AT6197U1 - PHARMACEUTICAL COMPOSITION FOR TREATING AND / OR PREVENTING LIGHT DERMATOSIS - Google Patents

Abstract

A pharmaceutical composition is described comprising (i) a medicinal drug from Nopal cactus and (ii) at least one active ingredient with light dermatotherapy properties.

Description

       

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   The invention relates to a pharmaceutical composition comprising (i) a
Medicinal drug from the Nopal cactus and (ii) at least one active ingredient with light dermatosis-treating properties for the treatment and / or prevention of
Light eruption. Furthermore, the present invention relates to methods for
Production of a pharmaceutical composition comprising (i) a medicinal drug from the Nopal cactus and (ii) at least one active ingredient with light dermatosis-treating properties.

   In addition, the invention relates to the use of the pharmaceutical composition comprising (i) a medicinal drug from Nopal cactus and (ii) at least one active ingredient with light dermatotherapy properties for the treatment and / or prevention of light dermatosis, in particular dermatitis solaris (sunburn), and the use thereof topical pharmaceutical formulations. In addition, the present invention relates to a pharmaceutical composition which can be used to intensify skin tanning and / or to intensify pigment formation in the skin.



  Skin cancer is a serious human health problem. The incidence of non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) in the United States was approximately 900,000 per year in the 1990s and 50,000 per year for melanoma. Annual deaths in the 1990s were 2,000 for non-melanoma skin cancer and 6,000 for melanoma, and 800,000 deaths from skin cancer are predicted for the next eighty years if current trends continue.

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The causal relationship between non-melanoma skin cancer and chronic
The effects of radiation from the sun's ultraviolet light have been clearly demonstrated, with the effects of the sun also being an important triggering factor
Melanoma appears to be.

   It is generally accepted that one of the main targets for ultraviolet light damage that leads to cancer is DNA.



   While the brown skin used to be a sign of physical agricultural work and the light, untinted skin seemed desirable as a status symbol, the tan now signals activity, health, athleticism and success. To achieve a quick and deep skin tan when sunbathing, many sit down
People are aware of the sunlight without being aware of the acute and chronic
Be aware of the effects.



   The radiation spectrum of the sun is very wide and only the narrow area of the
Wavelengths from 400 to 800 nm are visible to the human eye. In the direction of the longer wavelengths, the infrared range (IR) follows, which is perceived as heat. In the short-wave range, the visible light is followed by the ultraviolet range. Because of their different physiological effects, different UV ranges have been defined: The UV-C range covers the wavelengths from 100-280 nm. This wavelength range is completely absorbed by the ozone layer in the stratosphere of the earth and therefore occurs in the natural solar spectrum, as it is on the surface of the earth e.g. B. is measurable at sea level, not before.

   The UV-B range covers the wavelengths from 280-315 nm and causes sunburn and indirect skin tanning. The UV-A range, which includes wavelengths of 315-400 nm, hardly leads to sunburn, but causes a direct skin tan.



  Sunlight has both beneficial and damaging effects on the skin and the organism. At low doses, sun exposure increases this

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 physical well-being and performance. The UV-B component of sunlight promotes vitamin D synthesis and the formation of the skin's own protection.



   This intrinsic protection consists primarily of pigmentation (tanning of the skin) and thickening of the layer of ridges (formation of swelling of light). At the same time, excessive exposure of the skin to UV-B as acute damage triggers the formation of sunburn, which, depending on the UV dose and sensitivity of the skin, can range from reddening to severe burns with blistering. Chronic UV-B damage, i.e. H. Damage after chronic UV-B exposure lasting for years is the premature aging of the skin in the form of structural changes in the connective tissue of the skin and, as an extreme case of a neoplastic change (including after repeated exposure to extremely high individual UV doses) Development of skin cancer.



    UV-A radiation causes direct pigmentation and enhances the biological effect of UV-B radiation in a positive and negative sense. Since the UV-A
Radiation as longer-wave radiation that can penetrate into the connective tissue of the skin is the priority for chronic damage, especially with simultaneous UV-B radiation, the premature aging of the skin. The direct pigmentation triggered by the UV-A component of sunlight is usually relatively low and does not allow intensive tanning without indirect pigmentation.



  Today we know that both intense UV-A and UV-B radiation damage the deoxyribonucleic acid (DNA) in the cell nucleus of skin cells through secondary photochemical reactions. Here, free radicals react with DNA components and change them.



  The human organism has a variety of repair mechanisms. First, the cell cycle can be stopped until the damage to the DNA components is repaired. On the other hand, the misinformation can be prevented from being passed on to the daughter cells by leading cells with irreparable DNA damage into programmed cell death (apoptosis)

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 become. By eliminating these cells it is prevented from arising from them
Cells can degenerate cells and subsequently form malignant tumors.



   It is known today, however, that high and recurring radiation exposure overwhelms these body's own repair mechanisms and exhaust the so-called "solar capital" and thus acute and chronic over time
Light dermatoses, especially UV damage, are only partially reversible and thus cause premature skin aging and chronic light damage up to skin cancer. This not only weakens or damages the cells themselves, but also the immune system, which can prevent cancer growth.



   It was therefore an object of the present invention to provide a pharmaceutical composition which has properties which treat light dermatosis and / or which increases pigment formation in the skin. The increased pigment formation on the one hand increases the natural sun protection effect of the skin and on the other hand an increased skin tanning, as defined below, is achieved. Another object of the present invention is to provide a method for producing this pharmaceutical composition and its use for the treatment and / or prevention of light eruption.



  Surprisingly, it has now been found that a pharmaceutical composition comprising (i) a medicinal drug from Nopal cactus and (ii) at least one active ingredient with properties that treat light dermatosis is suitable for the treatment and / or prevention of light dermatosis. At the same time, pigment formation in the skin and thus skin tanning is not inhibited, but actually intensified.



  The present invention thus relates to a pharmaceutical composition comprising (i) a medicinal drug from a nopal cactus and (ii) at least one active ingredient with properties that treat light dermatosis.

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A "medicinal drug" is understood to mean a fresh or dried medicinal plant or parts thereof, such as roots, bark, leaves, flowers, seeds, fruits and secretions such as essential oils (see Hunnius; Pharmaceutical Dictionary, 8th edition, De Gruyter, 1998; ISBN 3-11-015793-4).



   The medicinal drug from the Nopal cactus here comprises a pharmaceutically active component of a Nopal cactus.



   The Nopal cactus is one of the more than 100 prickly pear species found in Mexico. Subspecies of the Nopal cactus are in particular Opuntia ficus Indica and Opuntia streptacantha Lemaire. The term “nopal cactus” is understood here to mean all types of prickly pear cactus, in particular Opuntia ficus indica and
Opuntia streptacantha Lemaire, prefers Opuntia ficus lndica.



  The nopal plant is called prickly pear in German, bears the generic name Opuntie and belongs to the Cactaceaes in the taxonomic classification. In Spanish the prickly pear cactus is called Nopal or also as Nopal carcón. The names Nopalito are also very common in Mexico, Tuna, which is otherwise known as the name of the fruit, in Argentina and Chile it is also known as Nopalnocheztli. All of these terms are referred to below under the term nopal cactus.



  In Mexico, the Nopal cactus is traditionally used both as a vegetable and as a natural medicine. It is known that nopal is rich in iron, calcium, potassium, magnesium, manganese, silicon, aluminum, furthermore in amino acids, vitamins A, B1, B2, B3 and C, but also in resins, tannins and carotenes. In addition, it has an extraordinarily high proportion of pectin. It has long been known that Nopal cactus can lower elevated cholesterol or triglycerin levels, lower blood sugar levels in patients with type 1 and type 2 diabetes, its high fiber content both inhibits the absorption of glucose in the intestine and stimulates digestion and when losing weight

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 helps (The healing powers of the Nopal cactus; H. Bankhofer, K.-H. Dolinschek, F.



   Reinisch, Kneipp Verlag, 1st edition 2002, ISBN 3-902191-01-5, pages 7 to 13).



   Surprisingly, it has now been found that a drug from Nopal cactus, in particular from Nopal cactus and DNA repair enzymes, has light dermatosis-treating, in particular anti-inflammatory and skin-calming properties, as defined below. In addition, the medicinal product from Nopal cactus, especially from Nopal cactus in combination with
DNA repair enzymes do not inhibit but intensify the pigment formation in the skin caused by UV radiation and thus intensify the tanning of the skin.



  The medicinal drug from Nopal cactus can consist of roots, leaves (= branches), flowers, seeds, fruits and cactus secretions (Muzilago), especially the cactus branches and cactus secretions. The medicinal drug particularly preferably consists of cactus secretion (Muzilago), which is contained in particular in the cactus branches (pencas). The term "branches" (pencas) is understood here as a botanical name and is often incorrectly referred to as a leaf.



  In a preferred embodiment, the drug from Nopal cactus can be obtained by crushing prickly cactus branches. The branches (pencas) of the nopal, in particular the Opuntia ficus Indica, at the age of one to two years are particularly preferred. The nopa branches are preferably washed in a machine, dried and then the spikes are burnt off using gas flames. Then they are washed well one more time. The nopal is then chopped and then dried slowly in a drying system over several days or weeks at approx. 30 degrees Celsius. The dried Nopal pieces are ground to a fine powder and centrifuged to separate the heavy components (= fibers) and thus to eliminate them.

   The finely ground powder with the Muzilago portion (cactus secretion) is particularly important for processing. In a particularly preferred embodiment

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   The resulting nopal powder is then again in one form
Screening plant screened to remove larger particles. For further processing, one tries to obtain the finest possible powder. The powder is sterilized by means of UV radiation.



   Alternatively, commercially available Nopal powder (available from
Hando, Graz, Austria) can be used as a drug. If necessary, the Nopal powder can be subjected to additional processing and / or cleaning steps, in particular centrifuging, in order to remove fiber constituents and larger particles from the powder and thus improve the formulation of the
To achieve the final product.



  In the context of the present patent application, the term “light dermatosis” can be an acute and / or chronic light dermatosis, as defined below: light dermatosis, or also called photodermatosis, can be a change and / or damage to the skin due to the action of light, in particular ultraviolet radiation. Light dermatoses can cause the physiological reactions of the skin, such as sunburn, increased melanin formation (hyperpigmentation), acanthosis and hyperkeratosis (light swellings), as well as pathological reactions of the skin, such as diseases from the group of so-called sun allergies (hypersensitivity reactions to sunlight), premature skin aging and / or Be skin cancer.



  Sun allergies can be photodermatoses in the medical sense, such as polymorphic light dermatosis, lupus erythematosus or drug-related light reactions.



  Light dermatoses can occur when the body's cellular repair mechanisms function normally or abnormally. Especially with illnesses

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 genes (such as the hereditary disease Xeroderma pigmentosum) with abnormal repair capacity for UV-induced damage to the deoxyribonucleic acid (DNA) that encodes the body's own genetic substance, it can often lead to acute and / or chronic photodermatosis in childhood come.



   An acute light dermatosis can a. especially dermatitis solaris (sunburn), which is characterized by a phototraumatic reaction with normal sensitivity to light, an overdose of UV light and an acute DNA damage at the cellular level and clinically the symptoms of skin redness,
Inflammation of the skin, possibly blistering and later desquamation of the light-exposed skin areas. In addition, acute light dermatosis can also be a sun allergy (hypersensitivity reactions to sunlight), in particular polymorphic light dermatosis, lupus erythematosus or a drug-related light reaction.



  Chronic light dermatoses can be based primarily on DNA damage and / or its consequences, and in particular tissue degeneration, premature skin aging, benign (benign) and malignant (malignant) cell changes, in particular atrophy of the epidermis and degeneration of the connective tissue in the corium due to years of excessive sun exposure with a coarsening of the skin relief, cysts, comedones, keratoses and / or an increased incidence of squamous cell carcinoma and malignant melanoma (see Pschyrembel, Klinisches Wörterbuch, 257th edition, de Gruyter, 1994, ISBN 3- 11-012692-3). The consequences of acute and / or chronic light dermatosis can also affect internal organs, such as in systemic photoallergies and / or lupus erythematosus.



  “Therapy” is understood here to mean the healing, relief or prevention (prevention) of disorders or diseases.

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“Light dermatosis-treating properties” is understood to mean an anti-inflammatory (anti-inflammatory), skin-calming and / or DNA-repairing property. All substances which are anti-inflammatory, skin-calming and / or DNA-
Have damage repairing properties. In a special embodiment, the active substance or substances can have anti-inflammatory and / or skin-calming properties, for example synthetically produced and / or nature-identical active substances and / or extracts and / or active substances
Medicinal plants, for example chamomile, aloe vera, witch hazel, etc.

   The active substance can preferably be bisabolol, panthenol, dexpanthenol, allantoin, vitamin E, extract from green tea, chamomile, aloe vera, witch hazel, in particular panthenol, dexpanthenol, allantoin, reishi (Ganoderma lucidum), extract from green tea, chamomile and / or vitamin E be.



  An active substance with DNA-repairing properties can contain at least one DNA repair enzyme, in particular endonuclease V, 06-methylguanine-DNA-methyltransferase, photolyase, uracil- and hypoxanthine-DNA-glycosylase, apyrimidine / apurine-endonuclease, DNA exonuelease, damaged base glycosylase, in particular 3-methyladenine DNA glycosylase, and / or correndonuclease or the DNA repair enzyme is contained in Micrococcus luteus and / or in Anacystis nidulans extract. In a particular embodiment, the DNA repair enzyme can be endonuclease V, photolyase and / or contained in Micrococcus luteus extract and / or Anacystis nidulans extract.



  In a particular embodiment, the at least one DNA repair enzyme can be contained in a carrier material, the carrier material being selected from liposomes, nanocapsules, nanoparticles and microparticles, in particular liposomes. The liposomes here can be unilamellar and / or, in particular multilamellar liposomes. The production and use of these carrier materials are known to the person skilled in the art and are used, for example, in Ru-

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 dolf Voigt; Pharmaceutical technology, 9th edition, Deutscher Apotheker Verlag, 2000, chapter 25.



   In a particularly preferred embodiment, the pharmaceutical composition can comprise the medicinal drug of the Nopal cactus in combination with endonuclease V, photolyase and / or Micrococcus luteus and / or Anacystis nidulans extract in liposomal form.



   Alternatively, an extract obtained from Micrococcus luteus (yellow micrococcus), which contains UV endonuclease with DNA glycosylase / AP (apyrimidine / apurine) endonuclease activity, can be used in multilamellar liposomal form, in particular commercially available as "Ultrasome" "" (AGI Dermatics Inc, Freeport, NY, USA). In addition, an extract obtained from the photosynthetic plankton Anacystis nidulans can also be used, which contains photolyase in multilamellar liposomal form, in particular as commercially available "Photosome" (AGI Dermatics Inc , Freeport, NY, USA).



  In a further particular embodiment, the pharmaceutical composition can contain approximately 1-40 parts by weight, preferably approximately 2-25 parts by weight, in particular approximately 2-15 parts by weight of component (i) and approximately 1-40 parts by weight, preferably approximately 2-25 Parts by weight, in particular about 2-15 parts by weight of component (ii), and as the remaining component (v) one or more additives, based on 100 parts by weight of a composition with the components (i), (ii) and (v).



  In the context of the present patent application, additives can include emulsifiers, lipids, substances for adjusting the pH, preservatives, dyes, perfumes and fragrances, auxiliaries and carriers, light protection substances, active substances for repelling insects, skin tanning agents, tanning accelerators,

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 Vitamins, active ingredient and / or active ingredient complexes, such as moisturizers and / or anti-aging complexes, and / or formulation aids.



  Anionic, cationic or nonionic (neutral) surfactants, for example alkali soaps, metal soaps, amine soaps, sulfurized and sulfonated compounds, invert soaps, high fatty alcohols, higher alcohols, fatty alcohol ethoxylates, especially glycerol, partial fatty acid esters of sorbi-
 EMI11.1
 Use water / oil emulsions.



  As lipids in the form of fatty and / or oil and / or wax-like components for the production of the ointments, creams, lotions or emulsions, petroleum jelly, silicones, natural or synthetic waxes and fats, fatty acids, fatty alcohols, fatty acid esters, e.g. B. as mono-, di- or triglycerides, paraffin oil or vegetable oils, hardened castor oil or coconut oil, lard, synthetic fats, e.g. B. based on caprylic, capric, lauric and stearic acid such. B. Softisanü or triglyceride mixtures such as Miglyol can be used.



  To adjust the pH, for example, osmotically active acids
 EMI11.2
 phat, Tris buffer or triethanolamine can be used. In a preferred embodiment, the organic acids are hydroxycarboxylic acids, such as, for example, fruit acid, especially lactic acid, mandelic acid, malic acid, tartaric acid and grape acid.



  To increase stability, preservatives such as glycerol, phenoxyethanol, methyl or propyl benzoate (parabens), methyl dibromoglutaronitrile, hydantoin, iodopropynyl butyl carbamate, quaternary compounds, triclosan, sorbic acid and / or their salts, in particular potassium sorbate, can also be used

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 and benzoic acid and / or its salts, in particular sodium benzoate, especially glycerol, potassium sorbate and sodium benzoate, are added.



  Furthermore, dyes, preferably all approved food and / or cosmetic dyes or dyes known to the person skilled in the art, for example yellow and / or red iron oxide and / or titanium dioxide, can be added for color matching.



  Perfumes and fragrances can be natural, nature-identical or synthetically produced substances. The production and use of these substances are known to the person skilled in the art.



  Suitable auxiliaries or carriers are, for example, sodium alginate as a gel former for producing a suitable base or cellulose derivatives such as
 EMI12.1
 Compounds and phospholipids into consideration. The gels can be present either as water-based hydrogels or as hydrophobic organogels, for example based on mixtures of low and high molecular weight paraffin hydrocarbons and petroleum jelly. The hydrophilic organogels can be prepared, for example, on the basis of high molecular weight polyethylene glycols. These gel-like shapes are washable. However, among the organogels, the hydrophobic organogels are preferred. Hydrophobic auxiliaries and additives such as petrolatum, wax, oleyl alcohol, propylene glycol monostearate and propylene glycol monopalmitostearate are particularly preferred.



  If the pharmaceutical composition processes substances in liposomal form, special regulations must be observed; for commercially acquired liposomes, especially the manufacturer's instructions. liposomes

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 can be aqueous suspensions of lipid vesicles in physiological saline containing 1% phenoxyethanol as an antimicrobial component.



   Any conditions that destroy the physical and chemical structure of the liposomes or change the material enclosed in them must be avoided. Base lotion can be a hydrogel when using such liposomes. Hydrophobic materials, especially oily bases, ethylene or
Polyethylene glycol is not suitable for this.



   The following conditions should preferably be avoided for the processing of substances in liposomal form: organic solvents or alcohols; surfactants or detergents above their critical micelle concentration; Temperatures about 25 degrees Celsius; a pH of approximately less than 6.0 and approximately greater than 8.0; an osmotic pressure due to an ionic strength which differs significantly from that of a physiological saline solution (0.9% by weight or 0.15 M sodium chloride solution) and foam-producing processing methods. All other constituents of the formulation are preferably processed first and the liposomes added in the last step.

   In a particular embodiment, approximately 1-30 parts by weight, preferably approximately 2-25 parts by weight, in particular approximately 2-15 parts by weight, of the liposomes, in particular liposomes containing at least one DNA repair enzyme, based on 100 parts by weight of the total composition, can be added.



  Light protection substances (UV filters) can be either light-absorbing or light-reflecting substances, organic or inorganic structure. Here, light-reflecting substances can be, for example, titanium dioxide, titanium oxide and / or zinc oxide, in particular titanium dioxide. Light absorbing fabrics, too
 EMI13.1
 For example, p-aminobenzoic acid, cinnamic acid and benzimidazole derivatives can be used as UV-B filters. Benzophenone derivatives can be used as broadband filters.

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 be applied. UV-A filters can be substances that contain a dibenzoylmethane
Have structure.



   In a preferred embodiment, the light protection substances (UV
Filters) especially all at the moment and in the future in the countries of the EU and / or the
United States of America approved UV filters such as octyl methoxycinnamate, zinc oxide, titanium dioxide, octocrylene, 4-
Methylbenzylidenkampfer, Butylmethoxydibenzoylmethan, Octylsalicylat, Titanium oxide, Phenylbenzimidazolsulfonat, Diethylhexylbutamidotriazon, Dioctylbutami- dotriazon, Terephthalylidendikampfersulfonic acid, Oetyltriazon, Ethylhexylololamino, Triloxamyl, Triloxamyl, Triloxamyl, Triloxo



  Repellents against insects and mosquitoes, especially mosquitoes, can be of synthetic or natural origin. Commercially available substances known to those skilled in the art are preferably used. Such substances are u. a. in Wilfried Umbach; Cosmetics: Development, production and use of cosmetic products, Thieme Verlag, 1988, ISBN 3-13 712601 0, page 135-140.



  Skin tanning agents as a subgroup of the additives are to be understood here as substances which cause the artificial tanning of the skin by staining or by chemical modification of the skin's skin layer (as defined below). These can be natural substances such as extracts from green walnut shells and / or henna, both of which are naphthoquinones, in particular 2-hydroxy-l, 4-naphthoquinone and / or 5-hydroxy-l, 4naphthoquinone, as active constituents. Chemical compounds such as hydroxyketones, hydroxyaldehydes and dicarbonyl compounds, in particular dihydroxycetone, can also be used.

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   All commercially available substances and all substances known to the person skilled in the art can be used as tanning accelerators, vitamins, active substance and / or active substance complexes, such as, for example, moisturizers and / or anti-aging complexes.



   In a particular embodiment, the pharmaceutical composition can preferably comprise approximately 1-25 parts by weight, preferably approximately 2-20 parts by weight, in particular approximately 2-15 parts by weight of component (i), approximately 1-30 parts by weight about 2-25 parts by weight, in particular about 2-15 parts by weight of component (ii), and as component (iii) about 20-40 parts by weight, preferably about 25-35
Parts by weight of glycerol and, as the remaining component (v), one or more additives, based on 100 parts by weight of a composition comprising the components (i), (ii), (iii) and (v).



  The pharmaceutical composition according to the invention is applied topically. For conventional application on the skin, customary lotions, emulsions, gels, ointments, creams, solutions for applying and / or spraying the mixed-phase or amphiphilic emulsion systems (oil / water-water / oil mixed phase) as well as liposomes and transfersomes, preferably lotions, emulsions , Gels, creams and / or solutions for application and / or spraying, particularly preferably lotions, gels and creams. The active ingredient is preferably applied locally in the area in which there is a skin change and / or disease and / or should be treated or prevented as a preventive measure.



  Pastes, powders or solutions can be mentioned as further topically applicable forms. The pastes often contain hydrophobic and hydrophilic auxiliaries as consistency-imparting bases, but preferably hydrophobic auxiliaries with a very high solids content. The powders or topically applicable powders can be used to increase the dispersity and the flow and gliding ability and to prevent agglomerates, e.g. B. types of starch, such as wheat or rice starch, flame-dispersed silicon dioxide or silica, which also serve as a diluent.

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The appropriate formulations in each case can be produced in accordance with the recipe regulations and procedures known to the person skilled in the art on the basis of pharmaceutical-physical principles.



   A “formulation aid” is understood here to mean all pharmaceutically acceptable auxiliaries and excipients which are known and suitable to the person skilled in the art in the customary manner on the basis of common pharmaceutical-technological processes, taking into account the various indications and application locations, suitable pharmaceutical forms, to produce pharmaceutical compositions and / or cosmetics.



   In a further aspect, the present invention relates to a method for producing a pharmaceutical composition comprising (i) a medicinal drug from a nopal cactus and (ii) at least one active substance with properties that treat light dermatosis, comprising the following steps: a) providing a medicinal drug from nopal Cactus, b) providing at least one active substance with properties that treat light dermatosis, c) mixing the drug from step a) with the active substance from step b) to obtain a pharmaceutical composition with properties that treat light dermatosis.



  In a particular embodiment, the mixing described in point c) for the production of a pharmaceutical composition relates to the mixing of approx. 1-25 parts by weight of the drug from step a) with approx. 1 to 30 parts by weight of at least one DNA repair enzyme contained in liposomes from step b) in each case based on 100 parts by weight of the total composition and at least one further suitable additive as the remaining constituent.

   

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The pharmaceutical composition according to the invention can be used for the treatment of light dermatoses, the light dermatosis being an acute and / or chronic light dermatosis, in particular reddening of the skin,
Skin inflammation and / or DNA damage and / or its consequence, especially
Solar dermatitis, tissue degeneration, benign and / or malignant cell changes can be.



   Furthermore, the pharmaceutical composition can be used as a sunscreen,
Sun lotion, sun gel, after-sun cream, after-sun lotion, after-sun gel and / or as a spray solution for the treatment and / or prevention of light eruption. Galenic formulations of such compositions are known to the person skilled in the art and u. a. in Wilfried Umbach; Cosmetics: Development, production and application of cosmetic products, Thieme Verlag,
1988, ISBN 3-13 712601 0, page 118-130 and Rudolf Voigt, Pharmaceutical Technology, 9th edition, Deutscher Apotheker Verlag, Stuttgart, 2000, in particular chapters 17 and 18.



  In a further aspect, the pharmaceutical composition according to the invention can also be added as an active ingredient complex for medical, pharmaceutical and / or cosmetic products for the treatment and / or prevention of light dermatosis. Medical products in the sense of the Medical Devices Act and pharmaceutical products can be medicinal products in the sense of the Medicinal Products Act and / or over-the-counter pharmaceutical compositions.



  The term “cosmetic products” is understood here to mean, for example, customary ointments, creams, lotions, gels, solutions, sprays, lipsticks for cosmetic, in particular care and / or decorative cosmetic use.

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   In a preferred embodiment, the pharmaceutical composition according to the invention can be used as an active ingredient complex in an amount of approximately 0. 1-50 parts by weight, preferably approximately 1-30 parts by weight, in particular approximately 1-10 parts by weight, based on 100 parts by weight of the medical, pharmaceutical and / or cosmetic product for the treatment and / or prevention of
Light dermatosis can be used.



   In yet another aspect, the pharmaceutical
Composition for enhancing skin tanning and / or enhancing pigment formation in the skin can be used.



  Skin tanning here can be tanning of the skin with and without Ut radiation. UV radiation causes the pigmentation in the skin to be caused both by the "indirect pigmentation" as a result of UV-B radiation and by the "direct pigmentation" as a result of UV-A radiation.



  The tanning of the skin without UV radiation can be divided into three groups, the decorative coloring of the skin with washable make-up preparations, the coloring of the skin through regular intake of carotene preparations and the artificial tanning of the skin through coloring or chemical changes the skin's skin layer with so-called self-tanning agents (see also Wilfried Umbach; cosmetics: development, manufacture and use of cosmetic agents, Thieme Verlag, 1988, ISBN 3-13 712601 0, pages 118-120 and 130-133).



  The drug from Nopal, in particular in combination with at least one DNA repair enzyme, causes skin tanning by intensifying the normal pigment formation as a result of UV radiation (see FIG. 1).
 EMI18.1
 

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   The following figures and examples are intended to explain the invention further, without restricting it thereto. The following claims are hereby incorporated by reference into the text of this description.



   Description of the figures
FIG. 1 shows the effect of a pharmaceutical composition formulated as an after-sun lotion on a sunburn reaction.



  The graphic shows the healing of skin reddening accelerated by the local application of the composition in comparison to untreated skin 24 hours after artificial sun-like UV radiation of the skin in the laboratory in volunteer subjects with 1, 0; 1, 25 and 1, 56 minimal erythema doses (minimal skin reddening or sunburn doses). The minimum erythema dose (MED) is plotted on the X axis and the mean erythema index increase (24 h) is plotted on the y axis (see method section: reflex spectroscopy).

   The reddening of the skin was determined by means of reflex spectroscopy in a total of 7 test persons (4 women, 3 men, average age 44 years, range 33-59 years) after irradiation of skin areas on the buttocks measuring 1 cm in diameter. * p <=. 001; Pharmaceutical composition formulated as an after-sun lotion vs. untreated skin (Student T-Test). The white bars show the erythema index increase of the untreated skin (control) and the dotted, dark bars the erythema index increase of the test subject's skin treated with the pharmaceutical composition, formulated as an after-sun lotion, after UV radiation.



  FIG. 2 shows the effect of the pharmaceutical composition formulated as an after-sun lotion on the tanning of the skin.



  The graphic shows the increase in skin tan in the same test subjects as a result of the local application of the composition compared to untreated skin

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 as in FIG. 1. The time of the measurement (24, 48 and 168 hours after the UV irradiation) is shown on the X axis. The average relative total pigment index (see method section: reflex spectroscopy) is plotted on the y axis. A relative value for skin pigmentation was determined by means of reflex spectroscopy 24 and 48 hours as well as 7 days (168 hours) after UV exposure.

   The white bars show the relative total pigment index of the untreated skin (control) and the dotted, dark bars the relative total pigment index of the skin of the test subject treated with the pharmaceutical composition, formulated as an after-sun lotion, according to UV irradiation.



  Example 1: Study of the pharmaceutical composition formulated as an after-sun lotion The effect of the pharmaceutical composition formulated as an after-sun lotion was tested in 7 volunteers (4 women, 3 men; average age 44 years, range 33-59 years). In the study, a pharmaceutical composition was tested with the following components: Components of the after-sun lotion: The after-sun lotion contains 5 parts by weight of the preferred active ingredient complex listed in Example 2, based on 100 parts by weight of the total composition of the after-sun lotion.
 EMI20.1
 
 <Tb>
 <Tb>



  ingredients <SEP> information <SEP> in <SEP> parts by weight <SEP> pro <SEP> 100
 parts by weight <SEP> the <SEP> overall composition
 <tb> Nopal <SEP> 0, <SEP> 3 <September>
 <Tb>
 

  <Desc / Clms Page number 21>

 
 EMI21.1
 
 <Tb>
 <tb> Micrococcus lysate <SEP> in <SEP> liposomal <SEP> 0, <SEP> 25 <September>
 <tb> shape, Containing <SEP> <SEP> UV <SEP> - <SEP> endonuclease <September>
 <tb> (Ultrasome)
 <tb> 0.25
 <tb> plankton extract <SEP> off <SEP> anacystis <SEP> nidulans
 <tb> in <SEP> liposomal <SEP> form, Containing <SEP> <SEP> photolyase <SEP> (Photosome)
 <tb> panthenol <SEP> 0, <SEP> 30 <September>
 <tb> tocopherol acetate <SEP> 0, <SEP> 30 <September>
 <tb> lecithin <SEP> 0, <SEP> 01 <September>
 <tb> Soy Glycine <SEP> 0, <SEP> 50 <September>
 <tb> methyl paraben <SEP> 0, <SEP> 18 <September>
 <tb> Allantoin <SEP> 0, <SEP> 10 <September>
 <tb> butyl paraben <SEP> 0, <SEP> 06 <September>
 <tb> ethyl paraben <SEP> 0,

    <SEP> 03 <September>
 <tb> propyl paraben <SEP> 0, <SEP> 03 <September>
 Caprylic acid / capric triglycerides <SEP> 5, <SEP> 00 <September>
 <tb> glycerin <SEP> 5, <SEP> 0 <September>
 <tb> decyl glucoside <SEP> 1, <SEP> 10 <September>
 <tb> Buxus <SEP> Chinensis <SEP> 1, <SEP> 00 <September>
 <tb> sodium carbomer <SEP> 0, <SEP> 75 <September>
 <tb> Squalane <SEP> 0, <SEP> 50 <September>
 <tb> Persea <SEP> Gratissima <SEP> 0, <SEP> 50 <September>
 <tb> Trilaureth-4-phosphate <SEP> 1, <SEP> 00 <September>
 <tb> water <SEP> on <SEP> 100 <SEP> parts by weight Fill up <SEP>
 <Tb>
   UV radiation: The UV radiation was carried out using an Oriel 1000 watt sun simulator (Oriel Corp., Darmstadt, Germany), equipped with a dichroic mirror, a WG320 / 1 mm and a UG5 / 1 mm glass filter.

   The intensity of the light source was checked regularly with a broadband thermopile during the study

  <Desc / Clms Page number 22>

 Radiometer (Dexter Research 2M model with quartz window) (Medical Physics, Drybum Hospital, Durham, U.K.) measured or monitored. This radiometer had previously been calibrated by the Regional Medical Physics Department, Royal Victoria Infirmary Unit (Newcastle upon Tyne) using a reference thermopile radiometer (Hilgar-swartz FT17). The UV radiation intensity during the entire study was 12.0 mW / cm2, measured at a distance of 20 cm from the outermost collecting lens of the system. This UV intensity was kept constant during the study with the built-in automated photofeedback system of the Oriel sun simulator.

   The wavelength spectrum of the Oriel sun simulator was compared with an international one
 EMI22.1
 Food and Drug Administration (FDA) and the European
COLIPA (Comité de Liaison des Associations Européennes de l'Industrie de la Parfumerie, des Produits Cosmetiques et de Toilette) standard for the determination of sun protection factors of sun protection products.



  Minimal erythema dose (MED) - testing: The MED was determined in the test subjects by UV radiation from a total of 6 skin areas measuring 2 cm in diameter each on the non-tanned buttocks, in accordance with the guidelines of the American FDA and the European COLIPA standard. The MED test was carried out without a sunscreen preparation, and immediately after UV irradiation, the lower halves of the irradiated areas were treated with the pharmaceutical composition according to the invention as an after-sun lotion, the applied concentration being 2 mg / cm 2.



  Reflex spectroscopy: Reddening and pigmentation of the skin was determined quantitatively in the area of the irradiated skin areas by means of reflex spectroscopy using a DermaSpectrometer (Cortex Technology, Hadsund, Denmark). This device gives

  <Desc / Clms Page number 23>

 a relative value or index for redness (erythema) and pigmentation of the
Skin, based on the absorption characteristics of the skin. The erythema index increase shown in FIG. 1 was subtracted from the erythema
Index values of the non-irradiated skin determined from the erythema index values of the UV-irradiated skin areas of the same subjects. The total pigment index was calculated by summing the pigment index values measured for the individual subjects for the specified times.



   Results :
The results of the study are shown in Figures 1 and 2. The administration of the pharmaceutical composition is formulated as an after-sun lotion containing a medicinal drug from Nopal and Ultrasome and Photosome as DNA
Repair enzymes, resulted in a significant reduction in UV-induced
Sunburn reaction (Fig. 1), whereby at the same time the tanning of the skin was not prevented, but on the contrary was even slightly increased (Fig. 2).



  The pharmaceutical composition formulated as an after-sun lotion with medicinal drug from Nopal in combination with ultrasomes and photosomes accelerates the healing of the acute sunburn reaction (FIG. 1). Remarkably, this anti-sunburn effect does not go hand in hand with a reduction in skin tanning. B. to expect an ordinary sunscreen preparation. In contrast, the application even leads to a slight increase in tanning (FIG. 2).

   This enhancement of the tan caused by UV radiation is not due to a discoloration of the skin, but most likely due to the pharmaceutical composition, formulated as an after-sun lotion with nopal in combination with ultrasomes and photosomes, increased production and / or release of Melanin (skin pigment). This conclusion is based, among other things, on the fact that the treatment of the skin by means of the after-sun lotion with medicinal drug from Nopal in combination with ultrasomes and photosomes without UV radiation does not lead to any discoloration of the skin.

  <Desc / Clms Page number 24>

 



  Example 2: Active ingredient complex which is suitable as an additive for medical, pharmaceutical and / or cosmetic products.



  A preferred active ingredient complex contains:
 EMI24.1
 
 <Tb>
 <tb> component <SEP> parts by weight
 <tb> glycerin <SEP> 30, <SEP> 0 <September>
 <tb> Nopal powder <SEP> 6, <SEP> 0 <September>
 <tb> Ultrasome <SEP> 10, <SEP> 0 <September>
 <tb> Photosome <SEP> 10, <SEP> 0
 Potassium sorbate <SEP> 0, <SEP> 3 <September>
 <tb> sodium benzoate <SEP> 0, <SEP> 2 <September>
 <tb> water <SEP> 43, <SEP> 5 <September>
 <Tb>
 To produce a preferred complex of active ingredients, Nopal powder is placed in glycerol and the corresponding amount of water is stirred in. The ultrasomes and photosomes are then added individually, with stirring, and stirred until a homogeneous mass has formed. In the further course, potassium sorbate and sodium benzoate are also added individually while stirring the mixture and stirred until a homogeneous mass has formed.


    

Claims (31)

 Expectations 1. A pharmaceutical composition comprising (i) a medicament drug Nopal cactus and (ii) at least one active ingredient with light dermatosis-treating properties, the light dermatosis-treating properties Anti-inflammatory, skin-soothing and / or DNA properties Damage repair properties. 2. Pharmaceutical composition according to claim 1, wherein the light dermatosis is an acute and / or chronic light dermatosis. 3. The pharmaceutical composition according to claim 2, wherein the acute Light eruption skin redness, skin inflammation and / or a DNA Damage is, in particular dermatitis solaris (sunburn) and / or Sun allergy. 4. Pharmaceutical composition according to claim 2, wherein the chronic light dermatosis is DNA damage and / or its consequence, in particular tissue degeneration, premature skin aging, benign and / or malignant cell changes. 5. Pharmaceutical composition according to one of claims 1 to 4, wherein the active substance with anti-inflammatory and / or skin-calming properties bisabolol, panthenol, dexpanthenol, Reishi (Ganoderma lucidum), allantoin, vitamin E and / or extract from green tea, chamomile, aloe vera, witch hazel.  <Desc / Clms Page number 26>   6. Pharmaceutical composition according to one of claims 1 to 4, wherein the pharmaceutical active ingredient with DNA damage repairing Properties is at least one DNA repair enzyme. 7. The pharmaceutical composition according to claim 6, wherein the at least one DNA repair enzyme endonuclease V, 06- Methyl guanine DNA methyl transferase, photolyase, uracil and  EMI26.1    Is methyladenine DNA glycosylase, and / or correndonuclease; or in Micrococcus luteus and / or contained in Anacystis nidulans extract. 8. Pharmaceutical composition according to claim 6 or 7, wherein the at least one DNA repair enzyme is contained in a carrier material, wherein the carrier material is selected from liposomes, nanocapsules, nanoparticles and microparticles, in particular liposomes. 9. Pharmaceutical composition according to one of claims 6 to 8, wherein the at least one DNA repair enzyme endonuclease V, Is photolyase and / or contained in Micrococcus luteus and / or in Anacystis nidulans extract. 10. A pharmaceutical composition according to any one of claims 1 to 9, wherein the composition of the drug in combination with Endonuclease V, Photolyase and / or Micrococcus luteus and / or in Anacystis nidulans extract includes in liposomal form. 11. A pharmaceutical composition according to any one of claims 1-10, wherein the composition about 1-40 parts by weight, preferably about 2-  <Desc / Clms Page number 27>   25 parts by weight, in particular approx. 2-15 parts by weight of component (i) and approx. 1-40 parts by weight, preferably approx. 2-25 parts by weight, in particular approx. 2-15 parts by weight of component (ii), and as the remaining component (v ) one or more additives, based on 100 parts by weight of a composition with the Components (i), (ii) and (v) contains.  12. Pharmaceutical composition according to one of claims 1-10, wherein the composition about 1-25 parts by weight, preferably about 2-20 parts by weight, in particular about 2-15 parts by weight of component (i), about 1-30 parts by weight, preferably about 2-25 parts by weight, in particular about 2-15 parts by weight of component (ii), and as component (iii) about 20-40 parts by weight, preferably about 25-35 Parts by weight of glycerin, and as the remaining component (v) one or more additives, based on 100 parts by weight of a composition with the Components (i), (ii), (iii) and (v) contains. 13. The pharmaceutical composition according to claim 1, wherein the Medicinal drug from Nopal cactus from the cactus branches and / or fruits, in particular the cactus branches, is available. 14. The pharmaceutical composition according to claim 13, wherein the Medicinal drug from Nopal cactus by crushing stingless Cactus branches is available. 15. A method for producing a pharmaceutical composition comprising (i) a medicinal drug from Nopal cactus and (ii) at least one  <Desc / Clms Page number 28>   Active ingredient with light dermatosis-treating properties, comprising the following steps: a) providing a drug from Nopal cactus, b) providing at least one active ingredient with light dermatosis-treating properties according to one of claims 2 to 10, and c) mixing the drug from step a) with the active ingredient Step b) to obtain a pharmaceutical composition with properties that treat light dermatosis.  16. The method according to claim 15, wherein the drug from Nopal cactus was obtained from the cactus branches and / or fruits, in particular the cactus branches.  17. The method of claim 15 or 16, wherein the drug from nopal Cactus was obtained by crushing stingless cactus branches. 18. The method according to any one of claims 15 to 17, comprising mixing about 1-25 parts by weight of the drug from step a) with about 1 to 30 Parts by weight of at least one DNA contained in liposomes Repair enzyme from step b) based in each case on 100 parts by weight of the Overall composition and at least one other suitable Additive as a remaining ingredient. 19. The method according to claim 18, wherein the DNA repair enzyme is endonuclease V, photolyase and / or is contained in Micrococcus luteus extract and / or in Anacystis nidulans extract. 20. Pharmaceutical composition obtainable by the method according to any one of claims 15 to 19.  <Desc / Clms Page number 29>      21. Use of the pharmaceutical composition according to one of the Claims 1 to 14 and 20 for the manufacture of a medicament for Treatment and / or prevention of light eruption.  22. Use according to claim 21, wherein the light dermatosis is an acute and / or chronic light dermatosis.  23. Use according to claim 22 or 23, wherein the acute light dermatosis Skin redness, skin inflammation and / or DNA damage, in particular dermatitis solaris (sunburn) and / or sun allergy. 24. Use according to any one of claims 21 to 23, wherein the chronic Light dermatosis is DNA damage and / or its consequence, in particular tissue degeneration, premature skin aging, benign and / or malignant cell changes. 25. Use of the pharmaceutical composition according to one of the Claims 21 to 24 as sunscreen, sun lotion, sun gel, after-sun Cream, after-sun lotion and / or after-sun gel. 26. Use of the pharmaceutical composition according to one of the Claims 10 to 12 and 15 to 19 as an active ingredient complex for medical, pharmaceutical and / or cosmetic products for treatment and / or Prevention of light eruption. 27. Use of the pharmaceutical composition according to claim 26 as an active ingredient complex in an amount of approximately 0. 1-50 parts by weight, preferably approximately 1-30 parts by weight, in particular approximately 1-10 parts by weight, based on 100 parts by weight of the medical, pharmaceutical and / or of the cosmetic product for the treatment and / or prevention of light eruption.  <Desc / Clms Page number 30> 28. Use of the composition according to any one of claims 1 to 14 and 21 for enhancing skin tanning. 29. Use of the composition according to one of claims 1 to 14 and 21 for enhancing pigment formation in the skin. 30. Cosmetic product containing a pharmaceutical composition according to any one of claims 1, 5-14. 31. Cosmetic product according to claim 31, wherein the cosmetic product is a sun cream, sun lotion, sun gel, after-sun cream, after-sun Lotion and / or after-sun gel.