EP1037606A1 - Preparation a temps de sejour prolonge dans la zone d'application - Google Patents
Preparation a temps de sejour prolonge dans la zone d'applicationInfo
- Publication number
- EP1037606A1 EP1037606A1 EP98966561A EP98966561A EP1037606A1 EP 1037606 A1 EP1037606 A1 EP 1037606A1 EP 98966561 A EP98966561 A EP 98966561A EP 98966561 A EP98966561 A EP 98966561A EP 1037606 A1 EP1037606 A1 EP 1037606A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- preparation according
- active ingredient
- preparation
- particles
- cellulose
- 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- Withdrawn
Links
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- 238000009472 formulation Methods 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- IQSHMXAZFHORGY-UHFFFAOYSA-N methyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound COC(=O)C=C.CC(=C)C(O)=O IQSHMXAZFHORGY-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 229940037525 nasal preparations Drugs 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229940023490 ophthalmic product Drugs 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- FSDZFXDDKLLPRB-UHFFFAOYSA-N phthalic acid;sulfuric acid Chemical compound OS(O)(=O)=O.OC(=O)C1=CC=CC=C1C(O)=O FSDZFXDDKLLPRB-UHFFFAOYSA-N 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000009912 pressing by method Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 239000007944 soluble tablet Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000019710 soybean protein Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000010345 tape casting Methods 0.000 description 1
- 229960005221 timolol maleate Drugs 0.000 description 1
- 230000001515 vagal effect Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2063—Proteins, e.g. gelatin
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
Definitions
- This invention describes solid, rapidly disintegrating preparations to ⁇ that the eye, extend the residence time at the site of action, for example.
- Too short a residence time of the active ingredient at the application site is a common problem when using medicinal forms on mucous membranes, particularly in the case of ophthalmic forms, but also in the case of vaginal, rectal or nasal preparations.
- the most commonly used ophthalmic drug forms are drug drops. Eye drops have several disadvantages. Most of the drops are immediately washed out of the eye or only partially attached to the eye due to incorrect application technology. To prolong the dwell time and thus the pharmacological effect, liquid systems have been developed that increase their viscosity in contact with the tear fluid through gelation. These liquid preparations contain polymers which gel either by pH or temperature change (US 5,192,535, US 5,077,033).
- the preparations according to the invention are solid preparations which, after application, e.g. on the eye, quickly disintegrate and increase the length of stay.
- the present invention relates to a solid preparation which rapidly disintegrates in water and which extends the residence time of the active ingredient at the application site.
- the active substance is a pharmacologically active substance. It is preferred that the active ingredient is enclosed in particles. It is further preferred that the active ingredient is enclosed in pellets.
- the active ingredient is enclosed in microparticles. It is in turn preferred that the active ingredient be enclosed in particles with a particle size predominantly smaller than 20 ⁇ m.
- the active ingredient is enclosed in colloidal particles. It is also preferred that the active ingredient be enclosed in liposomes. It is also preferred according to the invention that the active substance is enclosed in nanoparticles.
- the preparations according to the invention are further characterized in that the carrier material of the particles is a polymer. It is preferred here that the Tragermateri ⁇ al of the particles, a cellulose derivative (eg Ethylcellulo- se, acetate phthalate cellulose acetate, cellulose acetate butyrate, cellulose, Hydroxypropylmethylphthalat) or an acrylate derivative (for example, poly (methyl methacrylate), Eudragits, cyanoacrylates) is.
- a cellulose derivative eg Ethylcellulo- se, acetate phthalate cellulose acetate, cellulose acetate butyrate, cellulose, Hydroxypropylmethylphthalat
- an acrylate derivative for example, poly (methyl methacrylate), Eudragits, cyanoacrylates
- the carrier material of the particles is a biodegradable polymer from the group of polyanhydrides, polyesters (eg polylactide glycolides), polyorthoesters or polyacetals). It is particularly preferred that the carrier material of the particles is a lipid.
- the particles preferably also have bioadhasive properties.
- the active ingredient is bound to an ion exchange resin.
- the preparation according to the invention releases the active ingredient with a delay. According to the invention, they can also release the active ingredient more quickly.
- the preparation also contains bioadhasive substances. It is preferred here that the bioadhasive substances are polymers.
- Preparations according to the invention which contain polyacrylic acid, sodium algate, chitosan, methylethyl cellulose, hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose, gellan gum, lectins or their mixtures or derivatives are particularly preferred.
- Another object of the present invention is a method for producing a preparation according to the invention.
- the preparation is prepared by lyophilization.
- the active ingredient or active ingredient-containing particles are / are incorporated into a liquid phase and the liquid preparation is introduced into a mold and lyophilized.
- the preparation is produced by extrusion.
- the preparation is produced by pressing.
- a method is also in accordance with the invention, in which particles containing the active substance are incorporated into the preparation.
- proteins eg gelatin, albumins, etc.
- polysaccharides eg starch, agar-agar, carrageenan, tragacanth, dextran, dextrin, chitosan, alginates, gum arabic, pectin, xanthan gum, gellan
- cellulose derivatives methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose
- vinyl derivatives polyvinyl alcohol, polyvinyl pyrrolidone, etc.
- the present invention also relates to tablet- or pellet-like or film-like or rod-like preparations which contain a preparation according to the invention. According to the invention, preference is given to using the preparations according to the invention on the eye.
- Another object of the present invention is a device for applying a preparation according to the invention at the application site.
- the preparations according to the invention are solid, rapidly disintegrating preparations which are used on the eye, vaginally, rectally or nasally and which prolong the residence time at the application site.
- rapidly disintegrating is broad and does not only include, in the pure sense of the words, rapid disintegration, but means that the preparation quickly loses its original form after application, e.g. by complete or partial decay, swelling, or dissolution or dissolution or a combination of these processes. Ideally, the disintegration takes place within a few minutes.
- a special aspect of the preparations according to the invention is an extension of the residence time of the
- the solid preparations according to the invention form, for example, a viscous and / or bioadhasive mass, which extends the length of time of the active ingredient at the application site.
- the active ingredient can be absorbed over a longer period of time or be locally effective.
- Another advantage over normal inserts is that the preparation disintegrates quickly and is therefore not perceived as a foreign body for a long time.
- the preparations according to the invention can be produced in various forms and by different methods known to the person skilled in the art for the respective application site. These processes include lyophilization, extrusion, pressing into moldings and the production of films.
- the active ingredient or particles containing the active ingredient are mixed with a liquid carrier phase, this liquid phase is introduced into a mold (e.g. into the depressions of a blister pack), frozen and then lyophilized.
- the shape and dimensions of the freeze-dried dosage forms are predetermined by the shape and dimensions of the containers. These dosage forms can either be further packaged directly in the containers or after removal from these containers.
- the liquid preparations can also be appropriately lyophilized over a large area and the dosage forms of a specific format can then be produced from the freeze-dried areas by splitting, cutting and / or punching.
- the porosity of the preparation can be influenced by the content of solvent or by dispersed gas.
- the matrix obtained is porous and therefore allows rapid dissolution or rapid disintegration of the preparation. Preference is given to using water-soluble materials as carrier substances, since the fastest disintegration of the matrix can be brought about by placing the product in an aqueous medium.
- Carrier materials can be proteins (e.g. gelatin, albumins, soybean proteins, etc.), polysaccharides (e.g. starch, agar-agar, carrageenan, tragacanth, dextran, dextrin, chitosan, alginates, pectins, gum arabic, xanthan gum, gellan gum etc.) ), Cellulose derivatives (methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose Hydroxyethyl cellulose, sodium carboxymethyl cellulose), methyl derivatives (polyvinyl alcohol, polyvinyl pyrrolidone, etc.) or mixtures of these carriers can be used.
- proteins e.g. gelatin, albumins, soybean proteins, etc.
- polysaccharides e.g. starch, agar-agar, carrageenan, tragacanth, dextran, dextrin, chitosan, alginates, pectins
- Fillers such as sugar (eg lactose, glucose, mannitol, sorbitol, sucrose, etc.) can also be added.
- the disintegration time depends on the composition, in particular on the type of carrier, its molar mass and its concentration.
- the macromolecules can also be used in partially hydrolyzed form.
- Rapidly disintegrating preparations are produced by pressing by methods known to those skilled in the art, such as direct tableting or pelletizing and subsequent compression. In addition to those listed under Lyophilization
- Excipients and commonly used tableting excipients also excipients that are used in the rapidly disintegrating tablets intended for use in the oral cavity. In the case of vagal tablets in particular, it is also possible to use an effervescent mixture to accelerate the disintegration.
- the shaping in films can be carried out by generally known methods such as, for example, spreading / knife coating or extrusion methods.
- the division into single cans can be done by cutting, punching, embossing and comparable processes.
- the polymers described above can correspondingly increase the residence time at the application site by a viscosity-increasing effect or, in some cases, additionally by a bioadhasive effect after the preparation rapidly disintegrates.
- special bioadhasive substances can also be added to the preparation.
- bioadhasive polymers that swell in contact with water are primarily used and demand the liability of the preparation at the application site.
- the polymers include the polymers known to the person skilled in the art with bioadactive properties such as, for example, polyacrylic acid (Carbopol), sodium algmat, chitosan, methylethyl cellulose, sodium carboxymethyl cellulose, gellan gum, lectures etc. It is also possible to use polymers which, on the application site, are caused by pH, temperature or ions gel, increasing the viscosity of the preparation.
- All drugs that are administered to the eye, nasally, vaginally or rectally can be used as active ingredients.
- the active ingredients can act both locally and systemically. It is also possible to prepare solid, rapidly disintegrating preparations which contain polymers, e.g. Contain carboxymyl polymers (Carbopol) and, after dissolution, artificial tear fluids, e.g. to treat dry eyes.
- a preparation according to the invention but free of pharmaceutical substances can also have a positive effect at the application site.
- particles containing active ingredient is a special aspect of this invention.
- the active ingredient is enclosed in m particles, for example polymeric microparticles, and is then incorporated into the preparation during manufacture.
- Particulate drug carrier particles are mainly used to retard drug release.
- the inclusion in the particles can, however, also lead to a reduced irritation at the application site, to an improved stability of the active substance, and, especially with colloidal particles, also to an acceleration of the active substance release (for example in the case of lipophilic active substances).
- the term particle includes pellets (approx. 0.5 mm to 1.5 mm in diameter), microparticles and partial in the colloidal size range.
- inclusion of the active ingredient in the particles is broad and includes, among other things, physical or chemical adsorption, coating the active ingredient and embedding it in the particles in dissolved or dispersed form
- the active ingredient is made by various methods such as aqueous or organic phase separation, spray drying, solvent evaporation (solvent evaporation), melt solidification, melt emulsion formation, coating, etc. included.
- the colloidal particles include liposomes and polymer or lipid nanoparticles.
- the colloidal particles can be made by many methods known to those skilled in the art.
- the carrier materials for the particles are the
- Water-insoluble and water-soluble polymers of synthetic, semisynthetic and natural origin known to those skilled in the art and already listed above for example cellulose derivatives such as ethyl cellulose, cellulose acetate, cellulose acetate butyrate, cellulose sulfate phthalate, hydroxypropyl methyl phthalate, acrylates such as poly (methyl methacrylate), Eudragite, cyanoacrylate, Eudragite, Eudragite, eudragite, biudacrylite, Eudragite Degradable polymers such as polyanhydrides, polyesters (polylactide glycolides), polyorthoesters and polyacetal), and lipids (oils, fats, fatty acids, or waxes), and their derivatives or mixtures.
- cellulose derivatives such as ethyl cellulose, cellulose acetate, cellulose acetate butyrate, cellulose sulfate phthalate, hydroxypropyl methyl phthalate,
- Active ingredients can also be bound to ion exchange resins. This can lead to a delay in drug release or to a reduction in irritation.
- the active substance bound to an ion exchange resin can in turn be enclosed in particles.
- incorporating them into a solid preparation has many advantages compared to a liquid preparation.
- the active ingredient diffuses substance during storage from the particles into the dispersion vehicle, retarding properties are lost.
- undesired interactions between the solvent and the carrier material of the particles can occur in the liquid state, for example, this can lead to a change in the release profile during storage.
- the stability of the active ingredient and the carrier polymers of the particles in the liquid phase is to be viewed much more critically; in the aqueous phase, for example, hydrolysis can occur. Furthermore, physical stability problems, for example sedimentation of the particles, are eliminated in the case of solid preparations.
- ingredients in the preparations can be colorants, preservatives, buffer substances, substances to adjust the tonicity, plasticizers, etc.
- Another advantage of solid compared to liquid preparations is that preservatives can be dispensed with if prepared accordingly.
- biotechnologically manufactured active substances such as Peptides / proteins or oligonucleotides, penetration enhancers or enzyme inhibitors are added to the preparation. These auxiliary substances improve the absorption of the active substances.
- the preparations according to the invention can be used in both human and veterinary medicine. If necessary, they can be sterilized or prepared aseptically. The preparations can be applied analogously to other solid pharmaceutical forms by the patient or the doctor, but also with special applicators known to the person skilled in the art.
- Example 1 The invention is illustrated by the following examples, but should not be restricted thereby.
- Example 1 The invention is illustrated by the following examples, but should not be restricted thereby.
- the active ingredient / active ingredient-containing particles (0.1-20% by weight) are dissolved or dispersed in an aqueous gel solution (5-10% by weight) which has been autoclaved (121 ° C., 2 bar, 1 h).
- the liquid phase is placed in a well of a blister pack, frozen and then freeze-dried.
- a porous matrix is obtained which dissolves in water in a few minutes, sometimes within a few seconds.
- Active ingredients active ingredient-containing particles:
- Timolol maleate, Pilocarpm HCl and Betaxolol HCl in dissolved form were used as active ingredients.
- Pilocarpm base was precipitated by increasing the pH and dispersed in the aqueous solution e.
- Betaxolol was also bound to an ion exchange resin (Amberlite IRP-69) and then dispersed in the aqueous solution.
- Polycaprolactone, ethyl cellulose or polylactide glycolide - nano or micro particles produced by spray drying or solvent evaporation process, in the case of nanoparticles by subsequent homogenization
- lipid nano or micro particles produced by melt emulsion processes or spray solidification
- starch In addition to or instead of the gelatin, starch, sodium alginate, hydroxypropylmethyl cellulose, gellan gum, polyalcohol and polyvinylpyrrolidone were used as carrier material for the porous matrix. Mannitol was used as an additional filler. Polyacrylic acid, carbopol (0.1-0.5%) or sodium carboxymethyl cellulose were added to the aqueous phase as bioadhasive polymers before the lyophilization.
- the dwell time at the Kanmchen eye could e.g. with indium DTPA-labeled gelatin inserts (without special bioadhasive polymers) to 62 mm compared to 10 mm, achieved with an aqueous solution.
- the active ingredient / active ingredient-containing particles are mixed with various auxiliary substances and either wet granulated / pressed or pressed directly.
- Microcrystalline cellulose (MCC) eg Avicel
- MCC Microcrystalline cellulose
- effervescent mixture citric acid / sodium pumbicarbonate
- the polymers used in Example 1 were used as viscosity-increasing and / or bioadhasive substances.
- the disintegration was mainly influenced by the tablet hardness.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
Abstract
L'invention concerne des préparations solides, à décomposition rapide, qui prolongent le temps de séjour dans la zone d'application, par exemple dans l'oeil.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE1997156314 DE19756314C2 (de) | 1997-12-12 | 1997-12-12 | Zubereitung mit verlängerter Verweildauer am Applikationsort |
DE19756314 | 1997-12-12 | ||
PCT/DE1998/003739 WO1999030683A1 (fr) | 1997-12-12 | 1998-12-11 | Preparation a temps de sejour prolonge dans la zone d'application |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1037606A1 true EP1037606A1 (fr) | 2000-09-27 |
Family
ID=7852382
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP98966561A Withdrawn EP1037606A1 (fr) | 1997-12-12 | 1998-12-11 | Preparation a temps de sejour prolonge dans la zone d'application |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1037606A1 (fr) |
AU (1) | AU2410199A (fr) |
DE (1) | DE19756314C2 (fr) |
WO (1) | WO1999030683A1 (fr) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6299621B1 (en) | 1999-06-18 | 2001-10-09 | Novare Surgical Systems, Inc. | Surgical clamp pads with elastomer impregnated mesh |
DE19940795A1 (de) * | 1999-08-27 | 2001-03-01 | Lohmann Therapie Syst Lts | Schnellzerfallende Pellets auf der Basis von Chitosan |
WO2009125432A2 (fr) * | 2008-04-11 | 2009-10-15 | Lupin Limited | Systèmes d'administration de médicament expansible alimentés par gaz |
CN109908328A (zh) * | 2019-03-25 | 2019-06-21 | 华南理工大学 | 纳米透皮技术用于改善眼睛干眼症的眼贴及其制备方法 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3960150A (en) * | 1971-09-09 | 1976-06-01 | Alza Corporation | Bioerodible ocular device |
US3981303A (en) * | 1971-09-09 | 1976-09-21 | Alza Corporation | Bioerodible ocular device |
BE788575A (fr) * | 1971-09-09 | 1973-01-02 | Alza Corp | Dispositif oculaire pour l'administration d'un |
US3962414A (en) * | 1972-04-27 | 1976-06-08 | Alza Corporation | Structured bioerodible drug delivery device |
CA1311686C (fr) * | 1986-06-25 | 1992-12-22 | John Weldon Shell | Systeme d'administration de medicaments bioerodables a degagement controle |
NZ222698A (en) * | 1987-01-08 | 1990-02-26 | Squibb & Sons Inc | Bioadhesive suppository formulations comprising a medicament, water, a hydrocolloid and low melting point base |
FR2660193B1 (fr) * | 1990-04-03 | 1994-11-04 | Philippe Maincent | Produit opthalmique comportant des nanocapsules, son procede de preparation et utilisation des nanocapsules. |
GB9020544D0 (en) * | 1990-09-20 | 1990-10-31 | Sandoz Ltd | Improvements in or relating to organic compounds |
DE4122591C1 (en) * | 1991-07-08 | 1993-02-18 | Roland 8012 Ottobrunn De Bodmeier | Producing microcapsules of water insoluble polymer and active agent - includes dissolving or dispersing active agent in aq. polymer contg. gellable assistants |
DE4139883A1 (de) * | 1991-11-29 | 1993-06-03 | Michael Prof Dr Dittgen | Verfahren zur herstellung bioadhaesiver arzneimittel |
FR2688694B1 (fr) * | 1992-03-20 | 1999-06-25 | Vetoquinol Sa | Insert ophtalmique bioadhesif. |
WO1994005257A1 (fr) * | 1992-09-08 | 1994-03-17 | Allergan, Inc. | Liberation prolongee de medicaments ophtalmiques a partir d'un vehicule de diffusion de medicaments polymeres solubles |
GB9416884D0 (en) * | 1994-08-20 | 1994-10-12 | Danbiosyst Uk | Drug delivery compositions |
DE19549506C2 (de) * | 1995-03-07 | 1998-07-30 | Richard Prof Dr Sueverkruep | Darreichungsform zur äußerlichen Applikation und Verfahren zur Herstellung derselben |
US5869079A (en) * | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
WO1998056359A2 (fr) * | 1997-06-13 | 1998-12-17 | Roland Bodmeier | Compositions retardant la liberation de principes actifs |
-
1997
- 1997-12-12 DE DE1997156314 patent/DE19756314C2/de not_active Expired - Fee Related
-
1998
- 1998-12-11 AU AU24101/99A patent/AU2410199A/en not_active Abandoned
- 1998-12-11 EP EP98966561A patent/EP1037606A1/fr not_active Withdrawn
- 1998-12-11 WO PCT/DE1998/003739 patent/WO1999030683A1/fr not_active Application Discontinuation
Non-Patent Citations (1)
Title |
---|
See references of WO9930683A1 * |
Also Published As
Publication number | Publication date |
---|---|
DE19756314C2 (de) | 2000-06-29 |
AU2410199A (en) | 1999-07-05 |
DE19756314A1 (de) | 1999-06-24 |
WO1999030683A1 (fr) | 1999-06-24 |
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