CA2484100A1 - Novel biomaterials, their preparation and use - Google Patents

Novel biomaterials, their preparation and use Download PDF

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Publication number
CA2484100A1
CA2484100A1 CA002484100A CA2484100A CA2484100A1 CA 2484100 A1 CA2484100 A1 CA 2484100A1 CA 002484100 A CA002484100 A CA 002484100A CA 2484100 A CA2484100 A CA 2484100A CA 2484100 A1 CA2484100 A1 CA 2484100A1
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CA
Canada
Prior art keywords
precipitate
component
composition
pharmaceutical composition
cyclodextrin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002484100A
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French (fr)
Other versions
CA2484100C (en
Inventor
Lajos Szente
Jozsef Szejtli
Gyoergy Lajos Kis
Christian Schoch
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis AG
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2484100A1 publication Critical patent/CA2484100A1/en
Application granted granted Critical
Publication of CA2484100C publication Critical patent/CA2484100C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40Cyclodextrins; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7015Drug-containing film-forming compositions, e.g. spray-on
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/20Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602Type of release, e.g. controlled, sustained, slow
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/80Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special chemical form
    • A61L2300/802Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants

Abstract

The present invention relates to novel materials, particularly biomaterials, in form of a precipitate, comprising at least an anionic polymeric component which is as such soluble in water and an amphiphilic ammonium-type component , which precipitate is obtainable by a process including the following steps: contacting the anionic polymeric component and an cylcodextrin component in an aqueous medium, and adding to the mixture obtained in step 1 said amphiphili c ammonium-type component, wherein said components are present in amounts effective to form said precipitate, and preferably to corresponding precipitates additionally comprising said cycxlodextrin component. Both type s of precipitates may optionally comprise one or more further components. The precipitates are particularly useful as controlled-release depot formulation s suitable for long-lasting delivery of said further components. The further components incorporated into the precipitates can be pharmaceutical compound s, pesticides, agrochemicals, colorants, diagnostics, enzymes, foodstuffs etc.< /SDOAB>

Claims (28)

1. A precipitate, comprising at least an anionic polymeric component which is as such soluble in water and an amphiphilic ammonium-type component, which precipitate is obtainable by a process including the following steps:
1. contacting the anionic polymeric component and a cyclodextrin component in an aqueous medium, and
2. adding to the mixture obtained in step 1 said amphiphilic ammonium-type component, wherein said components are present in amounts effective to form said precipitate.
2. A precipitate according to claim 1 additionally comprising said cyclodextrin component.
3. A precipitate according to claim 1 or 2 additionally comprising one or more further component other than said cyclodextrin component which is added in course of step 1 and/or 2 of said process.
4. A precipitate according to claim 3 wherein said one or more other component is selected from pharmaceutically active agents, pesticides, agrochemicals, colorants, diagnostics, enzymes and foodstuffs.
5. A precipitate according to anyone of claims 1 to 4, wherein the anionic polymeric component is a member of the group consisting of hyaluronic acid, carboxymethyl cellulose, carboxymethyl starch, alginic acid, polyacrylic-acid-type polymeric components, pectin, xanthan gum, tragacantha gum, a water soluble salt of one of said components and a mixture of two or more of said members.
6. A precipitate according to anyone of claims 1 to 5, wherein said amphiphilic ammonium-type component comprises a cationic surfactant.
7. A precipitate according to anyone of claims 1 to 6, wherein said amphiphilic onium type component is selected from the group consisting of benzalkonium-chloride, benzoxonium-chloride, cetyl-pyridinium chloride, cetyltrimethylammonium bromide, cetyldimethyl(2-hydroxyethyl)ammonium dihydrogen phosphate (Luviquat® Mono CP), cocamidopropyl-N,N,N,trimethyl-glycine, acyl carnitines, in particular palmitoyl carnitine, sodium cocyl glutamate and mixtures of one or more members of said group.
8. A precipitate according to anyone of claims 1 to 7, wherein said amphiphilic onium type component comprises a cationic phospholipid.
9. A precipitate according to claim 8, wherein the cationic phospholipid is selected from lysophosphatidyl-choline compounds, phosphatidyl choline compounds, sphingomyelin, sphingosine derivatives and mixtures thereof.
10. A precipitate according to anyone of claims 1 to 9, wherein the cyclodextrin component is selected from alfa-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin and mixtures thereof.
11. A precipitate according to claim 4, wherein the one or more further components comprise a pharmaceutically active agent.
12. A precipitate according to claim 11, wherein the pharmaceutically active agent is selected from the group consisting of steroids, prostanoids, nitric-oxide prodrugs, antihistamines, antibiotics, cytostatic agents, antivirals, peptide hormones, local anesthetics, antiglaucoma agents, antiinflammatory agents, antihypertensives, antiangiogenic agents and suitable combinations thereof.
13. A process for manufacturing a precipitate according to anyone of claims 1 to 12, wherein .cndot. the anionic polymeric component, the cyclodextrin component and further components comprised in said precipitate which are soluble in water are dissolved in an aqueous medium to form a first composition;

.cndot. the amphiphilic component and further components comprised in said precipitate which are insoluble in water are blended with a suitable liquid carrier, preferably an aqueous medium, to form a second composition, and .cndot. said first and second composition are blended to form said precipitate.
14. A process according to claim 13, wherein the precipitate is brought into a desired shape.
15. A process according to claim 13 including a treatment of a non-liquid carrier for coating it with said first composition and a subsequent treatment of the so-treated carrier with said second composition for forming a coating of said precipitate on said carrier.
16. A pharmaceutical composition comprising a precipitate according to claim 11 or 12.
17. A pharmaceutical composition according to claim 16, which is a depot formulation.
18. A medical device comprising a precipitate according to claim 11 or 12.
19. A medical implant or insert according to claim 18.
20. A kit for administering a pharmaceutical composition according to claim 16 or 17 to a subject by simultaneous or preferably by consecutive administration of parts of said composition to said subject thereby forming the composition in situ at the place of administration, which kit comprises two or more than two partial compositions, each comprising one or more of the components of said pharmaceutical composition, whereby the components intended to form the precipitate are present in said compositions for consecutive or simultaneous administration in amounts effective to form the precipitate.
21. A kit according to claim 20 comprising .cndot. a first composition comprising the anionic polymeric component, the cyclodextrin component and the further components comprised in said precipitate which are soluble in water, dissolved in an aqueous medium; and .cndot. a second composition comprising the amphiphilic component and components comprised in said precipitate which are insoluble in water, blended with a suitable liquid carrier, preferably an aqueous medium.
22. A kit according to claim 20 or 21 adjusted to a subcutaneous or intramuscular administration of the pharmaceutical composition.
23. A kit according to claim 20 or 21 adjusted to the administration of the pharmaceutical composition onto wounds, skin or other solid surfaces by spraying.
24. A method of administering a pharmaceutically active compound to a subject in need thereof, comprising the administration of a pharmaceutical composition according to claim 16 or 17 comprising said pharmaceutically active compound.
25. A method for administering a pharmaceutical composition according to claim 16 or 17 to a subject including the simultaneous or preferably consecutive administration of two or more than two partial compositions, each comprising one or more of the components of said pharmaceutical composition, thereby forming the pharmaceutical composition in situ at the place of administration, wherein the components intended to form the precipitate are present in said partial compositions in amounts effective to form the precipitate when contacted with one another.
26. A method according to claim 25 including the simultaneous or preferably consecutive administration of a first composition comprising the anionic polymeric component, the cyclodextrin component and the further components comprised in said precipitate which are soluble in water, dissolved in an aqueous medium; and a second composition comprising the amphiphilic component and components comprised in said precipitate which are insoluble in water, blended with a suitable liquid carrier, preferably an aqueous medium.
27. A method according to claim 25 or 26 wherein the partial compositions are subcutaneously or intramuscularly injected in the subject.
28. A method according to claim 25 or 26 wherein the partial compositions are administered onto wounds, skin or other solid surfaces, preferably by spraying.
CA2484100A 2002-04-19 2003-04-17 Novel biomaterials, their preparation and use Expired - Fee Related CA2484100C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP02008809 2002-04-19
EP02008809.2 2002-04-19
PCT/EP2003/004076 WO2003089008A1 (en) 2002-04-19 2003-04-17 Novel biomaterials, their preparation and use

Publications (2)

Publication Number Publication Date
CA2484100A1 true CA2484100A1 (en) 2003-10-30
CA2484100C CA2484100C (en) 2012-01-03

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA2484100A Expired - Fee Related CA2484100C (en) 2002-04-19 2003-04-17 Novel biomaterials, their preparation and use

Country Status (20)

Country Link
US (3) US20050163853A1 (en)
EP (1) EP1499361B1 (en)
JP (1) JP4648632B2 (en)
KR (1) KR101121675B1 (en)
CN (1) CN1646171B (en)
AU (1) AU2003224099B2 (en)
BR (1) BR0309340A (en)
CA (1) CA2484100C (en)
CO (1) CO5611168A2 (en)
ES (1) ES2392964T3 (en)
HK (1) HK1073070A1 (en)
IL (1) IL164627A (en)
MX (1) MXPA04010325A (en)
NO (1) NO20044979L (en)
NZ (1) NZ535810A (en)
PL (1) PL215579B1 (en)
PT (1) PT1499361E (en)
RU (1) RU2321597C2 (en)
WO (1) WO2003089008A1 (en)
ZA (1) ZA200407794B (en)

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Also Published As

Publication number Publication date
AU2003224099B2 (en) 2006-11-09
JP2005529879A (en) 2005-10-06
CN1646171A (en) 2005-07-27
RU2321597C2 (en) 2008-04-10
US20120040901A1 (en) 2012-02-16
NO20044979L (en) 2004-11-16
US20080299166A1 (en) 2008-12-04
ZA200407794B (en) 2006-02-22
MXPA04010325A (en) 2005-06-08
AU2003224099A1 (en) 2003-11-03
JP4648632B2 (en) 2011-03-09
BR0309340A (en) 2005-03-08
IL164627A0 (en) 2005-12-18
HK1073070A1 (en) 2005-09-23
CA2484100C (en) 2012-01-03
PT1499361E (en) 2012-11-22
ES2392964T3 (en) 2012-12-17
NZ535810A (en) 2007-11-30
PL215579B1 (en) 2013-12-31
US20050163853A1 (en) 2005-07-28
CN1646171B (en) 2010-05-26
EP1499361A1 (en) 2005-01-26
WO2003089008A1 (en) 2003-10-30
KR101121675B1 (en) 2012-03-13
PL371595A1 (en) 2005-06-27
RU2004133887A (en) 2005-10-20
KR20040103968A (en) 2004-12-09
CO5611168A2 (en) 2006-02-28
IL164627A (en) 2009-11-18
EP1499361B1 (en) 2012-08-08

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