EP2680868A1 - Product of natural origin for ophthalmic treatment and obtaining procedure - Google Patents

Product of natural origin for ophthalmic treatment and obtaining procedure

Info

Publication number
EP2680868A1
EP2680868A1 EP11797277.8A EP11797277A EP2680868A1 EP 2680868 A1 EP2680868 A1 EP 2680868A1 EP 11797277 A EP11797277 A EP 11797277A EP 2680868 A1 EP2680868 A1 EP 2680868A1
Authority
EP
European Patent Office
Prior art keywords
product
obtaining
truffles
extract
glaucoma
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP11797277.8A
Other languages
German (de)
French (fr)
Inventor
Mi u MOSCOVICI
Angela Casarica
Ortansa Cosa
Sultana Nita
Iuksel Rasit
Ahmad Daas
Irina Minerva Panteli
Alexandra CRE U
Marwa Daas
Arij Daas
Morouj Daas
Daniela Ghera
Nour Daas
Anastasia Boghiu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Daas Mohammed Marwan
Original Assignee
Daas Mohammed Marwan
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Daas Mohammed Marwan filed Critical Daas Mohammed Marwan
Publication of EP2680868A1 publication Critical patent/EP2680868A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents

Definitions

  • the invention refers to a product of plant extraction having therapeutic action in ophthalmic disorders and its obtaining procedure.
  • corneal ulcer There are many ophthalmic affections that harm the cornea: corneal ulcer, keratitis (infections of different origins, namely viral or microbial). Other lesions are due to the abrasion brought on by foreign bodies or mechanical shocks.. On a global scale, corneal affections rank second, right after the cataract, among the decisive factors for blindness [ 1 -6].
  • antibiotics or antivirals are used, both local and systemic. Many of these preparations can cause adverse or allergic reactions, having unpleasant or even serious effects. Moreover, the healing can be accompanied by proliferative processes, with upsetting scars, affecting sight.
  • Glaucomas are a group of eye diseases characterized by progressive lesions of the optic nerve and of the visual field, due to the increase of the intraocular pressure, being the third cause of blindness on worldwide ranking.
  • Anti-glaucoma medication comprises topical agents (analogues of prostaglandin, B- blocking agents), as well as systemic medication.
  • topical agents analogues of prostaglandin, B- blocking agents
  • the administration of these can be limited by allergic reactions or adverse effects, some important, such as cardiac or central nervous system disorders [ 1 ,3,4,5,6,7].
  • the truffles are widely used in alimentation, having a high content of proteins and lipids, other nutritional substances being carbohydrates, amino acids and vitamins (especially vitamin C) [12].
  • the technical problem solved by this invention is the achievement of a natural origin product of therapeutic use which is very active in ocular affections of the cornea and moderately active in the treatment of glaucoma, by a procedure involving pre-established steps and parameters.
  • the plant source consists of brown desert truffles of the Terfezia type fungi.
  • the product according to the invention consists in an aqueous extract of brown desert truffles of Terfezia genus fungi, having a concentration of 13... 17%(w/v) as dry matter, containing %(w/v):
  • the product is sterile, for ophthalmic treatment as eye drops.
  • the product obtaining procedure according to the invention consists in that: Fresh or frozen truffles are extracted in demineralized water at 4 °C by a ratio of 2-3: 1 (v/w), the extract is separed by filtration on a filter aid layer (celite) or centrifugation and it is submitted to purification by ultrafiltration on membranes with a cut-off limit of 10 kDa.
  • the obtained permeate solution is then concentrated under vacuum to 1/6-1/9 (v/v) and benzalkonium chloride 0.01% (w/v), as well as sodium chloride 0.6 % (w/v) are added, after which it is sterilely filtered and thus an eye drops solution is obtained and filled in sterile bottles of 5-10 ml.
  • the advantages of the invention are mainly that: a product of natural origin from a single plant source is obtained, which is very active in the affections of cornea and moderately active in glaucoma, having no proliferative effect, the regeneration taking place without leaving any scars; the product is not toxic and non-irritative.
  • a 2 kg quantity of brown desert truffles (of the Terfezia genus), frozen for 4 months at - 17... - 19 °C is submitted to extraction by shaking with 4 1 demineralized water for 24 h at 4 °C.
  • the solid phase is separated through filtration under vacuum, on a Buchner funnel, through a filtration aid layer (celite).
  • a filtration aid layer celite
  • the extract is purified of the ballast proteins by ultrafiltration on a module with a cellulose membrane cassette with a cut-off limit of 10 kDa and a filtration area of 0.5 m 2 (PLCGC - Pellicon, Millipore), with the recirculation of the retentate and adding of demineralized water at the end in order to recover the active product.
  • 3250 ml of permeate solution (filtrate) having a protein concentration of 5.5 mg/ml is obtained, this being the active fraction and 150 ml of retentate with 17.4 mg/ml (protein ballast).
  • the filtrate is concentrated on a rotary evaporator, under vacuum (maximum temperature of 37°C) up to a volume of 450 ml.
  • the active solution so obtained has 35.8 mg protein/ml.
  • This is formulated as eye-drops by adding at 100 ml solution of 0.5 ml. benzalkonium chloride 2% (w/v) - 0.01% (w/v) as refered to the active solution and 0.6 g NaCl - 0.6% (w/v), followed by aseptic filtration on sterile filter with a membrane of 0.22 ⁇ and fills in sterile dropper bottles of 5 and 10 ml.
  • HPLC-MS-MS chromatograms (Zorbax-SB-C 18 column, two mobile phases, Agilent Triple Quad LC/MS chromatograph) showed a molecular weight of the components of up to 420 Da.
  • the product showed antimicrobial activity against Staphylococcus aureus ATCC 25923 si
  • Table 4 Compared assay of antimicrobial activity against Staphylococcus aureus ATCC 2592 (TSA Agar medium, buffer pH 6.0, final pH 7.4).
  • the single dose toxicity test was performed in NMR1 mice, after a single oral dose by intragastric gavage.
  • the maximum sample volume was 25 ml/kg bwt.
  • the animals were supervised and observed until the end of a 14 days period.
  • the testing of the ocular tolerance of the eye drops was carried out in New Zealand rabbits, in two steps, after single and repeated administration.
  • the single dose tolerance was performed by unique instillation of a drop (0,02 ml) on the eye conjunctiva with an observation period of 72 hrs.
  • the sample was instilled daily, for 28 days, with a 2 weeks watching period after ceasing the administration.
  • the product was classified as "non-irritative" by the local tolerance test after single administration and "practically non-irritative" after repeated administration for 28 days. .
  • Diagnosis of keratitis cases was performed by slit lamp examination and the use of ophtalmic dyes (fluorescein).
  • the treatment consisted in administering of 1-2 drops three times/day, for 14 days, for all of the affections considered in this trial.
  • the eye drops showed moderate action of decreasing the intraocular pressure (IOP).
  • IOP intraocular pressure

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Mycology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Ophthalmology & Optometry (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention refers to a natural product consisting in an aqueus extract of brown desert truffles of the Terfezia-genus fungi, which contains proteins, aminoacids, carbohydrates, utilizable as eye drops in the treatment of ocular affections of cornea and in glaucoma, as well as to its obtaining procedure. The truffles are extracted with demineralized water, in a ratio of 2-3: 1 (w/v) at 4°C; the extract is separated through filtration on filter aid layer or centrifugation, then it is purified through ultrafiltration on membranes with cut-off limit of 10 kDa; the permeate solution obtained is concentrated under vacuum to 1/6-1/9 (v/v), then benzalkonium chloride 0.01 % (w/v) and sodium chloride 0.6% (w/v) are added, thus obtaining an eye drops solution which fills in sterile bottles of 5-10 ml.

Description

PRODUCT OF NATURAL ORIGIN FOR OPHTHALMIC TREATMENT AND OBTAINING
PROCEDURE
The invention refers to a product of plant extraction having therapeutic action in ophthalmic disorders and its obtaining procedure.
There are many ophthalmic affections that harm the cornea: corneal ulcer, keratitis (infections of different origins, namely viral or microbial). Other lesions are due to the abrasion brought on by foreign bodies or mechanical shocks.. On a global scale, corneal affections rank second, right after the cataract, among the decisive factors for blindness [ 1 -6].
For the treatment of the affections mentioned above, antibiotics or antivirals are used, both local and systemic. Many of these preparations can cause adverse or allergic reactions, having unpleasant or even serious effects. Moreover, the healing can be accompanied by proliferative processes, with upsetting scars, affecting sight.
Glaucomas are a group of eye diseases characterized by progressive lesions of the optic nerve and of the visual field, due to the increase of the intraocular pressure, being the third cause of blindness on worldwide ranking.
Anti-glaucoma medication comprises topical agents (analogues of prostaglandin, B- blocking agents), as well as systemic medication. The administration of these can be limited by allergic reactions or adverse effects, some important, such as cardiac or central nervous system disorders [ 1 ,3,4,5,6,7].
The patent applications CN 101579488(A) and CN 101647913(A) present Chinese medicines of plant origin on traditional basis for the treatment of ophtalmic disorders.
The patent application CN 101579488(A) concerns to a medicine for cataracts and glaucoma treatment prepared with 8 natural ingredients, 5 of them being of natural origin [8].
In the patent application CN 101647913(A) a preparation procedure of a medicine for the treatment of senile cataracts and viral keratitis from 12 plant secies is claimed, promising statistical data regarding the improvement of patients'eyesight are shown [9].
From Islamic religious texts [10] and from popular medicine in the Middle East, one knows the use of the juice extracted from desert truffles in treating some eye diseases. [1 1 ].
Generally, the truffles are widely used in alimentation, having a high content of proteins and lipids, other nutritional substances being carbohydrates, amino acids and vitamins (especially vitamin C) [12].
Nevertheless, there are few scientific studies that have identified antimicrobial peptides in the extract of these desert truffles, without establishing any therapeutic action [13, 14].
The technical problem solved by this invention is the achievement of a natural origin product of therapeutic use which is very active in ocular affections of the cornea and moderately active in the treatment of glaucoma, by a procedure involving pre-established steps and parameters. The plant source consists of brown desert truffles of the Terfezia type fungi.
The product according to the invention consists in an aqueous extract of brown desert truffles of Terfezia genus fungi, having a concentration of 13... 17%(w/v) as dry matter, containing %(w/v):
-proteins 3.0...5.5
-aminoacids 0.1 ...0.2
-carbohydrates (as glucose) 0.4...0.6, to which are added
-benzalkonium chloride 0.01 as preservation agent
-sodium chloride 0.6 as isotonization agent and
-demineralized water to 100.
The product is sterile, for ophthalmic treatment as eye drops.
The product obtaining procedure according to the invention consists in that: Fresh or frozen truffles are extracted in demineralized water at 4 °C by a ratio of 2-3: 1 (v/w), the extract is separed by filtration on a filter aid layer (celite) or centrifugation and it is submitted to purification by ultrafiltration on membranes with a cut-off limit of 10 kDa. The obtained permeate solution is then concentrated under vacuum to 1/6-1/9 (v/v) and benzalkonium chloride 0.01% (w/v), as well as sodium chloride 0.6 % (w/v) are added, after which it is sterilely filtered and thus an eye drops solution is obtained and filled in sterile bottles of 5-10 ml.
The advantages of the invention are mainly that: a product of natural origin from a single plant source is obtained, which is very active in the affections of cornea and moderately active in glaucoma, having no proliferative effect, the regeneration taking place without leaving any scars; the product is not toxic and non-irritative.
The present invention is now illustrated by two following examples.
Example 1
A 2 kg quantity of brown desert truffles (of the Terfezia genus), frozen for 4 months at - 17... - 19 °C is submitted to extraction by shaking with 4 1 demineralized water for 24 h at 4 °C. Following extraction, the solid phase is separated through filtration under vacuum, on a Buchner funnel, through a filtration aid layer (celite). Thus 3370 ml filtered product (aqueous extract) having a protein concentration of 6.7 mg/ml (the Lowry method) is obtained.
The extract is purified of the ballast proteins by ultrafiltration on a module with a cellulose membrane cassette with a cut-off limit of 10 kDa and a filtration area of 0.5 m2 (PLCGC - Pellicon, Millipore), with the recirculation of the retentate and adding of demineralized water at the end in order to recover the active product. 3250 ml of permeate solution (filtrate) having a protein concentration of 5.5 mg/ml is obtained, this being the active fraction and 150 ml of retentate with 17.4 mg/ml (protein ballast). The filtrate is concentrated on a rotary evaporator, under vacuum (maximum temperature of 37°C) up to a volume of 450 ml.
The active solution so obtained has 35.8 mg protein/ml. This is formulated as eye-drops by adding at 100 ml solution of 0.5 ml. benzalkonium chloride 2% (w/v) - 0.01% (w/v) as refered to the active solution and 0.6 g NaCl - 0.6% (w/v), followed by aseptic filtration on sterile filter with a membrane of 0.22 μπι and fills in sterile dropper bottles of 5 and 10 ml.
The chemical and physical characterization of the active solution and of the eye drops was carried out by of high performance liquid chromatography HPLC-DAD, coupled with mass spectrometry (HPLC- MS-MS), atomic emission (ICP-MS) and atomic absorption spectrometry.
HPLC determination (Kromasil column 100-5CB, two mobile phases, Merck-Hitachi LaChrom chromatograph) showed a protein complex (polypeptides).
HPLC-MS-MS chromatograms (Zorbax-SB-C 18 column, two mobile phases, Agilent Triple Quad LC/MS chromatograph) showed a molecular weight of the components of up to 420 Da.
The spectrometric analysis of inductively coupled plasma atomic emission (ICP-MS Elan DRC-e Perkin Elmer) and atomic absorption (Analyst 800, Perkin Elmer) showed the presence as macro- and microelements of the metals Na, , Mg, Fe, Zn, Cu, Cr, Cd, As, Se, Pb. Zinc, chromium and selenium can be useful in the therapeutic action, and the toxic metals (Cd, As, Pb) are within the limits approved by the European Pharmacopoeia, the 6th edition.
In the following table the chemical composition and the metal content of the product are shown. Table 1. Chemical composition of the product.
Tabel 2. Metal content of the product. Cadmium 0,0323 0,00323
Lead < 0,0010 i < 0,0001
Example 2
One proceed as in example 1 , with the difference that the raw extraction material is represented by fresh truffles, extracted with demineralized water in a ratio of 3: 1 (w/v), and the extract is separated by centrifuging at 7000-8000 rpm. From 2 kg of fresh truffles 4580 ml of extract with 5.1 mg protein/ml are obtained; one proceed further as in example 1.
The product showed antimicrobial activity against Staphylococcus aureus ATCC 25923 si
Escherichia coli ATCC 25922.
The following tables give such examples.
Table 3. Antimicrobial activity assay at different dilution rates of the product (simple broth medium for bacteria, pH 7.4).
Table 4. Compared assay of antimicrobial activity against Staphylococcus aureus ATCC 2592 (TSA Agar medium, buffer pH 6.0, final pH 7.4).
The single dose toxicity test was performed in NMR1 mice, after a single oral dose by intragastric gavage. The maximum sample volume was 25 ml/kg bwt. The animals were supervised and observed until the end of a 14 days period.
After oral administration in mice, the product did not induce any toxic phenomena at this maximum possible dose.
The testing of the ocular tolerance of the eye drops was carried out in New Zealand rabbits, in two steps, after single and repeated administration.
The single dose tolerance was performed by unique instillation of a drop (0,02 ml) on the eye conjunctiva with an observation period of 72 hrs. In the repeated administration test, the sample was instilled daily, for 28 days, with a 2 weeks watching period after ceasing the administration. According to the Draize ocular assessment scale, the product was classified as "non-irritative" by the local tolerance test after single administration and "practically non-irritative" after repeated administration for 28 days. .
There was a clinical trial carried out which comprised a number of 16 cases (7 cats and 9 dogs), that had been diagnosed with secondary glaucoma (secondary to distopias of the crystalline lens, tumors of the ciliary body) and keratitis of various etiologies (chronic superficial, eosinophilic, proliferative secondary to scarring, corneal sequestrum).
Secondary glaucoma cases associated to anterior lens luxation were diagnosed by clinical examination, ophthalmoscopy, tonometry, eye echography. The intraocular pressure lOP (the pressure inside the eye) was carried out with Tono Vet, 2 hours, 6 hours and 24 hours after eye-drops administration.
Diagnosis of keratitis cases was performed by slit lamp examination and the use of ophtalmic dyes (fluorescein).
The treatment consisted in administering of 1-2 drops three times/day, for 14 days, for all of the affections considered in this trial.
In the cases of glaucoma secondary to the distopias of the crystalline lens, the eye drops showed moderate action of decreasing the intraocular pressure (IOP).
In the cases of chronic superficial keratitis (of dog) and eosinophilic keratitis (of cat), an important action of decreasing proliferation action in the conjunctival and corneal neovascularization was noticed.
Bibliography
Leonard A. Levin, Daniel M.Albert, Ocular Disease: Mechanisms and Management, 2010, Elsevier Inc., (2010);
Douglas J Coster, Fundamentals of Clinical Ophthalmology - Cornea, BMJ Books, London, (2002);
David A. Palay, Jay H. Krachmer, Primary Care Ophthalmology, Elsevier Mosby Inc., (2005); Jimmy D. Bartlett, Siret D Jaanus, Clinical Ocular Pharmacology, fifth edition, by Butterworth- Heinemann, Elsevier, (2008);
Jack J. anski, Clinical Ophthalmology - A Systematic Approach, sixth edition, by Butterworth- Heinemann, Elsevier, (2007);
Merck Manual Online, Corneal Disorders by Melvin I. Roat, Glaucoma by Douglas J. Rhee, (2008);
Peter A. Netland , Glaucoma Medical Therapy: Principles and Management, second edition, Oxford University Press, Inc., (2008);
ai Tang, CN 101579488 (A), 2009;
Jian Ren, Lan Zhang, Junling Yang, CN 101647913 (A), 2010;
Zaghloul El-Nagar "Prophetic Medicine Part 2"-Truffles healing the eye, June 2009; hUp://www.elakiri.com/forum/showthread.php2t=4830238highlight=Truffles
Abu-Rabia A. ( 1983) "Folk medicine among the Bedouin tribes in the Negev", Social studies center of the Jacob Blaustein Institute for Desert Research, Ben-Gurion University of the Negev, Ierusalem, p. 17;
Murcia M. A., Martinez - Tome M., Vera A., Morte A., Gutierrez A., Honrubia M., Jimenez A. M. (2003) J.Sci. Food Agr. 83, 535-541 ;
Janakat S., Al-Fakhiri S., Sallal A.-K. (2004) Phytother.Res. 18, 810-813;
Janakat S.M., Al-Fakhiri S.M., Sallal A.- .J. (2005) Saudi Med.J. 26 (6) 952-955.
8

Claims

PRODUCT OF NATURAL ORIGIN FOR OPHTHALMIC TREATMENT AND OBTAINING PROCEDUREPATENT CLAIMS
1. Product of natural origin for ophthalmic treatment, active in affections of the cornea and moderately active in glaucoma, characterized by the fact that it consists in an aqueous extract of brown desert truffles of Terfezia genus fungi, having a concentration of 13...17%(w/v) as dry matter, containing %(w/v):
-proteins 3.0...5.5
-aminoacids 0.1 ...0.2
-carbohydrates (as glucose) 0.4...0.6, to which are added
-benzalkonium chloride 0.01 as preservative
-sodium chloride 0.6 as isotonizant and
-demineralized water to 100,
sterile, for ophthalmic treatment as eye drops.
2. Obtaining procedure of the product according to claim 1 , characterized by the fact that brown desert truffles of the Terfezia-type fungi, fresh or frozen, are extracted with demineralized water, in a ratio of 2-3: 1 (w/v) at 4°C; the extract is separated through filtration on a filter aid layer (celite) or centrifugation and it is purified through ultrafiltration on membranes with a cut-off limit of 10 kDa, the permeate solution so obtained is concentrated under vacuum to 1/6-1 /9 (v/v), then benzalkonium chloride 0.01 % (w/v) and sodium chloride 0.6% (w/v) are added, thus obtaining an eye drops solution which fills in sterile bottles of 5-10 ml.
3. The use of the product according to claim 1 for cornea affections and glaucoma in animals.
6
EP11797277.8A 2010-12-15 2011-01-14 Product of natural origin for ophthalmic treatment and obtaining procedure Withdrawn EP2680868A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ROA201001351A RO126750A0 (en) 2010-12-15 2010-12-15 Natural product for ophthalmic treatment and process for obtaining the same
PCT/RO2011/000001 WO2012082003A1 (en) 2010-12-15 2011-01-14 Product of natural origin for ophthalmic treatment and obtaining procedure

Publications (1)

Publication Number Publication Date
EP2680868A1 true EP2680868A1 (en) 2014-01-08

Family

ID=44837900

Family Applications (1)

Application Number Title Priority Date Filing Date
EP11797277.8A Withdrawn EP2680868A1 (en) 2010-12-15 2011-01-14 Product of natural origin for ophthalmic treatment and obtaining procedure

Country Status (3)

Country Link
EP (1) EP2680868A1 (en)
RO (1) RO126750A0 (en)
WO (1) WO2012082003A1 (en)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101579488B (en) 2009-06-16 2011-01-26 唐凯 Chinese medicament for treating cataract and glaucoma
CN101647913B (en) 2009-09-04 2011-06-15 任健 Traditional Chinese medicine preparation for treating senile cataract and viral keratitis

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2012082003A1 *

Also Published As

Publication number Publication date
RO126750A0 (en) 2011-10-28
WO2012082003A1 (en) 2012-06-21

Similar Documents

Publication Publication Date Title
KR102661178B1 (en) Composition for Prevention or Treatment of Ocular Diseases Comprising Extracellular Vesicles derived from Lactobacillus paracasei
JP2023174959A (en) Flavonoid composition
JP6824270B2 (en) PEGylated lipid nanoparticles with bioactive lipophilic compounds
JP5627642B2 (en) Pharmaceutical composition for the treatment of dry eye and / or keratoconjunctival disorders
EP2119436A1 (en) Pharmaceutical compositions for preventing and treating eye pathologies
CN108025029B (en) Compositions for treating corneal or conjunctival diseases
KR101762797B1 (en) Compositions for preventing or treating dry eye syndrome comprising extract of maple leaves or fraction thereof
KR20240175240A (en) Composition for prevention and treatment of eye diseases containing Caulerpa lentillifera extract
CN102821773B (en) Composition for treating, preventing or improving macular degeneration comprising bilberry extract or part of bilberry as an active ingredient
CN105983004A (en) Composition capable of alleviating asthenopia and preparation method
CN113768995B (en) Composition for improving respiratory organ health due to continuous exposure to a fine dust atmosphere
WO2012082003A1 (en) Product of natural origin for ophthalmic treatment and obtaining procedure
RU2519553C1 (en) Complex action medication and method of its production
JP7396737B2 (en) Composition for preventing or treating eye diseases containing extracellular vesicles derived from Lactobacillus paracasei
KR101796923B1 (en) Composition for treating neurodegenerative disorders containing ginseng berry extracts
KR102571939B1 (en) A composition for improving dry eye syndrome comprising Tetraselmis chuii
EP2709643B1 (en) Compositions comprising extracts or materials derived from palm oil vegetation liguor for inhibition of vision loss due to macular degeneration
KR20190006925A (en) Novel dihydro-2&#39;H,3H-spiro[furan-2,3&#39;-furo[3,2-b]furan]-2&#39;,5(3a&#39;H,4H,5&#39;H)-dione derivative and composition for prevention or treatment of inflammatory eye disease comprising the same
CN110812323A (en) Ophthalmic composition, preparation method and application thereof
KR101401854B1 (en) Composition for cleaning eyeball comprising mineral water
RO127733A0 (en) Product of natural origin for ophthalmic treatment and process for preparing the same
TWI749568B (en) Ophthalmic compositions and medical uses thereof in treatment of myopia
KR20110078524A (en) Composition for the treatment of degenerative neuropathy containing ginseng fruit extract
US20170274035A1 (en) Compositions comprising extracts or materials derived from palm oil vegetation liquor for inhibition of vision loss due to angiogenesis and method of preparation there
US20190091287A1 (en) Plant fractions having anti-pathogenesis properties

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20120907

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

DAX Request for extension of the european patent (deleted)
RIN1 Information on inventor provided before grant (corrected)

Inventor name: RASIT, IUKSEL

Inventor name: DAAS, ARIJ

Inventor name: CRE U, ALEXANDRA

Inventor name: MOSCOVICI, MI U

Inventor name: DAAS,MOROUJ

Inventor name: NITA, SULTANA

Inventor name: GHERA, DANIELA

Inventor name: DAAS, MARWA

Inventor name: COSA, ORTANSA

Inventor name: PANTELI, IRINA MINERVA

Inventor name: BOGHIU, ANASTASIA

Inventor name: DAAS, AHMAD

Inventor name: DAAS, NOUR

Inventor name: CASARICA, ANGELA

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20140801