Newer Active Pharmaceutical Ingredients For Research 1

Abacavir- Nucleoside analog Reverse Transcriptase Inhibitor (NRTI)
Acarbose- Anti-diabetic
Acetyl sulfisoxazole- Antibacterial Sulfonamide
Acrivastine- second-generation H1-receptor antagonist antihistamine
Adapalene-third-generation topical retinoid primarily used in the treatment of acne and is also used (off-label) to treat keratosis pilaris
Adefovir dipivoxil-for the treatment of hepatitis B

Afloqualone (Arofuto) - an analogue of methaqualone developed in the 1980s in Japan. It has sedative and muscle relaxant effects, and has had some clinical use, although it causes photosensitization as a side effect which can cause skin problems such as dermatitis

Alacepril (INN) is an ACE inhibitor

Alclometasone 17,21-dipropionate- a synthetic corticosteroid for topical dermatologic use

Alkaloids

True alkaloids derive from amino acid and they share a heterocyclic ring with nitrogen. These alkaloids are highly reactive substances with biological activity even in low doses. All true alkaloids have a bitter taste and appear as a white solid, with the exception of nicotine which has a brown liquid. True alkaloids form water-soluble salts. Moreover, most of them are well-defined crystalline substances which unite with acids to form salts. True alkaloids may occur in plants (1) in the free state, (2) as salts and (3) as N-oxides. These alkaloids occur in a limited number of species and families, and are those compounds in which decarboxylated amino acids are condensed with a nonnitrogenous structural moiety. The primary precursors of true alkaloids are such amino acids as l-ornithine, l-lysine, l-phenylalanine/l-tyrosine, l-tryptophan and l-histidine2332. Examples of true alkaloids include such biologically active alkaloids as cocaine, quinine, dopamine, morphine and usambarensine

Protoalkaloids are compounds, in which the N atom derived from an amino acid
is not a part of the heterocyclic31. Such kinds of alkaloid include compounds
derived from l-tyrosine and l-tryptophan. Protoalkaloids are those with a closed ring, being perfect but structurally simple alkaloids. They form
a minority of all alkaloids. Hordenine, mescaline (Figure 5) and yohimbine are
good examples of these kinds of alkaloid. Chini et al.33 have found new alkaloids,
stachydrine and 4-hydroxystachydrine, derived from Boscia angustifolia, a plant
belonging to the Capparidacea family. These alkaloids have a pyrroline nucleus
and are basic alkaloids in the genus Boscia. The species from this genus have
been used in folk medicine in East and South Africa. Boscia angustifolia is
used for the treatment of mental illness, and occasionally to combat pain and
neuralgia.

Pseudoalkaloids are compounds, the basic carbon skeletons of which are not derived from amino acids31. In reality, pseudoalkaloids are connected with amino acid pathways. They are derived from the precursors or postcursors (derivatives the indegradation process) of amino acids. They can also result from the amination and transamination reactions32 of the different pathways connected with precursors or postcursors of amino acids. These alkaloids can also be derived from non-aminoacid precursors. The N atom is inserted into the molecule at a relatively late stage, for example, in the case of steroidal or terpenoid skeletons. Certainly, the N atom can also be donated by an amino acid source across a transamination reaction, if there is a
suitable aldehyde or ketone. Pseudoalkaloids can be acetate and phenylalaninederived or terpenoid, as well as steroidal alkaloids. Examples of pseudoalkaloids include such compounds as coniine, capsaicin, ephedrine, solanidine, caffeine, theobromine and pinidine.

Occurance of alkaloids
Alkaloids are substances very well known for their biological activity at the beginning of world civilization. They were used in shamanism, in traditional herbal medicine for the cure of diseases and in weapons as toxins during tribal wars and during hunting. They also had, and still have, socio-cultural and personal significance in ethnobotany34. Moreover, they have been and continue to be the object of human interest concerning new possibilities for their safe utilization
and ensuing health benefits. Of all secondary compounds, historically and contemporaneously, only alkaloids are molecules of natural origin with highly important benefits and diagnostic uses. They can be characterized as the most useful and also the most dangerous products of nature. They can be extracted and purified Alkaloids are most abundant in higher plants. At least 25% of higher plants contain these molecules. In effect this means that on average, at least one in fourth
plants contains some alkaloids. In reality, it is not impossible that alkaloids occur more commonly. Using the latest equipment and technology, such slight traces of alkaloids may be detected (e.g., less than 10 gigagrams per kg of plant mass) that these have no real influence on biological receptors and activity. Generally these species are not considered as alkaloid species. Hegnauer1213 has defined alkaloid plants as those species which contain more than 0.01% of alkaloids. This is right from the point of view of the classification. From the genetic point of view, and the genetic mechanism of alkaloid synthesis, it is a real limitation. Paying attention to slight traces of alkaloids in plants, we see the members of the plant family which are relatives. They have a genetically determined alkaloid mechanism with a species expression. Moreover, this expression is also on the hybrid level.

Fagonia cretica

The drug consists of dried whole plant of Fagonia cretica Linn. (Plate 2.1 A & B); syn. F. bruguiri DC. Incl., F. indica Burm. F., F. Arabica Linn., F. mysorensis Roth.; Fam. Zygophyllaceae. It is a small green, spiny, branched, woody plant occurring in dry regions of northwest India.

Other names
Hind. - Dhamasa, Hingua, Dhamhar, Ustarkhar, Usturgar, Hinguna, Damahan
Pan. - Dhamah, Dhamaha, Samada, Dama, Damiya.
Beng.- Duralabha, Dhanyavas
Sind. - Drammaha
Guj. - Dhramau, Dharama, Dhamasa, Dhamaso, Damasha
Assa. - Shukai
Mar. - Dhamasa, Kante chubuk, Dumaso, Dhamasa
Kan. - Valliduruve, Nelayindal
Tel. - Pilaregati, Dulgodi, Chittigara



Description
Macroscopic

It is a small spiny under shrub with branches, often more or less prostrate, twings slender, striate, glabrous and glandular. Leaves are opposite, 1-3 foliate, about 12 by 2.5 mm, entire, linear or elliptic mucronate. Petiole very variable, 0.3 cm long, sometimes leaf like stipules transformed into sharp slender spines up to 1-2 cm long, persistant and continuing growth after the fall of the leaves.
Flowers solitary, rose-colored, arising from between the stipules. Sepals are five, deciduous, imbricate half as long as petals. Petals are 6 mm long, spahulate with a marked claw, disk short, inconspicuous. Stamens are 10, inserted on the disk. Ovary 5 angled, 5 celled, tapering in to 5 – angled style. Stigma simple. Fruit 5- mm long of 5-seeded cocci, glandular pubescent, deeply 5partite almost to the axis, cocci dehishing along the ventral suture and separating a horny endocarp.
Microscopic
T.s

Diagrammatic T.S is circular with distinct eleation and depressions, showing hypodermal, mesocortical and pericyclic fibres, a narrow phloem, and wide xylem encircling a hollow center or rarly a small parenchymatous pith.
TS of the root
Transverse section of the root was circular in outline. In the centre lies the wood, occupied almost half the region of the whole section cortex and phloem tissue were characterized by the presence of nonlignified stone cells and fibers.
Cork
Outermost tissue consisted of about 5-6 raws of suberised rectangular cells.
Cortex
A wide zone of 10 to 15 paenchymatous cells consisted of isolated or groups of seleroids towards the inner region. Stone cells were rectangular, thick walled, pitted and measured 7-10 micron in breadth. Fibres were long, tapering and measured 110-120 micron in length and 3-6 micron in breadth. Few slit like pits were seen on the walls of some of fibres. Both stone cells and fibres were non lignified. The parenchymatous cells were filled with simple starch grains.
Phloem
It was a wide non lignified zone constited of 10-15 raws of cells contained sieve tissue, phloem lied adjacent to the xylem was entirely parenchymatous. The parenchymatous cells of the phloem contained simple starch grains.
Xylem
Young TS showed the diarch condition of the xylem in the centre which was occupid by wide lignified zone in the older root, xylem vessels were associeated with parenchyma, fibres and tracheids. The vessels were pitted and reticulate and measured 46-120 micron in length and 8-14 micron in breadth. Fifres were narrow, tapering, thick wqalled and occasionally exhibited slit like pits. Hey were measured 125-300 micron in length and 8-10 micron in breadth.
M ray were mostly uniseriate. The cells were thick walled and rectangular in shape. The cells of the M rays and xylem parenchyma contained simple starch grains. The starch grain of the xylem, phloem and cotex region of the root measured 1.1-3.1 micron in diameter.
Leaf-Diagrammatic TS passing through the midrib is broadly convex at lower side, with slight elevation on upper side, shows 3 to 5 centrally located meristeles, few rows of collenchymatous tissue under both the epidermii and broad lateral dorsiventral laminar extensions on either side.
Detailed TS shows a layer of upper and lower epidermis with undulated margin, covered with thick, cuticle exhibiting stomata and scars left by removal of trichomes at places, the cells of the upper epidermis being bigger in size than the lower ones; a narrow 2 to 5 celled wide collenchymatous band underneath the upper and lower epidermis of the midrib; the paranchymatous ground tissue embedded with 3 to 5 bicollateral meristeles, the centrally located being the biggest in size; mesophyll occupied by a layer of palisade underneath the upper epidermis and 8 to 10 rows of spongy parenchyma traversed with obliquely cut vascular strands, oil globules and few prismatic crystals of calcium oxalate.

Chemical constituents
Major
Saponin-I, saponin-II1,2
Others3-O-[β-D-glucopyranosyl (1→2)-α-L-arabinopyranosyl] hederagenin 28-O- β-D glucopyranosyl ester, 3-O-[ β -D-glucopyranosyl (1→2)- α -L-arabinopyranosyl] oleanolic acid 28-O-[ β –D glucopyranosyl (1→6)- β -D-glucopyranosyl] ester, 3-O-[ β -D- glucopyranosyl (1→2)- α –L arabinopyranosyl] 27-hydroxy oleanolic acid 28-O-[ β -D-glucopyranosyl (1→6)- β –D glucopyranosyl] ester, 3-O- β -D glucopyranosyl (1→2)- α -L-arabinopyranosyl] olean-12-en-27-al-28-oic acid 28-O-[β –D glucopyranosyl (1→6)- β -D-glucopyranosyl] ester3, 3-O-[ β -D-glucopyranosyl-(1→2)]-[ α -L-arabinopyranosyl-(1 → 3)]- α -L-arabinopyranosyl}-ursolic acid 28-O-[ β -D-glucopyranosyl] ester (indicasaponin A), 3-O-{[ β -D-glucopyranosyl-(1→2)]-[ α -L arabinopyranosyl-(1→3)]- α -L-arabinopyranosyl}-oleanolic acid-28-O-[β –D glucopyranosyl] ester (indicasaponin B), 3-O-[ β -D-glucopyranosyl-(1→3)- α –L arabinopyranosyl]-ursolic acid-28-O-[ β -D-glucopyranosyl] ester, 3-O-[ β -D-glucopyranosyl-(1→3)- α -L-arabinopyranosyl]-oleanolic acid-28-O-[ β -D-glucopyranosyl] ester4, 3-O- β -D-xylopyranosyl(1→2)-[β-D-glucopyranosyl (1→3)]- α -L-arabinopyranosyl oleanolic acid 28-O- β -D-glucopyranoside, 3-O- β -D-glucopyranosyl (1→2)-[ β -D-glucopyranosyl(1→3)]- α –L arabinopyranosyl oleanolic acid 28-O- β -D-glucopyranoside, 3-O- β -D-xylopyranosyl(1→2)-[ β -D-glucopyranosyl (1→3)]- α -L-arabinopyranosyl oleanolic acid, 3-O- β –D glucopyranosyl(1→2)-[ β -D-glucopyranosyl(1→3)]- α -L-arabino pyranosyloleanolic acid, 3-O- β -D-xyiopyranosyl(1→2)-[ β -D-glucopyranosyl (1→3)]- α -L-arabinopyranosyl 27-hydroxyoleanolic acid, 28-O- β -D-glucopyranoside, 3-O- β -D-xylopyranosyl(1→2)-[ β -D-glucopyranosyl(1→3)]- α -L-arabinopyranosyl ursolic acid 28-O- β -D-glucopyranoside and 3-O- β -D-xylopyranosyl (1→2)-[ β -D-glucopyranosyl (1→3)- α-L-arabinopyranosyl 27-hydroxyursolic acid 28-O- β -D-glucopyranoside,5 21,22 α -epoxy-23-O- β -d-glucopyranosyl-nahagenin623,28-di-O- β -d- glucopyranosyltaraxer-20-en-28-oic acid,3b,28-di-O- β -D glucopyranosyl 23-hydroxytaraxer-20-en-28-oic acid7, 3-O-( β-D xylopyranosyl (1→2) α -L-arabinopyranosyl) 27-hydroxyoleanolic acid 28-O-( β-D-glucopyranosyl (1→6) β-D-glucopyranosyl) ester, 3 β -O-( β -D-xylopyranosyl(1→2) α -L-arabinopyranosyl) olean-12-en-27-al-28-oic acid 28-O-(beta-D-glucopyranosyl(1→6) β -D-glycopyranosyl) ester,8 hederagenin-3-O-α-L-arabinopyranosyl-28-O-β-D-glucopyranoside, hederagenin-3-O-β-D-xylopyranosyl (1→2)-α-L-arabinopyranosyl-28-O-β-D-glucopyranoside, oleanolic acid 3-O-β-D-glucopyranosyl (1→2)-α-L-arabinopyranosyl-28-O-β-D glucopyranoside9; 15,16-dihydroxy-7-oxo-cis-ent-erythrox-3-ene (fagonone), 16-O-acetylfagonone10, 15,16-dihydroxy-7-β-hydroxy-cis-ent-erythrox-3-ene (7-β-hydroxyfagonene)11;Triterpene IV, Triterpene V, Triterpene VI 12; sulphated derivative of 3 β,27-dihydroxyolean-12-en-28-oic acid, 3 β,27-dihydroxyurs-12-en-28-oic acid, disulfated oleanene derivative13; isorhamnetin 3-glucoside, 3-rutinoside, herbacetin 8-rutinoside, herbacetin 8-methyl ether-3-rutinoside, 3,7-diglucoside, 3-rutinoside-7 glucoside14; quarcetin, caempferol 15; 3-glucosides of kaempferol, quercetin and isorhamnetin, 3-rutinoside of quercetin, 3,7-diglucoside of quercetin and isorhamnetin., kaempferol 3,7-diglycoside, quercetin 3-diglycoside16, Aglycon A(fagonin), Aglycon B17, genin A, genin B18; triterpenoid fagonin19; oleanolic acid19,20,21; Kaempferol, Quarcetine and isorhamnetine22, Quercetin, kaempferol23;Glucose, maltose, arabinose, rhamnose17; free amino acids alanine, arginine, glycine, isoleucine, lysine, phenylalanine, proline, tyrosine, and valine24, Lysine, threonine, aspartic acid, serine, glutamic acid25, Leucine, methionine, alanine, glutamic acid, aspartic acid26; β sitosterol27,28,29, stigmasterol, campesterol27, lanosterol29; caproic acid, caprylic acid, luaric acid, myristic acid, palmitic acid, stearic acid, oleic acid30; 1-triacontanol27, n-triacontanol28; free ascorbic acid31­; Betulin18; Quinovic acid32,33,methyl ester of quinovic acid33; Docosyl-Docosanoate34; harman 19,35; Harmine36; ceryl alcohol28; Nahagenin37; Diosgenin and kryptogenin29.

Taxol, anticancer drug from taxus family

TAXOL

DITERPENOID
100 years old tree of Taxus brevifolia is 6 – 9 meter in height is suitable for collection of trunk or stem bark.
Stem is having the diameter of 25 cm.
Bark is removed in May – August & bark of 3 matured tree would give 1 gm of Taxol.
Generally 2 gm Taxol is required for Cancer treatment.
Bark contains about 0.01 – 0.02% of Taxol & 0.2% of Bacatin – III.
Taxus plant i.e. Taxus brevifolia is known as “Pacific Yew” / “Yew Plant”.
In India, it is known as “Rakshala” or “Barhmi”.
The plant is known to have poisonous effect to children & animals.
Entire plant is toxic except Red Arillus of Seed.
HISTORY:
The Bark was used in the treatment of Rheumatism, Liver disorder & UTI.
In Western Himalayas, the dilute Decoction of Bark was taken during Winter by tribal people to increase the body resistance against Cold.
Due to high tensile properties of wood, it was used to make gows & implements.
The wood has high Caloric value, so was used in Potaries.
In Europe, it was used for habges.
Dried Leaves are used in “Havan” in India.
Taxol was isolated in 1971 from T. brevifolia by Dr. Wani & it was found to be useful in Cancer treatment.
Taxol is a Diterpene.
It affects Microtubule assembly in the dividing cells & stops the production of cells.
It is useful in Murine Leukemia (of Cavity).
Also is effective against Cancer of Lung, Breast, Colon & Ovary.
For activity of drug, 4 membered Oxygen ring, 2’ OH group, 3’ NH2 group & Acyl side chain are essential.
Taxus is also Antifungal & Insecticidal.
SYNONYMS:
Yew
Talispatra
Himalayan Yew
B.S:
Taxol is a Naturally occurring Diterpenoid belonging to Taxane group of compounds present in genus Taxus.

Different species of Taxus grown in World;

Taxus baccata è European Yew
T. cuspidata è Japanese Yew
T. chineusis è Chinese Yew
T. brevifolia è Pacific Yew
T. wallichiana è Himalayan Yew
T. canadensis è Ground Hemlock / American or Canadian yew
The Genus Taxus also called Yew consists of various species out of which 4 are of Medicinal importance viz;

T. baccata
T. cuspidata
T. brevifolia
T. canadensis
FAMILY: Taxaceae
HABITAT:
Plant is found in Temperate Forests.
It is a Small Evergreen tree, existing in under storey.
It has Dark Green, Long & Narrow shining Leaves.
Tree is found at an elevation of 7000 – 11,000 feet.
Taxane derivatives are also present in Leaves,
So, Leaves are harvested.
Therefore if Bark is taken, the Tree wood die.
In order to treat Breast & Ovary cancer è 2.5 g Taxol is required.
WORLD – WIDE TRADE:
World – Wide Trade of Taxol is reached to US $ 1.92 billion.
World’s requirement è 700 kg / year
Current Production è 350 kg / year
Present production of Taxol is only 350 kg & demand is double, therefore conserve / propagate the plant.
MANAGEMENT STRATEGY OF TAXUS IN INDIA:

RRL – Jammu has initiated programmes for conservation of Himalayan Yew, on following lines;

They have found out Taxus growing area & are trying for regeneration of plants.
They have started propagation & cultivation by new techniques.
Plants are found in Himachal Pradesh & North Eastern Himalayan region, mostly in / on inaccessible slopes.
The plants have been heavily debarked & most of damages are recent.
The plant regeneration is almost absent.
The potential areas of Taxus which were there few decades ago are now no more.

The availability of Taxane is better from the Leaves than bark.
Leaves contain small amount of Taxol.
But contain higher amount of Bacatin III.
Taxol is nowadays no more drug of choice.
Many Semisynthetics like Taxoterene shows better activity which is produced from Bacatin III.
Also, it has lesser Side Effects.

Propagation can be carried out through Stem cutting.
Cutting of the Terminal part of Axis / Twig will give 80 – 90% Rooting.
After Treatment with Indole Butyric Acid (IBA) ~ 200 ppm for 18 hours, would give better results.
The best time for planting the cuttings is November – February.

LAYERING METHOD:
Bandages containing GA3 (Gibberellic Acid) or IBA are applied on branch / twig & then after 90 days, cuttings are transplanted.
This plant is as good as 5 years old plant.

SEED SOWING METHOD:
Seeds take about 1 year to germinate.
However, Seeds are stratified & treated with Gibberellic acid (GA3).
Seeds can be cultivated in even poor soil, but water logging is harmful.
It can be planted at 40 x 40 cm distance.
Transplanting of Plant is dangerous.
Therefore plant will die due to shock of Roots.
Taxol amount is more in such plants.
Plant grows well in cool & moist places.

COLLECTION:
Collection Time è June – July for Bark & Needles (Leaves).

POST HARVESTMENT TREATMENT:
Leaves are dried in thin layers.
Active constituents would increase on storage for 9 days, regardless of storage temperature.
Cell culture & Biotechnology è Taxol production by this way fail to compete with the naturally cultivated plant.
Tribals called Taxus Tree “TREE OF DEATH” because in past it was believed that anybody who sleeps under this tree would go to eternal sleep forever.

USES:
Taxol affects Microtubule assembly in the dividing cells & stops the production of cells.
Inhibits Cell Migration.
Thus preventing spread of Metastatic Cancer cells.
It has also a promising role against Non – small cell;
Lung Carcinoma
Gastric Cancer
Cervical Cancer
Carcinoma of Head, Neck, Prostrate & Colon.

CHAPTER – 1WORLD – WIDE TRADE IN MEDICINAL PLANTS & DERIVED PRODUCTS

DIOSGENIN

Diosgenin belongs to class of Sapogenin.
i.e. Aglycone found in Steroidal Saponin Glycoside Dioscin.
It is used for synthesis of Steroidal hormones.
B.S:
Diosgenin is commercially available from;

~ Dioscorea floribunda
~ Dioscorea compositae
~ Dioscorea deltoida

Generally it is collected from wild source, as for Cultivation correct Soil, proper Drainage, Freedom from Weed, Fungi is required.
Depending upon different species, it requires 3 – 5 years for development.

FAMILY: Dioscoreaceae

NO B.S SAPOGENIN %
SAPOGENIN HABITAT
D. deltoida Diosgenin 2 – 5% Growing well in Sub Himalayan region
D. floribunda Diosgenin 2 – 5% Central America
D. compositae Diosgenin 2 – 4% Mexico
D. prazeri Diosgenin 1 - 3% North Eastern India

SYNONYM:
Dioscorea Root, Rheumatism Root, Yam (Starchy Tubers)
Dioscorea Root is known as “Rheumatism Root”.
It is also called Yam (Starchy Tuber).

Dioscorea is cultivated by sowing Rhizome pieces with buds & is harvested after 18 – 24 months.
Plant contains about 4 – 6% of Diosgenin.
It is mainly present as Glycoside in plant.
Diosgenin occurs as the Rhamno – rhamno – glucoside, Dioscin, in the Rhizome of several species of Dioscorea.

CULTIVATION & COLLECTION:
 In view of the Pharmaceutical significance of the drug, it is tried & successfully grown in various parts of India.
 Commercially, it is grown in Tamil Nadu, West Bengal, Maharashtra, Karnataka & Jammu & Kashmir.
 The crop can be raised from seeds, but variability in progeny & comparatively longer time for harvesting are the disadvantage with this method.
 Therefore, Healthy Tubers of about 70 – 80 g in weight with crown are selected for cultivation.
 For checking the Tuber, they are treated with Fungicide & sown in Nursery beds.

 It takes about 30 – 40 days for their sprouting.
 After 2 – 3 months of growth, tubers are transplanted in the field, which is treated with Insecticide earlier.
 While planting, the Tubers are placed at a distance of 30360 cm.
 Initially, the Veins are weak & tender& they need support for their optimum growth.
 Trellis of 2.5 m in height are provided for this purpose.
 Since the Tubers are very Exhaustive, a high dose of farmyard manure to the extent of 5 – 10 tones per hectare is applied in the beginning.
 Organic fertilizers should be applied subsequently in equal doses at an interval of 1 month.
 Irrigation should be done every 10 days

 It is a Climber with Alternate Leaves.
 Rhizomes are;

~ Soft
~ Horizontally arranged
~ Very close to the Soil

 Drug is covered with scattered Roots.
 Weight è 20 – 50 gm
STRUCTURE OF DIOSGENIN:



DIOSGENIN
DIOSGENIN è D5 25 a Spirostan b - ol
DIOSGENIN is Steroidal Saponin
Subtype è Spirostanol, since here all rings are fused.
Sugar is attached at 3 – position.

ISOLATION & DEGRADATION OF DIOSGENIN

ISOLATION:
Dioscorea Rhizomes
Dioscin

(1) Hydrolyse Milled Root with Mineral acid.

(2) Filter, Neutralize & Dry the hydrolysed Root.

(3) Extract & Crystallize Diosgenin.



DEGRADATION:

(1) Cleave Spiroketal ring with Ac2O to form  20 – 22.

(2) Oxidize to generate 20 – keto group.

(3) Split side chain to yield C – 21 steroid.


16 Dehydro Pregnenolone acetate is used for the synthesis of various steroidal hormones.
All 4 types of Hormones like;


NO. HORMONES TYPES

1. Corticosteroids Cortisone, Hydrocortisone, Prednisolone
2. Progestrene / Pregnenes Progesterone, 17  OH progesterone
3. Androstins Testosterone, Methyl Testosterone
4. Contraceptives / 19 – Nor steroids Estnone, 17  ethynyl estradiol, Norethisterone acetate

 Such Hormones are produced from such natural sources only after 1980’s.
 Before that they were produced from Cholesterol or Stigmasterol.
 Such Hormones today cover 25% of market.


INDUSTRIES INVOLVED FOR SUCH HORMONE PRODUCTION IN INDIA

(1) REGIONAL RESEARCH LABORATORY (RRL)

Jammu
Working on Dioscorea compositae.

(2)WIADH LABORATORY

Bombay

(3)CIPLA LABORATORY

Bombay

(4)CHEMICAL, INDUSTRIAL & PHARMACEUTICAL LABORATORY LIMITED

Bangalore

Upto 1990, India was importing such hormones but, nowadays Diosgenin is not exported but different hormones prepared from it are exported widely.

Due to Development of Industrial companies like above in this field, Export gradually rises after 1998.

WORLD WIDE TRADE:
Much of the world’s production has come from MEXICO, where Tubers from D. compositae (Barbasco), D. mexicana, D. floribunda mainly harvested from wild plants, are utilized.
Other important sources of Dioscorea used commercially now include;

~ India (D. deltoida)
~ South Africa (D. sylvatica)
~ China (D. collettii, D. pathaicu, D. nipponica)

Demand for DIOSGENIN for Pharmaceutical is Huge, equivalent to 10,000 tones of Dioscorea Tuber per Annum.
DATA FOR 2005 – 2006

HORMONE AMOUNT (TONS) Rs. (CRORES)

Hydrocortisone 63 3.4
Prednisolone 2 0.5
Ethisterone & Derivative 2.2 7
Methyl Testosterone 17.5 1
Dexamethasone 7 1
Betamethasone 1.3 10

ALLIED SOURCES OF DIOSGENIN:

(!)COASTAL SPECIES TUBER

It gives 2 – 3 % Diosgenin.
Less Expensive
Since Dioscorea is Climber & needs support, while this is a shrub so no support is needed.

(!!)BALENITE ROXBURGHII  FRUIT

Xerophytic plant & can be cultivated in waste land also.
Good plant for Indian production.
Gives 1 – 2 % of Diosgenin.

(!!!)FENUGREEK  SEEDS
Not used commercially.

B.S: Seeds of Trigonella foenum – graecum
FAMILY: Leguminaceae
1 – 2 % Sapogenin
Because of ease of cultivation of Fenugreek & its rapid growth make the plant potentially viable crop for Steroid production in Temperate countries.

Heat stroke

HEAT stroke is a life-threatening illness characterized
by an elevated core body temperature
that rises above 40°C and central nervous
system dysfunction that results in delirium, convulsions,
or coma.

Despite adequate lowering of the body
temperature and aggressive treatment, heat stroke is
often fatal, and those who do survive may sustain permanent
neurologic damage.

Data from the Centers
for Disease Control and Prevention show that from
1979 to 1997, 7000 deaths in the United States were
attributable to excessive heat.
The incidence of such
deaths may increase with global warming and the predicted
worldwide increase in the frequency and intensity
of heat waves.

Research performed during the past decade has
shown that heat stroke results from thermoregulatory
failure coupled with an exaggerated acute-phase response
and possibly with altered expression of heatshock
proteins.

The ensuing multiorgan injury results
from a complex interplay among the cytotoxic
effect of the heat and the inflammatory and coagulation
responses of the host.

In this article, we summarize
the pathogenesis of heat stroke as it is currently
understood and explore the potential therapeutic and
preventive strategies.