WO2016162486A1 - Traitement de la candidose par de l'extrait d'indigo naturel ou par de l'extrait de plante produisant de l'indigo - Google Patents

Traitement de la candidose par de l'extrait d'indigo naturel ou par de l'extrait de plante produisant de l'indigo Download PDF

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WO2016162486A1
WO2016162486A1 PCT/EP2016/057766 EP2016057766W WO2016162486A1 WO 2016162486 A1 WO2016162486 A1 WO 2016162486A1 EP 2016057766 W EP2016057766 W EP 2016057766W WO 2016162486 A1 WO2016162486 A1 WO 2016162486A1
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extract
indigo
candidiasis
oil
indigo naturalis
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PCT/EP2016/057766
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English (en)
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Philippe Andres
Laurent Chantalat
Yin-Ku Lin
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Galderma Sa
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Publication of WO2016162486A1 publication Critical patent/WO2016162486A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/19—Acanthaceae (Acanthus family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A61K36/315—Isatis, e.g. Dyer's woad
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders

Definitions

  • the present invention relates to a use of an Indigo Naturalis or Indigo-producing plant extract, particular in a use for treating candidiasis.
  • Candidiasis refers to a diverse group of infections caused by Candida albicans or by other members of the genus Candida. These organisms typically infect the skin, nails, mucous membranes, and gastrointestinal tract, but they also may cause systemic disease.
  • C. albicans is a dimorphic yeast that is responsible for 70 percent to 80 percent of all candidal infections, which makes it the most common cause of superficial and systemic candidiasis.
  • C. albicans is often found as a saprophyte and colonizes the mucous membranes of warmblooded animals. In up to 50 percent of normal individuals, the oropharynx is colonized. In addition, C. albicans exists as a commensal organism in the vaginal mucosa of 20 percent to 25 percent of asymptomatic, healthy women and up to 30 percent of pregnant women. The yeast is rarely isolated from normal human skin except occasionally from intertriginous areas. Likewise, the organism is infrequently found in soil, vegetation, and air samples.
  • Acute pseudomembranous candidiasis or thrush is the most common form of oral candidiasis. Oral candidiasis appears as discrete white patches that may become confluent on the buccal mucosa, tongue, palate, and gingivae.
  • Candida cheilosis (angular cheilitis), so-called perleche, is characterized by erythema
  • Chronic atrophic candidiasis (denture stomatitis) is a common form of oral candidiasis seen in 24 percent to 60 percent of those wearing dentures.
  • Acute atrophic candidiasis commonly occurs after sloughing of the thrush pseudomembrane. This condition is associated with broad-spectrum antibiotic therapy, glucocorticoid use, and human immunodeficiency virus infection.
  • VVC vulvovaginal candidiasis
  • C. albicans balanitis presents as small papules or fragile papulopustules on the glans or in the coronal sulcus. These break to leave superficial erythematous erosions with a collarette of whitish scale. Infection may spread to the scrotum and inguinal areas.
  • Intertrigo is the most common clinical presentation on glabrous skin. Usual locations for intertrigo include the genitocrural, axillary, gluteal, interdigital, and inframammary areas and between folds of skin on the abdominal wall. Cutaneous candidiasis appears as pruritic, erythematous, macerated skin in intertriginous areas with satellite vesicopustules. These pustules break open, leaving an erythematous base with a collarette of easily detachable necrotic epidermis.
  • Candidal diaper dermatitis is caused by yeast colonization from patients' gastrointestinal tracts. Chronic occlusion by wet diapers furthers the infection. Lesions appear first in the perianal area and spread to the perineum and inguinal creases, which show pronounced erythema
  • Candidal paronychia is common in individuals whose hands are habitually involved in wet work (e.g., housekeepers, bakers, fishermen, bartenders). Typically, there is redness, swelling, and tenderness of the paronychial area with prominent retraction of the cuticle toward the proximal nail fold. Secondary nail changes include onycholysis and transverse depressions of the nail plate (Beau's lines) with a brownish or green discoloration along the lateral borders.
  • Indigo Naturalis or Indigo-producing plant extract is particularly efficient for the treatment of candidiasis, more specifically for the topical treatment of candidiasis.
  • the present invention relates to an Indigo Naturalis or Indigo-producing plant extract that is effective for treating candidiasis.
  • the present invention provides a pharmaceutical or cosmetic composition comprising Indigo Naturalis or Indigo-producing plant extract for treating candidiasis.
  • the present invention provides use of Indigo Naturalis or Indigo- producing plant extract in the preparation of a medicament for treating candidiasis.
  • the present invention provides an Indigo Naturalis or Indigo-producing plant extract for a use in the treatment of candidiasis.
  • the present invention provides a method of treating candidiasis comprising administering therapeutically effective amount of Indigo Naturalis or Indigo- producing plant extract to a subject (e.g. human) in need thereof.
  • candidiasis in nail is suffering from nail psoriasis or not suffering from nail psoriasis.
  • candidiasis is caused by Candida albicans.
  • the present invention provides use of Indigo Naturalis or Indigo-producing plant extract in the preparation of a medicament for treating candidiasis.
  • the candidiasis is caused by Candida albicans infection.
  • the Indigo Naturalis or Indigo-producing plant extract includes any extract obtained from an Indigo Naturalis or Indigo-producing or Indigo-bearing plant as starting material.
  • Indigo Naturalis also known as Qingdai
  • Qingdai is obtained from one or more plants including Indigofera tinctoria L., Baphicacanthus cusia (Nees) Bremek (syn. Strobilanthes cusia (Nees), Persicaria tinctoria (Aiton) Spach. (syn. Polygonum tinctorium Aiton, P. tinctorium Lour. ) and Isatis tinctoria L. (syn. Isatis indigotica Fort.), such as from the plant leaves or stems, and the leaves and/or stems, after harvest and collection, may be processed by, for example, fermentation.
  • Qingdai is the current name for Indigo Natural is.
  • Indigo Natural is usually a dark-blue powder. It is obtained from Indigo-bearing or Indigo-producing plants with a NaOH or KOI 1 aqueous solution and corresponds to a mixture of around 5-15% organic compounds including alkaloids among which indigo and indirubin are present, and 85-95 % inorganic compounds such as calcium carbonate and calcium hydroxide.
  • An Indigo Naturalis or Indigo-producing plant extract refers to anextract from Indigo Naturalis or from the leaves and/or stems (or a part thereof) of one or more Indigo- bearing plant or Indigo-producing plant, where the extraction may be performed by using one or more organic solvents, one or more non-organic solvents, or a combination thereof.
  • the extract may include at least one enriched ingredient (having a higher w/w percentage than that existing in Indigo Naturalis) such as tryptanthrin, isatin, indirubin, indigo, or qingdainone.
  • the extract may be a solid, liquid, or any form in-between (e.g. , semi-solid).
  • the Indigo Naturalis or Indigo-producing plant extract is enriched in indirubin, for example the extract may contain indirubin in an amount of at least 65% w/w of the extract, for example, 65%-90% w/w of the extract.
  • the extract may further contain indigo in an amount of 0.1%- 15% w/w of the extract.
  • the extract may also contain tryptanthrin and/or qingdainone each in an amount of 0.1-5% w/w.
  • the Indigo Naturalis or Indigo-producing plant extract is an ethyl acetate extract (EA-extract), which may be prepared as illustrated by Example 2 in this application.
  • the content of each ingredient in the extract may vary.
  • the extract may contain indirubin in an amount of at least 65% w/w of the extract, for example, 65%-90% w/w of the extract.
  • the extract may further contain indigo in an amount of 0.1%- 15% w/w of the extract.
  • the extract may also contain tryptanthrin and/or qingdainone each in an amount of 0.1 -5% w/w.
  • a further example of the Indigo Naturalis extract is an oil extract, particularly an olive oil extract.
  • An oil extract can be prepared by the method disclosed in the patent US8784905. More specifically, the oil extract of is an oil-extracted product of Indigo Natural is which is obtained by a process comprising extracting Indigo Naturalis powder with an oil under heating. optionally followed by a refining treatment by filtration. More preferably, in said process, the oil-extracted product is obtained after the refining treatment has a decreased indigo content.
  • extracting Indigo Natural is powder is more particularly conducted at an elevated temperature not higher than 155° C, and preferably conducted at a temperature ranging from 100° C. to 155° C.
  • the oil used in said process is preferably selected from the group consisting of vegetable oils, animal oils, mineral oils, and combinations thereof. More preferably, the oil is a vegetable oil and can be selected from the group consisting of olive oil, cottonseed oil, sesame oil, sunflower seed oil, peanut oil, wheat germ oil, soybean oil, jojoba oil, evening primrose oil, coconut oil, palm oil, sweet almond oil, aloe oil, apricot kernel oil, avocado oil, borage oil, hemp seed oil, macadamia nut oil, rose hip oil, pecan oil. hazelnut oil, sasanqua oil, rice bran oil, shea butter, corn oil, camellia oil, grape seed oil, canola oil, castor oil, and combinations thereof.
  • the oil is a vegetable oil and can be selected from the group consisting of olive oil, cottonseed oil, sesame oil, sunflower seed oil, peanut oil, wheat germ oil, soybean oil, jojoba oil, evening primrose oil, coconut oil, palm oil, sweet almond oil, alo
  • each ingredient in the oil extract may vary.
  • the extract may contain indirubin in an amount of at least 65% w/w of the total amount of extracted alkaloids, for example, 65%-90% w/w of the total amount of extracted alkaloids.
  • the extract may further contain indigo in an amount of 0.1%- 15% w/w of the total amount of extracted alkaloids.
  • the extract may also contain tryptanthrin and/or qingdainone each in an amount of 0.1-5% w/w of the total amount of extracted alkaloids.
  • Indigo Naturalis or Indigo-producing plant extract is an extract prepared by a process comprising the following steps:
  • an extraction step extracting Indigo Naturalis or the leaves and/or stems of one or more Indigo-bearing plants or Indigo-producing plants, preferably selected from the group consisting of Indigofera tinctoria L., Baphicacanthus cusia (Nees) Bremek (syn. Strobilanthes cusia (Nees)), Persicaria tinctoria (Aiton) Spach. (syn. Polygonum tinctorium Aiton, P. tinctorium Lour.) and Isatis tinctoria L. (syn. Isatis indigotica Fort.) and/or Strobilanthes Formosanus, with a first polar solvent or moderately polar solvent to obtain a mixture of extraction;
  • a concentration step concentrating the filtrate to obtain a crude extract
  • a washing step washing the crude extract with a non-polar solvent, and optionally a second polar solvent, to obtain a washing mixture
  • a filtration step filtering the washing mixture to obtain a refined extract optionally after a drying step, for example, according to a conventional method for drying.
  • a crude extract obtained from the concentration step c) is subjected to the following procedure for at least one cycle till obtaining a refined extract: the crude extract is washed by a solvent (step d)), and filtered (step (e)) to yield a refined extract, optionally followed by a drying step.
  • the washing step d) and filtration step e) are performed by only one cycle to obtain the refined extract. When more than one cycle is applied, the same or different solvents for washing can be used.
  • the crude extract can be washed with a solvent under reflux, the mixture can be cooled to room temperature and then filtered to yield a refined extract, optionally followed by a drying step.
  • two cycles are performed.
  • the crude extract obtained by the concentration step c) is washed in a non- polar solvent, preferably hexane (step d) and filtered (step e), optionally followed by a drying step.
  • the hexane extract is then washed by an organic polar solvent, preferably ethanol (step d) and then filtered (step e) to obtain a refined extract, optionally followed by a drying step.
  • a micronization step is performed after step e), providing thereby a refined extract having a particle size between 25 and 35 ⁇ , preferably of about 30 ⁇ .
  • a refined extract may be prepared by a process comprising the following steps consisting of: a) (i) adding an extracting solvent, a polar or moderately polar solvent (such as an alcohol or ethyl acetate), to Indigo Naturalis powder to yield a mixture; (ii) heating and stirring the mixture for a period of time ⁇ e.g., 30 min, 1 hour, 2 hours); b) (iii) filtering the heated mixture while hot to remove insoluble by-products to yield a filtrate; c) (iv) concentrating the filtrate to yield a crude extract; d) (v) adding a washing solvent (for example, water a non-polar and/or a polar solvent or a mixture thereof) to the crude extract to yield a washing mixture; (vi) heating and stirring the washing mixture for a period of time (e.g.
  • step (vii) filtering the washing mixture, for example at room temperature (e.g. 18-35°C) to collect a refined extract; optionally (viii) repeating steps (v) to (vii) until the amount of indirubin (% w/w) in the refined extract is more than 55% (w/w), preferably more than 65%> (w/w) as measured by HPLC method, and optionally (ix) drying the residue according to a conventional method (e.g., air-drying, lyophilization) to obtain a dried extract.
  • the washing solvent in steps (v) and (viii) can be the same or different.
  • a refined extract is prepared by a process comprising the steps of:
  • the particle size is around 99% in the range 25 to 35 ⁇ , preferably of about 30 ⁇ .
  • refined extract refers to a solid, semi-solid or oily extract which contains less than 10% (w/w) of water and/or solvents used in the process for preparing the said refined extract.
  • a refined extract is more preferably characterized by an increase amount of active ingredients, including alkaloids among which indigo, indirubin, tryptanthrin, and/or qingdainone are present, preferably enriched in indirubin, compared to Qingdai or Indigo Naturalis. More specifically, the refined extract according to the invention comprises at least 60%, or more preferably more than 65 %, (w/w) of active ingredients, including indigo, indirubin, tryptanthrin, and/or qingdainone.
  • crude extract refers to a solid, semi-solid or oily extract which contains less than 15% (w/w) (e.g., 5-15%, 5-10%) of water and/or solvents used in the process for preparing the refined extract.
  • the crude extract is less enriched in indirubin, than the refined extract as compared to Qingdai or Indigo Naturalis.
  • the crude extract is obtained by the concentration step c) according to the invention.
  • the concentration step is more particularly carried out by sending the filtrate to a concentrator (for instance at reduced pressure), as to remove water and/or solvents used in the process and concentrating thereby the active ingredients present in the extract, including indigo, indirubin, tryptanthrin, and/or qingdainone.
  • a concentrator for instance at reduced pressure
  • one cycle refers to the two steps of the washing step d) and filtration step e) which are performed sequentially once
  • two cycles refers to the two steps of the washing step d) and filtration step e) which are performed sequentially twice.
  • the Indigo Naturalis or Indigo-producing plant extract according to the invention is an oil extract as defined above or an extract of Indigo- producing plant obtained by the process as above detailed comprising steps (a)-(e), optionally including one of the above described specific embodiments.
  • Candidiasis should be understood as a disease or disorder of skin, mucosa or nail caused by Candida albicans wherein Candida albicans is a primary cause of the disease or a superinfecting agent.
  • a therapeutically effective amount refers to a dose level of an Indigo Naturalis or Indigo- producing plant extract that yields a therapeutic benefit (for example, amelioration, reduction or cure of the diseases, disorder or symptoms of candidiasis) to a patient on average.
  • the present invention provides a composition comprising an Indigo Naturalis or Indigo- producing plant extract for treating candidiasis, preferably to treat topically candidiasis.
  • the composition comprises an Indigo-producing plant extract as the sole active ingredient.
  • the extract may be used directly without further formulation or included in a pharmaceutical or cosmetic composition that comprises the extract.
  • the extract may comprise indirubin in an amount of at least 65% w/w of the extract, for example, 65%-90% w/w of the extract. It may further comprise indigo in an amount of 0.1%- 15% w/w of the extract, and in another further embodiment, the extract may also comprise indigo in an amount of 0.1%- 15% w/w of the extract and tryptanthrin and/or qingdainone each in an amount of 0.1-5% w/w of the extract.
  • compositions, methods or uses of the invention may be used alone (i.e., in replacement of current treatments) or in combination with current treatments to improve their efficacy.
  • Indigo Naturalis or Indigo-producing plant extract is used as the sole active ingredient (e.g. as a single therapy).
  • the composition preferably comprises an Indigo-producing plant extract as the sole active ingredient.
  • the Indigo Naturalis or Indigo-producing plant extract can be used in combination with at least one other therapy.
  • a pharmaceutical composition may be formulated into a suitable dosage form for topical or oral administration using technology well known to those skilled in the art.
  • the pharmaceutical composition can additionally comprise a pharmaceutically acceptable carrier such as those widely employed in the art of drug-manufacturing.
  • the pharmaceutically acceptable carrier may include one or more of the following agents: solvents such as olive oil, olive oil refined, cottonseed oil, sesame oil, sunflower seed oil, peanut oil, wheat germ oil, soybean oil, jojoba oil, evening primrose oil, coconut oil, palm oil, sweet almond oil, aloe oil, apricot kernel oil, avocado oil, borage oil, hemp seed oil, macadamia nut oil, rose hip oil, pecan oil, hazelnut oil, sasanqua oil, rice bran oil, shea butter, corn oil, camellia oil, grape seed oil, canola oil, castor oil, and combinations thereof, preferably olive oil refined, emulsifiers, suspending agents, decomposers, binding agents, excipients, stabilizing agents,
  • a topical formulation suitable for the pharmaceutical composition according to the present invention may be an emulsion, a gel, an ointment, a cream, a patch, an embrocation, an aerosol, a spray, a lotion, a serum, a paste, a foam, or a drop.
  • the pharmaceutical composition is formulated into an external preparation by admixing the extract according to the present invention with a base such as those that are well known and commonly used in the art.
  • compositions, methods or uses of the invention are suitable for a topical treatment of candidiasis.
  • the dosage and the frequency of administration of the pharmaceutical composition according to the present invention may vary depending on the following factors: the severity of the disease to be treated, the route of administration, and the weight, age, physical condition and response of the subject to be treated.
  • the amount of the extract is in the range of about 0.001 to about 1000 mg/kg body weight/day, for example, about 0.01 to about 500, 300, or lOOmg/kg body weight/day.
  • administration can be performed daily or even several times per day, if necessary.
  • the extract of the invention can be administered once, twice, three, four, five or six times a week or more, or once, twice, three or four times a day or more. Duration of the treatment may vary and depends on the severity of the subject. It may last for instance from one week to several months (such as from 2, 3, 4, 5, 6 or 7 weeks to 12, 18, 24, 30, or 36 weeks).
  • the present invention also provides a cosmetic composition comprising the extract.
  • the composition may be present in a form adapted for topical application comprising a cosmetically or dermatologically acceptable carrier or medium.
  • Cosmetically or dermatologically acceptable means media which are suitable for a use in which they come into contact with the skin or human skin appendages without posing a risk of toxicity, intolerance, instability, allergic reaction, etc.
  • the extract may be previously solubilized in one or more cosmetically or dermatologically acceptable solvents, such as water, glycerol, ethanol, propylene glycol, butylene glycol, dipropylene glycol, ethoxylated or propoxylated diglycols, cyclic polyols, petroleum jelly, a vegetable oil or any mixture of these solvents.
  • cosmetically or dermatologically acceptable solvents such as water, glycerol, ethanol, propylene glycol, butylene glycol, dipropylene glycol, ethoxylated or propoxylated diglycols, cyclic polyols, petroleum jelly, a vegetable oil or any mixture of these solvents.
  • a composition may contain 0.001-10 mg, for example 0.01-1 mg of one or more active ingredients per lg composition.
  • the present invention provides a method of treating candidiasis, comprising administering a therapeutically effective amount of an Indigo Naturalis or Indigo-producing plant extract to a subject in need thereof.
  • the extract and compositions above can be used in the treatment or alleviation of a disease or condition.
  • treatment it is meant at least an alleviation of the symptoms associated with the pathological condition afflicting the subject, where alleviation is used in a broad sense to refer to at least a reduction in the magnitude of a parameter, e.g. symptom, associated with the pathological condition being treated.
  • treatment also includes situations where the pathological condition, or at least symptoms associated therewith, are completely inhibited, e.g., prevented from happening, or stopped, e.g., terminated, such that the host no longer suffers from the pathological condition, or at least the symptoms that characterize the pathological condition.
  • treatment includes both curing and managing a disease condition. Accordingly, the extract and compositions above can be used in the treatment or alleviation of candidiasis.
  • the efficacy of the extract and compositions can be evaluated by in vivo models with respect to their activities in treating diseases or disorders, for example, clinically trails on humans.
  • the subject in need of candidiasis treatment is any mammal, including a human or a non-human mammal, preferably a human mammal.
  • treatment denotes curative, symptomatic, and preventive treatment.
  • the compositions of the invention will not necessarily cure the patient who has candidiasis but will diminish in a satisfactory manner delaying or slowing thereby the progression or preventing thereby complications of candidiasis. This will ameliorate consequently the patients' skin condition.
  • the compositions of the invention can also be administered to those who do not have candidiasis yet but who would normally develop candidiasis or be at increased risk for said disease, they will not develop said disease.
  • Treatment also includes delaying the development of candidiasis in an individual who will ultimately develop said disease or would be at risk for the disease due to age, familial history, or genetic abnormalities. By delaying the onset of candidiasis, compositions of the invention have prevented the individual from getting candidiasis during the period in which the individual would normally have gotten candidiasis or reduce the rate of development of candidiasis or some of its symptoms.
  • Example 1 Preparation of a refined Indigo Naturalis extract
  • Qingdai as used in the following preparation is obtained from Delong Pharmaceutical (Indigo 2.62% and Indirubin 0.284% (HPLC method depicted in Example 7A) and tryptanthrin 0.0046%.
  • the micronization step of refined Indigo Naturalis extract obtained in the previous examples is performed with the following equipment:
  • this equipment is used for the dosage of powder to feed the micronizer.
  • the dosage is made thanks to two screws. This system allows a regularity of the flow.
  • Micronization consists to project grains of powder with jet of air. The contact of grains permits their explosion. Following parameters of micronization are recorded during the micronization:
  • the micronizer allows a cylindrical enclosure - holes around the enclosure for the injection of air.
  • Powder is introduced in the micronizer; grains are propelled thanks to jet of air. When grains have the good size, they are concentrated in the center of the micronizer and they are breathed. To avoid any contamination by foreign particles or broken pieces of the equipment, an additional sieving (sieve: 700 ⁇ ) is performed.
  • the step is done manually after the micronization and before the packaging.
  • the patients' characteristics are shown in table 1.
  • the age of these two patients is 72 (A) and 57 (B) years old.
  • Microbiological assay 3.1 The Preparation of Indigo Naturalis.
  • Indigo Naturalis The species for Indigo Naturalis varies in different parts of the world. Strobilanthes formosanus Moore, which is the species available in Taiwan, was harvested in Sansia, New Taipei City, Taiwan. The harvested leaves of Strobilanthes formosanus Moore were immersed in water for several days until the leaves were decomposed by microbial activities. After that, lime was the only substance added to the suspension to precipitate Indigo Naturalis. The chemicals included in Indigo Naturalis are different from Strobilanthes formosanus Moore due to the fermentation process.
  • the leaves of Strobilanthes formosanus Moore were dried in an oven (40 °C) for three days. Twenty-five g of the dried Strobilanthes formosanus Moore leaves were extracted with ethyl acetate (EA, 300 mL) at 40 °C for one hour. Indigo Naturalis (25 g) was also extracted by the same procedure. The EA-extractable compounds of the two samples were then separated from the residue by centrifugation (12,000 x g, 20 min) at 15 °C. The supernatant was recovered and evaporated to dryness under reduced pressure and stored at -20 °C for bioassays.
  • EA ethyl acetate
  • Indigo Naturalis extract extraction with ethyl acetate
  • Results showed A. fumigates and C. albicans were mildly inhibited by Indigo Naturalis extract in a dose-dependent manner (Table 2).
  • Indigo Naturalis extract also showed a weak inhibitory effect on S. cerevisiae and little, if any, effect on the other three tested dermatophytes (Table 2). Table 2.
  • Table 2 The antifungal effects of Indigo Naturalis extract on tested Fungi.
  • the diameters of the inhibition zones were measured in mm after incubation for 24 hours at the optimal temperature for the individual strains tested. Data are the means of triplicates ⁇ standard deviation of a representative experiment.

Abstract

L'invention concerne une composition pharmaceutique ou cosmétique comprenant de l'extrait d'indigo naturel ou de l'extrait de plante produisant de l'indigo, pour le traitement de la candidose, ainsi qu'une méthode de traitement de la candidose consistant à administrer une quantité thérapeutiquement efficace d'extrait d'indigo naturel ou d'extrait de plante produisant de l'indigo à un sujet en ayant besoin.
PCT/EP2016/057766 2015-04-09 2016-04-08 Traitement de la candidose par de l'extrait d'indigo naturel ou par de l'extrait de plante produisant de l'indigo WO2016162486A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2657807C1 (ru) * 2017-02-20 2018-06-15 Федеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный медицинский университет им. Н.Н. Бурденко" Министерства здравоохранения Российской Федерации Способ лечения кандидоза полости рта у пациентов со съемными ортопедическими конструкциями препаратами солкосерил и хофитол
CN110483365A (zh) * 2019-09-05 2019-11-22 章月贵 一种从青黛中分离出靛玉红的制备方法

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