Active ingredient: Dry extract from Devil‘s claw root

1. Active ingredient: Dry extract from Devil‘s claw root Indications: Rheumatism, arthrosis Downloaded from www.pharmacy123.blogfa.com

2. Botany Harpagophytum procumbens (Burch.) De Candolle Family: Pedaliaceae (sesame plants) Synonyms: Devil‘s claw Wood Spider Grapple plant Origin: Endemic in South and South-West Africa (Namibia, Kalahari desert). In sandy steppe regions, savannahs with few trees or by waysides.

3. Botany Medicinal drug: Dried secondary tuber (Harpagophyti radix), cut up into slices or pieces.

4. Brief profile • Enduring, weed-like plant. • Up to 1.5 m long sprouts, lying on the ground. • Water storage capacity of storage roots up to 90%. • Stalked leaves with deep lobes. • Flowers: bright violet-red in colour, funnel-shaped. • Widely branched system of primary and secondary roots. • Secondary storage roots can develop several tubers with a diameter of up to 6 cm. • Fruits: lignifying capsules with grapnel-like outgrowths containing about 50 seeds.

5. Drug Spectrum of ingredients: the same in both main and side roots Concentration of ingredients: higher in the side roots side roots are used for drug preparation Processing:Crushing of the secondary storage roots (tubers of the side roots) Root fragments: Colour: yellowish grey or pale pink Consistency: hard like horn Taste: bitter

6. Traditional medical use Africa: - indigestion - blood diseases - fever - pains - migraine Europe: - metabolic diseases - arthritis - diseases in liver, gall-bladder, kidney and bladder Further research towards the end of the 1950s gradually led to Devil’s claw being applied mainly for treating rheumatic diseases.

7. Phytochemistry • Extract from Devil's claw root: Mixture of substances (just like any typical phytopharmaceutical) • Most important ingredients: Iridoid glycosides • Active component: Full extract

8. Ingredients • iridoid glycosides (1.1-3.6%): among others harpagoside (at least 1.2%, very bitter), harpagide, procumbide • phenylethanol derivatives: verbascoside, isoacteoside • carbohydrates: among others stachyose, raffinose • flavonoids: kaempferol, luteolin • pharmacologically irrelevant are, among others, sterols, alkanes, fats, waxes, gum resin, essential oils

9. Iridoid glycosides

10. Mechanism of action • Up to now, there are no consistent research results as to the actual active ingredient(s) contained in the extract from Devil's claw root. • Possibility of a dual action profile with an inhibition of the cyclooxygenase or lipooxygenase way within the arachidonic acid metabolism is being discussed. • Results of an in vitro study:Devil's claw root extract contains additional substances besides harpagoside that act to selectively inhibit the lipooxygenase way and consequently the biosynthesis of leukotrienes.

11. Mechanism of action • Harpagoside seems to contribute to the analgesic but not the antiphlogistic effect • If rheumatism is considered to be a system disease  another action approach via the metabolism-regulating properties of Devil's claw might be possible

12. Inflammation cascade Noxa Cell membranephospholipids phospholipase arachidonic acid lipooxygenase cyclooxygenase leukotrienes prostaglandins immunocompetent cells (monocytes, T-cells) cytokinesTNF-a, interleukins

13. Toxicology LD50 (Harpagophytum procumbens, full extract): 13.5 g/kg body weight p.o. (tests conducted on mice)

14. Tolerability Side effects:In rare cases nausea, diarrhea, vomiting, dizziness and headache have been observed.Hypersensitivity reactions (skin rashes, urticaria, facial edema even including circulatory collapse (anaphylactic shock) have been described very rarely. When suffering from insulin-dependent diabetes mellitus, a blood-sugar increase - which decreased after stopping the intake - has been observed very rarely. Contra-indications:Patients suffering from gastric and duodenal ulcers (Devil‘s claw root extract contains bitter substances that increase gastric secretion).

15. Pharmacology Devil's claw has become a scientifically excellently researched and documented medicinal plant. Tests demonstrated the analgesic, antiedematic and antiphlogistic effects of the full extract. These findings could be confirmed in practice by clinical studies and physicians' empiric reports. For the most part, the conducted studies revealed a distinct antirheumatic potential.

16. Effects • antiphlogistic by COX- and LOX-inhibition • analgetic • muscle-relaxing

17. Application for treating rheumatic diseases • non-specific chronic backache (cervical spine area, neck-shoulder-arm syndrome, lumbar spine area, lumbago, ischialgia) • arthrosis (e.g. osteoarthrosis of the hip, osteoarthrosis of the knee, degenerative changes of the spine such as spondylosis, spondylarthrosis) • active muscle hardening caused by unbalanced postures, e.g. at computer workstations or due to athletic exertion

18. Application for treating rheumatic diseases • chronic arthritis (primary chronic polyarthritis, pcp) • non-articular rheumatism syndrome (affecting musculature, ligaments and tendons), e.g. fibromyalgia syndrome

19. Alternative to non-steroidal anti-inflammatory drugs • Devil‘s claw has a similar principle of effect about the COX-/LOX-inhibition (reduction of prostaglandins and leukotrienes). • in contrast to the potential spectrum of side effects of the NSAIDs, Cefatec® 480 is excellently tolerable. • No interaction in concentration or driving a car. • Onset of effect after few days to two weeks = in case of intense, acute pains possibly overlapping start of therapy.

20. Proven therapeutic success with Cefatec® 480 effervescent tablets Multicentre practice study Centres: 196 practices Indication: Degenerative disorders of the locomotor system Examination period: 8 weeks Patient collective: 614 patients (65.1 % of the patients were female and 34.0 % male,average age of the patients 60.8 years) Medication: The daily dosage was 2 effervescent tablets of Cefatec® 480 • Especially suitable for a long-term treatment • Reasonable alternative or accompanying therapy to non-steroidal antirheumatic agents

21. Proven therapeutic success with Cefatec® 480 effervescent tablets

22. Proven therapeutic success with Cefatec® 480 effervescent tablets

23. Cefatec® 480 - advantages at a glance • highly concentrated extract from Devil‘s claw root for a gentle therapy of inflammatory and wear-caused diseases of the locomotor system • analgetic, antiphlogistic, muscle-relaxing • increases the flexibility of the joints • easy dosing and application2 x 1 film coated tablet a day • good tolerability

24. Basic information Fields of application For supportive treatment of degenerative disorders of the locomotor system. Note: In acute conditions with reddening, swelling or hyperthermia of joints and if complaints persist, a physician should be consulted. Composition Active ingredient: 1 film coated tablet contains: Dry extract from Devil's claw root (4.4 - 5.0:1) 480 mg. Extraction solvent: Ethanol 60 % (v/v). Excipients: Maize starch, microcrystalline cellulose, lactose monohydrate, colloidal anhydrous silica, magnesium stearate, hypromellose, macrogol, talc, titanium dioxide E 171. The quantity of carbohydrates taken in with a daily dose equals a white bread exchange of 0.05.

25. Basic information Contra-indications This medicine may not be taken in cases of hypersensitivity to Devil's claw or one of the excipients or in cases of gastric or duodenal ulcers. In case of cholelithiasis, a physician should be consulted. There has not been sufficient research for the use of this medicine during pregnancy and lactation. Therefore, it should not be used during this period. Cefatec® 480 FT has not been researched for children's use. Therefore, please refrain from giving Cefatec® 480 FT to children under 12 years of age. Warning None known. Dosage, kind and duration of application Adults and children over 12 years take 1 film coated tablet twice daily. The film coated tablets should be taken in the morning and the evening with the meals with some liquid. Take Cefatec® 480 FT until you are free of pain.

26. Basic information Side effects In rare cases diarrhea, nausea, vomiting, dizziness and headache have been observed. Hypersensitivity reactions (skin rashes, urticaria, facial edema even including circulatory collapse (anaphylactic shock) have been described very rarely. When suffering from insulin-dependent diabetes mellitus, a blood-sugar increase - which decreased after stopping the intake - has been observed very rarely. Commercial forms Film coated tablets: 20 pcs., 50 pcs.

27. Monograph Devil’s Claw root, Harpagophyti radix Official Monograph of the Bundesinstitut für Arzneimittel und Medizin-produkte (BfArM) (German Federal Institute for Drugs and Medical Devices) Commission E (Phytotherapy), BAnz.-No. 43 dated March 02, 1989 (corr. BAnz.-No. 164, dated September 01, 1990) Name of Drug Harpagophyti radix, devil’s claw root. Composition of Drug Devil’s Claw root consists of the dried, secondary tubers of Harpagophytum procumbens (Burchell) de Candolle [Fam. Pedaliaceae], as well as their preparations in effective dosage. The drug contains bitter substances. Uses Loss of appetite, dyspepsia, supportive therapy of degenerative disorders of the locomotor system.

28. Monograph Contraindications Gastric and duodenal ulcers. With gallstones, use only after consultation with a physician. Side Effects None known. Interaction with Other Drugs None known. Dosage Unless otherwise prescribed: Daily dosage: For loss of appetite: 1.5 g of drug; preparations of equivalent bitter value; Otherwise: 4.5 g drug; equivalent preparations. Mode of Administration Comminuted drug for teas and other preparations for internal use. Actions Appetite-stimulating Choleretic Antiphlogistic Mildly analgesic