DESCRIPTION

The present invention relates to a composition for prop¬ hylactic and/or therapeutic treatment of impaired gingival conditions such as gingivitis and periodontitis. An object of the invention is to provide a prophylactic and/or therapeutic agent against periodontitis in a form which increases the effect of such agent. A further object is to provide such agent in a convenient and palatable form.

BACKGROUND

Periodontitis, the disease of tooth-loosening, is estimated to involve, in one form or another, every second adult person in the occidental world.

Gingival diseases affect 9 of 10 americans at least once in life and 25 % will lose all their teeth due to tooth- loosening before reaching the age of 60. Due to the serious nature of the disease, many dentists get in quandary when attempting to cure this often uncontrollable disease. Millions of patients every year are operated on in attempts to clear out inflamed tissue.

Many causes are believed to be behind the problem. The disease starts rather innocently with a bacterial membrane on the teeth which can be brushed away or removed with dental floss. Said membrane or layer is known as dental plaque and is concentrated to the neck of the tooth near the dental gum (gingiva) . Healthy dental gum and bone are the only means for holding the tooth in place. If the plaque on the tooth surface is not removed, bacteria will permanently

settle on the tooth surface. By-products from the bacteria cause inflammation in the dental gum, which turns red, soft and swollen and gets affected with an increased tendency of bleeding. The plaque will subsequently be converted into tartar.

The tissue closely adjacent to the teeth will be destroyed and the gingiva will be released from the teeth, forming pockets which are filled with plaque. Inflammation and infection occurs in the tissues surrounding the neck of the tooth, which leads to a gradual loosening of teeth, formation of pockets and bleeding gum, and, if appropriate measures are not taken, loss of teeth.

Research in later years in the field of tooth-loosening diseases indicate that such disease is not only a local problem in the gingiva, but part of the cells of the immunological defence system are involved in the reactions following plaque formation. This involvement in turn results in an impaired efficiency in these cells. Tooth loosening is currently considered to be a general disease condition, in which the immunological defence is strongly involved.

One of the problems occurring is the formation of free radicals and the maintenance thereby of degradation in the local area affected.

PRIOR ART

Coenzyme Q 10 or ubiquinone 50 has advantageous effects on the general health status. It has been employed with systemic and topical administration in treatment of various conditions.

JP-A-61286314 published 16 December 1986 discloses oral hygiene compositions containing ubiquinone-10 effective against gingival diseases. The oral hygiene compositions disclosed are dentifrices such as tooth pastes or mouth- washes wherein ubiquinone occurs in admixture with known pharmaceuticals. It has however turned out that ubiquinone in a homogenous aqueous liquid or viscous fluid composition is subject to oxidation and decomposition mediated by usual pharmaceutical additives. Furthermore, the prior art dentifrices provide insufficient contact area and contact time with the tissue affected by periodontitis.

DISCLOSURE OF THE INVENTION

The present invention provides a new chewable composition comprising one or more chewable gum bases, and optionally one or more sweeteners and/or further additives, flavouring and aroma, and is characterized in further comprising an amount of coenzyme Q 10 effective in prophylactic or therapeutic treatment of impaired gingival conditions.

The chewable composition of the invention has been found to increase the healing ability in inflamed gingiva and to counteract the formation of free radicals and the damage caused by those. The chewable physical form of the composition has been found to increase both the area and the time of contact with the gingiva. An unexpected advantage with the composition of the invention is the attainment of a dual effect of coenzyme Q 10 in that said coenzyme is absorbed both locally by the affected gingival tissue and systemically via saliva swallowed. Furthermore, the chewable composition has been found to provide a massage effect on the tooth supporting tissues, which enhances the valuable effect of the coenzyme Q ^' 10.

Chewable gum bases are wellknown in the art, and one of ordinary skill in the art can identify am appropriate gum base that will mix well with the active ingredient(s) and which provide an adequate resistance on chewing. The chewable gum bases employed may in particular be selected from chewing gum bases containing natural and/or synthetic elastomers such as styrene-butadiene copolymer, polyisobutadiene and isobutylene-isoprene copolymer. The chewable gum bases may further optionally comprise a plasticizer for the elastomer, a resinous compound, a plasticizer for the resinous compound, ester gums and further optional components.

The chewable composition of the invention is preferably formulated as a chewing gum, which may be in leaf or tablet form and may be uncoated or coated with coating composition soluble in the saliva.

The composition may comprise a sweetening agent as known in the art. Sugars or sugar alcohol may be employed. However sucrose and other teeth-damaging sugars are non-preferred. In a preferred embodiment of the invention, xylitol is used as a sweetener. Other particularly useful sweeteners include e.g. sorbitol and aspartam. Since coenzyme Q 10 is a lipid soluble compound, an emulsifying agent such as lecithin may be included in the composition. Further additives optionally employed in the composition of this invention include excipients as known in the art such as anti adhesive agents known from SE-B-7604236-5. The composition may optionally comprise further pharmacologically active agents, such as fluorides e.g. sodium fluoride, free radical scavengers such as vitamin E and superoxide dismutase, antiseptics, antibiotics, antiviral agents or enzymes.

According to a further preferred embodiment of the invention, coenzyme Q 10 is included in the composition in

a form providing for release thereof during an extended period of time. Thus, coenzyme Q 10 may be microencapsulated or in a form obtained by the method described in EP-B-0 320 552, alone or in admixture with one or more other constituents of the composition.

The amount of coenzyme Q 10 in the composition may vary within broad limits depending on whether a prophylactic or therapeutic effect is desired and depending on the recommended number of administrations per day. Thus, the amount may be 0.001 - 75 % by weight of the final composition. In a preferred composition, the amount is 0.1 - 0.5 % by weight of the final composition, and in particular about 0.3 %. The recommended daily dosage of coenzyme Q 10 to an adult human subject is 10 - 100 mg/day, preferably about 30 mg/day.

The invention is further illustrated by the following examples:

Example 1

A chewing gum base is made with the following general composition:

Elastomer: Styrene-butadiene copolymer 0.2-35% Plasticizer for the elastomer: Butyl stearate, glyceryl trioleate, oleic acid 0.2-35 %

Resinous compound: Polyvinyl acetate (mw > 30000) 1-70 % Plasticizer for the resinous compound: Triacetin, acylated monoglyceride 0.5-20 %

Optional further compounds: Fillers such as CaC0 ₃ 0-55 %, waxes 0-25 %, texturizing and emulsifying agents 0-15 %

The ingredients are mixed in a kettle mixer at a temperature of 90 °C by adding to the styrene-butadiene copolymer a first portion of polyvinyl acetate followed by butyl stearate. Then the remaining polyvinyl acetate is added together with glyceryl trioleate and acetylated monoglyceride.

Example 2

A chewing gum base is made with the following general composition:

Elastomer: Chicle gum 0.2-35%

Plasticizer for the elastomer: jojoba oil, petrolatum, squalane, squalene, peanut oil 0.2-35 %

Resinous compound: Gum arabic 1-70 %

Plasticizer for the resinous compound: Triacetin, acylated monoglyceride 0.5-20 %

Optional further compounds: Fillers such as CaC0 ₃ 0-55 %, waxes 0-25 %, texturizing and emulsifying agents 0-15 %

Example 3

A chewing gum base was made with the following composition:

Parts bv weight

Chicle gum 100 % 30

Gum arabic 10

Glycerol 5 Glyceryl triacetate 10

CaC0 ₃ 20

Texturizing components Paraffin wax 15 CaC0 ₃ 10

Chicle gum was mixed with gum arabic in a kettle mixer at a temperature of 90 °C to form an elasto-plastic mixture, which was then mixed with glycerol, glyceryl triacetate and CaC0 ₃ . The texturizing components were then added while stirring at the same temperature as previously.

The gum base thereby formed was found to be smooth, semi¬ fluid and flowed easily at the mixing temperature. On cooling no phase separation was observed;

Example 4

A chewing gum base was made with the following composition:

Parts bv weight of Elastomer component gum base

Styrene-butadiene copolymer 3

Styrene-butadiene elastomer 5 Ester gum 8

CaC0 ₃ 23

Resin component

Polyvinyl acetate (mw = 30000) 26 Polyvinyl acetate (mw = 10000) 3

Glyceryl triacetate 6

CaC0 ₃ 4

Third texturizing component Paraffin wax 7

Micro-crystalline wax 5

CaC0 ₃ 10

The components were mixed, and a chewing gum base was prepared according to the procedure of Example 1. On cooling no phase separation was observed.

Example 5

A chewing gum composition was prepared with the following formula:

Xylitol 450.00 g

Chewing-gum base (Example 1) 250.00 g

Sorbitol 168.00 g

Gum arabic 80.00 g

Lecithin 20.00 g Glycerol 15.00 g

Citric acid 10.00 g

Fruit flavour 6.00 g

Coenzyme Q 10 1.00 g

1000.00 g

The ingredients xylitol, gum base, sorbitol and gum arabic were mixed together with glycerol in a kettle mixer at a temperature of 90 °C. In a separate kettle mixer, lecithin was mixed with coenzyme Q 10 and citric acid at a temperature of 50 °C. The lecithin mixture was added to the first mixture at a temperature of 50 °C and stirred for 1 hour. The flavouring agent was then added to the final product.

Example 6

A chewing gum composition was prepared according to the procedure of Example 5 with the following formula:

Xylitol 400.00 g Chewing-gum base (Example 3) 200.00 g

Sorbitol 180.00 g

Gum arabic 161.50 g

Glycerol , 20.00 g

Flavour 8.00 g

Coenzyme Q 10 0.50 g

Lecithin 20.00 g

Citric acid 10.00 g

1000.00 g

Example 7

A chewing gum composition was prepared according to the procedure of Example 3 with the following formula:

Xylitol 500.00 g

Chewing-gum base 260.00 g Gum arabic 180.00 g

Glycerol 25.00 g

Citric acid 7.00 g

Flavour 5.00 g

Coenzyme Q 10 3.00 g Lecithin 20.00 g

1000.00 g

Example 8

A chewing gum composition was prepared with the following formula:

The ingredients sucrose, gum base, sorbitol and glycerol were mixed in a kettle mixer at a temperature of 100 °C to form a homogenous first mixture. In a separate kettle mixer lecithin and coenzyme Q 10 were mixed and added to the first mixture. Citric acid was added and the mixture was stirred at 50 °C for one hour. Finally, the flavouring agent was added to the product.