WO2006067797A1 - Formulation galenique servant d’anesthesique local - Google Patents

Formulation galenique servant d’anesthesique local Download PDF

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Publication number
WO2006067797A1
WO2006067797A1 PCT/IN2004/000403 IN2004000403W WO2006067797A1 WO 2006067797 A1 WO2006067797 A1 WO 2006067797A1 IN 2004000403 W IN2004000403 W IN 2004000403W WO 2006067797 A1 WO2006067797 A1 WO 2006067797A1
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WIPO (PCT)
Prior art keywords
formulation
spilanthus
herbal formulation
herbal
calva
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PCT/IN2004/000403
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English (en)
Inventor
Palpu Pushpangadan
Chandana Venkateswara Rao
Ajay Kumar Singh Rawat
Sanjeev Kumar Ojha
Sharad Kumar Srivastava
Subha Rastogi
Vivek Kumar
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Council Of Scientific And Industrial Research
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Priority to PCT/IN2004/000403 priority Critical patent/WO2006067797A1/fr
Publication of WO2006067797A1 publication Critical patent/WO2006067797A1/fr

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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)
    • A61K36/27—Asclepiadaceae (Milkweed family), e.g. hoya
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • 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)
    • A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A61P23/02—Local anaesthetics

Definitions

  • the present invention relates to a novel herbal formulation useful as local anaesthetic.
  • Local anaesthesia may be employed in hernia operations, either on its own or combined with general anaesthesia.
  • the choice of technique will be influenced not only by local resources and skills, but also by patient preference. With a careful technique, local anaesthesia causes minimal physiological disturbance. This may be particularly useful for patients with cardiovascular or respiratory disease for whom there may be advantages in avoiding a general aesthetic.
  • the absence of postoperative sedation or drowsiness allows early ambulation and diminishes the requirement for recovery facilities.
  • Local anaesthesia provides postoperative analgesia for up to four hours and may be administered by the surgeon.
  • inguinal and femoral hernia come from the anterior branches of the six lower intercostals nerves which continue forward on to the anterior abdominal wall accompanied by the last thoracic (subcostal) nerve.
  • the iliohypogastric and ilioinguinal nerves (T 12 and Ll) supply the lower abdomen. They are blocked by an injection of local anaesthetic between internal and external oblique muscles just medial to the anterior superior iliac spine.
  • the genitofemoral nerve (Ll, 2) supplies inguinal cord structures and the anterior scrotum via its genital branch and supplies the skin and subcutaneous tissues of the femoral triangle via the femoral branch.
  • Local anaesthetic agents are relatively free from side effects if they are administered in an appropriate dosage and in the correct anatomical location. However, systemic and localized toxic reactions may occur, usually from the accidental intravascular or intra-thecal injection, or the administration of an excessive dose of the local anaesthetic agent. Systemic reactions to local anaesthetics involve primarily the central nervous system and the cardiovascular system. The airway is maintained and oxygen administered by facemask, using artificial ventilation if apnoea occurs.
  • Convulsions are treated with anticonvulsant drugs such as thiopentone or diazepam repeated as necessary.
  • Profound hypotension and brady-arrhythmias should be treated with intravenous atropine and colloid or crystalloid infusions as plasma expanders may be necessary.
  • adrenaline may be required for severe hypotension or bradycardia.
  • the invention provides a novel herbal local anaesthetic used in minor surgery like tooth removal or in topical surgery or in hernia operations without any toxic symptoms.
  • the main object of the present invention is to provide a novel herbal formulation useful as a local anaesthetic, for spinal anaesthesia and for membrane stabilizing properties.
  • Another objective of the present invention is to prepare herbal ointment/ cream/ gel form that improves and acts as local anaesthetic.
  • Yet another object of the present invention is to prepare herbal dosage from in the form of topical solution/ spray, for easy acceptablity.
  • the invention provides a novel herbal formulation useful as local anaesthetic.
  • the herbal formulation is also useful for membrane stabilizing properties and in topical anaesthesia, nerve block conduction, extradural and infiltration anaesthesia.
  • an herbal local anesthetic synergistic formulation containing extracts of plants in pharmacologically effective form.
  • the plant used is Spilanthus calva. In still another embodiment, the plant used is Spilanthus oleraceae. In an embodiment, the plant used is Gymnema sylvestre.
  • plant used is Urtica dioica. In still another embodiment, the plant used is Piper longum.
  • the extract of Spilanthus calva is obtained from leaves/roots/flowers/rhizome/ fruits.
  • the extract of Piper longum is obtained from fruit extract.
  • the extract of Spilanthus oleraceae is obtained from leaves/flowers/rhizome/unriped fruits.
  • the extract of Gymnema sylvestre was aerial parts.
  • the extract of plant Spilanthus calva, Spilanthus oleraceae and Piper longum are mixed along with an additive to provide a topical application and intradermal injection form.
  • the extracts of plant Spilanthus calva, Spilanthus oleraceae, Urtica dioica, Piper longum and Gymnema sylvestre are mixed in equal proportion along with conventional additives to form an topical and intradermal injection form.
  • the composition is a topical or ointment or spray form.
  • the said formulation is use as an analgesic when applied for muscular pains and inflammation.
  • the formulation is used against toothache and gum trouble.
  • the said formulation has specific gravity ranging between 0.897- 1.127.
  • the formulation has refractive index ranging between 1.1325 -1.3642.
  • the additives used in the cream/ ointment selected from a group consisting of poly ethylene glycol bases, hydro emulsifying bases and bentonite.
  • the additives used in the intradermal injection being sterile water for injection.
  • the additives used are water-soluble bases.
  • the water-soluble base used are selected from a group consisting of tragacanth, pectin, acacia and gelatin.
  • the formulation at dose of 400 mg/kg did not show any toxicity in rats as well as no change in organ body weight.
  • the synergistic formulation at a dose ranging from 100-200 mg/kg is highly effective as local anaesthetic for around 5-7 min.
  • the present invention also provides a method of inducing anaesthesia, comprising the step of administering an effective amount of a herbal formulation to a subject together with or in combination with therapeutically acceptable additives.
  • a herbal formulation comprising Spilanthus calva (3%) and Spilanthus oleraceae, (3%) with conventional additives at a dose ranging from 100-200 mg/kg being moderately effective as local anaesthetic for around 20 min.
  • the present invention also provides for the use of herbal formulation as an anaesthetic at a dose ranging from 100-200 mg/ kg body weight is effective as local anaesthetic around for 5-20 min.
  • the present invention provides novel herbal formulation useful as a local anaesthetic, spinal anaesthesia and membrane stabilizing properties obtained from Spilanthus spp.
  • the herbal formulation comprising of Spilanthus calva, Spilanthus oleraceae,Urtica dioica, Piper longum and Gymnema sylvestre. It was shown that it produces a significant improvement in membrane stabilising local anaesthesia.
  • the plants used in the invention have the following properties reported.
  • Medicinal properties and uses The plant, boiled in water, is used to treat dysentery.
  • the decoction is also given as a diuretic and lithotriptic and used as a bath for relieving rheumatism and as a lotion for scabies and psoriasis.
  • the juice from the plant is a vulnenary.
  • the pounded herb is used as a poultice to dress wounds.
  • the pungent flower heads are chewed to relieve toothache and affection of the gums and throat, and paralysis of the tongue; it is used to treat stammering in children in western India.
  • a tincture, made from the flower heads is used as a substitute for the tincture of pyrethrum (prepared from the roots of Anacyclus pyrethrum: Asteraceae) to treat inflammation of the jaw and dental caries.
  • the roots are purgative.
  • the crushed plant is used as a fish poison.
  • a perennial herb closely related to spilanthes calva, but more robust, succulent, and with large flower heads. Leaves triangular or triangular-ovate, obtuse, attenuate below.
  • the dried roots, as well as the immature and mature fruits, are used extensively, alone and in combination with other plant drug to treat a broad range of ailments in traditional Indian medicine.
  • the dried roots and thicker stems known commercially as piplamul, are an important drug in the ayurvedic and unani systems.
  • the roots and fruits are used to treat dysentery and leucoderma, as a cholagogue for treating bileduct and gallbladder obstruction, and as a counter -irritant and analgesic for relieving muscularpains and inflammations.
  • a decoction of dried immature fruit and root, or the powdered fruits mixed with honey is used to treat chronic bronchitis, cough and cold.
  • An infusion of the powdered fruits is given to women after childbirth to check bleeding and fever. It is as important ingredient in medicated oil used externally for sciatica and paraplegia.
  • a genus of annual or perennial herbs commonly known as nettle, distributed in the temperate and sub-tropical zones.
  • U. pilulifera an exotic herb
  • Several species of this genus are armed with stinging hairs on the leaves and stems, which, on contact with the skin, cause irritation and symptoms of urticaria or nettle rash.
  • Sharp and fragile ends of the hairs penetrate the skin and break off and the irritating principles inside the hairs come in contact with the tissues, resulting in an uncomfortable itchy sensation accompanied by rash.
  • Some nettles, such as U. dioica and U. pilulifera yield a fibre, which is said to rival the best hemp in strength.
  • Hemostatic used in uterine hemorrhage, bleeding from the nose and vomiting of blood. Also used in sciatica and rheumatism.
  • leaves are used as a medicine known as alcohol, used for chronic hepatitis, cholengitis, habitual constipation and powerfully diuretic.
  • Gymnema sylvestre (Retz.) Family- Asclepiadaceae
  • the plant is considered antiperiodic, diuretic and stomachic.
  • Ayurvedic practice the root and leaf are used to treat headache, hydrocele, polyuria, leprosy, pruritis, poisoning, wounds and bronchial asthma.
  • the leaves are believed to be hypoglycaemic and are an important ingredient of Ayurvedic formulations for diabetes; they are also used to treat cough and fever.
  • the filtered extract of the ground leaf twigs is taken orally to relieve malarial fever.
  • the root is considered to possess astringent, emetic, expectorant, cooling, stomachic and tonic properties.
  • the invention provides a novel herbal formulation useful as local anaesthetic.
  • the herbal formulation is also useful for membrane stabilizing properties and in topical anaesthesia, nerve block conduction, extradural and infiltration anaesthesia.
  • the herbal formulation when used as an anesthetic contains extracts of plants in pharmacologically effective form.
  • the extracts/ juice of the plants are mixed in the ratio viz. Spilanthus calva (l-3%wt), Spilanthus oleraceae (l-3%wt), Urtica dioica (2-3%wt), Piper longum (l-2%wt), Gymnema sylvestre (2-3% wt) and the balance being the conventional additives.
  • the plant used is Spilanthus calva and/or Spilanthus oleraceae, and/or Gymnema sylvestre and/or Urtica dioica and/or Piper longum.
  • the extract of Spilanthus calva is obtained from leaves/roots/flowers/rhizome/ fruits.
  • the extract o ⁇ Piper longum is obtained from fruit extract.
  • the extract of Spilanthus oleraceae is obtained from leaves/flowers/rhizome/unriped fruits.
  • the extract of Gymnema sylvestre was aerial parts.
  • the extract of plant Spilanthus calva, Spilanthus oleraceae and Piper longum are mixed along with an additive to provide a topical application and intradermal injection form.
  • the extracts of plant Spilanthus calva, Spilanthus oleraceae, Urtica dioica, Piper longum and Gymnema sylvestre are mixed in equal proportion along with conventional additives to form an topical and intradermal injection form.
  • the composition can be used as topical or ointment or spray forms.
  • the formulation can be used as an analgesic when applied for muscular pains and inflammation.
  • the formulation is used against toothache and gum trouble.
  • the formulation has specific gravity ranging between 0.897- 1.127 and refractive index ranging between 1.1325 -1.3642.
  • the additives used in the cream/ ointment selected from a group consisting of poly ethylene glycol bases, hydro emulsifying bases and bentonite.
  • the additives used in the intradermal injection being sterile water for injection.
  • the additives used are water-soluble bases, selected from the group consisting of tragacanth, pectin, acacia and gelatin.
  • the formulation at dose of 400 mg/kg did not show any toxicity in rats as well as no change in organ body weight.
  • the formulation at a dose ranging from 100-200 mg/kg is highly effective as local anaesthetic for around 5-7 min. Anaesthesia is induced by administering an effective amount of the formulation to patient together with or in combination with therapeutically acceptable additives.
  • the herbal formulation comprises Spilanthus calva (3%) and Spilanthus oleraceae, (3%) with conventional additives at a dose ranging from 100-200 mg/kg being moderately effective as local anaesthetic for around 20 min.
  • Gymnema sylvestre (3%) with conventional additives at a dose ranging from 100-200 mg/kg is moderately effective as local anaesthetic for around 15 min.
  • the formulation can be used as an anaesthetic at a dose ranging from 100-200 mg/ kg body weight is effective as local anaesthetic around for 5-20 min.
  • the invention is further illustrated by the following non-limiting examples.
  • Spilanthus calva were collected and dried in shade.
  • the dried material (IKg) is then powdered and extracted with 50 % aqueous alcohol (3 L) for 5 days. At the end of this, the solvent is decanted and filtered if necessary to remove the plant debris.
  • the extract is then concentrated under vacuum at less than 50 0 C. Then the extract is lyophilised to obtain the extract in powder form. Mix the plant extract and dissolve them in simple ointment base. Then solution and add specified quantity of water to make 100 ml.
  • the formulation is useful to a Local anesthetic.
  • Spilanthus oleraceae were collected and dried in shade.
  • the dried material (IKg) is then powdered and extracted with 50 % aqueous alcohol (3 L) for 5 days. At the end of this, the solvent is decanted and filtered if necessary to remove the plant debris.
  • the extract is then concentrated under vacuum at less than 50 0 C. Then the extract is lyophilised to obtain the extract in powder form.
  • the formulation is useful to a Local anesthetic. Accordingly, the investigation deals with the topical application/ intradermal injection of the formulation.
  • the formulation F2 is effective for only 15 minutes observed from the time that is 30 to 45 minutes only, the results can be seen in the table 1.
  • Formulation (F3) is effective for only 15 minutes observed from the time that is 30 to 45 minutes only, the results can be seen in the table 1.
  • the formulation F3 is effective for only 15 minutes observed from the time that is 30 to 45 minutes only, the results can be seen in the table 1.
  • Formulation (F4) is effective for only 15 minutes observed from the time that is 30 to 45 minutes only, the results can be seen in the table 1.
  • Gymnema sylvestre were collected and dried in shade.
  • the dried material (IKg) is then powdered and extracted with 50 % aqueous alcohol (3 L) for 5 days. At the end of this, the solvent is decanted and filtered if necessary to remove the plant debris.
  • the extract is then concentrated under vacuum at less than 50 0 C. Then the extract is lyophilised to obtain the extract in powder form.
  • the formulation is useful to a Local anesthetic. Accordingly, the investigation deals with the topical application / intradermal injection of the formulation.
  • the formulation F4 is effective for only 30 minutes observed from the time that is 30 to 60 minutes only, the results can be seen in the table 1.
  • Formulation (F5) is effective for only 30 minutes observed from the time that is 30 to 60 minutes only, the results can be seen in the table 1.
  • Urtica dioica were collected and dried in shade.
  • the dried material (IKg) is then powdered and extracted with 50 % aqueous alcohol (3 L) for 5 days. At the end of this, the solvent is decanted and filtered if necessary to remove the plant debris.
  • the extract is then concentrated under vacuum at less than 50 0 C. Then the extract is lyophilised to obtain the extract in powder form.
  • the formulation is useful to a Local anesthetic. Accordingly, the investigation deals with the topical application / intradermal injection of the formulation.
  • the formulation F5 is effective for only 40 minutes observed from the time that is 20 to 60 minutes only, the results can be seen in the table 1.
  • Formulation (F6) Spilanthus calva 3wt. %
  • Spilanthus calva and Spilanthus oleraceae were collected and dried in shade.
  • the dried material (IKg) is then powdered and extracted with 50 % aqueous alcohol (3 L) for 5 days. At the end of this, the solvent is decanted and filtered if necessary to remove the plant debris.
  • the extract is then concentrated under vacuum at less than 50 0 C. Then the extract is lyophilised to obtain the extract in powder form.
  • the formulation F6 is effective for only 40 minutes observed from the time that is 20 to 60 minutes only, the results can be seen in the table 1.
  • Formulation (F7) is effective for only 40 minutes observed from the time that is 20 to 60 minutes only, the results can be seen in the table 1.
  • Simple ointment base 91.0% Spilanthus calva, Spilanthus oleraceae and Gymnema sylvestre were collected and dried in shade.
  • the dried material (IKg) is then powdered and extracted with 50 % aqueous alcohol (3 L) for 5 days. At the end of this, the solvent is decanted and filtered if necessary to remove the plant debris.
  • the extract is then concentrated under vacuum at less than 50 0 C. Then the extract is lyophilised to obtain the extract in powder form. Mix the plant extract and dissolve them in simple ointment base. Then solution and add specified quantity of water, required amount of water to make 100 ml.
  • the formulation is useful to a Local anesthetic. Accordingly, the investigation deals with the topical application / intradermal injection of the formulation.
  • Spilanthus calva , Spilanthus oleraceae, Gymnema sylvestre, Urtica dioica and Piper longum were collected and dried in shade.
  • the dried material (IKg) is then powdered and extracted with 50 % aqueous alcohol (3 L) for 5 days. At the end of this, the solvent is decanted and filtered if necessary to remove the plant debris.
  • the extract is then concentrated under vacuum at less than 50 0 C. Then the extract is lyophilised to obtain the extract in powder form. Mix the plant extract and dissolve them in simple ointment base. Then solution and add specified quantity of water, required amount of water to make 100 ml.
  • the formulation is useful to a Local anesthetic. Accordingly, the investigation deals with the topical application / intradermal injection of the formulation.
  • the formulation F8 is effective for 120 minutes observed from the time that is 5 to 120 minutes, and it is reversible at 120 minutes and therefore, it is highly effective than the other formulations evident from the table 1.
  • Drug Treatment group Time in minutes after topical application (100 mg/kg.b.wt) 0 5 10 15 20 30 45 60 120
  • Formulation (Fl) contains Spilanthus calva (3%) balance being conventional additives.
  • Formulation (F2) contains Spilanthus oleraceae (3%) balance being conventional additives.
  • Formulation (F3) contains Gymnema sylvestre (3%) balance being conventional additives.
  • Formulation (F4) contains Piper longum (1%) balance being conventional additives.
  • Formulation (F5) contains Urtica dioica. (3%) balance being conventional additives.
  • Formulation (F6) contains Spilanthus calva (3%) and Spilanthus oleraceae, (3%) balance being conventional additives.
  • Formulation (F7) contains Spilanthus calva (3%),
  • Formulation (F8) contains Spilanthus calva (3%), Spilanthus oleraceae (3%), Urtica dioica
  • Drug Treatment group Time in minutes after intradermal injection (mg/kg) 0 5 10 15 20 30 45 60
  • F6 contains Spilanthus calva (3%) and Spilanthus oleraceae, (3%) with balance being conventional additives
  • the formulation (F7) contains Spilanthus calva (3%), Spilanthus oleraceae (3%), Gymnema sylvestre (3%) with balance being conventional additives.
  • the formulation (F8) contains Spilanthus calva (3%), Spilanthus oleraceae
  • the formulation F8 is highly effective (Table2) and it is safe.
  • Lignocaine Dizziness, abnormal sensation like burning, pricking, pervertal sensation and in severe case will ultimately lead to epileptic seizures.
  • the formulation (F6) contains Spilanthus calva (3%) and Spilanthus oleraceae, (3%) with balance being conventional additives.
  • Formulation (F7) contains Spilanthus calva (3%), Spilanthus oleraceae (3%), Gymnema sylvestre (3%) with balance being conventional additives.
  • Formulation (F8) contains Spilanthus calva (3%), Spilanthus oleraceae (3%), Urtica dioica (3%), Gymnema sylvestre (3%) and Piper longum (3%) with balance being conventional additives.
  • the formulation F6, F7 and F8 is highly effective (Table3) and it is safe (Table3). Note: No mortality/ gross abnormality was observed in the animals during the treatment of formulations (F6, F7 and F8).

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Veterinary Medicine (AREA)
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  • Anesthesiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une nouvelle formulation galénique servant d’anesthésique local dans le cas d’opérations chirurgicales locales, de blocage de la conduction nerveuse, d’anesthésie extradurale et par infiltration. Les formulations comprend/comprennent un/des extraits de Spilanthus calva et Spilanthus oleraceae avec Gymnema sylvestre, Urtica dioica et Piper longum. Elles sont classiquement utilisées localement sous forme d'onguent, spray ou crème.
PCT/IN2004/000403 2004-12-24 2004-12-24 Formulation galenique servant d’anesthesique local WO2006067797A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3720762A (en) * 1970-07-11 1973-03-13 Lion Hamigaki Kk Spilanthol-containing compositions for oral use
WO2004041295A1 (fr) * 2002-10-29 2004-05-21 Council Of Scientific And Industrial Research Nouveaux inhibiteurs d'alpha-glucosidase provenant d'une source naturelle

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3720762A (en) * 1970-07-11 1973-03-13 Lion Hamigaki Kk Spilanthol-containing compositions for oral use
WO2004041295A1 (fr) * 2002-10-29 2004-05-21 Council Of Scientific And Industrial Research Nouveaux inhibiteurs d'alpha-glucosidase provenant d'une source naturelle

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
ANONYMOUS: "Gymnema sylvestre", March 2004 (2004-03-01), pages 1 - 2, XP002340922, Retrieved from the Internet <URL:http://66.249.93.104/search?q=cache:tFcSChk6ENEJ:www.dolphin-india.com/html/herbal/gymnema.asp+%22gymnema+sylvestre%22+and+anaesthetic&hl=en%20target=nw> [retrieved on 20050816] *
ANONYMOUS: "Herbage....plants", 2004, pages 1 - 6, XP002340929, Retrieved from the Internet <URL:http://www.omnicopia.com/herbage/files/H1364.htm> [retrieved on 20050811] *
ANONYMOUS: "Paracress (Spilanthes acmella Murr. and Spilanthes oleracea L.)", October 2002 (2002-10-01), pages 1 - 5, XP002340920, Retrieved from the Internet <URL:http://www.uni-graz.at/~katzer/engl/Spil_acm.html> [retrieved on 20050811] *
ANONYMOUS: "When stinging nettles get up the nose", ELECTRONIC TELEGRAPH / ETCETERA I GARDENING, 1996, pages 1 - 2, XP002341033, Retrieved from the Internet <URL:http://www.telegraph.co.uk/htmlContent.jhtml?html=/archive/1996/10/26/tgherb26.html> [retrieved on 20050817] *
CHRUBASIK ET AL: "Rheumatic pain treatment with stinging nettle (Urticae folium/herba)", October 2004 (2004-10-01), pages 1 - 4, XP002340921, Retrieved from the Internet <URL:http://66.249.93.104/search?q=cache:es4YbDQD2noJ:www.iaam.nl/coherence/msaima/199-4.html+%22urtica+dioica%22+and+anesthetic&hl=en%20target=nw> [retrieved on 20050816] *

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