MXPA00011082A - Biologically active composition - Google Patents

Abstract

The invention relates to a novel biologically active composition which comprises a biologically active agent to be released therefrom, said biologically active agent being dissolved and/or dispersed in a supersaturated state within a carrier, which carrier comprises a liquid and/or solid non-crystalline ester and/or polyester matrix, and where the precipitation of said biologically active agent is substantially, or completely, inhibited therein. Said supersaturated state is obtainable by subjecting one or more carrier starting substance(s) to such chemical reaction(s) that an ester and/or polyester matrix is provided,the biologically active agent being added after said chemical reaction(s) has (have) been completed.

Description

BIOLOGICALLY ACTIVE COMPOSITION Field of the Invention The present invention relates to a biologically active composition from which one or more biologically active components can be released. More specifically, the invention relates to a biologically active composition wherein the biologically active agent is present in a supersaturated state within a carrier without being precipitated therefrom.

Background of the Invention From the points of view, among others, toxicological, it is often preferred, during the treatment of diseases or symptoms thereof, to release drugs directly to their site (s) of action. It is well known that the risk of detrimental effects of systemic origin are often markedly reduced if the drug is released directly at its site (s) of action. In addition, the release Ref: 124947 systemically frequently involves the metabolism of the drug before it appears at the site of action, leading to a subsequent reduction of its biological effect. Another important aspect is that in, for example, cases of an impending overdose, allergic reactions or administration of contraindicated drugs, it is easy to remove topical compositions in contrast to drugs administered orally or by injection.

As used herein, topical administration comprises, among others, dermal, sub-lingual, gingival, buccal, transdermal, nasal, vaginal and rectal administration, therefore the resulting biological effect may be local and / or systemic.

In administration, for example, dermal, nasal, vaginal, buccal or sub-lingual, only a very limited number of drugs are able to penetrate the human body by themselves to a useful ratio. Consequently, a portion of resources have been conducted in order to investigate the possibility of both improving the traditional non-invading release techniques and developing drug delivery systems that do not invade novel or devices intended for systemic or internal use. Three fundamentally different approaches towards this objective have been described.

First, the possibility of improving the penetration properties of the drug by the chemical modification thereof is well known. After the drug has the whole body, its pharmacologically active form is obtained by chemical reaction (s) in vi vo. However, this so-called pro-drug procedure is only occasionally a successful alternative. Therefore these are several reasons, such as i) the penetration range of the pro-drug may still be very low, ii) the pro-drug may be toxic or otherwise harmful, or iii) the conversion in vi vo of the active form of the drug is very slow and / or partially results in inactive or toxic compounds. A distantly related procedure is the preparation of an even ion between a drug and an opposite ion. However, generally such an even ion exhibits no markedly improved penetration range through human barriers.

Second, the properties of the barrier may change in order to facilitate drug release. The methods for executing this are, for example, ultra-sonication, application of electric current or the use of putative increases in composition penetration. All these methods act by breaking the structure of the barrier, thereby facilitating the diffusion of the drug through the barrier in the body, and / or improving the solubility of the drug in the barrier. However, methods involving, for example, heat, ultrasonication and electric current, are generally not designed to be easily handled by the patient in a convenient manner, and therefore require hospitalization, which is a major disadvantage with such methods. In addition, all methods that are based on the procedure of changing the properties of the barrier are questionable from a toxicological point of view due to the observations that i) adverse effects on barrier cells have been demonstrated, and ii) a reduction in the protective properties of the barrier also results in an increased penetration range by any substance, not only the drug, which is present at the site of administration, it should also be mentioned, that most of the penetration enhancers Known chemicals require some time to initiate their action, that is, they exhibit a delay in the action time, since these must be established in the barrier before the current increase in the penetration range is observed.

Third, the force of handling the drug to enter the body can be changed. That is, the difference in the electrochemical potential of the drug between the reservoir of the drug and the body can be increased. Drug delivery systems based on this procedure result in a high flow of the drug through the barrier and usually also exhibit a reduction in the time delay of action.

In iontophoresis-based methods, this procedure is used by applying an electric potential gradient around the barrier. Obviously, these methods are mainly suitable for drugs that have a net charge and are therefore much less efficient for uncharged and heterotonic species, since the flow of the last two species improves mainly due to, for example, driving forces osmotic and electroosmotic. Iontophoresis methods also have the disadvantage that they can alter the structure of the barrier.

In another procedure, the flow of a drug in the body can be increased by increasing the chemical potential of the drug in the carrier thereof. This is usually performed by the chemical optimization of the drug composition by adjusting the degree of saturation of the drug in said carrier. The methods based on this method offer several disadvantages compared to the previously mentioned methods, since the flow of the drug increases in comparison with the unsaturated and saturated systems. In addition, the properties of the barrier itself are comparatively less affected and the delay time of onset for the pharmacological effect is reduced. These are two particularly important aspects in this procedure: i) the creation of a high initial chemical potential of the drug in the composition i i) the maintenance of a high chemical potential of the drug in the vicinity of the barrier after application of the composition.

Therefore, it is usually desirable to prepare pharmaceutical compositions that are saturated with respect to the drug. During the application, another important aspect of said composition is that the solubility and diffusion properties of the drug in the used vehicle can prevent the decrease of the drug in the vicinity of the barrier. Examples of compositions used for these purposes are microemulsions and emulsions.

Another method aimed at maintaining the saturated composition is the use of an excess amount of the drug (not solubilized) in the carrier, therefore the drug is subsequently dissolved by replacing the drug that has penetrated through the barrier.

Yet another method is the use of a supersaturated composition of the drug. Here, the force of drug handling to penetrate the barrier is greater than in the saturated composition, since the drug in a supersaturated composition has a greater chemical potential as compared to the corresponding saturated composition. For example, such compositions are prepared in accordance with the following meanings or principles: i) dissolving the drug at temperatures and / or pressures in which the solubility of the drug is greater compared to those temperatures and / or pressures that are relevant to the medication (WL Chou and S. Riegelmann, J. Pha rm Sci., Vol 60, No. 9, pages 1281-1302, 1971, WO 97/10812, ii) the use of solid dispersions or eutectic mixtures or drug particles. solid of low degree of crystallinity or high energy polymorphs ((WL Chou and S. Riegelmann, above), iii) mix a solution of the saturated drug with a non-solvent of the same, therefore executing a purely physical operation, in situ or before its application, with or without the presence of an antinucleating agent (US 4 940 701; US 4 767 751), iv) evaporation of the solvent in the surrounding air (Coldman et al., J. Pharm. Sci., 58, No. 9 (1969), pages 1098-1102), v) penetration n of the solvent in the human body, vi) incorporation of water in the composition of the human body, vii) changes of the pH in the composition caused by the incorporation of H + - of the human body, or viii) dispersing an aqueous solution or emulsion of a drug in an aqueous dispersion of a latex polymer (Lichtenberger et al., "Polymer films from aqueous polymer dispersions as carriers for transdermal delivery of lipophilic drugs", 15th Int Symp CRS: Basel 1988; Summary 89). An important common denominator of iv) -vii) is that supersaturation is not present initially in the composition, and is therefore, in fact, not realized until the composition is applied to the human body. In addition, a major problem with all compositions i) -viii) is that the drug generally precipitates in a relatively short time, in which case the degree of saturation becomes markedly reduced.

DD 217 989 describes a supersaturated composition, wherein the carrier matrix is an acrylate (Scopacryl D), optionally in combination with an excipient, whose matrix is claimed to prevent recrystallization of a supersaturated drug present therein.

.L. Chou and S. Riegelmann (J. Pha rm. Sci., Vol. 58, No. 12, pages 1505-1510, 1969) have reported that in the matrix of polyethylene glycols of high molecular weight, the precipitation of a dissolved supersaturated drug in it it is usually slow.

Another prior art of interest is the WO 97/10812, which describes a method for the preparation of supersaturated systems controlling the fusion of a mixture of a drug and a polymeric carrier material.

GB 2 306 885, which describes a composition, wherein the supersaturated state is reached in an aqueous matrix carrier can also be mentioned.

As a prior art, reference is also made to WO 97/00670, which describes a composition based on ingredients similar to those used in the present invention. However, said reference does not disclose or suggest any supersaturated state or even less those features of the present invention that have been found to be crucial in imparting a supersaturated, stable state to such a composition.

In summary, none of the above techniques describe or suggest the essential characteristics of the supersaturated composition of the present invention.

Brief description of the invention.

The inventors have now found a novel process for obtaining a biologically active composition that provides both unexpected stability and a high rate of release of a supersaturated active component present therein. In accordance with the disclosed invention, a biologically active agent is present in a substantially stable supersaturated state within a carrier thereof.

Briefly, it has been found that by subjecting the carrier starting substance (s) to such chemical reaction (s) in which a carrier matrix of substantially non-crystalline, or amorphous nature, is Thus, the carrier matrix thus obtained has the property, among others, of maintaining a biologically active agent in a surprisingly stable supersaturated state. In a biologically active composition thus prepared, the precipitation of said agent is substantially, or completely, inhibited by said carrier matrix by itself.

The term "biologically active agent", as used herein, also comprises such progenitors thereof which are readily transformable, eg enzymatically and / or hydrolytically, to a biologically active agent by itself.

In this manner, the present invention relates to a novel biologically active composition comprising a biologically active agent to be released therefrom, said biologically active agent being dissolved and / or dispersed in a supersaturated state within a carrier, which carrier is a matrix liquid and / or solid substantially non-crystalline, and where the precipitation of said biologically active agent is substantially, or completely, inhibited therein.

The term "liquid" as used in conjunction with the present invention is interpreted in a broad sense, seen as any material that is a viscous or mobile liquid, rubber, glass or plastic; in this way including solutions, creams, pastes, ointments and gels within the scope of the claims.

The present invention also relates to a method for the preparation of a biologically active composition comprising a biologically active agent dissolved and / or dispersed in a supersaturated state in a carrier thereof as well as said composition for use as a medicament.

The term "pharmaceutically active agent", as used herein, also comprises such progenitors, for example, pro-drugs, which are readily transformable, for example, enzymatically and / or hydrolytically, to a pharmaceutically active agent by itself.

One of the objects of the present invention is thus to provide a supersaturated composition which exhibits no significant precipitation or loss of effect during a long storage time at room temperature, or even above or below room temperature, during, for example, months. or even years.

Another object of the present invention is to provide a supersaturated composition that exhibits no significant precipitation or loss of effect during its application to a human or animal patient.

Still another object of the present invention is to provide a carrier matrix that is suitable in the preparation of a composition having a particularly high degree of supersaturation of a drug (seen at the top).

A further object of the present invention is to provide a carrier matrix that is particularly suitable for achieving supersaturation of biologically active agents that are sensitive to hydrolysis in water-based carrier matrices or otherwise are chemically and / or physically unstable.

Yet another object of the present invention is to provide a stable supersaturated composition that is easily handled and does not require professional assistance during the use thereof.

As a result of the high release range of its active component (s), still another object of the present invention is to provide a composition that allows for an efficient topical treatment, preferably dermal or transdermal, the administration to small areas, which is a general advantage in the topical administration of drugs. BRIEF DESCRIPTION OF THE FIGURE Figure 1. Shows the amount of permeated piroxicam of the X1-X4 cappositions as a function of the concentration of piroxicam.

Detailed description of the invention.

More specifically, the invention relates to a biologically active composition comprising a biologically active agent dissolved and / or dispersed in a carrier thereof, wherein said carrier comprises, or is, a liquid ester and / or substantially non-crystalline solid and / or a polyester matrix in which said biologically active agent is present in a supersaturated state and, the precipitation of said biologically active agent being substantially, or completely, inhibited in said matrix.

Said supersaturated state is obtained by subjecting one or more carrier starting substances to such chemical reaction (s) that provide a non-crystalline ester and / or a polyester carrier matrix, with a biologically active agent being added after which said chemical reaction (s) have (have) been completed.

Other preferred embodiments of the claimed composition can be defined in the claims and are referred to below in connection with the method.

Thus, the present invention also discloses a method for the preparation of a biologically active composition comprising a biologically active agent dissolved and / or dispersed in a carrier thereof, wherein: a carrier starting substance, or a mixture of two or more different starting substances, is (are) subjected to such chemical reaction (s) in which a non-crystalline liquid and / or solid ester and / or a polyester carrier matrix is formed, the biologically active agent being added to said carrier matrix after said chemical reaction (s) have been (have) been completed and in such an amount that a supersaturated state is obtained. Generally, this means that the reaction (s) that form the ester or polyester are (are) performed in the absence of said biologically active agent, after said agent is added to said non-crystalline matrix formed; the addition of said biologically active agent is done using an amount such that a supersaturated state is obtained.

In a preferred embodiment of the invention, said biologically active agent is added in a solid and / or liquid state, this is dissolved, and is subsequently dissolved in said non-crystalline matrix, preferably above room temperature.

In another embodiment of the invention, said biologically active agent is added to a solution or dispersion, which subsequently dissolves in said non-crystalline matrix, preferably above room temperature.

In yet another embodiment of the invention, said biologically active agent is added in the form of a high energy polymorph thereof, which subsequently dissolves in said non-crystalline matrix.

In accordance with the present invention, above the ambient temperature is a temperature above about 25 ° C, such as around 25-200 ° C, preferably around 30-150 ° C. Examples of other suitable temperatures are around 35-100 ° C and 40-80 ° C.

The particular addition method used for said agent can be any common inclusion technique available to a person skilled in the art, and said solution or dispersion of the biologically active agent can be prepared, inter alia, by evaporation of the solvent, freeze drying or using any of the methods i) -vi i) (seen above).

Preferably, in the composition according to the invention as well as in the method for the preparation thereof, the non-crystalline formed ester and / or the polyester matrix is used as a solvent or dispersing medium.

Said chemical reaction (s) generally comprises one or more esterifying reactions.

Said carrier substance (s), which are subsequently subjected to said chemical reaction (s) above (s), are selected from monomers, such as diacids, triazides and major acids, alcohols, including diols, triols and major alcohols, saccharides and derivatives thereof, acrylate saccharides, including acrylate starch, and oligomers, polymers or pre-polymers thereof.

It will be understood by a person skilled in the art, that said chemical reaction (s) are made to such a degree of completion that a non-crystalline ester and / or desired polyester carrier matrix is obtained, which matrix is optimal for a particular biologically active agent in a particular context. As a non-limiting example, said non-crystalline ester and / or polyester carrier matrix may contain a minor amount of starting substance (s), and is still within the scope of the present invention.

In a preferred embodiment of the present invention, the carrier starting materials are an acid and an alcohol, preferably citric acid and propylene glycol, said non-crystalline matrix comprising an ester and / or a polyester thereof.

In an alternative embodiment, the starting substance is only a bi- or multi-functional substance, which when subjected to said chemical reaction (s) provides the desired non-crystalline carrier matrix by chemical reaction (s) (s) with itself. In a non-limiting description, such a starting substance can be citric acid, which when subjected to esterification conditions provides a non-crystalline citric acid ester and / or polyester matrix according to the invention.

In another embodiment of the invention, an ester and / or a polyester are (are) subjected to such (such) chemical reaction (s), for example hydrolysis, which provides a non-crystalline ester and / or a matrix polyester carrier, after which a biologically active agent is added in an amount such that a supersaturated composition is obtained.

In accordance with. the present invention, the appropriate chemical reaction (s) involves (s) subjecting said carrier starting substance (s) to such esterification conditions that are normally used, in accordance with the standard reference literature, for the selection of the starting substance (s) or combinations thereof. In addition, such esterification conditions are chosen in order to optimize the manufacturing process, with respect to, for example, manufacturing time and achievable degree of supersaturation., for the particular biologically active agent used. Typically, said conditions comprise, for example, subjecting said carrier starting substance (s) at a temperature from about -50 ° C to about 300 ° C, preferably around 0-150 ° C. Other examples of useful temperature ranges are 20-100 ° C and 50-80 ° C. Said temperature ranges are particularly preferred when the starting substances are mixed with citric acid and propylene glycol. Naturally, said chemical reactions are selected and executed so that in each case the maximum or optimum range of release of said biologically active agent is obtained.

Preferably, said chemical reaction (s) are (are) performed for a period of time from 1 minute to 6 months, preferably from 0.5 hours to 4 months. As an example, said period of time may also be from 1 hour to 3 months or from 1 to 2 months.

In accordance with the present invention, monofunctional monomers can be introduced into said chemical reaction (s) as a means to control the endpoint of the reaction (s).

It is worth mentioning that the regulation of the molecular weight, and the distribution thereof, of the molecules that constitute the non-crystalline matrix formed allows controlling the solubility of the biologically active agent in said matrix. The molecular weight distribution is probably also of importance for the range of diffusion of said agent through said matrix.

Preferably, the biologically active composition according to the invention consists solely of a liquid or solid phase.

Non-limiting examples of biologically active agents, preferably pharmaceutically active agents, which are suitable for use in the present invention are, for example, guanosides, corticosteroids, psychopharmaceutical hormones, oxicams, peptides, proteins as well as agents selected from the group of antibiotics, antivirals, antimicrobials, anti-cancer agents, anti-fungal, estrogen, anti-inflammatory agents, neuroleptic agents, melanocyte stimulants and stimulants of the gland, preferably stimulators of the sebaceous and pilo-sebaceous glands, and agents with an effect on the barley cell secretion.

In a more preferred embodiment of the present invention, the carrier starting substances are subjected to an esterification reaction without the presence of said biologically active agent. To the non-crystalline ester and / or polyester matrix thus obtained, a biologically active agent is added in the solid state and subsequently dissolved at about room temperature. When the composition thus prepared is allowed to reach room temperature, a stable supersaturated composition is thus prepared.

For some biologically active agents it is preferred to prepare a small supersaturated composition prior to administration thereof. Indeed, the present composition is useful for such preparations as well as being suitable for supersaturated compositions intended for a long storage and application time. As for the choice of an appropriate degree of supersaturation of the biologically active agent in the present composition, it is known from the laws of thermodynamics that within a given period of time the danger of precipitation increases with the degree of supersaturation. Still, the present composition is also suitable in such particular preparations where a high degree of supersaturation is desirable, although the danger of precipitation is increased a little.

The scope of the present invention is not limited to the specific embodiments described above, and the described invention may, optionally, be combined with methods i) -vi i) (seen at the top) in any desired manner, if considers necessary in any particular case. As a non-limiting example, the pH of the composition prepared according to the invention may optionally be subsequently modified by the inclusion of an appropriate acidic or basic compound, if used in a particular context.

The following non-limiting example illustrates the present invention further.

Experimental part Reference composition An excess of piroxicam was added. to PEG400, and the mixture was stirred for 2 weeks at room temperature. After sedimentation and centrifugation, the HPLC analysis showed that the resulting solubility of s = 1.6% was obtained. Four supersaturated piroxicam solutions in PEG400 were then developed, each of which had a degree of saturation (DS = concentration / solubility) of 1.4, 1.8, 2.3 and 2.7, respectively. These were prepared by heating the corresponding amount of piroxicam in PEG400 to 80 ° C for 30 minutes under agitation, followed by equilibration at room temperature, thereby yielding supersaturated solutions. The precipitation time (tp) of the piroxicam to occur during storage at room temperature was observed by visual inspection, and the results are shown in Table 1.

Table 1. Piroxicam precipitation time: from a supersaturated solution thereof in PEG400.

* DS = ligual at 1.6% (w / w) of piroxicam in PEG400 (seen at the top).

Composition according to the invention A composition was manufactured by mixing 6 parts of citric acid and 4 parts of propylene glycol (starting substances) at room temperature in a glass vessel which was subsequently sealed. The temperature was raised and maintained at 80 ° C under agitation for 2 hours. The mixture was then allowed to reach room temperature, then subjected to 70 ° C for 26 days, freezing temperature for 235 days and finally room temperature for 1 day. The resulting mixture was a clear, viscous and almost colorless solution. The procedure outlined above resulted in the formation of ester bonds between citric acid and propylene glycol, thereby forming an ester carrier matrix. In accordance with HPLC analysis, said solution (ie, the carrier matrix) had a non-reactive citric acid content of only 4.5%.

Said solution was split into 4 separate solutions, each of which was added an appropriate amount of piroxicam (see Table 2), followed by heating at 97 ° C for at least 30 minutes or until all the piroxicam dissolved. After reaching room temperature, the supersaturated compositions X1-X4 were obtained, and their tD values were investigated.

Table 2. tp value for supersaturated piroxicam in compositions X1-X4 (s = weeks) * The saturation permeation range is assumed to be 82μg per 24 hours.

The DS values shown in Table 2 are obtained using the Franz cell diffusion measurement, and for a person skilled in the art, it is well known that the range of permeation of a compound through a Silastic membrane in a diffusion experiment Franz cell is a direct measure of the thermodynamic potential of said compound. On the other hand, a direct correlation between the thermodynamic potential and the degree of saturation (DS) can often be assumed. Therefore, the equation DS = permeation range / permeation range in saturation It is assumed to be valid when the DS values are estimated.

As can be seen in Table 2, the tp value for all compositions X1-X4 exceeds 2 weeks. At the time of presentation of the present application, no precipitation has yet been observed in compositions X1-X3. Indeed, the experiments described in Table 2 justify the precipitation prevention properties of the carrier matrix according to the present invention, particularly in comparison with the experiments described in Table 1 above.

In addition, the increased degree of supersaturation of piroxicam in compositions X1-X4 results in an increase in the permeation range, that is, an increased thermodynamic potential. This is evidenced by the investigation of the peroxicam permeation range through the membrane (Silastic NRV savanna, 0.005 inches (0.127 mm), series # SM097307) using Franz cell diffusion (FDC-400 Crown Glass Comapny) with an area of open cell of 2.001 cm2. The measurements of the permeation range were made for 24 hours at 25 ° C and a mixture of 7: 3 (w / w) of PEG400 / H2O was used as the acceptor phase on the opposite side of the membrane. The donor and acceptor phases were both sealed with paraffin, and each experiment was run in triplicate. As a reference, the permeation range from a saturated propylene glycol solution of the piroxicam was determined to be 82 μg per 24 hours in the Franz cell diffusion experiment. The results are shown in Figure 1 below.

In summary, it is clearly seen that the biologically active compositions that are prepared or obtained in accordance with the present invention are useful as medicaments. In addition, the biologically active compositions according to the invention are also useful in a non-medical context, such as in cosmetic products for the skin. More specifically, said compositions are highly efficient in dermal application to a mammal, preferably man, as well as in any general application where a biological barrier is penetrated by a biologically active agent.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Having described the invention as above, the content of the following is claimed as property.

Claims (22)

Claims

1. A biologically active composition, characterized in that it comprises a biologically active agent to be released therefrom, the biologically active agent being dissolved and / or dispersed in a carrier thereof, wherein the carrier comprises a non-crystalline liquid ester and / or a matrix of polyester to which the biologically active agent has been added to be in a supersaturated state.

2. The composition according to claim 1, characterized in that the supersaturated state is obtained by subjecting one or more carrier starting substances to such chemical reactions in which a non-crystalline liquid ester and / or a polyester matrix is formed, the biologically active agent being added to the liquid matrix after the chemical reactions have been completed.

3. The composition according to claim 2, characterized in that the non-crystalline ester and / or the polyester matrix acts as a solvent or dispersing medium for the biologically active agent.

4. The composition according to any of claims 2-3, characterized in that the biologically active agent is added as a solid and / or liquid that subsequently dissolves in the matrix, preferably above room temperature.

5. The composition according to any of claims 2-3, characterized. because the biologically active agent is added as a solution or dispersion which dissolves subsequently, preferably above room temperature.

6. The composition according to any of claims 2-3, characterized in that the biologically active agent is added in the form of a high energy polymorph thereof or as a solid with a low degree of crystallinity.

7. The composition according to any of claims 2-6, characterized in that the biologically active agent is added and / or dissolved at a temperature of about 25-200 ° C, preferably around 30-150 ° C.

8. The composition according to any of claims 2-7, characterized in that the chemical reactions comprise one or more esterification reactions.

9. The composition according to claim 8, characterized in that the esterification reactions are selected and executed to provide a range of optimal release of the biologically active agent.

10. The composition according to any of claims 2-9, characterized in that the chemical reactions involve subjecting the carrier starting substance at a temperature from about -50 ° C to about 300 ° C, preferably around 0-150. ° C.

11. The composition according to any of claims 2-10, characterized in that the chemical reactions are conducted for a period of time from 1 minute to 6 months, preferably from 0.5 hours to 4 months.

12. The composition according to any of claims 2-11, characterized in that the starting substance, or a mixture of two or more different carrier starting substances, is selected from acids, such as diacids, triazides and major acids, alcohols, including diols, triols and major alcohols, saccharides and derivatives thereof, acrylate saccharides, including acrylate starch, and oligomers, polymer or pre-polymers thereof.

13. The composition according to claim 12, characterized in that the acid is a monomeric acid and the alcohol is a monomeric alcohol.

14. The composition according to claim 13, characterized in that the monomeric acid is citric acid.

15. The composition according to any of claims 13 and 14, characterized in that the monomeric alcohol is propylene glycol.

16. The composition according to any of the preceding claims, characterized in that it consists of only one liquid phase.

17. The composition according to any of the preceding claims, characterized in that the biologically active agent is a pharmaceutically active agent.

18. The composition according to claim 17, characterized in that the pharmaceutically active agent is selected from the group consisting of guanosides, corticosteroids, psycho-pharmaceutical hormones, oxicams, peptides, proteins, antibiotics, antivirals, anti-microbes, anti-cancer agents, anti- fungi, estrogens, anti-inflammatory agents, neuroleptic agents, melanocyte stimulants and stimulants of the gland, preferably stimulators of the sebaceous and pilo-sebaceous glands, and agents with an effect on the secretion of barley cells.

19. The composition according to any of claims 17 and 18, characterized in that it is to be used as a medicament.

20. The composition according to any of the preceding claims for topical, preferably dermal, application to a mammal, preferably man.

21. A method for the preparation of a biologically active composition, characterized in that it comprises a biologically active agent dissolved or dispersed in a non-crystalline ester and / or a polyester carrier thereof, wherein a carrier starting substance, or a mixture of two or more different carrier starting substances, undergo such chemical reactions that form a liquid non-crystalline ester and / or a polyester carrier matrix, the biologically active agent being added to the liquid carrier matrix after the chemical reactions have been completed and in such a quantity that the supersaturated state is obtained.

22. The method according to claim 21, characterized in that the composition is as defined in any of claims 3-20.