WO2003068251A1 - Formulation a base d'herbes medicinales destinee a traiter des troubles deficitaires de l'attention (dca/thada) et procede de preparation correspondant - Google Patents

Formulation a base d'herbes medicinales destinee a traiter des troubles deficitaires de l'attention (dca/thada) et procede de preparation correspondant Download PDF

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WO2003068251A1
WO2003068251A1 PCT/IN2002/000042 IN0200042W WO03068251A1 WO 2003068251 A1 WO2003068251 A1 WO 2003068251A1 IN 0200042 W IN0200042 W IN 0200042W WO 03068251 A1 WO03068251 A1 WO 03068251A1
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extract
composition
extracts
oil
herbs
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PCT/IN2002/000042
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Panchapagesa Muthuswamy Murali
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Dalmia Centre For Research And Development
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484—Glycyrrhiza (licorice)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/80—Scrophulariaceae (Figwort family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system

Definitions

  • the present invention relates to a process for a synergistic herbal composition for the treatment of attention deficit hyperactivity disorder (ADHD or ADD) and the process for preparing the same.
  • ADHD attention deficit hyperactivity disorder
  • Attention deficit-hyperactivity disorder is a neurobehavioral disorder and most common psychiatric disorder that affects 3-5 percent of American children, though some respected experts suggest the rate is as high as 10 percent. It interferes with a person's ability to stay on a task and to exercise age-appropriate inhibition (cognitive alone or both cognitive and behavioral).
  • Some of the warning signs of ADHD include failure to listen to instructions, inability to organize oneself and school work, fidgeting with hands and feet, talking too much, leaving projects, chores and homework unfinished, and having trouble paying attention to and responding to details.
  • the usual course of treatment may include medications such as methylphenidate (Ritalin), dextroamphetamine (Dexedrine) or pemoline (Cylert), which are stimulants that decreases impulsivity and hyperactivity and increase attention.
  • medications such as methylphenidate (Ritalin), dextroamphetamine (Dexedrine) or pemoline (Cylert), which are stimulants that decreases impulsivity and hyperactivity and increase attention.
  • Most experts agree that treatment for ADHD should address multiple aspects of the individual's functioning and should not be limited to the use of medications alone. Treatment should include structured classroom management, parent education (to address discipline and limit-setting), and tutoring and/or behavioral therapy for the child. There is no "cure” for ADHD. Children with the disorder seldom outgrow it; however, some may find adaptive ways to accommodate the ADHD as they mature.
  • Boys and girls (and also men and women) cope differently with stress. Boys use “fight or flight” while girls “befriend or mend.” So boys, when stressed (primarily at school), try to take over the situation or punch someone. This does not sit well with authority figures (teachers, principals, cops and parents) who have the power to refer a boy to the school counselor or suggest a visit to the doctor. Girls, on the other hand, try to please or become invisible. In fact the learning problems of girls go far more undiscovered compared to those of boys who are more disruptive and get the attention of the adults.
  • the disturbance does not occur with a pervasive developmental disorder, Schizophrenia, or a Psychotic Disorder or with another mental disorder (Anxiety Disorders, Mood Swings, etc.) Symptoms
  • Symptoms of Inattention a) Often fails to give close attention to details or makes careless mistakes on school work, work ,other activities. b) often has difficulty in sustaining tasks or play activities c) often does not seem to listen when spoken to directly d) Often does not follow through on tasks or fails to finish work e) Often has difficulty organizing daily task and activities f) Often dislikes, avoids, or is reluctant to engage in tasks that require sustained mental effort. g) Often loses things necessary for task h) Often distracted by extraneous stimuli i) is often forgetful in daily activities
  • Symptoms of Hyperactivity a) Often fidgets with hands or feet, or squirms in seat b) often leaves seat in classroom or other situations c) often runs about or climbs (in adults or adolescents- may feel restlessness) d) often has difficulty playing quietly or engaging in leisure activities quietly e) is often "on the go” f) often talks excessively Symptoms of Impulsivity a) Often blurts out answers prior to questions being completed b) Often has difficulty waiting for a turn c) Often interrupts or intrudes on others
  • Attention Deficit Hyperactivity Disorder Combined Type If criteria for Inattention and Hyperactivity -Impulsivity are met
  • the dosage is not weight dependent and is dose-response relationship based.
  • the drug is generally titrated against the individuals.
  • the dosage can be higher or lower if there are associated side effects. 15-30% of children show motor tics. Other side effects are also observed.
  • the Anti-depressants administered to ADHD patients are:
  • Desipramine, Lrnprarnine and Bupropion are used for antihypertensive drugs used for the treating the ADHD pateients.
  • Clonidine is used for antihypertensive drugs used for the treating the ADHD pateients.
  • Cylert (Pemoline) Pemoline is similar to the other stimulants in its side effects, tending to cause insomnia and decreased appetite. It reaches a peak two to fours hours after it is taken, and has a half-life of 12 hours. This relatively long half life means that it can be taken once daily.
  • Pemoline is metabolized by the liver, and has been associated with some cases of liver iriflammation. Liver function should be tested prior to starting this medication and done periodically during the course of therapy to monitor for mflammation of the liver.
  • liver failure in children taking Cylert has prompted a recommendation that liver function tests be performed on a bi- weekly basis, and a number of programs no longer prescribe it.
  • Dexedrine or Dextroamphetamine
  • the short acting tablet comes in 5 mg dosages, and reaches a peak level two hours after administration.
  • the longer acting spansule is available in 5 mg, 10 mg, and 15 mg sizes and reaches a peak blood level eight to 10 hours after actaiinistration. This permits once daily dosing with the spansule.
  • the half-life of dexedrine (tablet) is approximately 10 hours, significantly longer than short acting Ritalin.
  • Ritalin form generally a start working about a half hour after it is given, peaks at 2 hours and is gone at 4 hours. It has a half-life of 2-3 hours. It must be taken several times daily to maintain effectiveness. It comes in 5 mg, 10 mg, and 20 mg tablets. The tablets tend to be bitter, and are best swallowed whole.
  • Ritalin SR The disadvantages of Ritalin are common side effects are headache or stomachache, usually minimized by taking the medication after having food.
  • the long acting form ( Ritalin SR) comes only in a 20 mg tablet. It is designed to slowly release its contents from a series of "microchannels", and the tablet can not be cut. This dosage form is quite variable, working well for some people but poorly for others. It may be worth trying if a child on Ritalin is very resistant to taking medication at school. It tends to start acting more slowly than regular Ritalin, often taking 1.5 hours to start working. For this reason, it is often given with a small dose of regular Ritalin in the morning to provide initial coverage.
  • Ritalin SR peaks at approximately 4.5 hours from the time it is administered.
  • the object of the present invention is to provides for a herbal formulation which not only treats the symptom of Attention deficit- hyperactivity disorder but also cures the disease with no side-effective.
  • the present invention provides a synergistic herbal composition for the treatment of Attention deficit- hyperactivity disorder comprising essentially the extracts of the following herbs in the proportion as indicated below:
  • the said herbs used are in the following proportions by weight %:
  • the parts of the herbs used in said composition are:
  • Bacopa monneri Whole plant Centella asiatica Leaves, Aerial parts Glcyrrhiza glabra Roots and rhizomes Withania somnifera Rhizome Celastrus paniculatus oil Seed and seed oil
  • the extracts of Bacopa monneri and Centella asiactica are water extracts
  • the Extracts of Glycyrriza glabra and Withania somnifera are hydro- alcoholic extract.
  • the extract of Celestrus paniculatus oil is an oil.
  • the present invention also relates to a process for the treatment of treatment of Attention deficit-hyperactivity disorder comprising: preparing a extracts of Bacopa monneri, Centella asiatica Glcyrrhiza glabra Withania somnifera and Celastrus paniculatus; filtering the extract; mixing the said extracts in a predetermined proportion and condensing the said formulation and drying to obtain the herbal composition; if desired adding filler or syrup base to the said composition.
  • the active ingredient of Bacopa monneri is obtained by: shade drying the fresh and dust free herbs, - subjecting the dried herb to extraction with hexane at a predetermined temperature for a pre-determined period for removing fat & oil component, further subjecting the extract to ethanol at a pre-determined temperature for maximum of 70 hrs. - solidifying the extract to a pasty mass, treating pasty mass with chloroform to remove unwanted alcholids, pigments and other insoluble fractions, removing the insoluble fraction by dissolving it in water and filtering it.
  • the active ingredient of Celestrus paniculatus is obtained by subjecting dried and dust free seeds of the plant extracting the dried seeds with hexane for a predetermined period at a predeteimined temperature to get brownish fixed oil volatile matter sterols and terpenics polyesters and polyol, removing the extractant by distillation and placing the extract over water bath to obtain the oil extract from the crude seeds of Celestrus paniculatus
  • the active ingredients of Centella asiatica is obtained by shade drying the fresh and dust free herbs, subjecting the dried plant of extraction with hexane at a predetermined temperature for a pre-determined period for removing fat & oil component, further subjecting the extract to ethanol at a pre-determined temperature for maximum of 70 hrs.
  • Brahmi consists of dried whole plant of Bacopa monnieri (Linn.)
  • Plant material of interest Plant material of interest:
  • Root - Shows a single layer of epidermis, cortex having large air cavities; endodermis single layered; pericycle not distinct; stele consists of a thin layer of phloem with a few sieve elements and isolated material from xylem shows vessels with reticulate thickenings.
  • Stem - Shows single layer of epidermis followed by a wide cortex of thin- walled cells with very large intercellular spaces; endodermis single layered; pericycle 3 consisting of 1-2 layers; vascular ring continuous, composed of a narrow zone of phloem towards periphery and a wide ring of xylem towards centre; centre occupied by a small pith with distinct intercellular spaces; starch grains simple, round to oval, present in a few cells of cortex and endodennis, measuring 4-14 ⁇ in dia., and 8.0-14.0 x 2.5-9.0 ⁇ in dia. respectively.
  • Leaf - Shows a single layer of upper and lower epidermis covered with thin cuticle; glandular hairs sessile, subsidiary cells present on both surfaces; a few prismatic crystals of calcium oxalate occasionally found distributed in mesophyll cells; mesophyll traversed by small veins surrounded by bundle sheath; no distinct midrib present.
  • POWDERED PLANT MATERIAL Yellowish-brown; shows xylem vessels with reticulate thickening, glandular hairs, simple, round and oval starch grains, measuring 4-14 ⁇ in diameter.
  • Brahmi consists of dried whole plant of Centella asiatica (L.)
  • Urbana asiatica L.
  • DESCRIPTION A prostarate herb, rooting at the nodes. Leaves usually glabrous, orbicular-reniform, entire, crenate or labulate. Bracts small, ovate. Flowers white, borne in 3-6 flowered umbels. Fruits and seeds laterally compressed.
  • GENERAL APPEARANCE A glabrous, succulent, small, prostrate or creeping annual herb, found throughout India in wet and damp places
  • Protein 3-glucosylquercetin, 3- glucosyl-and 7-glucosyl-kaemferols (leaves); polyacetylenes I-V and nine other acetylenes (root); amino acids, Asiatic, centic, centellic, centoic and pectic acids, carotene, centellose (oligosaccharide), hydrocotylin (an alkaloid), lipid, pectin, saponins; vellerine, asiaticoside (2, 3, 23-trihydroxy- urs-12-en-28-oic-acid-0-6-dexoy-(-L-mannopyranosyl-(l - 4)- 0-(-D- glucopyranosyl-(l - 6)- 0-(-D-gluco-pyranosyl ester), asiaticosides A and B (triterpenoid trisaccharides), indocentelloside, brahmoside, bra
  • ORGANOLEPTIC PROPERTIES The plant is bitter, sweet taste.
  • Macroscopic Slender, prostrate or creeping perennial herb, with long internodes and rooting at nodes. Leaves simple, orbicular-reniform, base cordate with angular sinus, margin crenate-dentate, apex rotund, basally 5-7 nerved; long-petioled, Flowers small, brownish in axillary few-flowered umbels. Fruit 2 seeded, indehiscent, laterally compressed; seeds brown, oblong. Odour characteristic and slightly bitter sweet taste.
  • Paracytic and diracytic type of stomata are present on both surfaces of the leaf.
  • Palisade cells two layered thick.
  • Spongy parenchyma three layers of cells with many intercellular spaces, some with rosette crystals of calcium oxalate. Hairs are absent.
  • Midrib region shows 2-3 layers of collenchyma cells below the epidermii.
  • Petiole shows 7 vascular bundles within parenchymatous zone.
  • Jyotismati consists of dried, brownish-orange, ripe seeds, devoid of capsule wall of Celastrus paniculatus Willd. (Fam. Celastraceae);
  • a large climbing unarmed shrub with long slender elongating branches which are reddish brown and covered with elongate white lenticels, leaves simple, alternate, ovate, or obovate, crenulate, coriaceous, glabrous, lateral nerves arching, flowers greenish white in terminal drooping panicles, fruits capsules, dipressed - globose, 3 lobed, bright yellow when ripe, opening to expose the brown seeds covered with orange red aril.
  • PLANT MATERIAL OF INTEREST Seed and seed oil.
  • ORGANOLEPTIC PROPERTIES The plant is astringent, bitter, sweet, cooling, laxative,
  • Seed Shows single layered epidermis covered externally with thick cuticle and filled with tannin, followed by 4-6 layers of thin-walled, collapsed, parenchymatous cells and layer of radially elongated stone cells; parenchyma of top one or two layers longer than of the below with triangular intercellular spaces; inner most layer of parenchyma containing prismatic crystals of calcium oxalate; beneath stone cells layer quadrangular to octagonal, tangentially elongated cells filled with brownish contents; endosperm composed of polygonal, thin-walled, parenchymatous cells having oil globules and aleurone grains;embryo spathulate in fleshy endosperm conta ⁇ ing oil globules and aleurone grains.
  • GENERAL IDENTITY 1 ⁇ STS Macroscopic and Microscopic tests, fatty acids using GC.
  • GLYCYRRHIZA GLABRA Family Fabaceae DEFINITION: Radix Glycyrrhizae consists of the dried roots and rhizomes of Glycyrrhiza glabra L. and its varieties (1-7) or of Glycyrrhiza uralensis Fisch. (6, 7).
  • Liquiritae officinalis Moench is a synonym of Glycyrrhiza glabra L.
  • DESCRIPTION A perennial plant, up to more than lm in height, erect, with highly developed stoloniferous roots. Leaves compound, 9-17 alternate imparipinnate leaflets, oblong to elliptical-lanceolate, acute or obtuse; racemes loose, shorter than the leaves or a little longer. Flowers 1 cm long. Flat pods oblong to linear, 1-3 cm long by 6mm wide, more or less densely echinate glandular, many-seeded or abbreviated, 2 or 3 seeded.
  • Macroscopic Stolen consists of yellowish brown or dark brown outer layer, externally longitudinally wrinkled, with occasional small buds and encircling scale leaves, smoothed transversely, cut surface shows a cambium ring about one-third of radius from outer surface and a small central pith; root similar without a pith; fracture, coarsely fibrous in bark and splintery in wood; odour, faint and characteristic; taste, sweetish.
  • Root- transverse section of root shows structure closely resembling that of stolon except that no medulla is present; xylem tetrarch; usually four principal medullary rays at right angles to each other; in peeled drug cork shows phelloderm and sometimes without secondary phloem; all parenchymatous tissues containing abundant, simple, oval or rounded starch grains, 2-20 ⁇ in length.
  • PLANT MATERIAL OF INTEREST The commercial variety , G. glabra var. typical criz & Herd, known as Spanish liquorice, consists generally of roots and rhizomes in nearly cylindrical pieces, up to lm long and 5-20mm in diameter; externally, the bark is brownish grey to dark brown, longitudinally wrinkled, occasionally bearing small dark buds in rhizomes or small circular or transverse rootlet-scars in roots.
  • the peeled root is yellow, smooth, fibrous, finely striated; fracture, fibrous in the bark and splintery in the wood; internally, bright yellow.
  • a distinct cambium ring separates the yellowish grey bark from the finely radiate yellow wood; central pith, only in rhizomes.
  • GEOGRAPHICAL DISTRIBUTION Glycyrrhiza glabra - Native to central and south-western Asia and the Mediterranean region. It is cultivated in the Mediterranean basin of Africa, in southern Europe, and in India.
  • GENERAL IDENTITY TESTS Macroscopic, microscopic and microchemical examinations; and thin layer chromatographic analysis for the presence of glycyrrhizin. WITHANIA SOMTNIFERA
  • Asvagandha consists of dried mature roots of Withania sominifera Dunal. a perennial shrub, found in waste land, cultivated field and open grounds throughout India; widely cultivated in certain areas of Madhya Pradesh and Bengal; roots collected in winter, washed and cut into short pieces.
  • Microscopic - Transverse section of root shows cork exfoliated or crushed; when present isodiamatric and non-lignified; cork cambium of 2-4 diffused rows of cells; secondary cortex about twenty layers of compact parenchymatous cells; phloem consists of sieve tubes, companion cells, phloem parenchyma; cambium 4-5 rows of tangentially elongated cells; secondary xylem hard forming a closed vascular ring separated by multiseriate medullary rays; a few xylem parenchyma.
  • Brahmi Extract (Bacopa monnieri) The shade dried course powder of fresh and dust free plant of
  • Brahmi/ Neer - Brahmi (Bacopa monnieri) was initially extracted with 100%) hexane at constant temperature of 40°C continuously for 40 hours using soxhlet extraction procedure to remove the fat and oil components along with maximum amount of chlorophyll, free terpenes and sterols etc. from the crude powder.
  • the exhausted powder was further extracted with 90% Ethanol (ethyl alcohol) at constant temperature of 70°C for maximum of 70 hours similar to above extraction procedure.
  • the extract ethanol was recovered from the extracted solution with the help of thermostatic single distillation apparatus at the constant temperature as above, to 85% concentration. This extract was solidified to pasty mass on steam water bath with total yield of 27.4% of alcohol free ethanolic extract of Brahmi from its crude plant material.
  • the pasty mass was treated with 100 % chloroform for the removal of unwanted alkaloids, remaining pigments and little oil matters, from the insoluble saponins (terpenoidal glycosides) and other insoluble fraction.
  • This fraction was dissolved in distilled water and the solution was filtered over Coleman filter paper no. 42.
  • the water soluble fraction containing glycosidal material, little tannins and minerals, separated from insoluble resinous matter etc. was subjected to dehydration at reduced pressure under vacuum rotatory evaporator at the temperature of 40 - 45°C.
  • Such a dried material was further dissolved in 100 % methanol (methyl alcohol) to separate out the alcohol soluble saponins from the trace of only water soluble compounds like tannins and mineral etc.
  • the alcohol soluble fraction was concentrated to 85% dryness and then precipitated in 100 % Acetone to the insoluble total saponins containing all Bacosides and other glycosides.
  • the precipitate was filtered over filter paper and then dried in oven at 110 ° C to find out the find powder of total saponins with the yield of 2.5 % from the crude powder as required organic extract of Brahmi.
  • the course powder of dried and dust free seeds of the plant was extracted with 100 % hexane at the constant temperature of 40 °C for 40 hours using soxhlet extraction procedure to get the brownish fixed oil, volatile matter, sterols and terpenic poly-esters and poly alcohol.
  • This extract was found to be free from alkaloids, tannin and resinous solid.
  • the extractant of hexane was recovered at the above temperature from the extracted solution with the help of thermostatic single distillation apparatus to 85% concentration. Furthermore, the extract was made completely free from hexane by placing it over water bath maintained at 40 °C with the yield of 38.31 % oil extract of jyotishmati from its crude seeds.
  • the shade dried course powder of fresh and dust free plant of Mandhukaparni / Brahmi - manduki was initially extracted with 100 % hexane at the constant temperature of 40 ° C continuously for 40 hours using soxhlet extraction procedure to remove the fatty oil matter along with maximum amount of chlorophyll, free terpenic compounds and sterols etc. from the crude powder.
  • the extracted powder was further extracted with 90 % ethanol at the constant temperature of 70 ° C for maximum of 70 hours, similar to above extraction procedure.
  • the extractant ethanol was recovered from the extracted solution with the help of thermostatic single distillation apparatus at the constant temperature as above, to 85% concentration. This extract was solidified to pasty mass on steam water bath with total yield of 24.85% of alcohol free ethanolic extract of Mandhukaparni from its crude plant material.
  • the pasty mass was further treated with 100% chloroform to remove the unwanted alkaloids, remaining pigments and other matters from the insoluble saponins and the insoluble fraction.
  • This fraction was dissolved in distilled water and the solution was filtered.
  • the water soluble fraction containing glycosidal material like tannins and minerals, separated from insoluble resinous matter etc. was subjected to dehydration at reduced pressure under vacuum rotatory evaporator at the temperature of 40 - 50 ° C.
  • This dried material was further dissolved in 100% methanol to separate out the alcohol soluble saponins from the traces of only water soluble compounds like tannins and minerals etc.
  • the alcohol soluble fraction was concentrated to 85% dryness and precipitated in 100 % Acetone to insoluble saponins.
  • the precipitate was filtered over filter paper and then dried at 110 °C to find out the fine powder of total saponins with the yield of 5.0 % from the crude powder as required organic extract of Mandhukaparni.
  • the dried powder of saponins of Brahmi was observed to contain the mixture of different tri-terpenoidal glycosides predominantly as Bacosides A & B (m.p. 275 ° C ) along with others as Hersaponin (m.p. 232 - 234 ° C), Bacosaponins A (m.p. 256 ° C), B (m.p..283 ° C), C (m.p. 222 ° C), D (m.p. 250 ° C) andmonnierin and D-mannitol (m.p. 166 - 167 ° C).
  • the oil extract of Jyotishmati was observed to contain predominantly the fixed oil (52.2%), volatile matter (0.15%), Sesquiterpenic alcohol - Malkanguniol and triterpene diol-paniculatadiol, sequiterpenoid esters as Malkangunin, Celapanin, Celpanigin and Celpagin along with traces of fatty acid components.
  • the oil extract showed the presence of terpenoidal and little steroidal compounds expressing violet-pink and greenish impressions respectively with Liverman-Burchard (Acetic anhydride - Sulphuric acid) reaction test.
  • the dried powder of withania was found to contain the mixture of different withanolides (steroidal lactones with ergostane skeleton) and alkaloids. These include withanone, withaferin A, withanolides and withasomidienone, withanolide C and alkaloids.
  • Solvent composition from 25 - 100 % B and flow from
  • the dry extract contains triterpenoid saponin glycrrhizin (2-9%), a mixture of potassium and calcium salts of glycyirhizinic (glycyrrhizic) acid.
  • the dried powder of saponins of Mandhukaparni was found to contain the mixture of different triterpenoidal glycosides predominantly as Brahmoside (m.p. 242 °C) and Brahminoside (m.p. 223 °C) along with some others as Thankuniside (m.p. 139 °C), Iso thankunisied (m.p. 250 °C), Medacassoside (m.p. 220 °C), Indocentelloside and Asiaticoside.
  • the protocol of the composition are evaluated for their toxicity.
  • Age of the animals used 8 to 10 weeks
  • Weight range 160 to 180gms
  • the dosage was arrived based on: • The Indian System of medicines practitioner/texts
  • a proforma was prepared as per DSM-IV to diagnose the children suffering from ADHD combined type. This was further confirmed by using the Conner's Rating Scale (developed in 1989). The children suffering from the disorders of endocrine, metabolic, hemopoetic, neurologic etc and other different psychiatric disorders were not included in the present series of study.
  • the inclusion criteria adopted was - average I.Q., low attention span, hyperactivity including impulsivity and poor academic performance
  • the electrophysiological measurements were carried out as per international methods.
  • the Brain mapping, electroencephalogram (EEG) and occipito-frontalis muscle action potential (EMG) were assessed as per prescribed method.
  • Memory span --
  • the short term and long term memory spans were assessed with the help of electronic device by using Hhefi-ee-recall method.
  • a list of 20 words consisting of non-sense syllables is presented on the screen. The word is displayed one by one with the controlled exposure time. The child has to look the words carefully. After complete presentation of the list, the child is asked to spell out the correct word one by one without any sequence. The number of correct response is the short-term memory span of the child. After that, the child is engaged for some other mental work for more than one hour. Then again, he is asked to recall the words (without displaying the list). The number of correct response is the long-term memory span of the child.
  • Attention span - The attention span was measured by using tachistoscopic method.
  • the audio-visual reaction time was measured by Electronic Reaction Time apparatus. It consists of three visual stimuli and two auditory stimuli. One stimulus is presented at a time and the child has to respond as quickly as possible. The reaction time is measured by the electronic watch of the apparatus. The mean reaction time is the response time of the child.
  • ATTENTIO Dosage ATTENTIO is recommended in a dose of 5 ml twice daily, for children below 5 years of age and 10 ml twice daily for children above 5 years of age. A higher dosage is recommended for more severe and chronic conditions and for older children.
  • ATTENTIO is syrup available in a bottle of 200 ml. The above therapeutic dosage was arrived after several trials done with the basic herbs alone. Also this dosage is safe and has been arrived based on the toxicological studies.
  • the primary objective of the study was to evaluate the efficacy of ATTENTIO in the treatment of children with ADD/ADHD.
  • a secondary objective was to determine if there was any evidence of side effects.
  • a randomized double blind placebo controlled design was employed in which the patient and his family and the physician conducting the study were blind as to treatment. However the Principal Investigator and designer of the study was not blind as to treatment.
  • the Consent form was signed by the Parents/Guardians during this visit after the investigator explained the study in detail. Patients not taking any treatment, who satisfy the inclusion and exclusion criteria are eligible to be admitted to the trial immediately, whereas those found to be taking another drug for ADHD were weaned from these drugs by parents/guardians and asked to return after 4 weeks to enter the trial.
  • ATTENTIO or the matched placebo was prescribed in a dose of 5 ml twice daily, for children below 5 years of age and 10 ml twice daily for children above 5 years of age.
  • Placebo contained all the ingredients except the herbs.
  • the placebo was identical in all physical properties. At the commencement of the trial drug/placebo was handed to the patient/relatives (either three or six 200 ml bottles depending on age). All participants were asked to return this bottle with its unused contents at their next visit to gain an estimate of compliance with the study protocol.
  • Visit at 4, 6,8,10 and 12 months During all the visits the investigations called for are the same as those described above.
  • Abnormal laboratory values during recruitment i.e., creatinine >1.2 mg/dl, or SGOT, SGPT > 2 times upper limit of normal; serum bilirubin or alkaline phosphatase >1.5 times upper limit of normal.
  • G6PD glucose-6-Phosphate Dehydrogenase
  • Each patient entering the study was assigned a unique identifying number, which, on the basis of a code provided by the DALMIA
  • CENTER FOR RESEARCH & DEVELOPMENT PCRD determined the patient's treatment assignment. An envelope containing each subject's assigned group was held by DCRD and the investigator kept a second set of these envelopes at the clinic/hospital in a secure, but accessible place. In addition, some patients in this study were asked to donate blood and urine samples to define the elimination kinetics of certain ingredients of ATTENTIO.
  • ATTENTIO effects significant improvements in short term and long-term memory and attention span compared to a placebo-treated control group.
  • Concept learning and arithmetic learning also showed significant improvement.
  • memory and attention span were significantly improved after continuous oral administration of ATTENTIO to patients with ADHD as shown on Conner's rating scale. Symptomatically, there was a significant reduction in over activity, restlessness, unpredictability, irritability, destructiveness and accident proneness (based on Conner's rating scale) Cognitive performance was also improved as was attention span and memory.
  • the herbal formulation of ATTENTIO has beneficial effect on cognitive performance thereby improving the learning ability among the cases of learning disability.

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
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  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Alternative & Traditional Medicine (AREA)
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  • Biomedical Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Neurology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

L'invention concerne une composition synergique à base d'herbes médicinales utilisée dans le traitement de troubles d'hyperactivité avec déficit de l'attention contenant essentiellement des extraits des herbes suivantes: Bacopa monneri, Centella asiatica, Glycyrrhiza glabra, Withania somnifera et Celastrus paniculatus. L'invention concerne également un procédé de préparation de cette composition.
PCT/IN2002/000042 2002-02-14 2002-03-12 Formulation a base d'herbes medicinales destinee a traiter des troubles deficitaires de l'attention (dca/thada) et procede de preparation correspondant WO2003068251A1 (fr)

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AU2002246308A AU2002246308A1 (en) 2002-02-14 2002-03-12 Herbal formulation for treating attention defienciency disorder (add/adht) and process for preparation

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IN120MA2002 2002-02-14
IN120/MAS/2002 2002-02-14

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1562618A1 (fr) * 2002-11-14 2005-08-17 Michigan State University Compositions de withanolides inhibant la cyclooxygenase-2 et methode associee
WO2006067796A1 (fr) * 2004-12-24 2006-06-29 Council Of Scientific And Industrial Research Formulation galenique servant de stimulateur de la memoire dans la maladie d’alzheimer
US8110229B2 (en) 2008-04-19 2012-02-07 Nisarga Biotech Pvt Ltd. Herbal composition for reducing ADD/ADHD and method thereof
RU2678840C1 (ru) * 2018-04-17 2019-02-04 Федеральное государственное бюджетное образовательное учреждение высшего образования "Московский государственный университет пищевых производств" Способ получения сапонинсодержащего экстракта
WO2020070742A1 (fr) * 2018-10-02 2020-04-09 Unv Medicine Ltd. Compositions comprenant du cbd pour le traitement de troubles mentaux

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GB2314270A (en) * 1996-06-20 1997-12-24 M S Raptakos Brett & Co Ltd Anti-AIDS Ayurvedic medicine
WO2000013696A1 (fr) * 1998-09-07 2000-03-16 Maharaj Krishen Pandita Composition pour ameliorer les capacites mentales chez les mammiferes
WO2000033659A1 (fr) * 1998-12-08 2000-06-15 University Of Washington Compositions pour le traitement de la maladie d'alzheimer et autres amyloidoses
WO2001003715A1 (fr) * 1999-07-13 2001-01-18 Natreon Inc. Composition de withania somnifera

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2314270A (en) * 1996-06-20 1997-12-24 M S Raptakos Brett & Co Ltd Anti-AIDS Ayurvedic medicine
WO2000013696A1 (fr) * 1998-09-07 2000-03-16 Maharaj Krishen Pandita Composition pour ameliorer les capacites mentales chez les mammiferes
WO2000033659A1 (fr) * 1998-12-08 2000-06-15 University Of Washington Compositions pour le traitement de la maladie d'alzheimer et autres amyloidoses
WO2001003715A1 (fr) * 1999-07-13 2001-01-18 Natreon Inc. Composition de withania somnifera

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Title
ALTERN MED REV, vol. 5, no. 4, August 2000 (2000-08-01), pages 334 - 346, XP002216001, Retrieved from the Internet <URL:http://www.thorne.com/altmedrev/.fulltext/5/4/334.html> [retrieved on 20021008] *
C. STOUGH ET AL: "The chronic effects of an extract of bacopa monniera (Brahmi) on cognitive function in healthy human subjects", PSYCHOPHARMACOLOGY, vol. 156, June 2001 (2001-06-01), pages 481 - 484, XP002216002 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1562618A1 (fr) * 2002-11-14 2005-08-17 Michigan State University Compositions de withanolides inhibant la cyclooxygenase-2 et methode associee
EP1562618A4 (fr) * 2002-11-14 2009-07-22 Univ Michigan State Compositions de withanolides inhibant la cyclooxygenase-2 et methode associee
WO2006067796A1 (fr) * 2004-12-24 2006-06-29 Council Of Scientific And Industrial Research Formulation galenique servant de stimulateur de la memoire dans la maladie d’alzheimer
US8110229B2 (en) 2008-04-19 2012-02-07 Nisarga Biotech Pvt Ltd. Herbal composition for reducing ADD/ADHD and method thereof
EP2288362A4 (fr) * 2008-04-19 2012-05-02 Nisarga Biotech Pvt Ltd Composition à base de plantes destinée à diminuer l add/l adhd, et procédé afférent
US8394429B2 (en) 2008-04-19 2013-03-12 Nisarga Biotech Pvt. Ltd. Herbal composition for reducing ADD/ADHD and method thereof
RU2678840C1 (ru) * 2018-04-17 2019-02-04 Федеральное государственное бюджетное образовательное учреждение высшего образования "Московский государственный университет пищевых производств" Способ получения сапонинсодержащего экстракта
WO2020070742A1 (fr) * 2018-10-02 2020-04-09 Unv Medicine Ltd. Compositions comprenant du cbd pour le traitement de troubles mentaux
EP3860587A4 (fr) * 2018-10-02 2022-06-29 UNV Medicine Ltd. Compositions comprenant du cbd pour le traitement de troubles mentaux

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