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
  • A61K31/70—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
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
  • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
  • A61L26/0023—Polysaccharides

Definitions

• the invention refers to stabilised composition containing hyaluronic acid, or derivatives thereof commonly used in cosmetic surgery, and a carboxyvinylpolymer capable of greater resistance to demolishing action of the enzymes to which are submitted all the implants made of such materials once applied to patients.
• Hyaluronic acid is a polysaccharide naturally present in the human tissues where it is continuously formed. In view of its viscoelastic properties it as been used for a long time in cosmetic surgery to eliminate wrinkles, indentations, scars and similar.
• Hyaluronic acid is injected for example by means of sterile prefilled syringes, in the subcoutaneous region where the unaesthetic aspect is present and forms a thickness which eliminates the folds caused by wrinkles or scars.
• hyaluronic acid is submitted to the demolishing action of natural enzymes and after a short time a new application is necessary.
• the hyaluronic acid was substituted by its derivatives as esters, salts, cross-linked derivatives but also these products, although allowing a greater permanence of the implant are not satisfactory since their life is always too short.
• compositions containing hyaluronic acids or derivatives thereof capable of greater resistance to the action of the enzymes and therefore capable of lengthening the time required before a new operation is necessary.
• the present invention provides a means of overcoming of the above said drawbacks thanks to compositions consisting of hyaluronic acid (or derivatives thereof commonly used in the cosmetic surgery and therefore pharmaceutically acceptable) and a carboxyvinylpolymer (Carbomer) of general formula: COOH COOH
• n is comprised between 50 - 55,000 and having a molecular weight comprised between 10,000 and 10,000,000, preferably 5,000,000 - 6,000,000.
• carboxyvinylpolymer is in a concentration of 0.001 % - 5% (quantity calculated as weight in respect of the total weight of the composition) more preferably 0.01 - 0.2%.
• hyaluronic acid derivatives used in the aesthetic surgery according to the invention we can cite in particular the esters (for example : methyl-, ethyl-, isopropyl-, butyl-, amyl-, isoamyl-ester), the organic or inorganic salts pharmaceutically acceptable (for example : natrium salt, thethylamine salt or the salts formed with basic aminoacids), cross-linked compounds (for example ethylen-glycole dimethacrylate, glutaric aldehyde, divinylsulphone).
• the composition according to the invention is prepared according to the methods commonly applied in the art. For example the hyaluronic acid (or the corresponding derivative) is mixed with the suitable quantity of polymer in a suitable mixer.
• the mixing is performed in the presence of, for example, p-toluensulphonic acid or ethyl-iodide.
• the obtained mixture is solved in sterile water in order to obtain the wanted concentration, the solution is filtered using a nylon filter bearing positive charges ; the obtained solution is lyophilised and the solid is dried and solved again, in the appropriated quantity, in sterile water under stirring up to the formation of a viscoelastic transparent gel.
• the product is packaged in the suitable forms (vials, bottles, sterile prefilled syringes ready to use, preferably in the following quantities : 0.1 , 0.5, 1 , 1.5, 2 ml.
• the solution is lyophilised to give a dry solid which is solved again in sterile water (1.3%) under stirring up to the formation of a viscoelastic transparent gel having the desired consistency.
• the product is packaged in sterile prefilled syringes ready for use of 0.1 , 0.5, 1 ,
• Example 3 Following the procedure described in example 1 but replacing the hyaluronic acid natrium salt with the corresponding thethylamine organic salt the corresponding formulation were prepared using the same quantities of polymer given in example
• Example 4 Following the procedure described in example 1 but replacing the hyaluronic acid natrium salt with hyaluronic acid cross-linked with ethylenglycole dimethacrylate the corresponding formulation were prepared using the same quantities of polymer given in example 1.
• Example 5 Following the procedure described in example 1 but replacing the hyaluronic acid natrium salt respectively with the methyl-, ethyl-, isopropyl-, butyl-, amyl-, isoamyl- esters of hyaluronic acid in the presence of p-toluensulphonic acid (6%) the corresponding formulation were prepared using the same quantities of polymer given in example 1.
• Example 6 Following the procedure described in example 1 but replacing the hyaluronic acid natrium salt respectively with the methyl-, ethyl-, isopropyl-, butyl-, amyl-, isoamyl- esters of hyaluronic acid in the presence of p-toluensulphonic acid (6%) the corresponding formulation were prepared using the same quantities of polymer given in example 1.
• Example 6 Example 6
• compositions analogous to those above described were prepared following the procedure described in example 1- 5 but replacing Carbomer 940 with Carbomer 4
• the enzyme hyaluronidase (type V SIGMA H6254) was used in the tests and the rate of enzymatic reaction was evaluated by kinematics viscosity measurements using a Brookfield RVF apparatus (spindle n° 5 at 10 rpm). The enzymatic degradation was conducted at 26°C and 37°C.
• the solution containing the carboxyvinylpolymer does not show any degradation of the polysaccharide after 60 minutes of contact with the enzyme both at 26°C as at 37°C
• the present invention refers also to a kit containing at least to pre-filled syringes ready for use containing the same or different quantities of a composition according to the invention in order to satisfy different needs.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Epidemiology (AREA)
• Pharmacology & Pharmacy (AREA)
• Dermatology (AREA)
• Molecular Biology (AREA)
• Medicinal Chemistry (AREA)
• Engineering & Computer Science (AREA)
• Materials Engineering (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicinal Preparation (AREA)
• Materials For Medical Uses (AREA)

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Publications (1)

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Cited By (5)

Citations (5)

• 1998
  • 1998-05-04 IT IT98FI000104A patent/ITFI980104A1/it unknown
• 1999
  • 1999-05-03 WO PCT/EP1999/002987 patent/WO1999056799A1/en active Application Filing
  • 1999-05-03 AU AU40361/99A patent/AU4036199A/en not_active Abandoned

Patent Citations (5)

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