Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers

Definitions

• the invention relates to new gel formulations for therapeutic and diagnostic purposes and to a method for producing these formulations.
• DE-OS 30 01 454 discloses lyophilisate formulations of hydroxyl-containing films with prostaglandins, which are converted into ready-to-use viscous solutions before use. The disadvantage of these formulations is that they form lumps which complicate the release of the active ingredient or prevent it.
• DE-OS 33 07 816 describes lyophilisates of alkali polyacrylates which are mixed with aqueous solutions of prostaglandins. Although the active ingredient is released better from this formulation, the partially inhomogeneous incorporation of the active ingredient into such gels with a consistently high viscosity and above all the applicability of these gels by the user remains unsatisfactory.
• the invention was based on the object of developing gel formulations for active ingredients with limited stability which are to be used in body cavities or on body surfaces.
• CA 1072-413 (Derwent Publication No. 18422C / 11) specifies the possible uses of polyoxyethylene-polyoxypropylene block copolymers as carriers for pharmaceuticals for therapeutic or prophylactic use on the body surface or in body cavities.
• the weight percentage of gel fractions is given as 15-50%.
• the preferred range emerges from the exemplary embodiment with 30% by weight: 20% Pluronic F 127 and 10% Pluronic L 44 in aqueous solution.
• Pluronic F-127 preparations can only be found for ophthalmic practice (DE-OS 27 03 152). It has now been found that for the therapeutic and diagnostic use of Pluronic F-127 gel formulations in body cavities or on body areas, the proportion of 18 to 19 percent by weight of Pluronic F-127 proves to be particularly advantageous in these formulations.
• the invention also relates to a method for producing Pluronic F-127 gel formulations for therapeutic and diagnostic use.
• Aqueous Pluronic F-127 solutions with a Pluronic F-127 content of 18-19 percent by weight are easily movable liquids with low viscosity at low and high temperatures and only form medium viscosity (20-50 ° C) highly viscous gels.
• This reversible sol-gel process allows the dissolved active ingredient to be easily incorporated homogeneously into a cooled Pluronic F-127 solution and drawn into a suitable application system (e.g. syringe with catheter tube).
• a highly viscous gel forms at the application site during and immediately after application.
• Figure 1 shows the temperature-dependent viscosity behavior of Pluronic F-127 solutions with different proportions of Pluronic F-127. It can be seen from this figure that an optimal viscosity for the body temperature range is achieved with solutions whose Pluronic F-127 content is between 13 and 19 percent by weight. A 20% Pluronic F-127 solution has to be cooled lower than a 13-19% solution in order to dissolve the active ingredient.
• Figure 2 in which the percentage of Pluronic F-127 was plotted against temperature, also shows why the 18-19% range is a particularly preferred range for galenical preparations.
• Pluronic F-127 formulations of the present invention have the advantage over the gels based on cellulose derivatives which have hitherto been customary in that the active ingredient in the cool state has no particular properties. Cooling can be incorporated, that Pluronic F-127 can be sterilized without changing its gel behavior and that the polymer in Pluronic F-127 solutions has short-term stability. All Pluronic F-127 formulations are easy to apply when cool and guarantee intensive fogging of the mucous membrane before they heat up and form gel. Pluronic F-127 is a good gel-forming agent that is compatible with the mucous membrane, is toxicologically harmless and is absorbed by the body after some time.
• the invention relates both to gel formulations with prostaglandins, steroid hormones, antifungals and antibiotics for theraneutic purposes and to gel formulations with X-ray contrast agents, ultrasound contrast agents and NMR contrast agents for diagnostic purposes.
• the invention also relates to a method for producing gel formulations with the substances mentioned above.
• the gel formulations according to the invention contain the
• Active ingredient in the therapeutically or diagnostically effective dose which is well known for the active ingredients under consideration. If necessary, known and customary auxiliaries are added to the new formulations in galenics.
• Pluronic F-127 are completely dissolved in 6.4g water (for injections) at a temperature of around 15 ° C.
• the solution cooled to 10 ° C., is filtered through a membrane filter with a pore size of 1.2 ⁇ m, filled into 10 ml vials and sterilized in an autoclave at 120 ° C. for 20 minutes.
• the Pluronic F-127 solutions are stored at temperatures below 8 ° C.
• the contents of an ampoule containing 100 pg of the active ingredient 16-phenoxyprostaglandin-E 2 -methanesulfonamide with 2.0 ml of water are taken up and added to the vial with the cooled Pluronic F-127 solution. After briefly shaking, a clear, homogeneous solution is formed which gels at temperatures above 18 ° C.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Gynecology & Obstetrics (AREA)
• Urology & Nephrology (AREA)
• Reproductive Health (AREA)
• Engineering & Computer Science (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Oil, Petroleum & Natural Gas (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
• Medicinal Preparation (AREA)

Applications Claiming Priority (2)

Publications (1)

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ID=6242046

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• 1984
  • 1984-07-27 DE DE19843428264 patent/DE3428264A1/de not_active Withdrawn
• 1985
  • 1985-07-18 WO PCT/DE1985/000237 patent/WO1986000813A1/de not_active Application Discontinuation
  • 1985-07-18 AU AU46723/85A patent/AU4672385A/en not_active Abandoned
  • 1985-07-18 EP EP85903649A patent/EP0227656A1/de not_active Withdrawn
  • 1985-07-18 JP JP60503347A patent/JPS61502817A/ja active Pending
  • 1985-07-26 IL IL75921A patent/IL75921A0/xx unknown
  • 1985-07-26 ES ES545616A patent/ES8705763A1/es not_active Expired
• 1986
  • 1986-03-11 DK DK111686A patent/DK111686A/da not_active Application Discontinuation

Non-Patent Citations (1)

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