HU227829B1 - Composition comprising oxigen, mixture comprising the composition for pharmaceutical, veterinary and cosmetic use, and process for producing the composition, and appartus for the process - Google Patents

Abstract

Oxygen-treatment (M1) of liquid unsaturated 6-26C compounds involves: (i) passing mixture of ozone and oxygen gas (O 2) through liquid material (LiqM) in reaction mixture chamber (RxnMC) at 40[deg]C; (ii) measuring temperature (t) of LiqM; (iii) continuing passage until measured (t) has reached maximum value; and (iv) controlling (t) in RxnMC during passage of LiqM below 100[deg]C by reducing rate of flow of LiqM. Oxygen-treatment (M1) of liquid unsaturated 6-26C compounds involves: (i) passing a mixture of ozone and oxygen gas (O 2) through the liquid material (LiqM) in a reaction mixture chamber (RxnMC) at 40[deg]C; (ii) continuously measuring the temperature (t) of LiqM; (iii) continuing the passage until the measured (t) has reached a maximum value; and (iv) controlling (t) in RxnMC during the passage of LiqM below 100[deg]C (preferably 80[deg]C) by reducing the rate of flow of LiqM. Independent claims are also included for the following: (1) a composition (C1) for therapeutic, veterinary and cosmetic application comprises: (a) hydroxyproline (less than 10 mass.%), and (b) a carrier material prepared according to (M1) (less than 20 mass.%); and (2) an apparatus for carrying out (M1) comprises: (a) a high voltage ozonizer (6) having a regulated ozone outflow line, (b) a reaction chamber (11) having an inflow and an outflow duct and a filter element permeable for the inflowing gas but non-permeable for O 2; (c) gas pump (13) coupled to the outflow duct of (11); (d) thermometer (12) for measuring (t) of O 2; and (e) a temperature regulator connected to (12) and coupled to (6) to reduce or cut off gas supply if (t) exceeds a pre-determined maximum. The inflow duct is connected to the outflow line of (6). (11) contains the LiqM.

Description

Oxygen-containing preparation, Mixture containing, for medical, veterinary and cosmetic uses, process for the preparation of the product, and equipment: the process

The present invention relates to an oxygen-containing composition, a composition containing the composition for medical, veterinary and cosmetic applications, to a process for the preparation of the composition and to an apparatus.

Is the BP 822 80? European Patent Bis and its corresponding US Patent No. 139,876 disclose a composition suitable for therapeutic, veterinary and cosmetic purposes containing the essential substances necessary for the metabolism of living cells, namely oxygen and · proline and hydroxyproline. that at the site of burns or mechanical injuries where the capillary blood vessels are damaged the natural healing process was initiated by the preparation, despite the lack of blood supply. The special wound healing effect was demonstrated by the experiments detailed in the cited patent.

Oxygen is present in the composition in the form of pressures substantially above atmospheric pressure, and the gelatin gel carrier used mechanically binds the oxygen in microscopic "inclusions" during cooling and curing, due to the high surface tension. The use of the preparation was made difficult by the fact that the increasing pressure had to be maintained until the time of use. The condition was only ensured by the use of special double-walled vials. A further difficulty arose from the fact that a covered treatment was suggested so that the released oxygen could only flow in the desired direction, i.e. towards the damaged surface. Covered treatment is well known for its complexity and limits its use.

Proline in gelatin was converted to bidroxyproline by the presence of high-pressure oxygen and made the gel consistently fluid, leading to a further decrease in surface tension and increased oxygen loss,

As described in the pharmaceutical, veterinary and cosmetic formulations, the presence of oxygen is closed. in space it was provided by gaseous high pressure oxygen. Cosmetic preparations in which the presence of oxygen by means of peroxidation is assured are already known. Such compositions are disclosed in European Patent Nos. 391780 B1 and 293 535 B1.

In these patents, peroxidation is characterized in that the oxygen-saturated corn oil is illuminated by ultraviolet light and the material irradiated in this way is

Of transformation has been established. None of the patents disclose the details and findings of the process employed, nor do they suggest that irradiation and oxygen saturation occur in an air-free atmosphere.

It is known, however, that intense ultraviolet radiation produces ozone, but the publications cited do not directly indicate the presence of ozone. Ultraviolet irradiated air inevitably reacts with nitrogen in the resulting roe deer and produces nitrogen compounds harmful to the living body. From the cited publication, it is not known how harmful nitrogen compounds are kept away from the starting material, and whether they can prevent such nitrogen compounds from entering the starting material at all. Since ultraviolet light can exert its action only on the surface,. it is not clear how the degree of restructuring referred to in this description can be triggered or demonstrated.

The documents cited do not mention the measures taken to control and control the reaction of unsaturated oils with ozone, the absence of which will inevitably lead to an explosion.

Because of the above considerations, it is not based on those documents. there is evidence that the structure of the treated maize oil described above has undergone a complete transformation in which the presence of nitrogen compounds is excluded and that the substance is capable of delivering sustained and homogeneous oxygen atoms,

The indicated cosmetic use does not imply that the substance acts as a slow and limited source of oxygen on its own, and as such can be used alone.

In addition to medical, veterinary and cosmetic uses, there is a need in other areas of engineering for a substance that is capable of delivering oxygen in small but persistent amounts when in contact with an oxygen-poor medium and that does not contain any harmful components for the human body. In view of this, there is a realistic need for such material.

It is a primary object of the present invention to provide a composition and a process for the preparation thereof which is capable of releasing oxygen from unsaturated fats and oils as feedstocks permanently but at a limited rate when the contact medium with it is poorer than oxygen.

It is a further object of the present invention to provide a composition which is advantageously used for medical, veterinary and cosmetic purposes, and does not require the use of pressurized bottles, using a substance created as a solution of the primary object. From this mixture we expect that. cited in BP 0 822 807 BI · ·>.

It should be at least equivalent to or better than the composition described herein, and should be easy to handle, store and have the consistency required for the intended use, i.e., in the form of gel, cream, foam or spray. Ease of use means easy application, i.e. uncovered treatment, and easy storage refers to the usual tubular, viable or standard vial formulation for pharmaceutical formulations, which does not require storage above atmospheric pressure.

Another object of the present invention is to provide an apparatus capable of performing a process to be created according to a primary task,

In order to accomplish this task, they had to look for a raw material that is tissue-friendly and can be used for therapeutic purposes.

In order to solve this primary object, we have provided a composition which is based on fatty acid diesters and is an initial unsaturated carbon derivative according to the invention and is prepared from this starting material in an atmosphere of up to 100 ° C-10 ° at maximum temperature, by refluxing a mixture of ozone and oxygen, you have a structure that differs from that of the starting material due to the presence of an epoxy structure and has different physical properties, in particular, an increased, e. has a higher density and a different viscosity.

A. The starting material is suitably vegetable oils, preferably olive oil, castor oil or oleic acid.

A second object of the present invention is to provide a composition comprising said composition for use in medical, veterinary and cosmetic applications, wherein the amount of the composition having an epoxy structure is less than 20% w / w of the composition, preferably less than 1% (w / v). it also contains between 2% and 5% of hydroxyproline, a gelling agent and optionally a preservative, and finally distilled water.

In a preferred embodiment, the amount of gelling agent is up to 5% and the amount of preservative is up to 2%.

The consistency of the composition can be positively influenced if it contains a pharmaceutically acceptable cream as a carrier for the desired composition.

According to a further object of the present invention there is provided a process for the preparation of the above-mentioned composition wherein the liquid starting material is bubbled in a reaction space with a variable mixture of ozone-oxygen and the resulting exothermic reaction temperature is reduced to ratio is adjusted to below KXFC - 105 ° C and the gas mixture is flushed with suction over the reaction space,

Complete conversion is achieved by maintaining the flow at least until peak temperature is reached,

From a security point of view, a. the reaction temperature is set below 80 ° C,

According to a further object of the present invention, there is provided an apparatus for carrying out the process described herein comprising an ozonator for producing a high-voltage ozone-oxygen mixture from oxygen having an adjustable gas outlet. connected to a gas receiving inlet of a conduit bubble reactor, a suction device connected to the outlet of the bubbling reactor, further comprising a thermometer measuring the temperature of the interior space of the bubbling chamber and connected to a volume of The carbon derivative is positioned as a starting material in the ozone oxygen flow pathway.

The most uniform mixing of the gas mixture and the starting material is provided by a permeable porous element within the bubble chamber, through the aroma of the gas mixture and impermeable to the starting material.

In a preferred embodiment, the oxonizer is coupled via an oxygen reservoir through a flow control valve and a shut-off valve, and is coupled to a thermometer shield circuit that closes the shut-off valve when the reactor peak temperature is exceeded.

When used in the mixture according to the invention, the composition according to the invention has proven to be excellent in both burns and mechanical injuries. These results were more favorable than those cited in EP 0 822 807 B1. patented gel.

The invention will now be described in more detail by way of examples and experiments, based on the drawing. The drawing shows;

Fig. 1 is a schematic diagram of a device used to produce a new epoxy structure containing oxygen; the

Figure 2. reaction temperature-time diagrams for various gas streams; the

Figure 3 is a graph of peak reaction temperature and time for various gas streams; the

Figure 4 is a schematic of the arrangement used to measure oxygen release; and that

Figure 5 is a diagram of the arrangement of Figure 4.

The ozone generator treatment apparatus depicted in Figure 1 is a ozone generator. The unit comprises a high pressure oxygen tank 1, a multi-stage pressure reducer 2 connected thereto, a pressure regulating valve 3 embedded in its outlet section, and a magnetically controlled shut-off valve 4, starting with water vapor in oxygen gas. of the column, preferably 5 columns filled with silica gel and a high-voltage ozoneizer 6. The ozonizer 6 is: a cylindrical column made of an insulating material, preferably glass or ceramic, having a high voltage electrode located along its axis, separated by a spacing providing a given radial distance? it is surrounded by a coolant in which coolant, preferably cooling water, flows. The amount of refrigerant flowing is indicated by a rotary flow meter 8. THE ? The outside of the cooling jacket is bordered by a glass column of ozonizer 6 which is grounded. One end of the cylindrical space surrounding the high voltage electrode passes through the outlet conduit of the column 5, and the other end is connected to a bubble reactor 11 via a rotary flow meter 9 and a safety shut-off valve 10 which also indicates the amount of gas flowing.

In the bubbling reactor 11, the inlet gas: passage is blocked by a filter element 11a, the opposite side of which is to be reacted with material 11b, for example! in case of contact with and holding olive oil. The filter element 11a has a pore size between 2 cm 3 and 10 µm and the pores are permeable to the inlet gas. The pores are not permeable to the high viscosity liquid or gel material Ib, at a given pressure (at or near atmospheric pressure), so material 11b cannot enter the gas system prior to the bubbling reactor 11. Conveniently, the bubbling reactor 11 and the Ha ' filter element can be constructed from commercially available s2Filter filters with porous glass filters, in which case the filter plate diameter is as in the example. 90 am and the volume above was SG0 ml. Above the bubbling reactor 11, it is also desirable to provide a second, slightly larger, storage space to collect any foaming material formed during the reaction. In the reaction space of the bubbling reactor 11, the temperature of the substance 11b is measured by a fast-response, preferably digital, thermometer 12, whose displays provide the basis for controlling the reaction, and its temperature output is connected to the inlet 15.

The bioreactor reactor 11 and the storage compartment above it are provided with an open suction device 13 connected via a funnel, the suction power of which is controlled by a control unit 14.

-6 ozone capture column, not shown, to ensure that the ozone content of the gas leaving the open space is below the allowable threshold.

The high-voltage electrode of the ozonizer is connected to the high-voltage output of the high-voltage transformer, and its primary coil is connected to the mains voltage via a ground-down transformer and a protective shield. A. By adjusting the voltage of the 16 toroidal transformer, the magnitude of the discharge on the ozonizer can be controlled. The control input of the protective circuit 15 is connected to such an output of the thermometer 12. which shows the voltage when the temperature detected by the thermometer 12 has exceeded a set maximum allowable value. It also actuates the shut-off valve 4 at the protective current 15.

The purpose of the apparatus outlined in Figure 1 is to produce an oxygen scavenging material from an unsaturated carbon derivative having a density of less than 1, from 6 to 26 carbon atoms, especially natural vegetable oils. A suitable starting material for this purpose was common olive oil (© lenni olivae), which had a sufficient purity of the pharma- ceutical raw material. used ordinary olive oil.

In the arrangement depicted in Figure 1, before switching on, the sterilization bubble reactor 11 was provided with 3 (1 ml olive oil) on the filter element before the high voltage was switched on to cool the ozonizer 6, As a second step, the exhaust fan 13 was started and then, by opening the pressure regulator valve 3, pure oxygen gas was injected into the system. The turret transformer 16 was connected to mains voltage and the turret transformer set a voltage that Oxygen entering the space is partly converted to ozone due to the electric field strength, the reaction generates abundantly and the heat generated is transported by the cooling water 8lnél ° C between normal and inlet cooling water ential should be configured. The silica gel in 5 column ensures that the concentration of water vapor be oxygen from 6 ózoulzátorba below 0.01 ppm, because content of water vapor, this significantly exceeds appreciably degrade ozone production efficiency and also can make the formation itself impossible.

When the voltage required for ozone formation is present, the amount of ozone to be bubbled through the bubbling reactor 11 is mainly determined by the position of the valve 3. The gas entering the bubbling reactor 11 (which is a mixture of ozone and oxygen) is distributed by capillaries of the filter element 1a.

The gas is bubbled through the liquid space above and contacts and reacts with the oil over a large area across its entire cross-section. This reaction results in intense skin formation.

With this in mind, by controlling the amount of ozone added, care must be taken to keep the reaction temperature below a maximum value. According to our experiments, the maximum reaction temperature should be kept below 10 10-105 1C.

For this purpose, the output of the thermometer 12 connected to the protective circuit 15 is set to SO ^C 'and when this is achieved the protective circuit 15 switches off the high voltage and interrupts the oxygen supply through the shut-off valve 4. The extraction device 13 is, of course, continuously operating, and special care is taken to ensure continuous extraction.

During the reaction, the distribution of gas flowing through the oil mass can be controlled by controlling the speed of the fan in the extraction device 13. It has been found that optimum conditions are obtained when a ring-shaped shape is formed on the free surface of the oil. As the reaction progresses, the viscosity of the oil decreases, so maintaining the ring requires increasing fan rotation. The storage space above Bubbles II is only required for safety reasons, because if the initially selected ozone flow is too strong, and the safe storage space is provided to accommodate this larger volume. With properly set parameters, this foaming and volume increase will not occur.

The temperature-time evolution of the reaction of the starting olive oil with ozone is illustrated in the diagrams in Figure 2. The difference between the individual diagrams was the position of the pressure regulator 3 valves, the delivered gas flow, a. was highest in the diagram, e. and the smallest in the case of a diagram. Each of the graphs is characterized by an initial rise in temperature and then a slow decrease after reaching a maximum value. The reaction assumes that, until the maximum is reached, one of the double carbon bonds in the precursor material splits the carbon chains and enters into one bond an oxygen atom with its two valencies, which is typical for epoxy bonding. This process generates heat and causes an initial increase in temperature. After reaching the maximum temperature, the temperature decreases continuously. It is believed that this process occurs by epoxidation of the double bond between 9 and 10 carbon atoms in the glyceride or triolein, which makes up a significant portion (about 70%) of the olive oil, i.e., triolein epoxide.

If the addition of the gas is maintained until it has returned to room temperature, the structure of the resulting material remains stable over time. The diagrams in Fig. 2 show that as the gas feed is reduced, the reaction becomes slower and the maximum flattens out. Although no significant differences were found in the properties of the material obtained. - e. Among the production methods outlined in the diagrams, the most stable material was produced with a maximum breast temperature of δ-80 ° C.

Figure 3 shows the temperature maxima for the various reaction rates and the time required to reach them. The diagram is not continuous, its points refer to the individual reaction data under different ozone flows. The dashed curve represents the range of the steady-state reaction without run.

The new epoxy structure material obtained during the stable reaction differs significantly in properties from the starting oil. The yellowish-translucent, viscous oil from the oil has turned into a milky white substance, which has a significantly lower viscosity, appears to be solid in a test tube, and has a slightly fluid consistency in a crucible. Density after removal from reaction space: 1.082 g / cm³ The substance has a noticeable smell of arc discharge.

The substance contains significant amounts of bound oxygen. The substance is also characterized by a small amount of spontaneous oxygen release, which is enhanced under appropriate environmental conditions (eg contact with oxygen-depleted tissues). corresponds to the normal atmospheric pressure in the epoxy material, which is about five times the partial pressure of oxygen in air, about 0.2 bar.

To illustrate the spontaneous release of oxygen, the time course of the Imi substance falcon during the first 50 hours after its formation was measured. Table 1 shows the following data:

Table 1

Torah) 1.) 1 2 4 5 6 50 Crowd UI 1,082 1,081 1.0805 1,080 1.0795 1,079 : 1.0565

For comparison, the initial inoculum oil depletion was also examined, and the initial volume of 0.8722 g per 1 ml volume decreased to 0.8715 g by the end of the first hour, and this value remained unchanged at the end of the 50th hour. The initial mass jerk was presumably due to the removal of a small amount of volatile material. The Comparative Study shows that the weight of the treated substance decreases monotonically over time.

_ <).

In addition to the density reduction measurements, the oxygen depletion was measured directly using the measuring scheme depicted in Figure 4. Made for the layout by the American Diamond General Company. A Chemical Microsensor 30 instrument equipped with a Clark electrode sensor 29 was used and. to which 31 plotters are attached. A constant temperature of 32 ° C was maintained in the hollow interior of the chamber 21 used for measurement. The stabilized temperature water enters through the inlet pipe 22 into the interior of the chamber 21 and exits through the outlet 23. The chamber 21 is provided with a 0.8 enC volumetric vessel 25, which is provided with the instrument 30 and has a housing 29 for receiving a sensor 29 in its side wall. The flask 25 is filled with physiological saline solution and is continuously agitated by magnetically operated agitators 24. The free surface of the measuring vessel 25 is 9 µm. two membranes made of thick PVC film, which are secured by 27 clamping rings along the stable rim. The interior of the clamping ring 27 was filled with the test substance 28 to be measured. It was assumed that when oxygen was released through the membrane 26, oxygen would be drawn into the saline vessel 25, as detected by the sensor probe 29.

Figure 5 shows the resulting regisbate having a time axis from right to left. The beginning; From the 20% value, the oxygen concentration measured nearly tripled, and then the large amount of oxygen present was gradually oxidized by the Clark electrode, and the measured signal returned to baseline. The valuable data here is the initial leap, and the fact that the Clark electrode is oxidized proves that enough oxygen has been added to the solution. Measurements were repeated with a newly activated Clark electrode, including storage of 28 test materials for seven days and eight days in open air, and the resulting diagram was similar to Figure 5.

If stored in a confined space, such as a crucible or tube, or mixed with an additive that forms a film of a few microns on its outer surface, this prevents the spontaneous release of oxygen and preserves its oxygen release capacity over a long period of time.

In the example shown, a 30 ml volume of inoculated oil is restructured in 45 minutes and requires an ozone content gas flow rate of 25 liters / hour. As an example; In this case, the corresponding power consumption is 200-250 W. The ozonizer has a significantly higher reaction power, approx. 25 l / min, therefore the amount of finished product that can be prepared per hour is about 20 l.

The formation of the epoxy structure was also investigated for other oils,

-10A selected starting material pharmacology? quality oil (acidum oleutn), of which 50 ml was placed in the 1.1 bncr. The flow rate of gas consisting of a mixture of ozone and oxygen was 120 to 130 l / h. With the transducer 16 torolt, the primary voltages of 200 V are connected to the 1? to the primary winding of a high voltage transformer. Table 2 summarizes the reaction temperature T as a function of treatment time.

2, Table acidnm oleum

t (h, min) ICC) t (h, min) T (° C) ί t (h, min) '1 ( ^U C) ooo 24.1 2000 76.0 4 00 67.7 0 15 56.7 2 15 76.8 4 15 58.8 fo 30 66.5 2 30 77.0 4 30 46.5 0 45 69.6 2 45 77.0 100 70.6 30.00 77.0 1 15 71.8 3 15 76.0 1 30 73.6 3 30 74.7; 1 45 75 3 45 ............... 72.3

After about 50 minutes of treatment, the color of the substance began to turn yellow, the first hour. by the end of the day it had turned orange-red currant color, it was getting darker, at the end of the second hour it was coffee-brown; After cooling to room temperature it has a density of 1.42 g / cm 2 and the substance is dense, sticky. The substance burns violently with a blue, almost UV-like flame.

In another experiment, ozone production was reduced and, under otherwise unchanged conditions, only 140 V was applied to the primary side of the 17 high voltage transformer. As a result, the temperature increased more slowly, that is. by the end of the first hour it was only 58 ° C.

The reaction was carried out with pharma-grade sunflower oil (oleum helianthe). The adjusted parameters were: test volume 30 ml, starting density 0.02 g / cm ² , primary voltage 150 V, gas flow 120 vol. Table 3 summarizes the temperature evolution over time:

-π3. Table oleum helianthe

i (h, u and) Γ foC) T (b, m in) T (Ab t (h, min) r ro 0 00 21.8 1 20 58.7 2 40 39.6 0 hits 5Ó.0 1 30 58.2 2 50 33.0 0 20 65.3 I4Ö 58.2 030 66.0 1 50 58.2 0 40 64.0 2000 58.3 ø50 61.4 2 10 56.8 100 60.5 2 20 54.1 1 10 59.6 2 30 47.7:

During the reaction the material is foaming, after cooling to room temperature ,, half after 20 minutes in a clear white color density 1,1.7 g / cc was ^first It burns with a huge yellow flame. The material has a significantly dense, gelatinous consistency than sunflower oil.

The reaction was carried out with pure linseed oil (oleum Unt). The set parameters were as follows; the test substance has a volume of 30 nt, an initial density of 0.925 gfonri, a primary voltage of 16 V, and a flow volume of 120 g of the gas mixture. Table 4 summarizes the temperature evolution over time:

Table 4 oleum Üni

t (h, min) τ co t (h, min) Ϊ CC j Ooo 19.5 1 20 49.0 0 10 48.0 1 30 47.7 0 20 54.0 1 40 42.5 030 55.0 1 50 38.2 O 40 53.0 0 50 52.6 1 0 (1 51.3 1 10 49.8

During the reaction, the material foams vigorously around the 10th pass, then the foam collapses at 2 (1 minute). The material thickens after 30 minutes, the reaction temperature drops rapidly at 30, and the flow of ozone oxygen is 1 hour SO minutes. After this time, the material was naturally cooled to room temperature, and the resulting epoxy material had a gelatinous consistency of 1.16 g / ctf at 20 ° C. It burns violently with a yellow flame.

The reaction of -12A was performed with curative grade quality castor oil (olive ricini), which is .4. one of the highest density vegetable oils (between 0.9 and 0.96 gfenr), The parameters set were: the volume of the substance to be tested is 30 volumes of the primary voltage, V »the flow volume of the gas mixture is 120 Iso, the temperature over time its evolution is summarized in Table 3:

Table 5. Default gender

t tb, min) T (° C) 0 00 : 20.0 0 10 52.5 0 20 63.5 030 55.0 0 40 43.0 0 50 36.8 100 51.0 1 10 26.0

No foam formation was observed during the reaction, however, the exotherm heat generation was very intense, the reaction was also relatively rapid and reached its peak by 20 minutes. Not only did the epoxy structure develop during the treatment, but the phoberization also took place, since after cooling, the substance is a jelly-like skin, has a crusty appearance and is not soluble in any conventional solvent other than ketones. We could not measure its density, as it has gas inclusions in the material during solidification. developed which made it impossible to use conventional measurement methods. The. the color of the substance is similar to milk and opalescent.

Of the unsaturated plant carbon derivatives of natural origin, coconut oil was last examined. This substance is a widely used cosmetic ingredient, at room temperature is similar to fat. Because of the need for a liquid carrier to bubble through the gas, the reaction was started at 36 ° C because at this temperature the coconut fat was already sufficiently liquid. The starting density of the starting material was 0.969 g / cnr. The amount of reaction material was 30 ml and the primary voltage was set to 200 V. The reaction temperature-time data are shown in Table 6.

-136, table cone fat

t (h, min) TfeC) 0 OO 36.0 10/05 64.0 0 horses 59.0 0 15 51.0 0 2 (1 39.5 0 40 34.8 0 50 32.5 OO 32.0

During the reaction, a sudden and rapid increase in temperature was observed, reaching the maximum temperature of 64 ° C in the 5th trial, and the temperature decreasing rapidly. The tithe lawsuit experienced a yawn, and this consistency was maintained throughout. After the reaction was completed, the density measured was 0.994 g / cnf

After experimentation with unsaturated vegetable oils and fats, it was desired to experimentally determine whether the epoxy formation and exothermic reaction outlined herein is solely the property of unsaturated carbon derivatives or the like in saturated oils. Successive experiments were performed with silicone oil, paraffin oil, and then as noted in the pharmacopoeia. with neutral oil. These oils contained only saturated hydrocarbons. During the reaction, a mixture of ozone and oxygen was bubbled through 30 ml samples of each. The primary voltage used was 200 'V and the bubbling volume was 120 1 / h. No increase in temperature or density greater than 1% has been observed in the oils listed here, and it can be reasonably stated that the exothermic reaction leading to the structural change occurs with the starting materials having unsaturated radicals,

The oxygen trapping agent produced as described is considered to be an effective source of oxygen and this property can be used in many applications.

One such application is the further development of the high-pressure oxygen and gelatin cream PROLÖXIN described in the patents cited.

Cellular metabolism requires the presence of oxygen and nutrients, and if any of these substances become blocked in their supply, the equilibrium is locally disrupted.

44Égés name. or, in the case of mechanical injuries, frostbite, lying in the affected areas, the blood supply is not or only insufficiently provided. PROLOX'IN contained oxygen and cellular hydroxyproline, and these. in the presence of the group, we have seen many examples of rapid, smooth and scar-free healing. Oxygen was added during the preparation of the gel to a value immediately above atmospheric pressure, whereas the hydroxyprolol, by contrast, was one of the constituents of the added gelatin produced from proline in the presence of oxygen.

We assumed that. oxygen is also provided by the epoxy oil described herein and does not require the use of pressures substantially above atmospheric levels. This. the carrier oil is prepared from a non-hazardous pharmacopoeial ingredient and can be processed by simple mixing with hydroxyproline and known inert gel or cream-forming ingredients and, if necessary, preservatives and other additives to give the desired composition,

In order to confirm the hypothesis outlined here, pre-hoc examinations were performed on New Zealand saliva. The combined effect of the olive oil-based epoxy structured oxygen scavenger and hydroxyproline at two concentrations of the latter was studied using a conventional cream base and a conventional gel base, and compared with a high pressure oxygen saturated gelatin gel.

Brief Description of Preclinical Experiments:

The experimental animals were neonatal rabbits weighing 2.5-3.0 kg. The animals were individually housed in standard stainless steel cages with a treadmill. The litter was changed daily as litter. The animal house temperature was 18 A at 2 ° C with a 10 minute air exchange. The relative humidity was 65 - SO%. Feeding was done with standard overfeeding, with the effect available on demand rainwater.

Two days prior to treatment, the hair from the back of the animals was first spit-shaved between the pelvis and the shoulder belt, and then the remaining hair was removed by cosmetic dressing.

Prior to treatment, animals were assigned to the following six different groups of five, and animals in each group were treated as follows.

For hair removal skin (about 12 x 8 cm area), an automatic 2 cm ² surface with a stamp of 182 ± 2 ° € for 15 sec. exposure time to tertiary burns in two diagonally opposite sites per animal. At two opposite locations of another diagonal of the same B&B interface. we sclarified the sin to the depth of the connective tissue beneath it.

The skin groups of the formed groups were treated twice daily with the composition corresponding to the group. The control group was treated twice daily with non-active hydrophilic base cream mead. The lesions and the degree of healing were monitored every two days by macroscopic data,

On day 9, histological sampling was performed on one of the affected skin areas of each animal, and healing was performed on healing days on healing days.

The cut wine samples were fixed in 3% neutral lysis and then subjected to histological processing.

Some groups were treated as follows:

1. A hydrophilic type Ph.Hg. VH. guideline cream containing 3% hydroxyproline 11 Hydrophilic Ph.Hg. Water according to guideline VII, containing 5% hydroxyproline HL Pharmacopoeial water containing 5% hydroxyproline IV. Aqueous Pharma Gel with 10% Hydroxyproline content V. Control

VI. Gel pressurized with O-Vcl containing 5% gelatin according to the aforementioned U.S. Patent.

Each of the materials in the 1-V groups contained 10% of the epoxy olive oil. In all cases, the hydroxyproline used was the L-hydroxyprofin formulation of the French REX1M of the Degossa-Büls group.

In Groups 1 and IL, the cream base is Ph, Hg. The unguyen hydrophyhcam non-ionicum, i.e. a nonionic emulsifying ointment, according to VII. The cream also contained 5% glycerol and 2% solutio conservants. The ingredients listed here (including the required amount of hydroxyproline) were mixed with each other and with the required amount of distilled water at 40 ° C to give a white cream.

IH. and AR. In contrast, in Group I, a gel was prepared by adding distilled water from hydroxyethyl cellulose, to which was added 5% glycerol, 5% and 10% hydroxyproline, and 2% solutio preservative as a preservative. The. in each of these examples, the percentages are by weight of the finished product.

Results:

During the first five days of the experiment, the following differences were observed with respect to the control group.

The IL, HL and IV. animals in groups did not show a thickened, scab-like hard layer on the burn surface, in these groups.

On day 9, two animals in the HL group were observed with a markedly different condition to each group. As a clear sign of healing, these two animals had a thin, non-scaly, yellowish-white parchment-like layer which had a peeled, smooth skin without any scarring.

On day 11, three animals were affected, their thermal surface was healed, and on day 13, all animals in the group 111 showed the healing image described above.

In the control group, complete healing occurred uniformly on day 19 in all animals. The healing in the animals of group Hl was free of scarring, whereas in the control group, the healed area showed severe scars on the hair.

Á VI. in the animals of group II, the result was between group HI and the control group.

The results of the histological examination confirmed the macroscopic findings, the fastest improvement was in the HL group. The effect is not only a. It appeared to be accelerated in the healing process but was uniform throughout the wound. The uniformity of the process resulted in the healed wound surface becoming almost identical to the intact surface. These properties were as evident in tertiary burns as in healing, ie, mechanical wounds.

The composition used in Groups 1 to 1V therefore has the properties shown to be suitable for direct use in both medical and veterinary applications, as well as in cosmetic formulations and for use as a raw material in the cosmetic field.

For extensive burns, especially at the beginning of treatment, where the wound surface cannot be subjected to mechanical stress caused by coating with a cream or gel, it is advisable to use a very high viscosity, almost completely liquid formulation or foam which is sprayed without mechanical stress on the surface. Such a composition may be prepared from the material used in the HL experiment, provided that the amount of hydroxyethyl cellulose is reduced to the required viscosity. Of course, as the healing process progresses, the use of a less viscous gel formulation may be used.

The preclinical experiments described herein were repeated in compositions containing epoxy structured materials made from oleic acid and castor oil. group, so the only difference was that we used the same structure oleic acid and castor oil instead of the epoxy olive oil as the oxygen carrier,

Experiments are still ongoing. the preliminary evaluation shows that all epoxy-based and castor oil-based formulations have a uniformly healing wound after roasting and the results so far are similar to those obtained with the olive oil carrier,

Claims (9)

Claims of Sahadahn ;. Preparation containing oxygen, the starting material of which is fatty acid glycerides, characterized in that the starting material is an unsaturated carbon derivative of from about 2 carbon atoms and that the preparation is ozone at a temperature not exceeding 100 to W5 ° C in a closed atmosphere. and oxygen, the mixture having a flow-through modified structure which differs from the structure of the starting material by the presence of an epoxy structure, and has different physical characteristics, in particular an increased density and viscosity of greater than 1.00. Composition according to claim 1, characterized in that the starting carbon derivatives are vegetable oils, preferably olive oil, castor oil or oleic acid. A composition for pharmaceutical, veterinary and cosmetic use according to claim 1 or 2, characterized in that the amount of the composition having an epoxy structure is less than 20% by weight, preferably less than 101%, of the composition. further comprising from 2% to 10% by weight of hydroxypiphohn, a gelling agent and optionally a preservative, and finally distilled water. 4. The composition of claim 3, wherein the gelling agent is present in an amount of up to about 2% and the preservative in an amount up to about 2%. A composition according to claim 3 or 4, characterized in that it contains a pharmaceutically acceptable cream as a carrier. 6. A process for the preparation of a composition according to claim I, wherein the liquid state starting material is bubbled through a reaction mixture with a variable ratio of ozone oxygen and the resulting exothermic reaction temperature is determined by the amount of bubbled gas and / or ozone and oxygen. the ratio is adjusted to between 100 and 105 and the gas mixtures are charged in the reaction space. with suction, . The method of claim 6, wherein the flow is maintained at least until the peak temperature is reached. 8. The O. or A process according to claim 7, characterized in that the reaction temperature is below 80 ^o C in. 9, Equipment of Figures 0 to 8. A process according to any one of claims 1 to 6, characterized in that it comprises an ozone oxygenate (O) blend of oxygen, using a high-throughput, which has an adjustable gas outlet and is connected to the gas receiving spout of the bubbling reactor (11). The suction device (13) is connected to the outlet of the bubbling reactor (ti) and includes a thermometer (12) for measuring the inside temperature of the bubble cavity (.11), which is connected to the gas volume control inlet of the ozonator (6) and the bubbling chamber (11). ) a certain amount of an unsaturated carbon derivative having from 6 to 26 carbon atoms as starting material (IIb) is placed in a stream of ozone oxygen. Apparatus according to Claim 9, characterized in that a filter element (Ha) which is permeable to the gas mixture and impermeable to the starting material (IIb) is provided inside the bubbling chamber (11). .1.1. Apparatus according to Claim 9 or 10, characterized in that the inlet of the ozonizer (6) is connected via a flow control valve (3), a shut-off valve (4) with oxygen (1) and a thermocouple (12) with a control circuit (1). 15), which, when the permissible peak temperature in the reaction space is exceeded, is. it closes the shut-off valve (4) and interrupts the power supply to the ozonizer (6).