Composition for treating erectile dysfunction

Abstract

A pharmaceutical composition for the treatment of erectile dysfunction is proposed, containing, in a pharmaceutically effective amount, active substances from the total venom cocktail of spiders of the genera Phoneutria, Viridasius and / or Ancylometes and / or the extract of young leaves of Urtica bianorii, as well as an amount of ointment base adapted to the intended use.

Description

[0001] Composition for the treatment of erectile dysfunction

[0002] A pharmaceutical composition for the treatment of erectile dysfunction is proposed, containing, in a pharmaceutically effective amount, active ingredients from the total venom cocktail of spiders of the genera *Phoneutria*, *Viridasius*, and / or *Ancylometes*, and / or the extract of young leaves of *Urtica bianorii*, as well as an amount of ointment base tailored to the specific application. Active ingredients have been isolated from the total venom cocktails of spider species from the genera *Ancylometes*, *Phoneutria*, and *Viridasius*, and from the leaves of *Urtica bianorii*, which, when applied externally as an ointment, exhibit therapeutically positive effects in the treatment of various forms of erectile dysfunction. This external treatment for the resolution of erectile dysfunction, excluding systemic diseases, including potentially traumatic injuries, as the underlying cause, is largely free of side effects.

[0003] In the search for new active ingredients for treating diseases or disorders of the human body, many private and public research institutes are increasingly focusing their research on naturally occurring chemical compounds. These include biogenic toxins and oral or skin secretions from various animal families, as well as substances with similar mechanisms of action that have now been identified in plants.

[0004] The use of biogenic toxins began in human history as early as prehistoric times, when they were used to displace prey with poisoned weapons. However, from the very beginning, a certain basic understanding of their handling and effectiveness was necessary for the safe use of these toxins. Further attempts to decipher the chemical composition of biogenic toxins later led to the targeted search for specific active ingredients as the actual causes of observed effects.

[0005] These efforts likely intensified, particularly after Paracelsus's (1483-1514) call to isolate the active ingredients of medicinal plants, which contributed to the development of latrochemistry, the branch of chemistry concerned with its medical applications. The art of distillation, in particular, was put to the service of research, yielding a wealth of essential oils and volatile compounds. However, the methods known at the time were inadequate for isolating other active ingredients or even for their chemical analysis. It wasn't until the beginning of the 19th century that the development of technical skills in chemistry had progressed sufficiently to usher in the era of isolating pure active ingredients from biological material. Initially, the differences in the solubility of the substances under investigation in various solvents were used to separate the desired active ingredients from accompanying substances.For example, the differences in distribution behavior between two immiscible liquid phases, in terms of volatility and chemical reactivity, were observed using precipitating agents. The development of chromatographic methods in the mid-20th century enabled a tremendous upswing in separation technology, paving the way for the identification of active ingredients to combat diseases.

[0006] Based on the distribution between a mobile and a stationary liquid phase, on adsorption, molecular sieving effects, ion exchange, the affinity (especially of proteins) for certain chemical compounds (e.g. enzyme substrates) and the mobility of charged molecules in an electric field, a variety of new separation techniques have been developed.

[0007] Currently, for example, tumors, considered among the most dangerous and feared diseases of our time, are still combated in a very radical and environmentally unfriendly manner, even though natural active ingredients derived from animal toxins could also initiate genuine cancer therapy. Similar approaches are now conceivable with plant-based active ingredients.

[0008] In contrast to conventional medicine, attempts have repeatedly been made here to develop a cancer therapy worthy of the name, albeit in a subtle way. For this purpose, the rich resources of nature have been utilized.

[0009] For this purpose, among other things, many highly potent substances isolated from toxic organisms are used in therapeutic doses as drugs.

[0010] German patent DE 19961141 A1 discloses a pharmaceutical active ingredient in which components of spider venom from the family Sicariidae were found to be suitable for the treatment of tumor diseases. This primarily involves peptide toxin from the venom of these spider species, another antagonistic substance derived from the venom, and / or a combination of these components.

[0011] Subsequently, numerous active ingredients against various types of tumors and other diseases or dysfunctions were developed based on biogenic toxins and other biogenic agents, which have also proven suitable for successfully and appropriately compensating for erectile dysfunction naturally. The current state of the art for treating erectile dysfunction involves prescription medications based on the biochemical principle of PDE-5 inhibitors.

[0012] These medications contain sildenafil as the active ingredient.

[0013] None of these medications work automatically. An erection only occurs with sexual stimulation, which can be mechanical and / or psychological.

[0014] Various press reports about the intended use of the medicinal herb "Elf Flower" are based on reports from traditional Chinese medicine and are still exclusively in the experimental stage or are not yet ready for market.

[0015] Currently, there are no ointments (with the exception of the present patent application) that are largely free of side effects, based on active ingredients from spider venom and intended for external use to temporarily relieve erectile dysfunction.

[0016] Currently, only the present patent application, based on the known state of research, claims to be virtually free of side effects with its developed application method. By applying the natural active ingredients only locally to the skin of the primary target organs (penis and testicles) as the direct site of action, the system avoids the burden on the entire body that would otherwise lead to side effects. This would inevitably result in higher dosages of the synthetic active ingredients commonly used in oral administration, such as PDE-5 inhibitors, sildenafil, tardalafil, and potentially others, which are associated with, for example, additional strain on the cardiovascular system.

[0017] Our previous research has refuted reports from other researchers claiming that only the bite of the comb spider Phoneutria nigriventer causes a prolonged erection of the penis, a fact also well known from the relevant literature (e.g. Mebs D. (2000); Venomous Animals: A Handbook for Biologists, Toxocologists, Physicians and Pharmacists, 2nd ed., Scientific Publishing Company Stuttgart).

[0018] We have discovered that in other members of the Ctenidae family, such as the genus Ancylometes (Betrau, 1880) and spiders of the genus Viridasius (Lenz, 1886), as well as in one of the Urticaceae we examined, penile erections were induced in those bitten. The object of the pharmaceutical composition according to the invention is to provide agents and methods for the treatment of erectile dysfunction. Furthermore, the composition according to the invention is intended to be used as an "ointment active ingredient". 1It can be used for external treatment. The problem with all currently known and commercially available erection aids that must be taken in the form of tablets or liquids lies in the more or less severe strain on the heart and circulatory system, other organ-related side effects, and impairments of well-being such as headaches, visual disturbances, stomach irritation, or nasal irritation.

[0019] The requirements of the new invention—an ointment for treating erectile dysfunction—therefore include the avoidance of all side effects of currently available orally administered medications for treating erectile dysfunction. This task is accomplished by active ingredients with suitable molecular weights, as components of the venom of certain hunting spiders, whereby the new classification of the genus Phoneutria is decisive and forms the basis of this patent specification. Ref.: Elksnat B. (2000).

[0020] The research results — ointment for treating erectile dysfunction — claim to produce a reliable and low-side-effect aid for overcoming erectile dysfunction through a targeted selection and even more differentiated extraction of spider venom.

[0021] Through the targeted and precisely dosed use of special, extracted active ingredients from selected spider venoms of the genera Phoneutria, Viridasius and Ancylometes, obtained using special methods, as well as extracts of Urtica bianorii, integrated into a carrier substance in ointment form, erectile dysfunction / weakness of the male penis, not exclusively caused by organic disease, can be resolved situationally at any time determined by the user without neglecting any lead time, while simultaneously increasing the feeling of pleasure for the relevant period of time.

[0022] According to one aspect of the present invention, it is an ointment containing animal and / or plant-based active ingredients for treating erectile dysfunction.

[0023] The ointment is applied externally to the base of the penis and testicles in sexually mature men and is free from the side effects / adverse effects / dangers that occur in various forms with conventional medical remedies. The invention – an ointment for treating erectile dysfunction – claims to be based exclusively on natural active ingredients obtained from the complete venom cocktails of hunting spiders of the genera Ancylometes, Phoneutria, and / or Viridasius (see Tables 1 and 2), as well as extracts from the leaves of Urtica bianorii. It claims to treat erectile dysfunction of the human penis caused by psychosomatic disorders, circulatory disorders, hormonal imbalances, and similar, possibly even previously unknown, disorders in a situation-specific and time-limited manner, according to the wishes, needs, and feelings of the user, without resorting to medication or incurring the dangers of known or previously unknown drugs.to avoid the potential side effects of conventional drug use. The invention claims to be low in side effects or even side-effect-free.

[0024] Further advantages of the invention — ointment for treating erectile dysfunction — are:

[0025] ■ Targeted and substance-neutral application possibilities

[0026] ■ No habituation to the active ingredients contained in the ointment

[0027] ■ Increased, natural pleasure

[0028] ■ Increased self-esteem

[0029] ■ Reduction of anxiety

[0030] ■ Confirmation that a suspected or feared serious pre-existing organic damage can largely be ruled out as the cause of the observed dysfunction.

[0031] The proposed invention has scientifically proven to have succeeded in

[0032] a) To develop and / or optimize a "milking process" for obtaining animal toxins that complies with all animal welfare / occupational safety regulations and the intended use. b) To determine, using physical and / or laboratory techniques, the components of the respective animal and plant toxins with erection-inducing effects that are suitable for the subject matter of the patent.

[0033] c) to extract and / or combine the components of the respective animal and plant toxins that are suitable for the subject matter of the patent.

[0034] d) to determine and / or test the total dose required for a reliable and side-effect-free, temporary elimination of erectile dysfunction.

[0035] e) to find and / or select and / or research a suitable carrier ointment for trouble-free and / or side-effect-free application.

[0036] The active ingredient(s) is / are obtained from the total venom cocktail of spiders and / or the Mallorcan nettle (Stinging nettle). The spiders are milked for this purpose. The nettle leaves are extracted using aqueous or alcoholic solutions. The milking process is carried out as described below. First, the spiders are immobilized. For this, the spiders and their container are placed in a refrigerator with a temperature of 7-17 degrees Celsius, preferably 10-15 degrees Celsius. After 15-30 minutes in the refrigerator, the spiders are paralyzed by the cold and can then be safely removed from the container. Right-handed people remove the spiders from the container with their left hand, and left-handed people with their right hand.

[0037] The spiders are held with their underside facing upwards. They are then allowed to bite into a sterile cotton swab at a preferred temperature of 20-23 degrees Celsius, with 22 degrees Celsius being particularly ideal.

[0038] The spiders are returned to the container.

[0039] According to one aspect of the present invention, the “milking” process should not exceed 5 minutes per spider.

[0040] The plants are extracted for the use according to the invention as follows:

[0041] The composition according to the invention is prepared in the following manner:

[0042] a)

[0043] A certain quantity of leaves, preferably fresh leaves from the leaf bud above the rhizome, is introduced into a certain quantity of 96% ethanol, or preferably 100% ethanol, or alternatively into a certain quantity of water for injection.

[0044] b)

[0045] The extract from a) is left to stand for at least 24 hours at temperatures preferably of 25 degrees Celsius. The leaves are then filtered out.

[0046] c)

[0047] This active extract from b) is incorporated into 150 ml of liquefied organic blossom honey while stirring constantly. Alternatively, the pure extract can also be used.

[0048] The extraction or production of the active ingredients required for the ointment with regard to composition, efficacy, scientific determinability and the required purity is based on the method of separating the poison cocktails via column chromatography, developed and patented by the inventor of the present application.

[0049] Column chromatography is a chromatographic separation technique in which a liquid or dissolved sample is passed through a column filled with a suitable support material (e.g., gel, silica, or resin). The different interactions of the components with the support material result in different residence times, allowing the components of the sample to be separated and subsequently fractionated.

[0050] During the process for manufacturing a pharmaceutical composition, it was found that the biogenic active ingredient (total toxin) of the respective specified genus or species:

[0051] ■ can be restricted,

[0052] ■ Can be frozen at minus 20 degrees Celsius,

[0053] ■ It can be placed in a vacuum and sublimated at plus 4 degrees Celsius, in order to be incorporated into an ointment or cream carrier substance at a later time.

[0054] The invention in question—an ointment for treating erectile dysfunction—is applied and massaged into the area of ​​the base of the penis and the testicles as needed and depending on the situation. Approximately two fingertip amounts (about 2 ml) are sufficient, without the possibility of a harmful overdose. The required dose was empirically determined by patients (see "Patient Examples") in consultation with their respective therapists.

[0055] According to patients, when used as intended, the ointment according to the invention triggers a natural erection of the penis lasting up to 40 minutes due to its active ingredients, provided that the user does not have any serious underlying organic diseases that already causally and mechanically hinder / prevent an erection.

[0056] Since the ointment according to the invention is designed in terms of the selection and dosage of the active ingredients in such a way that overdosing and thus practically all conceivable application errors are eliminated, the invention claims to be largely free of side effects or to have particularly few side effects.

[0057] Even accidental oral ingestion of the ointment is harmless, as all substances and active ingredients contained in the ointment are digested and thus broken down and excreted without damage or harmful side effects.

[0058] Based on our own research, the following spider venoms with the corresponding molecular weights are considered suitable: Phoneutria fera 13.6 kDa

[0059] Phoneutria depilata 14.1 kDA

[0060] Phoneutria boliviensis 16.2 kDa

[0061] Phoneutria eickstedtae 15.4 kDA

[0062] Phoneutria pertyi 15.2 kDA

[0063] Viridasius cf. fasciatus “forestform” 63.2 kDA

[0064] Ancylometes bogotensis 28.2 kDa

[0065] Ancylometes rufus 27.6 kDA

[0066] Urtica bianorii 15.3 kDA

[0067] Table 1

[0068] One aspect of the composition according to the invention is that, in the investigation of unpurified biogenic active ingredients, an increased effectiveness in male mammals with regard to their erectile function or erection process was found.

[0069] The milking technology required for the extraction of spider venom is optimized and refined by us as described below.

[0070] All three genera, Phoneutria, Viridasius, and Ancylometes, are representatives of the hunting spiders, which are very fast and usually not easy to catch. We reject immobilizing the animals using CO2 or shock freezing for animal welfare reasons, but this is possible according to our invention.

[0071] Nevertheless, the animals must first be sedated. To do this, place them, along with their container, in a refrigerator with a glass door and ventilation for about half an hour at approximately 10-15 degrees Celsius. Afterwards, test with long tweezers or a long bamboo stick whether the spider is sedated. If the spider is calm, carefully remove it (if right-handed) from its container and, using your left hand, grasp it from above and turn it onto its back so that its jaws are facing upwards. Then, take a sterile cotton swab and gently provoke the spider so that, as it awakens and warms up (the optimal and preferred temperatures for milking these spiders are between 20 and 30 degrees, especially 22 degrees Celsius), it bites the cotton and releases venom.The spider is then returned to its container. Before releasing it, it is secured with tweezers to prevent being bitten. Only after removing the hand from the container is the spider no longer held by the restraint, and the restraint removed from the container. Milking should not last longer than 5 minutes to avoid unduly stressing the spider. This mechanical milking method yields higher-quality venom cocktails compared to electric milking. However, killing the animal is entirely unacceptable, not least for ethical reasons, but is possible according to the invention. Furthermore, extracting the venom glands and purifying the venom obtained from them is more expensive than our developed method.

[0072] The active substances we isolated from the venom of the spider species listed in Table 1 are generally suitable for the temporary relief of erectile dysfunction.

[0073] However, as our own investigations have shown, the decisive factor for a physicochemical description of the respective active ingredient obtained is the molecular weight of the substances used.

[0074] The following molecular weights of substances leading to male penile erection were measured in some of the animals listed below:

[0075] Spider species Active ingredient Molecular weight in kDA

[0076] Phoneutria fera 13,6

[0077] Phoneutria boliviensis 16.2

[0078] Phoneutria eickstedtae 15,4

[0079] Phoneutria pertyi 15,2

[0080] Phoneutria cf. nigriventer 5.8

[0081] Viridasius cf. fasciatus “forestform” 63.2

[0082] Ancylometes bogotensis 28,2

[0083] Ancylometes rufus 27.6

[0084] Table 2

[0085] Tables 1 and 2 describe the spider genus on the left and the molecular weight of the active ingredient on the right. This ingredient has not yet been specified in detail, but can be clearly identified based on this molecular weight. "Cf." indicates an analogous active ingredient that has not yet been described, but is clearly characterized by having the same effect but a different molecular weight than indicated.

[0086] According to the invention, it is recognized that each of the active ingredients can be used individually or in combination with a quantity of the other active ingredients. The active ingredients can be combined in any way and can mutually enhance each other.

[0087] The substance from Urtica bianorii is obtained from young leaves (which are freshly cut). At the molecular-biochemical level, it can be shown that the active ingredient of the comb spider species Phoneutria nigriventer Tx2-6, which has a molecular weight of approximately 5 kDA and is discussed in the press, differs significantly from the substances we found.

[0088] It is therefore understandable that the substances according to the invention differ significantly from the prior art and can also be used more effectively. Due to their use as an ointment, the animal protein compounds are not subject to digestion as would occur in the gastrointestinal tract.

[0089] The substances obtained were separated or isolated, for example by column chromatography, as described in application DE 19961141 A1, and are then ready for incorporation into the carrier substance (ointment, gel, cream). The fraction of the respective types containing the active ingredient according to the invention is stored at minus 20 degrees Celsius until further processing.

[0090] An ointment base has proven to be the most suitable carrier substance for the application of the active ingredients described above (based on previous experience), as the following definition also makes plausible:

[0091] An ointment (Latin: unguentum, abbreviated: ungt.) is a semi-solid and homogeneous-looking preparation intended for application to the skin (e.g., as a wound ointment) or mucous membranes. It serves for the local application of active ingredients or for the care and protection of the skin or mucous membranes. It consists of a fatty base made of natural or synthetic substances and can be a single-phase (e.g., petrolatum) or multi-phase (water-in-oil emulsion) system. Active ingredients or drugs may be incorporated into the solution or dispersion. The release of drugs from ointments can be calculated using the Higuchi equation. Ointments in a broader sense are differentiated into:

[0092] ■ Ointments in the narrower sense, monophasic

[0093] ■ Creams

[0094] ■ Gels and / or

[0095] ■ Pastes.

[0096] An important point here is that the ointment base is also suitable for use on mucous membranes. According to the Higuchi equation, the active ingredient is released very effectively and can diffuse readily through the skin from the ointment solution. Experiments have shown that cantharidin analogues, which are to be described in a separate application and are not discussed further here, can significantly increase the absorption of the active ingredient and even achieve a mild, temporary effect on erection. These analogues are to be produced in Sierra Leone and on our European farms from live, home-bred cantharides.

[0097] According to one aspect, the ointment of the present invention comprises:

[0098] ■ Main ingredient: organic beeswax, especially preferred by certified West African beekeepers, in turn especially preferred by bee colonies from beekeepers in Sierra Leone (45%) or by German and European organic beekeepers

[0099] ■ Natural organic lecithin as an emulsifier (depending on the amount of active ingredient)

[0100] ■ Cocoa butter 30% in organic quality, preferably raw cocoa from Madagascar, Ghana, Sierra Leone, with cocoa from Sierra Leone being particularly preferred.

[0101] ■ Rest — Oils as needed, especially argan oil and jojoba oil

[0102] The oils showed that a mixture of 70% argan oil and 30% jojoba oil is preferable, as this provides optimal release and / or absorption of the active ingredients.

[0103] According to one aspect of the present invention, the ointment is pre-mixed and then mixed with the aqueous solution of the active ingredient(s) and homogenized. The solution contains 2-5 mg of the active ingredient, or preferably the same amount for each additional active ingredient related to the invention. The active ingredient(s) is dissolved with an emulsifier in double-distilled water (5 ml to 10 ml). After opening the packaging, the ointment can be used for approximately 4 weeks. It should be stored in a refrigerator at 5-9 degrees Celsius, preferably at 7 degrees Celsius.

[0104] The single dose can vary between 0.5 and 2 grams. It is recommended to incorporate the toxins or nettle extract into an ointment base of 25 to 70 grams. The spider should then bite into the cotton of a sterile cotton swab to release its venom. Alternatively, a sterile sponge can be used. Unlike the conventional electric milking method, our procedure allows for the extraction of native venoms.

[0105] The Mallorcan stinging nettle is known as Urtica bianorii. All other stinging nettle species known on Mallorca are not endemic there.

[0106] Biogenic toxins, also known as total toxins, comprise substances originating from plants, animals, bacteria, and fungi. The term total toxin or total toxin cocktail describes the entirety of substances released by actively venomous animals—that is, those that use their toxins specifically for hunting or defense—during these processes.

[0107] The total toxin is frozen at temperatures between -12 and -25 degrees Celsius for preservation. Sublimation preferably takes place at 4 degrees Celsius, but can be carried out gently in the range of 3.7 to 4.3 degrees.

[0108] For organic quality, an active ingredient concentration of approximately 45% is targeted, allowing for a fluctuation range of ±5%. Generally, numerical values ​​are variable by ±3% to cover a certain range.

[0109] Spiders are sedated before milking because stress or anxiety can cause vomiting – similar to electric milking. This leads to molecular changes that impair the extraction of pure substances.

[0110] The spider is removed by right-handed people taking it out of the container with their left hand. The spider is turned so that its underside faces upwards, as milking it from the back is not possible.

[0111] The venom is transferred to a sterile carrier medium. After the milking process, the spiders are placed back into their container.

[0112] The milking time must not exceed five minutes per spider. This period includes the entire time from removal to return to the container.

[0113] The present invention relates to a pharmaceutical composition for the treatment of erectile dysfunction, containing a pharmaceutically effective amount of active ingredients derived from the venom of spiders of the genus *Phoneutria*. The composition also includes an amount of ointment base tailored to the specific application. Likewise, a pharmaceutical composition can be provided containing active ingredients from the venom of spiders of the genera *Viridasius* or *Ancylometes*, each in combination with a suitable ointment base.

[0114] For the production of the active ingredients, species such as *Phoneutria fera*, *Phoneutria boliviensis*, *Phoneutria eickstedtae*, and *Phoneutria pertyi* are preferred. In the case of the genus *Viridasius*, the species *Viridasius fasciatus* is preferred, while for the genus *Ancylometes*, the species *Ancylometes rufus* and *Ancylometes bogotensis* are particularly favored. Another preferred variant of the pharmaceutical composition is characterized by the additional combination of biogenic active ingredients from various genera or species. The composition can also contain all seven defined active ingredients with the corresponding molecular weights of the respective genera or species.

[0115] The process for manufacturing this pharmaceutical composition comprises several steps. First, the biogenic active ingredient, i.e., the total venom of the respective spider genus or species, is concentrated and then frozen at a temperature between -12 and -25 degrees Celsius. Sublimation then takes place in a vacuum at a preferred temperature of approximately 4 degrees Celsius, although a gentler process can also be carried out in the temperature range of 3.7 to 4.3 degrees Celsius. Finally, the resulting active ingredient is incorporated into an ointment or cream carrier substance.

[0116] Various ingredients are used to produce the ointment base. A preferred composition contains organic beeswax at a concentration of approximately 45%, with beeswax from Sierra Leone being particularly valued. Additionally, organic cocoa butter (30%) and various oils (20-25%) are used. A mixture of 70% argan oil and 30% jojoba oil is especially preferred, as this combination improves the absorption of the active ingredients.

[0117] The active ingredients are extracted using a specific procedure in which the spiders are first immobilized. This is achieved by placing them in a refrigerator at a temperature of 10 to 15 degrees Celsius for 15 to 30 minutes. The spiders are then removed from the container with the user's non-dominant hand and held with their abdomen facing upwards. The venom is extracted by having the spider bite into a sterile carrier medium at a preferred temperature of 20 to 23 degrees Celsius, with 22 degrees Celsius considered particularly optimal. After extraction, the spiders are returned to their container. The entire extraction process must not exceed five minutes per spider, a timeframe defined as the period from removal to return to the container.

[0118] The pharmaceutical formulation for the treatment of erectile dysfunction offers several advantages resulting from the targeted selection of biogenic active ingredients and the specific manufacturing process. A key aspect is the use of active ingredients derived from the venom of the spider genera *Phoneutria*, *Viridasius*, and *Ancylometes*. These contain natural bioactive substances that have been shown to promote blood flow and have a muscle-relaxing effect. This makes the pharmaceutical formulation a promising alternative to synthetic PDE-5 inhibitors such as sildenafil. Furthermore, the local application allows for targeted action while minimizing systemic side effects that could occur with oral administration.

[0119] Another advantage lies in the individually tailored amount of ointment base. This allows for flexible dosing and facilitates application, as the active ingredients are absorbed directly at the affected area. Topical application ensures rapid action and reduces the risk of unwanted interactions with other medications.

[0120] The combination of biogenic active ingredients from different genera and species is particularly innovative. This approach allows for synergistic effects, thereby increasing the effectiveness of the treatment. The formulation can be individually tailored to achieve optimal results, depending on the patient's needs. This is especially beneficial for patients who react differently to specific active ingredients.

[0121] The manufacturing process also contributes significantly to the quality of the pharmaceutical composition. The active ingredients are extracted using a method in which the spiders are first immobilized at a temperature of 10 to 15 degrees Celsius. This prevents stress reactions such as vomiting, which could lead to molecular changes and compromise the purity of the active ingredients. The venom is then extracted through a natural biting action into a sterile carrier medium, with the spiders kept at an optimal temperature of approximately 22 degrees Celsius. This preserves the chemical integrity of the toxins, unlike conventional electric milking methods, which can alter the structure of the active ingredients.

[0122] A further advantage arises from the targeted preservation of the total toxin. By concentrating and freezing it at a temperature between -12 and -25 degrees Celsius, the shelf life of the active ingredients is extended. Subsequent sublimation under vacuum at approximately 4 degrees Celsius ensures particularly gentle processing, so that the bioactive components are preserved in their original form.

[0123] The choice of ointment base also contributes to the product's effectiveness. The combination of beeswax, cocoa butter, and high-quality organic oils ensures optimal absorption of the active ingredients into the skin. The blend of 70% argan oil and 30% jojoba oil, in particular, improves absorption and provides a long-lasting effect. Beeswax from Sierra Leone is preferred due to its exceptionally high quality.

[0124] In summary, the pharmaceutical formulation offers numerous advantages through the use of natural active ingredients, targeted application, the combination of various biogenic substances, and a gentle manufacturing process. This makes it an innovative and promising alternative to conventional treatment approaches for erectile dysfunction.

[0125] The active ingredients of the pharmaceutical composition are specifically identified by their molecular weight, as this allows for precise identification, standardization, and reproducibility of the formulation. Each active ingredient within the venom cocktail of a particular spider genus or plant consists of a multitude of different bioactive peptides and proteins. Since the composition of the venom itself can vary within a species, defining a specific molecular weight provides an unambiguous definition of the substances responsible for the desired pharmacological effect.

[0126] This procedure ensures that the pharmaceutical composition exhibits consistent quality and efficacy in every production run. Since natural variations can occur even within a single spider population, defining the molecular weight as a benchmark is essential to avoid undesirable variations and guarantee a standardized active ingredient concentration.

[0127] Furthermore, molecular weight is a crucial factor for the pharmacological activity of active ingredients. It significantly influences their absorption, distribution, and efficacy in the body. Smaller peptides, for example, can be absorbed and metabolized more quickly, while larger molecules have a longer half-life and can exert a more sustained effect. By specifically selecting active ingredients with certain molecular weights, the desired therapeutic effect can be optimized while simultaneously minimizing undesirable side effects.

[0128] In addition, this type of specification enables improved analytical control during the manufacturing process. Methods such as mass spectrometry or gel electrophoresis can ensure that precisely the defined bioactive substances are present in the pharmaceutical composition. This significantly contributes to quality assurance and facilitates regulatory approval processes, as the active ingredients can be objectively and reproducibly identified.

[0129] In summary, specifying the active ingredients by their molecular weight serves to ensure high pharmaceutical quality, precise dosage, and optimal efficacy of the composition. This enables targeted therapeutic application that meets the requirements of a standardized and effective treatment. A particularly preferred combination of active ingredients for the treatment of erectile dysfunction includes peptides from the venoms of *Phoneutria boliviensis* (16.2 kDa), *Phoneutria eickstedtae* (15.4 kDa), *Ancylometes rufus* (27.6 kDa), and *Viridasius cf. fasciatus* (“forest form”, 63.2 kDa). This combination offers an optimized vasodilatory effect by specifically modulating potassium and calcium channels, resulting in improved blood flow to the corpora cavernosa.In particular, the toxins from *Phoneutria* species are known for their strong vasodilatory effect, while *Ancylometes rufus* enhances this effect through its long-lasting modulation of smooth muscle. *Viridasius cf. fasciatus* also contributes to sustained vasodilation through increased nitric oxide release.

[0130] This combination is particularly suitable for the production of a topical ointment that is applied directly to the skin for rapid relief. Patients with mild to moderate erectile dysfunction especially benefit from this mixture, as it not only improves blood flow but also prolongs the duration of its effects.

[0131] Another preferred formulation includes *Phoneutria fera* (13.6 kDa), *Phoneutria cf. nigriventer* (5.8 kDa), and *Urtica bianorii* (15.3 kDa). This combination not only offers vasodilatory effects but also has anti-inflammatory properties, making it particularly interesting for patients with vascular erectile dysfunction or accompanying inflammatory processes. The constituents of the Mallorcan stinging nettle (*Urtica bianorii*) act as a natural modulator of the nitric oxide system, complementing the effect of the spider venom and ensuring consistent vasodilation.

[0132] For maximum duration of action, the combination of *Phoneutria pertyi* (15.2 kDa), *Ancylometes bogotensis* (28.2 kDa), and *Viridasius cf. fasciatus* (63.2 kDa) can be used. This mixture of active ingredients enables a long-lasting effect through targeted inhibition of phosphodiesterase-5 (PDE-5), which is responsible for the breakdown of cGMP in the corpora cavernosa. By blocking PDE-5, blood flow remains elevated for a longer period, resulting in prolonged erectile function. This composition is particularly suitable for patients with chronic erectile dysfunction who are looking for an alternative to conventional PDE-5 inhibitors.

[0133] The targeted selection of active ingredients with specific molecular weights ensures that each formulation has a consistent and predictable effect. The active ingredients can be combined depending on the desired effect to achieve either rapid, long-lasting, or synergistic vasodilation. This flexibility allows for individually tailored therapy that meets the needs of different patients. Organic quality in the pharmaceutical composition means that the raw materials used come from sustainable, controlled organic farming or certified natural sources. This ensures that no synthetic pesticides, herbicides, or chemical fertilizers are used, guaranteeing the purest and most natural quality of the ingredients.

[0134] For plant-based components, such as the oils and waxes used, organic quality means that they are produced and harvested without the use of genetically modified organisms (GMO-free). For example, the beeswax used in the pharmaceutical formulation comes from sustainable beekeeping practices where the bees are kept in species-appropriate conditions and no chemical additives or antibiotic treatments are used in the hive. Beeswax from Sierra Leone is particularly preferred, as it is known for its high purity and its special composition of natural esters and fatty acids, which improve the skin compatibility of the ointment base.

[0135] The oils used, including argan and jojoba oils, also meet high organic standards. They are extracted through mechanical pressing without chemical solvents to ensure maximum purity. Furthermore, they come from certified organic farming, meaning they are produced without synthetic additives and their natural active ingredients are fully preserved. The preferred blend of 70% argan and 30% jojoba oil not only improves the absorption of the active ingredients into the skin but also supports cell regeneration and hydration.

[0136] The cocoa butter in the pharmaceutical formulation is also organically grown and extracted using gentle processes to preserve its beneficial properties. Rich in natural antioxidants and fatty acids, it improves the skin permeability of the active ingredients and contributes to the stability of the ointment base.

[0137] Overall, organic quality in this pharmaceutical formulation means not only the avoidance of harmful chemicals in production, but also the sustainable sourcing and processing of raw materials. This ensures that the pharmaceutical ointment is not only highly effective, but also skin-friendly and environmentally compatible.

[0138] Patient examples:

[0139] The patient, now 37 years old, has suffered from erectile dysfunction (ED) since puberty. He first received the ointment at age 21 and achieved his first erection after the fifth or sixth application. According to the patient, he had to use the ointment for approximately five years, with a 1.5-year break (during which he had no partner). Since 1999, he has no longer needed the ointment and reports that he can achieve an erection independently when sufficiently aroused.

[0140] ■ The patient, now 55 years old, after separating from his wife and children, was no longer able to achieve an erection despite medical treatment. Upon using the ointment for the second time in 1992, he was able to achieve an erection again with his new partner and now wife. He was able to discontinue the ointment after three years and, according to his own statement, no longer has any "problems with sex".

[0141] ■ A patient who had never had an erection was diagnosed with erectile dysfunction. He is now 40 years old. I met him when he was 19 and we discussed his problems to some extent. He also wanted a custom-made ointment mixed for him. He got an erection after the very first application. He still has to use the ointment (possibly as a form of psychological support), but he gets an erection in 3 out of 5 attempts / applications.

[0142] ■ The patient, now 44 years old, has suffered – according to his own account – from erectile dysfunction his entire life, which was diagnosed when he was 20. Based on an acquaintance and trust, he used the ointment for five months but did not achieve an erection, even with an increased dosage of the active ingredient. After the active ingredient was changed (to include spiders of the genus Phoneutria as well as those of the genus Ancylometes) – resulting in three active ingredients in the ointment – ​​he achieved his first erection, including ejaculation, after approximately 20 applications (the patient is unsure of the exact number). According to his own statement, this patient still uses the ointment "as a precaution" whenever he has sex with his wife.

[0143] ■ The patient, now 38 years old, heard about the ointment from an acquaintance (the aforementioned patient, now 55) and presented himself with a doctor's report stating that he suffered from erectile dysfunction. At a meeting approximately three months after starting the treatment, he reported that applying the ointment to the base of his penis (neither by himself nor by his girlfriend) had been successful. Only when his girlfriend had the idea of ​​massaging the ointment under the foreskin, directly into the glans, did the man actually achieve an erection. This patient still needs the ointment today.

Claims

Patent claims 1. Pharmaceutical composition for the treatment of erectile dysfunction with a pharmaceutically effective amount of at least one active ingredient, comprising the amount of: Phoneutria fera 13.6 kDa; Phoneutria depilata 14.1 kDA; Phoneutria boliviensis 16.2 kDa; Phoneutria eickstedtae 15.4 kDA; Phoneutria pertyi 15.2 kDA; Phoneutria cf. nigriventer 5.8 kDa; Urtica bianorii 15.3 kDA Viridasius cf. fasciatus “forestform” 63.2 kDA; Ancylometes bogotensis 28.2 kDA; and / or Ancylometes rufus 27.6 kDA, where first a spider genus providing the active ingredient is specified, followed by a specific molecular weight of the respective active ingredient.

2. Composition according to claim 1, wherein the quantity is incorporated into an ointment base.

3. Composition according to claim 1 or 2 comprising at least one additive with oil, cocoa butter and / or beeswax.

4. Composition according to claim 3, wherein the at least one additive is of organic quality.

5. Composition according to claim 3 or 4, wherein the oil comprises argan oil and / or jojoba oil.

6. Composition according to claims 3 to 5, wherein the oil comprises 70% aran oil and 30% jojoba oil.

7. Composition according to one of the preceding claims, wherein the at least one active ingredient is present in a single dose of 0.5 to 2 grams.

8. Composition according to any one of the preceding claims, comprising Mallorcan nettle.

9. Method for producing a pharmaceutical composition according to any one of claims 1 to 8, characterized in that comprising: - immobilizing donor spiders at a temperature of 10 to 15 degrees Celsius; and - milking the spiders at a temperature of 20 to 23 degrees Celsius using at least one sterile biting block.

10. Method according to claim 9, wherein the at least one donor spider is immobilized for 15-30 minutes.

11. Method according to claim 9 or 10, wherein milking takes place at a temperature of 22 degrees Celsius.

12. Method according to one of claims 9 to 11, characterized in that the at least one active ingredient is frozen to minus 20 degrees and placed in a vacuum and sublimed to + 4 degrees Celsius.

13. Method according to one of claims 9 to 12, wherein the at least one active ingredient is incorporated into an ointment and / or cream carrier substance.

14. Method according to any one of claims 9 to 13, wherein the at least one active ingredient is incorporated into 5-10ml of double distilled H2O via an emulsifier.