WO1994008566A1 - Vehicule et procede d'emprisonnement de matieres actives - Google Patents

Vehicule et procede d'emprisonnement de matieres actives Download PDF

Info

Publication number
WO1994008566A1
WO1994008566A1 PCT/US1993/009892 US9309892W WO9408566A1 WO 1994008566 A1 WO1994008566 A1 WO 1994008566A1 US 9309892 W US9309892 W US 9309892W WO 9408566 A1 WO9408566 A1 WO 9408566A1
Authority
WO
WIPO (PCT)
Prior art keywords
cross
water immiscible
materials
group
incompatible
Prior art date
Application number
PCT/US1993/009892
Other languages
English (en)
Inventor
Kenneth Abate
Original Assignee
Micro Vesicular Systems, Inc.
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 Micro Vesicular Systems, Inc. filed Critical Micro Vesicular Systems, Inc.
Priority to AU53302/94A priority Critical patent/AU5330294A/en
Publication of WO1994008566A1 publication Critical patent/WO1994008566A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
    • A01N25/10—Macromolecular compounds
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/15—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators
    • A61F13/53—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators characterised by the absorbing medium
    • A61F2013/530481—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators characterised by the absorbing medium having superabsorbent materials, i.e. highly absorbent polymer gel materials
    • A61F2013/530583—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators characterised by the absorbing medium having superabsorbent materials, i.e. highly absorbent polymer gel materials characterized by the form
    • A61F2013/530649—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators characterised by the absorbing medium having superabsorbent materials, i.e. highly absorbent polymer gel materials characterized by the form in sponge or foam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/15—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators
    • A61F13/53—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators characterised by the absorbing medium
    • A61F2013/530481—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators characterised by the absorbing medium having superabsorbent materials, i.e. highly absorbent polymer gel materials
    • A61F2013/530795—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators characterised by the absorbing medium having superabsorbent materials, i.e. highly absorbent polymer gel materials being biodegradable
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/15—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators
    • A61F13/53—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators characterised by the absorbing medium
    • A61F13/534—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators characterised by the absorbing medium having an inhomogeneous composition through the thickness of the pad
    • A61F2013/53481—Absorbent pads, e.g. sanitary towels, swabs or tampons for external or internal application to the body; Supporting or fastening means therefor; Tampon applicators characterised by the absorbing medium having an inhomogeneous composition through the thickness of the pad being biodegradable

Definitions

  • the present invention relates to delivery vehicles having active materials entrapped therein. These delivery vehicles are suspended in water immiscible carriers.
  • the present invention allows two incompatible active substances to be delivered together without cross-reactivity so that they keep their full activity until the delivery vehicle is destroyed or the materials leach from the vehicles.
  • a number of different delivery vehicles have been developed for entrapment of materials. These delivery vehicles include microcapsules, liposomes, other types of lipid vesicles, cellulosic materials and polymer delivery systems. These vehicles are used primarily to carry aqueous solutions of active materials.
  • United States Patent No. 4,911,928, the disclosure which is incorporated herein by reference, is one of the few patents that concerns the entrapment of material in a water immiscible liquid, not an aqueous solution.
  • This patent discloses the making of paucilamellar lipid vesicles which have an amorphous central cavity that can be filled with a water immiscible material such as an oil.
  • the water immiscible material acts as a carrier for a material which is soluble or suspendable in that oil.
  • the oil is carried in the central cavity, not the external phase.
  • microcapsule work has aqueous solutions both as the entrapped material filling the central cavity and as the external phase.
  • Microcapsules are often made by reacting the monomers forming the polymer at an interface or by cross-linking a material such as an alginic acid derivative with a divalent metal ion. If the alginic acid procedure is used, the cross-linked material is formed into a capsule membrane by reaction with a second polymer.
  • United States Patent No. 4,690,682 describes such a procedure.
  • interfacial polymerization the material to be encapsulated and a hydrophilic monomer is emulsified within a hydrophobic continuous phase and a second monomer is then dissolved in the continuous phase. Polymerization occurs at the boundary between the two phases where the two monomers can interact to form the polymeric material.
  • United States Patent No. 4,251,387 discloses this type of technique. By modifying the conditions of reaction, improved microcapsule membranes can be formed.
  • Still another entrapment technique is shown in United States Patent No. 3,860,490.
  • a microorganism is mixed with acrylate and methacrylate monomers and polymerization is allowed to occur to form a gel lattice about the microorganism. After separation, an additional coating of the polymer may be formed about the entrapped material.
  • a particulate material is used as a carrier to which the microorganisms are absorbed and then the polymeric coating is formed by a polymerization reaction about the particulate.
  • an object of the invention is to provide a method of making a delivery vehicle which can be suspended in a water immiscible carrier without leaching of the active.
  • a further object of the invention is to provide a method of entrapping two incompatible materials while preventing them to cross-react.
  • Another object of the invention is to provide a delivery system for delivering two incompatible materials in a water immiscible carrier.
  • the present invention features a method of preparing a delivery vehicle having an entrapped active substance therein, a method of delivering two incompatible materials, and a system for delivering the two incompatible materials.
  • the active materials to be delivered are entrapped within a cross-linked particulate material which is then suspended in a water immiscible carrier.
  • the method of preparing a delivery vehicle having an entrapped active material has the initial step of suspending a particulate support material in an aqueous material solution containing the active material to be entrapped.
  • the term "suspended” or “suspension”, as used herein, means not just classical suspensions but also colloids, emulsions, and other forms of keeping the material in a non-precipitated, non-dissolved form.
  • the term “contained” means not just dissolved but also suspended, carried in the form of a colloid carrier, carried as part of an emulsion, or otherwise carried in non-precipitated form. If a material is dissolved in a phase, it is deemed “contained”, not “suspended”.
  • the support material is selected from the group consisting of carboxylated cellulosic materials, chitosan, guar gum, alginic acid and its salts, polymethacrylates, polyacrylates, and copolymers and mixtures thereof.
  • the support material does not dissolve in the aqueous solution and preferrably does not include monomers used to make a polymeric material.
  • the support material suspension is blended with a water immiscible carrier to form a suspension of the support material in the water immiscible carrier.
  • a cross-linking agent which is insoluble in the aqueous solution but soluble in the water immiscible carrier, is added and allowed to react with and cross-link the support material, thereby forming the delivery vehicle.
  • This final delivery vehicle has the active material entrapped in cross-linked support material which suspended in the water immiscible carrier.
  • the preferred cross-linking agents are metallo-organic complexes, particularly complexes of carboxylic acids or their active derivatives with divalent or multivalent metal ions.
  • active derivatives as used herein includes salts, amines, amides, ethers, esters, alkoxides, and carbanyls of the carboxylic acids.
  • the preferred carboxylic acids are high molecular weight carboxylic acids or branched carboxylic acids because of their insolubility in water.
  • the most preferred cross-linking agent is a primary or secondary aluminum or chromium alkoxide, most preferably aluminum isopropoxide.
  • the preferred support material is a carboxylated cellulosic material, specifically carboxymethylcellulose ("CMC"), most preferable CMC having a DS (or degree of substitution) of 0.5 or greater. While any water immiscible carrier could be used, oils, triglycerides, waxes and ethers which are flowable at the cross-linking conditions are preferred. Most preferred oils include mineral oil, soybean oil, castor oil and their mixtures.
  • the aqueous solution could be plain water but preferably is an electrolyte solution such as a saline solution and may include a pH modifier such as an acid, particularly a carboxylic acid or a base. The most preferred aqueous solution is a saline/acetic acid solution.
  • the main requirement for the active ingredient useful in the invention is that it can be contained in the aqueous phase.
  • Preferred active materials include levamisole, closantel, pyrethrins, pyrethroids, carbamates, water-insoluble organo-phosphorous compounds, benzoyl urea, triazines, avermectins, and milbemycins and other water insoluble ectoparasiticides and endoparasiticides.
  • any active that can be contained in aqueous solution but is not soluble in the selected water immiscible carrier can be used.
  • the water immiscible carrier may include a stabilization agent such as a nonionic or anionic surfactant. While this stabilization agent is not necessary, it can assist in forming stable oil-in-water emulsions prior to cross-linking.
  • a stabilization agent such as a nonionic or anionic surfactant. While this stabilization agent is not necessary, it can assist in forming stable oil-in-water emulsions prior to cross-linking.
  • a sorbitan derivative is preferred as a stabilization agent, but other surfactants could be used.
  • two incompatible active materials can be used to form a combination product which would not otherwise be stable.
  • a first delivery vehicle is formed by entrapping one of the incompatible materials using the procedure prescribed previously.
  • a second delivery vehicle is then formed to entrap the second of the incompatible materials, again using the same procedure.
  • Different materials can be used as the particulate support material, the carrier, the aqueous solution, and the other reactants so long as the water immiscible carriers are compatible with the support materials and each other.
  • the two delivery vehicles are blended and suspended in a common water immiscible carrier to form the combination product.
  • the incompatible materials cannot react until they are released from the cross-linked support material, something that will normally happen only by degradation or other breakdown.
  • ecto- and endoparasiticides can be delivered simultaneously.
  • ectoparasiticides are used as one of the materials, preferred ectoparasiticides include the group consisting of pyrethrins, pyrethroids, carbamates, water-insoluble organo-phosphorous compounds, benzoyl urea, triazines, avermectins, and milbemycins.
  • endoparasiticides are used, the thiazoles are preferred.
  • Still another aspect of the invention concerns the delivery vehicle itself for delivering these two incompatible materials.
  • This delivery of vehicle is a combination of a first delivery vehicle and a second delivery vehicle, each of the delivery vehicles being an acid-stablized cross-linked carboxymethylcellulose in a water immiscible carrier. These two delivery vesicles are blended to form the delivery system of the invention. Each of these delivery vehicles can be made using the methods and materials previously described. Other features of the invention will be apparent from the following description.
  • the present invention concerns a method of entrapping an active material in a particulate support material which is itself suspended in a water-immiscible material such as an oil.
  • This invention is particularly advantageous where two incompatible active materials are to be used. Each active can be entrapped separately and then a blend is made of the entrapped actives in the water immiscible material. If the actives are not soluble in the water immiscible material, the actives cannot leach from the carriers. Since each of these entrapped actives is kept separate from the other, no cross-reactivity or other interaction can occur.
  • the two actives are incompatible, it also could be used where the actives, although compatible, are to be kept separate until they are removed from the water immiscible material.
  • the actives although compatible, are to be kept separate until they are removed from the water immiscible material.
  • the active to be entrapped is dispersible, but not soluble, in aqueous solutions.
  • the active is kept dispersed with the particulate support material until entrapped by the addition of the cross-linking agent.
  • Cross-linking agents for this procedure are soluble in the external phase, the water immiscible carrier, but not in the aqueous phase. Aggregate size can be controlled by modifying the emulsion conditions and the cross-linking takes place only at the boundary of the phases.
  • many prior entrapping vehicles require that the active be aqueous soluble, not dispersible.
  • levamisole and closantel which are incompatible anthelmintics used for animal treatment, were entrapped in a single two-component system.
  • This system is particularly well adapted for use in animals such as sheep.
  • Levamisole in the form of levamisole-HCl, is water soluble, while closantel-Na is not soluble but rather is dispersible in aqueous solutions. These materials react if brought in contact, losing the efficacy of both.
  • the levamisole and closantel are available from Janssen Pharmaceutica NV. Vehicles entrapping these materials are made as follows. Three stock solutions for use in making both vehicles are prepared first: Solution A has 175.8ml of soybean oil with 1.87g of SPAN 60 (sorbitan monostearate) dissolved therein by heating the solution for approximately 50 ⁇ C until it becomes clear. This water immiscible carrier solution is approximately.1% by weight SPAN 60, which acts as a stabilizer.
  • SPAN 60 sorbitan monostearate
  • Solution B is 10% acetic acid in water. About 0.625ml is used in making each vehicle.
  • Solution C is a 10% MANALOX 130 (Rhone Poulenc) solution in soybean oil.
  • MANALOX 130 is itself a 10% solution of aluminum isopropoxide, yielding a final concentration of 1% aluminum isopropoxide in soybean oil.
  • About 12.5ml of Solution C is used in making each vehicle.
  • Solution D is 50ml of a 1% carboxymethyl ⁇ cellulose (9H4F from Aqualon Company) in normal saline (approximately 0.9% weight) to which 18.75g of levamisole-HCl is added.
  • Solution E is identical to Solution D except 25g of closantel-NA is added instead of the levamisole.
  • Solution D or E is added to Solution A, under agitation sufficient for dispersion into small particles, followed by the dropwise addition of Solution B.
  • the preferred procedure has Solution B added dropwise to Solution A before the addition of Solution D or E.
  • the combined solutions are homogenized by an overhead stirrer or a magnetic stirrer for at least five minutes, then Solution C, the cross-linking agent, is added drop-wise while stirring and homogenizing. The stirring and homogenizing is continued at approximately 7,500RPM for an additional 20 minutes.
  • Each of the two vehicles (those containing the levamisole and the closantel) are made separately. These vehicles in soybean oil may be kept separate or a combined product may be made by mixing equal amounts of the two materials.
  • the combination product will contain approximately 37.5mg/ml of levamisole-HCl and 50mg/ml closantel-Na.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Plant Pathology (AREA)
  • Environmental Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Dentistry (AREA)
  • Toxicology (AREA)
  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Manufacturing Of Micro-Capsules (AREA)

Abstract

La présente invention se rapporte à des véhicules de distribution emprisonnant des matières actives en suspension dans un support ne pouvant se mélanger à l'eau. On décrit des procédés de production de ces matières, utilisant de préférence une matrice de support de carboxyméthylcellulose. Les véhicules ci-décrits sont particulièrement bien adaptés à la distribution de substances actives incompatibles qui peuvent être emprisonnées séparément et maintenues séparées jusqu'au moment de la libération par le véhicule.
PCT/US1993/009892 1992-10-21 1993-10-18 Vehicule et procede d'emprisonnement de matieres actives WO1994008566A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU53302/94A AU5330294A (en) 1992-10-21 1993-10-18 Entrapment vehicle and method

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US96441892A 1992-10-21 1992-10-21
US964,418 1992-10-21

Publications (1)

Publication Number Publication Date
WO1994008566A1 true WO1994008566A1 (fr) 1994-04-28

Family

ID=25508520

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1993/009892 WO1994008566A1 (fr) 1992-10-21 1993-10-18 Vehicule et procede d'emprisonnement de matieres actives

Country Status (2)

Country Link
AU (1) AU5330294A (fr)
WO (1) WO1994008566A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997037653A1 (fr) * 1996-04-09 1997-10-16 Bayer Aktiengesellschaft Formulations a injecter d'avermectines et de milbemycines a base d'huile de ricin
US5968895A (en) * 1996-12-11 1999-10-19 Praecis Pharmaceuticals, Inc. Pharmaceutical formulations for sustained drug delivery
WO2000032064A1 (fr) * 1998-11-30 2000-06-08 Hercules Incorporated Hydrate de carbone a liberation controlee enveloppe dans un polysaccharide reticule
FR2839614A1 (fr) * 2002-05-14 2003-11-21 Virbac Sa Nouvelles compositions orales huileuses antiparasitaires
KR100483912B1 (ko) * 1996-04-09 2005-08-31 바이엘 악티엔게젤샤프트 피마자유를기초로한아버멕틴과밀베마이신의주사제제

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3969280A (en) * 1975-03-07 1976-07-13 S. C. Johnson & Son, Inc. Solid air freshener gels
US4010038A (en) * 1974-04-10 1977-03-01 Kanzaki Paper Manufacturing Co., Ltd. Process for producing microcapsules
US4090013A (en) * 1975-03-07 1978-05-16 National Starch And Chemical Corp. Absorbent composition of matter
US4402856A (en) * 1980-04-26 1983-09-06 Bayer Aktiengesellschaft Microcapsules with a defined opening temperature, a process for their production and their use
US4897308A (en) * 1975-06-30 1990-01-30 L'oreal Compositions comprising aqueous dispersions of lipid spheres
US4996150A (en) * 1984-10-29 1991-02-26 Amoco Corporation Biocatalyst immobilization in a gel of anionic polysaccharide and cationic polymer

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4010038A (en) * 1974-04-10 1977-03-01 Kanzaki Paper Manufacturing Co., Ltd. Process for producing microcapsules
US3969280A (en) * 1975-03-07 1976-07-13 S. C. Johnson & Son, Inc. Solid air freshener gels
US4090013A (en) * 1975-03-07 1978-05-16 National Starch And Chemical Corp. Absorbent composition of matter
US4897308A (en) * 1975-06-30 1990-01-30 L'oreal Compositions comprising aqueous dispersions of lipid spheres
US4402856A (en) * 1980-04-26 1983-09-06 Bayer Aktiengesellschaft Microcapsules with a defined opening temperature, a process for their production and their use
US4996150A (en) * 1984-10-29 1991-02-26 Amoco Corporation Biocatalyst immobilization in a gel of anionic polysaccharide and cationic polymer

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997037653A1 (fr) * 1996-04-09 1997-10-16 Bayer Aktiengesellschaft Formulations a injecter d'avermectines et de milbemycines a base d'huile de ricin
AU718807B2 (en) * 1996-04-09 2000-04-20 Bayer Intellectual Property Gmbh Injection formulations of avermectins and milbemycins based on castor oil
CN1095662C (zh) * 1996-04-09 2002-12-11 拜尔公司 以蓖麻油为基础的阿凡曼菌素或米尔倍霉素的注射制剂、其制备以及蓖麻油的相关应用
KR100483912B1 (ko) * 1996-04-09 2005-08-31 바이엘 악티엔게젤샤프트 피마자유를기초로한아버멕틴과밀베마이신의주사제제
US5968895A (en) * 1996-12-11 1999-10-19 Praecis Pharmaceuticals, Inc. Pharmaceutical formulations for sustained drug delivery
US6180608B1 (en) 1996-12-11 2001-01-30 Praecis Pharmaceuticals, Inc. Pharmaceutical formulations for sustained drug delivery
US6699833B1 (en) 1996-12-11 2004-03-02 Praecis Pharmaceuticals, Inc. Pharmaceutical formulations for sustained drug delivery
WO2000032064A1 (fr) * 1998-11-30 2000-06-08 Hercules Incorporated Hydrate de carbone a liberation controlee enveloppe dans un polysaccharide reticule
FR2839614A1 (fr) * 2002-05-14 2003-11-21 Virbac Sa Nouvelles compositions orales huileuses antiparasitaires
WO2003099259A1 (fr) * 2002-05-14 2003-12-04 Virbac S.A. Compositions orales huileuses antiparasitaires

Also Published As

Publication number Publication date
AU5330294A (en) 1994-05-09

Similar Documents

Publication Publication Date Title
US5132117A (en) Aqueous core microcapsules and method for their preparation
EP1255534B1 (fr) Preparation de microspheres contenant des systemes colloidaux
US4994281A (en) Polylactic acid microspheres and process for producing the same
US5324445A (en) Polymeric compositions
US4900556A (en) System for delayed and pulsed release of biologically active substances
JP2639844B2 (ja) 洗剤組成物
AU699080B2 (en) Sustained release particles
US5049322A (en) Process for the preparaton of dispersible colloidal systems of a substance in the form of nanocapsules
US5326572A (en) Freeze-dried polymer dispersions and the use thereof in preparing sustained-release pharmaceutical compositions
CA2251281C (fr) Preparation pharmaceutique a taux de liberation programme
Andrianov et al. Controlled release using ionotropic polyphosphazene hydrogels
CA1204058A (fr) Microcapsules doubles
GB2046209A (en) Encapsulation of chemically active, biologically active materials and viable tissue
Burgess Complex coacervation: microcapsule formation
EP0941068B1 (fr) Microparticules à libération contrôlée
WO1996001103A1 (fr) Encapsulation multiple de substances oleophiles
US5510117A (en) Entrapment vehicle and method
JP2003526503A (ja) ナノカプセルの形態にあるコロイド粒子の調製方法
WO1994008566A1 (fr) Vehicule et procede d'emprisonnement de matieres actives
JP2851302B2 (ja) 水溶性物質内包マイクロカプセルの製法
CN107412193A (zh) 以麦羟硅钠石为乳化剂的Pickering乳液模板法制备的纳米杂化药物载体及其制法
CA2352802C (fr) Preparation de microcapsules polymeres a parois multiples a partir de polymeres hydrophiles
US11052046B2 (en) Method for preparing micro-particles by double emulsion technique
CN100588422C (zh) 口服胰岛素组合物及其制备方法和使用方法
CA1331343C (fr) Composition a liberation prolongee, amelioree par des adjuvants, et methode pour sa fabrication

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU BR CA JP

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA