DE202007012343U1 - Amino acid-mineral-peptide complex, in particular modified by quantum mechanics, as a formula for regulating the skin - Google Patents

Abstract

Use of a multifunctional active substance mixture comprising a fraction of specific peptides having molecular weights of up to 10,000 daltons and a fraction of essential and nonessential amino acids obtained by
Incubation of cells at suitable growth temperatures,
- subsequent lysis,
- Harvest together with the maintenance medium and
- Separation of cell constituents having a molecular weight above 10,000 daltons, by ultracentrifugation / ultrafiltration and
Recovery of the fraction of specific peptides with molecular weights up to 10,000 daltons and the fraction of essential and nonessential amino acids,
for the preparation of a formula for regulating the condition of the outer skin of mammals, including man.

Description

The The invention relates to the use of a multifunctional active substance mixture for the Preparation of a formula for regulating the condition of the outer skin of mammals including of the human. Areas of application of the invention are the life sciences, especially the pharmaceutical and cosmetics industry.

The outer skin (lat. cutis) is the largest, heaviest and functionally most versatile organ of adult mammals. It forms as a sheath organ the boundary between inside and outside and acts as protection Environmental influences, e.g. as insulation layer against heat and cold. In particular, the protects Skin the body from water loss, sunlight, infiltration of pathogens or mechanical injuries and serves to maintain homeostasis (internal Balance) as well as communication and representation. Continue to take over the skin has important functions in the area of metabolism and the Immunology and has a variety of adaptation mechanisms.

The Skin consists principally of three main layers, the epidermis, the dermis (dermis) and the subcutis (subcutis), being the epidermis and dermis turn into several sublayers divide. While the epidermis is one of the epithelial tissues, there is the underlying Sclera consisting essentially of connective tissue fibers, in particular collagen as well as elastin, and is used for nutrition and anchoring the epidermis. The underlying subcutaneous tissue includes subcutaneous fat cells and loose connective tissue and forms the pad for the about that lying skin layers. The subcutis also includes the larger blood vessels and nerves, those with the capillary system and the fine nerve endings of the dermis.

Under Skin aging is the complex biological processes of aging age-related change of the skin. This includes in particular, degradation of the skin firmness-imparting keratin, and a deposit of fibers of skin elasticity mediating Elastin. This is accompanied by a loss of between the connective tissue fibers Stored water and a reduction of the skin supporting Fat, whereby it u.a. to dryness and wrinkling can come. In addition to the intrinsic aging, so the genetically controlled decreased reactivity skin cells play extrinsic factors (environmental factors such as UV light, chemical reagents, mechanical stress) an important Role.

There the skin most diverse influences inside and out is exposed, no other organ has such a high number on pathological changes on. inflammatory Disrupt skin diseases often due to itching or pain. In addition, many patients are subject tremendous psychological stress as they due to their skin disease be stigmatized. There are many different causes for skin diseases that when triggered the disease can interact. In addition to hereditary predisposition, e.g. for psoriasis or atopic dermatitis, This can be exacerbated by stress or infection. For many skin diseases is the exact mechanism of origin still unknown, where in many cases regulatory disorders of the immune system as the cause. So far, the most varied approaches been undertaken to regulate the condition of the skin and thereby positive influence on age-related processes and skin diseases to take.

to Tightening of the skin come in practice in particular certain peptides for use. In addition to botulinum toxin (Botox), which is injected under the skin is only temporary and is, for example, the synthetic Peptide acetyl-hexapeptide-3 (argirelin) suitable for external use and leads through Influencing the nervous signals to a long-term relaxation the facial muscles.

Because peptides function as messengers in the skin, defined peptides or peptide complexes are also used to regulate epidermis-dermis communication. From the document WO2006121610 is, for example, an anti-VEGF peptide or from the document WO03030860 a peptide-copper complex known for use in the manufacture of a skin care agent.

easier Skin diseases (such as allergic rash) can with anti-inflammatory Ointments or creams are treated. It is advantageous that through the external application the active ingredient acts only where it is needed; moreover, through the right choice of basis (ointment, cream, paste, solution, lotion) additional Effects are achieved. Because many of these ointments disinfect Contain ingredients or cortisone, their application is due potential Side effects, however, only advised in the short term.

adversely is that by using certain substances only individual operations from skin aging or inflammatory Skin diseases are addressable, which are the actual complex processes mostly only insufficiently taken into account.

task The invention is therefore a simple and effective to use Means for regulating the condition of the outer skin of mammals including of the human. Preferably, it is an object of the invention to provide an agent that addresses the factors of skin aging or Diseases UV light, free radicals and stress minimizes the Degradation of connective tissue fibers, especially keratin, inhibited, as well inflammatory Processes of the skin soothes.

These The object is achieved by the use of a mixture of active substances according to claim 1 solved. The other claims are preferred variants of the invention.

Completely surprising has the use of a multifunctional active substance mixture, comprising a fraction of specific peptides having molecular weights to 10 000 daltons and a fraction of essential and nonessential Amino acids, as suitable for the preparation of a particularly effective formulation for external use for the Regulation of the condition of the outer skin of mammals including of man.

The Recipe has the beneficial properties that they are in their formulation is stable, is absorbed by the skin and within the skin layers, especially the dermis, biologically is active.

Concerning the processes of skin aging leads the recipe of the invention with regular use to a significant reduction in skin roughness, wrinkle volume and the fold depth. In terms of Skin disorders, the formulation according to the invention for the prevention, Proven treatment and / or relief of various indications.

According to the invention is the multifunctional drug mixture by incubation of cells, preferably over a period of 2-8 Days, at suitable growth temperatures, followed by lysis of Cells, harvesting the cell lysate together with the maintenance medium, Separation of cell constituents of a molecular mass above 10,000 daltons by means of ultracentrifugation / ultrafiltration, preferably at a maturity of 12-36 h, as well as the extraction the fraction of specific peptides with molecular weights up to 10 000 Dalton and the faction more essential and not essential amino acids produced.

The exact composition of the multifunctional active substance mixture can not be determined analytically Therefore, it is present by its manufacturing process characterized. It contains Polypeptides of up to 80 amino acids Length, amino acids as well as salts and minerals. Among peptides are within the scope of the present Invention all possible, itself from at least two amino acid residues composed peptides or peptide chains or derived therefrom Understand structures, for example, peptides, in the Lysis of somatic cells are released. In this case, the peptide fraction Include peptides of various kinds, such as substance P (SP), delta-sleep-inducing Peptide (DSIP), Vasoactive Intestinal Peptide (VIP), Arginine Vasotocin (AVT), oxytocin, samatostatin, interleukin, enkephalins, β-endorphin, Neuropeptide Y, neurotensin, vasopressin, corticotropin-releasing hormones (Corticoliberin, CRH)., Thyrotropin-releasing hormones (Thyreoliberin, TRH). At the amino acids These are all essential and nonessential amino acids, in particular to glycine. Furthermore, the fraction includes minerals and salts of the elements magnesium, calcium, potassium, zinc, lithium, phosphorus, Silicon, manganese, chromium, selenium or molybdenum.

By the production-related combination of different peptides with different properties, a mechanism of action is made possible for the first time the one with the conventional one Skin remedies could not be observed so far. Advantageous is further that this novel drug mixture to a substantial proportion Peptides and amino acids contains which are suitable from the epidermis and the underlying skin layers to be absorbed. It has therefore proved to be suitable in practice for the Skin care, cosmetics, as well as for the prevention, treatment and / or Relief of inflammatory and allergic skin diseases, especially eczema and / or Psoriasis, proven. In particular, the findings indicate that the in the drug mixture contained peptides the damaging Effect of exposure to light, preferably UV light, or free Radicals on the skin is minimized. In particular, the degradation of fiber proteins, in particular keratin, at least diminished and thereby increasing the firmness and / or elasticity of the skin. Further become inflammatory and / or stress-related nervous Processes of the skin are inhibited by the immune or stimulatory modulating action.

Especially advantageous is the use of the active ingredient mixture according to the invention for the production a formula for regulating the condition of the epidermis, dermis and / or subcutis, especially of dermis and / or subcutis, especially preferred for regulating the condition of the dermis.

In In practice, the active ingredient mixture has especially for the production a skin care product and / or cosmetics proven.

• – Alterungsprozessen der Haut,
• – Lichteinwirkung auf die Haut,
• – allergischen Reaktionen der Haut, und/oder
• – entzündlichen Reaktionen der Haut

verwendet, insbesondere zur Vorbeugung, Behandlung und/oder Linderung von Faltenbildung, Augenringen, und/oder Trockenheit der Haut.In a particularly advantageous embodiment, the active substance mixture according to the invention for the preparation of an agent for the prevention, treatment and / or and relief of

• - aging processes of the skin,
• - light on the skin,
• - allergic reactions of the skin, and / or
• - inflammatory reactions of the skin

used, in particular for the prevention, treatment and / or alleviation of wrinkling, dark circles, and / or dryness of the skin.

Of the Advantage of the active ingredient mixture according to the invention is further that after saturation of the body's own Binding sites with drug substance no further enrichment the drug substance takes place at the destination, but the drug substance quickly out of the body is excreted and thus overdoses be avoided.

Prefers becomes a dermatologically suitable amount of the multifunctional Active substance mixture for the use according to the invention selected preferably a pharmaceutically acceptable carrier and / or thinner and / or excipient is added.

starting material for the Peptide and amino acid fraction of the multifunctional drug mixture are somatic cells. For example, cells of the diploid calf kidney cell line MDBK are suitable. chicken fibroblasts or cells of a porcine diploid epithelial cell line. For the Production of patient-specific active ingredients can, for example, the body's own Cells are used that are extracted from body fluids or tissues especially those derived from diseased tissue or body fluids were obtained, whereby the composition according to the invention is particularly specific and compatible is.

The Cells are used in the for the origin species typical ambient temperatures of 20 ° C to 39 ° C over a Period from 2-8 Incubated for days, then lysed and harvested with the maintenance medium.

to Removal of suspended particles can be followed by cell lysate filtered a filter with a pore size of 0.65 microns become. An additional Optional filtration through a filter of 0.1 μm pore size increases the efficiency the following ultracentrifugation. The permeate thus obtained becomes subsequently an ultracentrifugation over a filtration module with an exclusion size less than 10,000 daltons subjected. The ultracentrifugation preferably has a transit time from about 24 hours. In this way, a filtrate is recovered, that contains only substances, which are smaller than 10 000 daltons and thus also the mixture more specific Peptides with molecular weights up to 10,000 daltons and / or the fraction with essential and nonessential amino acids. But also with filters other pore sizes are suitable, the pore size being selected that the drug mixture the desired maximum molecular or Molecular aggregate sizes of up to 10,000 daltons.

Of the Essential advantage of ultracentrifugation is that at this process also a local Αufkonzentration of the drug mixture takes place within the centrifuged medium. Furthermore, the ultracentrifugation offered by the defined spatial Distribution of the active ingredients in centrifuged medium, which usually depends on the molecular weight or spatial Structure of the centrifuged constituents is the possibility also targeted fractions with a desired range of molecular weights or spatial Remove structures from the medium.

Prefers becomes a multifunctional drug mixture of a fraction more specific Peptides with a relative molecular weight between 200 to 6,000 daltons used. This mixture is increased by the concentration by the factor 1000 of the recovered fraction with proteins smaller than 10 000 daltons obtained by physical means.

Especially the dose-effect relationship of the active ingredient mixture according to the invention The principle of hyperbola allows specific inhibition the harmful Interaction of the outside one or more substances of the vaccine with the body's own substances or components of the immune system. The advantage of the invention in comparison to A linear dose-response relationship is that after saturation the body's own Binding sites with drug substance no further enrichment of the Drug substance at the destination takes place, but the drug substance quickly out of the body is excreted and thus overdoses be avoided even at high concentrations.

When Application form are all common Application forms for Active substances, in particular those for dermatological or pharmaceutical effective peptides and / or proteins suitable, preferably per os, for example. as a tablet or juice, or preferably over the skin, for example as an ointment or gel. The intranasal and sublingual forms predominate Question, an intramuscular Application, for example by injection is also suitable.

Around to take advantage of a specific mix smaller than 10kDa, the intranasal form is preferred, which is a fast, effective and easy application allows.

In addition to the actual active substance, in particular the administration method has a significant influence on the effectiveness of pharmaceutical compositions. In the context of the present invention, novel administration methods for the composition according to the invention are also particularly suitable. These new administration methods include in particular the method of AKUJECTUR ^® .

developments from the field of nanotechnology and applied quantum physics open the possibility for the preparation of a new spectrum of mixtures of active substances. such Active substance mixtures are in a particularly suitable embodiment the invention for the preparation of a pharmaceutical composition for treatment, Prophylaxis and / or metaphylaxis used by dementia.

The Object of the present invention was therefore also new multifunctional mixtures of active substances, using methods to provide the latest knowledge of physical phenomena Quantum control, associated with behaviors of biologicals and Minerals and theirs Complexes in EMF (Electro Magnetic Field) and their novel, exploit previously unknown modes of action on the organism, to methods of making efficient pharmaceutical compositions for the Treatment, prophylaxis and / or metaphylaxis of dementias specify. Thus, the multifunctional drug mixture is an amino acid-mineral-peptide complex that is quantum mechanically modified (AMIPEC-Q).

In a further embodiment Therefore, the multifunctional drug mixture includes further energized Silicon nanoparticles, zeolites, bentonites, montmorillonites or other mineral substances or mixtures intended for optimization the control processes of plant or animal cells, cell systems, organs or organisms have been loaded with information, by about 2 to 5 minutes exposed to microwave radiation of 2.45 gigahertz that were a change the crystal structures of mineral substances.

The Method for producing the energized silicon nanoparticles, Zeolites, bentonites, montmorillonites or other mineral Substances or substance mixtures in the sense of the invention, for the preparation of the active substance mixture, will be explained below using an example.

embodiment

Both zeolites with a diameter of less than 100 micrometers and finished nanoparticles and microparticles with SiO _{2 of} the product series Köstrosol (trademark) of the Chemiewerk Köstritz were used.

The used particles were using a magnetron with the frequency of 2450 megahertz different doses / pulses exposed to microwaves, causing changes in the crystal lattice and to receive information about the microwaves leads, which can be varied depending on the destination and indication. A the most physiological pulse frequencies crystallized, it is the Schumann frequency with 7.83 hertz. Others are as well possible and depending on the indication, all possibilities belong to the scope of the present invention.

Preferably, a special Krosrosol with a particle diameter of 7 nanometers is used, which is capable of loosely binding substances of similar particle size and serving as transporters for the preferred materials to the target site. At the destination it comes to the transmission of the applied vibration through the particles. The cell / cell systems take these up via the gel-sol formulation and are given an adhesive or include the described active substance mixture or its fractions, or the charged amino acid glycine, which is then similar to the mode of action of the substance P (FIG. Hecht / Oehme et al. ) acts, applied.

The Interplay of mineral, charged particles and the change of the behavior of the organic components, as in the present Invention listed are, in particular, the changed Behavior of the amino acid Glycine (neurotransmitter), leaves completely new indications. The mineral component serves here as data and information carrier different vibration quantities, the in a gel-sol formulation (like all body fluids) through the organic Nano- and micro-range components mediated to cells and cell aggregates become.

• a. Wasser gereinigt,
• b. Natriumhydroxid,
• c. Kollidon,
• d. Carbopol 940 Ph.Eur,
• e. Sorbinsäure.

For the preparation of the formulation according to the invention it is further preferred if the following constituents are used, in particular in the proportions according to the features of one of claims 16-18:

• a. Cleaned water,
• b. sodium hydroxide,
• c. Kollidon,
• d. Carbopol 940 Ph.Eur,
• e. Sorbic acid.

Especially proven especially if for the preparation of the recipe also glycine, especially in one dermatologically acceptable amount is used.

In a particularly suitable embodiment is glycine-loaded glycine in different doses, and applications in conjunction with SiO2 nano / micro particles, also loaded by microwave bombardment of different pulses and frequencies used.

For different ones Indications according to the invention have particular use of glycine proven in a mass fraction, the peptide content of the Active substance mixture corresponds.

The Manufacturing is extremely cost effective and possible Side effects can be largely excluded. Advantageously, by the recipe of the invention especially the natural one Regeneration process favors the skin without causing skin irritation to be observed.

All in the foregoing description and claims Features can both individually and in any combination for the realization the invention in its various embodiments of importance be.

Claims (21)

Use of a multifunctional active substance mixture, comprising a fraction of specific peptides having molecular weights to 10 000 daltons and a fraction of essential and nonessential Amino acids, won by - Incubation of cells at suitable growth temperatures, - subsequent lysis, - harvest together with the maintenance medium and Separation of cell components, the one molecular weight over 10,000 daltons by ultracentrifugation / ultrafiltration and - extraction the fraction of specific peptides with molecular weights up to 10 000 Dalton and the faction more essential and not essential Amino acids, for the production a formula for regulating the condition of the outer skin of mammals including of the human. Use according to claim 1 for the preparation of a recipe for regulating the condition of the epidermis, dermis and / or subcutis. Use according to claim 1, characterized that the formulation is a skin care and / or cosmetic. Use according to one of the preceding claims, characterized characterized in that the formulation is a means of prevention, treatment and / or and relief from Aging processes of the skin, light exposure onto the skin, allergic reactions of the skin, and / or inflammatory Reactions of the skin is. Use according to one of the preceding claims, characterized characterized in that the formulation is a means of prevention, treatment and / or Relieving wrinkling, dark circles, and / or dryness Skin is. Use according to one of the preceding claims, wherein the multifunctional active substance mixture minerals and / or salts includes. Use according to one of the preceding claims, wherein the multifunctional active substance mixture minerals and / or salts of the elements magnesium, calcium, potassium, zinc, lithium, phosphorus, Silicon, manganese, chromium, selenium and / or molybdenum. Use according to one of the preceding claims, wherein the multifunctional drug mixture at least one dermatologically acceptable carrier and / or diluent and / or excipient is added. Use according to one of the preceding claims, wherein the multi-functional drug mixture energized silicon nanoparticles, Zeolites and / or bentonites, montmorillonites or other mineral Substances and / or mixtures that optimize the control processes plant or animal cells, cell systems, organs, or organisms were loaded with information by using microwave radiation be exposed to a specific dose and frequency are. Use according to one of the preceding claims, wherein the incubation of cells at appropriate growth temperatures over a Period from 2-8 Days. Use according to one of the preceding claims, wherein the separation by means of ultracentrifugation / ultrafiltration with a Filter and / or run for 24 hours. Use according to one of the preceding claims, wherein a fraction of specific peptides with molecular weights between 200 and 6000 daltons and / or a fraction with essential and nonessential amino acids is used. Use according to one of the preceding claims, wherein the pharmaceutical composition for administration by acupuncture suitable is. Use according to one of the preceding claims, characterized that the recipe is made as a cream, ointment or gel becomes. Use according to one of the preceding claims, characterized marked that for the preparation of the recipe also uses the following ingredients become: a. Cleaned water, b. sodium hydroxide, c. Kollidon, d. Carbopol 940 Ph.Eur, e. Sorbic acid. Use according to claim 15, characterized by the following composition: component Share in total in percent - water cleaned 89-98% - Active ingredient mixture according to one of claims 1 or 6-12 0.5-4.0% - Sodium hydroxide 1.0-2.5% - Kollidon 0.5-2.5% Carbopol 940 Ph. Eur 0.1-1.1% - sorbic acid 0.01-1.0% Use according to one of claims 15-16, characterized by the following composition: component Share in total in percent - water cleaned 92-96.5% - Active ingredient mixture according to one of claims 1 or 6-12 1.0-3.0% - Sodium hydroxide 1,2-2,2% - Kollidon 1.0-2.0% Carbopol 940 Ph. Eur 0.3-0.9% - sorbic acid 0.05-0.5% Use according to any one of claims 15-17, characterized by the following composition: component Share in total in percent - water cleaned 94.1% Active substance mixture according to one of claims 1 or 6-12 2.0% - Sodium hydroxide 1.7% - Kollidon 1.5% Carbopol 940 Ph. Eur 0.6% - sorbic acid 0.1% Use according to one of the preceding claims, characterized marked that for the preparation of the recipe further glycine is used. Use according to claim 19, characterized that the glycine as loaded glycine in different doses, Indication and application purposes in conjunction with SiO2 nano / micro particles, also loaded by microwave bombardment of different pulses and Frequencies is formed. Formulation consisting of a composition according to a the claims 16-20.