Therapeutical composition comprising hydrolyzed carboxylalkyl ce

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

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1061972, 514781, 514867, 536 85, 536 89, 536 97, 536 98, A61K 3172, C08L 128

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active

053247175

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to the use of hydrolyzed carboxyalkyl cellulose as a therapeutical, a therapeutical composition comprising hydrolyzed carboxyalkyl cellulose, methods of preparing such a composition, and the use of hydrolyzed carboxyalkyl cellulose for the manufacture of the therapeutical composition.


BACKGROUND OF THE INVENTION

Laxatives and cathartics are drugs that promote defecation. Whereas laxative effect means the elimination of a soft, formed stool, the term cathartic implies a more fluid evacuation of the bowels. The laxatives can broadly be classified into four major groups, viz. emollient laxatives, bulk-forming laxatives, osmotic laxatives and irritants.
The emollient laxatives, or fecal softeners, are drugs that promote defecation by modest softening of the faeces. Examples are dioctyl sodium sulfosuccinate and some mineral oils.
Bulk-forming laxatives include various natural and semisynthetic polysaccharides and cellulose derivatives. These substances dissolve or swell in water to form an emollient gel or viscous solution that serves to maintain the faeces soft and hydrated. The resulting bulk promotes peristalsis, and transit time is reduced. Examples of bulk-forming laxatives are methylcellulose, sodium carboxymethyl cellulose, and vegetable fibers like Testa Isphaghula.
Osmotic laxatives are small non-absorbable molecules which by osmotic force draw water into the intestines and can either be fast-acting like Glauber's salt (Na.sub.2 SO.sub.4) or slow-acting like lactulose. From a mechanistic standpoint lactulose must be classified as an osmotic laxative, but the function will be that of a bulk laxative, since water, i.e. a mass, is drawn into the intestine.
Irritants, finally, induce water secretion and bowel mobility by chemical action. Examples are bisacodyl, castor oil, phenolphtalein, and anthraquinone glycosides (Sennosides A and B).
Bulk-forming laxatives like methyl cellulose and sodium carboxymethyl cellulose are hydrophilic semisynthetic cellulose derivatives marketed under various trade names. Their laxative effect is, however, not quite satisfactory. This is reflected by the numerous prior art disclosing the use of carboxymethyl cellulose as a carrier, thickener and additive for compositions with laxative or cathartic action where the pharmacological effect is largely due to the presence of an active agent, e.g. magnesium hydroxide, attapulgite, diphenolisatin; see, for example, EP-A-119 479, GB-A-1 158 169, JP-B-63026692, and FR-A-64982647.
The above mentioned osmotic laxative lactulose is a disaccharide consisting of fructose and galactose. The laxative effect of lactulose is thought to be due to the lower molecular weak acids formed in the degradation of the substance giving a bulk effect by osmotically binding water and thereby exerting a regulating effect upon the peristalsis. Lactulose has, however, several disadvantages in that it is needed in very large quantities, is very slow-acting and that the degradation thereof comprises the formation of substantial amounts of gases, which may cause abdominal pains and also is a social inconvenience.
There is therefore still a need for an efficient slowacting osmotic (bulk-forming) laxative with better efficiency than lactulose and lacking disadvantageous side-effects.


SUMMARY OF THE INVENTION

An object of the present invention is therefore to provide an osmotic laxative which is more efficient than conventional osmotic laxatives, such as lactulose.
Another object of the invention is to provide an efficient osmotic laxative substantially devoid of any detrimental side-effects.
Still another object of the invention is to provide an osmotic laxative which is cheap and readily available.
It has now surprisingly been found that hydrolysis products of carboxyalkyl celluloses, and more particularly hydrolyzed carboxymethyl, carboxyethyl or carboxypropyl cellulose, have remarkable osmotic laxative properties which far exceed those of lactulose and unhydrolyzed native carboxymethyl cellulose (bul

REFERENCES:
patent: 4444761 (1984-04-01), Spiller
patent: 4579943 (1986-04-01), Kamide et al.
Danhof, Ivan E., Pharmacotherapy, vol. 2, pp. 18-28 and table 1, (1982).
Pigman, W. W., Chemistry of the Carbohydrates, pp. 530, 532, 545, (1948).
Kennedy, John F., Carbohydrate Chemistry, pp. 48-49; 614, (1988).

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