WO1992014446A1 - Interaction entre des liposomes bioadhesifs et des sites cibles - Google Patents
Interaction entre des liposomes bioadhesifs et des sites cibles Download PDFInfo
- Publication number
- WO1992014446A1 WO1992014446A1 PCT/US1991/008112 US9108112W WO9214446A1 WO 1992014446 A1 WO1992014446 A1 WO 1992014446A1 US 9108112 W US9108112 W US 9108112W WO 9214446 A1 WO9214446 A1 WO 9214446A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- liposome
- component
- administration
- recognizing substance
- liposomes
- Prior art date
Links
- 239000002502 liposome Substances 0.000 title claims abstract description 121
- 239000000227 bioadhesive Substances 0.000 title abstract description 28
- 230000003993 interaction Effects 0.000 title description 6
- 239000000126 substance Substances 0.000 claims abstract description 48
- 229920001436 collagen Polymers 0.000 claims abstract description 19
- 102000008186 Collagen Human genes 0.000 claims abstract description 18
- 108010035532 Collagen Proteins 0.000 claims abstract description 18
- 230000001413 cellular effect Effects 0.000 claims abstract description 15
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims abstract description 15
- 230000014759 maintenance of location Effects 0.000 claims abstract description 14
- 102000009024 Epidermal Growth Factor Human genes 0.000 claims abstract description 13
- 101800003838 Epidermal growth factor Proteins 0.000 claims abstract description 13
- 229940116977 epidermal growth factor Drugs 0.000 claims abstract description 13
- 108010010803 Gelatin Proteins 0.000 claims abstract description 6
- 239000008273 gelatin Substances 0.000 claims abstract description 6
- 229920000159 gelatin Polymers 0.000 claims abstract description 6
- 235000019322 gelatine Nutrition 0.000 claims abstract description 6
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 30
- 230000007246 mechanism Effects 0.000 claims description 11
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 9
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 9
- 210000002744 extracellular matrix Anatomy 0.000 claims description 9
- 230000000699 topical effect Effects 0.000 claims description 9
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 3
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims description 3
- 239000002691 unilamellar liposome Substances 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 3
- 238000004132 cross linking Methods 0.000 claims 1
- 239000003431 cross linking reagent Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 33
- 239000003814 drug Substances 0.000 abstract description 33
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 abstract description 4
- 229920002674 hyaluronan Polymers 0.000 abstract description 4
- 229960003160 hyaluronic acid Drugs 0.000 abstract description 4
- 229960005188 collagen Drugs 0.000 abstract 1
- 229940014259 gelatin Drugs 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 48
- 230000027455 binding Effects 0.000 description 28
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 238000010494 dissociation reaction Methods 0.000 description 8
- 230000005593 dissociations Effects 0.000 description 8
- 238000001647 drug administration Methods 0.000 description 5
- 230000009871 nonspecific binding Effects 0.000 description 5
- 239000003446 ligand Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000004873 anchoring Methods 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 229910052722 tritium Inorganic materials 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 101000851196 Mus musculus Pro-epidermal growth factor Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010061363 Skeletal injury Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011158 quantitative evaluation Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 210000003370 receptor cell Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000003981 vehicle 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
Definitions
- the present invention relates to a novel drug delivery system, particularly to microscopic drug delivery systems (MDDS) utilizing drug-encapsulating "bioadhesive" liposomes for topical and local drug administration.
- MDDS microscopic drug delivery systems
- topical and local administration of a drug can be in Its free form, dissolved or dispersed in a suitable diluent, or in a vehicle such as a cream, gel or ointment.
- Examples of therapeutic or designated targets for topical or local drug administration include burns; wounds; bone injuries; ocular, skin, intranasal and buccal infections; ocular chronic situations such as glaucoma; and topically and locally accessed tumors.
- MDDS Microscopic drug delivery systems
- particulate systems such as cells, microspheres, viral envelopes and liposomes
- nonparticulate systems which are macromolecules such as proteins or synthetic polymers.
- drug-loaded MDDS can perform as sustained or controlled release drug depots.
- MDDS reduces drug degradation or inactivation.
- MDDS improves drug efficacy and allows reduction in the frequency of dosing. Since the pharmacokinetics of free drug release from depots of MDDS are different than from directly-administered drug, MDDS provides an additional measure to reduce toxicity and undesirable side effects.
- Liposomes offer a range of advantages relative to other MDDS systems. Liposomes are lipid vesicles composed of membrane-like lipid layers surrounding aqueous compartments. Composed of naturally-occurring materials which are
- liposomes are used to encapsulate biologically active materials for a variety of purposes. Having a variety of layers, sizes, surface charges and compositions, numerous procedures for liposomal preparation and for drug encapsulation within them have been developed, some of which have been scaled up to industrial levels.
- Liposomes can accommodate lipid-soluble drugs, aqueous soluble drugs and drugs with both hydrophilic and hydrophobic residues.
- Liposomes can be designed to act as sustained release drug depots and, in certain applications, aid drug access across cell membranes. Their ability to protect encapsulated drugs and other characteristics make liposomes a popular choice in developing MDDS, with respect to the previous practices of free drug administration.
- liposomes as MDDS have limited targeting abilities, limited retention and stability in circulation, potential toxicity upon chronic administration and inability to
- antibodies can be patient specific and therefore, add cost to the drug therapy.
- cell-associated entitles can participate in the binding between cells and recognizing substances. These are generally divided into three major types: receptors and non-receptor components of the cellular system and
- Receptors can be present in several species or states, differing in populations per cell and in binding affinity. Binding to such receptor entitles is usually referred to as "specific binding”. Non-receptor cell membrane components also differ in populations and in affinity. Binding to such non-receptor entitles is usually referred to as
- administration of drug-encapsulating liposomes should have specificity for and the ability to adhere to the designated target area and should facilitate drug access to intracellular sites.
- liposomes and other MDDS systems do not meet these performance requirements of topical and local drug administration.
- recognizing substances are molecules which can be utilized as an adhesive or glue, attaching a drug-encapsulating liposome onto a therapeutic target site.
- bioadhesive recognizing substances can perform either through receptor mechanisms or through associations with components within the extracellular matrix. Regardless of the specific mechanism of adhesion, these substances are referred to as “bioadhesive recognizing substances” based on their common end result.
- bioadhesive recognizing substances become an integral part of the liposome, yet remain accessible to the interaction counterpart at the target site. They endow the liposome and encapsulated drug with the ability to adhere to the target site.
- bioadhesive liposomes have been developed which are target adherent, sustained release drug depots. The identification of recognizing substances and the methodologies of modifying liposomes has been disclosed in concurrently filed applications. These bioadhesive liposomes offer several advantages over previous practices of topically or locally administered free drug and other MDDS, whether with regular liposomes or other MDDS systems.
- FIG. 1 shows the binding of bioadhesive liposomes
- Bound liposomes denoted as B, are in units of ng EGF per 10 6 cells.
- Free ligand concentration denoted as L, are in units of ng EGF per 10 6 cells for bioadhesive liposome (first row of L values) and in units of umoles lipid per 10 6 cells for the regular liposomes (second row of L values).
- FIG. 2 shows a time course of the binding of bioadhesive liposomes (collagen-modified) of the MLV type to A431 cells in culture (in monolayers). Collagen is tritium-labeled. The fraction of liposomes relative to the amount present in the initial reaction mixture at zero-time which is cell-associated is determined over time.
- FIG. 3 shows the binding of bioadhesive liposomes
- Collagen-modified and regular liposomes of the MLV type to A431 cells in culture (in monolayers). Collagen is
- Bound liposomes denoted as B, are 1n units of 3 -H DPM per 10 5 cells (left scale) and in units of 14 -C DPM per 10 5 cells (right scale).
- Free ligand concentration denoted as L, are in units of 3 -H or 14 -C DPM per 10 5 cells.
- Bloadheslve liposome with collagen labeled is depicted with open double triangles;
- bioadhesive liposome with the liposome labeled is depicted with crosses; and, regular liposome is depicted with asterisks.
- bioadhesive liposomes have bound to cell cultures having receptors or extracellular matrix which accommodate the recognizing substance bonded to the liposome.
- Liposomes in particular, multilamellar vesicles (MLV), microemulsified liposomes (MEL) or large unilamellar vesicles (LUVET), each containing phosphatidylethanolamine (PE), have been prepared by established procedures.
- MLV multilamellar vesicles
- MEL microemulsified liposomes
- LVET large unilamellar vesicles
- PE phosphatidylethanolamine
- Recognizing substances include epidermal growth factor (EGF), hyaluronic acid (HA), gelatin and collagen.
- EGF epidermal growth factor
- HA hyaluronic acid
- gelatin gelatin
- collagen a biological origin and are biodegradable and biocompatible.
- these recognizing substances have functional residues which can be utilized in covalent anchoring to the regular liposomal surfaces.
- n is the number of different cell-associated binding entities that a cellular system has for a specific recognizing substance
- [L] is the concentration of free ligand, which can be recognizing substance, free liposomes or bioadhesive liposomes
- B is the total quantity of bound recognizing substance per given number of cells, at a given [L]
- Bmax i and Kd i are the total number of sites of a given entity and the corresponding equilibrium dissociation constant.
- B and B max are normalized for the same number of cells.
- equation 1 can take the form: where the last term, K ns [L], is the contribution of the non-specific binding to B and K ns is the ratio of Bmax to Kd corresponding to the non-specific binding.
- A431 cells have been shown to have three classes of EGF receptors, differing 1n their affinities and populations.
- the first of these classes is the ultra-high affinity sites with an equilibrium dissociation constant of 0.07 nM and a population of 150-4000 sites per cell.
- the next class is the high affinity sites with an equilibrium dissociation constant of 0.7 nM and a population of 1.5 ⁇ 105 sites per cell.
- the final class is the low affinity sites with an equilibrium
- A431 cell cultures were grown in monolayers, in flasks, applying usual procedures for this cell line. Two to three days prior to an experiment, the cells were seeded into multiwell culture plates and the experiments were done when the systems were confluent.
- the EGF-recogniz1ng substance was labeled with a generally known radioactive marker.
- Preparation of EGF-modified LUVET was completed as disclosed in the concurrently filed applications.
- EGF-modified liposomes, free liposomes or free EGF, media was removed from the A431 cells and the cells were washed with a binding buffer.
- the reaction mixture and cells were incubated for 1-2 hours, at room temperature. Upon dilution and withdrawal of the reaction mixture at the end of incubation, 2-3 successive washings with a binding buffer of the wells were completed. Lysis of cells or detachment of cells from the wells was then followed by withdrawal and collection of the well content, denoted as the cell fraction. Assays of the cell fraction were completed by label counting of the fraction as compared with the counting of the immediate products created through the preparation process.
- EGF-modified liposome is considerably larger than and different from free EGF, which is expected to affect the binding parameters.
- the magnitudes of the dissociation constants for EGF-modified liposome systems are expected to be similar to or higher than those of free EGF.
- the number of receptors per cell that are available for the EGF-modified liposomes is expected to be equal to or lower than the number of available for free EGF. Based on these considerations, the binding data of the present example fit with the receptor classes of ultra-high and high affinities.
- EGF-modified liposomes bind to this cellular system with high affinity and with a sufficient number of sites for these modified liposomes to perform as the desired bioadhesive liposomes.
- Binding collagen-modified liposomes to A431 cells was carried out essentially according to the procedures detailed above.
- the A431 cell line is not known to contain receptors for collagen.
- the interaction of either free collagen or liposomally bound collagen with the A431 cell line is expected to result from association of collagen with components within the extracellular matrix. Referring to Figure 2, incubation periods up to 4 hours were completed with 3 hours being the optimal period for binding and collagen-liposome concentrations.
- the binding entitles are of the extracellular matrix type of
- the dissociation constant for collagen-modified liposomes is expected to be similar to or higher than those of free collagen.
- the number of available sites in the extracellular matrix available for collagen-modified liposomes is expected to be similar to or lower than free collagen.
- the example given in Table 2 fits with these considerations.
- the data for free collagen demonstrate that binding of this bioadhesive recognizing substance to this cellular system does occur and is a measurable phenomena, which can be processed to yield quantitative and meaningful parameters.
- the data in Table 2 show quite clearly that the binding of
- collagen-modified liposomes to this cellular system is of sufficiently high affinity and with a large enough number of sites, for the collagen-modified liposomes to perform as the desired bioadhesIve liposomes.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Seats For Vehicles (AREA)
- Electric Cable Arrangement Between Relatively Moving Parts (AREA)
Abstract
Des substances de reconnaissance, le facteur de croissance épidermique, la gélatine, le collagène et l'acide hyaluronique, ont été liés de manière covalente à des surfaces liposomiques et utilisés pour fixer les liposomes sur un site cellulaire cible. L'utilisation de ces liposomes 'bioadhésifs' présente plusieurs avantages dans le domaine de médicaments libres à administration locale ou topique. Ces avantages comprennent la protection réciproque à la fois de l'environnement biologique et du médicament, une amélioration de la biodisponibilité et de la rétention du médicament au niveau du site cible; et une adhérence améliorée au site cible désigné.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU12592/92A AU656173B2 (en) | 1991-02-14 | 1991-10-30 | Interaction between bioadhesive liposomes and target sites |
| JP92505165A JPH05506040A (ja) | 1991-02-14 | 1991-10-30 | 生体接着性リポソームと標的部位との相互作用 |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65501391A | 1991-02-14 | 1991-02-14 | |
| US655,013 | 1991-02-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1992014446A1 true WO1992014446A1 (fr) | 1992-09-03 |
Family
ID=24627144
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1991/008112 WO1992014446A1 (fr) | 1991-02-14 | 1991-10-30 | Interaction entre des liposomes bioadhesifs et des sites cibles |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0525154A1 (fr) |
| JP (1) | JPH05506040A (fr) |
| AU (1) | AU656173B2 (fr) |
| CA (1) | CA2079450A1 (fr) |
| WO (1) | WO1992014446A1 (fr) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994018955A1 (fr) * | 1993-02-22 | 1994-09-01 | Alza Corporation | Compositions destinees a l'apport oral d'agents actifs |
| US6096863A (en) * | 1996-08-23 | 2000-08-01 | Regents Of The University Of Minnesota | Self-assembling amphiphiles for construction of peptide secondary structures |
| US6890901B2 (en) | 1996-09-27 | 2005-05-10 | Jagotec Ag | Hyaluronic drug delivery system |
| EP1509612A4 (fr) * | 2002-03-22 | 2005-07-20 | Drugtech Corp | Systeme de distribution transcellulaire de medicaments |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9208339D0 (en) * | 1992-04-15 | 1992-06-03 | Unilever Plc | Treatment composition |
| JP5695308B2 (ja) * | 2009-10-02 | 2015-04-01 | 株式会社フェース | コラーゲン修飾リポソームからなる化粧料基剤およびそれを含有する皮膚化粧料 |
| JPWO2011083845A1 (ja) * | 2010-01-08 | 2013-05-16 | 富士フイルム株式会社 | 腫瘍部位に対する標的化剤 |
| JP5756602B2 (ja) * | 2010-04-16 | 2015-07-29 | 株式会社フェース | ゼラチンおよび／またはエラスチン構成ポリペプチドで修飾されたリポソームからなる化粧料基剤およびそれを含有する皮膚化粧料 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0295092A2 (fr) * | 1987-06-12 | 1988-12-14 | Unilever Plc | Composition pour le traitement de la peau |
| WO1990009782A1 (fr) * | 1989-02-24 | 1990-09-07 | Liposome Technology, Inc. | Composition liposomique sous forme de gel et son procede de preparation |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5000960A (en) * | 1987-03-13 | 1991-03-19 | Micro-Pak, Inc. | Protein coupling to lipid vesicles |
| AU652778B2 (en) * | 1990-10-15 | 1994-09-08 | Quest International B.V. | Treatment composition |
| CA2079447C (fr) * | 1991-02-14 | 2004-02-10 | Baxter International Inc. | Administration continue de medicaments par application topique de liposomes bioadhesifs |
-
1991
- 1991-10-30 CA CA002079450A patent/CA2079450A1/fr not_active Abandoned
- 1991-10-30 AU AU12592/92A patent/AU656173B2/en not_active Ceased
- 1991-10-30 WO PCT/US1991/008112 patent/WO1992014446A1/fr not_active Application Discontinuation
- 1991-10-30 JP JP92505165A patent/JPH05506040A/ja active Pending
- 1991-10-30 EP EP19920904871 patent/EP0525154A1/fr not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0295092A2 (fr) * | 1987-06-12 | 1988-12-14 | Unilever Plc | Composition pour le traitement de la peau |
| WO1990009782A1 (fr) * | 1989-02-24 | 1990-09-07 | Liposome Technology, Inc. | Composition liposomique sous forme de gel et son procede de preparation |
Non-Patent Citations (3)
| Title |
|---|
| Biochemical and Biophysical Research Communications, vol. 160, no. 2, 28 April 1989, (Duluth, Minn. US), Y. ISHII et al.: "Preparation of EGF labeled liposomes and their uptake by hepatocytes", pages 732-736, see the whole article * |
| G. GREGORIADIS: "Liposome Technology", vol. III, 1984, CRC Press, Inc., Boca Raton, US, see pages 75-94, in particular pages 88-89 * |
| Patent Abstracts of Japan, vol. 9, no. 74 (C-273)[1797], 3 April 1985, & JP,A,59210013 (AJINOMOTO K.K.) 28 November 1984, see the abstract * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994018955A1 (fr) * | 1993-02-22 | 1994-09-01 | Alza Corporation | Compositions destinees a l'apport oral d'agents actifs |
| US5620708A (en) * | 1993-02-22 | 1997-04-15 | Alza Corporation | Compositions and methods for the oral delivery of active agents |
| US5702727A (en) * | 1993-02-22 | 1997-12-30 | Alza Corporation | Compositions and methods for the oral delivery of active agents |
| US6096863A (en) * | 1996-08-23 | 2000-08-01 | Regents Of The University Of Minnesota | Self-assembling amphiphiles for construction of peptide secondary structures |
| US6890901B2 (en) | 1996-09-27 | 2005-05-10 | Jagotec Ag | Hyaluronic drug delivery system |
| EP1509612A4 (fr) * | 2002-03-22 | 2005-07-20 | Drugtech Corp | Systeme de distribution transcellulaire de medicaments |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0525154A1 (fr) | 1993-02-03 |
| CA2079450A1 (fr) | 1992-08-15 |
| AU1259292A (en) | 1992-09-15 |
| AU656173B2 (en) | 1995-01-27 |
| JPH05506040A (ja) | 1993-09-02 |
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