Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Utility Patent
1998-12-31
2001-01-02
Krass, Frederick (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C424S054000, C514S058000
Utility Patent
active
06169083
ABSTRACT:
TECHNICAL FIELD
The present invention relates to agents for treating and preventing stomatitis.
BACKGROUND ART
Stomatitis is caused on the basis of inflammation of an intraoral mucosa and means a symptom such as erosion, erythema or ulcer arising on an intraoral mucosa, angulus oris and/or labia oris. When the stomatitis becomes severe, it is accompanied by a pain and bleeding and gives a patient such serious problems that ingestion becomes difficult.
As causes attacked by stomatitis, severe diseases, dystrophy, infection with herpes simplex virus and the like have been well known. However, the mechanism of the attack has not been yet known.
It has also been known that severe stomatitis is induced by chemotherapy and radiotherapy for cancer as a side effect thereof. The stomatitis is one of dose limiting factors upon the administration of anticancer agent. In particular, the stomatitis often obliges the radiotherapy to stop the treatment or change the therapeutic scheme.
In general, intraoral cleaning, administration of various vitamin preparations, and the like have heretofore been conducted for treating stomatitis. In order to treat stomatitis attendant on chemotherapy and/or radiotherapy for cancer, it has also been conducted to administer a mouth wash containing allopurinol or sodium alginate [Archives of Practical Pharmacy, Vol. 55, No. 1, p. 28 (1995); Japanese Journal of Hospital Pharmacy, Vol. 18, No. 5, p. 510 (1992); Japanese Journal of Nursing Acts, Vol. 37, No. 15, p. 44 (1991); The Journal of Japan Society for Cancer Therapy, Vol. 25, No. 6, p. 1129 (1990); Japanese Journal of Cancer and Chemotherapy, Vol. 16, No. 10, p. 3449 (1989); and Nippon Acta Radiologica, Vol. 49, No. 8, p. 1047 (1989)].
However, the conventional therapies for stomatitis have involved such many problems as their improving effects on the symptoms are weak, and so the effects are insufficient for severe stomatitis, and it takes a long time to improve the symptoms.
Accordingly, there has been a demand for development of an agent which is excellent in therapeutic effect and capable of achieving treatment for a short period of time.
DISCLOSURE OF THE INVENTION
The present inventors have carried out an extensive investigation with a view toward solving the above-described problems. As a result, it has been found that an L-carnosine zinc salt or L-carnosine-zinc complex, or a combination of such a compound with sodium alginate is effective for the treatment and prevention of stomatitis, and particularly has marked therapeutic and preventive effects on stomatitis caused by chemotherapy and/or radiotherapy for cancer as a side effect thereof, thus leading to completion of the present invention.
According to the present invention, there is thus provided an agent for treating and preventing stomatitis, comprising an L-carnosine zinc salt or L-carnosine-zinc complex as an active ingredient.
According to the present invention, there is also provided an agent for treating and preventing stomatitis, comprising an L-carnosine zinc salt or L-carnosine-zinc complex, and sodium alginate.
According to the present invention, there is further provided a method of treating stomatitis, which comprises administering an effective amount of an L-carnosine zinc salt or L-carnosine-zinc complex.
According to the present invention, there is still further provided a method of treating stomatitis, which comprises administering effective amounts of any one of an L-carnosine zinc salt and an L-carnosine-zinc complex, and sodium alginate.
According to the present invention, there is yet still further provided use of an L-carnosine zinc salt or L-carnosine-zinc complex for the preparation of an agent for treating and preventing stomatitis.
According to the present invention, there is yet still further provided use of any one of an L-carnosine zinc salt and an L-carnosine-zinc complex, and sodium alginate for the preparation of an agent for treating and preventing stomatitis.
BEST MODE FOR CARRYING OUT THE INVENTION
The L-carnosine zinc salt or L-carnosine-zinc complex (hereinafter referred to as zinc L-carnosine), which is an active ingredient for the agents for treating and preventing stomatitis according to the present invention, is a salt or complex composed of L-carnosine and zinc. It has been known that two types of amorphous and crystalline forms exist in such a salt or complex (Japanese Patent Publication Nos. 5367/1991 and 116160/1995). A crystalline L-carnosine-zinc complex (the international general name: “polaprezinc”) is commercially available as an agent for treating gastric ulcer and is generally used in clinical treatment therefor.
Besides the anti-peptic ulcer effect (Japanese Patent Publication Nos. 5367/1991 and 116160/1995), preventive and therapeutic effects on hepatopathy (Japanese Patent Publication No. 62299/1992), therapeutic effect on pancreatitis (Japanese Patent Application Laid-Open No. 17022/1991), osteogenesis-facilitating effect (Japanese Patent Application Laid-Open No. 120257/1991), preventive and therapeutic effects on inflammatory bowel diseases (Japanese Patent Application Laid-Open No. 69338/1992), etc. have been known as the pharmacological effects of zinc L-carnosine. However, nothing has been known about the therapeutic and preventive effect of zinc L-carnosine on stomatitis.
On the other hand, sodium alginate is a polysaccharide constituting cell membranes of brown algae, and is commercially available and in common use in various preparation forms as an agent for protecting a mucosa and homostasis.
However, nothing has been known about the fact that sodium alginate exhibits therapeutic and preventive effects on stomatitis by using it in combination with zinc L-carnosine.
The zinc L-carnosine useful in the practice of the present invention may be either amorphous or crystalline. Crystalline zinc L-carnosine and amorphous zinc L-carnosine can be prepared in accordance with the processes described in Japanese Patent Publication No. 116160/1995 and Japanese Patent Publication No. 5367/1991, respectively.
The sodium alginate used in the present invention may also be a marketed product.
The agents for treating and preventing stomatitis according to the present invention are preferably provided in the preparation form of a mouth wash or intraoral ointment.
These preparations can be formulated by suitably selecting in combination proper additives from, for example, distilled water for injection, purified water, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, lactose, sorbit, mannit, sucrose, corn starch, crystalline cellulose, lactitol, cellulose derivatives, gum arabic, tragacanth gum, gelatin, polysorbate 80, talc, magnesium stearate, water, ethanol, white petrolatum, glycerol, fat, fatty oils, glycols, higher alcohols such as stearyl alcohol, plastibase, paraffin, beeswax, polyoxyethylene hydrogenated castor oil, saccharin, pine syrup, etc.
The mouth wash preparation is preferably used in the form of, for example, a suspension, syrup or emulsion. However, it is more preferably used in the form of the suspension because zinc L-carnosine is hardly soluble in water. Such a suspension may also be prepared just before use by formulating a tablet, powder or granule preparation from active ingredients in advance, grinding it in a mortar or by a grinder, adding the ground product to distilled water for injection or purified water and then optionally adding an excipient such as calcium carboxymethyl cellulose or sodium carboxymethyl cellulose thereto. The suspension may also be prepared for use by preparing an aqueous solution of sodium alginate in advance and adding and incorporating zinc L-carnosine into the aqueous solution.
In a clinical treatment, a commercially available polaprezinc preparation (trade name: “Promac Granule 15%”) may also be used to prepare a suspension just before use like the above powder or granule preparation. Besides, a commercially available liquid preparation of sodium alginate is used in place of the distilled water for injection or purified
Hirano Masaaki
Katayama Shirou
Krass Frederick
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
Zeria Pharmaceutical Co. Ltd.
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