Impact of Consciousness Energy Healing Treatment on the Physicochemical and Thermal Properties of an Anticancer Drug 6-Mercaptopurine

Journal: Open Access Journal of Cancer & Oncology PDF  

Published: February 07, 2019 Volume: 3 Issue: 1

DOI: 10.23880/oajco-16000137 ISSN: 2578-4625

Authors: Nayak G, Trivedi MK, Branton A, Trivedi D and Jana S

Citation: Nayak G, et al. Impact of Consciousness Energy Healing Treatment on the Physicochemical and Thermal Properties of an Anticancer Drug 6-Mercaptopurine. J Cancer Oncol 2019, 3(1): 000137.

  • 26
  • 5

Abstract

Mercaptopurine is an antineoplastic chemotherapy drug is used for the treatment of cancer, Crohn's disease, ulcerative colitis, autoimmune diseases, etc. In this scientific study, the impact of the Trivedi Effect®-Consciousness Energy Healing Treatment on the physicochemical and thermal properties of 6-mercaptopurine was evaluated using the modern analytical technique. The test sample 6-Mercaptopurine powder was divided and named into control and treated sample. The control sample did not receive the Biofield Energy Treatment; whereas, the treated sample received the Biofield Energy Treatment remotely by a well-known Biofield Energy Healer, Gopal Nayak. The particle size values in the treated 6-mercaptopurine sample were significantly decreased by 10.18% (d10), 10.59% (d50), 7.62% (d90), and 9.17% {D(4,3)}; thus, the specific surface area was significantly increased by 10.28% compared to the control sample. The powder XRD peak intensities and crystallite sizes of the treated 6-mercaptopurine were significantly altered ranging from -43.40% to 23.33% and -37.09% to 136.67%, respectively; whereas the average crystallite size was significantly decreased by 11.04% compared with the control sample. The latent heat of evaporation and latent heat of fusion of the treated 6-mercaptopurine were significantly increased by 11.81% and 14.97% compared with the control sample. The total residue amount was significantly increased by 6.44% in the treated sample compared with the control sample. The maximum thermal degradation temperature of the 1st, 2nd, and 3rd peaks of the treated sample was altered by 1.55%, 0.18%, and -1.29% compared with the control sample. It was concluded that the Trivedi Effect®-Consciousness Energy Healing Treatment might have generated a new polymorphic form of 6-mercaptopurine which would offer better solubility, absorption, and bioavailability compared with the control sample. The Biofield Energy Treated 6-mercaptopurine would be more efficacious against acute lymphocytic leukemia, chronic myeloid leukemia, Crohn's disease, ulcerative colitis, and autoimmune diseases.

Keywords:

6-mercaptopurine; The Trivedi Effect®; Complementary and Alternative Medicine; Consciousness Energy Healing Treatment; Particle size; Surface Area; PXRD; DSC; TGA/DTG.

Abbreviations:

NIH: National Institutes of Health; NCCAM: National Center for Complementary and Alternative Medicine; CAM: Complementary and Alternative Medicine; PSA: Particle Size Analysis; PXRD: Powder X-Ray Diffraction; DSC: Differential Scanning Calorimetry; TGA/DTG: Thermogravimetric Analysis/Differential Thermogravimetric Analysis; FWHM: Full Width at Half Maximum; SSA: Specific Surface Area.

Introduction

Mercaptopurine is an antineoplastic (or cytotoxic) chemotherapy drug belongs to a thiopurine-derivative antimetabolite. It inhibits the purine nucleotide synthesis and metabolism by hindering an enzyme called phosphoribosyl pyrophosphate amidotransferase interference [1,2]. It is used unaided or in combination with other anti-cancer medications for the management of chronic myeloid leukaemia, acute lymphocytic leukaemia, ulcerative colitis, autoimmune diseases, and Crohn's disease [3-5]. World Health Organization recommended it as an essential medicine and also approved since from 1953 for the medical use in the USA [6]. Some of the side effects related to the use of 6-mercaptopurine are nausea, vomiting, diarrhoea, stomach and abdominal pain, loss of appetite, mouth sores, yellowing of skin or eyes, fatigue, weakness, fever, sore throat, red spots on the skin, skin rash, darkening of the skin, hair loss, easy bruising or bleeding, black stools, bloody stools, dark urine, bloody urine, suppress the production of red and white blood cells, and genetic polymorphisms [7-9].

Mercaptopurine available in the form of tablets and liquid suspensions formulations for the administration [10-12]. The 6-mercaptopurine is insoluble in water, chloroform, acetone, diethyl ether, hot alcohol and dilute alkali solutions; slightly soluble in dilute sulphuric acid, but in it is soluble [12]. Scientists throughout the world doing the widespread research work in order to advance the solubility, dissolution, absorption, and bioavailability of the pharmaceutical and nutraceutical compounds [13]. The Trivedi Effect®- Consciousness Energy Healing Treatment fascinated to have a significant impact on the crystallite properties, particle properties, thermal behaviour, and bioavailability of the pharmaceutical and nutraceutical compounds [14-17]. The Trivedi Effect® is a natural and only scientifically established phenomenon in which a specialized person can harness this inherently intelligent energy from the “Universe” and transfer it anywhere on the planet via the possible mediation of neutrinos [18]. An infinite and para-dimensional electromagnetic field which be present surrounding the body of every living organism generated by continues moment of the charged particles (ions, cells) blood flow, heart movement, etc. inside the body is called a “Biofield”. The Biofield based Energy Healing Therapy, which was accepted and approved worldwide for its use against many diseases by the National Institutes of Health (NIH) and National Center for Complementary and Alternative Medicine (NCCAM) and included it under the Complementary and Alternative Medicine (CAM) along with hypnotherapy, meditation, yoga, Reiki, Ayurvedic medicine, traditional Chinese herbs and medicines in biological systems, etc. The CAM has been accepted by most of the USA people [19,20]. The Biofield Energy Treatment is important for the overall improvement of the quality of life and various other health conditions [21,22]. The Trivedi Effect®-Consciousness Energy Healing Treatment has a significant impact on the characteristic properties of metals, ceramics, and polymers, organic compounds, microbes, cancer cells [23-30], and also improve the yield of crops [31,32]. This study was designed to evaluate the influence of the Trivedi Effect®-Consciousness Energy Healing Treatment on the physicochemical and thermal properties of 6-mercaptopurine using particle size analysis (PSA), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis/differential thermogravimetric analysis (TGA/DTG).

Materials and Methods

Chemicals and Reagents

6-Mercaptopurine monohydrate was purchased from Tokyo Chemical Industry Co., Ltd., Japan and the other chemicals were purchased in India.

Consciousness Energy Healing Treatment Strategies

The test sample 6-mercaptopurine powder was divided into two parts. One part of the test sample was treated with the Trivedi Effect®-Consciousness Energy Healing Treatment remotely under standard laboratory circumstances for 3 minutes by the well-known Biofield Energy Healer, Gopal Nayak, India, and known as a Biofield Energy Treated 6-mercaptopurine. However, the other part of the 6-mercaptopurine test sample did not receive the Biofield Energy Treatment but, was treated with a “sham” healer and considered as a control sample. The “sham” healer totally ignorant about the Biofield Energy Treatment. After the treatment, both the samples were kept in sealed conditions and characterized using modern analytical techniques.

Characterization

The PSA, PXRD, DSC, and TGA analysis of the control and Biofield Energy Treated 6-mercaptopurine were performed. The PSA was performed with the help of Malvern Mastersizer 2000 (UK) using the wet method [33,34]. The PXRD analysis of the test samples was performed with the help of Rigaku MiniFlex-II Desktop X-ray diffractometer (Japan) [35,36]. The average size of crystallites was calculated from PXRD data using the Scherrer’s formula (1):

Where G is the crystallite size in nm, k is the equipment constant, λ is the radiation wavelength, β is the full width at half maximum (FWHM), and θ is the Bragg angle [37].

Similarly, the DSC analysis of the test samples was performed with the help of DSC Q200, TA Instruments. The TGA/DTG thermograms also performed with the help of TGA Q50 TA instruments [33,34].

The % change in particle size, specific surface area, peak intensity, crystallite size, melting point, latent heat, weight loss, and the maximum thermal degradation temperature of the Biofield Energy Treated sample was calculated compared with the control sample using the following equation 2:

Results and Discussion

Particle Size Analysis (PSA)

The particle size and surface area analysis data of both the control and Biofield Energy Treated 6-mercaptopurine were presented in Table 1. The particle size values in the treated mercaptopurine powder sample were significantly decreased by 10.18% (d10), 10.59% (d50), 7.62% (d90), and 9.17% {D(4,3)} compared to the control sample. The specific surface area (SSA) of the treated 6-mercaptopurine (0.118 m2/g) was increased by 10.28% compared to the control sample (0.107 m2/g). The results indicated that the Biofield Energy Healing Treatment might have acted like an exterior force, responsible for the breaking of the larger particles into smaller ones, therefore increased the surface area. The particle size properties have a huge impact on the solubility, absorption, bioavailability, and therapeutic efficacy of any pharmaceutical compound [38,39]. The solubility of mercaptopurine is very poor in many organic solvents [12]. Thus, the Biofield Energy Treated 6-mercaptopurine would the better for the pharmaceutical formulations, which may be more efficacious with improved solubility, dissolution, and absorption.

Table 1: Particle size distribution and surface area of the control and Biofield Energy Treated 6-mercaptopurine.
d10, d50, and d90: particle diameter corresponding to 10%, 50%, and 90% of the cumulative distribution, SSA: the specific surface area, and D(4,3): the average mass-volume diameter.

Powder X-ray Diffraction (PXRD) Analysis

The PXRD diffractograms of both the 6-mercaptopurine powder samples showed sharp and intense peaks in the diffractograms (Figure 1), this indicated that both the samples were crystalline. The control and Biofield Energy Treated samples showed the highest peak intensity at 2θ near to 27.57° and 27.47° (Table 2, entry 11). The peak intensities of the treated 6-mercaptopurine were significantly altered ranging from -43.40% to 23.33% compared to the control sample. Similarly, the crystallite sizes of the treated 6-mercaptopurine were significantly altered ranging from -37.09% to 136.67% compared to the control sample. Though, the average crystallite size of the Biofield Energy Treated 6-mercaptopurine (266.50 nm) was significantly decreased by 11.04% compared with the control sample (299.58 nm).

Table 2: PXRD data for the control and Biofield Energy Treated 6-mercaptopurine.

The change in the crystal morphology responsible for the change in the peak intensity of each diffraction face on the crystalline compound [40]. The alterations in the XRD pattern provide the evidence of polymorphic transitions [41,42]. Therefore, the Trivedi Effect®-Consciousness Energy Healing Treatment probably produced the new polymorphic form of mercaptopurine through the Biofield Energy via neutrino oscillations [18]. Thus, the treated mercaptopurine would show the significant effects on the drug performance, i.e., bioavailability and therapeutic efficacy because of their modified physicochemical properties like from the original one [43,44].

Differential Scanning Calorimetry (DSC) Analysis

Both the thermograms of control and Biofield Energy Treated sample presented the two sharp endothermic peaks (Figure 2). The 1st endothermic peak represents the evaporation of the bounded water and the 2nd endothermic peak indicated the melting point. The data closely matched to the data reported in the literature [44]. The evaporation temperature and the melting point of the Biofield Energy Treated 6-mercaptopurine did not show many alterations compared with the control sample (Table 3). However, latent heat of evaporation (∆Hevaporation) and latent heat of fusion (∆Hfusion) of the treated 6-mercaptopurine was significantly increased by 11.81% and 14.97% compared with the control sample (Table 3). The change in the latent heat of (∆H) can be attributed to the altered molecular chains and the crystal structure [45]. Thus, the Trivedi Effect®-Consciousness Energy Healing Treatment might have altered the molecular chains and crystal structure of mercaptopurine. Hence, increased the thermal stability of the Consciousness Energy Healing Treated 6-mercaptopurine compared to the control sample. The increased thermal stability will help the product for long term storage and improve self-life.

Table 3: DSC data for both control and Biofield Energy Treated samples of 6-mercaptopurine.

ΔH: Latent heat of evaporation/decomposition.

Thermal Gravimetric Analysis (TGA) / Differential Thermogravimetric Analysis (DTG)

The thermograms of both the 6-mercaptopurine samples showed three steps of thermal degradation (Figure 3). The total weight loss of the Biofield Energy Treated sample was reduced by 0.89% compared to the control sample (Table 4). However, the residue amount was increased by 6.44% in the Biofield Energy Treated sample compared to the control sample (Table 4).

Table 4: TGA/DTG data of the control and Biofield Energy Treated samples of 6-mercaptopurine.

Tmax = the temperature at which maximum weight loss takes place in TGA.

Similarly, both the 6-mercaptopurine samples showed three peaks in the DTG thermograms (Figure 4). The maximum thermal degradation temperature (Tmax) of the 1st, 2nd, and 3rd peaks of the Biofield Energy Treated 6-mercaptopurine were altered by 1.55%, 0.18%, and -1.29% compared with the control sample (Table 4). Overall, thermal analysis data of 6-mercaptopurine samples revealed that the thermal stability of the Biofield Energy Treated 6-mercaptopurine sample was increased compared with the control sample.

Conclusions

The experimental results have shown that the Trivedi Effect®-Consciousness Energy Healing Treatment has a significant impact on the particle, crystal, and thermal properties of 6-mercaptopurine. The particle size values in the Biofield Energy Treated 6-mercaptopurine sample were significantly decreased by 10.18% (d10), 10.59% (d50), 7.62% (d90), and 9.17% {D(4,3)}; thus, the specific surface area was significantly increased by 10.28% compared to the control sample. The powder XRD peak intensities and crystallite sizes of the Biofield Energy Treated 6-mercaptopurine were significantly altered ranging from -43.40% to 23.33% and -37.09% to 136.67%, respectively; whereas the average crystallite size was significantly decreased by 11.04% compared with the control sample. The ∆Hevaporation and ∆Hfusion of the Biofield Energy Treated 6-mercaptopurine were significantly increased by 11.81% and 14.97% compared with the control sample. The total residue amount was significantly increased by 6.44% in the Biofield Energy Treated sample compared with the control sample. The Tmax of the 1st, 2nd, and 3rd peaks of the Biofield Energy Treated sample was altered by 1.55%, 0.18%, and -1.29% compared with the control sample. It was concluded that the Trivedi Effect®-Consciousness Energy Healing Treatment might have generated a new polymorphic form of 6-mercaptopurine which would offer better solubility, absorption, and bioavailability compared with the control sample. The Biofield Energy Treated 6-mercaptopurine would be more efficacious against acute lymphocytic leukemia, chronic myeloid leukemia, Crohn's disease, ulcerative colitis, and autoimmune diseases.

Acknowledgements

The authors are grateful to Central Leather Research Institute, SIPRA Lab. Ltd., Trivedi Science, Trivedi Global, Inc., Trivedi Testimonials, and Trivedi Master Wellness for their assistance and support during this work.

References

1. Maese L, Raetz, E (2018) Simplifying 6-MP Delivery. The Hematologist: Ash News and Reports 15(1): 11-12.

2. Korelitz BI (2013) Expert opinion: Experience with 6-mercaptopurine in the treatment of inflammatory bowel disease. World J Gastroenterol 19(20): 2979-2984.

3. Present DH, Korelitz BI, Wisch N, Glass JL, Sachar DB, et al. (1980) Treatment of Crohn’s disease with 6-mercaptopurine: A long-term, randomized, double-blind study. N Engl J Med 302(18): 981-798.

4. Schmiegelow K, Glomstein A, Kristinsson J, Björk O (1997) Impact of morning versus evening schedule for oral methotrexate and 6-mercaptopurine on relapse risk for children with acute lymphoblastic leukemia. Nordic Society for Pediatric Hematology and Oncology (NOPHO). J Pediatr Hematol Oncol 19(2): 102-109.

5. Sack DM, Peppercorn MA (1983) Drug therapy of inflammatory bowel disease. Pharmacotherapy 3(3): 158-176.

6. WHO (2015) WHO Model List of Essential Medicines, 19th List, World Health Organization. April 2015.

7. Timmer A, Patton PH, Chande N, McDonald JWD, MacDonald JK (2016) Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database of Systematic Reviews 5: CD000478.

8. Yang JJ, Landier W, Yang W, Liu C, Hageman L, et al. (2015) Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J Clin Oncol 33(11): 1235-1242.

9. Moriyama T, Nishii R, Perez-Andreu V, Yang W, Klussmann FA, et al. (2016) NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity. Nature Genet 48(4): 367-373.

10. Lerner EI, Flashner-Barak M, Achthoven EV, Keegstra H, Smit R (2012) Formulations of 6-mercaptopurine. US patent US8188067B2.

11. Tiphaine Ade B, Hjalgrim LL, Nersting J, Breitkreutz J, Nelken B, et al. (2016) Evaluation of a pediatric liquid formulation to improve 6-mercaptopurine therapy in children. Eur J Pharm Sci 83: 1-7.

12. Xu LL, Chen JM, Yan Y, Lu TB (2012) Improving the Solubility of 6-Mercaptopurine via cocrystals and salts. Cryst Growth Des 12: 6004–6011.

13. Chereson R (2009) Bioavailability, bioequivalence, and drug selection. In: Makoid CM, et al. (Eds.), Basic pharmacokinetics 1st (Edn.), Pharmaceutical Press, London.

14. Nayak G, Trivedi MK, Branton A, Trivedi D, Jana S (2018) Impact of Consciousness energy healing treatment on the physicochemical and thermal properties of vitamin D3 (cholecalciferol). Food Sci Nutr Technol 3(5): 000162.

15. Nayak G, Trivedi MK, Branton A, Trivedi D, Jana S (2018) Evaluation of the consciousness energy healing treated berberine chloride using PXRD, PSA, and DSC Analysis. Food Sci Nutr Technol 3(6): 000168.

16. Branton A, Jana S (2017) Effect of The biofield energy healing treatment on the pharmacokinetics of 25-hydroxyvitamin D3 [25(OH)D3] in rats after a single oral dose of vitamin D3. American Journal of Pharmacology and Phytotherapy 2(1): 11-18.

17. Trivedi MK, Branton A, Trivedi D, Nayak G, Lee AC, et al. (2017) An investigation of The Trivedi Effect®-Energy of Consciousness Healing Treatment to modulate the immunomodulatory effect of herbomineral formulation in male Sprague Dawley rats. American Journal of Biomedical and Life Sciences 5(6): 144-153.

18. Trivedi MK, Mohan TRR (2016) Biofield energy signals, energy transmission and neutrinos. American Journal of Modern Physics 5(6): 172-176.

19. Koithan M (2009) Introducing complementary and alternative therapies. J Nurse Pract 5(1): 18-20.

20. Rubik B (2002) The biofield hypothesis: Its biophysical basis and role in medicine. J Altern Complement Med 8(6): 703-717.

21. Barnes PM, Bloom B, Nahin RL (2008) Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report 12

22. Frass M, Strassl RP, Friehs H, Müllner M, Kundi M, et al. (2012) Use and acceptance of complementary and alternative medicine among the general population and medical personnel: A systematic review. Ochsner J 12(1): 45-56.

23. Trivedi MK, Tallapragada RM (2008) A transcendental to changing metal powder characteristics. Met Powder Rep 63(9): 22-28, 31.

24. Trivedi MK, Nayak G, Patil S, Tallapragada RM, Latiyal O (2015) Studies of the atomic and crystalline characteristics of ceramic oxide nano powders after bio field treatment. Ind Eng Manage 4: 161.

25. Trivedi MK, Nayak G, Patil S, Tallapragada RM, Mishra R (2015) Influence of biofield treatment on physicochemical properties of hydroxyethyl cellulose and hydroxypropyl cellulose. J Mol Pharm Org Process Res 3: 126.

26. Trivedi MK, Branton A, Trivedi D, Nayak G, Sethi KK, et al. (2016) Gas chromatography-mass spectrometry based isotopic abundance ratio analysis of biofield energy treated methyl-2-napthylether (Nerolin). American Journal of Physical Chemistry 5(4): 80-86.

27. Trivedi MK, Branton A, Trivedi D, Nayak G, Panda P, et al. (2016) Isotopic abundance ratio analysis of 1,2,3-trimethoxybenzene (TMB) after biofield energy treatment (the Trivedi Effect®) using gas chromatography-mass spectrometry. American Journal of Applied Chemistry 4(4): 132-140.

28. Trivedi MK, Branton A, Trivedi D, Nayak G, Shettigar H, et al. (2015) Antibiogram of multidrug-resistant isolates of Pseudomonas aeruginosa after biofield treatment. J Infect Dis Ther 3: 244.

29. Trivedi MK, Branton A, Trivedi D, Shettigar H, Nayak G, et al. (2015) Assessment of antibiogram of multidrug-resistant isolates of Enterobacter aerogenes after biofield energy treatment. J Pharma Care Health Sys 2: 145.

30. Trivedi MK, Patil S, Shettigar H, Mondal SC, Jana S (2015) The potential impact of biofield treatment on human brain tumor cells: A time-lapse video microscopy. J Integr Oncol 4: 141.

31. Trivedi MK, Branton A, Trivedi D, Nayak G, Gangwar M, et al. (2015) Effect of biofield energy treatment on chlorophyll content, pathological study, and molecular analysis of cashew plant (Anacardium occidentale L.). Journal of Plant Sciences. 3(6): 372-382.

32. Trivedi MK, Branton A, Trivedi D, Nayak G, Mondal SC, et al. (2015) Evaluation of plant growth, yield and yield attributes of biofield energy treated mustard (Brassica juncea) and chick pea (Cicer arietinum) seeds. Agriculture, Forestry and Fisheries 4: 291-295.

33. Branton A, Trivedi MK, Trivedi D, Nayak G (2018) Evaluation of the physicochemical and thermal properties of the biofield energy healing treated ofloxacin. J Pharm Pharmaceutics 5: 80-87.

34. Nayak G, Trivedi MK, Branton A, Trivedi D, Jana S (2018) The energy of consciousness healing treatment: Impact on physicochemical and thermal properties of l-tryptophan. Journal of Food Science and Technology 5: 084-094.

35. (1997) Desktop X-ray Diffractometer “MiniFlex+”. The Rigaku Journal 14: 29-36.

36. Zhang T, Paluch K, Scalabrino G, Frankish N, Healy AM, et al. (2015) Molecular structure studies of (1S,2S)-2-benzyl-2,3-dihydro-2-(1Hinden-2-yl)-1H-inden-1-ol. J Mol Struct 1083: 286-299.

37. Langford JI, Wilson AJC (1978) Scherrer after sixty years: A survey and some new results in the determination of crystallite size. J Appl Cryst 11: 102-113.

38. Chereson R (2009) Bioavailability, bioequivalence, and drug selection. In: Makoid CM, et al. (Eds.), Basic pharmacokinetics 1st (Edn.), Pharmaceutical Press, London.

39. Khadka P, Ro J, Kim H, Kim I, Kim JT, et al. (2014) Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability. Asian J Pharm Sci 9(6): 304-316.

40. Raza K, Kumar P, Ratan S, Malik R, Arora S (2014) Polymorphism: The phenomenon affecting the performance of drugs. SOJ Pharm Pharm Sci 1(2): 10.

41. Brittain HG (2009) Polymorphism in pharmaceutical solids in Drugs and Pharmaceutical Sciences, 2nd (Edn.), Informa Healthcare USA, Inc., New York.

42. Censi R, Martino PD (2015) Polymorph Impact on the bioavailability and stability of poorly soluble drugs. Molecules 20(10): 18759-18776.

43. Blagden N, de Matas M, Gavan PT, York P (2007) Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev 59(7): 617-630.

44. Lv X, Zhao M, Wang Y, Hu X, Wu J, et al. (2016) Loading cisplatin onto 6-mercaptopurine covalently modified MSNS: A nanomedicine strategy to improve the outcome of cisplatin therapy. Dovepress 10: 3933-3946.

45. Zhao Z, Xie M, Li Y, Chen A, Li G, et al. (2015) Formation of curcumin nanoparticles via solution-enhanced dispersion by supercritical CO2. Int J Nanomedicine 10: 3171-3181.