FR2950254A1 - Composition, useful for preventing inflammatory effects caused by e.g. inflammatory agents, comprises water solutions (sugar solutions) exerting a higher osmotic pressure than that of the body fluids - Google Patents

Abstract

Composition (I) comprises water solutions exerting a higher osmotic pressure than that of the body fluids. ACTIVITY : Antiinflammatory. MECHANISM OF ACTION : None given.

Description

The present invention relates to and describes an original range of topical compositions, capable of preventing inflammatory body reactions caused by inflammatory agents being produced or injected superficially into or just under the skin. Such reactions or bodily effects can be caused by injuries, bites or bites from insects such as mosquitoes, spiders, wasps, bees and many others. The invention also relates to attacks on other animals such as jellyfish, worms and snakes but also plants, such as nettles and several other species.

The action of the compositions is preventative to the extent of removing the agents before the inflammatory reaction becomes extensive.

The discomfort and more or less serious health effects caused by acute inflammatory effects can, in today's times, be avoided in two ways: 1. Safeguarding and prevention measures. at. Repellents that discourage insects from biting or biting. Insects may be repelled by applying a large number of commercially available compositions. Lemon oils are usually among the most used. Although partially effective, occasional bites or stings, of course, continue to occur and are always unavoidable. 2. Anti-inflammatory measures. at. Pharmaceutical compositions.

Once the inflammatory agent has been injected and the allergic reaction has occurred, its effects can be relieved or alleviated by applying various compositions. Some are classified as pharmaceutical compositions, usually containing the antihistamine and / or other substances. 30 h. Treatments of traditional medicine - homeopathy.

A wide variety of traditional medicines are claimed to be effective in treating inflammation, caused by the causes mentioned above. The lightest cases can be treated by applying ice. The latter simply reduces the swelling.

The inflammatory process is well known. It follows the following order: 1. Perforation of the skin and injection of the inflammatory agent, leading thereafter to the inflammatory reaction. at. Inflammatory substances vary in nature, depending on the source. Stinging insects such as bees and wasps inject venom. Sharp insects, such as mosquitoes and many others, inject, among others, anticoagulant substances. Formic acid is also often found in the composition of these substances as well as more complex organic or biochemical substances. 2. Propagation of the substance by diffusion, due to blood flow and movement of lymphatic fluids, subsequently leading to the inflammatory reaction inside and / or under the skin. 3. The substance is then identified by the immune system at this time. It occurs within minutes of an immune response generated by the body's immune system, resulting in symptoms of inflammation. Histamine is then released naturally. This immune reaction can cause swelling, itching and in the most severe cases, symptoms of allergic shock.

No commercial product that removes the inflammatory agent before it has caused an immune reaction appears to exist.

United States Patent Application US2008085876 discloses a method of treatment for insect bites whereby a combination of the use of three compositions, a raw material, an immune suppressing agent and an agent is disclosed. nonvolatile (coal tar or Ichthammol), which is called a suction agent, the purpose of which is to keep the wound moist and open, allowing a number of drugs to enter the wound and heal the effects of insect bites or bites. This allows the tissue around the wound to "push" the foreign bodies out of the tissue.

Thus the purpose of said nonvolatile agent is only to keep the wound open, allowing the tissue to push the foreign bodies out of the tissue. However, it is not proposed that the agent should aspire inflammatory agents, whatever their natures. Moreover, coal tar is declared a carcinogen by the US Food and Drug Administration (FDA) and therefore completely banned as a drug in any method of treatment.

A multitude of so-called traditional medicine methods are described and are in the public domain. Those that include the use of honey, vinegar, extracts from many plants etc. They are said to attenuate all inflammatory effects and they do not claim to prevent inflammation.

Traditional treatments against bee stings include the application of "moist sugar," meaning sucrose, which is supposed to extract the venom. However, this treatment is neither widely known nor accepted, as treatment often fails because moist sugar is not in a form that can have any effect.

As explained below, an effective composition capable of extracting bee venom should be presented as a solution and not a solid. The solution must, further, be applied in sufficient volume and remain the long enough time applied to the puncture. If, however, too much moisture is added, then the sugar becomes too liquid, does not stay on the place of the sting and sinks sideways in an irregular manner. Thus, this treatment can at best be used on horizontal surfaces and if it is held manually in place long enough.

In reality, moist sugar must be very liquid in order to contain a sugar solution. This is explained later in this description. Moreover, the part of the body where the moist sugar has been applied, must still remain still for the duration of the extraction (about 30 minutes), because any movement makes fall the moist sugar. This moist sugar property is highly impractical and severely inhibits its effectiveness. In addition, because of this tendency of moist sugar to become liquid, if too much moisture is added, the amount left on the bite is usually too small and dries too quickly for the venom to be fully extracted.

The present invention opens a new way to prevent acute inflammation by removing inflammatory agents injected into the skin before they have caused an inflammatory reaction.

Surprisingly, the inflammatory reaction could be avoided by applying a topical absorbent locally to the site of contact just after contact with the inflammatory agent. Current remedies attempt to suppress the effects of such inflammatory substances only after the onset of an immune response. The present invention, for its part, claims to completely prevent the immune reaction from taking place, by extracting substances, which cause an inflammatory response, from the skin, by absorbing them before they have caused an immune reaction.

It was also amazing that the absorbent could be a simple water-based solution that can extract inflammatory agents before they cause an immune response.

These water-based solutions are thus formed to possess a very high inherent osmotic pressure (hereinafter referred to as "water-based solutions"), thus capable of causing flow of body fluids from the bite or point. In this way, the agents, which would otherwise have caused an immune reaction, are transported with the body fluids to the water-based solution where they are absorbed.

In a special claim, the water-based solution consists mainly of a solution of various forms of carbohydrates or sugars.

In a second claim the water-based solution is physically held above the puncture by enclosing it in a reservoir. Said tank may be in the form of a mechanical capsule, with at least one open side, or spongy material saturated with the water-based solution. The reservoir can also be made by making the water-based solution highly viscous or in the form of a gel.

In another possible claim, the water-based solution is made viscous by the addition of a set of suitable thickening agents.

A solution based on viscous water can also be converted into a gel, by the addition of a set of gelling agents.

In another embodiment of the invention, the water-based solution consists of a fructose solution, in the presence of calcium ions, a pH regulator and pectin.

The invention also depends on the techniques of preparation of the absorbent, so that it can be convenient to produce, package, distribute and simple application and handling.

The compositions of this invention:

The compositions, presented in the present invention, are intended to safely remove inflammatory agents by an aspiration phenomenon, related to said compositions having a higher osmotic pressure, than body fluids (generally referred to as isotonic in the medical context). Displacement of inflammatory agents occurs before and during the immune reaction process, thus obviating the use of formal drugs in many cases. Thus the use of compositions in the present invention provides a completely new preventative measure. It is surprising that a whole range of compositions, however simple, could prevent immune reactions, which often follow the injection of inflammatory agents. These compositions are water-based solutions or viscous gels having a very high osmotic pressure (hereinafter referred to as "high osmotic pressure solution") .The suction effect of the compositions of said high osmotic pressure solution. in this invention, is further enhanced by evaporation, or by drying, which occurs after topical application and increases the osmotic pressure.This enhancement of the osmotic "suction" by evaporation is completely contrary to the agent described in the US patent US2008085876, which assumes a nonvolatile agent Moreover, in said US patent, coal tar is not water-based and therefore exerts no osmotic pressure.

It is of vital importance that "the high osmotic pressure solution" is a true water solution and not a solid one. The limited efficiency encountered with the traditional method that uses moist sucrose sugar is undoubtedly due to the fact that sugar is not a solution but a solid. A solid has no osmotic pressure, that required according to this invention.

However, the solutions, by definition, flow and are thus unsuitable for application to a puncture of skin and much more difficult to maintain in place for the time necessary to absorb the inflammatory agent. According to this invention, solutions can be made viscous or gel-like by the addition of thickening agents. These gels consist of a three-dimensional structure and formed of macromolecules, encapsulating solutions or water. Usually this three-dimensional and dense structure prevents the free circulation of other macromolecules.

It was, contrary to universal belief, found that some gels could exert osmotic sucking of inflammatory agents. It was thus a great surprise that the inflammatory agents were still absorbed by the gel barriers, which is the essence of this invention.

The aqueous solutions of the inorganic salts and / or the organic molecules show what is called an osmotic pressure, which is equal to the equilibrium pressure exerted on a semi-permeable membrane, which separates the distilled water, on the one hand, of the solution on the other side.

Body fluids, which surround cells under the skin, are usually called "interstitial fluids" (sometimes in the medical context also called "isotonic" because they have the same osmotic pressure as blood or intracellular fluids).

These fluids have a salt concentration of about 0.9% (NaCl). This interstitial fluid shows an osmotic pressure of -8 * 105 Pascal at 37 ° C. In contact with the skin, any solution, having a higher osmotic pressure, will cause a transport of water through the skin, if the permeability is sufficient, from the interstitial fluid to the solution having a higher osmotic pressure and this process serves of the present invention.

The osmotic transport of the water, from the location of the puncture or injection of the inflammatory agent, to the high osmotic pressure solution, having a higher osmotic pressure, than the interstitial fluid, will also carry with it other substances such as inflammatory agents as well as other immune reaction agents.

This transport is made possible by the fact that the skin, pierced by the bite, is not completely sealed, but serves as a membrane, allowing the passage of water, dissolved minerals as well as a range of large molecules . In addition, the hole through the skin, due to the puncture and injection of the inflammatory agent, remains open until the tissue has closed the wound by clogging (usually in about ten minutes) . Water, mineral salts and larger molecules pass through this relatively easy hole. In this way, the injected inflammatory agents can be removed entirely or partially from the skin. It can be seen that if "high osmotic pressure solution", having a higher osmotic pressure than the interstitial fluid, is applied in a limited time after injection, then the immune reaction does not occur and the inflammation does not occur. 'not appear. In the best case topical application should be done immediately or within 10 to 30 minutes after the bite. Probably, also histamine, produced by first immune reaction, accompanies the extracted water, delaying and thus preventing inflammation.

The choice of a suitable "high osmotic pressure solution" must take into account a number of factors.

1. The high osmotic pressure solution should have as high a osmotic pressure as possible. The higher the osmotic pressure, the faster the transport of the liquid through the skin. If the transport is too slow, the inflammatory agents will not be removed until the sting hole is closed by the actions of the body's defense. 2. The high osmotic pressure solution should not per se cause an inflammatory effect. 3. The high osmotic pressure solution must not pose any adverse health risks in the short or long term. 4. The high osmotic pressure solution must also be practical to apply in sufficient quantity to be able to absorb the sufficient volume of liquid. 5. In addition, the high osmotic pressure solution must remain stationary above the injection site for the required time. 6. The high osmotic pressure solution should dry out by evaporation of water to increase the suction effect. 7. The high osmotic pressure solution should have a long shelf life and not be degraded and / or decomposed by microbial action or other reasons. 8. The high osmotic pressure solution should preferably be free of prolonged and expensive approval processes.

Although a countless number of solutions show a high osmotic pressure, these criteria make it possible to choose an appropriate solution for human and veterinary use. It seems better to choose a chemical approved as a normal ingredient or additive in food products. Such chemicals are classified as Generally Recognized As Safe (GRAS) generally recognized as safe by the US Food and Drug Administration. They are also listed as safe by the European Food Safety Authority.

By adding molecules to the water, the osmotic pressure increases. The osmotic pressure follows the Morse equation:

II = iMRT,

Where i is a dimensionless factor. M is the molarity.

R is the gas constant.

T is the absolute temperature.

The osmotic pressure is thus proportional to the molarity. As a result, the concentration should be as high as possible and the molecular weight as low as possible.

Concentrated salt solutions have high osmotic pressure. Seawater, for example, has an osmotic pressure of 10-27 * 105 Pa depending on the degree of salinity.

Saturated salt solutions have an even higher osmotic pressure and could potentially be useful. Although salt (NaCl) is a common additive of food substances, high concentration saline solutions cause pain and irritation and are not ideal. The same limitation is valid for most other mineral solutions.

Organic polymer solutions often show low values of osmotic pressure. However, some simple sugar solutions show some of the highest osmotic pressures that can be found. Thus a saturated solution of sucrose has an osmotic pressure which approaches 80 * 105 Pa at 25 ° C. Many other solutions of sugars show considerable osmotic pressures and some fructoses in particular can reach amazing levels. Thus a saturated solution of fructose has an osmotic pressure about twenty times higher than a medical isotonic solution. Thus, concentrated sugar solutions are very effective in causing the osmotic transfer of water from the low osmotic pressure interstitial fluids to the high osmotic pressure sugar solution. In other words, the osmotic power or suction potential is about twenty times higher for the concentrated solution of fructose compared to that of the interstitial fluid.

There are many forms of sugar, the most common of which are fructose, sucrose, sorbitol, xylitol, maltitol, lactitol, glucose, isomalt, lactose, mannitol and many more. The present invention is not limited to a special form of sugar while they can all be effective, alone or in mixtures of one with others.

The theoretical osmotic pressure, calculated using the Morse equation: II = iMRT, because saturated fructose solution is the highest of the most common sugars (187 * 105 Pa) and 80 * 105 Pa for sucrose in comparison with only 8 * 105 Pa for the interstitial fluid. Therefore the saturated fructose solution has the highest suction power among the substances studied. Many other sugars, alone or in combination with each other or with fructose and showing lower osmotic pressures, are still fully capable of absorbing sufficient amount of inflammatory agents. As mentioned above, the essential parameter is that the solution has a higher osmotic pressure than that of the interstitial fluids.

Sugars are also frequently used as dietary components and most of them are listed as authorized in food for human consumption. This is a clear indication that they are fully compatible with human tissue and, if used properly, should not cause adverse effects.

Sugars, in various forms, are clearly the preferred base, provided that they can be applied topically as a "high osmotic pressure solution" in sufficient quantity and also remain in place long enough for the inflammatory agents to be extracted and absorbed.

By adding a thickening gelling agent, the flow characteristics of the "high osmotic pressure solution" can be adjusted so that it can be easily applied topically while remaining in place over the puncture for the duration of time. of the extraction period even if this part of the body is moving.

It can be difficult to thicken the high solids sugar solutions. Often pectin or pectin derivatives are employed, sometimes in combination with gelatin, agaragar, starch, alginates, CMC, hydroxy methyl cellulose, carrageenan and many other gelling agents for thickening. The pH value can be critical to the rheological behavior of such gels and citric acid is often used as a pH regulator, but other acids such as acetic, sulfuric, phosphoric and hydrochloric acids as well as many others can also be used. Ionic strength influences the rheology and gel time of gels. In particular, the calcium concentration has an essential effect on gelation.

It has been found that certain special pectins could be used to make the appropriate gels, based on saturated solutions of sucrose and fructose. Calcium concentrations and pH were adjusted.

In another embodiment of the invention, "high osmotic pressure solution" is applied to the puncture as a spongy base (such as wadding, sponge and the like, saturated with "high osmotic pressure solution"). .

In yet another embodiment of the invention, the "high osmotic pressure solution" is first applied to a known type of dressing to protect superficial wounds. These dressings can be equipped with adhesive tapes or not. The dressing is then applied to the puncture in such a way that the high osmotic pressure solution is in contact with the puncture. These means of administering "the high osmotic pressure solution" on the puncture is particularly convenient because it allows "the high osmotic pressure solution" to remain in place on the puncture without the risk of sinking or falling. This configuration is particularly preferable when an open exposure of "high osmotic pressure solution" is undesirable, such as where clothing or a protective device is to be worn over the puncture.

In another claim, "high osmotic pressure solution" is applied to the puncture as a small cylinder or open capsule, with at least one open side. It is applied so that the "high osmotic pressure solution" comes into direct contact with the sting. The capsule or cylinder can be held in place by tape or a bandage. This configuration is preferred when the large absorbent volumes of the "high osmotic pressure solution" are needed, as in the case of severe injections of inflammatory agents.

Example 1

After a mosquito bite, a piece of sugar was placed immediately topically on the sting. A few drops of water were added, creating a suspension of sugar particles as well as a concentrated solution of sugar. The slurry was held on the puncture by means of a small cylindrical capsule to prevent flow. The capsule, containing the sugar suspension, was kept above the puncture for 15 minutes, after which it was removed and the remaining sugar was rinsed with water. No inflammatory effects occurred.

Example 2

Creation of a composition from 10 g of classic AF pectin 601, from the German company Herbstreith & Fox KG, which was dissolved in 390 g of water by boiling. 600 g of sucrose was added and also dissolved. The pH was adjusted to 5.

This hot solution was poured into a soft plastic tube and closed with a stopper. The solution was allowed to cool to room temperature. After one hour, the cap was unscrewed and it was checked whether the solution had crystallized and that it was still possible to remove it from the plastic tube. The composition had formed a viscous gel. After thirteen months of storage, the gel was still perfectly usable.

After a mosquito bite, a few ml of the composition was topically applied to the bite approximately 5 minutes after the bite occurred. After a few minutes the initial itching of the bite occurred. The composition was applied so that the gel formed a layer about 3 millimeters thick. After 20 minutes, the gel was rinsed with water. No inflammatory reaction occurred and the initial itching disappeared during treatment.

Example 3

In the composition described in Example 2, 20 g of alginate (Kelco International, Manugel, currently sold by FMC Biopolymers) are added before placing it in the plastic tube.

The alginate dissolves slowly and the resulting viscous composition was added dropwise to a solution of calcium chloride, 20 g / l.

The surface of the droplets solidified on contact with the calcium chloride solution and could be harvested. The droplets continued to solidify and formed capsules, about 3-5 millimeters in size.

The capsules were stored in an airtight container, preventing dehydration.

After a mosquito bite, such a capsule was placed on the sting and was held in place by a self-adhesive dressing. After 30 minutes, the dressing and capsule were removed. No inflammatory reaction occurred.

Example 4

80 g of crystalline fructose was mixed with 1.2 g of conventional AF pectin 601 from Herbstreith & Fox KG Germany. The powder was wetted with 20 g of water, to which was added 0.2 g of calcium chlorides. The pH was adjusted to 4 with citric acid. The suspension obtained was heated to boiling and maintained at this temperature for two minutes.

After cooling, the solution became highly viscous. In this case it could be applied to a sting, without sinking, falling or sliding.

After a mosquito bite, a quantity of said viscous solution was applied over the puncture. After 20 minutes the composition was removed with water. No inflammatory effects were observed.

Example 5

After a wasp sting on a hyper allergic child, the sting was removed by means of forceps. The puncture was rapidly covered with the sugar solution described in Example 4, 5-7 mm thick. After 30 minutes, the solution was removed with water. No inflammatory reaction occurred.

Claims (10)

Claims. 1. Compositions for preventing inflammatory effects, characterized in that they consist of water solutions, exerting a higher osmotic pressure, than that of body fluids. 2. Compositions according to claim 1, characterized by said water solutions are non-flowing. 3. Compositions according to claim 1, characterized by said water solutions are solutions of simple sugars dissolved in water. 4. Compositions according to the preceding claims, characterized by said solutions of sugars in water are rendered non-flowing by the addition of thickening or gelling compounds. 5. Compositions according to the preceding claims, characterized by the sugars are fructose and / or sucrose. 6. Compositions according to claim 5, characterized by said fructose and / or sucrose solutions having a dry solid content higher than 10%, preferably between 50 and 80%. 7. Compositions according to claims 4, characterized by the thickening agent is pectin, in a proportion between 0.1 to 10%, preferably between 0.7 to 2%. 8. Compositions according to claims 1-3, characterized by said sugar solution being held in a capsule, which has at least one open side of form to be able to place it on the place of ignition. 9. Compositions according to claims 1-3, characterized by said sugar solution is absorbed on a spongy material, preferably a self-adhesive dressing. 10. Compositions according to claim 7, characterized by said thickened sugar solution being supplemented with alginate, treated by the action of the calcium ions and / or the gelatin and / or the starch and / or other gelling agents so as to render it more viscous. 12