Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-12-04
1998-02-03
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514786, 536 21, A61K 31725, A61K 4714
Patent
active
057144770
DESCRIPTION:
BRIEF SUMMARY
INTRODUCTION
This application is the national phase of PCT/SE94/00595, filed Jun. 16, 1994.
The present invention relates to pharmaceutical compositions containing heparin or heparin fragments or their derivatives in combination with one or more glycerol esters of at least one fatty add as single absorption enhancer. The compositions are useful for oral administration, for administration through mucous membranes or for transdermal administration. The compositions will when necessary contain further physiologically acceptable additives, such as diluents and/or carriers, suitable for the adaptation to oral, buccal, rectal, sublingual, nasal, subcutaneous or transdermal administration. The compositions according to the invention provides excellent absorption and bioavailability without employing additional enhancers or promoters.
BACKGROUND OF THE INVENTION
Heparin is a sulphate-containing polysaccharide widely used as an anti-coagulant, which originates from the intestinal mucosa of swine or lungs from cattles. It has been used for decades for the treatment and prevention of thrombosis. In recent years several new generations of heparin derivatives and fragments with more efficient and specific activity have been developed and marketed. Such low molecular fragments of heparin are disclosed e.g. in EP-A-0 014 184. The product, known as Fragmin.RTM., is marketed by Pharmacia AB of Stockholm, Sweden.
It has been a considerable problem to find alternative administration routes to injections for all heparins and their fragments due to their poor absorbability, for example when administered orally or rectally. A safe and efficient alternative to injections is therefore demanded for increasing the convenience for patients subjected to long-term treatment with heparins or heparin fragments.
There are several disclosures of pharmaceutical systems for enhancing the penetration of heparins or low molecular weight derivatives thereof through body membranes. Different rectal or enteral compositions are described in the patent specifications U.S. Pat. No. 4,156,719, DE-A-3 331 009 and EP-A-0 037 943. In these disclosures the bioabsorption is enhanced by means of various surface active agents or by carboxylic adds such as salicylic acid and glutamic acid. Compositions containing sulfones and fatty alcohols for oral, buccal and sublingual administration of heparin are described in U.S. Pat. No. 3,510,561. WO-A-88/10117 relates to an oral heparin composition containing a monosaccharide and a salt of a metallic cation. EP-A-0 130 555 discloses pharmaceuticals containing heparins and non-ionic tensides with improved permeability in the mouth and the nose.
However, none of these disclosed compositions have successfully led to products which substitute parenteral administration of heparins or heparin fragments.
It is the object of the present invention to provide new compositions containing therapeutically effective amounts of heparin, heparin fragments or their derivatives, which have a bioavailability high enough to result in clinically relevant plasma levels, when administered orally or through mucous membranes or through the skin, comparable to those obtained from a subcutaneous or intramuscular injection. According to the present invention such compositions are conceivable by using heparin in combination with one or several glycerol esters of fatty adds in a pharmaceutical composition. Medium chain glycerides have previously been used as absorption enhancers both in rectal and topical compositions, but only successfully when smaller molecules and certain polypeptides such as calcitonin and insulin are used in the system, and in most applications together with additional enhancing vehicles, such as surface active agents. There are currently no successful compositions in terms of improved biological absorption with larger therapeutically useful hydrophilic polysaccharides (such as heparins and their fragments) with glycerides of fatty adds as absorption enhancing components.
DESCRIPTION OF THE INVENTION
The invention i
REFERENCES:
patent: 3510561 (1970-05-01), Koh
patent: 4156719 (1979-05-01), Sezaki et al.
patent: 4434159 (1984-02-01), Sekine et al.
patent: 4656161 (1987-04-01), Herr
Taniguchi K, Muranishi S, Sezaki H. Int. J. Pharm. 4, pp. 219-228, 1980.
Muranishi, S. Modification of Intestinal Absorption of Drugs by Lipoidal Adjuvants. Pharmaceutical Research 1985, pp. 108-118.
Huang Evelyn
Ivy C. Warren
Pharmacia & Upjohn Aktiebolag
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