CZ2002561A3 - Phospholipid gel - Google Patents

Abstract

Disclosed is a phospholipin gel which is stabilised against liquefying by adding a tetrahydric, pentahydric or hexahydric alcohol or sugar. The gel can be used for producing cosmetic and pharmaceutical formulations.

Description

Phospholipid gel

Technical field

The present invention relates to a phospholipid gel and to cosmetic and pharmaceutical compositions containing the same.

BACKGROUND OF THE INVENTION

Phospholipid gels are known. These gels find use as pharmaceutical carriers. The phospholipid is not only a carrier of the active ingredient but also controls the bioavailability of the drug. The reason for this is the special molecular arrangement of phospholipids that can form stable liposomes consisting of bilayers. The active compounds are better absorbed because phospholipids make it easier to absorb the active compounds into the target cells.

A process for preparing liposome solutions that may contain pharmacologically active compounds is disclosed, for example, in European Patent Application EP-B-0 069 307. In preparing these solutions, liposome gels are first obtained which can be used, for example, as an ointment base. In order to avoid gelation of the obtained liposome solutions, European patent application EP-B-0 0609 307 proposes the addition of an electrolyte, such as physiological buffer or sugar.

Patent application WO 95/35095 presents a liposomic composition for pharmaceutical or cosmetic use, which contains 0.5-10% phospholipids, 20-50% C ₂ _ ₄ -alcohol, 0 to 30% glycol, at least 20% water and at least one active compound.

German patent application DE 195 pharmaceutical composition which besides

659 discloses active compounds of acyclovir containing 5-35% by weight of phospholipid, 15-50% by weight of alcohol and 79-0% by weight of water, the alcohol being di- or trihydroxy alone C ₂ . _5- alcohol or a mixture of ethanol, 1-propanol and / or 2-propanol.

U.S. Patent No. 5,820,848 discloses liposome-containing gels which may contain a short chain alcohol such as methanol, ethanol, glycerol and ethylene glycol.

The prior art phospholipids have the disadvantage of easy liquefaction when applied to the skin. The liquefaction of the gel becomes stronger as the skin sweats. This is particularly disadvantageous in the case of gels intended for application to the mucous membranes. Patients often experience discomfort and subsequent dampness after application of conventional phospholipids as unpleasant.

Moreover, the known phospholipid gels have the disadvantage that they can only be liquefied by the introduction of a pharmaceutical buffer or salt, especially when readily soluble substances such as diphenhydramine hydrochloride are used. In such cases, said compositions can flow only by their own weight.

This effect is known, for example, from German patent application DE 4003 783 A1 which discloses a phospholipid gel preserved by the use of alcohols such as ethanol or 2-propanol. According to Examples 7 and 9-12, these gels are only liquefied by the addition of a buffer or salt solution.

SUMMARY OF THE INVENTION

Accordingly, it is an object of the present invention to provide a phospholipid gel that has greater stability when applied to the skin and when used with a pharmaceutical buffer or salt compared to other known phospholipid gels.

• · ·· ·:. : · ·:.

• · *: ··· * · ·· · .. · .. ......

··· ···· ··

It has now been discovered according to the present invention that this problem can be solved by adding a tetra-, penta- or hexahydric alcohol and / or sugar to the phospholipid gel.

Accordingly, the present invention relates to phospholipid gels containing 5-60% by weight of at least one phospholipid;

• at least 1% by weight of at least one di- or trihydric C ₂ _ ₄ -alcohol;

0.5 to 35% by weight of at least one tetra-, penta- or hexahydric alcohol and / or at least one sugar;

Optionally one or more additives and water up to 100% by weight.

The weight% always refers to the weight of the whole gel.

The phospholipid composition of the present invention comprises phospholipids which are preferably of natural origin. Particularly suitable are plant phospholipids, such as soya lecithin. Phospholipids can be characterized by the content of phosphatidylcholine, which is the major component of phospholipids.

«

In principle, either hydrogenated and / or non-hydrogenated phospholipids can be used according to the present invention. In the case of non-hydrogenated phospholipids, the phosphatidylcholine content is at least 70% by weight of phospholipids, suitably at least 75% by weight of phospholipids. In the case of hydrogenated phospholipids, the phosphatidylcholine content is at least 90% by weight.

The phospholipid used according to the present invention may also be a mixture of various phospholipids and in particular a mixture of phosphatidylcholine and lysophosphatidylcholine. In such a mixture, the weight ratio of phosphatidylcholine to lysophosphatidylcholine is from 97: 3 to 40:60. wherein the higher phosphatidylcholine constitutes at least 75% by weight (in the case of non-hydrogenated phospholipids) and suitably at least 90% by weight (in the case of hydrogenated phospholipids) of the total amount of phospholipids.

Known phospholipids meeting these conditions can be obtained, for example, from Nattermann Phospholipid GmbH under the names Fosfolipon® 80 and Fosfolipon® 90 H. Phospholipon 80 contains about 76% phosphatidylcholine and about 3% lysophosphatidylcholine, Fosfolipon 90 H (hydrogenated phosphatidylcholine) contains at least 90% phosphatidylcholine and a maximum of 4% lysophosphatidylcholine. Phospholipon 80 can also be obtained as a 75% solution in ethanol (NAT 8539) and as a 60% solution in propylene glycol (NAT 8450). However, phospholipids from other manufacturers can also be used to prepare the gel of the present invention.

In one embodiment, hydrogenated phospholipids are used. An advantage of this embodiment is that less phospholipids can be added. For example, about 20% of the non-hydrogenated 10 phospholipids can be replaced with about 10% of the hydrogenated phospholipids, which leads to cost savings.

The phospholipid content of the gel is from 5 to 60% by weight. At less than 5% gel formation is not possible and above 60% no gel formation can be formed. The preferred phospholipid content of the gel of the present invention is 5 to 35% by weight, more preferably 15 to 25% by weight.

As a further component comprises a gel of the present invention at least 1% by weight, preferably 20 to 30% by weight of at least one di- or trihydric C ₂ _ ₄ -alcohol. At higher concentrations, this alcohol acts as a preservative. Furthermore, this alcohol acts as a phospholipid solvent and can also serve as a solubilizer for the active compound. Furthermore, this component may promote penetration and, finally, may increase skin moisture. Particularly suitable dihydric alcohols are propanediol and especially propylene glycol (1,2-propanediol). Useful trihydric alcohols include, for example, glycerol. The gel may also contain mixtures of different types of these alcohols.

The contents of di- or trihydric C ₂ _ ₄ -alcohols in the gel of the present invention can vary greatly. Preferred is a content of 1-40% by weight, more preferably 15-30% by weight. When propylene glycol alone is used as the alcohol component, its content in the gel is preferably 25 to 30% by weight. When glycerol alone is used as the alcohol component, its content in the gel is 20 to 30% by weight. However, the gel of the present invention may also comprise a mixture of, for example, 15 to 30% by weight propylene glycol and 0 to 10% by weight, preferably 2.5 to 7.5% by weight, of glycerol.

As a key constituent of the phospholipid gel tendency, the liquid according to the present invention contains 0.5 to 35% by weight of at least one tetra-, penta- or hexahydric alcohol or sugar. The term "sugar" according to the present invention means a mono-, di- and / or oligosaccharide. Preferred sugar alcohols are tetra-, penta- or hexahydric alcohols. These include, for example, glucose, fructose, sucrose, trehalose, xylitol, maltitol, inositol, sorbitol, and mannitol. It is also possible to use mixtures of said additives, in particular mixtures of different alcohols and / or different sugars, such as a mixture of sorbitol and glucose.

In order to reduce the tendency of phospholipid gels to liquidate, the content of polyhydric alcohols or sugars in the composition may be liquid.

β vary considerably. The appropriate amount depends, for example, on the presence of other preservatives, the tendency of the drug, if any, to promote fluidization, the nature of the buffer, if any, and the other ingredients present. Further, the content of polyhydric alcohols or sugars may be adjusted according to the intended use of the gel of the present invention. When the gel of the present invention is intended, for example, to be applied to the nasal mucosa, it will be appreciated that on the one hand there is higher moisture in the nose and, on the other hand, salts are present in the nose which promote electrolyte liquidation. However, if the gel of the present invention is to be applied, for example, only to dry skin, the tendency to liquidate is less due to the lower moisture content and salt content of the skin. The alcohol, sugar or sugar alcohol content of the gel can then be adjusted according to these requirements. In the case of gels that may come into contact with the gastrointestinal tract, such as gels and / or oral mucosa, it should be considered that some sugars have a sweet taste. However, it may be appropriate not to use sugars if they are to use the gel also diabetics. Then sugar alcohols are preferred.

A polyhydric alcohol or sugar content of 2 to 20% by weight, in particular 2.5 to 10% by weight, is preferred.

If the gel of the present invention is to be used as a pharmaceutical composition, it additionally contains one or more pharmaceutically active compounds. The gel of the present invention is particularly advantageous for active compounds that readily dissolve in water, since they cause liquidation in existing gels. However, the gel according to the present invention is also advantageous for poorly soluble or even soluble pharmaceutical active compounds, since it then exerts its liquid-inhibiting activity on application, for example on the skin or mucosa.

·· ♦ ·

The pharmaceutically active compounds may be selected from the group consisting of anti-inflammatory agents, non-steroidal anti-inflammatory drugs, corticosteroids, peptides, hormones, enzymes, nucleic acids, virostatics, vitamins, local anesthetics, antifungals, antibiotics, antipsoriatics, circulatory agents, α-syphnpatomimetics and. nasal drops. Virostatics, particularly acyclovir, corticoids, hormones, and in particular peptides, may be suitably introduced into the gel of the present invention.

Pharmaceutically active compounds which may be mentioned are, for example, acyclovir, heparin, diclofenac, hydrocortisone, xylometazoline, cyclosporin, diphenhydramine, calcitonin and indamethacin or pharmaceutically acceptable salts thereof. An advantage of the compositions of the present invention is that they can be used without any problems not only for the active compounds but also for the pharmaceutically acceptable salts.

The phospholipid gel compositions of the present invention also allow for topical application of those drugs that cannot be administered orally and otherwise must be administered parenterally. These active compounds are, for example, insulin, which can be absorbed, for example, through the nasal mucosa.

However, it is also possible to administer vaccines, hormones or nucleic acids (suitable for vaccination) using the phospholipid gels of the present invention. Thanks to the phospholipids, the gels of the present invention allow good skin penetration. The phospholipid gel of the present invention therefore provides a non-invasive administration form of drugs that cannot be administered orally, such as peptides or nucleic acids (for example for vaccination). The gel structure available through the phospholipid gels of the present invention allows, for example

apply gel preparations to the nasal mucosa so that the active compounds can readily penetrate it.

However, instead of or in addition to the pharmaceutically active compounds, the gels of the present invention may also contain cosmetic ingredients. Examples are vitamins, sun filters or α-hydroxy acids.

As a further component, the gels of the present invention may contain up to 10% by weight of at least one alcohol selected from the group consisting of ethanol, 1-propanol and 2-propanol. However, these monohydric alcohols are only in addition to the above di- and trihydric alcohols in the gel.

A great advantage of the gels of the present invention is that in order to stabilize the phospholipid gel with polyhydric alcohol and / or sugar, a buffer can be added to the composition without liquefying the gel. The buffer should be selected to have a large buffering capacity in the region of optimal phosphatidylcholine stability. The optimum stability of phosphatidylcholine is at pH 6.5, so that the buffer should have a large buffering capacity in the range of pH 5.5 to 8.0, and preferably about pH 6.5. Gel buffering in the region of optimal stability of phosphatidylcholine results in increased gel storage stability. This is due to slower hydrolysis of phosphatidylcholine to lysophosphatidylcholine. For example, in an unbuffered gel, the phosphatidylcholine content reduction at 41 ° C is 58% after 25 weeks. For the same gel buffered with BISTRIS, the reduction after 36 weeks at 41 ° C but only 44%.

Particularly preferred buffers are BISTRIS (2- (bis (2-hydroxyethylimino) -2-hydroxymethyl) -1,3-propanediol) (pK _and 6.5), phosphate buffer (sec-phosphate buffer range 6.2-8.2) ), bicarbonate buffer (buffer range 5.4-6.9), maleate buffer (buffer range 6.0-6.8), TRIS: (trishydroxymethylaminomethane), MOPS: (3- [N-morpholino] propanesulfonic acid) and HEPES (N- [2-hydroxyethyl] piperazine-N- (2-ethanesulfonic acid). Especially preferred due to pK _and 6.5 BISTRIS .

The amount of buffer added is not critical, but should be large enough to provide the appropriate buffering effect. For example, a BISTRIS concentration of about 0.075M (1.57% by weight) is very preferred in the gel.

However, if desired, a predefined pH of the gel can be adjusted by the addition of an acid or a base such as NaOH.

The gel of the present invention may also contain other ingredients such as preservatives, colorants, perfumes, deodorants and flavors. Flavors may be particularly important if the substance itself does not have a pleasant taste. Phospholipids derived from soybeans sometimes have an unpleasant taste.

Unlike other gel formulations, the semi-solid gel phospholipid formulations of the present invention suitably contain no additional thickeners, emulsifiers, consistency modifiers or other gel-forming agents. Specifically, the gels suitably contain no other gelling agents such as acrylates, cellulose derivatives, starch and starch derivatives, gelatin and alginates.

Except . of the said components, the gels of the present invention contain water up to 100% by weight. For pharmaceutical compositions, it is necessary to use water purified according to the pharmacopoeia.

The gel of the present invention is particularly suitable for the preparation of cosmetic or pharmaceutical compositions. Amounts of cosmetics or pharmaceuticals incorporated into phospholipid · · 4

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4 gels for this purpose may vary considerably depending on the substance. Those skilled in the art will readily determine appropriate concentrations, for example, as a function of the active ingredient's efficacy and the intended purpose of using the gel obtained. For example, acyclovir may be incorporated into the composition, for example, in an amount of about 5% by weight, diphenhydramine hydrochloride in an amount of about 1% by weight, hydrocortisone in an amount of about 0.25 to 1% by weight, sodium heparin in an amount of 60,000 I.U. and calcitonin in an amount of 100,000 I.U. Other possible active compounds and amounts of active compounds are set forth in the examples.

A suitable gel base composition of the present invention for pharmaceutical compositions comprises about 23.5 wt% phospholipid, about 22.5 wt% propylene glycol, about 5 wt% ethanol, about 2.5 wt% sorbitol, BISTRIS at a concentration of about 1.57 wt% , an appropriate amount of the active compound and water up to 100% by weight.

The cosmetic and pharmaceutical compositions of the present invention are suitable for application to the skin or mucosa, such as the skin of the lips or mucous membrane in the mouth. However, the phospholipid gel compositions of the present invention may also be advantageously applied to the nasal mucosa, where the method of suppressing the liquid of the gel of the present invention is particularly advantageous because moisture is present in the nose and salts present in the nose are present. conventional gels.

However, the phospholipid gels of the present invention can also be applied to other mucous membranes. A suitable cosmetic or pharmaceutical composition may be, for example, a lip gel, nasal gel, ophthalmic gel, vaginal gel or anal gel, such as a hemorrhoid gel or gel for treating anal ruptures.

• to • 4 ·· ··.

• to · • * • to to to ·

The phospholipid gels of the present invention serve primarily for human use. However, these gels can also be used in animals, such as for veterinary medical purposes, particularly in the treatment of dogs, cats or horses.

The gel of the present invention and the cosmetic or pharmaceutical composition of the present invention can be prepared by mixing the ingredients under vacuum or under an inert gas atmosphere. The mixing of the components and the preparation of the gel can be carried out by conventional methods known in the art. The absence of oxygen, which can be achieved in a vacuum or inert gas atmosphere, is advantageous.

The gel of the present invention is preferably a gel with a semi-solid consistency. Gel consistency can be determined by rotary viscometer. For the purposes of the present invention, and especially for the following examples, a rotary viscometer from HAAKE (RheoStress RS 150) is used. Measurements are made at 20.0 ° C using 35 mm diameter measuring plates. The measuring hole is 0.5 mm. The measurement is performed as an oscillating measurement and the shear voltage has a constant frequency (1.0 Hz). During the measurement, the sample is placed in the measuring orifice and the measuring block is set for oscillating motion (desired oscillation) and the function of the sample reaction is measured. A detailed description of the procedure is given in D. Eidman's HAAKE Characterization of Contact Adhesives (PSA Systems).

By this measurement, the storage module G can be determined as a component of the stress energy that can be elastically accumulated by the system, a loss module G as a component of the stress energy that is irreversibly converted by the system into a viscous motion. shear stress τ.

ΦΦ φ · φφ Φ ··· • ·. * ♦ φ * ·· ΦΦΦ ·

The flow limit of a substance or composition is not precisely given. However, one possibility of determining the flow limit is the oscillation measurement described above. At small amplitudes (shear stress τ less than flow limit), the loss angle δ does not depend on τ (viscoelastic range). Due to the higher shear stress, δ increases significantly, which makes it possible to limit viscous behavior. The critical shear stress value of the transition from the linear viscoelastic region to the viscous region can be interpreted as a flow limit (cf. H.-M. Petři, HAAKE publication "Determination of the Flow Limit in Foodstuffs"). This value can be read from the graph where the loss angle δ is plotted against the shear stress τ at the transition of the resulting curve from its horizontal part to the slope part.

The increased flow limit, which is the increased value of the critical shear stress, confirms the increased stability of the measured sample with respect to liquidation. Qualitatively, this increased stability can also be recognized by increasing the maximum of the storage module G on the G curve versus τ. ,

The flowability guide may be. a split where the cosmetic milk has a critical shear flow limit of <10 Pa, a lotion with a critical shear flow limit of 10 to 20 Pa, and a cream critical flow shear limit of typically> 100 Pa. The gel flow limit of the present invention is suitably at a critical shear stress above 20 Pa and particularly suitably between 20 and 200 Pa. Gels with a flow limit at critical shear stress below 20 Pa start to flow according to practical experience with their own weight. Semi-solid gels are mainly those that do not flow by their own weight.

However, it should be emphasized that the above described critical shear stress at the gel flow limit of the present invention has

In addition, it is evident according to the present invention that sugar or alcohol containing gels have a higher liquid stability than conventional gels which do not contain sugar or alcohol. This effect results in a relative increase in the critical shear stress at the flow limit or in a relative increase in the maximum of the storage module G when compared to conventional gels.

The phospholipid gels of the present invention are particularly characterized by the stability of their consistency with respect to the introduction of ingredients such as drugs or buffers, and when applied to the skin or mucosa. The consistency of these gels is so stable that they retain their semi-solid state even when the ingredients are introduced. In addition, they maintain their application properties when applied to the skin or mucosa.

Figure 1A shows the dependence of the loss angle δ as a function of the shear stress τ of a conventional gel (not according to the present invention) with the addition of sodium chloride. No sodium chloride (♦), 0.2% sodium chloride (·), 0.4% sodium chloride () and 0.8% sodium chloride ( ^A ) were used. It is evident from Figure 1A that the shear stress τ changes with increasing sodium chloride concentration.

Figure IB shows the dependence of the storage module G on the shear stress τ of a conventional gel (not according to the present invention) with the addition of sodium chloride. No sodium chloride (♦), 0.2% sodium chloride (·), 0.4% sodium chloride () and 0.8% sodium chloride (^) were used (blank symbols). It is evident from Figure 1A that the shear stress τ changes with increasing sodium chloride concentration.

• ·· ·· ··· 4. 44 4 4 4 4 4 4 4444 444

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Figure 2Α shows the dependence of the loss angle δ on the shear stress τ of a gel of the present invention to which different amounts of sodium chloride have been added. The symbols correspond to Figure 1A.

Figure 2B shows that the gel values of the present invention do not differ greatly with the addition of sodium chloride. The symbols correspond to Figure 1B. The fact that the values do not differ greatly due to the addition of sodium chloride demonstrates the advantage of the gel of the present invention.

Figure 3 shows the dependence of the loss angle δ (solid symbols) and the accumulation module G '(open symbols) versus the shear stress τ of a conventional gel (not according to the present invention) with and without BISTRIS buffer.

Figure 4 shows the dependence of the loss angle δ (solid symbols) and the storage module G (open symbols) versus the shear stress τ of the gel of the present invention with and without BISTRIS buffer.

DETAILED DESCRIPTION OF THE INVENTION

The invention is further illustrated by the following non-limiting examples.

Example 1

In this example, gels of the present invention containing various drugs are prepared. Examples 1.1 to 1.4 show that different drugs have different solubility and the compositions of the present invention can be used at different concentrations.

• · · · · · · · · ·

Gels are prepared having the following composition (unless otherwise stated, percentages by weight):

Example 1.l

acyclovir 5.0% non-hydrogenated lecithin 23.5% propylene glycol 20.0% ethanol 10.0% sorbitol 2.5% phosphate buffer 0,05M water to 100.0 Example 1.2 diphenhydramine hydrochloride 1.0% non-hydrogenated lecithin 20.0% propylene glycol 22.5% ethanol 5.0% mannitol 5.0% water dto 100, Example 1.3 hydrocortisone 0.25% non-hydrogenated lecithin 25.0% propylene glycol 27.5% trehalose 10.0% BISTRIS 0,075M water to 100.0 Example 1.4 ' calcitonin 100 000 non-hydrogenated lecithin 18,0 g

Propylene glycol 25.0 g glycerol 5.0 g sucrose 6.0 g water to 100.0 g

Acyclovir is a substance that dissolves very poorly in water. Diphenhydramine hydrochloride is a hydrophilic substance that dissolves very easily in water as a salt. Hydrocortisone is a lipophilic substance that is more soluble in lipophilic solvents than in water. Calcitonin is a hydrophilic protein that dissolves in water.

This example shows that even with the addition of drugs with very different. solubility to obtain the phospholipid gels of the present invention.

Example 2

Table 1 below lists the compositions of other gels of the present invention. In addition to the base, these gels contain varying amounts of different drugs. The amounts of the individual components are given in% by weight of the total weight of the composition.

Table 1

Drug PL PG EtOH BIS- TRIS Sorbit ol heparin Na 60 000 I.U. 23.5 22.5 5 1.57 2.5 diclofenac at 1% 23.5 22.5 5 1.57 2.5 hydrocortisone 1% 23.5 22.5 5. 1.57 2.5 xylometazoline HCl 0.1% 23.5 22.5 '5. 1.57 2.5 indomethacin 1% 23.5 22.5 5 1.57 2.5

PL = phospholipid (Phospholipon 80); PG propylene glycol; EtOH = ethanol.

Example 3 • 4 4 ·· 4 4 4 4 4 4 ··

4 4 4 · · 4

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When introducing drugs or additives into phospholipid gels, electrolytes are often added to the compositions. In addition, when gels are applied to the skin and especially to the mucosa, electrolytes such as sweating salts dissolve therein. These electrolytes can lead to liquidation of the gels.

This example illustrates the effect of salt addition on phospholipid gel with and without sorbitol. The base gel had the following composition: 23.5% by weight of phospholipids ^PL80,! 22.5% propylene glycol, 5% ethanol, 1.57% BISTRIS, the rest being water.

To this base is added 0; 0.2; 0.4 and 0.8% by weight of sodium chloride, and using the oscillation measurement described generally above, the loss angle δ and the storage modulus G '(not the gel of the present invention) are determined for each base as a function of the shear stress τ. The results of these measurements are shown in Figures IA and 1B. It can be seen that the critical shear stress, which is the shear stress as the curve rises from the horizontal direction, decreases with increasing salt concentration. In addition, the maximum storage module G decreases with increasing salt content. This proves that the gel flow limit decreases with increasing salt content and thus gels with increasing salt content more easily liquid.

Figures 2A and 2B show the results of the same measurement but 2.5% by weight of sorbitol and 0.2 are added to each base; 0.4 and 0.8% by weight sodium chloride. It can be seen that the addition of sorbitol results in an almost suppressed influence of electrolyte on the flow limit and maximum of the accumulation module G.

This experiment demonstrates that the consistency of the phospholipid gels of the present invention remains stable despite the addition of an electrolyte such as sodium chloride.

Analogous measurements were made with the addition of various drugs.

such as acyclovir, heparin Na and diclofenac Na, and various sugar alcohols and sugars like glucose, sucrose, trehalose, xylitol and fructose, wherein they are obtained comparable results. Example 4 - In this example, 23.5% added to the gel base % by weight

phospholipid, 22.5 wt.% propylene glycol, 5.0 wt.% ethanol, and water up to 100.0 wt.% with and without the addition of 2.5% sorbitol, and the effect of this addition on the tendency of the composition to fluidize is monitored.

BISTRIS is added to the formulation as a buffer. The buffer concentration is

1.57% by weight.

The results of the oscillatory measurements described above for sorbitol-free gels (not gels of the present invention) with and without BISTRIS are shown in Figure 3. It can be seen that the value of the accumulation module G 'is reduced in the presence of BISTRIS as well as the critical shear stress .

The results of the oscillatory measurement of sorbitol gels of the present invention with and without BISTRIS are shown in Figure 4. It can be seen that neither the accumulation module G 'nor the critical shear stress is reduced. The measured waveform is almost identical.

This example shows that the addition of sorbitol to the phospholipid gel almost abolishes the tendency of the gel to fluid upon addition of buffer. In this way, a buffer can be introduced into the phospholipid gel in order to greatly increase the stability of the gel and thus its shelf-life.

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Example 5

This example examines the subjective sensation of topical application of the phospholipid gels of the present invention and conventional gels. The composition of the investigated gels is shown in Table 2, compositions A, B, D and F are in accordance with the present invention and composition C without sorbitol serves as a comparative which is not a composition according to the present invention. .

Table 2

AND (B) C D F NAT 8450 20.0 20.0 20.0 5.0 - PL 90 H 7.5 - 7.5 - 6.0 propylene glycol 20.0 30.0 20.0 30.0 20.0 glycerol - 7.5 12.5 - - sorbitol 5.0 10.0 - 10.0 10.0 acyclovir 5.0 5.0 5.0 5.0 5.0

PL 90 H = Phospholipon® 90 H (hydrogenated)

NAT 8540 = 60% solution of Phospholipon 80 in propylene glycol

The quantitative data in Table 2 is% by weight of the total weight of the composition, the remainder up to 100% by weight is always water.

t

The study is performed as follows. Before starting the experiment, both forearms and each patient's index finger are wiped again with a Kleenex handkerchief. After each application cycle (all 6 gels are applied), the application side is wiped with a tissue

Kleenex®. A total of 3 cycles are performed. In each cycle, the patient had a hem of gel on his forearm and rubbed it with his forefinger. 3 devices are applied to each forearm.

The diameter of the gel spread along the forearm is a maximum of 5 cm. The application areas must not overlap.

After each application, patients evaluate spreadability (consistency, cosmetic impression, etc.), the impression of the composition (hypo- / lipophilicity) and the feeling that the application leaves (tack, skin tightness, etc.) and give the composition a ranking by popularity. Number 1 is the best rating, number 6 is the worst.

The test is performed by 13 persons (spreadability and hydro- / lipophilicity) or 11 persons (left feeling).

The evaluation was carried out by a summary screening test procedure (L. Sachs, Statistical Methods, Planning and Evaluation, p. 85), in which the ranking assigned by each individual for each criterion (target criterion) is summed (rank sum) and compared to each other. The lower the sum of the order means the device is more popular than others and vice versa.

The results of this research are shown in Table 3. For each composition of A-F, the ranking for the target criterion (I = spreadability, TI = hydro- / lipophilicity, III = left feeling) assigned by each person (1-13) is shown. For example, Person 1 had as a favorite a composition C (rank 1) in assessing spreadability (target criterion I) and rated E as worst (rank 6). In addition, the standard deviation (sdv), the sum of the rankings (T = sum of all rankings) and the number of evaluators (j) are given for each composition and each target criterion.

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(μ III 40 U> rd Fd <N 1 * 1 fd IN <N rd 04 / t * rd O fa rd rt w H 10 rt W rd rd rd pď 40 w 10 rd 40 04 / rd 04 / CN ra Fd IM m Fd 10 iN rd •and NP rd fN rd 40 10 fd 40 04 / r ^ 40 on ra rd W H • h H w CN 40 CN 10 ra rd W na cn r1 O fN Γ- η rd p-4 M H 40 Λ ra 40 ra 40 ra «R w 40 · < ra fN fN * rH 40 40 ra rd H 40 40 Φ 40 40 40 40 40 40 40 40 ar 40 40 40 O rd Γ- ca pN 0 ►d W H ra 40 Γ0 10 40 rd 40 *E <N 40 40 CN r- rd 40 W Fd rd W H CN CN CN Í * J 10 W 40 40 (0 10 W < on 01 ra rd w ca • d H in CN CN W * 40 40 ra ca rd ra rd ra CN rd 40 rd O and· *and rd O M H H * d <* 5 10 «4 rd in <N on 40 ra rd 40 on f4 rd H M Fd «0 w · 40 <N it 40 40 40 w 40 40 w 40 40 rd 40 10 ra rd W rd (0 rd m CN 40 40 40 ra CN ra 40 r · rd r- <T ra rd PS H H H ŤN rd CN ca ca 40 40 ra 40 rd 04 / Γ- η 40 n rd Fd TO H ca 40 ÍM • r 40 CM CN ca CN ca CN 10 ua ï on rd 40 « on "E ca rd H ru w on fN ra 40 rd (N 10 «Ρ NP CN • d ua ra on rd 40 WHAT n ra rd M ►d Op 4Γ > 0 CN 40 CN 40 N> IN ua 10 on rd r * rd rd M H in 40 40 w 40 40 CN rd CN rd CN n fN 40 40 oa rd * 0 ua Ν ’ n rd M n on W ra IN 10 pM r-1 CN ra fd NP 40 IN ra ra ♦ d 40 O «R n rd <c '«Pra rd fN ra n · 10 40 P- WHAT m O rd rd rd CN rd _ ra rd > 03 / w • m

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For the sake of clarity, the results from Table 3 are presented again in Table 4, where they are categorized according to target criteria (T = ranking sum, j = number of persons) (ti λ:

«—I 3 X3 (ti E-«

here 30 ¹¹ P Ή O AT ρ γ — ί 0 and 0 and η 40 Ρ rM '> 1 Ο Ό · rH β β p O Φ ο 9-4 η Ρ β β Ν Ό r — 1 οα «*> r-t Η Η Η Ρ γΗ ρΗ σν η here <Ν Ρ β 4J ω m η ι — 1 m Ρ • Η 4-1 Ο «Φ η and ο rd • Η ι — 1 ι ο Ό Γ *) ο m ρΗ β Hyd « ιη (* Ί 13 Η Η σι m ρΜ here ΙΟ η σ> Ρ 4J Μ 1-1 ρ ω η- r-t ο ri Γ — ι ο 13 (D α Ρ (ΰ β ρ 'Η Ρ τΗ Ρ AT Τ Ν Ο 04 / ιη ρ CQ 00 Ρ Η η ιη ο r-i Ει ♦ Γΐ

'Η ΓΊ G , (ti β > 1 ρ I.E I — 1 34 • β 'rd 0 b ο > Ό β 0 0 rH and and '> 1 Μ b β Ή 0 β β > \ ω Ρ υ \ β Η β β β Ρ φ β Ρ 34 Ρ β 0 ω 34 Ν β -π Ρ > β b β β β β -ΓΙ ω Ρ ο 0 β 4β Ρ η β > ω • rd ο 'β and Ρ 34 0) β I — 1 01 I — 1 0 κΊ 'β ω Ρ Ν > Ν > Ν κΐ β Ρ ι — 1 Ρ b κ 'Ί 0 34 Ρ > ί> -ι β γΗ H β > β tn , β \ ι— | Ν κι Μ > ω ω and ι — I \ β β 'β β Ρ β 'β G β \ β 'β > > β 34 0 34 β ο β Ρ ρ 0 Η 'β and G β ιβ β > β —- η 'β > Ο β β 1—1 fc β Ν 34 > β b β β AND-[ Φ Ο 'β > β ο 34 β and ω ι — 1 « Η E* 0 b AT Ρ Ο 'β and β «Β β > 1 34 β b and. b -β 'β ω β β Ρ tn I — t Ρ 34 Ρ Ο b 'β Ν β β β > Ρ > β ω > Ν 1 ι — 1 -β -β OF β and β Ρ ω Ρ Ρ b 01 01 0 ω 0 and > Ν β • β Ρ G β β 4β 34 Ρ Ρ β b > 0) β b β b β β > β • β 'Ρ > Ρ > Ρ β ω Ν 01 0 ω Ο ο β b β b and

• 9 9 99 99 9 9 9 99 9 9 9 9 9 9 9 9 9 9 9 9 9

999 9999 99 99 9 »9999

14ί / Ιΰΰΐ- S14

Claims (23)

PATENT CLAIMS A phospholipid gel comprising 5 to 60% by weight of at least one phospholipid; at least 1% by weight of at least one di- or trihydric c _{2. 4} -alcohol; 0.5 to 35% by weight of at least one tetra-, penta- or hexahydric alcohol and / or at least one sugar; and optionally one or more additives and water up to 100% by weight, wherein the weight% is in all cases a proportion of the total weight of the gel. Phospholipid gel according to claim 1, characterized in that the sugar is a mono-, di- and / or oligosaccharide. 3. A phospholipid gel according to claim 1 or 2, characterized in that the phospholipid contains at least 70% by weight of phosphatidylcholine of the total weight of the phospholipid. 4. The phospholipid gel of claim 1, wherein the phospholipid is a non-hydrogenated phospholipid having a phosphatidylcholine content of at least 70% by weight based on the total weight of the phospholipid. 5. A phospholipid gel according to claim 4, wherein the phospholipid is a mixture of phosphatidyloholine and lysophosphatidylcholine and that the mixture comprises at least 75% by weight of phosphatidylcholine. The phospholipid gel of claim 1 or 2, wherein the phospholipid is a hydrogenated phospholipid containing at least 90% by weight of phosphatidylcholine. • ·· ·· * ··· 11 · ♦ 91 9 9 1 9 9 9 9 9 1 1 9 110 9 1 1 119 11 119 ·· 1 1 11 ·· 1 · 1 111 9199 ·· ·· ·· ···· Phospholipid gel according to any one of claims 1 to 6, characterized in that it contains 5 to 35% by weight and preferably 15 to 25% by weight of at least one phospholipid. 8th phospholipid gel as claimed in any of claims 1-7, characterized in that the di- or trihydric c _{2. The 4-} alcohol is propanediol, especially propylene glycol, glycerol or a mixture of these alcohols. 9th phospholipid gel as claimed in any of claims 1-8, characterized in that it contains 1-40% by weight and preferably 15 to 40% by weight of at least one di- or trihydric c _{2. 4} -alcohol. 10. Phospholipid gel according to claim 9, characterized in that it contains 15 to 30% by weight of propylene glycol and 0 to 10% by weight and preferably 2.5 to 7.5% by weight of glycerol. A phospholipid gel according to any one of claims 1 to 10, wherein the tetra-, penta- or hexahydric alcohol or sugar is selected from the group consisting of glucose, fructose, sucrose, trehalose, xylitol, maltitol, inositol, sorbitol and mannitol. Phospholipid gel according to any one of claims 1 to 11, characterized in that it contains 2 to 20% by weight and preferably 2.5 to 10% by weight of at least one tetra-, penta- or hexahydric alcohol or sugar. in A phospholipid gel according to any one of claims 1 to 12, characterized in that it comprises a pharmaceutically active compound selected from the group consisting of 9999 9 9 9 9 9 9 9 9 9 9 9 9 9 9 99 9 9999 9 9 9 9 ·· ··· * anti-inflammatory agents, non-steroidal anti-inflammatory drugs, corticosteroids, peptides, hormones, enzymes, nucleic acids, virostatics, vitamins, local anesthetics, antifungals, antibiotics, antipsoriatics, blood-enhancing agents, and- sympathomimetics and nasal drops. A phospholipid gel according to any one of claims 1 to 13 comprising a pharmaceutically active compound selected from the group consisting of acyclovir, heparin, diclofenac, hydrocortisone, xylometazoline, diphenhydramine, calcitonin, cyclosporin, indomethacin and insulin. A phospholipid gel according to any one of claims 1 to 14, characterized in that it contains up to 15%. 10% by weight of at least one alcohol selected from the group consisting of ethanol, 1-propanol and 2-propanol. A phospholipid gel according to any one of claims 1 to 15, characterized in that it comprises at least one buffer with a high buffering capacity in the range of pH 5.5 to 8.0 and preferably at a pH of about 6.5. 17. The phospholipid gel of claim 16, wherein the buffer is selected from the group consisting of BISTRIS, phosphate buffer, bicarbonate buffer, maleate buffer, HEPES, TRIS, and MOPS. A phospholipid gel according to any one of claims 1 to 17, characterized in that it does not contain further thickeners, emulsifiers, consistency-adjusting agents and / or gelling agents. • 4 4 44 4 4 «4444 44 · • 4 4 4444 4 4,444 · 4,444 444 4444 4 · ·· ·· ···· A cosmetic or pharmaceutical composition comprising a phospholipid gel according to any one of claims 1 to 18. 20. Cosmetic or indicative application. The pharmaceutical composition according to claim 19, characterized in that it is for topical use 21. A cosmetic or pharmaceutical composition according to claim 19 which is a lip gel, nasal gel, eye gel, vaginal gel or anal gel. Use of a phospholipid gel according to any one of claims 1 to 18 for the preparation of a cosmetic or pharmaceutical composition. A process for preparing a phospholipid gel according to any one of claims 1 to 18 or a cosmetic or pharmaceutical composition according to any one of claims 19 to 21, characterized in that the gel is prepared by mixing the components under vacuum or under an inert gas atmosphere.