EP2288350A1 - Method of treatment with potentised stereoisomer of glutamate - Google Patents
Method of treatment with potentised stereoisomer of glutamateInfo
- Publication number
- EP2288350A1 EP2288350A1 EP08841975A EP08841975A EP2288350A1 EP 2288350 A1 EP2288350 A1 EP 2288350A1 EP 08841975 A EP08841975 A EP 08841975A EP 08841975 A EP08841975 A EP 08841975A EP 2288350 A1 EP2288350 A1 EP 2288350A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- potency
- glutamic acid
- glutamate
- treatment
- potencies
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0004—Homeopathy; Vitalisation; Resonance; Dynamisation, e.g. esoteric applications; Oxygenation of blood
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
Definitions
- the present invention relates to a method of treatment, in particular to a method of treating an effect of glutamate or glutamic acid by administering a dilution or an ultra-high dilution or potentised preparation of glutamic acid or glutamate.
- Homoeopathy employs minute doses of usually harmful or toxic agents to stimulate organisms back to health.
- the agents used in homoeopathy are selected precisely on the basis of their ability to induce disease-like symptoms and signs in healthy people when administered in toxic doses, or one or more times in sub-harmful doses. These agents will, in properly diluted form, cure a sick person with similar symptoms.
- microdose effects are now well accepted, for example in the phenomenon known as hormesis, some homoeopathic solutions are attenuated beyond Avogadro's constant, i.e. in theory none of the original agent remains. There have been a great number of reported experiments that demonstrate that homoeopathic remedies are effective in treating a variety of symptoms.
- the inventor has now found that the effects of glutamate within the nervous system or within the organism generally can be treated by administering a dilution or an ultra high dilution or potentised dilution of a stereoisomer of glutamate or glutamic acid.
- glutamic acid or glutamate refers to one or more stereoisomers which induce the effect to be treated in the organism.
- a method of treatment of an organism suffering from the effects of glutamic acid or glutamate comprising the steps of potentising a stereoisomer of glutamic acid or glutamate, and administering said potentised glutamic acid or glutamate to the organism.
- Another aspect of the invention provides a method of treatment of an organism suffering • from the effects of glutamic acid or glutamate, said method comprising the steps of diluting a stereoisomer of glutamic acid or glutamate, and administering said diluted glutamic acid or glutamate to the organism.
- Still yet another aspect of the invention provides a method of treatment of an organism suffering from the effects glutamic acid or glutamate, said method comprising the steps of diluting a stereoisomer of glutamic acid or glutamate to an ultra-high dilution of said stereoisomer, and administering said ultra-high diluted stereoisomer to the organism.
- dilutions such as those used in investigations involving hormesis.
- Such dilutions exist below the toxic range of a given compound, substance or molecule.
- Such dilutions below the toxic range are stimulatory rather than toxic, but may be bilphasic or multiphasic in their effects, i.e., stimulatory or inhibitory in their effects, depending on the concentration below the NOAEL which is being used.
- this phenomenon exists in a narrow range of concentrations just below the toxic range. Put another way, the phenomenon exists just below the 'no observed adverse effect level' or 'NOAEL'.
- the method of the present invention may be used for the treatment of any organism, including for example, animals, plants, microorganisms and in particular, humans.
- Another aspect of the invention is the use of a dilution or an ultra-high dilution or potentised preparation of glutamate or glutamic acid, for the preparation of a medicament for the treatment of the toxic, physiological and/or pathological effects of said glutamate or glutamic acid.
- Still yet another aspect of the invention is the use of a dilution or an ultra-high dilution or potentised preparation of glutamate or glutamic acid, for the preparation of a medicament for the treatment of the addictive and other undesirable effects of drugs of addiction.
- Still yet another aspect of the invention is the use of a dilution or an ultra-high dilution or potentised preparation of glutamate or glutamic acid, for the preparation of a medicament for the alleviation of the physical and psychological effects of drugs of addiction.
- the present invention may be used for the following non-limiting examples:
- CFS Chronic Fatigue Syndrome
- the invention may be used for the preparation of a medicament for the alleviation of the physical and psychological effects of any of the conditions listed above and numbered from 1-34 inclusive.
- the enantiomer of the endogenously occurring isomer of glutamate or glutamic acid used to treat the organism, may be derived from other salts of glutamate or glutamic acid, e.g., instead of glutamic acid being used, sodium glutamate may provide a suitable isomer of glutamate.
- (+)-glutamate or L-glutamate
- (+)-glutamate or D-glutamate
- Potentization of the stereoisomer, glutamate or glutamic acid may be according to the practices used in homoeopathy, homotoxicology or any other system of medicine or treatment which uses potencies, for example, anthroposophical medicine.
- glutamate into potency
- AU 2003208170, AU 2005100336, AU 2005100337 and AU 2007100082 The description of manufacture of potencies in the following pages applies to any stereoisomer including Glutamic Acid.
- the stereoisomer is potentised by succussion or trituration.
- Attenuation or dilution of the medicinal substance is, in homoeopathy, usually performed in the decimal, centesimal and fifty millesimal (LM) systems as the standard scales of attenuation, under which each successive attenuation contains just 1/10, 1/100 or 1/50,000 as much of the medicinal substance as the preceding attenuation.
- the attenuated medicinal substance is succussed (typically between 10 to 100 times at each stage of attenuation) or triturated.
- soluble substances may be subjected to succussion and insoluble or solid substances may be subjected to trituration.
- Other forms of agitation may be used instead of succussion or trituration, e.g., sonication, Lab dancer, etc.
- a ml of tincture or B grams of medicinal substance are added to C ml or D grams or E parts of vehicle.
- Subsequent liquid or solid attenuations are made by serial progression, succussing or triturating one part of the preceding attenuation to C ml, D grams or E parts of the vehicle respectively.
- A, B, C, D, and E are any numbers greater than zero.
- A, B, C, D or E are any numbers greater than zero.
- the values of A could be Ai, A 2 , A 3 , A 4 , A 5 ... etc., where A 1 , A 2 , A 3 , A 4 , A 5 ... etc. represent any numbers greater than zero.
- the same principle applies for values of B, C, D, and E.
- nX 10 "n where n is an integer greater than 0.
- one millilitre (1 ml) of the first fifty millesimal attenuation (ILM) represents 4.OxIO "9 gram of dry crude medicinal substance.
- One millilitre (1 ml) of the second fifty millesimal attenuation (2LM) represents 8.OxIO '14 gram of dry crude medicinal substance.
- Each subsequent attenuation represents a further decrease in concentration of dry crude medicinal substance by a factor of 2xlO "5 .
- Each attenuation such as 2X, 3X or nX (2C, 3C or nC) (2LM, 3LM etc) is generally referred to as a potency.
- potency refers to a solution, which has undergone serial dilution and succussion and/or agitation whereas attenuation refers to a ' process of dilution, which may or may not involve succussion or agitation.
- potency also refers to solid attenuations as described herein.
- the term 'different potencies or attenuations' encompasses 2 potencies or attenuations of different dilutions as well as solutions which have undergone a different number of steps of serial dilution or attenuation with succussion, or, in the case of solid attenuations, a different number of steps of serial trituration as described herein.
- a person skilled in the art could add the fourth and twelfth potencies or attenuations together in equal or unequal quantities.
- the solution may then be succussed (shaken) N times, where N is any integer greater than zero.
- the solution is not succussed.
- the term 'different potencies or attenuations' also encompasses the situation where the same or different potencies, made from 2 or more different medicinal substances, are added or mixed together. Such mixtures are common practice in homeopathy and are called 'complexes'.
- One or more potencies, attenuations or dilutions of an enantiomer may be prepared in one mixture, and added to an equal or unequal number of the same or different or any combination of potencies or attenuations of the other enantiomer prepared in a separate mixture.
- all potencies, attenuations or dilutions could be added to the same mixture.
- (+)- and (-)- enantiomers may be mixed 50:50 or 25:75 or in any proportion.
- a mixture could be prepared by adding 2ml of 4th, 12th and 30th potencies of (+)- enantiomer to 2ml of 4th, 12th and 30th potencies of (-)- enantiomer, or vice versa.
- 0.5ml of 4th, 2ml of 12th and 3.4ml of 30th potencies could be used, and in fact the numbers 0.5, 2 and 3.4 could be replaced by any numbers greater than zero or equal to zero.
- the 4th, 12th and 30th potencies could be replaced by any potencies represented by integers greater than or equal to 1.
- (+)- and (-)-enantiomers prepared separately could then be administered separately or mixed together. If mixed together, the resulting solutions could be succussed or not succussed, and subsequently serially diluted or attenuated or potentised or not. Alternatively, the (+)- and (-)-enantiomers may not be prepared separately, and mixing could occur in the one container.
- 0.4ml of 3 rd potency, attenuation, or dilution of the (-)-enantiomer may be added to 1.2 ml of the 13 th , 5.2 ml of the 41 st , 4.5 ml of the 200 th ' and 3.7 ml of the 1000th potency, attenuation or dilution. This may then be succussed or not.
- this may then be added to a mixture of 5.1 ml of the 5 th potency, attenuation or dilution, 0.3 ml of the 37 th , and 6.3ml of the 105 th potency, attenuation or dilution of the (+)- enantiomer.
- This latter mixture may have been succussed or not.
- the resulting combination of mixtures may then be serially diluted, attenuated or potentised or not.
- the number denoting potencies, attenuations or dilutions can be replaced by any integers greater than zero. Numbers representing millilitres of potency, attenuation or dilution, can be replaced by any numbers greater than or equal to zero.
- (+)- and (-)- enantiomers may be mixed 50:50 or 25:75 or in any proportion.
- a mixture could be prepared by adding 2g of 4th, 12th and 30th potencies of (+)- enantiomer to 2g of 4th, 12th and 30th potencies of (-)- enantiomer, or vice versa.
- 0.5g of 4th, 2g of 12th and 3.4g of 30th potencies could be used, and in fact the numbers 0.5, 2 and 3.4 could be replaced by any numbers greater than zero or equal to zero.
- the 4th, 12th and 30th potencies could be replaced by any potencies represented by integers greater than or equal to 1.
- (+)- and (-)-enantiomers prepared separately could then be administered separately or mixed together. If mixed together, the resulting solutions could be succussed or not succussed, and subsequently serially diluted or attenuated or potentised or not. Alternatively, the (+)- and (-)-enantiomers may not be prepared separately, and mixing could occur in the one container.
- 0.4ml of 3 rd potency, attenuation, or dilution of the (-)-enantiomer may be added to 1.2g of the 13 th , 5.2g of the 41 st , 4.5g of the 200 th ' and 3.7g of the 1000th potency, attenuation or dilution. This may then be succussed or not. In turn, this may then be added to a mixture of 5.1g of the 5 th potency, attenuation or dilution, 0.3g of the 37 th , and 6.3g of the 105 th potency, attenuation or dilution of the (+)-enantiomer.
- This latter mixture may have been succussed or not.
- the resulting combination of mixtures may then be serially diluted, attenuated or potentised or not.
- the number denoting potencies, attenuations or dilutions can be replaced by any integers greater than zero.
- Numbers representing grams of potency, attenuation or dilution can be replaced by any numbers greater than or equal to zero.
- the administration of the potentised stereoisomer is typically by an oral route but may be administered intravenously, intramuscularly, transdermally, subcutaneously, topically, intrathecally, intraperitoneally or via any mucous membrane (typically sublingually). It is particularly preferable to administer the potentised stereoisomer orally or sublingually.
- potentised stereoisomer examples include tablets, globuli, liquid dilutions for injection and liquid external preparations.
- Administering potencies via different routes is part of routine optimization of therapy in homeopathy; i.e., one uses whichever route is most expedient.
- Another method of administering the potentised or attenuated stereoisomer is to use devices such as the MORA machine, Listen Machine or Vega Select Machine or other bioresonance or electrodermal testing devices to detect an electromagnetic or bioresonance signal from the potency or attenuation and then administer the signal in an unchanged, modified or inverted form to the organism to be treated.
- devices which are commercially available, claim to be able to copy the effects of medicines, dilution or potency and pass the attributes of a medicine, dilution or potency onto a heretofore placebo or medicinally inactive vehicle.
- modification or "inversion” of the signal includes changing the polarity of the signal.
- the vehicles used to attenuate the stereoisomer may be selected from the group consisting of water, such as water for injection B.P. or U.S.P., lactose B.P. or U.S.P., sucrose B.P. or U.S.P. ethanol typically in suitable concentrations (e.g. 15 - 95%). Also absolute ethanol, purified water, glycerol 85% or other ethanol/water mixture or dilution of glycerol may be used. Other vehicles will also be apparent to those skilled in the art of homoeopathy.
- the methods of preparation of solid or liquid stereoisomers of chemical agents into potentised attenuations include where water-soluble or alcohol-soluble isomers are to be prepared into potencies the use of water B.P. or purified water alone, or in a mixture of water and ethanol, say, 30-45% ethanol.
- Ethanol-soluble stereoisomers may be prepared using higher concentration ethanol solutions, say 55-95% ethanol or absolute ethanol. It is possible to start using lower and incrementally lower ethanol concentrations as the potency reaches 3 to 5X or 3 to 5C. Final homeopathic liquids often contain 30-40% ethanol.
- the stereoisomer may be prepared by a process of trituration.
- the process of trituration is particularly advantageous when the stereoisomer is not readily soluble in water, ethanol or water/ethanol mixes.
- liquid dilutions may be prepared by first making a trituration and then diluting it in liquid such as water for injection.
- one part of the medicinal substance when preparing the first potency, or one part of the preceding attenuation when preparing the second or subsequent potencies, is added to one third of the total vehicle (e.g. lactose B.P.) used for that potency.
- the process of trituration is typically performed with mortar and pestle for 15 to 20 minutes. The side of the mortar is then scraped for five minutes to dislodge any attenuated substance with the pestle or with a spatula. Then the second third of the vehicle for attenuation is added to the mortar and the contents subjected to a further 15 to 20 minutes trituration prior to scraping the sides of the mortar for a further five minutes to dislodge attenuated substance.
- the total vehicle e.g. lactose B.P.
- the remaining one third of the vehicle is added to the mortar and the combined mixture is subjected to trituration for a further 15 to 20 minutes to complete the trituration for that potency.
- the total vehicle may be added to the medicinal substance or preceding attenuation at each successive stage of potency preparation and subjected to 60 minutes of trituration. Each successive level of attenuation is called a potency.
- the process of the present invention may be used to reverse, or in another embodiment enhance, the effects in vivo, and in vitro, of glutamate or any of its compounds.
- Another aspect of the invention provides for the use of the method of the present invention to enhance or reverse the effects in vivo and in vitro of (-)-glutamate or any of its compounds or to enhance or reverse the effects in vivo and in vitro of (+)-glutamate or any of its compounds.
- Hyman describes how such conditions may be viewed as systemic disorders affecting the brain rather than primarily brain disorders, and describes how the problem may be approached from the perspective of nutritional and environmental medicine using a systems approach, and presents a case history with what was a well-demonstrated and obviously very satisfying outcome for patient, parents and practitioner. 18
- Glutamate is the major excitatory synaptic neurotransmitter in the brain and is found in 80% of neurons and there is increasing " evidence that antagonists of glutamate action at NMDA receptors have antidepressant-like action, 32 and anxiolytic action. 19 ' 32 Glutamate is characterized by a number of experts to be largely responsible for the ability of the nervous system to rapidly transmit information from one part of the body to another, and to be important in thought formation and memories.
- Excitotoxicity is a term applied to glutamate and is the excessive exposure to the neurotransmitter glutamate or to stimulation of its membrane receptors, and is considered a main contributor to neuronal injury and death in numerous conditions. 27 Excitotoxicity in this context was first described in 1969 35 (in Lipton). hi the case of the NMDA receptors these include Alzheimer's disease, Parkinson's disease, Huntington's disease, HTV- associated dementia, multiple sclerosis, amyotrophic lateral sclerosis, and glaucoma, obsessive-compulsive disorder, stroke, dementia and neuropathic pain, 3 and also anxiety and depression.
- Another group of glutamate receptors are the metabotropic glutamate receptors.
- Evidence suggests that inhibition of some receptors belonging to this category may play a part in counteracting nicotine addiction; other receptors in the same category may assist with depression occurring in early nicotine withdrawal and may be useful in treatment of depression generally.
- Metabotropic glutamate receptors may also be promising targets in the treatment for neurologic disorders derived from abused drugs such as cocaine, morphine and amphetamines, and may also play a part in the regulation of several neurodenerative disorders, epilepsy, and ischemia.
- Some metabotropic receptor agonists may be useful in the treatment of psychotic disorders including schizophrenia. 4 ' 5 Note that this sentence refer to agonism on a glutamate receptor function.
- glutamate-gated ion (or ionotropic.) channels There are 3 classes of glutamate-gated ion (or ionotropic.) channels, known as AMPA, kainite, and NMDA receptors. Excessive activation of the NMDA receptor leads to production of damaging free radicals and other enzymatic processes contributing to cell death. 28 ' 29 ' 33 In addition the are at least 10 types of metabotropic glutamate receptors. It should be noted that the functions and interactions of receptors in the brain do not act in isolation. GABA receptors for instance balance the actions of glutamate to prevent
- fear extinction involves the new learning of fear inhibition and is considered crucial for effective anti-anxiety treatment.
- NMDA antagonists may have anti-anxiety action, they also note that a partial NMDA receptor agonist may facilitate extinction. 13
- clinical experience using homeopathic potencies of enantiomeric glutamate indicate a likely anxiolytic, antidepressant and anti-stress action measurable after 4-6 weeks treatment, as measured by DASS questionnaire. 34 This has even been noted in patients with severe psychosocial problems and chronic pain. The effect on pain has not been measured at the present time, but it may be a good idea in such patients to record pain scales at baseline and at 2 weekly intervals together with the DASS questionnaires. 6 ' 16
- AMPA potentiators may be of benefit in enhancement of cognitive function.
- NMDA receptors such as aspartate and D-serine
- Glycine is a well known co-agonist of the NMDA receptor with glutamate. Accordingly, potencies of D-serine, aspartate and glycine may be used to modulate the activity of these agonists of the NMDA receptor, and could be utilized in combination either as a complex, or separately as simplexes, to modulate NMDA receptor function.
- Stereoisomers which are enantiomers of each other, are almost identical chemically. Stereoisomers have identical molecular formulae and structural formulae, but different configurational formulae, i.e., the molecules are identical to each other except for their spatial orientation. Enantiomers have the peculiarity that they are mirror images of each other.
- the 2 mirror images are typically differentiated with the notations (+)- and (-)- referring to the ability of the compound to rotate polarized light in a polarimeter, and (R)- and (S)- which refers to the Cahn-Ingold- Prelog convention specifying the orientation of the molecular weights of moieties attached to a chiral centre in the molecule.
- Their main identifying difference is that they rotate polarized light differently when analysed using a polarimeter.
- enantiomers rotate polarized light by an approximately equal number of degrees in a polarimeter, but in opposite directions. ' ' 10
- the profile of physiological actions of optical isomers and their enantiomers or diastereoisomers are typically very similar, however, the potency of each form of stereoisomer in terms of a given physiological action may vary widely, and the actual physiological actions are very different.
- adrenaline found in humans is the minus isomer and is about 15 times more active than the plus isomer physiologically.
- the ⁇ -receptor blocker (-)-propranolol is about 60-100 times more active than (+)- propranolol in blocking the inotropic, chronotropic, and vasodepressor actions of the ⁇ - receptor stimulant isoprenaline.
- the (+)-isomer is more effective at inhibiting oubain-induced arrhythmias in dogs. 17
- the simillimum principle says that to treat, a sickness one must administer a medicinal preparation which in suitably attenuated form, is capable of producing the same symptoms and signs which are being exhibited and experienced by the patient. Stereoisomer symptoms are different.
- the agents used in homeopathy are selected precisely on the basis of their ability to create the noxious symptoms and signs experienced by the patient, if given to healthy people in toxic doses, or repeatedly in sub harmful doses. 15 In homeopathy administration of substances in potentized form is believed to accompany the most dramatic effects clinically. It is hypothesized that the enantiomeric treatment of optical isomer effects will demonstrate larger effects than isopathic treatment, if the law of similars is being more faithfully mimicked.
- amino acid glutamic acid we use the amino acid glutamic acid.
- amino acids could also be of use. These include aspartate and glycine, hi fact aspartate, glutamate and glycine isomers could be used to perform experiments to modify plant metabolism, e.g., carbon fixation. Glutamine isomers could be used potentially to influence nitrogen fixation in plants.
- This study compares the ability of a (+)-Glutamic acid homeopathic complex with placebo, in terms of their respective abilities to improve DASS questionnaire scores over a 6-week period, in patients scoring an average of 14 or more points on the DASS questionnaire.
- Patients eligible for admission would be those with depression, anxiety or stress.
- Patients with bipolar disorder, PTSD, OCD and panic attacks would also be admissible.
- Patients with psychotic disorders or a history of psychosis would not be eligible.
- (+)-Glutamic acid homeopathic complex or simplex will be administered to 90 patients in the course of their normal treatment in a prospective randomized placebo controlled study. 45 patients will be in each arm. This sample is sufficient to detect a difference of 10 points in the DASS questionnaire score with power 0.95 at the 2.5% level.
- Bottles will be coded IA and IB up to 82 A and 82B or further depending on sample size. Either A or B will be medicine or placebo according to randomization and blinding. Consecutive patients will receive bottles 1 A,B up to 82A,B. Patient will take the 'A' bottles for 6 weeks. Alternatively, bottles will be randomized by coin toss to medicine or placebo groups and numbered consecutively 1 ,2,3,4. This latter method will be more practical in the performance of the study in view of the next paragraph, since each sequential bottle is randomized and has a 50% chance of being medicine or placebo.
- results When data for each patient is collected, results will be sent to Brauer who will record the result ' and then break the blinding for that patient. If the patient received placebo he will then be offered treatment with the active bottle if he so chooses. If the patient received the active treatment in bottle A, then he will be offered the chance of continuing treatment if he is favorably disposed.
- the minimal sample size needed for a plausible study would be 31 in each arm - see below.
- the DASS questionnaire consists of 42 questions divided into 3 groups of 14 questions relating to 3 areas: Depression (D), Anxiety (A) and Stress (S).
- the investigator can score for the individual items or take an average of the entire score. Scores for each of the D, A and S data range from a minimum of zero, to a maximum of 42. Up to approximately 14 is considered a normal score for all 3 items - depression, anxiety and stress. It is proposed to take an average score of all the items as the primary end-points in the study at baseline, 2 weeks, 4 weeks and 6 weeks, however, at the end of the study analyses will be performed on each of the 3 areas of Depression, anxiety and stress at the baseline, 2 week, 4 week and 6 week milestones. Therefore this will be a repeated measures study.
- the first person to be recruited and to receive potentized glutamic acid was case 1.
- the second was case 2 and so on. No cases are omitted.
- Data was extracted from the computerized records between approximately 17/7/2008 and 27/7/2008.
- the first case was recruited and commenced on potentized D-Glutamic acid therapy on 9 th November 2007. Patients were asked to perform DASS scores at a two weekly intervals for 6-8 weeks at least.
- Potencies were manufactured according to the Homeopathic Pharmacopeia of the United States, HPUS Revision Service General Pharmacy, 2004. 100 succussions occurred at each stage of potency preparation. Adding equal volumes of the individual constituent potencies together made final potencies, e.g., to make the LM 4/12/30 potency, equal volumes of the LM 4, 12 and 30 potencies were added together. No succession occurred. Potencies were prepared in 30% ethanol. All potencies given to patients were in drop form in 30% ethanol, unless otherwise stated. The results are presented in the attached Case Tables.
- the LM notation refers to the 50 th millesimal scale of attenuation in homeopathy.
- the second potency referred to is a mixture of 4 th , 12 th and 30 th centesimal potencies.
- 'C chord' and 'LM chord' in the following text means the 4/12/30 C potency chord of D-Glutamic acid and the LM 4/12/30 potency chord of D-Glutamic acid respectively.
- the reason for alternating potencies which is unusual if not unknown in homeopathic practice, was in order for the practitioner to obtain an impression of whether the two potency chords differed in their clinical efficacy, or indeed if they would work synergistically.
- New patient presents for consultation for first time on 9 th November 2007. Usually attends another practitioner. Also attends a psychiatrist for anxiety. recruited and commenced on D-Glutamic Acid LM 4/12/30 and D-Glutamic Acid 4/12/30 C potency chords, alternating them every 2 days.
- Case 4 has many years history of panic attacks and takes regular medication for this.
- Results are not consistent with an effect of D-Glutamic Acid potency chords, but in the context are difficult to interpret. Also, compliance is an issue. If the patient was not improving, then the usual practice would have been to modify the treatment after about 1 month from recruitment and commencement of potencies, e.g., change to exclusive use of the LM potency chord.
- Case 6 was recruited on 16/11/07. DASS was not done on that day. A questionnaire had been completed on 8/11/07 and this was used as baseline. Long term chronic back pain, anxiety and depression. Commenced on daily alternating LM 4/12/30 and 4/12/30 C D- Glutamic Acid potency chords.
- Glutamic acid LM 4/12/30 and 4/12/30 C potency chords alternating daily doses Patient had been using anti-depressant medication since at least 2003. 25.3.08: There had been no change over 6 weeks of treatment with alternating potency, therefore, C potency was stopped and the patient continued with daily D-Glutamic acid LM 4/12/30 potency.
- Pills (globules):
- H% (Icontrol - Isample) / Icontrol
- Vibrio fisher i is a suitable testorganism for testing potency.
- L-glutamic acid results in close to 90% reduction in the optical density of the culture in the nutrient medium. It means that the inhibition of cell growth is close to 100%.
- L-GA is a little-bit more toxic for E.coli, than D-GA.
- EC so of L-GA is: 2 mg/mL.
- E. coli is a suitable microorganism for testing potency.
- Pseudomonas is even more sensitive than E. coli, and both GA-s are equally toxic.
- EC so of L-GA is 0.5 mg/mL.
- concentration range between 0 and 2 mg/mL should be used for the potency-testing.
- Pink and blue H% are based on the optical density, yellow is based on cell count.
- the effect testing was carried out in a nutrient medium, which is a 2-fold dilution of the normal one (Control 1 A), to see better the acute effect of the GA on the cells propagation.
- 2 mg/mL GA concentration caused 100% growth inhibition and depletion in the cell number after two days, 5 mg/mL caused depletion already after 20 hours.
- the concentration range between 0 and 2 mg/mL should be used for potency testing.
- Tetrahymena could be used as test-organism for testing potency.
- test in this form is too complicate and durable, with a lot of labour requirement, so I would simplify the test for measuring not the whole growth curve, but only one point of time, e.g. after 68 hours growth.
- the goal of the study was to determine the effect of L- and D-glutamic acid on the survival and reproduction of Folsomia Candida (Collembola) in feeding experiments.
- the Collembolans commonly known as springtails, are the most numerous and widely occurring insects in terrestrial ecosystems.
- Microarthropods as e.g. springtails are said to have an important function regarding the maintenance of soil functions. Due to their short life cycles, high number of species and their high density, important requirements for using them as indicator organisms is fulfilled. Folsomia Candida is a little 3—4 mm long white animal.
- Test organism Folsomia Candida (Collembola: Isotomidae) obtained from synchronized culture
- Test endpoint acute test: survival (mortality) chronic test: number of newly born animals (inhibition of reproduction)
- the acute and chronic tests were performed simultaneously.
- the first assay (survival test) was terminated after 2 weeks and the second assay (reproduction test) will be terminated after 4 weeks.
- the pots were incubated for 14 days at a temperature of 25 0 C in the dark.
- the test containers were opened once a week for aeration. After 2 weeks surviving juveniles F. Candida were counted.
- D-GA potency D-Glutamic Acid potency
- L-GA L-Glutamic Acid
- Step 1 & 2 1.
- 'curing' is also referred to in the bioassay section of this specification as 'treatment' and means that potencies were only administered after L-GA was added to cultures (10 minutes after) and not before.
- the bioassay section starts with the section called 'Toxicity testing of L- and D-glutamic acid with different test organisms.
- 'pre-treatment' means that H2 was administered 24 hours before addition of L-GA to cultures.
- Pre-treatment' is also referred to as 'prevention'. Materials and methods General conditions
- potencies were prepared in glass tubes, taking care not to contact or being close to metal objects or electric wires. (This is possibly being over cautious in the case of electric wires, since it must be admitted that it has not been the experience of homeopaths in the clinic, that potencies lose efficacy, when they are stored in quite strong electric fields near power sockets.)
- Sterile glass tubes were used for the propagation of the bacterial cells.
- Potencies were all prepared and stored in 35% ethanol, except the final potencies, which were administered to organisms, because they were prepared in distilled water.
- test tubes 4, 12 and 30 were added to a 100 ml glass flask with plastic screw stopper.
- the content was given 20 forceful downward successions at 0.75-1 Hz.
- 20 ⁇ l of the content was removed using an automatic pipette and added to a 100 ml glass flask with plastic screw stopper containing 5 ml distilled water.
- This test flask was then succussed (by agitating the freshly diluted solution by rapping its container hard against a hard and elastic object such as a leather- bound book) 20 times.
- the placebo was prepared on the same way but without D-glutamic acid.
- test-organisms (bacteria) were prepared in two subsequent steps.
- the inocula were used immediately in the experiments: treatment by L-GLU and the potency.
- L-glutamic acid (L-GLU) were measured and placed into empty glass test tubes with plastic cups (sterilised by autoclaving at 121 0 C, for
- the cell growth in all of the test tubes was measured by the optical density at the 600 nm maximal absorption wavelength, which is proportional to the cell-concentration within a certain range.
- the optical density unit is not able to distinguish between dead and living cells. This means that dead cells or suspended material in the culture may cause light absorption.
- ODU Optical Density Unit
- Some members of the L-GLU concentration series were evaluated based on live cell counts. In the case of samples containing 25 mg L-GLU ⁇ Pseudomonas fluorescens) and 10 mg L-GLU ⁇ Escherichia col ⁇ ) cell counting by spread plate counting technique was also carried out. This technique is based on the cultivation of the cells and gives only the number/concentration of the living cells. The results were given as Colony Forming Unit (CFU/ml).
- optical density values (Tables ⁇ —i, below) were measured (600 nm) after 24 hours culturing of potentised and non-treated Pseudomonas fluorescens with and without L-GA, in the presence of water, placebo and D-glutamic acid potencies.
- optical density values (Tables 5-8, below) were measured (600 nm) after 24 hours culturing of potentised and non-treated Escherichia coli with and without L-GA, in the presence of water, placebo and D-glutamic acid potencies.
- the number in the placebo columns mean that these were the placebos made for the potencies indicated by the number, and it does not mean that a potency of glutamic acid was administered.
- the same interpretation applies to all tables 1-8 inclusive.
- the first 5 samples starting from the top of the table and going down, received just placebo 10 minutes after L-GA was added to the cultures.
- the next 5 samples received 5 th potency 10 minutes after L-GA was added to the cultures.
- the next 5 samples received the 4/12/30 complex of D-GA pre-treatment 24 hours before addition of L-GA to the cultures, and placebo 10 minutes after addition of L-GA.
- the final 5 samples in table 1 received the 4/12/30 complex of D-GA 24 hours before addition of L-GA and the 5 th potency of D-GA 10 minutes after addition of L-GA to the cultures.
- optical density is proportional to the cell concentration within a certain range.
- the difference between optical density and living cell number originates mainly from the dead cells: which are already naturally dead (at the end of the growth curve) or killed before time by the toxic agent. These two possibilities cannot be differentiated from each other.
- cell number is 1x10 5 cell/ml in the placebo grown culture, 18x10 5 cell/ml in the H2-pre-treated. 5 th potency resulted in 500-fold cell growth compared to the culture with placebo.
- the H2 pre-treated culture's cell number is 13 times higher in the 5 th potency treated arm compared with the placebo treated arm, i.e., 18xlO 5 cell/ml cf. 253xlO 5 cell/ml.
- the 1-glu concentration is in units of 0, 2.5, 5, 10 and 25mg per tube and not, as it appears sometimes 0, 2,500, 5,000, 10,000 and 25,000 mg per tube.
- H2 pre-treatment had minimal effect on the growth of Ps. fluorescens compared with the non-pre-treated arm shown in graph 1.
- the L-GLU toxicity shows inhibition at a higher concentration.
- the 5 th potency treatment of the pre-treated culture looks less effective compared with the non-pre-treated culture (previous graph).
- Table 2 The effect of the 13 th potency on the growth of H2 pre-treated and non-pre treated Pseudomonas fluorescens: optical density (ODU) and living cell concentration(CFU).
- cell number is 16x10 5 cell/ml in the placebo grown culture and 105x10 5 cell/ml in the H2-pre- treated. It is an 8-fold higher value.
- the H2 pre-treated culture's cell number on the effect of the 13 th potency (166x10 5 cell/ml) is similar to the placebo-treated culture (105x10 5 cell/ml) and is significantly higher, than the same for the placebo treated culture.
- Placebo treated Ps. fluorescens culture shows a curve similar to the culture treated with the 5 th potency.
- the L-GLU concentrations higher than 5 g/tube inhibit the growth considerably. 13 th potency is able to compensate this effect of the L-glutamic acid.
- the sudden drop in the growth in the tube of 10 mg L-GLU/tube is strange, and looks like a mistake on first impression.
- Pre-treatment of the culture with H2 resulted in lower sensitivity of the bacterial cell culture to the toxicity of L-GLU.
- Pre-treatment is able to defend the cells from the toxic effect of L-GLU even in the highest concentration.
- the 13 th potency line in Graph 4 represents a sample which received H2 potency 24 hours before addition of L-GA to the sample, and then received 13 th potency 10 minutes after addition of L-GA.
- the placebo line indicates a sample which also received H2 potency 24 hours before addition of L-GA, but 10 minutes after addition of L-GA, placebo was added to the culture and not potency.
- both the arms had pre-treatment with H2 24 hours before addition of L-GA as toxin.
- the toxicity inhibiting effect of the 31 st potency compared to the placebo-treated culture is weaker than that of the 5 or 13 .
- the toxicity inhibiting effect of the 31 st potency compared to the placebo-treated culture is weaker than that of the 5 or 13 .
- H2-pre-treated culture The last one is more realistic, but we have to accept, that every tube with a bacterial culture is a microcosm, which may have its individual fate and evolution.
- the 31 st potency was able to effectively increase or, alternatively, not allow a decrease in the growth rate, even in the case of treatment with 25.0 mg/tube L-GLU. 31 st potency was effective in both cases: with and without H2 pre-treatment.
- Placebo and H2 treatment do not show much difference.
- the drop at 10 mg of L-GLU maybe interesting, because it is not the only case, when this L-GLU concentration resulted in extremely low growth.
- Pre-treatment with H2 is able to stop or hinder the toxic effect of L-GLU.
- the differences cannot be explained easily, but knowing the statistics of microbial processes, the trend is the relevant issue; and the trend of the pre-treated and not pre-treated is significantly different.
- H2 pre-treatment has weaker but still significant effect against L-GLU (2.5-fold).
- the pre-treatment with H2 together with post-treatment with the 5 th potency was the most effective, as it is shown in Table 5.
- the 3 rd line shows the growth curve in the absence of L-GIu toxicity, but with pre-treatment with 13 th potency administered 24 hours prior to addition of L-GIu toxin.
- Figure 7 shows L-GIu + placebo: the L-GIu toxicated cells are not only fewer in number but the still living ones are much smaller than the healthy ones. Their inner structure is also different, less structured morphology.
- Figure 8 shows L-Glu+pre-treatment + treatment with potency and L-GIu + potency. The L- GLU toxicated cell with potency looks healthy, and their number is higher, than the L-GLU treated but not cured by potency sample. Only curative and preventive+curative are both very effective from the morphological point of view.
- the pictures can be compared according to the size: the same magnification was used for each.
- the sizes of the pictures are comparable by the engraving of the chamber. If the two lines are an identical distance apart, the magnification of the picture is the same (when no engraving can be seen, it is, because the cells were not co-operative in being fixed on a certain scratch.
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AU2008900291A AU2008900291A0 (en) | 2008-01-22 | Method of treatment | |
AU2008904478A AU2008904478A0 (en) | 2008-08-29 | Method of treatment | |
PCT/AU2008/001611 WO2009052591A1 (en) | 2008-01-22 | 2008-11-03 | Method of treatment with potentised stereoisomer of glutamate |
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EP0884042A1 (en) * | 1996-02-12 | 1998-12-16 | Oleg Iliich Epshtein | Medicament and method of treating an organism with medicaments |
WO2003072105A1 (en) * | 2002-02-28 | 2003-09-04 | Sempach Pty Ltd | Treatment of effect of chemicals with their ultradilute stereoisomers |
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2008
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EP0884042A1 (en) * | 1996-02-12 | 1998-12-16 | Oleg Iliich Epshtein | Medicament and method of treating an organism with medicaments |
WO2003072105A1 (en) * | 2002-02-28 | 2003-09-04 | Sempach Pty Ltd | Treatment of effect of chemicals with their ultradilute stereoisomers |
Non-Patent Citations (3)
Title |
---|
CORTESE BERNADETTE M ET AL: "The role of glutamate in anxiety and related disorders.", CNS SPECTRUMS OCT 2005 LNKD- PUBMED:16400245, vol. 10, no. 10, October 2005 (2005-10), pages 820-830, XP002664558, ISSN: 1092-8529 * |
JONAS W ET AL: "NEUROPROTECTION FROM GLUTAMATE TOXICITY WITH ULTRA-LOW DOSE GLUTAMATE", NEUROREPORT, LIPPINCOTT WILLIAMS & WILKINS, US, vol. 12, no. 2, 12 February 2001 (2001-02-12), pages 335-339, XP008076722, ISSN: 0959-4965, DOI: 10.1097/00001756-200102120-00031 * |
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