INTRODUCTION:

Man has been constantly waging a war against disease. Nature has gifted mankind with various powerful weapons to fight against the diseases he is suffering from. In the yester years man was dependent on drugs of natural origin to combat diseases but over a period of time he has invented synthesis of drugs as his own weapon against diseases he is suffering from; of late synthetic drugs has become more popular than the natural counter parts but still there are some areas were natural drugs are preferred to their synthetic counter parts, one such area is antiulcer drugs.

Mouth ulcer⁽¹⁾

A mouth ulcer (also termed an oral ulcer or a mucosal ulcer) is an ulcer that occurs on the mucous membrane of the oral cavity. They are painful round or oval sores that form in the mouth, mainly on the inside of the cheeks or lips. Mouth ulcers are very common, and they occur in association with many diseases and by different mechanisms, but usually there is no serious underlying cause. Common causes of mouth ulcers include nutritional deficiencies such as iron, vitamins especially B12 and C, poor oral hygiene, infections, stress, indigestion, mechanical injury, food allergies, hormonal imbalance, skin disease etc. Mouth ulcers, also known as aphthous ulcers, can be painful while eating, drinking or brushing teeth.

Types of mouth ulcer⁽¹⁾

On the basis of ulcer size and number, mouth ulcer can be classified as Minor, major, and herpetiform

Minor ulcers:

These are around 2-8mm in diameter and they usually clear up in 10 days to 2 weeks.

Major ulcers:

These are bigger and deeper, often with a raised or irregular border. This type of ulcer can take several weeks to heal and may leave a scar in the mouth.

Herpetiform ulcers:

This type of ulcer is a cluster of dozens of smaller sores about the size of pinheads.

Causes of mouth ulcers⁽²⁾

Mouth ulcers are not contagious. The exact cause of oral ulcers is not known, but there are several factors that are suspected of contributing to their appearance.

· Trauma or Tissue Damage:

Damage to the mouth lining is common. Damage from vigorous brushing, orthodontic braces, ill-fitting dentures or biting the inside of your mouth can cause a mouth ulcer to form.

· Infections:

Bacterial, viral or fungal infections may cause mouth ulcers.

· Stress Related Mouth Ulcers, Aphthous Ulcers:

Most common in teens, stress-related mouth ulcers will heal within a couple of weeks. Prevention is by resolving stress-related problems or using stress-busting relaxation strategies. Hormonal changes and allergic reactions may also cause mouth ulcers.

· Foods and Drinks:

Mouth ulcers may be triggered by acids in certain foods, including oranges, lemons, pineapples, strawberries, tomatoes, and others.

· Toothpaste or Oral Rinses:

Pastes or rinses that contain sodium lauryl sulfate may contribute to the appearance of mouth ulcers.

· Vitamin Deficiencies:

A deficiency of vitamins such as B-12, iron, folate or zinc could also be a cause of mouth ulcers.

· Quitting Smoking:

Immediately after quitting smoking you may get mouth ulcers. This is usually temporary.

Herbal Remedies for Mouth Ulcer⁽¹⁾

Phytogenic agents are traditionally used by herbalists and indigenous healers for the prevention and treatment of ulcer. Botanical compounds with anti-ulcer activity include flavonoids (i.e. quercetin, naringin, silymarin, anthocyanosides, sophoradin derivatives) saponins (i.e. from Panaxjaponicusand Kochia scoparia), tannins (i.e. from Lin deraeumbellatae), gums and mucilages (i.e. gum guar and myrrh). Among herbal drugs, liquorice, aloe gel and capsicum (chilli) have been used extensively. Ethno medical systems employ several plant extracts for the treatment of ulcer.

Herbal anti ulcer drugs:⁽³⁾

· Harra (Terminalia chebula)⁽⁴⁾chewed after dinner cures mouth ulcers.

· Basil leaves (Ocimum sanctum)⁽⁵⁾ and Tomato juice (Lycopersicum esculentum) are taken for mouth ulcers.

· Powder of nirgund (Vitex negundo) and Musli (Chlorophytum borivilicum) is prepared and taked four times a day for mouth ulcers.

· Mulberry (Morus alba) juice is given to infants for this ailment.

· Akarkara (Spilanthes calva) flower is chewed in mouth ulcers. It gives strength to the teeth.

· Ash of burnt fruit bark of the water melon is also given.

· Solanum and gingelly oil are also used for mouth ulcer.

Advantages of herbal medicines:

· Herbal medicines have a long history of use and better patient tolerance and public acceptance.

· Medical plants have a renewable source, so that we can have sustainable supplies of cheaper medicines for the worlds growing population.

· Because of the rich agro-climatic, cultural and ethnic bio diversity of developing countries like India availability of medicinal plants is not a problem.

· The cultivation and processing of medicinal herbs are eco-friendly.

· Prolong and apparently uneventful use of herbal medicines is safe and efficacious.

· Large numbers of medicinal plants and dietary nutrients have been shown to possess antiulcer activities such as Aloe, Terminalia chebula, Vetiveriaziziinoides, Ginseng, Capsicum etc.

Mouth ulcer treatment:

Mouth ulcers can heal within 2 weeks without treatment but medicine and treatment may provide relief ⁽⁶⁾. Treatment can numb the pain, protect the ulcer from further damage or decrease the chances of a bacterial infection; some medicines may speed up the healing if used early enough.

Paste treatments, gel treatments, mouth washes, liquid paint treatments, neutralizing acid and numbing of the pain, pain killers, corticosteroids⁽⁷⁾

Medicated Chewing gum:

Medicated Chewing Gum (MCG) is a novel drug delivery system containing masticatory gum base with pharmacologically active ingredient and intended to use for local treatment of mouth diseases or systemic absorption through oral mucosa. MCG is considered as vehicle or a drug delivery system to administer active principles that can improve health and nutrition. Medicated chewing gum is a solid or semisolid dosage form which consists of one or more active ingredient (water soluble or insoluble) incorporated in water insoluble base. Many scientific studies have explored the role of chewing gum in promoting healthy teeth. Gum chewing is a common habit in many countries⁽⁸⁾. Chewing gum has been used for centuries to clean the mouth and freshen the breath. A MCG containing Acetyl Salicylic Acid was commercially introduced in 1928⁽⁹⁾. Chewing gum was initially sweetened with sugar, which contributed to dental caries. Today, however, more than 50% of chewing gum sold in Europe is sweetened with sugar substitutes (polyols). Clinical evidence shows that sugar substituted chewing gum does not lead to caries, because the polyols do not lead to a clinically relevant production of metabolic acids in dental plaque. The objective of this systematic literature review is to appraise existing evidence concerning a possible therapeutic/anti-carcinogenic effect of sugar-free chewing gum for patients. MCG represents the newest system with potential uses in pharmaceuticals, over the counter medicines and nutraceuticals^(10,11).Unlike chewable tablets medicated gums are not supposed to be swallowed and may be removed from the site of application without resort to invasive means and MCGs are solid, single dose preparations. As for as patient convenience is concerned it is discrete and easy administration without water promotes higher compliance. Since it can be taken anywhere, a chewing gum formulation is an excellent choice for acute medication. The advantages for children and for patients who find swallowing tablets difficult are obvious.

History of Medicated Chewing Gum⁽¹²⁾

One thousand years ago, the Mayan Indians chewed tree resin from the sapodilla tree in order to clean their teeth and freshen the breath. Shortage of natural gum bases during World War II enhanced development of the synthetic gum bases that are used today. The first patent for the production of chewing gum was filed in 1869 and was issued to Mr. W. F. Semple in Ohio under U. S. Patent No. 98,304. The first medical chewing gum, Aspergum®, was launched in 1928. This chewing gum contains the analgesic substance acetylsalicylic acid known from Aspirin® tablets. Chewing gum did not gain acceptance as a reliable drug delivery system until 1978, when nicotine chewing gum became available. Another commercially available medical chewing gum is dimenhydrinate-containing chewing gum for motion sickness. Chewing gum has an old and long history, in 50 AD; the Greeks sweetened their breath and cleansed their teeth by using mastiche, a resin from the bark of mastic tree. (The English word "masticate" is derived from the root word mastiche) At the beginning of its history this product was not so much accepted by the public. Spruce gum, which was manufactured in 1848, became the first chewing gum product to be manufactured commercially Called "STATE OF MAINEPURE SPRUCE GUM." However, its use was eventually replaced by paraffin, which is still being chewed in some areas. The first patent for chewing gum, U.S. number 98,304 was filed on December 28, 1869 by Dr. William F. Sample, a dentist from Mount Vernon, Ohio. This product, consisting of liquorice and rubber dissolved in alcohol and naphtha, was initially intended to be used as a dentifrice. In 1891, William Wrigley Jr., arrived in Chicago with $32 in cash with a desire to market his special variety of soap. Eventually, he switched from soap to baking powder sales and offered chewing gum premiums to merchants who became his customers. By 1892, when the premiums had become more popular than the baking powder, Wrigley launched his first chewing gum products, LOTTA and VASSAR. A year later, he developed JUICY FRUIT, and shortly thereafter, WRIGLEY's SPEARMINT gum. Sugarless gum made its debut in the early 1950s, generally used sorbital as a sugar substitute. The first brand to be marketed was HARVEY's followed by TRIDENT and CAREFREE. In 1975, the Wm. Wrigley Jr. Company introduced the arrival of a new chewing gum product, FREEDENT, designed especially for denture wearers, which did not stick to most dentures as ordinary gums.

Merits of MCG^(13-17)

1. Does not require water to swallow. Hence can be taken anywhere.

2. Advantageous for patients having difficulty in swallowing.

3. Excellent for acute medication.

4. Counteracts dry mouth, prevents candidiasis and caries.

5. Highly acceptable by children.

6. Avoids first pass metabolism and thus increases the bioavailability of drugs.

7. Fast onset due to rapid release of active ingredients in buccal cavity and subsequent absorption in systemic circulation.

8. Gum does not reach the stomach. Hence G.I.T. suffers less from the effects of excipients.

9. Stomach does not suffer from direct contact with high concentrations of active principles, thus reducing the risk of intolerance of gastric mucosa.

10. Fraction of product reaching the stomach is conveyed by saliva delivered continuously and regularly. Duration of action is increased.

11. Aspirin, Dimenhydrinate and Caffeine show faster absorption through MCG than tablets.

12. Stimulates flow of saliva in the mouth.

13. Neutralizes plaque acids that form in the mouth after eating fermentable carbohydrates.

14. Helps whiten teeth by reducing and preventing stains.

Demerits of MCG^(18-22)

1. Risk of over dosage with MCG compared with chewable tablets or lozenges that can be consumed in a considerable number and within much shorter period of time.

2. Sorbitol present in MCG formulation may cause flatulence, diarrhea.

3. Additives in gum like flavoring agent, Cinnamon can cause Ulcers in oral cavity and Liquorice cause Hypertension.

4. Chlorhexidine oromucosal application is limited to short term use because of its unpleasant taste and staining properties to teeth and tongue.

5. Chewing gum has been shown to adhere to different degrees to enamel dentures and fillers.

6. Prolonged chewing of gum may result in pain in facial muscles and ear ache in children.

Chewing gum base: ⁽²⁴⁾

Sapota (Manilkara zapota):

Sapota popularly known in India as Ciku is native to tropical America most probably to south Mexico or Central America. This plant is also grown for its latex. Chicle and gutta parcha are extracted from its latex. These are used as a base material in chewing gum and in some other industrial products.

In India it is cultivated for fruits which are liked all over the country. The fruit is fleshy berry, variable in shape, size and weight (75-150g). The skin is thin, rusty brown somewhat scurfy looking like Irish potato, and the pulp

soft, melting, crumbling with a sandy or granular texture with 1-5 hard, black seeds. The fruit is a good source of digestible sugar (12-18%) and an appreciable source of protein, fat fiber and minerals, calcium and iron. It has become a very popular fruit crop in Gujarat, Maharashtra, Karnataka, Tamilnadu, Andhra Pradesh and Kerala.

Sapota Tree chewing gum:⁽²⁵⁾

In the recent years scientific and technological advancements have been made in there each and development of oral drug delivery systems. The reasons that the oral route achieved such popularity may be primarily due to its ease of administration; chewing gum is one of the very popular oral confectionery products. It is potentially useful means of administering drugs either locally or systematically via, the oral cavity. The medicated chewing gum has through the recent years gained increasing acceptance as a drug delivery system. Fresh latex of unripe fruits of Manikara zapota can be used as a chewing gum base which is natural and have no side effects. Latex itself has antiulcer property.

CONCLUSION:

An herbal medicated chewing gum can be formulated with the ingredients that have been scientifically proved in the management of mouth ulcer. In this respect, traditional medicine has introduced good protocols for treatment of various disorders. Chemical substances derived from plants have been used to treat human diseases since the dawn of medicine. Roughly 50% of new chemical entities introduced during the past two decades are from natural products. Recent technological advances have renewed interest in natural products in drug discovery. Therefore, efforts should be directed towards isolation and characterization of the active principles and elucidation of the relationship between structure and activity.

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3. Dr. Deepak Acharya, Medicinal plants for curing common Ailments in India, Listed in herbal medicine, originally published in issue 102-August 2004.

4. Praveen Sharma et al, Antiulcerogenic activity of Terminalia chebula fruit in experimentallu induced ulcer in rats, Journal of Pharmaceutical biology Volume 49, 2011-Issue-3

5. Sai Krishna. G, “Tulsi-the wonder Herb (Pharmacological Activities of Ocimum sanctum), American Journal of Ethnomedicine, 2014, Vol-1, No.1, 089-095.

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24. Jadhav SS, Value added products from sapota , International Journal of Food science and nutrition, Volume3; Issue 5; September 2018 page 114-120

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Received on 05.04.2019 Modified on 18.05.2019

Research J. Pharm. and Tech. 2020; 13(1): 481-484.

DOI: 10.5958/0974-360X.2020.00093.1

Commercially available medicated chewing gum⁽²³⁾
Trade mark	Active substance	Aim	Commercially available
Aspergum	Aspirin	Pain relief	North americal
NIcorette	Nicotine	Smoking Cessation	World wide
Stami Vitamin c	Vitamin c	General health	Australia
Vitamin	Vitamin c	General health	Australia
Stay alert	Caffine	Alertness	USA, Japan
Café Coffe	Caffine	Alertness	Japan
V6	Xylitol	Prevention of formulation of dental caries	USA, Australia
Fluorette	FLuoride	Canostatic	USA
Travel	Dimenhydrimate	Motion Scikness	USA, Australia