ITMI20091122A1 - PHARMACEUTICAL FORMULATIONS FOR INTRAVAGINAL USE IN THE PREVENTION AND THERAPY OF VAGINITE VULVUSES AND IN THE RESTORATION OF VAGINAL PHYSIOLOGY - Google Patents
PHARMACEUTICAL FORMULATIONS FOR INTRAVAGINAL USE IN THE PREVENTION AND THERAPY OF VAGINITE VULVUSES AND IN THE RESTORATION OF VAGINAL PHYSIOLOGY Download PDFInfo
- Publication number
- ITMI20091122A1 ITMI20091122A1 IT001122A ITMI20091122A ITMI20091122A1 IT MI20091122 A1 ITMI20091122 A1 IT MI20091122A1 IT 001122 A IT001122 A IT 001122A IT MI20091122 A ITMI20091122 A IT MI20091122A IT MI20091122 A1 ITMI20091122 A1 IT MI20091122A1
- Authority
- IT
- Italy
- Prior art keywords
- pharmaceutical formulations
- formulations according
- oligosaccharides
- vaginal
- hyaluronic acid
- Prior art date
Links
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- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 claims description 12
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
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- 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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
- A61K31/787—Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
- A61K31/79—Polymers of vinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dermatology (AREA)
- Zoology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Le vaginiti o vulvovaginiti sono le patologie ginecologiche più diffuse, tra queste la vaginosi batterica (VB) à ̈ considerata la più frequente e rientra in maniera determinante nel novero delle infezioni urogenitali, che si stima colpiscano almeno 1 miliardo di individui ogni anno, VB insieme ai classici sintomi di tutte le vulvo-vaginiti si caratterizza per la presenza di un elevato pH delle secrezioni vaginali e per la deplezione della flora vaginale ed in particolare di Lactobacilli (Bacilli di Doderlein). Tale condizione à ̈ considerata la causa principale che determina la crescita abnorme di batteri patogeni. Le riacutizzazioni e recidive sono inoltre un’altra costante di questa patologia. L’alta incidenza di questa patologia, l’alta frequenza di recidive determinano l’urgenza di identificare nuove strategie terapeutiche per queste patologie ed in particolare per VB, adatte alla loro prevenzione compresa quella delle recidive, infatti, VB à ̈ associata a complicanze della gravidanza, infezioni del tratto genitale superiore, infiammazioni pelviche, endometriosi, infezioni post-chirurgiche, cerviciti, infezioni urinarie, neoplasie ed aumentati rischi di contrarre per via sessuale il virus HIV ( Cauci S. et al J. Clin. Microbiol. 2002: 40: 2147-52), Il ruolo cruciale dellecosistema vaginale ed in particolare della presenza di Lactobacillus acidophilus nella prevenzione di malattie ginecologiche ed in particolare della VB sembra trovare attualmente un largo supporto nella comunità scientifica (Vasquez A et al. J. Clin, Microbiol. 2002; 40: 2746-9). La capacità della flora vaginale di proteggere da sovra-infezioni batteriche e fungine sembra essere essenzialmente legata alla capacità di Lactobacillus acidophilus di produrre sostanze acide, in particolare acido lattico, che mantenendo l' intorno vaginale ad un pH acido ( pH ~ 4) previene la colonizzazione di batteri patogeni. Vaginitis or vulvovaginitis are the most common gynecological pathologies, among these bacterial vaginosis (BV) is considered the most frequent and is decisively included in the category of urogenital infections, which are estimated to affect at least 1 billion individuals every year, BV together to the classic symptoms of all vulvo-vaginitis is characterized by the presence of a high pH of vaginal secretions and by the depletion of the vaginal flora and in particular of Lactobacilli (Bacilli of Doderlein). This condition is considered the main cause that determines the abnormal growth of pathogenic bacteria. Exacerbations and relapses are also another constant of this pathology. The high incidence of this pathology, the high frequency of relapses determine the urgency to identify new therapeutic strategies for these pathologies and in particular for VB, suitable for their prevention including that of relapses, in fact, VB is associated complications of pregnancy, upper genital tract infections, pelvic inflammations, endometriosis, post-surgical infections, cervicitis, urinary infections, neoplasms and increased risks of sexually contracting the HIV virus (Cauci S. et al J. Clin. Microbiol. 2002: 40: 2147-52), The crucial role of the vaginal ecosystem and in particular of the presence of Lactobacillus acidophilus in the prevention of gynecological diseases and in particular of BV seems to find a wide support in the scientific community (Vasquez A et al. J. Clin , Microbiol. 2002; 40: 2746-9). The ability of the vaginal flora to protect against bacterial and fungal over-infections seems to be essentially linked to the ability of Lactobacillus acidophilus to produce acidic substances, in particular lactic acid, which by keeping the vaginal area at an acidic pH (pH ~ 4) prevents the colonization of pathogenic bacteria.
Alio scopo di favorire la colonizzazione dei Lactobacillus vaginali sono stati effettuati alcuni studi clinici utilizzando la somministrazione orale di specie selezionate di Lactobacillus (Reid G et al. FEMS Immunol. Med. Mìcrobiol. In order to favor the colonization of vaginal Lactobacillus, some clinical studies have been carried out using the oral administration of selected Lactobacillus species (Reid G et al. FEMS Immunol. Med. Mìcrobiol.
2003; 35: 131-4). Analogamente l' instillazione vaginale di alcuni ceppi dì Lactobacillus ha determinato una riduzione delle iniezioni urinarie con un miglioramento della flora batterica (Reid G and Burton, 1. Microbes. Infect. 2003; 35: 131-4). Similarly, the vaginal instillation of some Lactobacillus strains resulted in a reduction in urinary injections with an improvement in the bacterial flora (Reid G and Burton, 1. Microbes. Infect.
2002; 4: 319-24). In questo contesto à ̈ imperativo stabilire l’identità dei vari ceppi di Lactobacillus in grado di colonizzare la vagina. Tuttavia sono emerse notevoli discrepanze legate a differenze tra razze o tra organi colonizzati (Velasquez A et al. J. Gin. Microbiol. 2002; 40:2746-9). Questa problematica à ̈ stata superata dalle domande di breveto (MI2003A000915 e FR2874825-A1) che rivendicano l’uso di oligosaccaridi prebiotici somministrati localmente nella vagina per ripristinare o mantenere la correta omeostasi della flora vaginale. E’ infatti noto nell’arte come tali oligosaccaridi prebiotìci siano in grado di favorire in modo selettivo la crescita dei Lattobacilli endogeni inibendo conseguentemente la crescita dì bateri patogeni (Rousseau V et al. Anaerobi 2005; 11: 145-53). Scopo della presente invenzione à ̈ quello di associare l’azione degli oligosaccaridi prebiotici, per favorire la crescita della flora vaginale autoctona, con agenti antibatterici in grado di ridurre seletivamente la carica batterica patogena qualora necessario. Tale potenziate combinazione e già nota nell'arte e à domanda dì brevetto MI2003A000915 riporta ad esempio fuso di oligosaccaridi prebiotici con farmaci antibiotici ed agenti naturali antibatterici, citando altresì l’uso di vari farmaci antibiotici ed oli essenziali come il TTO. Tuttavia la combinazione tra oligosaccaridi prebiotici e composti antibatterici potrebbe avere almeno 2 tipi di limitazioni. Una prima limitazione à ̈ costituita dal fatto che agenti antibatterici non selettivi potrebbero agire indiscriminatamente sia contro i Lattobacilli endogeni che contro i batteri patogeni con la conseguenza di eliminare non solo quest'ultimi ma anche la flora batterica endogena e ridurre ovviamente l'efficacia terapeutica degli oligosaccaridi prebiotici. Ad esempio à ̈ consuetudine consolidata prescrivere o consigliare fuso di Lattobacilli durante la terapia antibiotica sistemica allo scopo di ripristinare la flora batterica intestinale. Inoltre, tale eventualità à ̈ specificatamente avvalorata a livello vaginale anche nella domanda di brevetto FR2874825-A1. Un secondo ordine di limitazioni proviene dalla ben nota capacità dei farmaci antibiotici ed in generale di tutti i composti antibatterici di ingenerare resistenze nei batteri. Infatti si consiglia di non prolungare in modo arbitrario la terapia antibatterica perché questa favorisce l’insorgenza di ceppi di batteri patogeni resistenti (Guida all’uso dei farmaci. Agenzia Italiana del Farmaco, 2007 4, 7.1 pag 234). Ne risulta pertanto che un uso prolungato di agenti antibatterici à ̈ altamente sconsigliato in preparati che debbano essere utilizzati in modo continuativo per la prevenzione delle VB, così come per altre patologie caratterizzate da frequenti recidive. Per superare queste limitazioni la presente invenzione prevede l' uso di oligosaccaridi prebiotici in associazione a sostanze antibatteriche naturali fisiologicamente presenti a livello vaginale. I polipeptidi endogeni ad attività antimicrobica presenti nei fluidi vaginali sono numerosi, tra gli altri ricordiamo: Lisozima. Lattoferrina, SLP1 (secretory leukocyte protease inhibitor), HNP-1 -2 -3 (human neutrophil peptides) e HBDs (human β-defensin), Calgranulin A e B, Histone H2A family . Tra tali sostanze quelle che sono particolarmente preferite per un utilizzo nella presente invenzione sono: Lisozima e Lattoferrina in quanto disponibili commercialmente come principi attivi e che presentano una attività biologica analoga a quella espressa dal composto endogeno. Lisozima umano à ̈ una proteina basica con una catena polipeptidica di 130 aminoacidi avente un peso molecolare di circa 15000 dalton (Salton MRJ Bacteriol Rev, 1957; 21; 82-99). Questa proteina à ̈ naturalmente presente in alte concentrazioni nelle secrezioni vaginali umane in condizioni fisiologiche e determina, almeno in parte, la ben documentata attività antimicrobica del muco cervicale (Eggert-Kruse W et al. Human Reproduction 2000; 15(4): 778-84). La Lattoferrina à ̈ una glicoproteina basica con 703 residui amminoacidici e con un’alta capacità di legare ioni ferro. La Lattoferrina ha un ruolo essenzialmente difensivo nell’organismo umano, infatti oltre ad essere un potente agente batteriostatico ha anche un’attività battericida e può interferire nella proliferazione di funghi e virus (Levay PF et al. Haematologica 1995; 80: 252-67). La presenza di Lattoferrina nel muco vaginale à ̈ ben documentata e non solo risente del ciclo ormonale nella donna ma risulta anche evidente una consecutività cranio-caudale (utero, cervice, vagina) delle sue concentrazioni dipendendo dalle fluttuazioni ormonali (Newbold RR et al Biol Reproduct. 1992; 47: 903-15). E’ del tuto evidente che l’associazione di agenti prebiotici con sostanze antibatteriche naturali e già endogenamente presenti e livello vaginale; 1) riduce grandemente la possibilità di interferenza di queste con i lattobacilli endogeni, 2) ripristina il potenziale antibatterico endogeno la cui riduzione à ̈ una potenziale causa delle infezioni patogene. Pertanto le quantità in peso di Lisozima e Lattoferrina particolarmente preferite nella presente invenzione atte alla somministrazione topica intravaginale sono quelle che mediamente risultano essere presenti in maniera fisiologica a livello endo-vaginale. In particolare la quantità dì Lisozima à ̈ compresa tra 6.4 Î1⁄4g/ml e 391.4 gg/ml con una media di 33.0 Î1⁄4g/ml (Eggert-Kruse W et al. Human Reproduction 2000; 15(4): 778-84), Analogamente la concentrazione di Lattoferrina à ̈ compresa tra 3.8 Î1⁄4g/g proteine e 218 Î1⁄4g/g proteine ( Levay PF et al. Haematologica 1995; 80; 252-67). Lattoferrina e Lisozima possono essere utilizzate singolarmente od in associazione tra di loro o con altri peptidi antibatterici naturali. Ad ulteriore miglioramento dell' efficacia dell’associazione tra agenti prebiotici e peptidi antibatterici naturali, la presente invenzione prevede l’uso di Ac. Ialuronico che, sebbene già utilizzato a livello vaginale per le sue ben note attività idratanti e cicatrizzanti, sorprendentemente à ̈ in grado di potenziarne le azioni terapeutiche di detta associazione. Inoltre, sorprendentemente il Polivinilpirrolidone (PVP) può vantaggiosamente sostituire in toto od in parte l’Ac. Ialuronico nella sua efficacia nella presente invenzione. Se richiesto l'Ac. laluronico può essere vantaggiosamente sostituito in toto od in parte con Chitosano, 2002; 4: 319-24). In this context it is imperative to establish the identity of the various strains of Lactobacillus capable of colonizing the vagina. However, significant discrepancies related to differences between races or between colonized organs emerged (Velasquez A et al. J. Gin. Microbiol. 2002; 40: 2746-9). This problem has been overcome by patent applications (MI2003A000915 and FR2874825-A1) which claim the use of prebiotic oligosaccharides administered locally in the vagina to restore or maintain the correct homeostasis of the vaginal flora. It is in fact known in the art how these prebiotic oligosaccharides are able to selectively favor the growth of endogenous lactobacilli, consequently inhibiting the growth of pathogenic bacteria (Rousseau V et al. Anaerobi 2005; 11: 145-53 ). The purpose of the present invention is to associate the action of prebiotic oligosaccharides, to favor the growth of the native vaginal flora, with antibacterial agents capable of selectively reducing the pathogenic bacterial load if necessary. This enhanced combination is already known in the art and is patent application MI2003A000915 for example fusion of prebiotic oligosaccharides with antibiotic drugs and natural antibacterial agents, also citing the use of various antibiotic drugs and essential oils such as TTO. However, the combination of prebiotic oligosaccharides and antibacterial compounds could have at least 2 types of limitations. A first limitation is constituted by the fact that non-selective antibacterial agents could act indiscriminately both against endogenous Lactobacilli and against pathogenic bacteria with the consequence of eliminating not only the latter but also the endogenous bacterial flora and obviously reducing the therapeutic efficacy of the prebiotic oligosaccharides. For example, it is well-established practice to prescribe or recommend lactobacilli spindle during systemic antibiotic therapy in order to restore the intestinal bacterial flora. Furthermore, this possibility is specifically confirmed at the vaginal level also in the patent application FR2874825-A1. A second order of limitations comes from the well known ability of antibiotic drugs and in general of all antibacterial compounds to generate resistance in bacteria. In fact, it is advisable not to arbitrarily prolong antibacterial therapy because it favors the onset of resistant pathogenic bacteria strains (Guide to the use of drugs. Italian Medicines Agency, 2007 4, 7.1 pag 234). As a result, a prolonged use of antibacterial agents is highly discouraged in preparations that must be used continuously for the prevention of BV, as well as for other diseases characterized by frequent relapses. To overcome these limitations, the present invention provides for the use of prebiotic oligosaccharides in association with natural antibacterial substances physiologically present in the vagina. The endogenous polypeptides with antimicrobial activity present in vaginal fluids are numerous, among others: Lysozyme. Lactoferrin, SLP1 (secretory leukocyte protease inhibitor), HNP-1 -2 -3 (human neutrophil peptides) and HBDs (human β-defensin), Calgranulin A and B, Histone H2A family. Among these substances, those which are particularly preferred for use in the present invention are: Lysozyme and Lactoferrin as they are commercially available as active principles and which have a biological activity similar to that expressed by the endogenous compound. Human lysozyme is a basic protein with a polypeptide chain of 130 amino acids having a molecular weight of about 15,000 daltons (Salton MRJ Bacteriol Rev, 1957; 21; 82-99). This protein is naturally present in high concentrations in human vaginal secretions under physiological conditions and determines, at least in part, the well documented antimicrobial activity of cervical mucus (Eggert-Kruse W et al. Human Reproduction 2000; 15 (4): 778- 84). Lactoferrin is a basic glycoprotein with 703 amino acid residues and with a high capacity to bind iron ions. Lactoferrin has an essentially defensive role in the human organism, in fact in addition to being a powerful bacteriostatic agent it also has bactericidal activity and can interfere in the proliferation of fungi and viruses (Levay PF et al. Haematologica 1995; 80: 252- 67). The presence of Lactoferrin in the vaginal mucus is well documented and not only affected by the hormonal cycle in women but a cranio-caudal consecutivity (uterus, cervix, vagina) of its concentrations is also evident, depending on hormonal fluctuations (Newbold RR et al Biol Reproduct . 1992; 47: 903-15). It is evident that the association of prebiotic agents with natural and endogenously present antibacterial substances and vaginal level; 1) greatly reduces the possibility of interference of these with endogenous lactobacilli, 2) restores the endogenous antibacterial potential whose reduction is a potential cause of pathogenic infections. Therefore, the quantities by weight of Lysozyme and Lactoferrin particularly preferred in the present invention suitable for topical intravaginal administration are those which on average appear to be present in a physiological manner at the endo-vaginal level. In particular, the quantity of Lysozyme is between 6.4 Î1⁄4g / ml and 391.4 days / ml with an average of 33.0 Î1⁄4g / ml (Eggert-Kruse W et al. Human Reproduction 2000; 15 (4): 778 -84), Similarly, the concentration of Lactoferrin is between 3.8 Î1⁄4g / g protein and 218 Î1⁄4g / g protein (Levay PF et al. Haematologica 1995; 80; 252-67). Lactoferrin and Lysozyme can be used individually or in combination with each other or with other natural antibacterial peptides. To further improve the efficacy of the association between prebiotic agents and natural antibacterial peptides, the present invention provides for the use of Ac. Hyaluronic which, although already used vaginally for its well-known moisturizing and healing activities, surprisingly is able to enhance the therapeutic actions of said association. Moreover, surprisingly, Polyvinylpyrrolidone (PVP) can advantageously replace the Ac in whole or in part. Hyaluronic in its effectiveness in the present invention. If required the Ac. hyaluronic acid can be advantageously replaced in whole or in part with Chitosan,
Per agenti prebiotici si intendono nella presente invenzione tutte quelle sostanze in grado di favorire la crescita di lactobacilli e bifidoba ed in generale della flora microbica endogena, cosi come ad esempio sono definiti da Cummings JH et al Am, J. din. Nutr. 2001 73 (suppl). 415S-20S. Nella presente invenzione sono stati studiati più in particolare inulina e una serie di oligosaccaridi ad attività prebiotica come ad esempio i frutto-oligosaccaridi (FOS), xylo-oligosaccaridi, Polydextrose, Raffiline, Oligomate, Palatinose, Pyrodextrin. gluco-oligosaccaridi, galacto-oligosaccaridi e oligoglucosammine meglio conosciuti come Chitosano oligosaccaridi e miscele degli stessi. Per peptidi antibatterici naturali ed altre terminologie analoghe si intendono nella presente invenzione: Lisozima e Lattoferrina, e quanti riportati nella tabella 1 in Venkataraman N, et al. J. Immimol. 2005; 175: 7560-67 con la specìfica dizione antibatterica ovvero Neutrophil Gelatinase Associated Lipocafin, Histone-H2B -H2A Family — H4 Family, Calgranulin, HNP-1 -2 -3, inoltre SLPI (secretory leukocyte protease inbibitor e HBDs (human β-defensin) non riportati in tale tabella. Inoltre le concentrazioni fisiologiche di tali polipeptide si riferiscono a quelle riportate in tabella II della stessa pubblicazione, ad eccezione di Lattoferrina (3.8 Î1⁄4g/g proteine e 218 Î1⁄4g/g proteine) in quanto non riportata in tale tabella e Lisozima (6.4Î1⁄4 pg/ml e 391.4 Î1⁄4g/ml) in quanto le presenti concentrazioni sono state calcolate in base alla specifica attività antibatterica del composto in commercio (Eggert-Kruse W et al. Human Reproduction 2000; 15(4); 778-84). L’acido Ialutonico utilizzabile nella presente invenzione ha un peso molecolare compreso tra 5000 e 15.000.000 dalton e può essere di origine animale o preferibilmente fermentativa ad alto peso molecolare, ovvero superiore a 800.000 dalton. Le formulazioni farmaceutiche utili per somministrare trovato della presente invenzione sono quelle adatte per la somministrazione di farmaci intravaginali topici e comprendono, senza esclusione di altre formulazioni farmaceuticamente accettabili, ad esempio; gel e creme vaginali, lavande, ovuli e candelette, capsule molli, schiume vaginali ecc. By prebiotic agents in the present invention we mean all those substances capable of promoting the growth of lactobacilli and bifidoba and in general of the endogenous microbial flora, as defined for example by Cummings JH et al Am, J. din. Nutr. 2001 73 (suppl). 415S-20S. In the present invention, inulin and a series of oligosaccharides with prebiotic activity have been studied in particular, such as for example the fructo-oligosaccharides (FOS), xylo-oligosaccharides, Polydextrose, Raffiline, Oligomate, Palatinose, Pyrodextrin. gluco-oligosaccharides, galacto-oligosaccharides and oligoglucosamines better known as Chitosan oligosaccharides and their mixtures. By natural antibacterial peptides and other similar terminologies are meant in the present invention: Lysozyme and Lactoferrin, and those reported in table 1 in Venkataraman N, et al. J. Immimol. 2005; 175: 7560-67 with the specific antibacterial diction or Neutrophil Gelatinase Associated Lipocafin, Histone-H2B -H2A Family - H4 Family, Calgranulin, HNP-1 -2 -3, in addition SLPI (secretory leukocyte protease inbibitor and HBDs ( human β-defensin) not shown in this table. Furthermore, the physiological concentrations of these polypeptides refer to those reported in table II of the same publication, with the exception of Lactoferrin (3.8 Î1⁄4g / g proteins and 218 Î1⁄4g / g proteins ) as not shown in this table and Lysozyme (6.4Î1⁄4 pg / ml and 391.4 Î1⁄4g / ml) as the present concentrations have been calculated based on the specific antibacterial activity of the compound on the market (Eggert-Kruse W et al. Human Reproduction 2000; 15 (4); 778-84). The hyalutonic acid usable in the present invention has a molecular weight between 5000 and 15,000,000 daltons and can be of animal origin or preferably fermentative with a high molecular weight , or higher than 800 .000 dalton. The pharmaceutical formulations useful for administering the invention of the present invention are those suitable for administering topical intravaginal drugs and include, without excluding other pharmaceutically acceptable formulations, for example; vaginal gels and creams, douches, pessaries and candles, soft capsules, vaginal foams, etc.
Esempio 1 Gel vaginale. Composizione quali-quantitativa per 100 g di formulato: Lisozima 0.2g; Actilight 950P 8g; Ialuronico sale sodico 0.2g; Idrossietilcellulosa 50HHX Pharma 1.8g; Glicol propilenico 4,0g; Glicerina 2g; Nipaguard MPA 0.3g; Allantoina 0.2g; BHA 0.01g; Ac. Lattico q.b. pH 4.5; Η2O depurata q.b. 100g. Dosaggio consigliato per singola applicazione tramite cannula intravaginale 2.5 g. Example 1 Vaginal gel. Qualitative-quantitative composition per 100 g of formulation: Lysozyme 0.2g; Actilight 950P 8g; Hyaluronic sodium salt 0.2g; Hydroxyethylcellulose 50HHX Pharma 1.8g; 4.0g propylene glycol; 2g glycerin; Nipaguard MPA 0.3g; Allantoin 0.2g; BHA 0.01g; B.C. Lactic to taste pH 4.5; Î — 2O purified to taste 100g. Recommended dosage for single application through intravaginal cannula 2.5 g.
Esempio 2 Gel vaginale. Composizione quali-quantitativa per 100 g di formulato; Lisozima 0.2g; Lattoferrina 0.2g; Actilight 950P 8g; ialuronico sale sodico 0.2g; PVP K29/32 2g; idrossietilcellulosa 50HHX Pharma 1,8-2.0g; Glicol propilenico 4,0g; Glicerina 2g; Camomilla distillato acquoso 8g; Nipaguard MPA 0.3g; Allantoina 0.2g; BHA 0.01 g; Ac. q.b. pH 4.5; depurata q.b. 100g. Dosaggio consigliato come nell' esempio precedente Example 2 Vaginal gel. Qualitative-quantitative composition per 100 g of formulation; Lysozyme 0.2g; Lactoferrin 0.2g; Actilight 950P 8g; hyaluronic sodium salt 0.2g; PVP K29 / 32 2g; hydroxyethylcellulose 50HHX Pharma 1.8-2.0g; 4.0g propylene glycol; 2g glycerin; 8g aqueous distilled chamomile; Nipaguard MPA 0.3g; Allantoin 0.2g; BHA 0.01 g; B.C. q.s. pH 4.5; purified to taste 100g. Recommended dosage as in the previous example
Esempio 3 Lavanda vaginale. Composizione quali-quantitativa per 100 g di formulato; Lisozima 0.2g; Actilight 950P 8g; PVP K29/32 2g: Glicol propilenico 4,0g; Glicerina 2g; Camomilla distillato acquoso 8g; Nipaguard MPA 0.3g; Allantoina 0.2g; BHA 0.01 g; Ac. q.b. pH 4,5; H2O depurata q.b. 100g. Dosaggio consigliato per singola applicazione tramite cannula vaginale 150 ml Example 3 Vaginal lavage. Qualitative-quantitative composition per 100 g of formulation; Lysozyme 0.2g; Actilight 950P 8g; PVP K29 / 32 2g: Propylene glycol 4.0g; 2g glycerin; 8g aqueous distilled chamomile; Nipaguard MPA 0.3g; Allantoin 0.2g; BHA 0.01 g; B.C. q.s. pH 4.5; Purified H2O q.s. 100g. Recommended dosage for single application via vaginal cannula 150 ml
Esempio 4 Ovuli vaginali. Composizione quali-quantitativa per 1 ovulo da 2g: Lisozima 5mg; Actilight 950P 200mg; Ialuronico sale sodico 5mg; Suppocire S2X q.b 2g. Dosaggio consigliato 1 ovulo vaginale 2 volte al di. Example 4 Vaginal ovules. Qualitative-quantitative composition for 1 egg of 2g: Lysozyme 5mg; Actilight 950P 200mg; Hyaluronic sodium salt 5mg; Suppose S2X q.b 2g. Recommended dosage 1 vaginal ovule 2 times a day.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20210077516A1 (en) * | 2014-03-13 | 2021-03-18 | Singapore Ze&Z International Pte. Ltd | Vaginal composition and use thereof |
IT202100023030A1 (en) * | 2021-09-06 | 2023-03-06 | Proxenia Srl | COMPOSITION FOR THE TREATMENT OF INFECTIONS OF THE ENDOMETRIAL MUCOSA AND RELATED ADMINISTRATION KIT |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0591443B1 (en) * | 1991-06-27 | 1996-10-23 | Bioeurope | Use of cosmetic compositions containing oligosaccharides |
EP1444984A1 (en) * | 2003-02-06 | 2004-08-11 | B.S.D. BIO SCIENCE DEVELOPMENT SNC Di OMINI C. & ZUCCARI G. | Topical pharmaceutical compositions containing natural active constituents suitable for the prevention and treatment of mucosal inflammation processes |
WO2006030100A1 (en) * | 2004-09-08 | 2006-03-23 | Genibio | Uses of prebiotic oligosaccharides beneficial to vaginal flora |
EP1911454A1 (en) * | 2005-04-27 | 2008-04-16 | HK Phlora Health Sci. & Tech. Limited | A composition and method of regulating and maintaining the vaginal bacterial flora and the normal acidity in the vaginal |
-
2009
- 2009-06-25 IT ITMI2009A001122A patent/IT1398279B1/en active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0591443B1 (en) * | 1991-06-27 | 1996-10-23 | Bioeurope | Use of cosmetic compositions containing oligosaccharides |
EP1444984A1 (en) * | 2003-02-06 | 2004-08-11 | B.S.D. BIO SCIENCE DEVELOPMENT SNC Di OMINI C. & ZUCCARI G. | Topical pharmaceutical compositions containing natural active constituents suitable for the prevention and treatment of mucosal inflammation processes |
WO2006030100A1 (en) * | 2004-09-08 | 2006-03-23 | Genibio | Uses of prebiotic oligosaccharides beneficial to vaginal flora |
EP1911454A1 (en) * | 2005-04-27 | 2008-04-16 | HK Phlora Health Sci. & Tech. Limited | A composition and method of regulating and maintaining the vaginal bacterial flora and the normal acidity in the vaginal |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20210077516A1 (en) * | 2014-03-13 | 2021-03-18 | Singapore Ze&Z International Pte. Ltd | Vaginal composition and use thereof |
EP3117827B1 (en) | 2014-03-13 | 2021-11-03 | Singapore Ze&Z International Pte. Ltd. | Composition for vagina and use of the composition |
US11951116B2 (en) * | 2014-03-13 | 2024-04-09 | Singapore Ze&Zinternational Pte. Ltd | Vaginal composition and use thereof |
IT202100023030A1 (en) * | 2021-09-06 | 2023-03-06 | Proxenia Srl | COMPOSITION FOR THE TREATMENT OF INFECTIONS OF THE ENDOMETRIAL MUCOSA AND RELATED ADMINISTRATION KIT |
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