Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0031—Rectum, anus
• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/10—Dispersions; Emulsions
  • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
  • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Definitions

• the present invention concerns a butyric acid salt-based composition for rectal application for the treatment of proctology disorders, including haemorrhoidal syndrome, to which the description will refer without loss of generality.
• Haemorrhoidal syndrome is one of the most frequent disorders in the gastroenterological field. It has been calculated that in the western countries the prevalence is around 10%, occurring most often between the ages of 45 and 65, with equal frequency in men and women. Very often haemorrhoidal syndrome, and anorectal diseases in general, are the consequence of chronic constipation. The latter represents one, if not the most important, risk factor for the development of pathologies like haemorrhoid congestion, rectal prolapse, diverticulitis and complications thereof.
• the choice of the most suitable treatment to solve the problem of haemorrhoidal syndrome depends largely on the stage of the disease. For preventive purposes, it is possible to intervene by modifying dietary and hygiene habits and lifestyle in general, and in the initial phases of the disease the application of ointments and creams for local use can be extremely useful. If, on the other hand, the disease has progressed to a more advanced stage, the use of topical medicaments may not be sufficient and more targeted outpatient treatments will be necessary such as, for example, cryotherapy or laser therapy, or even surgery. As is known, the more advanced the stage of the disease, the greater the pain caused.
• the inventors of the present invention have produced a composition for rectal use based on a butyric acid salt able to meet the above need and applicable both in the form of a micro enema and in the form of a rectal cream.
• the subject of the present invention is a water-based composition for use in the rectal treatment of proctological disorders characterised in that it comprises sodium hyaluronate butyrate and a polymer compound belonging to the polysiloxane family and having a nominal viscosity ranging from 200 to 500 mm 2 /s; the weight ratio between sodium hyaluronate butyrate and the polymer compound ranges from 0.01 to 0.1.
• the nominal viscosity of the polymer compound belonging to the polysiloxane family is an important characteristic for the invention, since it gives the composition a viscosizing effect essential for its efficacy.
• the complex consisting of said sodium hyaluronate butyrate and said polymer compound is present in the composition in a quantity ranging from 1% to 20% by weight with respect to the quantity of water.
• said polymer compound is a polyalkylsiloxane, more preferably a polydimethylsiloxane.
• the weight ratio between sodium hyaluronate butyrate and the polymer compound ranges from 0.01 to 0.05.
• the complex consisting of sodium hyaluronate butyrate and polysiloxanes is present in a quantity ranging from 1% to 10% by weight with respect to the quantity of water.
• the presence of the polysiloxane is essential for providing a mechanical barrier at proctological level which has the purpose of protecting the mucosa from external insults, favouring restoration of the homeostasis of the surrounding environment. Furthermore, once the water has evaporated, the polysiloxane allows the formation of a film able to retain the functional substances. In other words, the polysiloxane helps the sodium hyaluronate butyrate to persist on the mucosa and is in turn useful for restoring the compromised mucosa. Lastly, the polysiloxane has a viscosizing action such as to give the composition the correct consistency. In fact, like all preparations applied rectally, also the compositions subject of the present invention must have a consistency that is not too liquid otherwise they tend to seep out without coming into contact with the mucosa.
• a further subject of the present invention is a micro-enema comprising the composition subject of the present invention.
• a further subject of the present invention is a cream for rectal use comprising the composition subject of the present invention.
• Tables I and II show the compositions in % by weight of the above-mentioned formulations.
• the preservative used is marketed under the name ISOCIDE® BAS.
• the dimethicone used is marketed under the name Acesil® 350.
• the sodium hyaluronate butyrate used is marketed under the name ITHABUT®. A procedure is reported below for preparation of the twelve compositions described above.
• a uniform emulsion was produced by placing the emulsifying agents, the thickening agents and an aliquot of water in a mixer (Laborall Kyro 350) or in a fuser (Laborall Antares Fuser) according to whether the compositions are intended for use in the form of cream or in the form of a micro-enema respectively.
• the system was set to quick stirring, leaving the mixture to emulsify for 20-25 minutes until obtaining a uniform emulsion.
• the sodium hyaluronate butyrate was cold-solubilized in a remaining aliquot of water until forming a transparent and uniform gel to which the dimethicone was added.
• the solution with sodium hyaluronate butyrate and dimethicone was combined with the emulsion previously produced, pouring it into the mixer (compositions usable in the form of cream) or into the fuser (compositions usable in the form of micro-enema) .
• the system thus obtained was left under stirring for 20 minutes.
• Two of the comparison compositions are compositions useful for administration with micro-enemas and differ from the composition 1 respectively due to the presence of the sodium hyaluronate instead of sodium hyaluronate butyrate and due to the absence of the dimethicone.
• compositions la and lb have a viscosity of 630 and 600 mm 2 /s respectively .
• Two of the comparison compositions (7a, 7b) are compositions useful for administration in the form of cream and differ from composition 7 respectively due to the presence of the sodium hyaluronate instead of the sodium hyaluronate butyrate and due to the absence of the dimethicone.
• compositions 7a and 7b have a viscosity of 650 and 620 mm 2 /s respectively.
• compositions 1, 7, la, lb, 7a and 7b were tested to verify their efficacy in the treatment of haemorrhoidal syndrome.
• the study concerned a daily administration of each of the above compositions (1, 7, la, lb, 7a and 7b) to a respective group of patients for two weeks.
• the patients recruited were all over the age of 18 and had haemorrhoidal syndrome and/or anorectal diseases.
• each group of patients was composed of ten men and ten women. Of these, nine patients were affected by irritable bowel syndrome (IBS) and eleven patients were affected by primary constipation.
• IBS irritable bowel syndrome
• compositions were verified in terms of clinical evaluation of the dominant symptoms such as: pain and burning sensation, bleeding, feeling of heaviness in the rectal area, secretions of mucous and itching.
• the evaluation was carried out by means of scores from 1 to 10 in terms of increasing intensity.
• Tables III and IV report the mean evaluations of the patients before and after the treatment with compositions 1 and 7 of the present invention and with the comparison compositions.
• compositions subject of the present invention have a high efficacy able to abate the symptoms connected with haemorrhoidal syndrome.
• compositions 1 and 7 respectively highlights the importance of the presence of the polysiloxane polymer in the composition.
• the importance of the presence of this polymer derives both from the viscosizing action produced, able to give the composition the correct consistency to guarantee the permanent contact thereof with the mucosa, and from the formation of a film able to retain the functional substances and, therefore, help the sodium hyaluronate butyrate to persist on the mucosa to aid the healing thereof.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Epidemiology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• Dermatology (AREA)
• Heart & Thoracic Surgery (AREA)
• Dispersion Chemistry (AREA)
• Inorganic Chemistry (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Vascular Medicine (AREA)
• Cardiology (AREA)
• Molecular Biology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicinal Preparation (AREA)

Priority Applications (1)

Applications Claiming Priority (2)

Publications (1)

Family

ID=70480457

Family Applications (1)

Country Status (3)

Cited By (1)

Citations (6)

• 2020
  • 2020-01-30 IT IT102020000001831A patent/IT202000001831A1/it unknown
• 2021
  • 2021-01-28 WO PCT/IB2021/050659 patent/WO2021152492A1/en active Search and Examination
  • 2021-01-28 EP EP21708364.1A patent/EP4096629A1/en active Pending

Patent Citations (6)

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events