EP0868199A1 - Particle compositions - Google Patents

Particle compositions

Info

Publication number
EP0868199A1
EP0868199A1 EP96943114A EP96943114A EP0868199A1 EP 0868199 A1 EP0868199 A1 EP 0868199A1 EP 96943114 A EP96943114 A EP 96943114A EP 96943114 A EP96943114 A EP 96943114A EP 0868199 A1 EP0868199 A1 EP 0868199A1
Authority
EP
European Patent Office
Prior art keywords
particles
composition according
enzymes
composition
antimicrobially active
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.)
Withdrawn
Application number
EP96943114A
Other languages
German (de)
English (en)
French (fr)
Inventor
Mark John Berry
Paul James Davis
Philip Porter
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.)
Givaudan Nederland Services BV
Original Assignee
Quest International BV
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 Quest International BV filed Critical Quest International BV
Priority to EP96943114A priority Critical patent/EP0868199A1/en
Publication of EP0868199A1 publication Critical patent/EP0868199A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D17/00—Detergent materials or soaps characterised by their shape or physical properties
    • C11D17/0034—Fixed on a solid conventional detergent ingredient
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6923—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/25—Silicon; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66—Enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/02—Inorganic compounds ; Elemental compounds
    • C11D3/12—Water-insoluble compounds
    • C11D3/124—Silicon containing, e.g. silica, silex, quartz or glass beads
    • C11D3/1246—Silicates, e.g. diatomaceous earth
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16—Organic compounds
    • C11D3/38—Products with no well-defined composition, e.g. natural products
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16—Organic compounds
    • C11D3/38—Products with no well-defined composition, e.g. natural products
    • C11D3/386—Preparations containing enzymes, e.g. protease or amylase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms

Definitions

  • the present invention relates to compositions for the delivery of antimicrobially active proteins to a microbial cell target site.
  • EP-A-0566368 (Unilever) describes cosmetic compositions for the delivery of a cosmetically effective benefit agent to a target site on the skin and/or hair comprising particles including the benefit agent and having means to bind to an organic surface at the target location.
  • Suitable particles disclosed are made of synthetic polymeric substances such as polycyanoacrylate or proteins such as albumin or gelatin.
  • Preferred particles which are disclosed and exemplified are liposomes in which benefit agent is encapsulated.
  • inorganic particles particularly biodegradable metal oxides or salts
  • a cell binding component i.e. a targetting molecule for a particular cell type
  • BE-A-844657 discloses porous inorganic particles, such as silica, coated with an aminated polysaccharide which reversibly bind various biologically active molecules. The particles can be used in chromatographic processes to purify such molecules.
  • JP-A-63031538 A similar material is disclosed in JP-A-63031538 in which a cationic polymer such as polyethyleneimine is used as the coating. In this case the binding is said to be irreversible.
  • antimicrobially active proteins adsorbed onto a positively charged inorganic porous carrier particle which is able to bind to a microbial cell target site, can efficiently be delivered to the target site with high affinity and specificity. Retention of the antimicrobially active proteins at the target site and prolonged action may thereby be achieved. Furthermore, by adsorbing the proteins onto the particle carrier, the need for chemical coupling reactions can be avoided, leading to a simple process of manufacture which can readily be scaled-up.
  • the present invention provides a composition comprising positively charged porous inorganic carrier particles having one or more antimicrobially active proteins adsorbed thereon.
  • the invention provides a method for delivering antimicrobially active proteins to microbial cell targets comprising applying to the targets a composition according to the first aspect, and thereby inhibit or kill the microbial cell.
  • the invention provides a method for the production of a composition according to the first aspect comprising providing the porous inorganic carrier particles with a positive electric charge and adsorbing one or more antimicrobially active proteins on the porous inorganic carrier particle.
  • Suitable porous inorganic particles for use according to the invention include silicas such as available from Crosfield, W-R Grace or Rhone Poulenc and hydrotalcites such as available commercially from Crosfield.
  • the porous particles will conveniently have a pore size to suit the molecular size of the proteins.
  • the mean pore size should preferably be such that sufficient pores greater that 20nm, more preferably greater than 50nm are present. Pore sizes are preferably less than 200nm, but it is technically possible to use larger pores. It will be appreciated that other porous inorganic materials having properties analogous to those of silica may suitably be employed.
  • An advantage of using carrier materials having a porous structure is that they have a large internal surface area able to accommodate a large payload of benefit agent .
  • Positively charged inorganic (e.g. silica) particles may be produced by physical adsorption of a positively charged ligand onto the surface of the negatively charged silica particle.
  • Suitable positively charged ligands which may be employed include organic polymers such as polyethylene imine or polylysine and metal ions such as Al 3* and Mg 2+ .
  • Porous hydrotalcites such as those commercially available from
  • Crosfield under the trade name Macrosorb naturally contain aluminium and magnesium ions and therefore carry an innate positive charge.
  • Such carrier particles are therefore particularly useful in the present invention as they do not need to be further derivatised with a particularly charged ligand prior to use.
  • antimicrobially active proteins refers to proteins which are either antimicrobially active themselves such that they directly act on the microorganism in such a way as to kill it or hinder its growth or multiplication, or to proteins which react with other compounds present in the microorganism or its environment thereby directly or indirectly producing compounds which have any of the above mentioned activities.
  • the antimicrobially active proteins to be adsorbed onto the carrier particles preferably include one or more enzymes which are antimicrobially active themselves or in combination with a suitable substrate produce antimicrobially active molecules.
  • enzymes which are antimicrobially active themselves or in combination with a suitable substrate produce antimicrobially active molecules.
  • oxidases can function as cytotoxic agents. Oxidases such as glucose oxidase and galactose oxidase generate hydrogen peroxidase which is cytotoxic. Peroxidases can use the hydrogen peroxide as a substrate to form hypohalite which is even more cytotoxic.
  • peroxidases which may suitably be used in conjunction with these oxidases include horseradish peroxidase and lactoperoxidase. Other suitable peroxidases are chloroperoxidases . Both hydrogen peroxide and hypohalite are rapidly decomposed in vivo, but nevertheless active because they can effectively be delivered to the intended site of action by the present invention.
  • compositions according to the invention may also include other enzymes which aid the antimicrobially active enzymes in their action e.g. by converting a substrate present near the microbial cell into a substrate which in turn can be used by the antimicrobially active enzymes, such other enzymes are preferably also absorbed on the carrier particles.
  • other enzymes are preferably also absorbed on the carrier particles.
  • An example of such other enzyme is invertase, as outlined below.
  • compositions according to the invention may conveniently be used for the delivery of antimicrobial agents as oral care active agents.
  • one application of the invention lies in the delivery of oral care active agents, particularly oxidative enzymes as discussed above against the microbial species in dental plaque.
  • Suitable target microorganisms include Streptococcus mutans and S sanguis.
  • the particles may carry some or all of the substrates for the enzymes or some or all of the enzyme substrates may be present at the target site. For example, where glucose oxidase is used and the intended target microorganism is in the mouth, dietary glucose may be relied upon as the enzyme substrate or the particles may incorporate glucose. Alternatively, the particles may incorporate invertase which converts sucrose to glucose.
  • Other enzymes may alter the pH of the environment, e.g. the dental plague, to a level which is not or less suitable for the microorganism to grow.
  • certain enzymes are capable of raising the pH to a level unsuitable for growth of microorganisms in the dental plaque; an example is urease which converts ureum to ammonia and carbon dioxide.
  • the target is microorganisms present on general household surfaces.
  • microorganisms include S . aureus, P . aeruginosa and E. coli .
  • Suitable benefit agents for use in this application include enzymes such as horseradish peroxidase, lactoperoxidase or vanadium chloroperoxidase.
  • compositions of the invention preferably include a vehicle to act as a diluant, dispersant or carrier for the particles so as to facilitate their application to and distribution at the site of application.
  • vehicle to act as a diluant, dispersant or carrier for the particles so as to facilitate their application to and distribution at the site of application.
  • vehicle will depend on the method and site of administration of the composition.
  • the vehicle must be acceptable for topical application in the mouth.
  • Conventional cosmetically acceptable vehicles are well known in the art and can include water or substances such as liquid or solid emollients, solvents, humectants, thickeners and powders .
  • compositions according to the invention intended for oral use may conveniently be formulated as a mouthwash, toothpaste or lozenge.
  • the compositions of the invention may be solid or semi-solid, for example sticks, creams or gels for use in conjunction with a suitable applicator.
  • the proportion of antimicrobially active protein in the compositions according to the invention varies depending upon the intended application.
  • the benefit agent provides from 0.01% to 10% by weight of the particles.
  • the benefit agent provides from 0.005% to 1.5% by weight of the composition.
  • compositions according to the invention will generally contain various other components known in the art, depending on the intended application.
  • such components will include the usual polishing agents.
  • Many compositions will also include some sort of surface active or detergent active component.
  • Tooth pastes and other compositions for oral care will also generally contain a suitable flavour, particularly a mint or menthol-like flavour.
  • the vials were rotated slowly for 4 hours at room temperature. Then the particles were separated by centrifugation (2,000 r.p.m for 5 minutes) . The amount of invertase remaining in the supernatant was determined spectrophotometrically after filtering through an 0.2 ⁇ m filter. This value was subtracted from the amount of enzyme that had been added to deduce the amount of enzyme that had been adsorbed onto the particles.
  • the invertase sensitised particles were resuspended in a 1.5mls volume of lOmM tris containing 2mgs of glucose oxidase (equivalent to 32mgs per gram of particles) .
  • the tubes were rotated overnight at room temperature.
  • the double-enzyme sensitised particles were separated by centrifugation and the amount of glucose oxidase that had been adsorbed was determined as previously. Particles were washed with and then stored in lOmM tris, pH8.
  • Macrosorb particles (CT 100) were successfully derivatised with both invertase and glucose oxidase.
  • the ratio of invertase to glucose had been efficiently controlled by sensitising with different amounts of invertase and a fixed amount of glucose oxidase in a two-step reaction (see Figure 2) .

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Wood Science & Technology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Birds (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Ceramic Engineering (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Cosmetics (AREA)
  • Manufacturing Of Micro-Capsules (AREA)
EP96943114A 1995-12-21 1996-12-05 Particle compositions Withdrawn EP0868199A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP96943114A EP0868199A1 (en) 1995-12-21 1996-12-05 Particle compositions

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
EP95309349 1995-12-21
EP95309349 1995-12-21
EP95309346 1995-12-21
EP95309347 1995-12-21
EP95309346 1995-12-21
EP95309347 1995-12-21
EP96943114A EP0868199A1 (en) 1995-12-21 1996-12-05 Particle compositions
PCT/EP1996/005601 WO1997023241A1 (en) 1995-12-21 1996-12-05 Particle compositions

Publications (1)

Publication Number Publication Date
EP0868199A1 true EP0868199A1 (en) 1998-10-07

Family

ID=27236942

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96943114A Withdrawn EP0868199A1 (en) 1995-12-21 1996-12-05 Particle compositions

Country Status (4)

Country Link
EP (1) EP0868199A1 (ja)
JP (1) JP2000503000A (ja)
AU (1) AU1194697A (ja)
WO (1) WO1997023241A1 (ja)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100359716B1 (ko) * 1998-09-11 2003-04-21 (주)나노하이브리드 유전자의보관및전달이가능한생-무기하이브리드복합체및그의제조방법
GB9924334D0 (en) * 1999-10-15 1999-12-15 Secr Defence Pharmaceutical products and methods of fabrication therefor
WO2001049869A1 (fr) * 1999-12-30 2001-07-12 Aventis Pharma S.A. Compositions comprenant des acides nucleiques incorpores dans des particules minerales bilamellaires
FR2803206A1 (fr) * 1999-12-30 2001-07-06 Aventis Pharma Sa Composition comprenant des acides nucleiques, preparation et utilisation
DE10021165A1 (de) * 2000-04-29 2001-11-08 Henkel Kgaa System für die Freisetzung von Wirkstoffen
US9540631B1 (en) * 2004-09-14 2017-01-10 Peter T. Pugliese Immobilized glucose oxidase for use in oral hygiene
JP2022525817A (ja) * 2019-04-02 2022-05-19 ユニリーバー・アイピー・ホールディングス・ベー・フェー クリーニング組成物
CN114585418A (zh) * 2019-05-28 2022-06-03 联合利华知识产权控股有限公司 口腔护理组合物

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LU73094A1 (ja) * 1975-07-29 1977-03-24
JPS6331538A (ja) * 1986-07-25 1988-02-10 Kensetsusho Doboku Kenkyu Shocho 固定化用担体
DK0425016T3 (da) * 1989-10-27 1996-05-06 Genencor Int Antimikrobiel fremgangsmåde og formulering med anvendelse af type II endoglycosidase og antimikrobielt middel
GB8928501D0 (en) * 1989-12-18 1990-02-21 Unilever Plc Reagents
AU642980B2 (en) * 1990-03-21 1993-11-04 Quest International B.V. Ultilization of enzymes
AU642979B2 (en) * 1990-03-21 1993-11-04 Quest International B.V. Utilization and delivery of enzymes
GB9119762D0 (en) * 1991-09-16 1991-10-30 Filler Aaron G Particulate agents for nmt
US5811382A (en) * 1991-12-20 1998-09-22 Novo Nordisk A/S Detergent compositions
EP0726767A4 (en) * 1993-11-01 1997-08-20 Univ California BIOCHEMICALLY ACTIVE ACTIVE SUBSTANCES FOR CHEMICAL CATALYSIS AND CELL RECEPTOR ACTIVATION

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9723241A1 *

Also Published As

Publication number Publication date
JP2000503000A (ja) 2000-03-14
WO1997023241A1 (en) 1997-07-03
AU1194697A (en) 1997-07-17

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