action on the smooth sphincter are born, and / or infiltrations with purified and diluted botulinum toxin, which act by paralyzing the anal sphincter with a fair result during application, associated with frequent effects local collateral: bleeding due to dilatation of the haemorrhoidal plexus, fecal incontinence, for over treatment with botulinum. Furthermore, systemic absorption for prolonged administration often generates headache and hypotension. The suspension of the therapy shows the reappearance of the painful symptoms in 50% of cases within 30-60 days.
RAZIONALE DELL’INVENZIONE RATIONALE OF THE INVENTION
Secondo l’inventore, la sintomatologia dolorosa à ̈ un condizione indotta dalla comparsa di uno stato infiammatorio locale, qualsiasi essa sia la causa, complicato da una evoluzione flogistica settica; questa aumenterebbe la risposta algogena dei tenso e chemio-recettori anali che rispondono ai comuni stimoli fisici e chimici (dilatazione meccanica dell’ano e sostanze acide e/o irritanti contenute nelle feci) evocati dal passaggio delle feci; di conseguenza s’innesca l’ipertono sfinteriale che aumenta e protrae la sintomatologia dolorosa. According to the inventor, painful symptoms are a condition induced by the appearance of a local inflammatory state, whatever the cause, complicated by a septic inflammatory evolution; this would increase the algogenic response of anal tense and chemo-receptors that respond to common physical and chemical stimuli (mechanical dilation of the anus and acid and / or irritating substances contained in the faeces) evoked by the passage of faeces; as a consequence, sphincter hypertonia is triggered, which increases and prolongs the painful symptoms.
Tale ipotesi nasce dall’osservazione clinica di pazienti affetti da ragade anale, che non presentavano alcuna sintomatologia dolorosa, in quanto priva di flogosi locale. Al contrario si possono osservare piccolissime ragadi appena evidenziabili clinicamente con fortissima sintomatologia dolorosa, che normalmente insorge dopo 2-3 giorni dalla comparsa di episodi traumatici legati a stipsi e/o diarrea. This hypothesis arises from the clinical observation of patients suffering from anal fissure, who did not present any painful symptoms, as they did not have local inflammation. On the contrary, very small fissures can be observed which are barely evident clinically with very strong painful symptoms, which normally arise after 2-3 days from the onset of traumatic episodes linked to constipation and / or diarrhea.
Il Metronidazolo svolge da tempo un ruolo significativo nel trattare un’ampia varietà di patologie anorectali. Interessanti lavori anglosassoni (citare) documentano inoltre l’efficacia della terapia antibiotica con Metronidazolo eseguito per via sistemica nel trattamento del dolore anale. Metronidazole has long played a significant role in treating a wide variety of anorectal diseases. Interesting Anglo-Saxon works (to quote) also document the efficacy of antibiotic therapy with metronidazole performed systemically in the treatment of anal pain.
Più recentemente à ̈ stata dimostrata l’efficacia dell’uso topico del Metronidazolo al 10 percento per ridurre i dolori e migliorare la cicatrizzazione delle ferite dopo una emorroidectomia. (Carapeti EA, Kamm MA, McDonald PJ. Phillips RK. Double blind randomized controlled trial the effect of metronidazole on pian after day case hemorrhoidectomy. Lancet 1998;351:169-72). More recently, the effectiveness of topical use of 10 percent metronidazole has been shown to reduce pain and improve wound healing after hemorrhoidectomy. (Carapeti EA, Kamm MA, McDonald PJ. Phillips RK. Double blind randomized controlled trial the effect of metronidazole on pian after day case hemorrhoidectomy. Lancet 1998; 351: 169-72).
Partendo da queste osservazioni, l’inventore ha iniziato a trattare pazienti con un prodotto galenico tipo unguento a base di Metronidazolo in una concentrazione compresa dal 2 al 4% in peso sul prodotto totale, associato ad Ossido di zinco dal 10 al 20% ed altri eccipienti. Starting from these observations, the inventor started treating patients with a galenic product such as ointment based on Metronidazole in a concentration ranging from 2 to 4% by weight of the total product, associated with zinc oxide from 10 to 20% and other excipients.
L’ossido di Zinco ha la funzione di formare una barriera protettiva sulle terminazioni nervose (presso-recettori e recettori chimici presenti nell’ano) ed inoltre fa da vettore per il Metronidazolo la cui azione à ̈ di contrastare la flogosi locale alimentata dalla flora batterica anorettale e di ridurre a guarigione completa la sintomatologia dolorosa fino a cicatrizzazione completa. Zinc oxide has the function of forming a protective barrier on the nerve endings (near-receptors and chemical receptors present in the anus) and also acts as a vector for Metronidazole whose action is to counteract the local inflammation fed by anorectal bacterial flora and to reduce painful symptoms to complete healing until complete healing.
Durante la sperimentazione, tale prodotto non veniva associato ad anestetici né cortisonici, allo scopo di testare l’ipotesi sopracitata, dimostrando che la noxa patogena generante il dolore fosse dovuta alla stato flogistico infiammatorio e non all’ipertono dello sfintere. During the experimentation, this product was not associated with anesthetics or cortisones, in order to test the aforementioned hypothesis, demonstrating that the pathogenic noxa causing the pain was due to the inflammatory inflammatory state and not to the hypertonicity of the sphincter.
Qui di seguito à ̈ riportata una formulazione ad uso topico comprendente i principi attivi dell’invenzione: à ̈ da notare che questo esempio à ̈ fornito solo per scopo illustrativo e la presente invenzione non à ̈ da considerarsi limitata ad esso. A formulation for topical use including the active ingredients of the invention is reported below: It should be noted that this example is provided for illustrative purposes only and the present invention is not to be considered limited thereto.
Formulazione di un unguento che chiameremo “Unguento A†Formulation of an ointment that we will call â € œOintment Aâ €
- Metronidazolo 2,5% - Metronidazole 2.5%
- Zinco Ossido 15% - Zinc Oxide 15%
- Alfa bisabololo 0,5% - Alpha bisabolol 0.5%
- Olio di vasellina legg . 10% - Vaseline oil legg. 10%
- Vaselina bianca 60,75% - White petroleum jelly 60.75%
- Olio di Jojoba 10% - Jojoba oil 10%
- Cera bianca 1% - White wax 1%
- Metil paraben 0,15% - Methyl paraben 0.15%
- Vitamina E 0,1% - Vitamin E 0.1%
STUDIO PRELIMINARE PER LA VALUTAZIONE DELL’UNGUENTO “A†. PRELIMINARY STUDY FOR THE EVALUATION OF THE â € œAâ €.
Lo studio à ̈ stato eseguito su 186 pazienti tutti affetti da disturbi anali come: dolore, bruciore, prurito spesso associato a sanguinamento e tenesmo ano-rettale. Tale sintomatologia si ritrovava in pazienti affetti da patologie anali acute come : emorroiditi, aniti, criptiti, ragade anale acuta ed inveterata riacutizzata, prolassi emorroidari complicati ed infine nel post-operatorio per fistulectomia peri-anale, asportazione di cisti sacro-coccigea infetta con chiusura per seconda intezione e deiscenza della sutura infraglutea per cisti coccigea . The study was performed on 186 patients all suffering from anal disorders such as: pain, burning, itching often associated with bleeding and anorectal tenesmus. This symptomatology was found in patients suffering from acute anal diseases such as: haemorrhoids, anitis, cryptitis, acute and inveterate acute anal fissure, complicated haemorrhoidal prolapses and finally in the post-operative period for peri-anal fistulectomy, removal of infected sacro-coccygeal cyst with closure by second integration and dehiscence of the infragluteal suture for coccygeal cyst.
Il protocollo terapeutico prevedeva: detersione con acqua tiepida priva di sapone, nelle ragadi anali, emorroiditi, criptiti ed aniti e detersione con sapone di betadine nelle grosse perdite di sostanza come fistulectomia e deiscenza della sutura peri-anale o sacro-coccigea. Alla detersione seguiva applicazione locale dell’unguento eseguita digitalmente per tutta la lunghezza dell’ano e /o all’interno della ferita. Tale operazione veniva eseguita mattina e sera e ripetuta dopo eventuale evacuazione. Inoltre veniva prescritto Movicol da somministrare da 1 a 3 bustine al di per tutta la durata del trattamento, a seconda della consistenza delle feci per la sola ragade anale. The therapeutic protocol included: cleansing with soap-free warm water, in anal fissures, hemorrhoids, cryptitis and anitis and cleansing with betadine soap in large losses of substance such as fistulectomy and dehiscence of the peri-anal or sacro-coccygeal suture. The cleansing was followed by local application of the ointment performed digitally along the entire length of the anus and / or inside the wound. This operation was performed morning and evening and repeated after any evacuation. Furthermore, Movicol was prescribed to be administered from 1 to 3 sachets per day for the duration of the treatment, depending on the consistency of the stool for the anal fissure alone.
Il parametro monitorato à ̈ stato: il beneficio e/o miglioramento del sintomo (dolore o bruciore, prurito e tenesmo) descritto soggettivamente come disagio con una riduzione della qualità della vita ( QL). The monitored parameter was: the benefit and / or improvement of the symptom (pain or burning, itching and tenesmus) subjectively described as discomfort with a reduction in quality of life (QL).
Per comodità abbiamo associato : For convenience we have associated:
una scala che va da 1 a 10 descrivendo il disagio, dove 1 Ã ̈ uguale a nessun sintomo, e 10 Ã ̈ uguale ad un dolore o una condizione insopportabile, ed a scale ranging from 1 to 10 describing discomfort, where 1 equals no symptoms, and 10 equals unbearable pain or condition, and
una scala che va da 10 a 1 che descrive il miglioramento della QL dopo applicazione del trattamento topico con il prodotto testato, dove 10 à ̈ la completa scomparsa del sintomo, ed 1 à ̈ uguale a nessun miglioramento clinico o invariato rispetto all’inizio del trattamento. a scale ranging from 10 to 1 describing the improvement in LQ after application of topical treatment with the tested product, where 10 is the complete disappearance of the symptom, and 1 is equal to no clinical improvement or unchanged from the start of the treatment.
I parametri sono stati valutati soggettivamente in quattro tempi ( 2 ore dopo la prima applicazione, poi 2 – 7 – 14 – 30 - 45 giorni dopo inizio trattamento.) The parameters were subjectively assessed in four stages (2 hours after the first application, then 2 - 7 - 14 - 30 - 45 days after the start of treatment.)
Lo studio iniziato nel trattamento della ragade anale, Ã ̈ stato esteso successivamente alle aniti, criptiti, emorroiditi, ed infine nel post-intervento di fistulectomia peri-anale e sacro coccigea complicata, con ampia asportazione di cute perianale. The study started in the treatment of anal fissure, was subsequently extended to anitis, cryptitis, haemorrhoiditis, and finally in the post-surgery of peri-anal fistulectomy and complicated sacrum coccygeal, with extensive removal of perianal skin.
I risultati sono stati riportati separatamente per le diverse origini fisiopatologiche e della noxa patogena. The results were reported separately for the different pathophysiological and pathogenic noxa origins.
TEST TEST
Ragade anale: Anal fissure:
Sono stati arruolati 118 pazienti (65 donne e 53 uomini) con un età che varia dai 21 ai 78 anni (media di 43). Di questi 92 erano affetti da ragade acuta e 118 patients were enrolled (65 women and 53 men) with an age ranging from 21 to 78 years (mean of 43). Of these 92 were suffering from acute fissure and
26 da ragade cronica inveterata riacutizzata. 26 from chronic inveterate exacerbated fissure.
Tutti hanno eseguito lo stesso protocollo, in 14 pazienti si à ̈ dovuto associare iniziale terapia antidolorifica (Orudis supposte per 3 gg. Mattina e sera) per ridurre il dolore e spasmo che impediva l’applicazione della terapia topica. All followed the same protocol, in 14 patients it was necessary to associate initial pain relief therapy (Orudis suppositories for 3 days morning and evening) to reduce the pain and spasm that prevented the application of topical therapy.
Risultati: Results:
TABELLA 1 TABLE 1
RAGADE ACUTA in 92 pz.: QL dopo trattamento con il prodotto ACUTE RAGADE in 92 pcs .: QL after treatment with the product
Numero 2 ore 2 giorni 7 giorni 14 giorni 28 giorni 42 giorni 56 giorni pazienti Number 2 hours 2 days 7 days 14 days 28 days 42 days 56 patient days
59 1-2 2-3 5-8 9-10 10 10 10 sospende 11 2-3 5-7 6-8 10 10 10 Idem 9 1-2 1-2 4-5 8-9 10 10 Idem 5 1-2 1-2 5 6-7 6-7 8-9 8-9 continua 3 1 1-2 6-7 4-5 Decidono ---------- ----------per interv. -La tabella 1 riporta una bassa risposta iniziale, ad eccezione di un gruppo di 11 pazienti che mostra soddisfazione già dal secondo giorno. 59 1-2 2-3 5-8 9-10 10 10 10 suspend 11 2-3 5-7 6-8 10 10 10 Idem 9 1-2 1-2 4-5 8-9 10 10 Idem 5 1- 2 1-2 5 6-7 6-7 8-9 8-9 continue 3 1 1-2 6-7 4-5 They decide ---------- ---------- for interv. -Table 1 reports a low initial response, with the exception of a group of 11 patients who show satisfaction as early as the second day.
Tutti mostrano un miglioramento medio del 60 % dopo 7 gg. con risoluzione completa della sintomatologia in 85 pazienti su 92 dal 14 giorno d’applicazione. All show an average improvement of 60% after 7 days. with complete resolution of symptoms in 85 out of 92 patients from the 14th day of application.
5 pazienti con miglioramento clinico costante ma non risolutivo, decidono di non passare ad intervento ma di continuare la terapia al bisogno. 5 patients with constant but not decisive clinical improvement, decide not to go to surgery but to continue the therapy as needed.
3 pz con scarsi risultati che decidono di sottoporsi ad intervento. 3 patients with poor results who decide to undergo surgery.
TABELLA 2 TABLE 2
RAGADE CRONICA RIACUTIZZATA in 26 pz. QL dopo trattamento CHRONIC RAGADE RELEASED in 26 pcs. QL after treatment
N° 2 ore 2 giorni 7 giorni 14 giorni 28 giorni 42 giorni 56 giorni 19 3-4 7-8 9-10 10 10 10 sospende --------3 5 4-5 7-8 6-7 10 10 10 4 2-3 4 3-4 3-4 4 Intervento -------La tabella 2 riporta un miglioramento vivace già dalla prima applicazione con risoluzione del disagio entro 14 giorni in 19 pazienti. 2 hours 2 days 7 days 14 days 28 days 42 days 56 days 19 3-4 7-8 9-10 10 10 10 suspend -------- 3 5 4-5 7-8 6-7 10 10 10 4 2-3 4 3-4 3-4 4 Intervention ------- Table 2 reports a lively improvement from the first application with resolution of the discomfort within 14 days in 19 patients.
Per 4 pazienti c’à ̈ stata un lieve e costante miglioramento che impone intervento. For 4 patients there was a slight and constant improvement that requires intervention.
I restanti 3 mostrano una risposta più valida al trattamento nei confronti delle ragadi acute nei primi 14 giorni con graduale miglioramento fino a guarigione . The remaining 3 show a more valid response to treatment against acute fissures in the first 14 days with gradual improvement until healing.
ANITE E CRIPTITE: in 59 pazienti trattati col prodotto ANITE AND CRYPTITIS: in 59 patients treated with the product
TABELLA 3 TABLE 3
N° pazienti 2 ore 2 giorni 7 giorni 14 giorni 28 giorni 42 giorni 56 giorni 45 3-4 8-9 10 10 sosp. T Ok Ok Ok 13 5 10 10 sosp. T Ok Ok Ok Ok 1 1 1 Sospende Per Intolleranza Al Prodotto Sono stati arruolati 59 pz ai quali à ̈ stato applicato lo stesso protocollo sopradescritto. No. of patients 2 hours 2 days 7 days 14 days 28 days 42 days 56 days 45 3-4 8-9 10 10 susp. T Ok Ok Ok 13 5 10 10 susp. T Ok Ok Ok Ok 1 1 1 Suspend Due to Product Intolerance 59 patients were enrolled to whom the same protocol described above was applied.
I risultati sono stati: scomparsa della sintomatologia entro 2 giorni per 13 pazienti, con sospensione della terapia al settimo giorno. The results were: disappearance of symptoms within 2 days for 13 patients, with suspension of therapy on the seventh day.
45 pazienti mostravano risoluzione completa del sintomo nei primi 7 giorni, sospensione della terapia 45 patients showed complete resolution of the symptom in the first 7 days, discontinuation of therapy
a 14 giorni. to 14 days.
1 paziente sospende terapia dopo 2 giorni per intolleranza del prodotto. 1 patient suspends therapy after 2 days due to product intolerance.
FISTULECTOMIA in 9 pazienti trattati col prodotto FISTULECTOMY in 9 patients treated with the product
TABELLA 4 TABLE 4
N° 2 ore 2 giorni 7 giorni 14 giorni 28 giorni 42 giorni 56 giorni pazienti 2 hours 2 days 7 days 14 days 28 days 42 days 56 patient days
5 4-5 8-9 10 10 10 10 5 4-5 8-9 10 10 10 10
sospende suspends
4 2-3 6-7 10 10 10 10 Sospende La tabella 4 riporta 9 pazienti arruolati, tutti hanno iniziato il trattamento alla III giornata postoperatoria. 4 2-3 6-7 10 10 10 10 Suspend Table 4 reports 9 enrolled patients, all of whom started treatment on the 3rd postoperative day.
Tutti hanno mostrato un miglioramento con un QL maggiore di 6 dal secondo giorno, QL = 10 Dopo 7 giorni dall’inizio trattamento proseguito fino al termine della cicatrizzazione avvenuta tra 30 e 45 All showed an improvement with an QL greater than 6 from the second day, QL = 10 After 7 days from the start of treatment continued until the end of the healing occurred between 30 and 45
giorni. days.
La soddisfazione del paziente ha dato un QL = 10 per tutto il trattamento post/operatorio, con delle comuni attività quotidiane senza presentarsi a ripetute e fastidiose medicazioni ambulatoriali con zaffi locali che impediscono la ripresa lavorativa e le cure igieniche quotidiane. Patient satisfaction gave an LQ = 10 for the entire post-operative treatment, with common daily activities without presenting to repeated and annoying outpatient dressings with local patches that prevent the resumption of work and daily hygiene care.
CONCLUSIONI CONCLUSIONS
I risultati ottenuti hanno ampiamente dimostrato che il prodotto oggetto della presente domanda, nella sua associazione farmacologica (ossido di zinco e metronidazolo), ottiene un risultato clinico sintomatologico nettamente superiore ai suoi costituenti (ossido di zinco, metronidazolo) usati singolarmente nel trattamento della ragade anale, aniti, emorroiditi, criptiti e come medicazione nel post-operatorio delle fistole peri-anali, sacro coccigee complicate e nel post operatorio dell’emorroidectomia, già testati e descritti in letteratura. Questo grazie ad una azione sinergica, che viene a crearsi tra ossido di zinco e metronidazolo. The results obtained have amply demonstrated that the product object of the present application, in its pharmacological association (zinc oxide and metronidazole), obtains a clinical symptomatological result clearly superior to its constituents (zinc oxide, metronidazole) used individually in the treatment of anal fissure. , anitis, haemorrhoiditis, cryptitis and as a dressing in the post-operative of peri-anal fistulas, complicated sacral coccygeal and in the post-operative of haemorrhoidectomy, already tested and described in the literature. This is thanks to a synergistic action, which is created between zinc oxide and metronidazole.
Il primo costituente ha la funzione di barriera nei confronti delle secrezioni locali muco-sierose, riduce l’umidità della ferita ed evita il depositarsi di residui fecali a contenuto acido sul fondo della ferita stessa che entrano in contatto con le fibre algogene determinando dolore. Ma la funzione principale di questo elemento à ̈ di agire da veicolo per il metronidazolo senza alterarne la funzionalità . The first constituent acts as a barrier against local mucus-serous secretions, reduces the humidity of the wound and prevents the deposition of fecal residues with acid content on the bottom of the wound itself which come into contact with the algogenic fibers causing pain. But the main function of this element is to act as a vehicle for metronidazole without altering its functionality.
Questo fa sì che il metronidazolo venga rilasciato in forma inalterata, favorendone l’assorbimento lento e graduale sulla mucosa e/o sottomucosa esposta nella ferita anale o peri-anale, creando un’azione antisettica specifica e costante nei confronti dei colibacilli anerobici presenti. This ensures that metronidazole is released in an unaltered form, favoring its slow and gradual absorption on the mucosa and / or submucosa exposed in the anal or peri-anal wound, creating a specific and constant antiseptic action against anerobic colibacilli present.
Il Metronidazolo determina abbattimento della sepsi, bloccando la cascata infiammatoria (Tumor, Rubor, Dolor e Functio Lesa), riducendo le secrezioni umide siero ematiche ed il dolore che a sua volta determina spasmo anale e disturbo del microcircolo. Metronidazole reduces sepsis, blocking the inflammatory cascade (Tumor, Rubor, Dolor and Functio Lesa), reducing moist blood serum secretions and pain which in turn causes anal spasm and microcirculation disturbance.
Pertanto l’azione antisettica del Metronidozolo blocca la sepsi e i processi flogistici locali, dando all’ossido di zinco l’opportunità di favorire la cicatrizzazione. Therefore, the antiseptic action of Metronidozole blocks sepsis and local inflammatory processes, giving zinc oxide the opportunity to promote healing.
In conclusione si evince che l’Ossido di Zinco ha tre funzioni: In conclusion, it is clear that Zinc Oxide has three functions:
1) funzione di barriera, 1) barrier function,
2) à ̈ un Assorbente per l’umidità , 2) It is an absorbent for humidity,
3) Ã ̈ un Supporto inerte veicolante del Metronidazolo con lento rilascio, 3) It is an inert carrier of Metronidazole with slow release,
mentre il Metronidazolo ha due funzioni: while Metronidazole has two functions:
1) Ã ̈ un Antibiotico mirato per enterobacilli ed anaerobi; e 1) It is a targeted antibiotic for enterobacilli and anaerobes; And
2) cura e/o previene flogosi locali supportate dalla flora batterica. 2) cures and / or prevents local inflammation supported by bacterial flora.
In associazione, l’ossido di zinco favorisce la cicatrizzazione in assenza di flogosi settica e migliora l’azione antisettica del metronidazolo grazie all’azione assorbente riducendo l’umidità della ferita sfavorendone l’accrescimento batterico Lo studio clinico ha ampliamente dimostrato come l’interazione sinergica dei due principi (Ossido di zinco e Metronidazolo ) aumenti le caratteristiche farmaco-cliniche e cinetiche tanto da determinare l’ipotesi di un nuovo principio farmacologico. In association, zinc oxide promotes healing in the absence of septic inflammation and improves the antiseptic action of metronidazole thanks to the absorbent action, reducing the humidity of the wound, disfavouring bacterial growth. demonstrated how the synergistic interaction of the two principles (zinc oxide and metronidazole) increases the pharmaco-clinical and kinetic characteristics so as to determine the hypothesis of a new pharmacological principle.
Claims (5)
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US20060240123A1 (en) * | 2002-08-26 | 2006-10-26 | S.L.A. Pharma Ag | Pharmaceutical composition |
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US6322820B1 (en) * | 1999-05-25 | 2001-11-27 | Sylvain Simoneau | Composition of matter and method for the relief of hemorrhoidal conditions |
EP1206937A1 (en) * | 1999-07-16 | 2002-05-22 | Shoei Co., Ltd. | Nitroimidazole external preparations for dermatosis |
US20060240123A1 (en) * | 2002-08-26 | 2006-10-26 | S.L.A. Pharma Ag | Pharmaceutical composition |
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