Recent Patents on Drug Delivery & Formulation 2009, 3, 221-228 221

1872-2113/09 $100.00+.00 © 2009 Bentham Science Publishers Ltd.

Herbal Remedies for the Treatment of Periodontal Disease - A Patent Review

Pramod Kumar1, Shahid H. Ansari2 and Javed Ali*1

1Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110 062, India, 2Department of Pharmacognosy & Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi - 110 062, India

Received: April 5, 2009; Accepted: June 17, 2009; Revised: June 19, 2009

Abstract: Periodontal diseases, if left unchecked, can lead to major health problems. There are a number of traditional herbal remedies for the treatment and management of diseases related to teeth, gum and oral hygiene. Use of clove oil is an age old remedy still practiced for periodontal problems. Our aim is to present an overall view of the current strategies adopted for the formulation and application of traditional herbal remedies. The article provides a review of the patents obtained on herbal remedies for the treatment of periodontal diseases. In addition, it also provides an overall view of potent herbal remedies widely used for periodontal diseases.

Keywords: Herbal remedies, periodontal, gingivitis.

INTRODUCTION

Periodontal diseases affect the tissues surrounding the teeth. Gums and bone supporting the teeth come under the term periodontal. Gingivitis, the mildest form of periodontal disease, is generally caused by insufficient oral hygiene. Inadequate oral hygiene can lead to plaque buildup. A variety of triggering factors like bacterial causes, dyscrasias, avitaminosis etc. cause inflamed gums leading to gingivitis. Salivary tartar has an additive effect to these causative factors in causing gingivitis. Aggressive periodontitis, chronic periodontitis and those resulting from conditions like HIV, diabetes, malnutrition and immunosuppression are the other types of periodontitis [1]. Periodontal disease is recognized as a major public health problem throughout the world and is the most common cause of tooth loss in adults. Periodontal disease is a general term used to describe several pathological conditions that affect the supporting structures /tissues of teeth [2]. Pain, discom-fort and cosmetic considerations are some of the factors that demonstrate severity of the problems associated with dental diseases and hence, it is of utmost importance to minimize and control dental diseases [3]. Periodontal treatment aims to cure inflamed tissue, reduce the number of pathogenic bacteria and eliminate the diseased pockets. Mechanical therapy, chemotherapy and systemic administration of antibiotics are some of the clinical methods being utilized currently. Conventional therapy includes scaling - removal of the calculus and the plaque, curettage clearing the inflamed soft tissue, and root planning - removal of necrotic tissues on the root surface. Periodontal diseases are associated with bacterial infections; therefore antibacterial treatment seems to be an appropriate method of improving the condition of the inflamed tissues. One of the major

*Address correspondence to this author at the Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi - 110 062, India; Tel: + 00- 91- 9811312247; Fax: + 00- 91- 11- 2605 9663; E.mail: javedaali@yahoo.com, jali@jamiahamdard.ac.in

problems associated with conventional treatment of systemic administration of antibiotics is the distribution of drug throughout the body, which is not required and it can also give rise to toxicity problems. One method of minimizing the distribution of therapeutic agents in the body is through the use of local drug delivery system. Many antibacterial are applied directly to the mouth for the treatment of periodontal diseases. Mouth rinses, irrigating solutions and sustained release devices are some of the local delivery systems [4]. Periodontal local delivery devices that have been used for the targeted delivery of antimicrobial agents include: fibers (hollow and monolithic), strips and compacts, films, microparticles, gels and nanoparticles.

COMMONLY USED HERBAL REMEDIES

There are many natural ways to treat periodontal disease some of which even help in preventing it from occurring. There are a number of herbs that can help eliminate inflammation and infection associated with periodontal diseases. Proper oral hygiene, of course, goes a long way in treating and preventing periodontal disease. Coenzyme Q-10, a natural supplement helps to increase tissue oxygenation in the body that helps to provide healthy blood flow to the gums. A reported clinical trial demonstrated improvement in plaque and calculus levels by twice daily intake of 25mg of Coenzyme Q-10 in patients suffering from periodontal disease [5]. A number of neutraceuticals are currently being used in the prevention and treatment of periodontal disease. Evidences have been reported for the relation between Vitamin C and periodontal disease. Significant gum bleeding can occur in vitamin C deficiency [6, 7]. Vitamin C along with bioflavonoids helps to speed up the healing process. Clinical studies have also been reported to lower plague, gingival and bleeding indices by use of formulations containing extracts of bloodroot [8]. Aloe vera gel has been reported to sooth gum tissue and relieve pain and discomfort when applied on gums. Clove oil reduces infection and

222 Recent Patents on Drug Delivery & Formulation, 2009, Vol. 3, No. 3 Ali et al.

relieves pain. Echinacea and goldenseal have also been reported to relieve infection and inflammation [9]. Clove oil will reduce infection and relieves pain. Clove oil is commonly used for the relief of toothache [8]. In dentistry, clove oil is applied in an undiluted form using a plug of cottonwool soaked in the oil and applied to the cavity of the tooth [8]. A study by Cai et al. (1996) reported preferential activity of crude methanolic extract of clove against Gram-negative anaerobic oral pathogens which cause periodontal diseases [10]. This study included isolation of eight active constituents and the antibacterial effect of these isolated compounds were studied. The authors reported kaempferol and myricetin to have significant growth-inhibitory effect against periodontal pathogens. Chan et al. (2003) evaluated the effects of herbal medi-cines in treating periodontal diseases. Three Chinese herbal compositions widely used for periodontal diseases were tested for their ability to retard progression of experimental periodontitis in hamsters, inhibit bacterial growth, and induce mutations. The study also included evaluation of major components of these compositions. The results showed that between the animal groups there were no signi-ficant differences in terms of the degree of inflammation, alveolar bone resorption, and rate of repair with or without the use of Chinese herbal medicine but hamsters treated with one composition (Conth Su) showed early regeneration of epithelium. Among the evaluated herbs, Chi Tong Ning demonstrated superior bacterial inhibition ability of MIC 0.025gmL-1. While both of the above mentioned compo-sitions were capable of inhibiting bacterial growth, none of the individual herb components showed comparable bacterial inhibition abilities. Also no signs of induction of cell mutations were observed for the tested herbal composites or their components using the Ames test. The results of the study demonstrated that traditional Chinese herbal medi-cines, which have been used for hundreds of years by Chinese people to treat periodontal diseases, could effec-tively inhibit bacterial growth without causing cell mutation [11]. Cao et al. (1998) reviewed articles published on the effects and mechanisms of herbal medicine on periodontal disease. Particularly, two modifications of an ancient compound prescription, Guchiwan (Tooth-firming pills) and Guchigao (Tooth-firming extract), were serially studied. It was pointed out in the review that various herbal extracts had shown suppressive effects on bone resorption by isolated osteoclasts during in vitro studies. The author emphasized an indepth study on traditional Chinese medicine for their possible use in periodontal diseases [12]. Cai et al. (2000) demonstrated the growth inhibitory effect of methanolic extract of Diospyros lycioides on oral pathogens that could cause periodontal diseases. The twigs of this plant were used to clean teeth by people in Namibia as chewing sticks. The active compounds were isolated and structures were elucidated. The compounds showed growth inhibitory effect on oral cariogenic baceria and periodontal pathogens [13]. Table 1 [14-18] displays more possible herbals remedies for periodontal diseases which have been used traditionally

for the care of teeth and gums. These plants/herbs represent potential candidates for being patented as constituents of herbal remedies for periodontal diseases. A phase II clinical trial (NCT00731432) is under progress for the evaluation of efficacy of a transmucosal herbal periodontal patch in reducing gingival inflammation in diabetic patients. The study is being sponsored by Izun Pharma Ltd., New York, USA [19].

PATENTS FOR HERBAL REMEDIES

Piramal et al. (2008) described a composition for treatment and prevention of periodontal diseases using a bioadhesive formulation comprising curcuminoids as an active agent. The composition included curcumin, tetrahy-drocurcumin, bishydrocurcumin, crude drug and solvent extracts of Curcuma longa, one or more bioadhesive polymers such as hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, hydroxy-ethyl cellulose and carbomers and sodium chloride, sodium bicarbonate or mixtures and one or more excipients. This orally applicable composition can be used for the treatment of gingivitis and other periodontal diseases [1]. Greve et al. (2005) described the use of vervain (ironweed, Verbena officinalis, Verbenaceae) and/or ribwort (Plantago lanceolata / P. angustifolia, Plantaginaceae) either alone or as a mixture of these two herbs or of their constituents or extracts. Aerial parts of the plants were preferred for the composition though all parts could be used. A combination of these two herbs or of the constituents or extracts of the two herbs were claimed to be very effective. Pharmaceutical additives and/or adjuvants such as fillers, extenders, binders, wetting agents, stabilizers, colorants, buffers, aroma chemicals, flavouring agents and/or preser-vatives could be included in addition to active ingredients. Use in the form of extracts or constituents of the two plants was preferred The extracts had herb/extract ratio from 50:1 to 1:1. The extracts could be prepared in such a way that 0.2 to 100 parts of liquid extract, or 0.1 part of dry extract was obtained from dried or fresh plant material with the aid of suitable liquid extractants such as water, alcohols, in parti-cular ethanol or ethanol-water mixtures. The composition could be liquid, gel-like or pasty and could contain diluents compatible with vervain and/or ribwort. Twenty drops of 2.5% of an extract which contained nearly 60% v/v ethanol preparation per half a glass of water (50ml) was sufficient for achieving adequate inhibition of microorganisms. The semi-solid forms such as toothpaste or oral gels contained approximately 2.5% of an extract which contained almost 80%v/v ethanol. In the case of lozenges, chewable tablets and (chewable) pastilles, it was preferred that such preparations contain approximately 250mg of dry extract per unit. A dry extract prepared by concentrating the liquid extract which originally had an herb/extract ratio of approximately 1:1 and an alcohol component of appro-ximately 80% v/v was claimed to be advantageous [20]. Kim et al. (2006) provided a herbal mixture extract of Pleurotus eryngii, Acanthopanacis Cortex and Notoginseng Radix and a composition for prevention and treatment of periodontal disease. The herbal mixture extract had potential of inhibiting the generation and activation of osteoclasts and

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Table 1. List of Plants/Herbs Used Traditionally for Care of Teeth and Gums

Plant/Herb Part Used Dosage Form Ref.

Foeniculum vulgare (Fennel) Seed - [14]

Potentilla arbuscula Rootstock Tooth powders [14]

Sibbaldia parviflora Tooth powders [14]

Wahlenbergia marginata Herb Topical [14]

Zanthoxylum armatum (Toothache tree, Indian Prickly Ash) Bark

Essential oil of fruit Tooth powder [14]

Zanthoxylum americanum (toothache tree) Bark, berries - [8, 14]

Zanthoxylum acanthopodium Seeds Tooth powder [14]

Zanthoxylum budrunga Fruits - [14]

Zanthoxylum nitidum Roots - [14]

Zanthoxylum oxyphyllum / Xanthoxylon violaceum Fruits - [14]

Acacia farnesiana Bark, Extract - [14]

Acacia chundra Bark, Leaves - [14]

Anacardium occidentale Bark, Leaves - [14]

Anacyclus pyrethrum Root - [14]

Dicoma tomentosa - - [14]

Quercus infectoria Galls Tooth powder, toothpaste [14]

Salvadora persica (Tooth Brush tree, Miswaak) Root As tooth brush [14]

Salvia officinalis Herb Tooth powder, Mouth rinse [14]

Salvia plebeia Leaves [14]

Spermacoce hispida (Madana Ghanti) Root Mouthwash [14]

Spilanthes oleracea Flowers - [14]

Tabernaemontana coronaria Root - [14]

Trachyspermum ammi (Thyme) Essential oil Toothpaste [8,14, 15]

Barleria prionitis Herb - [14]

Barleria cristata (Ottamulli) Leaves - [14]

Begonia laciniata var.

nepalensisFresh shoots - [14]

Borreria articularis Root Mouthwash [14]

Cinnamomum zeylanicum (Daarchini) Bark, Essential oil Toothpaste [14]

Dracaena cinnabari (Dragon‘sBlood) Root Toothpaste [14]

Ervataemia coronaria (East Indian Rosebay) Herb - [14]

Gymnosporia spinosa Leafy twigs Mouthwash [14]

Hovenia dulcis Fruit and seed extracts Toothpaste [14]

Humulus lupulus Extract Toothpaste [14]

Juniperus communis var. saxatillis Plant extract Toothpaste, mouth-rinses [14]

Lannea coromandelica Bark Decoction [14]

224 Recent Patents on Drug Delivery & Formulation, 2009, Vol. 3, No. 3 Ali et al.

(Table 1) Contd….

Plant/Herb Part Used Dosage Form Ref.

Peltophorum pterocarpum Bark Tooth powders [14]

Azadiracta indica (Neem) Leaves, Extract Gel, Toothpastes [14]

Sanguinaria canadensis (Blood root) Rhizomes, Extracts Tincture, Capsules, Toothpaste,

Oral rinses [8]

Tanacetum parthenium Leaf, Aerial parts - [8]

Anemopsis californica (Yerba mansa), Echinacea angustifolia, Gentiana lutea (Gentian), Rumex crispus (Yellow duck), Taraxacum officinale(Dandelion), Mahonia aquiffolium (Orange Grape), Piper methysticum

(Kava), Panax quinqefolium

Root - [16]

Zingiber officinale (Ginger) Rhizome - [16]

Avena sativa (Oat) Seed - [16]

Calendula officinalis Flower - [16]

Scutellaria laterifolia (Skull Cap), Centella asiatica (Gotu kola), Matricaria reticulate, Spilanthus sp.

Herb - [16]

Symphytum officinale (Comfrey) Root, Leaf Gargle [16]

Stachys betonica (Bishopswort) Herb Powder, Syrup [16]

Mentha Piperita (Peppermint) Essential oil, Leaves Aromatic water, Toothpaste, Gel [17]

Spearmint Essential oil Toothpaste [17]

Anise Essential oil Toothpaste [17]

Commiphora molmol (Myrrh) Gum resin Tincture [18]

Plantago lanceolata (Plantain) Leaf, Seed Tea, Capsules [18]

Krameria triandra (Rhatany) Root Tincture [18]

inhibiting the proliferation of osteoclasts and maintaining the growth of cells of periodontal ligament and gingival fibro-blasts. Inhibition of generation and activation of osteoclasts was by enhancing the expression of osteoprotegerin (OPG) in osteoblasts, preventing alveolar bone from destruction by inhibiting the proliferation of osteoclasts [21]. Thame (1989) described an oral hygiene method for treatment of periodontal diseases of bacterial etiology and for reducing plaque by use of a dried methanolic extract of Vinca rosea in the oral cavity. The composition contained 0.03 - 50% w/w of methanolic extract. The oral rinse and toothpaste formulations of the compositions contained suitable excipients [22]. Zhu (2006) described a Chinese herbal preparation for treating periodontitis, consisting of fleece-flower (18-25%), dried rehmanria (11-18%), liquorice (3-7%), fresh-water turtle shell (11-17%), dogwood fruit (7-15%), dodder seed (4-11%), Derla andrographis (4-12%) and Tokyo violet herb (8-15%). The formulation could be administered in dosage forms such as hard capsule, soft capsule, tablet, pill, granule, oral liquid etc. The active ingredients of the above herbs prepared by supercritical carbon dioxide fluid extraction could also be used [23].

Pawar (2005) explained a dentifrice herbal tooth powder which removed plaque, stain or patches and cleaned and polished tooth surfaces without any abrasive action. The composition comprised the powder of Acacia catechu,Menthol and camphor in the proportion of 91%, 2.7% and 6.3% respectively. The powder of Acacia catechu was used to remove tarter, plaque and stain and in cleansing and polishing tooth surface without any abrasion action. The powders of menthol and camphor were used as a flavouring agent. A clinical study on this dentifrice herbal tooth powder reported 87-95%, 70-72% and 80-95% reductions in plaque, gingivitis and dental calculus respectively, in merely 15 days [24]. Behl et al. (2004) developed a synergistic herbal formulation comprising of active fractions from Azadirachta indica, Citrullus colocynthis and Cucumis sativus extract and a carrier or additive. They also explained a process for preparation of formulation comprising of extraction of neem bark and leaves in aqueous solution or polar solvents, Citrullus colocynthis, preferably underground parts using a homogenizer in an aqueous polar solvent and the anti-oxidant portion from Cucumis sativus by cold extraction using aqueous polar solvents at temperature. They claimed

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the composition to be useful for teeth and gums as mouth-wash or mouth rinse. This herbal formulation was described to be useful for preventing dental plaque and gingivitis in humans and also as an antimicrobial agent for preventing periodontal diseases. A clinical study conducted on 60 volunteer subjects to evaluate the efficacy of fraction from neem, fraction from Citrullus colocynthis and a mixture of them on the reduction of dental plaque led to significant reductions of dental plaque [25]. Dulin (2006) explained the use of a natural plant herb, herbal extract or essential oils like eucalyptus oil and clove oil either alone or in combination with an anti-microbial compound, a fluoride ion-providing compound, analgesic, enzyme etc. The composition was formulated in the form of a liquid or a gel which moistened a single-use disposable sterile cotton roll to be received in a buccal vestibule. The system was therapeutically effective in treatment of periodontal diseases on topical administration [26]. Shi et al. (2003) developed compositions of herbs and methods of using these compositions for the treatment and prevention of microbial infection, in particular for dental caries or periodontal disease. The composition consisted of mixture of any two or more herbs such as Phellodendron amurense, Paris polyphylla , Prunus mume, Glycyrrhiza uralensis, Aframomum villosum, Sanguisorba officinalis, Elsholtzia splendens, Eugenia caryophyllata, Rhus chinensis, Atractylodes chinensis Koidz, Perilla frutescens , Coptis chinensis, Sophora flavescens, Bletilla striata , Aframomum cardamomum, Sophora tonkinensis, Melia toosendan, and Medicinal rhubarb root. The authors conducted evaluation of the herbal formula using human cell lines and Ame’s DNA mutagenesis tests and found the formulation to be safe [27]. Musick (2006) detailed the use of the herb, mastic gum (Isle of Chios) in alone or combination with antimicrobials like metronidazole, Keflex, amoxicillin, tetracycline, clarithromycin, bismuth in a method for treating the cause of a diagnosed non-gastric disease such as periodontal disease and gingivitis. Mastic gum might be helpful in maintenance therapy. The therapy could extend up to 120 days. Optimal success was claimed by a 90-day therapy for preventing recurrence and was found to be effective in treating Helicobacter sp. infections outside or involving the upper GI tract [28]. Levine et al. (2002) described compositions containing extracts of Echinacea purpurea and Sambucus nigra and the extract(s) of one or more plants such as Hypericum perforatum, Commiphora molmol and Centella asiatica. In the management of inflammatory mucosal diseases of both viral and non-viral origin these compositions were described to have significant application. The composition was found to be useful in many mucosal diseases including gingivitis and periodontal diseases. Tissue samples taken during a double-blind matched-sample clinical trial of a transmucosal adhesive patch of this herbal composition in sixteen patients for the treatment of gingival inflammation showed no protease activity. The result suggested significant inhibitory effect of the herbal composition [29]. Romanowski (2005) described compositions that were safe and effective for preventing and treating oral disease

and for maintaining good oral health for both humans as well as animals. They could be used regularly. They claimed compositions which contained xylitol, a preservative and an antimicrobial agent in a carrier. The composition might further contain a herbal ingredient such as olive leaf extract, black walnut green hulls, clove leaf, thyme herb, grapefruit seed extract, Aloe vera, Calendula flower, Echinacea pupurea, gota kola extract, chamomile flower, green tea leaf, Oregano leaf, Peppermint oil, Cinnamon bark, Eucalyptus leaf, Lavender oil etc. This invention provided long-term improvement in oral care and provided permanent solution to oral disorders. The composition might be formulated as a solution which could be diluted before use, as powders that may be added to beverages, candies, dental chew, oral gels toothpaste, lozenges, whitening molds etc. Use of pleasant flavors was said to make the formulation more appealing, especially for children and elderly. The composition was particularly useful for treating and preventing oral problems such as gingivitis, periodontal disease, stomatitis and halitosis. It also prevented build-up of tartar on teeth and also suppressed oral and throat cancer. The composition may optionally contain antimicrobials, immunomodulators and/or anticancer agents. The composition could exert both local and systemic effects. For animals, food and water could be used for incorporating these compositions [30]. Chen (2005) described the use of an extract of a herb from the family Scutellaria which served as a phytoestrogen and a method of treating estrogen-related disorder such as periodontal disease, tooth loss etc. The extract could be of Glycyrrhiza uralensis, Glycyrrhiza glabra, Taraxacum mongolicum, Medicago sativa, Brassica oleracea or Eclipta prostrata [31]. Reddy et al. (2000) explained that the effect of herbal remedies for periodontal diseases can be enhanced by the use of probiotics using genera such as Lactobacillus and Propionibacterium. They conducted clinical trials on herbal tooth powder and tooth paste formulations intended for bad breath, bleeding gums and periodontal disorders. Khadira, shilajit, guggulu, arka, cinchona, eucalyptus, vidonga karkata, shringi beejarasa, ardhraka, amlaki and scariva were the herbal ingredients whereas Lactobacillus acidophilus and Propionibacterium shermanii were the probiotics used. The formulations containing probiotics were found to enhance the activity of the herbal remedy than those without probiotics. Similar results were observed when probiotics were added to a marketed herbal toothpaste [32]. Domb (2003) described the usefulness of a solid, self-bioadhesive composition for reducing the depth of periodontal pockets in a patient by topical application that adheres to the oral mucosal tissue. The composition consisted of atleast one herbal or homeopathic active agent. The herbal active may be herbal extracts, tinctures, essential oils either alone or in mixtures. Essential oils such as Lemon oil, Citronella oil, Citron oil, Cedarwood oil, Juniper Berries oil, Pomela Peel oil, Lemon basil oil, Cinnamon oil, Cajeput oil, Eucalyptus oil, Fennel oil, Girofle oil, Lavender oil, Geranium oil, Clove oil, Myrte oil, Oregano oil, Pine oil, Rosemary oil, Sarriette oil, Thyme oil, Spearmint oil and Tea-tree oil could be used. Gotu Kola, Salvia offincinalis,Echinacea, Hypericum, Myrrah, Elder, Plantago, Baptisia,

226 Recent Patents on Drug Delivery & Formulation, 2009, Vol. 3, No. 3 Ali et al.

Camphoria, Uncaria, Calendula, Phytolaca, Catechu black,Krameria, Tsuga, Coneflower, grape fruit seed extract, Rosmarinus, Crataegus, Glycerrhiza, Angelica, Styrax, Krameria, Matricaria, Mallow, Propolis, Sage, Barberinefrom Hydrastis canadensis L. and other plant from the family Berberidaccae, gentian from the Gentianaceae family of plants for the treatment of fungal infections, Lonicera flower extract, Taraxacum extract, Scutellaria root extract, Gardenia fruit extract, Pueraria root extract, Radix gentianae,

Pulsatilla root extract, Longdancao antifungal agent and combinations thereof can be used for herbal tincture actives. A solid bioadhesive carrier in 40-99% w/w was used in the formulation for bioadhesivity [33]. Basu (2002) described a composition useful for the treatment of disorders such as periodontal disease and any periodontal disorder caused as a result of smoking. The composition consisted of either or both extract of Citrus reticulata and Prunus mume with one or more of the extracts

Table 2. Summary of Patents

Plant/Herb Dosage Form Ref.

Curcuma longa Bioadhesive [1]

Verbena officinalis, Plantago lanceolata, P.angustifoliaToothpaste, Oral gel, Lozenges, Chewable tablets and (chewable)

pastilles [20]

Pleurotus eryngii, Acanthopanacis, Notoginseng - [21]

Vinca rosea Oral rinse, Toothpaste [22, 37]

Fleece-flower, Rehmanria, Liquorice, Dogwood fruit, Dodder seed, Derla andrographis and Tokyo violet herb

Hard capsule, Soft capsule, Tablet, Pill, Granule, Oral liquid

[23]

Acacia catechu Wild, Menthol and camphor Dentifrice [24]

Azadirachta indica, Citrullus colocynthis, Cucumis sativus Mouthwash or Mouth rinse [25]

Eucalyptus oil, clove oil Gel [26]

Phellodendron amurense, Paris polyphylla , Prunus mume, Glycyrrhiza uralensis, Aframomum villosum, Sanguisorba officinalis, Elsholtzia splendens, Eugenia caryophyllata, Rhus chinensis, Atractylodes chinensis Koidz, Perilla frutescens , Coptis chinensis, Sophora flavescens, Bletilla

striata, Aframomum cardamomum, Sophora tonkinensis, Melia toosendan, Rhubarb

- [27]

Isle of Chios - [28]

Echinacea purpurea, Sambucus nigra, Hypericum perforatum, Commiphora molmol, Centella asiatica - [29]

Olive leaf extract, Black walnut, Clove leaf, Thyme herb, Grapefruit seed extract, Aloe vera,Calendula flower, Echinacea pupurea, Gota kola extract, Chamomile flower, Green tea leaf, Oregano

leaf, Peppermint oil, Cinnamon bark, Eucalyptus leaf, Lavender oil

Beverages, candies, Dental chew, Oral gels toothpaste, Lozenges,

Whitening molds [30]

Glycyrrhiza uralensis, Glycyrrhiza glabra, Taraxacum mongolicum, Medicago sativa, Brassica oleracea, Eclipta prostrata

- [31]

Lemon oil, Citronella oil, Citron oil, Cedarwood oil, Juniper berries oil, Pomela peel oil, Lemon basil oil, Cinnamon oil, Cajeput oil, Eucalyptus oil, Fennel oil, Girofle oil, Lavender oil, Geranium oil,

Clove oil, Myrte oil, Oregano oil, Pine oil, Rosemary oil, Sarriette oil, Thyme oil, Spearmint oil, Tea-tree oil, Gotu kola, Salvia officinalis, Echinacea, Hypericum, Myrrah, Elder, Plantago, Baptisia,

Camphoria, Uncaria, Calendula, Phytolaca, Catechu black, Krameria, Tsuga, Coneflower, grape fruit seed extract, Rosmarinus, Crataegus, Glycerrhiza, Angelica, Styrax, Krameria, Matricaria, Mallow,

Propolis, Sage, Hydrastis canadensis, Taraxacum extract, Scutellaria root extract, Gardenia fruit extract, Pueraria root extract, Radix gentianae, Pulsatilla root extract

Topical Bioadhesive [33]

Citrus reticulate, Prunus mume, Magnoliae officinalis, Coptis chinensis, Agastaches rugosa,Phellodendron chinense, Zingiberis officinalis, Fraxinus rynchophylla and Glycyrhizae inflate. Citrus

reticulate, Prunus mume- [34]

Pine, Liquorice, Cassia seed, Cinnamon, Nothosmyrnium root, Sophora, lonicera flower, Platycodon, green tea, dayflower, Korean Angelica root, liriope rhizome, moutan, Arabian myrrh, seseleos radix,

Angelicae Dahuricae Radix, Lagerstroemia indica, morus bark, ginger, Sanguinaria, asarum, cimicifuga, Chinese galls, Grapefruit seed, lycium root, cnidium, Alpinia katsumadai Hayata,

Gardenia, Lythrum salicaria L., dandelion, propolis, flavonoid, nepta herb, Reynoutria japonica Houtt,Scutellaria, machilia, black adzuki bean, Camomile, ratanhia, Sage oil

Powder, Toothpaste, Oral cleaner, Oral purifier

[36]

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of Magnoliae officinalis, Coptis chinensis, Agastaches rugosa, Phellodendron chinense, Zingiberis officinalis,Fraxinus rynchophylla and Glycyrhizae inflate. Citrus reticulata and Prunus mume were reported to show significant inhibition of LPS-induced TNF-alpha secretion in human peripheral blood mononuclear leukocyte cells. The extracts of other seven herbs mentioned earlier exhibited significant inhibition of TNF-alpha induced release of PGE sub 2 [34]. Compositions of a mixture of two or more ingredients from a list of myrrh extract or oil, mulberry bark extract, Cimicifuga heraleifolia extract and green tea extract have been patented by Suh et al. (1993). Each of the above ingredients was in quantities of 0.001-10 %w/w of the mixture. The extraction was done with water, alcohol or acetone. Toothpastes, breath fresheners, mouthwashes, chewing gums or sweets were the claimed formulations of these compositions. Antibacterial activity was claimed against cariogenic and plaque-forming bacteria. They also claimed their use in inhibiting bacterial glycosyltransferase. Use of these compositions was proposed for prophylaxis of caries and periodontal disease and also for treating bad breath [35]. Moon et al. (2003) described method for preparation of plant extract powder and use of this extract in oral formulations for prevention and treatment of periodontal diseases and tooth decay. The plant extract was loaded into a porous powder carrier, which was further coated by a water insoluble coating material. The extracts was used in quantities of 0.05 - 5.0%w/w. Pine, Liquorice, Cassia seed, Cinnamon, Nothosmyrnium root, Sophora, Lonicera flower, platycodon, green tea, dayflower, Korean angelica root, liriope rhizome, moutan, Arabian myrrh, seseleos radix, Angelicae Dahuricae Radix, Lagerstroemia indica, morusk, ginger, Sanguinaria, Asarum, Cimicifuga, Chinese galls, Grapefruit seed, Lycium root, Cnidium, Alpinia katsumadaiHayata, Gardenia, Lythrum salicaria L., dandelion, propolis, flavonoid, nepta herb, Reynoutria japonica Houtt, scutellaria, machilia, black adzuki bean, camomile, ratanhia or Sage oil as single or in combination. The carriers may be inorganic abrasives, high molecular weight substances, colloidal humed silica etc. Colloidal humed silica having submicron particle size was advantageous in liquid formulations. The water insoluble coating agent was claimed to be easily disintegrated in the mouth and the active is released when applied in the mouth. The composition may be formulated as toothpaste, oral cleaner, oral purifier etc. [36]. Use of dried ethanolic extract of periwinkle (Vinca rosea) in the oral cavity as a method for treatment of periodontal diseases has been described by Thame (1990). The formulation contained 0.03 - 50% w/w of the extract. A carrier such as water, glycerin and lower alcohols could be used for the extracts. The composition could be oral rinse or toothpaste and may include anionic surface active agents such as sodium lauryl sulfate. The ethanolic extract was shown to possess enhanced antimicrobial action with sodium lauryl sulphate [37]. Table 2 summarizes the patents granted on herbal remedies for periodontal infections.

CURRENT & FUTURE DEVELOPMENTS

Pharmacologically active phytochemicals useful for the prevention, treatment and maintenance of periodontal diseases have been widely identified. They may be tannins, terpenoids, flavanoids, alkaloids etc. Antimicrobial activities of these have been found to be particularly useful for periodontal diseases. Clinical trials for assessment of safety and efficacy of these herbal remdies are in its infant stage. These herbal remedies are expected to be a widely used in future. The herbal remedies have an edge over conventional antibiotic treatment which suffer the limitation of low benefit to high risk as compared to herbal treatment which possess high benefit to low risk ratio. Standardization and quality assurance of these herbal remedies is also a key area to be focused in future and efforts have been initialized towards this target. There are much more opportunities for further research in the utility of herbal remedies for periodontal diseases. More organized and long-term research is to be carried out to support the use of established remedies. Development of novel drug delivery systems for these herbal ingredients is likely to be one of the thrust areas of research in future. Research on colloidal drug delivery systems such as nanoparticles, nanoemulsion etc seems to be promising.

CONFLICT OF INTEREST

There is no conflict of interest in the present manuscript.

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