EP0928188A1 - Structures a deux membranes de lipides ou a base de peptides - Google Patents

Structures a deux membranes de lipides ou a base de peptides

Info

Publication number
EP0928188A1
EP0928188A1 EP97909321A EP97909321A EP0928188A1 EP 0928188 A1 EP0928188 A1 EP 0928188A1 EP 97909321 A EP97909321 A EP 97909321A EP 97909321 A EP97909321 A EP 97909321A EP 0928188 A1 EP0928188 A1 EP 0928188A1
Authority
EP
European Patent Office
Prior art keywords
molecules
lipophilic
region
peg
peptides
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Withdrawn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
EP97909321A
Other languages
German (de)
English (en)
Inventor
Jörg SCHREIBER
Wolfgang Meier
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.)
Beiersdorf AG
Original Assignee
Beiersdorf AG
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 Beiersdorf AG filed Critical Beiersdorf AG
Publication of EP0928188A1 publication Critical patent/EP0928188A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • 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
    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
    • A61Q1/14—Preparations for removing make-up
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q15/00—Anti-perspirants or body deodorants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin

Definitions

  • the present invention relates to structures with planar or curved lipid double membranes. Furthermore, the present invention relates to the cosmetic, medical or pharmaceutical use of such structures and methods for their production. In addition, the present invention relates to processes for the production of certain new substances which are advantageous for the production of structures with planar or curved lipid double membranes.
  • the invention further relates to structures based on peptides, the cosmetic, medical or pharmaceutical use of such structures and methods for their production.
  • the present invention relates to methods for producing certain new substances which are advantageous for producing the structures based on peptides.
  • this term is understood to mean a group of water-insoluble molecules which are distinguished by at least one pronounced hydrophilic molecular region and at least one pronounced lipophilic molecular region.
  • the phosphoric acid esters of acylated glycerols, the so-called “phospholipids” and other compounds belong to this group of chemical compounds, which is quite inhomogeneous overall.
  • lipids do not usually form real molecular solutions in vitro, for example in a mixture with water, but rather they either form colloids, they usually combine to form so-called micelles, in which the lipophilic molecular areas of the lipid molecules are located inside the micelle are located and the hydrophilic regions of the lipid molecules represent the outer region of the micelles, as described in FIG. 1, or else they form liquid-crystalline phases.
  • the lipid molecules have a hydrophilic area (h) and a lipophilic area (I).
  • the micelle (M) shown in FIG. 1 represents a sphere of lipid molecules, the interior of which is filled by the lipophilic residues of the molecules. Since the micelles are present in an aqueous environment (W), it is obvious that the outer shell of the micelle is formed by the hydrophilic groups of the lipid molecules.
  • Lipid membranes can, for example, be linear, curved (cubic phases, L 3 phases) or self-contained (vesicles, L 4 phases).
  • the individual lipid molecules attach to one another in such a way that two monomolecular layers of lipid molecules arranged in parallel come to lie on one another at their lipophilic regions.
  • the lipid molecules have a hydrophilic area (h) and a lipophilic area (I).
  • the lipid bilayer (L) shown in FIG. 2 represents a membrane made of lipid molecules, the interior of which is filled by the lipophilic residues of the lipid molecules. Since the lipid bilayer is present in an aqueous environment (W), it is obvious that the outer shell of the lipid bilayer is formed by the hydrophilic groups of the lipid molecules.
  • Vesicles or liposomes are spherically closed microscopic objects which are delimited on the outside by a lipid bilayer and which contain a water phase inside. This is shown in Fig. 3.
  • the lipid molecules have a hydrophilic area (h) and a lipophilic area (I).
  • the lipid bilayer is present in an aqueous environment (W), it is obvious that the outer shell of the lipid bilayer is formed by the hydrophilic groups of the lipid molecules.
  • the center of the vesicles is filled by an aqueous phase.
  • the diameter of liposomes usually ranges from a few (typically around 25) nanometers to around 1 ⁇ m.
  • a so-called multiiamellar vesicle (M) is shown in cross section and with enlarged sections. It consists of several - here two - lipid double membranes as the outer shell, the lipid double membranes consisting of lipid molecules with a hydrophilic region (h) and a lipophilic region (I).
  • a thin layer of a polar, in particular aqueous phase (w) is generally arranged between the lipid double membranes.
  • a polar phase inside the multilamellar vesicle is another polar, usually aqueous phase, which can also be loaded with active substances (here: Q)).
  • Q active substances
  • the lipid double membrane can also be loaded with active substances, which are then generally of an iipophilic nature.
  • liposomes for example, is well known to the person skilled in the art.
  • One method is, for example, an ultrasound treatment of a lipid water system, with the liposomes obtained only having to be filtered off when choosing suitable lipids.
  • vesicle extrusion of suitable lipids through a membrane filter with a pore size of typically about 100 nm also leads to the formation of liposomes.
  • the basic components of the lipid double-membrane covering the liposomes are normally selected from the group of phospholipids, often lecithin. Occasionally, especially with the so-called niosomes, non-ionic surfactants are also used as the covering material.
  • niosomes non-ionic surfactants are also used as the covering material.
  • empty liposomes which consist of a shell and an aqueous interior
  • loaded liposomes the interior of which represents an aqueous phase which is provided with water-soluble active substances, or whose shell is provided with lipophilic active substances.
  • Microorganisms can be encapsulated in a liposomal manner, "transfersomes" should penetrate the epidermis intact in contrast to "normal" liposomes.
  • liposomes do not penetrate intact, but adsorb on or in the uppermost layers of the stratum corneum. There is much to suggest that liposomes are endocytotically absorbed into the body cell. In addition to the topical administration of preparations containing liposomes, intravenous administration is also possible.
  • Cell membranes can also be regarded as closed microscopic objects, which are delimited on the outside by a double lipid layer and which house a water phase inside. This is shown in FIG. 4.
  • the lipid molecules have a hydrophilic area (h) and a lipophilic area (I).
  • the lipid bilayer (L) of the cell shown in FIG. 4 represents a membrane of lipid molecules which forms a hollow body and the interior of which is filled by the lipophilic residues of the lipid molecules. Integral proteins (B) and peripheral proteins (C) are embedded in the cell membrane. Since the lipid bilayer is present in an aqueous environment (W), it is obvious that the outer shell of the lipid bilayer is formed by the hydrophilic groups of the lipid molecules. The center of the cell is filled by the cell plasma (E), ultimately also an aqueous phase. In the interior of the cell there are also cell organelles (D) which can perform a wide variety of biological functions.
  • the phospholipids in particular are of the highest biological interest since they represent the basic substance of the cell membranes of all living cells or their cell organelles.
  • phospholipids are important components of the plasma membrane, the myelin, the endoplasmic reticulum and certain organelles, for example the chloroplast photosynthetic organisms.
  • R ⁇ and R 2 typically represent unbranched aliphatic radicals with 15 or 17 carbon atoms and up to 4 cis double bonds.
  • Lecithins are not only important in the living cell, they are also preferably used as a basic component for the outer layer of the most common commercially available liposomes.
  • the basic structure of the sphingolipids is sphingosine or phytosphingosin, which are characterized by the following structural formulas:
  • Modifications of sphingolipids are characterized, for example, by the general basic structure in which R 1 and R 3 independently of one another represent saturated or unsaturated, branched or unbranched alkyl radicals of 1 to 28 carbon atoms, R 2 is selected from the group: hydrogen atom, saturated or unsaturated, branched or unbranched alkyl radicals of 1 to 28 carbon atoms, sugar radicals, with organic radicals esterified or unesterified phosphate groups, with organic radicals esterified or unesterified sulfate groups and Y represents either a hydrogen atom, a hydroxyl group or another hetero-functional radical.
  • sphingolipids include the naturally occurring ceramides, cerebrosides, gangliosides, sphingophospholipids, of which in particular the sphingomyelins, sphingosulfatides and glycosphingosides as well as analogues obtainable by chemical synthesis, examples of which are listed below:
  • R and R 3 represent alkyl radicals, R «represents an organyl radical.
  • Sphingomyeline are organylphosphorylated sphingolipids of the type
  • R 2 is selected from the group of sugar residues in the structural formula of the ceramides, a distinction is usually made between whether monoglycosylceramides or di, tri or generally oligoglycosylceramides are present.
  • Monoglycosylceramides are commonly called cerebrosides:
  • Oligoglycosylceramides are mostly called gangliosides.
  • sphingoiipids are ceramide I, II, III and IV, glucosylceramide, lactosylceramide and the gangliosides GM 1, 2 and 3.
  • cholesterol is integral components of plasma membranes. Because of its lipophilic nature, the cholesterol is present inside the lipid bilayer, that is, surrounded by the lipophilic regions of the lipid molecules.
  • peptides are present in an aqueous environment, the hydrophilic areas usually face the aqueous phase, whereas the lipophilic areas tend to be shielded as far as possible from the water phase. In this respect they are similar to the structures with lipid bilayers. Examples of substances with a peptide structure are proteins and enzymes.
  • Gels are the usual and increasingly popular cosmetic and dermatological preparation forms.
  • gels are understood to mean: relatively dimensionally stable, easily deformable disperse Systems consisting of at least two components, which usually consist of a - usually solid - colloidally divided substance made up of long-chain molecular groups (e.g. gelatin, silica, polysaccharides) as a scaffold and a liquid dispersion medium (e.g. water).
  • a - usually solid - colloidally divided substance made up of long-chain molecular groups (e.g. gelatin, silica, polysaccharides) as a scaffold and a liquid dispersion medium (e.g. water).
  • the colloidally divided substance is often referred to as a thickening or gelling agent. It forms a spatial network in the middle of the dispersion, whereby individual colloidal particles can be more or less firmly linked to one another via electrostatic interaction.
  • the dispersing agent which surrounds the network is distinguished by electrostatic affinity for the gelling agent, i.e. a predominantly polar (in particular: hydrophilic) gelling agent preferably gels a polar dispersing agent (in particular: water), whereas a predominantly non-polar gelling agent preferably gels non-polar dispersing agent.
  • a predominantly polar (in particular: hydrophilic) gelling agent preferably gels a polar dispersing agent (in particular: water)
  • a predominantly non-polar gelling agent preferably gels non-polar dispersing agent.
  • Lipogels and oleogels are also common in cosmetic and pharmaceutical galenics.
  • oleogels which are practically anhydrous
  • hydrogels which are practically fat-free.
  • gels are transparent.
  • gels are usually characterized by a semi-solid, often flowable consistency.
  • Liposomes for example, are generally thermolabile above a certain temperature, usually around 40.degree. C., or are not or not sufficiently stable against the action of surfactants or other substances such as UV filter substances. Solutions are available, for example so-called “stealth” liposomes, which are liposomes with polyethoxylated components in their outer skin [Allen, TM (1989) in “Liposomes: the therapy in infectious diseases and cancer”, Lopez-Berestein, G and Fiedler, I.7., Eds., Pages 405-415, Alan R. Liss, New York], nevertheless disadvantages of the prior art had to be accepted.
  • Another object of the present invention was therefore to develop new cosmetic and pharmaceutical dosage forms which should have significant improvements over the previously known dosage forms based on lipid bilayers.
  • gels based on liposomes - which are not simply gels (for example based on polyacrylates) containing liposomes, were previously unknown to the prior art.
  • a further task was therefore to provide structures with lipid double membranes, in particular unilamellar or multilamellar vesicles or liposomes, with increased stability.
  • Milk of bovine origin contains about 87% water, furthermore proteins such as casein, lactoglobulin, blood serum albumin, immunoglubulin, transferrin lactoferrin, further lactose, minerals (D. Walstra, R. Jennes, Dairy Chemistry and Physics, pp. 1-11, John Wil ⁇ y & Sons, 1984).
  • An object of the present invention was also to remedy this particular problem.
  • the objects are achieved according to the invention by structures based on lipid double membranes or peptides, one or more hypophile regions of one or more molecules being immersed in the inner lipophilic region of the lipid double membranes or a lipophilic region of the peptides, or such molecules being hydrophobic interactions on lipid double membranes or dock peptides, and wherein such molecules consist of at least one hydrophilic region and at least one lipophilic region.
  • Chem. Techn. Lab. 43 (1995) No. 1, p. 9 ff. Chain-like, hydrophilic molecules are described for crosslinking microemulsion droplets, each of which has a hydrophobic residue at the two chain ends.
  • hydrophobic residues are immersed in microemulsion droplets, the hydrophilic chain regions being in the continuous water phase. In the strict sense, it is probably not necessary for the hydrophobic residues to "immerse". In individual cases, it may also be sufficient if the hydrophobic residues come into contact with the surface of the microemulsion droplets through hydrophobic interaction and adhere more or less strongly to it
  • the above-mentioned crosslinkers are polyol (ethylene glycols with oleyl groups as hydrophobic end groups. This principle is illustrated in FIG.
  • microemulsion droplets (O) of an O / W microemulsion surrounded by a continuous water phase (W) are represented by the crosslinking molecules shown as lines are connected to one another, which are characterized by hydrophilic regions (hh) and also carry Hpophile residues (II) symbolized at both ends by rectangles. It can be seen that an emulsion droplet can in principle also accommodate several hydrophobic residues, so that one stronger networking and three-dimensional network can be guaranteed. Nevertheless, this document could not give any indication of the structures according to the invention and their properties.
  • FIG. 6a Structures, as shown in Figures 6a and 6b, are for example in accordance with the invention.
  • vesicles such as liposomes, which are surrounded by a continuous water phase (W), and in the inner lipophilic region of the lipid double membranes the hypophile region (II) of one or more molecules, which are composed of at least one hydrophilic region (hh) and at least one lipophilic region (II).
  • W continuous water phase
  • II hypophile region
  • hh hydrophilic region
  • III lipophilic region
  • the structure according to the invention which is shown in FIG. 6b, consists of a vesicle or a liposome which is surrounded by a continuous water phase (W) and which has an essentially hollow spherical, closed lipid double oil membrane as the outer shell, with the inner lipophilic region the lipid double membranes of said vesicles immerse an iipophilic region (II) of a molecule which consists of a hydrophilic region (hh) and two lipophilic areas (II).
  • the second hypophile area is freely movable in this embodiment of the invention.
  • the structure according to the invention which is shown in Fig. 6c, consists of a vesicle or a liposome which is surrounded by a continuous water phase (W) and which has a substantially hollow spherical, closed lipid double membrane as the outer shell, with the inner dip the lipophilic region of the lipid double membranes of said vesicles into the two lipophilic regions (II) of a molecule which consists of a hydrophilic region (hh) and two lipophilic regions (II).
  • the structure according to the invention which is shown in FIG. 7, consists of a multiplicity of vesicles or liposomes which are surrounded by a continuous water phase (W) and which have a substantially hollow spherical, closed lipid double membrane as outer shells, these vesicles or Liposomes are linked to one another by a large number of molecules, each of which has a hydrophilic region (hh) and two Hpophile regions (II). Similar structures can be assumed for the connection of multiiamellar vesicles.
  • the structure according to the invention which is shown in FIG. 7a, consists of a multiplicity of vesicles or liposomes which are surrounded by a continuous water phase (W) and which have a substantially hollow spherical, closed lipid double membrane as outer shells, these vesicles or Liposomes are linked to one another by a large number of molecules which each have a hydrophilic region (hh) and a large number of lipophilic regions (II) (hydrophobically modified water-soluble polymers, associative thickeners). Similar structures can be assumed for the connection of multiiamellar vesicles.
  • the structure according to the invention which is shown in FIG. 8, consists of a large number of living (or possibly also killed) cells which are surrounded by a continuous water phase (W), for example body fluid, and which have a substantially hollow spherical, closed lipid double membrane have as outer shells, these cells being one below the other which are linked by a large number of molecules, each of which has a hydrophilic region (hh) and two hypophile regions (II).
  • W continuous water phase
  • II hypophile regions
  • the structure according to the invention which is shown in FIG. 8a, consists of a large number of living (or possibly also killed) cells, which are surrounded by a continuous water phase (W), for example body fluid, and which have an essentially hollow spherical, closed lipid double membrane have as outer shells, these cells being linked to one another by a multiplicity of molecules which each have a hydrophilic region (hh) and a multiplicity of lipophilic regions (II).
  • W continuous water phase
  • II multiplicity of molecules which each have a hydrophilic region
  • II multiplicity of lipophilic regions
  • the structure according to the invention which is shown in Fig. 9, consists of several planar lipid double membranes (LC), which are surrounded by a continuous water phase (W), and which are linked to each other by a large number of molecules, each of which has a hydrophilic region (h ) and each have two hypophile areas (II).
  • LC planar lipid double membranes
  • W continuous water phase
  • h hydrophilic region
  • II hypophile areas
  • crosslink planar or curved structures consisting of several planar or curved lipid double membranes (LC), which are surrounded by a continuous water phase (W), as shown in FIG. 9a, by molecules, each of which is hydrophilic Area (hh) and a variety of lipophilic areas (II), for example as in cetylhydroxyethyl cellulose, cholesteryl hydroxyethyl cellulose, stearyl hydroxyethyl cellulose, dodecyl polyacrylate, polyvinylpyrrolidones substituted with cholesteryl groups, polyvinyl alcohols and the like types of compounds.
  • Curved and planar lipid double membranes exist, for example, in cubic phases, cubic vesicle gels and in Cubosomen®.
  • the structure according to the invention which is shown in FIG. 13, consists of a large number of peptides which are surrounded by a continuous water phase (W), the hydrophilic regions of which are in the immediate vicinity of the water phase (W), the lipophilic molecular residues L im Form a lipophilic region inside the peptides, and these peptides are linked to one another by a multitude of crosslinking molecules, each of which has a hydrophilic region (hh) and a multiplicity of lipophilic regions (II). With In their lipophilic regions (II), these crosslinker molecules are immersed in the lipophilic region of the peptides.
  • B symbolizes a hydrophilic region of the respective crosslinker molecule and A each represents hydrophobic regions, which may also be of a different chemical nature within a molecule.
  • Z represents a central unit, which can be hydrophilic or hydrophobic and usually consists of an oligo- or polyfunctional molecular residue.
  • linker substances with a higher degree of branching also fall within the scope of the present invention.
  • Z can consist of a glyceryl residue, the three OH functions of which merge into regions B, which in turn can represent polyoxyethylene chains of the same or different lengths, and whose terminal OH group is esterified with a longer-chain fatty acid. Partial substitution of glycerol is also conceivable, which can result in structures which correspond to scheme (9).
  • the hydrophilic groups B can advantageously be chosen so that the overall linker substance is water-soluble or at least dispersible in water, in which case the hydrophobic portion of groups A should then be overcompensated.
  • the structure scheme (1) for example, the following more specific structure schemes can be followed:
  • R 1, R 2 , R 3 , R, R_ and R ⁇ can independently represent branched or unbranched, saturated or unsaturated, cyclic or chain-shaped aliphatic, aromatic or heteroaromatic radicals, for example branched or unbranched or cyclic alkyl or alkanoyl radicals, with alkyl or aryl substituents, substituted or unsubstituted aryl or aroyl residues or also alkylated or arylated organylsilyl residues.
  • x means numbers that allow the entire molecule to be soluble or at least dispersible in water typically selected from the range greater than 10, advantageously from the range 20 to 10 7 .
  • a and b are numbers which are chosen as a function of x in such a way that the linker substance has at least sufficient water solubility or water dispersibility.
  • x can possibly have values much higher than, for example, 300, even several million. This is known per se to the person skilled in the art and requires no further explanation.
  • R 1, R 2 and R 3 can independently represent branched or unbranched, saturated or unsaturated, cyclic or chain-like aliphatic, aromatic or heteroaromatic radicals, for example branched or unbranched or cyclic alkyl or alkanoyl radicals, aryl substituted or unsubstituted by alkyl or aryl substituents - or aroyl residues or also alkylated or arylated organylsilyl residues.
  • x, y and z mean, independently of one another, numbers which allow the entire molecule to be soluble or at least dispersible in water, typically selected from the range greater than 10, advantageously from the range 20 to 10 7 .
  • Partial substitution is also conceivable, one or more of the indices x, y or z being able to assume the value zero and one or more of the radicals R 1 f R 2 or R 3 being hydrogen atoms.
  • R 1, R 2 , R 3 and R can independently represent branched or unbranched, saturated or unsaturated, cyclic or chain-like aliphatic, aromatic or heteroaromatic radicals, for example branched or unbranched or cyclic alkyl or alkanoyl radicals, substituted by alkyl or aryl substituents or unsubstituted aryl or aroyl residues or also alkylated or arylated organylsilyl residues.
  • u, v, w and x mean, independently of one another, numbers which allow the entire molecule to be soluble or at least dispersible in water, typically selected from the range greater than 10, advantageously from the range 20 to 10 7 .
  • R 1, R 2 , R 3 and R can independently represent branched or unbranched, saturated or unsaturated, cyclic or chain-like aliphatic, aromatic or heteroaromatic radicals, for example branched or unbranched or cyclic alkyl or alkanoyl radicals, substituted by alkyl or aryl substituents or unsubstituted aryl or aroyl residues or also alkylated or arylated organylsilyl residues.
  • x and y mean, independently of one another, numbers which allow the entire molecule to be soluble or at least dispersible in water, typically selected from the range greater than 10, advantageously from the range 20 to 10 7 .
  • R 1, R 2 and R 3 can independently represent branched or unbranched, saturated or unsaturated, cyclic or chain-like aliphatic, aromatic or heteroaromatic radicals, for example branched or unbranched or cyclic alkyl or alkanoyl radicals, substituted or unsubstituted by alkyl or aryl substituents Aryl or aroyl residues or also alkylated or arylated organylsilyl residues.
  • x, y and z mean, independently of one another, numbers which allow the entire molecule to be soluble or at least dispersible in water, typically selected from the range greater than 10, advantageously from the range 20 to 10 7 .
  • R 1, R 2 , R 3 and R can independently represent branched or unbranched, saturated or unsaturated, cyclic or chain-like aliphatic, aromatic or heteroaromatic radicals, for example branched or unbranched or cyclic alkyl or alkanoyl radicals, substituted by alkyl or aryl substituents or unsubstituted aryl or aroyl residues or also alkylated or arylated organylsilyl residues.
  • u, v, w and x mean, independently of one another, numbers which allow the entire molecule to be soluble or at least dispersible in water, typically selected from the range greater than 10, advantageously from the range 20 to 10 7 .
  • R 1, R 2 , R 3 , R and R 5 can independently represent branched or unbranched, saturated or unsaturated, cyclic or chain-like aliphatic, aromatic or heteroaromatic radicals, for example branched or unbranched or cyclic alkyl or alkanoyl radicals, with alkyl - Aryl or substituted or unsubstituted aryl or aroyl radicals or alkylated or arylated organylsilyl radicals.
  • u, v, w, x and y mean, independently of one another, numbers which allow the entire molecule to be soluble or at least dispersible in water, typically selected from the range greater than 10, advantageously from the range 20 to 10 7 .
  • R 1 ( R 2 , R 3 , R 4 , R 5 and Re can independently represent branched or unbranched, saturated or unsaturated, cyclic or chain-like aliphatic, aromatic or heteroaromatic radicals, for example branched or unbranched or cyclic alkyl or Alkanoyl radicals, substituted or unsubstituted aryl or aroyl radicals with alkyl or aryl substituents or also alkylated or arylated organylsilyl radicals.
  • U, v, w, x, y and z mean, independently of one another, numbers which allow the entire molecule to be soluble or at least dispersible in water to be, typically selected from the range greater than 10, advantageously from the range 20 to 10 7 .
  • linking substances have been found to be those selected from the group of the polyethylene glycol ethers of the general formula RO - (- CH 2 -CH 2 -O-) n -R ⁇ where R and R 'independently of one another are branched or unbranched alkyl, aryl, or alkenyl radicals and n represent a number greater than 100, of the etherified fatty acid ethoxylates of the general formula R-COO - (- CH 2 -CH 2 -O-) n -R ', where R and R' independently of one another are branched or unbranched alkyl, aryl or alkenyl radicals and n is a number greater than 100, the esterified fatty acid ethoxylates of general formula R-COO - (- CH 2 -CH 2 -O-) "-C (O) -R ⁇ where R and R 'independently of one another are branched or unbranched alkyl,
  • R-COO - (- CH 2 -CH (CH 3 ) -O-) n -C (O) -R ' where R and R' independently of one another are branched or unbranched alkyl, aryl or alkenyl radicals and n is a number larger represent as 100, the polypropylene glycol ether of the general formula
  • RO-Xn-Ym-R ' where R and R' independently represent branched or unbranched alkyl, aryl or alkenyl radicals, where X and Y are not identical and each have either an oxyethylene group or an oxypropylene group and n and m are independent represent numbers from one another, the sum of which is greater than 100 of the etherified fatty acid propoxylates of the general formula R-COO-X n -Y m -R ', where R and R' independently of one another represent branched or unbranched alkyl, aryl or alkenyl radicals, where X and Y are not identical and each represent either an oxyethylene group or an oxypropylene group and n and m independently of one another are numbers whose sum is greater than 100 of the hydrophobically modified water-soluble polymer of hydroxyethyl cellulose, polyacrylates (of the Pemulen type), of polypvinylpyrrolidone , polyvinyl alcohol, polyly
  • the PEG-800 disteatate and the PEG-800 dioleate can be used particularly advantageously.
  • the PEG-1600 pentaerythrityl tetraisostate, the PEG-800 methyl glucose dioleate, the PEG-1200 sorbitan triisostearate, the PEG-2400 sorbitol hexaisostearate and the PEG-1200 glyceryl triisostearate, the PEG-800 diretinate, the PEG-800 diglystate and the PEG-800 diglystate PEG-800-Drtocopherolat are advantageous to use as linking substances.
  • linking substances which are distinguished by smaller hydrophilic regions, that is to say that it is possible and advantageous, to give preference to a linking substance with a lower degree of polyethoxylation than one with a higher degree of polyethoxylation.
  • Advantageous linker substances are selected, for example, from the group with the following structural motifs:
  • Z sets a hydrophilic range, which can be selected particularly advantageously from the group of polyoxyethylene groups with degrees of polyethoxylation of up to 10 7 .
  • Z 1 and Z 2 can be selected independently of one another from the group single bond, ester group, carbonic acid ester group, oxygen, acid amide group, acid imide group, thiocarboxylic acid ester group, urethane or carbamate group.
  • Dicholesteryl compounds of the type have proven to be particularly advantageous linker substances proven, which we want to collectively call PEG-n-Chol 2 , where n means numbers which allow the entire molecule to be soluble or at least dispersible in water, typically selected from the range greater than 10, advantageously from the range 20 to 10 7 , very particularly advantageous from the range 120 to 1,200.
  • n means numbers which allow the entire molecule to be soluble or at least dispersible in water, typically selected from the range greater than 10, advantageously from the range 20 to 10 7 , very particularly advantageous from the range 120 to 1,200.
  • PEG-n-Chol 2 can be obtained by the usual chemical methods.
  • PEG-n-Chol 2 can be obtained particularly advantageously by adding polyethylene oxide with the desired degree of polymerization n with a cholesteryl derivative of the general structure
  • reaction scheme is implemented, it being advantageous to create reaction conditions which favor the elimination of the substance HX, for example according to the following reaction scheme:
  • PEG-n-Chol 2 can be obtained particularly advantageously by reacting polyethylene oxide with the desired degree of polymerization n under basic conditions with cholesteryl chloroformate according to the reaction scheme
  • An advantageous method of obtaining the PEG-n-Chol 2 linker substances preferred according to the invention is to add an excess of cholesteryl chloroformate and a base, for example pyridine, to polyethylene oxide with the desired degree of polymerization n under largely or completely anhydrous conditions, and to add the reaction product , which is usually a solid, to be processed according to the usual preparation methods.
  • a base for example pyridine
  • hydrophobically modified polymers have also been found to be particularly advantageous linker substances: cetylhydroxyethyl cellulose, stearyl hydroxyethyl cellulose, oleyl hydroxyethyl cellulose, cholesteryl polyacrylate, dodecylamide polyacrylate, C.
  • alkyl acrylate (Pemulene), stearyl polyacrylate acrylate, chearyl polyacrylate acrylate, cholesteryl polyacrylate acrylate, cholesteryl polyacrylate acrylate, glucosamide, copolymer from polyvinylpyrolidone and cholesteryl methacyiate, stearyl polyvinyl alcohol, copolymers from methacrylic acid amide and cholesteryl methacrylate,
  • the invention can advantageously be implemented if the structures according to the invention are based on a content of 0.001-50% by weight of crosslinking according to the invention. It is preferred to select concentrations of 0.1-10% by weight, in particular 0.1-5% by weight, in each case based on the overall composition. It is of course clear to the person skilled in the art that by varying the ratio of the individual components to one another it is possible to optimize a preparation or an object or a special use without having to leave the bottom of the present invention.
  • the basic structures based on lipid double membranes can advantageously be chosen on all common lipids of natural, synthetic or partially synthetic origin. Particularly advantageous are the phospholipids such as phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, cardiolipins (diphosphatidylglycerols) and sphingomyelins, furthermore glycolipids or glycerolipids.
  • phospholipids such as phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, cardiolipins (diphosphatidylglycerols) and sphingomyelins, furthermore glycolipids or glycerolipids.
  • lecithins sphingolipids such as sphingosine or phytosphingosine, ceramides, cerebrosides, gangliosides, sphingophospholipids, of which in particular the sphingomyelins, sphingosulfatides and glycosphingosides, and analogues obtainable by chemical synthesis.
  • lipids which can be used according to the invention are, for example, dimethyldioctadecylammonium chloride, dimethyldioctadecylammonium bromide, 1-palmrtoleyl-2-oleyl-sn-glycero-3-phosphatidylcholine, dimyristoleylphosphatidylcholine, 1-palmrtoleyl-2-oleyl-3-phosphate.
  • the use of substances, the molecules of which consist of at least one hydrophilic region and at least one lipophilic region, for crosslinking or linking structures based on lipid double membranes or peptides is the use of substances whose molecules consist of at least one hydrophilic region and at least one lipophilic region for crosslinking or linking liposomes or liquid-crystalline structures.
  • Cistola et.al. describe lamellar systems based on oleic acid / potassium oleate (Biochemistry 25, 2804 (1986), which can be crosslinked according to the invention.
  • Lieckfeldt et.al. describe lamellar systems based on a stratum corneum fatty acid mixture (9.39 mol% stearic acid, 38.7 mol% palmitic acid, 4.49 mol% myristic acid, 31.6 mol% oleic acid, 12 mol% linoleic acid, 3, 82 mol% palmitoleic acid; Coll. Surfaces A90, 225 (1994), which can be crosslinked according to the invention.
  • the crosslinking agents according to the invention for example as a hydrogel, as a microemulsion gel, as a liposome gel, as a milk gel, as liquid-crystalline phases crosslinked according to the invention, as protein gels crosslinked according to the invention, as O / W emulsions crosslinked according to the invention, as W / O crosslinked according to the invention
  • UV emulsions, ointments, as a spray, etc. take on an immobilizing function (eg, hemostatic) by physically cross-linking the components of body fluid cores (blood, etc.) after application.
  • the crosslinking agents according to the invention with hemostatic function can be used in facial tonic, aftershave, pre-shave products, aftershave lotions based on an emulsion obtainable with the aid of phase inversion technology (“PIT emulsion”) or a lotion or cream with ethylene oxide-free emuigators, shaving oils, foaming and non-foaming shaving gels, shaving soaps, shaving foams, post-foaming shaving gels based on microemulsions, shaving gels based on polyacrylics, hydrogels, hair removal agents, etc.
  • PIT emulsion phase inversion technology
  • the crosslinking agents or a dosage form for these crosslinking agents can also be incorporated into devices for razor blades.
  • liposome preparations for example from Kuhs ("Probiol 05018"), Gattefosse, Vesifact AG (Vesisomes®), Rovi (Rovisomes®), Laboratories Collaborative (Catezomes®), Applied Genetics (Photosome®) and Liposome Technology, Inc.
  • Step®-Li ⁇ osome are to be used advantageously and can, if desired, be used with active ingredients, eg skin moisturizers, vitamin C, superoxide dismutase, UV filters, plasmid DNA, epidermal growth factors, ⁇ -glucocosylrutin, coenzyme Q ⁇ 0 , cyclic adenosine monophosphate AMP, tyrosine, amphotericin B, daunorubicin, ibuprofen, doxorubicin, cyclosporin, T 4 endonuclease and the like can be loaded, but also lead to gels according to the invention as unloaded vesicles.
  • active ingredients eg skin moisturizers, vitamin C, superoxide dismutase, UV filters, plasmid DNA, epidermal growth factors, ⁇ -glucocosylrutin, coenzyme Q ⁇ 0 , cyclic adenosine monophosphate AMP, tyrosine, ampho
  • liposomes or lamellar liquid crystals e.g. based on phospholipids
  • a high concentration of lipophilic or surface-active ingredients e.g. cosmetic oil components
  • the lipid double membranes become unstable; a lipid single layer (e.g. made of phospholipids) is formed, which contains the ingredients (e.g. Example of an oil component) micellized.
  • liposome gels according to the invention or liquid crystal gels according to the invention can be converted into nanoemulsion gels or can be present side by side.
  • the principles presented can also be used for bioseparation (precipitation of lines, proteins, enzymes). This succeeds if the hydrophobically modified hydrophilic polymer is adjusted so that it just dissolves in water. Crosslinking changes the solubility of the hydrophobically modified polymer. Protein gels as acid material are then suitable, for example, for the production of enantiomerically pure compounds.
  • Another particularly advantageous embodiment of the present invention is the use of substances whose molecules consist of at least one hydrophilic region and at least one lipophilic region for crosslinking or linking living or killed cells.
  • the living cells linked together according to the invention are capable of division and growth.
  • the peptide components of the blood can be crosslinked at the same time by crosslinking agents used according to the invention.
  • the crosslinking agents used according to the invention were able to convert milk into a "milk glass".
  • the crosslinking agents are stirred into milk at room temperature.
  • the advantages of milk with its numerous ingredients are known in cosmetics, medicine and nutritional science. It is advantageous here that the milk is physically crosslinked
  • these gels are also interesting as a new presentation for yoghurt or as cocoa gel
  • Milk precursors such as milk powder can be used. Since milk spoils quickly, the crosslinking agents according to the invention can also simply be dissolved in water. The user then adds milk to the crosslinking agent water mixture and thus receives the “milk gel”.
  • cosmetic face masks can also be produced on the basis of these milk gels.
  • cell suspensions, retroviruses and even enzymes can be linked or crosslinked with the aid of the linking substances used according to the invention.
  • enzymes and proteins protes, lipases, superoxide dismutase, T-endonucieases.
  • These enzyme or protein gels can also be provided with other fillers. Gels based on superoxide dismutase are particularly interesting for the treatment of wounds and sunburn, since pure protein solutions are difficult to apply topically.
  • crosslinking agents according to the invention therefore make it possible to dispense with a wound dressing, plasters, sutures, etc. in certain areas of application. In other areas of application, it may be advantageous to also incorporate crosslinking agents and preparations according to the invention into wound dressings and the like. They can also be used for the storage and preservation of transplant tissue or for the production of contact lenses and biosensors.
  • Crosslinkers whose hydrophilic regions are based on polyoxyethylene are particularly advantageous for internal applications and in contact with blood, since they are biocompatible and do not cause an immune response or inflammation.
  • the attachment of cells and proteins (fibrinogen, immunoglobulin, leucocytes, etc.) is prevented by the hydrophilicity and rapid changes in the conformation of the polyoxyethylene block.
  • Crosslinkers whose hydrophilic regions are based on polyoxyethylene in particular advantageously carry hydrophobic groups from the body's own substances such as cholesterol, also bioactive substances that release, for example, an antibiotic or a group that promotes wound healing. When the polymers are broken down enzymatically, defined toxicologically harmless products are produced or bioactive substances are released.
  • the physical crosslinking of cells with crosslinkers according to the invention makes it possible, for example, to combine skin or nerve cells into a cell bandage, which is particularly advantageous for medical applications (artificial skin after burns, cancer therapy, etc.).
  • Polyurethanes substituted with poly (amidoamine) are also known, which are formed by reacting polyurethane with hexamethylene diisocyanate and further reacting the free isocyanate group with poly (amidoamine) (Barbucci et al, Advances in Biomedical Polymers, S259-276, GC Gebelien (Ed), Plenum Press, New York, 1985.
  • a bis-modified polyethylene oxide is first coupled to the carrier.
  • polyethylene oxide can be reacted with 2 mol of hexamethylene diisocyanate.
  • the intermediate product thus obtained is covalently coupled via an isocyanate function to free hydroxyl or amino groups of the wound dressing (for example made of polyurethane).
  • the free second isocyanate group enables a hydro- attach phobic group such as cholesterol.
  • a wound dressing with hydrophilic polyethylene oxide series chains is obtained, at the respective ends of which there is a hydrophobic group.
  • the wound dressings modified in this way are suitable, for example, for the physical crosslinking of blood.
  • hydrophobic groups for example cholesterol
  • a linker substance used according to the invention is embedded in a carrier (B).
  • the hypophilic region (II) docks into the lipid double membrane of a living cell, while the hydrophilic region (hh) is in an aqueous medium, for example wound exudate.
  • a further astonishing embodiment of the present invention has been found to be the fact that polymers, copolymers and / or polymer mixtures can be incorporated into the lipid double membrane of the structures according to the invention which can help the structures according to the invention to have astonishing properties.
  • This is shown in Fig. 11.
  • a polymer with lipophilic properties, for example polystyrene, is embedded in the lipid double membrane of a vesicle suspension crosslinked according to the invention with linking molecules.
  • the structures according to the invention are to be used as constituents of a cosmetic or pharmaceutical preparation, then, as already indicated, preparations are possible which are only advantageous to be obtained from water and, for example, liposomes and one or more linking substances.
  • preparations are possible which are only advantageous to be obtained from water and, for example, liposomes and one or more linking substances.
  • the structures according to the invention in other dosage forms, for example the usual emulsions, that is to say preparations which, in addition to one or more water phases, also have one or more oil phases.
  • the usual simple and multiple emulsions, furthermore microemulsions emulsions, and largely emulsifier-free and hydro- or lipodispersions are advantageous, but even pure oil phases have proven to be a suitable basis for preparations according to the present invention.
  • the oil phase of oil-containing preparations according to the invention is advantageously selected from the group of the esters from saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols Chain length of 3 to 30 carbon atoms, from the group of esters of aromatic carboxylic acids and saturated and / or unsaturated, branched and / or unbranched alcohols of a chain length of 3 to 30 carbon atoms.
  • ester oils can then advantageously be selected from the group of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyistearate, isononyonisononanoate, 2-ethylhexyl ethylhexyl palatate 2- Octyldodecytpaimrtat, Oleyloleat, Oleylerucat, Erucyloleat, Erucylerucat as well as synthetic, semi-synthetic and natural mixtures of such esters, for example Jojoba oil.
  • the oil phase can advantageously be selected from the group of branched and unbranched hydrocarbons and waxes, the silicone oils, the dialkyl ethers, the group of saturated or unsaturated, branched or unbranched alcohols, and also the fatty acid triglycerides, especially the triglycerol esters, saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 8 to 24, in particular 12 - 18, carbon atoms.
  • the fatty acid triglycerides can, for example, advantageously be selected from the group of synthetic, semisynthetic and natural oils, for example olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil and the like. Any mixtures of such oil and wax components can also be used advantageously for the purposes of the present invention.
  • the oil phase is selected from the group 2-ethylhexyl advantageous, octyl dodecanol, isotridecyl isononanoate, isoeicosane, 2-Ethylhexylcoc ⁇ at, C ⁇ 2 - benzoate 15 alkyl, caprylic-capric acid triglyceride, dicaprylyl ether.
  • hydrocarbons paraffin oil, squalane and squalene can be used advantageously for the purposes of the present invention.
  • the oil phase can advantageously also have a content of cyclic or linear silicone oils or consist entirely of such oils, although it is preferred to use an additional content of other oil phase components in addition to the silicone oil or the silicone oils.
  • Cyclomethicone (octamethylcyclotetrasiloxane) is advantageously used as the silicone oil to be used according to the invention.
  • other silicone oils can also be used advantageously for the purposes of the present invention, for example hexamethylcyclotrisiloxane, polydimethylsiloxane, poly (methylphenylsiloxane).
  • the preparations according to the invention advantageously contain electrolytes, in particular one or more salts with the following anions: chlorides, furthermore inorganic oxo-element anions, of which in particular sulfates, carbonates, phosphates, borates and aluminumates.
  • Electrolytes based on organic anions can also be used advantageously, for example lactates, acetates, benzoates, propionates, tartrates, crtrates and others. Comparable effects can also be achieved with ethylenediaminetetraacetic acid and its salts.
  • Ammonium, alkylammonium, alkali metal, alkaline earth metal, magnesium, iron and zinc ions are preferably used as cations of the salts.
  • elec- trolyte there is no need to mention that in cosmetics only physiologically harmless elec- trolyte should be used.
  • Special medical applications of the microemulsions according to the invention can, at least in principle, require the use of electrolytes, which should not be used without medical supervision.
  • Potassium chloride, sodium chloride, magnesium sulfate, zinc sulfate and mixtures thereof are particularly preferred. Salt mixtures as they occur in the natural salt from the Dead Sea are also advantageous.
  • the concentration of the electrolyte or electrolytes should be approximately 0.1-10.0% by weight, particularly advantageously approximately 0.3-8.0% by weight, based on the total weight of the preparation.
  • the preparations according to the invention also make an excellent contribution to smoothing the skin, especially if they are provided with one or more substances which promote smoothing of the skin.
  • odor maskers such as the common perfume components
  • odor absorbers for example the layered silicates described in patent application DE-P 40 09 347, of which Mont in particular - Morillonite, kaolinite, hit, bothilite, nontronite, saponite, hectorite, bentonite, smectite, and furthermore, for example, zinc salts of ricinoleic acid.
  • Germ-inhibiting agents are also suitable for being incorporated into the microemulsions according to the invention.
  • Advantageous substances are, for example, 2,4,4-trichloro-2'-hdroxydiphenyl- ether (Irgasan), 1,6-di- (4-chlorophenylbiguanido) hexane (chlorhexidine), 3,4,4'-trichlorocarbanilide, quaternary ammonium compounds, clove oil, mint oil, thyme oil, triethyl crtrate, farnesol (3,7,11.trimethyl-2,6,10-dodecatrien-1-ol) as well as those in the patent publications DE-37 40 186, DE-39 38 140, DE-42 04 321, DE-42 29 707, DE-42 29 737, DE-42 37 081, DE-43 09 372, DE-43 24 219 described active agents.
  • the customary antiperspirant active ingredients can likewise advantageously be used in the preparations according to the invention, in particular astringents, for example basic aluminum chlorides.
  • the cosmetic deodorants according to the invention can be in the form of aerosols, that is to say from aerosol containers, squeeze bottles or preparations sprayable by a pump device, or in the form of liquid compositions which can be applied by means of roll-on devices, but also in the form of preparations which can be applied from normal bottles and containers.
  • Suitable blowing agents for cosmetic deodorants according to the invention which can be sprayed from aerosol containers are the customary, known volatile, liquefied blowing agents, for example hydrocarbons (propane, butane, isobutane), which can be used alone or in a mixture with one another. Compressed air can also be used advantageously.
  • hydrocarbons propane, butane, isobutane
  • Cosmetic preparations according to the invention can, for example, be very advantageously in the form of conditioning preparations for the hair or the scalp
  • Such embodiments of the preparations according to the invention maintain hair damaged or damaged by environmental influences or prevent such environmental influences. Furthermore, the preparations according to the invention give the hairstyle loose fullness and firmness without being sticky. They serve to increase the fullness of the hair, to improve the hair body and volume as well as to maintain the hair style.
  • Cosmetic and dermatological preparations which are in the form of a sunscreen are also favorable.
  • these preferably additionally contain at least one UVA filter substance and / or at least one UVB filter substance and / or at least one inorganic pigment.
  • UV-A or UV-B filter substances are usually incorporated into day creams.
  • Preparations according to the invention can advantageously contain substances which absorb UV radiation in the UVB range, the total amount of filter substances e.g. 0.1% by weight to 30% by weight, preferably 0.5 to 10% by weight, in particular 1 to 6% by weight, based on the total weight of the preparations.
  • the UVB filters can be oil-soluble or water-soluble.
  • oil-soluble substances e.g. to call:
  • 4-aminobenzoic acid derivatives preferably 4- (dimethylamino) benzoic acid (2-ethylhexyl) ester, 4- (dimethylamino) benzoic acid amyl ester;
  • Esters of cinnamic acid preferably 4-methoxycinnamic acid (2-ethylhexyl) ester,
  • Esters of salicylic acid preferably saiicylic acid (2-ethylhexyl) ester, salicylic acid (4-isopropylbenzyl) ester, saiicylic acid homomethyl ester;
  • benzophenone preferably 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone;
  • Esters of benzalmalonic acid preferably 4-methoxybenzalmalonic acid di (2-ethylhexyl) ester;
  • 2-phenylbenzimidazole-5-sulfonic acid and its salts e.g. Sodium, potassium or triethanolammonium salts
  • Sulfonic acid derivatives of benzophenones preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts;
  • Sulfonic acid derivatives of 3-benzylidene camphor e.g. 4- (2-oxo-3-bornylidenemethyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bornylidenemethyl) sulfonic acid and their salts.
  • UVB filters which can be used according to the invention, is of course not intended to be limiting.
  • the invention also relates to the combination of a UVA filter according to the invention with a UVB filter or a cosmetic or dermatological preparation according to the invention which also contains a UVB filter.
  • UVA filters in the preparations according to the invention, which are usually contained in cosmetic and / or dermatological preparations.
  • Such substances are preferably derivatives of dibenzoylmethane, in particular 1- (4'-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione and 1-phenyl-3- (4 '-isopropylphenyl) propane-1,3-dione.
  • Preparations containing these combinations are also the subject of the invention.
  • the same amounts of UVA filter substances can be used, which have been mentioned for UVB filter substances.
  • Cosmetic and / or dermatological preparations according to the invention can also contain inorganic pigments which are usually used in cosmetics to protect the skin from UV rays. These are oxides of titanium, zinc, iron, zirconium, silicon, manganese, aluminum, cerium and mixtures thereof, as well as modifications in which the oxides are the active agents. It is particularly preferred to use pigments on the Base of titanium dioxide. The amounts given for the above combinations can be used.
  • preparations according to the invention are very good vehicles for cosmetic or dermatological active ingredients in the skin, advantageous active ingredients being antioxidants which can protect the skin against oxidative stress.
  • the preparations advantageously contain one or more antioxidants. All of the antioxidants suitable or customary for cosmetic and / or dermatological applications are used as inexpensive, but nevertheless optional antioxidants. It is advantageous to use antioxidants as the only class of active ingredient, for example when cosmetic or dermatological application is in the foreground, such as combating the oxidative stress on the skin. However, it is also favorable to provide the preparations according to the invention with a content of one or more antioxidants if the preparations are to serve another purpose, e.g. as deodorants or sunscreens.
  • Amino acids e.g. histidine, tyrosine, tryptophan
  • imidazoles e.g. urocanic acid
  • peptides such as D, L-carnosine, D-carnosine, L-carnosine and their derivatives (e.g. anserine), carotenoids, carotenes (e.g.
  • buthionine sulfoximines in very low tolerable dosages (e.g. pmol to ⁇ mol / kg), furthermore (metal ) Chelators (e.g. ⁇ -hydroxy fatty acids, ⁇ -hydroxypalmrtin acid, phytic acid, lactoferrin), ⁇ -hydroxy acids (e.g.
  • citric acid citric acid, lactic acid, malic acid
  • humic acid bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and their derivatives
  • unsaturated fatty acids and their derivatives eg ⁇ -linolenic acid, linoleic acid , Oleic acid
  • folic acid and its derivatives unsaturated fatty acids and their derivatives
  • ubiquinone and ubiquinol their derivatives e.g. ascorbyl palmitates, Mg ascorbyl phosphates, ascorbylacetates
  • tocopherols and derivatives e.g.
  • vitamin E acetate
  • vitamin A and derivatives vitamin A palmitate
  • coniferyl benzoate of benzoin guajaretklare rutinic acid and derivatives thereof, ferulic acid and derivatives thereof, butylhydroxytoluene, butylhydroxyanisole, Nordihydroguajakharzklare, Nordihydro-, trihydroxybutyrophenone, uric acid and derivatives thereof, zinc and derivatives thereof (for example ZnO, ZnSO 4) selenium and derivatives thereof (eg Selenomethine), stilbenes and their derivatives (eg stilbene oxide, trans-stilbene oxide) and the deri suitable according to the invention vate (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these active ingredients.
  • vate salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids
  • Oil-soluble antioxidants can be used particularly advantageously for the purposes of the present invention.
  • the amount of the antioxidants (one or more compounds) in the preparations is preferably 0.001 to 30% by weight, particularly preferably 0.05 to 20% by weight, in particular 1 to 10% by weight, based on the total weight of the preparation .
  • vitamin E and / or its derivatives represent the antioxidant (s)
  • vitamin A or vitamin A derivatives or carotenes or their derivatives represent the antioxidant or antioxidants, it is advantageous to use their respective concentrations in the range from 0.001-10% by weight, based on the total weight of the formulation, to choose.
  • active ingredients can also be selected very advantageously from the group of lipophilic active ingredients, in particular from the following group:
  • vitamins for example ascorbic acid and its derivatives
  • vitamins of the B and D series very cheap the vitamin B *, the
  • hydrophilic active substances are naturally also favored according to the invention, a further advantage of the preparations according to the invention is that even oil-soluble or hypophilic active substances with particularly great effectiveness are made biologically available.
  • the cosmetic and dermatological preparations according to the invention can contain cosmetic auxiliaries as are usually used in such preparations, e.g. Preservatives, bactericides, virucides, perfumes, substances to prevent foaming, dyes, pigments that have a coloring effect, further thickeners not covered by the definition of the thickeners according to the invention, surface-active substances, emulators, softening, moisturizing and / or moisturizing substances, anti-inflammatory substances Substances, drugs, fats, oils, waxes or other usual components of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents.
  • cosmetic auxiliaries e.g. Preservatives, bactericides, virucides, perfumes, substances to prevent foaming, dyes, pigments that have a coloring effect, further thickeners not covered by the definition of the thickeners according to the invention, surface-active substances, emulators, softening, moisturizing and / or moisturizing
  • Hydroxyethylcellulose is mbar 24 hours at 60 ° C and a pressure of 10 "2.
  • a mixture of 2 g of dried hydroxyethylcellulose, 120 ml of anhydrous N-methylpyrrolidone and 30 ml of anhydrous pyridine is degassed and stirred for 38 hours at 60 ° C under argon.
  • the slightly yellow, highly viscous solution is mixed with 0.09 g (0.20 mmol) of cholesterol chloroformate in 7 ml of N-methylpyrrolidone and stirred under argon for 18 hours at 60 ° C.
  • the cholesteryl-hydroxyethyl cellulose is precipitated in acetone and mbar at 10. for purification, the reteren Cholesterylhydroxyethylcelluose is extracted 24 hours in Soxhlet extractor with benzene and then 24 hours at 10 -2 mbar.
  • Hydroxyethylcellulose is mbar 24 hours at 60 ° C and a pressure of 10 '. 2
  • a mixture of 2 g of dried hydroxyethyl cellulose, 120 ml of anhydrous N-methylpyrrolidone and 30 ml of anhydrous pyridine is degassed and stirred under argon at 60 ° C. for 38 hours.
  • the slightly yellow, highly viscous solution is mixed with 0.06 g (0.20 mmol) of stearic acid chloride in 5 ml of N-methylpyrrolidone.
  • the mixture is stirred under argon at 60 ° C. for 24 hours.
  • the stearylhydroxyethyl cellulose is precipitated in acetone and dried at 10 mbar. Dissolving the stearyl hydroxyethyl cellulose in 200 ml of water (24 hours of stirring), precipitated from acetone and dried for 24 hours at 10 "2 mbar.
  • Hydroxyethylcellulose is mbar 24 hours at 60 ° C and a pressure of 10 "2.
  • a mixture of 2 g of dried hydroxyethylcellulose, 120 ml of anhydrous N-methylpyrrolidone and 30 ml of anhydrous pyridine is degassed and stirred for 38 hours at 60 ° C under argon.
  • the slightly yellow, highly viscous solution is mixed with 0.06 g (0.20 mmol) of oleic acid chloride in 5 ml of N-methylpyrrolidone and stirred under argon for 24 hours at 60 ° C.
  • the oleylhydroxyethyl cellulose is precipitated in acetone and dried at 10 mbar .
  • Hydroxyethylcellulose is mbar 24 hours at 60 ° C and a pressure of 10 '. 2
  • a mixture of 2 g of dried hydroxyethyl cellulose, 120 ml of anhydrous N-methylpyrrolidone and 30 ml of anhydrous pyridine is degassed and stirred under argon at 60 ° C. for 38 hours.
  • the slightly yellow colored, highly viscous solution is mixed with 0.05 g (0.20 mmol) of palmitic acid chloride in 5 ml of NMetylpyrrolidone.
  • the mixture is stirred under argon at 60 ° C. for 24 hours.
  • the palmitylhdroxyethyl cellulose is precipitated in acetone and dried at 10 mbar. Dissolve the palmityl hdroxyethylcellulose in about 200 ml of water (24 hours of stirring), precipitated from acetone and dried for 24 hours at 10 -2 mbar.
  • polyurethane film polymer network of polyethylene oxide and hexamethylene diisocyanate
  • 2 g of Cholest ⁇ rylchlorofomiat and 2 ml of absolute pyridine are added to this mixture under an argon atmosphere and the mixture is left to react for 8 hours at room temperature.
  • the mixture is then poured into 400 ml of acetone and the film is extracted 5 times with 50 ml of methylene chloride and 5 times with 50 ml of acetone.
  • the film is then dried in an oil vacuum for 48 hours.
  • polyurethane film from I.
  • 50 ml of absolute methylene chloride together with PEG diisocyanate and 1 ml of absolute pyridine under an argon atmosphere.
  • the mixture is left to stand for 12 hours at room temperature.
  • To clean the film it is extracted 10 times with 50 ml of absolute methylene chloride and then dried in an oil vacuum for 48 hours.
  • the synthesis of the triblock copolymers A, F and H was carried out by esterification of polyethylene oxide with a carboxylic acid chloride and the synthesis of the triblock copolymers B, C, D and G was carried out by esterification of polyethylene oxide with a carboxylic acid
  • the triblock copolymer is then precipitated again in 1.5 liters of diethyl ether and 1.5 liters of petroleum ether, filtered and evaporated to dryness on a rotary evaporator.
  • the fine white powder is dissolved in 1dl of benzene with gentle heating until a clear solution becomes visible, frozen in liquid nitrogen and freeze-dried under vacuum on the oil pump for about 45 hours.
  • 176 mg of dimethyldioctadecylammonium chloride are suspended in 8 ml of double-distilled water at 60 ° C.
  • the suspension is sonicated for 45-60 min at 60 ° C. in an ultrasonic bath (Laboratory Supplies Co.). After cooling, a vesicle suspension is obtained.
  • 176 mg of dimethyldioctadecylammonium bromide are suspended in 8 ml of double-distilled water at room temperature.
  • the suspension is sonicated for 45-60 minutes at room temperature in an ultrasonic bath (Laboratory Supplies Co.) under nitrogen.
  • a vesicle suspension is obtained.
  • 176 mg of 1-palmitoleyl-2-oleyl-sn-glycero-3-phosphatidylcholine are suspended in 8 ml of double-distilled water at room temperature.
  • the suspension is sonicated for 45-60 minutes at room temperature in an ultrasonic bath (Laboratory Supplies Co.) under nitrogen.
  • a vesicle suspension is obtained.
  • 176 mg of 1-palmitoleyl-2-oleyl-sn-glycero-3-phosphatidylcholine are suspended in 8 ml of double-distilled water at room temperature.
  • the suspension is sonicated for 45-60 minutes at room temperature in an ultrasonic bath (Laboratory Supplies Co.) under nitrogen.
  • a vesicle suspension is obtained.
  • dimyristoleylphosphatidylcholine 176 mg are suspended in 8 ml of double-distilled water at 60 ° C. The suspension is suspended for 45-60 min at room temperature. dated. The suspension is sonicated for 45-60 minutes at room temperature in an ultrasonic bath (Laboratory Supplies Co.) under nitrogen. A vesicle suspension is obtained.
  • a vesicle suspension obtained in preparation example 1 for vesicles is added to a dispersion of 50 mg PEG-800-Chol 2 in 2 ml bidistilled water. The mixture gels over a few minutes.
  • a vesicle suspension obtained in preparation example 2 for vesicles is added to a dispersion of 50 mg PEG-800-Chol 2 in 2 ml bidistilled water. The mixture gels over a few minutes.
  • a vesicle suspension obtained in preparation example 3 for vesicles is added to a dispersion of 50 mg of PEG- ⁇ OO-Chob in 2 ml of bidistilled water. The mixture gels over a few minutes.
  • a vesicle suspension obtained in preparation example 4 for vesicles is added to a dispersion of 50 mg PEG-800-Chol 2 in 2 ml bidistilled water. The mixture gels over a few minutes.
  • a vesicle suspension obtained in preparation example 5 for vesicles is added to a dispersion of 50 mg PEG-800-Chob in 2 ml bidistilled water. The mixture gels over a few minutes.
  • a vesicle suspension obtained in preparation example 56 for vesicles is added to a dispersion of 50 mg of PEG-800-Chol 2 in 2 ml of double-distilled water. The mixture gels over a few minutes.
  • a dispersion of 50 mg PEG-800-Chol 2 in 2 ml bidistilled water is added to 5 ml fresh human blood.
  • the blood gels in the course of a few minutes, the viability of the blood cells involved being determined in the subsequent tests.
  • d) 0.5 g of dimethyldidodecylammonium bromide are dissolved in 10 ml of double-distilled water.
  • the resulting lamellar structure can be converted into an opaque lamellar gel by adding 200 mg PEG (35,000) distearate.
  • e) 0.5 g of dimethyldidodecylammonium bromide are dissolved in 10 ml of double-distilled water. Addition of 100 mg Chol ⁇ sterylhydroxyethylcellulose leads to the formation of an opaque lamellar gel.
  • stearic acid 496 mg of palmitic acid, 51 mg of myristic acid, 446 mg of oleic acid, 168 mg of linoleic acid and 49 mg of palmitoleic acid (total 1.344 g, (“5 mmol”) are mixed with 2.05 ml of 1M NaOH and 10 ml of double distillation A milky, birefringent emulsion is formed which can be converted into a gel by adding 200 mg PEG (35,000) distearate.
  • n-octyl-ß-D-glucopyranoside 100 mg are dissolved in 2 ml of double-distilled water. Addition of 50 mg PEG (35,000) distearate leads to the formation of a transparent, lamellar gel.
  • phosphatidylcholine Epikuron 200
  • phosphatidylcholine Epikuron 200
  • 20 mg of cholesterol are dissolved in 10 ml of chloroform.
  • the solvent is removed on a rotary evaporator (so that a uniform lipid film is formed on the glass surface) and the residue dried in an oil vacuum for 12 hours.
  • the resulting suspension is treated with ultrasound for 30 min at room temperature.
  • a transparent liposome suspension is created. Adding 400 mg PEG (35,000) dicholesterate leads to a transparent gel.
  • Glyceryl stearate PEG-100 stearate 1, 50
  • Mrt propellant and Vemetzem invention offset lamellar phase
  • Lamellar phase mixed with propellant and Vemetzem according to the invention

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Birds (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dermatology (AREA)
  • Dispersion Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)

Abstract

Structures à base de deux membranes de lipides ou de peptides. Une ou plusieurs régions lipophiles d'une ou plusieurs molécules s'enfoncent dans la région lipophile interne des doubles membranes de lipides ou dans une région lipophile des peptides, lesdites régions lipophiles étant constituées d'au moins une région hydrophile et d'au moins une région lipophile.
EP97909321A 1996-09-28 1997-09-26 Structures a deux membranes de lipides ou a base de peptides Withdrawn EP0928188A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE1996140092 DE19640092A1 (de) 1996-09-28 1996-09-28 Strukturen mit Lipid-Doppelmembranen, in deren lipophilen Bereich längerkettige Moleküle eintauchen oder durch hydrophobe Wechselwirkungen an solche Moleküle angedockt sind
DE19640092 1996-09-28
PCT/EP1997/005287 WO1998013025A1 (fr) 1996-09-28 1997-09-26 Structures a deux membranes de lipides ou a base de peptides

Publications (1)

Publication Number Publication Date
EP0928188A1 true EP0928188A1 (fr) 1999-07-14

Family

ID=7807288

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97909321A Withdrawn EP0928188A1 (fr) 1996-09-28 1997-09-26 Structures a deux membranes de lipides ou a base de peptides

Country Status (4)

Country Link
EP (1) EP0928188A1 (fr)
JP (1) JP2001500886A (fr)
DE (1) DE19640092A1 (fr)
WO (1) WO1998013025A1 (fr)

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19726131A1 (de) * 1997-06-20 1998-12-24 Beiersdorf Ag Mittels kovalent verknüpfter Netzwerke, disperse Zwei- oder Mehrphasensysteme
JP4593048B2 (ja) * 1999-12-24 2010-12-08 協和発酵キリン株式会社 分岐型ポリアルキレングリコール類
JP3807926B2 (ja) * 2000-11-02 2006-08-09 株式会社ヤクルト本社 アスコルビン酸類を含む皮膚外用剤
DE10057769A1 (de) * 2000-11-22 2002-05-23 Beiersdorf Ag Haarpflegeprodukte mit einem Gehalt an dispersen Flüssigkristallen, welche kubische Phasen darstellen
US20040018237A1 (en) * 2002-05-31 2004-01-29 Perricone Nicholas V. Topical drug delivery using phosphatidylcholine
EP1596828B1 (fr) 2003-02-14 2011-12-28 Children's Hospital & Research Center at Oakland Vehicule d'administration de medicament lipophile et methodes d'utilisation correspondantes
WO2005039534A1 (fr) * 2003-10-01 2005-05-06 Children's Hospital & Research Center At Oakland Vehicule d'administration de medicament lipophile et methodes d'utilisation de ce vehicule
US9393315B2 (en) 2011-06-08 2016-07-19 Nitto Denko Corporation Compounds for targeting drug delivery and enhancing siRNA activity
DE102005042884B3 (de) * 2005-09-09 2007-01-18 Gesellschaft zur Förderung der Analytischen Wissenschaften e.V. Verfahren und Vorrichtung zur Herstellung von kugel- oder schlauchförmigen künstlichen Membranen
WO2009158678A1 (fr) 2008-06-27 2009-12-30 Children's Hospital & Research Center At Oakland Véhicule d'administration d'acide nucléique lipophile et ses procédés d'utilisation
DE102008046075A1 (de) * 2008-09-08 2010-03-11 Evonik Röhm Gmbh (Meth)acrylatmonomer, Polymer sowie Beschichtungsmittel
JP2014508166A (ja) 2011-03-17 2014-04-03 トランスダーマル バイオテクノロジ インコーポレーテッド 局所的一酸化窒素システム及びその使用方法
US9011903B2 (en) 2011-06-08 2015-04-21 Nitto Denko Corporation Cationic lipids for therapeutic agent delivery formulations
RS59380B1 (sr) * 2011-06-08 2019-11-29 Nitto Denko Corp Jedinjenja za ciljanje isporuke leka i pojačavanje sirnk aktivnosti
US10196637B2 (en) 2011-06-08 2019-02-05 Nitto Denko Corporation Retinoid-lipid drug carrier
TWI658830B (zh) 2011-06-08 2019-05-11 日東電工股份有限公司 Ｈｓｐ47表現調控強化用類視色素脂質體
US8871255B2 (en) 2012-09-19 2014-10-28 Transdermal Biotechnology, Inc. Treatment of skin and soft tissue infection with nitric oxide
US8871258B2 (en) 2012-09-19 2014-10-28 Transdermal Biotechnology, Inc. Treatment and prevention of learning and memory disorders
US8871260B2 (en) 2012-09-19 2014-10-28 Transdermal Biotechnology, Inc. Methods and compositions for muscular and neuromuscular diseases
US8871254B2 (en) 2012-09-19 2014-10-28 Transdermal Biotechnology, Inc. Systems and methods for treatment of acne vulgaris and other conditions with a topical nitric oxide delivery system
US8871256B2 (en) 2012-09-19 2014-10-28 Transdermal Biotechnology, Inc. Methods and systems for treatment of inflammatory diseases with nitric oxide
US8871257B2 (en) 2012-09-19 2014-10-28 Transdermal Biotechnology, Inc. Prevention and treatment of cardiovascular diseases using systems and methods for transdermal nitric oxide delivery
US8871261B2 (en) 2012-09-19 2014-10-28 Transdermal Biotechnology, Inc. Cancer treatments and compositions for use thereof
US8871262B2 (en) 2012-09-19 2014-10-28 Transdermal Biotechnology, Inc. Compositions and methods for treatment of osteoporosis and other indications
US8871259B2 (en) 2012-09-19 2014-10-28 Transdermal Biotechnology, Inc. Techniques and systems for treatment of neuropathic pain and other indications
US20140271938A1 (en) 2013-03-13 2014-09-18 Transdermal Biotechnology, Inc. Systems and methods for delivery of peptides
US9314423B2 (en) 2013-03-13 2016-04-19 Transdermal Biotechnology, Inc. Hair treatment systems and methods using peptides and other compositions
US9295647B2 (en) 2013-03-13 2016-03-29 Transdermal Biotechnology, Inc. Systems and methods for delivery of peptides
US9339457B2 (en) 2013-03-13 2016-05-17 Transdermal Biotechnology, Inc. Cardiovascular disease treatment and prevention
US9241899B2 (en) 2013-03-13 2016-01-26 Transdermal Biotechnology, Inc. Topical systems and methods for treating sexual dysfunction
US9320758B2 (en) 2013-03-13 2016-04-26 Transdermal Biotechnology, Inc. Brain and neural treatments comprising peptides and other compositions
US9724419B2 (en) 2013-03-13 2017-08-08 Transdermal Biotechnology, Inc. Peptide systems and methods for metabolic conditions
US9750787B2 (en) 2013-03-13 2017-09-05 Transdermal Biotechnology, Inc. Memory or learning improvement using peptide and other compositions
US9687520B2 (en) 2013-03-13 2017-06-27 Transdermal Biotechnology, Inc. Memory or learning improvement using peptide and other compositions
US9314422B2 (en) 2013-03-13 2016-04-19 Transdermal Biotechnology, Inc. Peptide systems and methods for metabolic conditions
US9320706B2 (en) 2013-03-13 2016-04-26 Transdermal Biotechnology, Inc. Immune modulation using peptides and other compositions
US9393265B2 (en) 2013-03-13 2016-07-19 Transdermal Biotechnology, Inc. Wound healing using topical systems and methods
US9849160B2 (en) 2013-03-13 2017-12-26 Transdermal Biotechnology, Inc. Methods and systems for treating or preventing cancer
US9387159B2 (en) 2013-03-13 2016-07-12 Transdermal Biotechnology, Inc. Treatment of skin, including aging skin, to improve appearance
US9295637B2 (en) 2013-03-13 2016-03-29 Transdermal Biotechnology, Inc. Compositions and methods for affecting mood states
US9393264B2 (en) 2013-03-13 2016-07-19 Transdermal Biotechnology, Inc. Immune modulation using peptides and other compositions
US20140271937A1 (en) 2013-03-13 2014-09-18 Transdermal Biotechnology, Inc. Brain and neural treatments comprising peptides and other compositions
US9314433B2 (en) 2013-03-13 2016-04-19 Transdermal Biotechnology, Inc. Methods and systems for treating or preventing cancer
US20140271731A1 (en) 2013-03-13 2014-09-18 Transdermal Biotechnology, Inc. Cardiovascular disease treatment and prevention
US9295636B2 (en) 2013-03-13 2016-03-29 Transdermal Biotechnology, Inc. Wound healing using topical systems and methods
US9314417B2 (en) 2013-03-13 2016-04-19 Transdermal Biotechnology, Inc. Treatment of skin, including aging skin, to improve appearance
CN104045823B (zh) * 2014-06-26 2016-01-13 武汉大学 一种甘草次酸衍生物及其制备方法和应用
US10576456B2 (en) * 2014-06-30 2020-03-03 Arizona Board Of Regents On Behalf Of The University Of Arizona Systems and methods of preparing stabilized lipid assemblies
WO2017155906A1 (fr) 2016-03-08 2017-09-14 Living Proof, Inc. Compositions cosmétiques longue durée
AU2018333932B2 (en) 2017-09-13 2024-05-02 Living Proof, Inc. Long lasting cosmetic compositions
JP7244494B2 (ja) 2017-09-13 2023-03-22 リビング プルーフ インコーポレイテッド 色保護剤組成物
JP7214730B2 (ja) 2017-11-20 2023-01-30 リビング プルーフ インコーポレイテッド 長期持続性の化粧品性能を達成するための特性
EP3784711A1 (fr) 2018-04-27 2021-03-03 Living Proof, Inc. Compositions cosmétiques longue durée

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5001048A (en) * 1987-06-05 1991-03-19 Aurthur D. Little, Inc. Electrical biosensor containing a biological receptor immobilized and stabilized in a protein film
US5192507A (en) * 1987-06-05 1993-03-09 Arthur D. Little, Inc. Receptor-based biosensors
FR2616659A1 (fr) * 1987-06-16 1988-12-23 Sederma Sa Procede pour favoriser la penetration de macromolecules a travers l'epiderme utilise pour la realisation de preparations cosmetiques
WO1991004013A1 (fr) * 1989-09-21 1991-04-04 Micro Vesicular Systems, Inc. Vesicules de lipides paucilamellaires hybrides
FR2653334B1 (fr) * 1989-10-19 1991-12-20 Erphar Ste Civile Preparation cosmetique de bronzage.
US5229104A (en) * 1991-04-29 1993-07-20 Richardson-Vicks Inc. Artificial tanning compositions containing positively charged paucilamellar vesicles
IT1251497B (it) * 1991-09-18 1995-05-15 Mivett Nuovi Lab Di Pavani& C Uso di 1,2 dipalmitoil-l-alfa-fosfatidil-n,n-dimetiletanolammina, in composizioni dermatologiche
JP2699038B2 (ja) * 1992-02-21 1998-01-19 株式会社ノエビア 温度感受性リポソーム
FR2701396B1 (fr) * 1993-02-12 1995-04-21 Oreal Procédé de stabilisation de vésicules de lipide(s) amphiphile(s) et composition pour application topique contenant lesdites vésicules stabilisées.
FR2708616B1 (fr) * 1993-08-04 1995-10-27 Lvmh Rech Procédé de préparation d'une composition aqueuse sous forme de gel et compositions susceptibles d'être obtenues par ce procédé, notamment composition contenant des vésicules, en particulier des liposomes.
JPH11510837A (ja) * 1995-07-28 1999-09-21 フォーカル，インコーポレイテッド 薬物送達のための制御された放出薬剤および組織処置薬剤としての使用のためのマルチブロック生分解性ヒドロゲル

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9813025A1 *

Also Published As

Publication number Publication date
JP2001500886A (ja) 2001-01-23
DE19640092A1 (de) 1998-04-16
WO1998013025A1 (fr) 1998-04-02

Similar Documents

Publication Publication Date Title
WO1998013025A1 (fr) Structures a deux membranes de lipides ou a base de peptides
EP1513492B1 (fr) Microemulsions presentant une differentiabilite de phase binaire et de substance active, leur production et leur utilisation en particulier pour administrer de l'oxygene par voie topique
EP0934053A1 (fr) Microemulsions cosmetiques ou dermatologiques
DE3537723C2 (fr)
EP0930866B1 (fr) Gels cosmetiques ou dermatologiques a base de microemulsions
EP1140008A1 (fr) Gels contenant de la lecithine, ou micro-emulsions huile dans l'eau, contenant de la lecithine, de basse viscosite, a usage cosmetique ou pharmaceutique
EP2815737A1 (fr) DMS employée dans des crèmes se présentant sous forme de mousse
US20090098172A1 (en) Surfactant, and emulsion cosmetic and liposome each containing the same
DE10106288A1 (de) Revitalisierender Wirkkomplex für die Haut
KR101727974B1 (ko) 세라마이드를 포함하는 천연리포좀, 그 제조방법, 및 이를 포함하는 화장료 조성물
KR101572216B1 (ko) 세포간 지질 성분의 마이셀을 함유하는 가용화 제형
KR101176523B1 (ko) 성상 변화를 갖는 화장료 조성물
KR102263449B1 (ko) 고순도 발효계면활성제 조성물 및 그 제조방법
KR101142010B1 (ko) Ｍｑｃ를 유효 성분으로 함유하는 화장료 조성물
KR101870512B1 (ko) 고형 지질 나노입자로 안정화한 코디세핀을 함유하는 화장료 조성물
EP1083861B1 (fr) Sticks aqueux a usage cosmetique ou pharmaceutique
WO2018130390A1 (fr) Introduction de substances actives faiblement solubles et/ou non solubles dans l'eau au moyen de nanoparticules/vésicules à base de lipides dans un reseau tridimensionnel hydrophile de cellulose
KR101822152B1 (ko) 헵타소듐헥사카복시메틸다이펩타이드­１２를 포함하는 나노베지클, 이의 제조방법, 및 이를 함유한 화장료 조성물
KR20200136194A (ko) 락토바실러스발효물, 락토코쿠스발효물, 효모폴리펩타이드, 락토바실러스 아시도필루스 포도발효물을 유효성분으로 하는 화장료 조성물
JPH0616536A (ja) リン脂質／糖脂質の混合物よりなるベシクルを含有する、化粧品用または皮膚科製薬用組成物
DE4310015C2 (de) Verfahren zur Herstellung eines Mittels zur Pflege der Haut
DE19642090A1 (de) Kosmetische oder dermatologische Gele auf der Basis von Mikroemulsionen
KR100858626B1 (ko) 세라마이드 및 합성 팔미토일펜타펩타이드를 유효성분으로함유하는 입술 보호용 화장료 조성물
KR100501309B1 (ko) 알부틴 함유 나노유화 화장료 조성물의 제조방법
KR102667625B1 (ko) 피부장벽 및 피부 보습 개선용 화장료 조성물 및 이의 제조방법

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19990309

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): DE ES FR GB IT SE

17Q First examination report despatched

Effective date: 20010227

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20030401