DE19640092A1 - Structures with lipid double membranes, in the lipophilic area of which longer-chain molecules are immersed or which are docked to such molecules through hydrophobic interactions - Google Patents

Abstract

Structures based on double lipidic membranes or peptides are disclosed. One or several lipophilic zones of one or several molecules which consist of at least one hydrophilic zone and at least one lipophilic zone penetrate into the inner lipophilic zone of the double lipidic membranes or into a lipophilic zone of the peptides of which these structures are composed.

Description

The present invention relates to structures with a planar or curved lipid double skin membranes. Furthermore, the present invention relates to the cosmetic or pharmaceutical zeutische use of such structures and processes for their manufacture. About it the present invention also relates to methods of making certain new ones Substances used to create structures with planar or curved lipid double membranes are advantageous.

Certain, structurally non-uniform biomolecules are in the bio chemical terminology summarized under the term lipids. In the original The meaning of lipids is to be understood as fats (Greek το λ℩ποζ = the fat, oil) Carboxylic acid ester of glycerin.

In a broader sense, this term includes a group of water-insoluble moles understood cool, which is characterized by at least one pronounced hydrophilic molecule range and distinguish at least one pronounced lipophilic molecular range. The Phosphoric acid esters of acylated glycerols, the so-called "phospholipids" and others Compounds belong to this generally quite inhomogeneous group of chemical Links.

Due to the structural conditions, lipids do not usually form real molecular solutions in vitro, e.g. in the amount of water, but rather they either form colloids, they usually combine to form micelles in which the lipophilic molecular areas of the lipid molecules are located inside the Micelles 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 (l). 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.

The ability of the lipids to arrange themselves in the known lipid bilayers is of the greatest biological importance. The individual lipid molecules accumulate in an aqueous or generally polar environment in such a way that two monomolecular layers of lipid molecules arranged in parallel come to lie on each other with their lipophilic areas. This is shown in Fig. 2. The lipid molecules have a hydrophilic area (h) and a lipophilic area (l). 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.

Although, as mentioned before, due to the structural conditions usually merge into so-called micelles, it is under certain conditions also technically possible to process lipids into vesicles or liposomes.

Vesicles or liposomes are spherically closed microscopic objects, which are delimited on the outside by a lipid bilayer and contain a water phase inside. This is shown in Fig. 3. The lipid molecules have a hydrophilic area (h) and a lipophilic area (l). The lipid bilayer (L) of the vesicles shown in FIG. 3, as can be better seen in the enlarged detail, is a hollow spherical 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. The center of the vesicles is filled with an aqueous phase. The diameter of liposomes usually ranges from a few (typically about 25) nanometers to about 1 µm.

In Fig. 12, a so-called multilamellar 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 (l). A thin layer of a polar, in particular aqueous phase (w) is generally arranged between the lipid double membranes. Inside the multilamellar vesicle is another polar, usually aqueous phase, which can also be loaded with active substances (here: Q)). It is also true for multilamellar vesicles that the lipid double membrane can also be loaded with active substances, which are then generally lipophilic in nature.

The preparation of liposomes, for example, is well known to the person skilled in the art. One method is, for example, ultrasound treatment of a lipid was sersystems, with the choice of suitable lipids merely the liposomes obtained need to be filtered off. But vesicle extrusion is also more suitable Lipids through a membrane filter with a pore size of typically about 100 nm for the formation of liposomes.

Usually the basic components of the liposome enveloping the liposomes Pel membrane selected from the group of phospholipids, often lecithin. Occasionally, too sometimes with the so-called niosomes, non-ionic surfactants are also used as coating materials rial used.

In general, a distinction is made between "empty" liposomes, which consist of a shell and an aqueous interior, and "loaded" liposomes, the interior of which is one represents aqueous phase, which is provided with water-soluble active ingredients, or de ren envelope is provided with lipophilic active ingredients. Microorganisms can be liposomal as it were encapsulated, "transfersomes" should be, in contrast to "normal" Li penetrate into the epidermis intact. In general, however, lipo penetrate not just intact, but adsorb on or in the top layers of the Stratum corneum. There is much evidence that liposomes endocytotically into the body cell be included. In addition to topical administration of liposo preparations containing menopause also intravenous administration.

Cell membranes can also be regarded as closed microscopic objects, which are delimited on the outside by a lipid bilayer and which house a water phase inside. This is shown in FIG. 4. The lipid molecules have a hydrophilic region (h) and a lipophilic region (l). 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.

Of the lipids in particular, the phospholipids are of the highest biological in interest, since this is the basic substance of the cell membranes of all living cells or de represent cell organelles.

Well over a thousand lipids from cell membranes have so far been isolated and identified graces. By far the largest share is taken up by the phospholipids with about 40 to over 90% of the total lipid portion of the cell. Five types of phospholipids are domi nating: phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, cardiolipin (Diphosphatidylglycerol) and sphingomyelin. Glycolipids are important components of the Plasma membrane, myelin, the endoplasmic reticulum and certain Or ganelle, for example the chloroplast photosynthesis of organisms.

Of great importance among the phosphatidylcholines, for example, are the lecithins, which are characterized by the general structure

distinguish, wherein R ₁ and R _{2 are} typically unbranched aliphatic radicals having 15 or 17 carbon atoms and up to 4 cis double bonds. Lecithins are not only important in the living cell, they are also preferred 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 , phosphate groups esterified or unesterified with organic radicals, sulfate groups esterified or unesterified with organic radicals and Y represents either a hydrogen atom, a hydroxyl group or another heterofunctional radical.

The most common sphingolipids include the naturally occurring ceramides, Ce rebroside, gangliosides, sphingophospholipids, of these in particular the sphingo myeline, sphingosulfatide and glycosphingoside as well as by chemical synthesis available analogues, examples of which are given below:

Ceramides:

R ₁ and R ₃ represent alkyl radicals, R ₂ = H.

Sphingophospholipids:

R ₁ and R ₃ represent alkyl radicals, R ₄ represents an organyl radical.

Sphingomyeline are organylphosphorylated sphingolipids of the type

If R _{2 is} selected from the group of sugar residues in the structural formula of the ceramides, a distinction is usually made as to whether monoglycosylceramides or di-, tri- or generally oligoglycosylceramides are present. Monoglycosylceramides are commonly called cere broside:

Oligoglycosylceramides are mostly called gangliosides.

Common sphingolipids are ceramide I, II, III and IV, glucosylceramide, Lac tosylceramide and the gangliosides GM 1, 2 and 3.

It is also known that certain other ingredients, such as cholesterol, in are integral parts of plasma membranes. Because of its lipophilic nature the cholesterol inside the lipid bilayer, i.e. surrounded by the lipophilic Areas of lipid molecules.

So it should be noted that there are both animate and inanimate structures, their represents or represent essential features of one or more lipid bilayers.

Usual, and more and more widespread cosmetic and dermatological forms of preparation are gels. In the technical sense, under Gels understood: Relatively dimensionally stable, easily deformable disperse systems made of  at least two components, which usually consist of a - usually solid - colloid divided material from long-chain molecular groups (e.g. gelatin, silica, poly saccharide) as a scaffold and a liquid dispersant (e.g. water) stand.

The colloidally divided substance is often referred to as a thickening or gelling agent. He bil det a spatial network in the dispersant, with individual colloidal Particles more or less solidly ver by electrostatic interaction can be knotted.

The dispersant that surrounds the network is characterized by electrostatics cal affinity for the gelling agent, d. that is, a predominantly polar (in particular: hydro philes) gelling agent preferably gels a polar dispersing agent (in particular: Water), whereas a predominantly non-polar gelling agent preferably non-polar di dispersant gelled.

Strong electrostatic interactions, for example in hydrogen bonds bonds between gelling agent and dispersing agent, but also between disper Sion agent molecules are realized with each other, can lead to strong crosslinking also lead the dispersant. Hydrogels can be almost 100% water stand (in addition to, for example, about 0.2-1.0% of a gelling agent) and definitely have a firm consistency. The water content lies in ice-like structural elements so that gele therefore gave its name origin [from lat. "gelatum" = "frozen" the alchemical expression "gelatina" (16th century) for nhdt. "Gelatin"] is definitely used become right.

In cosmetic and pharmaceutical galenics there are also lipogels and Oleogels (from waxes, fats and fatty oils) and carbogels (from paraffin or Petrolatum) common. In practice, a distinction is made between oleogels, which practically what are water-free, hydrogels that are practically fat-free. Mostly gels are through visible. In cosmetic and pharmaceutical galenics, gels are common Usually characterized by a semi-solid, often flowable consistency.

So far, however, it was not possible to have two or more individual structures whose essential The characteristic of the lipid bilayer is that it crosslinks with one another. Especially when busy Structures always had to be assumed that an organism, the link  with a second or even more organisms, or at least not survives undamaged. It was therefore an object of the present invention To remedy evils.

For example, the prior art, such as at least one, was not previously known certain proportion of the free cells present in body fluids or given if more or less agglomerated cells are linked together can be, which increases the viscosity of the body fluid in question could be allocated. For wounds in the human or animal body first of all the discharge of a more or less large amount of blood, its coagulation plays an important role in wound healing. The blood lies until it clots however, quite low-viscosity, so that blood flowing out only through the body Lack of volume weakens, but makes no contribution to wound healing. Wu It would be worthwhile to add a viscosity increase to the blood locally, i.e. extracorporeally help to the lack of volume, which in the rest, especially with heavily bleeding Prevent wounds from causing life-threatening lack of volume shock.

To remedy this particular bad situation was also a task of the present the invention.

Such a disadvantage that it is not possible or not possible in a satisfactory manner was two or more individual structures, the essential feature of which is the lipid double layer is to network with each other, also existed for inanimate structures like at for example the cosmetically and galenically highly interesting liposomes.

Stabilizing such individual structures was also a problem. Liposomes in example are generally above a certain temperature, usually about 40 ° C, thermolabile or against the action of surfactants or other substances such as UV filter substances not or not to a satisfactory extent stable. Solutions are in place, for example, so-called "Stealth ^® liposomes", which are liposomes with polyethoxylated components in its outer skin [Allen, TM (1989) in "Liposomes: the therapy in infectious diseases and cancer 'Lopez-Berestein, G and Fiedler , 1.7., 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 thus to develop new cosmetic and to develop pharmaceutical dosage forms, which compared to the previously be knew dosage forms based on lipid bilayers considerable Should show improvements. For example, gels based on Liposomes - which does not simply mean gels containing liposomes should be unknown to the state of the art.

Yet another task was to create structures with lipid double membranes, in particular unilamellar or multilamellar vesicles or liposomes for increased stability help.

Surprisingly, the tasks are solved according to the invention by structures the basis of lipid double membranes, with the inner lipophilic area of the Lipid double membranes one or more lipophilic areas of one or more moles immerse cooler, or where such molecules by hydrophobic interactions Docking lipid double membranes, and such molecules consisting of at least one hydrophilic area and at least one lipophilic area exist.

In Nachr. 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. Those 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 that the hydrophobic residues "immerse". It may also be sufficient in individual cases if the hydrophobic residues come into contact with the surface of the microemulsion droplets through hydrophobic interaction and adhere more or less strongly to them. As cross-linkers are given polyoxyethylene glycols with oleyl groups as hydrophobic end groups. This principle is illustrated in FIG. 5: The microemulsion droplets (O) of an O / W microemulsion surrounded by a continuous water phase (W) and shown as hatched circles are connected to one another by the crosslinking molecules shown as lines, which are separated by hydrophilic areas (h ) and also carry lipophilic residues (II) symbolized by rectangles on both ends. It can be seen that an emulsion droplet can in principle also accommodate several hydrophobic residues, as a result of which stronger networking and three-dimensionality of the network can be ensured. Nevertheless, this document could not give any indication of the structures according to the invention and their properties.

Structures as shown in Figs. 6a and 6b are, for example, in accordance with the invention. There are sectional images of vesicles, such as liposomes, which are surrounded by a continuous water phase (W), and in which the lipophilic region (II) of one or more molecules, which consist of at least one hydrophilic region, are immersed in the inner lipophilic region of the lipid double membranes (hh) and at least one lipophilic region (II) exist. In Fig. 6a, two vesicles are linked together by linker substances.

The structure according to the invention, which is shown in Fig. 6b, consists of a vesicle or a liposome which is given by a continuous water phase (W) around, and which has a substantially hollow spherical, closed lipid double membrane as the outer shell, in the inner Dip a lipophilic region of the lipid double membrane of said vesicles into a lipophilic region (II) of a molecule, which consists of a hydrophilic region (hh) and two lipophilic regions (II). The second lipophilic region 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 given by a continuous water phase (W) around, and which has a substantially hollow spherical, closed lipid double membrane as the outer shell, in 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 lipophilic regions (II). Similar structures can be assumed for the connection of multilamellar 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 linked to one another by a large number of molecules which each have a hydrophilic region (hh) and two lipophilic regions (II).

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 interconnected by a large number of molecules, each of which is hydrophilic Area (hh) and two lipophilic areas (ll).

The substances used according to the invention, whose molecules with their lipophilic region should dip into the inner lipophilic region of lipid double membranes, which consist of at least one hydrophilic region and at least one lipophilic region, and which we use in the context of the present disclosure with terms such as “linking molecules”, Want to prove "linker substances" and the like, usually follow structure schemes as follows:

 where B symbolizes a hydrophilic region of the respective crosslinker molecule and A each hydrophobic areas, which are also different within a molecule may be chemical in nature.

But also structure schemes like

 and analogously formed, even more complex structures definitely fall within the scope of the hereby submitted invention.

Structural schemes also fall within the scope of the invention presented here:

 where Z represents a central unit, which can be hydrophilic or hydrophobic and usually consists of an oligofunctional or polyfunctional molecular residue.

Of course, linker substances with a higher degree of branching are also included the scope of the present invention.

For example, Z in scheme (10) may consist of one glyceryl residue, three of which OH functions pass into areas B, which in turn, for example, polyoxy  can represent ethylene chains of the same or different lengths, and their terminals OH group are esterified with a longer-chain fatty acid. Also partial substitution Glycerin is conceivable, whereby structures can arise, which scheme (9) correspond.

The hydrophilic groups B can advantageously be chosen so that the linkers Overall substance is water soluble or at least dispersible in water, wherein then the hydrophobic portion of groups A should be overcompensated.

For the structural scheme (1), for example, the following more special structural schemes can be followed:

where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R _{6 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 or aroyl radicals substituted or unsubstituted by alkyl or aryl substituents or also alkylated or arylated organylsilyl radicals. 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. In an individual case, for example if the thickener is selected from the group of the derivatized polysaccharides, x may possibly have significantly higher values than z. B. 300, even several million. This is known per se to the person skilled in the art and requires no further explanation.

For the structural scheme (2), for example, the following more special structural schemes can be followed:

where R ₁ , R ₂ and R _{3 can} independently represent branched or unbranched, saturated or unsaturated, cyclic or chain-like aliphatic, aromatic or hetero roaromatic 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, 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 , R ₂ or R _{3 being} hydrogen atoms.

For the structural scheme (3), for example, the following more special structural schemes can be followed:

where R ₁ , R ₂ , R ₃ and R _{4 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, sub-substituted 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 .

Here too, it goes without saying that partial substitution is conceivable, where one or more of the indices u, v, w, x can assume the value zero and one or more of the radicals R ₁ , R ₂ , R ₃ or R ₄ can represent hydrogen atoms. The substances naturally go into other structural schemes.

For the structural scheme (9), for example, the following more special structural schemes can be followed:

where R ₁ , R ₂ , R ₃ and R _{4 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, sub-substituted 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 .

For the structure scheme (10), for example, the following more specific structure schemes can be followed:

where 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, with alkyl or aryl substituents sub substituted or unsubstituted 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 .

For the structure scheme (11), for example, the following more specific structure scheme can be followed:

where R ₁ , R ₂ , R ₃ and R _{4 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, sub-substituted 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 .

For the structure scheme (12), for example, the following more specific structure scheme can be followed:

where R ₁ , R ₂ , R ₃ , R ₄ and R _{5 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 radicals or also 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 .

For the structure scheme (13), for example, the following more specific structure scheme can be followed:

where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R _{6 can} independently display or represent 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 or aryl substituents substituted or unsubstituted aryl or aroyl radicals 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, typically selected from the range greater than 10, advantageously from the range 20 to 10 ⁷ .

It may also be advantageous to use the structure schemes described above to modify that branching occurs again at the end of the thickener molecule, for example as it is realized in the group of so-called dendrimers.

Particularly suitable linking substances have been found to be those selected from the group

• the polyethylene glycol ether 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 is a number greater than 100,
• - 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 the general formula R-COO - (- CH ₂ CH ₂ O-) _n -C (O) -R ', where R and R' independently of one another ver branched or unbranched alkyl, aryl or alkenyl radicals and n represent a number greater than 100, the polypropylene glycol ether of the general formula RO - (- CH ₂ CH (CH ₃ ) -O-) _n -R ', where R and R' independently of one another are branched or unbranched alkyl, aryl or alkenyl radicals and n represents a number greater than 100 of the esterified fatty acid propoxylates of the general formula R-COO - (- CH ₂ CH (CH ₃ ) -O-) _n -C (O) -R ', where R and R' independently branched or unbranched alkyl, aryl or alkenyl radicals and n represent a number greater than 100, the polypropylene glycol ether of the general formula ROX _n -Y _m -R ', where R and R' independently of one another are branched or unbranched alkyl, aryl or alkenyl radicals represent, wherein X and Y are not identical and each have either an oxyethylene group or an oxypropylene group and n and m independently represent numbers, the sum of which is greater than 100,
• - The etherified fatty acid propoxylates of the general formula R-COO-X _n -Y _m -R ', where R and R' independently of one another are branched or unbranched alkyl, aryl or alkenyl radicals, where X and Y are not identical and in each case either an oxyethylene group or an oxypropylene group and n and m independently represent numbers, the sum of which is greater than 100.

The PEG-800 distearate and the PEG-800 dioleate are particularly advantageous. Also the PEG-1 600 pentaerythrityl tetraisostearate, the PEG-800 methyl glucose dioleate, the PEG-1200 sorbitan triisostearate, the PEG-2400 sorbitol hexaisostearate and the PEG 1200-glyceryl triisostearate are advantageously used as linking substances.  

However, it can be observed that it is possible the higher the concentration of the single structures with lipid double membranes is so simple linker sub to use punches, which are characterized by smaller hydrophilic areas, So that it is possible and advantageous, a linker substance with a lower Degrees of polyethoxylation of those with higher degrees of polyethoxylation to give train.

Advantageous linker substances are selected, for example, from the group with the following structural motifs:

and related substances. Z sets a hydrophilic region, which can be selected from the group of polyoxyethylene groups with polyethoxylation degrees, particularly advantageously, of up to 10 ⁷ .

Dicholesteryl compounds of the type have proven to be particularly advantageous linker substances

proven, where 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

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 800. These substances and the process for their preparation described below are also the subject of the invention.

PEG-n-Chol ₂ can be obtained by the usual chemical methods. In particular, PEG-n-Chol ₂ can be obtained before by adding polyethylene oxide with the desired degree of polymerization n with a cholesteryl derivative of the general structure

are 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 rylchloroformate according to the reaction scheme

An advantageous method of obtaining the preferred linker substances PEG-n-Chol ₂ according to the invention is to mix polyethylene oxide with the desired degree of polymerisation n under largely or completely anhydrous conditions with an excess of cholesteryl chloroformate and a base, for example pyridine, and to prepare the reaction product, which is usually a solid, by the usual preparation methods.

The person skilled in the art knows how to use the above information and, moreover, also due to his general knowledge of other desired chemical In dividuen can reach which molecules represent that in the lipophilic range immerse a lipid bilayer, and which of at least one hydrophilic Area and at least one lipophilic area.

The basic structures based on lipid double membranes can be advantageous on all courses lipids of natural, synthetic or semi-synthetic origin to get voted. The phospholipids such as phosphate are particularly advantageous  idylcholines, phosphatidylethanolamines, phosphatidylserines, cardiolipins (diphosphate idylglycerols) and sphingomyeline, also glycolipids or glycerolipids.

Of particular importance are the lecithins, sphingolipids such as sphingosine or phytosphingosine, ceramides, cerebrosides, gangliosides, sphingophospholipids, of these in particular the sphingomyeline, sphingosulfatide and glycosphingoside and analogues available through chemical synthesis.

Examples of lipids which can be used according to the invention are, for example, dimethyldiocta decylammonium chloride, dimethyldioctadecylammonium bromide, 1-palmitoleyl-2-oleyl-sn-gly cero-3-phosphatidylcholine, dimyristoleylphosphatidylcholine, 1-palmitoleyl-2-oleyl-3-pho sphatidylglyerin.

As a particularly advantageous embodiment of the present invention, the Use of substances whose molecules consist of at least one hydrophilic Be rich and at least one lipophilic area exist for networking or linking structure based on lipid double membranes.

As a very special advantageous embodiment of the present invention the use of substances whose molecules consist of at least one hydrophilic Area and at least one lipophilic area exist for crosslinking or Ver formation of liposomes or liquid crystalline structures.

It has surprisingly been found that if you follow the invention according to the teaching, only using water and liposomes, without the addition of other thickening substances, gel-like cosmetic or pharmaceutical table preparations with excellent cosmetic or pharmaceutical properties and excellent rheological behavior. This is all the more so significant when the skilled person knows how difficult it is to keep liposomes intact.

Furthermore, it was astonishing that with the structures according to the invention it is possible the stability of vesicular objects, i.e. unilamellar, bi- or multilamellar vesicles or To increase liposomes significantly, and particularly advantageous against the action of temperature, surfactants but also other substances such as UV-Fil substances.  

Also as a very special advantageous embodiment of the present Er Invention is the use of substances whose molecules consist of at least one hydrophilic area and at least one lipophilic area exist for crosslinking or linking living or killed cells.

According to the invention it is possible, for example, to include the living cells of fresh blood other and to give the blood a high viscosity without that the blood cells sew damage by the linker substances according to the invention men. It could also be observed that linked according to the invention living cells are capable of division and growth.

Furthermore, cell suspensions, retroviruses and even enzymes can be created using the inventions Linker substances used in accordance with the invention are linked or crosslinked will.

It is even possible to incorporate products according to the invention into medical aids to which cellular objects can be bound. In Fig. 10, for example, a linker substance used in the present invention is embedded in a carrier (B). The lipophilic 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.

As yet another amazing embodiment of the present invention, it has been found that poly mers, 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 amazing 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. It is possible to incorporate substances that are already polymeric into the finished vesicles or liposomes, or to incorporate substances that are already polymeric into the base lipids for the finished vesicles or liposomes and then to produce these vesicles or liposomes by methods known per se, or else the polymers underlying monomers to incorporate the finished vesicles or liposomes and then to initiate the polymerization reaction, for example by UV irradiation, or else to incorporate the monomers on which the polymers are based into the basic lipids for the finished vesicles or liposomes and then these vesicles or liposomes in a manner known per se To produce processes and then, for example by UV radiation, to initiate the polymerization reaction, or to apply modifications of such processes.

The structures according to the invention are intended as components of a cosmetic or pharmaceutical preparations are used, as already indicated, entirely possible and advantageous, preparations consisting only of water and for example, to obtain liposomes and one or more linking substances. Of course, it is also possible and advantageous to use the inventive Structures to incorporate other dosage forms, for example the usual ones Emulsions, i.e. preparations that are in addition to one or more water phases also have one or more oil phases. For example, the usual single and multiple emulsions, furthermore microemulsions emulsions, as well as largely emulsifier-free and hydro- or lipodispersions, but even pure ones Oil phases have proven to be a suitable basis for preparations according to the present highlighted the invention.

The oil phase of oil-containing preparations according to the invention is advantageously chosen 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 sown saturated and / or unsaturated, branched and / or unbranched alcohols Chain length of 3 to 30 carbon atoms, from the group of esters from aromatic car bonic acids and saturated and / or unsaturated, branched and / or unbranched ten alcohols with a chain length of 3 to 30 carbon atoms. Such ester oils can then advantageously selected from the group of isopropyl myristate, isopropyl palmitate, Isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooc tyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl blue Rat, 2-hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, olerlerucate, erucyl oleate, Erucylerucat as well as synthetic, semi-synthetic and natural mixtures of such Esters, e.g. B. Jojoba oil.

Furthermore, the oil phase can advantageously be selected from the group of the branched ones and unbranched hydrocarbons and waxes, the silicone oils, the dialkyl ethers,  the group of saturated or unsaturated, branched or unbranched alcohol le, and the fatty acid triglycerides, especially the saturated and / or triglycerol esters unsaturated, branched and / or unbranched alkane carboxylic acids of a chain length from 8 to 24, in particular 12-18 C atoms. The fatty acid triglycerides can For example, advantageously selected from the group of synthetic, half synthetic and natural oils, e.g. B. 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 are also advantageous To use the sense of the present invention.

The oil phase is advantageously selected from the group consisting of 2-ethylhexyl isostearate, octyldecanol, isotridecylisononanoate, isoeicosane, 2-ethylhexyl cocoate, C _12-15 alkyl benzoate, caprylic capric acid triglyceride, dicaprylyl ether.

Of the hydrocarbons, paraffin oil, squalane and squalene are advantageous in the sense of the present invention.

The oil phase can also advantageously contain cyclic or linear silicone oils have or consist entirely of such oils, although it is preferred besides the silicone oil or oils an additional content of others To use oil phase components.

Cyclomethicone (octamethylcyclotetrasiloxane) is advantageous as according to the invention using silicone oil. But other silicone oils are also beneficial in the Sin to use ne of the present invention, for example hexamethylcyclotrisiloxane, Polydimethylsiloxane, poly (methylphenylsiloxane).

Mixtures of cyclomethicone and isotridecylisono are also particularly advantageous nanoate, from cyclomethicone and 2-ethylhexyl isostearate.

The preparations according to the invention advantageously contain electrolytes, in particular one or more salts with the following anions: chlorides, also inorganic oxo Element anions, of these in particular sulfates, carbonates, phosphates, borates and Aluminates. Electrolytes based on organic anions can also be advantageous  are used, for example lactates, acetates, benzoates, propionates, tartrates, Citrate and others. Comparable effects are also due to ethylenediaminetetraes to achieve acetic acid and its salts.

The cations of the salts are preferably ammonium, alkylammonium, alkali metal, Alkaline earth metal, magnesium, iron or zinc ions used. It does not in itself require Ner mention that only physiologically acceptable electrolytes are used in cosmetics should be det. Special medical applications of the invention Microemulsions, on the other hand, can, at least in principle, use Electrolytes require, which should not be used without medical supervision.

Potassium chloride, sodium chloride, magnesium sulfate, zinc sulfate and Mi are particularly preferred made from it. Salt mixtures such as those found in natural salt are also advantageous occur from the Dead Sea.

The concentration of the electrolyte or electrolytes should be about 0.1-10.0% by weight, especially advantageously be about 0.3-8.0% by weight, based on the total weight of the accessories riding.

The preparations according to the invention also contribute excellently to the skin smoothing, especially if they contain one or more substances are that promote skin smoothing.

The preparations according to the invention provide the basis for cosmetic deodorant antiperspirants, all common active ingredients can be used to advantage are, for example, odor maskers such as the common perfume ingredients, Ge odor absorber, for example that in the patent application DE-P 40 09 347 be layered silicates, of which in particular montmorillonite, kaolinite, ilite, Beidellite, nontronite, saponite, hectorite, bentonite, smectite, and furthermore, for example, zinc salts of ricinoleic acid. Germ inhibitors are also suitable in the inventions microemulsions according to the invention. Favorable substances are for example 2,4,4'-trichloro-2'-hydroxydiphenyl ether (irgasane), 1,6-di- (4-chlorophenylbi guanido) hexane (chlorhexidine), 3,4,4'-trichlorocarbanilide, quaternary ammonium compound dung, clove oil, mint oil, thyme oil, triethyicitrate, famesol (3,7,11.trimethyl-2,6,10-dode catriën-1-ol) and those in the patent application 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 effective agents.

The usual antiperspirant active ingredients can also be advantageous in the Invention Appropriate preparations are used, especially astringents, for example basic aluminum chlorides.

The cosmetic deodorants according to the invention can be in the form of aerosols, So spray from aerosol containers, squeeze bottles or by a pump device presentable preparations or in the form of those that can be applied using roll-on devices liquid compositions, but also in the form of from normal bottles and Preparable preparations for containers.

As a propellant for cosmetic sprayable from aerosol containers according to the invention Deodorants are the usual known volatile, liquefied propellants, For example, hydrocarbons (propane, butane, isobutane) suitable alone or in Mixture can be used together. Compressed air is also advantageous use.

Of course, the skilled person knows that there are non-toxic propellants per se, the reason would also be suitable for the present invention, but nevertheless due to be environmental effect or other accompanying circumstances should, especially chlorofluorocarbons (CFCs).

Those cosmetic and dermatological preparations which are in the Form of a sunscreen. In addition to the active ingredient combinations according to the invention additionally at least one UVA Filter substance and / or at least one UVB filter substance and / or at least one inorganic pigment.

However, it is also advantageous for the purposes of the present invention to use such cosmetics human and dermatological preparations, their main purpose is not protection from sunlight, but it does contain UV protection contain substances. So z. B. in day creams usually UV-A or UV-B Filter substances incorporated.  

Preparations according to the invention can advantageously contain substances which have UV Absorb radiation in the UVB range, taking the total amount of filter substances e.g. B. 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. As oil-soluble substances such. B. To name:

• - 3-Benzylidene camphor and its derivatives, e.g. B. 3- (4-methylbenzylidene) camphor,
• - 4-aminobenzoic acid derivatives, preferably 4- (dimethylamino) benzoic acid (2-ethyl hexyl ester, 4- (dimethylamino) benzoic acid amyl ester;
• Esters of cinnamic acid, preferably 4-methoxycinnamic acid (2-ethylhexyl) ester, 4- Isopentyl methoxy cinnamate;
• - Esters of salicylic acid, preferably salicylic acid (2-ethylhexyl) ester, salicylic acid (4-iso propylbenzyl) ester, salicylic acid homomethyl ester;
• Derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2- Hydroxy-4-methoxy-4'-methylbenzophenone 2,2'-dihydroxy-4-methoxybenzophe non;
• - Esters of benzalmalonic acid, preferably 4-methoxybenzalmalonic acid di (2-ethyl hexyl) ester;
• - 2,4,6-trianilino (p-carbo-2'-ethyl-1'-hexyloxy) -1,3,5-triazine.

The following are advantageous as water-soluble substances:

• - 2-Phenylbenzimidazole-5-sulfonic acid and its salts, e.g. B. sodium, potassium or Triethanolammonium salts,
• - Sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxy-benzo phenon-5-sulfonic acid and its salts;
• - Sulfonic acid derivatives of 3-benzylidene camphor, such as. B. 4- (2-Oxo-3-bornylidene methyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bornylidenemethyl) sulfonic acid and their salts.

The list of the UVB filters mentioned, which can be used according to the invention, should of course not be limiting.  

The invention also relates to the combination of a UVA fil according to the invention ters with a UVB filter or an inventive cosmetic or dermatolo gische preparation, which also contains a UVB filter.

It can also be advantageous to use UVA filters in preparations according to the invention usually put in cosmetic and / or dermatological preparations are included. Such substances are preferably derivatives of Dibenzoylmethane, especially 1- (4'-tert-butylphenyl) -3- (4'-methoxyphenyl) -pro pan-1,3-dione and 1-phenyl-3- (4'-isopropylphenyl) propane-1,3-dione. Also accessories Equations containing these combinations are the subject of the invention. It can the same amounts of UVA filter substances that are used for UVB Filter substances were called.

Cosmetic and / or dermatological preparations according to the invention can also contain inorganic pigments that are commonly used in cosmetics to protect the Skin against UV rays. These are oxides of titanium, Zinc, iron, zirconium, silicon, manganese, aluminum, cerium and mixtures thereof, as well as variations in which the oxides are the active agents. Especially it is preferably pigments based on titanium dioxide. It can be used for the amounts mentioned above combinations are used.

An astonishing property of the present invention is that according to the invention Preparations very good vehicles for cosmetic or dermatological active ingredients in the Skin are, with beneficial active ingredients are antioxidants that protect the skin from oxi can protect dative stress.

According to the invention, the preparations advantageously contain one or more antioxidants dantien. As inexpensive, yet optional antioxidants all for cosmetic and / or dermatological applications suitable or customary Antioxidants are used. It is beneficial to have antioxidants as the only ones Active ingredient class to be used, for example, when a cosmetic or dermatolo The focus is on application, such as combating the oxidative bean stress on the skin. However, it is also favorable to use the preparations according to the invention to contain one or more antioxidants if the  Preparations are to serve another purpose, e.g. B. as deodorants or son protective agents.

The antioxidants are particularly advantageously selected from the group consisting of
Amino acids (e.g. histidine, tyrosine, tryptophan) and their derivatives, imidazoles (e.g. urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine, L-carnosine and their derivatives (e.g. Anserin), carotenoids, carotenes (e.g. α-carotene, β-carotene, lycopene) and their derivatives, lipoic acid and their derivatives (e.g. dihydroliponic acid), Au rothioglucose, propylthiouracil and other thiols (e.g. Thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl, cholesteryl - and glyceryl esters) as well as their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) as well as sulfoximine compounds (e.g. buthioninsulfoximines, homocysteine sulfoximine, pentahione insulin f -, Heptahioninsulfoximin) in very low tolerable doses (e.g. pmol to µmol / kg), fe Core (metal) chelators (e.g. B. α-hydroxy fatty acids, α-hydro xypalmitic acid, phytic acid, lactoferrin), α-hydroxy acids (e.g. 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 (e.g. γ-linolenic acid, linoleic acid, oleic acid), folic acid and their derivatives, ubiquinone and ubiquinol their derivatives, vitamin C and derivatives (e.g. ascorbyl palmitates, Mg ascorbyl phosphates, ascorbylacetates), tocopherols and derivatives (e.g. vitamin E acetate), vitamin A and derivatives (vitamin A palmitate) as well as coniferyl benzoate of benzoin, ruinic acid and its derivatives, ferulic acid and its derivatives, butylhydroxytoluene, butylhydroxyanisole, nordihydroguajakharzäure, nordihydroguajarylacetate, trihydroxy acid, trihydroxy acid , Uric acid and its derivatives, zinc and its derivatives (e.g. ZnO, ZnSO ₄ ) selenium and its derivatives (e.g. selenomethionine), stilbenes and their derivatives (e.g. stilbene oxide, Trans-stilbene oxide) and the derivatives suitable according to the invention (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these active substances.

Oil-soluble antioxidants can be particularly advantageous for the purposes of the present invention tien be used.  

The amount of antioxidants (one or more compounds) in the preparations is preferably 0.001 to 30% by weight, particularly preferably 0.05-20% by weight, in particular 1-10 wt .-%, based on the total weight of the preparation.

If vitamin E and / or its derivatives are the antioxidant (s) advantageous, the respective concentrations of which range from 0.001-10% by weight, based on the total weight of the formulation.

If vitamin A or vitamin A derivatives or carotenes or their derivatives the or the antioxidants are advantageous, their respective concentrations from the Range of 0.001-10% by weight based on the total weight of the formulation choose.

It is of course known to the person skilled in the art that sophisticated cosmetic preparations mostly are not conceivable without the usual auxiliaries and additives. Beneath it tough len, for example, consistency agents, fillers, perfume, dyes, emulsifiers additional active ingredients such as vitamins or proteins, light stabilizers, stabilizers, insects tenrepellants, alcohol, water, salts, antimicrobial, proteolytic or keratolytic effective substances etc.

According to the invention, active ingredients can also be selected very advantageously from the group of lipophilic active ingredients, in particular from the following group:
Acetylsalicylic acid, atropine, azulene, hydrocortisone and its derivatives, e.g. B. Hydrocor tison-17-valerate, vitamins, e.g. B. ascorbic acid and its derivatives, vitamins of the B and D series, very cheap vitamin B ₁ , vitamin B _12, vitamin D ₁ , but also bisabolol, unsaturated fatty acids, especially the essential fatty acids (often called vitamin F) ), in particular γ-linolenic acid, oleic acid, eicosapentaenoic acid, docosahexaenoic acid and its derivatives, chloramphenicol, caffeine, prostaglandins, thymol, camphor, extracts or other products of plant and animal origin, e.g. B. evening primrose oil, borage oil or currant seed oil, fish oils, cod liver oil but also ceramides and ceramide-like compounds and so on.

Although of course the use of hydrophilic active substances according to the invention is moderately favored, another advantage of the preparations according to the invention is that especially oil-soluble or lipophilic active ingredients with particularly high effectiveness be made biologically available.

The cosmetic and dermatological preparations according to the invention can Contain cosmetic auxiliaries, as they usually ver in such preparations be applied, e.g. B. preservatives, bactericides, virucides, perfumes, substances to prevent foaming, dyes, pigments that have a coloring effect, further Ver not falling under the definition of the thickener according to the invention thickeners, surface-active substances, emulsifiers, softening, moistening Tending and / or moisturizing substances, anti-inflammatory substances, Medicines, fats, oils, waxes or other common components of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers gates, electrolytes, organic solvents.  

Production example for PEG-140-Chol ₂

36 g (6 mmol) of polyethylene oxide (M = 6,000 gmol ^-1 , n ≈ 140) are dissolved in 50 ml of benzene and freeze-dried to remove traces of water. The polyethylene oxide is then taken up in 70 ml of freshly absolute dichloromethane. 10.8 g (24 mmol) of cholesteryl chloroformate and 5 ml of pyridine (the latter distilled over CaH ₂ ) are added under a nitrogen atmosphere. The polymer is precipitated in 1.5 l of diethyl ether and purified by repeated reprecipitation (three times) from dichloromethane / diethyl ether. The pre-dried product is dissolved in approx. 1 l warm acetone and precipitates quantitatively at 0 ° C.
Yield: 33 g of PEG-140-Chol ₂ (4.8 mmol), corresponding to 81% of theory.

Production example for PEG-18O-Chol ₂

48 g (6 mmol) of polyethylene oxide (M = 8,000 gmol ^-1 , n ≈ 180) are dissolved in 70 ml of benzene and freeze-dried to remove traces of water. The polyethylene oxide is then taken up in 100 ml of freshly absolute dichloromethane. 10.8 g (24 mmol) of cholesteryl chloroformate and 5 ml of pyridine (the latter distilled over CaH ₂ ) are added under a nitrogen atmosphere. The polymer is precipitated in 1.5 l of diethyl ether and purified by repeated reprecipitation (three times) from dichloromethane / diethyl ether. The pre-dried product is dissolved in approx. 1 l warm acetone and precipitates quantitatively at 0 ° C.
Yield: 44 g of PEG-1 80-Chol ₂ (4.8 mmol), corresponding to 80% of theory.

Production example for PEG-45O-Chol ₂

120 g (6 mmol) polyethylene oxide (M = 20,000 gmol ^-1 , n ≈ 450) are dissolved in 170 ml benzene and freeze-dried to remove traces of water. The polyethylene oxide is then taken up in 100 ml of freshly absolute dichloromethane. 10.8 g (24 mmol) of cholesteryl chloroformate and 5 ml of pyridine (the latter distilled over CaH ₂ ) are added under a nitrogen atmosphere. The polymer is precipitated in 2.5 l of diethyl ether and purified by repeated reprecipitation (three times) from dichloromethane / diethyl ether. The pre-dried product is dissolved in approx. 1 l warm acetone and precipitates quantitatively at 0 ° C.
Yield: 90 g of PEG-450-Chol ₂ (4.8 mmol), corresponding to 80% of theory.

Manufacturing example for PEG800-Chol ₂

58 g (6 mmol) of polyethylene oxide (M = 35,000 gmol ^-1 , n ≈ 800) are dissolved in 130 ml of benzene and freeze traces of water are removed. The polyethylene oxide is then taken up in 100 ml of freshly absolute dichloromethane. 10.8 g (24 mmol) of cholesteryl chloroformate and 5 ml of pyridine (the latter distilled over CaH ₂ ) are added under a nitrogen atmosphere. The polymer is precipitated in 1.5 l of diethyl ether and purified by repeated reprecipitation (three times) from dichloromethane / diethyl ether. The pre-dried product is dissolved in approx. 1 l warm acetone and precipitates quantitatively at 0 ° C.
Yield: 160 g PEG-800-Chol ₂ (4.8 mmol), corresponding to 80% of theory.

Preparation example 1 for vesicles

176 mg of dimethyldioctadecylammonium chloride in 8 ml of double-distilled water suspended at 60 ° C. The suspension is ultrasound for 45-60 min at 60 ° C bad (Laboratory Supplies Co.) sonicated. After cooling, a vesicle suspension receive.

Preparation example 2 for vesicles

176 mg of dimethyldioctadecylammonium bromide in 8 ml of double-distilled water suspended at room temperature. The suspension is 45-60 min at room temperature sonicated in an ultrasonic bath (Laboratory Supplies Co.) under nitrogen. It will receive a vesicle suspension.

Preparation example 3 for vesicles

176 mg of 1-palmitoleyl-2-oleyl-sn-glycero-3-phosphatidylcholine are bidestilized in 8 ml water at room temperature. The suspension is at 45-60 min Room temperature in an ultrasonic bath (Laboratory Supplies Co.) under nitrogen sonicated. A vesicle suspension is obtained.

Preparation example 4 for vesicles

176 mg of 1-palmitoleyl-2-oleyl-sn-glycero-3-phosphatidylcholine are bidestilized in 8 ml water at room temperature. The suspension is at 45-60 min Room temperature in an ultrasonic bath (Laboratory Supplies Co.) under nitrogen sonicated. A vesicle suspension is obtained.

Preparation example 5 for vesicles

176 mg of dimyristoleylphosphatidylcholine are dissolved in 8 ml of double-distilled water at 60 ° C suspended. The suspension is suspended at room temperature for 45-60 min. The Suspension is 45-60 min at room temperature in an ultrasonic bath (laboratory Supplies Co.) sonicated under nitrogen. A vesicle suspension is obtained.  

Preparation example 6 for vesicles

176 mg of 1-palmitoleyl-2-oleyl-3-phosphatidylglyerin are double-distilled in 8 ml Water suspended at room temperature. The suspension is 45-60 min at room temperature in an ultrasonic bath (Laboratory Supplies Co.) sonicated under nitrogen. A vesicle suspension is obtained.

example 1

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.

Example 2

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.

Example 3

A vesicle suspension obtained in preparation example 3 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.

Example 4

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.

Example 5

A vesicle suspension obtained in preparation example 5 for vesicles is added to a dispersion of 50 mg of PEG-800-Chol ₂ in 2 ml of bidistilled water. The mixture gels over a few minutes.

Example 6

A vesicle suspension obtained in preparation example 6 for vesicles is added to a dispersion of 50 mg of PEG-800-Chol ₂ in 2 ml of bidistilled water. The mixture gels over a few minutes.

Example 7

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.

Claims (10)

1. Structures based on lipid double membranes, being in the inner lipo one or more lipophilic areas of one or immerse several molecules, or such molecules by hydrophobic Interactions to dock on to lipid double membranes, and such molecules from at least one hydrophilic area and at least one lipophilic area consist. 2. Structures according to claim 1, characterized in that their outer shape by delimits a substantially self-contained curved lipid double membrane will. 3. Structures according to claim 2, characterized in that they are chosen from the group of living or killed eucaryotic or procaryotic cells or isolated organelles of such cells, the inner lipophilic region of the these cells or cell organelles delimiting lipid double membranes of the lipophilic Immerse area of one or more molecules, or where such molecules pass through Dock hydrophobic interactions on lipid double membranes, and such Molecules from a hydrophilic area and at least one lipophilic area consist. 4. Structures according to claim 1, characterized in that in the inner lipophilic area of the lipid double membranes the lipophilic area of one or more molecules are immersed, which are selected from the group of substances which correspond to the following structural schemes:
where B symbolizes a hydrophilic region of the respective crosslinking molecule and A each represents hydrophobic regions, which can also be of different chemical nature within a molecule, and Z represents a central unit, which can be hydrophilic or hydrophobic and generally consists of an oligo- or polyfunction there is a small molecular residue. 5. Structures according to claim 1, characterized in that one or more lipophilic regions of one or more molecules are immersed in the inner lipophilic region of the lipid double membranes, or wherein such molecules dock onto lipid double membranes through hydrophobic interactions, which are selected from the group

• the polyethylene glycol ether 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 is a number greater than 100,
• - 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 the general formula R-COO - (- CH ₂ -CH ₂ O-) _n -C (O) -R ', where R and R' independently of one another ver branched or unbranched alkyl, aryl or alkenyl and n represents a number greater than 100, the polypropylene glycol ether of the general formula R-O + CH ₂ CH (CH ₃ ) -O-) _n -R ', where R and R' independently of one another are branched or unbranched alkyl, aryl or alkenyl radicals and n represents a number greater than 100, of the esterified fatty acid propoxylates of the general formula R-COO - (- CH ₂ CH (CH ₃ ) -O-) _n -C (O) -R ', where R and R' independently of one another ver branched or unbranched alkyl, aryl or alkenyl radicals and n represent a number greater than 100, the polypropylene glycol ether of the general formula ROX _n -Y _m -R ', where R and R' independently of one another are branched or unbranched alkyl, aryl or Represent alkenyl radicals, where X and Y are not identical and each have either an oxyethylene group or an oxypropylene group and n and m independently represent numbers, the sum of which is greater than 100,
• - The etherified fatty acid propoxylates of the general formula R-COO-X _n -Y _m -R ', where R and R' independently of one another are branched or unbranched alkyl, aryl or alkenyl radicals, where X and Y are not identical and in each case either an oxyethylene group or an oxypropylene group and n and m independently represent numbers, the sum of which is greater than 100.

6. Structures according to claim 1, characterized in that in the inner lipophilic Area of the lipid double membranes one or more lipophilic areas of one or immerse several molecules, or such molecules by hydrophobic changes docking interactions with lipid double membranes, and these molecules selected are from the group PEG-800 distearate and the PEG-800 dioleate. The PEG 1600-pentaerythrityl tetraisostearate, the PEG-800 methyl glucose dioleate, the PEG-1200-  Sorbitan triisostearate, the PEG-2400 sorbitol hexaisostearate and the PEG-1200- Glyceryl triisostearate. 7. Structures according to claim 1, characterized in that one or more lipophilic regions of one or more molecules are immersed in the inner lipophilic region of the lipid double membranes, which are selected from the group of dichloro steryl compounds of the type
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 20-300, very particularly advantageously from the range 120-200. 8. Use of substances whose molecules consist of at least one hydrophilic Be rich and at least one lipophilic area exist for networking or linking structure based on lipid double membranes. 9. Use of substances whose molecules consist of at least one hydrophilic Be rich and at least one lipophilic area exist for networking or linking of liposomes or liquid crystalline structures. 10. Use of substances whose molecules consist of at least one hydrophilic Area and at least one lipophilic area exist to increase stability vesicular objects, i.e. unilamellar, bi- or multilamellar vesicles or liposomes.