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WO2009032325A1 - Objets profilés contenant un composant de phéromone humaine - Google Patents

Objets profilés contenant un composant de phéromone humaine Download PDF

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Publication number
WO2009032325A1
WO2009032325A1 PCT/US2008/010459 US2008010459W WO2009032325A1 WO 2009032325 A1 WO2009032325 A1 WO 2009032325A1 US 2008010459 W US2008010459 W US 2008010459W WO 2009032325 A1 WO2009032325 A1 WO 2009032325A1
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WO
WIPO (PCT)
Prior art keywords
shaped article
compounds
shaped articles
alginate
pheromone
Prior art date
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Ceased
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PCT/US2008/010459
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English (en)
Inventor
Philip Braginsky
Barry J. Marenberg
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Flow Science Inc
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Flow Science Inc
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Filing date
Publication date
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Publication of WO2009032325A1 publication Critical patent/WO2009032325A1/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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/362—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0216—Solid or semisolid forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0241—Containing particulates characterized by their shape and/or structure
    • A61K8/0279—Porous; Hollow
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/731—Cellulose; Quaternized cellulose derivatives
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
    • 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
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q13/00—Formulations or additives for perfume preparations
    • 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

Definitions

  • the invention relates to a process for the manufacture porous and/or sponge-like shaped articles containing a human pheromone component, as well as to the shaped articles available thereafter and their use.
  • Pheromones are chemicals emitted by living organisms to send messages to individuals of the same species.
  • the classes most widely explored are the sex pheromones produced by female moths which are used to attract conspecif ⁇ c males for mating. Bombykol, the sex pheromone of the silkmoth, was first synthesized in 1959.
  • pheromones consist of blends of two or more chemicals which need to be emitted at exactly the right proportions to be biologically active.
  • the female effluvia or sex gland can contain additional compounds which are related to the pheromone components and whose biological function is often unclear.
  • many attractants of male moths have been discovered simply by field screening, hi several cases it could later be shown that the attractant found with this technique was identical to the natural pheromone produced by the female, hi most others, the composition of the true pheromone is still unknown. While it is known that pheromone systems exist in insects, an increasing number of studies have shown that pheromones play a role in many species, including humans.
  • Pheromones in humans are believed to be produced by the apocrine glands. These glands become functional after reaching puberty, which could explain why most people develop an attraction for others at that time. Pheromones could also be the reason why a person can sense "chemistry", or feel an instant attraction or dislike when first meeting someone. Certain compounds believed to have pheromone properties affect a specific behavioral or physiological response in human subjects, e.g., a reduction of negative affect, mood, and character traits.
  • nasal administration provides for contacting neurochemical receptors of a heretofore poorly understood neuroendocrine structure, commonly known as the vomeronasal organ ("VNO); also known as “Jacobson's organ”), with one or more steroid(s) or with compositions containing the steroid(s).
  • VNO vomeronasal organ
  • This organ is accessed through the nostrils of most higher animals— from snakes to humans, and has been associated, inter alia, with pheromone reception in certain species (see generally Muller-Schwarze & Silverstein, Chemical Signals, Plenum Press, New York (1980)).
  • the distal axons of terminalis nerve neurons may also serve as neurochemical receptors in the VNO. Stensaas, L. J., et al., J. Steroid Biochem. and Molec. Biol. (1991) 39:553. This nerve has direct synaptic connection with the hypothalamus.
  • the present invention comprises external application of shaped articles containing active and inactive substances including pheromones comprising skeletal-forming agents that are both protein and non-protein based.
  • active and inactive substances including pheromones comprising skeletal-forming agents that are both protein and non-protein based.
  • These shaped articles should exhibit sufficient cohesion, that is to say, mechanical strength, may dissolve readily in the course of application on the skin, and should result in a pleasant application sensation.
  • these shaped articles should be suitable to receive various active substances, such as, in particular, cosmetic active substances and therapeutic or pharmaceutical active substances, and to act as carriers for such substances.
  • the shaped articles may be applied to the dermis or hair of a subject.
  • the invention consequently provides the use of a shaped article containing at least one skeletal-forming agent, optionally one or more pheromones, optionally one or more active substances and also optionally one or more auxiliary substances for the purpose of external application.
  • a "shaped article” in the sense of the invention is to be understood to mean any shaped body; for example, in particular, polygons, spheres, cuboids, pyramids, stars, but also shaped articles modeled on natural shapes, such as, for example, those in the form of animals such as, for example, marine animals such as starfish, plants and parts of plants, such as leaves etc., as well as shapes to conform to human body parts such as, forehead, lips, nose, chin, cheeks, arms, legs, hands, feet and back. All these shapes and others are available in accordance with the process for producing the shaped articles that are used in accordance with the invention, which is described further below.
  • a plurality of the stated shaped articles in a container is also encompassed in accordance with the invention.
  • the shaped articles may be individually packed. However, particularly in the cosmetic application, a plurality of the shaped articles are preferably present in a container, in contact alongside one another.
  • the volumes of the shaped articles that are used are not restricted as such by reason of the process for their production.
  • the volumes expediently amount to at least approximately 0.1 cm , preferably 0.3 cm , more preferably at least approximately 0.5 cm , still more preferably at least approximately 0.8 cm'.
  • the volumes that are used are expediently restricted in the upward direction to up to approximately 6 cm , preferably up to approximately 5 cm , more preferably up to approximately 4 cm .
  • the size of the shaped articles is determined, inter alia, by the site of external application of the shaped articles. For instance, application on relatively large areas of the body or on the hair (for example, direct application of the moistened shaped articles on the back etc., or use as a bath additive) makes the use of relatively large shaped articles possible, whereas smaller shaped articles are preferred in the case of application on smaller parts of the body (for example, the cheek etc.).
  • alkali alginates such as sodium alginate are water-soluble, whereas earth- alkaline alginates such as calcium alginates are insoluble in water.
  • thin water-insoluble layers can be produced, for example, by spraying a thin sodium alginate film with a CaCl2 solution.
  • manufacture of thicker layers is intended, difficulties arise from the fact that the homogeneous incorporation of free calcium ions into a sodium alginate solution is made difficult by the large increase of the solution's viscosity, so that disjointed calcium alginate agglomerates are the result instead of uniform products. While this is not the preferred method of manufacture, it is a method provided for in the present invention.
  • the present invention incorporates by reference this disclosure and further provides this carrier comprising a human pheromone component.
  • U.S. Pat. No. 5,718,916 suggests, for example, adding a water-soluble complexing agent such as sodium citrate to the aqueous solution of the alginate composition. If, for example, an easily soluble calcium salt such as calcium chloride is subsequently added, the immediate precipitation of calcium alginate is prevented by the presence of the complexing agent, which is supposed to prevent the formation of insoluble calcium alginate globules in the product.
  • the gelation time of the alginate solution only spans 30 to 60 seconds.
  • GB 2357765 discloses a process for the manufacture of water-insoluble alginate sponges or foam products for the manufacture of adhesive plasters or surgical products, in which water-soluble alginate is also being cross-linked by adding polyvalent metal ions in the presence of a foam- producing agent.
  • a complexing agent is not present.
  • ammonium hydroxide is present in order to decrease the viscosity of the calcium alginate.
  • calcium for example, is added, followed by an acid. This process also has the disadvantage that the formation of the alginates cross-linked by means of the calcium ions proceeds relatively quickly after the acid has been added, so that homogeneous thick layers cannot be obtained.
  • the process necessitates the presence of a foaming agent, of surface-active agents, of a borate buffer as well as the above- mentioned ammonium compounds.
  • a foaming agent of surface-active agents, of a borate buffer as well as the above- mentioned ammonium compounds.
  • This makes the process difficult to control, and the products obtained contain a plurality of components whose physiological effects must be taken into consideration. While this is not the preferred method of manufacture, it is a method provided for in the present invention.
  • the present invention incorporates by reference this disclosure and further provides this carrier comprising a human pheromone component.
  • pads are described for dermatological use comprising a polymeric carrier material, in particular alginic acid.
  • the present invention incorporates by reference this disclosure and further provides this carrier comprising a human pheromone component.
  • DE 43 28 329 discloses freeze-dried biomatrices for the moisturization of the skin and for the topical transdermal application of pharmaceutical cosmetically active substances containing natural polysaccharides and modified polysaccharides. This publication also mentions the stabilization of the biomatrix by the formation of calcium alginate skeletals by the addition of calcium ions.
  • the present invention incorporates by reference this disclosure and further provides this carrier comprising a human pheromone component.
  • a process for the manufacture of polysaccharide foams, in particular based on an alginate, is known from WO 94/00512.
  • this patent specification also discloses a variant in which an insoluble carbonate or bi-carbonate salt are dispersed in the foamed polysaccharide by polyvalent metal cations and the foam subsequently treated with a strong acid in order to release carbon dioxide and to crosslink, by the cations that form, the polysaccharide while a dimensionally stable foam structure is formed.
  • foams of a thickness of up to 5 mm can be stabilized in this manner.
  • the present invention incorporates by reference this disclosure and further provides this carrier comprising a human pheromone component.
  • alginate sponges Another process for the manufacture of alginate sponges is known from U.S. Pat. No. 3,653,383.
  • calcium alginate is at first produced from alginic acid and calcium carbonate, the calcium alginate formed is then ground, and the resulting gel is subjected to freeze-drying. Relatively large- format sponge-like materials can be produced in this manner.
  • the present invention incorporates by reference this disclosure and further provides this carrier comprising a human pheromone component.
  • the present invention also provides a relatively large- format, substantially homogeneous shaped articles based on compounds of alginates and polyvalent metal ions, which have a high degree of wet-strength, in particular with regard to wet breaking strength, and which can be cut into thin layers using commonly-used cutting devices, and that preferably have an attractive appearance, i.e. in particular a high degree of whiteness, and which can therefore be used in cosmetic or medical applications such as cosmetic skin pads or medical plasters etc. It is contemplated that the pads are laid on a subject's dermis or hair, wetted or otherwise activated and left for an appropriate amount of time for the incorporated compounds to have an effect. This maybe any amount of time appropriate but preferably from 10 seconds to 1 hour.
  • this invention makes possible the provision of substantially homogeneous thick porous alginate layers, from which suitable cosmetic or medical forms of application that can also be administered orally can easily be manufactured by compressing and/or punching out, such as, for example, shaped articles for implants, satiation comprimates, means for the controlled, (i.e., retarded) release of active substances or the like.
  • the present patent application provides a preferred process for the manufacture of alginate-containing porous shaped articles comprising the steps of: a) preparing an aqueous solution of a water-soluble alginate, bl) adding one or more salts of a polyvalent metal ion with a multidentate complexing anion to the aqueous solution of the water-soluble alginate, and shifting of the complex-formation equilibrium of the polyvalent metal ion and the multidentate complexing anion while increasing the available concentration of the polyvalent metal ion in the alginate solution, and thus formation of salts of the alginate with the above- mentioned polyvalent metal ion, or b2) adding a multidentate complexing agent for a polyvalent metal ion to the aqueous solution of the water-soluble alginate and admixing one or more poorly water-soluble salts of a polyvalent metal ion c) pouring the (still) flowable aqueous alginate composition in to a mould, and, d)
  • the water-soluble alginates used in step (a) are preferably alkali metal alginates such as alginates of sodium, potassium, etc.
  • the underlying algin acid is a natural acid polysaccharide primarily extracted from so-called brown algae (Phaecophyceae) with a high molecular weight between 30,000 and 200,000, which contains chains formed from D-mannuronic acid and L- guluronic acid.
  • brown algae Phaecophyceae
  • the degree of polymerization changes depending on the kind of alga used for extraction, on the season during which the algae were collected, the geographic origin of the algae as well as the age of the plants.
  • algin acid or alkali alginates can also be obtained microbiologically, for example by fermentation with Pseudomonas aeruginosa or mutants of Pseudomonas putida, Pseudomonas fluorescens or Pseudomonas mendocina, see. e.g. EP-A-251905 and Rompp Chemie Lexikon "Naturstoffe” (Encyclopedia of Natural Products) published by Thieme Verlag, 1997 and documents cited therein.
  • alginates with an average particle size of up to about 0.2 mm and a viscosity in aqueous solution of from 300 to 800 mPas (1% solution, pH 7, 20 0 C) are preferred.
  • sodium alginate is particularly preferred.
  • the aqueous solution of the water-soluble alginate used in step (a) preferably has such a concentration, that, in the aqueous suspension formed according to step (b) a concentration is formed of 0.2 to 3 wt %, more preferably 0.3 wt % to 2.5 wt %, and still more preferably 0.4 wt % to 1.2 wt % of alginate in relation to the amount of water used.
  • the solution can be prepared by suspending the desired amount of alginate in, e.g., distilled water.
  • concentration of the alginate in the aqueous suspension influences the hardness of the porous shaped articles formed. Concentrations of more than 2 wt % lead to relatively hard and brittle, respectively, shaped articles, which less preferred. Concentrations below 2 wt % lead to less brittle shaped articles, which is more preferred.
  • Step (bl) In step (bl), one or more salts of a polyvalent metal ion with a multidentate complexing anion are added to the aqueous solution of the water-soluble alginate obtained in step (a).
  • Such polyvalent metal ions are suitable which form poorly soluble compounds with the alginate used, i.e. which act as cross-linking metal ions.
  • Such polyvalent metal ions include, for example, alkaline-earth metal ions and transition metal ions which form poorly soluble compounds with alginates.
  • Alkaline-earth metal ions such as beryllium, magnesium or calcium are preferred.
  • Calcium is particularly preferred. Beryllium and magnesium are less preferred, since the former is not acceptable from a cosmetic point of view and since the cross-linking effect of the magnesium is small.
  • calcium salts are particularly preferred according to the invention for they are physiologically and, particularly, cosmetically acceptable and have a strong cross-linking and/or gelation effect compared to alginates.
  • barium, strontium, zinc, manganese, iron, aluminum can also be used.
  • the multidentate complexing anion in the complex salt of the polyvalent metal ion is preferably a carboxylate of a polycarboxylic acid.
  • Carboxylates of aliphatic dicarboxylic to tetracarboxylic acids such as, for example citric acid (2-hydroxy-l,2,3- propanetricarboxylic acid), malic acid, oxalic acid, 1,3-propanetricarboxylic acid, agaric acid, ethylenediamine tetraacetic acid (EDTA), 1,2,3-propanetricarboxylic acid etc. are preferred.
  • Polycarboxylic acids that are physiologically tolerable, particularly tolerable for the skin, are particularly preferred.
  • this includes carboxylates of ⁇ -hydroxypolycarboxylic acids such as citric acid.
  • Citrate, malate and the anion of the EDTA are particularly preferred as multidentate complexing anions. Citrates are most preferred.
  • calcium citrate (stoichiometry: Ca 3 Citrate 2 ) is particularly preferred as the complex salt of a polyvalent metal ion with a multidentate complexing anion that is added in step (bl).
  • Addition of the complex salt of a polyvalent metal ion with a multidentate complexing anion in step (bl) may take place by admixing in solid or dissolved form.
  • Addition of the complex salt to the alginate solution expediently takes place in a temperature range of between 5 °C and 80 °C, preferably, however, at room temperature (20 °C).
  • the amount of the complex salt added in step Ib) is expediently selected so, that the concentration of the complex salt in the resulting solution amounts to around 0.1 to 500 mmol/litre.
  • the amount of the added complex salt in relation to the amount of the alginate in the solution is preferably selected so that the molar ratio of the complex salt and the alginate amounts to about 0.001 to 0.1.
  • step (bl) carried out according to the invention takes place, for example, by reducing the concentration of the complexing anion in the solution.
  • concentration of the uncomplexed polyvalent metal ion in the solution is thus increased.
  • the shift of the equilibrium can be effected by a change, particularly by an increase in temperature, since the equilibrium constant depends on temperature, among other things.
  • the addition of another metal salt would have an influence on the balanced reaction complexed anion/free anion without, however, forming insoluble alginates.
  • shifting of the equilibrium is preferably effected by a reduction of the concentration of the free complexing anion in the solution, particularly preferably by the addition of at least one acid.
  • the added acid is a stronger acid than the conjugated acid of the complexing anion, and is therefore capable of protonating it.
  • the conjugated acid itself can also be added, such as citric acid in the case of citrate as an anion. Since the citrate, which results from the dissociation of the salt of the polyvalent cation such as, e.g. Ca 2+ , is formed in the form of Citrate 3' , it is protonated in an aqueous solution by adding citric acid while hydrogen citrates are formed, and is thus withdrawn from the complex formation equilibrium.
  • Preferred acids are, for example, inorganic mineral acids, such as hydrochloric acid, sulfuric acid, phosphoric acid or aliphatic carboxylic acids, such as acetic acid, etc.
  • the amount of the acid added depends on the complex salt used and its complex formation constant in aqueous solution. For example, it may amount to around 0.1 to 20 times (mol/mol) the concentration of the complex salt.
  • the molar ratio of calcium citrate to an acid such as citric acid preferably amounts to between 0.1 to 20, more preferably from 0.5 to 10.
  • the pH adjustment to less than about 6.0 is sufficient to shift the complex formation constant far enough for the concentration of the polyvalent metal salt to increase enough that the solubility product of the alginate salt is exceeded, i.e. that the insoluble alginate of the polyvalent metal salt precipitates or that the solution gels.
  • the pH value adjusted in this step influences the breaking strength of the porous shaped articles obtained.
  • pH values of less than 6 are preferable, more preferably less than 5. These low pH values are particularly preferable in combination with a low alginate concentration of less than 2 wt % adjusted in step (b) in the total suspension.
  • the rate of formation of the insoluble alginate and thus the flowability or pourability of the alginate solution or suspension, can be controlled very exactly and easily by the amount and rate at which the acid is added, as well as by temperature control if necessary, particularly because of the high diffusion rate of the protons in the aqueous solution. It is thus possible to obtain homogeneous shaped articles with high thicknesses of at least around 1 cm after drying, which have a sufficient wet-strength, in particular with regard to wet breaking strength, so that they can be used as cosmetic or medical sponge- like wet-strength materials, as described below, if necessary after subsequent cutting into thinner layers or by compressing and/or punching out.
  • step (b2)) of the process according to the invention the further retardation—in comparison to the state of the art—of the formation of the insoluble alginate in the alginate solution which facilitates a more homogeneous incorporation of the polyvalent metal salt into the solution of the alginate and thus a homogeneous quality of the porous shaped article, takes place, not (as in the state of the art) by adding to the alginate solution of step a) a soluble salt of a polyvalent metal ion which forms poorly soluble salts with the alginates (such as calcium chloride), but rather by adding poorly soluble salts of these polyvalent metal salts, such as CaSO 4 .
  • a polyvalent metal ion which forms poorly soluble salts with the alginates (such as calcium chloride)
  • a multidentate complexing agent for a polyvalent metal ion is added to the aqueous solution of the water-soluble alginate in step (b2).
  • the multidentate complexing agent is added in the form of an ionic compound or as a covalent compound, e.g. in the form of a conjugated acid.
  • the multidentate complexing agent can be added to the solution of the alginate in solid or dissolved form.
  • the above-mentioned complexing agent can be salts of polyvalent metal ions that form poorly soluble alginates, as well as salts of monovalent or polyvalent metal ions that do not form poorly soluble compounds with alginates. Mixtures of such metal salts can also be used.
  • Salts of monovalent or polyvalent metal ions that do not form poorly soluble compounds with alginates are preferred, since the retarding effect of the multidentate anion on the formation of free polyvalent metal ions, which can serve to form poorly soluble alginates, is more pronounced.
  • the salts of polyvalent metal ions with multidentate complexing anions used in step (bl) such as e.g. calcium citrate, can also be added.
  • acid is added if necessary, after or during mixing a poorly soluble metal salt of a polyvalent metal ion such as e.g. calcium sulfate, in order to increase the concentration of free metal ions that form poorly soluble compounds with alginates and to accelerate the homogeneous cross-linking of the alginates.
  • Preferred acids are, for example, inorganic mineral acids such as, e.g., hydrochloric acid, sulfuric acid, phosphoric acid or aliphatic carboxylic acid, such as, e.g., acetic acid. Particularly preferred is hydrochloric acid.
  • step (b2) it can be seen that the set pH value has an influence on the breaking strength of the porous shaped articles obtained. Therefore, in order to obtain a higher ) breaking strength, a pH value of less than 6 is preferred, more preferably of less than 5, also in step (b2). Again, these low pH values are particularly preferable in combination with a small alginate concentration of less than 2 wt % adjusted in step (b) in the total suspension.
  • the adjustment of the pH value in principle, may also take place by a prior addition of an acid, such as HCl to the alginate solution or the alginate solution to which a complexing agent has been added, such as sodium citrate or citric acid, and subsequent addition of the poorly soluble metal salt, such as CaSO ⁇
  • the concentration of the added multidentate complexing agent for a polyvalent metal ion amounts to about 0.0001 to 1 mol/liter, preferably from 0.001 to 0.5 mol/liter.
  • the molar ratio of the amount of the water-soluble alginate in relation to the molar amount of the added multidentate complexing agent for a polyvalent metal ion amounts to preferably 0.0001 to 1, more preferably 0.001 to 0.5.
  • the polyvalent metal ions that are added in the form of their poorly soluble salts in the second adding step of step (b2) are those metal ions that form poorly soluble salts with alginates or cross- linked alginates, and in this regard, we may refer to the salts mentioned in step (bl).
  • the corresponding anions can be selected arbitrarily, however, in water, they must form poorly soluble salts with the polyvalent metal ions or cations.
  • calcium salts are also preferred, particularly calcium sulfate. CaC ⁇ 3 and other carbonates are less preferred, since CO2 may form in the preferably acid conditions of the preparation of the poorly soluble alginate, which makes controlling the reaction or the qualities of the alginate-containing shaped body more difficult.
  • the solubility, in water at 20 0 C, of the poorly water-soluble salt of the polyvalent metal ion added in step (b2) preferably amounts less than 10 g/liter, more preferably 5 g/liter, still more preferably 0.1 to 3 g/liter. If the solubility is higher, a more rapid formation of the poorly soluble alginates may occur which leads to a reduction of the possible processing time and thus, to an inhomogeneous product. If solubility is less than the above-mentioned range, the formation of the poorly soluble or cross-linked alginates may take place too slowly, which is also undesirable.
  • further salts in particular such salts that do not form poorly soluble alginates, such as e.g. sodium sulfate, sodium chloride etc., the solubility of the poorly water-soluble salts of polyvalent metal ions can be reduced even further, and thus, the processability or homogeneity can be enhanced.
  • the amount of the poorly soluble salt of the polyvalent metal ion is expediently selected, so that the concentration of the salt in the resulting solution is between about 0.1 and 500 mmol/litre, whereby, in this case, the total amount of the salt in relation to the volume of the solution is meant, even if the salt does not dissolve completely.
  • the amount of the added poorly soluble salt of the polyvalent metal ion in relation to the amount of the soluble alginate is preferably selected so that the molar ratio of the alginate to the poorly soluble of the polyvalent metal ion is between 0.001 and 1.
  • the amount of the added poorly soluble salt of the polyvalent metal ion in relation to the amount of the submitted multidentate complexing agent is preferably selected so that the molar ratio of the poorly soluble salt of the polyvalent metal ion and the multidentate complexing agent is between 0.1 and 10.
  • the formation of the poorly soluble alginates is expediently controlled so that the increase of the concentration of the uncomplexed divalent metal ion is so small, that a flowability of the alginate solution, expressed as viscosity at room temperature (20 0 C), of under about 1000 mPas is made possible for at least 1 minute, preferably for about 2 minutes, still more preferably for about 3 minutes.
  • the formation of the alginate gels or the mixing, respectively, according to steps (bl) and (b2) is preferably carried out in mixers with stator/rotor system, such as, e.g., a colloid mill.
  • pouring the (still) flowable alginate composition into a mold desired for later drying can take place in a known manner.
  • layer thicknesses of the flowable alginate composition of up to 50 cm are possible.
  • Preferred shapes are box shapes with a rectangular layout.
  • Pouring can take place at any suitable stage of the process.
  • the solution of the water-soluble alginate from step (a) may already be poured into the mould used for later drying if a sufficiently thorough mixing can be ensured in this mould.
  • pouring takes place after cross-linking or the precipitation of the poorly soluble alginate in step (bl) or (b2) has been initiated.
  • step (d) takes place in a known manner. Freeze-drying is particularly preferred. This can also take place in a known manner, and, for example, DE 4328329 C2 or DE 4028622 C2 can be referred to in this context, which shall expressly be referred to with regard to step (d) of the process according to the invention, and which are thus part of the process according to the invention.
  • the addition of one or more human pheromones preferably takes place prior to step d) and most preferably to step c).
  • the present invention is not limited in the pheromone composition used, nor to the amount of pheromone composition added to the solution.
  • Exemplary human pheromone compounds include, but are not limited to, copulins (such as short chain aliphatic acids), estrene steroids, vomeropherins, such as 19-nor-cholane steroids, 19-nor-pregnane steroids such, and androstene and androstenedione compounds. Combinations and metabolites of the above-recited human pheromone compounds are also contemplated.
  • addition of at least one other component takes place prior to step d), in particular prior to step c), the component being selected from a group consisting of: cosmetic or medical active substances, further natural or synthetic hydrocolloid-forming polymers and cosmetic or medical adjuvants or additives.
  • Further natural or synthetic hydrocolloid-forming polymers include (partially) water-soluble, natural or synthetic polymers that form gels or viscous solutions in aqueous systems. They are expediently selected from further natural polysaccharides, synthetically modified derivatives thereof or synthetic polymers. Further polysaccharides include e.g.
  • homoglycans or heteroglycans such as, for example, carrageenan, pectins, tragacanth, guar gum, carob-bean gum, agar, gum arabic, xanthan gum, natural and modified starches, dextrans, dextrin, maltodextrins, chitosan, glucans, such as ⁇ -1,3- glucan, ⁇ -l,4-glucan, such as cellulose, mucopolysaccharides, such as, in particular hyaluronic acid etc.
  • carrageenan such as, for example, carrageenan, pectins, tragacanth, guar gum, carob-bean gum, agar, gum arabic, xanthan gum, natural and modified starches, dextrans, dextrin, maltodextrins, chitosan, glucans, such as ⁇ -1,3- glucan, ⁇ -l,4-glucan
  • Synthetic polymers include e.g.: cellulose ethers, polyvinyl alcohol, polyvinyl pyrrolidone, synthetic cellulose derivatives, such as methylcellulose, carboxycellulose, carboxymethylcellulose, in particular sodium carboxymethycellulose, cellulose esters, celluloses ethers such as hydroxypropylcellulose, polyacrylic acid, polymethacrylic acid, poly(methyl methacrylate) (PMMA), polymethacrylate (PMA), polyethylene glycols etc. Mixtures of these polymers may also be used.
  • Hyaluronic acid and/or its salts and/or their derivatives are particularly preferably added.
  • Hyaluronnic acid is a highly viscous glucosaminoglycan with alternating ⁇ i -3 -glucuronic acid and ⁇ i ⁇ -glucosamine moieties; its molecular weight lies between 50000 and several million.
  • Hyaluronic acid is often used as a sodium salt, e.g. in therapy, mainly in ophthalmology, surgery and in cosmetics.
  • the salts of the hyaluronic acid which are formed with alkaline ions, alkaline-earth ions, magnesium ions, aluminum ions, ammonium ions or substituded ammonium ions, can be used as carriers for increasing absorption of medicaments, see. e.g. Rompp Chemie Lexikon “Naturstoffe” (Encyclopedia of Natural Products) published by Thieme Verlag, 1997 and documents cited therein.
  • sodium hyaluronate with a molecular weight of about 1,000,000 to 2,500,000 is particularly preferred.
  • hyaluronic acid additive of the hyaluronic acid to the process according to the invention leads, totally surprisingly, to a increased whiteness of the obtained alginate-containing porous shaped articles, in particular in the process variant (bl), but also in process variant (b2). For aesthetic reasons, this is particularly very much preferred in cosmetic applications. Moreover, hyaluronic acid also develops its therapeutic effect in particular in topical or local application, such as e.g., moisturization of the skin or support of wound healing.
  • the hyaluronic acid or its salts are added to the alginate-containing porous shaped articles according to the invention in an amount of about 0.1 to 90 percent by weight, preferably up to about 70 wt %, relative to the dried shaped article.
  • the porous shaped articles according to the invention comprise carboxymethylcellulose, in particular sodium carboxymethylcellulose.
  • carboxymethylcellulose in particular sodium carboxymethylcellulose.
  • the addition of sodium carboxymethylcellulose leads to an improvement of the optical density of the porous shaped articles according to the invention without increasing the hardness or brittleness of the shaped articles.
  • the addition of sodium carboxymethylcellulose leads to an improvement of the flexibility of the porous shaped articles obtained.
  • the addition carboxymethylcellulose, in particular sodium carboxymethylcellulose leads to a stabilization of the shaped articles.
  • the carboxymethylcellulose, in particular sodium carboxymethylcellulose surprisingly prevents the sedimentation of the poorly soluble salt, in particular of the CaSO 4 .
  • the carboxymethylcellulose in particular sodium carboxymethylcellulose, can be present in the shaped articles according to the invention in an amount of up to 90 wt % relative to the dry content of the shaped article. This corresponds to preferred ranges that are to be set in the aqueous suspension of up to 3 wt %, preferably 0.2 wt % to 3 wt %.
  • a preferred embodiment of the shaped articles according to the invention comprises the carboxymethylcellulose, in particular sodium carboxymethylcellulose, and hyaluronic acid and/or their salts and/or their derivatives.
  • active substances added include cosmetic or therapeutic or pharmaceutical active substances, particularly active substances suitable for external application.
  • the shaped article manufactured according to the invention contains at least cosmetic and/or pharmaceutical active substance.
  • the shaped articles preferred according to the invention preferably are cosmetic or therapeutic active substances.
  • Cosmetic shaped articles or shaped articles manufactured using cosmetic active substances within the sense of the invention are essentially active substances within the sense of the Anlagen of the Anlagenstande exiges (LMBG) (German Foostuffs and Commodities Act), i.e., substances or preparations derived from substances that are intended to be applied externally on humans for the purpose of cleansing, grooming, or for the purpose of influencing appearance or body odor, or for the purpose of conveying impressions of odors, unless they are predominantly intended for relieving or eliminating diseases, ailments, physical defects or pathological complaints, hi this sense, the cosmetic shaped articles manufactured in accordance with the invention are, for example cosmetic applications such as, e.g., face masks etc., which can serve as skin- washing and skin-cleansing agents, skin-care products, in particular skin-care products for the face, eye cosmetics, lip-care products, nail-care products, foot- care products, as well as hair-care or dental-care
  • cosmetically effective compounds include: anti-acne agents, antimicrobial agents, antiperspirants, astringent agents, deodorizing agents, depilatories, conditioning agents for the skin, skin-smoothing agents, agents for increasing the hydration of the skin, such as e.g. glycerin or urea, sun-screening agents, keratolyses, radical-interceptors for free radicals, antiseptic substances, agents for the treatment of the symptoms of ageing of the skin and/or agents that modulate the differentiation and/or proliferation and/or pigmentation of the skin, vitamins such as vitamin C, agents with irritating side- effects, such as e.g.
  • ⁇ -hydroxy acids ⁇ -hydroxy acids, ⁇ -keto acids, ⁇ -keto acids, retinoids (retinol, retinal, retinic acid), anthralines (dioxyanthranol), anthranoids, peroxides (in particular, benzoyl peroxide), minoxidil, lithium salts, antimetabolites, vitamin D and its derivatives; catechols, flavonoids, ceramides, fatty substances, such as mineral oilks, such as paraffin oils or Vaseline oils, silicone oils, vegetable oils such as coconut oils, sweet almond oil, apricot oil, corn oil, jojoba oil, olive oil, avocado oil, sesame oil, palm oil, eucalyptus oil, rosemary oil, lavender oil, pine oil, thyme oil, mint oil, cardamom oil, orange-blossom oil, soybean oil, bran oil, rice oil, rapeseed oil and castor oil, wheat-germ oil and vitamin E isolated thereform, evening-primrose oil
  • soybean lecithin soybean lecithin
  • sphingolipids/ceramides isolated from plants, animal oils or fats, such as tallow, lanolin, butyric oil, fatty-acid esters, esters of fatty alcohols, and waxes with a melting point corresponding to skin temperature (animal waxes such as beeswax, carnauba wax and candelilla wax, mineral waxes, such as microcristalline waxes, and synthetic waxes, such as polyethylene waxes or silicone waxes), as well as all oils that are suitable for cosmetic purposes, such as, for example, those mentioned in the CFTA treatise entitled Cosmetic Ingredient Handbook, 1st edition, 1988, The Cosmetic, Toiletry and Fragrance Association, Inc., Washington, polyunsaturated fatty acids, essentially fatty acids (e.g. ⁇ -linolenic acid), enzymes, coenzymes, enzyme inhibitors, hydrating agents, skin-soothing agents, detergents or foam-producing agents
  • plant active-substance extracts or essences obtained therefrom or individual substances may be mentioned, that can be added to the porous shaped bodies manufactured according to the invention.
  • the plant active-substance extract is selected, as a rule, from the group consisting of solid plant extracts, liquid plant extracts, hydrophilic plant extracts, lipophilic plant extracts, individual plant constituents, and also mixtures thereof, such as flavonoids and their aglycones: rutin, quercetin, diosmin, hyperoside, (neo)hesperidin, hesperitin, Ginkgo biloba (e.g. ginkgo flavone glycosides), Crataegus extract (e.g.
  • oligomeric procyanidines oligomeric procyanidines
  • buckwheat e.g. rutin
  • Sophora japonica e.g. rutin
  • birch leaves e.g. quercetin glycosides, hyperoside and rutin
  • elderflowers e.g. rutin
  • lime blossoms e.g. ethereal oil with quercetin and farnesol
  • hypericum oil e.g. olive-oil essence
  • calendula arnica (e.g. oleaginous essences of the flowers with ethereal oil, polar essences with flavonoids), melissa (e.g. flavones, ethereal oil); immunostimulants: Echinacea purpurea (e.g.
  • alkaloids rauwolfia (e.g. prajmaline), myrtle (e.g. vincamine); other phytopharmacons: aloe, horse chestnut (e.g. aescin), garlic (e.g. garlic oil), pineapple (e.g. bromelain), gins
  • kava kava e.g. kavalactones
  • hop flowers e.g. hop bitters
  • extr. passiflorae e.g. ethanolic extract
  • gentian e.g. ethanolic extract
  • anthraquinone-containing tinctures e.g. aloin-containing aloe-vera juice, pollen extract, algae extracts, liquorice-root extracts, palm extract, galphimia (e.g. mother tincture), mistletoe (e.g. aqueous ethanolic essence), phytosterols (e.g. ⁇ -sitosterol), mullen flowers (e.g. aqueous alcoholic extract), drosera (e.g.
  • sea-buckthorn fruits e.g. juice obtained therefrom or sea-buckthorn oil
  • marshmallow root e.g. sucrose-root extract
  • fresh plant extracts from mallow, comfrey, ivy, horsetail, yarrow, ribwort e.g. pressed juice
  • stinging nettle celandine, parsley
  • plant extracts from Norolaena lobata Tagetes lucida, Teeoma siems, Momordica charantia and aloe-vera extracts.
  • Preferred cosmetic active substances are natural and synthetic moisturizing factors such as, for example, glycerin, urea and ceramides, skin-protecting agents, skin lighteners, vitamins, antioxidants, so-called anti-ageing agents, anti-irritation agents, sun-screening agents, etc.
  • Further preferred cosmetic active substances are natural fats and oil, i.e. triglycerides of natural fatty acids, e.g. because of the moisturizing effect on the skin.
  • a particularly preferred cosmetic active substance is urea, which is thought to have the effect of a local anesthetic.
  • urea which is thought to have the effect of a local anesthetic.
  • agents or active substances are intended for external application, in which case it may be a question of dermally active substances but also of transdermal active substances.
  • agents for the treatment of skin diseases include, for example: agents for the treatment of skin diseases, externally applicable analgesics, e.g. dextropropoxyphene, pentazocine, pethidine, buprenorphine; antirheumatics/antiphlogi sites (NSAR), e.g. indomethacin, diclofenac, naproxen, ketoprofen, ibuprofen, flurbiprofen, salicylic acid and salicylic-acid derivatives such as acetylsalicylic acid, oxicams; steroid hormones, e.g.
  • betamethasone dexamethosone, methylprednisolone, ethynyl estradiol, medroergotamine, dihydroergotoxine; gout remedies, e.g. benzbromarone, allopurinol; external dermatological agents, including antibacterial agents, antimycotics, antiviral active substances, antiinflammatory active substances, antipruritic active substances, anaesthetising active substances, e.g. benzocaine, corticoids, anti-acne agents, antiparasitic active substances; externally applicable hormones; venous therapeutic agents; immunosuppressives etc., all for external application.
  • external dermatological agents including antibacterial agents, antimycotics, antiviral active substances, antiinflammatory active substances, antipruritic active substances, anaesthetising active substances, e.g. benzocaine, corticoids, anti-acne agents, antiparasitic active substances; externally applicable hormones; venous therapeutic agents; immuno
  • Preferred therapeutic agents are analgesics, e.g. immunosuppressives, hormones, agents for the treatment of skin diseases such as neurodermatitis, atopic dermatitis etc., and anti-herpes agents.
  • the porous shaped articles manufactured according to the invention may contain one or more auxiliary substances.
  • Auxiliary substances include: fillers, pH-adjustment agents, such as buffering substances, stabilizers, co-solvents, pharmaceutically and cosmetically conventional or other dyestuffs and pigments, preservatives, plasticizers, lubricants and slip additives, etc.
  • Squalane an oil derived from squalene, is a particularly preferred auxiliary substance. Squalane has a soothing and smoothing effect on the skin.
  • the invention relates to the use of a salt of a polyvalent metal ion with a multidentate complexing anion for the manufacture of porous alginate-containing shaped articles.
  • a salt of a polyvalent metal ion with a multidentate complexing anion for the manufacture of porous alginate-containing shaped articles.
  • a salt of a polyvalent metal ion with a multidentate complexing anion for the manufacture of porous alginate-containing shaped articles.
  • porous shaped articles containing alginate of polyvalent metal ions can be manufactured which have a thickness of at least one centimeter, preferably at least 2 cm, and which are obtained by cross-linking (or precipitating) of alginate-containing aqueous solutions with salts of polyvalent metal ions and subsequent drying of the aqueous suspension of the obtained cross-linked alginate.
  • the thickness of the shaped article means the shortest distance between two points in such a shaped article.
  • the porous shaped articles according to the invention When suspending Ig of the shaped article in lOOg of water at 2O 0 C, the porous shaped articles according to the invention have a pH value of the aqueous phase of less than 7, preferably less than 6. Such an acid pH is preferred in particular in cosmetic application on the skin.
  • the porous shaped article according to the invention preferably has a density of 0.005 to 1 g/cm ⁇ , preferably from 0.01 to 0.5 g/cm ⁇ (determined according to DIN 53420).
  • the porous shaped article according to the invention preferably has a wet-strength of at least about 10 mN/mm layer thickness (determined according to DIN 53328).
  • the above-mentioned porous shaped articles according to the invention can, as has been mentioned above, additionally contain at least one further component selected from the group including: cosmetic or medical active substances, further natural or synthetic hydrocolloid-forming polymers and cosmetic or medical adjuvants or additives. These may be contained in the porous shaped articles according to the invention in amounts of up to 0.75 g/g, preferably less than 0.5 g/g of the porous shaped article.
  • the above-mentioned porous shaped articles according to the invention are eminently suitable for the manufacture of layered shaped articles by cutting the porous shaped articles according to the invention in the manner known. For example, this is not possible with the sponge-like materials obtained by freeze-drying of ground insoluble alginates. By cutting the porous shaped articles according to the invention, layer thicknesses of, for example, 0.5 to 20 mm are obtained.
  • the invention also relates to the layered porous shaped articles thus obtained.
  • Such layered porous shaped articles are particularly suitable for external application, such as cosmetic or medical pads, such as material for wound dressing, primary wound dressing, implant material, and cell cultivation matrix.
  • porous shaped articles according to the invention are eminently suitable for the manufacture of compressed, expandable, sponge-like shaped articles as described, for example, in the applicant's EP 0901792, based on collagen. They can be easily manufactured from the large- format porous shaped articles, which were obtained in particular after freeze-drying, by punching out and/or compressing, in particular on an industrial scale, which, until now, is not possible without problems according to the processes of the state of the art.
  • Such comprimates are suitable in particular for oral, buccal or nasal application, such as, for example, satiation comprimates, which may additionally contain active substances, substances for dietary supplements or vitamins (see, e.g. DE 19942417).
  • satiation comprimates which may additionally contain active substances, substances for dietary supplements or vitamins (see, e.g. DE 19942417).
  • they are suitable for the manufacture of forms loaded with active substances, in which the active substance is released in a controlled, in particular retarded, manner.
  • Such forms include sponges containing active substances, such as implants, vaginal suppositories, as well as forms that can be administered orally, the latter especially as comprimates that expand to several times their compressed volume in a moist state, and that release the active substance contained from the sponge- like matrix (see, e.g.. WO 98/09617).
  • the present invention relates to porous shaped articles comprising alginates of polyvalent metal ions and hyaluronic acid and/or their salts and/or their derivatives.
  • these shaped articles completely surprisingly, have an increased degree of whiteness which is very much preferred particularly in cosmetic, but also in medical application.
  • the hyaluronic acid-containing porous shaped articles are preferably manufactured according to the process according to the invention.
  • the present invention relates to the use of the porous shaped articles according to the invention or the shaped articles obtained by the process according to the invention as cosmetic agents.
  • the porous shaped articles contain, for cosmetic application, alginates of polyvalent metal ions and hydroxycarboxylic acids, in particular hydroxypolycarboxylic acids such as, in particular, citric acid, which can be added, in the shape of the above-mentioned multidentate complexing agent, already during the manufacture of the porous shaped articles according to the invention.
  • the use in cosmetics of the porous shaped articles according to the invention preferably takes place in the shape of cosmetic skin pads that are applied to the skin in moistened form and are taken off after a certain exposure time, for example after the active substances contained therein have been absorbed.
  • the alginate itself also has a cosmetic effect such as hydration and smoothing of the skin. It is contemplated that the pads are laid on a subject's dermis or hair, wetted or otherwise activated and left for an appropriate amount of time for the compounds to have an effect. This maybe any amount of time appropriate, but preferably from 10 seconds to 1 hour.
  • the wetting substance may be a carrier with one or more human pheromones.
  • the carrier is preferably an alcohol, aqueous or oil based solution and most preferably a water based solution.
  • the present invention relates to the use of the porous shaped articles according to the invention or the shaped articles obtained by the process according to the invention for the manufacture of a medical product.
  • medical products include, for example, wound dressings, transdermal dressings, wound plasters, implants, substrates for cultivating cells, means for the controlled, in particular retarded, administering of active substances in the form of said implants, but also as a preparation to effect such retardation that can be administered orally, or as so-called satiation comprimates that have a satiation effect because of the expansion of the compressed porous shaped article in the stomach.
  • the latter may also be loaded with dietary supplements, vitamins, minerals or other active substances.
  • porous shaped articles according to the invention or the shaped articles obtained by the process according to the invention preferably serve the purpose of external application, such as, in particular, cosmetic or medical pads. Additionally, as has been mentioned, oral, buccal, vaginal, nasal application etc. is possible. As has been said, the homogeneous thick porous shaped articles made of alginates provided according to the invention permit the manufacture of any of those forms of application on an industrial scale with known processes, such as cutting, pressing, or compressing and/or punching out.
  • Particularly preferred shaped articles contain, relative to the dried substance, i.e. without residual moisture: about 6 to 100 wt % alginate,
  • citric acid or the salts thereof correspond to the preferred ranges in the aqueous suspension in step (c), to be freeze-dried of: about 0.2 to 3 wt % alginate,
  • the shaped articles according to the invention preferably have the form of a layer, i.e. length and width of the shaped articles are at least ten times, preferably 20 times as large as the thickness of the shaped article.
  • Such layers can also be cut into certain shapes, e.g., in the form of a facial mask.
  • the layers preferably have an area of at least 25 cm , more preferably at least 50 cm , still more preferred at least about 100 cm .
  • the invention also relates to laminates containing at least one layer described above, which is laminated on at least one side thereof with at least one further carrier layer.
  • the layer according to the invention is only laminated on one side, preferably with only one carrier layer.
  • the carrier layer preferably consists of a Rayon web (viscose).
  • Such laminates are preferably used as dressings or plaster for wounds, and are especially preferred as cosmetic masks.
  • the invention also relates to a combination containing at least one shaped article according to the invention as well as at least one solution, preferably aqueous, that contains one or more active substances and/or adjuvants in matching spatial arrangement (application package, set, kit-of-parts, etc.).
  • the solution of the active substances may be, e.g., solutions of readily volatile active substances or adjuvants that, because of the production process by freeze-drying, should not be or cannot be introduced into shaped articles, such as, e.g. certain portions of ethereal oils, perfumes, etc.
  • the solution can also comprise pharmaceutical or cosmetic active substances.
  • the solution may also comprise a human pheromone component.
  • the present invention also relates to the use of a shaped article containing at least one skeletal-forming agent, one or more pheromone components, optionally one or more active substances and also optionally one or more auxiliary substances for the purpose of external application, to a process for producing the stated shaped articles, and also to novel shaped articles.
  • the pheromone component may be incorporated into the auxiliary substance and/or the the shaped article.
  • pellets for pharmaceutical or cosmetic application which comprise skeletal-forming agents based on proteins.
  • the pellets serve, in particular, for the production of oral medicinal formulations.
  • the pellets are produced by dispersions consisting of the proteinic skeletal-forming agents and optionally of cosmetic or pharmaceutical active substances being instilled into intensely cold inert liquids, preferably liquid nitrogen, and by the frozen pellets subsequently being separated and freeze-dried.
  • intensely cold inert liquids preferably liquid nitrogen
  • the frozen pellets subsequently being separated and freeze-dried.
  • proteinic skeletal-forming agents in particular collagen or collagen derivatives
  • the size of the pellets that are produced in accordance with the cited German printed patent specifications is specified in the general part of the descriptions at 0.2 mm to 12 mm.
  • the present invention contemplates collagen and other protein based matrices.
  • proteinic skeletal-forming agents are not preferred.
  • some consumers increasingly prefer the application of purely vegetable products, particularly in the cosmetic field. The reasons for this have resulted from, inter alia, fundamental ethical considerations.
  • the shaped article that is used in accordance with the invention comprises at least one skeletal- forming agent and at least one pheromone.
  • the skeletal-forming agent it is generally a question of collagen or so-called hydrocolloids—that is to say, (partially) water-soluble, natural or synthetic polymers that form gels or viscous solutions in aqueous systems.
  • the skeletal-forming agents are expediently selected from collagens, polysaccharides or synthetic polymers.
  • the skeletal-forming agent is preferably selected from the group of the polysaccharides.
  • Polysaccharides include, for example, homoglycans or heteroglycans, such as, for example, alginates, especially sodium alginate, carrageenan, pectins, tragacanth, guar gum, carob-bean flour, agar, gum arabic, xanthan gum, natural and modified starches, dextrans, dextrin, maltodextrins, chitosan, glucans such as ⁇ -l,3-glucan, ⁇ -l,4-glucan, such as cellulose, mucopolysaccharides, such as hyaluronic acid etc.
  • alginates especially sodium alginate, carrageenan, pectins, tragacanth, guar gum, carob-bean flour, agar, gum arabic, xanthan gum, natural and modified starches, dextrans, dextrin, maltodextrins, chitosan, glucans such as ⁇ -l
  • Synthetic polymers include, for example: cellulose ethers, polyvinyl alcohol, polyvinyl pyrrolidone, synthetic cellulose derivatives, such as methylcellulose, carboxycellulose, carboxymethylcellulose, cellulose esters, cellulose ethers, such as hydroxypropylcellulose, polyacrylic acid, polymethacrylic acid, poly(methyl methacrylate) (PMMA), polymethacrylate (PMA), polyethylene glycols etc.
  • PMMA poly(methyl methacrylate)
  • PMA polymethacrylate
  • Mixtures of several skeletal-forming agents may also be used.
  • Particularly preferred in accordance with the invention are alginates, sodium alginate being particularly preferred.
  • skeletal-forming agents which preferably have a viscosity of less than 2000 mPa.s, still more preferably less than 1000 mPa.s, most preferably less than 100 mPa.s (i.e. a solution of 1 g of the skeletal-forming agent in 99 ml of distilled water (1% solution w/w) at 20 °C. and at a pH value of 6-8 has a viscosity of, respectively, less than 2000 mPa.s, less than 1000 mPa.s, less than 100 mPa.s).
  • low-viscosity skeletal-forming agents such as sodium alginate is, on the one hand, preferred, owing to the manner of preparation; on the other hand, the application of such low- viscosity skeletal-forming agents results in readier solubility of the formulation or, in the case of addition of water, in a higher rate of disintegration or rate of dissolution and hence in readier distributability on the skin.
  • the use of low- viscosity types of alginate can result in a greater rate of dissolution of the shaped articles that are used in accordance with the invention.
  • the use in cosmetics of the shaped articles according to the invention preferably takes place in the shape of cosmetic skin pads that are applied to the skin in moistened form and are taken off after a certain exposure time, for example after the active substances contained therein have been absorbed.
  • the alginate itself also has a cosmetic effect such as hydration and smoothing of the skin. It is contemplated that the pads are laid on a subjects dermis or hair, wetted or otherwise activated and left for an appropriate amount of time for the compounds to have an effect. This maybe any amount of time appropriate but preferably from 10 seconds to 1 hour.
  • the polysaccharides that are preferably used as skeletal-forming agents in accordance with the invention expediently have average molar masses of approximately 10 ⁇ up to approximately 10°, preferably approximately 10 ⁇ to 10 ⁇ .
  • the skeletal-forming agents are skin-compatible and, in the case of application on the skin, preferably result in the formation of a film that has a protective function.
  • the shaped articles that are used in accordance with the invention optionally contain one or more active substances, preferably at least one active substance. Active substances include, in particular, cosmetic or therapeutic or, to be more exact, pharmaceutical active substances that are suitable for external application.
  • the shaped article that is used in accordance with the invention preferably contains at least one cosmetic and/or pharmaceutical active substance. Accordingly, in the case of the shaped articles that are used in accordance with the invention it is preferably a question of cosmetic or therapeutic agents.
  • cosmetically effective compounds optionally also, for example, of dermatological, therapeutically effective compounds, include: anti-acne agents, antimicrobial agents, antiperspirants, astringent agents, deodorizing agents, depilatories, conditioning agents for the skin, skin-smoothing agents, agents for increasing the hydration of the skin, such as, for example, glycerin or urea, sun-screening agents, keratolyses, radical-interceptors for free radicals, anti-seborrhoeics, anti-dandruff agents, antiseptic active substances, active substances for treating the symptoms of ageing of the skin and/or agents that modulate the differentiation and/or proliferation and/or pigmentation of the skin, vitamins such as vitamin C, active substances with irritant side-effect, such as ⁇ -hydroxy acids, ⁇ -hydroxy acids, ⁇ -keto acids, ⁇ -keto acids, retinoids (retinol, retinal, retinic acid), anthralins (di)
  • soybean lecithin soybean lecithin
  • sphingolipids/ceramides isolated from plants, animal oils or fats, such as tallow, lanolin, butyric oil, fatty-acid esters, esters of fatty alcohols, and waxes with a melting-point corresponding to the temperature of the skin (animal waxes such as beeswax, carnauba wax and candelilla wax, mineral waxes such as microcrystalline waxes, and synthetic waxes such as polyethylene waxes or silicone waxes), as well as all oils that are suitable for cosmetic purposes, such as, for example, those mentioned in the CFTA treatise entitled Cosmetic Ingredient Handbook, 1st Edition, 1988, The Cosmetic, Toiletry and Fragrance Association, Inc., Washington, polyunsaturated fatty acids, essential fatty acids (e.g.
  • the plant active-substance extract is selected, as a rule, from the group consisting of solid plant extracts, liquid plant extracts, hydrophilic plant extracts, lipophilic plant extracts, individual plant constituents, and also mixtures thereof, such as flavonoids and their aglycones: rutin, quercetin, diosmin, hyperoside, (neo)hesperidin, hesperitin, Ginkgo biloba (e.g. ginkgo flavone glycosides), Crataegus extract (e.g. oligomeric procyanidines), buckwheat (e.g. rutin), Sophora japonica (e.g. rutin), birch leaves (e.g.
  • quercetin glycosides, hyperoside and rutin elderflowers (e.g. rutin), lime blossoms (e.g. ethereal oil with quercetin and farnesol), hypericum oil (e.g. olive-oil essence), calendula, arnica (e.g. oleaginous essences of the flowers with ethereal oil, polar essences with flavonoids), melissa (e.g. flavones, ethereal oil); immunostimulants: Echinacea purpurea (e.g. alcoholic essences, fresh plant juice, pressed juice), Eleutherokokkus senticosus; alkaloids: rauwolfia (e.g.
  • prajmaline myrtle (e.g. vincamine); other phytopharmacons: aloe, horse chestnut (e.g. aescin), garlic (e.g. garlic oil), pineapple (e.g. bromelain), ginseng (e.g. ginsenosides), sow-thistle fruits (e.g. extract standardised with respect to silymarine), butcher's-broom root (e.g. ruscogenine), valerian (e.g. valepotriates, tct. Valerianae), kava kava (e.g. kavalactones), hop flowers (e.g. hop bitters), extr. passiflorae, gentian (e.g.
  • ethanolic extract anthraquinone-containing tinctures, e.g. aloin-containing aloe- vera juice, pollen extract, algae extracts, liquorice-root extracts, palm extract, galphimia (e.g. mother tincture), mistletoe (e.g. aqueous ethanolic essence), phytosterols (e.g. ⁇ -sitosterol), mullen flowers (e.g. aqueous alcoholic extract), drosera (e.g. liqueur- wine extract, sea-buckthorn fruits (e.g.
  • Preferred cosmetic active substances are natural and synthetic moisturising factors such as, for example, glycerin, urea and ceramides, skin-protecting agents, skin-lighteners, vitamins, antioxidants, so-called anti-ageing agents, anti-irritative agents, sun-screening agents, and the like.
  • moisturising factors such as, for example, glycerin, urea and ceramides, skin-protecting agents, skin-lighteners, vitamins, antioxidants, so-called anti-ageing agents, anti-irritative agents, sun-screening agents, and the like.
  • agents or active substances are intended for external application, in which case it may be a question of dermally active substances but also of transdermal active substances. They include, for example: agents for the treatment of skin diseases, externally applicable analgesics, e.g. dextropropoxyphene, pentazocine, pethidine, buprenorphine; antirheumatics/antiphlogistics (NSAR), e.g. indomethacin, diclofenac, naproxen, ketoprofen, ibuprofen, flurbiprofen, salicylic acid and salicylic-acid derivatives such as acetylsalicylic acid, oxicams; steroid hormones, e.g.
  • betamethasone dexamethosone, methylprednisolone, ethynyl estradiol, medroergotamine, dihydroergotoxine; gout remedies, e.g. benzbromarone, allopurinol; external dermatological agents, including antibacterial agents, antimycotics, antiviral active substances, anti-inflammatory active substances, antipruritic active substances, anaesthetizing active substances, e.g. benzocaine, corticoids, anti-acne agents, antiparasitic active substances; externally applicable hormones; venous therapeutic agents; immunosuppressives etc., all for external application.
  • external dermatological agents including antibacterial agents, antimycotics, antiviral active substances, anti-inflammatory active substances, antipruritic active substances, anaesthetizing active substances, e.g. benzocaine, corticoids, anti-acne agents, antiparasitic active substances; externally applicable hormones; venous therapeutic agents
  • Preferred therapeutic agents are analgesics, e.g. immunosuppressives, hormones, agents for the treatment of skin diseases such as neurodermatitis, atopic dermatitis etc., and anti-herpes agents.
  • the skeletal-forming agents in particular the polysaccharides, may also have certain therapeutic effects (for instance, the skeletal-forming agent that is preferably used, (sodium) alginate, acts antivirally to a certain extent), but they are not active substances in the sense of the invention.
  • auxiliary substances include: surface-active agents in addition to the aforementioned washing surfactants, such as dispersing agents, emulsifiers etc., fillers, pH-adjusting agents, such as buffering substances, stabilisers, co-solvents, pharmaceutically and cosmetically conventional or other dyestuffs and pigments, preservatives, plasticisers, lubricants and slip additives, etc.
  • surface-active agents such as dispersing agents, emulsifiers etc.
  • fillers such as buffering substances, stabilisers, co-solvents, pharmaceutically and cosmetically conventional or other dyestuffs and pigments, preservatives, plasticisers, lubricants and slip additives, etc.
  • pH-adjusting agents such as buffering substances, stabilisers, co-solvents, pharmaceutically and cosmetically conventional or other dyestuffs and pigments, preservatives, plasticisers, lubricants and slip additives, etc.
  • Squalane is a particularly preferred auxiliary substance.
  • the shaped articles according to the invention serve for external application on humans or animals and it is contemplated that nonhuman pheromones might be used. However, it is preferred that species specific pheromones are used depending on the subject. External application is effected in such a way that the shaped article according to the invention is preferably moistened with water or with an aqueous solution that may contain one or more active substances and/or auxiliary substances, or such is dissolved in water/solution.
  • the water/solution comprises a pheromone component and most preferably a human pheromone component.
  • an oil or alcohol based solution may also be used.
  • the shaped article may be totally dissolved, forming a solution, or may substantially disintegrate, forming a gel.
  • the shaped article according to the invention is dissolved in a relatively large quantity of water, it is a question, as a rule, of a bath application, and according to the invention this application is included in external application.
  • application is preferably effected in such a way that the shaped articles are moistened with a small quantity of water or of an active-substance and/or auxiliary-substance solution, forming a gel directly on the skin or in the hair.
  • the present invention is not limited in the pheromone composition used, nor to the amount of pheromone composition added to the solution.
  • exemplary human pheromone compounds include, but are not limited to, copulins (such as short chain aliphatic acids), estrene steroids, vomeropherins, such as 19-nor-cholane steroids, 19-nor- pregnane steroids such, and androstene and androstenedione compounds. Combinations and metabolites of the above-recited human pheromone compounds are also contemplated. It is preferred that the invention comprises 0.0000001 wt. % to up to 85 wt. %, preferably from 0.000001 wt. % up to 50 wt. % of the pheromone composition.
  • the present invention also relates to a combination including at least one of the shaped articles that are used in accordance with the invention and also at least one aqueous solution that contains one or more human pheromones and may contain an active substances and/or auxiliary substances, in a spatial arrangement (application pack, set, kit of parts, etc.).
  • active- substance solution it may be a question of, for example, solutions of readily volatile active and/or auxiliary substances that, by reason of the production process by freeze drying, should not be or cannot be introduced into the shaped article, such as, for example, certain portions of ethereal oils, perfumes, etc.
  • the shaped article that is used in accordance with the invention preferably contains at least approximately 10 wt. % of the skeletal-forming agent, relative to the total weight of the shaped article, preferably at least 15 wt. %, more preferably 30 wt. %, still more preferably at least approximately 50 wt. % up to 100 wt. % of the skeletal-forming agent, especially polysaccharides such as sodium alginate.
  • the shaped articles generally also contain residues of water. Depending on the type of the active substance (hydrophilic, hydrophobic), the water content may amount to up to 20 wt. %. The water content may change in the course of storage after production of the shaped article by freeze drying; as a rule, it may increase.
  • the water content of the shaped article after production preferably amounts to approximately 2 wt. % to 15 wt. %, more preferably 2 wt. % to 12 wt. %.
  • the shaped articles that are used in accordance with the invention contain from 0 wt. % to up to 85 wt. %, preferably from 0.000001 wt. % up to 50 wt. %, of one or more active substances.
  • the quantitative ratios depend very much on whether the active substance is a cosmetic active substance or a therapeutic active substance. In particular, the therapeutic active substances find application in very small quantities in certain circumstances.
  • the shaped articles contain from 0 wt. % to 85 wt. % of one or more auxiliary substances.
  • the shaped articles may contain 0.1 wt. % to 70 wt. % of the auxiliary substances, still more preferably 5 wt. % to 60 wt. % auxiliary substances.
  • shaped articles can also be applied that consist merely of the hydrophilic skeletal-forming agent and, optionally, additional auxiliary substances.
  • a preferred auxiliary substance is squalane.
  • the squalane surprisingly brings about an improved solubility of the shaped article, which alleviates external application on the skin.
  • squalane also has skin-caring effects, even though it is not an active substance in the sense of the invention.
  • the shaped article contains from approximately 10 wt. % to 60 wt.
  • a particularly preferred shaped article contains: at least 10 wt. % of one or more skeletal- forming agents, in particular polysaccharides, such as sodium alginate, in particular calcium-free sodium alginate, the 1 per-cent-by-weight solution or suspension of which in water (1 g in 99 ml water at 2O 0 C, pH 6-8) preferably has a viscosity of less than 2000 mPa.s, preferably less than 1000 mPa.s, particularly preferably less than 100 mPa.s, 0.000001 wt. % up to 50 wt. % of a human pheromone one or more active substances, 0.000001 wt. % up to 50 wt.
  • shaped article does not comprise any proteins by way of skeletal- forming agents.
  • the shaped article that is used in accordance with the invention preferably comprises optionally one or more active substances and also optionally one or more auxiliary substances, for the purpose of external application, a density from 0.005 g/cm-' up to 0.8 g/ cm , preferably 0.01 g/ cm ⁇ up to 0.8 g/ cm ⁇ , a volume from 0.1 cm ⁇ to 6 cm-% preferably 0.8 cm ⁇ to 6 cm , and a diameter (maximum spacing between two points in the shaped article) of at least
  • the shaped articles that are used in accordance with the invention constitute porous shaped articles with homogeneous distribution of the constituents (apart from coatings which are optionally present).
  • the rate of dissolution of the shaped articles that are used in accordance with the invention measured in accordance with a method for measuring the "Zerfallszeit von Tabletten und Kapseln" ("Disintegration-time of tablets and capsules") with a test apparatus according to PharmEU, preferably amounts to less than 4 minutes, still more preferably less than 1 minute (in the case of shaped articles with a diameter of 9 mm, complete hydration obtains after ⁇ 20 seconds without any discernible nucleus).
  • the shaped articles that are used in accordance with the invention are obtainable by means of a process that comprises the following steps: (a) producing a solution or suspension that contains at least one biopolymer, optionally one or more physiologically effective active substances and also optionally one or more auxiliary substances,
  • step (c) further steps may be implemented; in particular, it is possible after step (c) to carry out a treatment of the surface of the shaped articles by machining or by spraying with, for example, a pheromone composition, active-substance solutions, dyestuff solutions and/or with agents modifying the rate of dissolution.
  • the shaped article preferably has no surface coating and is homogeneously structured, in the sense of a uniform distribution of the constituents over the entire shaped article.
  • the procedure in the course of production is expediently such that, firstly, an aqueous solution of the skeletal-forming agent is produced and, subsequently, optionally the pheromone composition and optionally one or more active substances or alternatively one or more auxiliary substances are added and mixed.
  • the solution or suspension has a certain concentration of the keleton- forming agent. This concentration depends, of course, on the type of the skeletal-forming agent that is used. It expediently amounts to approximately at least 0.1 wt. %, relative to the total quantity of the solution, preferably at least approximately 0.25 wt. % up to approximately 20 wt. %, preferably less than 15 wt.
  • the quantity of the skeletal-forming agent that is contained in the solution or suspension decisively influences the density (weight of the shaped article relative to the volume of the geometrical shape of the shaped article) of the shaped article that is obtained.
  • the density is, in turn, an important variable for the rate of dissolution of the shaped article in the course of moistening with water or with an active-substance and/or auxiliary-substance solution.
  • the concentration of the skeletal-forming agent in the solution or suspension that is produced in step (a) is preferably selected from a range of approximately 0.25 wt. % to approximately 15 wt. %.
  • the densities of the shaped articles that are used in accordance with the invention expediently amount to approximately 0.01 g/cm 3 up to 0.8 g/cm 3 , preferably approximately 0.015 g/cm 3 up to 0.5 g/cm 3 , preferably approximately 0.02 g/cm 3 up to 0.1 g/cm 3 .
  • the concept of "density" as used in the present document designates the weight of the shaped article relative to the volume of the external geometrical shape of the shaped article.
  • the weight of the individual shaped articles depends, of course, on the size thereof. In general, the weight of the individual shaped articles amounts to approximately 10 mg to 200 mg, preferably 20 mg to 100 mg. For example, spheres with a diameter of 12 mm have a weight within the range of, preferably, 20 mg to 80 mg, more preferably 30 mg to 60 mg. For spheres having different diameters, corresponding preferred ranges are calculated.
  • Production of the solution that is subjected to freeze drying is preferably effected in such a way that, firstly, an aqueous solution of the skeletal-forming agent is produced and, subsequently, the pheromone composition, active substances or auxiliary substances which are optionally present are worked into the solution of the skeletal- forming agent. If use is made of oil-soluble active substances, these are preferably dissolved in oils (in particular, squalane) which are optionally used as auxiliary substances, and are subsequently added to the solution of the skeletal- forming agent.
  • oils in particular, squalane
  • the solution that has been produced in this way is then poured into a mould that exhibits cavities having the desired geometrical shapes corresponding to the shaped articles.
  • the mould preferably consists of natural rubber, silicone rubber, vulcanized rubber etc. Vulcanized-rubber molds are preferred.
  • the materials of the mould may optionally be coated.
  • the cavities of the shaped articles into which the solution is poured generally exhibit the shape of the desired shaped article. That is to say, the volume of the cavity corresponds substantially to the volume of the shaped articles that are later obtained.
  • Cooling or freezing of the solution can be affected as such in arbitrary manner. Cooling is preferably effected in the process that is used in accordance with the invention by blowing in cold air. Other processes include, for example, the immersion of the moulds in liquid gases, such as, for example, immersion in liquid nitrogen.
  • the rate of cooling influences the size of the ice crystals that are formed. These in turn influence the pore-size distribution of the shaped article that is formed. If few large crystals are formed, the shaped article exhibits few large pores. If many small crystals are formed, the shaped article exhibits many small pores. The crystals become smaller, the higher the rate of cooling of the solution or suspension.
  • the freezing- temperature that is required depends, inter alia, on how great the lowering of the freezing-point is by virtue of the active substances or auxiliary substances that are contained in the solution.
  • the temperature expediently lies below the freezing-point of water down to the temperature of liquid nitrogen (-196 0 C).
  • the freezing-temperature is preferably approximately -20 0 C to -80 0 C.
  • After-treatment can be effected mechanically, for example by means of a surface treatment (grinding, roughening, etc.).
  • a coating treatment is possible, such as, for example, spraying with a salt solution, for example with a view to forming less soluble shapes of the skeletal-forming agents, in particular in the case where use is made of sodium alginate and salt solutions of multivalent metal ions.
  • a dye solution may also be applied superficially onto the frozen shaped articles, resulting in colored shaped articles.
  • Freeze drying can be effected in a manner known as such, as described, for example, in DE 4328329C2 or DE 4028622C2.
  • a "pheromone” is a substance that provides chemical means of communication between members of the same species through secretion and peripheral chemoreception. In mammals pheromones are usually detected by receptors in the vomeronasal organ of the nose. Commonly, pheromones effect development, reproduction and related behaviors.
  • the pheromone compositions according to the present invention are intended to cause a change in human hypothalamic function, thereby altering certain behavior and physiology mediated by the hypothalamus of individuals.
  • pheromones can be identified by their species specific binding to receptors in the vomeronasal organ (VNO).
  • VNO vomeronasal organ
  • human pheromones bind to human receptors. This can be demonstrated by measuring the change in the summated potential of neuroepithelial tissue in the presence of the pheromone.
  • Human pheromones induce a change of at least about -5 millivolts in human neuroepithelial tissue of the appropriate sex (the binding of pheromones is generally sexually dimorphic, i.e., different in the effect of, or response to, a compound or composition between males and females of the same species).
  • Human pheromones induce sexually dimorphic changes in receptor binding potential in vivo in the human VNO.
  • Naturally occurring human pheromones can be extracted and purified from human skin and they can also be synthesized.
  • Human pheromones are pheromones which are naturally occurring in humans and effective as a specifically binding ligand in human VNO tissue, regardless of how the pheromone was obtained. Thus, both a synthesized and purified molecule may be considered a human pheromone.
  • the present invention is not limited in the pheromone composition used.
  • exemplary pheromone compounds include, but are not limited to, copulins (such as short chain aliphatic acids), estrene steroids, vomeropherins, such as 19-nor-cholane steroids, 19-nor-pregnane steroids, and androstene and androstenedione compounds. Metabolites of the above-recited human pheromone compounds are also contemplated.
  • the human pheromone Upon the VNO sensing of the pheromone in the shaped articles in accordance with the present invention, the human pheromone will exert its effect by altering hypothalamic and other brain function of an individual. Such alteration of brain function will bring about physiological and behavioral changes in individuals. The changes in physiological functions may cause the individual exposed to the shaped articles of the present invention to experience a unique, mood- altering effect or an overall sense of well-being.
  • the present invention is not limited to the use of a specific pheromone compound in the shaped articles and it is contemplated that certain shaped articles directed for men will contain a human pheromone compound different from the shaped articles directed for women or that a shaped article may contain a mix of human pheromone compounds.
  • Step 1
  • RO-water deinated water, reverse osmosis
  • Step 2 - lOO g RO-water
  • the citric acid is added to 100 ml RO-water under agitation.
  • Step 3 The solution of steps 1 and 2 are mixed intimately for about 30 seconds.
  • Step 4 The mixture from step 3 is poured into a mold and left to react for about 2 hours.
  • Step 5 The gelled shaped article is quick-frozen and freeze-dried.
  • Step 6 The freeze-dried, large- format, porous or sponge-like shaped article which, if necessary, is loaded with additional substances, can be prepared in the above-mentioned manner.
  • Manufacturing Method 2 Addition of a poorly soluble calcium salt to a multidentate complexing agent.
  • Step l
  • RO-water deinated water, reverse osmosis
  • Step 2 Work the alginate powder into the RO-water with a mixer until a homogeneous mixture is the result. Then, stir in the citric acid and pheromone component. At this stage, cosmetic and/or medical active substances and/or oils or other substances expediently may be worked into the solution if needed.
  • Step 3 The solution of steps 1 and 2 are mixed intimately for about 30 seconds.
  • Step 4 The mixture from step 3 is poured into a mould and left to react for about 1 h.
  • Step 5 The gelled shaped article is quick-frozen and freeze-dried.
  • Step 6 The freeze-dried, large-format, porous or sponge-like shaped article which, if necessary, is loaded with additional substances, can be prepared in the above-mentioned manner.
  • Example 7 2 g Na alginate and 1 g urea are dissolved in 96.0 g water, subject to stirring. Subsequently androstenone, 1.0 g squalane is added, subject to stirring. The homogeneous (degassed) mixture is poured into moulds, frozen out by blowing in air, taken out of the mould and subsequently freeze- dried in a manner known as such.
  • Example 7

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Abstract

La présente invention concerne des procédés de préparation d'articles profilés pour une application cutanée et qui peuvent contenir des substances actives et inactives, incluant des phéromones comprenant des agents formant squelette qui sont à la fois à base de protéines et non à base de protéines. Ces articles profilés devraient présenter une cohésion suffisante, à savoir, une force mécanique, devraient se dissoudre facilement lors de l'application sur la peau, et devraient donner une sensation agréable lors de l'application. De plus, en plus des phéromones, ces articles profilés devraient être appropriés pour recevoir diverses substances actives, telles que, en particulier, des substances cosmétiques actives et des substances actives thérapeutiques ou pharmaceutiques, et pour agir en tant que véhicules pour de telles substances. Les articles profilés peuvent être appliqués sur le derme ou les cheveux d'un sujet ou à l'intérieur du sujet.
PCT/US2008/010459 2007-09-06 2008-09-08 Objets profilés contenant un composant de phéromone humaine Ceased WO2009032325A1 (fr)

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US60/967,850 2007-09-06

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017103684A3 (fr) * 2015-12-17 2017-08-24 Performance Labs Pte, Ltd. Dispositif et procédé d'utilisation de composés organiques volatils qui affectent l'humeur, l'émotion ou un état physiologique
CN115282128A (zh) * 2022-08-02 2022-11-04 上海弗艾柏生物科技有限公司 猫面部信息素凝胶球及其制备方法
WO2023118255A1 (fr) * 2021-12-21 2023-06-29 Universitat Internacional De Catalunya, Fundació Privada Produit solide de soins personnels et procédé d'obtention d'un tel produit

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5718916A (en) * 1997-02-03 1998-02-17 Scherr; George H. Alginate foam products
WO2007034250A1 (fr) * 2005-09-19 2007-03-29 Mta Kémiai Kutatóközpont, Anyag És Környezetkémiai Intézet Substances de support pour pesticides destines a tuer des larves de moustique, produits pour tuer les larves de moustique, et procede de fabrication
US20070116742A1 (en) * 2005-11-22 2007-05-24 Braginsky Philip Y Confectionary products containing a human pheromone component

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5718916A (en) * 1997-02-03 1998-02-17 Scherr; George H. Alginate foam products
WO2007034250A1 (fr) * 2005-09-19 2007-03-29 Mta Kémiai Kutatóközpont, Anyag És Környezetkémiai Intézet Substances de support pour pesticides destines a tuer des larves de moustique, produits pour tuer les larves de moustique, et procede de fabrication
US20070116742A1 (en) * 2005-11-22 2007-05-24 Braginsky Philip Y Confectionary products containing a human pheromone component

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017103684A3 (fr) * 2015-12-17 2017-08-24 Performance Labs Pte, Ltd. Dispositif et procédé d'utilisation de composés organiques volatils qui affectent l'humeur, l'émotion ou un état physiologique
US10517879B2 (en) 2015-12-17 2019-12-31 Performance Labs PTE. LTD. Device and method of using volatile organic compounds that affect mood, emotion or a physiologic state
WO2023118255A1 (fr) * 2021-12-21 2023-06-29 Universitat Internacional De Catalunya, Fundació Privada Produit solide de soins personnels et procédé d'obtention d'un tel produit
CN115282128A (zh) * 2022-08-02 2022-11-04 上海弗艾柏生物科技有限公司 猫面部信息素凝胶球及其制备方法
CN115282128B (zh) * 2022-08-02 2024-03-19 上海弗艾柏生物科技有限公司 猫面部信息素凝胶球及其制备方法

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