HK1131040A - Method for solubilizing, dispersing, and stabilizing materials, products manufactured according to said method, and use thereof - Google Patents

Abstract

Disclosed is a method in which poloxamer, a resin, and/or a tocopherol is/are fused, and the material that is to be treated is intimately dispersed with said melt. After being introduced into the melt, the material that is to be treated is coated with water to prevent hardening, and the spontaneously forming gel is homogenized. The obtained product is composed of a transparent gel that is based on at least one poloxamer, a resin or a tocopherol, and an active substance which is solubilized, dispersed, and stabilized therein and whose consistency ranges from solid, semisolid, i.e. aspic-like, to liquid. The micelles of said solubilized matter remain stable even when the same is diluted well below the CMC of poloxamer. The inventive products can be used for dissolving fats, peptides, resins, and all types of resinous materials, removing fats, peptides, resins, and all types of resinous materials from surfaces, cleaning, and lubricating, according to the solubilized active substances used. If a vegetable substance is intimately dispersed in such a melt, the melt is cooled instead of being coated with water. The melt turns brittle and can then be coarsely chopped and ground in a chopper-grinder without producing dust and can then be finely ground in a wet state with water in a hammer mill or an emulsifying mill until the crystals of the melt have been reduced to a diameter of less than 5 micrometers. The crystals of the melt are then dissolved or dispersed in additional water and are added to the humus soil in order for the crystals to be absorbed by the plant via the roots thereof, or the crystals are sprayed directly to the part of the plant that lies above the ground.

Description

process for the solubilization, dispersion and stabilization of substances, products prepared by this process and their use

Technical Field

The present invention relates to a basic method for solubilizing, dispersing, stabilizing and, if desired, also separating different substances. These substances are concerned, for example, with not only lipophilic and resin-like active agents in hydrophilic environments and hydrophilic substances in hydrophilic environments, but also hydrophilic substances which are separated in aqueous environments, for example substances having a bitter or fish taste. Isolation refers to the inhibition of the odor and taste of a substance. And eventually solid particles such as pollen and dandruff, which remain in the aqueous environment. Even when these materials are active agents, stabilization of such materials in aqueous environments can be achieved with dissolution and dispersion of such materials. The invention also relates to various semi-finished products, concentrates and finished products such as commercial products produced according to this method. The invention makes it possible in particular to provide active agents which have proven advantageous for the growth of plants, in a form which is easy to use. In this way, the activator can be dustless comminuted, dissolved, dispersed and stabilized as desired and then applied for plant uptake and effective uptake by plants. The solubilization method can greatly increase the application efficiency of the plant active ingredients, and the dust-free implementation can really save the cost because the high toxicity of the active agent (herbicide, bactericide, acaricide, insecticide) steam is not required to be prevented under the production environment. This method for solubilization and dispersion of plant actives also enables the stabilization of these actives in an aqueous environment. By stability is meant not only the stability of solubilization but also the stability of the active during penetration of the ground to the roots. The invention therefore also includes a dosage form for a plant active agent developed according to the method of the invention. Finally, the invention also includes such solubilized products for various commercial uses, as long as the products are not involved in the treatment of the human or animal body.

Background

In general, auxiliary substances are sought which cause, permit, support or simplify dissolution or dispersion. It is desirable that such auxiliary substances are in no way suspect and are not objected or restricted by health authorities or worried by consuming groups or other interested groups, and therefore may be included in the ingredients of pharmaceuticals or feeds. However, because it is often necessary to stabilize a soluble active agent so that the active agent can fully develop its effect for a period of time, as well as improve its resorption, the goal is not merely to fully dissolve and disperse a substance, i.e., an active agent.

There are several active agents whose efficiency is well known to the skilled person, however, their use is also problematic because they are not readily soluble and stable. Coenzyme Q10 may be exemplified. Studies from USA have shown that one active agent can play an important role in combating parkinson's disease and alzheimer's disease, and that this active agent has a positive effect in cancer, aids and other infectious diseases. Coenzyme Q10 has been found to accelerate regeneration after injury in sports medicine. However, coenzyme Q10 is a fat-soluble powder and insoluble in aqueous solutions. The bioavailability of water-insoluble active agents is often low, i.e., there is little effect and little target in an organism. In the case of the use of such very expensive active agents, it is unpleasant that a large part of the administered active agent is not available to the organism, but is washed away or separated off. Thus, an expensive active agent such as coenzyme Q10 is practically only 10% bioavailable.

After disclosing the results of this study, coenzyme Q10, as described above, is important against parkinson's disease, alzheimer's disease, cancer and aids, and its market price is rapidly doubled, and at present its price is about 2000 swiss francs per kg. It is clear that enhancing its bioavailability not only means a major technical advance, but also means a significant improvement in economy. If the bioavailability is now doubled, twice the number of people currently treatable can be treated with the same amount of active agent.

The possibility of dissolving a fat-soluble active agent of this or the same quality and at the same time stabilizing it opens up new, hardly imaginable prospects. Thus, an active agent treated in this manner can be administered not only orally in the form of a capsule, but also mixed with a beverage, for example, a beverage consumed by a sportsman. In view of the fact that lipid-soluble active agents will be soluble in beverages and will remain stable, a completely new commercial area will be opened up for the whole life style. Furthermore, the amount of active agent suspended in an aqueous environment that adheres to the inner wall of the PET bottle will no longer exceed 80%, but will remain completely in the bottle with the liquid carrier and then enter the human body by drinking.

Another important active agent is insulin, which is also difficult to apply. Insulin is a helical peptide with many amino acids and exhibits a particularly sensitive spatial structure. In order to achieve a proper bioavailability, insulin must be injected into the body. This is very unpleasant for the patient and each time a very cumbersome procedure. It would be desirable and a significant breakthrough if there were a substance that would allow insulin to be administered orally. In the west, 1/5 population suffers from more or less hyperglycemia and the percentage of obese people is constantly increasing, and therefore, the number of people with type II diabetes is also increasing. The importance of insulin also increases, since there is a great demand for this unique and better form of administration. Insulin is a hormone, by definition, a small number of substances that control important functions of the human body. A strong and effective control substance must be used at low doses. The solubilizing auxiliary substances usually used are also low doses. During oral administration, the applied solubilizate is further diluted so that the critical micelle concentration (cmc) of the surfactant used in the solubilizate is significantly reduced as expected. In this way, the lysate breaks down, after which insulin no longer prevents the enzymes and the change in pH, and thus loses activity. It is this reason that oral administration of insulin fails.

A closest prior art is THE solubilization method disclosed in WO 01/19329A (THE PROCTER & GABLE COMPANY) patent document, 3/22/2001, which makes a melt containing poloxamer and propylene glycol, wherein an ethanol premix of THE active agent, which is insufficiently dissolved in water, is added to THE active agent, and then THE whole is mixed with water uniformly. Micelle movement in this melt was as described in the specification: micelles separate below the critical micelle concentration (cmc) and the lipophilic active agent precipitates. In addition, active agents dissolved in this manner do not intermix in any proportion, and individual dissolved preparations that otherwise become cloudy or undergo a physical or chemical change are not included. Heretofore, such solubilization systems, which make micelles of various active agents and which remain stable below cmc so as not to produce precipitates, milkiness or opalescence with increasing dilution amounts, have never been mentioned in the literature of the art.

Along with medically active agents, there are a range of non-medical substances that have not been dissolved or dispersed to date. These active agents are, for example: lipophilic or resin-like active agents in a hydrophilic environment, also hydrophilic substances in a lipophilic or hydrophilic environment, and solid particles such as suspensions in an aqueous environment. In the experiments, for example: the granules of the plant active ingredient are mixed in a higher percentage of the dissolved substance and the dissolved substance is ground moist. The final expanded suspension is further milled in a hammer or emulsion mill until the particle size of the powder in the suspension is reduced to about 2-5 microns. If this dissolving action is applied, i.e. the dissolved substance is put into the soil in the vicinity of the root system of the plant for the plant to absorb, and after that water is injected, the root system of the plant absorbs only water and emulsifier with its roots, as desired, instead of absorbing the plant active ingredient itself.

Ideally, it is desirable that the authorities, consuming groups or other interested parties do not object or retain the provided plant active ingredient when it is licensed. However, it is also important that the active ingredient is only dissolved and dispersed, not the only thing that is of exclusive importance, so that it is actually and effectively available to the plant, so that it is actually absorbed by the root system of the plant and can maintain its effectiveness in the plant until the plant is rotten.

The efficacy of some plant actives is well known to those skilled in the art, however, the use of plant actives can also lead to difficulties because solubilization of plant actives is as difficult as their absorption by the plant. In the case of the use of particularly expensive or concentrated plant active ingredients, it is annoying that the majority of the administered amounts are not made available to the plants and instead remain in the ground and contaminate the soil. The possibility of plants to solubilize and at the same time stabilize fat-soluble active ingredients opens up an unthinkable prospect. The active ingredient treated in this way can be absorbed intact by the plant.

Disclosure of Invention

It is a first object of the present invention to provide a basic method to help such materials be solubilized, dispersed and stabilized. The process of the invention is reliable, simple and economically feasible and is suitable for use with different substances.

A second object of the present invention is to develop and provide products prepared by the process of the present invention.

A third object of the invention is to provide the use of certain solutes for specific purposes, which are produced according to the method of the invention.

The first object of the invention is achieved by a method for solubilizing, dispersing and stabilizing a substance, characterized in that poloxamer on the one hand is melted together with resins and/or tocopherols on the other hand to prepare a combined melt, and the substance to be treated is dispersed and dissolved in said melt.

The second object of the invention is achieved by a product comprising a melt of a transparent gel based on at least poloxamer in combination with natural or synthetic resins and/or tocopherols; and an active substance which is soluble and stable in the melt and has a viscosity which ranges from a solid state through a semi-solid state, i.e. a jelly-like state, to a liquid state.

The third object of the present invention is achieved according to the various uses of the products of the above composition, which comprise, in soluble form, a specific substance which is used for a specific commercial purpose according to the needs of use.

The auxiliary substances have proven to be particularly important, i.e. poloxamers, resins or tocopherols and the active agent to be treated are bound on a molecular basis and then form micelles to prevent hardening only after the addition of moisture, which micelles as loaded micelles maintain stability even when diluted 1000 times below the critical micelle concentration (cmc). Tocopherol is a defined substance, present in four different stereoisomers, and is dependent on having or not having an "in vivo" vitamin E effect. In order to determine the very important stability of micelles at low concentrations, it is important to combine the poloxamer with natural or synthetic resins and/or tocopherols to make a melt and disperse the active agent to be dissolved therein. Thereafter the melt is covered with a layer of water at the same temperature to form a gel, which is then homogenized. A significant advantage of this solubilization method is that it achieves micellar stability at 10 units below the critical micelle concentration. This result is only obtained if the molten poloxamer and the active agent used, as well as the prepared natural or synthetic resins and/or tocopherols, are dispersed in the melt.

If the poloxamer is not contaminated with solvent, it can remain in a liquid state at about 57-58 deg.C. It was then found that a large amount of lipophilic and hydrophilic substances was well dissolved in the poloxamer melt. The addition of natural or artificially prepared resins, the addition of tocopherol, or the addition of tocopherol in place of resins, and the mixing of the substances to be solubilized in the melt with these auxiliary substances on a molecular or pseudo-molecular basis in this type of solubilization prove to be critical for increasing the loading index of the active agent micelles produced and for achieving the stability of the micelles produced below the critical micelle concentration. In this way, not only can more active agent be surrounded by the auxiliary substance to form micelles, but these formed micelles can also remain completely stable well below the critical micelle concentration. In addition, only soluble active agents made with resins and/or tocopherols according to this melting method can be mixed with each other in any ratio, not including individual soluble products that otherwise become cloudy or undergo a physical or chemical change.

The key point in the method of the invention is the temperature of the poloxamer-melt. Peptides are known to react violently at high temperatures. Many peptides are denatured at temperatures ranging from 40-60 ℃. The appearance of white color of the protein at 56 ℃ when the egg is fried is a proof of this structural change of the protein, which can be observed by anyone. High fever above 40 ℃ is very unsafe for the patient, since the protein starts to change at temperatures above 40 ℃. The temperature of the poloxamer-melt can be lowered by adding a suitable amount of solvent. Non-toxic solvents such as glycerol, polypropylene glycol, polyethylene glycol 400, and the like are suitable for this purpose. By adding appropriate amounts of these solvents, the melting temperature of the poloxamer can be lowered to the degree that known thermolabile active agents are thermolabile, such as insulin or a sensitive plant active agent can also be solubilized and stabilized.

Another step of the method of the invention, which is preferred for certain applications and which in this case is a very important step, is that the active agent is covered by a water layer of sufficient thickness at approximately the same temperature immediately after dissolution in the poloxamer melt. This helps to form a clear gel below the aqueous layer. The melt becomes as hard as plastic at the same temperature without such a water covering and cannot be applied directly in this form. Therefore, to prevent hardening, the melt can be overfilled or covered with water at the same temperature until it is liquid. This gelling can also occur with cold water, but then primarily the dispersion of the active agent occurs. After water has been added at the same temperature and this water forms a covering layer of the melt-the natural floating of water on the melt-the gelling action occurs naturally and the gel grows rapidly upwards in the melt towards the water surface as the melt absorbs water. This gelation (freezing) was aided by contacting the melt with water and gentle agitation, as viewed from outside the gel. The gel has a micellar structure with a droplet diameter of less than 80nm, whereby the gel does not refract light, and the gel is completely transparent, even if it can be read through the gel, even if about 5-10% of the components in the gel are fat-soluble active agents, about 10-20% of the components are poloxamers, and 1-15% of the components are natural or artificially prepared resins and/or tocopherols. These micelles maintain thermal stability, and therefore no turbidity occurs when the gel is boiled, and the micelle structure thereof is not destroyed after addition of a large amount of water. The viscosity of the micelles is slurried or more dilute. The gel is homogenized by stirring and diluted to the appropriate viscosity by the addition of water or a water solvent mixture. However, if subjected to homogenization with strong shear forces, harmful gels may form. The newly produced gel was opaque, indicating that the gel would also disperse with dissolution. If a standard blade stirring is used, such as a Stefan stirring machine (Stefan stirring machine) having a rotational axis projecting perpendicularly from the bottom of the vessel and a sharp blade arranged perpendicularly thereto, the blade cutting the melt to be stirred; or Diosna tumbling machine, whereby a clean, good and transparent gel with few bubbles can be obtained. In such a matrix the microbial contamination progresses more slowly than in the liquid state.

Broadly speaking, the basic principle of the method of the invention is that the method of the invention mixes the active agent with two required auxiliary carriers, namely a poloxamer and a dendritic and/or tocopherol as well as optionally additionally a solvent such as glycerol, propylene glycol, polyethylene glycol etc. when a very low melting point is desired or required in order to produce a melt at a temperature in the range of about 40-100 ℃. In this melt, all components to be dissolved are brought into direct surface contact, after which they are covered with moisture or a water composition and optionally a solvent, whereby the covering has a temperature of 1-100 ℃.

By solubilizing and stabilizing the desired active agent coenzyme Q10, which coenzyme Q10 stimulates the cell mitochondria, a dark red transparent gel appears when covered with warm water. When the active agent propolis was used, the clear gel turned dark yellow. But in any case, a homogeneous, transparent gel was produced by moisture coverage. Once the gel is present, excess water is poured off and the gel can be removed from the container. The gel has been shown to be capable of being kneaded, pressed, pulled or twisted without changing its viscosity. The different colors appearing in the gel are dependent on the type of active agent solubilized by the poloxamer and the resin or tocopherol according to the method of the invention. The viscosity of the gel can be varied by using more additives and by quantifying the amount of water used. The more water added, the more fluid the gel. Conversely, the less water added, the more viscous the gel until it is near the consistency of a frozen paste. This change in viscosity provides new uses, such as for lubricants in care products or greases to easily broaden the viscosity, use of aqueous concentrates in beverages, or use of viscous gels in cosmetics.

Using the method of the present invention, the bioavailability of active agents such as coenzyme Q10 can be increased to about 85% in the case of oral administration, since the current active agents are encapsulated on a molecular basis and remain stable even below the cmc of poloxamers by being coated with resins and/or tocopherols by means of poloxamers. If it is considered that about 100 tons of coenzyme Q10 was used worldwide in 2004 and the price per kilogram was 2000 swiss farads, the economic impact of the actually increased bioavailability could be judged.

One focus associated with the disclosed methods is on the reference books of pharmacists and the pharmaceutical industry, i.e. in the international pharmacopoeia where poloxamers, resins and tocopherols are mentioned. If the use of these substances is permitted, the known active agents and auxiliary substances are not only described in detail in the pharmacopoeias but can also be found in the references, i.e. what properties they should have. The purity, content, residue and the like of these substances are specified. In addition, how to use these auxiliary substances and active agents, etc. is also described. There is the US pharmacopoeia of the FDA for US, the EU pharmacopoeia applicable in Europe, the British pharmacopoeia of its own in British, and also the Japanese pharmacopoeia. The pharmacopoeia is a pioneer because of the particularly strict use of drugs. Russian and china also have their own pharmacopoeias. When auxiliary substances are added to a pharmaceutical formulation, the conditions are within the ranges described in the pharmacopoeia wherever they are used.

Poloxamers, various resins and tocopherols have their own monograph, i.e. complete material descriptions, in different pharmacopoeias. Poloxamers are completely inert. The resin is almost formally unusable and is generally ineffective and slightly effective when tocopherol (vitamin E) is used. There is no restriction on these substances in all countries, and these substances are also used in a variety of cosmetic, pharmaceutical and animal nutritional supplement preparations.

The following describes a method applicable to the solubilization and stabilization of a few active agents. Vitamin C is such a very effective and water-soluble active agent. However, vitamin C is not very stable in light, air and neutral pH ranges. When vitamin C is dissolved in water, it turns pale yellow after 2-3 days, then yellow and finally reddish brown, a clear sign of a structural change and loss of its activity. For this reason, even if one recognizes that its effect is desired, vitamin C is used only in small amounts or not in many products such as cosmetics and in food supplements. Vitamin C can be stabilized by the disclosed methods.

Another important active agent is insulin. Insulin itself is water soluble, but its stability is very poor. Most applications requiring rapid injections result in the inactivation of insulin. If administered orally and delivered through the gastrointestinal tract, insulin encounters hydrochloric acid and pepsin in the stomach and subsequently encounters small amounts of intestinal fluid containing cholesterol and bile acids. These digestive juices can reduce the activity of insulin. By the above dispersion and stabilization method, the bioavailability of insulin can be greatly enhanced, and thus, administration by oral administration can be performed.

Another group of active agents is sprayed into the nasal cavity, usually by means of a nasal spray. Many of these sprays contain auxiliary substances which, especially when used for a long period of time, can produce allergic reactions on the nasal mucosa, in the respiratory tract or in the lungs. If these agents can be solubilized and stabilized with poloxamers and tocopherols as described above, then the sensitive patient can no longer develop soluble allergies. The poloxamer and tocopherol do not cause any allergic reaction when used in nasal spray or drinking solution, and can effectively isolate the allergic reaction.

It is known to produce a melt from poloxamer and a resin or tocopherol, and to coat the melt with moisture at the same temperature for a particular use. A particular poloxamer, lutrol f68, produces a lower viscosity in this method and can be used to solubilize and stabilize the active agent to be applied for subsequent parenteral infusion or injection. Therefore, in the case of commercial production, since the active agent treated by this method does not precipitate in blood, the risk of causing lipid embolism by using a lipophilic active agent is small.

Regular cleaning of contact lenses is very important and contact lenses can be cleaned by using a cleaning solution based on the solubilization method of the present invention without producing a burning sensation in the eye. The contact lens is thus very carefully cleaned. The solution made according to the disclosed technique of the present invention can now be suitably or fully applied to the cleaning of contact lenses, even without removing the lenses from the eye.

If poloxamers, resins or tocopherols are used in accordance with the present invention, both the fat-soluble and resin-like active agents and the hydrophilic substances in the lipophilic environment are soluble in the hydrophilic environment. Solid particles can also be dissolved and dispersed in an aqueous environment. For example, one application of this is the isolation and delivery of pollen in an aqueous environment. Can produce a nasal spray which can disperse pollen penetrating into nasal cavity and irritating mucosa in nasal cavity, thereby preventing pollinosis. Dandruff can also be combated in shampoos by dispersing it in an aqueous environment in a similar manner and releasing it easily from the skin, in particular from the scalp, without any mechanical action. This makes possible cosmetic and dermatological applications to humans or to animals.

In addition, it is possible to produce beverages and syrups which can be used as food supplements for humans and animals, and also as pure drinks for humans and animals, which are also rich in oxygen and from which the "active agent" is well resorbed. As already stated, the method of the invention is very suitable for drugs for topical application to humans and animals, as well as for drugs and solutions for parenteral application to humans and animals, wherein both the drugs and the solutions are enriched in oxygen. The cold deep spring water of 5-10 deg.C contains 12-18mg of oxygen per liter, and when the water is heated, the oxygen content is rapidly reduced. The micelles produced according to the process of the invention have an enlarged inner surface and store oxygen in their inner surface. The 1% micelle-loaded free aqueous solution can keep more than 100mg of medical oxygen per liter of water stable for more than 5 days at 18 ℃ in a 10L volume uncovered barrel when the injection amount reaches 2/3 of the barrel volume. The numerous new applications of the products prepared according to the process of the invention also lead to the application of the technology. On the one hand, the product does not have fat residues. On the other hand, lubricants or care products containing fat can also be produced by dissolving fat.

The process of the invention is particularly suitable for the following substances and uses: mainly for solubilizing lipophilic and hydrophilic substances, in the case of food supplements, cosmetic and dermatological products, such as coenzyme Q10, vitamin C, vitamin E, beta-carotene, vitamin A, vitamin D3, lutein, lycopene, folic acid, vitamin B12, omega-3 and omega-6 fatty acids; for substances for preventing the contamination of resin-like substances, preserving the substances, and producing wound dressings, such as propolis, selenium dioxide, tar and mineral oil. In addition, the method of the present invention can make the peptides orally taken to have biological effectiveness, for example, dissolving insulin (antidiabetic), cyclosporin A, etc., and plant extracts of Silybum marianum, Passiflora edulis, Petasites japonicus, etc., and derivatives thereof (e.g., silymarin, chrysin, etc.). In general, the dissolution of polyphenolic compounds according to the process of the invention does not involve any difficulty, and the concentration of active agent in the solute can always reach 2-5%.

The following quantitative gel compositions formed from poloxamer and resin (or tocopherol) melts are representative: 1-10% of active agent, 10-20% of total poloxamer, 1-20% of resin or tocopherol and the balance of water by weight of 100% of gel. The gels are produced via the melt according to the process of the invention and are characterized by the transparency of the gel, which remains transparent even if diluted to a large extent with water or a mixture of aqueous solvents. This high concentration of active agent can only be dissolved into a completely transparent gel by means of a preparation and optionally a solvent, wherein the preparation is made via poloxamer with a resin or tocopherol melt and the active agent. By adding a suitable amount of solvent, the viscosity of the gel can be reduced and/or a melt can be made at a lower temperature. In the production process according to the invention, the coated auxiliary substance melt enables the dissolution of the majority of the substance: the active agent solubilizing the solubilized, hydrophilic vitamin C is approximately 10% in oil, and as such, the lipophilic coenzyme Q10 is solubilized in water by 2% -6% in the same manner as propolis, a gum.

In the case of insulin as the active agent, not only can a homogeneous, stable and concentrated dispersion be achieved, but also the bioavailability of the orally active agent can be greatly increased. Since poloxamers are mentioned in all medical books and also in switzerland as additives in feed formulations, it can be used for oral administration and even poloxamer 188 for parenteral administration. The following examples illustrate how the process of the invention can be applied.

Detailed Description

Example 1

Stabilization of vitamin C and ACC in shampoos containing ACC, vitamin C and vitamin E:

a has 74.11 percent of water

B lauryl alcohol ether sodium sulfate 11.67%

C Cocoamidopropyl betaine 2.00%

D cocoyl diethanolamide 1.70%

Disodium lauryl polyoxyethylene ether sulfosuccinate 1.32%

F perfume 1.00%

G poloxamer 4071.40%

H1880.60% of poloxamer

I vitamin C1.00%

J acetylcysteine 1.00%

K alpha-tocopherol 0.50%

0.80 percent of L-lauryl sodium sulfate

0.50 percent of M phenoxyethanol

0.20 percent of N imidazolidinyl urea

0.10 percent of O polyethylene glycol-120 methyl glucose dioleate

0.10 percent of tetrasodium edetate P.

The production process of the product is as follows:

g, H and K are heated to 60 ℃ until they melt,

mixing I and J and dispersing them in the melt with stirring,

covering with 1/4A (60 deg.C heat) and waiting until the gel forms a gel,

3/4A was removed and then a weighed amount of B, C, D, E, F, L, M, N, O, P was added to A with stirring to make a clear solution,

adding the gel under stirring, and then adding the solution prepared in the previous step.

Example 2

Examples of the solubilisation of coenzyme Q10 in gels containing vitamin C and vitamin E:

the water content is 71.43 percent

1888.93% of poloxamer

4078.93% of poloxamer

Alpha-tocopherol 5.00%

Coenzyme Q102.14%

3.57 percent of vitamin C

Example 3

Examples of solubilization of propolis-containing gel:

the water content is 70%

Poloxamer 18818%

Propolis 12%

For the sake of accuracy and clarity, some definitions and explanations are given below:

surfactants are compounds that contain in the molecule two moieties, hydrophilic (affinity for water) and lipophilic (affinity for fat).

Due to this fact, these surfactants concentrate themselves on the surface of the aqueous phase, i.e. they are surface-active. The aqueous phase is surface active whether it is in contact with a gas phase, a liquid phase or a solid phase.

Furthermore, beyond a certain surfactant concentration, the surfactant forms a large number of molecular structures in solution, these molecular structures remaining in equilibrium with the individual molecules. The molecular structures may have different shapes and sizes, but in the simplest case all have a spherical shape.

Above a certain surfactant concentration, each surfactant is characterized by: the surfactant molecules are grouped together in a shape-forming manner, including lipophilic groups inside and hydrophilic groups on their surface, which are in contact with water and determine the solubility of the structure in water.

Such aggregates are called micelles and these molecular groups are re-soluble, and when this system is diluted with water for a long time, the concentration of the surfactant falls below a characteristic value, and the lowest concentration that exhibits this characteristic is called the "critical micelle formation concentration" or simply "cmc".

The higher the "cmc" of the surfactant, the less lipophilic, non-polar part of the surfactant.

The interior of the micelle is in a liquid state.

In most cases, below "cmc" only surfactant monomer is present in solution. Above "cmc" the amount of aggregate remains constant at all times. Above "cmc" all added surfactant material forms micelles, and therefore micelle formation is taken as the formation of new phases, wherein, however, the amount of aggregates does not grow indefinitely.

Thus, above "cmc", the concentration of dissolved surfactant monomer does not increase.

At a temperature known as the Krafft point (kraft point) of the surfactant, surfactant dissolution occurs due to the onset of micelle formation. Since the force point represents a well-defined temperature, the undissolved surfactant will melt when the krafft point is reached. Therefore, the Krafft point is often compared with the melting point.

Nonionic surfactants, which form clear solutions in water, exhibit special properties in contrast to other surfactants. If the temperature rises, the solution becomes cloudy beyond a specific, relative, well-defined temperature characterized by the respective surfactant, and the solution separates into two liquid phases. This temperature is called a cloud point (turbidimetric point).

The reason for this depends on the hydration of the hydrophilic, nonionic groups. In the case of a temperature increase, partial dehydration takes place, which leads to the formation of a new phase. For this reason, the cloud point is hardly dependent on the total concentration of the surfactant. However, this turbidity can be reversed by cooling. The cloud point can be influenced by the additive: the additives can be preserved in the micelle space and change the properties of the micelle or change the properties of the water, i.e., the environment of the micelle. The latter mechanism is particularly useful for adding electrolytes, which generally push the cloud point to lower temperatures as the concentration increases.

The micelles appear in spherical form because the hydrophilic head groups are to be separated from each other as much as possible by electrostatic repulsion and at the same time to be in contact with the surrounding water molecules. The lipophilic molecular part inside the micelle is not contacted with water; the size of the micelle is based on the space required for the lipophilic group.

The following data apply to poloxamers (pluronics):

polymer and method of making same	Molecular weight	HLB value	CMC(g/lt)	Micelle diameter
					Poloxamer P85	4600	26	1.058	1.5nm
Poloxamer F68	8400	29	1.344	1.3nm
					Poloxamer F127	12600	22	0.869	3.3nm

(Z.Sezgin et al/European Journal of Bio-pharmaceuticals 64[2006]261-268)

The following are some further descriptions:

when the micelle is spherical, its radius can only be increased to the length of the lipophilic molecule part. The amount of surfactant monomer per spherical micelle (═ aggregate number) is limited at an upper limit, based on the volume required for a proportion of the lipophilic molecular fraction in the total volume of the micelle.

As the concentration of surfactant increases, the size of the micelles remains constant, but the amount increases.

An important property of micelles is their ability to solubilize other molecules. Micelles are lipophilic in nature because they behave as small droplets of hydrocarbons and therefore dissolve lipophilic substances. These water-insoluble materials are accumulated in the interior of the micelle and are no longer in contact with the aqueous phase. However, since the micelle surface is hydrophilic, the dissolved active agent floats in water. This process is called solubilization. Micelles are stable systems in thermodynamic detection. The concentration of particles dissolved by the surfactant is mainly below 5%. Haze is often observed in such systems upon interface-induced light scattering (the Tyndall effect).

Solubilization (deposition of lipophilic materials inside the micelle) increases the micelle, so that the added surfactant precipitates on the micelle surface. Thus, the diameter of the micelles rose from 1.3nm (uncharged) with poloxamer F68 and from 3.3nm (uncharged) with poloxamer F127. The diameter of the micelle is usually 140nm or less. However, these gel beam sources can result in a lysate particle size of up to 500nm, wherein the lysate exhibits transparency with bluish light. In the case of particle sizes below 140nm, the solubilizate exhibits only transparency.

HLB value (hydrophilic-lipophilic balance) quantifies the lipophilic and hydrophilic moieties on the surfactant molecule. This value is a value indicating the molecular properties of the surfactant. Poloxamer F68 had an HLB value of 29 and poloxamer F127 had an HLB value of 22. Both of these surfactants are strong hydrotropes.

For the solubilization of sesame oil, essential oils and oil-soluble vitamins, surfactants with an HLB value of 14-17 can be used. These materials are considered hydrotropes or solubilizers. Due to the high HLB value of the solubilizer, the solubilizer generally has a tendency to generate foam, which causes technical problems. However, both poloxamers (F68 and F127) were able to remove foam.

Sesame oil is poorly soluble in water and must be dissolved in water systems, and sesame oil mainly consists of resins, resinoids, terpenes, esters or ketones.

Resins, resin-type substances and esters thereof are in turn very good solvents for essential oils, oil-soluble vitamins, polyphenolic compounds and other lipophilic active agents. Meanwhile, the resin, resin type and esters thereof can be well dissolved by the surfactants poloxamer F127, poloxamer F68 and poloxamer P85.

The abamectin is more than 80% of abamectin Bla (M: 873.1; C)₄₈H₇₂O₁₄) And less than 20% abamectin B1B (M: 859.1, respectively; c₄₇H₇₀O₁₄) A mixture of (a). They are colorless to pale yellow crystals, have a melting point of 161.8-169.4 ℃ (under decomposition) and a density of 1.18 at 25 ℃. Abamectin stably prevents hydrolysis from occurring in aqueous solutions at pH 5, 7, 9(25 ℃). Approximately 2g of abamectin are well distributed in 1000 litres of water and can be sprayed for approximately 1 hour on an area of one hectare (two football fields). By forming a sample of the active agent abamectin, which is a very effective insecticide (against mites), showing that the easily soluble abamectin is separated in the resin mixture and a better solubilized resin-abamectin-solution is separated by means of a poloxamer, the stability of the dissolved substance prepared by the method of the invention is also unique, never observed before, even at characteristic "cmc" values below poloxamer (F68)1.344g/lt or poloxamer (F127)0.869g/lt and above the solubility limit of abamectin in water (25 ℃)7-10 mcg/lt.

The anhydrous component, which contains the possible very high concentration of abamectin, can be mixed with water in any ratio without any problem and always produces a transparent substance, with the following results:

composition at poloxamer F127 "cmc" value (═ 0.869 g/lt):

at the "cmc" value of poloxamer F127, the concentration of abamectin in water is 122,000, mcg/lt, which is higher than 7-10mcg of abamectin dissolved per liter of water. The lysate remained stable and transparent upon more water dilution. This result cannot be produced by any other known production method using the same components so far. Thus, when the resin used is not only a solvent for abamectin and is suitably dissolved by poloxamer, but is also specifically bound to poloxamer, and micelles can be kept stable in this way even when extremely diluted with water, the resulting micelles can be kept stable below cmc. A typical concentration of abamectin used is 2,000mcg/lt, i.e. a concentration above the water-soluble limit of abamectin, and therefore abamectin can be dissolved in micelles.

Composition of resin mixture (resin):

the following components were used:

resin:

benzyl benzoate (M: 212.2; C)₁₄H₁₂O₂) Is a colorless liquid or a colorless crystal; practically insoluble in water (crystallization prevention).

Cinnamomyl benzyl ester (M: 238.29; C)₁₆H₁₄O₂(ii) a Density: 1.106) is a white, aromatic crystal; is practically insoluble in water.

Or alternatively benzylconiferyl ester.

Antioxidant: alpha-tocopherol.

Solvent: cinnamyl alcohol, benzyl alcohol, ethyl diglycol, dipropylene glycol, polyethylene glycol 400 and benzoic acid.

If the concentration of the aqueous active agent of abamectin is adjusted between 2% and 0.5%, a transparent product in the form of a gel is obtained, which is capable of emitting sound when hit on a glass with a hard surface covered with the gel. The "ringing" sound emitted also has a noticeable vibration. This "ringing" gel is very stable both when heated and when cooled. The effect of this stable structure is also that the active agent which is sensitive to hydrolysis remains stable due to its deposition in the system at high temperatures.

Example (b):

abamectin dissolved substance 1.6% -ig	Content g	Percentage content%
Poloxamer F68	130.17	13.0
			Poloxamer F127	130.17	13.0
Alpha-tocopherol	34.2	3.4
			Resin composition	68.48	6.8
Abamectin 85% -ig	18.6	1.9
Water (W)	618.38	61.8
Total amount of	1000.00	100.0

Abamectin solute 0.88% -ig	Content g	Percentage content%
Poloxamer F68	83.35	8.3
			Poloxamer F127	83.35	8.3
Alpha-tocopherol	21.94	2.2
			Resin composition	43.82	4.4
Abamectin 85% -ig	10.24	1.02
Water (W)	757.3	75.7
Total amount of	1000.00	100.0

When the dry solid is stored unprotected in air filled with water vapor, absorption occurs, i.e., water vapor absorption, depending on the water content of the air and the hygroscopic nature of the solid. In this process, only a small molecular layer is bound to the solid surface by adsorption or penetrates into the solid substance, a process known as adsorption. On the other hand, absorption occurs when the moist solids consume water vapor in the drying air.

According to the method described in the invention, solid or semi-solid active agent concentrates are extracted by preparing an active agent melt or gel, which exhibits hydrophilic and/or water-soluble solids with water vapor and large surfaces or surface enlargement due to spraying and/or freeze-drying, which provide excellent resorption properties of the active agent in the human or animal body. The properties are independent of whether or not the active agent concentrate is ultimately desorbed. Thus, using the above process, solid active agent concentrates for oral administration can be prepared which can be filled into gelatin capsules, packaged in powder doses into sachets, or compressed into tablet form as well as effervescent tablets. After dissolution and dispersion of the solid active agent concentrate in water or in the gastric juices of a human or animal, the active agent comes in dissolved and/or dispersed form and is rapidly and completely absorbed. Similarly, the resulting semi-solid active agent concentrate is then filled into soft gelatin capsules, also having this good resorption property.

The following are substances (surface coefficients) suitable as hydrophilic and/or water-soluble solids having large surfaces or surfaces enlarged by spraying and/or freeze-drying>0.01m²/g, BET method):

exudates, such as acacia, tragacanth, karaya, ghatti;

seed powders, such as guar gum, carob flour, tara stone flours, tamarind gum;

detergents, such as pine gum, pectin, agar, alginates, carrageenans, furcellaran;

biosynthetic hydrocolloids, such as flavins;

modified hydrocolloids, such as propylene glycol alginate, amidated pectins;

cellulose derivatives, such as methyl cellulose, methyl ethyl cellulose, methyl hydroxyethyl cellulose, methyl hydroxypropyl cellulose, sodium carboxymethyl cellulose;

silica, such as silica aerogel;

proteins, such as gelatin, skim milk powder;

sugars, such as lactose, mannitol, xylitol, sorbitol, dextran.

As another aspect of the present invention, the use of an active agent applied to a plant will be explained below. First, a method of solubilizing and stabilizing a plant active agent will be described in more detail. The importance of the active agent and the auxiliary substances, here abamectin and poloxamer, has been demonstrated, in combination with the resin and the tocopherol on a molecular basis and forming a similarly active-auxiliary-composition. All ingredients are simply mixed and stirred so that the added plant active agent reaches a maximum content of a few tenths of a percent. Pure poloxamers have a melting point of about 57-58 ℃. In this type of dissolution, the plant active agent to be dissolved is incorporated into a poloxamer, resin or tocopherol melt on a molecular or pseudo-molecular basis, which proves itself to be critical for improving the treatment of the active agent.

In principle, a broader formulation method is to mix the two necessary auxiliary substances, poloxamer and resin or tocopherol, with an optional solvent and with a plant active agent, to produce a melt of these substances at a temperature in the range of 40-100 ℃, with the result that the main components are brought into contact with one another on a pseudo-molecular basis inside the melt. A poloxamer is melted and a plant active agent to be treated is dispersed within the melt, wherein the poloxamer is poloxamer 188 and/or poloxamer 407 and/or a substitute and/or derivative thereof. The melting temperature can be made lower by adding a solvent. These solvents may be, for example: water, glycerol, propylene glycol, polyethylene glycol (PEG)400, ethanol, polyethylene glycol (Macrogol)400, or isopropanol. After the plant active agent to be treated is added to the melt, it is cooled to become brittle. The cooling process can be accelerated by adding dry ice. Thereafter, the hardened melt is put into a mill, crushed by a blade in the mill, and then water-wet milled in an emulsion mill until the melted crystals are reduced to the extent that their diameter is 5 μm or less. Advantageously, the emulsion mill has a cooled shear head so that the melted crystals do not become overheated and retain their brittleness during milling. These processes are carried out dust-free even if the material is brittle. In the emulsion mill, the drive system for reducing the melt suspension can be cycled several times so that crystals become smaller and smaller until a sufficient fineness is reached. These minimal crystals remain thermally stable and the active surface is not "washed off" when more moisture is added. The melted crystals are then dissolved in water or dispersed and placed in the ground adjacent to the plants to allow the plants to be absorbed through their roots, or the solution is sprayed directly onto the plant parts on the ground. Another advantage results from the stability of the micelles. The active agent is sprayed as a solution onto the plant as described above and dries out on the surface of the plant due to evaporation, and the active agent on the surface of the plant can be easily washed away after harvesting. Thus, the skinned apples sprayed with the active agent did not have a bitter taste after washing with water.

With this method, the bioavailability of the plant active agent can be greatly improved because the active agent is synthesized on a molecular basis and is covered with poloxamer-resin-tocopherol (pseudocompound) to be stable even when diluted with a large amount of water. If combined in water into different active agent-poloxamer-resin-tocopherol melts, the melts of each combination retain their own physical properties. There is no effect on each other, nor do other surface active agents affect these compositions in water. Basically, the poloxamer-resin-tocopherol used in the present method is used to solubilize and dissolve and disperse each lipophilic plant active agent.

As mentioned above, poloxamers are subject to different pharmacopoeias, i.e. a complete description of the active agent. Poloxamers are completely inert. Can be used in agriculture, cosmetics and animal nutrition. Individual poloxamers are used in parenteral medicine. Thus, poloxamers are harmless.

If poloxamers, resins or tocopherols are used in accordance with the present invention, lipophilic and resin-like plant active agents can be dissolved in a hydrophilic environment, as can hydrophilic substances. Solid particles can also be dissolved and dispersed in an aqueous environment. Applications in this regard, such as dissolving pollen in water.

The following quantitative components are representative of poloxamer melts: 0.1% -8% of a plant active agent, about 10-20% of a poloxamer and 1% -15% of a natural or artificially prepared resin (or alternatively tocopherol). This composition is then dissolved or suspended in water.

According to the method described in the invention, a solid or semi-solid active agent concentrate is extracted by preparing an active agent melt, which is a large surface of the grinding aid or active agent, usually by spraying and/or freeze-drying, which provides excellent absorption properties of the active agent in the plant. The properties are independent of whether desorption of the active agent ultimately occurs. Thus, using the above method, a solid state plant active agent can be prepared. The dissolved crystals, which are then absorbed by the plant through its root system together with water, are dissolved in water.

Additionally, as mentioned above, the present invention also includes the use of the melt on water-soluble macromolecules that can further increase the contact surface of the poloxamer-resin-tocopherol composition of the active agent. The following are substances (surface coefficients) suitable as hydrophilic or water-soluble solids having large surfaces or surfaces increased by spraying and/or freeze-drying>0.01m²/g, BET method):

exudates, such as acacia, tragacanth, karaya, ghatti;

seed powders, such as guar gum, carob flour, tara stone flours, tamarind gum;

detergents, such as pine gum, pectin, agar, alginates, carrageenans, furcellaran;

biosynthetic hydrocolloids, such as flavins;

modified hydrocolloids, such as propylene glycol alginate, amidated pectins;

cellulose derivatives, such as methyl cellulose, methyl ethyl cellulose, methyl hydroxyethyl cellulose, methyl hydroxypropyl cellulose, sodium carboxymethyl cellulose;

silica, such as silica aerogel;

proteins, such as gelatin, skim milk powder;

sugars, such as lactose, mannitol, xylitol, sorbitol, dextran.

The claims (modification according to treaty clause 19)

1. A method of solubilizing, dispersing, stabilizing a substance, wherein poloxamer together with a resin and/or tocopherol is melted into a combined melt and the substance to be treated is solubilized dissolved or dispersed in said melt without the addition of water, so that by adding water to the melt thereafter a plurality of water-stable micelles can be made to hold and/or bind the substance.

2. The method for solubilizing, dispersing, stabilizing substance according to claim 1, characterized in that the produced melt is coated with a layer of water at the same temperature to prevent hardening and the gel formed spontaneously so far is homogenized.

3. The method for solubilizing, dispersing or stabilizing a substance according to claim 1, characterized in that the poloxamers bound with resins and/or tocopherols are melted together and the substance to be treated is dispersed in the melt so that the intervening substance to be treated is also coated with water to prevent hardening thereof and the melt is homogenized, wherein the poloxamers are poloxamer 188 and/or poloxamer 407 and/or their substitutes and/or their derivatives.

4. The method for solubilizing, dispersing or stabilizing a substance according to any one of the preceding claims, characterized in that the poloxamer combined with the resin and/or the tocopherol is melted at the melting point, the melting point temperature of the melt is lowered by adding a solvent, the substance to be solubilized is dispersed in the melt, the melt is coated with water at the same temperature to prevent hardening thereof, and the melt is homogenized, said melt forming a transparent gel as the solubilized substance.

5. The method for solubilizing, dispersing or stabilizing a substance according to any one of the preceding claims, wherein the poloxamer in combination with the resin and/or the tocopherol melts at a temperature of about 40-60 ℃, the melting point temperature of the melt being lowered by the addition of one or more solvents selected from the group consisting of: water, glycerol, propylene glycol, polyethylene glycol (PEG)400, ethanol, polyethylene glycol (Macrogol)400 or isopropanol, and then the substance to be solubilized is dispersed in the melt, which is coated with water at the same temperature to prevent hardening thereof, and which is homogenized, said poloxamer producing a transparent gel as the solubilized substance, said substance to be solubilized possibly being thermally altered, in particular insulin.

6. The method for solubilizing, dispersing or stabilizing a substance according to claim 1, wherein at least one poloxamer in combination with a resin and/or a tocopherol is melted and the plant active agent to be treated is dispersed or dissolved in the melt, and the melt is cooled

Sodium dodecyl sulfate 0.80%

0.50 percent of phenoxyethanol

Imidazolidinyl urea 0.20%

Polyethylene glycol-120 methyl glucose dioleate 0.10%

Tetrasodium edetate 0.10%.

13. A stabiliser according to claim 10, which is in the form of a gel comprising coenzyme Q10, vitamin C and vitamin E, and:

the water content is 71.43 percent

1888.93% of poloxamer

4078.93% of poloxamer

Alpha-tocopherol 5.00%

Coenzyme Q102.14%

3.57 percent of vitamin C.

14. A stabiliser according to claim 10, in the form of a gel comprising propolis having the following composition:

the water content is 69%

Poloxamer 18818%

13% of propolis.

15. A stabiliser according to claim 10 in a solid or semi-solid state comprising an active agent concentrate, the melt or gel of the solid or semi-solid stabiliser being a water vapour bearing solid and being a hydrophilic and/or water soluble solid with a large surface area which is compressed into gelatin capsules, powder dose sachets or tablets and effervescent tablets.

16. The solid or semi-solid state of claim 10Contains an active agent concentrate, the melt or gel of said solid or semi-solid stable substance being a water vapour-bearing solid and being a hydrophilic and/or water-soluble solid having a large surface, which solid is compressed into a gelatin capsule, a powder dose sachet or tablet and an effervescent tablet, such a hydrophilic and/or water-soluble solid having a large surface or having a surface enlarged by spraying and/or freeze-drying (surface coefficient)>0.01m²Per g, BET method) includes one or more of the following:

Claims (31)

1. A method for solubilizing, dispersing and stabilizing a substance, characterized in that poloxamer is melted together with a resin and/or a tocopherol to prepare a combined melt and the substance to be treated is dispersed and dissolved in said melt.

2. The method for solubilizing, dispersing, stabilizing substance according to claim 1, characterized in that the produced melt is coated with a layer of water at the same temperature to prevent hardening and the gel formed spontaneously so far is homogenized.

3. The method for solubilizing, dispersing or stabilizing a substance according to claim 1, characterized in that the poloxamers bound with resins and/or tocopherols are melted together and the substance to be treated is dispersed in the melt so that the intervening substance to be treated is also coated with water to prevent hardening thereof and the melt is homogenized, wherein the poloxamers are poloxamer 188 and/or poloxamer 407 and/or their substitutes and/or their derivatives.

4. The method for solubilizing, dispersing or stabilizing a substance according to any one of the preceding claims, characterized in that the poloxamer combined with the resin and/or the tocopherol is melted at the melting point, the melting point temperature of the melt is lowered by adding a solvent, the substance to be dissolved is dispersed in the melt, the melt is coated with water at the same temperature to prevent hardening thereof and the melt is homogenized, said melt forming a transparent gel as the solubilized substance.

5. The method for solubilizing, dispersing or stabilizing a substance according to any one of the preceding claims, wherein the poloxamer in combination with the resin and/or the tocopherol melts at a temperature of about 40-60 ℃, the melting point temperature of the melt being lowered by the addition of one or more solvents selected from the group consisting of: water, glycerol, propylene glycol, polyethylene glycol (PEG)400, ethanol, polyethylene glycol (Macrogol)400 or isopropanol, and then the substance to be dissolved is dispersed in the melt, which is coated with water at the same temperature to prevent hardening thereof, and which is homogenized, said poloxamer producing a transparent gel as a solubilisate, said substance to be dissolved possibly being heat-altered, in particular insulin.

6. The method for solubilizing, dispersing or stabilizing a substance according to claim 1, characterized in that at least one poloxamer in combination with resins and/or tocopherols is melted and the plant active agent to be treated is dispersed or dissolved in the melt, the melt is cooled until it becomes brittle and then milled, after which it is moistened by wrapping it with water in an emulsifier or wet-milled in a hammer mill until the melted crystals are reduced to a diameter below 5 microns, said melted crystals forming a suspension which is added to the plant or the humus area of the plant to be absorbed.

7. A method for solubilizing, dispersing, stabilizing a substance according to claim 6, characterized in that at least one poloxamer with bound resins and/or tocopherols, wherein poloxamer 188 and/or poloxamer 407 and/or their substitutes and/or their derivatives, is melted and the plant active agent to be treated is dispersed in the melt, after such addition of the active agent the melt is cooled for a period of time until it becomes brittle and then milled to reduce the diameter of the melt to below 5 microns, and the melted crystals are then dissolved or dispersed in water, the solution being able to be poured into the ground for absorption by the root system of the plant or being able to be sprayed directly onto the plant parts of the ground.

8. The method for solubilizing, dispersing or stabilizing a substance according to claim 6 or 7, characterized in that the poloxamer in combination with the resin and/or the tocopherol melts at a temperature of about 40-60 ℃, the temperature of the melt can be lowered by adding one or more solvents, the plant active agent to be dissolved is dispersed in the melt, after which the melt is cooled for a period of time until it becomes brittle, then it is coarsely ground in a crushing mill, then it is finely ground with water in a hammer or emulsion mill until the dissolved crystals are reduced to a diameter below 5 microns, after which the dissolved crystals are further dissolved or dispersed in water, the solution can be poured into the plant humus at the root system of the plant or can be sprayed directly onto the plant parts on the ground.

9. The method for solubilizing, dispersing or stabilizing a substance according to any one of claims 6 to 8, wherein the poloxamer in combination with the resin and/or the tocopherol melts at a temperature of about 40-60 ℃, and the temperature of the melt is lowered by adding one or more solvents selected from the group consisting of: water, glycerol, propylene glycol, polyethylene glycol (PEG)400, ethanol, polyethylene glycol (Macrogol)400 or isopropanol, then the substance to be dissolved is dispersed in the melt, after which the melt is cooled for a period of time until it becomes brittle, then it is coarsely ground in a pulverizing mill, then it is finely ground with water in a hammer or emulsion mill until the molten crystals are reduced to a diameter below 5 microns, after which the dissolved crystals are further dissolved or dispersed in water, the solution being able to be poured into the plant humus at the root system of the plant or being able to be sprayed directly onto the plant parts on the ground, said substance to be dissolved being a heat-labile plant active agent.

10. A stabilizer comprising a melt or a transparent gel based on at least one poloxamer in combination with natural or synthetic resins and/or tocopherols; and an active substance which is soluble and stable in the melt, the gel viscosity ranging from a solid state through a semi-solid state, i.e. a jelly-like state, to a liquid state.

11. A stabiliser according to claim 10, comprising a transparent gel having a viscosity ranging from a semi-solid, i.e. frozen cream, to a liquid, the gel being based on at least one poloxamer in combination with natural or synthetic resins and/or tocopherols, a solvent selected from: water, glycerol, propylene glycol, polyethylene glycol (PEG)400, ethanol, polyethylene glycol (Macrogol)400 or isopropanol, and a lipophilic or hydrophilic active agent solubilized, dispersed and stabilized in the gel, wherein the poloxamer is poloxamer 188 and/or poloxamer 407 and/or a substitute and/or derivative thereof.

12. A stabiliser according to claim 10, comprising vitamin C, E and ACC and comprising the following components in shampoo form:

the water content is 74.11 percent

Sodium laureth sulfate 11.67%

Cocoamidopropyl betaine 2.00%

Coconut oil base diethanolamide 1.70%

Disodium laureth sulfosuccinate 1.32%

Perfume 1.00%

4071.40% of poloxamer

1880.60% of poloxamer

1.00 percent of vitamin C

Acetylcysteine 1.00%

Alpha-tocopherol 0.50%

Sodium dodecyl sulfate 0.80%

0.50 percent of phenoxyethanol

Imidazolidinyl urea 0.20%

Polyethylene glycol-120 methyl glucose dioleate 0.10%

Tetrasodium edetate 0.10%.

13. A stabiliser according to claim 10, which is in the form of a gel comprising coenzyme Q10, vitamin C and vitamin E, and:

the water content is 71.43 percent

1888.93% of poloxamer

4078.93% of poloxamer

Alpha-tocopherol 5.00%

Coenzyme Q102.14%

3.57 percent of vitamin C.

14. A stabiliser according to claim 10, in the form of a gel comprising propolis having the following composition:

the water content is 70%

Poloxamer 18818%

13% of propolis.

15. A stabiliser according to claim 10 in a solid or semi-solid state comprising an active agent concentrate, the melt or gel of the solid or semi-solid stabiliser being a water vapour bearing solid and being a hydrophilic and/or water soluble solid with a large surface area which is compressed into gelatin capsules, powder dose sachets or tablets and effervescent tablets.

16. Stabiliser according to claim 10 in solid or semi-solid form, comprising an active agent concentrate, the melt or gel of the solid or semi-solid stabiliser being a solid with water vapour and being a hydrophilic and/or water-soluble solid with a large surface which is compressed into a gelatin capsule, a powderAmount of sachets or tablets and effervescent tablets of hydrophilic and/or water-soluble solids (surface coefficient) having a large surface or surface enlargement by spraying and/or freeze-drying>0.01m²Per g, BET method) includes one or more of the following:

exudates, such as acacia, tragacanth, karaya, ghatti;

seed powders, such as guar gum, carob flour, tara stone flours, tamarind gum;

detergents, such as pine gum, pectin, agar, alginates, carrageenans, furcellaran;

biosynthetic hydrocolloids, such as flavins;

modified hydrocolloids, such as propylene glycol alginate, amidated pectins;

cellulose derivatives, such as methyl cellulose, methyl ethyl cellulose, methyl hydroxyethyl cellulose, methyl hydroxypropyl cellulose, sodium carboxymethyl cellulose;

silica, such as silica aerogel;

proteins, such as gelatin, skim milk powder;

sugars, such as lactose, mannitol, xylitol, sorbitol, dextran.

17. A stabiliser according to claim 10, comprising one or more hydrophilic or lipophilic substances suitable for use in food supplements, cosmetics and dermatological preparations, namely coenzyme Q10, vitamin C, vitamin E, beta-carotene, vitamin a, vitamin D3, lutein, lycopene, folic acid, vitamin B12, omega-3 and omega-6 fatty acids.

18. A stabilizer according to claim 10, comprising one or more substances such as insulin (antidiabetic), cyclosporin A, and extracts of plants such as Silybum marianum, Passiflora edulis, Petasites japonicus, etc., and derivatives thereof (such as silymarin, chrysin, etc.).

19. A stabiliser according to claim 10, comprising a polyphenolic compound that comprises an active agent in an aqueous environment in an amount of from 2% to 5%.

20. A stabiliser as claimed in claim 10, comprising an anti-infective resin-like substance or a preservative substance.

21. A stabiliser substance according to claim 10, comprising a substance for wound application based on propolis, selenium dioxide, tar and/or mineral oil.

22. A stabiliser in the form of an active agent concentrate for use in plant growth comprising an aqueous suspension or solution containing an active agent or a dissolved particulate of an active agent in a transparent mixture based on at least one poloxamer, resin and/or tocopherol, wherein the maximum value of the dissolved crystals is measured to be 5 microns.

23. A stabiliser in the form of an active agent concentrate for plant growth according to claim 22, comprising a dissolved crystalline solid based on at least one poloxamer, resin and/or tocopherol and an active agent for plant solubilisation and stabilisation in the dissolved crystalline solid, wherein the size of the dissolved crystalline solid is 5 microns or less.

24. A stabiliser in the form of an active agent concentrate for plant growth according to claim 22 or 23, comprising a dissolved crystalline solid based on at least one of poloxamer 188 and/or poloxamer 407 and/or a substitute thereof and/or a derivative thereof, a resin and/or a tocopherol, and a solvent selected from the group consisting of: water, glycerol, propylene glycol, polyethylene glycol (PEG)400, ethanol, polyethylene glycol (Macrogol)400 or isopropanol, and lipophilic or hydrophilic active agents for plant solubilization, dispersion and stabilization in said melted crystals.

25. Stabiliser in the form of an active agent concentrate for plant growth according to any of claims 22-24, characterised in that it is dissolved in a hydrophilic and/or water-soluble solid (surface coefficient) with a large surface or surface enlargement by spraying and/or freeze-drying>0.01m²Per g, BET method), wherein these substances are one or more of the following:

exudates, such as acacia, tragacanth, karaya, ghatti;

seed powders, such as guar gum, carob flour, tara stone flours, tamarind gum;

detergents, such as pine gum, pectin, agar, alginates, carrageenans, furcellaran;

biosynthetic hydrocolloids, such as flavins;

modified hydrocolloids, such as propylene glycol alginate, amidated pectins;

cellulose derivatives, such as methyl cellulose, methyl ethyl cellulose, methyl hydroxyethyl cellulose, methyl hydroxypropyl cellulose, sodium carboxymethyl cellulose;

silica, such as silica aerogel;

proteins, such as gelatin, skim milk powder;

sugars, such as lactose, mannitol, xylitol, sorbitol, dextran.

26. Use of the product according to claim 10 or 11 for dissolving all types of fats, proteins, resins and resin-like substances, for releasing all types of fats, proteins, resins and resin-like substances from a surface.

27. Use of the product according to claim 10 or 11 for maintenance and cleaning of articles.

28. Use of the product according to claim 10 or 11 as a lubricant.

29. Use of the product according to claim 10 or 11 for separating substances to suppress their odour and/or taste.

30. Use of a stabiliser in the form of an active agent concentrate prepared according to the method of any one of claims 22-25 in the form of an aqueous suspension or solution comprising a molten particle of an active agent or active agent in a transparent mixture based on at least one poloxamer, resin and/or tocopherol, wherein the maximum value of the molten crystals is measured to be 5 microns, for influencing the growth of plants by adding the suspension or solution in a dissolved or suspended state in water to the humus area of the plant or spraying the suspension or solution directly onto the plant parts on the ground.

31. Use of a stabiliser in the form of an active agent concentrate according to any of claims 22 to 25 for influencing plant growth by adding the suspension or solution in water in dissolved or suspended state to the root zone of the plant or spraying the suspension or solution directly onto plant parts on the ground.