藥科二 報告
藥三A
B114098054
Natural Product Research
Volume 25
,
Issue 19
, 2011
•
In vivo antioxidant activity of
Pinus koraiensis nut oil obtained
by optimised supercritical carbon
dioxide extraction
•
DOI:
– 10.1080/14786419.2010.483229
•
Xiaoqiang Chen
a*,
Ying Zhang
a,
Zhenyu Wang
b &
Yuangang Zu
a
pages 1807-1816
•
Abstract
In this study, an orthogonal array design OA9 (34) was employed to optimise the
conditions of supercritical carbon dioxide (SC-CO2) extraction of Pinus koraiensis
nut oil. The effects of pressure, temperature and extraction time on the oil yield
were investigated.
Next, the fatty acid composition of the oil was examined by gas
chromatography-mass spectrometry (GC-MS). The in vivo antioxidant activity of the oil was
determined by estimating the superoxide dismutase (SOD) and glutathione
peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and the content of
malondialdehyde (MDA) in rats fed with a high-fat diet. The results showed that
extraction pressure and time were the main variables that influenced the oil yields.
The optimal conditions with which to obtain highest yield of oil were determined to
be 5760.83
psi, 50°C and 3.0 h (extraction yield was 458.5 g kg−1); nine
compounds, constituting about 99.98% of the total oil, were identified.
The most abundant polyunsaturated fatty acids identified in the oil, linoleic acid and
α-linolenic acid, constituted 41.79% and 15.62% of the oil, respectively. Moreover,
the results on their antioxidant activities showed that the oil could improve the
activities of SOD, GSH-Px and T-AOC, and reduce the content of MDA
significantly, in the serum. These results indicate that P. koraiensis nut oil obtained
by SC-CO2 extraction had excellent antioxidant activities.
Protective Effects of Curcumin against
Fluoride-Induced Oxidative Stress in the Rat Brain
•
By:
S. F. Nabavi
,
Sh. Eslami
,
A. Hajizadeh Moghaddam
and
S. M. Nabavi
•
Abstract
We examined effects of a plant polyphenolic compound, curcumin, against
fluoride-induced oxidative stress in the rat brain. Five experimental groups
of male rats (10 animals each) were compared. Animals of these
experimental groups were treated with curcumin (10 and 20 mg/kg body
mass), vitamin C (10 mg/kg), and sample solvent (0.5 ml) for a week prior
to sodium fluoride intoxication. After treatment, rats of the experimental
groups, except for the normal control group, were intoxicated with sodium
fluoride (600 ppm through drinking water) for a week.
Then, brains were collected and homogenized, and activities of superoxide
dismutase and catalase and levels of reduced glutathione and lipid
peroxidation final products were evaluated in the brain tissue homogenates.
Treatment with curcumin prior to fluoride intoxication significantly
normalized the above biochemical parameters; the intensity of protective
effects of 20 mg/kg curcumin was close to that of vitamin C.
Journal of Agronomy and Crop
Science
•
Volume 197, Issue 6,
pages 454–
465, December 2011
•
作者
É. Darkó1, J. Fodor2, S. Dulai3, H.
Ambrus1, A. Szenzenstein1, Z.
Király2, B. Barnabás1
•
Article first published online: 18
JUL 2011
•
DOI:
10.1111/j.1439-037X.2011.00479.x
© 2011 Blackwell Verlag GmbH
Improved cold and drought tolerance of doubled
haploid maize plants selected for resistance to
prooxidant tert-butyl hydroperoxide
•
By: Darko, E.; Fodor, J.; Dulai, S.; Ambrus, H.; Szenzenstein, A.; Kiraly, Z.; Barnabas, B.
•
Abstract
To improve the abiotic stress tolerance of maize (Zea mays L.), doubled haploid (DH) plants
were produced by in vitro selection of microspores exposed to tert-butyl hydroperoxide
(BuOOH) as a powerful prooxidant This study investigated the tolerance of the progenies of
t-BuOOH-selected DH lines to oxidative stress, cold and drought in controlled environment pot
experiments by analyses of photosynthetic electron transport and CO2 assimilation processes,
chlorophyll bleaching and lipid peroxidation of leaves.
Our results demonstrated that the t-BuOOH-selected DH plants exhibited enhanced tolerance
not only to oxidative stress-induced by t-BuOOH but also to cold and drought stresses. In
addition, they showed elevated activities of antioxidant enzymes such as superoxide
dismutase, ascorbate peroxidase, catalase, glutathione reductase and glutathione S-transferase
when compared with the DH lines derived from microspores that were not exposed to
t-BuOOH and to the original hybrid plants.
The results suggest that the simultaneous up-regulation of several antioxidant enzymes may
contribute to the oxidative and cold stress tolerance of the t-BuOOH-selected DH lines, and
that the in vitro microspore selection represents a potential way to improve abiotic stress
tolerance in maize.
Effects of Na+ on the growth and superoxide
dismutase of non-salt plant wheat seedlings
•
By: Fu, Wei
•
Abstract
The purpose was to discuss the changes of growth increment and superoxide
dismutase (SOD) activity of wheat seedlings under the influence of Na+.
[Method] With Yanmai19 as tested wheat variety, the wheat seedlings were treated
with Na+ solns. of different concn. and different matches and the SOD activity was
detd. by using colorimetry.
[Result] The aerial growth increments of wheat in various treatments were lower
than that in CK and that in the treatment with 0.200 mol/L·NaCl was lowest; the
growth increments of wheat in the treatments with 0.100, 0.150 and 0.200 mol/L
NaNO3 were obviously higher than that in the other treatments. The growth
increments of wheat in the treatment groups 1 and 2 all showed decreasing trend;
that in the treatment groups 3 and 4 all showed the trend of first increasing and then
decreasing; that in the treatment group 5 showed the trend of first decreasing and
then increasing. As the concn. of Na+ and Cl- were increased, the SOD activity was
decreased.
[Conclusion] Na+ at high concn. had obvious inhibition action on wheat growth.
Under the same concn. of Na+, Cl- at high concn. reduced the growth increment of
wheat and Cl- at low concn. had some promoting action on wheat growth. The SOD
activity was related to absorbed dose of Cl-.
Effects of perinatal disease on the
content of SOD, MDA in serum of cattle
•
By: Sun, Ying-xiang
•
Abstract
To investigate the relationship between perinatal disease and serum
superoxide dismutase (SOD), malondialdehyde (MDA) in cattle.
[Method] A total of 38 cattle in the perinatal period were used as the test
cattle, in which 22 healthy cattle, 5 cattle affected by ketosis, 4 cattle
affected by fatty liver, 7 cattle affected by RFM. SOD and MDA content
were detd. at different times, resp.
[Result] The SOD activity of disease cattle was lower than the healthy
cattle, and MDA content was higher than the healthy cattle at perinatal
period.
[Conclusion] The antioxidant capacity of disease cattle was lower than the
Effect of zinc on the antioxidase
activity in wheat
•
By: Wang, Pei
•
Abstract
The purpose of this research was to discuss the action of endogenous antioxidase
system in resistance of crops to exogenous heavy metal stress.
[Method] The potted wheat seedlings were treated with different concn. of zinc
(Zn2+) soln. till the seedlings grew slowly, then the materials were fetched for detg.
the indexes, such as peroxidase (POD), superoxide dismutase (SOD), catalase
(CAT) and malondialdehyde (MDA).
[Result] Compared with CK group, the POD activities in wheat treated with 20, 50,
100, 200, 400 and 800 mg/L Zn2+ soln. were enhanced by 54.8%, 58.2%, 115.2%,
157.8%, 408.5% and 564.0% resp.; the SOD activities in wheat treated with 200,
400 and 800 mg/L Zn2+ soln. were 77.1%, 68.4% and 61.2% resp.; the CAT
activities in wheat treated with 20, 50, 100, 200 and 400 mg/L Zn2+ soln. were
enhanced by 1.7%, 4.0%, 13.2%, 16.3% and 22.8% resp.; the MDA contents in
wheat treated with 20 and 50 mg/L Zn2+ soln. were 96.4% and 97.5% resp.; the
MDA contents in wheat treated with 100, 200, 400 and 800 mg/L Zn2+ soln. were
enhanced by 57.7%, 92.7%, 235.4% and 464.4% resp.
[Conclusion] In the scavenging system of active oxygen in wheat under Zn2+ stress,
Superoxide dismutase mimics for the
treatment of ocular disorders and diseases
• Assignee/Applicant專利權人:
Original: Novartis AG, Basel, CH
• Inventor :
Klimko Peter G., Fort Worth, TX, US Collier Jr. Robert J.,
Arlington, TX, US Hellberg Mark R., Arlington, TX, US
• Publication Date (Kind Code) : 2011-11-29 (B2)
• Application Number / Date :US2010730820A
/ 2010-03-24
• Priority Number / Date / Country :
•
Abstract
This application is directed to the use of mimics
of the enzyme, superoxide dismutase to treat
persons suffering from the exudative and
non-exudative forms of AMD, diabetic retinopathy,
which includes preproliferative diabetic
retinopathy (collectively DR) and retinal edema.
•
結構
•
A
is a pharmaceutically acceptable anion
•
X1-4
are independently selected from the group
consisting of H, halo, aryl, aralkyl, alkyl, cycloalkyl,
aryloxy, free or functionally modified hydroxy, and
free or functionally modified amino
•
Y1-6
are independently selected from the group
consisting of H, alkyl, cycloalkyl, aryl, aralkyl, free or
functionally modified hydroxy, and free or
functionally modified amino and
•
Z, Z1, and Z2
together can form a cyclohexane,
pyridine, or phenyl ring
Z
is a direct bond, and
Z1 and Z2
are each a CH2 group,
independently and optionally substituted with aryl,
heteroaryl, alkyl, alkoxy, aralkyl, acyl, alkoxycarbonyl,
or acyloxy.
DESCRIPTION OF THE INVENTION
•
Posterior segment neovascularization is the vision-threatening pathology responsible for the
two most common causes of acquired blindness in developed countries: exudative age-related
macular degeneration (AMD) and proliferative diabetic retinopathy (PDR). Currently the only
approved treatments for the posterior segment NV that occurs during exudative AMD are
laser photocoagulation or photodynamic therapy with Visudyne®; both therapies involve
occlusion of affected vasculature which results in localized laser-induced damage to the retina.
Surgical interventions with vitrectomy and membrane removal are the only options currently
available for patients with proliferative diabetic retinopathy. No strictly pharmacologic
treatment has been approved for use against posterior segment NV, although several different
compounds are being evaluated clinically, including, for example, anecortave acetate (Alcon,
Inc.), EYE 001 (Eyetech), and rhuFabV2 (Genentech) for AMD and LY333531 (Lilly) and
Fluocinolone (Bausch & Lomb) for diabetic macular edema.
•
In addition to changes in the retinal microvasculature induced by hyperglycemia in diabetic
patients leading to macular edema, proliferation of neovascular membranes is also associated
with vascular leakage and edema of the retina. Where edema involves the macula, visual
acuity worsens. In diabetic retinopathy, macular edema is the major cause of vision loss. Like
angiogenic disorders, laser photocoagulation is used to stabilize or resolve the edematous
condition. While reducing further development of edema, laser photocoagulation is a
cytodestructive procedure, that, unfortunately will alter the visual field of the affected eye.
•
An effective pharmacologic therapy for ocular NV and edema would likely provide
substantial efficacy to the patient, in many diseases thereby avoiding invasive surgical or
damaging laser procedures. Effective treatment of the NV and edema would improve the
patient's quality of life and productivity within society. Also, societal costs associated with
providing assistance and health care to the blind could be dramatically reduced.
Citations
Publication Number Publication Date Application Date Inventor Assignee/Applican t TitleUS5075116A 1991-12-24 1989-04-20 LaHaye Peter G. LAHAYE LAB INC
Composition and method for treatment of macular degeneration
US6046188A 2000-04-04 1998-03-11 Malfroy Camine Bernard
EUKARION INC Synthetic catalytic free radical scavengers useful as antioxidants for prevention and therapy of disease
US6127356A 2000-10-03 1996-06-07 Crapo James D. UNIV DUKE Oxidant scavengers
WO200007289 3A2
2000-12-07 2000-05-26 ORNBERG Richard
MONSANTO CO BIOMATERIALS MODIFIED WITH SUPEROXIDE DISMUTASE MIMICS
US6214817B1 2001-04-10 1999-09-16 Riley Dennis P. MONSANTO CO Substituted pyridino
pentaazamacrocyle complexes having superoxide dismutase activity
WO200001999 3A2 2000-04-13 1999-10-06 BROWNLEE Michael BROWNLEE MICHAEL
METHODS AND COMPOSITIONS FOR DECREASING MITOCHONDRIAL
OVERPRODUCTION OF REACTIVE OXYGEN SPECIES IN CELLS
US2006003588 0A1
2006-02-16 2005-05-12 Klimko Peter - Superoxide dismutase mimics for the treatment of ocular disorders and diseases
US5696109A 1997-12-09 1995-06-07 Malfroy Camine Bernard
EUKARION INC Synthetic catalytic free radical scavengers useful as antioxidants for prevention and therapy of disease
US654149 0B1
2003-04-01 2000-11-27 Campbell Ian Baxter EUKARION INC Bipyridine manganese complexes
WO19980 58636A1
1998-12-30 1998-06-15 SALVEMINI Daniela SEARLE & CO ANALGESIC METHODS USING SYNTHETIC CATALYSTS FOR THE DISMUTATION OF
SUPEROXIDE RADICALS US551038
3A
1996-04-23 1993-08-03 Bishop John E. ALCON LAB INC Use of cloprostenol, fluprostenol and their salts and esters to treat glaucoma and ocular hypertension
US599433 9A
1999-11-30 1995-06-07 Crapo James D. UNIV ALABAMA RES FOUND
Oxidant scavengers
US618062 0B1
2001-01-30 1998-04-09 Salvemini Daniela SEARLE & CO Analgesic methods using synthetic catalysts for the dismutation of superoxide radicals
WO19990 23097A1
1999-05-14 1998-11-03 FRIDOVICH Irwin UNIV DUKE SUBSTITUTED PORPHYRINS
WO20000 07584A2
2000-02-17 1999-08-03 LEVIN Leonard A. WISCONSIN ALUMNI RES FOUND
METHOD OF REDUCING RETINAL GANGLION CELL DEGENERATION
US617741 9B1
2001-01-23 1999-08-17 Campbell Ian Baxter EUKARION INC Bipyridine manganese complexes
WO20040 52283A2
2004-06-24 2003-12-05 KLIMKO Peter G. ALCON INC SUPEROXIDE DISMUTASE MIMICS FOR THE
TREATMENT OF OCULAR DISORDERS AND DISEASES
Citations
USE OF S-ADENOSYLMETHIONINE (SAM) AND
SUPEROXIDE DISMUTASE (SOD) FOR THE
PREPARATION OF MEDICAMENTS
FOR THE TREATMENT OF ALZHEIMER'S DISEASE
•
Assignee/Applicant專利權人:
Standardized: GNOSIS S P A,
Original: GNOSIS S.P.A., Milano, IT
•
Inventor :
Scarpa Sigfrido, Roma, IT Fuso Andrea, Pomezia, IT
Damiani Rosellina, Desio, IT Rossini Mauro, Desio, IT
•
Publication Date (Kind Code) : 2011-01-27 (A1)
•
Application Number / Date :
US2010919515A
/ 2010-10-13
•
Priority Number / Date / Country :
EP2008425123A / 2008-02-29 / EP
US2010919515A / 2009-02-25 / US
WO2009EP1323A / 2009-02-25 / EP
•
Abstract
• A method of treatment for Alzheimer's disease comprising administering to a patient in need thereof an effective amount of medicaments comprising S-adenosylmethionine (SAM) in combination with superoxide dismutase (SOD). • The method as claimed in claim 1, wherein the medicaments inhibits overexpression of PS1 and BACE.
• The method as claimed in claim 1, wherein the medicaments are administered orally.
• Products containing as the sole active ingredients (i) S-adenosylmethionine or a derivative thereof and (ii) superoxide dismutase, in the form of a combined preparation for the simultaneous, separate or sequential administration in the treatment of Alzheimer's disease.
• Products as claimed in claim 4, wherein SAM takes the form of tosylate, butanedisulphonate, disulphate tosylate, disulphate ditosylate or disulphate
monotosylate, or is contained in Saccharomyces
cerevisiae cells enriched with SAM.
• The method of claim 1 wherein said effective dose is between 200 and 2000 mg/day for SAM and 50 and 1000 mg/day for SOD
FIG. 5 shows the effect of SAM and SOD on oxidative status in eythrocytes and brain of mice treated with B-deprived diet.
DESCRIPTION OF THE INVENTION
• It has now been found that the activity of S-adenosylmethionine can be surprisingly improved when it isadministered in combination with superoxide dismutase (SOD). This enzyme has not only proved able to facilitate the passage of S-adenosylmethionine through the blood-brain barrier, but also interacts
synergically with SAM in reducing the expression of the PS1 and BACE genes overexpressed as a result of vitamin B deficiency.
• One aspect of the invention therefore relates to products containing S-adenosylmethionine or a derivative thereof and superoxide dismutase in the form of a combined preparation for simultaneous, separate or sequential administration in the treatment of Alzheimer's disease.
• The doses can vary within a wide range in view of the very low toxicity of SAM and SOD, and will depend on a number of factors, such as the patient's weight, sex and age. However, broadly speaking, they will be between 200 and 2000 mg/day for SAM and between 50 and 1000 mg/day for SOD.
• SAM can be administered, preferably orally, either as such or in the form of a stable salt thereof such as tosylate, butanedisulphonate, disulphate tosylate, disulphate ditosylate or disulphate monotosylate. An advantageous form of administration is Saccharomyces cerevisiae cells enriched with SAM, described in WO 2006/131382.
• SOD, obtained by fermentation from strains of Saccharomyces cerevisiae as described in WO 2006/131382 filed by the Applicant, can also be administered orally, supported on gliadin film, or using other
gastroprotection techniques. As an alternative to the oral route, both SAM and SOD can be administered parenterally, e.g. by intramuscular injection.
• Examples of these formulations include tablets film-coated with acrylic or methacrylic polymers, gastroresistant capsules, microcapsules and the like.
• SAM and SOD can be present in the same dose unit or formulated and administered separately: in that case, kits could be provided comprising the two drugs in separate dose forms accompanied by instructions for their sequential, simultaneous or separate use.
Family (Collapse INPADOC Family )
Publication
Number Publication Date Inventor Assignee/Applic ant
Title US2011002
0301A1 2011-01-27 Scarpa Sigfrido GNOSIS S P A
USE OF S-ADENOSYLMETHIONINE (SAM) AND SUPEROXIDE DISMUTASE (SOD) FOR THE PREPARATION OF MEDICAMENTS FOR THE TREATMENT OF ALZHEIMER'S DISEASE AU2009218
723A1 2009-09-03 FUSO ANDREA GNOSIS S P A
Use of S-adenosylmethionine (SAM) and superoxide dismutase (SOD) for the preparation of medicaments for the treatment of Alzheimer's disease CA2716893
A1 2009-09-03 SCARPA SIGFRID O
GNOSIS S P A
USE OF S-ADENOSYLMETHIONINE (SAM) AND SUPEROXIDE DISMUTASE (SOD) FOR THE PREPARATION OF MEDICAMENTS FOR THE TREATMENT OF ALZHEIMER'S DISEASE CN1019651
97A_ 2011-02-02 SCARPA S GNOSIS S P A
Use of s-adenosylmethionine (sam) and superoxide dismutase (sod) for the preparation of medicaments for the treatment of alzeimer's disease EP2095828
A1 2009-09-02 Scarpa Sigfrido GNOSIS S P A
Use of S-adenosylmethionine (SAM) and superoxide dismutase (SOD) for the preparation of medicaments for the treatment of Alzeimer's disease EP2249868
A1 2010-11-17 SCARPA Sigfrido GNOSIS S P A
USE OF S-ADENOSYLMETHIONINE (SAM) AND SUPEROXIDE DISMUTASE (SOD) FOR THE PREPARATION OF MEDICAMENTS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
Family (Collapse INPADOC Family )
IL207807D0 2010-12-30 - GNOSIS S P A
USE OF S-ADENOSYLMETHIONINE (SAM) AND SUPEROXIDE DISMUTASE (SOD) FOR THE PREPARATION OF MEDICAMENTS FOR THE TREATMENT OF ALZHEIMER'S DISEASE JP20115132
57A_ 2011-04-28 -
-KR2010126
326A_ 2010-12-01 SCARPA SIGFRIDO GNOSIS S P A
USE OF S-ADENOSYLMETHIONINE(SAM) AND SUPEROXIDE DISMUTASE(SOD) FOR THE PREPARATION OF MEDICAMENTS FOR THE TREATMENT OF ALZHEIMER'S DISEASE MX2010009
384A_ 2010-12-21 SCARPA SIGFRIDO GNOSIS S P A
USE OF S-ADENOSYLMETHIONINE (SAM) AND SUPEROXIDE DISMUTASE (SOD) FOR THE PREPARATION OF MEDICAMENTS FOR THE TREATMENT OF ALZHEIMER'S DISEASE. WO2009106
302A1 2009-09-03 SCARPA Sigfrido GNOSIS S P A
USE OF S-ADENOSYLMETHIONINE (SAM) AND SUPEROXIDE DISMUTASE (SOD) FOR THE PREPARATION OF MEDICAMENTS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
Superoxide Dismutase Mimics For The
Treatment Of Optic Nerve And Retinal Damage
•
Assignee/Applicant專利權人:
Standardized: ALCON INC,
Original: ALCON INC., Hunenberg, CH
•
Inventor :
Klimko Peter G., Fort Worth, TX, US
•
Publication Date (Kind Code) : 2011-05-05 (A1)
•
Application Number / Date :
US2010971143A
/ 2010-12-17
•
Priority Number / Date / Country :
US2003528830P / 2003-12-11 / US
US2004213A / 2004-11-30 / US
US2010971143A / 2010-12-17 / US
• Abstract
Methods for preventing and treating damage to the optic nerve and/or retina by the use of SOD mimics, particularly pentaazacycle Mn(II) complex SOD mimics, are disclosed .The present invention overcomes these and other drawbacks of the prior art by providing
methods to treat persons suffering from chronic or acute optic nerve and/or retinal damage. The present invention discloses compositions and methods for systemic, topical, and
intraocular administration of at least one SOD mimic in an amount effective to prevent or to treat retinal and/or optic nerve head tissue damage.
• 結構
• R1-20 are independently H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl,
heteroaryl, heterocycloalkyl, or heterocycloalkenyl, each of which is optionally substituted with an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, halo, trihalomethyl, acyl, alkoxycarbonyl, alkylsulfonyl, or
arylsulfonyl group, or a free or functionally modified hydroxyl, amino, or thiol group; • or two of the R groups on the same (e.g., R1 and R2, or R3 and R4, or R5 and R6, etc.) or
adjacent (e.g., R1 and R3, or R3 and R5, or R6 and R7, etc.) sites, together with the carbon atoms to which they are attached, form an optionally unsaturated or aromatic C3-20
carbocycle, the carbocycle being optionally substituted with alkyl, alkenyl, alkynyl,
cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, halo, trihalomethyl, acyl, alkoxycarbonyl, alkylsulfonyl, or arylsulfonyl group, or a free or
functionally modified hydroxyl, amino, or thiol group; if form an optionally unsaturated or
aromatic C2-20 nitrogen-containing heterocycle, the heterocycle being optionally
substituted optionally substituted with alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, halo, trihalomethyl, acyl,
alkoxycarbonyl, alkylsulfonyl, or arylsulfonyl group, or a free or functionally modified hydroxyl, amino, or thiol group
• it being understood that in all cases the nitrogens binding the Mn centerin the drawing for I will lack hydrogens when the nitrogen is already trisubstituted (e.g., when the relevant nitrogen is part of a pyridine ring);
• X, Y, and Zare pharmaceutically acceptable anions; and
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Publication Numbe r Publicatio n Date Inventor Assignee/Ap plicant Title US2011010 5453A 12011-05-05 Klimko Peter G. ALCON INC Superoxide Dismutase Mimics For The Treatment Of Optic Nerve And Retinal Damage
AU2004305
531A1 2005-07-07 KLIMKO PETER G ALCON INC Superoxide dismutase mimics for the treatment of optic nerve and retinal damage
AU2004305
531B2 2009-11-26 KLIMKO PETER G ALCON INC Superoxide dismutase mimics for the treatment of optic nerve and retinal damage
BR2004175
49A_ 2007-03-27 KLIMKO PETER G ALCON INC miméticos de superóxido dismutase para o tratamento de lesão de nervo óptico e retinal
CA2545762
A1 2005-07-07 KLIMKO PETER G. ALCON INC SUPEROXIDE DISMUTASE MIMICS FOR THE TREATMENT OF OPTIC NERVE AND RETINAL DAMAGE
CN1889961
A_ 2007-01-03 KLIMKO PETER G ALCON INC Superoxide dismutase mimics for the treatment of optic nerve and retinal damage
EP1691815
A1 2006-08-23 KLIMKO Peter G. ALCON INC SUPEROXIDE DISMUTASE MIMICS FOR THE TREATMENT OF OPTIC NERVE AND RETINAL DAMAGE
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EP1691815A4 2010-03-31 KLIMKO PETER G ALCON INC SUPEROXIDE DISMUTASE MIMICS FOR THE TREATMENT OF OPTIC NERVE AND RETINAL DAMAGE JP200751394
8A_ 2007-05-31 - -
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1A_ 2006-09-25 KLIMKO PETER G. ALCON INC SUPEROXIDE DISMUTASE MIMICS FOR THE TREATMENT OF OPTIC NERVE AND RETINAL DAMAGE MX2006PA006
187A_ 2006-08-25 KLIMKO PETER G ALCON INC SUPEROXIDE DISMUTASE MIMICS FOR THE TREATMENT OF OPTIC NERVE AND RETINAL DAMAGE. RU200612474
6A_ 2008-01-20 - -
-US200501309
51A1 2005-06-16 Klimko Peter ALCON INC Superoxide dismutase mimics for the treatment of optic nerve and retinal damage
US200700605
57A1 2007-03-15 Klimko Peter G. - Superoxide dismutase mimics for the treatment of optic nerve and retinal damage
WO20050609
74A1 2005-07-07 KLIMKO Peter G. ALCON INC SUPEROXIDE DISMUTASE MIMICS FOR THE TREATMENT OF OPTIC NERVE AND RETINAL DAMAGE ZA200603347
A_ 2009-02-25 KLIMKO PETER G ALCON INC Superoxide dismutase mimics for the treatment of optic nerve and retinal damage
