Clinical Evaluation & Synergistic Effect of CMT Anticold Drop in the Treatment of Rhinitis & Cold: A Prospective Study

Medicinal Plants have been widely used in traditional systems of medicine & are of increasing interest in modern pharmacology for their therapeutic potentials. The common cold is an acute, self-limiting viral infection of the upper respiratory tract involving the nose, sinuses, pharynx and larynx. The infection is spread by physical contact with secretions from an infected person (direct or indirect). The incubation period varies but is just under two days for rhinovirus. Symptoms, which generally relate to the infected mucosa, typically peak at 1-3 days and last 7-10 days, although they occasionally persist for three weeks. They include sore throat, rhinitis, rhinorrhoea, cough and malaise. The severity and type of symptoms will vary among individuals and with different infective agents. For example, fever is common in children but rare and mild in adults. The incidence of the common cold declines with age. Among these ASMANTARA [Mentha], KHADE KAPUR [camphor], OVA PHUL [thymol] have attracted considerable attention due to their bioactive compounds & extensive medicinal properties. Camphor a natural product derived from the wood of the tree Cinnamomum camphor, has a long history of use as an antiseptic, analgesic, antipruritic, counter irritant and rubefacient. Belongs to family Lauraceae. Menthol is a natural compound of plant Mentha piperita, belongs to family Lamiaceae known to produce cool sensation. Menthol, is widely used in preparations for pain relief in sports injuries, arthritis, and other painful conditions. Trachyspermum Ammi, commonly known as an ajwain, is a plant from the Apiaceae family. It has long been used in Ayurvedic and Unani medicine for its strong antimicrobial, antifungal, and anti-inflammatory activities. The primary bioactive component of ajwain seeds is thymol, which is traditional potential herb, known for its therapeutic benefits, particularly in treating digestive disorders and respiratory ailments. One of the important and effective parts of herbal plants is essential oil and substances present in different parts of plants. Essential oils are components which are oil soluble that have effective smell and aroma and are separated by use of water and steam distillation and prepared by extraction with solvents and enzymatic hydrolysis. The solvent system chosen was able to solubilize the drug at the desired concentration and an environment was provided where the drug has sufficient chemical stability. However, limited information is available on the pharmacological properties of the above individual ingredients and mixture of the above in the form of formulation. Based on the above claims, the present study is undertaken to evaluate anti-cold & cough effect of the formulation & against the nasal congestion & asthma.

OBJECTIVE

1. To prepare ANTI-COLD drop using plant essential oils.
2. The use of essential oils of CMT against Nasal congestion.

ANATOMY AND PHYSIOLOGY OF NASAL CAVITY

Researchers became interested in the nasal route for the systemic delivery of medication due to a high degree of vascularization and permeability of the nasal mucosa. In humans and other animal species the major functions of the nasal cavity are breathing and immune defence. However, it also affords an important protective activity once it filters, heat and humidity the inhaled air before reaching the lowest airways. Passage of the nasal cavity which runs from nasal vestibule to nasopharynx has a depth of approximately 12-14cm. The total surface area of the nasal cavity in human adult is about 150 cm and total volume is about 15 ml. Each of two nasal cavities can be subdivided into different regions: nasal vestibule, inferior turbinate, middle turbinate, superior turbinate, olfactory region, frontal sinus, sphenoidal sinus, and cribriform plate of ethmoid bone. The nasal cavity also contains the nasal associated lymphoid tissue (NALT), which is mainly situated in the nasopharynx. Nasal cavity is lined with mucous layer and hairs which are involved in those functions are trapping inhaled particles and pathogens. Moreover, mucociliary clearance, immunological activities and metabolism of endogenous substances are also essential functions of nasal structures. The nasal cavity is covered with a mucous membrane which can be divided into two areas; non-olfactory and olfactory epithelium, the non-olfactory area includes the nasal vestibule which is covered with skin-like stratified squamous epithelium cells, whereas respiratory region, which has a typical airways epithelium covered with numerous microvilli, resulting in a large surface area available for drug absorption and transport. Nasal cavity is divided by middle septum into two symmetrical halves, each one opening at the face through nostrils and extending posterior to the nasopharynx. Both symmetrical halves consist of four areas (nasal vestibule, atrium, respiratory region and olfactory histological characteristics.

EUTECTIC MIXTURE

A eutectic mixture is a combination of substances that, when mixed, lowers the melting point of each component & compared to their individual melting points. camphor, menthol, and thymol are combined to form a eutectic mixture, their mechanism of action in anti-cold drops is enhanced due to their unique physical and chemical interactions.

What is a Eutectic Mixture?

A eutectic mixture is a combination of two or more substances that, when mixed together, lowers the melting point of each component compared to their individual melting points. At the eutectic point, solid components melt together at a specific ratio & temperature, forming a homogenous mixture.

Mechanism of Action

1. Enhanced Skin and Mucosal Permeation: The eutectic mixture disrupts the lipid barrier of the skin or mucosa, increasing the penetration of the active ingredients. Camphor, menthol, and thymol quickly reach deeper layers of the skin or nasal mucosa, providing faster relief from symptoms.
2. Cooling and Soothing Effect: Menthol activates the TRPM8 (cold-sensitive) receptors, creating a cooling sensation that soothes irritated mucous membranes and skin. The cooling sensation provides symptomatic relief from nasal congestion and irritation.
3. Decongestion: Camphor acts as a counterirritant, stimulating sensory nerve endings and causing a sensation of warmth that enhances blood flow. This helps reduce nasal congestion by promoting drainage and reducing swelling in the mucosal tissues. Topical decongestant products are applied topically to the nasal tissues via spray or drops. Topical decongestants stimulate the α-adrenergic receptors in the arterioles of the nasal mucosa, leading to vasoconstriction and shrinkage of nasal tissues. There is minimal systemic absorption if used as directed. Systemic decongestants are adrenergic receptor agonists (sympathomimetic) that produce vasoconstriction within the mucosa of the respiratory tract, temporarily reducing the swelling associated with inflammation of the mucous membranes.
4. Antimicrobial Action: Thymol provides antiseptic and antimicrobial effects, helping to clear infections or prevent bacterial growth in the nasal passages and throat. The synergistic action of thymol with camphor and menthol enhances antimicrobial efficacy.
5. Analgesic and Anti-inflammatory Effects: The ingredients act on sensory neurons to reduce the perception of pain (analgesia). They also exhibit mild anti-inflammatory activity, reducing irritation and inflammation in the respiratory tract.
6. Improved Stability and Efficacy: The eutectic mixture ensures that the active components remain stable and bioavailable in liquid form, increasing their effectiveness in relieving cold symptoms.

KEY ADVANTAGES OF EUTECTIC MIXTURE IN ANTI-COLD DROPS

1. Better Solubility: The mixture stays in a liquid state, improving application and spread ability.
2. Enhanced Absorption: Increased skin and mucosal permeability ensure rapid onset of action.
3. Synergistic Effects: The combination enhances the individual effects of camphor, menthol, and thymol, making the formulation more effective.

This mechanism makes eutectic mixtures of camphor, menthol, and thymol highly effective in providing relief from cold-related symptoms such as nasal congestion, throat irritation, and mild pain.

MATERIAL & METHODS

CMT formulation is formulated by using three different ingredients as follow-

MATERIAL

1. Camphor
2. Menthol
3. Thymol

PROFILE OF INGRIDIENTS

1.  CAMPHOR

• Biological Name: - Cinnamomum Camphora
• Family: - Lauraceae
• Generic Name: - Khade Kapur
• IUPAC Name: - 1,7,7-Trimethylbicyclo [2,2,1] heptan-2-one
• Melting Point: - 175 -177 °C
• Boiling Point: - 209°C
• Chemical formula: - C10H16O
• Molar mass: - 152.237 g·mol−1
• Appearance: - White, translucent crystals
• Odour: - Fragrant and penetrating
• Structure: -

• Uses: - Counter Irritant, Anti-Inflammatory, Antiseptic, Antipruritic, Analgesic

2. MENTHOL 

• Biological Name: - Mentha piperita
• Family: - Lamiaceae
• Generic Name: - Asmantara
• IUPAC Name: - 2-isopropylidene-5-methylcyclohexanone
• Melting Point: - 42-43 °C
• Boiling Point: - 215°C
• Chemical formula: - C10H16O
• Molar mass: - 965.516720000001 g/mol
• Appearance: - White, translucent crystals
• Odour: - Strong, cool, refreshing
• Structure: -

• Uses: - Antiseptic, Stimulant, Carminative, Soothers, Flavour, Perfumes

3. THYMOL

• Biological Name: - Trachyspermum ammi
• Family: - Apiaceae
• Generic Name: - Ova phul 
• IUPAC Name: - 5-methyl-2-(propan-2-yl) phenol
• Melting point: - 50°C
• Boiling point: - 175°C
• Chemical formula: - C10H14O
• Molar mass: - 150.22 g/mol
• Appearance: - White, translucent crystals
• Odour: - Aromatic, Pungent 
• Structure: -

• Uses: - Antispasmodic, Antifungal, Antiseptic, Anthelmintic, Carminative, Stimulant

INSTRUMENTS

The instrumental methods followed for CMT formulation are-

1. pH meter
2. UV spectrometer
3. Incubator
4. Colony Counter

AUTHENTICATION CERTIFICATE

We’re affix an authentication certificate for the materials used in the formulation

METHODOLOGY

Procedure For ‘CMT’ Formulation

CMT formulation is a Eutectic Mixture & it defined as, ‘A eutectic mixture that a combination of substances that, when mixed, lowers the melting point of each component compared to their individual melting points, two or more components are mixed at a specific ratio & melts together at a room temperature or at lower temperature.’ For camphor, menthol & thymol, the mixture becomes a liquid at room temperature or at a lower temperature than the individual components. This liquid state improves solubility, absorption, and delivery of the active compounds to the site of action. When camphor, menthol, and thymol are combined to form a eutectic mixture, their mechanism of action in anti-cold drops is enhanced due to their unique physical and chemical interactions.

1.  PHYSICOCHEMICAL EVALUATION

Physicochemical evaluation refers to the testing &analysis of both physical &chemical properties of substance, typically done to ensure quality, purity, stability &suitability especially in pharmaceutical, cosmetics, food or herbal formulations.

1. Skin Irritancy Test
2. pH Test     
3. Solubility

Skin Irritancy Test

Skin irritancy is the ability of a substance refers to the adverse reaction to the skin after a single or repeated application. resulting in redness, itching, swelling or other signs of inflammation or damage to the skin’s surface.

pH Test

A quantitative analytical method used to measure the concentration of hydrogen ion in solution, to determine its acidity or alkalinity.

Solubility Test

Solubility is an ability of maximum amount of solute that can dissolve in prescribed quantity of solvent at a specific temperature & pressure to form saturated solution.

2.  THIN LAYER CHROMATOGRAPHY

Thin layer chromatography is an analytical technique & chromatographic method used to separate, identify & analyse the components of a mixture based on their differential affinity towards a stationary phase & mobile phase.

• • Identification Test
  • Confirmatory Test

Identification Test

An identification test in TLC is a qualitative method helps to determine the presence of a specific compound in a sample by comparing its mobility & appearance to the known reference.

Visual Appearance Under UV cabinet

3. PHYTOCONSTITUENT CHEMICAL TESTS

Phytoconstituent chemical tests are qualitative chemical tests used to screen, identify &detect the presence of bioactive phytochemicals in herbal plant or extract.

Confirmatory Test for Camphor

Chemical Test	Observation	Result	Image
Vanillin-Sulfuric Acid Test   H2SO4+sample	Yellow colour changes to orange	Camphor confirmed

Confirmatory Test for Menthol

Chemical Test	Observation	Result	Image
Nitric Acid  Test   5mlHNO3+Sample +Heat	Liquid Develops Blue Colour, Which on Heating Shows Copper Colour, fluorescence Further It Develop Golden Yellow	Menthol Confirmed

Confirmatory Test for Thymol

Chemical Test	Observation	Result	Image
Salkowaski Test   Sample + conc. H2SO4	Reddish Brown Ring Formed	Thymol Confirmed