Turmeric for joint healthThere is more to Turmeric than just Curcuminoids!

This presentation is meant for Business to Business communication. The information given here is not meant for consumers.

Deepak MundkinajedduNatural Remedies Pvt LtdBangalore, India

My introduction

• Pharmacy background with a PhD in natural products • Key research interests

• Bioactivity profiling of medicinal plants• Bioassay guided fractionation and isolation of active constituents• Taking science from preclinical to clinical stage• Intellectual properties and regulatory aspects

• Collaborations• Pharmacopoeial bodies – USP, API /UPI, IP• Government bodies – NMPB, DST and DBT• Universities – Manipal (adjunct faculty), JSS

This presentation is meant for Business to Business communication. The information given here is not meant for consumers.

Contents of this presentation

• Use of Turmeric in India• Medicine and Food

• Turmeric - Market scenario• Unexplored gaps between tradition and market

• R&D - water soluble components of Turmeric for joint health• Turmerosaccharides as active constituents• Development of Turmacin® • Preclinical and clinical trials for efficacy and safety

• Application to current market needs• Supplements and foods

This presentation is meant for Business to Business communication. The information given here is not meant for consumers.

Turmeric comes from cultivated sources• The global production of turmeric is around

11 lakh MT per annum. India dominates the

world production scenario contributing 78 %

• Domestic demand. Livelihood of many

farmers.

• NGOs, companies…..

• Supply chains established

• Availability of organic gradesThis presentation is meant for Business to Business communication. The information given here is not meant for consumers.

India- Traditional uses of turmeric as medicine

Kashaya / tea

• Water based preparations 1

Ghrita / khanda

• Fat (oil, ghee etc.) based preparations2

Churna

• Straight powders3

51. Sahsra Yoga | 2. Bhaishajyaratnavali | 3. Bhavapraksha Nighantu

Turmeric properties indicated in AyurvedaRujahara - alleviating painShopha - oedemaJvara - fever

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India - Uses of turmeric in foods & beverages

Turmeric – market scenario

Current turmeric market Unexplored part

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Turmeric whole powdersPurified curcuminoids

Volatile oil

Bioavailability Multiple health indications

Formulation science

Water soluble components

(~15% w/w of rhizomes)

Taken up by R&D at Natural Remedies Pvt Ltd

Research and Development (R&D)Water soluble part of

turmeric

Active constituents:Bioactive polysaccharides

(Turmerosaccharides)

Bioactivity guided fractionation

Synergy study

Synergistic combination

Turmerosaccharides – Biological actions

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Control Turmerosaccharides

Wet

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Turmerosaccharides reduced Chronic inflammation

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TLF TRF

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Pain reducing potential of water soluble components

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Control Turmerosaccharides

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Turmerosaccharides reduced acute inflammation

Turmerosaccharides showed anti-inflammatory and pain reducing potential in specific in vivo models

Illuri et al. Anti-inflammatory and Anti-allergy Agents in Medicinal Chemistry 2015, 14(1): 53-62Bethapudi et al. Pharmacognosy Magazine 2017, 13(Suppl 3): S623-S627.

TRF- Turmerosaccharide™ rich fraction; TLF- Turmerosaccharide™ less fraction

Discover the power of Turmerosaccharides. There is more to Turmeric than just Curcuminoids!

Turmacin® is the first clinically tested water soluble composition derived from Turmeric

completely untouched by solvents. Turmacin® is standardized to contain bioactive

polysaccharides ‘Turmerosaccharides’ and does not contain curcuminoids.

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Clinical Studies

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Turmacin® for joint health: A randomized placebo controlled clinical trialCondition Subjects with primary knee osteoarthritis

Dose 500 mg twice a day

Participants 30 subjects per group (Age: ≥40 years)

Duration 42 days

Evaluation On day 21 and day 42 using WOMAC, VAS and CGIC scales

Outcome Turmacin® effectively managed the symptoms of knee osteoarthritis and supported physical function of knee joints

WOMAC - Western Ontario and McMaster Universities Osteoarthritis Index; VAS – Visual Analogue Scale; CGIC – Clinician Global Impression Change

Madhu et al. Inflammopharmacology 2013, 21(2): 129-136.

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Turmacin® in Knee Osteoarthritis

• Reduced knee pain• Improved joint function• Reduced joint stiffness• Reduced joint tenderness

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VAS WOMAC CGIC

Placebo

Turmacin

Glucosamine

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Number of subjects

Placebo

Turmacin®

Glucosamine

Rescue medication use

Data on file

Step mill

Isokinetic Dynamometer

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Condition Healthy volunteers (exercise induced pain and discomfort)

Study design Randomized Double-blind placebo-controlled study

Dose 0.5 g and 1 g per day

Participants 90 (with 30 per group; Age: 18-65 years)

Duration 84 days

EvaluationPain using VAS on days 5, 7, 28, 56 & 84Mobility using digital goniometry on days 5, 28 and 84Muscle strength on day 84 using isokinetic dynamometry

Clinical study in Healthy Volunteers (New study)

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Turmacin® in Exercise Induced Pain

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Effect of Turmacin® on Exercise Induced Pain

Turmacin 1 g Turmacin 0.5 g Placebo

DayVAS Pain Score

Turmacin® 1g Turmacin® 0.5g Placebo

Day 0 4.5 4.03 4.2Day 5 3.7 3.2# 4.4Day 7 3.5# 3.1 4.5

Day 28 3.3# 3.1# 4.2Day 56 2.8# 2.8# 4.2Day 84 2.8# 2.7# 4.2

Turmacin® showed pain reduction on day 5

#Significantly different (p<0.05) from placebo

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Turmacin® increased the pain-free exercise duration

*Significantly different (p<0.05) from placebo

Turmacin® at 1 g dose prevented the decrease in muscle strength during physical inactivity

Effect of Turmacin on mobility

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Day 5 Day 28 Day 84

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Range of Motion

Turmacin 1 g Turmacin 0.5 g Placebo

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Turmacin® improved mobility as evidenced from the increase in range of motion

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#Significantly different (p<0.05) from placebo

Can Turmacin® be combined with curcuminoids?

Yes, towards creating a holistic Turmeric formulation

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Clinical study on combination of Turmacin®and curcuminoids

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Product Turmacin®+ Curcuminoids; 80:20

Condition Osteoarthritis subjects with effusion synovitis

Study design Randomized Double-blind placebo-controlled study

Dose 1000 mg per day

Participants 70 (Age: >40 years)

Duration 12 weeks

EvaluationKnee Pain, Function, Effusion-synovitis, OMERACT–OARSI & Quality of life.Cartilage composition, Physical function, Biomarkers & concomitant pain medication usage.

Key preliminary findings…

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Turmacin® in combination with curcuminoids significantly reduced the knee pain compared to placebo from day 5

Values in the graph represents the percentage OARSI-OMERACT Responders, n/N (%) after 12 weeks in the treatment and placebo groups

Preclinical Studies

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Effect of Turmacin® on inflammation and pain severity – in vivo studies

% Pain Reduction

Time Turmacin® (90 mg/kg)

Tramadol (10 mg/kg)

1 hr 29 343 hr 53 42

6 hr 50 64

24 hr 47 50

Sasikumar et al. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 2017, 16, 193-202

MIA- monosodium iodoacetate

Turmacin® reduced pain severity by 50% in 3 hours & the effect was maintained till 24 hours

Additional data on classical anti-inflammatory models available on file

How Turmacin® works?Modes of Action

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Turmacin® - Modes of action

DEGRADATION• Pro-inflammatory

mediators • Inflammatory mediators• Reactive oxygen species • Aging

SYNTHESIS• Collagen synthesis• Proteoglycan synthesis• Anti-inflammatory cytokines

Integrity of Joint Cartilage

Turmacin® supports joint health by maintaining equilibrium between degradation and synthesis of cartilage matrix

This presentation is meant for Business to Business communication. The information given here is not meant for consumers.Chandrasekaran et al. Inflammopharmacology (2018) https://doi.org/10.1007/s10787-017-0433-1

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Mode of action

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Joint with healthy cartilage Due to ageing/strenuous exercise

Cartilage cell death

Structural components - GAG & Type II

collagen

Cartilage damage

IL-1β

Inflammatory mediators

Turmacin®

Turmacin®More IL-1β is released

IL-1βInhibits

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Human safety study

Variable

Turmacin® 1g (n=27)

Placebo(n = 27)

p value

Mean ± SD Mean ± SD

AST 26.63 ± 25.99 18.11 ± 6.26 0.134

ALT 30.48 ± 19.54 30.63 ± 13.36 0.833

Glucose 89.33 ± 7.55 92.67 ± 7.65 0.255

Creatinine 0.81 ± 0.17 0.83 ± 0.17 0.206

Haemoglobin 14.45 ± 2.01 14.10 ± 2.01 0.806

No significant differences between groups and no clinically relevant changes in the

safety parameters after treatment with Turmacin ® at 1g for 84 days

Heartburn observed in 1 participant of Turmacin ® (1g)

and in 3 of 4 subjects of Placebo group

Turmacin® (1g) Turmacin® (2g)

Day 0 Day 42 Day 84

Incidence of adverse events Clinical laboratory parameters (including haematological, biochemical,

and urinalysis parameters), vital signs, electrocardiogram (ECG)

Haematological, biochemical, urinalysis, ECG , vitals normal in the treated volunteers.

Mild nausea (1) observed in Turmacin® (1g)

Mild abdominal pain (2), mild abdominal bloating (1), moderate GI upset (1) and mild nausea (1)

observed in Turmacin ® (2g)

Shots Sprays

Dose:0.5 to 1g per day

Novel formulations possible –

Scientific publications on Turmacin®

1. Madhu et al. Inflammopharmacology 2013, 21(2): 129-136

2. Illuri et al. Anti-inflammatory and Anti-allergy Agents in Medicinal Chemistry 2015, 14(1): 53-62

3. Senthilkumar et al. Journal of Korean Society Food Science and Nutrition 2014, 43(1): 612-617

4. Chandrasekaran et al. Pharmacognosy Research 2013, 5(2): 71-79

5. Chandrasekaran et al. BioMed Research International 2013, 2013: 158348, 10 pages

6. Bethapudi et al. Pharmacognosy Magazine 2017, 13(Suppl 3): S623-S627.

7. Velusami et al. Inflammopharmacology. 2018 Jan 8. doi: 10.1007/s10787-017-0433-1.

8. Sasikumar et al. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 2017, 16, 193-202

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Summary

• Concept of • There is more to turmeric than just curcuminoids -

Scientifically supported with a novel ingredient for joint health – Turmacin• Turmerosaccharides are the other bioactive constituents of Turmeric• The efficacy, safety and mechanisms of action supported with

• Human clinical studies• In vivo studies• In vitro studies

• Formulation ideas• Combination with curcuminoids • Food and beverages

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Thank you team!

• Sangli• Vineet• Bharathi• CVC• Murugan• Edwin• Sasi• ……….

30This presentation is meant for Business to Business communication. The information given here is not meant for consumers.

Thank You!

This presentation may contain statements and classification about the ingredient which may not be in line with the regulations of your country. The statement or claims made are in reference to ingredient only and therefore do not refer to the finished productdirectly or indirectly. The claims made on the finished product containing the ingredient are the sole responsibility of manufacturer or the marketer. We urge manufacturer and marketer to ensure that the claims made on the finished product comply with the lawand regulation of the country in which the product is to be sold.

The statements used in the presentation have not been evaluated by USFDA. This ingredient is not intended to diagnose, treat, cure or prevent any disease.

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