Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1996-08-30
1998-05-12
Leary, Louise
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536124, 536112, 536104, 435136, 435135, 435134, 562887, 562405, 562400, 560 1, 560 2, 560 5, 252351, C08B 3716, C08B 3702, C07G 1700, C12P 740
Patent
active
057506787
DESCRIPTION:
BRIEF SUMMARY
The invention relates to water-soluble dextran fatty carboxylates, a process for their preparation and their use as solubilizers for pharmaceutical or cosmetic active substances which are sparingly soluble in water. The dextran fatty carboxylates according to the invention are macromolecular surfactants which, surprisingly, in contrast to most low molecular weight surfactants have no haemolyzing properties and which therefore enable the formulation and production of pharmaceutical and cosmetic preparations which are better tolerated.
Pharmaceutical and cosmetic active substances are not always sufficiently soluble in water. Inadequate water solubility of active substances means that homogeneous preparations with an acceptable appearance cannot be obtained and also that in many cases the effect being striven for cannot be achieved to the optimum extent. This type of active substance, therefore, has to be solubilized with amphiphilic agents, eg surfactants. Not only the appearance but also the bioavailability and the efficacy are improved by this means and in this way. The bioavailability of the active substance also depends on the conditions prevailing at the site of re-sorption in the patient, such as the degree of fullness of the stomach and digestive tract and on peristalsis. In the case of topically applied transdermal and cosmetic preparations, analogous problems also occur during penetration or permeation of the active substance in the parts of the skin or mucous membrane involved, these being associated with the ability to disperse and with diffusion properties. Unsatisfactory dissolution of the active substance also produces non-uniform distribution and thus a non-uniform effect.
In WO 92/10211 pharmaceutical preparations are described which contain sparingly soluble active substances and which are intended for intravenous application. To solubilize the sparingly soluble active substance a polymer is used which consists of three parts A, B and C. Preparation of the polymer requires several steps, which is a disadvantage.
Preparations made from pure dextran, hydroxyethyl starch or other suitable polymers are used as plasma expanders in hypovolemic conditions, ie. they are assumed to be pharmacologically harmless. Dextran 60 with an average molecular weight of 60,000 (varying between 25,000 and 110,000) and dextran 40 with an average molecular weight of 40,000 (varying between 15,000 and 70,000) are used as 6% or 10% strength solutions. Dextran 40 is capable of improving microcirculation. Aggregates of erythrocytes and thrombocytes are broken up and the viscosity of the blood is lowered.
Dextran 40 has a half-life in blood of about 6 hours, dextran 60 has a half-life of more than 24 hours. The upper threshold for the ability of dextran to pass through or be present in the kidneys is located at a relative molecular weight of about 50,000. Thus dextrans are largely eliminated via the kidney. The proportion remaining in the body is slowly and completely degraded by endogenous enzymes to produce water and carbon dioxide. Tolerance to dextrans is good.
Dextran esters of a variety of fatty acids (C.sub.4 to C.sub.18) have been known for some time. However, up to the present only water-insoluble products have been described on the whole. At the moment there are still no satisfactory systems known by means of which sparingly soluble drugs or sparingly soluble cosmetic agents can be converted into a form which is suitable for use in humans or animals. Thus, in particular, sparingly soluble pharmaceutical active substances cannot be converted into a form which is suitable for parenteral or oral or dermal or trans-dermal application, or only with great difficulty.
The present invention is based on the object of providing surfactants which have the property of solubilizing cosmetic and pharmaceutical active substances which are sparingly soluble or insoluble in water or in a physiological substrate.
According to the invention, oligomeric or polymeric surfactants will be provided which are characterized by a lack
REFERENCES:
patent: 5264460 (1993-11-01), Jakobson et al.
patent: 5576012 (1996-11-01), Bauen et al.
Die Pharmazie, vol. 50, No. 6, Jun. 1995 DE, pp. 403-407, T. Reinhart, et al. "Untersuchungen zum Hamolyse-und . . . ".
Chemical Abstracts, vol. 79, No. 16, 22 Oct. 1973, Columbus, OH, US; abstract No. 93706d.
Bauer Kurt H.
Reinhart Thomas
Bauer Kurt H.
Leary Louise
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