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WO1994019005A1 - Preparation pharmaceutique ou cosmetique comportant des enzymes, son procede de fabrication et son utilisation - Google Patents

Preparation pharmaceutique ou cosmetique comportant des enzymes, son procede de fabrication et son utilisation 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
Prior art date
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Ceased
Application number
PCT/DE1994/000208
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German (de)
English (en)
Inventor
Albert Scheller
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Individual
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Individual
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Application filed by Individual filed Critical Individual
Priority to AU63730/94A priority Critical patent/AU6373094A/en
Publication of WO1994019005A1 publication Critical patent/WO1994019005A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66—Enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01017—Lysozyme (3.2.1.17)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/22—Cysteine endopeptidases (3.4.22)
    • C12Y304/22002—Papain (3.4.22.2)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/22—Cysteine endopeptidases (3.4.22)
    • C12Y304/22004—Bromelain (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.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Public Health (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Birds (AREA)
  • Dermatology (AREA)
  • Cosmetics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne des préparations pharmaceutiques ou cosmétiques comportant une ou plusieurs enzymes du groupe protéinases, lysozymes, élastases, alpha-lipases et alpha-amylase ainsi que, le cas échéant, des excipients et substances auxiliaires pharmaceutiquement ou cosmétiquement acceptables. L'invention concerne en outre un procédé pour la fabrication d'une telle préparation pharmaceutique ou cosmétique et son utilisation.
PCT/DE1994/000208 1993-02-23 1994-02-22 Preparation pharmaceutique ou cosmetique comportant des enzymes, son procede de fabrication et son utilisation Ceased WO1994019005A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU63730/94A AU6373094A (en) 1993-02-23 1994-02-22 Enzyme-containing pharmaceutical or cosmetic composition, process for preparing the same and its use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19934305460 DE4305460C2 (de) 1993-02-23 1993-02-23 Pharmazeutische oder kosmetische, Enzyme enthaltende Zubereitung, Verfahren zu deren Herstellung und deren Verwendung
DEP4305460.9 1993-02-23

Publications (1)

Publication Number Publication Date
WO1994019005A1 true WO1994019005A1 (fr) 1994-09-01

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PCT/DE1994/000208 Ceased WO1994019005A1 (fr) 1993-02-23 1994-02-22 Preparation pharmaceutique ou cosmetique comportant des enzymes, son procede de fabrication et son utilisation

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AU (1) AU6373094A (fr)
DE (1) DE4305460C2 (fr)
WO (1) WO1994019005A1 (fr)

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US5945102A (en) * 1994-11-22 1999-08-31 Phairson Medical Inc. Crustacean and fish derived multifunctional enzyme
US5958406A (en) * 1994-11-22 1999-09-28 Phairson Medical Inc. Acne treatment with multifunctional enzyme
US6030612A (en) * 1994-11-22 2000-02-29 Phairson Medical Inc. Antimicrobial uses of multifunctional enzyme
US6232088B1 (en) 1995-02-08 2001-05-15 Phairson Medical, Inc. Treatment and prevention of immune rejection reactions
WO2005120555A1 (fr) * 2004-06-10 2005-12-22 Mi An Utilisation de lysozyme humain pour preparer un medicament destine au traitement de l'acne
US7947270B2 (en) 1992-05-22 2011-05-24 Arcimboldo Ab Removing dental plaque with krill enzymes
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