Fixed-Dose Combination (FDC) Formulation of Quinine Sulphate-Doxycycline (Qidox) for Malaria Therapy

Background: One of the deadliest parasite infections is malaria. A combination of quinine sulphate and doxycycline is another therapeutic option for malaria that is resistant to chloroquine and is anticipated to be able to both combat the issue of anti-malarial medication resistance as well as the compliance to malaria therapy that is still raging in certain locations of Indonesia. Aim: This study will focus on evaluating the possibility of interaction between quinine sulphate and doxycycline followed by formulating the fixed-dose combination of both active pharmaceutical ingredients. Method: The study was designed as a laboratory experiment and applied some examinations. The examination from the organoleptic test of active pharmaceutical ingredients powder, crystallography analysis, and physical analysis of fixed-dose tablet including hardness, friability, and disintegration time testing. Result: The crystallography study reported there was no physical interaction found between quinine sulphate and doxycycline. The formula found excellent tablet printability with a composition of Quinine sulphate and doxycycline (Qidox). Conclusion: quinine sulphate with doxycycline can be combined into one tablet as Fixed-Dose Combination (FDC).

Identification, Characterization and Evaluation of Crystal Forms of Quinine Sulphate

Crystal engineering concept has been utilized to modify the physico-chemical parameters of a naturally occurring alkaloid, quinine sulphate, by exploring its H-bond interactions to generate different forms. Quinine sulphate is found to exist in four different crystal forms. The Forms I and II depict endo/exo events suggesting conversion of metastable low melting forms to higher melting and stable form indicated by sharp melting endotherms. The low melting form IL is found to be monotropically related to high melting Form IH while low melting Form IIL is enantiotropically related to high melting Form IIH. The Form III and IV showed broad endotherms accompanied by mass loss in TGA prior to melting indicating the existence of solvatomorphism. The solvent molecules are tightly bound in the crystal lattice of the drug molecules which is shown by high values of the binding energies of the solvents in these two forms. The enthalpy of solution was found to be endothermic for all the forms which followed the order: Form O > Form II > Form III > Form I > Form IV and is further related to the lattice energy suggesting Form II to be least crystalline. The solubility for Form II was found to be highest with maximum release rate in dissolution studies. The effectiveness of new polymorphic forms was confirmed by performing in vivo antimalarial activity against P. berghei infection. The studies have shown an increase in antimalarial activity of Form IV concluding a successful development of new polymorphic form.

Comparative study of chloroquine and quinine on malaria rodents and their effects on the mouse testis

Objective:To evaluate the effects of quinine and chloroquine against mole mice infected with Plasmodium berghei and their adverse effects on the mice testes.Methods:In this study,48 adult male mice,(20-23 g).aged 8 to 12 weeks were divided into four groups.This study was carried out from December 2009 until May 2010 in the School of Public Health,Tehran University of Medical Sciences.Results:The results showed that 58.33%of mice treated with chloroquine were completely recovered.Parasitemia was 4%on day 8 when compared to that on day 0,whereas it was 9%on day 9.There was no orchitis found in this group.The mortality of mice after exposing to quinine on day 5 was 8.3%,whereas from day 10 to day 14 it was 91.7%.We found 73%orchitis occurred in quinine treated group.There was a significant difference between quinine and chloroquine effects on the parasite and also mice testes(P<0.05).Conclusions:In this study,It can be concluded that male mice have full resistance to the quinine.Quinine does not only make male mice recover completely,but also cause inflammation on mice testicles tissue.

Benefits of Artesunate versus Quinine in the Treatment of Children with Severe Malaria at the National University Teaching Hospital of Cotonou

Introduction: Severe malaria is one of the leading causes of death in Sub-Saharan African countries, and artesunate is recommended as a first-line treatment by the Word Heath Organization (WHO.). Objective: Identify the advantages of artesunate compared with quinine in the treatment of severe malaria in children. Methods and patients: This study was a cross-sectional, descriptive and analytical study focused on children hospitalized for severe malaria in the CNHU who were treated with quinine or artesunate. Findings: The hospital-based frequency rate of severe malaria in pediatric patients was estimated to be 28.3% (n = 848). One hundred five children were treated with artesunate, and 743 were treated with quinine. The mean age of the children was 47 months old. The primary signs of severity were anemia (n = 776), neurological manifestations (n = 309) and hemolysis (n = 137). The average duration of treatment was 1.95 days for artesunate versus 2.45 days for quinine, and the difference was statistically significant (p = 0.001). The average length of stay (ALOS) in the hospital was 5 days for the artesunate group versus 5.75 days for the quinine group, and the difference was statistically significant (p < 0.001). Six of the children who received artesunate died, whereas 24 children who treated with quinine died. The total average cost of healthcare was 50,600 FCFA (77 euros) per child treated with artesunate versus 57,100 FCFA (87 euros) per child treated with quinine. Conclusion: The treatment of severe malaria with artesunate is superior to quinine-based treatment.

Study on Adsorption Behavior of Au、Pd、Pt by Quinine Loded Resin With ICP-AES

A new adsorbent QCR was prepared with quinine impregnated on cation exchange resin. It was found that QCR was stable in the solution of HCl(0.1～3.0 mol/L). Separation and preconcentration of noble metal ions (Au、Pd、Pt) by QCR have been studied by Inductively Coupled Plasma Atomic Emission Spectronetry (ICP\|AES). More than 93% of noble metal ions were adsorbed by QCR in 0.1mol/L HCl; and the analyte could be eluted quantatively by using 2 g/L thiourea -0.1 mol/L HCl as the eluant. The adsorption selectivity to Au、Pd、Pt is good at the existence of some non\|noble ions. This method has been applied to the analysis of catalysts and anticancer drugs with satisfactory results.\;

NBO Analysis by ONIOM and DFT (B3LYP) Calculations of Intramolecular and Intermolecular Interactions of Artemisinin, Quinine and Thirteen Manzamenones with H2O or Alanine

This work was undertaken to analyze intramolecular and intermolecular interactions of Manzamenones from natural bond orbitals (NBO method). For their use in the treatment of malaria, the results of these molecules are compared to those of Artemisinin and Quinine. Manzamenones are a class of atypical fatty acids. They are isolated from a marine sponge of the genus Plakortis kenyensis. The analysis of intramolecular interactions compares the results of each molecule (Manzamenones, Artemisinin and Quinine) in the non-complexed state with those of its complex with a water molecule. Thus, for the same electron donors (i) and associated acceptors (j), the electron density (ED), stabilization energy E2 related to the delocalization of i to j, the energies of the NBO orbitals εi and εj of the donor and acceptor, respectively, and element of the Fock matrix Fi,j are determined and compared. The change in E2 is used to deduce whether or not the molecule is stabilized after complex formation. These analyses allowed to match each Manzamenone to one of the two antimalarials. The intermolecular interactions were analyzed, for each molecule (Manzamenones, Artemisinin and Quinine), in two complexes. These complexes are obtained with a water molecule on the one hand and with an alanine molecule on the other hand. For these interactions, the electron donor and its electron density, the electron acceptor and its electron density as well as the donor—acceptor stabilization energy have been calculated. The ONIOM 2 method is used to study Manzamenones. Theoretical calculations were done using density functional theory (B3LYP) by combining one of the two function bases 6-31++G(d,p) and 6-31+G(d,p).

Quality Control of Quinine in Pharmaceutical Forms Tablets Find East of the Democratic Republic of Congo

The present study focuses on the quality control of quinine in the compressed pharmaceutical forms circulating in eastern Democratic Republic of Congo. The analyses performed on the collected samples included disintegration of the tablets, identification of quinine in the formulations by color reaction methods and thin-layer chromatography. The quantitative analysis was performed by spectrophotometric and volumetric methods. The most significantly observed findings were abnormalities of release;underdosing, overdosing and absence of the active ingredient, Which brings us to the conclusion that more than 30% of the samples analyzed are of inferior quality and adulterated.

Post-Quinine Bilious Hemoglobin Fever in an 8-Year-Old Child Monitored for Severe Malaria at the Yalosase Health Center, Isangi, DR Congo

It has been known since March 2013 that Artesunate is considered the gold standard treatment for severe malaria [1] [2] [3]. However, in our regions, the drug of choice available to treat patients with severe malaria remains quinine until today. However, frequent and sequential use of quinine is associated with the occurrence of hemoglobinuria [2]. We report a probable case of bilious hemoglobin fever (BHF) in an 8-year-old child. This was an 8-year-old child with a history of frequent and recent treatment with quinine, received in consultation for coca-cola urine emission with rapid diagnostic test (RDT) positive. In search of a particular terrain, the retroviral and syphilitic serologies were negative. Considering the context, the diagnosis of post-quinine hemoglobin bilious fever (BHF) was retained and the patient had progressed well after administration of artemisinin and its derivatives. The child was followed, on an outpatient basis, without any sequelae. It would therefore be prudent for the time being to avoid them in prophylaxis and self-medication.

New Method for Injectable Quinine Quality Assurance Control Using a Multi-Spectral Microscope

Africa is the world region that is most affected by malaria. Among the therapies used, injectable quinine is considered to be one of the effective antimalarial drug, however non-quality assured antimalarials clearly have a strong market penetration across Africa. To overcome this problem, it becomes more and more necessary to set up quantitative and qualitative analysis system for antimalarial quality control. The objective of the present investigation is an attempt to use customized multispectral microscope equipped with UV-Visible lasers for injectable quinine quality assurance control routinely. For that, we have established the calibration curve of quinine solution concentration as a function of area under light intensity histogram crossing the solution. From this calibration curve, we can check the conformity of any injectable quinine according to the pharmacopoeia involved. The proposed technique is a promising alternative for drug quality control routinely.

Quinine induced thrombotic microangiopathy and thrombocytopenia: A teaching hospital’s perspective

Although quinine is an infrequently prescribed drug, with malaria treatment being its only FDA-approved indication, unwitting exposure via beverages (e.g., tonic water), over the counter herbal remedies and illegal recreation drugs still occur. We present a unique case of a female patient who denied any known prior history of quinine exposure, who after being prescribed quinine tablets for restless leg syndrome, developed an immune-related thrombotic microangiopathy with thrombocytopenia and subsequent multi-organ failure. It was later elucidated that her only known potential source of prior quinine exposure was a remote history of crackcocaine use. The patient survived this rare and severe inflammatory response with recovery of renal function and was able to discontinue dialysis.

Interactions of Aurein with Model Membranes and Antimalarials

Aurein is a cationic antimicrobial peptide, rich in phenylalanine residues. Although the peptide has been extensively studied, its mechanism of action is not fully understood and has not been established. This project is focused on studying the interactions of aurein with model biological membranes and antimalarials using Fourier Transform Infrared (FTIR), fluorescence, dynamic light scattering (DLS), atomic force microscopy (AFM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) techniques. FTIR data revealed conformational changes to the secondary structure of the peptide in the presence of the model membranes. The strongest interactions of aurein were found with DOPC and lipid raft systems. Fluorescence data revealed some differences in the mechanism of interaction between aurein and lipid rafts. Topographical analysis was performed using atomic force microscopy (AFM). AFM images of the peptide with its lipid rafts showed a change in surface roughness suggesting a different mechanism of interaction. DLS data in agreement with FTIR confirmed that aurein interacts differently with the lipid rafts. The results gathered from this study provided new insights on the interaction of aurein. On the other hand, drug-drug interaction issues continue to present a major dilemma for the clinician caring for complex patients such as those infected with infectious disease. This study has examined the interaction of aurein with quinine, primaquine, and chloroquine. Significant interactions between aurein and antimalarials occured at a higher concentration of antimalarials. Interactions between aurein and anti-malarials reveal a strong interaction between aurein and primaquine. Interactions between aurein and quinine or chloroquine were found to be weak and negligible. FTIR, TGA, and DSC may be used in a complementary way to gain insights into the possible drug-drug interactions involving aurein. These studies are needed to initiate in vivo controlled interaction studies between antibiotics and antimalarials.

A fully bio-sourced adsorbent of heavy metals in water fabricated by immobilization of quinine on cellulose paper

The fabrication of a fully bio-sourced adsorbent of Cd(Ⅱ)by covalent immobilization of quinine on cellulose paper is described.The double bond of commercially available quinine was converted to a terminal alkyne function which was reacted with cellulose paper,chemically modified with azide functions,through a 1,3-dipolar cycloaddition,leading to Cell-Quin.The adsorption efficiency of Cell-Quin was investigated to determine the optimal pH,contact time and dose of adsorbent,ultimately leading to high levels of removal.The mechanism of adsorption of Cell-Quin was deeply rationalized through kinetic experiments and isotherm modeling.We also showed that Cell-Quin could adsorb other heavy metals such as Cu(Ⅱ),Pb(Ⅱ),Ni(Ⅱ)and Zn(Ⅱ).

TRANSFER MECHANISM OF QUININE DRUG ACROSS THE OIL/WATER (O/W) INTERFACE

The transfer phenomena of quinine drug at the aqueous 1,2- dichloroethane (DCE)interface have been studied by the current- scanning polarography. The relationships be-tween the wave height and pH of aqueous phase, concentration of quinine as well as therate of water drop are discussed. The effect of supporting electrolyte, buffer solution andthe nature of organic solvent on the polarographic wave is studied. The transfer char-acteristics of quinine in aqueous phase and in organic phase are compared, The mono- pro-tonated and diprotonated quinines can both transfer at the interface so as to produce twopolarographic waves. The transfer process of quinine at the interface is simultaneouslycontrolled by diffusion and reestablishment of the disturbed protonated equilibrium ofquinine. A further investigation is made by chronopotentiometry. On the basis of thetheoretical analysis, the formulae of the limiting current are derived and discussed. Thetheoretical results are in agreement with the experimental ones.

Activating PPARy Increases NQO1 and γ-GCS Expression via Nrf2 in Thrombin-activated Microglia

The present study aimed to explore the molecular mechanisms underlying the increase of nicotinamide adenine dinucleotide phosphate:quinine oxidoreductase 1(NQO1)and y-glutamylcysteine synthetase(γ-GCS)in brain tissues after intracerebral hemorrhage(ICH).The microglial cells obtained from newborn rats were cultured and then randomly divided into the normal control group(NC group),model control group(MC group),rosiglitazone(RSG)intervention group(RSG group),retinoic-acid intervention group(RSG+RA group),and sulfbraphane group(RSG+SF group).The expression levels of NQO1,γ-GCS,and nuclear factor E2-related factor 2(Nrf2)were measured by real-time polymerase chain reaction(RT-PCR)and Western blotting,respectively.The results showed that the levels of NQO1,γ-GCS and Nrf2 were significantly increased in the MC group and the RSG group as compared with those in the NC group(P<0.01).They were found to be markedly decreased in the RSG+RA group and increased in the RSG+SF group when compared with those in the MC group or the RSG group(P<0.01).The RSG+SF group displayed the highest levels of NQO1,γ-GCS,and Nrf2 among the five groups.In conclusion,a medium dose of RSG increased the anti-oxidative ability of thrombinactivated microglia by increasing the expression of NQO1 and γ-GCS.The molecular mechanisms underlying the increase of NQO1 and γ-GCS in thrombin-activated microglia may be associated with the activation of Nrf2.

Resolution pattern of jaundice among children presenting with severe malaria in rural South-West Nigeria

Objective:To compare the pattern of jaundice resolution among children with severe malaria treated with quinine and artemether.Methods:Thirty two children who fulfilled the inclusion criteria were recruited for the study from two hospitals with intensive care facilities.They were divided into two groups:'Q' and 'A',receiving quinine and artemether.respectively.Jaundice was assessed by clinical examination.Results:Sixteen out of 32 children recruited(representing50%) presented with jaundice on the dav of recruitment.The mean age was(7.00±2.56) years.On day 3,tour patients in 'A' and six patients in 'O' had jaundice.By day 7.no child had jaundice.Conclusion:The study has shown that hoth drugs resolve jaundice although artemether relatively resolves it faster by the third day.

Application of Total Error Strategy in Validation of Affordable and Accessible UV-Visible Spectrophotometric Methods for Quality Control of Poor Medicines

In the framework of fighting against the poor quality medicines sold in developing countries using classical analytical methods easily accessible in those countries, four UV-Visible spectrophotometric methods for one antimalarial (quinine) and two antibiotics (amoxicillin and metronidazole) have been developed and validated according to the total error strategy using the accuracy profiles as a decision tool. The dosing range was 2 - 10 μg/mL (for quinine sulfate in tablet), 4 - 12 μg/mL (for quinine bichlorhydrate in oral drop-metronidazole benzaote in oral suspension) and 15 - 35 μg/mL (for amoxicillin trihydrate in capsule). The validated methods were then applied in determining the content of some analogous medicines sold in the Democratic Republic of Congo. Thus, the proposed UV-Visible spectrophotometric methods are simple and suitable to quantify quinine, amoxicillin and metronidazole in different pharmaceutical forms.

ACUPUNCTURE TREATING 32 CASES OF MUSCULUS QUADRICEPS FEMORIS INJURY CAUSED BY QUINIMAX

Quinimax injection causes side effect characterized by pain and atrophy in mus-culus quadriceps femoris.Pain predominates in acute stage and corresponds to the Bi Syndrome,whileatrophy is seen in chronic stage,and refers to the Wei Syndrome.The pain should be treated by acti-vating Qi and blood circulation.The atrophy should be treated on the principle of tonifying blood andnourishing tendons.The points of the stomach moridian are mostly selected for the treatment purposebecause they are abundant in Qi and blood.My try is successful.The cured rate is 61.76% and all 34diseased lower extremities are improved.

The Epidemiological, Clinical, Paraclinical and Prognostic Aspects of Severe Malaria at the Regional Hospital of Thies

Introduction: Malaria, the first parasitical endemic disease in the world, is a serious disease with 407,000 deaths in Africa in 2016. It is the main cause of morbidity and mortality in Senegal [1] [2]. Methods: Our retrospective study carried out from 1st January 2010 to 31 December 2013, at the department of internal medicine in the regional hospital of Thies was aimed at studying the epidemiological, clinical, paraclinical and prognostic profile of severe malaria in the autochthonous adults with 15 years and more. Results: Over this 3-year period, 57 patients were hospitalized in 1275 patients due to severe malaria that is to say a hospital prevalence of 4.47%. The average age was 64.21. A clear male predominance has been observed, around 61% (34/57) against 39% (23/57) with a sex ratio of 1.6. The highest malarial infestation rate was found at the end of the rainy season and at the beginning of the dry season (September to November). The clinical picture which predominates is the neurological affection which represented 33.3% of the cases. The different aspects of this neurological affection were of coma type, convulsion and prostration in 87%;21.7% and 8.6% respectively. The cerebral malaria was associated or not with other symptoms of severity that are anemia in 41.6%;icterus was represented in 21% of the cases, cardio-vascular collapse in 15.8% and hypoglycemia in 5.5% of the cases. The complications were observed during the hospitalization in 73.6% of the cases with the type of bacterial pneumonia (47.6%) and urinary infections (26.2%). The curative treatment was based on quinine salts through intravenous track in 100% of the case with a shift to the Artemisinin combination therapy (ACT) associated with intense care measures. In our study the whole lethality is 17%. Conclusion: The results of our study shows that the severe forms of malaria are still affecting our tropical endemic area, in spite of the prevention efforts made to fight against this plague. This research illustrates the difficulties to provide optimum medical care when combining antimalarial treatment and resuscitative measures in the decentralized reception facilities.

Role of traditional herbal medicine in the treatment of malaria

Malaria is one of the world's major public health concerns and numerous medicinal plants are commonly used for treating malaria.Traditional health care uses medicinal plants widely,but no scientific documentation is available and,there is a growing risk of losing this knowledge.Thus,this study aims to document the traditional use of medicinal plants in treating malaria and related conditions.In this review,numerous herbal medicines for antimalarial potential are explained.The literature survey was done using keywords i.e.,malaria,herbal,herbal,traditional use,antimalarial,quinine,artemisinin,and traditional medicine by using PubMed,Science Direct,Google Scholar,and HINARI database.This review discusses the life cycle of the malarial parasite,what makes you attractive to mosquitoes,and the role of traditional herbal medicine in malaria.

Black Water Fever in Severe Falciparum Malaria: A Case Report

Introduction: Black water fever (BWF) is a complication of severe Plasmodium falciparum infection in hemolysis of erythrocytes into the bloodstream releasing the hemoglobin directly into the blood vessels and causes severe anemia and passage of dark/cola color urine, leading to acute renal failure. Hemoglobinuria or BWF is a rare and severe manifestation of falciparum malaria characterized by sudden intravascular hemolysis followed by fever and presence of abnormal hemoglobin in the urine. Aim: The aim of this study was to diagnose and treat severe malaria infection in a Nigerian patient admitted to the Casualty of the IDH Hospital. Case Presentation: A 20-year-old Nigerian boy came to Kuwait and started complaining abdominal pain, nausea, vomiting and fever two days after his arrival. The investigation revealed high fever (40.8˚C), heart rate 125, blood pressure of 100/60 mmHg. The physical examination was unremarkable, including a normal neurologic examination, no hepatosplenomegaly, rash and neck rigidity. The Giemsa stained thick and thin blood examination confirmed the severe infection of Plasmodium falciparum with 41.0% parasitemia. The patient was admitted to the hospital and started intravenous Quinine (1200 mg loading dose in 5% glucose over 4 hours). The patient was feeling much better on next morning but became unconscious by evening and shifted to ICU. His all CBC parameters were higher and started passing dark/cola color urine. The 12 units of whole blood were exchanged on next morning and became fully conscious on 4th day and his anemia and thrombocytopenia were improved and the color of the urine also became normal. Conclusion: Quinine is used in both complicated and uncomplicated malaria and may cause black water fever in severe infection of P. falciparum. It is caused by the hemolysis of erythrocytes due to malaria and also with the metabolism of quinine, making these cells more vulnerable to hemolysis in falciparum malaria and also in G6PD deficiency.