Safety and Evaluation of the Immune Response of Coronavirus Nosode (BiosimCovex) in Healthy Volunteers: A Preliminary Study Extending the Homeopathic Pathogenetic Trial.

Objectives: Regulatory clinical Phase I studies are aimed at establishing the human safety of an active pharmaceutical agent to be later marketed as a drug. Since homeopathic medicines are prepared by a potentizing method using alcohol, past a certain dilution, their toxicity/infectivity is assumed to be unlikely. We aimed to develop a bridge study between homeopathic pathogenetic trials and clinical trials. The primary purpose was to evaluate the safety of a nosode, developed from clinical samples of a COVID-19 patient. The secondary objectives were to explore whether a nosode developed for a specific clinical purpose, such as use during an epidemic, may elicit laboratory signals worthy of further exploration. Methods: An open-label study was designed to evaluate the safety and immune response of the Coronavirus nosode BiosimCovex, given orally on three consecutive days to ten healthy volunteers. Clinical examinations, laboratory safety and immune parameters were established. Interferon-gamma, Interleukin-6, and CD 4 were measured. (CTRI registration number: CTRI/2020/05/025496). Results: No serious/fatal adverse events were reported. Laboratory tests to measure safety were unchanged. Three subjects showed elevated Interleukin-6 (IL-6) on day 17 in comparison to the baseline, and ten subjects showed elevated IL-6 on day 34. A significant difference between IL-6 observations, calculated by repeated measures ANOVA, was found to be highly significant. On day 60, the IL-6 values of nine subjects were found to return to normal. Corresponding CD4 cell elevation was observed on day 60, when compared to day 34. Conclusions: HPT may potentially extend into physiological changes with regards to immune response and should encourage future studies.

In-Vitro Evaluation of Antimicrobial Activities of Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Neisseria gonorrhoeae, and Candida albicans Nosodes.

BACKGROUND: This study presents the results of the minimum inhibitory concentration (MIC) assay of a series of nosodes: namely Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Neisseria gonorrhoeae, and Candida albicans. Each was tested against its corresponding infection as well as cross infections. METHODS: In-vitro efficacy of polyvalent nosodes was tested using the MIC assay technique. The nosodes, namely C. albicans polyvalent nosode (35c, 100c), N. gonorrhoeae (35c), K. pneumoniae (35c, 100c), E. coli polyvalent nosode (35c, 100c) and Salmonella typhi polyvalent nosode (30c, 100c), were tested along with positive and negative controls. Nosodes were studied in different potencies and at 1:1 dilution. RESULTS: C. albicans polyvalent nosode 35c, 100c, N. gonorrhoeae 35c, and positive control amphotericin B showed inhibition of the growth of C. albicans species. K. pneumoniae 35c, E. coli polyvalent nosode 100c, and meropenem (positive control) showed inhibition of the growth of K. pneumoniae; this effect was not seen with ceftriaxone, ofloxacin and amoxicillin antibiotics. E. coli polyvalent nosode 30c in 10% alcohol (direct and dilution 1:1) and the positive controls ciprofloxacin, ofloxacin, and amoxicillin showed inhibition of the growth of E. coli. The S. typhi polyvalent nosode 30c in 10% alcohol showed inhibition of growth of S. typhi. CONCLUSION: This study reveals that the tested nosodes exhibited antibacterial potential against the corresponding micro-organisms and against other selected organisms studied using this assay.

Randomized Double-Blind, Placebo-Controlled Feasibility Study, Evaluating the Efficacy of Homeopathic Medicines in the Prevention of COVID-19 in a Quarantined Population.

INTRODUCTION: Exploring preventive therapeutic measures has been among the biggest challenges during the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We explored the feasibility and methods of recruitment, retention, and potential signal of efficacy, of selected homeopathic medicines as preventive measure for developing COVID-19 in a multi-group study. METHODS: A six-group, randomized, double-blind, placebo-controlled prophylaxis study was conducted in a COVID-19 exposed population in a quarantine facility in Mumbai, India. Each group received one of the following: Arsenicum album 30c, Bryonia alba 30c, a combination (Arsenicum album 30c, Bryonia alba 30c, Gelsemium sempervirens 30c, and Influenzinum 30c), coronavirus nosode CVN01 30c, Camphora 1M, or placebo. Six pills twice a day were administered for 3 days. The primary outcome measure used was testing recruitment and retention in this quarantined setting. Secondary outcomes were numbers testing positive for COVID-19 after developing symptoms of illness, number of subjects hospitalized, and days to recovery. RESULTS: Good rates of recruitment and retention were achieved. Of 4,497 quarantined individuals, 2,343 sought enrollment, with 2,294 enrolled and 2,233 completing the trial (49.7% recruitment, 97.3% retention). Subjects who were randomized to either Bryonia alba or to the CVN01 nosode signaled (p <0.10) a lower incidence of laboratory-confirmed COVID-19 and a shorter period of illness, with evidence of fewer hospitalizations, than those taking placebo. The three other groups did not show signals of efficacy. CONCLUSION: This pilot study supports the feasibility of a larger randomized, double-blind, placebo-controlled trial. Bryonia alba 30c and CVN01 30c should both be explored in disease prevention or shortening the course of disease symptomatology in a COVID-19-exposed population.

Preparation and Standardization of Nosodes Sourced from Klebsiella Pneumoniae, Salmonella Typhi, Neisseria Gonorrhoeae and Candida Albicans Strains.

BACKGROUND: Homeopathic nosodes prepared from organisms and pathological tissues have shown biological effects, encouraging more research. There is a need to develop some new nosodes systematically and to re-make others that were developed over a century ago. In our program of work on nosodes, the bacterial strains Klebsiella pneumoniae (BAA 2146), Salmonella typhi and Neisseria gonorrhoeae (ATCC 43069), and the single-celled fungus Candida albicans (24433, 26790, and 60193) have been identified for preparation. MATERIALS AND METHODS: The systematic and scientific method of preparation of nosodes includes identification, culture, quantification, characterization, preparation, and standardization. Under laminar flow, a suspension of respective bacterial and fungal cells (20 billion cells/mL) was processed as per the Homoeopathic Pharmacopoeia of India (HPI). Culture tests, sterility tests and molecular testing (polymerase chain reaction) were performed to establish the absence of contamination, live organisms and DNA material. RESULTS: K. pneumoniae, S. typhi (single, bivalent, or polyvalent), N. gonorrhoeae, and C. albicans nosodes (single and polyvalent) were sourced and prepared from different strains of respective cultures. The nosode preparations were processed by serial dilution and potentization, normally following the HPI guidelines. Molecular test results showed the absence of live organisms or DNA material; culture and sterility test results demonstrated the safety profile of the potentized nosodes. CONCLUSION: K. pneumoniae, S. typhi, N. gonorrhoeae and C. albicans nosodes were successfully prepared. Their therapeutic potential may now be evaluated.

An open-label, exploratory documentation of proving-symptoms of CVN01 (Coronavirus nosode from the clinical sample) in healthy volunteers

Homeopathic Pathogenetic Trials (Proving) are human studies to examine the pathogenetic effects of investigational drugs in high dilution on healthy volunteers. As a part of the new coronavirus nosode development process for prophylactic use, the phase 1 study was conducted. The documentation of proving symptoms for a fast-track nosode development for a pandemic condition was the objectives of this study. An open-label trial to evaluate the safety and proving symptoms of Coronavirus nosode given orally to 10 volunteers (18-65 years age and of both the genders). Volunteers were administered 6 doses of nosode as 6 pills twice daily for 3 consecutive days. Pre and post examinations (physical), vital signs, and laboratory investigations, were done at day 0, 17, 34. Symptoms experienced by the volunteers were recorded. RESULTS Symptoms reported by volunteers were analyzed. The symptoms reported were mild to severe but reversible and matching with the symptoms produced by the viral infection. There were no serious/fatal adverse events during the study. The basic biochemistry and Liver Function tests were not affected by the Nosode. New nosode developed during a pandemic condition produced certain symptoms in the homeopathic pathogenetic trial as a part of the Phase 1 study.

Preparation and Standardization of Escherichia coli Nosodes Sourced from Select E. coli Strains.

BACKGROUND: The nosodes are well-known preparations in homeopathy that are sourced from organisms and diseased materials. More than 40 known nosodes have been used in homeopathic practice for over a century. Having identified the need for scientifically developed new nosodes sourced from organisms that are currently prevalent, the preparation of Escherichia coli nosodes from different strains of the bacterium is presented in this article. MATERIALS AND METHODS: Escherichia coli strains (E. coli ATCC 11775E, ATCC 25922, and ATCC 8739) were identified, cultured, and tested for purity, and 20 billion cells were processed following the nosode preparation method given in the Homoeopathic Pharmacopoeia of India, group N1. Serial dilution and potentization for liquid potency were done up to 30c potency. Nosodes were prepared by two methods: from cell-free extract (endotoxin) and from entire-cell extract. RESULT: Six nosodes were developed in total. Three univalent nosodes were prepared using individual endotoxins, one from each of the three E. coli strains; those three univalent nosodes were also combined as "Trivalent nosode-I". "Trivalent nosode-II" was prepared by mixing entire cells of the three E. coli strains. A mix of both Trivalent nosode-I and Trivalent nosode-II was labeled "EC-Polynosode". The safety profile of the potentized nosodes was documented by the non-detectability of traces of source material (absence of contamination, live organisms, or DNA material) through a culture test, sterility test, and molecular testing (polymerase chain reaction). CONCLUSION: Different variants of E. coli nosodes were systematically and scientifically prepared and standardized using the cultures. Homeopathic pathogenetic trials, in-vitro efficacy studies, and clinical evaluation of E. coli nosodes (single, trivalent, or polyvalent nosodes) will be required in future.

Preparation of Coronavirus nosodes sourced from a clinical sample of SARS-Cov-2 positive patient, inactivated strain, and spike glycoprotein

IntroductionNosodes, the homeopathicpreparationssourcedfrom biological materials including clinical samples, cultures of organisms, and diseased tissues have been in use against the source-specific infections as well as other diseases. The nosodes have demonstrated some efficacy in managing epidemics, such as influenza, dengue, and leptospirosis.This article presents the need and process of development ofnosodes from the SARS-CoV-2 to explore its prophylactic and therapeutic potentials against certain related viral diseases.Materials and methodsA clinical sample of SARS-Cov-2 positive patient,based on the cycle threshold (CT) value of the qRT-PCR, heat-inactivated SARS-CoV-2, and spike glycoprotein all were processed for making nosodesas per the method described in Homoeopathy Pharmacopoeia of India.Molecular tests, such as qRT-PCR and sterility tests were performed to establish the live organisms, RNA material, and the absence of contamination.ResultsThree variants of CoronavirusNosodewere developed using a clinical sample,heat-inactivatedSARS-CoV-2, and spike glycoprotein.In potencies 3c and above, no detectableSARS-CoV-2 RNA material was found by PCR.The analytical results for nosodes were reported as compliant for sterility testing as per the IP.ConclusionThree variants of Coronavirus nosodes were preparedwhich need to be evaluated further through pre-clinical and clinical studies.(AU)

An In-Vitro Assay Estimating Changes in Melanin Content of Melanoma Cells due to Ultra-Dilute, Potentized Preparations.

INTRODUCTION: The authors had previously conducted an in-vitro study to observe the effect of homeopathic medicines on melanogenesis, demonstrating anti-vitiligo potential by increasing the melanin content in murine B16F10 melanoma cells. A similar experiment was performed using further homeopathic preparations sourced from kojic acid (KA), hydrogen peroxide (H2O2; HP), 6-biopterin (BP), and [Nle4, D-Phe7]-α-melanocyte-stimulating hormone (NLE), some of which are known to induce vitiligo or melano-destruction at physiological dose. MATERIALS AND METHODS: The homeopathic preparations of BP, KA, NLE, and HP were used in 30c potency. Alcohol and potentized alcohol were used as vehicle controls. Prior to starting the main experiment, the viability of B16F10 melanoma cells after treatment with study preparations was assayed. Melanin content (at 48 h and 96 h) and tyrosinase activity in melanocytes were determined. RESULTS: At the end of 48 hours, NLE and HP in 30c potency had a significantly greater melanin content (p = 0.015 and p = 0.039, respectively) compared with controls; BP and KA in 30c potency had no significant effects. No significant changes were seen at the end of 96 hours. KA, NLE, HP, and vehicle controls showed an inhibition of tyrosinase activity. CONCLUSION: The study demonstrated melanogenic effects of two homeopathic preparations. Further research to evaluate the therapeutic efficacy of these medicines is warranted.

Preparation of Cancer Nosodes from specific cancer tissues

Nosodes are ultra-dilute preparations made from diseased tissues or organisms used in homeopathy since 1830, more frequently used since 1880. Carcinosin is a commonly used nosode prepared over 100 years ago from cancer tissues in the last part of the nineteenth century, of which the exact scientific information on the histopathological characterization of the source material is not available. The current therapeutic indications of Carcinosin have been largely empirical and clinically derived. In such a scenario, understanding the paramount importance of the Cancer nosode, it's revamping in the light of current scientific knowledge has been identified by the author. Specific cancerous tissue samples were sourced for nosode preparation. Identified pieces of tissue were histopathologically diagnosed, thoroughly washed, quantified and triturated with powder of Saccharum lactis to prepare decimal potencies, as per standard method suggested in the Homoeopathy Pharmacopoeia of India. Centesimal potencies were prepared using electromechanical potentizer, documenting the force parameters. The Cancer nosodes from specific cancer tissues were prepared in a systematic manner, which could be used for research as well as in clinical practice. The author has attempted scientific preparation of new Cancer nosodes making them available to the profession. On similar lines, more of cancer tissues could be explored for making other nosodes. (AU)

Preparation, standardization and in vitro safety testing of Mycobacterium nosodes (Emtact- polyvalent nosode).

BACKGROUND: Most of the nosodes in the homeopathic pharmacopeia have been sourced from obscure pathological material over a century ago; of which no scientific documentation is available. METHOD: A method for preparation and standardization of univalent and polyvalent Mycobacterium nosodes (labeled as Emtact), using different strains of Mycobacterium tuberculosis was developed. The committee comprising microbiologists, scientist, pharmacist, homeopaths and clinicians had reviewed and approved the method of preparation of nosode. Preparation of the nosode was based on the reference in the Homeopathy Pharmacopoeia of India (HPI), group N-IV. Strains of M. tuberculosis viz. Standard strain H37Rv, multi-drug resistant (MDR) M. tuberculosis, Mycobacterium bovis (BCG vaccine) and Mycobacterium avium were identified, procured and documented. Twenty billion viable cells for each strain were taken for Original Stock Nosode (OSN). The original stock was prepared by suspending the microbial cells into water for injection (WFI) (1 ml). As per the Indian Pharmacopoeia (IP) monograph, sterility testing was done for different potencies. Polymerase Chain Reaction (PCR) was performed for 30c potency for detection of any DNA material of the source organisms. RESULT: A polyvalent (multi-strain) and univalent M. tuberculosis nosodes were prepared for research and clinical use. No growth of Mycobacterium was observed in any of the samples above 5c potency. The in-vitro testing for nosode (30c) was found to be free from any organism and DNA material. CONCLUSION: Mycobacterium nosodes sourced from individual strain and polyvalent Emtact nosode in vitro testing results found to be satisfactory for its handling and utilization. The nosode seems to be safe and may be tested further in vivo to explore its therapeutic application.