Use of heparin or heparan sulphate in combination with...

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

Reexamination Certificate

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Details

C514S056000, C514S057000

Reexamination Certificate

active

06207653

ABSTRACT:

TECHNICAL AREA
The present invention refers to the use of certain sulphated polyanionic glucoseaminoglycans for the manufacture of medicaments that can be used for preventing or treating infections caused by herpes virus.
BACKGROUND OF THE INVENTION
Herpes is the common name for a family of viruses which generate infectious disease in mammals including man. Contrary to the majority of infections herpes viruses usually generate what is called latent infections, thus residing dormant in nerve roots of the central nervous system and subsequently causing active disease when activated by some unknown factor. There is today no method available for the treatment of such infections. Factors activating the disease are mostly unknown but it is believed that stress, fever, menstruation, sunlight etc. can be the cause of activation of the virus. From a practical viewpoint the herpes viruses typically cause a skin rash as a major manifestation.
Two main types of herpes simplex viruses are known, HSV-1 causing oral herpes and HSV-2 causing genital herpes. The viruses cause reoccurring, painful skin and mucosa lesions in about 10% of the population. The pain and cosmetic effects of the disease are of primary concern for most patients and pain relief and more rapid healing would represent a major advance in the art. It is essential to note that healing occurs spontaneously in most patients and one major object of the effort should therefore be directed to hasten the healing process and to provide analgesic effect.
SUMMARY OF THE INVENTION
The present invention has for its main object to provide for new techniques for the prevention or treatment of infection disease caused by herpes virus in mammals including man.
Another object of the invention is to provide for a new combination of active ingredients to be used for the manufacture of a medicament for such prevention or treatment.
Yet another object of the invention is to provide a process for the treatment of infections in mammals including man caused by herpes virus.
For these and other objects which will be clear from the following disclosure the invention provides for new techniques residing in the use of heparin or heparan sulphate in combination with chlitosan for the manufacture of a medicament for the prevention or treatment of infectious diseases caused by herpes virus in mammals including man.
In such use it is preferred that the manufacture of said medicament is based on a combination of heparin and chitosan.
Both heparin and heparan sulphate are commercially available on the market from several manufacturers. Also partially hydrolyzed forms of these ingredients can be used provided that their biological activity remains substantially unaltered.
The medicament to be used to prevent or combat infectious disease caused by herpes viruses can be presented in different physical forms, for example as powders, ointments, pastes, gels, suspensions or solutions. The form to be used is, of course, adapted to the nature of the disorder to be treated.
One of the main components in the present medicament is the polysaccharide chitosan which is a linear 1,4-bound polysaccharide built up from &bgr;-D-glucoseamine entities. The chitosan is manufactured by N-deacetylation of chitin, a polymer which forms the shell of inter alia insects and crayfish. Commercial chitin is recovered from crab and shrimp shells which constitute waste products from the fishing industry. By regulating the alkali treatment of chitins it is possible to manufacture chitosans of varying degrees of N-acetylation. When treating chitin with alkali, such as sodium hydroxide, N-deacetylation takes place wherein acetamido groups are converted to amino groups thus forming chitosan.
The physical properties of chitosan affecting its utility depend on the degree of N-acetylation, molecular weight and homogeneity. Chitosan is biodegradable, both by chitinas from the digestive system and by lysozyme in body fluids.
It is preferred in connection with the use of the present invention that the chitosan has a degree of N-acetylation of at most about 90% and preferably at most about 50%. It is particularly preferred that the degree of N-acetylation is less than about 25%.
The two main components of the medicament involved in the present invention, heparin or heparan sulphate and chitosan, are suitably used in combination with conventional carriers or excipients of a medicinally acceptable character. Quite generally it is preferred that the matrix is an aqueous matrix, and the carrier or the excipient may contain a viscosity-increasing polysaccharide, which can be selected from hemicelluloses, for example arabino xylanes and glucomannanes, plant gums, for example guar gum, locust bean gum, celluloses and derivatives thereof, for example methylcellulose, ethylcellulose, hydroxiethylcellulose, carboximethylcellulose, starch and starch derivatives, for example hydroxiethylstarch or crosslinked starch, microbial polysaccharides, for example xanthan gum, curdlan, pullulan, dextran. Also algi polysaccharides, for example agar, carrageenans, alginic acid, can be used as a constituent in the carrier or excipient.
A preferred polysaccharide for use in the carrier or excipient is a cellulose derivative, for example methylcellulose.
In the subject medicament it is preferred that the combined amount of viscosity-increasing polysaccharide and said chitosan is less than about 10% by weight based on the total weight of the medicament.
A preferred physical form of the medicament is the gel form, and in such gel-formed medicament said combined amount of polysaccharide and chitosan is preferably within the range about 0,5 to about 5% by weight based on the medicament as a whole.
Said heparin or heparan sulphate is preferably present in the medicament in an amount of from about 0,1 to about 2% by weight.
The present invention also provides for a process for the prevention or treatment of infectious diseases in mammals including man caused by herpes viruses. This process comprises the step of applying onto a site in need of treatment an active amount of a medicament containing in combination heparin or heparan sulphate and chitosan.


REFERENCES:
patent: 4465666 (1984-08-01), Lukas et al.
patent: 0000133A1 (1979-01-01), None
patent: 0240098A2 (1987-10-01), None
patent: 0497341A2 (1992-08-01), None
Takizawa et al 117 CA:178315, 1992.*
Baba et al 110CA:349, 1988.

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