WO1994019005A1 - Enzyme-containing pharmaceutical or cosmetic composition, process for preparing the same and its use - Google Patents

Enzyme-containing pharmaceutical or cosmetic composition, process for preparing the same and its use Download PDF

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Publication number
WO1994019005A1
WO1994019005A1 PCT/DE1994/000208 DE9400208W WO9419005A1 WO 1994019005 A1 WO1994019005 A1 WO 1994019005A1 DE 9400208 W DE9400208 W DE 9400208W WO 9419005 A1 WO9419005 A1 WO 9419005A1
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Prior art keywords
preparation according
preparation
pharmaceutical
skin
enzyme
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PCT/DE1994/000208
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German (de)
French (fr)
Inventor
Albert Scheller
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Albert Scheller
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Application filed by Albert Scheller filed Critical Albert Scheller
Priority to AU63730/94A priority Critical patent/AU6373094A/en
Publication of WO1994019005A1 publication Critical patent/WO1994019005A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66Enzymes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/465Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/47Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/48Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4873Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y302/00Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01017Lysozyme (3.2.1.17)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/22Cysteine endopeptidases (3.4.22)
    • C12Y304/22002Papain (3.4.22.2)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/22Cysteine endopeptidases (3.4.22)
    • C12Y304/22004Bromelain (3.4.22.4)

Definitions

  • composition comprising enzymes Process for their preparation and their use
  • the invention relates to pharmaceutical or cosmetic preparations comprising enzymes, in particular pharmaceutical or cosmetic preparations with enzymes which are able to prevent the enzymatic breakdown of sebum in the skin at pH values existing in the skin.
  • the invention also relates to a method for producing such pharmaceutical or cosmetic preparations.
  • the invention relates to the use of such pharmaceutical preparations, for example in the treatment of and the prevention of acne vulgaris.
  • the invention relates to the use of such cosmetic preparations in the eventual preventive care of the skin.
  • a large number of influencing factors which can be seen in FIG. 1, have been proven for medical acne vulgaris.
  • hyperkeratosis ie thickening of the horny layer of the skin, for example due to increased formation of horny cells, can occur due to exogenous influencing factors (soot, dust, hormones or pharmaceuticals).
  • exogenous influencing factors dust, hormones or pharmaceuticals
  • the skin can be stimulated to produce more taig. This is often caused by an excess of androgenic hormones, for example during puberty.
  • Such microorganisms are, for example, Corynebacterium acnes and Staphylococcus albus and lipophilic yeasts of the genus Pityrosporum.
  • the formation of free fatty acids leads to so-called "sterile inflammation”.
  • a comparable "reaction sequence” also frequently occurs when the sebum gland outputs are blocked by external factors such as dust and soot, but also cosmetic preparations.
  • conventional acne therapy was essentially conducted in three ways (1), (2) and (3). Most acne therapeutics intervene in the area of inhibiting increased taig production and / or eliminating hyperkeratosis.
  • preparations containing sulfur, resorcinol, hormones, alcohols or vitamin A acid were regularly administered. Preparations containing sulfur, resorcinol, salicylic acid, vitamin A acid and thioxolone were administered against hyperkeratosis.
  • Preparations containing vitamin A acid also have toxic side effects, depending on the dose, skin region and individual factors. In addition, redness, scaling and burning may appear on the skin. Vitamin A acid is also incompatible with a variety of other agents or medications. In addition, the sensitivity of the skin to sunlight is increased.
  • hormones - in the present case predominantly estrogenic hormones - for the therapy of acne vulgaris also leads to side effects, which are primarily due to the undesirable effect of the estrogen hormones on the overall hormonal balance. Hormone treatment also led to further side effects.
  • the external treatment of the skin with antibiotics and local disinfectants primarily leads to the elimination or inhibition of the activity of the microorganisms on the skin or in the skin which induce the breakdown of the triglycerides into free fatty acids and glycerol.
  • Disadvantage of the - necessary for the acne vulgaris treatment Frequent treatment of the skin with disinfectants, however, is that the natural colonization of the skin with microorganisms is unselectively destroyed and an important protective function of the microorganisms for protection against skin diseases is thus revealed.
  • the pharmacological mechanism of action should be prevented from influencing only one of the many factors which are decisive for the triggering of acne vulgaris.
  • Another object of the invention was to provide a pharmaceutical preparation which can be adapted to the severity of the "acne vulgaris" disease and which at the same time attacks several factors which trigger the disease.
  • Another object of the invention was to provide a pharmaceutical preparation which combats the causes of acne vulgaris on the broadest possible level without leading to side effects on the skin areas involved or in the whole organism.
  • Another object of the invention was to provide a cosmetic preparation which is skin-friendly and skin-care and does not lead to skin reactions which result in a reaction mechanism for the development of acne.
  • Another object of the invention was to provide a method for producing a pharmaceutical or cosmetic preparation, in which the components involved can either be prepared on an industrial scale for application or can be made available for preparation by the user.
  • a pharmaceutical or cosmetic preparation according to the invention is suitable both for the treatment of acne vulgaris with almost no side effects and for the prevention of acne vulgaris without the occurrence of undesirable side effects.
  • the invention relates to a pharmaceutical or cosmetic preparation which comprises one or more enzyme (s) from the group proteinases, lysozymes, elastases, ⁇ -lipases and ⁇ - acting in the pH range between 4.0 and 8.5.
  • Amylase and optionally pharmaceutically acceptable carriers and excipients.
  • the invention relates to a method for producing such a pharmaceutical or cosmetic preparation, in which one or more enzyme (s) provided in a plurality of containers and optionally pharmaceutically or cosmetically acceptable additives, carriers and / or auxiliaries and if appropriate, a pharmaceutically or cosmetically acceptable solvent suitable for the desired application form is intimately mixed with one another to provide the ready-to-use preparation.
  • one or more enzyme (s) provided in a plurality of containers and optionally pharmaceutically or cosmetically acceptable additives, carriers and / or auxiliaries and if appropriate, a pharmaceutically or cosmetically acceptable solvent suitable for the desired application form is intimately mixed with one another to provide the ready-to-use preparation.
  • the invention also relates to the use of such a pharmaceutical preparation for the treatment of and / or for the prevention of acne vulgaris.
  • the invention also relates to the use of a cosmetic preparation for the care and cleaning of the skin and / or decorative application to the skin.
  • the pharmaceutical or cosmetic preparation according to the invention comprises one or more enzyme (s) from the group proteinases, lysozymes, elastases, ⁇ -lipases and ⁇ -amylase, which acts in the pH range between 4.0 and 8.5, and optionally pharmaceutically or cosmetically acceptable carriers and adjuvants.
  • the specified pH value range for the spectrum of action of the enzyme (s) used according to the invention in the pharmaceutical or cosmetic preparation comprises the natural and the The presence of acne vulgaris may change the pH range of the skin areas involved.
  • the enzyme or the enzymes which belong to the enzyme subclass "proteinases” are selected from trypsin, chymotrypsin, bromelain, papain and ficin.
  • the proteinases bromelain and papain are particularly preferred.
  • the enzyme or the enzymes from the class of the proteinases can be used alone to provide pharmaceutical or cosmetic preparations according to the invention which are active against acne vulgaris. However, it is also possible to use several proteinases from the group mentioned together or together with other enzymes.
  • the pharmaceutical or cosmetic preparation according to the invention comprises, as lysozymes, that is to say the enzymes which dissolve the cell walls of microorganisms, muramidase, which is known in the narrower sense under the name "lysozyme” (EC 3.2.1.17).
  • lysozyme the enzymes which dissolve the cell walls of microorganisms
  • muramidase which is known in the narrower sense under the name "lysozyme” (EC 3.2.1.17).
  • lysozyme EC 3.2.1.17
  • This can also be used alone or together with other enzymes.
  • proteinases such as for example with trypsin, chymotrypsin, bromelain, papain and ficin
  • a pharmaceutical or cosmetic preparation which comprises an enzyme combination of bromelain, papain and lysozyme is particularly preferred.
  • the pharmaceutical or cosmetic preparation comprises pancreatin as an enzymatically active component.
  • Pancreatin usually contains a mixture of all digestive enzymes in the pancreas, primarily proteinases such as trypsin and chymotrypsin, elastases, lipases, ⁇ -amylase and possibly also ribonuclease.
  • Pancreatin can be used in the pharmaceutical or cosmetic preparation according to the invention either alone or together with other enzymes.
  • Pharmaceutical or cosmetic preparations are particularly preferred which, in addition to pancreatin, also comprise one or more of the enzymes bromelain, papain and lysozyme.
  • the pharmaceutical or cosmetic preparation according to the invention comprises a complexing agent in addition to the enzymes mentioned.
  • Complexing agents are advantageous because they complex metal ions, especially calcium ions, in the form of so-called chelates, which are therefore suitable for the. bacterial metabolism are no longer available.
  • all pharmaceutically acceptable complexing agents are suitable for the purposes according to the invention.
  • Particularly preferred are pharmaceutical or cosmetic preparations in which as a complexing agent ethylenediaminetetraacetic acid (EDTA) and its complexing salts, citric acid and its complexing salts, ascorbic acid and its complexing salts, nitrilotriacetic acid (NTA) and their complexing salts and possibly combinations of several such Connections are included.
  • Salts which can be mentioned are primarily salts which are soluble in the natural environment of use, in particular alkali metal salts, very particularly preferably sodium salts.
  • the pharmaceutical or cosmetic preparations according to the invention can additionally comprise one or more pharmaceutically or cosmetically acceptable additives. These serve special purposes, the provision of certain formulations or aesthetic purposes.
  • Pharmaceutically or cosmetically acceptable additives can be, for example, buffers for setting or buffering a specific pH of the pharmaceutical or cosmetic preparation. So-called “Tris buffers” (tris (hydroxymethyl) aminomethane) may be mentioned as such. However, other pharmaceutically or cosmetically acceptable buffer substances can also be used.
  • emulsifiers for certain applications, emulsifiers, stabilizers and preservatives can also be present. Such substances are known as such from the prior art. Of course, only those additives can be used which are compatible with the other components of the pharmaceutical or cosmetic preparation according to the invention and with the skin.
  • the pharmaceutical or cosmetic preparation can also comprise carriers and auxiliaries which are matched to the administration form. These can be, for example, fragrance and aroma substances which give the ready-to-use pharmaceutical or cosmetic preparations a fragrance which is pleasant for the user.
  • gelling agents, ointments, bases, powder carriers, spray or aerosol carriers or liquid solvents or carrier agents for solutions and lotions can also be present, tailored to the desired form of use or administration.
  • cosmetic preparations can comprise auxiliaries suitable for cosmetic purposes, for example moisturizers, skin-care or cleansing substances or auxiliaries which are suitable or suitable for decorative cosmetic purposes; eg color pigments. It applies to all the substances mentioned that they not only have to be compatible with the other components - also in the long term - but also have to be tailored to the desired form of use, in particular must be compatible with the skin.
  • a pharmaceutical or cosmetic preparation according to the present invention can also generally contain further substances which are customary for such preparations, as are known to the skilled worker familiar with the compounding, ready-to-use preparation and use from the prior art.
  • additives that they must be compatible with the other components, in particular with the enzymes acting in the pH range between 4.0 and 8.5, and furthermore must not be incompatible with the field of application of the pharmaceutical or cosmetic preparation, in particular, no incompatibility with human skin.
  • pharmaceutical or cosmetic preparations according to the invention contain an amount of one or more enzymes in the range from 0.1 to 33.3% by weight, an amount of one or more complexing agents - if present - in the range from 0 to 4% by weight. % and for the remainder pharmaceutically or cosmetically acceptable additives, carriers and / or auxiliaries, in particular such additives, carriers and / or auxiliaries as have been specified above in detail.
  • Cosmetic preparations regularly contain smaller amounts of the enzymes and complexing agents mentioned than pharmaceutical preparations.
  • compositions according to the invention are preferably provided with the components specified above in the form of a cream, an emulsion, an ointment, a gel, a solution, a lotion, a powder, a spray or an aerosol. All of the above-mentioned forms of preparation represent externally applicable forms of preparation. This has the advantage that they can be applied specifically to the area affected by acne vulgaris. Particularly for cosmetic preparations according to the invention, creams, emulsions, ointments, gels, solutions, lotions and powders are preferred preparation forms.
  • the active substances present in the pharmaceutical preparations according to the invention specifically attack the factors triggering acne vulgaris according to path (2) and (3) in FIG. 2.
  • the digested protein fragments also have - as was surprisingly found - emulsifying and thus support the cleaning and healing effects of the preparations according to the invention.
  • Lysozyme is a muramidase that is physiologically occurring in humans and has a bacteriostatic and bactericidal effect. Lysozyme is found in the lacrimal fluid, the nasal and intestinal mucosa as well as in bacteriophages and polymorphonuclear leucocytes. Lysozyme is also used pharmacologically in throat tablets or eye drops or ointments. It destroys the cell wall material (murein) of the bacteria located on the skin and in the execution ducts of the sebum and sweat glands.
  • the complexing agents such as EDTA also act as pH buffers. In addition, they activate and strengthen the action of the enzymes and prevent the growth of fungi and bacteria or increase their lysis because they bind the calcium ions, sodium ions and aluminum ions required for the growth of the bacteria in the form of complexes.
  • the pharmaceutical or cosmetic preparations according to the invention if they are not in solid form (for example as a powder), are formulated on an essentially aqueous basis. Consequently, aqueous preparations are preferred for preparation forms such as creams, emulsions, ointments, gels, solutions, lotions, sprays or aerosols.
  • solvents which are compatible with the enzymes, provided that they are compatible with the skin. Examples include mixtures of water with physiologically acceptable alcohols or alcohols alone.
  • the pharmaceutical or cosmetic preparations are produced by intimately mixing the enzyme or enzymes and, if appropriate, pharmaceutically or cosmetically acceptable additives, carriers and / or auxiliaries and, if appropriate, a pharmaceutically acceptable solvent suitable for the desired form of application.
  • a preparation ready for use is regularly provided.
  • the process according to the invention can consist in mixing the components desired for the respective pharmaceutical preparation with one another on an industrial scale and in filling the ready-to-use mixture into dispensing containers suitable for administration or removal for administration by the user.
  • dispensing containers suitable for administration or removal for administration by the user can be, for example, bottles, tubes, aerosols, sprays, etc.
  • the dispensing containers used in individual cases are of course based on the form of administration.
  • the components are filled into a plurality of containers suitable for removal for administration and the separately provided components - as users - are provided immediately before administration, for example immediately before topical application of the ready-to-use preparation.
  • the last-mentioned, preferred embodiment can consist, for example, of providing the enzyme or the combination of enzymes together with suitable additives, for example with one or more complexing agents, one or more, in suitable containers, for example in bags, in separate compartments in a chamber Aroma or fragrance and / or one or more emulsifiers, while in the other compartment ultrapure water is provided.
  • the user mixes the contents of both compartments ("double-chamber bags") and applies the pharmaceutical or cosmetic preparation prepared in this way to the affected skin areas.
  • compositions in order to take into account the different pharmacological requirements at the beginning of the treatment and after the first treatment results.
  • specific treatment requirements can advantageously be taken into account depending on the individual clinical picture.
  • Cosmetic preparations can moreover be provided in a preferred embodiment in different compositions, for example different skin conditions (e.g. dry or oily skin), different skin types (e.g. robust or sensitive skin) or different purposes (e.g. As moisturizer, nutrient cream, night cream, day cream) take into account.
  • the components of such preparations - also in the long term - must be compatible with the enzymes and possibly complexing agents, as well as the other components, but also with the human skin.
  • the preparations according to the invention are used - optionally also in different compositions - either for the treatment of acute acne vulgaris and skin impurities and hyperkeratoses or can also be used to prevent acne vulgaris and skin impurities and hyperkeratoses or to condition the skin accordingly.
  • preparations according to the invention can also be used for other purposes, for example for a bacteriostatic or bactericidal treatment of the skin surface, if this should be indicated for certain reasons.
  • Cosmetic preparations according to the invention can be used to care for the skin, to clean the skin or to keep the skin moist.
  • Another area of use of the cosmetic preparations according to the invention is in the field of so-called decorative cosmetics: preparations according to the invention can also be used for decorative application to the skin, for example as a powder or blush.
  • the bactericidal or bacteriostatic activity of pharmaceutical preparations according to the invention was investigated as follows: Commercially available culture media (agar, blood agar) were provided in conventional dishes. The entire surface of the culture medium was coated with bacteria from the following strains:
  • a pharmaceutical preparation consisting of 1 mg lysozyme, 1 mg EDTA and 1 drop of aqua destillata was filled.
  • the culture media were incubated at 37 ° C for 24 hours.
  • Example 2 An experimental setup corresponding to Example 1, but with only one hole into which distilled water had been filled, was provided. There was no bacteria-free yard in the agar around the punched hole.
  • the experimental setup essentially corresponded to the experimental setup according to Example 1. However, only agar culture media were used. The bacterial strain used was Staphylococcus epidermidis.
  • the amounts of the enzymes tested were 1 mg in all cases.
  • the courtyards formed were in an area ratio of 1: 2.
  • the bacteria-free courtyards formed were in an area ratio of 1: 3.
  • the bacteria-free courtyards formed were in an area ratio of 1: 3.
  • the bacteria-free courtyards formed had an area ratio of 2: 3.
  • a 2-hole bowl according to the experimental setup of Examples 1 and 2 was used. Only aqua dest. filled. An aqueous EDTA solution was filled in the other hole. After the incubation, no bacteria-free yard had formed around the first-mentioned hole. An extremely narrow, bacteria-free courtyard, hardly distinguishable from the first hole, had formed around the second hole.

Abstract

Pharmaceutical or cosmetic compositions contain one or several enzymes from the group of the proteinases, lysozymes, elastases, alpha-lipases and alpha-amylase, as well as if required pharmaceutically or cosmetically admissible excipients and additives. Also disclosed is a process for preparing such a pharmaceutical or cosmetic composition and its use.

Description

Pharmazeutische oder kosmetische, Enzyme umfassende Zubereitung Verfahren zu deren Herstellung und deren Verwendung Pharmaceutical or cosmetic preparation comprising enzymes Process for their preparation and their use
Die Erfindung betrifft pharmazeutische oder kosmetische, Enzyme umfassende Zubereitun¬ gen, insbesondere pharmazeutische oder kosmetische Zubereitungen mit Enzymen, die in der Lage sind, den enzymatischen Abbau des Talgs in der Haut bei in der Haut bestehenden pH-Werten zu verhindern. Die Erfindung betrifft auch ein Verfahren zur Herstellung derartiger pharmazeutischer oder kosmetischer Zubereitungen. In einem weiteren Aspekt betrifft die Erfindung die Verwendung derartiger pharmazeutischer Zubereitungen, beispielsweise bei der Behandlung von und der Vorbeugung gegen Acne vulgaris. Außerdem betrifft die Erfindung die Verwendung derartiger kosmetischer Zubereitungen bei der gegebenenfalls vorbeugenden Pflege der Haut.The invention relates to pharmaceutical or cosmetic preparations comprising enzymes, in particular pharmaceutical or cosmetic preparations with enzymes which are able to prevent the enzymatic breakdown of sebum in the skin at pH values existing in the skin. The invention also relates to a method for producing such pharmaceutical or cosmetic preparations. In a further aspect, the invention relates to the use of such pharmaceutical preparations, for example in the treatment of and the prevention of acne vulgaris. In addition, the invention relates to the use of such cosmetic preparations in the eventual preventive care of the skin.
Acne vulgaris ist eine in ihren Ursachen immer noch nicht bis ins letzte geklärte Erkrankung der Talgdrüsen-reichen Hautbezirke (vornehmlich Gesicht, Nacken, Brust und Rücken), die vornehmlich in der Pubertät erstmalig auftritt und meist erst in der Mitte des dritten Lebensjahrzehnts zurückgeht.The causes of acne vulgaris are still not fully resolved in the sebum-rich areas of the skin (primarily the face, neck, chest and back), which primarily occurs during puberty and usually does not return until the middle of the third decade of life.
In der medizinischen Forschung wurde für Acne vulgaris eine Vielzahl von Einflußfaktoren nachgewiesen, die aus Figur 1 ersichtlich sind. So kann durch exogene Einflußfaktoren (Ruß, Staub, Hormone bzw. Arzneimittel) eine Hyperkeratose, d.h. eine Verdickung der Hornschicht der Haut, beispielsweise durch vermehrte Bildung von Hornzellen auftreten. Andererseits kann - ebenfalls durch exogene Einflußfaktoren verursacht - die Haut zu einer erhöhten Taigproduktion angeregt werden. Diese ist häufig durch einen Überschuß androgener Hormone, beispielsweise während der Pubertät, verursacht. Hyperkeratose wie erhöhte Taigproduktion im Inneren der Haut fuhren - mitunter auch synergistisch - zur Bildung sogenannter Talgpfröpfe (Comedonen, auch "Mitesser" genannt). In der Haut bzw. auf der Haut vorhandene Mikroorganismen und von ihnen produzierte Enzym-Systeme (Esterasen, Lipasen) bauen die Triglyceride des Taigpfropfes in Glycerin und freie Fettsäuren ab. Diese führen zu einer starken Verschiebung des natürlichen Haut-pH-Wertes in den stark sauren Bereich, mitunter bis zum pH- Wert von 1. Derartige Mikroorganismen sind beispielsweise Corynebacterium acnes und Staphylococcus albus sowie lipophile Hefen der Gattung Pityrosporum. Die Bildung freier Fettsäuren führt zu sogenannten "sterilen Entzündungen". Eine vergleichbare "Reaktionsfolge" läuft auch häufig bei Verstopfung der Talgdrüsen¬ ausgänge durch äußere Einflußfaktoren wie Staub und Ruß, aber auch kosmetische Präparate ab.A large number of influencing factors, which can be seen in FIG. 1, have been proven for medical acne vulgaris. For example, hyperkeratosis, ie thickening of the horny layer of the skin, for example due to increased formation of horny cells, can occur due to exogenous influencing factors (soot, dust, hormones or pharmaceuticals). On the other hand - also caused by exogenous influencing factors - the skin can be stimulated to produce more taig. This is often caused by an excess of androgenic hormones, for example during puberty. Hyperkeratosis and increased production of taig inside the skin lead - sometimes also synergistically - to the formation of so-called sebum plugs (comedones, also called "blackheads"). Microorganisms present in the skin or on the skin and enzyme systems produced by them (esterases, lipases) break down the triglycerides of the graft into glycerol and free fatty acids. These lead to a strong shift in the natural skin pH value into the strongly acidic range, sometimes up to the pH value of 1. Such microorganisms are, for example, Corynebacterium acnes and Staphylococcus albus and lipophilic yeasts of the genus Pityrosporum. The formation of free fatty acids leads to so-called "sterile inflammation". A comparable "reaction sequence" also frequently occurs when the sebum gland outputs are blocked by external factors such as dust and soot, but also cosmetic preparations.
Wie sich aus Figur 2 ergibt, wurde die herkömmliche Akne-Therapie im wesentlichen über drei Wege (1), (2) und (3) geleitet. Die meisten Akne-Therapeutika greifen im Bereich einer Inhibierung der erhöhten Taigproduktion und/oder eine Beseitigung der Hyperkeratose ein. Zur Inhibierung der erhöhten Taigproduktion wurden regelmäßig Schwefel, Resorcin, Hormone, Alkohole bzw. Vitamin A-Säure enthaltende Präparate verabreicht. Gegen Hyperkeratose wurden Schwefel, Resorcin, Salicylsäure, Vitamin A-Säure bzw. Thioxolon enthaltende Präparate verabreicht.As can be seen from FIG. 2, conventional acne therapy was essentially conducted in three ways (1), (2) and (3). Most acne therapeutics intervene in the area of inhibiting increased taig production and / or eliminating hyperkeratosis. To inhibit the increased production of taig, preparations containing sulfur, resorcinol, hormones, alcohols or vitamin A acid were regularly administered. Preparations containing sulfur, resorcinol, salicylic acid, vitamin A acid and thioxolone were administered against hyperkeratosis.
Alle Präparate sind mit zum Teil erheblichen Nebenwirkungen verbunden. So führt die Behandlung mit Schwefel häufig dazu, daß sich in noch stärkerem Umfang Comedonen (Mitesser) bilden. Darüber hinaus kann Schwefel - in höheren Dosen verabreicht - durch Resorption auch toxische Schäden hervorrufen.All preparations are sometimes associated with considerable side effects. Treatment with sulfur often leads to the formation of comedones (blackheads) to an even greater extent. In addition, sulfur - administered in higher doses - can also cause toxic damage through absorption.
Vitamin A-Säure enthaltende Präparate üben - abhängig von Dosis, Hautregion und individuellen Faktoren - ebenfalls toxische Nebenwirkungen aus. Darüber hinaus können auf der Haut Rötung, Schuppung und Brennen auftreten. Vitamin A-Säure ist auch mit einer Vielzahl anderer Mittel bzw. Medikamente unverträglich. Außerdem wird die Empfindlich¬ keit der Haut gegen Sonnenlicht gesteigert.Preparations containing vitamin A acid also have toxic side effects, depending on the dose, skin region and individual factors. In addition, redness, scaling and burning may appear on the skin. Vitamin A acid is also incompatible with a variety of other agents or medications. In addition, the sensitivity of the skin to sunlight is increased.
Auch die Behandlung mit Hormonen - im vorliegenden Fall überwiegend östrogene Hormone - zur Therapie von Acne vulgaris führt zu Nebenwirkungen, die in erster Linie in der unerwünschten Einwirkung der Östrogen-Hormone auf den Gesamt-Hormonhaushalt liegen. Auch die Hormonbehandlung führte zu weitergehenden Nebenwirkungen.Treatment with hormones - in the present case predominantly estrogenic hormones - for the therapy of acne vulgaris also leads to side effects, which are primarily due to the undesirable effect of the estrogen hormones on the overall hormonal balance. Hormone treatment also led to further side effects.
Die äußerliche Behandlung der Haut mit Antibiotika sowie lokalen Desinfektionsmitteln führt in erster Linie zu einer Beseitigung bzw. Inhibierung der Aktivität der Mikroorganismen auf der Haut bzw. in der Haut, die den Abbau der Triglyceride zu freien Fettsäuren und Glycerin induzieren. Nachteil der - bei der Acne vulgaris-Behandlung erforderlichen - häufigen Behandlung der Haut mit Desinfektionsmitteln ist jedoch, daß die natürliche Besiedlung der Haut mit Mikroorganismen unselektiv zerstört und damit eine wichtige Schutzfünktion der Mikroorganismen für den Schutz vor Erkrankungen der Haut preisgegeben wird.The external treatment of the skin with antibiotics and local disinfectants primarily leads to the elimination or inhibition of the activity of the microorganisms on the skin or in the skin which induce the breakdown of the triglycerides into free fatty acids and glycerol. Disadvantage of the - necessary for the acne vulgaris treatment - Frequent treatment of the skin with disinfectants, however, is that the natural colonization of the skin with microorganisms is unselectively destroyed and an important protective function of the microorganisms for protection against skin diseases is thus revealed.
Es war daher eine Aufgabe der Erfindung, eine pharmazeutische Zubereitung zur Verfügung zu stellen, die zur Behandlung von Acne vulgaris oder sogar zur Vorbeugung gegen Acne vulgaris geeignet ist, ohne daß die oben genannten Nebenwirkungen auftreten. Insbesondere sollte verhindert werden, daß der pharmakologische Wirkungsmechanismus in der Beeinflussung nur eines der vielen für die Auslösung von Acne vulgaris entscheidenden Faktoren besteht.It was therefore an object of the invention to provide a pharmaceutical preparation which is suitable for the treatment of acne vulgaris or even for the prevention of acne vulgaris, without the above-mentioned side effects occurring. In particular, the pharmacological mechanism of action should be prevented from influencing only one of the many factors which are decisive for the triggering of acne vulgaris.
Eine weitere Aufgabe der Erfindung war, eine pharmazeutische Zubereitung zur Verfügung zu stellen, die der Schwere des Krankheitsbildes "Acne vulgaris" angepaßt werden kann und gleichzeitig mehrere die Krankheit auslösende Faktoren angreift.Another object of the invention was to provide a pharmaceutical preparation which can be adapted to the severity of the "acne vulgaris" disease and which at the same time attacks several factors which trigger the disease.
Eine weitere Aufgabe der Erfindung war, eine pharmazeutische Zubereitung bereitzustellen, die die Ursachen von Acne vulgaris auf möglichst breiter Ebene bekämpft, ohne an den beteiligten Hautpartien oder im Gesamtorganismus zu Nebenwirkungen zu führen.Another object of the invention was to provide a pharmaceutical preparation which combats the causes of acne vulgaris on the broadest possible level without leading to side effects on the skin areas involved or in the whole organism.
Eine weitere Aufgabe der Erfindung war, eine kosmetische Zubereitung zur Verfügung zu stellen, die hautfreundlich und hautpflegend aufgebaut ist und nicht zu Reaktionen der Haut führt, die in einem Reaktionsmechanismus zur Entstehung von Acne münden.Another object of the invention was to provide a cosmetic preparation which is skin-friendly and skin-care and does not lead to skin reactions which result in a reaction mechanism for the development of acne.
Eine weitere Aufgabe der Erfindung war, ein Verfahren zur Herstellung einer pharmazeuti¬ schen oder kosmetischen Zubereitung bereitzustellen, bei dem die beteiligten Komponenten entweder im industriellen Maßstab für die Applikation fertig vorbereitet oder für die Vorbereitung durch den Anwender bereitgestellt werden können. Überraschend wurde gefunden, daß eine pharmazeutische oder kosmetische Zubereitung gemäß der Erfindung sowohl zur nahezu nebenwirkungslosen Behandlung von Acne vulgaris als auch zur Vorbeugung gegen Acne vulgaris ohne Auftreten von unerwünschten Nebenwirkungen geeignet ist.Another object of the invention was to provide a method for producing a pharmaceutical or cosmetic preparation, in which the components involved can either be prepared on an industrial scale for application or can be made available for preparation by the user. Surprisingly, it was found that a pharmaceutical or cosmetic preparation according to the invention is suitable both for the treatment of acne vulgaris with almost no side effects and for the prevention of acne vulgaris without the occurrence of undesirable side effects.
Die Erfindung betrifft eine pharmazeutische oder kosmetische Zubereitung, die ein oder mehrere im pH-Wert-Bereich zwischen 4,0 und 8,5 wirkende(s) Enzym(e) aus der Gruppe Proteinasen, Lysozyme, Elastasen, α-Lipasen und α-Amylase sowie gegebenenfalls pharmazeutisch annehmbare Träger und Hilfsstoffe umfaßt.The invention relates to a pharmaceutical or cosmetic preparation which comprises one or more enzyme (s) from the group proteinases, lysozymes, elastases, α-lipases and α- acting in the pH range between 4.0 and 8.5. Amylase and optionally pharmaceutically acceptable carriers and excipients.
Die Erfindung betrifft in einem weiteren Aspekt ein Verfahren zur Herstellung einer derartigen pharmazeutischen oder kosmetischen Zubereitung, worin man gegebenenfalls in einer Mehrzahl von Behältnissen bereitgestellte(s) Enzym(e) und gegebenenfalls pharmazeu¬ tisch oder kosmetisch annehmbare Zusatzstoffe, Träger und/oder Hilfsstoffe und gegebenenfalls ein für die gewünschte Applikationsform geeignetes pharmazeutisch oder kosmetisch annehmbares Lösemittel miteinander innig unter Bereitstellung der anwendungs¬ fertigen Zubereitung vermischt.In a further aspect, the invention relates to a method for producing such a pharmaceutical or cosmetic preparation, in which one or more enzyme (s) provided in a plurality of containers and optionally pharmaceutically or cosmetically acceptable additives, carriers and / or auxiliaries and if appropriate, a pharmaceutically or cosmetically acceptable solvent suitable for the desired application form is intimately mixed with one another to provide the ready-to-use preparation.
Die Erfindung betrifft in einem weiteren Aspekt auch die Verwendung einer derartigen pharmazeutischen Zubereitung zur Behandlung von und/oder zur Vorbeugung gegen Acne vulgaris.In a further aspect, the invention also relates to the use of such a pharmaceutical preparation for the treatment of and / or for the prevention of acne vulgaris.
Die Erfindung betriff in einem weiteren Aspekt auch die Verwendung einer kosmetischen Zubereitung zur Pflege und Reinigung der Haut und/oder dekorativen Auftragung auf die Haut.In a further aspect, the invention also relates to the use of a cosmetic preparation for the care and cleaning of the skin and / or decorative application to the skin.
Die erfindungsgemäße pharmazeutische oder kosmetische Zubereitung umfaßt ein oder mehrere im pH-Wert-Bereich zwischen 4,0 und 8,5 wirkende(s) Enzym(e) aus der Gruppe Proteinasen, Lysozyme, Elastasen, α-Lipasen und α-Amylase sowie gegebenenfalls pharmazeutisch oder kosmetisch annehmbare Träger und Hilfsstoffe. Der angegebene pH- Wert-Bereich für das Wirkungsspektrum des/der erfindungsgemäß in der pharmazeutischen oder kosmetischen Zubereitung verwendete(n) Enzym(e) umfaßt den natürlichen und den bei Vorhandensein von Acne vulgaris gegebenenfalls veränderten pH-Wert-Bereich der beteiligten Hautpartien. In einer bevorzugten Ausführungsform der erfindungsgemäßen pharmazeutischen oder kosmetischen Zubereitung ist das Enzym bzw. sind die Enzyme, die der Enzym-Unterklasse "Proteinasen" zugehörig sind, gewählt unter Trypsin, Chymotrypsin, Bromelain, Papain und Ficin. Besonders bevorzugt sind die Proteinasen Bromelain und Papain.The pharmaceutical or cosmetic preparation according to the invention comprises one or more enzyme (s) from the group proteinases, lysozymes, elastases, α-lipases and α-amylase, which acts in the pH range between 4.0 and 8.5, and optionally pharmaceutically or cosmetically acceptable carriers and adjuvants. The specified pH value range for the spectrum of action of the enzyme (s) used according to the invention in the pharmaceutical or cosmetic preparation comprises the natural and the The presence of acne vulgaris may change the pH range of the skin areas involved. In a preferred embodiment of the pharmaceutical or cosmetic preparation according to the invention, the enzyme or the enzymes which belong to the enzyme subclass "proteinases" are selected from trypsin, chymotrypsin, bromelain, papain and ficin. The proteinases bromelain and papain are particularly preferred.
Das Enzym bzw. die Enzyme aus der Klasse der Proteinasen kann bzw. können allein verwendet werden, um gegen Acne vulgaris wirksame pharmazeutische oder kosmetische Zubereitungen gemäß der Erfindung bereitzustellen. Es ist jedoch auch möglich, mehrere Proteinasen der genannten Gruppe miteinander oder auch zusammen mit anderen Enzymen zu verwenden.The enzyme or the enzymes from the class of the proteinases can be used alone to provide pharmaceutical or cosmetic preparations according to the invention which are active against acne vulgaris. However, it is also possible to use several proteinases from the group mentioned together or together with other enzymes.
In einer weiteren, ebenfalls bevorzugten Ausführungsform umfaßt die pharmazeutische oder kosmetische Zubereitung gemäß der Erfindung als Lysozyme, also die Zellwände von Mikroorganismen auflösende Enzyme, Muramidase, die im engeren Sinne unter dem Namen "Lysozym" bekannt ist (EC 3.2.1.17). Auch diese kann allein oder zusammen mit anderen Enzymen verwendet werden. Bevorzugt ist eine Verwendung zusammen mit Proteinasen, wie beispielsweise mit Trypsin, Chymotrypsin, Bromelain, Papain und Ficin. Besonders bevorzugt ist eine pharmazeutische oder kosmetische Zubereitung, die eine Enzymkom¬ bination aus Bromelain, Papain und Lysozym umfaßt.In a further, likewise preferred embodiment, the pharmaceutical or cosmetic preparation according to the invention comprises, as lysozymes, that is to say the enzymes which dissolve the cell walls of microorganisms, muramidase, which is known in the narrower sense under the name "lysozyme" (EC 3.2.1.17). This can also be used alone or together with other enzymes. Use together with proteinases, such as for example with trypsin, chymotrypsin, bromelain, papain and ficin, is preferred. A pharmaceutical or cosmetic preparation which comprises an enzyme combination of bromelain, papain and lysozyme is particularly preferred.
In einer weiteren, ebenfalls bevorzugten Ausführungsform umfaßt die pharmazeutische oder kosmetische Zubereitung als enzymatisch wirksamen Bestandteil Pankreatin. Pankreatin enthält üblicherweise ein Gemisch aus sämtlichen Verdauungsenzymen des Pankreas, vornehmlich Proteinasen wie Trypsin und Chymotrypsin, Elastasen, Lipasen, α-Amylase und gegebenenfalls auch Ribonuclease. Pankreatin kann in der pharmazeutischen oder kosmetischen Zubereitung gemäß der Erfindung entweder allein oder zusammen mit anderen Enzymen verwendet werden. Besonders bevorzugt sind pharmazeutische oder kosmetische Zubereitungen, die neben Pankreatin auch eines oder mehrere der Enzyme Bromelain, Papain und Lysozym umfassen. In einer weiteren bevorzugten Ausführungsform umfaßt die pharmazeutische oder kosmetische Zubereitung gemäß der Erfindung zusätzlich zu den genannten Enzymen einen Komplexbildner. Komplexbildner sind von Vorteil, da sie Metallionen, insbesondere Calciumionen, in Form von sogenannten Chelaten komplexieren, die damit für den . bakteriellen Stoffwechsel nicht mehr zur Verfügung stehen. Grundsätzlich sind alle pharmazeutisch annehmbaren Komplexbildner für die erfindungsgemäßen Zwecke geeignet. Besonders bevorzugt sind pharmazeutische oder kosmetische Zubereitungen, in denen als Komplexbildner Ethylendiamintetraessigsäure (EDTA) und ihre komplexbildend wirksamen Salze, Citronensäure und ihre komplexbildend wirksamen Salze, Ascorbinsäure und ihre komplexbildend wirksamen Salze, Nitrilotriessigsäure (NTA) und ihre komplexbildend wirksamen Salze und möglicherweise Kombinationen mehrerer derartiger Verbindungen enthalten sind. Als Salze sind vornehmlich in der natürlichen Anwendungsumgebung lösliche Salze, insbesondere Alkalimetallsalze, ganz besonders bevorzugt Natriumsalze, zu nennen.In a further, likewise preferred embodiment, the pharmaceutical or cosmetic preparation comprises pancreatin as an enzymatically active component. Pancreatin usually contains a mixture of all digestive enzymes in the pancreas, primarily proteinases such as trypsin and chymotrypsin, elastases, lipases, α-amylase and possibly also ribonuclease. Pancreatin can be used in the pharmaceutical or cosmetic preparation according to the invention either alone or together with other enzymes. Pharmaceutical or cosmetic preparations are particularly preferred which, in addition to pancreatin, also comprise one or more of the enzymes bromelain, papain and lysozyme. In a further preferred embodiment, the pharmaceutical or cosmetic preparation according to the invention comprises a complexing agent in addition to the enzymes mentioned. Complexing agents are advantageous because they complex metal ions, especially calcium ions, in the form of so-called chelates, which are therefore suitable for the. bacterial metabolism are no longer available. In principle, all pharmaceutically acceptable complexing agents are suitable for the purposes according to the invention. Particularly preferred are pharmaceutical or cosmetic preparations in which as a complexing agent ethylenediaminetetraacetic acid (EDTA) and its complexing salts, citric acid and its complexing salts, ascorbic acid and its complexing salts, nitrilotriacetic acid (NTA) and their complexing salts and possibly combinations of several such Connections are included. Salts which can be mentioned are primarily salts which are soluble in the natural environment of use, in particular alkali metal salts, very particularly preferably sodium salts.
In einer weiteren bevorzugten Ausführungsform können die pharmazeutischen oder kosmetischen Zubereitungen gemäß der Erfindung zusätzlich auch einen oder mehrere pharmazeutisch oder kosmetisch annehmbare Zusatzstoffe umfassen. Diese dienen besonderen Anwendungszwecken, Zwecken der Bereitstellung bestimmter Formulierungen oder auch ästhetischen Zwecken.In a further preferred embodiment, the pharmaceutical or cosmetic preparations according to the invention can additionally comprise one or more pharmaceutically or cosmetically acceptable additives. These serve special purposes, the provision of certain formulations or aesthetic purposes.
Pharmazeutisch oder kosmetisch annehmbare Zusatzstoffe können beispielsweise Puffer zur Einstellung bzw. Abpufferung eines bestimmten pH-Wertes der pharmazeutischen oder kosmetischen Zubereitung sein. Als solche sind beispielsweise sogenannter "Tris-Puffer" (Tris(hydroxymethyl-)aminomethan) zu nennen. Es sind jedoch genauso gut andere pharmazeutisch oder kosmetisch annehmbare Puffersubstanzen verwendbar.Pharmaceutically or cosmetically acceptable additives can be, for example, buffers for setting or buffering a specific pH of the pharmaceutical or cosmetic preparation. So-called "Tris buffers" (tris (hydroxymethyl) aminomethane) may be mentioned as such. However, other pharmaceutically or cosmetically acceptable buffer substances can also be used.
Für bestimmte Anwendungszwecke können auch Emulgatoren, Stabilisatoren und Konservierungsmittel zugegen sein. Derartige Substanzen sind als solche aus dem Stand der Technik bekannt. Selbstverständlich können nur solche Zusatzstoffe verwendet werden, die mit den anderen Komponenten der erfindungsgemäßen pharmazeutischen oder kosmetischen Zubereitung sowie mit der Haut verträglich sind. Darüber hinaus kann in einer weiteren bevorzugten Ausführungsform die pharmazeutische oder kosmetische Zubereitung auch auf die Verabreichungsform abgestimmte Träger und Hilfsstoffe umfassen. Dies können beispielsweise Duft- und Aromastoffe sein, die den anwendungsfertigen pharmazeutischen oder kosmetischen Zubereitungen einen für den Anwender angenehmen Duft verleihen. Selbstverständlich können auch auf die gewünschte Verwendungs- bzw. Verabreichungsform abgestimmte Gelbildner, Salben, Grundlagen, Puderträger, Spray- bzw. Aerosol-Träger oder flüssige Löse- bzw. Trägermittel für Lösungen und Lotionen zugegen sein. Genauso ist es möglich, daß kosmetische Zubereitun¬ gen für kosmetische Zwecke geeignete Hilfsstoffe umfassen, beispielsweise Feuchtespender, die hautpflegende oder reinigende Substanzen oder für dekorative kosmetische Zwecke bestimmte oder geeignete Hilfsstoffe; z.B. Farbpigmente. Für alle genannten Substanzen gilt, daß sie nicht nur mit den anderen Komponenten - auch auf lange Sicht - verträglich sein müssen, sondern auch auf die gewünschte Anwendungsform abgestimmt sein müssen, insbesondere hautverträglich sein müssen. Darüber hinaus kann eine pharmazeutische oder kosmetische Zubereitung gemäß der vorliegenden Erfindung in einer weiteren bevorzugten Ausführungsform auch allgemein für derartige Zubereitungen übliche weitere Stoffe enthalten, wie sie der mit der Compoundierung, anwendungsfertigen Herrichtung und Anwendung vertraute Fachmann aus dem Stand der Technik kennt. Auch für diese Zusatzstoffe gilt, daß sie mit den anderen Komponenten, insbesondere mit den im pH- Bereich zwischen 4,0 und 8,5 wirkenden Enzymen, verträglich sein müssen und darüber hinaus keine Unverträglichkeit mit dem Anwendungsgebiet der pharmazeutischen oder kosmetischen Zubereitung aufweisen dürfen, also insbesondere keine Unverträglichkeit mit der menschlichen Haut.For certain applications, emulsifiers, stabilizers and preservatives can also be present. Such substances are known as such from the prior art. Of course, only those additives can be used which are compatible with the other components of the pharmaceutical or cosmetic preparation according to the invention and with the skin. In addition, in a further preferred embodiment, the pharmaceutical or cosmetic preparation can also comprise carriers and auxiliaries which are matched to the administration form. These can be, for example, fragrance and aroma substances which give the ready-to-use pharmaceutical or cosmetic preparations a fragrance which is pleasant for the user. Of course, gelling agents, ointments, bases, powder carriers, spray or aerosol carriers or liquid solvents or carrier agents for solutions and lotions can also be present, tailored to the desired form of use or administration. It is also possible for cosmetic preparations to comprise auxiliaries suitable for cosmetic purposes, for example moisturizers, skin-care or cleansing substances or auxiliaries which are suitable or suitable for decorative cosmetic purposes; eg color pigments. It applies to all the substances mentioned that they not only have to be compatible with the other components - also in the long term - but also have to be tailored to the desired form of use, in particular must be compatible with the skin. In addition, in a further preferred embodiment, a pharmaceutical or cosmetic preparation according to the present invention can also generally contain further substances which are customary for such preparations, as are known to the skilled worker familiar with the compounding, ready-to-use preparation and use from the prior art. It also applies to these additives that they must be compatible with the other components, in particular with the enzymes acting in the pH range between 4.0 and 8.5, and furthermore must not be incompatible with the field of application of the pharmaceutical or cosmetic preparation, in particular, no incompatibility with human skin.
Erfindungsgemäße pharmazeutische oder kosmetische Zubereitungen enthalten in einer weiteren bevorzugten Ausführungsform eine Menge eines oder mehrerer Enzyme im Bereich von 0,1 bis 33,3 Gew.-%, eine Menge eines oder mehrerer Komplexbildner - sofern vorhanden - im Bereich von 0 bis 4 Gew.-% und zum Rest pharmazeutisch oder kosmetisch annehmbare Zusatzstoffe, Träger und/oder Hilfsstoffe, insbesondere solche Zusatzstoffe, Träger und/oder Hilfsstoffe, wie sie oben im einzelnen angegeben wurden. Kosmetische Zubereitungen enthalten regelmäßig geringere Mengen der genannten Enzyme und Komplexbildner als pharmazeutische Zubereitungen. Pharmazeutische oder kosmetische Zubereitungen gemäß der Erfindung werden mit den oben angegebenen Komponenten vorzugsweise in Form einer Creme, einer Emulsion, einer Salbe, eines Gels, einer Lösung, einer Lotion, eines Puders, eines Sprays oder eines Aerosols bereitgestellt. Alle genannten Zubereitungsformen stellen äußerlich anwendbare Zuberei¬ tungsformen dar. Dies hat den Vorteil, daß sie gezielt auf die Stelle aufgebracht werden können, die von Acne vulgaris befallen ist. Besonders für kosmetische Zubereitungen gemäß der Erfindung sind Cremes, Emulsionen, Salben, Gele, Lösungen, Lotionen und Puder bevorzugte Zubereitungsformen.In a further preferred embodiment, pharmaceutical or cosmetic preparations according to the invention contain an amount of one or more enzymes in the range from 0.1 to 33.3% by weight, an amount of one or more complexing agents - if present - in the range from 0 to 4% by weight. % and for the remainder pharmaceutically or cosmetically acceptable additives, carriers and / or auxiliaries, in particular such additives, carriers and / or auxiliaries as have been specified above in detail. Cosmetic preparations regularly contain smaller amounts of the enzymes and complexing agents mentioned than pharmaceutical preparations. Pharmaceutical or cosmetic preparations according to the invention are preferably provided with the components specified above in the form of a cream, an emulsion, an ointment, a gel, a solution, a lotion, a powder, a spray or an aerosol. All of the above-mentioned forms of preparation represent externally applicable forms of preparation. This has the advantage that they can be applied specifically to the area affected by acne vulgaris. Particularly for cosmetic preparations according to the invention, creams, emulsions, ointments, gels, solutions, lotions and powders are preferred preparation forms.
Ohne an eine konkrete Theorie gebunden zu sein, geht man davon aus, daß die erfindungs¬ gemäß in den pharmazeutischen Zubereitungen vorhandenen Wirkstoffe gezielt die Acne vulgaris auslösenden Faktoren gemäß Weg (2) und (3) in Figur 2 angreifen. So lockern Papain und Bromelain die dicke, überflüssige Hornhaut auf und lösen sie (Keratolyse). Sie schwächen darüber hinaus die Wirkung der Talg lösenden Enzymgruppen der Esterasen und Lipasen ab und wirken ly tisch auf die Proteine von Pilzen und Bakterien, bis deren Zeil wand angedaut oder zerstört ist (bakterizide bzw. bakteriostatische Wirkung). Die angedauten Proteinbruchstücke wirken darüber hinaus - wie überraschend gefunden wurde - emulgierend und unterstützen damit die Reinigungs- und Heilwirkung der erfindungsgemäßen Zubereitungen.Without being bound to a specific theory, it is assumed that the active substances present in the pharmaceutical preparations according to the invention specifically attack the factors triggering acne vulgaris according to path (2) and (3) in FIG. 2. This is how papain and bromelain loosen and dissolve the thick, superfluous cornea (keratolysis). They also weaken the action of the sebum-releasing enzyme groups of the esterases and lipases and act ly on the proteins of fungi and bacteria until their cell wall is digested or destroyed (bactericidal or bacteriostatic effect). The digested protein fragments also have - as was surprisingly found - emulsifying and thus support the cleaning and healing effects of the preparations according to the invention.
Lysozym ist eine beim Menschen physiologisch vorkommende Muramidase, die bakterio- statisch und bakterizid wirkt. Lysozym findet sich in der Tränenflüssigkeit, der Nasen- und Darmschleimhaut sowie in Bakteriophagen und polymorphkernigen Leucozyten. Pharmakolo- gisch wird Lysozym auch in Halstabletten oder Augentropfen bzw. -salben verwendet. Es zerstört das Zellwand-Material (Murein) der auf der Haut sowie in den Ausführungsgängen der Talg- und Schweißdrüsen angesiedelten Bakterien.Lysozyme is a muramidase that is physiologically occurring in humans and has a bacteriostatic and bactericidal effect. Lysozyme is found in the lacrimal fluid, the nasal and intestinal mucosa as well as in bacteriophages and polymorphonuclear leucocytes. Lysozyme is also used pharmacologically in throat tablets or eye drops or ointments. It destroys the cell wall material (murein) of the bacteria located on the skin and in the execution ducts of the sebum and sweat glands.
Die Komplexbildner wie beispielsweise EDTA wirken auch als pH-Puffer. Zusätzlich aktivieren und verstärken sie die Wirkung der Enzyme und verhindern das Wachstum von Pilzen und Bakterien bzw. verstärken deren Lyse, weil sie die für das Wachstum der Bakterien benötigten Calciumionen, Natriumionen und Aluminiumionen in Form von Komplexen binden. Es versteht sich, daß die pharmazeutischen oder kosmetischen Zubereitungen gemäß der Erfindung dann, wenn sie nicht in fester Form (beispielsweise als Puder) vorliegen, auf im wesentlichen wässriger Basis formuliert sind. Folglich sind bei Zubereitungsformen wie Cremes, Emulsionen, Salben, Gelen, Lösungen, Lotionen, Sprays oder Aerosolen wäßrige Zubereitungen bevorzugt. Selbstverständlich ist es auch möglich, andere, mit den Enzymen verträgliche Lösungsmittel zu verwenden, sofern sie hautverträglich sind. Als Beispiele sind Mischung von Wasser mit physiologisch annehmbaren Alkoholen oder auch Alkohole allein zu nennen.The complexing agents such as EDTA also act as pH buffers. In addition, they activate and strengthen the action of the enzymes and prevent the growth of fungi and bacteria or increase their lysis because they bind the calcium ions, sodium ions and aluminum ions required for the growth of the bacteria in the form of complexes. It goes without saying that the pharmaceutical or cosmetic preparations according to the invention, if they are not in solid form (for example as a powder), are formulated on an essentially aqueous basis. Consequently, aqueous preparations are preferred for preparation forms such as creams, emulsions, ointments, gels, solutions, lotions, sprays or aerosols. Of course, it is also possible to use other solvents which are compatible with the enzymes, provided that they are compatible with the skin. Examples include mixtures of water with physiologically acceptable alcohols or alcohols alone.
Erfindungsgemäß werden die pharmazeutischen oder kosmetischen Zubereitungen dadurch hergestellt, daß man das Enzym bzw. die Enzyme und gegebenenfalls pharmazeutisch oder kosmetisch annehmbare Zusatzstoffe, Träger und/oder Hilfsstoffe und gegebenenfalls ein für die gewünschte Applikationsform geeignetes pharmazeutisch annehmbares Lösemittel innig miteinander mischt. Dabei wird regelmäßig eine für die Anwendung fertige Zubereitung bereitgestellt.According to the invention, the pharmaceutical or cosmetic preparations are produced by intimately mixing the enzyme or enzymes and, if appropriate, pharmaceutically or cosmetically acceptable additives, carriers and / or auxiliaries and, if appropriate, a pharmaceutically acceptable solvent suitable for the desired form of application. A preparation ready for use is regularly provided.
In einer bevorzugten Ausführungsform kann das erfindungsgemäße Verfahren darin bestehen, daß man die für die jeweilige pharmazeutische Zubereitung gewünschten Komponenten im industriellen Maßstab miteinander vermischt und die anwendungsfertige Mischung in für die Verabreichung bzw. Entnahme zur Verabreichung durch den Anwender geeignete Abgabebehältnisse einfüllt. Dies können beispielsweise Flaschen, Tuben, Sprühdosen, Stäuber usw. sein. Die im Einzelfall verwendeten Abgabebehältnisse richten sich selbstverständlich nach der Verabreichungsform.In a preferred embodiment, the process according to the invention can consist in mixing the components desired for the respective pharmaceutical preparation with one another on an industrial scale and in filling the ready-to-use mixture into dispensing containers suitable for administration or removal for administration by the user. This can be, for example, bottles, tubes, aerosols, sprays, etc. The dispensing containers used in individual cases are of course based on the form of administration.
Alternativ dazu entspricht es einer weiteren bevorzugten Ausführungsform der Erfindung, daß man die Komponenten in eine Mehrzahl von für die Entnahme zur Verabreichung geeignete Behältnisse einfüllt und die getrennt bereitgestellten Komponenten - als Anwender - unmittelbar vor der Verabreichung, beispielsweise unmittelbar vor der topischen Applikation, unter Bereitstellung der anwendungsfertigen Zubereitung vermischt. Die letztgenannte, bevorzugte Ausführungsform kann beispielsweise darin bestehen, daß in geeigneten Behältnissen, beispielsweise in Beuteln, in getrennten Kompartimenten in einer Kammer das Enzym bzw. die Kombination von Enzymen zusammen mit geeigneten Zusatzstoffen bereitgestellt wird, beispielsweise mit einem oder mehreren Komplexbildnern, einem oder mehreren Aroma- oder Duftstoffen und/oder einem oder mehreren Emulgatoren, während in dem anderen Kompartiment Reinst- Wasser bereitgestellt wird. Der Anwender vermischt die Inhalte beider Kompartimente ("Doppelkammerbeutel") miteinander und appliziert die so zubereitete pharmazeutische oder kosmetische Zubereitung auf die befallenen Hautstellen.As an alternative to this, it is a further preferred embodiment of the invention that the components are filled into a plurality of containers suitable for removal for administration and the separately provided components - as users - are provided immediately before administration, for example immediately before topical application of the ready-to-use preparation. The last-mentioned, preferred embodiment can consist, for example, of providing the enzyme or the combination of enzymes together with suitable additives, for example with one or more complexing agents, one or more, in suitable containers, for example in bags, in separate compartments in a chamber Aroma or fragrance and / or one or more emulsifiers, while in the other compartment ultrapure water is provided. The user mixes the contents of both compartments ("double-chamber bags") and applies the pharmaceutical or cosmetic preparation prepared in this way to the affected skin areas.
In gleicher Weise ist es möglich, daß man pharmazeutische Zubereitungen unterschiedlicher Zusammensetzung bereitstellt, um den unterschiedlichen pharmakologischen Erfordernissen zu Beginn der Behandlung und nach ersten Behandlungserfölgen Rechnung zu tragen. So kann es beispielsweise von Vorteil sein, anfangs eine mehrere Enzyme in Kombination miteinander enthaltende pharmazeutische Zubereitung, gegebenenfalls mit sonstigen, oben genannten Zusatzstoffen, Trägern und/oder Hilfsstoffen, bereitzustellen, während man für die Fortsetzung der Behandlung pharmazeutische Zubereitungen gemäß der Erfindung bereit¬ stellt, die nur noch ein Enzym oder gegebenenfalls auch eine andere Kombination von Enzymen enthalten als die für die Erstbehandlung vorgesehene phamazeutische Zubereitung. In vorteilhafter Weise kann hierdurch konkreten Behandlungserfordernissen in Abhängigkeit von dem individuellen Krankheitsbild Rechnung getragen werden.In the same way, it is possible to provide pharmaceutical preparations of different compositions in order to take into account the different pharmacological requirements at the beginning of the treatment and after the first treatment results. For example, it may be advantageous to initially provide a pharmaceutical preparation containing several enzymes in combination with one another, optionally with other additives, carriers and / or auxiliaries mentioned above, while pharmaceutical preparations according to the invention are provided for the continuation of the treatment which contain only one enzyme or possibly a different combination of enzymes than the pharmaceutical preparation intended for the initial treatment. In this way, specific treatment requirements can advantageously be taken into account depending on the individual clinical picture.
Kosmetische Zubereitungen können darüber hinaus in einer bevorzugten Auführungsform in unterschiedlichen Zusammensetzungen bereitgestellt werden, die beispielsweise unterschiedlichen Hautgegebenheiten (z. B. trockene oder fette Haut), unterschiedlichen Hauttypen (z. B. robuste oder empfindliche Haut) oder unterschiedlichen Anwendungs¬ zwecken (z. B. Feuchtigkeitscreme, Nährcreme, Nachtcreme, Tagescreme) Rechnung tragen. Selbstverständlich müssen die Komponenten derartiger Zubereitungen - auch langfristig - mit den Enzymen und gegebenenfalls Komplexbildnern, sowie den anderen Komponenten, aber auch mit der menschlichen Haut verträglich sein. Die erfindungsgemäßen Zubereitungen werden - gegebenenfalls auch in unterschiedlicher Zusammensetzung - entweder zur Behandlung von akuter Acne vulgaris und Hautunrein¬ heiten sowie Hyperkeratosen verwendet oder können auch herangezogen werden, um gegen Acne vulgaris und Hautunreinheiten sowie Hyperkeratosen vorzubeugen bzw. die Haut entsprechend zu konditionieren.Cosmetic preparations can moreover be provided in a preferred embodiment in different compositions, for example different skin conditions (e.g. dry or oily skin), different skin types (e.g. robust or sensitive skin) or different purposes (e.g. As moisturizer, nutrient cream, night cream, day cream) take into account. Of course, the components of such preparations - also in the long term - must be compatible with the enzymes and possibly complexing agents, as well as the other components, but also with the human skin. The preparations according to the invention are used - optionally also in different compositions - either for the treatment of acute acne vulgaris and skin impurities and hyperkeratoses or can also be used to prevent acne vulgaris and skin impurities and hyperkeratoses or to condition the skin accordingly.
In gleicher Weise sind die erfindungsgemäßen Zubereitungen auch für andere Zwecke verwendbar, beispielsweise für eine bakteriostatische bzw. bakterizide Behandlung der Hautoberfläche, wenn diese aus bestimmten Gründen indiziert sein sollte.In the same way, the preparations according to the invention can also be used for other purposes, for example for a bacteriostatic or bactericidal treatment of the skin surface, if this should be indicated for certain reasons.
Kosmetische Zubereitungen gemäß der Erfindung können zur Pflege der Haut, zur Reinigung der Haut oder zum Feuchthalten der Haut verwendet werden. Ein weiterer Verwendungsbereich der erfindungsgemäßen kosmetischen Zubereitungen liegt im Bereich der sogenannten dekorativen Kosmetik: Erfindungsgemäße Zubereitungen können auch zur dekorativen Auftragung auf die Haut, beispielsweise als Puder oder Rouge, verwendet werden.Cosmetic preparations according to the invention can be used to care for the skin, to clean the skin or to keep the skin moist. Another area of use of the cosmetic preparations according to the invention is in the field of so-called decorative cosmetics: preparations according to the invention can also be used for decorative application to the skin, for example as a powder or blush.
Die Erfindung wird nachfolgend unter Bezugnahme auf die Beispiele näher erläutert.The invention is explained in more detail below with reference to the examples.
Beispiel 1example 1
Die bakterizide bzw. bakteriostatische Wirkung von pharmazeutischen Zubereitungen gemäß der Erfindung wurde wie folgt untersucht: Im Handel erhältliche Nährböden (Agar, Blutagar) wurden in üblichen Schalen bereitgestellt. Die gesamte Nährbodenoberfläche wurde mit Bakterien der folgenden Stämme bestrichen:The bactericidal or bacteriostatic activity of pharmaceutical preparations according to the invention was investigated as follows: Commercially available culture media (agar, blood agar) were provided in conventional dishes. The entire surface of the culture medium was coated with bacteria from the following strains:
Staphylococcus areus, Staphylococcus epidermidis, Escherichia coli, Bacillus subtilis, und Klebsiella. In die Nährböden wurden jeweils zwei Löcher gestanzt. In eines der Löcher wurde eine pharmazeutische Zubereitung aus 1 mg Lysozym und 1 Tropfen Aqua destillata gefüllt. In das zweite Loch wurde eine pharmazeutische Zubereitung aus 1 mg Lysozym, 1 mg EDTA und 1 Tropfen Aqua destillata gefüllt.Staphylococcus areus, Staphylococcus epidermidis, Escherichia coli, Bacillus subtilis, and Klebsiella. Two holes were punched in each of the culture media. A pharmaceutical preparation consisting of 1 mg lysozyme and 1 drop aqua destillata was filled into one of the holes. In the second hole, a pharmaceutical preparation consisting of 1 mg lysozyme, 1 mg EDTA and 1 drop of aqua destillata was filled.
Die Nährböden wurden 24 Stunden bei 37 °C inkubiert.The culture media were incubated at 37 ° C for 24 hours.
Es zeigte sich in allen Fällen, daß sich um das ausgestanzte Loch, in das die aus Lysozym, EDTA und Wasser bestehende Zubereitung gefüllt worden war, ein deutlich größerer bakte¬ rienfreier Hof gebildet hatte als um das Loch, in das nur eine Zubereitung aus Lysozym und Wasser gefüllt worden war.It was shown in all cases that a significantly larger bacteria-free courtyard had formed around the punched-out hole, into which the preparation consisting of lysozyme, EDTA and water had been filled, than around the hole, into which only a preparation made from lysozyme and water had been filled.
Vergleichsbeispiel 1Comparative Example 1
Ein Beispiel 1 entsprechender Versuchsaufbau, jedoch mit nur einem Loch, in das destilliertes Wasser gefüllt worden war, wurde bereitgestellt. Um das ausgestanzte Loch zeigte sich kein von Bakterien freier Hof im Agar.An experimental setup corresponding to Example 1, but with only one hole into which distilled water had been filled, was provided. There was no bacteria-free yard in the agar around the punched hole.
Beispiel 2Example 2
Der Versuchsaufbau entsprach im wesentlichen dem Versuchsaufbau gemäß Beispiel 1. Es wurden jedoch nur Agar-Nährböden verwendet. Der eingesetzte Bakterienstamm war Staphylococcus epidermidis.The experimental setup essentially corresponded to the experimental setup according to Example 1. However, only agar culture media were used. The bacterial strain used was Staphylococcus epidermidis.
Die verwendeten Mengen der getesteten Enzyme waren in allen Fällen 1 mg.The amounts of the enzymes tested were 1 mg in all cases.
In die ausgestanzten Löcher wurden folgende pharmazeutischen Zubereitungen gemäß der Erfindung eingefüllt: (a) Lysozym + Aqua dest. und Lysozym + EDTA + Aqua dest.The following pharmaceutical preparations according to the invention were filled into the punched holes: (a) Lysozyme + aqua dest. and lysozyme + EDTA + aqua dest.
Die jeweils gebildeten Höfe standen in einem Flächenverhältnis von 1 : 2.The courtyards formed were in an area ratio of 1: 2.
(b) Papain + EDTA + Aqua dest. und Papain + Lysozym + EDTA + Aqua dest.(b) Papain + EDTA + Aqua dest. and papain + lysozyme + EDTA + aqua dest.
Die gebildeten bakterienfreien Höfe standen in einem Flächenverhältnis von 1 : 3.The bacteria-free courtyards formed were in an area ratio of 1: 3.
(c) Bromelain + EDTA + Aqua dest. und Bromelain + Lysozym + EDTA + Aqua dest.(c) Bromelain + EDTA + aqua dest. and bromelain + lysozyme + EDTA + aqua dest.
Die gebildeten bakterienfreien Höfe standen in einem Flächenverhältnis von 1 : 3.The bacteria-free courtyards formed were in an area ratio of 1: 3.
(d) Papain + Bromelain + EDTA + Aqua dest. und Papain + Bromelain + Lysozym + EDTA + Aqua dest.(d) papain + bromelain + EDTA + aqua dest. and papain + bromelain + lysozyme + EDTA + aqua dest.
Die gebildeten bakterienfreien Höfe standen in einem Flächenverhältnis von 2 : 3.The bacteria-free courtyards formed had an area ratio of 2: 3.
Vergleichsbeispiel 2Comparative Example 2
Es wurde eine Schale mit 2 Löchern gemäß dem Versuchsaufbau der Beispiele 1 und 2 verwendet. In eines der Löcher wurde nur Aqua dest. gefüllt. In das andere Loch wurde eine wäßrige EDTA-Lösung gefüllt. Um das erstgenannte Loch hatte sich nach der Inkubation kein bakterienfreier Hof gebildet. Um das zweitgenannte Loch hatte sich ein extrem schmaler, von dem ersten Loch kaum unterscheidbarer bakterienfreier Hof gebildet. A 2-hole bowl according to the experimental setup of Examples 1 and 2 was used. Only aqua dest. filled. An aqueous EDTA solution was filled in the other hole. After the incubation, no bacteria-free yard had formed around the first-mentioned hole. An extremely narrow, bacteria-free courtyard, hardly distinguishable from the first hole, had formed around the second hole.

Claims

P a t e n t a n s p r ü c h e Patent claims
1. Pharmazeutische oder kosmetische Zubereitung, die ein oder mehrere im pH- Wert- Bereich zwischen 4,0 und 8,5 wirkende(s) Enzym(e) aus der Gruppe Proteinasen, Lysozyme, Elastasen, α-Lipasen und α-Amylase sowie gegebenenfalls pharmazeutisch oder kosmetisch annehmbare Träger und Hilfsstoffe umfaßt.1. Pharmaceutical or cosmetic preparation which comprises one or more enzyme (s) from the group proteinases, lysozymes, elastases, α-lipases and α-amylase, which act in the pH range between 4.0 and 8.5 optionally includes pharmaceutically or cosmetically acceptable carriers and adjuvants.
2. Zubereitung nach Anspruch 1, worin das Enzym/die Enzyme aus der Gruppe der Proteinasen gewählt ist/sind unter Trypsin Chymotrypsin, Bromelain, Papain und Ficin.2. Preparation according to claim 1, wherein the enzyme (s) from the group of proteinases is / are selected from trypsin, chymotrypsin, bromelain, papain and ficin.
3. Zubereitung nach Anspruch 2, worin das Enzym/die Enzyme aus der Gruppe der Proteinasen gewählt ist/sind unter Bromelain und Papain.3. Preparation according to claim 2, wherein the enzyme (s) from the group of proteinases is / are selected from bromelain and papain.
4. Zubereitung nach einem der Ansprüche 1 bis 3, worin Lysozyme die Zellwände von Mikroorganismen auflösende Enzyme, bevorzugt Muramidase ("Lysozym"), umfassen.4. Preparation according to one of claims 1 to 3, wherein lysozymes comprise the cell walls of microorganism-dissolving enzymes, preferably muramidase ("lysozyme").
5. Zubereitung nach einem der Ansprüche 1 bis 4, die Pankreatin als enzymatisch wirksamen Bestandteil umfaßt.5. Preparation according to one of claims 1 to 4, which comprises pancreatin as an enzymatically active ingredient.
6. Zubereitung nach einem oder mehreren der Ansprüche 1 bis 5, die zusätzlich einen Komplexbildner umfaßt. 6. Preparation according to one or more of claims 1 to 5, which additionally comprises a complexing agent.
7. Zubereitung nach Anspruch 6, worin der Komplexbildner gewählt ist unter Ethylendi- amintetraessigsäure (EDTA) und ihren komplexbildend wirksamen Salzen, Citronensäure und ihren komplexbildend wirksamen Salzen, Ascorbinsäure und ihren komplexbildend wirksamen Salzen, Nitrilotriessigsäure (NTA) und ihren komplexbildend wirksamen Salzen <und Kombinationen mehrerer derartiger Verbindungen.7. Preparation according to claim 6, wherein the complexing agent is chosen from ethylenediaminetetraacetic acid (EDTA) and its complexing salts, citric acid and its complexing salts, ascorbic acid and its complexing salts, nitrilotriacetic acid (NTA) and its complexing salts <and Combinations of several such connections.
8. Zubereitung nach einem oder mehreren der Ansprüche 1 bis 7, die zusätzlich einen oder mehrere pharmazeutisch oder kosmetisch annehmbare Zusatzstoffe aus der Gruppe pH- Puffer, Emulgatoren, Stabilisatoren, Konservierungsmittel und auf die Verabreichungs- oder Anwendungsform abgestimmte Träger und Hilfsstoffe umfassen.8. Preparation according to one or more of claims 1 to 7, which additionally comprise one or more pharmaceutically or cosmetically acceptable additives from the group pH buffers, emulsifiers, stabilizers, preservatives and carriers and auxiliaries which are matched to the administration or use form.
9. Zubereitung nach einem oder mehreren der Ansprüche 1 bis 8, die9. Preparation according to one or more of claims 1 to 8, the
0,1 bis 33,3 Gew.-% eines oder mehrerer Enzyme;0.1 to 33.3% by weight of one or more enzymes;
0 bis 4 Gew.-% eines oder mehrerer Komplexbildner;0 to 4% by weight of one or more complexing agents;
und zum Rest pharmazeutisch oder kosmetisch annehmbare Zusatzstoffe, Träger und/oder Hilfsstoffe umfaßt.and the remainder pharmaceutically or cosmetically acceptable additives, carriers and / or auxiliaries.
10. Zubereitung nach einem oder mehreren der Ansprüche 1 bis 9, die eine Enzymkom¬ bination aus Bromelain, Papain und Lysozym umfaßt.10. Preparation according to one or more of claims 1 to 9, which comprises an enzyme combination of bromelain, papain and lysozyme.
11. Zubereitung nach einem oder mehreren der Ansprüche 1 bis 10 in Form einer Creme, einer Emulsion, einer Salbe, eines Gels, einer Lösung, einer Lotion, eines Puders, eines Sprays oder eines Aerosols.11. Preparation according to one or more of claims 1 to 10 in the form of a cream, an emulsion, an ointment, a gel, a solution, a lotion, a powder, a spray or an aerosol.
12. Verfahren zur Herstellung einer pharmazeutischen oder kosmetischen Zubereitung nach einem oder mehreren der Ansprüche 1 bis 11, worin man gegebenenfalls in einer Mehrzahl von Behältnissen bereitgestellte(s) Enzym(e) und gegebenenfalls pharmazeutisch oder kosmetisch annehmbare Zusatzstoffe, Träger und/oder Hilfsstoffe und gegebenenfalls ein für die gewünschte Applikationsform geeignetes pharmazeutisch oder kosmetisch annehmbares Lösemittel miteinander innig unter Bereitstellung der anwendungsfertigen Zubereitung vermischt.12. A process for the preparation of a pharmaceutical or cosmetic preparation according to one or more of claims 1 to 11, wherein one or more enzyme (s) provided in a plurality of containers and optionally pharmaceutically or cosmetically acceptable additives, carriers and / or auxiliaries and optionally a pharmaceutically or cosmetically acceptable one suitable for the desired application form Solvents are intimately mixed together to provide the ready-to-use preparation.
13. Verfahren nach Anspruch 12, worin man die Komponenten in industriellem Maßstab vermischt und in für die Verabreichung bzw. Entnahme zur Verabreichung geeignete Abgabe-Behältnisse einfüllt.13. The method according to claim 12, wherein the components are mixed on an industrial scale and filled into dispensing containers suitable for administration or removal for administration.
14. Verfahren nach Anspruch 12, worin man die Komponenten in für die Entnahme zur Verabreichung geeignete Behältnisse einfüllt und die getrennt bereitgestellten Komponenten unmittelbar vor der Verabreichung unter Bereitstellung der anwendungsfertigen Zubereitung vermischt.14. The method according to claim 12, wherein the components are filled into containers suitable for removal for administration and the separately provided components are mixed immediately before administration to provide the ready-to-use preparation.
15. Verwendung einer Zubereitung nach einem oder mehreren der Ansprüche 1 bis 11 zur Behandlung von Acne vulgaris.15. Use of a preparation according to one or more of claims 1 to 11 for the treatment of acne vulgaris.
16. Verwendung einer Zubereitung nach einem oder mehreren der Ansprüche 1 bis 11 zur Vorbeugung gegen Acne vulgaris.16. Use of a preparation according to one or more of claims 1 to 11 for the prevention of acne vulgaris.
17. Verwendung einer Zubereitung nach einem oder mehreren der Ansprüche 1 bis 11 zur Pflege der Haut.17. Use of a preparation according to one or more of claims 1 to 11 for skin care.
18. Verwendung einer Zubereitung nach einem oder mehreren der Ansprüche 1 bis 11 zur Reinigung der Haut.18. Use of a preparation according to one or more of claims 1 to 11 for cleaning the skin.
19. Verwendung einer Zubereitung nach einem oder mehreren der Ansprüche 1 bis 11 zur dekorativen Auftragung auf die Haut. 19. Use of a preparation according to one or more of claims 1 to 11 for decorative application to the skin.
PCT/DE1994/000208 1993-02-23 1994-02-22 Enzyme-containing pharmaceutical or cosmetic composition, process for preparing the same and its use WO1994019005A1 (en)

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