WO2022085028A1 - Formulation homéopathique à base de nano-curcumine pour le traitement du paludisme - Google Patents

Formulation homéopathique à base de nano-curcumine pour le traitement du paludisme Download PDF

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WO2022085028A1
WO2022085028A1 PCT/IN2021/051000 IN2021051000W WO2022085028A1 WO 2022085028 A1 WO2022085028 A1 WO 2022085028A1 IN 2021051000 W IN2021051000 W IN 2021051000W WO 2022085028 A1 WO2022085028 A1 WO 2022085028A1
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curcumin
formulation
nano
malaria
treatment
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PCT/IN2021/051000
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English (en)
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Santosh Kar
Bhaskar Saha
Debadatta NAYAK
Anil KHURANA
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Central Council For Research In Homoeopathy
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • A61P33/02Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06Antimalarials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/12Ketones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/906Zingiberaceae (Ginger family)
    • A61K36/9066Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0004Homeopathy; Vitalisation; Resonance; Dynamisation, e.g. esoteric applications; Oxygenation of blood
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to a homeopathic formulation for prevention of malaria. More particularly invention relates to nano-curcumin based formulation for treatment and prevention of malaria including cerebral malaria.
  • Malaria is an infectious disease, transmitted by mosquitoes and caused by five species of Plasmodium parasites (P. falciparum, P. vivax, P. ovale, P. malariae and P. knowelsi). Symptoms include fever, chills, headache, muscle aches, tiredness, nausea and vomiting, diarrhoea, anaemia, and jaundice. Convulsions, coma, severe anaemia, and kidney failure can also occur. It remains a leading cause of death globally killing 409,000 persons in 2019 as per WHO report. While repeated chronic infections may leads to partial immunity in endemic areas, however people still suffer significant morbidity and loss of productivity.
  • CM Cerebral malaria
  • IN670/DEL/2009 describes a process and method for preparation of curcumin nanoparticles from ethanol solution of commercially available curcumin.
  • the curcumin nanoparticles have improved bioavailability.
  • IN201811011436 describes a process for potentization of homeopathic medicines.
  • the process comprises of mixing together a homeopathic substance with a suitable solvent in a ratio of 1:9 to 50:50 followed by number of succussions to obtain a 1C potency and diluting 1 part of 1C potency obtained in step (i) with 99 parts of suitable solvent and dilution and succussions are repeated to obtain different formulations.
  • Curcuma longa rhizome powder (turmeric) is a well-known indigenous herbal medicine. It is known for its diverse biological actions and pharmacological activities including antiinflammatory, antioxidant, antiproliferative, antimicrobial, anticarcinogenic and antiangiogenic properties. Curcumin is one of the biologically active components of Curcuma longa rhizome powder (turmeric). However, the systemic bioavailability of curcumin is low, most of it being excreted in the faeces and only traces appeared in the urine (Wahlstrom B, Blennow G. A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol (Copenh). 1978 Aug;43(2):86-92).
  • the primary object of the present invention is to provide a nano-curcumin based therapeutic homeopathic formulation for treatment of inflammatory diseases.
  • Another object of the present invention is to provide a nano-curcumin based homeopathic formulation for management of malaria.
  • object of the present invention is to provide a homeopathic formulation of a defined potency prepared from pure nanoparticles of curcumin.
  • Yet another object of the present invention is to develop a potent nano-curcumin homeopathic formulation for cerebral malaria.
  • present invention aims to provide a nano particle based homeopathic formulation for treatment of chronic inflammatory diseases. Further, the present invention aims to provide a nano-curcumin based homeopathic formulation for prevention and therapy of malaria including cerebral malaria.
  • the present invention provides a therapeutic curcumin nanoparticles for the treatment and prevention of malaria and inflammatory diseases, wherein said curcumin nanoparticles are of 200 nm average diameter.
  • the present invention provides a process for preparation of a therapeutic curcumin nanoparticles for the treatment and prevention of malaria and inflammatory diseases, said process comprising of: a) dissolving natural curcumin in ethanol and filtering to obtain a clear solution; b) stirring the above obtained clear solution in a high-speed homogenizer along with simultaneous and slow addition of Milli Q water containing citric acid to obtain pure curcumin nanoparticles from the solution; and c) homogenizing the entire suspension over ice in a high-pressure homogenizer for > 20 cycles to obtain curcumin nanoparticles of 200 nm average diameter.
  • the process for preparation of a therapeutic curcumin nanoparticles for the treatment and prevention of malaria and inflammatory diseases, as described in present invention is performed at the homogenizing speed of 12,000 - 15,000 RPM.
  • the process for preparation of a therapeutic curcumin nanoparticles for the treatment and prevention of malaria and inflammatory diseases, as described in present invention is performed with the Milli Q water contains 0.1% citric acid.
  • the process for preparation of a therapeutic curcumin nanoparticles for the treatment and prevention of malaria and inflammatory diseases, as described in present invention is performed with the Milli Q water containing citric acid in step b), which being added over a period of 60 minutes.
  • the process for preparation of a therapeutic curcumin nanoparticles for the treatment and prevention of malaria and inflammatory diseases, as described in present invention is performed with the Milli Q water containing citric acid in step b), which being added until the ethanol concentration became 40% (V/V).
  • the process for preparation of a therapeutic curcumin nanoparticles for the treatment and prevention of malaria and inflammatory diseases, as described in present invention is performed with the pressure of homogenizer at 30,000 PSI in step c).
  • the present invention provides a homeopathic formulation for the treatment and prevention of malaria and inflammatory diseases, wherein said formulation comprises of a) a nano-curcumin; and (b) a solvent.
  • the homeopathic formulation for the treatment and prevention of malaria and inflammatory diseases as described in present invention is comprises a nano- curcumin in a potentized, ultra-low dilution of 100-30.
  • the homeopathic formulation for the treatment and prevention of malaria and inflammatory diseases as described in present invention is comprises solvent selected from a group consisting of water, ethanol, or a mixture thereof.
  • the homeopathic formulation for the treatment and prevention of malaria and inflammatory diseases is reduces the expression of PD1, PDL1, PDL2, CTLA4, CD 80, CD86, CD40, CD40L, IFN gamma, TNF alpha, IL 1 beta, IL 6, and IL 12, MIP 1 beta, CCR7, CXCL10, CXCR3 and ICAM 1 and increases the expression of GATA3, FOXP3, IL 4, and IL 10.
  • the present invention provides a process for preparation of a homeopathic formulation for the treatment and prevention of malaria and inflammatory diseases, said process comprising steps of: a) suspending the curcumin nanoparticles of 200 nm average diameter in water followed by homogenization and filtration; b) drying the filtered slurry to obtain nano-curcumin powder; and c) suspending the above obtained nano-curcumin powder in a solvent selected from the group consisting of water, ethanol, or a mixture thereof.
  • the process for preparation of a homeopathic formulation for the treatment and prevention of malaria and inflammatory diseases, as described in present invention is performed with the water provided with 0.1% polysorbate 80 in step a), and wherein the homogenization is carried-out for 1 hour at 12,000 - 15,000 RPM, and wherein the drying temperature in step b) is 60°C.
  • the process for preparation of a homeopathic formulation for the treatment and prevention of malaria and inflammatory diseases, as described in present invention is potentized to an ultra-low dilution (100-30) in step c).
  • the process for preparation of a homeopathic formulation for the treatment and prevention of malaria and inflammatory diseases, as described in present invention is carried out by dissolving 4 gm of nano-curcumin in 1 L ethanol, followed by addition of 99 parts of alcohol/water to obtain formulation of a potency of 1c, and to the one part of a formulation of potency 1c is added 99 parts of alcohol/water and is succussed progressively for 30 times to produce final formulation (NC 30c) in step c).
  • the third, fourth, fifth and sixth groups were treated with Homeopathic Curcuma longa 30c (CL 30c), Nano-curcumin 6c (NC 6c), Nano-curcumin 18c (NC 18c), Nano-curcumin 30c (NC 30c) formulations respectively, diluted with 200pl PBS twice daily from day 2 to day 8 post infection. The trend in blood parasitemia has been depicted. Data is representative of three independent experiments.
  • FIG. 2 Effect of different homeopathic drug treatments on the survival of mice infected with P. berghei ANKA. 6-8-week-old female C57BL/6 mice were divided into 6 different groups as mentioned in description to Figure 1. The survival curve of all the groups has been depicted. Data is representative of three independent experiments.
  • BBB Blood-Brain Barrier
  • the Evan’s blue dye was extracted out from the brain tissue after 2 hours using 100% formamide and the absorbance was measured at 620 nm to quantify the extent of BBB damage by Evan’s Blue Dye Extravasation. Data is expressed as mean ⁇ S.D and is representative of three independent experiments.
  • Data has been normalized to GAPDH and expressed as mean ⁇ S.D of relative fold change in mRNA expression and is representative of three independent experiments. Serum from different groups was collected on day 12 post-infection and ELISA was performed to determine the levels of IFN gamma, TNF alpha, IL 12, IL6, IL4, and IL 10 in the blood. Data are expressed as mean ⁇ S.D of serum cytokine concentration (pg/ml) and are representative of three independent experiments (* P ⁇ 0.05, **P ⁇ 0.01, ***P ⁇ 0.001, n.s: not significant).
  • a tissue processor using an automated tissue processor (Leica, Germany) to remove the water from the tissues.
  • the specimens were embedded into melted paraffin wax using a histoembedder (Leica, Germany), sectioned into a 4.0pm thick slice with a microtome (Leica, Germany) and stained with hematoxylin and eosin (H&E) using an auto Stainer.
  • A) Brain, B) spleen, and C) liver from different groups were analyzed after H&E staining under 60x magnification using a light microscope.
  • the present invention aims to provide a nano particle based homeopathic formulation for treatment of inflammatory diseases.
  • Homeopathic medicines have been used as an alternative for the treatment of inflammatory diseases, including malaria.
  • the present invention aims to provide a nano-curcumin based homeopathic formulation for treatment and prevention of malaria including cerebral malaria.
  • the nano-curcumin based formulation is prepared from pure nanoparticles of curcumin by potentization and succuction.
  • the present invention provides a homeopathic formulation comprising: (a) a nano-curcumin; and (b) a solvent.
  • the invention describes a homeopathic formulation comprising a nano-curcumin and a solvent selected from a group consisting of water, ethanol (98%) or a mixture thereof.
  • nano-curcumin based homeopathic formulation described in present invention is prepared by potentization and succussions.
  • nano-curcumin based formulation in preventing the disease severity brought about by Plasmodium berghei (P. berghei) ANKA infection in a C57BL/6 mice modelwasevaluated.
  • Treatment with homeopathic formulation of Nano-curcumin 30c (NC 30c) potency delayed the death of the infected animals by 10 days in comparison to infected untreated animals.
  • Oral feeding of Homeopathic Nano- curcumin formulation 30c to mice protected against damage to the blood brain barrier and haemorrhages in the brain and prevented the development of Experimental Cerebral Malaria (ECM) in the infected mice by reducing excessive inflammation, thereby improving the period of survival in the P. berghei ANKA infected mice.
  • ECM Experimental Cerebral Malaria
  • the entire suspension was homogenized over ice in a high-pressure homogenizer (Avestin C5 High Pressure Homogeniser BPS, UK) at 30,000 PSI for 20 cycles or more till uniform particles of 200 nm average diameter were obtained.
  • the aqueous suspension was then made to 0.1% polysorbate 80 (Sigma, USA) and homogenized at 12,000-15,000 RPM (T 25 digital ULTRA-TURRAX, IKA, USA) again for 1 hr and filtered.
  • the filtered slurry was dried at 60°C in an oven to get nano-curcumin powder. Particle size was determined by a high-resolution transmission electron microscope (JEM 21 OOF, JEOL, USA).
  • the therapeutic efficacy of homeopathic formulation of Nano- curcumin in preventing the disease severity brought about by Plasmodium berghei (P. berghei) ANKA infection in a C57BL/6 mice model C57BL/6 mice were infected with P. berghei ANKA and infected mice were orally fed with different potencies of homeopathic Nano-curcumin formulation to assess the efficacy of the homeopathic formulation in controlling the infection observed over a 30-day period.
  • Nano-curcumin 6c (NC 6c): Nano-curcumin mother tincture was prepared by dissolving 4 gm nano-curcumin powder in 1 L ethanol. Next, to one part of mother tincture in a glass container, was added 99 parts of alcohol/water and the mixture was succussed giving it a potency of 1c. To one part of a solution of potency 1c in a fresh container, was further added 99 parts of alcohol/water, and the mixture was similarly succussed progressively for 6 times to produce NC 6c.
  • Nano-curcumin 18c (NC 18c): Nano-curcumin mother tincture was prepared by dissolving 4 gm Nano-curcumin powder in 1 L ethanol. Next, to one part of mother tincture in a glass container, was added 99 parts of alcohol/water and the mixture was succussed giving it a potency of 1c. To one part of a solution of potency 1c in a fresh container, was further added 99 parts of alcohol/water, and the mixture was similarly succussed progressively for 18 times to produce NC 18c.
  • Nano-curcumin 30c (NC 30c): Nano-curcumin mother tincture was prepared by dissolving 4 gm Nano-curcumin powder in 1 L ethanol. Next, to one part of mother tincture in a glass container, was added 99 parts of alcohol/water and the mixture was succussed giving it a potency of 1c. To one part of a solution of potency 1c in a fresh container, was further added 99 parts of alcohol/water, and the mixture was similarly succussed progressively for 30 times to produce NC 30c.
  • Table 1 depicts the results after feeding nano-curcumin homeopathic formulation NC 6c for the determination of LD50.
  • the LD50 of NC 6c when delivered orally in BALB/c mice was found to be 200pl (200ul of 6c diluted in 200pl of PBS (pH 7.2).
  • Table 2 depicts the results for LD50 for NC 30c. There was no death observed in Groups 1-3 and therefore the LD50 of NC 30c in female BALB/c mice is higher than 300ul. The oral toxic dose of NC 30c in BALB/c mice was taken to be 200pl (200ul of30c diluted with 200pl of PBS (pH 7.2).
  • mice 8-12-week-old BALB/c mice were divided into different groups each consisting of 3 male and 3 female mice as described below in Table 3:
  • Table 7 depicts the results for determination of LD50 for NC 6c.
  • the LD50 of NC 6c when delivered orally in Wistar rats was taken to be 200pl (200ul of 6c diluted in 200pl of PBS (pH 7.2).
  • Table 8 depicts the results for determination of LD50 for NC 30c.
  • the LD50 of NC 30c when delivered orally in Wistar rats was taken to be 200pl (200ul of 6c diluted in 200pl of PBS (pH 7.2).
  • EXAMPLE 6 Determination of Acute toxicity of 6c and 30c nano-curcumin homeopathic formulation given orally for 28 days at less than LD 50 dose to 12-14 weeks old Female/ Male Wistar rats 12-14-week-old Wistar rats were divided into 3 groups each consisting of 3 male and 3 female mice as described below in Table 9:
  • P. berghei ANKA parasites were maintained in 6-8 weeks old female C57BL/6 mice. The animals were injected with 1X10 6 parasitized Red Blood Cells (pRBCs) intraperitoneally and monitored daily for symptoms of infection and determining the survival period. Each mouse in the treatment group was orally fed with 50pl of Homeopathic nano-curcumin 30c (NC30c) formulation diluted with 200pl PBS to evaluate the efficacy of the formulation to protect against infection.
  • the vehicle control (infected potentized EtOH treated) group received only 50pl of potentized ethanol (vehicle) diluted with 200pl PBS. Animals were treated twice daily for 7 days starting from day 2 post-infection up to days 8 post-infection. The untreated control (Infected untreated) received no treatment. Parasitemia was determined by taking blood smears from the tail of the mice and staining with Acridine Orange (Sigma, St Louis, MO) followed by observation in a fluorescent microscope.
  • each mice in the treatment group was orally fed with 50pl of Homeopathic Curcuma longa 30c (CL 30c) or nano-curcumin 6c (NC 6c), or nano-curcumin 18c (NC 18c), or nano-curcumin 30c (NC 30c) formulation diluted with 200pl PBS to evaluate the efficacy of different formulations to protect against infection.
  • the median survival period of P. berghei ANKA infected C57BL/6 mice, in the preliminary study was around 10 days (Fig. 1).
  • BBB Blood-Brain Barrier
  • the extent of extravasation of the dye can be determined by spectrophotometrically after extracting the dye and measuring O.D at 620 nm.
  • the extent of Evan’s Blue Dye Extravasation in infected-untreated and infected potentized EtOH treated was significantly higher than untreated group. There was no significant change in NC30c treated group as compared to the untreated group (Fig. 6).
  • Spleens were collected from the experimental animals on the 12 th day post-infection. Splenocytes were isolated from the spleen and subjected to RBC lysis and blocked with blocking buffer (30% FBS in PBS) for 30 minutes at 4 °C. The cells were then washed with 2 ml PBS, counted, and split into respective tubes keeping the count to 1X10 6 cells per tube. Surface staining for each sample from each group was done with a cocktail of anti-mouse CD3 FITC conjugated antibodies (Biogene India, CAT no. 100203) and anti-mouse CD4 PB conjugated antibodies (Biogene India, CAT no. 100427).
  • the samples were additionally stained with anti-mouse CD25_APC-Cy7 conjugated antibodies (Biogene India, Cat no. 102025). Following surface staining, the samples were then permeabilized and intracellular staining for the different sets was done using anti-mouse Tbet_APC conjugated antibodies (Biogene India, Cat no. 644813), anti-mouse GATA3 APC conjugated antibodies (Biogene India, Cat no. 653805), and anti-mouse FoxP3_Alexa Fluor® 647 conjugated antibodies (Biogene India, Cat no. 320013) respectively. Following intracellular staining, the cells were fixed with 1% paraformaldehyde and stored in dark at 4 degree C till FACS was done. FACS analysis was done using a FACS Canto II machine.
  • Flow cytometric analysis indicated a change in the Thl/Th2 ratio of infected untreated animals on day 12 post-infection in comparison to uninfected animals with the response in the case of the control animals being more Thl skewed as evidenced by an increase in the percentage of CD3+CD4+Tbet+ T cells and reduction in the percentage of CD3+CD4+GATA3+ T cells and CD4+CD25+Foxp3+ T cells in the spleen (Fig. 7).
  • CD3+CD4+Tbet+ T cells were reduced and CD3+CD4+GATA3+ T cells and CD4+CD25+Foxp3+ T cells was increased in the spleen of infected NC30c treated mice (Fig. 7).
  • Cytokine levels were measured in serum samples collected on day 12 post-infection from the experimental groups using DuoSet mouse ELISA kits (R&D systems) as per the manufacturer’s protocol. Biotinylated Detection Antibody and strept avidin-HRP conjugate were used with TMB liquid substrate (R&D systems) to give a colored product. Reaction was stopped using 2N H2SO4 and absorbance at 450 nm was measured to detect and quantify the levels of different cytokines in the serum.
  • ECM is characterized by an uncontrolled increase in the level of inflammation in the brain which subsequently leads to disruption of the specialized endothelial cells that help regulate the flow of substances into and out of the brain.
  • the pathophysiology associated with ECM as a consequence of heightened, prolonged inflammatory responses is orchestrated by a multitude of factors that collectively mediate the process of disruption of the Blood- Brain Barrier which subsequently leads to neuronal damage.
  • Key factors that play a role in the process involve the expression of cell adhesion molecules, chemokines and their receptors, pro-inflammatory cytokines, co-stimulatory, and co-inhibitory molecules which collectively determine the extent and magnitude of the immune responses elicited as a result of the infection.
  • NC 30c Treatment with NC 30c lowered the expression of PD1, PDL1, PDL2, CTLA4, CD 80, CD86, CD40, CD40L, IFN gamma, IL 12, IL 1 beta, MIP 1 beta, CCR7, CXCL10, CXCR3 and ICAM 1 in the brain of infected animals (Fig. 8).
  • the liver of infected untreated and infected potentized EtOH treated groups showed heavy deposition of hemozoin (Fig. 10C).
  • the deposition was present in lesser magnitude in the group treated with NC30cindicating that NC30c treatment did not lead to the elimination of the infection but prevented the pathological features in the brain that is associated with the development of ECM.

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Abstract

La présente invention concerne de la nano-curcumine et une formulation homéopathique à base de nano-curcumine pour la prévention et le traitement du paludisme et d'autres maladies inflammatoires. L'invention concerne également un procédé de préparation de nano-curcumine et d'une formulation homéopathique à base de nano-curcumine. L'invention concerne notamment une nanoparticule de curcumine présentant un diamètre moyen de 200 nm et une formulation homéopathique associée pour la prévention et le traitement du paludisme et d'autres maladies inflammatoires.
PCT/IN2021/051000 2020-10-21 2021-10-21 Formulation homéopathique à base de nano-curcumine pour le traitement du paludisme WO2022085028A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101711740A (zh) * 2009-12-18 2010-05-26 苏州大学 一种溃疡性结肠炎靶向姜黄素纳米粒的制备方法
US20110190399A1 (en) * 2008-07-31 2011-08-04 Santosh Kumar Kar Curcumin nanoparticles and methods of producing the same
WO2019227169A1 (fr) * 2018-05-31 2019-12-05 The University Of Queensland Nanoparticule polymère cœur-écorce
CN110652503A (zh) * 2019-10-21 2020-01-07 广州中医药大学(广州中医药研究院) 一种姜黄素纳米粒子及其制备方法与应用

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110190399A1 (en) * 2008-07-31 2011-08-04 Santosh Kumar Kar Curcumin nanoparticles and methods of producing the same
CN101711740A (zh) * 2009-12-18 2010-05-26 苏州大学 一种溃疡性结肠炎靶向姜黄素纳米粒的制备方法
WO2019227169A1 (fr) * 2018-05-31 2019-12-05 The University Of Queensland Nanoparticule polymère cœur-écorce
CN110652503A (zh) * 2019-10-21 2020-01-07 广州中医药大学(广州中医药研究院) 一种姜黄素纳米粒子及其制备方法与应用

Non-Patent Citations (4)

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Title
DATABASE WPI Week 201044, Derwent World Patents Index; AN 2010-G56361, XP002805456 *
DATABASE WPI Week 2020, Derwent World Patents Index; AN 2020-055141, XP002805457 *
IPAR VINOD S ET AL: "Enhancing Curcumin Oral Bioavailability Through Nanoformulations", EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, EDITIONS MEDECINE ET HYGIENE, CHENE-BOURG, CH, vol. 44, no. 4, 15 February 2019 (2019-02-15), pages 459 - 480, XP036831756, ISSN: 0378-7966, [retrieved on 20190215], DOI: 10.1007/S13318-019-00545-Z *
WAHLSTROM BBLENNOW G.: "A study on the fate of curcumin in the rat", ACTA PHARMACOL TOXICOL (COPENH, vol. 43, no. 2, August 1978 (1978-08-01), pages 86 - 92

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