SENNAE FOLIUM 6 - Sennoside 2

SENNAE FOLIUM 6 - Sennoside 2

INTRODUCTION Sennosides are hydroxyanthracene glycosides derived from Senna leaves. They have been used as natural, safe time-tested laxatives in traditional as well as modern systems of medicine. Available in various convenient dosage forms they can be used to relieve occasional as well as habitual constipation C. angustifolia or Tinnevelly Senna, Senna Indica, C. elongata is an annual growing in the Yemen and Hadramaut provinces of Arabia Felix, in Somaliland, Mozambique, Sind, and the Punjab. In Southern India it is cultivated and grows to a larger size. In the German and Swiss Pharmacopoeias, the official drug is restricted to Tinnevelly Senna, and also in the British Pharmacopoeia and the Pharmacopoeia of India. Senna Indica also includes the variety known as Arabian, Mocha, Bombay, or East Indian Senna. Both varieties, as well as Alexandrian Senna, C. acutifolia, are official in the United States Pharmacopoeia. There is a certain difference in the qualities and also in the names of the species imported into Britain and America. The fine Tinnevelly Senna goes from Madras or Tuticorin to Britain. The leaflets are unbroken, from 1 to 2 or more inches long, thin, flexible, and green.

Historical or traditional use (may or may not be supported by scientific studies): People in northern Africa and southwestern Asia have used senna as a laxative for centuries. It was considered a “cleansing” herb because of its cathartic effect. In addition, the leaves were sometimes made into a paste and applied to various skin diseases. Ringworm and acne were both treated in this way.   Medical uses : [1]  Besides being a laxative, senna is used as a febrifuge, in splenic enlargements, anaemia, typhoid, cholera, biliousness, jaundice, gout, rheumatism, tumours, foul breath and bronchitis, and probably in leprosy. It is employed in the treatment of amoebic dysentery as an anthelmintic and as a mild liver stimulant. Leaves are astringent, bitter, sweet, acrid, thermogenic, catharitic, depurative, liver tonic, anthelmintic, cholagogue, expectorant, ferbifuge. Usefull in constipation, abdominal disordes, leprosy, skin disorders, leucoderma, splenomegaly, hepatomegaly, dyspepsia, cough, and bronchitis. Chemistry and Pharmacology Pharmacology [2]: Senna leaves and pods have been shown to have laxative activity. It is usefull in habitual constipation. Pharmacological investigations show that sennosides A and B account for the entire activity of the senna leaves and pods. [3]   Leaves contain glycosides, sennoside A, B, C & D. Two naphthalene glycosides have been isolated from leaves and pods. Active constituents: Senna contains anthraquinone glycosides known as sennosides. These molecules are converted by the normal bacteria in the colon into rhein-anthrone, which in turn has two effects. It first stimulates colon activity and thus speeds bowel movements. Second, it increases fluid secretion by the colon.[4] Together, these actions work to get a sluggish colon functional again. Several controlled studies have confirmed the benefit of senna in treating constipation.[5] Constipation induced by drugs such as the anti-diarrhea medicine loperamide (Imodium®) has also been shown to be improved by senna in a clinical trial.[6] Citations [1] a The wealth of India, P.I.D., C.S.I.R., New Delhi (CD ROM Version). b Orient Longman, Indian Medical Plants. 1993; 2 : 23.) [2] a. Grote et al., J Am. Pharm. Assoc. 1951; 40(52);3. b. Fairbairn & Michaels, "Vegetable Purgatives - Part III ") [3] a. Tanaka, H. et al., Chem. Pharm Bull., 1982; 30 : 5; b. Lemli, J et al., Planta Medica. 1981; 43:11) [4] Leng-Peschlow E. Dual effect of orally administered sennosides on large intestinal transit and fluid absorption in the rat. J Pharm Pharmacol 1986;38:606–10.) [5] a.Passmore AP, Davies KW, Flanagan PG, et al. A comparison of Agiolax and Lactulose in elderly patients with chronic constipation. Pharmacol 1993;47(suppl 1):249–52.  b.Kinnunen O, Winblad I, Koistinen P, Salokannel J. Safety and efficacy of a bulk laxative containing senna versus lactulose in the treatment of chronic constipation in geriatric patients. Pharmacol 1993;47(suppl 1):253–5.) [6] Ewe K, Ueberschaer B, Press AG. Influence of senna, fibre, and fibre+senna on colonic transit in loperamide-induced constipation. Pharmacol 1993;47(suppl 1):242–8

Pharmacology & Toxicology 1.Senna-containing laxatives: excretion in the breast milk? Faber P; Strenge-Hesse A, Geburtshilfe Frauenheilkd 1989 Nov;49(11):958-6 2.Two-year carcinogenicity study with sennosides in the rat: emphasis on gastro-intestinal alterations. Lyd’en-Sokolowski A; Nilsson A; Sioberrg P, Pharmacology; VOL 47 Suppl 1, 1993, P209-15 3. Acute hemorrhagic colitis following administration of sennosides A and B (letter), Villand J, Presse Med, 14(2):104-5 1985 Jan 19 4. Influence of a highly purified senna extract on colonic epithelium. van Gorkom BA; Karrenbeld A; van Der Sluis T;  Koudstaal J; de Vries EG; Kleibeuker JH, Digestion, 61(2):113-20 2000 5. Analytics of senna drugs with regard to the toxicological discussion of anthranoids., Grimminger W; Witthohn K, Pharmacology, 47 Suppl 1(-HD-):98-109 1993 Oct 6. Genotoxicity of sennosides on the bone marrow cells of mice. Mukhopadhyay MJ; Saha A; Dutta A; De B;Mukherjee A, Food Chem Toxicol 36(11):937-40 1998 Nov 7. Sennosides and human colonic motility. Staumont G; Frexinos J; Fioramonti J; Bu’eno L Pharmacology, 36 Suppl 1 (-HD-):49-56 1988 8. Long-term mucosal alterations by sennosides and related compounds. Dufour P; Gendre P Pharmacology 36 Suppl 1(-HD-):194-202 1988 9. Laxative potency and acute toxicity of some anthraquinone derivatives, senna extracts and fractions of senna extracts. Hietala P; Marvola M; Parviainen T; Laininen H, Pharmacol Toxicol, 61(2):153-6 1987 Aug 10. Toxic effects of sennosides in laboratory animals and in vitro. Mengs U, Pharmacology, 36 Suppl 1(-HD-):180-7 1988 11. Review article: anthranoid laxatives and their potential carcinogenic effects. van Gorkom BA ; de Vries EG ; Karrenbeld A ; Kleibeuker JH, Aliment Pharmacol Ther, 13(4):443-52 1999 Apr 12. Measurement of the intestinal clearance of alpha 1-antitrypsin and the exchangeable potassium pool in elderly patients treated with anthraquinone glycosides. Emeriau JP ; Manciet G ; Borde C ; Raynal F ; Galley P, Gastroenterol Clin Biol; VOL 7, ISS 10, 1983, P799-801 13. Two-year carcinogenicity study with sennosides in the rat: emphasis on gastro-intestinal alterations. Lyd´en-Sokolowski A ; Nilsson A ; Sj¨oberg P, Pharmacology, 47 Suppl 1(-HD-)  :209-15 1993 Oct 14. Ultrastructure of mouse intestinal mucosa and changes observed after long term anthraquinone administration. Dufour P ; Gendre P, Gut; VOL 25, ISS 12, 1984, P1358-63 15. The genotoxicity status of senna. Heidemann A ; Miltenburger HG ; Mengs U, Pharmacology, 47 Suppl 1(-HD-) :178-86 1993 Oct 16. Effects of ‘contact laxatives’ on intestinal and colonic epithelial cell proliferation. Geboes K ; Nijs G ; Mengs U ; Geboes KP ; Van Damme A ; de Witte P, Pharmacology, 47 Suppl 1(-HD-):187-95 1993 Oct 17. Effect of sennosides and related compounds on intestinal transit in the rat. Leng-Peschlow E, Pharmacology, 36 Suppl 1(-HD-):40-8 1988 18. Reproductive toxicological investigations with sennosides. Mengs U, Arzneimittelforschung, 36(9):1355-8 1986 Sep 19. Effect of sennosides on colon motility in dogs. Fioramonti J ; Staumont G ; Garcia-Villar R ; Bu´eno L, Pharmacology, 36 Suppl 1(-HD-):23-30 1988 20. Effects of sennosides on colonic myoelectrical activity in man. Frexinos J ; Staumont G ; Fioramonti J ; Bueno L, Dig Dis Sci, 34(2):214-9 1989 Feb 21. Effects of long-term sennoside treatment on in vitro motility of rat colon. Odenthal KP ; Leng-Peschlow E ; Voderholzer W ; M¨uller-Lissner S, Pharmacology, 47 Suppl 1(-HD-):146-54 1993 Oct 22. Chronic sennoside treatment does not cause habituation and secondary hyperaldosteronism in rats. Leng-Peschlow E ; Odenthal KP ; Voderholzer W ; M¨uller-Lissner S, Pharmacology, 47 Suppl 1(-HD-):162-71 1993 Oct 23. Evaluation of the potential carcinogenic activity of Senna and Cascara glycosides for the rat colon. Mereto E ; Ghia M ; Brambilla G, Cancer Lett, 101(1):79-83 1996 Mar 19

QUALITY CONTROL Sennosides as calcium salts are assayed as Total hydroxyanthracene glucosides estimated as Sennoside B. As per BP, E (1%,1cm) value of 240 or 200  for color development at 515nm and 500nm respectively) is used. USP employs spectroflurometric method necessitating the use of standard every time. There is an increased tendency nowadays to use HPLC method declaring Sennosides A + B. A rapid and useful method based on the BP is popularly used all over the world.

Analytical Methods   1.Quantitative chromatographic determination of the active principles of senna (sennoside A, sennoside B), Longo R; Meinardi G, Bull. Chim Farm., 104(8):503-10 1965 Aug 2. A comparative study of various new methods for the determination of sennosides in Senna leaf and Senna fruit, Os FH van; Zwaving JH; Richters AR,  Pharm Weekb1, 103(13):317-32 1968 Mar 29 3. Spectrophotometric estimation of sennosides and rhein glycosides in senna and its preparations. Habib AA; El-Sebakhy NA, J Nat Prod, 43(4):452-8 1980 Jul-Aug 4. Spectrofluorometric determination of sennosides in tablets. Wahbi AM; Unterhalt B, Planta Med, 33(4):393-5 1978 Jun 5. Determination of eight constituents of hsiao-cheng-chi-tang by high-performance liquid chromatography. Sheu SJ; Lu CF, J Chromatogr A, 704(2):518-23 1995 Jun 9 6. High performance liquid chromatography of the evolution of sennosides A and B in solution. Merle J; Barthes D;Besson J, Farmaco [Prat],39(7):233-42 1984 Jul 7. Analytical studies on the active constituents in crude drugs. IV. Determination of sennosides in senna and formulations by high-performance liquid chromatography. Hayashi S; Yoshida A; Tanaka H; Mitani Y; Yoshizawa K, Chem Pharm Bull (Tokyo), 28(2):406-12 1980 Feb 8. High-pressure liquid chromatographic analysis of sennosides A and B purgative drugs. Komolafe OO, J Pharm Sci, 70(7):727-30 1981 Jul 9. Quantitative determination of sennosides in senna pods and senna leaves. I. Method (author’s transl). Brendel WD ; Schneider D, Planta Med, 25(1):63-7 1974 Feb 10. Estimation of individual sennosides in plant materials and marketed formulations by an HPTLC method. Shah SA ; Ravishankara MN ; Nirmal A ; Shishoo CJ ; Rathod IS ; Suhagia BN, J Pharm Pharmacol, 52(4):445-9 2000 Apr 11. Sennosides Reference Standard (Control 951) of the National Institute of Health Sciences Okada S ; Kitajima A ; Tanimoto T ; Suzuki H ; Satake M, Eisei Shikenjo Hokoku, -HD-(114):106-12 1996

Chemistry, Isolation and Constituents   1. Isolation of a new aloe-emodin dianthrone diglucoside from senna and its potentiating effect on the purgative activity of sennoside A in mice. Nakajima K; Yamauchi K; Kuwano S, J Pharm Pharmacol; VOL 37, ISS 10, 1985, P703-6 2. Senna—an old drug in modern research. Lemli J,  Pharmacology, 36 Suppl 1(-HD-):3-6 1988 3. Isolation and structural definition of a new sennoside from Cassia senna L. (author’s transl), Christ B ; P¨oppinghaus T ; Wirtz-Peitz F ,Arzneimittelforschung, 28(2):225-31 1978 4. The effect of different storage conditions on the chemical stability, laxative effect and acute toxicity of sennoside solutions. Lainonen H ; Marvola M ; Hietala P ; Parviainen T Pharmacol Toxicol; VOL 63, ISS 1, 1988, P37-41 5. The senna drug and its chemistry. Franz G, Pharmacology, 47 Suppl 1(-HD-):2-6 1993 Oct

Mechanism of Action 1. Effects of sennosides A + B and bisacodyl on rat large intestine. Leng-Peschlow E Pharmacology, 38(5):310-8 1989 2. The mechanism of action of sennosides, Lemli J , Ann Gastroenterol Hepatol (Paris), 32(2):109-12 1996 Mar-Apr 3. Metabolism and pharmacokinetics of anthranoids. de Witte P, Pharmacology, 47 Suppl 1(-HD-):86-97 1993 Oct 4. Title Sennoside-induced secretion and its relevance for the laxative effect Leng-Peschlow E, Department of Pharmacology, Madaus AG, K¨oln, FRG., Pharmacology, 47 Suppl 1(-HD-):14-21 1993 Oct 5. Metabolism of sennosides—an overview. Lemli J, Pharmacology, 36 Suppl 1 (-HD-):126-8 1988 6. [Mechanism of action of sennosides], Lemli J, Bull Acad Natl Med, 179(8):1605-11 1995 Nov 7. [Transport and mode of action of sennosides, Dobbs HE ; Lane AC ; Macfarlane IR, Farmaco [Sci], 30(2):147-58 1975 Feb

Manufacture of Calcium Sennosides A.Short description of process : Senna leaves are tested before and after grinding for Sennosides contents and are extracted with methanol. The above methanolic extracts are collected and Calcium sennosides are separated by addition of Calcium Salt solution. The precipitated Calcium sennosides are centrifuged and washed with methanol & dried under vacuum. The dried Calcium sennosides are ground, tested and packed. B.Process Control Test : The following control parameters are monitored during manufacture : PH of Aqueous suspension Heavy metals Residue on igination. L.O.D Assay

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